THE LIBRARY OF THE UNIVERSITY OF CALIFORNIA PRESENTED BY PROF. CHARLES A. KOFOID AND MRS. PRUDENCE W. KOFOID MICROSCOPICAL MORPHOLOGY MICROSCOPICAL MORPHOLOGY ANIMAL BODY IN HEALTH AND DISEASE. BY C. HEITZMA^^T, M.D. LATE LECTURER ON MORBID ANATOMY AT THE UNIVERSITY IN VIENNA, AUSTRIA. WITH 380 ORIGINAL ENGRAVINGS. i NEW-YORK : J. H. VAIL & COMPANY, 21 ASTOR PLACE, 1883. Copyright, 1882, by C. HEITZMANN, M. D. Press of KICAM is HART & Co. New-York. Lib PREFACE. T~N presenting this book, the result of ten years' intense labor, to the -*- public, I am aware that not all the facts and conclusions here laid down will meet the immediate approval of professional microscopists. The cell-theory, which for more than thirty years held sway over the minds of scientists, was contradicted by me in 1873, when I demonstrated the continuity of all elements engaged in the construction of tissues. In 1872, 1 discovered the connections between cartilage-corpuscles, which, thanks to a simplified method, are now easily seen. Shortly afterward, the intimate structure of " protoplasm" was discovered, and it was found that the same structure is present throughout all the interstitial sub- stances which had hitherto been considered lifeless. As many of the assertions made in 1872 and 1873 have already been found correct by good observers, I confidently expect that the others too will, in time, be accepted, although directly contrary to the cell- theory. In the autumn of 1874 I left Vienna, and, on the first of November of the same year, opened a laboratory for microscopical investigation in New- York. This has proved successful beyond all expectation. Over seven hundred attendants, among them some of the most intellectual and independent members of the medical profession, have here satisfied themselves of the correctness of my assertions. A number of these have made valuable investigations in my laboratory, the results of which will be found embodied in various articles in this book.' In view of these facts, I can await patiently the approval of scientists abroad. A doctrine which is accepted by good observers in America cannot be lost, but will develop independently of European microscop- ists, who, to a great extent, are prejudiced by the teachings of the older masters. Again have facts made it evident that the United States of America are ahead whenever new ideas of practical importance are to be acknowl- edged. I have received, in New- York, much encouragement from my students and co-workers. I have also been magnanimously supported by a friend, who is not a medical man, but a prince in character and wealth, and who surpasses most European princes in that he will not allow me to inscribe his name upon the dedicatory page. The illustrations of this book are, without exception, my own draw- ings, and have been transferred on metal to my complete satisfaction by the Moss Engraving Company, of this city. C. HEITZMANN. 39 WEST 45Tii STREET, NEW-YORK, August, 1882. CONTEXTS. PACK. I. METHODS 1 Infusion 2 Cutting 6 Moist chamber 3 Mounting 7 Heatable stage. ., 3 Staining 9 Electricity 4 Injections 10 Preparation of fresh tissues. . . 4 How to ivor7c with the microscope 10 Preservation of tissues 5 II. GENERAL PROPERTIES OF LIVING MATTER 13 Chemistry 13 Generation 15 Manifestation of life 14 Historical sketch of the study of living Properties of living matter 14 matter 18 III. THE ARRANGEMENT OF THE LIVING MATTER IN " PROTOPLASM ".. 21 AmoebcB 21 Colorless blood-corpuscles of man 26 Blood-corpuscles of the craw- Colostrum corpuscles 28 fl*h 23 Conclusions 28 Blood of the newt 25 Analysis of the assertions made in 1873 30 Only a part of "protoplasm " is Analysis of contraction and extension, 34 living matter 33 Analysis of tetanus 35 Chemical re-agents 33 Analysis of investing layers 35 Analysis of rest 34 Analysis of vacuoles 36 Comparison of amoeba and man 36 The Structure of the Blood-corpuscles of the Oyster. By A. M. Hurlbutt 37 The Structure and Growth of Some Forms of Mildew. By William Hassloch 40 IV. THE PHASES OF DEVELOPMENT OF LIVING MATTER 46 Amoeba* 46 Corpuscles of the medulla of bone 50 Cartilage-corpuscles 47 Conclusions 51 Bone-corpuscles 50 The cell-theory in the light of these researches 53 Structure of plants 57 Nomenclature 57 The general constitution of the body, as recognized by single plastids 58 V. THE STRUCTURE AND ORIGIN OF COLORED BLOOD-CORPUSCLES .... 64 The Structure of Colored Blood-corpuscles. By Louis Elsberg. . 64 Observations 64 Conclusions 94 History 73 viii CONTENTS. PAGE. The origin of colored blood-corpuscles 98 Formation of blood from carti- Formation of blood in inflamed bone. . 100 lage 98 Formation of Blood in Cartilage and Bone of Birds. By L. Schoney . 103 Experimental and Microscopical Studies on the Origin of the Blood- globules. By A. W. Johnstone 105 VI. TISSUES IN GENERAL . Ill Origin Ill Definition . 114 Division 114 1. Connective tissue 114 3. Nerve-tissue 115 2. Muscle-tissue 115 4. Epithelial tissue 115 The relation of living matter to the interstitial substance 115 Life of cartilage-corpuscles 116 Blood-vessels 127 Medullary tissue 117 Muscle-tissue 127 Tissue of the umbilical cord .... 120 Structure-elements of the nervous system 128 Tissue of tendon 122 Epithelial tissue 130 Tissiie of periosteum 124 Conclusions 131 Tissue of bone 126 Is blood a tissue ? 134 Researches and deductions since 1873 135 VII. CONNECTIVE TISSUE 143 Definition and division 143 1. Myxomatous or mucoid tissue 146 (a) Medullary tissue 147 (c) Myxomatous tissue of the umbilical (b) Reticular tissue 147 cord 150 Fat-tissue 155 2. Striated or fibrous connective tissue 158 (a) Delicate connective tissue dies running in a longitudinal composed of fibrillce or of direction 164 comparatively thin bundles (d) Dense connective tissue composed of fibrillce 159 of interlacing ribbons 168 (b) Dense connective tissue (e) Coalesced layers of elastic basis- composed of coarse, interlac- substance, arranged in a sheath- ing bundles 162 like manner 168 (c) Dense connective tissue (f) Lamellated layers of fibrous inter- composed of coarse bun- lacing connective tissue 169 Researches on the Microscopical Structure of the Cornea. By William Hassloch 171 Development of fibrous connective tissue 179 Secretion theory 181 Territories 182 Transformation theory 181 Bioplasson theory 182 Elastic substance 182 3. Cartilage-tissue 185 History. By Louis Elsberg 185 Varieties of cartilage tissue 190 (a) Reticular or elastic cartilage 191 (c) Hyaline cartilage 195 (b) Striated or fibrous cartilage 193 The structure of hyaline cartilage 198 The Structure of the Thyroid Cartilage. By Louis Elsberg 206 Development of cartilage 212 CONTENTS. ix PAGE. 4. Bone-tissue 218 History 218 Bone-corpuscles 221 Methods 220 Varieties of bone-tissue 223 (a) Cancellous, epiphyseal, or Periosteum 228 spongy bone-tissue 223 Blood-vessels 230 (b) Cortical or compact bone- Medulla of bone 230 tissue 225 The relation of the systems of lamellae to the blood-vessels 231 Development of bone 236 (A) Development of bone from (c) Formation of red blood-corpuscles cartilage 238 and blood-vessels 243 (a) Calcification 238 (d) Formation of bone from medulla. . 247 ( b) Formation of medullary tis- sue 242 The Process of Ossification in Birds. By A. L. Schoney 251 (B) Development of bone from (C) The growth and retrogression of fibrous connective tissue 254 bone 258 VIII. MUSCLE-TISSUE 262 1. Smooth or unstriped muscle 263 2. Striped muscle 265 The Structure of the Muscle of the Lobster. By M. L. Holbrook. . 274 IX. NERVE-TISSUE 279 1. Nerve-centers 280 (A) Brain 280 (E) The connective tissue investments The origin of the cerebral of the brain and the spinal cord ... 292 nerves 282 Dviramater 292 (B) Gray substance 283 Arachnoidea 293 (C) Ganglionic elements 285 Pia mater 293 (D) White substance of the (F) The ganglia 293 spinal cord 290 2. Nerves 294 (a) Medullated nerves 295 (b) Non-medullated nerves 298 3. Terminations of nerves 298 (a) Termination of medullated (b) Termination of non-medullated nerve-fibers 299 nerve-fibers 300 Development of nervous tissue 302 Methods for the preparation of nerve-tissue 303 Analysis of bioplasson in its relations to nerve-action 305 X. EPITHELIAL AND ENDOTHELIAL TISSUE 311 Definition 311 Peritoneum 315 Crystalline lens 316 Division - 318 Single epithelial layers 321 Stratified epithelial layers 322 Termination of nerves 323 Glands 325 Performances of epithelium 327 (a) Watery secretion 328 (c) Fatty secretion 332 (b) Mucous secretion 329 X CONTENTS. I'AGK. The vascular system 333 1. The heart 333 2. The arteries 335 3. The veins 337 4. The capillaries . 339 Development of capillaries 341 The lymphatic system . 343 Lymph-vessels. 343 Thyroid body 348 Lymph -ganglia and lymph- Supra-renal capsule 349 tissue 345 Spleen 350 Thymus body 348 XI. INFLAMMATION 353 Historical sketch 353 1. Inflammation of connective tissue 356 (A) Inflammation of the perios- Injuries at the lateral portions of the teum 356 articular cartilage 363 Inflammation of the tendon. . . . 360 Feeding of cartilage-corpuscles with in- (B) Inflammation of cartilage. 361 soluble gramdar substances 364 Superficial injuries in the mid- ( C) Inflammation of bone 367 die of the condyle 361 New formation of blood-vessels in in- Simultaneous injuries of the flamed bone-tissue 373 articular cartilage and the Conclusions arrived at in 1873 370 subjacent epiphyseal bone.. 362 The healing process of fractured bones 381 Necrosis. By C. F. W. Bodecker 390 Rachitis and osteomalacia 393 Rachitis. Rickets 395 Osteomalacia 399 2. Inflammation of muscle. Trichinosis 401 3. Inflammation of nerve-tissue 407 Microscopical Studies on Abscess of the Brain. By H. G. Beyer. . . 407 (a) Wall of abscess 410 (d) Non-medullated nerve-fibers 414 (b) White substance 412 (d) Gray substance 414 4. Inflammation of epithelia and endothelia 418 Varieties of inflammation 422 (a) Catarrhal inflammation ... 423 (c) Suppurative inflammation 424 (b) Croupous inflammation. . . 423 Healing process of wounds 424 Diphtheritic inflammation 424 Secondary changes 425 Fatty degeneration 425 Waxy degeneration ... 427 Pigmentary degeneration 426 Colloid corpuscles. 429 Waxy Degeneration of the Cerebellum. By J. Baxter Emerson . 430 Waxy Degeneration of the Brain. By John A. Rockwell 434 XII. TUBERCULOSIS 439 Tuberculosis of the lungs 440 Chronic tuberculosis 440 Tuberculous pneumonia 445 Subacute tuberculosis 442 Acute miliary tuberculosis 447 Tuberculosis of the serous and mucous membranes 448 Chronic tuberculosis 448 Acute miliary tuberculosis 44» Subacvite tuberculosis 449 CONTENTS. xi PAGK. Tuberculosis of the mucous membranes 450 Tuberculosis and scrofulosis of the lymph-ganglia 451 Tuberculosis of the kidneys. Concomitant nephritis 453 Theory of tuberculosis 45(3 Anatomical signs of Hie tubercle 456 Comparison with suppuration 462 Origin of tubercle 458 Tuberculous and scrofulous diathesis. . 464 Further changes of tubercle 461 Recent theories 466 XIII. TUMORS ' 468 Definition 468 Origin 469 Composition and localization 470 Benignity and malignity . 471 • (a) Clinical and pathological (b) Histological features 474 features 472 Secondary changes 476 Classification 477 1. Myxoma. Mucoid tumor 479 (a) Myxoma of reticular struct- (c) Myxoma of the structure of the thy- ure 479 roid body — so-called lymph-ade- (b) Myxoma of the structure of noma 482 the umbilical cord 481 2. Fibroma. Fibrous tumor • 483 (a) Fibroma of loose, fibrous (c) Fibroma of dense, interlacing bun- connective tissue 484 dies of fibers 486 (b) My xo- fibroma, or soft fibro- (d) Scar-shaped fibroma. Keloid 486 ma 484 Combinations 486 3. Chondroma. Cartilaginous tumor 486 4. Osteoma. Osseous tumor 489 (a) Cancellous or epiphyseal or (b) Compact or eburneal osteoma 490 spongy osteoma 489 Psammoma ... 491 5. Myeloma or sarcoma • 492 (A) Globe-myeloma 493 (a) Globo-myeloma composed of (b) Globo-myeloma composed of small large plastids 493 plastids—lympho-sarcoma 493 (c) Glioma or glio-sarcoma 493 (B) Spindle-myeloma • 494 (a) Spindle-myeloma composed (c) Spindle-net my eloma ... .. 495 of large plastids 495 Giant-cell sarcoma of Virchow 496 (b) Spindle-myeloma composed Melanotic myeloma 497 of small plastids 495 Combinations of myeloma • 498 (a) Fibro-myeloma 498 (d) Osteo-myeloma (b) Myxo-myeloma 499 Alveolar myeloma 502 (c) Chondro-my eloma 500 Clinical features .503 The Changes of Epithelia produced by Growth of Myeloma. By Eud. Tauszky 504 Inflammatory changes 506 Transformation of epithelium into mye- loma-elements 509 6. Lipoma. Fatty tumor 7. Angioma. Vascular or erectile tumor • 512 xii CONTENTS. I'AGE. (a) Simple angioma 513 Lympliangioma 515 (b) Lobular angioma 513 Endothelioma 517 (c) Cavernous angioma 513 Myoma. Muscle-tumor 517 9. Neuroma. Nerve-tumor 519 10. Papilloma. Warty tumor 521 (a) Horny papilloma 522 (b) Myxomatous papilloma 523 Microscopical Study of Papilloma of the Larynx. By Louis Elsberg 524 11. Adenoma. Glandular tumor 528 Adenoma of the skin 529 Adenoma of the female breast 530 Adenoma of mucous membranes 530 Adenoma of the thyroid body 531 Cysts 531 12. Carcinoma. Cancer 533 (a) Scirrhus or hard cancer 534 Cc) Medullary cancer 536 (b) Epithelioma 535 Pathological features of cancer 536 The Origin of the Carcinoma Elements. By E. W. Hoeber 539 Local origin and transmission 544 The Development of Carcinoma in Lymph-ganglia. By A. W. Johnstone ' 545 Secondary changes of cancer 547 (a) Fatty metamorphosis 548 (d) Cystic metamorphosis 548 (b) Waxy metamorphosis 548 (e) Pigmentary metamorphosis 548 (c) Colloid metamorphosis 548 The Development of Colloid Cancer. By H. Gr. Beyer 549 XIV. THE SKIN 553 1. Subcutaneous tissue 554 2. The derma or cutis 554 3. Blood-vessels 558 4. Lymph-vessels 559 5. Nerves 559 6. The epithelial cover of the integument 561 7. Implantation of the hair 563 8. The hair 569 Shedding of the hair 570 Development of the hair 572 9. The sebaceous glands 572 10. The sudoriparous glands 574 11. The nails 576 12. The lacteal glands 578 Inflammation of the skin 580 Tumors of the skin 583 XV. THE DIGESTIVE TRACT 586 1. The oral cavity 588 2. The tongue 589 (a) Filiform papilla} 589 (c) Circumvallate papillae 590 (b) Fungiform papillae, 590 3. The pharynx and oesophagus , 592 4. The stomach 593 5. The small intestine 597 597 Absorption of fat-granules 599 CONTENTS. xiii PAGE. 6. The large intestine 605 Blood-vessels of the intestines . . 607 Nerves of the intestines 608 Lymph-vessels of the intestines. 607 7. The salivary glands 608 Saliva 610 Croupous and diphtheritic inflamma- Thrnsh 610 tion 610 Catarrhal stomatitis 610 XVI. THE TEETH 612 Dentine, Cement, and Enamel. By C. F. W. Bodecker 613 Dentine 613 Enamel 621 Cement 616 Results 623 Neck of tooth 619 History 624 Dentine and Enamel of Deciduous Teeth. By Frank Abbott 629 Secondary Dentine. By C. F. W. Bodecker 630 Secondary dentine, resembling Secondary dentine of lamellated primary dentine 636 structure 636 Osteo-dentine 638 The Pulp of the Tooth. By C. F. W. Bodecker 640 1. Methods 640 (b) Pulp-stones composed of regularly 2. The minute structure of nor- developed lamellated bone 648 mat pulp-tissue 640 (c) Pulp-stones composed of a mixture 3. Pulpitis 643 of regular bone and dentinal 4. Calcification and waxy de- tissue 648 generation 645 (d) Pulp-stones composed of dentine, 5. Dentinifi cation, eburnifica- with the features of primary den- tion, and ossification 646 tine 648 (a) P^llp-stones of the character History 649 of secondary dentine 647 The Pericementum. By C. F. W. Bodecker , 652 (A) Forms and development. . . . 652 Alveolar abscess 660 (B) Pericementitis 655 Literature 661 Hyperplasia 658 Results 662 Pyorrhoea alveolar is 659 Caries. By Frank Abbott 663 Methods 663 Caries of cement 669 Caries of enamel 663 Results 670 Caries of dentine 665 History. . . 671 Destruction of the temporary teeth . 673 Development of the teeth ... 673 XVII. THE LIVER 675 Portal vein 675 Capillaries of the lobules 676 Hepatic vein 677 Liver epithelia 678 Bile-capillaries 679 Bile-ducts 681 Gall-bladder ... 683 The Termination of the Nerves in the Liver. By M. L. Holbrook. 684 Pathology : 687 Catarrhal or Interstitial Hepatitis. By H. Chr. Miiller. . .688 Miliary tuberculosis of the liver 694 Syphilitic gumma 694 xiv CONTENTS. Microscopical Studies on Abscess of the Liver. By J. C. Davis . Pycemic abscess of Cue liver 699 Pigmentary degeneration 702 Fatty degeneration 701 Waxy degeneration 703 Yellow Atrophy of the Liver. By J. A. Rockwell 703 XVIII. THE EESPIRATORY TRACT 709 1. The nasal cavities 700 2. The larynx . 711 3. The trachea ..-. 712 4. The lungs 713 Pathology 710 (Edema of the lungs 716 Cb) Catarrhal pneumonia 722 Pigmentation 717 Tuberculosis 723 Emphysema 718 (c) Plastic interstitial pneumonia- — 725 Inflammation. Pneumonia 718 (d) Suppurative pneumonia 726 (a) Croupous pneumonia 719 Syphilitic Hepatitis and Syphilitic Pneumonia. By J. H. Ripley. . 727 Examination of the sputa 730 Tuberculous ulceration 731 Myeloma of the lungs 731 Echinococcus of the lungs 731 XIX. THE URINARY TRACT 733 1. The kidneys 734 Renal artery 734 Uriniferous tubules 739 Tufts 735 Lymphatics 743 Veins 738 Nerves 743 Researches in the Minute Anatomy of the Epithelia of the Kidney. By Henry B. Millard 744 The endothelia of the urinary tubules 747 Nephritis 751 Acute Inflammation of the Kidneys. By Alfred Meyer 753 1. Catarrhal (desquamative, in- 2. Croupous (parenchymatous) terstitial) nephritis 755 phritis 3. Suppurative nephritis Chronic Inflammation of the Kidneys. By Jeannette B. Greene. . . 767 1. Chronic catarrhal nephritis. 3. Chronic Suppurative nephritis 774 Cirrhosis 768 Formation of cysts 775 2. Chronic croupous nephritis. . 771 Fatty degeneration 776 Atrophy 772 Waxy degeneration 777 Hypertrophy 773 Results 779 2. The calices, the pelvis, and the ureter 770 3. The urinary bladder 781 4. The urethra 781 XX. THE URINE 783 Normal urine 783 Pathological urine 785 Amount of urine 786 Albumen 786 Pathological constituents 786 Determination of the specific gravity 787 CONTENTS. Chemical tests Tests for sugar Moore's test Bottyer's test Microscopic examination . Extraneous matters Crystalline sediments 1. Uric acid 2. Oxalate of lime 3. TJrate of soda 4. Hippuric acid Cystine Tyrosine Leucine 5. Urate of Ammonia 6. Triple phosphates 7. Simple phosphates 8. Calcium carbonate Epithelia Male urine Female urine. . . XV PAGE. 788 789 Trommer's test 789 Roberts' s fermentation test . . . 789 Fehling's volumetric method. 790 792 792 793 794 794 795 795 795 795 795 793 796 801 803 789 790 790 Magnesium phosphate 796 Mucus 796 Sperm 796 Colloid corpuscles of the prostate gland 797 Pus-corpuscles 797 Diagnosis of the general constitution. . 797 Ciliated pus-corpuscles 797 Pigmented pus-corpuscles 798 Red blood-corpuscles 798 Hcematoidin 798 Shreds of connective tissue 798 Fat-granules and fat-globules 799 Common to both sexes. 800 . . 803 Tubular casts , . 804 Hyaline and epithelial casts 805 Granular and fatty casts. Blood-casts 805 Waxy casts Entozoa Hooldets of echinococci. I>istoma hwmatobium . . THchomonas vaginalis. Ascaris lumbricoides. . . Diagnosis from examination of urine Urethritis 808 Villous tumors Prostatitis 809 Vaginitis 809 Cervicitis 809 Endometritis 809 Cystitis 809 XXI. THE MALE GENITAL TRACT . . Spermatozoids 1. Testis . . Pyelitis Haemorrhage from the kidneys. Catarrhal nephritis Croupous nephritis Suppurative nephritis Formation of spermatozoids Terminations of Nerves in the Testicle. By H. G. Beyer. 2. Epididymis 3. Vas deferens 4. Ampulla and seminal vesicles 5. Remnants of embryonal formations The paradidymis 820 Hydatid of Morgagni Vas aberrans Halleri 820 Pedunculated hydatid 6. Prostate gland 7. Cowper's glands 8. Penis. . . 805 . . 806 808 808 .. 810 . . 810 . . 810 .. 810 . . 811 . . 811 812 812 813 . . 814 816 818 819 819 820 . . 820 .. 820 820 821 822 XXII. THE FEMALE GENITAL TRACT. 824 xvi CONTENTS. PAGE. The ovum 824 Determination of sex 824 1. Ovary 825 Follicles 826 Remains of embryonal formations 829 Corpus luteum 827 Epoophoron 829 Paroophoron 829 2. Oviducts 829 3. Uterus 829 Pathology of the uterus 831 Catamenial decidua. By Jeannette B. Greene 832 4. The vagina and external genitals 838 The placenta and the umbilical cord 839 A Contribution to the History of the Development of the Human Deeidua. By J. W. Frankl 839 Waxy Degeneration of the Placenta. By Jeannette B. Greene. . . . 842 Waxy degeneration of the am- Waxy degeneration of the umbilical nion 847 cord 847 Conclusions 849 LIST OF CONTRIBUTORS. FRANK ABBOTT, M. D., New- York. The Minute Anatomy of Dentine and Enamel. The Dental Cosmos, Philadelphia, 1880. Abstract: "Dentine and Enamel of Deciduous Teeth." Page 629. Caries of Human Teeth. The Dental Cosmos, Philadelphia, 1878 and 1879. Abstract: "Ca- ries." Page 663. H. G. BEYER, M. D., M. R. C. Sv Passed Assistant Surgeon, U. S. Navy. Microscopical Studies on Abscess of the Brain. Journal of Nervous and Mental Dis- ease, Chicago, July, 1880. Abstract. Page 407. A Contribution to the History of the Development of Colloid Cancer.. The Medical Gazette, New- York, April, 1880. Abstract. Page 549. The Terminations of the Nerves in the Testicle. Printed in abstract from the author's manuscript. Page 816. C. F. W. BODECKER, D. D. S., M. D. S., New- York. Necrosis. The Dental Cosmos, Philadelphia, 1878. Abstract. Page 390. The Distri- bution of Living Matter in Human Dentine, Cement, and Enamel. The Dental Cosmos, Philadelphia, 1878 and 1879. Abstract: "Dentine, Cement and Enamel." Page 613. Secondary Dentine. The Dental Cosmos, Philadelphia, 1879. Abstract. Page 630. On Pericementum and Pericementitis. The Dental Cosmos, Philadelphia, 1879-80. Abstract : " The Pericerneutum." Page 652. The Minute Anatomy of the Dental Pulp in its Physiological and Pathological Conditions. The Dental Cosmos, Philadelphia, 1882. Abstract : " The Pulp of the Tooth." Page 640. J. C. DAVIS, M. D., New- York. Microscopical Studies on Abscess of the Liver. Archives of Medicine, August, 1879. Abstract. Page 695. Louis ELSBERG, M. D., New- York. Notice of the Bioplasson Doctrine. Transactions of the American Medical Associa- tion, 1875. Pages 57, 135. The Structure of Colored Blood-corpuscles. Annals of the New-York Academy of Sciences. Vol. I. 1879. Page 64. Microscopical Study of Papilloma of the Larynx. Archives of Laryngology, New- York. Vol. I. 1880. Abstract. Page 524. Contributions to the Normal and Pathological Histol- ogy of the Cartilages of the Larynx. Archives of Laryngology, New- York. Vol. II., 1881. Vol. III., 1882. Pages 57, 185, 206, 305. J. BAXTER EMERSON, M. D., New- York. Periencephalitis. Journal of Nervous and Mental Disease, Chicago, April, 1880. Abstract: "Waxy Degeneration of the Cerebellum." Page 430. J. W. FRANKL, M. D., New- York. A Contribution to the History of the Development of the Human Decidua. Ameri- can Journal of Obstetrics and Diseases of Women and Children. Vol. XL October, 1878. Abstract. Page 839. xviii LIST OF CONTRIBUTORS. JEANNETTE B. GREENE, M. D., New- York. Chronic Inflammation of the Kidneys. Printed from tlie author's manuscript. Page 767. Waxy Degeneration of the Placenta. American Journal of Obstetrics and Diseases of Women and Children. Vol. XIII. 1880. Abstract. Page 842. Microscopical Studies on the Catamenial Decidua. The American Journal of Obstet- rics and Diseases of Women and Children. Vol. XV. April, 1882. Abstract. Page 832. WILLIAM HASSLOCH, M. Dv New-York. The Structure and Growth of Some Forms of Mildew. Weiv Tork Medical Journal. November, 1878. Page 40. Researches on the Microscopical Structure of the Cornea. Archives of Opthalmology and Otology. Vol. VII. 1878. Page 171. C. HEITZMANN, M. D., New-York. Zur Kenntniss der Diinndarmzotten. Sitsungsber. der Akademie der Wissen- schaften in Wien, Iviii. Bd. 1868. Abstract. Pages 401, 600. Studien am Knochen und Knorpel. Wiener Medizinische Jahrbiicher. 1872. Pages 98, 115, 198, 221, 250, 356. Ueber die Riick- und Neubildung von Blutgefassen im Knochen und Knorpel. Wiener Medizinische Jahrbiicher. 1873. Pages 118, 231, 244, 342, 356, 373. Ueber Kiinstlichc Erzeugung von Rachitis und Osteornalacie an Thieren. Anzeiger der Akademie der Wissenschaften in Wien. 19 Juni, 1873. Vortrag in der Gescllschafl der Aerzte in Wien. October, 1873. Untersuchungen iiber das Protoplasma. I. Bau des Protoplasnias. Sitsungsber. der Kais. Akademie der Wissenschaften in Wien. April, 1873. Page 21. II. Das Verhiiltniss zwischen Protoplasnia uud Grundsubstanz im Thierkorper. Sitzungsber. der Kais. Akademie der Wissen- schaften in Wien. Mai, 1873. Page 115. III. Die Lebensphasen des Protoplasnias. Sitzungsber. der Kais. Alcademie der Wissenschaften in Wien. Juni, 1873. Page 46. IV. Die Entwickelung der Beinhaut, des Knochens und des Knorpels. Sitsungs- ber. der Kais. Akademie der Wissenschaften in Wien. July, 1873. Pages 179, 212, 247. V. Die Entziindung der Beinhaut, des Knochens und des Knorpels. Sitzungsber. der Kais. Akademie der Wissenschaften in Wien. July, 1873. Page 356. Ueber Tuberkelbildung. Wiener Medizinische Jahrbiicher. 1874. Page 439. The Cell Doctrine in the Light of Recent Investigations. A paper read before the County Medical Society of New York, 1876. New York, Medical Journal. 1877. Pages 13, 30. On the Nature of Suppurative Processes of the Skin. A paper read before the County Medical Society of New York, 1877. Uupriuted. Page 59. The Aid which Medical Diagnosis Receives from Recent Discoveries in Mi- croscopy. A paper read before the County Medical Society of New York, 1878. Archives of Medicine, New York, February, 1879. Pages 58, 140, 474. Epithelium and its Performances. A paper read before the American Dermatological Associa- tion, at their meeting in Saratoga, August 27, 1878. Published in abstract. New Tork Medical Journal. 1878. Page 311. Microscopical Studies on Inflammation of the Skin. Read before the American Dermatological Association, New York, August 27, 1879. Published in abstract in The Chicago Medical Journal and Examiner, Octo- ber, 1879. Page 580. Tumors of the Skin. Read before the American Dermato- logical Association, Newport, R. I., August, 1880. Printed in abstract in Archives of Dermatology, Philadelphia, October, 1880. Page 583. A Contribution to the Minute Anatomy of the Skin. Read before the American Dermatological Asso- ciation, Newport, R. I., September 1, 1881. The Chicago Medical Journal and Examiner, December, 1881. Page 563. E. W. HOEBER, M. D., New- York. Ueber die erste Entwicklung der Krebselemente. Sitzungsber ichte der Kais. Aka- demie der Wissenschaften in Wien, 1875. Abstract : " The Origin of the Carcinoma- Elements." Page 539. M. L. HOLBROOK, M. D., New- York. The Structure of the Muscle of the Lobster. Printed from the author's manuscript. Page 274. The Termination of the Nerves in the Liver. Printed in abstract from the author's manuscript. Page 684. LIST OF CONTRIBUTOES. xix A. M. HURLBUTT, New- York. The Structure of the Blood-corpuscles of the Oyster. New- YorJc M edicalJournal, January, 1879. Abstract. Page 37. A. W. JOHNSTONS, M. D., Danville, Ky. Experimental and Microscopical Studies on the Origin of the Blood-globules. Archives of Medicine. Vol. VI. August, 1881. Page 105. The Development of Car- cinoma in Lymph-ganglia. Printed in abstract from the author's manuscript. Page 545. ALFRED MEYER, New- York. Uiitersuchungen liber acute Nierenentzttndung. Sitzungsberichte der Kais. Aka- dcmie der Wissenschaften in Wien, Ixxv. Bd., 1877. Translated by the author. Abstract. Page 753. HENRY B. MILLARD, A. M., M. D., New- York. Researches in the Minute Anatomy of the Epithelia of the Kidney. The New-York Medical Journal, June, 1882. Abstract. Page 744. H. CHR. MULLER, M. D., New- York. Beitriige zur Kentniss der interstitiellen Leberentziindung. Sitzungsberichte der Kais, .Akademieder Wissenschaften in Wien, Bd. Ixxiii. 1876. Abstract. Page 688. J. H. RIPLEY, M. D., New- York. Syphilitic Hepatitis and Syphilitic Pneumonia. Printed from the author's manu- script. Page 727. JOHN A. ROCKWELL, M. D., New- York. A Contribution to the Pathology of the Brain. The New England Medical Gazette, March, 1882. Abstract : " Waxy Degeneration of the Brain." Page 434. Micro- scopical Studies in Yellow Atrophy of the Liver. The New England Medical Gazette, June, 1882. Abstract. Page 703. L. SCHONEY, M. D., New- York. Ueber den Ossificationsprocess bei Vogeln, uud die Neubildung von rothen Blut- korperchen an der Ossiflcationsgrenze. Archiv filr Mikroskopische Anatomic, Bd. xiii. Abstract. Pages 103, 251. RUDOLPH TAUSZKY, M. D., New- York. Ueber die durch Sarcom-Wucheruug bedingten Vera'nderungen des Epithels. Sitz- niKjsberichte der Kais. Akademie der Wissenschaften in Wien, Bd. Ixxiii. 1875. Translated by the author. Abstract. Page 504. I. METHODS. riTHE methods of preparation of the liquid and solid constit- JL uents of the animal body are of the utmost importance. Every progress in histology is largely due to an improvement in the methods of preparation employed as well as of the optical apparatus. The main purpose obviously must be to examine liquids and tissues in a condition as nearly as possible like that in which they exist within the living body. The history of histology teaches that the greatest errors have resulted from a neglect of this rule. From the moment a specimen for examination with the microscope is allowed to dry, such a specimen has become a mummy, and unfit for further research. Almost all tissues, in former times, were allowed to dry before their minute structure was examined. The results of such researches are considered worthless nowadays. Despite of all experience gained in the last four decades, — that is, the time in which microscopic mor- phology has gradually developed into a science, — even in our day, dry bone-tissue is examined in all laboratories ; but such examinations are necessarily of very small value. Another objectionable procedure is the tearing, teasing, and pulling of tissues. By such methods, the parts which in the body are connected become broken and disfigured, debris are produced, sometimes with the greatest skill, which, as a matter of fact, are useless for fruitful microscopic investigations. Both me- chanical and chemical isolation of the constituent parts of tissues should be used to a very limited degree only. Just as objection- 2 METHODS. able is "boiling, or a complicated chemical treatment, which, as a rule, yields results far from the truth. Infusion. Among the liquids useful to be examined for bio- logical purposes first ranks the " infusion." Torn blades of grass are, with the careful avoidance of the admixture of particles of earth, transferred to a china soup-plate, common water is poured upon them, and they are left uncovered and undisturbed at the temperature of the laboratory. To make up for evaporation, some water may cautiously be added from time to time. After from six to ten days, sooner in summer than in winter, this liquid will swarm with newly formed organisms, the study of which is most fascinating to the biologist. A droplet of the infusion is brought on a glass slide, covered with a thin covering- glass, and is a ready specimen for microscopic research. If we mix together some water with organized bodies, such as grass, apparently destined to decay, there will sprout up a remarkably rich gener- ation both of plants and animals. To explain this fact is quite difficult. Some observers believe that the decaying particles of vegetables themselves change into new organisms under favorable circumstances ; while others, and doubtless the majority, are of the opinion that there are floating in the air millions of invisible germs of plants and animals, which, on finding a favorable soil for development, begin to grow and prosper. The germ-theory, first thoroughly established by Pasteur, has not as yet been contradicted in a satisfactory manner; we have, therefore, every reason still to adhere to it. Certainly no development of infusoria takes place if the air be prevented from reaching the infusion. Among the numerous organisms in a drop of infusion perhaps the most elementary is the amoeba, which is best obtained from the border of the infusion in the plate, or from the blades of the decaying grass, gently scraped with a knife. The amoebae are pale, with lower powers of the microscope finely granular, trans- parent lumps, which continually change their shape and locality. In the first few weeks after the preparation of the infusion, we obtain amoebae of the shape and motion of caterpillars, which are the most suitable for microscopic examination, especially if in slow motion. It is remarkable that I succeeded in raising almost identical forms of living organisms on mixing together the same material several thousand miles away from New York, viz., in Vienna. There is a slight difference, however, im- portant enough to be mentioned. In Vienna I never saw an amoeba without a distinct lump in its interior, the nucleus ; while in New York, the more common occurrences are amoebae without nuclei. As these animalcules are identical in every other respect, both in Vienna and New York, this fact METHODS. 3 disproves the opinion of many histologists that the nucleus is something essential to the so-called " unicellular " organism. Haeckel's view, viz., that there is a marked difference between forms devoid of a nucleus, termed by him "cytodes," and those with nuclei, termed " cells," must be considered to be untenable. Moist Chamber. Von Recklinghausen invented the moist chamber for the purpose of preventing microscopic specimens from evaporation, without cutting off the supply of air. Many devices have been invented for this purpose. One of the simplest is L. Ranvier's — a slide on which a circular furrow, for holding air, surrounds the central plane surface ; on the latter a droplet of the liquid is placed, and the covering-glass, which must be large enough to cover the whole of the furrow at its edges, is hermetically sealed to the slide by a frame of melted paraffine. S. Strieker uses a slightly elevated frame of glazier's cement, on the top of which he sticks the covering-glass holding the speci- men, while a droplet of water on the bottom of the chamber supplies moisture. The same investigator uses a moist chamber, which, for examinations not exceeding one or two hours7 dura- tion, proves to be the best and simplest of all. He oils the edge of one side of the covering-glass, and after having transferred a droplet of the fresh liquid to the slide, he covers it so that the oil-frame of the covering-glass adheres to the surface of the slide around the specimen. Heatable Stage. Max Schultze introduced the so-called heatable stage with the view of keeping up in a specimen the temperature of the body, or raising it at will. As a matter of course, liquids of cold-blooded animals, especially their blood, need no such apparatus. A droplet of blood of the newt (triton, salamandra), which we obtain by cutting off the end of the tail of the animal with a pair of scissors, may be transferred upon the slide by simply touching the wound. The specimen must immediately be covered with a very thin covering-glass, the edges of which have been oiled beforehand. With a little skill, a specimen is obtained fit for examination even with the highest powers of the microscope. The warmer the temperature of the room the sooner the colorless blood- corpuscles will begin to change their shape and location. They will prove to be identical with the amoebae found in an infusion of grass. The examination of the colorless blood-corpuscles, or other isolated bioplasson bodies of warm-blooded animals, by means of the heatable stage, has proved their identity also with amoebae. Such bodies within the 4 METHODS. tissues may, as long as they remain alive, exhibit under the heatable stage changes of shape, but, on account of their being imbedded in basis or cement substance, no locomotion. The heatable stage of S. Strieker is a shallow metal case, the central cavity of which is connected with small pipes for the conduction of gases to be brought in contact with the living specimen. The latter rests on the lower surface of the covering- glass. In front of the case a metal peg can be connected with a spiral copper wire, the distal extremity of which is heated over an alcohol or gas lamp. The temperature is shown by a small thermometer outside the case. If a drop of blood be inclosed between two thin covering-glasses, with greased edges, the phenomena of amoeboid motion and locomotion are much better observed than in a drop hanging on the lower surface of one cover only. For high powers of the microscope, a condenser of light must be put into the diaphragm of the stage, as a good deal of light is lost on account of the unavoidable depth of the stage. Electricity. Living specimens are sometimes exposed to the influence of the electric current, preferably the induced, inter- rupted, as that alone admits of proper action upon the specimen. Both the constant and an induced current extending over several minutes are objectionable, as electrolysis with formation of gas- bubbles occurs, and the thermic action may destroy the effects of electricity upon the specimen. The simplest apparatus for applying electricity under the microscope is that of E. Brucke. A glass slide is covered with strips of tin-foil, between which, in the center of the slide, rests the specimen. The lower surface of the glass slide, also covered with tin-foil, is moved on two parallel copper supports attached to a larger glass plate, and in connection with the electrodes. Preparation of Fresh Tissues. Tissues from the freshly killed animal are, as a rule, unfit for microscopic research beyond a limited time. There is no liquid which keeps the specimen un- changed, and, without the addition of some liquid, the specimen soon dries. As preserving fluids have been used the liquid of the anterior chamber of the eye, serum of blood, the amniotic liquid of calf or sheep embryos, with the addition of a little metallic iodine, normal urine, one-half per cent, solution of chloride of so- dium, very dilute solution of bichromate of potassa, etc. The two latter answer all purposes. Water is objectionable, as the bio- plasson matter swells and becomes destroyed by it ; the same destructive action is noticeable on the addition of glycerine. METHODS. 5 Fresh specimens, if in the shape of delicate membranes, are spread over the glass slide, while, if in the shape of masses not transparent, they are cut with the razor in a frozen condition. The freezing mixture may be snow or broken ice with salt in one compartment of a metal box, while the other compartment holds the specimen, fixed, if necessary, by mucilage of gum arabic. Numerous freezing microtomes have been invented; in some, rhigolene or ether- spray is produced, by means of which a fresh specimen may in a few minutes be frozen to such a consistence that it can be cut with a razor. Specimens so obtained are useful for temporary examinations or for staining, especially with chloride of gold. Freshly cut specimens may be preserved by the addition of a very dilute solution of bichromate of po- tassa, which is allowed to flow under the covering-glass, and is drained off by strips of filtering paper held against the edge of the cover. Preservation of Tissues. The best method of preservation and hardening of normal and morbid specimens is to divide a large mass of the tissue by incisions into small pieces, of one or two inches diameter, and to place these pieces in a wine-yellow solu- tion (one-half per cent.) of chromic acid. The chromic acid is kept ready in strong solution, of which a small quantity is added to the water holding the specimen in a glass jar. It is important that the specimens be placed in a large quantity of liquid, its bulk exceeding that of the specimen at least five or six times. These precautions are necessary, as the hardening action of chromic acid does not penetrate very deeply. In one or two days, the liquid having become cloudy, the chromic acid solution must be renewed, and such renewal is to be repeated every few days until the solution remains clear. Specimens of bone or teeth are treated in the same manner, and the extraction of the lime-salts may be hastened by a very cautious addition of dilute muriatic acid every fourth or fifth day. If the chromic acid be applied in this way, it hardens the tissues in a few days or weeks, with no other change than a slight shrinkage, and renders them fit for cutting with the razor. After the specimens have been hardened, we still may keep them in very dilute solutions of chromic acid, to which we add small quantities of alcohol in order to prevent the growth of mildew, the most unpleasant enemy of a laboratory for microscopic research. A dark wine-yellow solution of bichromate of potassa is also suitable for the preservation of specimens, though in such a 6 METHODS. solution hardening goes on very slowly, or not at all. The hardening may be accomplished by the solution of chromic acid as described above, or by alcohol. The latter method is the best for preservation of brain specimens, which, by the slightest excess of chromic acid, become too brittle to be cut. Eyes are placed fresh into Muller's liquid (two parts of bichromate of potassa, one part of sulphate of soda, and 100 parts of water). After a few weeks the eye may be cut open and transferred into a one-half per cent, solution of chromic acid, or into strong alcohol, in order to accomplish the hardening process. The advantage of these re-agents is that they do not interfere with the structure of the tissue, and render all constituent parts very distinct. Chromate of ammonia or picric acid solutions are by no means superior to the above- described liquids. Alcohol, for preser- vation of specimens, is objectionable, as it makes the tissues shrink, and leaves them too pale and indistinct for good observa- tion. Specimens kept in alcohol for a while should be placed in a one-half per cent, solution of chromic acid, in which they harden very quickly, and become well adapted for microscopic purposes. Bone and teeth, after a long-continued action of chromic acid, on account of the reduction of the latter, assume a dark green color, without change of their structure. Cutting. After the specimens have become sufficiently hard, they are ready to be sliced into thin and transparent sections. For this purpose a good razor, flattened on the side which slides on the specimen, is the simplest and most convenient tool. The specimen is rid from chromic acid by being placed in water • it is held in the left hand, flattened out by one stroke of the razor, and the flat surface is kept in a horizontal position over a china soup-plate filled with water. We take up a little water on the hol- low surface of the razor, and, while the water runs over the level of the specimen, the razor is drawn slowly and uniformly through the tissue without producing ridges. The thinner the specimen the better. With the assistance of a flat copper spoon and a needle, the thin sections are transferred to a china saucer hold- ing water, in which, if desired, staining re-agents are applied. Common water answers all purposes, and neither alcohol nor distilled water are required. Small or hollow specimens, which cannot be held in the left hand, such as halved eyes, teeth, etc., must be imbedded in the following way: The hardened specimen is placed in strong alcohol for twelve to twenty-four hours, in order to be rid of its water. A square paper box, according to METHODS, 7 the size and shape of the specimen, is made ; we fill the bottom with a melted mixture of paraffine and wax, six or eight parts of the former to one of the latter, with the addition, perhaps, of a little mutton-tallow. As soon as the layer of the mixture in the box becomes cloudy, the specimen, from which the surplus of alcohol meanwhile was allowed to evaporate, is transferred into the box, and the paraffine mixture, not too hot, is poured over it. The box, when full, is placed in cold water, where the surrounding paper is destroyed, and the fat becomes hard in a short time. The sections are made simultaneously through the paraffine and the specimen, in the same way as described before. No clearing re-agents, such as turpentine or oil of cloves, should be used before imbedding the specimen, as such re-agents render the details of the structure indistinct. Small specimens may be ntted into two pieces of the best so-called velvet-cork, properly hollowed out, and cut together with the cork. Everybody can learn to cut sections by more or less practice, though a certain amount of cleverness and steadiness of the hands is required to reach perfection. The rule is, that the section should be very thin, transparent, while its size is of much less importance. Valuable specimens, of which very little ought to be lost, may be cut with a section-cutter. The simplest style is a metal tube mounted at right angles with a circular black- glass or India-rubber plate. The central perforation of the plate opens into a cylindrical metal box of varying diameter, which, by means of a screw, slides within the metal tube. The paraffine mixture is poured into the metal box, and the imbedded speci- men is gradually lifted to the level of the plate, over which the flat surface of the razor-blade is passed. Complicated cutting- machines, in which the blade of the knife works on the principle of a plane, are invented in large number, and prove to be satisfactory in the hands of their inventors, or whenever a large number of specimens is required for distribution or for trade. The greater the complication, the less is the value of such machines. Mounting. The sections, after being stained, are transferred on a metal spoon with the assistance of a needle. The best spoon for the purpose is one made of hammered copper wire, the flattened and rounded extremity of which is at a right angle to the wire, the latter constituting the handle. Perforations of the spoon are superfluous. The surplus water is soaked away from the lower surface of the spoon by means of good white 8 METHODS. filtering-paper ; a drop of dilute glycerine is added — best with the glass stem of the bottle holding glycerine — to the specimen, which is then worked down to the center of a glass slide. Here the specimen is spread out, if necessary, with two needles, its position corrected, and the covering-glass gently placed over the drop, so as to avoid including air-bubbles. With a little practice and skill we learn to add the exact quantity of glycerine. Should the drop prove to be too small, — viz., if a corner or edge of the covering-glass wants glycerine, — a small droplet is approached to that edge, and will flow under by capillary attraction. If too much glycerine be taken, it must be drained off by moist filtering-paper, and the slide cleansed carefully with a piece of such paper folded up and moistened. The sealing together of both glasses should be accomplished by painting varnish in the shape of a narrow but heavy rim along the edge of the covering-glass ; but great care must be taken to have both slide and cover first absolutely clean and dry. The only liquid which can be fully recommended for mount- ing hardened specimens is glycerine in the purest chemical condition, to which distilled water (about one part of water to three parts of glycerine) is added. Mounting in Canada balsam or in damar varnish is objectionable, as the specimens in these liquids in time clear up to such an extent as to become unfit for amplifications of the microscope exceeding 300 or 500 diameters: Long-continued trials, as regards the value of both methods, have led me to this conviction. Specimens of any description, mounted in Canada balsam or in damar varnish, are not suitable as test objects. To-day, the power of definition of a lens should be tested exclusively on living objects, such as infusion organ- isms, fresh blood corpuscles, saliva corpuscles, etc. The process of mounting in glycerine is simpler and easier than any other method, and, if all precautions mentioned are carried out with care, no change of the specimen will take place. True, glycerine specimens need more careful handling than balsam specimens, but their value is decidedly greater than that of the latter. In order to make glycerine mounting safe, it is preferable to delay applying the varnish for twenty -four hours, as the surplus water by that time will have evaporated. Should too little glycerine be used, the inclosing varnish will run under the cover and deprive the specimen of its neat appearance; should too much glycerine be left between the two glasses, it often happens that after months or years the glycerine finds its way through METHODS. f 9 the rim of varnish, and the specimen becomes spoiled. As an inclosing varnish, asphalt dissolved in turpentine is generally used, though any other varnish answers the purpose if put on in sufficient quantity. The mounting and varnishing of glycer- ine specimens is easier with square than with circular covering- glasses. Staining. The ammoniacal carmine solution (Gerlach) is the most satisfactory for staining specimens obtained after hardening in chromic acid solution. To the best cochineal powder we add distilled water and a few drops of aqua ammoniae fortis, until the cochineal is completely dissolved. The amount of the car- mine solution to be poured into the saucer holding the sections depends on the concentration of the solution. The best way is to take but little carmine, and let it act on the specimen for twenty-four hours. The various compounds of carmine in use may be dispensed with, as all carmine staining is very unreliable, and, except for the handsome appearance it gives . to the speci- men, of no material value. Haematoxylon (logwood) and eosine are re-agents used for alcohol specimens exclusively, but not suitable for chromic acid preparations. The action of the picric acid is kindred to that of chromic acid. Aniline colors as a rule are not fast, neither are- solutions of picro-indigo. Osmic acid (M. Schultze) in a one per cent, solution stains fat black in both the fresh and the preserved condition of the speci- men ; it renders the contours of the tissue, especially nervous tissue, more distinct, but otherwise has a very limited value. Important re-agents are the nitrate of silver (Von Eeckling- hausen) and the chloride of gold (Cohnheim) ; though specimens treated with either of these re-agents become indistinct after five or six years. Nitrate of silver is brought into contact, in a one per cent, or two per cent, solution (kept in black bottles), exclu- sively with fresh specimens, for only a few minutes, or used for injections into blood and lymph vessels.' Distilled water is needed for washing off the re-agent. The solid nitrate of silver may be applied directly on dense tissues, such as cornea or cartilage, though the layers which come in direct contact with the stick are destroyed. Silver-stained specimens are suitable for glycer- ine mounting. Chloride of gold is invariably used in a one-half per cent, solution, and is fit for fresh and frozen specimens, as well as for those preserved in chromic acid ; in the latter case, after careful 10 METHODS. soaking in distilled water. The exposure to this re-agent may vary from fifteen to sixty minutes, or even over this time. After the re- agent is washed off with distilled water, especially for staining nerves, a few drops of acetic, tartaric, or formic acid may be added. Such specimens are mounted in glycerine. Absolute alcohol (Spina) is a re-agent which has recently become of importance for bringing to view certain features in the varieties of connective tissue. The tissue is kept for only two or three days in alcohol, cut and examined in alcohol, but cannot be preserved. Injections. In order to render the vessels of a tissue plainly visible, stained liquids are driven into them. The best liquid is fine melted gelatine, stained red with carmine, or blue with soluble Prussian blue. As a rule, the injection is made into a larger artery, whence the liquid spreads through capillaries and veins. The artery is fastened to a small metal or glass tube fitting at one end the caliber of the artery, at the other end the caliber of the tube of the syringe or other apparatus. All other vessels must be ligated except one vein, which, by emptying the injected liquid, indicates a complete filling of the vascular system. Both the gelatine and the tissue must be kept at a temperature preventing coagulation. The injection is made by a syringe, or by more complicated pressure apparatus, which latter, by their slow action, yield better results than the former. Injected specimens are placed and kept in alcohol, as the chromic acid solution destroys the colors added to the gelatine. Spon- taneous injection has been used on frogs. So-called parenchy- matous injections, in which colored liquids are driven with a pointed syringe directly into the tissue, were thought to be of great value at one time, but they are abandoned nowadays. How to Work with the Microscope. After a specimen is trans- ferred to the table of the stage of the microscope, and by the coarse adjustment or by pushing the tube is brought into focus, one hand is placed on the fine adjustment, the micrometer screw, and should not be removed during the examination. Both eyes must be kept open, and no ocular accommodative power exercised, as the careful handling of the micrometer screw renders accommo- dation superfluous. Every specimen should be examined at first with low powers of the microscope, and a gradual increase of the power is accomplished by changing the systems of the objectives. For illumination of the object we use dispersed day- light or kerosene-light, which latter is far superior to gas-light. METHODS. 11 For low powers, the plane mirror and the large diaphragm are in order, while higher powers require the use of the concave mirror and small diaphragms. All powers of the microscope exceeding 800 diameters are reached to-day by immersion lenses. If an immersion lens be employed, the microscope should be placed at a certain distance from the window, or else kerosene- light be resorted to. For researches with immersion lenses in daylight, the time between eleven and twt) o'clock is the best, though light-condensing lenses placed below the level of the specimen may prove useful at other times of the day. As soon as investigation commences, the note-book and the pencil must be on hand, in order to fix every observation on paper, though even in no better shape than that of a rough sketch. Nobody can be a good observer with the microscope unless he is a draughtsman. If the eyes be not educated in seeing, and the hand in reproducing on paper what the eyes perceive, all efforts to gain correct ideas of what the microscope teaches are in vain. To see with the microscope is a difficult art, requiring many years of thorough education. The assistance of a reliable teacher cannot be dispensed with, for in the art of microscopy no autodidact can reach perfection any more than in any other art. Learn to draw, if you desire to see with the microscope. A number of devices have been invented for facilitating the drawing of microscopic specimens by means of prismatic glasses. All these are superfluous. If we want to represent a microscopic image on paper, exact in size and shape, we place the paper at the height of the stage of the microscope, very near the right side of the specimen. Looking into the eye-piece with the left eye, keeping the right open, the image is seen projected on the paper, and the point of the pencil can exactly follow the outlines on the image itself. A great deal of time is wasted by applying manifold staining methods to microscopic specimens, and they are deceived persons who imagine that the value of a specimen is the greater the nearer it approaches a rainbow appearance. In wasting time by projecting images on screens by means of complicated mechan- isms, many forget that microscopy can really be learned only by handling the microscope, and both eyes and judgment can be educated only by looking into the microscope itself. Too great stress is laid, also, on photographing microscopic specimens. Those who are delighted with nice staining of microscopic specimens, splendid projections on screens, and large micro- 12 METHODS. photographs, generally lose sight of the aim of the microscope. We have better things to do than to play with methods of stain- ing and projections. We study the relations of physiological and morbid appearances to their anatomical bases — a more serious and difficult task. Photographing microscopical specimens has reached its highest perfection in America, where technical talent is so remarkably developed. Although such photographs are useful in certain respects, their value should not be over- estimated, because they are indistinct wherever the specimen is not even, or shows several strata. Under such circumstances, photographs can hardly replace drawings made by an experi- enced and conscientious observer. II. GENERAL PROPERTIES OF LIVING MATTER.^ LIVING-, or organized, matter is the substance which builds up plants as well as animals — the simplest infusorium as well as the most highly developed mammal. Chemistry. The question what living matter really is, cannot yet be answered from a chemical stand-point, and there is reason to doubt whether it ever will be settled, inasmuch as it is impos- sible to obtain pure living matter in a quantity sufficient for chemical analysis. As every substance, also, the living matter must necessarily be composed of minute particles, which can never be seen, even with the highest magnifying powers, i. e., the simplest units, the so-called molecules, which admit of no further division. After Elsberg's at present almost generally adopted designation, we shall term the molecules of the living matter " plastidules." Molecules, again, are composed of simple ele- mentary atoms, the quantity and nature of which give the essential character to every substance. While the molecules of inorganic bodies are formed by relatively few atoms, we know that the plastidules are much more complicated in their atomistic construction. Every plastidule is constituted by at least five elements, namely: carbon, oxygen, nitrogen, hydrogen, and sulphur. The nature of the union of these elements is a very complicated one in every plastidule, but not as yet elucidated. We generally call the organic substances simply proteinates, or * "The Cell Doctrine in the Light of Recent Investigations, " New York Medical Journal, IS 77. 14 GENERAL PEOPEETIES OF LIVING MATTER. albuminates, comprehending by these terms both the living matter and its derivations or products. According to Hoppe- Seyler, the proteinates are composed of : carbon, 51.5 to 54.5 per cent. ; oxygen, 20.9 to 23.5 per cent. ; nitrogen, 15.2 to 17.0 per cent, j hydrogen, 6.9 to 7.3 per cent. ; and sulphur, 0.3 to 2.0 per cent. Manifestation of Life. While chemical examination has re- vealed very little of the intimate nature of living matter, we know certain properties to be essential to living matter as long as it is really alive, and we know, also, some of its morphological features, to as great an extent as direct observation is possible with our best modern magnifying apparatus. The physiological proper- ties are visible in every moving and growing organism, and they must be attributed to the minutest living particles as well as to the whole organism. We consider living matter alive only so long as it exhibits to us certain physiological properties j when motion and reproduction cease, it is dead. Life is evidently a peculiar kind of motion of the molecules (plastidules) of living matter, of a relatively short duration. A change of the motion is disease ; cessation is death. The chemical changes of living matter are different during life and death ; the former are mani- fested by motion and reproduction, the latter by decomposition, which means simplification of the atomic construction. The shape of living matter is changed by decomposition, but by preservation we succeed in retaining the shape of the substance, which we know was once the seat of life, and microscopic morphology is largely based upon observation of dead but pre- served living matter. Properties of Living Matter. The physiological properties are mainly two: motion and reproduction — viz., the capability of producing its own kind. In speaking of the motion of living matter, we do not mean the motions to which every substance is subject, and of which light, heat, electricity, etc., are peculiar manifestations. There are certain forms of motion dependent on the contractility or irritability of living matter which do not occur in inorganic bodies, nor in organic matter after it has ceased to be alive. This kind of motion enables living matter to work, at least to a certain limited degree, against the law of gravity. It is controlled by complicated laws, which we term the " will » and the " spontaneity " of living matter. According to M. Foster, the term " automatic motion » is preferable to " spon- taneous," inasmuch as it does not necessarily carry with it the GENERAL PEOPEETIE8 OF LIVING MATTER. 15 idea of irregularity, and bears no reference to a "will." This motion is of two varieties : one leading to changes of shape — the amoeboid motion; the other to changes of place — locomotion. Both kinds are due to a peculiar structure of the living matter in a certain stage of its development, and will occupy us after- ward. Here I will only mention that, in former times, locomo- tion was considered as a characteristic quality of animals. To-day we are aware that a great many of the low forms of vegetable life in different stages of development are endowed with locomotion, apparently depending on a certain degree of individual will. The property of producing its own kind is exclusively possessed by living matter, and is also of two varieties, viz. : production for the benefit of the individual itself, with the result of increase of size — growth ; and production of new individuals — generation. We know that every living body is originally small ; the ovum of the largest animal is just perceptible to the naked eye, but it increases by taking up nourishing material from without — it grows. After having reached a certain size it does not grow larger, but only reproduces, renews the used-up material, until at last it ceases to renew anything, and then becomes what we term dead. To-day, scientists have arrived at the conviction that the building-material of plants cannot be essentially different from that of animals. With advancing knowledge of natural philosophy, the boundaries between the animal and vegetable kingdoms have more and more faded away. It is impossible, in many cases, to say exactly at which point of development an organism is a plant or an animal. It has been claimed that the only distinguishing character between plants and animals is that the former feed on simple or elementary inorganic material, while the latter take in organized food ; but this opinion can hardly be maintained, inasmuch as it is impossible to say how the lowest forms of animals are nourished at all. We know, moreover, through Charles Darwin's researches, that there are carnivorous plants. Generation. The property of generation may be looked upon, in accordance with E. Haeckel's definition, as a growth of the indi- vidual beyond its individual limits ; at least, every organism must reach a certain degree of development before it is fit for propa- gation. It is known that among the lowest forms of organisms propagation takes place without sexual intercourse, whereas there is a division of labor among the higher organisms, both vegetable 16 GENEEAL PEOPEETIES OF LIVING MATTEE. and animal; in the former case, one individual gives rise to a new one ; in the latter, two individuals (male and female) are required to produce a third. It is known, furthermore, that the simplest form of propagation is division, when one individual, after having increased in size, splits into two organisms of smaller size. A variety of this process is the " gemmation " : e. , solid, vacuoled corpuscle. Magnified 800 diameters. shining substance are less frequent than in the cartilage of a newly born animal, and the substance often exhibits larger vacuoles. DEVELOPMENT OF LIVING MATTEE. 49 In the thin layer of cartilage of a dog, eight to ten years old, the compact shining substance is relatively scarce, and, as a rule, traversed by vacuoles. Most of the cartilage-cavities con- tain a pale granular protoplasm and vesicular nuclei with dark contours, and a varying ^^SSHSte number of nucleoli. (See ?||, Fig. 16.) These features were H found in the middle re- j| ! gion, between the articu- lar surface and the border of the epiphyseal bone. In / ^ ' ' - young animals, the yellow mjBjil substance, on an average, occurs the more the nearer to the bone the examina- tion is made. Immediately FIG. 16. — CARTILAGE-CORPUSCLES FROM A on the border of the bone SAGITTAL SECTION OF THE CONDYLE OF THE FEMUR OF A DOG, EIGHT TO TEN YEARS OLD. A, corpuscle with several gray lumps besides the vesicular nucleus ; _B, corpuscle with an hour-glass- shaped nucleus ; C, corpuscle with an oblong central nucleus. Magnified 800 diameters. the centers of the large cartilage-cavities, which are inclosed by a calcined . baSlS-SUDStance, are OCCU- T^prq "hvloyo-p Tna««p«i of thp P16CL DJ large maSS( yellow substance, which in this situation is supplied with numerous vacuoles, and with lower powers appears coarsely granular. Each central lump is surrounded by a zone of a pale, finely granular or structureless substance, which is separated by a light, narrow rim from the FIG. 17.— BONE-CORPUSCLES FROM A LONGITUDINAL SECTION OF THE THIGH-BONE OF A PUP, FIVE DAYS OLD. -P, corpuscle with a vacuoled shining nucleus; B, basis-substance. Magnified 800 diameters. 4 50 THE PHASES OF calcareous basis-substance. Such formations are absent in old animals. Bone-corpuscles. In comparing bone-corpuscles of a newly born with those of an old dog, a difference in the structure is apparent. The cavities of the former contain a central globular, oblong, or angular vacuoled lump of a yellowish color, and intensely shining. Around this lump there is a pale, finely granular protoplasm; the spokes springing from the central lump blend with the pale protoplasm, or, in places where the latter is apparently wanting, with the basis-substance of the bone. We not infrequently meet with bone-cavities entirely filled with the yellow, shining substance. (See Fig. 17.) In the bone of a dog, about ten years old, there are but few corpuscles, with pale yellow shining nuclei ; whereas cavities with pale protoplasmic bodies and pale nuclei largely prevail. FIG. 18. — BONE-CORPUSCLES FROM A LONGITUDINAL SECTION OF THE THIGH-BONE OF A DOG, EIGHT TO TEN YEARS OLD. P, corpuscle, with a vesicular nucleus ; B, basis-substance. Magnified 800 diameters. The latter represent gray, vacuoled lumps or vesicles, with one to two yellow shining, or one to three gray opaque nuclei, of which the former usually are larger than the latter. (See Fig. 18.) Corpuscles of the Medulla of Bone. The medulla of bone also exhibits marked differences of age. In the medullary spaces of a shaft-bone of a new-born pup, the apparently homogeneous basis-substance holds small, yellowish, shining lumps, either globular or elongated, either homogeneous or vacuoled. Besides, there are pale protoplasmic bodies with globular nuclei, similar in aspect to the lumps just described ; also pale bodies are seen without nuclei, but in their place cavities with one or two.opaque DEVELOPMENT OF LIVING MATTER. 51 corpuscles ; and, lastly, we meet with pale, finely granular proto- plasmic bodies devoid of nuclei and nucleoli. As the growth of the animal advances, no medullary spaces are found in the bone, but canals for vessels instead. The medul- lary elements ' in the space between the wall of the blood-vessel and the border of the bone are mostly spindle-shaped, and either yellowish, vacuoled lumps, or pale protoplasmic bodies, with and without distinct nuclei and nucleoli. In all instances the com- pact lumps, the pale protoplasmic bodies, the nuclei and nucleoli, are bordered by light rims, which are traversed by radiating spokes. In old animals, protoplasmic bodies of the above description are rare ; in the marrow spaces of the shaft-bones they are usually transformed into fat. My conclusion, drawn from these observations, is that the protoplasma shows differences according to its age. The shape of the youngest protoplasm is that of a compact lump of the living matter, with the following properties : It is homogeneous, has a yellow tint of varying intensity and shade, a considerable luster, and admits of being stained red by a solution of carmine, and violet by a solution of chloride of gold. In this condition, with our present means of examination, no reticulum is demonstrable. This condition is similar to that of a tetanic lump of a contracted amoaba, and identical with the condition of the living matter which I termed, in 1872, " haematoblastic," in which the living matter produces both red blood-corpuscles and the wall of the blood-vessel. For small lumps of this substance, which are directly converted into red blood-corpuscles, the term " hseinatoblastic " remains applicable, though the hsematoblastic substance has a significance wider in sense than it seemed to have at the time the name originated. The first noticeable differentiation in young protoplasm con- sists in an accumulation of liquid in vacuoles. The vacuoled condition of haematoblastic substance is the first step in devel- opment, as observed in the lumps and nuclei of the tissues of somewhat older animals. The first formation of the walls of a vessel depends on this differentiation, inasmuch as the vacuole represents the earliest cavity of a vessel. Owing to an accumulation of a liquid in several closed cavi- ties of the young protoplasm, the living matter assumes the shape of a frame- work. The points of intersection of the frame becoming granules by a rupture of many of the walls of the vac- 52 THE PHASES OF uoles, a net-work is established, which represents a later phase of development of protoplasm. The more coarse, yellow, and shining, and the more densely arranged the points of intersection of the living reticulum are, the nearer it is to its yonth ; on the contrary, the more delicate, devoid of color and luster, the gran- ules are, the more advanced is the age of the protoplasm. That under certain circumstances the living matter in the proto- plasmic lump, by endogenous formation, reproduces its own kind, is proved by observations of older amoebae. Here the coarse granules are newly formed living matter in a juvenile condition. With this explanation we can easily understand the differ- ences of age in the elements of tissues, described above. The originally homogeneous lump of protoplasm, with increase of size, is transformed in its peripheral portion into a net-work, whereas the central portion, the nucleus, remains homogeneous. Next a differentiation into a frame- work, and in turn into a net- work, takes place in the central lump, the nucleus, so as to leave smaller, compact centers, the nucleoli. This condition furnished the scheme of the " cell" of the authors. At last the differentiation into a net-work has involved the whole protoplasmic body. At this stage no nucleus, and later on even no nucleolus, is perceptible, for the whole body is split up into a reticulum, with coarser and finer points of intersection, and this condition immediately precedes the formation of a basis- substance. The living matter passes through these stages, not only in the normal, progressive development of all tissues, but, as I will demonstrate later, also in the process of inflammation, though here in a reversed manner. The first assertions as to a difference of the nuclei depend- ing on age are made by Th. Schwann.* According to this author, the nuclei in the juvenile condition are solid, later become hol- lowed, and at length completely disappear, or are absorbed. S. Strieker t maintains that the nucleus of the first globule of seg- mentation originates in the protoplasm, and that the nucleus in its youth represents a lump, while with advancing age it may be transformed into a vesicle. * Mikroskop. Untersuchungen iiber die Uebereinstimmung in der Struetur und dem Wachsthum der Thiere und Pflanzen. 1839. Pages 205 and 211. t Handbuch der Lehre von den Geweben. Art. " Allgemeines iiber die Zelle." 1868. Page 24. DEVELOPMENT OF LIVING MATTER. 53 Lastly, I would take into consideration a peculiarity in the phases of life of the protoplasm, as evidenced by obser- vations on living corpuscles in a healthy as well as a diseased condition. Young, compact protoplasm is in a high degree possessed of the property of coalescing with analogous protoplasm, and thus change its configuration, whereas it exhibits the property of active mobility in a slight degree only. The power of locomo- tion is entirely absent. Under certain circumstances — f. i., on the border of ossification of the epiphyseal and intermediate carti- lage— the living matter is split into pieces, broken apart. The best representation of a normal division I have observed in the haematoblastic substance within the cavities of the cartilage, the results of which division are the haematoblasts. The power of active motion evidently increases by degrees j the more the liquid accumulates in the mesh-spaces of the proto- plasm, within certain limits of its bulk, the smaller and paler, therefore, the granules become. The "pale and finely granular" protoplasm of the authors, which holds a very delicate reticulum, has also the most marked capacity of locomotion, upon raising its temperature to that of the whole body in a normal condition and in fever. The capacity of compact nuclei and nucleoli of changing shape and place, on the contrary, seems to be very limited or wanting. We must consider the protoplasma of the latter formations as relatively the younger, so far as its shape is concerned. The Cell-theory in the Light of these Researches. The theory of the animal cells, as established by Th. Schwann,* was greatly altered in 1861, by the researches of Max Schultze.t Since then, the best observers have agreed that " cell" was to designate a lump of protoplasm, without a membrane and even without a nucleus. It was added that the protoplasm appeared structureless. E. Briicke'st attempt to show that the lump was an u elementary organism " was, for that time, in a certain sense, progress. The term " cell " remained, although a different meaning was attached to it than at the time of its origin, and all observers * Mikroskopisehe Untersuchungen iiber die Uebereinstimmung in der Structur und dem Wachsthum der Thiere und Planzen. Berlin, 1839. t Ueber Muskelkorperchen und das, was man eine Zelle zu nennen habe. Miiller's Archiv. 1861. t Die Elementarorganismen. Sitzungsber. d. Wiener Akademie der Wis- sensch. 1861. 54 THE PHASES OF seemed to consider it a necessity to include all possible form- elements within this improved scheme of a cell. S. Strieker,* in 1868, for instance, discusses the question how large a lump of protoplasm ought to be to entitle it to the name of a cell, and comes to the conclusion that we should speak of a cell only if the lump exhibits growth and repro- duction. At that time it was already known that, with the highest powers of the microscope, very minute, just perceptible, granules grow under our very eyes. The doctrine of the so-called zymotic diseases almost necessitates the assumption that the carriers of the contagion are organisms, not subject to our observation even with the best lenses. Are not the innumerable corpuscles in decomposing liquids individual organ- isms in spite of their minute size, which renders them hardly perceptible even with our best optical apparatus? And all these minute organisms should be called cells. Very probably, a granule of living matter may be altogether too small to be perceived, and such a granule will agree as little with the idea of a cell as it will with the idea of an elementary organism. What at that time was called a structureless, elementary organism, a " cell/7 I have demonstrated to consist only in part of living matter, while even the minutest granules of this matter are endowed with manifestations of life. The cell of the authors, therefore, is not an elementary, but a rather compli- cated organism, of which small detached portions will exhibit amoeboid motions. The nucleus cannot be considered an essential part of the cell, for all good observers know that there are cells destitute of nuclei, and some authors have distinguished nucleated cells from " cytodes" — cell-like bodies devoid of nuclei. (See page 2.) We can escape from the difficulties of a definition only by abandoning the designation " cell/7 in the sense of the zoologists. By this, our usual terminology will remain unaltered. The amoeba, f. i., or the colorless blood-corpuscle, the protoplasmic lump in the colostrum, the pus-corpuscle, are formations to which the term " cell " is not usually applied. We need no such word for properly designating what we mean by saying the amoeba, the colorless blood-corpuscle, etc., are alive ; or the amoeba, the colorless blood-corpuscle, are organisms. Such were my conclusions in 1873 (I. c.J, and here I wish to add a few remarks more as to the propriety of the term " cell." *Handbuch der Lehre von den Geweben. Art. " Allgemeines iiber die Zelle." 1868. DEVELOPMENT OF LIVING MATTER. 55 The size of a living body is not included in the definition of an organized individual. In the infusion, f. i., we see growing granules, just perceptible to the highest magnifying powers of the microscope, in a fluid in which none were seen a short time before. The smallest individuals which we are capable of seeing with the best microscopes of to-day, are granules ; but we must admit that germs or particles of living matter may be present in the air or in fluids in infinite numbers, which cannot be seen at all, and become visible only after having attained a certain size. How complicated the structure of a minute particle of living matter may be, we can hardly imagine ; what we do know is, that the so-called "cell" is composed of innumerable particles of living matter, every one of which is endowed with properties formerly attributed to the cell-organism. The observation of the phases of development of the living matter demonstrates that the term " cell " was attached to only a limited number of forms, during the changes that take place in a growing granule of a substance known to be the seat of life. As the term "protoplasm" was adapted to the original idea of the cell, it also meant only one or a few phases in the development of a lump of living matter. (See Fig. 19.) © FIG. 19.— DIAGRAM OF THE PHASES OF DEVELOPMENT OF THE LIVING MATTER. L, series of development of a small granule, a, into a vaouoled lump, b and c, and into a frame-work, d. P, series of development into protoplasm of a reticular structure ; the so-called " cell," e, with a solid, /, g, Ji, with vacuoled nuclei. B, series of development tending toward the formation of basis-substance ; in i, the nucleus reticular, the nucleolus solid ; in fc and I, the nucleolus splitting; and in m, the original granule a transformed into a finely reticular mass, destitute of nucleus and nucleolus. 56 THE PHASES OF The series of progressive changes, tending toward the forma- tion of protoplasm, proves that the original granule is the morphologically simplest appearance for our present means of observation. The growth and splitting of the granule results in the appearance of a reticular lump, a rather complicated organism, hitherto termed " protoplasm "; and thus the relation between the two is about the same as that between an ovum and a grown animal body. That a single lump of protoplasm — f. i., an amoeba — is endowed with all fundamental vital properties attrib- uted to the whole organism — f. i., a mammal — is acknowledged to-day by all physiologists. M. Foster attributes to the amoeba, which he considers an " undifferentiated protoplasm/' the follow- ing properties : It is contractile ; it is irritable and automatic ; it is receptive and assimilative; it is metabolic and secretory; it is respiratory ; it is reproductive. All this holds good for isolated lumps of living matter, sus- pended in the liquids of the animal body. Is it applicable to complex masses of this matter — to tissues ? As I shall demonstrate later, there is no such thing as an isolated, individual cell in the tissues, as all cells prove to be joined throughout the organism, thus rendering the body in toto an individual. What was formerly thought to be a cell is, in the present view, a node of a reticulum traversing the tissue. Neither is there a good reason for speaking of proto- plasm, or for claiming that it is protoplasm which builds up the animal body; for living matter appears in the organism in various shapes, and it is but one of these, viz., an advanced stage of development of the living matter, which was hitherto termed " protoplasm." According to my observations, we have not to deal with cells as form-elements, either in the fluids or in the tissues of the animal body, but only with living matter, varying in its ap- pearance from the just perceptible granule to the bulk of the body of the largest animal. Single lumps of living matter may either look homogeneous or show a net-like arrangement, whereas the ' body of an animal is a continuous mass of living matter or net- work arrangement, and contains fluids in blood and lymph vessels, in which there are suspended isolated bodies, either homoge- neous or reticular in structure, as analogous to the granules which float in the vacuoles of an amoeba. The diiference in the aspect of the tissues depends on the presence of a lifeless basis-substance only, a derivative of the lifeless " protoplasmic DEVELOPMENT OF LIVING MATTER. 57 fluid/' while the living matter of the tissues exists mainly in the reticular stage, and is interconnected without interruption throughout the body. The question arises, are we justified in speaking of u cells " as the formative elements of plants ? The living matter of plants is not materially different from that of animals, so far as its appear- ance is concerned. W. Kuehne discovered vegetable lumps of protoplasm exhibiting amoeboid motion and locomotion, almost identical with that of amoebae. In fresh tissues of plants the liv- ing matter was for a long time known to be endowed with motion, as the granules were seen by E. Briicke and others, floating briskly in a liquid. My own limited researches enable me to assert that the granules of living matter in vegetable protoplasm are, as a rule, united in the shape of a reticulum in the same manner as in animal protoplasm. Besides, the researches of W. Hassloch (see page 40) elucidate the identity of both animal and vegetable liv- ing matter in a satisfactory manner. I may add that all cells of the vegetable organism are uninterruptedly connected by means of delicate offshoots, piercing the walls of the cellulose. The granules of amylum are transformed living vegetable matter. The plant in toto is an individual, and not composed of indi- vidual cells. The present generation of histologists will very probably never realize the harm done by the misnomer " cell," so firmly established during the last forty years. Nevertheless, I shall make an attempt to replace former misnomers by new words and terms, the originator of which is L. Elsberg.* He says : The formerly unquestioned " cell" views of histologists are giving way to a more correct appreciation of the living matter of the body. In pathology, as in physiology, the cell doctrine has led to great advances in accurate knowledge as an aid and means of research, but it has outlived its useful- ness. Instead of adhering to Virchow's comparison, ' ' that every higher organ- ism is like an organized social community or state, in which the individual citizens are represented by the cells, each having a certain morphological and physiological autonomy, although, on the other hand, interdependent and subject to the laws of the whole," we now compare the body to a machine in which, though there are single parts, these are materially connected to- gether, and no part is at all autonomous, but. all combine to make up one individual. According to the former view, the body is composed of colonies of amoabse ; according to the latter, the body is composed of one complex * Notice of the Bioplasson Doctrine. Transactions of the American Medical Association, 1875. Contrihutions to the Normal and Pathological Histology of the Cartilages of the Larynx. Archives of Laryngology, 1882. 58 THE PHASES OF amoeba. I have named this biological doctrine, which is based on Heitzmann's discoveries, the "bioplasson doctrine," using the word "bioplasson " only as a technical synonym for the two words " living matter" ; and I use the term " plastid," proposed by Haeckel, or that of " bioplast," proposed by Beale, to denote a so-called "protoplasmic body," or a form-element, a formerly so-called 11 cell." Perhaps it would be the best to restrict the word " bioplast " to a small mass of living matter exhibiting no differentiation, and to distinguish from it as * ' plastid " the larger mass showing an interior structure more or 1 ess like the fully developed corpuscles. Thus, I would always use the term " plastid " in the place of " cell." The word "protoplasma" is etymologically incorrect for designating living and formative matter, as it has already been used by some authors with a meaning other than the simple one here intended ; and as it has not yet be- come so common that its retention or rejection is a matter of much conse- quence, I propose the designation "bioplasson doctrine." The word plasma (TO irXda^a) really means the formed, that which is formed, and plasson (TO TrXaooov) the forming, that which forms or does the forming. The distinction is the one so justly insisted upon by Beale in his discrimination between germinal or living matter and formed material. The term plasm may, perhaps, be appropriately applied to the material formed from the fluid of living matter, the intermediate or intercellular substance of authors ; but the term plasson only can be applied to active, living, forming matter. Proto (TipuiToc) is a prefix signifying first, primary, primordial; and protoplasma has been used by some to denote the original or first-formed organic matter. But the term we are in need of for our biological doctrine is one that shall be an expression for living formative matter in its simple elementary form ; and for this purpose, it seems to me, bioplasson may appro- priately be chosen. The General Constitution of the Body, as Recognized ~by Single Plastids. In 1879* I published facts which, perhaps, are of some value to practical medicine, and certainly elucidate the prac- tical value of the new discoveries. I reprint my assertions with the only alteration that, in accordance with the new terminology, as suggested in the foregoing article, instead of " protoplasm7' and " protoplasmic body," I use the terms " bioplasson" and "plastid." The amount of living matter within a limited bulk of a plastid varies greatly in diif erent individuals. It is obvious that what is called a healthy or vigorous constitution is based upon a large amount of living matter in the body, the new growth of which in morbid processes is very lively ; while a strumous or scrofu- lous or phthisical constitution must be caused by a relatively small amount of living matter, the new growth of which is * " The Aid which Medical Diagnosis Receives from Recent Discoveries in Microscopy." Archives of Medicine, February, 1879. DEVELOPMENT OF LIVING MATTER. 59 scanty in morbid processes. In other words, a plastid will exhibit coarse granulations, or it will be almost homogeneous-looking under the microscope, owing to the large amount of living matter in strong individuals of good constitution, while a plastid taken from a person with weak or strumous constitution will be finely granular, as but little living matter is present in it. Two years ago, I announced* that pus-corpuscles show remarkable differences in their minute structure in different individuals. Those from otherwise healthy and strong persons are yellow, almost homogeneous, or coarsely granular, I said, while those from broken-down, weakened, or strumous persons are pale gray and finely granular. This fact has been made use of in hundreds of cases, when pus-corpuscles, mainly in urine, were brought by different physicians to my laboratory for exam- ination, for telling whether the pus belongs to a good or a bad constitution, of course without any knowledge of the patients themselves. I was right in every instance ; not one mistake has occurred. About one year ago I announced t that the colorless blood- corpuscles also demonstrate striking differences as to their minute structure, according to the general constitution. I said that the colorless blood-corpuscles are coarsely granular and slow in their amoeboid motions under the microscope, if taken from healthy, vigorous, strong persons; on the contrary, they are pale gray, finely granular — viz., poorly provided with living matter — in broken-down or phthisical individuals. I expressed my hopes that at some future time practical use might be made of these differences. To-day my hopes have turned, after three years' earnest study, into accomplished facts. The method of examination of the blood for our purpose is extremely simple. We oil the edges of a thin covering-glass on one side with a curled piece of paper, serving as a brush. Prick with a pointed pin the palmar surface of the thumb, near the wrist- joint, thus giving a good convex surface, and being least incommoded by the injury. Squeeze out a small drop of blood, the size of which has to be learned by some practice. Place the glass slide on the drop for transportation, and immediately cover up the specimen with the covering-glass, the oiled edges looking toward the slide. Such a specimen holds the blood in a living * See page 32. t "On the Nature of Suppurative Processes of the Skin." A paper read "before the County Medical Society of New York, 1877. Unprinted. 60 THE PHASES OF condition at least one hour. It is not necessary to use the heated stage, because the colorless blood-corpuscles exhibit their struct- ure in an ordinary comfortable temperature of the room — nay, sometimes show slight amoeboid motions. The magnifying power should be at least 800 diameters, the lens to be used being best a one-tenth of an inch immersion. As a matter of course, the lens we use must be first-class. Considerable skill is required for such studies, which embrace first the knowledge of the structure of the bioplasson in general. A few months' — nay, a few weeks' — thorough study under the direction of a reliable teacher will suffice to enable every one to see what really can be seen in the plastids, and to entitle him to judge also of the differences. I never had difficulties in demonstrating the net- work structure of the plastids to any one who was in earnest with his microscopical studies, and took them for more than play. After having ob- tained a certain practice, one is enabled to tell differences in the anatomy of the colorless blood-corpuscles with a power of 500 diameters only. Several years ago, I was first struck by the fact that the ele- ments establishing the condition of catarrhal pneumonia and of tuberculosis, both acute and chronic, are decidedly pale and finely granular. Next I leaTned that pus and colorless blood-corpuscles of strong men are partly homogeneous, or at least coarsely granular. Then I followed these studies by examining the blood of different physicians who came to work in my laboratory, and who could give reliable histories of both their families and their own bodies. Thus I have arrived at a point of perfection which allows me to tell the constitution of a person without knowing anything of his former life. Besides the differences in the structure of the colorless blood- corpuscles, as described above, valuable hints may be obtained from other circumstances. The number of colorless blood-cor- puscles in a given drop of blood is surprisingly different in differ- ent persons; the better the constitution, the fewer are these bodies. A sleepless night, however, is sufficient to increase their number, which fact often enabled me to tell physicians, by exam- ination of their blood, whether business was going slowly or lively, the latter inducing sleepless nights, or repeated awakening by patients, or so-called nervousness. Catarrhal processes, so-called colds, of any of the mucous membranes, lead to increase of the number of the colorless blood- corpuscles j a chronic condition of these processes is indicative DEVELOPMENT OF LIVING MATTER. 61 of a poor constitution per se. The colored blood-corpuscles greatly vary in their yellow tinge in different persons ; the paler this tinge is, the more readily we can tell pale looks of the face or chlorosis. The colored blood-corpuscles stick together in coin- like rows only when the plasma holds a larger amount of fibrin ; in the blood of persons with a poor constitution, such rows do not occur ; in individuals of moderate vigor, the rows temporarily may be missing, at other times present. In the blood of persons of good constitution, who had passed through severe ailments, I several times found both coarsely and finely granular colorless blood-corpuscles, just as in originally healthy persons who, by chronic diseases, become broken down. Inf fact, the microscope reveals so much of the general health of a person that more can be told by it, in many instances, than by the naked eye, or by physical examination. Life insurance should be based upon microscopical examination, as well as on percussion and auscultation. Marriages should be allowed, in doubtful cases, only upon the permit of a reliable microscopist. Last season a young physician asked me whether I believed in the marriage among kindred. He fell in love with his cousin, and so did the cousin with him. I examined his blood, and told him that he was a " nervous" man, passing sleepless nights, and had a moderately good constitution. The condition being suspected in the kindred lady, marriage was not advisable for fear that the offspring might degenerate. So great was his faith in my assertions that he gave up the idea of marrying his cousin — offering her the last chance, viz., the examination of her blood. This beautiful girl came to my laboratory, and, very much to my surprise, I found upon examination of her blood a first-class constitution. The next day I told the gentleman, " You had better marry her." As a matter of course, every particle of the organism, either in a normal or in a morbid condition, will exhibit characteristics as attributed to the colorless blood-corpuscles. The bioplasson is one uninterrupted mass throughout the body, and is connected from the top of the head to the heels, in what we call tissues. Several months ago, Dr. Paul F. Munde" brought me a specimen of the size of a pea, which, he said, he found in a large amount of fluid blood vomited out half an hour before by a patient. After immediate examination of a section from the specimen, I told the doctor that his patient was a pale, emaciated, narrow-chested person, who had catarrhal pneumonia, which led by localized gangrene to sloughing of the piece of the lung, on which a broken blood-vessel was visible. I foretold, besides, that the patient would die within one year. I explained to the doctor and to Dr. L. Elsberg, who also was present in the laboratory, what led me to such a diagnosis and prognosis. There were visible alveoli of the lung, and both the walls of the alveoli and their calibers were crowded with inflammatory corpuscles, coagulated fibrin being absent. These are symptoms of catarrhal pneumonia. In some parts 62 THE PHASES OF clusters of microeocci could be seen — characteristic of putrefaction, there- fore gangrene of the tissue. The inflammatory corpuscles looked very pale and finely granular, the evidence of a bad, phthisical constitution, and all these signs together allowed the diagnosis of a limited viability, hence the disastrous prognosis. The doctor told us that no physical symptoms could be found in the lungs justifying my diagnosis. Still he admitted right away that the patient was a pale-looking, thin, and narrow-chested young man, whose brother had been sent to Florida some time ago for chronic tubercu- losis of the lungs. One week afterward, the doctor came to tell me that the physical symptoms at present were so marked in the lungs, that the diagnosis of catarrhal pneumonia was evident. Seven weeks afterward the patient was dead. The facts here laid before the medical profession may con- vince even the most skeptical physician that microscopy is destined to play an impor- tant part in the science of medicine. Let us proceed in skillful, honest work, and we shall succeed in raising the standard of microscopy still higher, and make it not only a valuable, but rather an indispensable, assistance to clinical work. Much more could and should be done in this country by the profes- sion at large than is done at present, for the perfection of that most interesting and useful science, the science of ourselves — Biology. Only little is to be added to these assertions. Several years' more study has con- vinced me of their correct- ness, and the difference in the appearance of bioplas- son, according to the differ- ence in the general consti- tution, is so striking as to admit of a diagrammatic representation, for which we may choose pus-corpus- cles. (See Fig. 20.) •tt** Cot* •"•ttV" *«5 FIG. 20. — DIAGRAM OF PUS-CORPUSCLES OF PERSONS OF A DIFFERENT CONSTI- TUTION. E, pus-corpuscle of an excellent constitution ; the bioplasson nearly compact, containing a few small vacuoles, alive in a, alive and contracted in b, dead and contracted in c. G, pus-corpuscles of a good constitution; the bioplasson coarsely granular, alive in a, alive and contracted in b, dead and contracted in c. M, pus-corpuscle of a middling good constitution ; the bioplasson less coarse, with a compact nucleus ; alive in a, amoeboid in &, dead in c. P, pus-corpuscle of a poor constitution ; the bioplasson comparatively scarce, finely granular, vesicular nuclei very distinct ; alive in a, amoeboid in b, dead and bursted in c. DEVELOPMENT OF LIVING MATTER. 63 Whenever we meet with pus-corpuscles in a specimen of urine or sputa, or, for instance, with colorless blood-corpuscles in a drop of blood, which exhibit the features here illustrated in a uniform manner, the conclusion as to the general constitution of the individual can be made with certainty. The exclusive presence of pus-corpuscles of the series P is a sure sign of a so-called " tuberculous or phthisical " constitution. Should pus or blood corpuscles of the series E be mixed with those of the series G and M, this means that an originally excel- lent constitution has become lowered by disease — the more so the greater the number of the corpuscles like those of the series P. Persons of a moderately good constitution, broken down by chronic ailments, or by circumstances not favorable to their nutrition, gradually exhibit, mixed with corpuscles of the series Jf, those of the series P. The presence of the series P admits of longevity rarely, and only under the most favorable external conditions ; the more the formations c of the series P prevail, the surer it is that the death of the individual is approaching. Many other conclusions as to the significance of the amount of bioplasson present must be postponed, as they are not as yet sufficiently proved. Obviously, these may in the future lead to an important medical achievement in the prevention of disease. The features I have described as to the stages of develop- ment of living matter must be combined with the conclusions just stated, because the plastids of tissues — I am sure of those of bone and cartilage — exhibit, in all stages of development, differences due to differences in general constitution. V. THE STRUCTURE OF COLOEED BLOOD- CORPUSCLES. BY Louis ELSBERG.* THE discovery of red corpuscles in the blood was one of the first results of microscopical study, over two hundred years ago. Since that time no other constituent of the body has been more frequently examined. Nevertheless, the structure of col- ored blood-corpuscles has not heretofore been ascertained. The examination of a small drop of fresh human blood, mixed with a drop of from 40 per cent, to 50 per cent, saturated solu- tion of bichromate of potash, and highly magnified,! reveals in the, course of a few hours the following : Perhaps the first thing noticed is that the colored corpuscles vary in size. * " Annals of the New York Academy of Sciences," vol. i., 1879. t My investigations were made with a jV immersion objective, manu- factured by Tolles, of Boston, and a No. 12 immersion made by Verick, of Paris, either of which, with the eye-piece that was used, magnifies about 1000 times. An exceedingly thin cover having been oiled near the edges, the drop of blood obtained from a pin-prick in the palm of the hand, and transferred on a slide, is mixed with a drop of the solution previously prepared, covered, and without delay placed on the microscope stage. By a 50 per cent, satu- rated solution, I mean a saturated solution diluted with an equal quantity of distilled water; by a 40 per cent., one containing three-fifths water; by a 60 per cent., one containing two-fifths water, etc. : I always prepare a sat- urated solution, and then dilute. STRUCTURE OF COLORED BLOOD-CORPUSCLES. 65 Having made a number of measurements, I can state that in every person's blood that I have examined, there are some as small as, or smaller than, the ^grr? an -00422 and .01016 mm.). If the detached globules, which I shall describe, be counted as blood- corpuscles, there are even still smaller ones. In each speci- men of blood, the majority of red corpuscles, however, are of about one size, which differs in different specimens, but is most fre- quently between the ggVT and the g-TVo of an inch (.00655 — .00819 mm.), or somewhere about the ^yo of an inch (.0075 mm.). The calculated average of the size of the red corpuscles in a drop — i. e., the arithmetical mean of the measurements — is usually a little higher than the size of the majority of the corpuscles. A very few, especially the smallest, but occurring exception- ally also among the larger, seem more or less globular ; all others are bi-concave disks, the periphery being more shining and thick than the central portion. So-called "rosette" and "thorn-apple" forms may be seen, either immediately or in the course of a little while. I have often watched the individual corpuscles while these forms, and many others, were being produced j and in Part III. of this communica- tion I shall offer an explanation of their production. Concentrating our attention upon the shape of the circular disks, we soon find that the round outline of a few (and the same is at times also true of the smooth surface) begins to be made 66 STRUCTURE OF COLORED BLOOD-CORPUSCLES. irregular at one or more points. This occurs in either of two ways, viz. : by indentation and by protrusion ; sometimes the one, sometimes the other, first takes place 5 frequently both appear in different corpuscles at about the same time; occa- sionally both are met with in the same corpuscles ; in differ- ent preparations either the one or the other predominates. First. In from fifteen min- utes to an hour a very slight indentation may appear, and b gradually deepen, so that the corpuscle be nearly cleaved through; then the clefts may gradually become shallower, so c that again a mere indentation is seen j finally, even this may disappear, and the corpuscle be rounded again (see Fig. 21, a). Division into two separating halves I have never observed under these circumstances, al- though I have often watched for it. The furrow of every corpuscle that I have caught nearly cleaved through, either remained stationary, or usually retrogressed to a greater or less extent. The retrogression may stop at any point, and the fur- rowing again increase j and this going and coming of a cleft, though taking place slowly, may continue for some time, and then stop at any stage of indentation. Sometimes indentations appear at two or more points of the same corpuscle, and in their progress give rise to a great variety of angular, regular, and irregular "rosette," " scal- loped," " crenated/' "thorn-apple/' and " stellate" forms (see Fig. 21, &, c, d). The sharp-pointed ends seen in the last figure of d are the extremes met with, and exceptional ; usually the ends are plump and rounded. These forms, as well as those of single cleft, after changing backward and forward, either persist or become finally rounded off to a greater or less degree ; in some FIG. 21. — SHAPE-CHANGES OF COLORED BLOOD - CORPUSCLES BY INDENTA- TION. a, progressing and retrogressing furrowing ; b, indentations leading to irregular forms; c, indentation s leading to more or less regular forms; d, instances of extreme and excep- tional forms, especially the sharp-pointed stel- lated figure; e, four phases of form-change, observed in one corpuscle, with separation of a constricted portion. STRUCTURE OF COLORED BLOOD-CORPUSCLES. 67 cases constriction of portions more or less minute occurs, with separation following constriction (see Fig. 21, e). Sometimes con- stricted portions remain attached for a long time by a more or less long and slender pedicle. Transitionally or permanently, in any of the cases mentioned, the most curious and grotesque shapes may be met with. In the cases, too, of constriction and separa- tion, the corpuscles, with the portions attached and unattached, sometimes gradually become rounded off so as to look like a parent globule surrounded by a number of little ones. Secondly. Usually in the course of half an hour, the protrusion of little round or roundish, more or less light colored, knobs takes place. At first, only very few corpuscles show knobs, and the knobs are extremely small and few in number, say only one, or at most two or three, on a corpuscle ; but in the course of an hour or two, more cor- puscles protrude knobs, more knobs are pro- truded from one corpus- cle, and the knobs grow larger (Fig. 22, a). Occa- sionally a knob is drawn in again, and the former contour reestablished. In some instances protru- sion and retraction occur repeatedly, SO that knobs and FIG. 22. — KNOB-FORMATION, PRINCIPALLY BY PROTRUSION. a, Nos. I and 2, progressive and retrogressive protru- m* 8ion; No' 3* one Pedunculated and tnree sessile knobs ; U.I NO. 4, detachment of two knobs; ft, protrusion of knobs become larger and Small- at tne periphery and on the surface ; in No. 3, the knobs , , , surround the whole body of the corpuscle ; and in No. 4, er, Very Slowly but repeat- they are still more numerous. edly, for some time. Oc- casionally a knob is pedunculated, and sometimes becomes de- tached from the corpuscle, while, on the other hand, some knobs are quite sessile. I have measured portions detached in either of the two ways described, and found them to vary from the ^oWo to the ^^ of an inch (.00084 — .00338 mm.). All except the very largest may usually be seen in constant oscillatory (molecular) movement, and, unless entangled between larger stationary corpuscles, easily moving across the field (the latter probably caused by minute vari- ation from absolute equilibrium level of the microscope stage). In some dentated or so-called " mulberry" forms, knobs or small eminences protrude from the face of the disk, which may 68 STRUCTURE OF COLORED BLOOD-CORPUSCLES. give to the inexperienced observer the impression of internal granules; but proper focusing corrects this impression, and shows the knobbed surface. (Fig. 22, I). FIG. 23. — COALESCENCE OF Two OR MORE CORPUSCLES, GIVING EISE TO CHAINS AND IRREGULARLY SHAPED COMPOUND BODIES, WITH THE NET- WORK STRUCTURE VISIBLE. In addition to the protean changes in shape initiated by in- dentation and protrusion, there are still others occasionally met with, due to combination or coalescence of two or more cor- puscles. In the course of twenty-four hours or more — though this occurs in by far the smaller number of prep- arations of blood examined — two or more adjacent colored blood-cor- puscles may, with a larger or smaller portion of their periphery, unite and form compound bodies, some- times chains or other strange shapes. (Fig. 23.) Almost immediately on being ready for examination, a very few colored blood-corpuscles show a light central vacuole. In the course of the examina- tion, a number of vacuoles, either of different sizes or all of the same size, may appear in a corpuscle. Usually, a vacuole is round or roundish, but it to be close together and in the third may assume various irregular fomiS figure, the separating walls of ap- J parently five vacuoles have broken SOme of which may perhaps have resulted from a union of several, and the breaking down of the separating walls. (See Fig. 24. The three lower figures show appearance of vacuoled corpuscles seen on edge.) Vacuoles sometimes persist, and sometimes, after a longer or FIG. 24.— VACUOLED COR- PUSCLES. In the upper line are seen three corpuscles, each with a different sized central vacuole ; in the middle line, the first figure shows three vacu- oles in one corpuscle; these vacuoles are represented in the second figure down, and one irregularly shaped larger vacuole is seen. The lower line shows the appearance of vacu- oled corpuscles seen on edge. STRUCTURE OF COLORED BLOOD-CORPUSCLES. 69 shorter continuance, suddenly disappear. They are either empty or else contain one or more granules. Soon after the corpuscles are studied, sometimes from the first, a difference is noticeable as to the intensity of their colora- tion $ some are paler than others. Gradually a larger number of corpuscles become pale, and the degree of paleness, too, increases. There is a great difference in respect to the rapidity of "paling" of colored corpuscles, in blood taken from different persons, even in blood of the same person taken at different times, and with different strengths of the admixed solution of bichromate of potash. Usually, in blood of healthy persons, examined as I have described, in about an hour from the time the drop of blood is placed on the slide, a few of the corpuscles that are least deeply colored appear to have become somewhat granular in their inte- rior. Focusing shows that this is not the optical illusion alluded to in the case of knobbiness of the surface. Soon the granules or dots seem more distinct ; short, conical thorns, or more delicate spines, appear to issue from one or two of the largest of them ; and, on close inspection and focusing, some appear to be connected by irregularly concentric filaments. In the course of five minutes more, a complete net- work is dis- tinctly seen in the interior of one or more corpuscles, and what at first appeared to be granules turn out to be thickened points of intersection of the threads forming this reticulum. These points or dots are irregularly shaped, and vary in size. (See Fig. 25.) FIG. 25.— THE STRUCTURE OF FIVE COLORED BLOOD-CORPUSCLES. In the first, there is seen an encircling band of uniform thickness, in which are inserted numerous threads of a net- work ; a number of knots are in the interior, which are seen to be the points of intersection of threads constituting a net-work ; in the lower portion of the disk there is a larger knot, which may be called a nucleus. In the fifth corpuscle the com- plete net- work structure is best seen ; in this corpuscle there is seen at the periphery, instead of an encircling baud, a number of knots united by threads, having the appearance described as beads, eacli a little separated from its neighbors on the string. The second corpuscle shows the net- work and encircling band, as the majority of corpuscles show them. In the third, a lighter band is seen, and an irregular flap, produced by either indentation or protru- sion, or both. The fourth exhibits a large flap or knob at its lower portion, with a stretched or extended net-work. Radiary threads of the net- work terminate at the periphery of the corpuscle, either with thickened ends connected by threads 70 STRUCTURE OF COLORED BLOOD- CORPUSCLES. — giving an appearance of unevenness to the outer boundary, as though it were constituted by a wreath of beads, each bead sepa- rated from its neighbors on the string — or, far more frequently, with terminal points lost in an encircling band of a uniform thickness, often greater than either the interior threads or most points of intersection. From this appearance, as well as that of the so-called " ghosts," to be presently described, it is not to be wondered at that careful observers have ascribed to colored blood- corpuscles the possession of an investing membrane. As the " paling'7 progresses, an increasing number of cor- puscles show the interior net- work, essentially as I have just described, and identical in construction with the net-work discovered by C. Heitzmann in amoeba?, colorless blood-corpuscles, and other living matter of the body, a discovery which I communicated to the American Medical Association more than three years ago. Gradually an interior net- work structure becomes visible in nearly all the corpuscles in the field, except the smallest, which appear more or less compact; and occasionally a APPROPRIATE So- corpuscle is met with having a central, or LUTION OF BICHRO- slightly eccentric, dot of such relatively large size that it might be interpreted as a nucleus. Some movement takes place in the net- work j for sometimes the threads change in length, regularly Amassed ^natter, and perhaps in thickness, and the dots change their position and their size. In the course of another half -hour or hour, the net-work becomes less distinct in the palest corpuscles ; and in these gradually fades away. Then, for some time, the net- work remains visible in nearly all corpuscles FIG. 26.— THE FINAL PHASES OF COLORED BLOOD - CORPUSCLES TREATED WITH AN MATE OF POTASH. In the upper left-hand figure there is a double- contoured ring, with ir showing traces of a net- work; in the lower right- hand figure this is less distinct; and in the two lower left-hand figures are -I™ "t^e there is detritus —i. e., two or three detached por- tions; and to the right- hand upper figure there is except those that are too pale or too small: attached a mass ivhich has apparently been extruded, vacuoles, one or more, appear in many of the latter ; while the former occasionally show indications of irregularly massed matter in their interior, though usually nothing is seen of them but double-contoured rings which have been called their " ghosts" (see Fig. 26). During this time, also, a quantity, sometimes rather large, of detritus accumulates. STRUCTURE OF COLORED BLOOD- CORPUSCLES. 71 It appears as though the net- work is most plain in corpuscles that have suffered either not at all or but little from detach- ment of a portion of their substance. The active changes of indentation and protrusion have usually disappeared in a large number of corpuscles, by the time " paling n has sufficiently progressed to render the interior structure visible. As before stated, some corpuscles permanently retain scalloped and knobbed forms, while the majority are finally more or less rounded off ; but the play of changing shape of many corpuscles is going on at the same time that this net- work is seen. After a while, further " paling" stops, and the net- work structure of all corpuscles which show it, remains visible indefinitely long. Blood-corpuscles, from hemorrhage in the bladder, in the urine of the late Dr. H****y, preserved with some bichromate of potash, still show the net- work after three years. Specimens of blood taken from different individuals exhibited all the phenomena described, but with some slight differences among each other as to the order and time of appearance. A 40 per cent, saturated solution of bichromate of potash, admixed with the blood, was found entirely satisfactory for the demonstration of all the phenomena ; and some variation of strength — i. e., between the limits of a 35 per cent, and a 50 per cent, saturated solution — made no appreciable difference. Of other solutions of bichromate of potash, it is sufficient to state the following : With a 30 per cent, saturated solution, the phenomena are also to be seen, but appear more slowly, and quite a number of corpuscles usually remain more or less unpaled. With a 20 per cent, saturated solution, the changes proceed still more slowly; comparatively few indentations occur; the' net- work of the majority of corpuscles is visible after the lapse of twenty-four hours, but many remain entirely unaffected. With a 10 per cent, saturated solution, vacuolation appears, also a little changing indentation and protrusion, but not suf- ficient paling to render the net-work visible even after several days. With a 60 per cent, saturated solution, the majority of the corpuscles had already become pale by the time the specimen was in place for examination. Some showed interior net- work, some only double-contoured rings. Protrusions were seen, 72 STRUCTURE OF COLORED BLOOD-CORPUSCLES. especially in the corpuscles not much paled; in one instance, a pale ring was also seen with a large pedunculated protrusion (Fig. 26). During two hours, changes of scalloping and of knobs took place faster than is usual with blood mixed with a 40 per cent, or 50 per cent, saturated solution, but they could not be fol- lowed so distinctly. Extreme paling rapidly proceeded, and much detritus filled the field, with only very few compact globules. With a 90 per cent, saturated solution, the process of scallop- ing was completed in twenty minutes ; and in thirty minutes a net-work was visible in a few roundish corpuscles, surrounded by masses of granular detritus. In addition, a large number of " ghosts " could be seen. Here and there a u ghost " would show a faint net- work. With a saturated solution added undiluted, the net- work was after one hour visible in some corpuscles, but most of them were destroyed ; of a few left intact, some looked homogeneous, and some vacuoled. The field was full of faint, double-contoured rings and a large quantity of granular detritus. The net- work structure of colored blood-corpuscles is visible also in anatomical preparations which have been kept for a length of time in Mutter's fluid. In some of my examinations, especially the earlier, I used the heated stage ; but as the phenomena described were seen at the ordinary temperature of a well-warmed room, I deem it best not to say anything here of variations of temperature. In this communication I omit the mention, also, of the remarkably varying amount of fibrine threads seen in different preparations of blood ; nor do I enter at length into the question of " detritus formation," or whatever else one may interpret as the appearance in the field of an increasing number of free gran- ules, and granular masses or plaques.* In addition to human colored blood-corpuscles, I have exam- ined those of lower animals. Essentially the same intimate structure as that which I have described exists in all. As exam- ples, I will quote from my note-book a few words referring to the examination of the colored blood-corpuscles of the ox and the newt — the one an example of the unnucleated, the other of the nucleated corpuscles. * Max Schultze, who saw some of these granules and granular plaques in healthy blood, prefers the designation " granule formation," as being non- committal.— Archiv fur Mikroskopische Anatomic, vol. 1, p. 38. STEUCTUEE OF COLOEED BLOOD-COBPUSCLES. 73 A drop of fresh ox-blood, mixed with a 50 per cent, saturated solution of bichromate of potash, and highly magnified (Tolles's j^ immersion) exhibited, within twenty minutes, vacuolation beginning in several red corpuscles. Within forty minutes, knobs were protruded, though not copiously. In the course of an hour, " paling " proceeded regularly, so that the net-work became visible in some, and within two hours in a large number, of the corpuscles. After three hours the net-work, the note-book says, was very distinct in many corpuscles, with some detritus and a few " ghosts." Twelve hours later, about one-half of the whole number of corpuscles showed the reticulum, while the other half were either vacuoled or unchanged. No further change was observable for two days. After the third day, some few corpuscles, per- haps, that had not shown the net-work structure before, now did; but the paled ones had become too pale to do so, except a very few which showed it finally. The rest had become " ghosts," with much detritus. A week later, nearly all the corpuscles that had exhibited the net-work had become " ghosts," only in a very few of which faint traces of the reticulum could be made out. The rest were still unchanged, as on the first day, and remained so as long as the specimen was kept. The red blood-corpuscles of the newt, examined in a 50 per cent, saturated solution of bichromate of potash, into which a drop of the blood from the freshly cut tail had been allowed to fall, presented peculiar changes of shape, consisting mainly in contractions of the body around the nucleus. The nuclei always exhibited the net-work structure, either perfect, and more distinct than in specimens unmixed with the solution, or, when the nucleus was swelled to double or treble its original size, with the net-work torn. Just as in the case of the colorless corpuscles, there were seen two kinds of red corpuscles, finely granulated and coarse granular, the granules always being the points of intersection of the threads of the net-work. In both kinds, the body as well as the nucleus exhibited the reticu- lum structure. The net- work of the body and that of the nucleus were connected by fine threads passing through the nuclear envelope. In many instances the body was reduced, either to two polar flaps, bulging from each side of the nucleus, or to one flap, more or less colored, at the side of the nucleus ; in other instances, it was uniformly contracted around the enlarged nucleus. Many colored corpuscles contained vacuoles, in varying num- ber, which were either empty or traversed by an exceedingly delicate, apparently stretched, reticulum, or else contained irreg- ular accumulations of matter with remnants of the net- work. n. My observations as to amoeboid movements of colored blood- corpuscles, as well as to varieties of size and shape, — observations 74 STRUCTURE OF COLORED BLOOD-CORPUSCLES. which were really only incidental while investigating the struct- ure, the main object of my researches — have been anticipated by previous investigators. One saw, and reported as an extraor- dinary finding, one or more forms or active form-changes like those I have described ; another others ; some a far greater num- ber than I. " Fehlt leider nur das geistige Band." The band which connects and explains the phenomena observed is the discovery of the structural arrangement. In the following historical sketch of points bearing on my observations, I shall refer to a few only of the legion who have made colored blood-corpuscles the subject of their investi- gation. More than a hundred years ago, William Hewson, after asserting that the red corpuscles are of different sizes in different animals, added : "I have like- wise observed that they are not all of the same size in the same animal, some being a little larger than others/'* etc. Hewson's editor, Gulliver, who has made a very large number of measurements of red blood-corpuscles of different animals, and is "our highest authority upon the subject," said of his own elaborate tables : "We are only speaking now of the average size, for they vary like other organisms ; so that in a single drop of the same blood you may find corpuscles either a third larger or a third smaller than the mean size, and even still greater extremes" ; t and more recently,! " But as I have long since shown, the corpuscles in one species of the vertebrate class, as seen in a single individual thereof, vary so much in size that their average dimensions cannot be determined with absolute precision; and were this fact kept in view much needless discussion might be spared." Beale, also, long ago called attention to the fact that "corpuscles may be found which are not more than the fifth or sixth of the size of an ordinary blood-corpuscle. "§ Again : " The red corpuscles vary in size, and more than is usually supposed "; || and again: "It is generally stated that the red blood- corpuscles of an animal exhibit a certain definite size ; but it will be found that they vary extremely, so that corpuscles exist of various dimensions." H Welcker ** found in the blood of Dr. Schweigger-Seidel colored blood-cor- puscles as small as. 0051, and as large as .0085 mm. Altogether, the inini- * "Philosophical Transactions," vol. Ixiii., Part n., p. 320 (read June 24, 1773). The works of William Hewson, F. R. S., Edited, with an Introduction and Notes, by George Gulliver, F. R. S., London. Published by the Sydenham Society, 1846 ; p. 234. t " Lectures on the Blood of Vertebrate." Medical Times and Gazette, vol. ii. of 1862, p. 157. t "Comparative Photographs of Blood-disks." Monthly Microscopical Journal, Novem- ber, 1876, p. 240. I " Archives of Medicine," vol. ii. (No. 8), p. 236, and Quarterly Journal of Microscopical Science, April-May, 1861 ; p. 249. II " Observations upon the Nature of the Bed Blood-corpuscles." Transactions of the Microscopical Society of London (read Dec. 9, 1863), vol. xii., N. S., p. 37. Quarterly Journal of Microscopical Science, Jan., 1864. T " The Microscope in its Application to the Practice of Medicine," third edition. Re- published in Philadelphia, 1867 ; p. 170. ** " Grb'sse, Volum und Oberflache und Farbe der Blutkb'rperchen bei Menschen und bei Thieren." Zeitschrift fur rationelle Medicin, S. iii., vol. xx. (1863), p. 237. STRUCTURE OF COLORED BLOOD-CORPUSCLES. 75 mum measurement recorded in his table is .0045 mm., and the maximum, though not in the same specimen, .0097 mm. He remarks : " I have always, both in animals and in man, found the transverse diameter of the blood- corpuscles of one and the same individual vary from one-fourth to one-half of the mean measurement ; and it appears that all the sizes lying between the two extremes are present in tolerably equal numbers, with the exception of the smallest corpuscles, which occur for the most part singly and at intervals." * Max Schultze distinguished in his own and other persons' healthy blood two forms of colored corpuscles, viz. : globular and disk-like ; the globular, few in number, vary from .005 to .006 mm. in size ; and from these there are grad- ual transitions to the ordinary disks, which measure from .008 to .010 mm. t The smallest colored corpuscles which Klebs reported t having found in his own blood varied from .0058 to .0066 mm. ; but in blood from the corpse of a leucaemic child he observed a few as small as .00416 mm. Woodward said : " The truth is that not only do the individual corpuscles in every drop of blood vary considerably in size, but as might be anticipated from this very fact, the average size obtained by measuring a limited number of corpuscles (50 to 175, still more in the case of but 10 to 50, as usually practiced), varies considerably, not only between different individuals, but also between different parts of the very same drop of blood." Both the maxi- mum and the minimum which he found — viz.: the 396 millionths and the 216 millionths of an inch, or .01005 and .00548 mm. — were present in the same field of one drop. § Berchon and Perrier|| state that the colored blood-corpuscles of the fo3tus and the newly born are on an average smaller than those of adults. The extremes given are: minimum, .0031 to .0062 mm., and maximum, .0091 to .0093 mm. ; but they do not mention that the extremes occurred in one and the same case. More recently, PerrierU measured blood-corpuscles of thirty-five individuals of different ages, and found that those of .010 mm. were very frequent in the first days after birth, while later they occurred much more rarely. After the first year, blood-corpuscles meas- uring .0093 mm. were rarely present in greater proportion than ten in a hun- dred ; and in adults often absent. Such of .0043 mm. occurred most often in the aged and in children. The diameter of the great mass at every age varies from .0050 to .0087mm. ; within these limits those of .0075 mm. are most frequent and never absent. The form of the smaller is more or less globular ; the larger are flattened. * Cited by Woodward, " On the Similarity between the Bed Blood-corpuscles of Man and those of certain other Animals, especially the Dog : considered in connection with the diagno- sis of Blood-stains in criminal cases." American Journal of Medical Sciences, Jan., 1875. Monthly Microscopical Journal, Feb. 1, 1875, p. 69. t " Ein heitzbarer Objecttisch uud seine Verwendung bei Untersuchungen des Blutes." Archiv fur Mikroskopische Anatomie, vol. i. (1865), p. 35. t " TJeber die Kerne und Scheinkerne der rotlien Blutkorperchen der Saugethiere." Virchow's Archiv fiir pathologische Anatomie und Physiologie und f iir Kliuische Medicin : vol. xxxviii. (1867), p. 195. § " The Application of Photography to Micrometry, with special reference to the micro- metry of blood in criminal cases." Transactions of the American Medical Association, vol. xxvii. (1876), p. 303-315. || " Note sur les globules du sang chez le fo3tus." Bordeaux Medical., p. 123 and 237 ; Canstadt's Jahresbericht for 1875, I., p. 46. f " Sur les variations du diametre des globules rouges du sang dansl'espece humaine, au point de vue de 1'espertise legale." Compt. liendus, torn. 84 (1877), No. 24, p. 1404. 76 STRUCTURE OF COLORED BLOOD-CORPUSCLES. According to Hayem,* the red blood-corpuscles in the newly born are much less uniform in size than in adults ; corpuscles larger than the largest and smaller than the smallest adult corpuscles occur comparatively often. The size varies between .00325 and .01025mm. Hayem also calls atten- tion t to the still smaller ones — measuring only .002 mm. — which he considers young and growing blood-corpuscles, so-called hsematoblasts. He asserted having observed all transition sizes between these and the largest. He found heematoblasts increased whenever, under physiological or pathological condi- tions, a reparation of blood occurs — e. g., he found them more abundant in children than in adults, and more abundant during menstruation, and after losses of blood, also during reconvalescence after acute diseases.! Netsvetzki reported § having found minute corpuscles moving in all direc- tions, as constant constituents of normal human blood. [Although my obser- vations as to the diversity of size of colored blood-corpuscles refer to healthy blood, I will not omit to mention here that Vanlair and Masius having, in the blood of a patient who had symptoms of interstitial hepatitis, found a number of small globular corpuscles, gave them the name of microcytes, and called the patient's disease " microcythsemia," which they considered to be a peculiar alteration of the blood. || Cases of so-called microcythemia have since been reported by Litten, in a tuberculous individual ; If by Osier in pernicious anaemia ** ; and by Lepine and Germont in cases of cancer of the stomach, tt Soernsen distinguished in disease between oligocythemia, in which the num- ber of red blood-corpuscles is diminished, achroiocythemia, in which their richness in coloring matter is diminished, and microcythemia, in which their size is diminished. In a case of chlorosis observed by him, the average size of the colored corpuscles was found to be only .0045, instead of the normal .006 to .0075 mm.tt Hicks §§ found in the fluid from an ovarian cyst small, transparent, color- less, globular bodies, which had been detached from red blood-corpuscles, and which were of a diameter of about the TFOTTO of an inch. Laptschinsky reported |||| finding very small corpuscles, only one-third as • " Des caracteres anatomiques du sang chez le nouveau-ne pendant les premiers jours de la vie." Compt. Rendus, torn. 84 (1877), p. 1166. t " &ur la nature et la signification des petits globules rouges du sang." Ibid., No. 22, p. 1239. t " Note sur 1'evolutiou des globules rouges dans le sang des vertebres ovipares." Compt. Rendus, torn. 85, No. 20, p. 907-909. " Sur Involution des globules rouges dans le sang des animaux superieurs" (verteb. ovipares). Ibid., No. 27, p. 1285. % " Zur Histologie des Menschen brutes. Kleine sich nach alien Richtungen Inn bewe- gende Korperchen als constante Bestandtlieile des normalen Menschenblutes." Centralzeit- ung fur die Medicinisclien Wisseuschaften, 1873, No. 10. || " De la Microcythemie, Bruxelles, 1871 ; 101 pp. If " Aus der Klinik des Herrn Geh. Rath. Prof. Frerichs, " Ueber einige Veranderungen rother Blutkorperchen." Berliner Klinische Wochenschrift; 1877, No. 1. " Ueber die Eutwickelung von Blutkorperchen in KnocluMimarlv bei pernicioser Aiue- mie." Centralblatt fiir die mediciuischen Wissenschaften ; 1877, No. 28 ; 1878, No. 26. tt Note sur la presence temporaire dans le sang uumaiii rt'un grand nombrede globules rouges tres petits (microcytes)." Gazette Medicale de Paris ; 1877, No. 18, pp. 218 and 219 ; and " Note relative a I'infiuence des saignees sur 1'apparition dans le sang humain des petits globules rouges (microcytes)." Id., No. 24, p. 296. tt " Undersogelser om Antallet af rode og hoide Blodlegemer under forskjellige physio- logiske og pathologiske Tilstande." Inaugural Dissertation, Kopeuhagen ; 1876, 236 pp. p. 660 and 661. ** " Ueber Diapedesis." Virchow's Archiv, vol. Iviii. (1873), pp. 203-254. tt " Ueber die Veranderungen der rothen Blutkorperclien nebst Bemerkungen iiber Microcyten." Centralblatt f. d. Med. Wiss., 1874, Nos. 21, 25. \\ " De la deformation des Globules rouges du Sang." Bruxelles, 1874. 47 pp. W " Aufib'sung der rothen Blutzellen." Centralblatt f. d. Med. Wiss., 1874, No. 27, p. 419. HII " Ueber Formveranderungen der rothen Blutkorperclien." Greifswald, 1875. HIT " Ueber einige Veranderungen welche die rothen Blutkorperclien in Extravasaten erleideu." Virchow's Archiv, vol. 69 (1876), p. 295-307. Also in other articles which I quote in this review. *** "Beitragzur Kenntniss des Froschblutes und der Froschlymphe.' Virchow's Archiv, vol. 71 (1877), pp. 78-107. ttt " The Structure of the Colored Blood-corpuscles of Amphiuma tridactylum, the Frog, and Man." Journal of tJie Microscopic Society of London, May and July, 1878, pp. 66, 68, 110, etc. STRUCTURE OF COLORED BLOOD-CORPUSCLES. 81 sented by two straight and parallel lines, connected at their extremities by two semicircular ones, and not showing merely their central concavity, as usually represented. The question whether or not colored blood-corpuscles possess an investing membrane has been much discussed, Hewson, who, as I have already stated, showed that these corpuscles are not perforated, contended that the dark spot in the middle, believed by Torre to be a perforation, " is a solid particle con- tained in a flat vesicle, whose middle only it fills, and whose edges are hollow, and either empty or filled with a subtile fluid."* He detailed the following experiments : " Take a drop of the blood of an animal that has large particles, as a frog, a fish, or, what is still better, of a toad ; put this blood on a thin piece of glass, as used in the former experiment, and add to it some water — first one drop, then a second, and a third, and so on, gradually increasing the quantity; and in proportion as water is added, the figure of the particle will be changed from a flat to a spherical shape ; ... it will roll down the glass stage smoothly, without those phases which it had when turning over when it was flat ; and, as it now rolls in its spherical shape, the solid middle particle can be distinctly seen to fall from side to side in the hollow vesicle, like a pea in a bladder." He added: "From the greater thickness of the vesicles in the human subject, and from their being less transparent when made spherical by the addition of water, and likewise from their being so much smaller than those of fish or frogs, it is more difficult to get a sight of the middle particles rolling from side to side in the vesicle, which has become round ; but with a strong light (these experiments were all made with daylight, in clear weather) and a deep magnifier, I have distinctly seen it in the human subject, as well as in the frog, toad, or skate." Another experiment he describes thus : "If a saturated solution of any of the common neutral salts be mixed with fresh blood, and the globules (as they have been called, but which for the future I shall call flat vesicles) be then examined in a microscope, the salt will then be found to have contracted or shriveled the vesicles, so that they appear quite solid, the vesicular substance being closely applied all around the central piece." Furthermore, "the fixed vegetable alkali and the volatile alkali were tried in a pretty strong solution, and found to corrugate the vesicles." The vesicular nature of colored blood-corpuscles, thus announced more than sixty years before the publications of Schleiden and Schwann, so per- fectly fits into their cell-schema that many suppose that they have originated this view of the constitution of the corpuscles. But in point of fact they have in this respect followed Hewson. According to Schwann, t the red blood- corpuscle is a cell, and consists, like every other cell of the body, of a membraneous envelope, a nucleus, and liquid contents; the credit of the observation of the "rolling around" of the nucleus is given by Schwann to C. * " On the Figure ami Composition of the Bed Particles of the Blood, commonly called the Bed Globules." Philosophical Transactions, vol. 63, Partn., p. 310 et seq. (read June 17 and 20, 1773). "A Description of the Bed Particles of the Blood in the Human Subject and in other Animals, being the remaining part of the Observations and Experi- ments of the late Win. Hewson." By Magnus Falconer. London, 1777, p. 221 et seq. t " Mikroskopische Untersuchungen iiber die Uebereiustimmung in Structur und Wachs- thurn der thierischen und pfianzlichen Organismen." Berlin, 1839, pp. 74, 75. 6 82 STEUCTUEE OF COLORED BLOOD-CORPUSCLES. H. Schultz, who, however, has only repeated and confirmed * the experiments of Hewson. Although not accepted without some opposition, it was not until the year 1861 that the existence of a cell- wall was positively denied. Beale declared : t " I have never succeeded in seeing the cell-wall said to exist, neither have I been able to confirm the oft-repeated assertions with regard to the passage of liquid into the interior of the corpuscle by endosmose, its bursting, and the escape of its contents through the ruptured cell-wall. When placed in some liquids, many of the corpuscles swell up and disappear ; but I have never seen the ruptured cell- walls." He also published observations which he considered " fatal to the hypothesis that each corpuscle is composed of a closed membrane with fluid contents." t Briicke expressed the opinion that the rolling around of the nucleus is illusory, that other phenomena do not conclusively prove the presence of a membrane, and that " the unanimity with which the vesicular nature of blood-corpuscles had for a long time been taught was owing more to the silence of the opponents than to the force of the arguments of the believers." $ Vintschgau|| and RollettH" also argued against the existence of an investing membrane ; and the opinion seemed doomed. But before the end of the year in which Beale and Briicke contested the existence of an investing membrane, Hensen defended it. ** He reports having observed in the blood of frogs, both in fresh preparations — i. e., in red corpuscles examined without the addition of any re-agent — and in corpuscles placed in various mixtures, especially a solution of sugar, that sometimes the membrane, as a distinct outer contour, is lifted up from the interior contents at one or more points of the circumference, these interior contents being retracted more or less densely upon the nucleus. A few years later, tt Hensen reiterated his conviction as to the presence of a membrane ; it is certain, therefore, that Lankester ft has misapprehended his meaning. Kolliker, who had previously asserted that the red blood-corpuscle possesses ' ' a very delicate but nevertheless tolerably firm and at the same time elastic colorless cell-membrane, composed of a protein substance closely allied to fibrin," §§ continued to uphold their vesicular constitution. |||| Preyer reported that the * " Das System der Circulation." Stuttgart and Tubingen, 1836, p. 19, et seq. t " Lectures on the Structiare and Growth of the Tissues of the Human Body. Delivered at the Royal College of Physicians. Lecture III., April 22, 1861." Archives of Medicine, vol. ii., No. 8 (May, 1861), p. 236. Republished in Quarterly Journal of Microscopical Science, vol. i., N. S. (April-May, 1861), p. 240. t " Observations upon the Nature of the Red Blood-corpuscle." Transactions of the Micro- scopical Society, vol. xii., N. S., p. 37. Quarterly Journal of Microscopical Science, Jan., 1864. § " Die Elementarorganismen." Sitzungsberichte der Wiener Akademie, vol. xliv., Div. u., p. 389 (read Oct. 17, 1861). || " Sopra i Corpusculi Sanguigni della Rana." Atti del Institute Veneto, vol. viii., Ser. ill. IT " Versuche und Beobachtungen am Blute." Sitzungsberichte der Wiener Akademie, vol. xlvi. (1862), p. 65. ** " Untersuchungen zur Physiologie der Blutkorperchen sowie iiber die Zellennatur derselben." Zeitschrift fur wissenschaftliche Zoologie, vol. xi., Heft 3 (Ausgegeben Dec. 23, 1861), pp. 253-278. tt In a foot-note of an article entitled " Ueber das Auge einiger Cephalopoden." ttid., vol. xv., Heft 2 (April 1, 1865), p. 170. it Laukestcr, in las article on the red blood-corpuscle, in the Quarterly Journal of Microscopical Science, October, 1871, already cited, says, p. 366, that Hensen " distinguishes a layer of fluid protoplasm surrounding the coloring matter, by cadaveric alteration of which he believes the supposed membrane of the corpuscle to be formed." §§ " Manual of Human Histology." Translated and edited by George Busk and Thomas. Huxley, London, Sydenham Society, 1854, vol. ii., p. 326. till Handbuch der Gewebclehre, 1863, p. 627. STEUCTUEE OF COLORED BLOOD-COEPUSCLES. 83 early observation of the rolling nucleus (erroneously ascribed by him, after Schwann, to Schultz instead of to Hewson) agreed with what he himself had seen, and, at least so far as red corpuscles of the blood of salamanders are concerned, positively declared a membrane normally to exist.* As proof of the existence of a membrane, and of its taking no part in the formation of blood-crystals, Bryanowski refers to his success in demonstrating it by means of distilled water, t Owsjannikow says : "To prove with certainty the exist- ence of the membrane is no easy task. Preparations occur which seem to be convincing that there is no membrane ; but other preparations show it with- out the addition of any re-agent. The interior contents retract away from it, so that between it and the yellowish colored contents an empty space remains. Still more distinctly than in pure blood is the membrane seen on the addition of a weak solution of sugar, either without or with admixture of a little alcohol. Then it appears in many, or perhaps in most, of the blood-corpuscles." Furthermore, he describes interior crystallization in which he has seen the membrane pushed out lengthwise by a crystal, and other cases in which " the membrane becomes very distinctly visible as it passes from nucleus to crystal." With high magnifying power, he says, human red blood-corpuscles not seldom show a very delicate membrane ; and one of his conclusions is : u In the blood-corpuscles of most animals an independent membrane can be proved to exist, which behaves toward serum, water, etc., differently from the cell-contents, and which occasionally possesses considerable firmness. " J Richardson argued § in favor of the same view, mainly on account of experi- ments upon the gigantic blood-disks of the menobranchus, in which " crystals of haamato-crystallin were seen to prop out a visible membraneous capsule." More recently, Richardson exhibited before the members of the Section on Biology of the International Medical Congress of Philadelphia, a slide with a colored blood-corpuscle of the amphiuma tridactylum, of which it is reported that "the imperfectly crystallized cell-contents occupy the upper end, while the oval granular nucleus fills the inferior extremity, leaving the membraneous capsule relaxed and wrinkled longitudinally, hanging like part of a half-flaccid balloon between them." || Arloing, as the result of his observations, H ascribed a membrane to red blood-corpuscles. Kollmann, after expressly declaring that when he uses the word membrane in relation to red blood-corpuscles, he means to speak of what maybe called an "artefact," *. e., "that apparent membrane which is made visible by the action of reagents,"** discusses the arguments pro and con, and concludes that "the adherents of a membrane have for their opinions at least as many reasons as the opponents." tt He himself believes in " the existence of a membrane in the fresh condition, * " Ueber amceboide Blutkorperchen." Virchow's Archiv, vol. xxx. (1864), p. 437. t " Beobachtungeu iiber die Blutkrystalle." Zeitschrift fur wissenschaftliche Zoologle, vol. xii., Heft 3 (November 17, 1862), p. 317. t"Zur Histologie der Blutkorperchen." Bulletin de 1'Academie des Sciences de St. Petersbourg, t. viii. (1865), pp. 564, 568-570. \ " On the Cellular Structure of the Red Blood-corpuscle." Transactions of the American Medical Association for 1870, pp. 259-271. || Transactions of the International Medical Congress of Philadelphia, held in 1876. Philadelphia, 1877, p. 488. IT " Recherches sur la nature du Globule Sanguin." Compt. Rendus, t. Ixxiv. (1872), No. 19, pp. 1256-1259. **"Bau der rotheu Blutkorperchen." Zeitschrift fiir wissenschaftliche Zoologie, vol. xxiii., Heft 8 (November 18, 1873), p. 467. \M\)iil., p. 482. 84 STRUCTURE OF COLORED BLOOD-CORPUSCLES. which can be made visible by the action of re-agents by depriving the cor- puscle of coloring matter, and which, when it does not become visible, has been destroyed by the re-agent." * According to Bottcher, the outer layer of the same blood-corpuscle is not the same at all times and under all circum- stances. He seems to regard the appearance of a distinct membrane as an artificial production; but considers "the cortical layer as the result of a process of development which deprives the blood-cells more and more of their protoplasm, and finally converts them into homogeneous bodies." He, therefore, classes it "with the capsule of cartilage cells, and with the cellu- lose membrane of 'vegetable cells, "t Fuchs observed a membrane of a certain power of resistance in frogs7 red blood-corpuscles after keeping them a few days on the slide without addition of any re-agent, which membrane was particularly obvious when the nucleus made its exit out of the corpuscular mass. t According to A. Bechamp, § and J. Bechamp and Baltus, || the red blood-corpuscles of mammals, birds, and amphibia possess a distinct mem- brane, which can be thickened by adding a solution of starch to the blood, and then becomes more resistant to the action of water. It has even been supposed that blood-corpuscles had more than a single membrane; thus Roberts said^F his observations had led him "to the belief that the envelope of the vertebrate blood-disk is a duplicate membrane ; in other words, that within the outer covering there exists an interior vesicle which incloses the colored contents, and in the ovipara, the nucleus." Bottcher has refuted this notion, ** and it is characterized by Wedl, too, as incorrect ; according to Wedl, when the cortical layer becomes swelled and condensed, the double contour which is seen indicates its thickness — but he is "quite certain that whether it be called membrane or not, it is not simply an artificial product." tt Lankester, in his conclusions regarding the verte- brate red blood-corpuscle, says : "Its surface is differentiated somewhat from the underlying material, and forms a pellicle or membrane of great tenuity, not distinguishable with the highest powers (whilst the corpuscle is normal and living), and having no pronounced inner limitation." tt Ranvier thinks that the double contour — the effect of dilute alcohol — "proves the existence, if not of a membrane, at least of a differentiated cortical layer. " §§ Schmidt |||| calls attention to the double contour as being "the only proof * i bid., p. 480. t Compare " Neue Untersuchungen iiber die rothen Blutkorperchen." Memoires de 1' Academic Imperials des Sciences de St. Petersbourg, vii. Serie, t. xxii. (1876), No. 11, p. 8 ; and the " Untersnchungen " in Virchow's Archiv, vol. xxxvi. (1866), pp. 357, 383, 387-9, and 404, with Archiv fur Mikroskopische Anatomie, vol. xiv. (1877), p. 93, or "On the Minute Structural Relations of the Red Blood-corpuscles " (translated from the preceding in), Quarterly Journal of Microscopical Science, October, 1877, p. 392. \ " Beitrag zur Kenntniss des Froschblutes," etc., 1. c., p. 91. §"Recherches sur la Constitution Physique du Globule Sanguin." Compt. Rendus, t. Ixxxv. (1878), No. 16, pp. 712-715. || " Sur la structure du Globule Sanguin, et la resistance de son envelioppe h 1'action de 1'eau." IUd., No. 17, p. 761. IT £• e. ** Op. cit. Virchow's Archiv, vol. xxxvi. (1866), pp. 392-395. tt L. c., p. 408. t* L. c., p. 386. §§ " De 1'Emploi d'Alcool Dilu6 en Histologie." Archiv de Physique, 1874, pp. 790-793. And again, " Recherches sur les Elements du Sang." Id., 2 Serie, vol. ii. (1875), pp. 1-15. III! "The Structure of the Colored Blood-corpuscles of Amphiuma tridactylum, the Frog, and Man." Journal of the Royal Microscopical Society ; containing its Transactions and STRUCTURE OF COLORED BLOOD- CORPUSCLES. 85 of the presence of a membrane, whether preexistent or artificially produced." In fresh blood of amphiuma he has observed colored blood-corpuscles with a greenish border, indicating ' ' the existence of a thin layer at the surface, dif- fering, if not in chemical composition at least in density, from the substance of the disks." He has frequently met with "specimens of blood-corpuscles, on which, by a contraction of the protoplasm representing the greater portion of the whole body, the pellicle in question appears separated from the latter." Once he saw a fragment of a corpuscle on which " the membraneous layer was seen projecting on the torn surface " ; and at another time he found " a fresh blood-corpuscle of the amphiuma on which the membraneous layer had appar- ently burst and retracted, leaving a portion of the underlying material, the protoplasm, exposed." He says: "The changes taking place in these blood- corpuscles, when treated with the solution of the hydrate of chloral, are very interesting and important; as they manifestly show the existence of the mem- braneous layer of these bodies, such as I have described it. Thus, after the solution has been applied, the protoplasm of the blood-corpuscle, without much or any alteration of form, gradually contracts upon the nucleus. As the result of this contraction, it becomes entirely separated from the membraneous layer, which manifests itself in the form of a delicate double contour. The inter- space left between the contracted protoplasm and the double contour repre- senting the membraneous layer is very considerable, as will be seen from the drawings, and, it seems to me, should be sufficient evidence to prove the existence of such a layer to an unbiased mind." In the colored blood- corpuscles of the frog, he has also seen a distinct stratum, or membraneous layer. " The colored blood-corpuscles of man show a double contour under vari- ous circumstances and conditions, indicating the existence, if not of an enveloping membrane, at least of a membraneous layer on its surface." As one proof, Schmidt recommends the experiment of pressing down, by means of the point of a forceps, a small round covering-glass upon a very small drop of fresh human blood placed upon the slide, " with the object of compressing or crushing the blood-corpuscles as far as possible." " Carefully examined with a first-class objective of sufficient amplification, it will be found that they have not run into each other; but that, on the contrary, the outlines of almost every individual may be discerned, however distorted they may be." Almost all investigators nowadays agree that the colored blood-corpuscles of birds, reptiles, amphibia and fishes have a nucleus ; while in those of man and other mammalia, except in developmental forms, a; nucleus does not occur. On this difference, Gulliver has founded his division of all vertebrate animals into pyrenaemata and apyrenaamata.* But the existence of a nucleus in living corpuscles of oviparous vertebrata has been denied on the one hand ; while, on the other, the opinion has been advanced that the mammalian red corpuscles, as well as those of other vertebrata, are in reality nucleated. Proceedings, with other Microscopical Intelligence. London, vol. i., No. 2 (May, 1878), pp. 57-78; No. 3 (July, 1878), pp. 67-120. * " Lectures on the Blood of Vertebrata," I. c. ; in Journal of Anatomy and Physiology, vol. ii. ; Proceedings of the Zoological Society of February 25, 1862 ; and Hunterian Oration, 1863, referred to in " Observations on the sizes and shapes of the red corpuscles of the blood of vertebrates, with drawings of them to a uniform scale, and extended and revised tables of measurement." Proceedings of the Zoological Society of London, for the year 1875, Part ill., p. 479. 86 STRUCTURE OF COLORED BLOOD-CORPUSCLES. Not to cite older authors, I will mention that Funke* asserts that the nucleus of nucleated blood-corpuscles does not exist during life, but is a prod- uct of decomposition after death. Likewise Savory, in a paper t read before the London Eoyal Society, urged that "when living, no distinction of parts can be recognized ; and the existence of a nucleus in the red corpuscles of ovipara is due to changes after death, or removal from the vessels"; and furthermore, "the shadowy substance seen in many of the smaller oviparous cells, after they have been mounted for some time, is very like that seen under similar circumstances in some of the corpuscles of mammalia." But Bottcher has reported]: seeing nucleated blood-corpuscles in the capillaries of living frogs, and more recently Hammond saw a nucleus in the red blood-corpuscles of young trout, varying as to age from a day to three weeks, swimming in a cell full of water ; § and afterward also in those of the tail of frog-embryos and in other animals. || Bottcher has by numerous methods and for a long time sought to demon- strate the existence of a nucleus in mammalian red blood-corpuscles. In his first publication^ he gave a historical sketch of the literature of the subject, and described the effects of chloroform, magenta, tannin, and other re-agents. He also treated corpuscles with serum of other blood; next** he placed them in aqueous humor (* i methods which alter the red blood-corpuscles as little and as slowly as possible"); afterward tt he treated them with alcohol and acetic acid, and still more recently U by means of a concentrated alcoholic solution of corrosive sublimate (methods of i i hardening the blood-corpuscles and then extracting the haematin from them "). Freer, using reflected instead of transmitted light (by means of Wales' Illuminator), affirmed §§ independently of Bottcher the existence of a nucleus in human blood; and Piper |||| seems very desirous to confirm Freer. Brandt, having, HIT in the red blood-corpuscles of living sipunculus, occasionally found a nucleus, though usually there is none, thought that perhaps the nuclei are unstable formations which by slight influences are produced or made visible, and by others are destroyed or made invisible ; on examining a drop of blood from his finger, on which he had before pricking placed a little fresh chicken albumen, he usually found in * " Lehrbuch der Physiologie." Leipzig, 1863, vol. i., p. 17. t "On the Structure of the Red Blood-corpuscle of Oviparous Vertebrata." Proceedings of the Boyal Society, vol. xvii., 1868, 1869 (read March 18, 1869). Monthly Microscopical Journal, April, 1869, p. 235. t " Untersuchungen iiber die rothen Blutkorperchen der Wirbelthiere." Virchow's Archiv, vol. xxxvi. (1866), (pp. 342-423), p. 351. §" Observations on the Structure -of the Red Blood-corpuscles of a Young Trout." Monthly Microscopical Journal, June, 1876, pp. 282, 283. || "Observations on the Structure of the Red Blood-corpuscles of Living Pyremematous Vertebrates." Id., September, 1876, p. 147. If The "Untersuchungen" just cited, pp. 359, 363, 367, etc., and 376. ** " Nachtragliche Mittheilung iiber die Entfarbuiig rother Blutkorperchen und iiber den Nachweis von Kernen in denselben." Virchow's Archiv, vol. xxxix. (1868), pp. 427-435. tt " Neue Untersuchungen iiber die rothen Blutkorperchen." Memoires de 1'Acad. Imp. des Sci. de St. Petersbourg, vii. Ser., t. xxii., No. 11. tt " Ueber die feineren Structurverhaltnisse der rothen Blutkorperchen." Archiv fiir Mikrosk. Anatomie, vol. xiv. (1877), pp. 73-93. §§ " Discovery of a new Anatomical Feature in Human Blood-corpuscles." Chicago Medi- cal Journal, May 15, 1868, and April 15, 1869. Illl " Contraction of Blood-corpuscles through the Action of Cold." New York Medical Journal, March, 1877, p. 244. HIT " On the Nucleus of Red Blood-corpuscles." Arbeiten der St. Petersb. Gesellsch. d. Naturf., vol. vii. (1876), p. 129. (In the Russian language.) STRUCTURE OF COLORED BLOOD-CORPUSCLES. 87 many red corpuscles what he was inclined to interpret as a central nucleus, in confirmation of the observations of Bottcher.* More recently, Stowell has written a communication to corroborate Bottcher. t And Strieker has ex- pressed the opinion that the nuclei of embryonal colored blood-corpuscles of mammals persist as circular thin disks; he argues that these " disks are so large that the body proper of the corpuscle appears on a surface view as only a narrow zone ; and that, therefore, except with high powers, the exist- ence of a nucleus is easily overlooked ; and he asserts that, by means of objective No. 15, he has in the blood-corpuscles of man, dog, rabbit, and cat seen the nucleus in both surface and profile views, t On the other hand, Schmidt and Schweigger-Seidel, who repeated Bott- cher's early methods, using especially chloroform as he had done, failed in finding nuclei, and suspected optical illusion. § Klebs contradicted Bottcher's statements as to the presence of nuclei in normal mammalian red blood-cor- puscles ; but described the occurrence of nucleated red corpuscles in blood taken from the corpse of a child who had suffered from leucaemia, agreeing in so far with a like observation of Bottcher. || Brunn said H that he had con- vinced himself that the appearances produced by both of Bottcher's later methods are artificial and optical effects, due to action of the re-agents on the substance of the corpuscles. And, similarly, Eberhardt has come to the conclusion that the remains after the action of different decolorizing re-agents are not nucM, but stromata deprived of coloring matter ; and that a forma- tion unmistakably a nucleus has not yet been demonstrated in adult human and mammalian red blood-corpuscles.** " Among other questions as to the red blood-corpuscle stated by Beale,tt he asks: "Is it a living corpuscle that distributes vitality to all parts of the organism, or is it simply a chemical compound which readily absorbs oxygen and carbonic acid gases and certain fluids? Is it composed of formative living matter, or does it consist of matter that is inanimate ? Does it absorb nutrient matter, grow, divide, and thus give rise to other bodies like itself, or does it consist of passive material destitute of these wonderful powers, and about to be dissolved into substances of simple composition and more nearly related to inorganic matter ? n He answers the first parts of these interrogatories in the negative, and holds that it is "not living, but results from changes occurring in colorless living matter, just as cuticle, or tendon, or cartilage, or the formed material of the liver-cell, results from changes occurring in the germinal matter of each of these cells." He says: "The colorless corpuscles, and those small corpuscles which are gradually undergoing conversion into red corpuscles, * " Bemerkungen iiber die Kerne der rothen Blutkorperchen." Archiv fur Mikrosk. Anatomic, xiii. 2 (1876), p. 392. t " Structure of Blood-corpuscles." American Journal of Microscopy and Popular Science, New York, June, 1878, p. 140. t " Vorlesungen iiber allgemeine und experimentelle Pathologie." II. Abtheilung. Wien, 1878, p. 438. § " Einige Bemerkungen iiber die rothen Blutkorperchen." Bericht der Konigl. Sach- sischen Gesellschaft der Wissenschaften, 1867, p. 190. || " Ueber die Kerne uud Scheinkerne der rothen Blutkorperchen der Saugethiere." Virchow's Archiv, vol. xxxviii. (1867), p. 200. IT " Ueber die den rothen Blutkorperchen der Saugethiere zugeschriebenen Kerne." Archiv fiir Mikroskopische Anatomie, vol. xiv., Heft 3 (1877), pp. 333-342. ** " Ueber die Kerne der rothen Blutkorperchen der Saugethiere und des Menschen." Inaugural- Dissertation der medizinischen Fakultat zu Kouigsberg. April, 1877, p. 30. ft " Observations upon the Nature of the Bed Blood-corpuscle" ; 1. c., p. 32. 88 STEUCTUEE OF COLORED BLOOD-CORPUSCLES. are living, but the old red corpuscles consist of inanimate matter. They are no more living than the cuticle or the hard, horny substance of nail or hair is living." * He therefore denied the contractility and amo3boid movement of colored blood-corpuscles. Klebs was the first who accorded them life and contractility, t He did this because, on preventing evaporation and raising the temperature of blood, he noticed, aside from motion of the corpuscles, the protrusion and retraction of knobs, and the formation and disappearance of scallops. But though the correctness of his observation was not doubted, his inferences were strenu- ously contradicted by Rollett and others, t Lankester observed " amoeboid figures " when colored blood-corpuscles had been subjected to the action of dilute ammonia and acetic acid, of which he says : § " The behavior of these corpuscles under alternate weak ammoniacal and acid vapors furnished a very curious parallel to the movements of amoeboid proto- plasm, and a careful consideration of the phenomena may throw some light on the nature of protoplasmic contractility." Bottcher admits the possibility of vital contractility, but thinks it cannot be compared to that of colorless blood-corpuscles. || Briicke,1[ also, admits cautiously this possibility. Preyer** uses many qualifying expressions, such as "only in part," u under certain circumstances," " in some degree," " temporarily," "at certain times." He observed active form-changes of red corpuscles in extravasated amphibian blood, examined in the moist chamber, which led him to the conclusion that " the substance of these corpuscles consists of dis- solved coloring matter and a colorless material (protoplasma) which, both when still in connection with the coloring matter and when free from this, shows under certain circumstances phenomena of contractility similar to those observed in many lower organisms." He adds : " As a rule it evinces no con- tractility, and constitutes, as a modified protoplasm, the stroma of amphibian blood-corpuscles." tt Max Schultze, who denied the contractility of red blood- corpuscles of man and mammals (although when subjected to a very high temperature — fifty to fifty-two degrees C., nearly enough to kill them — he saw protrusions and detachments of portions), admitted that the red blood- corpuscles of very young chicken-embryos are contractile, tt Friedreich§§ observed in an enfeebled anaemic patient polymorphous red blood-corpuscles, with active though very slow form-changes, which he could not but interpret as the result of contractility. In the post mortem blood of a woman who had been leucsemic he saw similar polymorphous corpuscles ; and in a case of albuminous urine he repeatedly observed colored blood-corpuscles from which minute portions became constricted and separated, as well as those which * Ibidem, p. 43. t Centralblatt fur mediziiiiscue Wissenscli., 1863, No. 514, p. 851. t For the views of Rollett, Max Schultze, Kiihne, etc., see "Strieker's Hamlbuch," cit., Leipzig (1869) edition, p. 287 ; American reprint (1872), p. 286. § Op. c., p. 378. || Archiv fur Mikr. Anat., vol. xiv. cit. p. 91 ; translated in Quarterly Journal of Micro- scopical Science, Oct., 1877, p. 391. U i.e. ** Op. c., p. 417 et seq. tt Ibid., p. 440. $t Verhandlungen der Niederrheinischen Gesellschaft fur Natur und Heilkuude in Bonn, am 8 Juni, 1864 ; Berliner Klinische Wochenschrift, 1864, No. 36, p. 358. §§ " Bin Beitrag zur Lebensgeschichte der rothen Blutkorperchen." Virchow's Archiv, vol. 41 (1867), p. 395. STRUCTURE OF COLORED BLOOD-CORPUSCLES. 89 exhibited amoeboid protrusion and retraction of short blunt projections, whereby a slow locomotion of the corpuscle was accomplished. He assumed that the contractility which the colorless corpuscles possess in so high a degree is preserved in undiminished strength in the red corpuscles in certain patho- logical cases. According to Charlton Bastian, * red blood-corpuscles leave under certain circumstances the vessels by virtue of active amoeboid movements ; and he thinks it would be well if "the attention of future observers should be directed to these peculiarities, and to the particulars above mentioned, in order to determine more certainly than has yet been done how far amoeboid movements and contractions do take place in the much-examined and much- written-about red blood-corpuscles." Lieberkuhn observed in the red corpuscles of salamandra and pike's blood active protrusion and retraction of bead-like processes. He also saw move- ments of granules or small molecules in the interior of the red blood-corpuscles of living frog embryos, t Faber, { in addition to his own observations of contractility and spontane- ous locomotion of colored blood-corpuscles in albuminous urine, — phenomena which continued to be manifested for a longer time in colored than in colorless .corpuscles, — has given a rather complete account of the literature of these phenomena, including the reports of diapedesis observed by Virchow, Strieker, Cohnheim, Prussak, and Hering. The observations of amoeboid movements by Bastian (just cited), Owsjannikow, § Winkler,|| and Brandt If seem to have escaped him; Arnold's experiments concerning diapedesis,** and Belfield's observation of emigration of certain small-sized red corpuscles of the frog,tt were published more recently. Since the publication of Faber's article, fur- thermore, Kommelaere has described amoeboid movements of colored blood- corpuscles ; U Brandt §§ has spoken of the peculiar forms of the red blood-cor- puscles of sipunculus and phascolosoma referable to amoeboid movements, and of the fact that occasionally in the temperature of an ordinarily warmed room considerable movements are accomplished ; and Schmidt has observed spontaneous motion (expansion and contraction) in a fresh colored blood- corpuscle of amphiuma in one instance, |||| and in those of man in a number of instances. He reports that he had witnessed the phenomenon in the col- ored blood-corpuscles of man as early as the summer of 1871. He says: "In examining a specimen of human blood, and whilst my attention was directed to the colored corpuscles as they were carried along by a moderate current of the liquor sanguinis under the covering-glass, I noticed on some of * " Passage of the Red Blood-corpuscles through the Walls of the Capillaries in Mechan- ical Congestion." British Medical Journal, May 2, 1868, pp. 425, 426. t " Ueber Bewegungserscheinungen der Zellen." Schriften der Gesellschaft zur Beforde- rung der gesammten Naturwissenschaften zu Marburg, vol. ix. (1870), p. 335. t " Ueber die rothen Blutkorperchen." Archiv der Heilkunde, xiv. (1873), pp. 481-511. § Op. cit., p. 563. || " Textur, Structur, und Zellleben in den Aduexen des Menschlichen Eies," Jena, 1870, p. 33. If " Anatomisch-hist. Untersuchungen iiber d. Sipunculus nudus, L." Memoires de 1' Academic Imperiale des Sciences de St. Petersbourg, vii. Serie, t. xvi., No. 8. ** Loc. cit, ft "Emigration in Passive Hyperaemia." American Quarterly Microscopical Journal, October, 1878, p. 39. n " De la Deformation des Globules Rouges du Sang." Bruxelles, 1874, p. 47. & In afoot-note to his " Bemerkungen iiber die Kerne der rothen Blutkorperchen," I. c., pp. 391, 392. Illl Op. cit., p. 67. 90 STRUCTURE OF COLORED BLOOD-CORPUSCLES. them the projection and immediate withdrawal of minute, conical, thorn-like processes, whenever one blood-corpuscle came into the vicinity of another, without, however, actual contact. It seemed almost as if one corpuscle were attracting or drawing out the thorn-like process from the surface of the other. In other instances, however, I observed the shooting forth and quick with- drawal of these processes from the margins of corpuscles not in close vicinity to others. As these processes appeared at the marginal surfaces of the blood- corpuscles, before the latter had come in contact with other of their fellows, I naturally regarded the phenomenon as one of spontaneous motion, mani- fested by the colored blood-corpuscle. But- as in most instances the phenom- enon was observed in corpuscles passing near each other, I was inclined to attribute it to a certain power of mutual attraction, residing under certain conditions in the colored blood-corpuscles. Having taken the precaution of slightly warming the glass slide before putting the blood, quickly taken from the vessels of the skin of a vigorous young man, upon it, and the tem- perature of the surrounding air being ninety-six degrees F., or even more, at the time, I also considered a certain amount of heat, at least ninety-eight degrees F., as essential to the manifestation of the phenomenon. This view, how- ever, proved to be erroneous, as I shall show directly. Although I have wit- nessed this phenomenon on blood-corpuscles when in a state of rest, it nevertheless is more frequently observed on blood-corpuscles in motion, as when they are carried along by a current arising in the specimen under the covering-glass, and resembling in character the current in the capillary vessels. With this view, the drop of blood should be thinly spread upon the glass slide, and quickly covered with the thin plate of glass. While the blood-corpuscle is projecting the thorn-like process, its body elongates, resembling a uni- polar cell, but with the withdrawal of the process generally assumes its original round form ; bipolar or lemon-shaped corpuscles are also very fre- quently met with in specimens of human blood. The same process is also observed when the margins of two corpuscles actually touch each other very slightly, and then slowly separate again. While separating, the thorn-like processes will be drawn out at the exact place of contact, and either remain permanent or disappear again after the separation has taken place. " That the normal heat of the human blood is not essential to the manifesta- tion of spontaneous motion in the colored corpuscles, I discovered during the past winter, while repeating my examinations of the structure of these bodies. I then witnessed the phenomenon above described, without having warmed the glass slide and covering-glass, and at the temperature of a moderately warmed room. However, I observed a colored corpuscle of a constricted form, similar to a figure of eight, slowly expanding, and finally resuming its original round form. "From this we may conclude that the colored blood-corpuscle of man pos- sesses not only a certain inherent power of contracting its body, but also of resuming its original form by a subsequent expansion, a characteristic property of the living protoplasm enabling the colored corpuscle to manifest spontaneous motions, though not to so great an extent as is seen in the color- less."* In his "General Conclusions and Summary," Lankestert says that the viscid mass constituting the red blood-corpuscles of the vertebrata " consists * Op. cit., pp. 113-115. t Op. cit., p. 386. STRUCTURE OF COLORED BLOOD-CORPUSCLES. 91 or rather yields, since the state of combination of the components is not known) a variety of albuminoid and other bodies, the most easily separable of which is haemoglobin ; secondly, the matter which segregates to form Robert's macula ; and thirdly, a residuary stroma apparently homogeneous in the mammalia (excepting so far as the outer surface or pellicle may be of a differ- ent chemical nature), but containing in the other vertebrata a sharply defin- able nucleus; this nucleus being already differentiated but not sharply delineated during life, and consisting of (or separable into) at least two com- ponents, one (paraglobulin) precipitable by CO2, and removable by the action of weak NH3 ; the other pellucid and not granulated by acids." A residuary stroma, such as Lankester here speaks of, seems to have been first recognized by Nasse, who said* that the red blood-corpuscle " consists of a basis tissue, insoluble in water, which is penetrated by a red substance, probably dissolved, or at least in water easily soluble (the red coloring matter of the blood), and some water, and within which there is an aggregation of solid granules not connected with the coloring matter." Rollett, t also, assumed that a stroma or matrix enters into the structure of the colored elastic extensible substance of the red blood-corpuscle, to which the form and the peculiar physical properties of the corpuscle are due. This stroma is, however, according to Bottcher, an artificial product, " nothing more than a residue of the colorless part of the red blood-corpuscles, varying much in form and extent, which remains after the dissolution of the original structural relations." + Briicke considered the most probable interpretation of the forms of colored blood-corpuscles, based on their appearances after the addition of boracic acid, to be the existence of a porous mass of motionless, very soft, colorless, hyaline substance, which he calls cecoid, in the interspaces of which is imbedded the living body of the corpuscle ; which body he calls zooid, and which consists of the nucleus (where that exists) and all the remaining part of the corpuscle containing the haemoglobin . § But Rollett insisted that the forms on which Briicke based this interpretation are products of decompo- sition. || Strieker agrees with Briicke as to the existence of the oecoid, but separates, in oviparous corpuscles, the remaining portion into nucleus and body. 1[ Of the three views thus presented, Lankester gives, after Strieker, the following tabular statement : ** ( Stroma. Coloring matter. , T , CEcoid = outer part of stroma. Membrane = «ecoid. Body =zooid minus nucleus. Nucleus = zooid minus body. According to Rollett. According to Briicke. f According to ( Strieker. * " Blut." B. Wagner's " Handworterbuch der Physiologic." Braunschweig, 1842, vol. i., p. 89. t"Versuche uud Beobachtungen am Blute." Moleschott's Untersuchungen, ix. ; also Hitzungsberichte der Wiener Akademie, vol. xlvi., Div. 2 (1862), pp. 65-98; and Strieker's " Handbuch," cit. Leipzig edition, 1869, p. 295 ; American, p. 284. • i Op. cit., Archiv fur Mikroskopische Anatomie, p. 90, translated in Quarterly Journal of Microscopical Science, October, 1877, p. 390. §"Ueber den Bau der rothen Blutkorper"; Sitzungsberichte der Wiener Akademie, vol. Ivi., Div. 2 (1867), p. 79. || " Ueber Zersetzungsbilder der rothen Blutkorperchen " ; Untersuchungen aus dem Institute der Physiologic und Histologie in Graz. Leipzig, 1870, p. 1. H"Mikrochemische Untersuchungeu der rothen Blutkorperchen"; Archiv fur die ge- sannnte Physiologie des Mensehen and der Thiere (Pniiger's), vol. i. (1868), p. 592. ** Op. cit. in a foot-note to p. 374. 92 STRUCTURE OF COLORED BLOOD-CORPUSCLES. If it had not been for the deserved eminence in other respects of the three investigators, Rollett, Briicke, and Strieker, these notions of the structure of colored blood-corpuscles would probably never have attracted any attention. Laptschinsky * considered colored corpuscles to consist of two kinds of substance, — viz., one which appears smooth, soft, extensible, assumes mostly a roundish form, and altogether possesses some if not all of the proper- ties of the so-called stroma ; the second, visible under the microscope only when through the action of different re-agents it is precipitated, or swelled, or both. It is this second substance which, on staining, takes up the coloring matters, and, by separating in the interior of the corpuscle from the first substance, or protruding from it, gives rise to the various shapes observed. At present it cannot be determined in what relation these two substances stand to each other previous to the precipitation of the stainable portion. The separating the blood-corpuscles into the two substances men- tioned is brought about by various external influences. In amphibian, i. e., frogs' and salamanders', red blood-corpuscles, Hensen, Bottcher, Kollmann, and Fuchs have seen a net-work ; and although they have failed to interpret it correctly — as is evident from the context of their descriptions — I beg to call special attention to their observations. Hensen ascribed to the corpuscle the possession of protoplasm accumulated at the nucleus and at the inner surface of the membrane ; the two being connected by delicate radiating filaments, in the spaces between which the colored cell-liquid lies.t Bottcher, from his observations, " inferred that around the nucleus of the amphibian blood-corpuscles a mass of protoplasm is collected, which radiates in the form of filaments into the homogeneous red substance. . . . The pro- toplasm appears sometimes collected uniformly round the nucleus, at other times it is accumulated more to one side of it. It is either provided with only a few processes, or is arranged round the nucleus in the shape of an elegant star, whose points extend to the margin of the corpuscle, or else it forms round the nucleus a peculiar lobed figure. Very often it appears beset on one or all sides with fine, hair-like processes. Then, again, it may represent a sort of net-work, which either appears separated from the less darkly colored cor- tical layer and more contracted, or else it throws out into the cortex innu- merable very fine radiating filaments, so that its processes approach the extreme periphery of the blood-corpuscles. In this case, therefore, the whole blood-corpuscle is permeated by a net-work of fine filaments, "t According to Kollmann, the membrane incloses a net-work of delicate slightly granular albumen threads. These in their totality constitute the stroma, and in the small spaces between the threads of the stroma lies the haemoglobin. The soft, elastic albumen threads are stretched between mem- brane and nucleus. Only by a certain degree of their tension is the charac- teristic form of the blood-corpuscle possible. The haemoglobin in the meshes counteracts excessive shortening of the threads. § Fuchs expresses himself similarly as to the net-work of fibers emanating from the nucleus, and going to the periphery of the frog's red blood-corpuscle. r " Ueber das Verhalten der rothen Blutkorperchen," loc. cit., pp. 173, 174. t " TJntersu chun gen," 1. c., p. 261. t " On the Minute Structural Relations of the Red Blood-corpuscles." Quarterly Journal of Microscopical Science, Oct., 1877, pp. 388-390. § "Ban der rothen Blutkorperchen," 1. c., p. 482. I STRUCTURE OF COLORED BLOOD-CORPUSCLES. 93 He adds that the net-work gives the coipuscle its shape, and fixates the nucleus in the center. Death of the corpuscle produces first coagulation, afterward liquefaction of the fibers of the net-work. Whenever the fibers are coagulated they are shortened, and produce indentations at the surface by drawing upon the points where they are attached ; when the shortening pro- ceeds too far, the fibers are torn off from the membrane, and in both cases of shortening there are places at the surface which look protruded. Liquefac- tion of the fibers is assumed when the corpuscle has a vesicular appearance, when it seems to contain a semi-fluid mass in which the nucleus may take any position, and from which it sometimes exudes, proving in exuding the exist- ence of a membrane as already described.* Schmidt seems to have seen something like an arrangement of filaments, but, if so, has misinterpreted it entirely. He has reported observing in blood of amphiuma treated first with water under the microscope, and then with a very weak solution of chromic acid (strength not ascertained), "a series of fine lines, radiating from the periphery of the nucleus through the protoplasm to the inner surface of the membraneous layer of the blood-corpuscle." He remarks : " Now this picture would almost seem to corroborate the theory of Hensen, as well as that of Kollmann ; the fine double lines representing the filaments, which they suppose to radiate from the nucleus to the enveloping membrane. But this is not the case ; for a closer examination reveals that these lines represent nothing but fissures in the protoplasm, which appears to have assumed some form of crystallization. This becomes more evident by observing some of these fissures deviating from their course, and giving rise to subordinate branches." t He has also reported a somewhat analogous appearance in the colored blood-corpuscles of the frog, both fresh and treated with the same re-agents. This he explained by contraction of the interior mass. He says : " The protoplasm in such a case retracts upon the nucleus, which it completely surrounds, while the membraneous layer appears isolated, manifesting itself by a double contour. And again, if the same process should take place without entirely separating the protoplasm from the membraneous layer, but leaving at certain small points a union between the two parts, the result must be the production of a number of filamentary processes, arising from the main bulk of the protoplasm, and passing to those points of the membraneous layer." J Kneuttinger considered the two surfaces of the biconcave disk of blood- corpuscles to be connected at the place of the depression by protoplasma threads ; if these tear, the biscuit form changes to a sphere. § According to Krause, the red blood-corpuscle consists of : 1. A colorless stroma formed by a solid albuminous matter arranged into radial fibers, and 2. Haemoglobin, which is a colored fluid albuminous matter lying in the interspaces of these fibers. || Lieberkiihn has found that the free nuclei of red blood-corpuscles of salamandra and tritons (the blood having been kept for some time in colored glass tubes) consists of two substances, of which one forms the * Op. cit., p. 95. t Op. cit., p. 72. t Ibid., p. 106. $ " Zur Histologie des Blutes." Wiirzburg, 1865, p. 22. II " Allgemeine und Mikroskopische Anatomic," p. 325-334. 94 STEUCTUEE OF COLOEED BLOOD-CORPUSCLES. envelope and septa or threads passing more or less regularly through the inte- rior, the other being contained between these septa. * In the nuclei of colored blood-corpuscles, Biitschli, W. Flemming, and Klein have reported the existence of a net-work, viz. : In the nuclei of red blood-corpuscles of frog and newt, Biitschli observed fibrils, with granular thickenings, traversing the nucleus and passing to and connecting with its envelope. t Flemming saw a very delicate and dense net-work of fibers pervading the interior of the nucleus, and attached to the nuclear membrane in many so- called cellular elements of the bladder of curarized salamandra maculata. He inferred that the net-work is present also in the nuclei of the red blood- corpuscles, though he did not see it there, t Speaking of some capillary blood-vessels of a newt, Klein said: "Some such capillaries contained blood-corpuscles, and the nuclei of these showed a very distinct net-work." § Also : " The examination of the nuclei of fresh epithelium of frog, toad, or newt, the nuclei of fresh colored corpuscles of these animals, especially of toad, with a Zeiss's F lens, or a Hartnack's immersion, No. 10, reveals fibrils in the nucleus, and also shows that the ' granules' are due to the twisted or bent condition of them." III. The method employed in my investigation, viz. : treatment of fresh blood with solution of bichromate of potash, and examina- tion with high magnifying power, has revealed certain appear- ances as the structural arrangements of colored blood-corpuscles. Do these arrangements exist in the living corpuscle, or are they artificial productions of the re-agent ? Dilute solutions of bichromate of potash and Miiller's fluid are known as the best preserving media for the most delicate animal structures : nervous tissue, the eye, embryos, etc., are kept in them unchanged for any length of time. In the fecundated chicken-egg of only twenty hours, placed in such a solution, the heart, but just formed, has been known to continue for a time to beat. Rollett has investigated the influence of bichromate of potash on protoplasm, and found that no alterations were pro- duced. In my series of observations, the weakest solutions (ten per cent, saturated solution or less) produced no paling of the colored corpuscles 5 while, on increasing the strength up to a * Loc. cit. t " Studien liber die ersten Entwickelungsvorgange der Eizelle, die Zelltheiluug und die Conjugation der Infusorien." Abhandlungen der Senckenbergischen Naturforschenden Gesellschaft, vol. x., Heft 3, 4 (1876), p. 260. t " Beobachtungen iiber die Beschaffenheit des Zellkernes." Archiv fur Mikroskopisclie Anatomie, vol. xiii. (1876), p. 693 et. scq. § "Observations on the Structure of Cells and Nuclei." Quarterly Journal of Micro- scopical Science, July, 1878, p. 337. || Ibid., p. 332. STEUCTUEE OF COLORED BLOOD-COEPUSCLES. 95 certain point, paling occurred in an increasing degree, and a morphological structure became visible at the same time that the manifestations of life (contraction and amoeboid movement) con- tinued. From this we certainly may infer that the re-agent has not altered, at all events not seriously impaired, the living matter ; and when we find that the structural arrangements thus revealed are the same as those demonstrable without re-agents in other living matter, the inference that they were preexisting, and not artificially produced by the re-agent, becomes a certainty. The knowledge of the structure of colored blood-corpuscles will not enable us to solve all the problems regarding their nature ; but some questions are answered pretty conclusively by my investigation. The colored blood-corpuscle is not a cell in any proper sense of that word, but, like the colorless corpuscle, is an unattached portion of the living matter (bioplasson) of the body. Broadly speaking, the essential difference between the two kinds of cor- puscles is the presence of haemoglobin, using this term to desig- nate the substance or substances — no doubt chemically very complicated — constituting the coloring matter under all the varying physiological circumstances. In size, human colored blood-corpuscles vary so much, that claims to be able to distinguish them by their size from certain other mammalian colored blood-corpuscles are inadmissible. The colored blood-corpuscle has no separate investing mem- brane j nevertheless, the outer portion, essentially like the inner substance forming the net- work, may be considered to be differ- entiated from the latter, especially at the periphery of the disk, where it constitutes an encircling band of uniform thickness, or occasionally of a wreath-of -beads appearance. In the colored blood-corpuscles of the lower classes of vertebrate animals there is usually a nucleus to be seen, which is not the case, as a rule, in those of man, and other mammalians j but there is in the interior of these an accumulation of matter occasionally met with, which may be interpreted as a nucleus. In the communication to the Vienna Academy, in 1873, Heitzmann demonstrated the existence of a net- work in amcebae, blood-corpuscles of astacus and of triton, human colorless blood- corpuscles and colostrum corpuscles ; and, from direct observa- tion of the changes in the reticulum during the contraction of the living body, announced that the substance constituting the net-work is itself the living matter or bioplasson — i. e., "the 96 STRUCTURE OF COLORED BLOOD-CORPUSCLES. nucleolus, the nucleus, the granules with their threads, are the living contractile matter proper." Aside from some conditions which do not here concern us, he described and illustrated three states of the net- work — viz., that of rest, that of contraction, and that of extension. A fourth state of the living matter is assumed (hypothetically) by the same investigator, to account for the formation of a flat layer of living matter, such as forms the walls of a vacuole, the membrane of a nucleus, or the outer layer of the whole bioplas- son mass. Heitzmann believes that each of these states may at any time change into the other — i. e., that the net- work may from the condition of rest be transformed into that of contraction, or of extension, or of flattening, and from each of these into either of the others. At all events, there may arise in the bioplasson body a vacuole having a continuous thin wall, and containing lifeless fluid and detached particles of the living matter. Or, a bioplasson mass may take into its interior foreign bodies by forming around them a cul-de-sac, which then opens toward the center and closes at the periphery, and the net- work, rent during the process, reestablishes itself. Again, a bioplasson body, which by flap or knob protrusion and separation has lost a portion of its substance, as well as the portion detached, may become rounded off — the rupture at the place of detachment healing in each case without loss of life. And further, two bio- plasson bodies may coalesce, and a portion of the periphery of each be transformed into the uniting net- work. By adopting these views, and applying them to the living matter of colored blood-corpuscles, we may explain the changes which they have been observed to be subject to. What are the changes that occur on the addition of a 40 per cent, saturated solution of bichromate of potash ? I have described indentations and protrusions which either persist or are leveled again ; pro- trusion of knobs, either pedunculated or sessile, which sometimes are so numerous that they surround the body of the corpuscle like a wreath ; decrease of the size of the main* body by detach- ment of knobs j appearance of net- work structure, most marked in the corpuscles which have not lost much of their substance ; vacuolation of corpuscles, and transformation of many of the portions detached into vacuoled globules which increase in size ; finally, change into faint, almost structureless disks, the so-called " ghosts." STEUCTUEE OF COLORED BLOOD-CORPUSCLES. 97 The regular rosette, stellated, and thorn-apple shapes are caused by a uniform concentric contraction of the living matter ; —the fluid in the interior, being pressed toward the outer layer between the points of attachment of the threads, will produce a bulging out at the periphery. Irregular contractions of the living matter will give rise to irregular flaps at the periphery. An indentation is due to locally limited contraction of the net-work in the interior of the corpuscle. Contraction of the living matter at one part of the periphery will bring about a protrusion of a flap at another, the flap being bounded by the outer layer of the corpuscle. Segmental contraction of the net- work will produce a rupture of the outer layer of the corpuscle, with projection of a pedun- culated granule or knob, formerly a part of the interior net-work. Continued contraction will be followed by the rupture of the pedicle and the production of either so-called detritus or small granules, or when the protruded knob is larger, or has become swelled, of a pale-grayish disk.* Lastly, a large amount of the net- work having been separated from the parent body, the latter becomes transformed into a pale disk, in which no traces of a net- work, or but very indistinct ones, are visible, a so-called ghost. At every stage of the protrusion of either flaps or pedunculated knobs or granules, the living matter may be overtaken by death, and the contraction become fixed by cadaveric rigidity. It may perhaps be worth while to notice that irregular contractions have a somewhat greater tendency to such permanency than regular ones ; these more frequently yielding, by relaxation of the net- work, or reestablishment of the state of rest, at impending death. But in the blood-corpuscles kept for over two years in bichromate of potash, all the described forms can be observed just as well as in freshly made specimens. * The peculiar corpuscles believed to be characteristic of syphilis by Los- torfer, and proved by Strieker to be present in the blood of individuals broken down by that and various other diseases, are nothing but such disks — i. e., portions of the colored blood-corpuscles protruded from the interior, detached and more or less swelled. As persons in low states of health have a relatively small amount of living matter in the same bulk, or, in other words, only a delicate net-work within the bioplasson body or plastid (the so-called " cell ")» such a net-work suspended in a relatively large amount of fluid can much more easily contract and bring about a rupture of the outer layer, than in the case of healthy persons, within whose plastids there is relatively less room for contraction to take place. 7 98 ORIGIN OF COLORED BLOOD-CORPUSCLES. The reason why the corpuscles of the smallest size do not change in the solution of bichromate of potash of medium con- centration, is, perhaps, that, being compact masses of living mat- ter in which the haemoglobin is not as yet accumulated within meshes, the solution does not reach and cannot extract the hemoglobin. These small globules are probably intermediate stages of development of colored blood-corpuscles, or the so-called hematoblasts of Heitzmann * and of Hayem.t The Origin of Colored Blood-corpuscles. In 1872, J at a time when I was ignorant of the structure and differences of bio- plasson, according to its development, and consequently adhered to the cell-theory, I made the following statements : Formation of Blood from Cartilage. In a horizontal section of the condyle of a femur of a recently killed dog, several weeks old, we .recognize, upon adding a drop of a one-half per cent, solution of chloride of sodium, with moderate powers of the microscope, two kinds of cartilage-corpuscles, — first : large, pale granular, distinctly nucleated cartilage-corpuscles; and second: smaller shining, yellowish, indistinctly granular corpuscles^ devoid of nuclei. There are transitions between these two kinds. Still more marked is the difference in sagittal (antero-posterior) sections of the cartilaginous epiphysis of the same dog. Near the articular surface, the corpuscles, closely arranged, look uniform ; but the nearer we come to the diaphysis, the more marked is the difference between the pale and the yellow, shining corpuscles. The glistening substance is often found in a crescent shape around the pale granular, or it occupies the center of the latter in the shape of a globular or irregularly angular body. Close to the border of the calcined basis-substance, the difference between the two kinds of cartilage-corpuscles is very marked. In a cavity of the basis-substance we often find the shining, coarsely granular substance characterized by thorny offshoots, and surrounded by a pale, granular zone, between which and the basis-substance there is an apparently structure- less rim. Solution of chloride of gold renders the finely granular bodies pale violet, whereas the coarsely granular ones assume a dark violet color, retaining their luster. " Studien am Knochen undKnorpel." Med. Jahrbiicher, 1872. t "Sur revolution des Globules rouges dans le Sang des Vertebres." Compt. rend. Acad. des Sci., Nov. 12, 1877; Idem. Soc. de Biologie, Nov. 24, 1877. "Sur revolution des Globules rouges dans le Sang des Animaux supe"rieurs." Compt. rend. Acad. des Sci., Dec. 31, 1877. t " Studien am Knochen und Knorpel." Medic. Jahrbiicher, Wien, 1872. ORIGIN OF COLORED BLOOD-CORPUSCLES. 99 older an animal (dog, cat, or rabbit) we examine, the we find its articular cartilage, and the less of shining, coarseiy granular corpuscles ; in the cartilage of a very old dog such corpuscles were entirely wanting — only pale granular nucleated were present. • On the calcified border of the articular cartilage of a young rabbit, I found large spaces in the narrow calcified basis-substance, which were partly filled with a colorless, finely granular proto- plasm, and their centers exhibited the glistening substance. In the large spaces below these, groups of bright lumps of differ- FlG. 27. — CONDYLE OF FEMUR OF A YOUNG RABBIT, AT THE BORDER OF CALCIFICATION OF THE DIAPHYSEAL CARTILAGE. SAGITTAL SECTION. [PUBLISHED IN 1872.] CC, cartilage-corpuscles, filling the spaces of the calcified basis-substance, CA ; changing in one level into hsematoblasts, L, and below this level into medullary corpuscles, P. The spindles in the middle of the medullary spaces are forming blood-vessels. Magnified 800 diameters. 100 ORIGIN OF COLORED BLOOD-CORPUSCLES. ent shapes were present, which had the appearance of having originated by the splitting up of larger lumps. (See Fig. 27.) As the shining, solid corpuscles exhibited stages of develop- ment advanced to the formation of nearly perfect red blood- corpuscles, I considered them as juvenile forms of the latter, and proposed for their designation the term " haematoblasts." I concluded that a part of the carti- lage-corpuscles, or a portion of the body of such a corpuscle, had be- come transformed into haematoblasts. Formation of Blood in Inflamed Bone. In speci- mens obtained FIG. 28.— BONE-CORPUSCLES FROM THE COMPACT fr°P a d.°^s tlbia> PQRTION OF A DOG'S TIBIA, INJURED WITH A which, eight days RED-HOT IRON, EIGHTH DAY OF INFLAMMATION, before the death of CHROMIC ACID SPECIMEN. [PUBLISHED IN 1872.] the animal, was The number ol blood-corpuscles varies in A, B, C. Magnified pUTDOSely iniured 800 diameters. -. -, , . with a red-hot iron, without opening the central medullary space, I found in the bone-tissue numerous cavities, which, besides a finely granular protoplasm, contained red blood-corpuscles. (See Fig. 28.) The suspicion arose that the blood-corpuscles had formed from the bone-corpuscles, which might be confirmed by finding stages of transition. Such stages were really discovered in many of the specimens. I met in the cavities of the bone-tissue with manifold formations of a substance the characteristics of which were : absence of a visible structure, a high degree of luster, and a yellow color. This substance appeared either in the shape of ledges bordering the pale, granular protoplasm, or of lumps with fine scallops or of glistening disks, and lastly, of corpuscles looking like red blood-corpuscles with the central cup-shaped depression, and, in side-view, biscuit- shaped. Lumps of this substance may some- times be composed of coarse granules. (See Fig. 29.) Identical formations were also found in blood-vessels. We are justified in calling corpuscles that we find within blood- vessels, blood-corpuscles of some kind. Now, as these corpuscles ORIGIN OF COLORED BLOOD-CORPUSCLES. 101 do not, either inside or outside of the vessels, which themselves are not fully developed, exhibit the features of perfect red blood- corpuscles, but show the most convincing transitions toward such, we are certainly justified in saying that they are stages of development of colorless protoplasm into colored corpuscles. We may designate such formations as haematoblasts. I thus saw formations also met with by W. H. Carmalt and S. Strieker * in the inflamed cornea of the frog and rabbit, and B — FlG. 29. — ELEMATOBLASTS IN BONE-CORPUSCLES OF A DOG'S TlBIA, PURPOSELY INJURED WITH A BED-HOT IRON. EIGHTH DAY OF INFLAMMATION. [PUB- LISHED IN 1872.] Bright homogeneous lumps, Ll and L*, contain a few vacuoles, V, or numerous vacu- oles, J). The shining substance borders the bone-corpuscle at M ; a fully formed red blood-corpuscle at B. Magnified 800 diameters. could corroborate the statement of C. Rokitanskyt that in " mother-cells/7 when they ramify in order to produce a capillary system of vessels, blood originates. In 1873 (page 46), I claimed all the formations described to be living matter at an early, juvenile stage, from which, in turn, by vacuolation and reticulation, protoplasmic bodies may arise. * Medic. JahrMcher. Wien, 1871. t Handbuch der allg. patholog. Anatomie. Wien, 1846. 102 OEIGIN OF COLORED BLOOD-CORPUSCLES. Lumps of living matter, however, separated from the neighbor- ing formations and suspended in plasma, in blood-vessels, I still considered as blood-formers — haematoblasts. The idea prevailed at that time that red blood-corpuscles originate from nucleated, colorless corpuscles, although no other support was found for this idea except that in the embryo there are numerous nucleated corpuscles in the blood-vessels. All attempts to transform colorless into colored blood-corpuscles outside the body, by their exposure to oxygen gas, proved to be failures. I have shown that whenever one tissue is transformed into another, — f. i., cartilage into bone, and also in an inflamed tissue, f. i., that of bone, — colored blood-corpuscles grow from granules of living matter in a way entirely different from that supposed by other histologists. E. Neumann* first drew attention to a difference in the shape of the corpuscles of the medulla of bone. In the liquid pressed out of this tissue he found colorless, granular lymph- corpuscles and yellow corpuscles, characterized by a homogeneous appearance, and a size only a little exceeding that of red blood- corpuscles. He met with colored cells in the medulla of bone, in numbers the greater the younger the individual, and inter- preted these to be stages of transition to red blood-corpuscles. He also concluded that during life a continuous transformation of lymphoid into red J)lood-cells takes place. G. Bizzozero t found in the medulla of bone, besides colorless protoplasmic bodies, such with homogeneous, reddish-yellow nuclei, and also bodies about to divide, which contained two homogeneous reddish-yellow nuclei. He also interpreted these bodies as transitions of colorless to colored cells, and came to the conclusion that the medulla of bone was of importance in the production of colorless and red blood-corpuscles, and that the formations of the latter started from the nuclei of the former. It is obvious that the formations described by these investi- gators are identical with those I had termed haematoblastic, which occur not only in the medulla of bone, but also in bone and cartilage in the normal process of ossification. The yellow lumps which all of us have seen are by no means blood-cor- puscles, though under certain circumstances they may furnish the material for the formation of blood-corpuscles. * Centralblatt f iir die med. Wissenschaften, 1868. Archiv der Heilkunde, x. t Gazetta medica Lombarda, 1868 and 1869. ORIGIN OF COLORED BLOOD-CORPUSCLES. 103 Based upon researches in cartilage and bone of birds, Schoney, in 1876,* makes the following statements : " E. Neumann t has denied the new formation of red blood- corpuscles on the border of ossification of the cartilage. At the same time he draws attention to Aeby, who already in 1858 suggested such a new formation. From the quotation of Aeby's words, it follows that he only supposed the new formation on the border of ossification, as his researches in this direction did not yield positive results, whereas Heitzmann positively asserts the fact of such a new formation. " E. Neumann's reasoning I cannot consider correct ; he, f. i., could not understand that hasmatoblasts should stain with carmine, while perfect red blood-corpuscles remain unstained. Heitzmann claims that the haematoblasts are in a juvenile con- dition of the protoplasm, from which, after certain changes have taken place, red blood-corpuscles arise. Corpuscles may react on being stained, in a different way, in their youth and old age. " E. Neumann, furthermore, makes a point of the absence of nuclei in haematoblasts, assuming, as he does, that blood- corpuscles in their juvenile condition must have nuclei, though they are destitute of such later. My own researches may also clear up this point. " E. Metschnikow f found in the impregnated and hatched germ of fowl, at first nucleated, slightly colored, and later, nucleated, distinctly colored, blood-corpuscles, and concluded that the latter had originated from the former. This conclusion is not fully justified, as it is possible that, from the same source, at first slightly and afterward deeply colored blood-corpuscles may arise and pass into the circulation without necessarily having directly changed from one into the other. The same reasoning also holds good for the blood-corpuscles of mammals. If at first nucleated and afterward non-nucleated blood-corpuscles are visible, who is willing to maintain that the latter have originated from the former, and that each red blood-corpuscle must have had a stage of nucleation ? * " Ueber den Ossificationsprocess bei Vogeln, und die NeuMldung von rothen Blutkorperchen an der Ossificationsgrenze." Archiv fiir mikrosko- pische Anatomie. Bd. xii. t Heitzmann's " Heematoblasten." Archiv fur mikroskopische Anatomie, November, 1874. t " Zur Entwicklimgsgeschichte der rothen Blutkorperehen." Virchow's Archiv, 41 Bd., 1867. 104 ORIGIN OF COLORED BLOOD-CORPUSCLES. " On watching specimens from the border of ossification of a growing chicken, we see within melted portions of the calcified basis-substance, homogeneous, shining lumps, in club-shaped spaces, inclosed by spindle-shaped elements. These spaces are not connected with perfect blood-vessels. The authors agree in considering such club-shaped formations as the first appearance of blood-vessels in the center of a medullary space. What are the shining corpuscles in the interior of a future vessel ? What else than not fully de- veloped blood - corpus- cles ? — therefore, hae- matoblasts. It is re- markable that these corpuscles have no nu- clei, and corpuscles crowded in blood-ves- sels toward the bone- tissue, the connection of which with older blood-vessels is not yet evident, also want nu- clei. Nucleated blood- corpuscles, so charac- teristic in birds, are visible only in deeper layers of the fully formed bone-tissue. If we admit that the youngest medullary formations are found in the ossifying borders of the cartilage, and that in the medullary spaces there are pres- ent corpuscles, to be considered as blood-corpuscles, we may readily accept the possibility that the nucleus is not an early, but rather a later, formation. This would agree with the state- ment of E. Briicke, concerning the formation of the nucleus in different other protoplasmic bodies. (See Fig. 30.) " The specimen illustrated above admits of but one interpreta- tion, viz. : that in fowls the first formed blood-corpuscles, the haematoblasts, have no nuclei; whereas complete red blood- FIG. 30. — OBLIQUE SECTION THROUGH THE BORDER OF OSSIFICATION OF THE CONDYLE OF FEMUR OF A YOUNG CHICKEN. The central medullary space is surrounded by the calcined frame, C, of the hyaline cartilage, and in its mid- dle there are several club-shaped spaces containing hsematoblasts, H. In the lowest space, B, the red blood- corpuscles do not yet exhibit nuclei. Magnif. 700 diam. ORIGIN OF COLORED BLOOD-CORPUSCLES. 105 corpuscles have nuclei. The nucleus is evidently not a require- ment of juvenile red blood-corpuscles. "In full-grown birds such a new formation of blood-cor- puscles does not occur. In a pigeon nine months old, the layer of globular cartilage-corpuscles is directly bounded by bone- tissue, containing medullary spaces tilled with fat. The blood- vessels of these spaces at their upper ends, looking toward the cartilage, are looped. The intermediate stage of ossification of the basis-substance and new formation of blood-vessels and haemato- blasts is absent. In still older animals, in which the layer of hyaline cartilage is much reduced in thickness, the upper ends of the medullary spaces toward the cartilage are closed by concentric systems of lamellae of completely formed bone-tissue." Hayem (see page 98) in 1877 described small shining lumps in the fluid of blood, more numerous in the foetus than in the adult, which he, I think justly, termed " haematoblasts." Red blood-corpuscles are very early formations of the middle layer (mesoblast) of the embryo. Probably they originate in every part of the body wherever there is living matter, especially in all varieties of that tissue which is exclusively supplied with blood-vessels, viz. : the connective tissue. Red blood-corpuscles are produced from lumps of living matter whenever, in the young, one variety of connective tissue is transformed into another — f . i., cartilage into bone. After the organism has reached full develop- ment, the production of colored blood-corpuscles continues in that variety of connective tissue which longer than any other remains in a juvenile condition, namely, the lymph-tissue. This tissue is present in large quantity in the body — the larger the younger the individual. It exists in all mucous layers, in the medulla of juvenile bone, in the lymph-ganglia, and in the spleen. Unfortunately, in consequence of former misapprehension of the nature and significance of this tissue, it bears the misnomer "adenoid tissue.'7 That this tissue is a source of red blood- corpuscles during the entire life-time, will be demonstrated in the next article. EXPERIMENTAL AND MICROSCOPICAL STUDIES ON THE ORIGIN OF THE BLOOD- GLOBULES. BY A. W. JOHNSTONE, M. D., DANVILLE, KY.* The objects of this paper are to give the result of a repetition of Onimus's experiments on the " origin of the white blood-corpuscles," and to place on record an account of an undescribed method of development that is constantly * " Archives of Medicine," vol. vi.. August, 1881. 106 OEIGIN OF COLORED BLOOD-CORPUSCLES. going on in the adenoid tissues. His conclusions are that the corpuscles have sprung up de novo from the blastema, and by analogy he argues that there is a spontaneous generation going on in serum wherever it is found. As given by Flint, these experiments on animals are as follows : The serum from quickly drawn blisters, after having been freed by nitration, etc., etc., from all its organized elements, is placed in bags of gold-beater's skin. These sacks are then placed in the subcutaneous tissues of rabbits, and after a sojourn of two or three days their serum is found to contain a variable number of leucocytes. I have repeated these investigations, and in two directions have pushed them farther than their author ; that is, instead of the blastema, in the course of the experiments I used four different liquids, and in all cases, besides the fluids, I examined the gold-beater's skin after its removal. In addition to the serum, I used a weak solution of chloride of sodium in water, a mixture of this with the white of an egg, and lastly the clear part of the egg alone. The animals used were cats ; the length of experiments from seventeen to fifty hours ; the thickness of the inclosing membranes was in most instances one, but in two cases two, layers of the gold-beater's skin. In all cases I examined both membrane and blastema before the introduction to the cat, and thus made sure that no organisms were present. My results were that in every case, except where I used a varnished membrane, I found leu- cocytes in the blastema, and wherever they were found in the liquid, the walls of the inclosing bag were sure to be crowded with the same organisms. The only things that seemed to influence the number of the corpuscles were the condition of the containing membrane and the length of time the sack remained under the skin. If these conditions were the same, there were just as many corpuscles in the solution of chloride of sodium, or the egg mixt- ures, as there were in the serum. In the cases where the skin was doubled after a longer time than was ordinarily employed, a few corpuscles made their appearance in the blastema, a few were found in the inner layer of the bag, whilst the outer one contained a great many. From these facts we are forced to the conclusion that the corpuscles migrated through the walls of the bags, just as they do to the interior of the catgut ligatures that are left in similar conditions. This, however, is only a negative kind of proof, and for something positive I will ask the reader's attention to my recent study of the so-called adenoid tissue. It is not necessary here for me to give the histology of the organs that contain this tissue, and to repeat that in the lymph-ganglia it is arranged into lymph follicles, lymph cords, and interfollieular strings ; in the alimentary canal into follicles such as are contained by the tonsil, base of the tongue, pharynx, stomach, solitary glands, Peyer's patches, etc. ; in the spleen into the ensheathing coats of the arteries, and the so-called Malpighian corpuscles, etc. But for our purpose, all that we need to know is that, wherever this tissue may be, there is a stream of fluid coming into it on one side, which, after working its way through the sponge-like mass, passes out on the other, and eventually empties into the blood. The two questions to which we will now address ourselves are : Whence comes and what is the function of the " adenoid" tissue. All histologists agree that in the animal kingdom we find but four varieties of connective tissue, and that they are the myxomatous, the fibrous, the cartilaginous, and the osseous. The myxomatous connective tissue is met ORIGIN OF COLORED BLOOD-CORPUSCLES. 107 with almost exclusively in the earliest stages of development of the embryonal connective tissue, and in transient foetal organs, such as the umbilical cord and placenta. This tissue appears in two varieties : first, in the shape of a protoplasmic reticulum of greatly varying size, with nuclei at its points of intersection, the meshes of which hold the jelly-like mucoid basis-substance (umbilical cord). In the centers of the meshes, globular and apparently isolated bodies are seen. The other form consists of a delicate fibrous reticulum, having oblong nuclei at the points of intersection, the meshes being filled with single protoplasmic bodies (so-called " decidua cells" of the placenta), or with a mucoid basis-substance with scanty bodies (derma and mucosa of the embryo in the earliest stages). Recent researches have proved that this mucoid basis-substance is not a structureless mass, but that it is pierced by a living reticulum, which is continuous with a smaller net-work pervading all protoplasmic formations. As the fibrous reticulum of myxomatous tissue is a protoplasmic formation, its fibers, too, contain a fine reticulum of living matter, which is also con- tinuous with the fine reticulum of its neighbors. So the basis-substance, in either its mucoid or fibrous variety, differs from protoplasm only by a chemi- cally altered substance within the meshes. This substance in the protoplasm is a liquid, in the basis-substance a semi-solid, though not strictly glue- yielding mass. As has been known for a long time, comparatively low powers, when brought to bear on the adenoid tissue, demonstrate the presence of a delicate fibrous reticulum, which at the points of intersection is generally slightly thickened and flattened so as to present a plate-like appearance. These intersections are sometimes provided with nuclei, and the meshes of the net-work are always filled with lymph-corpuscles. Although these cor- puscles are so closely packed that they often flatten each other, still each one is generally separated from its neighbors by a narrow, light substance which is probably liquid. Unless the lymph-corpuscles be torn apart by mechanical injuries, such as cutting, washing, etc., etc., they are all connected with each other by ex- tremely delicate, grayish spokes, which traverse the intermediate substance in all directions. A like connection always exists between the lymph- corpuscles and the fibrous reticulum nearest to them. Most authors claim that this fibrous reticulum of the adenoid tissue is structureless, and exhibits nuclei only at its points of intersection. This assertion must be based on Canada balsam specimens, for it makes all minute details fade away. My own specimens, cut from fresh lymph-ganglia, or such as had been preserved in a dilute solution of chromic acid, show a well- marked net-work in the fibrous reticulum, both in the unstained and in the carmine specimens. While we are on this subject of the preparation of specimens, let me say, once for all, that if we hope to see the minute structure of this tissue, our sec- tions must be cut from fresh or from chromic acid preparations, for alcohol or water destroys the details. If stained at all, it should be done with carmine, or, what is better, the one-half per cent, of chloride of gold. This last-named agent has a peculiar faculty for taking hold of the living matter of the most minute organisms and making it stand out in a very satisfactory manner. Lastly, I would state that glycerine seems to be the only mounting substance now known that will preserve tissues absolutely unchanged. 108 ORIGIN OF COLORED BLOOD- CORPUSCLES. Reasoning by analogy, it seems that we are forced to conclude that adenoid tissue is myxomatous, and therefore a remnant of f ratal tissue. We know that the myxomatous tissue is abundant in the embryo, and relatively scarce in the fully developed foetus. In the adult, the vitreous body was considered the only remnant of embryonal myxomatous tissue. To this, however, we should add the adenoid, and thus answer our first question. To get a better idea of this tissue, let us turn to its most minute anatomy, and for the present we will confine our attention to its frame-work. As I FIG. 31. — LYMPH-GANGLION OF CAT. B, myxomatous reticulum, exhibiting in its interior a delicate reticulum of living matter ; G, granules of living matter arising from the growth of the intersections of the contained reticulum ; V, granules grown into vacuoled corpuscles and intermediate stages of develop- ment; L, full grown nucleated lymph-corpuscles; M, mesh of the myxomatous net-work, tilled with lymph-corpuscles of all stages of development. Magnified 1200 diameters. have already said, in the frame-work, which looks perfectly homogeneous under a 500, with a 1200 (immersion) we can readily recognize a delicate reticulum piercing nearly all its fibers and plates. In some places, even without the use of a staining re-agent, this net-work is just as plain as in the OEIGIN OF COLORED BLOOD-CORPUSCLES. 109 corpuscles themselves, the only difference being that its meshes are a little wider than those in the globule. But the point to which I wish to draw particular attention is that the granules, at the points of intersection, vary very much in size. Sometimes, where they are seen along the edges of broad fibers, or in the centers of very fine ones, they give it a beaded appearance. At others they are so small that they are just barely appreciable. This inequality in size is most probably due to a growth that is constantly going on in these granules, and our finding different ones at different stages of it. (See Fig. 31.) This process does not stop where the lump of living matter can be called a granule, but it keeps on until it has converted it into what is known as a corpuscle. This is accomplished by the smaller granule increasing until it has become so large that the fiber can no longer contain it without showing a slight bulging at the point where the granule lies. This is what gives the beaded appearance just referred to. But as the bead still grows, it protrudes more and more from the free surface of the fiber, until it has the appearance of a small homogeneous yellowish corpuscle sticking to the side of the fiber. The corpuscle is not separated from the fiber in this immature state, but retains a connection in the shape of very delicate grayish spoke-like threads, that can be traced directly to the granules within the fiber. This connection is constant in all the different-sized corpuscles, except the very largest, and in all probability is the route through which the corpuscle draws its nourish- ment. We can see no differences in these growing corpuscles until they are about three-quarters the size of a red blood-globule. Then, however, they seem to be divided into two classes. Whether there are two sets of fibers that produce the different corpuscles, or how else it is done, is more than I can say; but I am sure that, at the stage I have indicated, one set become more highly refracting than the other, and take more and more of the char- acteristics of a red blood-globule, which they eventually become. The others, however, follow the course that C. Heitzmann has described, as the ele- mentary homogeneous granule takes in its development into a higher grade of protoplasm. After they reach the size I have already spoken of, a cavity containing a small amount of liquid forms, then similar excavations show themselves, until only a frame-work of the living matter is left between the vacuoles. There are communications established between these cavities, and the frame-work is transformed into a net-work with thickened points of intersection, which are the granules. With this view of the development of protoplasm we are better able to understand the meaning of the vacuoled corpuscles that we so often meet with. But the different sizes of the corpuscles, the different numbers of their granules, and the varying conditions of their nuclei and reticula, speak for themselves. They are the different stages through which an original granule of the fine reticulum contained by the fibrous net-work is developed into a full-grown lymph-corpuscle. This is further substantiated by the fact that the connection, already described, between the granule that has just passed to the outside of the fiber and the reticulum within it, is kept up through all sizes and shapes of cor- puscles, until the full-grown condition is reached. Then, however, this attach- ment is severed, and the globule passes away with the lymph stream in which it has been bathed so long. This is true of both sets of corpuscles, and can be shown as well in the young red as in the white. Thus we add a new proof 110 ORIGIN OF COLORED BLOOD-CORPUSCLES. to the old idea that a red globule is nothing but a mass of protoplasm contain- ing haemoglobine within its meshes ; for the elaboration of this subject I refer to the researches of L. Elsberg. The organs that I have used in these investigations are the lymphatic ganglia of man, horse, and cat, the spleen of man and cat, as well as the tonsil and thymus gland of children. The characteristics of the adenoid tissue were found to be the same in all, the principal differences being in the proportion of red to white globules. In the tonsil and lymphatic ganglia, the red are very scanty, though they can be found in most fields ; but in the spleen they are far more frequent. In this organ, like the rest, the corpuscles are formed by the development of the granules of the net-work within the frame, and not by budding of the eiidothelial plates, as claimed by some. We are now ready to give the reason for the lymph of the efferent vessels containing so many more corpuscles than that of the afferent, as well as to say where the few red globules that are found in the lymph of the thoracic duct come from. The lymph stream, as it passes through each successive ganglion, carries along an increased number of the fully grown elements that have become detached from the parent fiber, and eventually empties them into this duct, through which they reach the blood. In answering these questions, we are also giving the function of the ade- noid tissue, which is to produce the corpuscular elements of the blood. It has been known for a long time that as age advances the adenoid tissue becomes more and more scarce, and that the mucous layers and other organs that were once so rich in it, at extreme old age present scarcely a trace. In reality, the thymus gland may be taken as the type of the whole class. For while their degeneration is by no means so rapid, still they all show a tendency to follow its example. This is most strikingly shown in the history of Peyer's patches, as has been brought out by the study of typhoid fever. From this we would conclude that a young animal is the best subject for the study of the adenoid tissue. This I can testify is the case, for as age advances the gran- ules of the reticulum within the fibers become more scanty, and the retic- ulum itself is by no means so rich as in the early days of life. Should it ever be conclusively proved that the white blood-corpuscles share in the formation or repair of the structures of the body, we would then have the complete chain of their history ; for we are now sure that they represent only one stage of a development that is going on as long as life lasts, and I am not inclined to believe that this stage is the highest of the series. The conclusions that I have drawn from these studies are : 1st. We must have more and better proof before we can believe that a lymph-corpuscle ever arises from a blastema. 2d. That both red and white blood-corpuscles are developed from the gran- ules of the reticulum of living matter within the fibers of all adenoid tissues. 3d. That in different organs there is a difference in the proportion of red to white globules that are produced. 4th. That the adenoid tissue is myxomatous, and, properly speaking, a remnant of foatal life. 5th. That this tissue is stored-up material, from which the blood-corpuscles are made throughout life. 6th. That it is highly probable that the exhaustion of this material plays an important part in senile atrophy, and the other torpid conditions of the aged. VI. TISSUES IN GENERAL. ORIGIN, DEFINITION, AND DIVISION OF TISSUES. ORIGIN. All complex organisms, the higher developed ani- mals, originate from an ovum of the female impregnated by the admixture of spermatozoids of the male. The ovum, inclosed by a hyaline layer (zona pellucida *of Von Baer), is composed of living matter in reticular arrangement (the germ of Remak), which contains a nucleus-like body, the vesicula germ- inativa, with a varying number of coarser granules, the nucleoli, the macula? germinativae. In mammals and some amphibia, the germ, in toto, is transformed into the animal, whereas in the eggs of birds, scaly amphibia, and osseous fishes, a portion of the £erm is changed to yolk, which serves as a pabulum. After the spermatozoids have entered the germ — viz. : after fructification has taken place — its living matter increases rapidly, the vesicula germinativa disappears, and the germ, by a process of division, splits at first into two portions, separated from each other by a light narrow rim, but connected by extremely delicate filaments, which traverse the light rim. Each half of the germ splits into a number of lumps, which, in the same manner as the first half, remain connected ; thus the segmentation of the ovum results in the formation of numerous corpuscles, which by col- lecting in a flat layer represent the germinal disk of Pander, in 112 TISSUES IN GENERAL. the germ of the impregnated egg of the chicken. The segmenta- tion was first observed by Prevost and Dumas (1824) in the ovum of frog ; by Coste (1848) in the ovum of fowls ; and by Bischoff (1842) in the ovum of mammals. According to this last-named observer, the subdivision into smaller elements in the rabbit's germ does not go on uniformly throughout its whole extent, inasmuch as in the germ a cavity is formed, around which the elements of segmentation accumulate, in order to build up the germ-membrane proper, with a slightly thickened spot, the germ-hill of Von Baer. The first differentiation of the germ-disk, or the germ- membrane, consists in the formation of layers, of which at first two, shortly afterward three, are recognizable. The formation of such layers became known first through the researches of Caspar Friedrich Wolff (1768), who claimed that the whole system of the intestines is developed from simple laminae. Pander, in 1817, perfected the theories of Wolff ; he knew that after hatching had continued for twenty-four hours, three easily separable layers could be found in the germ-membrane. Von Baer, in 1822, described four layers, of which the two upper he termed the animal, the two lower ones the vegetative. Remak, in 1855, maintained that the germ-membrane of the impregnated but unhatched egg consists of two layers, and upon hatching the* lower is again split into two layers, the lower of which lines the one above it like an epithelial cover. Having ascer- tained the individuality of each of these three layers, he endeavored to find out their relation to the developing organs ; he called the upper layer the horny or sensorialj the middle layer the motorial and germinative j the under layer intestinal and glandular. According to S. Strieker's researches (1860- 1870), the original under layer of Remak consists— at least above the germ-cavity, and before the middle layer has made its appear- ance— of only a single stratum of flattened cells, and the formation of the middle layer is due to the immigration between the two layers of new cells. He termed the upper layer of Remak the combined horny and nervous layer, as he found that in batrachia the horny layer is quite distinct from the nervous layer, the former being uniformly thin j the latter, on the con- trary, thickened even in the earliest stages in that part where later the brain is formed. He is unable to confirm, despite of Remakes positive assertions, that nervous elements are also developed from the middle layer. TISSUES IN GENERAL. 113 Strieker (" Manual of Histology," American edition, 1872), in speaking of the development of the fowl's germ, says : " The cells of the tinder layer change their form and arrangement during the first hours of incubation. They become flattened, and, when seen in transverse section, appear spindle- shaped. Hence, after incubation has gone on for a few hours, we can ascer- tain, beyond even the shadow of a doubt, that there are two and only two layers. . . . The under layer, immediately after its separation from the subdivided germ, consisted in some places of a single thickness of cells, while in other places, in a transverse section, small heaps of cells could be recognized projecting from the layer. . . . Peremeschko, however, has made the communication that the large granular cells lying on the bottom of the germ-cavity increase very considerably in numbers during the first hours of incubation. Now, since with this increase in numbers there is not at the same time a corresponding diminution in size, it is very natural to suppose that the cells which project from the under germ-layer fall to the bottom of the cavity. This supposition appears all the more probable when we recall the fact that some of the elements of segmentation which are situated in the lower portion of the germ, remain lying at the bottom of the cavity at the time when the germ, in the production of this very cavity, separates itself from the subjacent parts. . . . We are led to conjecture that the process is one of trans- location ; that the granular bodies, which before lay at the bottom of the cavity, have found their way to the space between the two first germ-layers." Strieker, based upon Oellacher's researches, says that similar relations are also found in the trout's germ. At present, investigators agree that the body of vertebrates is at first a flat sheet, consisting of three main layers, for the desig- nation of which the following names, have been proposed : Exo- derma, Mesoderma, and Entoderma, or, preferably, epiblast, the tipper layer ; mesoblast, the middle layer; and hypoblast, the under layer. Of these, the epiblast and hypoblast are very thin, composed of but one layer of plastids, whereas the mesoblast is a bulky heap of plastids, all of which are interconnected and represent the main mass of the future organism. As the originally flat sheet of the germ becomes curved downward, so that the two lateral halves are bent toward the median line, where they grow to- gether, cavities are formed in the interior of the germ, which are lined by the under layer and its derivatives. The horny layer furnishes the external covering of the body and the lining of the external glands, while the under layer provides the lining of the intestinal cavity and its glandular organs. Linings of this descrip- tion are called " epithelia," and it follows that the epiblast and hypoblast give rise to all epithelia, viz. : the epiblast to those of the skin and its epithelial formations (including the crystalline lens) ; the hypoblast to those of the intestines and their glandu- lar elongations and accumulations. The main bulk of the body 114 TISSUES IN GENERAL. is a product of the mesoblast; from it proceed the tissues termed connective tissue, which alone contains blood and lymph- vessels, muscles, and nerves, the latter arising from the uppermost portions of the mesoblast. DEFINITION. In comparing the earliest formations of the germ with a single plastid formerly called a " uni-cellular organism" or a "protoplasmic body," such as the amoeba, valuable hints may be obtained as to the significance of the three germinal layers. The amoeba is covered by an extremely thin layer of living matter. If the amceba be flattened out and bent, its cover will represent the upper and under thin layer of the germ, which exclusively serves as an investing layer of both the outer surface and all cavities of the body, being directly or indirectly con- nected with the outer world. The main bulk of the amoeba is living matter in reticular arrangement, with thickened points of intersection of the threads of the net- work; this matter, retaining in the mesoblast and its derivations its reticular shape, furnishes in higher organisms the tissues, as a result of a sort of division, of labor. The nature of the tissues is determined, first, by the manner in which the living matter is distributed, and, secondly, by the chemical changes of the fluid contained in the meshes of the reticulum. Tissues are complex formations of living matter in a net- work arrangement. The meshes of the net-work contain a liquid which allows the living matter to exhibit contractility in a high degree, as in muscles and nerves, or the net- work contains a more or less solidified basis- substance, which limits its contractility, as in the connective tissue. The latter, on account of the presence of this basis-substance, mainly serves as a support for the more active tissues (muscles and nerves), and as a carrier of liquids in closed spaces. DIVISION. According to this view there are but four element- ary tissues in the animal body. All these are interconnected and built upon one and the same plan. 1. Connective tissue. In this the reticulum of living matter con- tains in its meshes a more or less solid, nitrogenous (glue-yield- ing) basis-substance j while points of intersection rich in living matter, suspended in a liquid, represent the connective tissue corpuscles. Of all tissues only the connective tissue carries in closed vessels the liquids which serve for nutrition, such as blood and lymph. Aside from this, and acting as support for other tissues, its physiological activity is relatively small. , TISSUES IN GENERAL. 115 Muscle tissue. The reticulum of living matter at its points of intersection consists of more or less regularly distributed large prismatic, cylindrical, or granular thickenings (sarcous elements), connected by thin filaments, while the meshes contain a liquid which admits of powerful contractions of the living matter in large territories. This tissue is the motor apparatus proper. It is accompanied by and attached to connective tissue, carrying the vessels. 3. Nerve tissue. Here the living matter is arranged in the shape of either a very delicate reticulum, with very small points of intersection (ganglionic corpuscles, gray matter), or delicate solid cords (axis-cylinders), while the meshes contain a liquid which allows the living matter in limited territories to contract rapidly. This tissue serves as an apparatus of sense-impression, intellect, and sensory and motor conduction. It is largely accompanied by and mixed with connective tissue, carrying blood-vessels. 4. Epithelial tissue. The reticulum of living matter is very delicate, and arranged in flat layers, which at certain regular in- tervals contain a horny cement substance. The function of epi- thelial tissue is to cover the surface and the cavities of the body j it alone serves as apparatus of secretion, and for the formation of the essential parts of reproduction — spermatozoids and ovum. THE RELATION OF LIVING MATTER TO THE INTERSTITIAL SUBSTANCE. This article is translated from a publication in German made in 1873,* with some unimportant statements omitted. In my studies of bone and cartilage, t I have demonstrated that the cartilage-corpuscles send numerous offshoots into the basis-substance termed " hyaline," and that these offshoots freely anastomose and connect the " cells" with one another. The material was furnished by fresh living hyaline cartilage, silver- tinction, gold-tinction, normal calcification of cartilage, and inflammatory calcification after simultaneously wounding car- tilage and bone. The deposition of lime-salts in hyaline cartilage, in conse- * " Untersuchuiigen iiber das Protoplasma. II. Das Verhaltniss zwisehen Protoplasma und Grundsubstanz im Thierkorper." Sitzungsber. der Akademie d. Wissensch. in Wien. Mai, 1873. t " Studien am Knochen und Knorpel." .Med. Jahrbiicher, 1872. 116 TISSUES IN GENERAL. quence of inflammation, especially served for bringing to view a delicate reticulum in the basis-substance, as such a deposition took place in the chondrogenous substance, while the protoplas- mic bodies and their offshoots remained unchanged. This reticu- lum corresponded with the light (negative) figures obtained by treatment with nitrate of silver and with the violet (positive) figures after gold-tinction. I wish to add a few more observations concerning the life and the structure of cartilage-corpuscles. If we examine a thin section from the condyle of femur of a middle-sized rabbit, in a one-half per cent, solution of chloride of sodium, or a little serum of blood, with high amplifications, we will see in many cartilage-corpuscles a structure identical with that I have described in colorless blood-corpuscles of man. The nucleus, if visible, appears either homogeneous or constructed of a dense reticulum of a shining substance, — the living matter, — and in- closed by a continuous layer of the same substance. The nucleus sends delicate conical filaments into the reticulum of the cor- puscle, and the points of intersection of this reticulum are thick- enings, granules, or lumps of living matter. In the narrow light rim between the protoplasm and the basis-substance we also see delicate spokes emanating from the cartilage-corpuscles, which are lost to sight in the finely granular but in some places distinctly reticular basis-substance. If we heat a fresh specimen to 30-35 degrees C. (86-91 degrees F.), we can observe in cartilage-corpuscles having a reticular structure a continuous though very slow change in the configu- ration of the living matter. Points of intersection flow together into homogeneous lumps ; the latter again are differentiated into a reticulum, and such change continues until rest of the living matter occurs — these changes in the reticulum not noticeably altering, however, the general shape of the corpuscle. A direct proof is thus obtained that cartilage-corpuscles are alive, which was made probable by R. Heidenhain and A. Rollett by observations of cartilage- corpuscles of the frog and newt on the application of induced electricity. A one-half per cent, solution of chloride of gold is a suitable re- agent for plainly bringing to view the structure of cartilage- corpuscles,* and for this purpose a slight tinction is sufficient. (See Fig. 32.) * Method of J. Cohnheim. " Ueber die Endigung der sensiblen Nerven in der Hornhaut." Virchow's Archiv, 38. Bd. 1867. TISSUES IN GENERAL. 117 To these observations in cartilage I add a series of researches in different other tissues of the body. Medullary tissue. The medulla between the trabeculae of a shaft-bone of a newly born pup consists of lumps of protoplasm, which are imbedded in a homogeneous basis- substance. These lumps vary greatly in their aspect. However the corpuscle may look, invariably spokes emanate from it which pierce the sur- rounding light zone radiatingly, and are visible with high ampli- fication only. Where the lumps are near each other, the spokes directly connect them; if, on the contrary, the lumps are separated from each other by broad layers of basis-substance, the spokes of a lump enter the latter, and in most instances disap- pear. (See Fig. 33.) The elements of the medulla termed u osteoblasts n by Gegen- baur* exhibit the same features both in the medullary spaces of FIG. 32. — CARTILAGE CORPUSCLES FROM THE CONDYLE OF FEMUR OF A NEW-BORN PUP. [PUBLISHED IN 1873.] Chromic acid specimen slightly stained with chloride of gold. C1, corpuscle with one compact, vacuoled nucleus ; C*, with a pale heap of granules above it ; Cs, with two nuclei and several heaps of granules. Magnified 1000 diameters. newly born pups, close to the bony trabeculae, and in the vascular canals of shaft-bones of older animals. Where the elements lie close to the bone- wall, they are sepa- rated from the latter by a light rim, and the filaments, springing * Jenaische Zeitschr. f. Mediz. und Naturwissensch. I. Band. 1864. This observer knew already delicate offshoots, like cilia, emanating from osteo- blasts. 118 TISSUES IN GENERAL. from the medullary corpuscles, pass through the rim into the basis- substance. Where the medullary corpuscles are near the border of a vessel, their offshoots traverse the light, perivascular rim and inosculate with the wall of the blood-vessel. * Upon slight gold tinction of chromic acid specimens previously exposed to water, the spokes exhibit a distinct violet color. The longer the solution of gold acts, the more distinct will be a differ- entiation in the basis-substance. The protoplasmic lumps at last appear as dark violet, densely reticular corpuscles with numerous FIG. 33. — MEDULLARY TISSUE FROM A LONGITUDINAL SECTION OF THE FEMUR OF A NEW-BORN PUP. CHROMIC ACID SPECIMEN. [PUBLISHED IN 1873.] B, bone-corpuscle; pi, vacuolecl plastid ; PZ, reticular nucleated plastid; M, apparently struct- ureless basis-substance ; C, capillary blood-vessel. Magnified 800 diameters. delicate radiating spokes, which blend with a partly coarse, partly delicate, reticulum. (See Fig. 34.) * Confr. "Ueber die Kiick- und Neubildung von Blutgefassen im Knochen und Knorpel." Med. Jahrbiicher, 1873. TISSUES IN GENERAL. 119 The basis-substance is traversed by a reticulum which has for points of intersection of its threads coarser and finer granules. By tracing the action of the gold solution, we can satisfy ourselves that the densest reticulum with the smallest mesh-spaces belongs to the yellowish, shining medullary elements, and the larger violet lumps are either homogeneous nuclei or nucleoli. The most delicate reticulum with smallest granules as points of inter- section, and the largest mesh-spaces, corresponds to those places FIG. 34. — MEDULLARY TISSUE FROM A LONGITUDINAL SECTION OF THE FEMUR OF A NEW-BORN PUP. THE BONE-TISSUE DECALCIFIED BY CHROMIC ACID, AND THE SPECIMEN INTENSELY STAINED WITH A SOLU- TION OF CHLORIDE OF GOLD. [PUBLISHED IN 1873.] BB, bone-corpuscles ; P, partly vacuoled, partly roticular plastids ; M, the basis-substance exhibiting a reticular structure. Magnified 800 diameters. of the medullary tissue which, in the unstained condition of the specimen, appeared as an apparently homogeneous and structure- less basis- substance. 120 TISSUES IN GENERAL. Tissue of the Umbilical Cord. Longitudinal sections of the human umbilical cord, hardened in a chromic acid solution, exhibit, as is well known, a striated or fibrous structure. The fibers are densest at the periphery of the cord and around the blood-vessels, and these layers are interconnected by a relatively coarse reticulum of fibers, the meshes of which contain a homo- geneous substance. In the fibrous layers we meet with large, nucleated, freely branching protoplasmic masses, also with smaller, spindle-shaped bodies, and with very small protoplasmic cords and lumps, devoid of nuclei. In the mesh-spaces, traversed by a few fibers which the cutting has partly torn, we encounter apparently isolated globular corpuscles, having one or several nuclei, but no offshoots.* The amount of living matter in the protoplasmic bodies is variable. We find compact lumps char- acterized by a nearly homogeneous structure, considerable luster, and yellow color; furthermore, coarsely and finely granular corpuscles, with either homogeneous, shining, or finely granular pale nuclei, some containing nucleoli; lastly, very pale, deli- cately granular bodies destitute of both nuclei and a marked boundary line toward the basis-substance. The periphery of all these corpuscles, while they are in connection with the tissue, looks more or less scalloped or thorny, and the same is the case with their nuclei. Upon rubbing a fresh umbilical cord with a stick of nitrate of silver, and exposing the specimen, kept in water, to the daylight, it will soon become brown, t Longitudinal sections of an umbilical cord colored in this way exhibit, even with lower amplifications, numerous many- shaped light and colorless fields in the brown basis-substance. High amplifications demonstrate that the light fields in different directions send branches into the basis-substance, f and that from *For reference: Rud. Virchow's " Cellularpathologie," 4 Aufl., 1871. Weisman, "Zeitschrift fiir rat. Mediz." 3 Reihe, Bd. xi., 1861. K. Koster, "Ueber die feinere Structur der menschl. Nabelschnur," Wiirzburg, 1868. Koster found the globular corpuscles in the mesh-spaces, and the spindle- shaped cells near the spaces without fibrils, to be amoeboid. t Method of F. von Recklinghausen ("Die Lyinphgefasse und ihre Bezie- hung zum Bindegewebe." Berlin, 1862). Specimens containing black, granular precipitations I consider as useless. The features described can be observed only when the basis-substance is stained light or dark brown, and the fields corresponding to the protoplasmic bodies are colorless. t Koster (I. c.), by means of the silver tinction, brought to view the larger light fields only. TISSUES IN GENERAL. 121 all these light fields and their offshoots a delicate varicose reticulum starts, which traverses the whole of the brown basis- substance. (See Fig. 35.) Slight gold tinction shows that the violet nucleated bodies and their coarser offshoots correspond, both in size and shaper with the large light fields brought to view by nitrate of silver. In specimens deeply stained with chloride of gold, we observe that, from each dark violet corpuscle and its offshoots, numerous FIG. 35. — LONGITUDINAL SECTION FROM THE CORTICAL PORTION OF THE HUMAN UMBILICAL CORD, STAINED WITH NITRATE OF SILVER. [PUB- LISHED IN 1873.] [PUBLISHED IN 1873.] AAt acini lilied bv epithelia (termed also "enchyma- cells"); C, connective-tissue frame. Magnified 300 diameters. ±ne animal body, as a whole, is one protoplasmic mass, in which are imbedded a relatively small number of isolated protoplasmic corpuscles (migrating, color- less, and colored blood-corpuscles), and various other non-living substances (glue-yielding and mucous substances, fat, pigment- granules, etc.). 132 TISSUES IN GENERAL. Just as the amoeba is a protoplasmic lump, in which the living matter is arranged in the form of a reticulum, whose points of intersection are also living matter, so the body of even a highly organized mammal is a lump, traversed by a living reticulum, whose points of intersection are living matter in the shape of protoplasmic corpuscles, hitherto termed cells. FIG. 46. — SCHEMA OF THE STRUCTURE OF THE VARIETIES OF CON- NECTIVE TISSUE. [PUBLISHED IN 1873.] Every tissue, as the history of development teaches, is built up by a number of protoplasmic lumps, which we may consider as the elements of the tissue. In a completely formed tissue, the cell and its territory (Virchow) represent the unit of the tissue, wn TISSUES IN GENERAL. 133 which is by no means an individual, as each unit is in direct, living connection with all neighboring units. Let us begin with the analysis of the units in the formations termed " connective tissue." In the center of the element is the nucleolus, around this the nucleus, and next a protoplasmic body, hitherto termed " cell" j this is surrounded by a protoplasmic mass, infiltrated with a glue-yielding basis-substance, and within this unit of the tissue the living matter is uninterruptedly connected. It is accumulated in the center in the shape of a compact nucleolus; next it constitutes a sometimes narrow, sometimes wide, reticu- lum, and incloses this reticulum as a continuous layer in the shape of the nucleus; then it forms a somewhat wider reticulum, holding protoplasmic liquid, and, as a rule again, a continuous shell, inclosing this reticulum in the shape of the cell; and, lastly, is spread out in the shape of a relatively wide reticulum, whose meshes are infiltrated with basis-substance, as the cell-territory. (See Fig. 46.) This schema may exhibit modifications if either the nucleus in toto or the whole element in toto is a compact, homogeneous mass of living matter. Such conditions are due, as I have explained before (see page 46), to differences of age of the protoplasm. Each of the constituents of a unit described is separated from the neighboring constituents by a space, as a rule, containing a liquid, traversed not by a reticulum, but simple filaments of the living matter. Such spaces, therefore, exist around the nucleolus, around the nucleus, around the protoplasm, or cell, and around the infiltrated portion of the unit, although until the present time only the pericellular spaces were known. In all these spaces a circulation of liquids can take place, and each may be filled by parenchymatous injection with colored substances. Such injec- tions have been made around the nucleus (by Mac-Gillavry) j around the cell (by Kowalewsky and others) j around the bor- ders of the units of the tissue, and, lastly, around the perivascu- lar spaces. By such forcible injections the connecting filaments are torn and the protoplasmic bodies become displaced and com- pressed. We can readily understand how lymph-clefts, desti- tute of walls, could be manufactured by such parenchymatous injection. The schema of the units of epithelium is different. In the center of the element is the nucleus with the nucleolus. Both are imbedded in a protoplasmic body surrounded by the shell of cement-substance common to all neighboring elements, 134 TISSUES IN GENERAL. which contains the spokes or prickles connecting the elements. Features similar to those of epithelia may also be exhibited by some connective-tissue corpuscles, especially those of the medul- lary tissue (osteoblasts) and the endothelium j the same are found in the tissue of smooth muscle. I intend to demonstrate here- after that the development of a unit of connective tissue is invariably preceded by a stage which corresponds to the schema of epithelial formation ; we are therefore not justified in making an essential difference between the elements of connective tissue and those of epithelium, exclusively based on differences in their shape. Just as each independent protoplasmic lump, and within it each vacuole, is bordered by a continuous layer of living matter, so the body of a mammal, and in its interior every cavity, is covered by a continuous layer of protoplasm. Based upon the facts hereinbefore described, we may obtain, as I shall later show, a clear view of the development of the tissues and of the inflammatory process. During inflammation, especially that of certain tissues, conclusive proofs are furnished that there is in the basis-substance a large amount of living matter which is liable to become diseased. Is Blood a Tissue? As one of the consequences of the modern views regarding individuals, it is held that blood, pus, secretions, etc., are fluid tissues. I have demonstrated that every animal tissue is a continuous mass of protoplasm, with zones of different structure. An " intercellular substance" exists here as little as u cells," in the modern sense, are present. We are justified in speaking only of basis-substance. That single lumps, as migrating cells, discovered by Von Recklinghausen, are, for a time, disconnected from other ele- ments and execute locomotion of their own, does not alter the general rule. Migrating corpuscles are not essential constituents of a tissue. In the blood, isolated protoplasmic lumps, the red and colored blood-corpuscles, float in a liquid plasma. Protoplasmic lumps are likewise suspended in liquids such as pus, colostrum, bile, sperm, etc. Such liquids we have no right to call tissues. The analogy between a living amoeba and the body of a higher animal as to its living blood-corpuscles is apparent enough. In the amoeba there arise transient vacuoles, in some of which, as I have demonstrated before (see page 22), granules TISSUES IN GENERAL. 135 of the contractile matter may be suspended; and blood-vessels arise from the formation of vacuoles (see page 36), containing from their very origin a liquid in which isolated lumps of living matter are suspended. RESEARCHES AND DEDUCTIONS SINCE 1873. I have purposely given an accurate translation of my assertions in 1873, in order to show that the cell-theory and its consequences, in the light of my investigations, had to be abandoned. At present, after nine years' further research, I have nothing to alter in my previous statements, and but little to add. Various publications, based on studies made in my laboratory during the last seven years by unprejudiced observers, fully corroborate the new views. Not only physiological and histo- logical research, but pathological investigation as well, will become more fruitful. Inflammation, tuberculosis, formation of tumors — in short, all morbid processes — will be better under- stood than is possible with cellular-pathological views. L. Elsberg, in 1875,* makes the following statements : " Not only in the wide domain of organic physiology, but especially also in human pathology, the cell doctrine has been accepted so universally that it seems to me eminently proper to bring the new views to the notice of the American Medical Asso- ciation, even at this early stage of their crystallization into a complete doctrine. All that I shall present to you as histological fact has been repeatedly observed and demonstrated by C. Heitz- mann, both at Vienna and New York ; and a number of others, as well as I, have been enabled to confirm his observations. " The ideas of humoral and solidistic pathologists long con- tinued to influence medical teachings after Schwann's dis- coveries of the elementary structure of tissues were generally acknowledged as correct, and more or less consistently applied. It was really not until Virchow promulgated his celebrated lectures on cellular pathology, less than twenty years ago, — lectures which reached and deeply impressed the medical pro- fession in every portion of the globe, — that the cell-doctrine has had undisputed sway." * Notice of the Bioplasson Doctrine. Transactions of the American Medical Association, 1875. 136 TISSUES IN GENERAL. In Lecture I., delivered February 16, 1858, Virchow said: "'If we con- sider the extraordinary influence which Bichat, in his time, exercised upon the state of medical opinion, it is indeed astonishing that such a relatively long period should have elapsed since Schwann made his great discoveries without the real importance of the new facts having been duly appreciated. This has certainly been essentially due to the great incompleteness of our knowledge with regard to the intimate structure of our tissues, which has continued to exist until quite recently, and, as we are sorry to be obliged to confess, still even now prevails with regard to many points of histology, to such a degree that we scarcely know in favor of what view to decide. Especial difficulty has been found in answering the question from what parts of the body action really proceeds, what parts are active, what passive ; and yet it is already quite possible to come to a definite conclusion upon this point, even in the case of parts the structure of which is still disputed. The chief point in this application of histology to pathology is to obtain a recognition of the fact that the cell is really the ultimate morphological element in which there is any manifestation of life, and that we must not transfer the seat of real action to any point beyond the cell." And further on he said: " According to my ideas, this is the only possible starting-point of all biological doctrines. If a definite correspondence in elementary form pervades the whole series of all living things, and if in this series something else which might be placed in the stead of the cell be in vain sought for, then must every more highly developed organism, whether vegetable or animal, necessarily, above all, be regarded as a progressive total, made up of a larger or smaller number of similar and dissimilar cells. Just as a tree constitutes a mass arranged in a definite manner, in which, in every single part, in the leaves as in the root, in the trunk as in the blossom, cells are discovered to be the ultimate elements, so it is also with the forms of animal life. Every animal presents itself as a sum of vital unities, every one of which manifests all the character- istics of life. The characteristics and unity of life cannot be limited to any one particular spot in a highly developed organism (for example, to the brain of man), but are to be found only in the definite, constantly recurring, struct- ure which every individual element displays. Hence it follows that the structural composition of a body of considerable size, a so-called individual, always represents a kind of social arrangement of parts, an arrangement of a social kind, in which a number of individual existences are mutually depend- ent, but in such a way that every element has its own special action, and even though it derive its stimulus to activity from other parts, yet alone effects the actual performance of its duties. I have therefore considered it necessary, and I believe you will derive benefit from the conception, to portion out the body into cell-territories (Zellen-territorien). I say territories, because we find in the organization of animals a peculiarity which in vegetables is scarcely at all to be witnessed, namely, the development of large masses of so-called intercellular substance. Whilst vegetable cells are usually in imme- diate contact with one another by their external secreted layers, although in such a manner that the old boundaries can still always be distinguished, we find in animal tissues that this species of arrangement is the more rare one. In the often very abundant mass of matter which lies between the cells (intermediate, intercellular substance) we are seldom able to perceive at a glance how far a given part of it belongs to one or another cell ; it presents the aspect of a homogeneous intermediate substance. According to Schwann, TISSUES IN GENERAL. 137 the intercellular substance was the cytoblastema destined for the development of new cells. This I do not consider to be correct, but, on the contrary, I have, by means of a series of pathological observations, arrived at the conclu sion that the intercellular substance is dependent in a certain definite manner upon the cells, and that it is necessary to draw boundaries in it also, so that certain districts belong to one cell, and certain others to another. You will see how sharply these boundaries are defined by pathological processes, and how direct evidence is afforded that any given district of intercellular sub- stance is ruled over by the cell which lies in the middle of it, and exercises influence upon the neighboring parts. " It must now be evident to you, I think, what I understand by the terri- tories of cells. But there are simple tissues which are composed entirely of cells, cell lying close to cell. In these there can be no difficulty with regard to the boundaries of the individual cells, yet it is necessary that I should call your attention to the fact that, in this case, too, every individual cell may run its own peculiar course, may undergo its own peculiar changes, without the fate of the cell lying next to it being necessarily linked with its own. In other tissues, on the contrary, in which we find intermediate sub- stance, every cell, in addition to its own contents, has the superintendence of a certain quantity of matter external to it, and this shares in its changes — nay, is frequently affected even earlier than the interior of the cell, which is ren- dered more secure by its situation than the external intercellular matter. " Finally, there is a third series of tissues, in which the elements are more intimately connected with one another. A stellate cell, for example, may anastomose with a similar one, and in this way a reticular arrangement may be produced similar to that which we see in capillary vessels and other analo- gous structures. In this case it might be supposed that the whole series was ruled by something which lay, who knows how far off ; but upon more accu- rate investigation, it turns out that even in this chain-work of cells a certain independence of the individual members prevails, and that this independence evinces itself by single cells undergoing, in consequence of certain external or internal influences, certain changes confined to their own limits, and not necessarily participated in by the cells immediately adjoining." * " Now, according to Heitzmann, what Virchow asserts of ' a third series of tissues ' is really true of all tissues. Not only are there contained no cells as isolated individuals in any tissue of the body, but no tissue in the body is isolated from the others. He prefers not to use the term ' cells ' ; he speaks of ' living matter/ and this he asserts is continuous throughout the whole body. If we desire to retain the use of the word gell to desig- nate the living-tissue elements, we must regard each cell to contain a net- work of living matter within it, and every cell connected by threads of living matter with every other cell in its neighborhood. . . . " Cellular Pathology, as based upon Physiological and Pathological Histology." By Rudolf Virchow. Translated from the second edition by Frank Chance, B. A., M. B., Cantab., etc. New York : Robert M. DeWitt, Pp. 29, 40, et seq. 138 TISSUES IN GENERAL. "Allow me to impress this fact upon you, that these are things which each and every one of you can see for himself if he only has a good microscope, good eyes, and an unprejudiced mind. Don't look for any so-called ' cells/ and don't imagine, as I used to do, that it is given to only a favored few to be able to pene- trate these mysteries of nature. The only danger is that you become so much fascinated with histological investigations as to neglect other important things. " It is the merit of Heitzmann to have discovered, in the first place, that the living matter in its simple form, as seen in an amoeba, the so-called basis-matter of life, to which hitherto the name of protoplasma has been applied, but which I propose to designate as bioplasson, is not without structure, as has before his accurate investigations been supposed, and that its structure is that of a net-work, in the meshes of which the bioplasson fluid, or the not contractile, not living portion of the organism exists. He discovered that the granules, which had been observed before, are not foreign or accidental occurrences, but that they are part and parcel of the living matter — that, in fact, they are the thick- ened points of intersection of the threads of bioplasson consti- tuting the living net- work. Extending his investigations, he found that what was true of the structure of bioplasson in the amoeba, where a single unit-mass of living matter constitutes the entire individual, is true of the structure of bioplasson of all, even the highest, living organisms. The idea connected with the word cell, when this term was first applied to the organic form element, had, with the advance of microscopical and histological knowledge, gradually undergone such changes that the name had become a complete misnomer. Although i cells ' were still spoken of, it was understood that their essential constituent was living matter individualized into small, distinct masses. The existence in these of a nucleus, a nucleolus, even a nucleolinus and gran- ules, was known j even thorns and processes had been observed occasionally. But all this knowledge of the structure of these elementary masses was fragmentary, until Heitzmann announced that the nucleus, nucleolus, granules, and threads are really the living contractile matter ; that it is arranged in a net- work con- taining in its meshes the non-contractile matter which is trans- formed into the various kinds of matrix characterizing different tissues ; and that the tissue unit-masses of bioplasson throughout the whole body are interconnected with fine threads of the same living matter. TISSUES IN GENEEAL. 139 " On the significance of these discoveries, and their bearing upon the question of physiology and pathology, I can here say but a few words. The more our knowledge of the minute anatomy, or rather morphology, of the organism advances, the more explicable becomes the functional activity of the various parts and tissues. So long as the cell was looked upon as the simplest form element of the body, we could not hope to go beyond the cells, and their performances in health and disease. Unfortunately, their investigation could not explain essential vital phenomena, the real activity of living matter. To-day we have it in our power to examine almost all tissues of the animal body while they are alive, by preventing, in thin sections placed under the microscope, evaporation or drying upon the one hand, and by supplying, on the other, such artificial temperature and other conditions as are necessary for the vital manifestation of the particular tissue under investigation. And, enabled directly to observe the phenomena which accompany movement of living matter, its contraction, we may hope to attain clear conceptions of the mysterious activity of muscles, of nerves, even of epithelia, which form secretory organs. I may instance Heitzmann's dis- covery of the manner in which primary muscle-bundles are constituted, as showing how easy it is to understand the observed phenomena of muscular contraction and innervation, if we have correct information as to the morphological arrangement. With- out going into the details, I may say that a primary bundle is made up of rows of sarcous elements and muscle fluid, the former united by threads of living matter, as mentioned before. Con- traction of the whole muscle consists in this : that the sarcous elements become larger, and the threads shorter. Kiihne has shown that the motor nerve does not enter the muscle fiber, but ends knob-like at its side, in about the middle 5 here the con- traction commences, and proceeds toward each end. In fact, we find everywhere that definite physiological functions depend upon definite morphological arrangements, and we may well make deductions from the latter as to the former. " Pathology will doubtless derive much advantage from the bioplasson doctrine. We are enabled to observe quantitative and qualitative changes of living matter in the smallest con- stituents of the body. We know that the disposition of living matter is different in different persons, and that, in the case of increased supply of food, the reaction is different in strong and healthy people on the one hand, and the sick and weak on the 140 TISSUES IN GENEEAL. other. Indeed, upon this knowledge rests, to-day, the whole doctrine of tuberculosis. It may be that we shall yet learn to know the differences in the behavior of living matter toward different re- agents, or differences in its quantitative arrangement, so that we may, perhaps, become able, from the examination of a few colorless blood-corpuscles, to gain an insight into the condition and vital power of the whole individual. If this come to pass, it will be possible to recognize certain diseases by means of the microscope before they are sufficiently developed to do much harm ; and we may thus come a step nearer to the highest aim of the physician — the prevention of disease. At all events, every exact scientific investigation, even though at first of theo- retical value only, sooner or later brings with it some practical benefit." The hopes here expressed have already, to a certain degree, been realized, and the practical value of the new discoveries demonstrated. In 1879, I said in the introduction of an essay : * " I am far from blaming any physician who, perhaps ten or even five years ago, has studied microscopy, and left it disgusted or in despair. The standard doctrine of l cells ' and the ' cellular pathology' was unsatisfactory indeed. Beyond the proof of the presence of cells, microscopy did not advance, and the examiners have been satisfied if they could see cells, the greatly varying shape and size and appearance of which they had to admit, without knowing any of the causes of the variations. " To-day the cell-doctrine is surpassed by new discoveries. Instead of looking at the shape of the cell, we have learned to study the minute structure of its mass, the so-called protoplasm, of which we know that it represents a constituent part of the organism. Many of the morbid relations of the protoplasm have been revealed, and made use of for practical purposes. We climb upward upon the shoulders of the ingenious founder of the cellular pathology, R. Virchow j and that the new doctrine, for which has been proposed the term * bioplasson-doctrine/ has really arrived at a certain point of perfection, I presently intend to demonstrate." For the researches and deductions here alluded to, 'see page 58. "The Aid which Medical Diagnosis receives from Recent Discoveries in Microscopy." Archives of Medicine, 1879. TISSUES IN GENERAL. 141 The re-agents which I used in 1873, with predilection, viz., the nitrate of silver and chloride of gold, are not always reliable, and I admit, had my assertions been based exclusively on specimens treated with these re- agents, they would justly have been considered as nearly worthless. Besides, a certain amount of skill in using those re-agents, and a well-trained eye, are required to see what really can be seen. This is evidently the reason why in Europe, of the many investigators who tried to bring to view the connections of cartilage-corpuscles after 1872, when I first found these connections, only very few have suc- ceeded. Still it was absolutely necessary to demonstrate the presence of such connections, because on cartilage-tissue have mainly rested, for the last forty years, our biological views. A. Spina * deserves great credit for the discovery of a new method, by which the connections of cartilage-corpuscles become readily demonstrable even to a relatively untrained eye. This method is as follows : the cartilage, best from the articular ends of bone, for three or four days is placed in alcohol, cut and examined in alcohol. " We are satisfied," Spina says, " that from the cells of the hyaline cartilage project solid offshoots; these, as is easily seen, arise from the bodies of the shriveled cells, pervade the basis-substance, and blend with the offshoots of other cells. The thickness and number of the offshoots greatly vary j the most numerous and most delicate were found in specimens from the superficial portion of articular cartilages of middle- sized frogs," etc., etc. From what I have seen, I can heartily recommend this method for the demonstration of the connections, though it is, on account of the shrinkage due to the preservation in alcohol, imperfect. This method brings to view, also, the delicate, mostly rectangu- lar reticulum in the basis-substance of fibrous connective-tissue formations, adjacent to cartilage. S. Strieker t recently makes the following statements: " The so-called migrating cells in the substantia propria of the cornea, so far as can be ascertained by direct, continuous observation, are neither migrating nor isolated cells. We can easily see, under suitable conditions, that portions of their bodies gradually assume the looks of basis-substance, while new * " Ueber die Saftbahnen des hyalinen Knorpels." Sitzungsber. d. Wiener Akad. der Wissensch., 1879. t " Mittheilung iiber Zellen und Grundsubstancen." Wiener Mediz. Jahr- biicher, 1880. 142 TISSUES IN GENEEAL. additions to the cell-body are formed from the neighboring basis- substance. " The basis-substance, under favorable conditions, exhibits in its interior form-changes like those of amoeboid cells. A net- like arrangement, fibrillae, and other forms, come and go. The basis-substance and the migrating cells in it represent a continuous mass, which, according to circumstances, may assume the features of basis-substance or of wandering cells. A lump of this mass becomes a real migrating cell only if separated from its surroundings, which, however, does not occur in the con- tinuity of the substantia propria. " The epithelia of the cornea, with their so-called cement- ledges, likewise form a continuous living mass. Under favorable conditions, we can easily realize that neither the cement-ledges nor the cells are stable formations. The cement-ledges are transformed into constituent parts of the neighboring cells, while within the cells new cement-ledges arise, so that after a while the configuration of the epithelium has changed, or else the whole form of the cells of the anterior epithelium is lost to sight, and it appears as a uniform mass, such as is the rule in the normal living cornea. " Changes of the branching cells in the substantia propria are easily seen during the first few minutes after excision of the cornea, by suitable methods of preparation. " The interior of the cell-bodies undergoes manifold visible variations. One of the most remarkable instances is furnished by the saliva-corpuscles. The assumption that a so-called molec- ular motion takes place in the saliva-corpuscles, is erroneous. The granules seen with insufficient amplifications are transverse sections of trabeculae. The saliva-corpuscle is traversed by a sharply marked trabecular structure (Balkenwerk), which, so long as the corpuscle is fresh, executes lively wavy motions. The waving gradually ceases on the addition of solutions of salts in certain concentration, and the reticular structure disappears. The waving is now replaced by very slow form-changes in the interior mass." VII. CONNECTIVE TISSUE. DEFINITION AND DIVISION. THE term connective tissue is applied to that tissue which con- stitutes the frame of the body (skeleton), covers the articular surfaces of bones (articular cartilage), incloses the whole body (derma of skin), supports and surrounds muscles and nerves (tendon, perimysium, perineurium), produces flat layers for all epithelial formations (basement layers), contains as a physiologi- cal product fat-globules (fat-tissue), and forms the blood and lymph vessels. It is composed of living matter which, having a reticular structure, contains in its meshes a lifeless, more or less solid, interstitial basis-substance. At certain regular intervals the reticulum is nodulated, and these nodules are the formerly so- called connective-tissue cells, preferably termed connective-tissue corpuscles. The distinguishing feature of connective tissue is the inter- stitial basis-substance, which is generally termed " glue-yielding," because some of its varieties on being boiled furnish gelatine, although other varieties, by the same treatment, yield a substance which is not strictly glue, but kindred to it. For twenty years (1840-1860) a lively controversy was carried on regarding the relation between the basis or intercellular substance and the plastids, the connective-tissue cells. Henle was the main repre- sentative of the view that the intercellular substance contains only 144 CONNECTIVE TISSUE. cavities, while Virchow asserted that the intercellular substance contains " cells/' the seats of life. Between 1860 and 1870, his- tologists began to be aware that the intercellular substance contains cavities, in which the cells are imbedded. Virchow^ in 1851, was also the first to recognize that all varieties of connect- ive tissue belong to one group, for the designation of which he proposed the rather unsatisfying term " connective substances." As A. Rollett * says : " The connective tissues are developed from "the middle germinal layer, in which blood and muscle also originate. The typical connective substances are recognized histologically by the circumstance that they contain extensive and continuous layers of material (intercellular substance), which, when compared with the cellular structures distributed through its substance (protoplasma), or the morphological elements in other tissues, always appears as a more passive substance and one which participates but slightly in the processes characteristic of life. These masses consist, for the most part, of gelatine -forming substances, such as collagen, chondrogen, and ossein. The connective tissues frequently pass by substitution or genetic succession into one another; they appear, therefore, to be morphologically equivalent, so that in many instances certain organs, or parts of organs, belonging to animals nearly allied to one another, are formed sometimes of one, sometimes of another, of these tissues." The basis-substance, the hitherto called intercellular substance, is a product of the lifeless bioplasson liquid which, probably nitrogenous from the very beginning, is transformed by chemical changes into the nitrogenous, more or less solid, mass termed basis-substance. In the same variety of connective tissue, espe- cially in the fibrous, the basis-substance may exhibit different degrees of solidification. Bundles of fibrous connective tissue arer f. i., built up of striated, glue-yielding basis-substance; the bundles are separated from each other by the less solid cement-sub- stance ; and they are bounded, both at their peripheries and around the plastids, by a more solid, dense, and chemically indifferent elastic substance. The so-called elastic fibers are but a variety of the glue-yielding basis-substance, in a high degree of solidi- fication. According to the nature of the interstitial substance, the morphological properties of which are far better known than the chemical, we may distinguish four varieties : Myxomatous or mucoid basis-substance, a jelly-like, translucent substance, not yielding gelatine ; * "A Manual of Histology," by S. Strieker. American translation edited by Albert H. Buck, 1872. Chapter: "The Connective Tissues." CONNECTIVE TISSUE. 145 Fibrous basis-substance , a semi-solid, opaque substance, char- acterized by a striated, fibrous, or lamellated appearance, yielding, on being boiled, glue or a substance kindred to glue ; Cartilaginous or cliondrogenous basis-substance, a dense, opaque substance of a uniform hyaline or striated appearance, which on being boiled also yields a liquid kindred to glue, as indicated by its odor ; and Osseous or bony basis -substance, a dense, opaque, glue-yielding substance, of a striated or lamellated appearance, infiltrated with lime-salts. The character of any variety of connective tissue is exclu- sively defined by the character of its basis-substance, whereas the connective-tissue corpuscles, though greatly varying in size and shape, are all essentially the same, viz. : living matter hitherto called " protoplasm." These protoplasmic bodies, plastids, as a rule nucleated, lie in cavities of the basis-substance, representing what has been termed the " fixed cells " of connective tissue. Be- sides, in some varieties of connective tissue, plastids are met with which, under favorable conditions, exhibit rapid changes of shape and locomotion. Von Recklinghausen* first drew attention to the presence of these u migrating cells." Such corpuscles can change their location only in the interstitial liquid portions of the basis-substance. Their presence is by no means the rule. Of the connective- tissue corpuscles, of course the " fixed cells " alone are united with each other. In myxomatous tissue the cor- puscles are connected by thick and wide offshoots, constituting the " stellate cells" of Virchow. In hyaline cartilage the union is by delicate offshoots j while in the fibrous tissue, in fibrous car- tilage and bone, the corpuscles are joined by both thick and slender offshoots. The basis-substance, which was formerly supposed to be structureless, is to-day known to be traversed by a delicate reticulum of living matter, the meshes of which are somewhat larger than that of the plastids j by means of this reticulum the connection between the plastids is established. The reason why the reticular structure of the basis-substance is not, or so little, marked in the fresh condition of the tissue, is that there is not sufficient difference between the refracting power of basis-substance and of living matter. It can be brought to view either by staining re-agents, such as nitrate of silver and chloride of gold, or by alteration of the refraction of the basis-substance, such as its liquefaction in the inflammatory process or deposition of lime-salts. The latter occurrence, both in normal and morbid * Virchow's Archiv. Bd. xxviii. 10 146 CONNECTIVE TISSUE. conditions, is an excellent means to render the reticulum in the basis- substance of cartilage visible, without any re-agent. In ground specimens of dry bone the cavities (lacunas) and their offshoots (the canaliculi) are very marked, especially if filled with air or other extraneous matter, because the difference in the refraction of the calcified basis-substance and the cavities, deprived of their bioplasson, is very great. The more the lime-salts are extracted from the basis-substance — f. i., by a solution of chromic acid, which at the same time preserves the bioplasson — the less visible are the cavities and their offshoots. A small amount of lime-salts, left behind even after chromic-acid treatment, renders both cavities and canaliculi, both the bone-corpuscles and their offshoots, plainly visible. The development of basis-substance invariably takes place from the bioplasson liquid. Either single plastids are infiltrated with basis-substance and rendered pale, apparently structureless, or the process takes place in a number of coalesced plastids, from which the formation of a territory results. Within this territory unchanged plastids are left, the connective-tissue corpuscles proper. The first manner of formation of basis-substance occurs in the simplest and earliest varieties of myxomatous connective tissue, the latter manner in all higher developed forms of fibrous, cartilaginous, and bony connective tissue. (1) Myxomatous or Mucoid Tissue. Myxomatous tissue is the earliest connective-tissue formation in the embryo, and all later varieties of connective tissue arise from this. As soon as the mesoblast is produced, we recognize it by the presence of numer- ous plastids, uniform in size and shape, some homogeneous, others granular and nucleated. All are connected by means of delicate filaments, traversing the light rim around each plastid. This tissue is called the embryonal or indifferent tissue, the latter term meaning that no difference can be discovered in the char- acter of the plastids. During the first few weeks of embryonal life we meet with myxomatous connective tissue only, and also during the entire period of intra-uterine development this kind of tissue largely pre- vails ; it also forms the tissues destined for the attachment of the embryo to the womb and for its nutrition, viz. : the placenta and the umbilical cord. With advancing development of the body the myxomatous tissue is replaced by more advanced formations, and in the full-grown individual only the vitreous body of the eye exhibits features similar to those of the umbilical cord (Virchow). We also meet with it in all remnants of embryonal development, such as medulla of bone, adenoid or lymph-tissue (lymph- ganglia, spleen, submucous adenoid layers), and tooth-pulp. CONNECTIVE TISSUE. 147 FIG. 47. — MEDULLARY TISSUE OF CHEST HUMAN EMBRYO, FOUR WEEKS OLD. OF C, medullary tissue, probably tending toward the forma- tion of cartilage of ribs ; P, medullary tissue, probably tend- ing toward the formation of fibrous perichondriuin. Magni- fied 600 diameters. In the animal organism, myxomatous tissue appears in the following varieties : (a) Medullary Tissue, found in medulla of bone at an early stage of development. The human embryo exhibits this tissue in the first few weeks. Plastids, either solid, or granular and nu- cleated, globular or spindle-shaped, and of varying size, are scattered in a scanty jelly-like basis- sub- stance. This sub- stance, examined without any re-agent, looks granular with lower powers of the microscope, but with high powers exhibits a delicate reticulum, which blends with the delicate, thread-like offshoots from the plastids. Each field of the basis-substance corresponds in size and shape to one plastid or to a small group of plastids ; the earliest formations of basis- substance arise from single plastids, by a chemical alteration of the bioplasson liquid, without the formation of territories. (See Fig. 47.) The medulla of bone exhibits this variety of myxomatous tissue at the fourth and fifth month of embryonal life of man, and in the case of pup or kitten at the corresponding stage, viz. : time of birth. Fig. 33 represents this tissue in a chromic-acid specimen ; Fig. 34, stained with chloride of gold, in order to demonstrate the structure of the basis-substance. The plastids in medullary tissue often assume the spindle shape, and here, too, we are satisfied that every field of basis- substance arose from an original plastid, without formation of territories. The embryonal and the medullary tissue in both va- rieties are prototypes of tumors, termed " round-cell and spindle- cell sarcoma" (globo and spindle myeloma). (See Fig. 48.) (bj Reticular Tissue. This is the next stage in the development of myxomatous connective tissue. It consists of a reticulum of 148 CONNECTIVE TISSUE. either plastids or fibers, with nuclei at their points of intersec- tion, inclosing a jelly-like basis-substance. The center of a field of basis-substance often contains a nucleus, which indicates that the field has originated from a plastid, the peripheral portion of which, by a chemical change of its liquid, was transformed into basis-substance, while the nucleus remained unchanged. The placenta is, to a great extent, composed of this tissue, the reticulum being of a fibrous character, while distinctly nucle- ated plastids, the so-called " decidua-cells," fill the mesh-spaces of the reticulum. The villi of the placenta consist of a reticulum of plastids with thickenings at the points of intersection, in close connection FIG. 48. — MEDULLARY TISSUE OF BONE FROM THE SCAPULA OF A NEW-BORN KITTEN. B, bone-tissue ; 8, myxomatous tissue composed of spindle-shaped plastids, traversed by a capillary blood-vessel. Magnified 800 diameters. with the endothelial wall of the capillaries. Most of the mesh- spaces exhibit central nuclei. (See Fig. 49.) The tissues of the body, which after more advanced develop- ment show the structure of fibrous connective tissue, are origi- nally reticular. In many instances we encounter in very young embryos spaces, inclosed by a fibrous or plastid reticulum, which contain a jelly-like basis-substance, too large for admitting them to have originated from a single plastid. In some other instances CONNECTIVE TISSUE. 149 of reticular tissue no doubt a single plastid has become basis- substance, but here two or more plastids must have coalesced in order to produce a nucleated field of basis-substance — the first evidence of a territory. Formations of both these varie- ties, however, may occur in one and the same specimen. (See Fig. 50.) FIG. 49.— RETICULAR MYXOMATOUS TISSUE OF A VILLUS OF THE PLACENTA OF A HUMAN EMBRYO, FOUR MONTHS OLD. EE, epithelial cover of thevillus; B, solid bud of a growing villus; CO, capillary blood- vessels, overlapped by the myxomatous reticulum. Magnified 500 diameters. The lymph-ganglia, including the thymus of embryos and the spleen during the whole of life, exhibit the reticular myxomatous structure in a marked manner. (See Fig. 31.) The reticulum is either fibrous or composed of nucleated branching plastids,* while the meshes, varying greatly in size, contain plastids, either single or in groups, in all stages of development : the lymph-corpuscles. Of this variety of lymph-tissue the substance of the thyroid body may perhaps consist, although the spaces holding the lymph- * C. Toldt has demonstrated that in the thymus of low vertebrates (frog, newt) the reticulum retains its protoplasmic character for life. Lehrbuch der Gewebelehre, 1877. 150 CONNECTIVE TISSUE. corpuscles in that substance are closed alveoli, and the walls of the alveoli are distinctly fibrous in character. The reticular myxomatous tissue of the lymph-ganglia is the prototype of tumors termed Myxo-Sarcoma (Myxo-Myeloma). The more advanced tissue of the character of the thyroid body is found in all formations called lymph-adenoma. Some histolo- gists claim that the connective tissue which surrounds the epi- thelial formations in the kidneys, in the salivary glands, and the connective tissue in the central nervous system, are reticular in structure. M. Schultze found this structure in the retina. FIG. 50. — RETICULAR MYXOMATOUS TISSUE OF THE MUSCLE-FASCIA OF A HUMAN EMBRYO, Two MONTHS OLD. R, reticulum of plastids, or fibers with oblong nuclei at the points of intersection ; M, striped muscle at an early stage of formation ; C, capillary blood-vessel; V, vein. Magni- fied 500 diameters. (c) Myxomatous Tissue of the Umbilical Cord. Virchow discov- ered in 1851 that the umbilical cord, formerly considered as a gela- tinous formation (Wharton's jelly), is a regular mucoid tissue, traversed by a delicate reticulum of branching cells, in the meshes rvf wViipli CONNECTIVE TISSUE. 151 of which is deposited the jelly-like "intercellular" substance. In this substance globular and isolated cells occur. Virchow found that, besides the three main blood-vessels (two arteries carrying- venous blood, and one vein carrying arterial blood), there are no other vessels throughout the entire length of the umbilical cord. Capillaries exist only at a short distance (about one-half inch) close above the insertion of the cord into the abdominal wall. Virchow draws attention to the heavy coats of the vessels, the muscular character of which was discovered afterward by Kolliker, and concludes that these coats play an important part in the occlusion of the vessels whenever they are severed or torn, FIG. 51.— SEGMENT OF THE UMBILICAL CORD OF A HUMAN EMBRYO. FOUR MONTHS OLD, IN TRANSVERSE SECTION. A , artery ; V, vein ; M, myxomatous tissue, the common adventitia ; E, epithelial cover. Magnified 25 diameters. without ligature. The mucous tissue, Virchow * says, is attached to the imperfectly developed adventitial coat of the three vessels. In my conception the umbilical cord in toto is the adventitial coat, common to the three blood-vessels, of which the vein, as a rule, has a much narrower muscle-coat than the two arteries. (See Fig. 51.) No capillary blood-vessels and no lymphatics have been discovered in this tissue, neither is anything certain in re- gard to nerves, though it is probable that the three vessels are * "DieCellularpathologie." Vierte Auflage. Berlin, 1871. 152 CONNECTIVE TISSUE. under the control of vasomotor nerves. The myxomatous tissue is often found to contain spaces, greatly varying in size and num- ber, filled with liquid ; these, doubtless, are secondary formations, so-called cysts. The outer surface of the umbilical cord is covered byi^a single layer of flat epithelia. Now, if we compare a transverse section of the umbilical cord with an amoeba (see page 21), the similarity between the two becomes evident. The epithelial coat of the cord corresponds to the continuous layer of living matter in amoeba ; the complex reticulum of plastids corresponds to the simple reticulum of living matter in the amoeba ; the closed cavities of the blood-vessels holding isolated plastids, the blood-corpuscles of the cord, cor- respond to the closed spaces, the vacuoles containing isolated granules of living matter. In fact, the simple amoeba is the representative of the com- plex structure of the umbilical cord, as well as of all other tissues of the human body. FIG. 52. — UMBILICAL CORD OF A HUMAN FCETUS, NINE MONTHS OLD. CHROMIC ACID SPECIMEN. P, bioplasson cords with nuclei at their points of intersection ; JB, partly homogeneous, partly fibrous, basis-substance. Magnified 500 diameters. With lower powers of the microscope we recognize in sec- tions of the umbilical cord of a fully developed human foetus, both fresh and preserved and hardened in a chromic acid solution, a relatively coarse reticulum of plastids, Virchow's branching cells. The best sections are obtained from the portion about midway between the vessels and the surface, because nearer the vessels and the surface the reticulum, being very dense, does not admit of dis- tinct demonstration. We see ramifying so-called protoplasmic strings of a delicate granular structure, containing oblong nuclei CONNECTIVE TISSUE. 153 usually at the points of intersection.* In the meshes the basis-sub- stance is in part homogeneous, in part traversed by delicate flbrillae. Not infrequently a nucleated string passes directly into a bundle of nbrillse. In the center of a mesh-space we encounter sometimes a globular plastid, apparently isolated — i. e., unattached to the strings forming the reticulum. (See Fig. 52.) If we rub a stick of nitrate of silver over the surface of a piece of a fresh umbilical cord, it will soon become brown on exposure to daylight. Sections from such an umbilical cord will show light, branching spaces in a dark brown basis- FIG. 53. — UMBILICAL CORD OF A HUMAN FOETUS, NINE MONTHS OLD. STAINED WITH NITRATE OF SILVER. S, light spaces, corresponding to the bioplasson cords in Fig. 52, branching and anas- tomosing; B, dark brown basis-substance, indistinctly striated and granular. Magnified 500 diameters. substance. The light spaces correspond in size and shape to the strings seen in specimens preserved in chromic acid. They anas- tomose, and some of them send into the basis-substance smaller branches, which often divide and subdivide so much as to show a delicate, pencil-like appearance. The contours of the light spaces and their branches are in many places serrated. The brown * In the umbilical cord of the pig-foetus the nuclei of the cord are much more numerous than in the human. 154 CONNECTIVE TISSUE. basis- substance appears indistinctly striated and granular. (See Fig. 53.) If we expose a piece of the fresh, umbilical cord for some hours to the action of a large quantity of a one-half per cent, solution of chloride of gold, the specimen assumes in the daylight a dark violet color. Sections exhibit branching and connecting strings of dark violet color, whose nuclei at the points of inter- section are either black or pale violet, while the basis-substance is but faintly stained either pale violet or pink. The strings in their general features and size correspond both to those seen in specimens preserved in chromic acid and to the light spaces found in specimens stained with silver. The pale basis-substance FIG. 54. — UMBILICAL CORD OF A HUMAN FCETUS, NINE MONTHS OLD. STAINED WITH CHLORIDE OF GOLD. P, dark violet bioplasson cords, corresponding to those in Fig. 52, and to the light spaces in Fig. 53 ; B, pale pink basis-substance, indistinctly striated. Magnified 500 diameters. exhibits an indistinct striation, and some smaller offshoots from the violet strings pass into and are lost in striated bundles. (See Fig. 54.) By comparing the chromic-acid, the silver-stained, and the gold-stained specimens, it is apparent that the light spaces are identical with the violet tracts, and these again identical with the bioplasson strings of the unstained specimen. In other wori CONNECTIVE TISSUE. 155 words, the nitrate of silver has stained the myxomatous basis- substance, and left the strings unstained, whereas the gold has stained the strings very much, the basis-substance, on the con- trary, very little. These facts convince us that Von Recklinghausen's theory, that lymph-spaces traverse the basis-substance and contain cells, is erroneous. The spaces produced by silver stain are not lymph-spaces, but bioplasson spaces, viz. : they are the bioplasson itself, unstained, or the cavities containing the unstained bioplasson. Unquestionably, such light spaces in silver specimens of various other tissues anastomose with the light spaces of the lymphatics, as bioplasson formations (plas- tids) are directly attached to the walls of the latter, and neither are stained by nitrate of silver. For further details of the minute structure of the umbilical cord I refer the reader to page 120, and to Fig. 35 and Fig. 36. The development of the myxomatous tissue of the umbilical cord has not as yet been sufficiently studied for any positive statement. Of the minute structure of the vitreous body very little is known. From what I have seen in gold-stained specimens, and in the changes that occur on the borders of tumors of the choroid growing into the vitreous, I am convinced that the plastids of the vitreous body, most numerous at its peripheral portions, send delicate offshoots of living matter into the myxomatous basis-substance, which is alive throughout and liable to active morbid changes. The myxomatous tissue of the pulp of the tooth will be dwelt upon in the chapter treating of teeth. Fat-tissue. Our knowledge of fat-tissue is very limited. The main facts are as follows : Fat-granules may arise from any bioplasson granule in isolated plastids and in plastids producing tissues of any descrip- tion. The granules of living matter assume a higher degree of luster and increase slightly in size whenever they are about to change into fat-granules. As I have observed in colostrum cor- puscles, the fat-granule at first remains connected by delicate fil- aments with the rest of the reticulum, and S. Strieker has observed that on the heating-stage fat-granules are expelled from a colostrum corpuscle. (See page 28.) The chemical change by which the nitrogenous substances are converted into fat is not understood. It is even possible, according to a suggestion of L. Elsberg, that the plastidules are not directly transformed into molecules of fat, but are only mixed with them, so that in early stages of development of fat, 156 CONNECTIVE TISSUE. the plastidules may, by a retrograde metamorphosis, be reestab- lished in their original structure. * The fat-tissue met with in other varieties of connective tis- sue, chiefly the fibrous, consists of a number of fat-globules, aggregated into groups, which are termed fat-lobules. Such formations are seen, in greatly varying amount, in the subcuta- neous tissue, the female breast, the omentum, and around the heart and the kidneys. The lobules being freely supplied with capillary blood-vessels, besides these contain only a small amount of a delicate fibrous connective tissue between the fat-globules. Fat-globules, which vary greatly in size, are inclosed by a delicate continuous layer, termed the capsule of the globule. In this capsule there is almost invariably found an oblong, nucleus- like body, which in edge view appears to be fusiform, and blends with the capsule. The fat substance proper contained in the capsule is semi-fluid, and can be pressed out on artificially ruptur- ing the capsule. Alcohol renders the fat coarsely granular, and causes it to shrink. Chromic acid solution, after a certain length of time, produces vacuoles in the fat-globule. Turpentine and oil of cloves dissolve the fat, and the nucleated capsule becomes plainly visible after the application of these re-agents. In fat-globules preserved for a period of several months in a one-half per cent, solution of chromic acid, J. A. Rockwell, in my laboratory, discovered bioplasson masses in the middle of the fat. These masses, as a rule, appear coarsely granular with lower powers of the microscope, often branch, and sometimes contain a central nucleus-like body. High amplifications show that the granules and the nucleus are interconnected by means of delicate filaments. It also occurs that the bioplasson forma- tion is flattened out near the capsule, or its granules are scattered at greater distances through a portion of the fat. Small globules contain one such granular formation, while large globules may hold two 6r more in addition to a varying number of scattered * According to L. Ranvier ("Des Lesions du Tissu Cellulaire lache dans PCEdeme," Comptes Rendus, 1871), in oedema produced by ligation of the vena cava and discision of one sciatic nerve of dogs, the connective tissue infil- trated with serum, twenty-four hours after the beginning of the oedema, shows cells, the peripheral protoplasma of which contains granules of a fatty appearance. Their refracting power is lower than that of fat, but if treated with a weak solution of chromic acid or bichromate of potassa, they become more highly refracting and smaller. These peripheral granules seem to be composed, he says, of fat and an albuminous substance, just as in the devel- oping fat-cells. CONNECTIVE TISSUE. 157 granules. The granules are, in most instances, of a dim, gray color, and readily distinguished from the surrounding yellow fat. These formations are evidently those long known in specimens obtained from emaciated persons, and preserved in alcohol, as the nucleated, stellate protoplasmic bodies within the capsule. The intra-capsular protoplasm, according to C. Toldt,* retains its vital contractility even in the highest degrees of emaciation, and from it starts, under favorable conditions, the formation of new fat. Fat-globules often contain a coloring matter, either diffused or in the form of pigment-granules j and even in the fresh con- dition they may contain needle-like formations, usually termed margaric acid crystals. More recent chemical researches show that these crystals are much more complicated formations of fat- acids than was thought formerly. Such crystals are frequently seen in rancid fat, where they produce large, dark clusters of radiating needles, standing out like the bristles of a porcupine. Fat-globules originate from indifferent or embryonal plastids, which are considered by C. Toldt to be specific fat-formers. At first small granules of fat appear, which by coalescence produce globules. It has been maintained that each plastid will furnish a complete fat- globule, often of large size ; whereas the researches of Flemming, Czajewicz, and others make it highly probable that a number of plastids are fused together in order to produce a large fat- globule. Flemmiug drew attention to the fact that, in highly emaciated fat-tissue, cells are often found which exhibit a proliferation of their nuclei, and even contain a large number of " young cells." He terms this condition the " pro- liferating atrophy/7 in contradistinction to the simple " serous atrophy.'7 Czajewicz asserts that the fat in rabbit disappears after a few days7 abstinence from food, but rapidly re-appears in the original globules upon the resumption of abundant feed- ing. The substance which under these conditions replaces the fat is said to be serum or mucus. In inflammation, the same observer noticed a splitting of the fat-globules into numerous plastids. From all these facts we may conclude that fat-tissue is closely allied to myxomatous connective tissue, although the metamor- phosis in each is materially different. A certain number of plastids changed to fat may coalesce into what we know to be a territory, in which unchanged portions of bioplasson are left. * Lehrbuch der Gewebelehre. 1877. 158 CONNECTIVE TISSUE. Around the territory a connective-tissue capsule originates, in a way similar to the formation of the myxomatous reticulum of fibers, and the nucleus in the capsule of the fat-globule is analo- gous to the nuclei found at the points of intersection of the myxomatous reticulum. (2) Striated or Fibrous Connective Tissue. The term " connect- ive tissue" was employed by Johannes Miiller, in 1835, for desig- nating the tela cellulosa of older anatomists. B. Reichert, in 1845, first maintained the continuity of this tissue, and, considering it to be structureless, attributed the fibrous appearance to the presence of folds or striations. Virchow, in 1851, demonstrated the presence of corpuscles, the supposed hollow and so-called " connective-tissue cells," imbedded in the fibrous intercellular substance ; and W. Kiihiie, in 1864, proved by the means of electricity that these corpuscles possess vital properties — viz., contractility. At present we know that the tissue corpuscles, being bioplas- son formations, are imbedded in cavities of the basis-substance. The latter is eminently glue-yielding, and composed of numerous delicate spindles, arranged in lines. It is only after teasing of the specimen that an isolated fiber is discovered, while in the continuity of the tissue isolated fibers are not observed. We know, furthermore, that the fibrous basis-substance (syn- onymous with the matrix and intercellular substance of former histologists) is traversed by a delicate reticulum of living matter, whose meshes present an almost uniformly rectangular arrange- ment. This reticulum is visible within delicate bundles in speci- mens preserved in chromic acid, without the addition of any re-agents; or in other specimens by the use of re-agents, as described before (page 122). The alcohol treatment (page 141) also serves for bringing the reticulum to view. The basis-substance varies greatly in its degrees of density. It is very dense in the tendon, the sclerotic, the cornea, and less dense in the formations termed a loose connective tissue." The delicate spindles, which constitute the fibrillae by coalescing in a longitudinal direction, are separated from each other by a less dense so-called cement-substance, while bundles of fibers are separated from each other by a more liquid substance, which, as a rule, contains, besides the blood-vessels and lymphatics, numer- ous plastids, all being connected with each other as well as with the walls of the vessels and the reticulum in the basis-substance proper. In some varieties of this tissue the basis-substance, CONNECTIVE TISSUE. 159 instead of being fibrous, is composed of ribbon-like formations, as in the periosteum; and in others it is disposed of in flat layers, as in the cornea. In many instances we meet with an extremely dense basis-substance, termed the elastic substance, which either occurs in the shape of fibers at the boundary of territories, or almost entirely replaces the glue-yielding basis- substance. This formation appears in the shape of either a dense reticulum or a uniform flat layer. Examples of fibrous elastic basis-substance are found in the connective tissue of the derma of the skin, in the periosteum, etc. ; examples of an elastic retic- ulum are furnished by the Lig. nuchae, the adventitial coat of arteries, etc. ; examples of flat elastic layers are found in all the so-called u hyaline or structureless membranes," beneath epithe- lial and endothelial formations, in the sarcolemma, etc. The different varieties of fibrous connective tissue may be classified according to the following characteristics : Delicate bundles of fibrous tissue, running mainly in one direction, and being separated by a basis-substance of slight density, form the so-called loose connective tissue — f. L, in the omentum and the arachnoid; Bundles of fibrous connective tissue, interlacing in all direc- tions, produce a felt- work structure — f. i., in the derma, the interarticular ligaments, the sclerotic ; Coarse bundles arranged in only a longitudinal direction are found in the tendons and in the articular ligaments j Flat bundles transformed into ribbons, freely interlacing, appear in the periosteum, the dura mater, the pericardium, and the aponeuroses ; A coalesced layer of elastic basis-substance produces a flat, sheet-like formation — f. i., in the hyaline or basement layers, and in sarcolemma ; Lamellated layers of considerable breadth, freely interlacing, build up the cornea. (a) Delicate Connective Tissue Composed of Fibrillce, or of Comparatively Thin Bundles of Fibrittoe. This variety, usually termed " loose connective tissue," is arranged in bundles, in which the fibers are connected by a small amount of a cement-sub- stance, soluble in lime and baryta water. Between the bundles are spaces which contain either a semi-fluid, viscid, myxomatous basis-substance or a lymph-like liquid. These spaces may become expanded by accumulation of a serous liquid, as in oedema, or of air or liquids introduced from without. 160 CONNECTIVE TISSUE. The plastids in the bundles are flat corpuscles, either irreg- ularly scattered or presenting a chain-like arrangement ; these bodies are frequently small, not surpassing the size of nuclei. In the myxomatous portion, however, they are larger, and have coarse offshoots, sometimes directly joining in a stellate form. The myxomatous portion may also contain, in a varying number, the " mi- grating cells n of Von Recklinghausen and the coarsely granular " plas- ma-cells " of Waldeyer, es- pecially in the neighbor- hood of capillary blood- vessels. Their significance 8 is not yet understood, nor is their presence constant. The delicate bundles, if treated with dilute acetic acid, swell and are con- stricted in such a manner as to give the bundle an hour-glass or rosary-like appearance. These con- strictions are due, accord- FIG. 55.— ARACHNOID OF THE SPINAL CORD ing to Henle, to the pres- OP AN ADULT. ence of elastic fibers twined around the bundle, which are not acted upon by the acetic acid. Their origin is explicable, as I shall show hereafter, by the formation of territories, a number of which compose the bundle, while at the boundaries of the ter- ritories the basis-substance is solidified into elastic substance. A. Rollett maintains that the elastic fibers are offshoots of cells similar to the reticular variety of connective tissue 5 according to Franz Boll, these cells, originally twined around the bundle in shape of a reticulum, fuse in advancing development into an elastic membrane, which envelops the bundle and exhibits linear thickenings, branching after the manner of veinlets in leaves. The best examples of loose connective tissue are the arach- noid and the trabeculae traversing the sub-arachnoideal space. (See Fig. 55.) Delicate bundles of fibrous connective tissue, B, run in different directions and contain very small plastids in the shape of oblong nuclei. The inter- stitial basis-substance slightly fibrous. E, a portion of the covering endothelium. Magnified 500 diams. CONNECTIVE TISSUE. 161 In serous membranes, especially in the omentum, the delicate bundles of fibrous connective tissue are arranged in the shape of a reticulum, the meshes of which are very large, constituting what has been termed " areolar connective tissue " (Hassal). The fibrillae, composing delicate bundles, freely interlace in the papillary layer of the derma of the skin, and in the mucous membranes; while in the subcutaneous tissue the bundles are coarser and their interstices contain the fat-lobules. Similar features are observed in the loose connective tissue around the eyeball and in the female breast. The delicate bundles of the pia mater are also interlaced, and generally enter the gray cortex of the brain and the white cortex FIG. 56. — DELICATE FIBROUS CONNECTIVE TISSUE FROM THE BORDER OF THE THYROID CARTILAGE OF A YOUNG MAN. C, cartilage ; B, V, blood-vessels in transverse and oblique section ; O, dense fibrous con- nective tissue. Magnified 800 diameters. of the spinal cord in radiating directions. They are freely sup- plied with blood-vessels in their interstices, and upon entering the nervous tissue gradually divide, and their fibers form a delicate reticulum which supports the nerve-formations, the " neuroglia " of Virchow. In muscle, a delicate loose connective tissue is found around the muscle-fibers and their bundles (perimysium internum and 11 162 CONNECTIVE TISSUE. externum); this tissue, especially in its juvenile condition, is freely supplied with large and branching plastids. Delicate fibrous connective tissue is often largely intermixed with other varieties of connective tissue in the form of either scattered fibrillae or interlacing bundles of fibrillae. It blends with the true myxomatous tissue, as well as with the dense fibrous varieties. Bundles of the latter, in the tendon and the interarticular ligaments, are surrounded and inclosed by loose FIG. 57. — INTERARTICULAR LIGAMENT FROM THE KNEE-JOINT OF A GROWN DOG. L, bundles cut in a longitudinal direction : C, bundles cut in a transverse direction ; P, the nucleated, finely granular plastids forming a continuous layer around the bundles. Mag- nified 500 diameters. connective tissue, which is the exclusive carrier of blood-vessels. (See Fig. 56.) fbj Dense Connective Tissue composed of Coarse Interlacing Bundles. The essential feature of this variety is the presence of comparatively coarse bundles, which, interlacing either at right angles or in an oblique direction, produce a very CONNECTIVE TISSUE. 163 bundles exhibit scattered reduced to the size Iirm and dense felt-work. The )blong or spindle-shaped plastids, often of nuclei. The interstices be- tween the bundles, the inter- fascioular spaces, being filled with a more or less liquid substance, contain a continuous layer of plastids and a few blood-vessels. The bioplasson is freely supplied with nuclei, and by its arrange- ment between and around the bundles presents a reticulum simi- lar to that in the myxomatous tis- sue of the umbilical cord, the dif- ference being that in the latter the meshes contain a jelly-like, myxomatous basis-substance, in the former a solid, fibrous one. The peripheral portions of the intervertebral disks and the inter- articular ligaments are examples of this tissue. We may cut through such a tissue in any di- rection, and invariably meet with longitudinal, oblique, and trans- verse sections of bundles. While the longitudinal sections exhibit a dense striation or fibrillation, the transverse sections look ho- mogeneous or slightly dotted, cor- responding with the transverse sections of the fibrillae. (See Fig. 57.) In the derma of the skin, the FlG. 5 8.- SCLEROTIC OF THE BULL'S mndles or groups of bundles are he nearerthey aresituated to the SubcutaneOUS tissue j tO- tion ; T, bundles cut in a transverse direc- n j-i a i-t j 11 tion; O, bundles cut in an oblique direction ; ward the surface they gradually p> tne 'coutinuou8 illterstitfai uiopiasson become finer, and in the Uppermost layer' containing numerous pigment gran- . . ules. Magnified 500 diameters. portion, the papillary layer, the bundles are extremely delicate. In the derma, too, the bundles are separated from each other by a continuous layer of nucleated EYE. VERTICAL SECTION. bundles cut in a longitudinal direc. 164 CONNECTIVE TISSUE. plastids, and in this layer scanty capillary blood- and lymph- ves- sels are found. Both blood- and lymph-vessels ramify the more the nearer they approach the surface, so that the papillary layer has the greatest number of vessels. In every direction we meet with longitudinal, oblique, and transverse sections of bundles, the latter being characterized by a dull luster and a homogeneous or finely dotted appearance. At the periphery of the bundles we see elastic fibers branching at acute angles, in correspondence with the territories composing a bundle. The elastic basis-substance is FIG. 59. — TENDON OF ACHILLES IN A LONGITUDINAL SECTION. STAINED WITH CHLORIDE OF GOLD. 1-8 are the bundles, between which the interfascicular spaces are seen ; T, torn bundles exhibiting isolated fibrillse. Magnified 100 diameters. marked by yellow color and high degree of luster ; it increases in amount with the age of the individual. The sclerotic shows bundles and groups of bundles, interlac- ing usually at right angles. In transversely cut groups we see that the single bundles are separated from their neighbors by a cement-substance, which, on account of its lower degree of den- sity, refracts the light less than the basis-substance of the bundles themselves. The groups of bundles are separated by a continuous layer of bioplasson, which therefore exhibits a reticular arrange- ment. In specimens from the sclerotic of dark-colored cattle this bioplasson layer is very prominent, owing to the presence of black pigment granules. (See Fig. 58.) (c) Dense Connective Tissue composed of Coarse Bundles run- ning in a Longitudinal Direction. The principal representative of this variety is the tendon. J CONNECTIVE TISSUE. 165 In thin sections from a fresh tendon, or a tendon preserved in chromic acid solution, either stained with chloride of gold or not, we recognize with lower powers of the microscope that the tendon is made up of bundles of a finely striated tissue. All bundles are spindle-shaped, and vary greatly in size j they are separated from each other by light interstices, in which, particularly in the injected specimens, the blood-vessels are seen to course along and around the bundles. The appearance of a bundle is striated as long as the continuity of the tissue is unbroken. But where the IT FIG. 60. — TENDON OF ACHILLES OF A YOUNG PERSON. SECTION. CHROMIC ACID SPECIMEN. LONGITUDINAL £, bundles of striated connective tissue, here and there finely dotted; TO, tendon puscles within the bundles or between the smallest bundles ; IT, interstitial medul- lary tissue carrying capillary blood-vessels, C. Magnified 500 diameters. >r has torn the bundle, isolated fibrillae appear, which, owing their elasticity, retract and curl. (See Fig. 59.) Higher amplifications reveal that the larger bundles divide into a number of smaller ones, all of which exhibit a spindle shape, and in correspondence with the boundary lines of the sec- ondary bundles we see spindle-shaped plastids, either single or in rows or chains, and either nucleated, and, as a rule, pale granular, or reduced to the size of homogeneous or granular nuclei. All of these are included under the term u tendon corpuscles." In advanced age the apparently isolated nuclei prevail, especially in the middle of the tendon, while in younger 166 CONNECTIVE TISSUE. individuals, and afc the periphery of the bundles at any age, the rows and chains are more numerous. The interstices between the larger bundles contain, besides a few capillary blood-vessels, a large number of nucleated plastids, either isolated or united in a continuous layer. The sum total of these plastids, together with a slight amount of basis-substance, constitutes what we have called (see page 147) medullary tissue. In advanced age the medullary corpuscles are much less numerous, and a loose fibrous connective tissue carries the blood-vessels. Elastic fibers are, as a rule, not present at the borders of the bundles. A comparison between the plastids within and those between the bundles shows them to be alike in size and general appearance, with the only difference that those within the bundles are rela- tively few in number, while those in the interstices are very numerous. The view can, therefore, be maintained that between the larger bundles there are numerous, and between the small fasciculi, composing one bundle, there are few, plastids — a view which, as I shall later on demonstrate, proves useful for under- standing the structure of the tendon as well as its development. (See Fig. 60.) In the transverse section of a tendon we notice fields of basis- substance very finely dotted, the dots being the transverse sec- tions of the fibrilla?. In the bundles we recognize the granular, usually nucleated, plastids or tendon corpuscles, with numerous stellate offshoots, the " wings " of authors. Offshoots connect the plastids with each other and with the medullary tissue, or the loose fibrous connective tissue, present in the interfascicular spaces. The smaller bundles do not usually show distinctly marked outlines, as neighboring bundles frequently coalesce, and are not separated by offshoots of the tendon corpuscles. When we recall the spindle shape of each bundle, we can readily under- stand why their sizes vary in transverse section. We may call a bundle a field which is completely surrounded by interfascicular tissue, and contains in its center a branching plastid, or, we may say, a larger bundle is composed of a number of smaller ones, though not distinctly separated, between which lie the branching plastids. The blood-vessels are met with only in the interfas- cicular spaces, running both in transverse and longitudinal direc- tions ; they penetrate the tendon through the tenaculum, which connects it with its sheath, and the elongations of which con- stitute the interstitial formations between the tendon bundles. (See Fig. 61.) CONNECTIVE TISSUE. 167 In old animals, the loose interfascicular connective tissue is sometimes found freely supplied with elastic fibers. As Treitz and Kolliker have shown, the tendons attached to smooth muscle bundles are composed mainly of elas- tic fibers. L. Ranvier discovered at the periphery of the bundles of tendon flat "cell-plates," arranged in rows, exhibiting elastic ridges, either single or in numbers up to five. His method of examination of tendon is teasing and pulling, and he pulled from preference rats' tails, in order to obtain the broken, fringy ends of the delicate tendons along the vertebral column. After he had pulled and severed the tendons, he transferred the fringe to the glass slide, and, in order to prevent it from shrinking, sealed it at both ends to the slide. Although this method is not very inviting, pulling rat-tails became quite fash- ionable in the laboratories in Europe a number of years ago. Ranvier denies the existence of cell-formations in the tendon other than the endothelial plates. Perhaps these are flat, endothelial investments of the larger bundles FIG. 61. — TENDON OF ACHILLES OF A YOUNG PERSON. SECTION. CHROMIC ACID SPECIMEN. TRANSVERSE B, bundles finely dotted ; C, tendon-corpuscle with offshoots, connecting with the inter- lascicular tissue, IT,- the latter contains the capillary blood-vessels, BV. Magnified 500 diameters. similar to the investing sheath of Boll, unquestionably present around the periphery of the tendon. Lowe has maintained that such an investment is also found around the bundles of the tendon, but he has been contradicted by other observers. The elastic ridges are probably the place of attachment of neighboring bundles. One of the greatest difficulties encountered by former observ- ers was to explain satisfactorily the wing-like offshoots of the 168 CONNECTIVE TISSUE. tendon corpuscles seen in transverse sections, as no trace of such formations is visible in longitudinal sections. This difficulty was overcome by the discovery of offshoots of the tendon corpuscles, brought into view in longitudinal sections by the silver and gold staining. The minutest features in the structure of the tendon are described on page 122, and illustrated in Fig. 37 and Fig. 38. The articular ligaments are formations closely allied to ten- don ; between their bundles, however, a greater amount of loose connective tissue is found than in the tendon. (d) Dense Connective Tissue composed of Interlacing Ribbons. This variety is essentially constructed in the same manner as tendons, but instead of spindle-shaped bundles, we find flat, rhom- boidal ribbons. Periosteum is representative of this tissue, a description of which is given on page 125. The elastic fibers bor- der each ribbon or subdivide it into smaller rhomboidal fields, a feature which is explicable by the history of development of the territories of the ribbons. In the dura mater and the pericardium, the bundles are dis- tinctly striated and not quite so flat as those in the periosteum. In aponeuroses, the bundles, in accordance with the general sheet-like form of this tissue, are flattened and interlaced, chiefly in a rectangular direction. The interstices between the bundles are quite narrow, but plastids are observed here as well as in the tendon. C. Ludwig, who forced colored liquids into these inter- fascicular spaces, mistook the beautiful rectangular reticulum thus obtained for lymph- spaces. Formations kindred to apon- euroses are the fascia? and the tendinous capsules of different glandular organs — f. i., the capsule of the kidney, the albuginea of the testis, the sheath of the cavernous bodies of the penis, etc. In some ligamentous formations, such as the Lig. sub-flava of the vertebrae, the Lig. nucha3, the membr. thyro-cricoidea, the Lig. stylo-hyoideum, etc., the fibrous basis-substance is almost completely transformed and condensed into the yellow, elastic substance which appears in the form of branching reticular fibrillaB, between which are scantily found bundles of striated connective tissue. (e) Coalesced Layers of Elastic Basis-substance, arranged in a sheet-like manner, are often found at the borders of connective- tissue formations, close beneath epithelial and endothelial layers. They bear the names of hyaline, structureless, or basement mem- branes, in contradistinction to "cuticular formations" of a similar CONNECTIVE TISSUE. 169 appearance found between epithelial layers — f. i., between the root-sheaths of the hair. Elastic membranes certainly are not structureless, but exhibit a reti<5ulum of living matter of extreme delicacy, concealed in the fresh condition by the highly refracting elastic basis-substance. I am positive that such a reticulum is present in Bowman's and Descemet's layers of the cornea. By means of this reticulum, the connective tissue is held in living union with the epithelium. Such membraneous formations may vary greatly in width, even in the same tissue, — f. i., the cornea, — and sometimes they may be entirely absent. They, when present, resist the action of acids and alkalies, and, to some extent, the inflammatory process. Elastic membranes of the connective-tissue series are the fol- lowing: Bowman's layer at the outer and Descemet's layer at the inner surface of the cornea; the capsule of the crystalline lens and the hyaloid membrane of the vitreous body ; the layer between the outer root-sheath and the follicle of the hair ; the elastic layer beneath the endothelial coat of larger arteries ; and the investing, sometimes fenestrated, layers beneath epithelia of glands — f. i., the salivary, the mammary glands. In the kidneys, the connective tissue of the capsule of the tuft, also that which lies between the tubular formations, contains a large amount of elastic substance, which produces a very firm support for the epithelia. The striated muscle-fibers, with the exception of those of the heart, are invested by an elastic membrane, termed sarcolemma ; so are the medullated nerves around the axis-cylinder and around the myeline — i. e., axis-cylinder sheath and myeline sheath. (f) Lamellated Layers of Fibrous Interlacing Connective Tissue. The only representative of this variety is the cornea of the eyeball, the basis-substance of which, although morphologically closely allied to that of elastic substance, is chemically different from both " elastine" and " chondrine." A. Rollett (1859) proved that the " amorphous " basis-substance of former histologists consists of bundles of connective tissue, which are connected by a kind of cement-substance soluble in lime-water and in baryta-water. The main feature of the cornea is that the bundles join to form very thin flat layers, the lamellae; while these lamellae them- selves are connected by somewhat looser bundles, traversing the less condensed interstices between them. In the fresh cornea no trace of plastids (cornea corpuscles) is visible ; but if the cornea be kept in an indifferent liquid, after a 170 CONNECTIVE TISSUE. while faint traces of these corpuscles become perceptible, exhibit- ing a few scanty offshoots. The shape of these corpuscles varies greatly in different portions of the cornea, as well as in the cor- nea of different animals. A clear idea of the nature of the cornea corpuscles can be obtained only by resorting to re-agents. Von Recklinghausen (1862) first brought to view the beautiful light and branching spaces in a dark basis-substance by applying nitrate of silver. He considered them as lymph-spaces or juice-canals, supposing them to be the beginnings of the lymphatics proper. In these spaces, he thought, the "cornea-cells" were suspended. (See Fig. 62.) FIG. 62. — LAMELLA OF THE CORNEA OF A GROWN CAT, STAINED WITH NITRATE OF SILVER. H, light branching spaces with serrated edges, traversing the dark brown granular basis-substance. S, F, fibers connecting the lamellae and torn by the process of splitting the lamellae. Magnified 500 diameters. Later researches have shown that the " lymph-spaces " of the cornea are closely related to the cornea-cells, which were mean- while demonstrated by W. Kuehne (1864) and others to be composed of contractile protoplasm, and endowed with properties of life. The method of gold-staining has proved to be the most valuable for revealing the structure of the cornea corpuscles and their relation to the basis-substance. (See Fig. 63.) CONNECTIVE TIS8UE. 171 RESEARCHES ON THE MICROSCOPICAL STRUCTURE OF THE CORNEA. BY WILLIAM HASSLOCH, OF NEW YORK.* It is generally acknowledged that the substantia propria of the cornea is made up of fibrils united into fascicles ; that the majority of these bundles, by being more or less parallel to the surface of the cornea, form the lami- nated structure of the latter, at the same time crossing one another, and so giving rise to a kind of lattice-work ; while other fibers and bundles traverse the cornea in various directions. The fibrils, as well as the fascicles and lamellae, are connected with one another by an intermediate cement-sub- stance, which somewhat differs from the fibrils in its chemical reaction. MossCNsCmN.Y. FIG. 63. — LAMELLA OF THE CORNEA OF A GROWN CAT, STAINED WITH CHLORIDE OF GOLD, AFTER PREVIOUS TREATMENT WITH DILUTE LAC- TIC ACID. C, dark violet nucleated cornea corpuscles, traversing the pale violet granular basis- substance, B. N, nerve-fibrill®, connecting with cornea corpuscles. Magnified 500 diameters. But, concerning the relation of the protoplasm to the basis-substance, observers are of very different opinions. Some of them do not admit the existence of the protoplasmic bodies at all, asserting that within the basis- substance of the cornea only a tubular system is present, lined with " cell- plates." Other histologists hold the view that there is a certain quantity of protoplasm (cells of the cornea) inclosed in the " serous spaces," in which it ramifies, but which it does not completely fill. One of the most prominent advocates of the latter opinion is W. Waldeyer,t deriving his views chiefly "Archives of Ophthalmology and Otology," vol. vii., 1878. t Article " Cornea," in Graefe-Saemisch's Hand-book, 1874. 172 CONNECTIVE TISSUE. from the results of injections made by him and other recent observers into the tissue of the cornea. Fluids, pressed into the corneal parenchyma, produce, indeed, ramified figures resembling the " corneal corpuscles." W. Kuehne, S. Strieker, and A. Eollett state that there are complete corneal cells with protoplasmic bodies, with nuclei and nucleoli, within the ramifying spaces, and that they fill these spaces completely. W. Engelmann denies the existence of preformed spaces inclosing corneal cells, etc. He states that there are spaces containing nothing but protoplasm, and this is, in my opinion, the only correct view, as I shall endeavor to prove. In order to study the relation of the protoplasm to the basis-substance, I chose the cornea of the dog and of the cat, giving preference, after repeated trials, to that of the cat, as has previously been done by S. Strieker, on account of its easy splitting. With some practice one may succeed in obtain- ing lamellae which present two or even only one layer of corneal corpus- cles, and which, therefore, are sufficiently transparent to admit of being examined even with the highest powers of the microscope. FIG. 64. — LAMELLA OF CORNEA OF A CAT, AGED ONE YEAR AND A HALF, STAINED WITH A Two PER CENT. SOLUTION OF NITRATE OF SILVER. Two LAYERS. [PUBLISHED IN 1878.] 8, light fields with pale granular contents, faintly marked nuclei, and coarse and fine processes. Every light field has perforated borders, and thus abundantly communicates with a delicate light net-work which traverses the dark brown basis-substance, J3, in all directions. Magnified 1000 diameters. To stain the cornea, I at first tried nitrate of silver. The cornea of a cat was taken out immediately after death, and was put into a two per cent, solution of nitrate of silver for one-half to one hour ; then it was washed with distilled water, and, finally, for several days left under the influence of a very mild dilution of acetic acid. Instead of the acetic acid, in later experiments, I substituted lactic acid, which proved even more satisfactory than the former. After being prepared in this way, the cornea of the cat was ready CONNECTIVE TISSUE. 173 to be split into lamellae. The specimens were mounted with equal parts of glycerine and water. With enlargements of 300-500 such lamellee show in a dark ground — basis-substance — light fields with numerous connecting branches, generally known as Von Recklinghausen's serous canaliculi ; and even an enlargement of 500 is sufficient to prove that the outlines of these light spaces do not appear smooth at all, but granular — viz., abundantly perforated, and that the brown or gray-brown looking basis-substance is finely granular. With higher powers (immersion lenses, with enlargements of 800-1200) the following facts are observed : Within the light spaces oblong nuclei, with very faint contours and a great number of extremely pale granules, are visible. The light spaces are connected with their neighbors by light processes of various sizes, traversing the basis-substance. The borders of these light fields and their branches are abundantly perforated, like a sieve, throughout, so that .true outlines do not exist. Fine, light tracts run from every light space and its branches through the basis-substance, profusely ramifying and anastomosing, sometimes radiating, and thus forming an extremely delicate light net-work, the threads of which traverse the basis-substance in all directions, and connect with the light fields and their processes at the whole circumference. What with lower power was recognized as granular struct- ure is by higher enlargements elucidated as a very fine light net-work, the meshes of which are filled by the dark brown basis-substance. (See Fig. 64.) FIG. 65. — CORNEA OF A CAT, Two YEARS OLD, STAINED WITH NITRATE OF SILVER. TRANSVERSE SECTION. [PUBLISHED IN 1878.] S, light fields containing fine pale granules, with coarse and fine light offshoots. N, nerve- fibers in connection with the light reticulum, which traverses the dark brown basis-sub- stance, B, throughout. Magnified 1000 diameters. On thin transverse sections the silver-stained cornea of the cat shows the same ramifying light fields as in split preparations, with the only difference that their vertical diameters are notably smaller, while their horizontal diam- eters are the same as those of the light fields of the lamellae. The light spaces branch out in all directions, so that not only the light fields of the same stratum are connected with each other, but even those of different layers anastomose by ascending and descending — more or less oblique — processes. Besides these ramifications, especially in the outer strata of the cornea, some fine straight light lines are met with, which, for reasons given below, are proved to be nerve-fibers. On transverse sections, also, the brown basis- substance is traversed by light ramifying tracts, to such an extent that the 174 CONNECTIVE TISSUE. cement-substance cannot be distinguished from the other components of the cornea. (See Fig. 65.) Further, I tried to stain the cornea of the dog and of the cat with chloride of gold. Many experiments failed, though I had exposed the cornea to the influence of the chloride of gold for hours. The after-treatment with acetic and tartaric acid gave only negative results. I could never see distinct cornea corpuscles with their ramifications until, at last, by the aid of lactic acid, I succeeded in obtaining specimens of such beauty and clearness, that all doubt with regard to the finest structure of the cornea disappeared. My method is the following : The cornea of a cat is taken out immediately after death, soaked in a ten per cent, solution of lactic acid for a period of about twelve hours ; then during one or two hours it is kept in a one-half per cent, solution of chloride of gold, slightly acidulated by the addition of a few drops of lactic acid, and finally exposed to the influence of daylight. The superficial strata of the cornea and a peripheral border of one mm. turn yellow, FIG. 66. — LAMELLA OF THE CORNEA OF A CAT, Two YEARS OLD, SOAKED IN DILUTED LACTIC ACID AND THEN STAINED WITH A ONE-HALF PER CENT. SOLUTION OF CHLORIDE OF GOLD. [PUBLISHED IN 1878.] P, dark violet fields, the cornea corpuscles, the nuclei of which are mostly hidden, with offshoots of different sizes. The cornea corpuscles and their offshoots are connected with a dark violet net- work traversing the pale violet basis-substance B ; the latter net- work shows broader meshes than that of the corpuscles and their branches. Magnified 1000 diameters. and are of no use for examination, but the other part, the characteristic purplish tint of which shines through the yellow envelope, is invaluable for research. After having made the above described experiments, I learned that F. S. W. Arnold, of New York, had previously used lactic acid for the reduction of chloride of gold ; but he informed me that his method differs from mine, inasmuch as he uses the chloride of gold in the first stage of the preparation, followed by the lactic acid — just the reverse of my plan of treatment. The co CONNECTIVE TISSUE. 175 The cornea of the cat, prepared after my method, splits readily, and its lamellae, after turning dark enough by the influence of daylight, appear under the microscope throughout their whole extent strewn over with numerous, richly ramifying, dark violet corpuscles. In many of the latter the nuclei are distinctly visible ; the corpuscles themselves crowded with dark granules ; the basis-substance light, pale violet, and also having a granular appearance. I have searched through a great many lamellae, but I have never found any corpuscles that did not shoot off into branches ; everywhere and always I met with only ramifying, dark violet corpuscles, with numerous connections and in different strata of varying sizes. The dark violet fields fully coincide with the light spaces of the silver-stained cornea as to size, figure, and connections, as has been stated by W. Kuehne. The only difference is that in the silver I FIG. 67. — LAMELLA OF THE CORNEA OF A CAT, Two YEARS OLD, STAINED WITH A ONE-HALF PER CENT. SOLUTION OF CHLORIDE OF GOLD, AFTER HAVING BEEN SOAKED WITH DILUTED LACTIC ACID. [PUBLISHED IN 1878. ] P, dark violet fields, the cornea corpuscles, with only a few broad offshoots, but numerous dark violet, thread-like connections, non-medullated nerve-fibers, N, the latter partly travers- ing the cornea corpuscles and partly joining the net- work of the same ; between the cornea corpuscles and the net- work of the basis-substance, _B, extremely fine retiform connections are present ; the latter net-work also connects with delicate nerve fibrillse, JR. Magnified 1000 diameters. specimen light fields are visible in a dark ground, while in the gold specimen the dark corpuscles appear in a light ground — pictures which correspond with each other as the negative with the positive photograph. Gold specimens examined with high powers (800-1200) show that the dark violet ramifying corpuscles, without exception, have a retiform structure, and that the nucleoli, the contours of the nuclei, and all the granules are con- nected with one another by innumerable fine threads. The whole net-work 176 CONNECTIVE TISSUE. is tinted equally dark violet, while its extremely narrow meshes appear pale violet. (See Fig. 66.) The borders of the corpuscles and their branches are nowhere distinct; contours in the real sense of the word are wanting in the gold specimen as well as in the silver specimen, inasmuch as from the whole circumference of these ramifying, dark violet fields immense numbers of fine threads protrude, to join their neighboring dark violet granules within the basis-substance. The examination of any portion of such a specimen will not fail to convince the observer that also in the basis-substance nearly all dark granules are inter- connected by fine threads. The cause of the difference between the shade of the cornea corpuscles and that of the basis-substance is, that in the former the granules are larger and lie close together, and consequently the meshes are very small, while within the basis-substance the granules are mostly fine and more dispersed, and for this reason are separated from one another by larger meshes. In some lamellae, and, as it seemed to me, principally in the outer layers of the cornea, many corpuscles are connected with one another, not by broad branches, but by dark violet, more or less straight lines, which, for their characteristic rosary-like structure must be considered uon-medullated nerve- fibers. (See Fig. 67.) In profile, the gold-stained cornea of the cat offers another proof of the coincidence of the positive gold image with the negative silver specimen. FIG. 68. — CORNEA OF A CAT, Two YEARS OLD, STAINED WITH A ONE- HALF PER CENT. SOLUTION OF CHLORIDE OF GOLD, AFTER BEING TREATED WITH DILUTED LACTIC ACID. TRANSVERSE SECTION. [PUB- LISHED IN 1878.] P, dark violet fields with broad branches and with fine offshoots, the latter being nerves, N; the net- work ol the dark fields everywhere is in connection with that of the basis-sub- stance, B, Magnified 1000 diameters. Flat, elongated, dark violet bodies are visible, which, in the horizontal direc- tion, anastomose with one another by means of fine long processes ; while broad, rather oblique, dark violet branches ascend and descend to connect the corpuscles of different layers. The net-work of the dark fields and that of the basis-substance are shown with the same clearness as in split speci- mens. The laminate structure of the cornea is just as imperceptible in these transverse sections as it is in those of the silver-stained cornea. ( See Fig. 68. ) In transverse sections of the gold-stained cornea of a dog I observed, espe- cially in the central parts of the cornea, formations which sufficiently explain CONNECTIVE TISSUE. Ill the views of W. Waldeyer, who maintains that the cornea corpuscles do not completely fill the " serous spaces." There I saw groups of cornea corpuscles which leaned mainly against one of the walls of the space, while a more or less considerable portion of the latter appeared empty. A closer exam- ination, however, proved that these apparent voids are artificial products, namely, vacuoles. It can be observed that the eccentric cavity is situated within the cornea corpuscle, and on its whole circumference is inclosed by the protoplasm of the cornea corpuscle. No matter how thin the strip of pro- toplasm which is interposed between the vacuole and the periphery of the " serous space " may be, it is always present. It is known that such vacuoles can arise from contraction of the living matter within the protoplasm. The question why these contractions, perhaps as a result of the action of the chloride of gold, were observed only in certain groups of cornea corpuscles, remains unsolved. In the cornea of the cat I have never met with any forma- tions of this kind. From these observations it clearly follows that a tubular system, as described by Von Eecklinghausen, does not exist in the cornea at all. The light fields which the silver specimens of the cornea show are not " serous spaces," but protoplasmic bodies, as stated by W. Engelmann and others, viz., spaces which are wholly filled with protoplasm. The strongest proof of this assertion is found in the result of the method of staining the cornea with chloride of gold, improved by the treatment with lactic acid, as it exhibits the cornea corpuscles in perfectly clear images, which in every particular corre- spond to the negative silver images. Whether an interstice filled with fluid remains between the wall of the so-called serous space and the protoplasmic body or not, I will not yet venture to decide ; but as the protoplasm itself contains a considerable amount of fluid, it is not necessary to admit the pres- ence of peripheral cavities filled with serum. Wherever an interspace between a cornea corpuscle and the wall of the " serous space" can be observed,' its presence depends upon the formation of a vacuole, and cannot, therefore, be maintained in opposition to my view. Nor do the parenchymatous injections prove anything contrary to it, for it is apparent that colored fluids, which are forced into the protoplasmic spaces, will press the soft protoplasmic bodies against the walls of such spaces, and thus assume the principal forms of the latter. My observations further show that the protoplasm of the cornea cor- puscles has a retiform structure, which can be demonstrated by the above- described method of staining the cornea with chloride of gold. The question whether or not this reticulum be an artefact should no longer be a matter of dispute, since in the creeping amoeba, in colorless blood-corpuscles, and in pus-corpuscles the same net-work has been demonstrated, and by photogra- phy made visible even to the naked eye. That this net-work (nucleoli, bor- dering layer of the nucleus, granules, and connecting threads) is the living matter, the meshes of which inclose the lifeless protoplasmic fluid, is proved as well by the reaction of the chloride of gold, as also by the appearances observed in inflammation, which S. Strieker has so carefully studied and illustrated. Finally, my observations show that the living matter thoroughly traverses the fibrous basis-substance of the cornea in the form of an exquisitely deli- cate net-work, the existence of which is proved beyond all doubt by the correspondence of the negative silver with the positive gold specimens, 12 178 CONNECTIVE TISSUE. though in the fresh condition of the cornea it is as imperceptible as are the cornea corpuscles themselves. If wandering bodies exist within the normal cornea, — I have never met with them,— such bodies will find their paths only in the cement-substance, never within the lamellae. As the lamellae are con- nected with each other by innumerable fine threads of living matter, which FIG. 69. — PERIOSTEUM OF THE FEMUR OF A NEW-BORN PUP. SECTION. [PUBLISHED IN 1873.] TRANSVERSE F, striated tissue of periosteum ; 8, spindle-shaped plastids in the formation of a striated basis-substance; M, medullary tissue between the periosteum and the bone; O, medullary corpuscles in the formation of bone-tissue; B, fully developed bone-tissue. Chromic acid specimen. Magnified 800 diameters. penetrate the cement-substance, — not taking into consideration the connect- ing broad, oblique bundles of fibers, — the reason why such wandering bodies move in zigzag lines is readily comprehended. As for the finer structure of the cornea, I fully agree with C. Heitzmann's views regarding the connective tissue in general. The living connection of CONNECTIVE TISSUE. 179 the protoplasmic bodies, which this observer has discovered in the myxoma- tous and fibrous connective tissue, as well as in that of the cartilage and bone, has been successfully demonstrated by me in the cornea also. The living matter presents in connective tissue two different net-works : a narrow one, the meshes of which are filled with fluid, — protoplasm, — and another with broader meshes, traversing the basis-substance. Development of Fibrous Connective Tissue. This article is a translation of a publication which I made in 1873.* I have lothing to add to the conclusions drawn at that time, but shall make the explanation of the observations a little more detailed. 'IG. 70. — PERIOSTEUM OF THE FEMUR OF A NEW-BORN PUP. LONGITU- DINAL SECTION. CHROMIC ACID SPECIMEN, SLIGHTLY STAINED WITH CHLORIDE OF GOLD. [PUBLISHED IN 1873.] M, layer of medullary corpuscles; I, layer of corpuscles in the stage of indifference, pre- ling the formation of basis-substance ; C and (7i, spindles of basis-substance of fibrous icctive tissue ; E, elastic ledge. Magnified 800 diameters. In transverse sections of a shaft-bone of a newly born pup, we cognize between the striated periosteum and the bone-tissue a xroad layer of medullary tissue, into which project a few striated mndles of the periosteum proper. t (See Fig. 69.) Untersuchungen iiber das Protoplasma. IV. Die Entwickelung der dnhaut, des Knochens und des Knorpels." Sitzungsber. der Kais. Akad. 3r Wissenschaften in Wien. July, 1873. t Th. Billroth ("Archiv f. Klin. Chirurgie," Bd. vi.) termed this layer " cambium." A. Rollett ("Manual of Histology," by S. Strieker) illustrates it in a transverse section of the fore-arm bone of a human embryo, five months old. 180 CONNECTIVE TISSUE. In longitudinal sections from the surface of a shaft-bone of the same animal, we see in the periosteal tissue different forma- tions corresponding to the stages of development of protoplasma. Between longitudinal bundles of narrow, bright ribbons we recognize fields of corpuscles like those of the medullary tissue, or chains of such corpuscles with distinct vesicular nuclei. Fur- thermore, we see fields of flat, spindle-shaped protoplasmic bodies of greatly varying size, and with either indistinct nuclei or none. There are fields composed of flat, rhomboidal protoplasmic bodies, some of which exhibit formations like nucleoli. We also meet with fields, the rhomboidal bodies of which appear homo- geneous, and slightly shining. Lastly, we encounter ribbons and ledges, composed of very much elongated rhombs, character- ized by a peculiar yellowish color and a considerable luster. The slightly shining fields are the connective-tissue ribbons proper of the periosteum ; while the highly refracting ribbons and ledges are termed elastic. (See Fig. 70.) The examination of good chromic acid specimens, better still such specimens slightly stained with chloride of gold, convinces us that each larger field is separated from the neighboring fields, and within the fields each granular or homogeneous corpuscle from the neighboring corpuscles, by a narrow light rim, which is invari- ably traversed by delicate grayish spokes. Even in the narrow elastic ribbons a faint transverse striation is here and there seen. In such a specimen, deeply gold-stained, the differentiation of fields and ribbons disappears, and there become visible at certain intervals spindle-shaped, dark violet bodies, corresponding to the protoplasmic bodies, while the rest of the tissue is split up into a reticulum, with either fine or coarse granules as nodular points. The periosteal tissue is composed of narrow, spindle-shaped fields, wherever it exhibits a striated or fibrous appearance. In portions made up of broad ribbons, on the contrary, each field represents an elongated rhomb, in which lie, at pretty regular intervals, oblong, flat, nucleated protoplasmic bodies (the " peri- osteum cells"). Between the rhombs are narrow, bright ledges, the elastic fibers, which either connect several rhombs into large bundles, or subdivide a single rhomb into smaller rhomboidal fields of varying size. At the corners of the rhombs the elastic fibers are interconnected with acute angles. If, owing to a laceration of the tissue with the razor, a broader, slightly shining ribbon projects from the border of the specimen, we often see at its edge, either on one side or on CONNECTIVE TISSUE. 181 both, a very bright strip demarcating the ribbon from adjacent protoplasmic bodies. In the periosteal tissue of a new-born pup, therefore, we are enabled to trace the transitions of different forms of medul- lary elements into sometimes narrow, sometimes broad and flat, spindle-shaped protoplasmic bodies. We become convinced that by a gradual change of the latter arise both the " connective tis- sue" and the " elastic fibers." The development of the connective tissue in general is a much disputed, and to this day unsolved, question. In looking over the vast literature on this subject, we may sum up all the views of prominent observers into two theories. One of these may be termed the secretion theory; it implies that the intercellular- or basis-substance is pro- duced by a sort of secretion of the cells frpm an originally homogeneous mass between the cells. The other, which may be styled the transformation theory, maintains that the cells themselves are transformed into basis-sub- stance, either by a process of splitting in their entirety, or by a process of transformation of the cell-protoplasm at its peripheral portions. Secretion Theory. Henle * was the first to assert that an originally homogene- ous substance splits into nbrillee and bundles of fibrillae. According to Eeichert, the homogeneous substance proceeds from a fusion of the cell-membranes with an intercellular substance, and the fibrillae are only the optical expression of the foldings of this substance. The fusiform cells present in embryonal connect- ive tissue, according to Virchow, Bonders, Gerlach, and Kolliker, do not share in the formation of fibers, but persist, as Virchow expressed it, as cells, or are converted into a plasmatic canal-system. The last-named observer is the originator of the idea that the intercellular-substance is a product of secretion of the cells, and this view prevailed for quite a time. Among the recent observers, A. Eollett, L. Eanvier, and I. Kollmann advocate the modi- fied theory that fibrous basis-substance may, to a certain extent at least, orig- inate independently of cells. Transformation Theory. Th. Schwann t first maintained that the cells, after being elongated, split into bundles. After Max Schultze's discoveries concern- ing the protoplasma, t the theory of Schwann was modified. Max Schultze held that the fibrous basis-substance of connective tissue arises from a coalescence of embryonal cells composed of protoplasm, and destitute of an investing mem- brane, and that a thin layer of unchanged protoplasm remains around the nucleus of the primary cell representing the connective-tissue cell. Lionel Beale, in England, § independently of the German observers, expressed sim- ilar views ; he claimed that the connective tissue is originally made up of elementary parts, consisting of germinal matter, and that subsequently a part of the germinal matter is converted into formed material. According to these views, the originally living protoplasm is, by chemical and morpho- logical changes, transformed into the lifeless basis-substance, though the cen- * "Allgemeine Anatomie." Canstatt's Jahresbericht, 1845. t " Mikroskopische Untersuchungen," etc. Berliii, 1839. \ Reichert and Du Bois Reymond's Archiv. 1861. § " The Structure of the Simple Tissues of the Human Body." 1860. 182 CONNECTIVE TISSUE. tral portion of the cell may remain unchanged protoplasm. This theory was adopted, with more or less modification, by E. Briicke, Franz Boll, Waldeyer, and others. Briicke's pupils corroborated the original view of Schwann — viz. : that the fibers of connective tissue originate directly from offshoots of the cells. Elastic Substance. The elastic fibers, first discovered by Bonders,* were thought to be by this observer the product of embryonal fusiform cells which have passed through transitional forms into a plexus of elastic fibers. This view was confirmed, with certain changes adapted to the protoplasma theory, by F. Boll and A. Spina. Territories. An important discovery concerning the structure of the basis- substance was made by Furstenbergt — viz. : that certain chemical re-agents may break up the basis-substance of cartilage into globular or polyg- onal fields, inclosing the central cell. He took these fields, the " territo- ries," for products of secretion of the cells. Virchow+ corroborated this discovery, and based very important biological views upon their presence (see page 136). He considered the. central cell the queen of the territory, and all changes of the latter as depending upon the changes of the cell. R. Hei- denhain § also made noteworthy researches as to the territories of the hyaline cartilage. I have stated on a previous occasion (see page 132) that the territories, which are traceable in all higher developed varieties of connective tissue, are the true units of this tissue j so that anybody who understands the development of a single territory understands that of connective tissue in toto. From what I have described as to the basis-substance of the earliest formation,— viz. : the myxomatous basis-substance of medullary tissue (see page 118, Fig. 33 and Fig. 34, and page 147, Fig. 47), — it is obvious that I essentially agree with those observ- ers who have maintained a direct transformation of the proto- plasm into basis-substance. I assert, in entire accord with Max Schultze and Lionel Beale, that every territory originates from coalescence of protoplasmic bodies — plastids. If we recaU the fact (see page 133) that the basis-substance of a number of tissues is traversed by a delicate reticulum of living matter, we can realize that in the process of the formation of a tissue no living matter, certainly not all of it, perishes, but that it merely becomes invisible in the portions infiltrated with basis- substance. If we, furthermore, recall the fact (see page 46) that the pro- toplasma itself goes through phases of development, we can also realize that the living matter appears in varying groups and *"Zeitschrift f. Wissenwliaftliohe Zoologie." Bd iii "Miiller's Archiv." 1857. t "Cellular Pathologic," i. Aufi., 1858. " Stmlien des Physiolog. Institutes zu Breslau," ii. 1863. CONNECTIVE TISSUE. 183 accumulations — viz. : as a compact lump, as a nucleated body (plastid), or as a reticulum infiltrated with basis-substance. It is not proved that the living portion of protoplasma is really ever changed into basis-substance ; I have discovered the living matter, just as seen in medullary tissue, in places in which the FIG. 71. — DIAGRAMS OF THE DEVELOPMENT OF CONNECTIVE TISSUE. 8, diagram of the secretion theory : a, the embryonal cell; b, the cell enlarged and its periphery transformed into basis-substance; c, the cell in middle of the considerably aug- mented basis-substance. T, diagram of the transformation theory : a, a number of medullary corpuscles, grouped in the shape of the future territory ; b, the peripheral portion of proto- plasm transformed into basis-substance ; c, the cell in middle of basis-substance, sprang from a transformation of the peripheral protoplasm. B, diagram of the bioplasson theory: a, a number of plastids grouped in the shape of the future territory, all being reticular in struct- ure and interconnected ; b, the plastids coalesced, of the peripheral ones only the nuclei left; c, the formation of basis-substance accomplished, the central free plastid being the connective- tissue corpuscle, with coaivse and delicate offshoots into the basis-substance. protoplasm was formerly thought to have perished ; nor is there any necessity, indeed, to assume that the basis-substance is a product of the living matter; for it may just as well be held that nothing but the liquid originally filling the meshes of the living reticulum is transformed into basis-substance. 184 CONNECTIVE TISSUE. In this case, we have simply to assume that solution or lique- faction of an already formed basis-substance sets free the living matter, and that the new grouping into lumps and elements (plastids) depends upon the formation of a new basis-substance in the mesh-spaces. This newly formed basis-substance will look striated or fibrous if the groups be spindle-shaped, such as in tendon and young bone-tissue 5 it will be ribboned if the groups be flat plates, such as in periosteum ; it will appear lamellated should the groups be lenticular bodies, such as in bone-tissue ; or, lastly, it will become globular with the formation of globular masses, such as in hyaline cartilage. Within the basis-substance, the reticulum of living matter and the central portion of the protoplasma, the " cell/' or " plastid," remains intact. From the central corpuscle the reticulum ema- nates, according to the shape of the unit of the tissue, either in a prevailing bipolar, or rectangular, or uniformly radiating direc- tion. The forms of the fields of basis-substance will necessarily be determined by the main directions in which the living matter is distributed. The formation of basis-substance seen in that of a territory is illustrated in Fig. 71. In order to elucidate in accord with the new views the forma- tion of a fibrous basis-substance, we must consider the fact that one territory may contain several plastids interconnected. If each of the plastids, including those sharing in the formation of basis-substance, become elongated and split into delicate spindles, the result will be a large spindle- or rhomb-shaped territory, com- posed of numerous delicate spindles, which coalesce into fibrillae, between which remain elongated plastids unchanged. As men- tioned before (page 158), each fibrilla in reality is composed of a number of delicate spindles. Between the territories a larger number of plastids is left, and the blood-vessels take their course j or a more solid fibrous reticulum is developed, inclosing the territories, as, f . i., in myxomatous connective tissue. The gradual development of basis-substance, therefore, admits of the following analysis : In medullary tissue, a single plastid, or a small number of such, is converted into myxomatous basis-substance without the formation of territories ; In reticular tissue, a single plastid, or a small number of such, changes into myxomatous basis-substance, the territories of which are separated by a reticulum of plastids or fibers. The plastids within the territory remain unchanged in the lymph-tissue ; CONNECTIVE TISSUE. 185 In the umbilical cord, a large number of plastids coalesce into territories of a partly myxomatous, partly fibrous, basis- substance, and these territories are separated by a broad reticu- lum of plastids, the " stellate mucoid-cells " ; In fibrous connective tissue, each bundle is the result of coalescence of plastids much elongated and split up, and is composed of one or a number of territories, in which remain the connective-tissue corpuscles. A large number of plastids is left between the bundles $ In tendon, each bundle is a large territory containing a number of plastids arranged in chains, with numerous smaller bundles between them ; In periosteum, the plastids have flattened out so as to build up a rhomboidal ribbon, with a number of unchanged plastids, each ribbon being composed of one territory or of a number of them ; In the cornea, the flattened bundles or ribbons have coalesced into layers, traversed by the cornea corpuscles ; each lamella is a flattened territory, and between the territories are plastids similar to those within. Between the groups, composed of plastids in many instances, and at an early stage of development, a very dense basis- or cement- substance appears. This is the " elastic tissue," seen in the periosteum in the shape of narrow plates or strips at the borders of the ribbons and their constituent fields. In the finished tissue, the elastic strips in varying amount border one or several terri- tories, sometimes even smaller fields in one territory. The glue- yielding basis-substance, formed later, is by no means as dense and resistant as the first-formed elastic substance. This is proved by observations in inflamed periosteum. The basis-substance, however, is densified and made resistant, not only at the borders of the territories, but also around the cavities containing the plastids. This is the case in fibrous connective tissue as well as in cartilage- and bone-tissue. The so-catted " elastic tissue " is evidently no tissue sui generis, but a basis- or cement-substance, of an early formation and of con- siderable density. It arises from plastids, just as the glue-yielding basis-substance proper. (3) CARTILAGE TISSUE. History.* From the earliest time of histology to the present, true cartilage, such as the thyroid cartilage, has been looked upon as one of the simplest * Written by Louis Elsberg : "Contributions to the Normal and Pathological Histology of the Cartilages of the Larynx," Archives of Laryngology, vol. ii., 1881. 186 CONNECTIVE TISSUE. tissues. To distinguish it from other kinds of cartilage, in which either a fibrous or a reticular aspect has been recognized, it is called hyaline, i. e., resembling glass. The description of its structure by Meckauer, in 1836,* is essentially as that by Klein in 1880,t viz. : that it consists of a firm homoge- neous basis-substance, in which are imbedded numerous small cartilage corpuscles. Meckauer wrote before the cell-doctrine, which has exercised so powerful an influence upon the medical mind, had been thought of. In- deed, that doctrine itself, as its founder, Schwann, J: has recorded, was based to a large extent upon investigations of the constitution of cartilage. After J. Miiller had described cartilage corpuscles that were hollow, and Gurlt had spoken of some as vesicles ; when Schwann had succeeded, as he thought, " in actually observing the proper wall of the cartilage corpuscles, first in the branchial cartilages of the frog's larvae, and subsequently also in the fish," he was led by these and other researches to conjecture "that the cellular forma- tion might be a widely extended, perhaps a universal, principle for the forma- tion of organic substances." Schwann considered that the cartilage corpuscles, or cartilage cells, as they were thenceforth called, are imbedded in a matrix which is capable of produc- ing the cells, and which he therefore called cytoblastema. Groodsir, Naegeli, and finally Virchow advanced the histology of cartilage in so far as they claimed that the cartilage cells cannot possibly arise from the matrix or inter- cellular substance. Even Virchow adhered, however, to the idea of Schwann, that the cartilage cell is a vesicle filled with a more or less transparent fluid, in which is suspended the nucleus ; and, although he was aware of the life of the cell in general, nothing was suggested by him as to the life of cartilage. It is true, Bonders and H. Meyer had observed that the cells of hyaline carti- lage were capable of proliferation ; § nevertheless the idea became prevalent, more perhaps from implication — because, on account of the absence of blood- vessels, it was believed not liable to inflammation — than from any direct state- ment to that effect, that cartilage was devoid of life. The vitality of cartilage corpuscles was made clearly probable by the observation of the effect of elec- trical shocks upon them, by Heidenhain, || and by Bollett,1F and the investi- gations of Eeitz,1 Boehm,2 Hutob,3 and Bubnoff,4 — investigations which except Boehm's, were made under Strieker ; it was proved positively by Heitz- mann in 1873.6 With the question whether or not the so-called cartilage cell is alive, * " De Penitiori Cartilaginum Structura Symbolse." Diss. anat.-phys., auctore M. Meckauer, M. D. Breslau : Schultz & Co., 1836, tab. 4, p. 16. t " Atlas of Histology." London : Smith, Elder V ^V-^M VJ>,V# supposition that carti- e\^^^^/^^''t\^ The capsules are noth- ing but the optical ex- pression of different de- grees of densification, found in all other va- rieties of connective tis- sue. Condensed basis- substance in the form of a capsule may occur around single cartilage corpuscles or around corpuscles grouped to- gether, and frequently such capsules are alto- gether absent. Their production is closely FIG. 74. — HYALINE CARTILAGE FROM THE CON- connected with the DYLE OF FEMUR OF A NEW-BORN PUP. CHRO- formation of territo- MIC ACID SPECIMEN- rieS duHno1 devplrm C'the tissue of the hyaline cartilage, with scattered 1UP~ groups of cartilage corpuscles ; M, Medullary spaces, con- ment, and their power taining blood- vessels and medullary tissue.. Magnified of resistance can be 10° diaraeter8- proved by long-continued boiling, especially in acidulated water. Hyaline cartilage, when fully developed, is scantily supplied with blood-vessels ; large masses of the tissue are met with which are entirely destitute of vessels. Undeveloped, embryonal car- tilage, however, is traversed by a relatively large number of medullary canals, in which a complete system of blood-vessels — 196 CONNECTIVE TISSUE. arteries, veins, and capillaries — is found, besides a certain amount of medullary tissue, filling the space between the blood- vessels and the walls of the canals. The medullary canals, according to C. Langer, appear in the epiphyseal cartilage of shaft-bones (femur) after the third month of embryonal life. These canals are all in connection with the outer fibrous investment of the cartilage — i. e. the perichondrium, from which the blood- vessels enter the canals. The vascular medullary spaces decrease with the age of the individual, although a few such spaces have been traced up to the thirtieth year of life (Bubnoff). They are in intimate relation with both the progressive and regressive development of cartilage. (See Fig. 74.) The cartilage corpuscles are never scattered uniformly throughout the basis-substance, but always massed together, and the amount of basis-substance between the different mem- bers of a group of corpuscles is less than that which surrounds the groups. The groups vary in their general form in different portions even of the same cartilage. In epiphyseal cartilage of young animals, the corpuscles are arranged in flat groups around the articular surface ; they produce more or less globular or elongated clusters in the middle portion, and on approaching the diaphysis they are arranged in elongated rows. In a sagittal (antero-posterior) section through such an epiphyseal cartilage, the corpuscles appear oblong or spindle-shaped along the articu- lar surface, which indicates that their broadest diameter runs parallel with the outer surface. In the middle portion they are more or less globular. Near the diaphysis they again become discoid, appear flattened, oblong, or spindle-shaped if cut in a sagittal direction, and circular in a direction vertical to the shaft of the bone. With higher powers (300-500) of the microscope we recognize that, especially in the middle portions of cartilaginous formations, some corpuscles not infrequently lie very close to each other, so as to mutually flatten their proximal surfaces. Between so- called twin formations there is either a very narrow light rim or a somewhat broader layer of basis- substance, and if an entire group of corpuscles exhibit such twin formations (seen most dis- tinctly in the cartilage of the trachea), the narrow frame between the corpuscles in its regular arrangement presents a very pretty appearance. These double formations have been considered, for the last twenty years or more, proofs of the division of cartilage cells. This is a very mistaken idea, for it is impossible to under- CONNECTIVE TISSUE. 197 stand how corpuscles imbedded in a dense and tough basis-sub- stance could enlarge and divide — cartilaginous tissue itself, moreover, being perhaps the most inactive of all tissues. These multiple bodies cannot be the products of a division, as they are obviously formed simultaneously with the cartilage, and corre- spond to the double or treble, etc., corpuscles so often seen in the territories of other varieties of connective tissue. They cannot alter, unless the dense basis-substance around them is liquefied, or they themselves are transformed into basis-substance. Hyaline cartilage is a very common tissue in the body, and is found in an amount varying with the age of the individual. At a certain period of embryonal development, the entire skele- ton is composed of hyaline cartilage, and from this is devel- oped the whole osseous system, with the exception of the flat skull-bones. In the fully developed body this cartilage consti- tutes all articular surfaces of the bones, the anterior portions of the ribs, and the frame of the nose, the larynxr the trachea, and the bronchi. The articular cartilage is covered with a single, often indis- tinct, endothelial layer on the gliding surfaces, and surrounded by a richly vascularized delicate fibrous connective tissue — the synovial membrane — on the lateral surfaces. All other forma- tions of hyaline cartilage are invested by a layer of a dense fibrous connective tissue, the perichondrium, holding numerous blood- vessels, and in its construction more or less identical with that of the periosteum (see page 124). A distinct boundary-line between cartilage and perichondrium does not exist, as a gradual transition of the hyaline into the fibrous basis-substance takes place, and the cartilage corpuscles, which are always flattened near the surface, blend with the oblong or spindle-shaped plas- tids of the fibrous connective tissue. Hyaline cartilage is prone to secondary changes. The solid constituents increase with advancing age. According to E. Von Bibra, the ash-remnants of the cartilage of ribs of man continually increase with advancing age to such a degree that, while the solid remnants of a child six months old were only 2.29 per cent., those of a man forty years old were 6.1 per cent. Even in middle age, many of the cartilage-corpuscles contain fat-granules, which often coalesce into fat-globules, replacing to a certain extent the living matter. Granular depositions of lime-salts are often met with in the basis-substance of cartilage of the aged, especially in the ribs and the laryngeal cartilages. Sometimes 198 CONNECTIVE TISSUE. these are transformed into regular bone. The older a person grows, the less hyaline cartilage is found in his body. Kolliker made the curious discovery of a " parenehymatous or cellular" cartilage, constructed wholly of cells, without any trace of basis-substance. Among others, the chorda dorsalis, a light line close above the earliest forma- tion of the central nervous system in the embryo, is considered to be such a parenehymatous cartilage. Such a thing, however, is contrary to all we know of what could possibly be any variety of connective tissue. According to V. v. Mihalkovics, the chorda dorsalis is no cartilage at all, but a duplicature of the outer, epithelial germ-layer (Toldt). If this be correct, it would be another instance of an epithelial elongation which, after returning to the condition of an embryonal and medullary tissue, gave rise to connective-tissue forma- tions. We know that this is the case with the thyroid body and the enamel- tissue of the teeth. THE STRUCTURE OP HYALINE CARTILAGE.* Fresh, articular cartilage is a suitable object for the study of the histology of hyaline cartilage. If we place a thin section, to which is added a drop of one-half per cent, solution of common table-salt, under the microscope, with an immersion lens No. 10, we will find a number of details heretofore overlooked. The following description is a study of a specimen taken from a hori- zontal section of the condyle of femur of a young, full-grown dog ; it answers to the corresponding cartilages of the cat and the rabbit. The bodies of the cells appear finely granular, bounded by a somewhat denser layer. The contour of the cartilage cell being accurately in focus, there appears between the cell and the basis- substance a light, very narrow rim, which is traversed by numer- ous extremely delicate, radiating, grayish thorns or streaks. All these thorns are conical, the broad base emanating from the body of the cell and the thin point directed toward the basis-substance. Wherever two cells lie close together, the light rim between them is pierced in a transverse direction by grayish threads. When in the cell the nucleus is distinctly visible, its shape will be found to correspond to the shape of the cell- body, and in its finely granular interior the bright nucleolus will be usually apparent. A narrow light rim is found to surround the nucleus, which, on being sharply focused, shows radiating thorns, whose * Translated from "Studien am Knochen und Knorpel." Wiener Mediz. Jahrbiicher, 1872. CONNECTIVE TISSUE. 199 bases emanate from the nucleus, and whose points blend with the protoplasma of the cell. These conical spokes are clearly denned only when the light rim around the nucleuses distinct. On carefully examining the basis-substance, a very delicate, almost granular, conformation is recognizable, as if dark fields were alternating with light ones, and in some places giving the impression that the light fields formed ramifications, or even a delicate net- work. With the knowledge that from the cartilage cells offshoots emanate, and the basis-substance has an indistinct reticular for- FIG. 75. — HYALINE CARTILAGE FROM THE BORDER OF THE CONDYLE OF FEMUR OF A YOUNG DOG. TRANSITION INTO FIBROUS CARTILAGE. STAINED WITH NITRATE OF SILVER. [PUBLISHED IN 1872.] S, light spaces with indistinct cartilage corpuscles, freely brandling and connecting ; E, dark brown basis-substance, traversed by a light reticulum. Magnified 800 diameters. mation, and under the impression of pictures of inflamed carti- lage, which will be dwelt upon later, I proceeded to stain the cartilage with nitrate of silver. I prepared the articular extremity of the femur by removing the muscles and severing the shaft at a certain distance above 200 CONNECTIVE TISSUE. the knee-joint, and in this way obtained the condyles, as it were, on a handle formed by the stump of the femur. After the syno- via was washed off, I rubbed a stick of nitrate of silver for several minutes over the eondyles, transferred the specimen to water, and exposed it to daylight. After a few days, the parts which had been brought in contact with the re-agent became dark brown. The most superficial layer was removed as useless, and the next layer was examined. I would remark that sections from deeper portions, which at first are but slightly tinted by the silver-salt, assume a deep color on exposure to daylight. The deeper layers of the condyle, too, are dyed brown, and to a certain depth are well adapted for new sections. The following description is that of specimens taken from the condyles of a young and an old dog : they showed the same features. From the stained specimens taken from the anterior and under portions of the condyle, I could obtain nothing satisfactory for establishing the idea of a reticular structure. As soon, how- ever, as I reached the lateral surface, close to the edge, the aspect of things at once became changed. (See Fig. 75.) The basis-substance at the borders of the cartilage cavities is stained dark brown, in other portions light brown-red. From the cavities of varying shapes light offshoots are thrown out in different directions, which may be grouped in three orders, according to their calibers. The broadest offshoots, those of the first order, either connect cartilage cavities, or run merely into the basis-substance. The somewhat narrower offshoots, those of the second order, project from either the cartilage cavities or the broader offshoots, and ramify freely into the very narrow ones, those of the third order. The latter shoot out from the cartilage cavities and the processes of the first and second order, as well as from the ends of coarser processes, and traverse the basis-substance throughout. Thus a rich, extremely delicate reticulum of light, irregular lines is produced, with numerous varicose enlargements, the meshes of which reticulum are filled with the brown basis- substance. In the cavities we recognize the dim, unstained cell-bodies, with their enlarged, thorny nuclei and their offshoots, which are traceable into the processes of the cavities of the first order. In specimens taken from the anterior and under surface of the condyles, offshoots of the third, and occasionally some of the second, order are found, which are readily distinguished, wherever CONNECTIVE TISSUE. 201 the borders of the cartilage cavities are pierced by radiating light lines. The lateral surfaces of the condyles, on the contrary, con- stantly exhibit cartilage cells with offshoots of the first order, which are more numerous the farther away from the border of the articular surfaces. In the region where the basis-substance of the cartilage begins to be striated, we find the most beautiful silver images j here the coarse offshoots, interconnected by deli- cate ones, are very numerous, and remain so in the fibrous car- tilage proper, and also in the tissue of the periosteum and the tendon, adjoining the hyaline cartilage. My next purpose was to stain cartilage with chloride of gold. I placed the condyles of the knee-joint — the stump of the femur FIG. 76.— HYALINE CARTILAGE FROM THE CONDYLE OP THE FEMUR OF AN OLD DOG, STAINED WITH CHLORIDE OF GOLD. [PUBLISHED IN 1872.] C, dark violet cartilage corpuscles, with indistinct nuclei and numerous delicate' dark violet offshoots. £, pale violet basis-substance, traversed by a partly dark violet, partly light, reticulum. Magnified 800 diameters. again serving as a handle — into a one-half per cent, solution of chloride of gold, and traced its action on the cartilage for from ten minutes to twelve hours, always after rejecting the most superficial sections. The gold stain of the cartilage corpuscles appeared in fifteen minutes ; in the violet cell-body the nucleus became easily seen and sharply marked ; the contour of the cell-body was also rendered more distinct. In many places the conical spokes 202 CONNECTIVE TISSUE. arising from the cell-bodies became violet, but could not be traced into the basis-substance any farther than in uncolored specimens j in specimens from the lateral surfaces, numerous coarse and thorny offshoots of a violet color were seen, similar to that of the cell-bodies themselves, while the basis-substance remained uncolored or was pale bluish-red. After one hour's action of the gold solution, the coarse off- shoots and the cells appeared dark violet, the offshoots of the second order became distinctly visible; some of the offshoots of the third order could be traced far into the basis-substance, or directly into cells near each other. After twelve hours' action of the gold-solution, formations were brought into view which, being granular and crumbly, did not deserve attention. The cartilage cells were dark violet, the nucleus recognizable, if at all, as a lighter field. From all around the cell-body projected delicate offshoots, most of which looked finely granular, and in many places joined a granular reticu- lum. The reticulum is most abundant in the immediate vicinity of the cell and on the borders of the cell territories ; it connects directly with neighboring cells, and in some places is so compli- cated that a precise definition is impossible, even with an immer- sion lens No. 10. In places where the image is incomplete, we can satisfy ourselves that we have to deal with a reticulum which is richly supplied with granular and varicose nodulations, and the connection of which with the cell-bodies is beyond doubt. Fig. 76 illustrates such a picture. At the points of transition of cartilage into bone, there exists, as is well known, a layer of cartilage cells, the basis-substance of which is calcified. A calcareous deposition in the cartilage can be produced also by inflammation, following certain injuries of the cartilage. In horizontal sections of fresh, calcified specimens, as well as in specimens deprived of their lime-salts by chromic acid, we recognize that the basis-substance is traversed by chan- nels, which hold offshoots emanating from the cell cavities, and producing a net work. The image of these offshoots is the same whether much or little lime-salt be present, either in the wall of the cavity bordering the cell- body or at the boundaries of the cell territories. We are satisfied that in all cases a deposition of lime-salts has taken place in the fields of the basis-substance, while the cell and its offshoots have remained unchanged. In old animals, where the calcified cartilage directly borders the bone-tissue, positive proof can be obtained that the "osteoid" CONNECTIVE TISSUE. 203 cells are, by means of offshoots, directly connected with the bone-cells. The results of my researches lead to the following con- clusions : The bodies of the cartilage cells have radiating offshoots. These offshoots form a delicate varicose reticulum in the basis-substance. At the points of transition of hyaline cartilage into striated, fibrous cartilage and into periosteum, the offshoots are very large and broad ; they connect neighboring cells, either directly or indi- rectly, by means of delicate offshoots. In 1872 I was not yet acquainted with the structure of bioplasson — i. e., the cell-body, nor had I then recognized the FIG. 77.— HYALINE CARTILAGE IN TRANSITION TO STRIATED CARTILAGE, FROM THE BORDER OF THE CONDYLE OF FEMUR OF A GROWN DOG. STAINED WITH CHLORIDE OF GOLD. C, dark violet cartilage corpuscles with distinct nuclei, projecting offshoots, O, which directly or indirectly connect the corpuscles ; B, pale violet basis-substance, exhibiting a partly dark violet, partly light, reticulum. Magnified 800 diameters. significance of the interconnection of cartilage corpuscles for elucidating biological views in every respect contradictory of the cell theory. Still, I felt confident that, on account of the sim- 204 CONNECTIVE TISSUE. plicity of the methods used, other investigators would encounter no difficulty in producing what I had produced and seeing what I had seen. But what happened was just the contrary. A large bulk of literature was produced on this subject; nevertheless, almost all observers failed in bringing to view the connections existing between the cartilage corpuscles. Some claimed that it was the synovial liquid which assumed, on treatment with nitrate of silver, the figures I described; others that the connections between the cartilage cavities could be found only in the super- ficial portions of the condyles ; still others believed the forma- tions seen by me to be artificial products, due to a precipitation of the metal-salt I had employed. All, however, agreed that the light reticula which eventually became visible in the silver- stained specimen were only juice-canals, according to views taken by Von Recklinghausen. Meanwhile I had convinced many hundred students, in my laboratory in New York, that the cartilage corpuscles are really connected with each other, and an unprejudiced observer, L. Elsberg (see page 138), publicly announced his conviction of the correctness of my assertions. In the first place, there could be no doubt that the negative image produced by the silver in every respect answers to the positive image brought out by the gold. The negative silver image obtained from the border of the condyles, where the hya- line cartilage begins to change into fibrous cartilage (see Fig. 75), fully corresponds with the positive gold image produced in the same place. Fig. 77 is an illustration of specimens which for years I have used for demonstrations in my laboratory. Secondly, I was desirous of satisfying myself if the method of treatment with silver was really so unreliable as claimed by some writers. I gave Dr. W. Hassloch, a physician of unusual cleverness, attending my laboratory in 1878, my printed pam- phlet containing directions for procedure, and the fresh condyles of a human foetus, six months old. A few days later, without any further advice on my part, the gentleman showed me a large number of specimens, exhibiting images precisely similar to those illustrated in Fig. 78. The identity of the light spaces with cartilage corpuscles was beautifully demonstrated in the thin sections, where dark brown layers were directly followed by slightly stained or unstained layers. I admit, however, that my assertions would not have deserved much attention had the staining methods with nitrate of silver CONNECTIVE TISSUE. 205 and chloride of gold been the only foundation on which they were based. But I said, in 1872, that calcined portions of the hyaline cartilage, the calcification being a product either of a normal process preceding ossification, or of a process of inflam- mation artificially induced, exhibited the reticulum and the offshoots of the cartilage corpuscles in the larger projections of the cavities, without the application of any re-agent. The increased refracting power of the calcified basis-substance is sufficient by itself to bring to view everything that can be seen in the silver and gold specimens, and everything which can be deduced from a comparison of both. The images obtained in the earliest stages of inflammation of any variety of connective tissue are very valuable means of convincing ourselves of the FIG. 78.— HYALINE CARTILAGE FROM THE CONDYLE OF THE FEMUR OF A HUMAN FCETUS, Six MONTHS OLD. STAINED WITH NITRATE OF SILVER. S1, single light space; S*, twins, directly connected by light lines; J?, dark brown basis- substance pervaded by a light reticulum. Magnified 1000 diameters. presence of a large amount of living matter within the basis- substance. There is, indeed, no way to understand the inflam- matory process unless explained in this manner. A. Spina (see page 141), by the alcohol treatment of the car- tilage, discovered an excellent method for demonstrating the connections of the cartilage corpuscles. An eye with very little experience can observe to-day what, in 1872, 1 first maintained, after a long and tedious research and laborious experiments. 206 CONNECTIVE TISSUE. THE STRUCTURE OF THE THYROID CARTILAGE. BY L. ELSBERG.* Longitudinal sections through the lateral plates of the thyroid cartilage of a man of about twenty-five years, hardened in chromic acid and stained with an ammoniacal carmine solution, exhibit with low powers of the microscope 2 I !f 2 "3 S I 1 1 "3 u, II I! el .« a (150 to 200 diameters) the following : The cartilage corpuscles, either single, in pairs, or in groups of from three to six, or even more, are imbedded in a basis-substance which, for the most part, is homogeneous-looking or indis- * " Contributions to the Normal and Pathological Histology of the Cartilages of the Larynx," Archives of Laryngology, vol.il., 1881. CONNECTIVE TISSUE. 207 tinctly granular, but in some portions finely striated. The homogeneous or indistinctly granular-looking basis-substance is that which bears the name hyaline basis-substance ; the striated is termed fibrous, although actual fibrillee appear only on the edges of the specimen, or when the tissue is torn and mutilated. The fibrous basis-substance is intermixed, without any regularity, with the hyaline, and usually sharply separated from it. Not infrequently a number of cartilage corpuscles, or groups of cartilage corpuscles, are sur- rounded by fibrous basis-substance, the striations of which run, as a rule, in a sagittal direction, i. e., vertical to the surface. Within the fibrous basis- substance the cartilage corpuscles are at most points sparsely scattered or absent ; here and there, however, they are more numerous, in rows or elon- gated, corresponding to the direction of the striations. It also occurs that striated portions of the basis-substanee contain very minute globular or oblong corpuscles, sometimes to such an extent that the striated structure is concealed by the large number of these corpuscles. (See Fig. 79.) The fibrous portion is seen to occupy the center of a longitudinal section of one of the plates of the thyroid cartilage. This is not regularly the case in every cut, and was exceptionally well marked in the section from which the drawing was made. In some sections the fibrous cartilage is altogether absent, but every laryngeal cartilage contains some fibrous mixed with hya- line portions. Under higher magnifying powers (500 to 600 diameters), single cartilage corpuscles exhibit features, frequently before described, with coarsely granu- lar nuclei. Around the nucleus finer granules are visible. At the periphery of the cartilage corpuscle there are several strata of higher refracting power, especially the zone nearest the basis-substance, which, as a rule, appears very shining and is what is termed the capsule of the cartilage corpuscle. Not infrequently the cartilage corpuscle is very indistinct, being but slightly more granular than the surrounding basis-substance ; then almost nothing but the nucleus marks its presence and its place. In twin formations of car- tilage corpuscles, which are often met with, the zone of division between the two corpuscles is identical with that surrounding both, in the shape of a cap- sule. Of the same nature are the zones of division that are seen in clusters of cartilage corpuscles. The so-called hyaline basis-substance throughout its whole extent now appears finely granular ; as a rule, the granulation is more distinct midway between the corpuscles than in their immediate vicinity. The fibrous por- tions of the basis-substance are seen to be made up of extremely minute spindles, which, by being grouped longitudinally, produce the aspect of striation. The spindles or fibers are separated from each other by light rims, and both the spindles and the rims look finely granular. Between the spindles may often be seen small globular bodies, sometimes scattered, some- times in clusters, of which the size and shape greatly vary, reaching occa- sionally the size and shape of a regular cartilage corpuscle. In some striated fields, blood-vessels, both arterial and capillary, can be seen ; the former with the characteristic muscle-coat, the latter with the endothelial wall, besides holding red blood-corpuscles in their calibers.* The highest powers of the microscope (1000 to 1200 diameters) reveal * These striated fields are remnants of former medullary spaces, for the striated portions in the center of the cartilage never contain Wood- vessels. 208 CONNECTIVE TISSUE. the retieular structure of cartilage corpuscles, as it is known since 1873. All granules within the nucleus and all granules within the corpuscle are unin- terruptedly connected by delicate threads. The intranuclear net-work is con- nected with the corpuscular retieulum by radiating conical spokes traversing the light rim around the nucleus; and, at the periphery of the corpuscle, similar conical spokes pierce a narrow light rim and enter the basis-sub- stance, in which, especially in the highly refracting zone termed capsule, they are usually lost to sight. Cartilage corpuscles, even, which have become so pale as to leave only a dim trace of their former contour visible, still exhibit more or less distinct traces of the retieular structure. The same structure may be seen throughout the so-called hyaline basis- substance »— more distinct in the middle of the space between the corpuscles than immediately around the corpuscles themselves. The fibrous portion of FIG. 80. — THYBOID CARTILAGE OF ADULT. SAGITTAL SECTION. C, C, cartilage corpuscles; B, indistinctly reticular hyaline basis-substance ; F, fibrous basis-substance. Magnified 1200 diameters. the basis-substance has also a reticular structure. The bodies of the slender spindles show a net-work without the application of any re-agent, and the light rims between the spindles are traversed by delicate threads running in a vertical direction to the longitudinal diameter of the spindles. All granules and lumps scattered through the fibrous basis-substance are surrounded by light rims, which are pierced by conical spokes inosculating with the retieu- lum of the neighboring spindles. (See Fig. 80.) I have treated sections of the same cartilage, after they had for several days been washed out with distilled water, with a one-half per cent, solution CONNECTIVE TISSUE. 209 of gold chloride, whereupon they assumed a dark purple color, and showed all the features described, somewhat more distinctly than simple carmine preparations. I deem their detailed description unnecessary. When I became acquainted with Spina's researches (see page 141), I deemed it of importance to repeat the examination according to his method. I therefore placed a larynx, immediately after removal from the body of a girl, aged twenty-four years, into strong alcohol, and after four days made thin sections from the thyroid cartilage in a horizontal direction, transferred them in alcohol to the slide, and examined them with both low and high pow- ers, adding, from time to time, a drop of strong alcohol to prevent the speci- men from drying. The appearance presented by such a specimen is truly surprising. As a matter of course, the cartilage corpuscles are shriveled up, so that more or less space is left between their jagged periphery and the bor- FIG. 81. — THYROID CARTILAGE OF ADULT, KEPT IN STRONG ALCOHOL. HORIZONTAL SECTION. 0, shriveled cartilage corpuscle; O, longitudinal offshoots; JB, reticuluin in basis-sub- stance ; G, granules of living matter. Magnified 1200 diameters. der of the basis-substance. With an amplification of 500 diameters, the basis-substance is seen pierced by light filaments, which, in many instances, can be traced through the intervening space into the body of the cartilage corpuscle. Most of these filaments radiate around the corpuscle, and, imme- diately after penetrating the basis-substance, diverge and form a reticulum throughout its extent. Cartilage corpuscles located near each other are directly connected by non-ramifying, and occasionally by ramifying, offshoots, or by bundles of such offshoots of a more or less parallel course. The reticu- lum in the basis-substance is either radiating or irregularly arranged around 14 210 CONNECTIVE TISSUE. the corpuscle. Contrary to the assertion of Spina, the filaments or offshoots do, as a rule, ramify, except those that directly connect the neighboring cor- puscles. Sometimes thick bundles of offshoots emanate from opposite poles of the corpuscles, while intervening portions of the periphery are almost devoid of offshoots. Toward the periphery of the thyroid cartilage, — where, as is well known, the cartilage corpuscles elongate, becoming smaller and spindle-shaped and more or less parallel to each other, — the offshoots are given off rectangularly to the axis of the corpuscles. * High magnifying powers, immersion lenses No. 10 and No. 12, con- clusively prove the connection of the offshoots with the cartilage corpuscles. Portions of the basis-substance which, with lower powers, looked only granu- lar, now show a delicate reticulum, which, even when coarser offshoots are FIG. 82. — THYROID CARTILAGE OF ADULT. HORIZONTAL SECTION. v C, C, cartilage corpuscles; F, fibrous portion of cartilage; G, granules of living matter. Magnified 600 diameters. wanting, is connected with the cartilage corpuscle through delicate and more or less conical offshoots from the surface of the corpuscle. The light interstices between the fibers of striated basis-substance are also traversed by delicate grayish thorns. Such thorns are visible even in the perichondrium. Through the fibrous bundles of the perichondrium run, in a nearly rectangular direction, delicate light streaks, while the interstices between the bundles, and the spaces left between the corpuscular elements and the bundles, exhibit delicate conical grayish threads, the direction of which corresponds to these light streaks. (See Fig. 81.) The highest powers of the microscope disclosed in one of the specimens examined another feature in the hyaline basis-substance, viz. : the presence of a number of granules or minute lumps of varying shape, some interwoven CONNECTIVE TISSUE. 211 with the direct offshoots of the corpuscles, and some with the threads forming the finer net-work of the basis-substance. They appeared to be thickened points of intersection, knots, or nodes, composed of the same material as the offshoots and threads themselves. They were unquestionably granules of living matter. I found their greatest development in a case examined without Spina's method — a case which I shall describe presently. The observation which I am now about to record was made in specimens of the thyroid cartilage removed from the body of a rather stout man, forty-eight years old. After having been hardened in chromic acid solution, without any other re-agent, they exhibited formations in the basis-substance which, so far as I am aware, have never before been described. I have alluded to them as FIG. 83. — THYROID CARTILAGE OF ADULT. HORIZONTAL SECTION. C, .cartilage corpuscle ; S, hyaline basis-substance ; G, grannies of living matter. Mag- nified 1200 diameters. found in one of the specimens examined, with the highest powers of the microscope, by the alcohol method of Spina. As to the cartilage corpuscles in these specimens, many of them were larger and more coarsely granular than are commonly observed ; otherwise, their characters and the arrangements of the basis-substance, both so-called hyaline and fibrous, were like those described before. The intranuclear, intracorpuscular, and intercorpuscular net-works were with high powers well shown. The very remarkable feature was that, with quite low power, the basis- substance was seen to be speckled and studded with granules or lumps, varying from that of a point at the limit of the visible to that approaching the dimen- 212 CONNECTIVE TISSUE. sions of a regular cartilage corpuscle. Of course, no one must for a moment think of anything like the pathological conditions that have been described, either as granular degenerations of the cartilage basis-substance, or as in- crustations of the corpuscles. Not only were the appearances entirely differ- ent and the cartilage healthy, — as otherwise ascertainable, as well as from the known condition of the man and of the cause of his death, — but the true nature of the lumps was made perfectly clear by examination with higher powers. (See Fig. 82.) When magnified to the extent of 600 diameters, the same relative appear- ance was preserved. The lumps in the basis-substance still varied in size, from the limit of the visible to the magnitude of ordinary cartilage corpuscles ; but, in all the larger lumps, differentiations were visible which approached them in structure, as well as in size, to cartilage corpuscles. In some, one or more vacuoles, in others, a small or large nucleus, or even two nuclei, could be made out; and a few (i. e., occasionally one in some fields) showed irregular twin, or even triplet, formation. The highest power threw a wonderful light upon these lumps. They were seen to be masses of living matter. The larger showed a net-work in their interior, some without and some with a nucleus, and the latter, when present, was sometimes homogeneous and sometimes reticulated. All the lumps, except the smaller, were surrounded by a distinct light seam, through which radiating conical offshoots passed to the net-work in the basis-substance; and all of them, even the smallest, sent delicate offshoots connecting them with that net-work, or were themselves part and parcel (i. e., thickened points of intersection of the threads) of that net-work. (See Fig. 83.) After having studied such a specimen, it was easy to interpret correctly the intrareticular granules seen in the alcohol specimen represented in Fig. 81. Development of Cartilage* Hyaline cartilage is developed, in the same way as fibrous tissue and bone, from the indifferent medullary elements which, in human embryos, between the fourth and fifth month, and in newly born dogs, cats, and rabbits, are stored up in a still considerable amount in the vascularized medullary spaces of the cartilage. Upon the authority of Schwann, the erroneous view has been generally held that blood-vessels are found in hyaline cartilage only a short time before commencing ossification. In early periods of development of cartilage, medullary spaces are pres- ent containing blood-vessels, — viz. : arteries, veins, and capil- laries,— which, as Bubnofff has demonstrated, are preserved to quite an advanced age. In such spaces we find, besides a varying number of blood- * " Untersuchungen iiber das Protoplasma. IV. Die Entwickelung der Beinhaut, des Knochens und des Knorpels." Sitzungsber. der Akad. d. Wissensch. in Wien, 1873. t Sitzungsber. der Wiener Akademie d. Wissensch., 1868. CONNECTIVE TISSUE. 213 vessels, medullary tissue, consisting of globular or spindle-shaped corpuscles, with a slight amount of a myxomatous and fibrous reticular basis-substance. Lower powers of the microscope reveal that the boundary line between medullary and cartilage tissue in some places is sharply defined, while in other places it is indistinct or invisible. In the most peripheral portions of the medullary tissue, i. e.j nearest the cartilage, we see rows of spindle-shaped or oblong bodies, bear- ing a close resemblance to the medullary cor- puscles found on the boundaries of forming bone-tissue. (See Fig. 84.) In the cartilage of the knee-joint, at the extremity of the femur of new-born pups, we meet not infrequently, at the borders of a medullary space, close to the fully formed car- tilage, with groups of medullary corpuscles, the peripheral portions of which are beginning to be infiltrated with an apparently homoge- neous basis-substance, while the central por- tion retains the charac- ^IG. 84< — HYALINE CARTILAGE OF THE CONDYLE ^-p 4-1,^ »4--\ OF TIBIA OF A HUMAN EMBRYO, FOUR MONTHS ter of the cartilage cor- OJD SAGITTAL SECTION. CHROMIC ACID puscle. Under these SPECIMEN. [PUBLISHED IN 1873.] conditions, homoffene- 7 . & . M, medullary canal, transversely cut, containing blood- OUS (in the Optical dl- vessels and medullary tissue; C, cartilage, with marked ameter Semicircular) ter"tories in tne basis-substance. Magnified 200 diam- fields are projected into the caliber of the medullary space. Or a gradual transition of medullary into cartilage tissue takes place at the border of the medullary space, with the result that a number of spindle-shaped medullary corpuscles are transformed into a territory of cartilage tissue, which in this situation sometimes exhibits a delicate 214 CONNECTIVE TISSUE. striation. In the first case, the result is a globular territory with a central cartilage corpuscle j in the latter, a spindle-shaped terri- tory, containing an elongated, spindle-shaped corpuscle. (See Fig. 85.) There is a marked difference, however, between the territories of the cartilage in very young and in fully developed animals. In the articular cartilage of human embryos from four to five FIG. 85. — HYALINE CARTILAGE OF THE CONDYLE OF FEMUR OF A NEW-BORN PUP. SAGITTAL SECTION. CHROMIC ACID SPECIMEN, SLIGHTLY STAINED WITH CHLORIDE OF GOLD. [PUBLISHED IN 1873.] V, loop of a capillary blood-vessel in a medullary canal of the cartilage : J, elongated medullary corpuscles in the stage of indifference ; J5', boundary zone of basis-substance ; B*t fully developed basis-substance. Magnified 800 diameters. months old, and that of newly born dogs and cats, the latter being at birth as far advanced in development as man at four or five months, we see territories only, with numerous cartilage cor- puscles, between which the basis-substance is scanty, as if sprung CONNECTIVE TISSUE. 215 from a few embryonal (medullary) corpuscles, or from a single corpuscle. In the full-grown animal, on the contrary, the terri- tory contains but one or a few cartilage corpuscles, the double and triple formations, between which the basis-substance is very scanty or even absent, while in the peripheral portion of the terri- tory a large amount of basis-substance is found, which must have originated from a corresponding large number of embryonal (medullary) corpuscles. Although the cartilage corpuscles of very young animals are decidedly smaller than those of the full-grown, there is not the slightest evidence of a so-called " interstitial growth," i. e., an increase of the bulk of the corpuscle as well as of the basis-substance already formed. It is far more probable that the embryonal cartilage is not the same formation from which the cartilage of the adult arises j it certainly is not in the same loca- tion as far as the size of the whole body is concerned. Besides, a fully formed cartilage, or any other tissue, grows, during the time that the cartilage is returning to the medullary condition, only in limited places, when a new grouping of medullary cor- puscles takes place, and a new basis-substance is developed. Those who maintain that an "interstitial" growth takes place, forget that a cartilage corpuscle, once imbedded in the dense, chondrogenous basis-substance, cannot increase in size unless a liquefaction of the basis-substance has occurred, at least at the borders of the cavity containing the corpuscle. The same objec- tion can be raised against the hypothesis of the division of carti- lage corpuscles in the fully developed tissue. The probability is far greater that cartilage grows with the growth of the whole body, from medullary corpuscles at the periphery, while the central portions are reduced into medullary tissue for the benefit of the growing bone-tissue. The " apposition theory" considered in this light is the only legitimate one, as there is no difficulty in understanding that from the perichondrium, or other peripheral formations of connective tissue, always, of course, through the intervening stage of medullary tissue, new cartilage is produced during the whole period of development of the body. The process of development of cartilage with striated basis- substance is materially the same as that of hyaline cartilage, as I could trace on the lateral surfaces of the condyle of femur of growing rabbits. Here we find intermediate striated cartilage between the hyaline cartilage and the tendon or ligamentous tissue ; and the intermediate striated portions may be found to contain fields of hyaline cartilage. With such evidences it is not 216 CONNECTIVE TISSUE. difficult to convince oneself that the character of the cartilaginous basis-substance, whether hyaline, striated, or fibrous, depends upon the shape and the grouping of the original, indifferent medullary corpuscles alone. The cartilaginous callus, obtained after subcutaneous fract- ures of the leg-bones of dogs and cats, I found very suitable for the study of the development of cartilage. Here the new forma- tion of cartilage arises from nests, identical with medullary spaces, which in their center contain blood-vessels, at their periphery spindle-shaped elements, as the result of the inflamma- tory new formation. The medullary elements close around the blood-vessel* are globular, and are succeeded by layers of spindle- shaped bodies, the nuclei of which are partly faded, indicating that these formations are in the stage of transition from a uni- form granulation into the stage of infiltration with glue-yielding basis-substance. In such inflammatory nests, also, we observe the transformation of capillary blood-vessels into solid strings, and afterward into small medullary elements. The process is the same as in the involution of bone-tissue, due to normal senile changes. In the same cartilaginous callus we also encounter numerous nests in which red blood-corpuscles and blood-vessels arise from cartilage corpuscles (see page 98), and these forma- tions precede the liquefaction of the calcified cartilaginous basis- substance, which occurs previously to the production of new medullary tissue and of bone. The embryonal or medullary elements are, under all circum- stances, the formers of tissue. Those from which bone arises have been termed " osteoblasts " by Gegenbaur, who considered them to be, specifically and exclusively, bone-formers. We are far from understanding the specific nature and limits of embry- onal corpuscles, and the designation "osteoblasts" is therefore superfluous. We might with equal propriety speak of " periosto- blasts," " chondroblasts," etc., while, in fact, all these tissues originate from one and the same source — namely, the medullary tissue. What character the territory will assume, what will be the nature of the basis-substance in the territory, depends upon the grouping of these many-named " blasts " in the stage of indif- ference preceding the new formation of a tissue. In 1873, I admitted the possibility that, under certain physio- logical conditions and changes, one variety of basis-substance might be directly transformed into another ; periosteum, f . i., into bone or into cartilage, hyaline into striated cartilage, etc. This CONNECTIVE TISSUE. 217 possibility seems to me, to-day, to be very slight, so much so that even a direct transformation of hyaline into fibrous carti- lage is doubtful. I am positive that one variety of basis-substance, one kind of connective tissue, can never be transformed into another except through the intermediate stage of medullary tissue. A com- pletely developed tissue must first return to the embryonal condition, before a new and different tissue can develop from it. Remak * was the first to approach our present views respect- ing the formation of basis-substance of cartilage. He maintained that it is deposited between the outer and the inner membrane of the cartilage-cell, whereupon the outer membrane perishes, and the shells of the " parietal substance " fuse together in order to form the intercellular substance. E. Briicke, t in accordance with the views held by Max Schultze, considered the outermost layer of the cartilage cells, destitute of a membrane, to be the former of basis-substance proper. The layer close around the unchanged portion of the cell-body he asserts to be more dense than the rest of the basis- substance, and this condensation causes the appearance of a capsule. Similar views are held by E. HeidenhainJ concerning the formation of single and stratified capsules. If these views were correct in every respect, we ought to find in developing cartilage enormous corpuscles, corresponding in size with the whole territory, before the changes at their periphery had ensued. But the facts are just the contrary to this, for in the embryonal cartilage the corpuscles are decidedly smaller than in that of the adult. A. Spina§ demonstrates that, in fully developed cartilage, with advancing age the amount of basis-substance increases at the expense of the cartilage corpuscles. These become pale, finely granular, destitute of nuclei, and then disappear in the basis-substance. The protoplasmic reticulum of the cells, he says, does not perish, but remains, somewhat altered in its character, in the basis-substance. This explains why, in the articular cartilage of the very aged, the corpuscles are so extremely scanty and small. * Miiller's Archiv, 1852. t " Die Elementarorganismen." Sitzungsber. d. Wiener Akademie d. Wissensch., 1861. t Studien des Physiol. Instit, zu Breslau, 1863. § ' ' Untersuchungen iiber die Bildung der Knorpelgrundsubstanz." Sitzungsber. d. Wiener Akademie d. Wissensch., 1880. 218 CONNECTIVE TISSUE. I can fully corroborate Spina's assertions from my own observations. (4) BONE TISSUE. History. The growth of the bones was the subject of careful studies in the seventeenth and eighteenth centuries, long before anything positive was known as to their structure. Adrianus Spigelius * was the first to maintain that the bones grow either from cartilage or by apposition. Clopton Havers t found that bone arises from cartilage. Robert Nesbittt says that " there is not one single phenomenon to sup- port the notion of bones being nothing but indurated cartilage, or that they are produced only by a transmutation of a cartilaginous substance, and all bony productions are caused entirely by the apposition of cretaceous matter." In the middle of the eighteenth century, Duhamel, § after experiments by systematically feeding various animals with madder, asserted that the bones grow from the periosteum, and was contradicted by A. Von Haller, who denied any participation of the periosteum in the process. Exactly the same fight is carried on even in our day. John Hunter || found in the growth of bones "two processes going on at the same time, and assisting each other : the arteries bring the supplies to the bone for its increase ; the absorbents at the same time are employed in removing portions of the old bones, so as to give to the new the proper form. By these means the bone becomes larger, without having any material change produced in its external shape." J. Howship H speaks of lining-membranes of the canals of the bone carry- ing the blood-vessels ; he did not see the lining in full-grown bone, " possibly because the circulation of the red blood is more limited in full-grown than in young bone." He gives illustrations of lacunar widenings of the canals, evidently caused by a morbid process. After the bone-corpuscles (lacunee) and their canaliculi were made known byPurkinje and Deutsch (1834), Johannes Miiller l pointed out their con- nection, and suggested that all these spaces are filled with lime, and should, therefore, be termed canaliculi chalicophori. Lessing 2 first drew attention to the fact that the dark appearance of the lacunas and canaliculi, seen in specimens from dry bone, is due to their con- taining air, and was inclined to regard them as a lacunar system, filled, in living bones, with fluid. Klebs, much later, made the wonderful discovery that the contents of these spaces in older, even fresh bones, are of a gaseous nature. *"De Forraatione Fcetu," 1631. The early literature is found in Alb. Kolliker: "Die Normale Resorption des Knocheugewebes." Leipzig, 1873. The later literature, from 1836 to 1878, is given by M. Kassowitz : " Die Norunale Ossification," etc. Wiener Med. Jahrbiicher, 1879. t " Osteologia Nova ; or, Some New Observations in the Bones." London, 1691. t Human Osteogeny, explained in two lectures. London, 1731. $ " M6moires de I'AcadSmie de Paris." 1742. || "Experiments and Observations on the Growth of Bone," from the papers of the late Mr. Hunter, by Everard Home. London, 1798. 11 "Microscopic Observations on the Structure of Bone." Medico-Chirurgical Transac- tions. London, 1816. 1 Muller's Archiv, 1836. 2 "Ueberein plasmatisches Gefass-System in alien Geweben, iusbesonders in Knochen und Zahnen." Hamburg, 1846. CONNECTIVE TISSUE. 219 R. Virchow * claimed that the lacunar and canalieular spaces are really plasmatic, and can be isolated, as true " bone-cells," by the treatment of dry bone with acids. He was contradicted by E. Neumann, t who con- clusively proved that Virchow's branching cells are nothing but the densified walls of the lacunae and the larger canaliculi resisting the action of strong acids and alkalies (elastic substance). Such a substance was found to line also the Haversian canals. A. Kolliker \ declared that on the external surfaces of growing bones an absorption takes place. Virchow, in 1853,§ agreed that such an absorption occurs on the cerebral surfaces of the skull-bones. Virchow had, in 1852, asserted that the bay-like excavations (so-called Howship's lacuna) on the surface of pathological bones are due to a melting of the substance of the bone, in correspondence with the cell territories ; afterward, he maintained that the bone-cells set free by the solution of the intercellular substance, are transformed into medullary cells. Tomes and De Morgan || observed erosions in carious and provisional teeth, and argued in the following manner : " When we connect this condition with the fact that the nucleated cells, which form the embryo, have the power of appropriating the material which lies about them to the purpose of their own growth, ... it is difficult to resist the belief that the cells which lie in con- tact with wasting bone and dentine take up those tissues. . . . An objection may be raised to the supposition that the bone is absorbed by cells, on the ground of the density of the former ; but it must be borne in mind that, as the density is gradually imparted to the bone through the agency of the adjoining soft parts, there seems no good reason for disbelieving that they may also be instrumental in its removal." 1f Heinrich Miiller, in 1858,1 published his epoch-making researches on development of bone, which are the foundation of our modern views on this subject. His observations will be dwelt upon in the article on development of bone. Reference will there also be made to the researches of Gegenbaur (1865) and Waldeyer (1865). Ed. Lang 2 was the first to ascertain that, in bone-specimens of recently killed animals, the lacunae contain protoplasm, which is, to a certain degree, endowed with the property of amoaboid motion, and from which starts the inflammatory new formation. In the last decennium, a lively controversy was carried on regarding the question whether or not a growth of the bone by expansion, a so-called inter- stitial growth, occurs. Ruge,3 as the result of his counting and measuring the distances between bone-corpuscles, became a defender of the theory of interstitial growth. Jul. Wolff 4 energetically maintained an interstitial growth, and denied any appo- * " Wiir/.burger Verhandlungen," 1850. f'Beitrage zur Kenntniss des norm. Zalmbein- und Knochengewebes." Konigsberg, 1863. t " Mikroskopisclie Anatomic," 1850. $ Virchow's Archiv, Bd. iv. 1852 ; Bd. v. 1858. || " Observations on the Structure and Development of Bone," 1852. Philosophical Transactions, 1853. II All quotations from authors in this historical sketch are from Kolliker (I. c.). 1 "Zeitschrift fur Wissensch.-Zoologie." Bd. ix. 2 " Uutersuchuugen iiber die ersten Stadien tier Kuochenentziindting." Wiener Mediz. Jahrb., 1871. s Virchow's Archiv. Bd. 49. 4 Virchow's Archiv. Bd. 50. 220 CONNECTIVE TISSUE. sition from cartilage and periosteum. Lieberktihn, * on the contrary, fully corroborated the old and well-established views of an apposition. Recently, again, Strelzofft favored the view of an interstitial growth, and was con- tradicted by Steudener, t who demonstrated that the bone-corpuscles with advancing age decrease somewhat in size, and consequently appear to become farther apart as the bulk of the basis-substance increases. V. Ebner § has arrived at the conclusion, based on macerations of bone in a ten to fifteen per cent, solution of chloride of sodium, to which he added one to three per cent, muriatic acid, that the lamellae of bone-tissue are composed of fibrillse. These fibers, according to him, can be isolated only for short distances, as they are interwoven and held together by a cement-substance containing the lime-salts, while the fibrillse themselves are glue-yielding, but destitute of lime-salts. Fibers running from a lamella to the surface of the bone consti- tute the perforating fibers of Sharpey. C. Langer || added valuable contributions to the knowledge of the distribu- tion of blood-vessels in shaft and flat bones. M. Kassowitz If published an extensive article on the formation of bone, with special reference to the periosteal cartilage. Methods. It is one of the strangest facts in histology that, although for a number of years dry specimens of tissue have been acknowledged to be worthless for microscopical research, bone even in our day is studied in the dry condition. All books of all nations on histology give accurate directions for slicing dry bone and grinding the sections thin for mounting in Canada-balsam. Such specimens are of little value for examinations with the microscope. Specimens of dry bone are about as useful for obtaining histological facts as are the silver- stained specimens of other tissues — i. e., both exhibit the frame of the tissue, while all the soft parts, the real seats of life, are destroyed. There is but one way to render bone-tissue suitable for study, and that is by softening fresh bone in a one-half per cent, solution of chromic acid, to which from time to time very small quantities of dilute hydrochloric acid may be added. If the chromic acid solution be changed every fourth or fifth day, and if a large quan- tity of the liquid be used for small pieces of bone, in a few weeks the specimens can be easily cut with the razor. This method was introduced by H. Miiller in 1858, but has been far too much * Sitzungsb. d. Marburger Gesellsch., 1872. I Untersuchungeu aus dem Pathol. Inst. zu Zurich, 1873. f'Beitrftge zur Lehre von d. Knochenentwicklung." Abh. der Naturf. Ges. zu Halle, 1875. § " Ueber den feincren Bau der Knochensubstanz." Sitzungsber. d. Wiener Akad. d. Wissensch., 1875. || " Ueber das Geiass-System der Kohrenknochen." Denkschrif tender Wiener Akademie d. Wissensch., 1875. " Ueber die Blutgefftsse der Knochen des Schftileldaches." Denkschrif. ten d. Wiener Akademie der Wissensch., 1877. U " Die Normale Ossification," etc. Wiener Mediz. Jahrbiicher, 1879. CONNECTIVE TISSUE. 221 neglected. The best specimens are obtained from portions in which the basis-substance is not entirely decalcified, as in these the bone-corpuscles arid their offshoots, as well as the corre- sponding cavities in the basis-substance, the lacunae and canal- iculi, are best preserved. For mounting, only dilute glycerine should be used. ' A number of examiners have attempted to settle the question whether the lime-salts are deposited mechanically in the basis- substance, or whether there is a chemical union of the molecules of lime and glue. The question probably will never be satisfac- torily answered. This much is certain, that by the extraction of the lime-salts by means of chromic acid, no material changes are produced in the glue-yielding basis-substance. Bone-corpuscles. As early as in 1850, E. Virchow discovered the identity of the "bone-cells" with other " connective-tissue cells.77 Though he at first held the mistaken idea that the walls of the cavities were the bone-cells proper, he admitted later that the cavities, being hollow and filled with a liquid, hold the bone-cells. He was the first who recognized them to be the seats of life, and able to proliferate and produce medullary tissue. As late as 1871, Ed. Lang, in Strieker's laboratory, recog- nized the bone-corpuscles to be living matter or protoplasm in the fresh condition, endowed with the property of amoeboid change. In this view the bone-tissue, as well as every other variety of connective tissue, is built up by a calcified, glue- yielding basis-substance, containing scattered cavities and outlets of the cavities — the lacuna? and canaliculi of former histologists ; the lacunas are filled with living matter, the bone-cells or bone- corpuscles. Nothing positive was known at that time as to the contents of the canaliculi. In 1872,* I undertook to study bone-tissue, both in fresh and preserved specimens. In fresh sections, taken from the con- dyle of the femur of young rabbits, transferred to the slide together with a drop of a one-half per cent, solution of table-salt, or, still better, of Muller's liquid, with an immersion lens No. 10 of Hartnack, I recognized the bone-corpuscles. They were round or oblong bodies of a grayish tint, lying in a shining basis- substance, which appeared traversed by numerous light canals. * " Studien am Knoehen und Knorpel." Wiener Mediz. Jahrbiicher, 1872. 222 CONNECTIVE TISSUE. In the bodies, which were indistinctly spotted, I could often see a nucleus-like formation, with scalloped outlines. "The cell- body/' I said, " is surrounded by a light, narrow zone, in which numerous conical offshoots are visible, emanating from the cell- body, and exhibiting the same character as the cell-body." In many places I could trace these extremely delicate, branching offshoots for a considerable distance in the basis-substance, and saw them unite with the offshoots of neighboring corpuscles. When the offshoots could not be followed far away from the body, I found their continuations to be the light, branching canals in the basis-substance. The offshoots and their anastomoses I could see very plainly in specimens stained with chloride of gold, where the dark violet bone-corpuscles were seen sharply denned upon the pale violet basis. The offshoots were likewise distinctly visible in speci- mens of bone, decalcified by lactic acid. With this method the corpuscles seemed not to have shriveled, as the rim be- tween them and the basis-substance was not broader than in fresh specimens. In specimens preserved in chromic acid, the bone-corpuscles appeared somewhat shriveled. The basis-substance inclosing their cavity was traversed by numerous canals. Most of the offshoots of the corpuscle resembled conical thorns, which terminated in fine points toward the calibers of the canals, but only in a few of these could I discern a granular substance which possessed the characteristics of the corpuscle. In normal bone, I was convinced that the bone-corpuscles had offshoots which partly projected in the canaliculi, partly inoscu- lated with each other. A plain view of these offshoots, however, could be obtained only in bone, in which an inflammation had been artificially induced. . One of the first noticeable changes in osteitis was the swelling of the corpuscle and the increased dis- tinctness of its offshoots. These observations are illustrated on page 126, Fig. 40. In 1872 I was not aware of the significance of the union of the bone-corpuscles, and it was not until a year later that I made use of the structure of bone-tissue for pointing out new biological views. I have been led, by careful researches of osteitis, to the conviction that the basis-substance must be pervaded by a large amount of living matter in reticular arrangement, which after liquefaction of the basis-substance is freed and participates largely in the inflammatory new formation. Direct proofs of the presence of CONNECTIVE TISSUE. 223 this extremely delicate reticulum I could not obtain, as all trials with silver and gold staining of bone proved to be failures. The bone-corpuscles, as well as all other connective-tissue corpuscles, are formations of living matter, which in a juvenile condition are found to be compact, homogeneous, or vacuoled lumps, while in full development they are nucleated plastids. Their shape varies, to some extent, with that of the territories of basis-substance in which they exist. We find globular bone- corpuscles, which have assumed a star-shape by the appearance of numerous radiating offshoots, in the earliest formations of globular territories. We also meet with globular bone-corpuscles at the peripheral portions of fully developed Haversian systems, owing to the presence of the first formed territories of this sys- tem, and again in the interstitial bone-tissue between the systems, in places where no lamellae are formed. In striated or lamellated bone-tissue the corpuscles are oblong or spindle-shaped bodies, slightly bent in the direction of the striae or lamellae, intercon- nected by larger offshoots, emanating from both poles, and by numerous delicate offshoots, traversing the basis-substance in a rectangular direction. The latter offshoots arise at right angles from both the periphery of the corpuscles and their larger longi- tudinal branches. In the Haversian systems the bone- corpuscles are slightly flattened, and in longitudinal sections exhibit their broadest oblong surface whenever the razor strikes a peripheral portion of a Haversian system, while they have the appearance of narrow spindles, when the razor runs through the middle of a lamellated system. In transverse sections of the system the corpuscles exhibit irregular shapes, and again vary in their diam- eters according to the depth to which they are cut by the razor. A spindle will necessarily look broader if the section has been made transversely through the middle, and narrow if near the ends. Varieties of Bone-tissue. There are two kinds of bone-tissue, which, in the fully developed subject, however, are always com- bined with each other, viz. : the cancellous, epiphyseal, or spongy bone-tissue, and the compact or cortical bone-tissue. (a) Cancellous, Epiphyseal, or Spongy Bone-tissue is built up by trabeculae, arranged as a frame-work inclosing the medul- lary spaces. It is the only kind found in early stages of develop- ment of bone. In the fourth, fifth, and sixth months of embryonal life of human beings, and in dogs, cats, and rabbits at birth, no other bone-tissue but the cancellous is found. In 224 CONNECTIVE TISSUE. the juvenile skeleton, this structure composes the epiphyseal ends and the central portions of the shaft-bones, and the central portions of flat and short bones. (See Fig. 86.) Cancellous bone-tissue of the embryo is invariably striated and non-lamellated. In the fully developed skeleton it exhibits usually indistinct lamellae. The spaces between the trabeculee of cancellous bone are in youth filled with a richly vascular- ized medullary tissue, the "red medulla" of Virchow; while with FIG. 86. — TIBIA OF A NEWLY BORN PUP. LONGITUDINAL SECTION. CHROMIC ACID SPECIMEN. [PUBLISHED IN 1873.] T, trabeculae of bone-tissue containing bone corpuscles; M, medullary spaces filled •with medullary tissue, holding blood-vessels in the most central portions. Magnified 200 diameters. advancing age the spaces exhibit fat- tissue, Virchow's " yellow medulla." In very old persons there is an increasing deficiency of both the cancellous and compact bone-tissues j the bone corpuscles are also very small and few in number, as many of them have been transformed into basis-substance. The relation between the cancellous and the compact structure differs in different bones. As a rule, the short bones are largely CONNECTIVE TISSUE. 225 made up of cancellous tissue, with only a thin layer of compact bone at their peripheries. Flat bones exhibit the cancellous structure in the middle portion, the diploe of skull-bones, while the layers on the outer and inner surface are formed entirely of compact bone, the outer layer being generally broader and richer in blood-vessels than the inner. Thin, small, flat bones, such as the ethmoideal, turbinate, etc., may be con- sidered as flattened trabecula3 of the cancellous variety. The shaft-bones have a broad investment of compact structure in their middle, i. e., diaphyseal portion, while this tissue gradually decreases toward the ends, the epiphyses. These parts, as well as the large central marrow space, exhibit the cancellous struct- ure in greatly varying amounts. H. Meyer first drew atten- tion to the fact that the trabeculae of the cancellous structure, especially in the epiphyseal extremities of shaft-bones, were built up according to a certain law, and J. Wolff, with the assistance of Culmann, has explained, according to mathematical principles, the regular arrangement of the trabeculae in the directions of lines of pressure and traction. (b) Cortical or Compact Bone-tissue is composed of parallel lamellae, closely packed together in intimate relation with the blood-vessels. The cortex of both flat and shaft bones consists of a concentric system of lamellae surrounding the central marrow space, and this concentric system in its middle portion is trav- ersed, usually at right angles, by a number of systems of lamellae, each surrounding a central blood-vessel. Thus, two peripheral systems of lamellae originate, of which the outer is always the broader, and well marked, the inner often but little developed. The middle portion, lying between the two peripheral sys- tems, is traversed more or less rectangularly by the Haversian systems. In transverse sections of the cortex of shaft-bones, the lamellae of the two peripheral systems run longitudinally, while the Haversian systems are cut transversely or obliquely. Be- tween the latter there are the longitudinal lamellae of the so-called " interstitial or intermediate " bone-tissue. (See Fig. 87.) The Haversian system is composed of lamellae which are dis- posed in concentric layers around capillary blood-vessels. Such systems of lamellae are regularly arranged in the cortex of the long bones, and irregularly in the cortex of flat bones. The outer contour of a system is never smooth and even, but composed of a number of shallow protrusions, viz., the first-formed territories, and the aggregation of these formations gives the outer contour 15 226 CONNECTIVE TISSUE. of a Haver sian system a fluted appearance. The systems are sometimes found close to each other, with very little inter- mediate bone-tissue between them; or they may be more or less apart, with a distinctly lamellated intermediate Bone-tissue l §1 11 a [>, 0 ® £ o I! between them, the lamellae of which run in a direction more or less parallel with the peripheral lamellge. This probably depends upon the original distribution of the blood-vessels, which, if rami- CONNECTIVE TISSUE. 227 tying at very acute angles, will make their systems of lamellae lie close together ; but if ramifying at less acute angles, will leave in- terstices filled with distinctly lamellated intermediate bone-tissue. In order to render the formation of cortical bone easily understood, the following illustration is often used : take a number of matches, around each of which is twined a cord, and wind the cord around the bundle, the match representing the Haversian canal, the twines around each match the systems of lamellae, and the twines around the bundle the peripheral lamellae. This comparison holds good, of course, only for the case in which the intermediate bone-tissue is absent. The law, however, according to which the peripheral FIG. 88. — TIBIA OF A GROWN DOG. CORTICAL PORTION, TRANSVERSE SECTION. CHROMIC ACID SPECIMEN. •V, Haversian system of lamellae, containing the bone-corpuscles, C, with their radiating offshoots ; M, central medullary, so-called Haversian canal, containing a capillary blood- vessel ; I, interstitial bone-tissue indistinctly lamellated. Magnified 500 diameters. and the Haversian systems of lamellae are formed, has not yet been explained. With higher amplifications of the microscope each Haversian system proves to be composed of a number of concentric lamellae, which are not perfect throughout the system. Both within and between the lamellae, bone-corpuscles are visible with radiating offshoots, a number of which traverse the lamellae, without being in direct connection with a bone-corpuscle. (See Fig. 88.) 228 .CONNECTIVE TISSUE. The center of the Haversian system is pierced by the medul- lary or vascular canal, which is of a varying caliber, according to the age of the individual, and contains, besides a certain number of medullary corpuscles, one or two central capillary blood- vessels. Whenever the extremity of the animal from which the shaft-bone was taken had been in a pendent position after death, the vessels are found filled with blood-corpuscles. Longitudinal Sections are easily understood after the study of transverse sections. Here, too, the Haversian system is bordered by a fluting contour, due to the presence of globular territories of an early formation, and between the systems we find the inter- mediate bone-tissue, which in this situation, as a matter of course, will not exhibit lamination. In the intermediate portion we find the bone-corpuscles cut transversely, with most of their offshoots cut either obliquely or transversely, the latter being represented by a number of delicate dots. In the Haversian system the lamellae take a longitudinal course ; within and between them are found the spindle-shaped bone-corpuscles, exhibiting, for reasons explained before, the greater bulk the nearer the periphery of the system. The off- shoots of the bone-corpuscles emanating from their periphery, as well as from their polar projections, pierce the lamellae at right angles. The central canal contains a varying number of medul- lary corpuscles, and in its middle one or two straight capillaries. Even with moderate powers of the microscope delicate filaments are recognizable, by which the offshoots of the bone-corpuscles connect with the medullary corpuscles, and the latter with the endothelial wall of the blood-vessel. (See Fig. 89.) Periosteum. The investing fibrous connective-tissue layer of all bones, the periosteum as well as the cartilage, takes consid- erable part in the development of the osseous system. In human embryos of four to six months, the outermost layer of the peri- osteum consists of bundles of fibrous connective tissue, and between this layer and the cancellous bone there is a broad layer of medullary corpuscles, in continuity with the medullary forma- tion in the spaces of the bone-tissue. From the outer fibrous portion of the periosteum oblique bundles of considerable density are seen to pass into the medullary spaces of the bone, and these bundles remain unchanged even after the compact portions of the bone have attained full development. Such bundles, faintly visible in chromic acid specimens, .are termed " perforating or Sharpey's fibers" (described by Sharpey in 1856, but previously CONNECTIVE TISSUE. 229 by Troja, in 1814). They traverse the outer peripheral system of lamellae, sometimes in the form of single cords, sometimes as a broad reticulum, but often they are entirely absent. FIG. 89. — TIBIA OF A GROWN DOG. CORTICAL PORTION, LONGITUDINAL SECTION. CHROMIC ACID SPECIMEN. S, Haversian system of lamellae, containing the bone-corpuscles, C, with their transverse offshoots; M, central medullary, so-called Haversian canal, containing a capillary blood- vessel ; I, interstitial bone-tissue. Magnified 500 diameters. In fully developed bone the periosteum consists of two layers, the outer fibrous portion being supplied with numerous blood- vessels, which inosculate directly with the blood-vessels of the 230 CONNECTIVE TISSUE. bone-tissue, while the innermost portion, closely attached to the surface of the bone, is a dense ribboned layer, with a scanty supply of blood-vessels, but rich in elastic substance. This layer is often the seat of calcareous deposition, and owing to this fact its plasticl! assume irregular, jagged contours similar to those of bone-corpuscles. The calcined periosteum, however, is not true lamellated bone. It is often described under the name of the " osteoid layer" The periosteum is very thick at the points of the attachment of tendons and ligaments. The inner surface of the flat skull-bones, after the fifth or sixth year of life, is destitute of a periosteal investment proper. This can be clearly understood by the study of the development of these bones. Blood-vessels. The bone-tissue, its investment, — the perios- teum,— and its contents, — the medulla, — are plentifully supplied with blood-vessels. They enter the periosteum mainly at the points of attachment of the large ligamentous formations men- tioned above. Arteries and veins are most abundant in the outermost 'portion of the periosteum, where extensive ramifica- tion of these vessels takes place. The arterioles enter the larger canals at the surface of the bones and branch into capillaries, which unite to form the efferent veins accompanying the arteri- oles. At the inner surface of the compact bone, also, there is a free anastomosis with the capillaries of the medulla. The medulla is supplied with numerous capillaries, arising from the so-called nutrient arteries of the bone, which pierce the cortical substance obliquely and split at acute angles, both within the canal and after entering the medulla. The veins collect the blood from tassel-like bundles of capillaries and accompany the afferent arteries. The epiphyseal portions of shaft-bones, besides the general medullary vessels, receive blood from the vessels which supply the articulations. The capillaries terminate, in the shape of loops, close below the articular cartilage. The veins in the bone-tissue are without valves, but as soon as they reach the surface of the bone, we find valves are present (C. Langer). Lymphatics are not yet known to exist in the bone-tissue. Nerves, both of the medullated and non-medullated variety, accompany the larger blood-vessels, but they are not abundant in the bone-tissue. In different places in the periosteum, Pacin- ian corpuscles are found. The medulla of the bone is, in juvenile condition, a myx- omatous tissue, at first of the medullary, later of the reticular variety (see pages 147 and 148), and, being freely vascularized, is CONNECTIVE TISSUE. 231 termed " red medulla." With advancing age the medulla is almost entirely transformed into fat-tissue, while the blood- vessels decrease in number on account of the large proportion of fat 5 it is then termed the " yellow medulla." THE RELATION OF THE SYSTEMS OF LAMELLAE TO THE BLOOD-VESSELS.* The cortical substance of the shaft-bones of a newly born pup is composed of trabeculae, which form a reticulum, elon- gated in the longitudinal axis of the bone, the meshes being the medullary spaces. The width of a trabecula is about the same as the diameter of a neighboring medullary space. The trabecu- lae are bone-tissue of a striated appearance, and contain flat bone-corpuscles in a concentric arrangement. In the medullary spaces we find the globular elements of the medulla closely packed together with ramifying blood-vessels, principally in the center. (See Fig. 90, and also Fig. 86.) FIG. 90. — TIBIA OF A NEW-BORN DOG. TRANSVERSE SECTION. CHROMIC ACID SPECIMEN. P, fibrous portion of the periosteum; SM, subperiosteal medullary layer; T, trabecula' of bone ; M, medullary spaces. Magnified 25 diameters. In the compact substance of the bone of a dog about six months old, the bulk of bone-tissue several times exceeds that of the medullary tissue. We still meet with medullary spaces con- taining blood-vessels and globular elements. Far more numer- * Translated from "Ueber die Eiick- und Neubildung von Blutgefassen im Kiiochen und Knorpel." Wiener Mediz. Jahrb., 1873. 232 CONNECTIVE TISSUE. cms than medullary spaces, however, are the so-called " vascular canals " — /. e., cylindrical or oval tubes, with one or two much elongated blood-vessels, and oblong or spindle-shaped medullary corpuscles. The larger the diameter of a medullary space or a vascular canal, the narrower, as a rule, is the surrounding bony layer 5 the broadest layers of lamellae correspond to the narrow- est vascular canals. The blood-vessels of the medullary spaces anastomose with those of the vascular canals by means of trans- verse and oblique branches 5 the vessels of the canals anastomose with each other, and with every vessel we find a varying thick- ness of lamellae. (See Fig. 91.) In the diaphysis of the tibia of a dog a little over a year old, the area of the bone-tissue surpasses that of the vascular canals, in FIG. 91.— TIBIA OF A DOG, Six MONTHS OLD. TRANSVERSE SECTION. CHROMIC ACID SPECIMEN. M, medullary space, with a relatively small amount of surrounding lamellas ; Si, narrow system of lamellae around a medullary space; /S2, broader system around a vascular canal. Between the systems is the lamellated intermediate hone-tissue. Magnified 200 diameters. a linear direction, six to eight times. In the compact bone, larger medullary spaces are found only in the vicinity of the central marrow-canal. The vascular canals are surrounded by broad systems of lamellae, containing the bone-corpuscles in a concen- tric arrangement. Sometimes we meet, in transverse sections, with two smaller systems, each with a central canal, -the two encircled by a common layer of an hour-glass shape. The inter- stices between the systems are filled by a non-lamellated bone- tissue, whose corpuscles are somewhat larger than those of the lamellae, and irregularly distributed. The territories of such cor- CONNECTIVE TISSUE. 233 puscles are sometimes sharply marked. Into the intermediate bone-tissue we can also trace vascular canals — the lateral branches of the longitudinal vessels of the compact bone. In the tibia of a dog several years old, the area of the bone- tissue surpasses that of the vascular canals by twelve or fifteen linear diameters. Large medullary spaces are found only near the central marrow-tube, while the rest of the cortex exhibits vascular canals of varying calibers, the larger of which contain some reticular connective tissue and fat-globules around the vessel. The parallel systems of lamellae belong either to a single vascular canal or to two or three narrower systems which are surrounded by a large common system. The intermediate tissue is usually lamellated ; in portions where lamellae are wanting, semicircular or circular contours of territories are found surround- FIG. 92.— TIBIA OF A DOG, TEN YEARS OLD. TRANSVERSE SECTION. CHROMIC ACID SPECIMEN. S, system of lamellae with a central vascular canal ; O, system of lamellae with a central bone-corpuscle ; J, intermediate lamellated bone-tissue. Magnified 200 diameters. ing small, bay-like spaces. Not infrequently we meet with sys- tems of lamellae, the centers of which are not occupied by a vas- cular canal, but by a bone-corpuscle. Similar conditions are found in the tibia of a dog eight to ten years old, although the solid systems of lamellae are still more numerous. The central marrow-tube is inclosed by a common lamellated bone-layer, while the layer between the periosteum and the bone is lamellated only in part. (See Fig. 92.) The femur of the same animal is encircled by a broad, lamel- 234 CONNECTIVE TISSUE. lated layer beneath the periosteum, as well as at the border of the central marrow-tube. Where these layers are pierced by vertical vascular canals, such canals, as a rule, are surrounded by more or less perfect sheaths of lamellae. From these observations it follows that, independently of the general growth of the bone, the living matter stored up in the medullary spaces is the forming material of bone. The ele- ments termed " medullary cells/' as well as " osteoblasts," are transformed into bone-tissue, and in this way the lamellated layers of the bone become broader, and the medullary spaces, 011 the contrary, narrower. The systems produced by the contents of a medullary space surround smaller systems, the formation of which depends upon the single blood-vessels of the former medullary space, which now occupy the centers of the vascular canals. All systems of lamellae, therefore, are vascular territories, — as it were, stratified pillars, — the main longitudinal direction of which agrees with the course of the blood-vessels in their centers. From the main longitudinal course of this structure, branch sys- tems, frequently in the oblique, rarely in the transverse, direction. The formation of non-lamellated intermediate bone-tissue also depends upon the blood-vessels. Watching the contents of the vascular canals with high ampli- fications, I observed the following features : In the bone of a dog about six months old, each vascular canal contains one or two blood-vessels, of varying caliber and of a straight course. I have several times seen nerves running along with the vessels, though my method of preparation was not favorable to the clearing up of nerve-tissue. The wall of the blood-vessel, as a rule, exhibits the simple structure of a capillary, with occasional spindle-shaped thickenings. The vessel is sur- rounded by a light rim, traversed by delicate grayish spokes, connecting the wall of the vessel with the neighboring spindle- shaped elements. The latter ensheath the perivascular space, either in a single flat layer or in several strata, and are also inter- connected by short projections. Between the spindles and the bone- wall there is again a light rim, traversed by delicate off- shoots, which directly connect the spindles with the offshoots of the bone-corpuscles. In the tibia of a dog over a year old, I found similar vascular canals ; besides numerous canals which, sometimes in places and sometimes in their whole length, contained only a capillary CONNECTIVE TISSUE. 235 vessel. I met with this arrangement most frequently in the older animals. Between the wall of the vessel and that of the bone there is always a light, narrow rim, crossed by projections of the neighboringbone-corpuscles,unit- ing with the w^all of the blood- vessel. The rim is absent only when the blood-vessel is overfilled with an injection mass. In the compact portion of shaft-bones and scapulae of dogs, cats, and rabbits of middle or old age, I often encountered vascular canals, which were either con- stricted in an hour-glass shape or terminated in points. This condition was positively recog- nizable by the fact that, above and below the vascular canal, layers of bone-tissue (respectively bone-corpuscles) could be brought into focus. Closer examination of such vascular canals in longitud- inal sections, as a rule, revealed the presence of but one blood- vessel. (See Fig. 93.) Toward the pointed end the wall of the vessel became thick- ened, as if composed of spindle- shaped corpuscles, between which tne caliber either narrowed sud- denly or gradually, terminating close to a spindle-shaped body. In the caliber of the vessel red FIG. 93. — HORIZONTAL SECTION blood-corpuscles were occasion- OF THE SCAPULA OF A GROWN ally present and T repeatedly saw DOG. SPECIMEN DECALCIFIED <* *y 5 . . J WITH PYROLIGNIC ACID. [Pun- the injected mass penetrating the LISHED IN 1873.] pointed end. The corpuscle which 0, capillary blood-vessel, containing a OCCluded the fine point of the VCS- £55 ^XJSiXZSZSi medullary corpuscle, and B, bone-corpus- cle, lioth sprung from the solidified blood- vessel. Magnified 800 diameters. sel Proved to be a and in the direction of the VCSSel, , intprval^ similar formations at intervals Similar 236 CONNECTIVE TISSUE. were visible, separated from each other by finely granular or homogeneous shining masses. The same condition was also observed in transverse sections. I found in the center of a system of lamellae solid, finely granular corpuscles, which, in both an upward and downward direction, blended with the transverse cavities of bone or with the calibers of vessels. (See Fig. 94.) The conclusions I arrived at are as follows: The material contained in the vascular canals is, with advancing growth, transformed into bone, leaving only the blood-vessel behind. FIG. 94. — TRANSVERSE SECTION OF THE INJECTED TIBIA OF A GROWN DOG. CHROMIC ACID SPECIMEN. A COMMON SYSTEM OF LAMELLAE INCLOSES Two SMALLER SYSTEMS. [PUBLISHED IN 1873.] £V, the central vascular canal, with a capillary blood-vessel; JBC, a central solid corpuscle sprung from a former blood-vessel. Magnified 800 diameters. After a time, a transformation of the blood-vessels themselves to bone-tissue takes place by a solidification of the hollow proto- plasma of the wall of the vessels, and thereupon a differentia- tion into bone-corpuscles and bony basis-substance. DEVELOPMENT OF BONE. It is a fact, well known for centuries, that the skeleton in the embryo is first formed of cartilage. The main question at all CONNECTIVE TISSUE. 237 times has been : How does bone arise from cartilage ? A satis- factory answer to this question was impossible so long as the minute structure of cartilage was unknown, and, indeed, a full understanding of the process of ossification is of a very recent date. Through the researches of Rathke, Reichert, Kolliker, and others, we know that there are bones which do not develop from cartilage, but from fibrous connective tissue, formerly thought to be a u blastema.'7 All bones of the skeleton arise from pre- existing cartilage, except the flat skull-bones — viz. : the squam- ous portion of the occipital and temporal bones, the parietal, frontal, and portions of the sphenoid bone, and the nasal, lachrymal, vomer? malar, palatine, and upper maxillary bones. The clavicle was in former times thought to be destitute of a cartilaginous basis, but recently it was found to be cartilaginous, at least at its extremities (M. Kassowitz). There is, however, a great similarity between the formation of the so-called " carti- laginous" bones and that of bones termed " covering. " In all cartilaginous bones the formation of bone proceeds simultane- ously both from the cartilage and from the perichondrium, the fibrous investing membrane. The ossification of cartilage was first studied. In former times it was believed that, by the deposition of lime-salts, the cartilage was directly transformed into bone — the "cartilage cells" directly converted into "bone-cells." Observers were much puzzled over the formation of the u canaliculi," and Kol- liker, in 1852, imagined that he had settled the matter by assum- ing that the cartilage-cells were transformed into bone-cells by a thickening of their walls, with a simultaneous formation of canaliculi, similar to the pore-canals of "wood-cells" of plants. A new era was inaugurated in 1858 by H. Miiller, * who, after very careful researches, came to the conclusion that the cartilage first breaks down into medullary tissue, and from this tissue bone is developed. H. Miiller, however, admitted that a direct ossifi- cation of cartilage (metaplasia of authors) may also occur. Although he was ignorant of the fact that the whole medullary tissue giving rise to bone is an offspring of cartilage, the great merits of this accurate observer must always be recognized. To-day we know that a direct transformation of cartilage or fibrous * " Ueber die Entwicklung der Knochensubstanz, nebst Bemerkungen iiber den Ban rachitischer Kiiochen." Zeitschr. f. Wissensch. Zoologie. Bd. ix. 238 CONNECTIVE TISSUE. tissue into bone never occurs ; that between these two kinds of com- pleted tissues the intermediate medullary, or embryonal tissue, stage is invariably present. For the study of this -highly interesting question the best subjects are the bones of human embryos, between the fourth and seventh months of intra- uterine life, or the correspondingly developed bones of newly born pups or kit- tens. These animals, at the time of birth, are, as I have already stated, advanced in development as far as human beings in the middle of intra- uterine life. Dogs and cats one year of age correspond in development of this tissue to human beings in the twentieth year of life, and dogs and cats ten to twelve years old are as far advanced in this regard as men of sixty years. The phases of development of bone can, of course, be studied with greater ease in dogs than in human beings, and a number of facts obtained from the bones of animals have not as yet been established by investiga- tion of human bones. All specimens must be preserved in, and partly or wholly decalcified by, a one-half per cent, solution of chromic acid; many of the blunders of former histologists, regarding development of bone, re- sulted from the examination of dry specimens. DEVELOPMENT OP BONE FROM CARTILAGE. In sagittal (antero-posterior) sections of shaft-bones of a human embryo, about five months old, we see that both ends of the future bone are composed of hyaline cartilage, containing many medullary spaces. With low powers of the microscope we recognize that the cartilage corpuscles are closely packed together in the outermost portions of the rounded extremities ; next, the corpuscles are less crowded, but arranged, at regular intervals, in globular heaps, and gradually become arranged in rows, as the cartilaginous head slopes toward the middle portion, the future shaft. It is a mistake to suppose that these changes of shape and situation of the cartilage corpuscles are due to their own activity — that, -as Virchow has expressed it, the corpuscles " direct themselves into rows." Before the third month of em- bryonal life we can easily ascertain the fact that, from the earli- est stages of formation of cartilage, the rows are present in the middle portion. It is impossible to understand how cartilage corpuscles, being imbedded in a dense and tough basis-substance, could perform active locomotions without the basis-substance having been-previously liquefied. (a) Calcification. At a certain point, nearer the middle, in the younger embryo, the basis- substance is found to be the seat CONNECTIVE TISSUE. 239 of a calcareous deposition. This occurs first in the middle of the shaft, and gradually proceeds toward both extremities, vary- ing considerably, both in time and extent, in different human embryos and in different ani- mal embryos. In specimens decalcified by chromic acid, the basis-substance, which was the seat of a deposition of lime-salts, readily takes up the carmine stain. (See Fig. 95.) The calcareous deposition occurs only in the broad masses of basis-substance be- tween the territories, of the cartilage corpuscles, in con- sequence of which an elon- gated reticular frame is visi- ble, which at first surrounds the territories of the cartilage corpuscles, and deeper below, in a nearly level line, it sur- rounds the spaces filled with medullary corpuscles. The calcification is sharply de- fined by pointed ends toward the unchanged cartilaginous portion. «In the deeper por- tions of the calcified frame the first traces of newly formed bone-tissue are no- ticeable in the shape of bright crescentic fields, at- tached by their convex sur- faces to the calcified frame. This investment of bone soon produces a continuous layer around the frame at its bor- ders toward the medullary spaces. In the cartilaginous heads of shaft-bones of human embryos, at a somewhat later period, a FIG. 95. — HUMERUS OF A HUMAN EM- BRYO, FIVE MONTHS OLD. SAGITTAL SECTION. CHROMIC ACID SPECIMEN. C, rows of cartilage corpuscles in elongated groups, due to their territories ; F, frame of calci- ned basis-substance, around which, in the lower portions, the first traces of bone-tissue are no- ticeable ; M, medullary space, containing medul- lary corpuscles. Magnified 300 diameters. 240 CONNECTIVE TISSUE. deposition of lime-salts starts from the center of each head, inde- pendently of the calcified shaft. The frame of calcined basis- substance in this situation is of a roundish form, agreeing with the general shape of the cartilaginous head. In some cartilagi- nous heads of long bones, the calcification occurs at a very early period, f. i., in the vertebral ends of ribs ; while in short bones the calcification, always starting from the center of the pre- CONNECTIVE TISSUE. 241 formed cartilage, is of a later date ; f. i., in the vertebra?. (See Fig. 96.) In new-born pups, kittens, and rabbits these features are very similar, though sometimes the calcification preceding the ossification is wanting, even in shaft-bones (see, f. i., Fig. 98). It is wanting, as a rule, at the cartilaginous border of the plate of the scapula. FIG. 97. — VERTEBRAL EXTREMITY OF THE BIB OF A HUMAN EMBRYO, TEN WEEKS OLD. HORIZONTAL SECTION. CHROMIC ACID SPECIMEN. H, hyaline cartilage, with mostly multiple formations of corpuscles in the territories; C, calcified frame of basis-substance ; P, cartilage corpuscles with jagged offshoots, enlarged by liquefaction of the basis-substance. Magnified 500 diameters. We know that the calcification of cartilage is the first step in the development of bone, and as this process takes place inde- pendently in three portions of the shaft-bones, three nuclei of 16 242 CONNECTIVE TISSUE. bony tissue are formed — one in each epiphysis and one in the diaphysis. The outer portion of the epiphyseal cartilage is the articular cartilage proper 5 the cartilaginous portion between the epiphysis and the diaphysis is termed the diaphyseal or intermediate cartilage, which in human beings completely disap- pears about the twentieth year of life. (~b) Formation of Medullary Tissue. The cartilage corpuscles close above the place of calcification always have a coarse gran- ular appearance, and are without a distinct nucleus. We under- stand from this that the bioplasson of the corpuscle has increased in amount, and thus begins a retrogression toward the juvenile condition. In the spaces surrounded by calcified basis-substance the cartilage corpuscles assume a very coarse granulation ; many of them are nearly homogeneous, have a bright and vacuoled appearance, and are furthermore marked by radiating offshoots. (See Fig. 97.) At the same time the cartilage corpuscles increase in bulk, also, by the addition of living matter, which, after the liquefac- tion of the basis-substance, simply re-appears from where it before was concealed. This re-appearance of living matter is indicated first by a somewhat coarser granulation of the basis-substance, and subsequently by the formation of new lines of demarkation, corresponding to the liquefied portion of the basis-substance. Even with moderate powers of the microscope all stages of the re-appearance of bioplasson are traceable, from a distinct granu- lation of the basis-substance up to the formation of fields exhib- iting the features which in former times were termed " pale protoplasm." Such fields either surround the original cartilage corpuscle, or are joined to a part of the corpuscle. If the razor has struck the peripheral portions in a space surrounded by the calcified frame, only pale granular bioplasson is visible, and there will be seen basis-substance alone if the section reached the outermost portion. The next stage is the splitting of the bioplasson masses into numerous smaller indifferent — i. e., embryonal or medullary — corpuscles, each of which assumes a coarse granulation. It is obvious that at first only those embryonal corpuscles will appear which once themselves took part in the formation of the terri- tory. By an increase of the bulk of their bioplasson these cor- puscles become nucleated, and at first are finely, and later coarsely, granular. Small lumps of bioplasson may also show themselves, of a homogeneous appearance, a high degree of luster, CONNECTIVE TISSUE. 243 and a distinct yellow color. This indicates a new formation of living matter. In 1872, I named these solid lumps "haemato- blastic" (see page 98), as I had observed the new formation of red blood-corpuscles arising from them. In 1873, I proved this condition to be the juvenile state of living matter in general (see page 51). H. Miiller asserted that many of the medullary corpuscles are the productions of the original cartilage corpuscles, and in this he was quite correct. But later observers, their number unfort- unately being great, have disposed of the cartilage corpuscles by saying that they fade and perish, and that all medullary cor- puscles are " leukocytes" — colorless blood-corpuscles, which have migrated from the blood-vessels of the medullary spaces, or of the perichondrium, through the cartilage and into the medullary spaces. There is no ground whatever for such assertions. To assume that leukocytes migrate through newly formed blood- vessels, which are not yet in connection even with the old vascu- lar system, sounds whimsical enough. Further to insist, however, that leukocytes creep through the dense and unyielding basis- substance (for, at that time, nothing was known of " juice- canals'7), is simply an absurdity. These hypotheses fall to the ground when we know that the basis-substance contains a large amount of living matter ; that a liquefaction only of this basis- substance is required to free the bioplasson, from which, by its rapid growth and by the splitting of its lumps, new medullary corpuscles arise. The process, in short, is : re-appearance, division, and new formation of bioplasson. That really the whole medullary tissue, filling the space inclosed by a calcified frame, is a production of both the car- tilage corpuscles and the living matter in the surrounding basis- substance, is best illustrated by specimens where, with- out a preliminary deposition of lime-salts, the territories of cartilage tissue are immediately followed by medullary spaces. (See Fig. 98.) Here we see, in certain territories of the cartilage, masses of medullary corpuscles in no way connected with the medullary spaces below. The spaces are exactly in a line with the terri- tories directly above, and are filled with bioplasson lumps in all stages of development. (See page 46.) The centers of the masses exhibit a new formation, also, of red blood-corpuscles and blood- vessels. (c) Formation of Red Blood-corpuscles and Blood-vessels. 244 CONNECTIVE TISSUE. Having ascertained the fact that red blood-corpuscles originate in places where a transformation of cartilage into bone takes place, I studied the development of blood-vessels in the same FIG. 98. — FEMUR OF A NEWLY BORN PUP. TRANSITION OF THE EPIPHYSIS INTO THE DlAPHYSIS. No CALCIFICATION OF THE BASIS-SUBSTANCE. SAGITTAL SECTION. CHROMIC ACID SPECIMEN. C, heaps of cartilage corpuscles ; If, newly formed medullary corpuscles in a territory ; M, both cartilage corpuscles and basis-substance changed into medullary tissue, with traces of newly formed blood-vessels. Magnified 500 diameters. situation. My subjects for investigation were condyles of the femur of pups and rabbits and the cartilaginous border of the plate of the scapula of kittens.* * Translated from " Ueber die Ruck- und Neubildung von Blutgefassen im Knochen und Knorpel." Wiener Mediz. Jahrb., 1873. CONNECTIVE TISSUE. 245 The hyaline epiphyseal cartilage of young animals, as is well known, is traversed by elongated medullary spaces, which contain, besides blood-vessels, including arteries, a large number of ele- ments similar to those filling the medullary spaces of the bone. Such spaces also pervade the hyaline cartilage at the border of the plate of the scapula. FIG. 99.— FROM THE CALCIFIED NUCLEUS OF THE CONDYLE OF FEMUR OF A DOG, Six WEEKS OLD. FRESH SPECIMEN. [PUBLISHED IN 1873.] C, coarsely granular cartilage corpuscles with offshoots; Jf, haematoblasts, iii a club-like space, which is inclosed by delicate spindles and terminates in a solid point, P ; L, calcified basis-substauce. Magnified 800 diameters. In the epiphyseal cartilage of the knee-joint of a newly born rabbit's femur, I found a radiating frame-work of calcified basis- substance, which, bordering a larger central medullary space, inclosed in its trabeculae a number of cartilage corpuscles and 246 CONNECTIVE TISSUE. their non-calcified basis-substance. In the corresponding epi- physeal cartilage of a pup of five days there was no deposition of lime-salts present ; while the same cartilage of a pup six weeks old contained a central semi-lunar calcareous nucleus, with its concavity directed toward the diaphysis, the trabecula? of which inclosed a number of medullary spaces. The significance of this calcareous deposition was already known to Heinr. Muller. Within the calcified portions of the cartilage metamorphoses occur in the medullary spaces, which, with a simulta- neous solution of the calcareous frame, lead to the transformation of the cartilage corpuscles into blood-corpuscles and blood-vessels, as well as into medullary elements. (See Fig. 99.) The process is the same in advancing development of bone-tissue at the bor- ders of the diaphyseal or intermediate cartilage, at the border between the epiphysis and the articular cartilage, and at the bor- der between the cartilagi- naus and the bony plate of the scapula. The central yellow and shining portion of the cartilage corpuscle is transformed into a vesi- cle, usually club-shaped, containing red blood-cor- puscles. The swelled blunt extremity of the club is directed toward the periphery, while the more solid pointed end lies toward the larger central medul- FIG. 100.— FROM THE CARTILAGINOUS BOR- DER OF THE SCAPULA OF A KITTEN. FRESH SPECIMEN. [PUBLISHED IN 1873.] C, yellow, bright, vacuoled cartilage corpuscles ; B, closed cartilage cavity, containing red blood-cor- puscles ; M, club-shaped spaces, holding red blood- corpuscles and haematoblasts. Magnified 800 diams. CONNECTIVE TISSUE. 247 lary spaces. I also occasionally met with club-shaped formations, holding a light, finely granular, or an apparently structureless mass. (See Fig. 100.) If several of these club-like formations, whether empty or holding red blood-corpuscles, were crowded together, they assumed the appearance of a cauliflower-like rosette, the same as after perforation of the calcareous wall between two neigh- boring cartilage cavities, when the spindle- or club-shaped forma- tions come next to each other. The solid points or the walls of older formations of this kind became, after a time, hollowed o.ut, and thus a varicose reticulum of blood-vessels arose which, from the very earliest period of their formation, contained red blood- corpuscles. Still later, the newly formed vessels may connect with older blood-vessels, and their contents be taken into the circulation. (d) Formation of Bone from Medulla* In newly born pups, the formation of bone-tissue takes place within the medullary tissue from the medullary elements. The bone-tissue appears in the form of trabeculae, which occupy the middle, between two blood-vessels or groups of vessels (see Fig. 86). The basis-sub- stance of the trabecula? is finely striated, and here and there is also indistinctly lamellated. The transition of medullary into bone-tissue is demonstrated by the following forms : In larger medullary spaces, between two blood-vessels, in the longitudinal section of the bone, we often meet with groups and tracts of spindle-shaped medullary elements. These are either homogeneous, bright, of a yellowish color, or granular, and sup- plied with vesicular nuclei, or they may be without nuclei. They are all separated from their neighbors by narrow rims. In transverse sections these tracts appear as roundish or oblong fields, composed partly of shining and partly of pale granular lumps, which are the cross sections of the spindles. We also encounter similar groups at the borders of already developed bony trabeculae, and their general shape always corresponds to an elongated spindle or a rhomb. From these groups the trabeculae arise, by means of a deposi- tion of lime-salts at regular intervals in one portion of the * Translated from " Untersuchungen iiber das Protoplasma. IV. Die Entwickelung der Beinhaut, des Knochens," etc. Sitzungsber. d. Wiener Akad. d. Wissensch., 1873. 248 CONNECTIVE TISSUE. medullary corpuscles, while another portion remains unchanged and represents the bone- corpuscles. In accordance with the spindle shape of all medullary elements constituting a tract, the basis-substance assumes a striated appearance. In growing animals, we often see rows of medullary corpuscles at the borders of bone-tissue toward the medullary space, which have been termed the " osteoblasts " by Gegenbaur. * That the elements of these rows really produce the bone was acknowledged FIG. 101. — CORTICAL SUBSTANCE OF THE TIBIA OF A DOG, Six MONTHS OLD. TRANSVERSE SECTION. CHROMIC ACID SPECIMEN. M, medullary spacefilled with medullary elements, which at the border of the bone-tissue have assumed the shape of " osteoblasts." The center of the medullary space is occupied by a blood-vessel. S, first trace of the formation of a Haversiau system, composed of lenticular territories, which give to the circumference of the system a fluted appearance. T, globular territories, evidently the starting formations of new systems of lamella}. Magnified 500 diameters. also by later observers, as Waldeyer t and A. Rollett. { A row of osteoblasts is evidently the basis of a future lamella of bone. Before the infiltration with lime-salts takes place, a number of the osteoblasts are transformed into finely granular bodies, * Jenaisehe Zeitschr. f. Mediz. u. Naturwissenseh. 1864 and 186(5. t " Ueber den Ossificationsprocess." Archiv f. Mikroskopische Anatomic. Bd. i. 1865. t " Handb. d. Lehre von den Geweben." Herausg. v. S. Strieker. CONNECTIVE TISSUE. 249 destitute of nuclei, the connection of which with each other and with neighboring formations of the same nature is established by the delicate spokes which traverse the intervening light rims. After the infiltration with lime-salts is accomplished, an optical differentiation of the lamella into single " osteoblasts " is pos- sible in exceptional instances, when the lamella has the appear- ance of being composed of polygonal fields. More frequently the optical boundaries of the single osteoblasts fade, and only central portions of the lamella remain intact in the form of bone-corpuscles. In this case, therefore, a number of proto- plasmic bodies have coalesced into a slightly curved lenticular formation, a tissue-unit, the center of which is the bone-cell. yi£M$OTSlSRr FIG. 102.— VERTEBRA OF A HUMAN EMBRYO, FIVE MONTHS OLD. HORIZONTAL SECTION. CHROMIC ACID SPECIMEN. M, medullary space, with central blood-vessels and medullary tissue ; J?, first-formed globular territories, containing one or two central bone-corpuscles, with radiating offshoots. The territories lie against the trabecula of the original calcified basis-substance of the cartilage, F. Magnified 500 diameters. A number of such lenticular territories constitutes a single lamella of bone-tissue. In the compact and the so-called intermediate substance of 250 CONNECTIVE TISSUE. shaft-bones of growing and adult animals, we encounter numer- ous circular fields, containing one or more bone-corpuscles. We also find within the medullary spaces globular bodies, containing several nuclei, or only a number of nucleoli, sometimes exhibit- ing a uniform coarse granulation, due to the large points of intersection of the living matter. These masses, termed " myelo- plaxes " by their discoverer, Ch. Robin, are likewise the predeces- sors of bone formation, as I demonstrated in 1872.* Here a portion of the protoplasma is transformed into basis-substance, which at once becomes calcified, while the central portion is not changed into basis-substance, and remains as the bone-corpuscle or the bone-cell. (See Fig. 101.) We often find lenticular, multinuclear masses in the shaft- bones of growing animals, not only in the epiphysis at the borders of medullary spaces, but also in the vascular canals of the diaphysis. Such masses are separated from their neighbors by light rims, but also connected with them by delicate spokes of living matter. These are the first traces of a third kind of tissue-units of the bone, the lone-globules, which are known by Virchow to be the cell-territories proper. Each of these origi- nates from a multinuclear mass, and each contains one or more bone -corpuscles. Formations of this globular variety are met with also in the calcareous nucleus of the epiphyseal cartilage, at the ossifying border of the diaphyseal or intermediate cartilage, " and in the centers of calcification of short bones." [The last words are newly added.] (See Fig. 102.) The multinuclear bodies, which have sprung from medullary elements, are, therefore, the regular bone-formers, appearing first around the trabeculaB of the calcified basis-substance of cartilage, and later independently of. other formations. It depends entirely on the original shape of the medullary lumps, whether the bone-tissue assumes a striated, lamellated, or globular structure. Bone, therefore, as well as all other varieties of connective tissue, is a product of the medullary or embryonal tissue, the elements of which either split into delicate spindles, resulting in the formation of a striated basis-substance, or coalesce into len- ticular masses, a number of which unite in the construction of a lamella, or else coalesce into globular masses, from which arise the globular territorial formations of the bone-tissue. * " Studien am Knochen u. Knorpel," Mediz. Jahrb., 1872. CONNECTIVE TISSUE. 251 THE PROCESS OF OSSIFICATION IN BIRDS. BY L. SCHONEY.* My observations were made on a number of chickens and pigeons of different ages, the cartilages of the knee-joint, preserved and decalcified in chromic acid, being my subjects of study. Sagittal sections through the knee- joint of birds demonstrate that the bulk of the hyaline cartilage decreases with age, and that a transformation of cartilage directly into medullary ele- ments and indirectly into bone takes place only in young animals. In older ones completed bone-tissue bounds the cartilage, and in old pigeons the medullary spaces of the bone produce elongations which at a certain height penetrate the cartilage. In sagittal sections of young animals, we see with low powers of the microscope the following: At the articular surface, and near the perichon- drium, elongated, spindle-shaped cartilage corpuscles are found, which gradu- ally change into globular, nucleated corpuscles. The latter are met with in the middle portion of the cartilage, which is pervaded by medullary spaces, containing blood-vessels. The layer of the globular, nucleated corpuscles is followed by a narrow layer, in which there are small, flat cartilage corpuscles of a yellow-red color, bounding the district of calcification. The calcified basis-substance produces a pretty frame-work, which blends with the first- formed trabeculsB of bone-tissue, surrounding the medullary spaces of the epiphysis. With higher powers, we ascertain that the calcareous frame penetrates the basis-substance of the unchanged cartilage by means of pointed ends. Within the frame the cartilage corpuscles are distinctly recognizable. In many places the trabeculse of bone are directly attached to the calcareous frame, the feature distinguishing these formations being the bone-corpuscles of the tra- beculse. The medullary spaces are filled with globular, oblong, or spindle- shaped medullary elements ; besides these we often encounter protoplasmic masses of varying size, either multinuclear or destitute of nuclei, but uni- formly granulated. Spindle-shaped elements are most prevalent in the center of the medullary space, where the spindles are in connection with blood- vessels. (See Fig. 103.) The formation of medullary spaces is best studied in horizontal sections. First we recognize that at certain intervals a dissolution of the calcified basis- substance of cartilage takes place. It is true that the direct transformation of the cartilage into free protoplasma, with the formation of bright lumps, filling the medullary spaces, cannot be directly observed, but we may readily deduce such a transformation, as all medullary spaces in the neighborhood are inclosed by a calcified cartilage tissue, and the calcareous frame projects into the medullary space, as if broken. The transition of cartilage into medullary elements is initiated by the deprivation of a cartilage tissue unit or territory of its lime-salts. Adjoining the zone of decalcified cartilage there is found a layer of protoplasma con- sisting of numerous glistening lumps. These lumps are surrounded by a light narrow rim, which is seen occasionally to be traversed by filaments. The lumps bear a close resemblance to like formations in mammals, which have been described under the name of " hgematoblasts." The char- * Extracted from the essay of Dr. L. Schb'uey, in New York. " Ueberden Ossifications- process bei Vogclu." Archiv f. Mikroskop. Anatomic," Bd. xii., 1875. For the second part of this publication, see page 103. 252 CONNECTIVE TISSUE. aeter of many places, one of which I have illustrated, forces us to the conclu- sion that not only the cartilage corpuscles, but the whole mass of living matter stored up in the basis-substance of the cartilage, participates in the formation of medulla. No other interpretation is admissible, for a sudden transition of an apparently structureless basis-substance into a protoplasmic FIG. 103. — ARTICULAR CARTILAGE OF A YOUNG CHICKEN. SECTION. CHROMIC ACID SPECIMEN. SAGITTAL O, hyaline cartilage; CB, calcified basis-substance of hyaline cartilage; M, medullary space; B, trabecuUe of newly formed bone. Magnified 450 diameters. mass takes place without a trace of an intervening division of the cartilage corpuscles. (See Fig. 104.) At the border where the cartilaginous basis-substance is dissolved, we not infrequently meet with cartilage corpuscles, partly imbedded in the basis- substance, partly freely projecting into the previously formed medullary space, but I never saw marks of division of such corpuscles. Instead of CONNECTIVE TISSUE. 253 assuming, as is generally done, that a division of cartilage corpuscles takes place, it would be better to hold that, in the protoplasma set free by liquefac- tion of the basis-substance, there is at certain intervals a new formation of living matter, which results in the formation of the compact, glistening lumps. The multinuclear protoplasmic bodies, the " myelopaxes," according to this view, are simply freed territories of the cartilage tissue, and we can easily understand that occasionally a number of such territories coalesce into a common layer, before a further differentiation occurs. Unquestionably, the cartilage tissue is directly transformed into medullary tissue. The question how bone-tissue arises from medullary tissue is answered by the careful study of places where newly formed bone is closely attached to calcined cartilage. Here we notice a regular layer of finely granular psteoblasts FIG. 104. — KNEE-JOINT CAETILAGE OF A YOUNG CHICKEN, CLOSE TO THE BORDER OF OSSIFICATION. HORIZONTAL SECTION. CHROMIC ACID SPECI- MEN. C, calcified frame of basis-substance of hyaline cartilage ; H, zone from which the lime-salts have been dissolved ; M, newly formed medullary space. Magnified 700 diameters. between the decalcified basis-substance of cartilage and the newly formed bone. We can also trace every transition of free, uninfiltrated osteoblasts from the first steps till they finally fade in the basis-substance. The delicate granulation of the new osteogeneous basis-substance indicates that in the formation of bone the structure of the osteoblasts has not been completely lost. The bone of birds is essentially constructed like that of mammals. We find systems of lamellae around vascular canals ; we also find in the cavities of the basis-substance the bone-corpuscles, with their characteristic stellate offshoots. How far the presence of living matter within the basis-substance of the bones of birds corresponds with that of the mammal, further researches must reveal. 254 CONNECTIVE TISSUE. DEVELOPMENT OF BONE FROM FIBROUS CONNECTIVE TISSUE. A great part of the skeleton grows from fibrous connective tissue, independently of preformed cartilage. The strict distinc- tion which in former times was made between "cartilaginous" and "covering7' bones (see page 237) can be upheld only to a certain extent. It is true that in the production of covering bones no preformed cartilage participates, yet all the other bones of the skeleton, including the flat, the short, and the shaft bones, obtain only a part — viz., their cancellous portion, from preformed cartilage. Their cortical or compact portion is formed entirely from periosteum. Many observers have noticed, in dif- ferent places beneath the periosteum, cartilaginous layers ; but no importance need be attached to the presence of such a layer, as the formation of bone-tissue is materially similar, whether it is developed, from cartilage or from fibrous connective tissue. In the shaft-bones of human embryos ten to twelve weeks old, when no trace of calcification is yet noticeable, the cartilage is found to be surrounded by a delicate fibrous investment, — the .perichondrium, — between which and the surface of the cartilage there is a broad layer of medullary tissue. From the latter tissue arises the future cortex, simultaneously with the calcifica- tion and ossification of the cartilage in the center. At the four- teenth week there is already a distinct cortex around the diaphysis, at the same time when the transformation of the cartilage into medulla and cancellous bone has also commenced in the central portion of the diaphysis. The cortex and the calcified cartilage occupy about the same height, the middle por- tion always being the starting-point for their formation. Both portions, however, at first exhibit the cancellous structure, while the formation of regular lamellae begins to appear much later. The first-formed cancellous bone of the cortex has a striated structure agreeing with the spindle-shaped territories of the mother-tissue— the periosteum. The first-formed cancellous bone of the center, on the contrary, is composed of globular ter- ritories corresponding to the globular territories of the mother- tissue — the cartilage. It is only on this ground that we are able to understand the difference in the structure of the earliest- formed bones, the formation of "perforating fibers/' and the vascular system of the cortex. The law, however, according to which the peripheral lamellae and the Haversian lamellae are formed is not known. Probably there are three main layers in CONNECTIVE TISSUE. 255 the original periosteum, the fibers and blood-vessels of which stand at right angles to each other. The formation of bone from fibrous connective tissue is best studied in the skull of the human embryo, at about the fourth month of development. (See Fig. 105.) FIG. 105. — SKULL OF A HUMAN EMBRYO, FOUR MONTHS OLD. HORIZONTAL SECTION. CHROMIC ACID SPECIMEN. M, muscle-layer of the scalp ; SM, submuscular loose, freely vascularized connective tis- sue ; P, dense connective tissue of external pericranium ; B, first-formed trabeculae of bone ; O, layer of osteoblasts, attached to the trabecula) ; DM, dense connective tissue of internal pericranium — the future dura mater. Magnified 100 diameters. 256 CONNECTIVE TISSUE. We observe in the middle of a layer of fibrous connective tissue medullary corpuscles in longitudinal tracts (if cut trans- versely) 5 we see that a number of such corpuscles coalesce in order to be transformed into basis-substance, which almost instantaneously becomes infiltrated with lime-salts. In this way FIG. 106. — SKULL OF HUMAN EMBRYO, FOUR MONTHS OLD. HORIZONTAL SECTION. CHROMIC ACID SPECIMEN. F. fibrous connective tissue of the pericranium ; M, medullary space, with central blood-vessel ; £, first-formed trabecula of bone ; O, row of osteoblasts ; C, medullary cor- puscles of the inner pericranium, infiltrated with lime-salts. Magnified 500 diameters. trabeculae of bone, with large and irregular bone-corpuscles, are formed between two layers of fibrous connective tissue, the outer of which is the future external, the inner the future inter- CONNECTIVE TISSUE. 257 nal, pericranium. Five or six years after birth, the latter separates from the skull-bone and furnishes the dense investment of the brain, the dura mater. The first trace of a bony formation is invariably found in the middle field between two blood-vessels, in those localities, therefore, where there is the least nutrition, in the same manner in which the bony formation arises from carti- lage. The further growth of the trabeculae always proceeds from the medullary tissue, particularly from the medullary corpuscles, usually of only one side, lying close to the border of the tra- becula. This process is identical with that of the growth of trabeculae which have arisen from original cartilage. For studying the details of the formation of bone from fibrous connective tissue, with high amplifications of the microscope, the best subject also is the skull of a human embryo. (See Fig. 106.) We observe at first that, from single medullary corpuscles, often grouped together, basis-substance originates, which is at once infiltrated with lime-salts. The embryonal condition is next reestablished in these corpuscles by liquefaction of the basis- substance, and they are again plastids, which may afterward coalesce to form a larger mass, the first indication of a territory, exhibiting a central bone-corpuscle. Still later, a number of such masses, always through the intervening condition of uncal- cified medullary tissue, coalesce, and a trabecula arises, with a number of large and irregular bone-corpuscles, with their stellate offshoots. It makes no difference whether a blood-vessel is pres- ent from the beginning of the process, or whether it is formed afterward; it will always occupy the center of a medullary space. Upon close observation of the distances between the single bone-corpuscles, we are satisfied that at first from only a single corpuscle, and later from a limited number of medullary corpuscles, calcified basis- substance arises in the same manner, therefore, in w^hich the myxomatous basis-substance is formed (see page 148). At first, no distinct territories are present ; these are only recognized later, when the lamellated structure begins to appear. Obviously, the originally formed bone-tissue is not perma- nent. The bony trabeculae in turn are repeatedly reduced by liquefaction of their basis-substance to the embryonal or medul- lary condition, and new bone-tissue continues to form up to the time of full development of the body. A continuous absorption and reformation of bone is probably going on throughout life. 17 258 CONNECTIVE TISSUE. This, to some extent, is influenced by certain conditions — for example, on the skull-bones by the growth of the brain, both in a progressive and regressive way (Virchow). The regression is shown by the absorption in advancing age, producing the thin- ning of the bones so characteristic of the senile skeleton. THE GROWTH AND RETROGRESSION OF BONE. In the light of my researches, continued for ten years, the theory of an interstitial growth of the bone is no more tenable than is the interstitial growth of any other tissue. Basis-sub- stance, once formed, cannot increase in bulk by simple expansion. The observation that the bone-corpuscles in the old are farther separated than in the young is no proof of an interstitial growth, since Steudener has demonstrated (see page 220) that the periph- eral portion of each bone-corpuscle in advancing age is trans- formed into basis-substance. New tissue forms exclusively from embryonal or medullary tissue, and an already formed tissue must return to its embryonal condition, by liquefaction of the basis- substance, before a new tissue can arise. An augmentation of the bulk of a tissue can take place only by new formation of the living matter of the embryonal corpuscles, that is, an increase of the number of the embryonal corpuscles. This law was first, though incompletely, established by H. Miiller, in 1858 j it was asserted as to the growth of bone-tissue by L. Ranvier in 1865, and announced to be a universal law for all tissues by myself in 1873. The process of inflammation, first accurately studied by S. Strieker, also illustrates the law. In- flamed tissue, according to S. Strieker, returns first to its embry- onal condition before new formation arises. We are indebted to A. Kolliker's accurate researches * for the discovery that every growing bone on its surfaces exhibits regu- larly recurring " planes of resorption " (Resorptions-flachen). The bone to the naked eye looks rough, as if corroded ; under the microscope the bone-tissue proves to be spongy, provided with bay-like erosions or excavations, which, as a rule, contain multi- nuclear bioplasson masses. Kolliker maintains that these bodies are growing into the bone-tissue from without, and that they actually absorb and destroy the bone structure. For this reason "Die Normale Resorption des Knochengewebes u. ihre Bedeutung fiir die Entstehung der Typischen Knochenformen." Leipzig, 1873. CONNECTIVE TISSUE. 259 he proposed for their designation the rather alarming name of bone-breakers — " osteoklasts." The multinuclear bioplasson bodies were first described by Robin under the title of " myeloplaxes." Virchow termed the same formations " giant-cells " ; English authors, " myeloid cells." They are, as I demonstrated in 1873 (see chapter on inflammation), the bioplasson formations of the bone-tissue itself , the territories of the basis-substance of bone, either after decalci- fication and liquefaction of the basis-substance, or before the formation of a territory of bone. (See Fig. 107.) FIG. 107.— SURFACE OF THE SCAPULA OF A KITTEN. CHROMIC ACID SPECIMEN. C, lamellated bone, with bone-corpuscles ; G, a single territory of bone-tissue liquefied, resulting in the formation of a multinuclear plastid ; M, coalesced masses of multinuclear plastids. Magnified 600 diameters. We see these bodies, not only in medullary spaces of all juvenile bones, but also in the planes of absorption at the surface of growing bones, beneath the periosteum, and in inflamed bone. They certainly are not extraneous, but the medullary corpuscles themselves, coalesced into larger layers for the production of 260 CONNECTIVE TISSUE. territories in forming bone. An already formed bone, being- deprived of its basis- substance either by advancing growth or by the inflammatory process, at once falls back into the bioplasson stage, and exhibits first bioplasson territories, which later again divide into medullary corpuscles. All territories and all medul- . 3 ifi'trjy <***+*+ Mi «t ««•.<*• Q* * *W. '•'••i.%;r:« Mv **^ '< '.'*•••• # • g"3 s »o0^o «. ' » f ' V Ortk "^ » «" ,*3 V ' ^ • f *-«« W**A*\*£*&ftt~f 1 1 •s-s lary plastids remain interconnected by means of delicate filamentsr which traverse the surrounding light rims, and such a connection is also established with the adjacent reticulum of bioplasson of unchanged bony basis-substance. In these masses we usually observe all stages of development of bioplasson, from the solid CONNECTIVE TISSUE. 261 homogeneous lump into a nucleated plastid, and from this into plastids with nucleoli only, and finally into granular plastids, destitute of nuclei and nucleoli. (See page 55.) The interpretation here given does not, however, explain the appearance of such bioplasson bodies in dead bone. Ivory sticks, driven into living bone for surgical or experimental purposes (Billroth), and necrotic bone likewise, exhibit bay-like excava- tions at their surfaces, filled with multinuclear bioplasson masses. Obviously, these masses could not have originated from the dead ivory and the necrotic bone. Their bay-like excavations are ex- plicable, as Virchow has already shown at length, by assuming in them a decalcification and liquefaction of the basis-substance, corresponding with the territories ; and, since Ziegler has demon- strated that even between two thin glass plates, placed into the subcutaneous tissue of animals, migrating plastids accumulate and coalesce into multinuclear masses, a similar process may be admitted for the filling of these bay-like excavations. That the multinuclear bodies really arise from the liquefied living bone-tissue itself I have ascertained in provisional teeth, the erosions of which were studied, in the last few years, in my laboratory, by Dr. Frank Abbott; and there can be no doubt that they are a growth of medullary corpuscles from without, whenever the bone is deprived of its life. Cartilage with advancing age gradually decreases in amount ; in the aged we find only a thin layer of articular cartilage. In old dogs, the thin layer of the articular cartilage, toward the marrow spaces, is bordered by a well-marked lamellated zone of bone. (See Fig. 108.) That the bone-tissue itself does decrease in bulk with advanc- ing age is best illustrated by the toothless jaws of the aged. The cause of this absorption and atrophy of the bone-tissue, invading both the cancellous and compact structure, has not yet been elucidated. VIII. MUSCLE-TISSUE. MUSCLE, the motor apparatus proper, is a formation of living matter . in a reticular arrangement. The points of intersection in smooth muscle • are irregularly scattered ; in striated muscle, they are arranged with great regularity in the so-called sarcous elements. The connecting filaments are ex- tremely delicate, allowing slow but, considering the bulky forma- tions of muscle, powerful contractions of the living matter. Muscle is constructed on the plan of an amoeba, or that of any other plastid. The difference is that the points of inter- section of the living matter in the amoeba are small and irregu- larly distributed, while in muscle the nodules of the reticulum are large and more or less regular in their arrangement. The fluid contained in the meshes of the reticulum in the amoeba corresponds to the muscle fluid between the rows of sarcous ele- ments. Contractility is inherent in the amoeba and every plas- tid; therefore, also in muscle, independently of nervous influence. The independent contractility of muscle was proved by J. Miiller, in 1834, after division of the nerves, and by Claude Bernard, in 1857, after abolishing the action of the motor nerves by curara. The enlargement of the nodules of living matter, the shortening of the connecting filaments, and the narrowing of the mesh- spaces produces the contraction in the amoeba, as well as in the muscle (see page 29). The difference is that, while in the amoeba one portion of the body is in contraction, the other, on the con- trary, in extension : in all highly developed animals one muscle, or a group of muscles, is in the state of contraction, while MUSCLE-TISSUE. 263 another muscle, or a group of muscles, is in that of extension. Muscles which simultaneously work in such an opposite manner are termed " antagonists." Muscle formations are of two varieties. In the tissue of the unstriped, smooth, or involuntary muscle the Moplasson is stored up, without much regularity, in comparatively small spin- dles. In the tissue of the striped or voluntary muscle the bioplas- son is distributed regularly in the shape of sarcous elements, in relatively large spindles. 1. SMOOTH OR UNSTRIPED MUSCLE. Smooth muscle is constructed of spindle-shaped plastids, which are usually nucleated, and are held together in bundles by means of a delicate cement-substance, surrounding each spindle. Ensheathing the bundles there is a delicate layer of fibrous connective tissue, the perimysium. The muscle nature of these spindles was discovered by A. Kolliker in 1847. The spindles vary greatly in size. Very small spindles are found in the skin and large arteries, medium-sized spindles in the muscle-layers of the mucous membranes, and very large spindles in the pregnant uterus. In all instances the separating cement-substance can be stained brown by nitrate of silver, and the brown line thus produced is pierced at right angles by deli- cate light lines which correspond to the minute transverse spokes interconnecting all spindles. The spokes are visible with high powers of the microscope, without the addition of a re-agent. The granules of the spindle are, as a rule, coarse, so as often to conceal the central oblong or rod-like nucleus, which, however, is easily seen in transverse sections. The granules not infre- quently exhibit a partially regular arrangement, especially toward their tapering ends, which produces an appearance resembling the sarcous elements of striated muscles. The out- lines of the spindle are smooth and regular when in a state of rest ; but they become slightly scalloped by contraction, when the body of the spindle is shortened and broadened. The bundles of smooth muscles of the skin are most abundant in the region of the nipple and in the scrotum. They run in oblique directions, interlacing sometimes at acute angles. The oblique section of a bundle is characterized by short spindles ; 264 MUSCLE-TISSUE. the transverse section by disks, exhibiting, when the razor has passed through the middle of the spindle, the bright central nucleus. (See Fig. 109.) Bundles of smooth muscle are often found connecting into a reticulum — f. i., in the scrotum, the labia majora, the prostate gland, the urinary bladder. The bundles are spread in flat layers throughout all larger tubular formations of the ali- mentary and the genito-urinary tract. We find in these tubes at least two layers, of which the one nearest the epithelial sur- FIG. 109. — BUNDLES or SMOOTH MUSCLE IN THE DERMA OF THE SKIN OF THE NIPPLE. CHROMIC ACID SPECIMEN. L, longitudinal, O, oblique, T, transverse section of a bundle ; D, derma of the skin ; N, probably termination of a nerve. Magnified 500 diameters. face is circular, and the other longitudinal. In the intestinal tract the mucous membrane has two delicate layers (transverse and longitudinal), while the tube possesses in addition two layers, of which the circular is far more developed than the longitudinal. In the stomach, the bladder, and the uterus, numerous oblique bundles run between the circular and longitudinal. In the lower third of the oesophagus smooth MUSCLE-TISSUE. 265 muscles appear, replacing the striped muscles, which are present in the two upper thirds ; the boundary line between the two is not sharply marked, as the fibers of both varieties blend with each other (Treitz). The pregnant uterus is constructed of numerous and large muscle-fibers, also arranged in longitudinal, transverse, and oblique bundles. The bioplasson in this situation is very abun- dant, giving the spindles a coarsely granular, nearly homogene- ous, appearance, without a distinct nucleus. Every large spindle is composed of a number of smaller ones. The boundary line between the latter is often marked at the periphery of the large spindle only, or else a faint oblique trace of demarcation may be observed within a large spindle. (See Fig. 110.) Blood- and Lymph-vessels are numerous in the smooth muscle- tissue, producing an elongated, more or less rectangular, retic- ulum. Larger blood- and lymph-vessels are found in the denser formations of connective tissue between groups of bundles, while the delicate perimysium surrounding the bundles contains only capillaries. The nerves of smooth muscle bundles, after repeated plexi- form ramifications, branch in the form of delicate axis fibrillae in the cement-substance between the spindles (M. Lowit). Some observers claim that the axis fibrillse enter the spindles and ter- minate in the nucleolus (Frankenhauser), or pierce the nucleus and the nucleolus, in order to again reach the plexus on the opposite side of the spindle. Here, as well as in striated muscle, a terminal nerve-hill may exist, as indicated in Fig. 109, though its relations are not yet sufficiently studied. 2. STRIPED MUSCLE. Striped muscle is composed of comparatively large fusiform and sometimes blunt spindle-shaped fibers, which are separated from each other by means of a delicate connective-tissue forma- tion, and are held together in bundles by means of broader lay- ers of the same tissue. Each bundle is composed of a varying number of fibers. The fiber is built up by more or less regularly arranged layers of sarcous elements, — formations of bioplasson, — which are interconnected in all directions by delicate filaments of bioplasson, while the meshes between the sarcous elements contain a non-contractile, non-living fluid, which can be artifi- cially pressed out of every muscle. 266 MUSCLE-TISSUE. The distribution of the muscle-fibers in the belly of a muscle is best observed in transverse sections, with lower powers of the microscope. (See Fig. 111.) Each fiber is surrounded, and a certain number of them are inclosed, by fibrous connective tissue, the former being termed FIG. 110. — BUNDLES OF SMOOTH MUSCLE OF THE HUMAN UTERUS, SHORTLY AFTER DELIVERY. CHROMIC ACID SPECIMEN. L, longitudinal, O, oblique, T, transverse section of bundles : P, perimysium, containing blood-vessels, C ; JK, plastids in the connective tissue, probably the first trace of muscle-fibers. Magnified 500 diameters. internal perimysium, the latter, external perimysium. The con- nective tissue is the exclusive carrier of blood- and lymph-ves- sels, also of the nerves, and often contains fat- globules. The M USCLE-TISSUE. 267 external perimysium unites into tendinous septa, and these unite to form the fasciae and aponeuroses. Each muscle-fiber, besides, is again inclosed by an extremely delicate hyaline, elastic membrane, — the sarcolemma, — first de- scribed by Th. Schwann, in 1839. This sheath has not yet been found in the muscle of the heart. The sarcolemma is distinctly FIG. 11]. — RECTUS MUSCLE OF THE EYEBALL OF MAN. VERSE SECTION. CHROMIC ACID SPECIMEN. TRANS- PE, external perimysium, containing, besides fat-globules and capillary blood-vessels, also an artery, A, and bundles of medullated nerves, N; PI, internal perimysium, ensheath- ing the single muscle-fibers. F. Magnified 200 diameters. seen only in transverse sections of muscle-fibers, but it becomes visible also in longitudinal fibers, when broken through, or after treatment with dilute acids, which destroy the muscle- tissue without attacking the sarcolemma. The sarcolemma appears as an apparently structureless, extremely thin, cor- rugated membrane, destitute of nuclei. (See Fig. 112.) The attachment of the muscle-fiber to tendinous or periostea! tissue is by means of the internal perimysium, while the sarco- lemma terminates around the blunt or sharp point of the muscle- fiber (C. Toldt). The tendons often exhibit rounded excavations r in which rest the blunt ends of the muscle-fibers 5 thickened elongations of the tendon penetrate to various depths between the blunt extremities of the muscle-fibers. The perimysium,, 268 M USCLE-TISSUE. after blending with the tendon or periosteum, is, as a rule, sup- plied with a large number of plastids. Groups of plastids are sometimes seen filling the triangular space above the point of -v/ FIG. 112.— MUSCLE OF TONGUE OF MAN. CHROMIC ACID SPECIMEN. L, longitudinal muscle-fiber, broken off and exhibiting its structureless sheath — the sar- colemma, 8; N, medullated nerve-fiber, terminating in the motor hill, H; T, transverse sec- tion of a muscle-fiber ; P, the perimysium, holding capillary blood-vessels, C, and nerves, ATl. Magnified 500 diameters. the muscle-fiber, which often looks as if split into small spindles, with sarcous elements irregularly distributed. (See Fig. 113.) Regarding the minute structure of striped muscle-fibers, there is the widest divergence in the views of histologists. Still, the MUSCLE-TISSUE. 269 structure is extremely simple, and proved to be so by the description of E. Briicke, in 1857 (see page 127). The only addi- tion I have to make is that all sarcous elements, whatever may be their size and arrangement, are uninterruptedly connected in both longitudinal and transverse directions. The division of the muscle-fiber into the longitudinal fibrillas of Schwann depends upon a very close aggregation of the sarcous elements in a longitudinal direction. The beaded appearance of these fibrillaa can be explained only by the presence of filaments, con- necting the sarcous elements in a lengthwise direction. Muscles kept in alcohol ex- hibit this characteristic very p. distinctly. If, on the con- trary, sarcous elements are aggregated more closely in transverse direction, either after mechanical injuries, by teasing, or after the applica- tion of certain re-agents, such as dilute muriatic, nitric, lactic acid, or the stomachic juice, Bowman's disks will be the result. The smaller the sarcous elements in a muscle-fiber are, the more rapid and con- tinuous the action of the mus- FlG us.— ATTACHMENT OF MUSCLE- cle, and vice versd. The heart, FIBERS TO PERIOSTEUM. FROM THE being the most active of all SCAPULA OF A CAT. CHROMIC ACID muscles, has the smallest sar- SPECIMEN. C011S plpTYlPTlt^ TllP blower M' P°inted end of muscle-fiber; S, the sarco- lemma, closely attached to the perimysium, P, ail ailimal in its motions, the which blends with the fibrous connective tissue of ., T periosteum. Magnified 500 diameters. larger are its sarcous ele- p ments. In accordance with what I said on the structure of bio- plasson in general, it will be readily understood that contracti- bility is increased with the smallness of the points of intersection of the reticulum. Normal, fresh muscle-fibers sometimes exhibit very small and irregularly distributed sarcous elements and active contractions under the microscope. Muscles of the craw- fish, the lobster, and the water-beetle are, on account of the large size of their sarcous elements, excellent objects for study. As 270 MUSCLE-TISSUE. S2 Briicke has stated, the arrangement of the sarcous elements in the live muscle-fiber greatly varies ; the reasons for this are not yet clearly understood. Nevertheless, the schema of the struct- ure of muscle-fiber was established by Heiisen under conditions when the rows of sarcous elements were divided by a single transverse light line, and Merkel divided this line into two. A. Schafer adopted the schema of two narrow rows between two broad ones. All these conditions are sometimes met with, but they are not by any means the only, or the most common, ones. The theories of Krause's muscle-caskets, and Schafer's connect- ing lines, between the two narrow distal row's, have arisen from the erroneous idea that the filaments run between the sareous elements, while in reality they directly connect them, often at their edges. Not infrequently -SI tne sarcous elements, under the microscope, appear in oblique position, owing to the general die shape of the muscle- fiber, and a dark line is seen on one end of the sarcous element, which is a shortened view of its breadth. This dark line, also, had led observers to wrong con- clusions. Chloride of gold is a good re-agent for bringing to view with great distinctness all the above-described features. That 114.— STRIPED MUSCLE OF THE the narrow rows themselves are WATER-BEETLE (HYDROPHILUS Pi- composed of small, sarcous ele- CEUS). STAINED WITH CHLORIDE OF ments is shown in Fig. 114. This condition is exceptional, «», row of large, and s* row of smaii, sar- and still more so is the appear- cous elements, the latter stained deeper violet « -, , , than the former. All rows interconnected by 81106 OI double narrow TOWS, delicate filaments. Between the rows an un- comnared With thp armPflrflnop colored liquid. Magnified 1200 diameters. illustrated in Fig. 41, page 128. That in one muscle-fiber different arrangements of the sarcous elements may occur, can be seen in the muscle of craw-fish. Often in the fresh muscle the regular rows disappear, and a uniform granulation is for a moment visible, while in the next moment the rows are reestablished. In aU these conditions the muscle-fiber executes contractions. (See Fig. 115.) MUSCLE-TISSUE. 271 The contraction of a muscle to the naked eye consists in the shortening and the broadening of its belly. Accordingly, we see under the microscope, in a contracted muscle-fiber, all the rows of sarcous elements approaching each other, and every sarcous element becoming broader. This is done at the expense of the connecting filaments, which become shortened. The liquid be- tween the rows spreads by pressure in the transverse direction. By contraction, nothing is lost from and nothing added to the mus- cle-fiber. In extension the muscle-fiber is elongated, and accordingly the sar- cous elements gain in length and their rows sepa- rate. Kanvier drew atten- tion to the presence of two lands of muscles even in mammals, especially in rabbits — the pale trans- parent and the red opaque varieties. He claims that the pale muscles contract more rapidly, upon appli- cation of the galvanic cur- rent, than the red ones; that the pale muscles have a more marked transverse and the red a more marked longitudinal striation, and also that the nuclei of the pale muscles are less numerous than those of the red. In transverse sections of muscle-fibers (see Fig. 112) we often notice a central, pale, irregularly granular nucleus, or sometimes two such nuclei. Instead of, or in addition to, granular nuclei, we also see small, irregular, solid lumps of bioplasson in the midst of sarcous elements, which formations correspond to the oblong nuclei and to the rows of coarse granules in a longitudinal sec- tion. From the central nucleus radiating offshoots emanate, which interconnect the coarse granules, and group the sarcous elements in circular or radiating formations, which are sometimes very gracefully arranged. These are the celebrated muscle-nuclei FIG. 115. — STRIPED MUSCLE OF THE CRAW- FISH (ASTACUS FLUVIATILIS). STAINED WITH CHLORIDE OF GOLD. Si, row of large sarcous elements, splitting into rows of smaller ones, S* ; between the rows of large sarcous elements rows of small ones ; all rows inter- connected ; N, nuclei on the surface of the fiber. Magnified 1200 diameters. 272 M US OLE- TISS UE. of Max Schultze. They are evidently remnants of the embryonal development, " undifferentiated protoplasm," as M. Schultze himself said. They often fall out, especially from very thin sections, and leave one more central or two more peripheral openings, bounded by a jagged or stellate outline. The formations termed nuclei really reveal the history of development of the muscle-fiber. Each fiber is constructed on the plan of a bundle of connective tissue — for example, the tendon. It is likewise composed of one large or a number of smaller territories, and each territory has resulted from the coalescence of a number of plastids, some or portions of which remain unchanged solid or granular Moplasson, while in all surrounding plastids the points of intersection of the bioplasson re- ticulum assume the regular ar- rangement of sarcous elements. At the borders of the territories sometimes a layer of elastic sub- stance is formed, and a whole system of territories is, as a rule, ensheathed by a solidified, so- called elastic substance, the sar- colemma, an offspring of the bio- plasson liquid. Th. Mar go was the first observer who proved positively that each muscle-fiber arises from a number of plas- tids, the so-called " sarcoplasts," against the view inaugurated by LoN" Schwann, that a single muscle- CHROMIC «, ° , fiber is an enormously grown " cell." In some places the muscle- fibers have been found bifurcat- FIG. 116. — MUSCLE OF THE HEART OF A NEWLY BORN CHILD. GITUDINAL SECTION. ACID SPECIMEN. NN, nuclei on the surface of the nmscle- nber ; CP, delicate perimysium, with oblong nuclei and capillary blood-vessels. Magni- fied 500 diameters. ing, f. i., in the tongue, the muscles of the eyeball, and the heart. In the heart the muscle- fibers are very small, freely branching, and united into bundles in the manner of a felt- work. It was said before that here the sarcous elements are extremely small, while the nuclei are very numerous. This is the only muscle which for eighty or more years is in continuous activity — the first to begin and the last to stop. (See Fig. 116.) The medullated motor nerves, upon entering the muscle, split into numerous branches, which course in a transverse or oblique MUSCLE-TISSUE. 273 direction along the fibers ; the branches, repeatedly bifurcating and connecting, produce a plexus in the perimysium. From this plexus arise the terminal nerve-fibers, each of the muscle-fibers being supplied with at least one fiber. In some amphibia, the medullated nerve-fiber penetrates the sarcolemma and divides into a number of longitudinal axis fibrillae on the surface of the muscle. In most animals there has been observed a terminal disk, the " motor hill" of Doyere. This is a finely granular discoid, slightly elevated formation, curving with the surface of the muscle-fiber, with a num- ber of faintly outlined nuclei. The medullated nerve-fiber on reaching the hill becomes deprived of its myeline in- vestment, while the elastic myeline sheath (Schwann's sheath) fuses with the sarco- lemma, so that the motor hill, according to the views of most observers, lies un- derneath the sarcolemma. W. Krause maintains its position outside the sarco- lemma (see Fig. 111). Kiihne has found a broad layer of fused medullated nerves upon the hill in all higher animals. The axis cylinder of the nerve-fiber connects directly with the delicate bioplasson reticulum within the motor hill, and this is A, artery ; V, vein. Magnified 800 diameters. again connected by delicate filaments to the next sarcous elements. Thus a continuous con- nection between the nerve and the muscle is established by bridges of living matter. Some medullated and perhaps sensorial nerve- fibers branch in the perimysium without entering the formation of the motor hills. 18 FIG. 117. — STRIPED MUSCLE OF CAT. INJECTED. 274 MUSCLE-TISSUE. Blood-vessels are very numerous in striped muscles. They are seen running in the external perimysium as larger arteries and veins, and when reaching the surface of the bundle they ramify into capillaries, which are found in the internal perimy- sium without entering the muscle-fiber itself. All vascular for- mations of the striped muscle are characterized by very marked bifurcations at right angles, and this is especially a prominent feature of the branches of the arterioles and the first capillaries arising from them. (See Fig. 117.) Lymph-vessels are also numerous formations in the tissue of the striped muscle, and, as regular injections show, they always form a closed system of capillaries, which accompany the arterial and venous blood-vessels. THE STRUCTURE OF THE MUSCLE OF THE LOBSTER. BY M. L. HOLBROOK, M. D.* When we read the history of those scientific investigations which have been made by our most excellent observers during the last forty years, we can hardly fail to be convinced that even the simplest facts of natural philosophy are only established after long-continued and patient research. Truth is rarely or never reached in a straight line, but only by a tortuous and zigzag course. At times we seem to have it almost within our grasp, and then it becomes lost to view, and we are compelled to seek for it in a new direction. All this is true when applied to the research of muscular structure, as we shall see. The muscular system, as we know, constitutes the motor apparatus of all complex animal bodies. By it all movement from place to place, all change of shape and form, are accomplished. All motions of the body are based upon the contraction of the two Varieties of muscle-fibers, for they possess in the highest degree the same property seen in every portion of living matter, in every simple organism, in every plastid — the power to contract. From this it is fair to conclude that muscle must also be living matter. Our modern views on the structure of striated muscle date back as far as the year 1839, when Th. Schwann,t in his celebrated researches on the iden- tity of the structure of the animal and plant, maintained that the striated muscle is composed, of- innumerable, extremely delicate fibrillae, of a beaded or rosary-like appearance. A number of such fibrillse, the beads of which stand in one line close together, would, according to his view, form a muscle bundle. If we look at a muscle-fiber, we notice alternating light and dark lines of a definite width, and these, according to Schwann's view, originated in the regularity in which the thick and thin portions of the fibrillse are placed side by side. W. Bowman t demonstrated that the fibers sometimes break up, when sub- * Printed from the author's manuscript. t " Uutersuchungen iiber die Uebereinstimmung," etc. Berlin, 1839. t Todtl's Cyclopedia, 184P. MUSCLE-TISSUE. 275 jected to mechanical injuries or chemical re-agents, into transverse disks. The cleavage of the fiber lengthwise gives us the fibrillae, while a transverse cleavage gives the disks. By splitting the fibers in a longitudinal and trans- verse direction, this investigator obtained innumerable small cylindrical or square pieces, which he called the sarcous elements. He maintained with great positiveness that the striations in the muscle-fiber are due to a difference in the refracting power of the intermediate substance, and that the longitudinal and transverse splitting are not essential properties of the muscle, but are due to mechanical or chemical injuries. The next investigator who has thrown light on this subject was E. Briicke.* This observer maintains that the sarcous elements are by no means invariable and unchangeable formations in the living muscle, but that they are rows of corpuscles, differently arranged at the moment of death. On examining the fiber with polarized light, he came to the conclusion that the sarcous elements are constructed of very small, invisible particles, which he named disdlaklasts. Upon the grouping of these minute bodies, he believed, depended the varying formation of the sarcous elements. Briicke argues that the rows of sarcous elements are double refracting, while the spaces between them are only simple refracting. As to the nature and consistence of these intermediate layers he offers no opinion. C. Heitzmannt pointed out an interconnection of the sarcous elements, both longitudinally and transversely, by means of delicate filaments of living matter, in the same manner as the granules of bioplasson in the amoeba are connected. My own observations point strongly to the correctness of this assertion. The observations of the investigators now mentioned are the principal sources of our knowledge of striped muscle. The later researches on this subject made by Hen sen, W. Krause, W. Engelmann, Heppner, and Alb. Schafer have added little to our knowledge, as these authors have ex- plained the structure of striped muscle in a complicated manner, and far differently from what we really see. Perhaps Cohnheim's discovery of the peculiar fields in transverse sections of frozen muscle deserve a remark, as they appear to have been formed by the process of freezing, as we shall see later on. If we take from the lobster a minute piece of perfectly fresh muscular tissue and transfer it, together with a drop of the blood of the animal, to a glass slide, and cover it quickly with a thin cover-glass, we may see, with moderate powers of the microscope, the fibers composing it, of a nearly uniform breadth. These fibers are separated from each other by exceedingly narrow light spaces or rims, which in some places contain a granular mass. A number of fibers are kept together by a delicate fibrous tissue, in which are held the vessels and nerves. These latter features are seen best in a trans- verse section of the muscle. Within the fiber may be noticed two kinds of substance ; one is opaque, of a dim luster ; the other is light, uncolored, not shining. In many places the two substances alternate with each other in such a way .as to form rows, running in the transverse direction of the fiber, or we may sometimes observe that the opaque substance is distributed without * " Untersuchungen iiber den Bail 'd. Muskelfasern mit Hiilfe des polar. Lichtes." Denk- schr. d. Wiener Akad. Bd. xv., 1857. t " Untersuchungen liber das Protoplasnia." Sitzungsber. d. Wiener Akad. d. Wissensch., 1873. 276 MUSCLE-TISSUE. regularity in the form of granules in the light substance. The rows composed of the bright substance vary greatly in their width. Sometimes a line of it is as broad as the light substance ; or the shining substance may very much surpass the light one in breadth ; or a broad line may be split in the center by an exceedingly narrow light line. In other words, the bright substance varies greatly in its amount in relation to the light substance. When we come to use higher powers of the microscope, we find that each shining line is composed of a large number of square, cylindrical, or prism- shaped pieces, which are the sarcous ele- c z> ments of Bowman. (See Fig. 118.) We also see that the light layer between the rows of sarcous elements is traversed by extremely delicate grayish filaments, connecting all the rows within a muscle- fiber. When the sarcous elements are separated, so as to render the light inter- stices between them visible, we again see the grayish filaments connecting the sar- cous elements in a transverse direction. Lastly, we see that all the interstices be- tween the muscle-fibers are traversed by delicate grayish threads or spokes, con- necting the adjoining muscle-fibers, and also connecting the sarcous elements with the granules present between the fibers. From this it is evident that the mi- nute structure of the fresh muscle of the lobster is reticular. The uodulations of the reticulum correspond to the sarcous elements, and vary greatly in size, while the rectangular connecting fibrillse always are very delicate. All observers agree that the sarcous elements are the active agents in mus- cular contraction, because they are the formations that change their shape and place during the contraction of the muscle, while the intermediate light spaces are filled with a non-contractile liquid. In order to bring out more perfectly the structure of muscle than could be done in its natural state, I used, with success, a one-half per cent, solution of chloride of gold, which is known to stain living matter violet. I also tried the freezing of the muscle by means of rhigoline-spray, in order to cut the sections more easily and perfectly. But this changed the texture, at times even completely destroying it, and I was compelled to resort to other means. Here I may state that I suspect the peculiar condition of the muscle discovered by Cohnheim, and previously mentioned, may have been caused by freezing. I did not succeed in obtaining those peculiar fields, described by him, in transverse sections of the muscle of the ox, made while the tissue was slightly frozen. The next re-agent which I used was a one-half per cent, solution of FIG. 118. — MUSCLE OF LOBSTER. A, muscle-fiber with single rows of sarcous elements; _B, muscle-fiber with divided rows of sarcous elements ; C, sin- gle torn fibrilla, composed of divided rows of sarcous elements ; D, single fibrilla without distinct structure. CD, features from specimens preserved in chromic acid solution. Magnified 1200 diameters. MUSCLE-TISSUE. 277 chromic acid, which is known to preserve and harden living matter, but not to destroy its character or otherwise injure it. The results with the chromic acid specimens were found to be the same as those observed in the fresh muscle. Here, too, the alternating layers of sarcous elements and the inter- stitial layers were plainly recognized. The rows of sarcous elements varied greatly in breadth and form. If we tease a chromic acid specimen, we obtain delicate longitudinal fibrillse, because we break the transverse connec- tions— the filaments of living matter which unite them together. Such an artificially isolated fibrilla may appear beaded, as was asserted by Th. Schwann, or it may exhibit a nearly uniform width throughout its entire length, or the entire fibrilla may appear bright and homogeneous, and show no trace of any difference in its optical properties in any part. This can be explained by the fact that the sarcous elements within the muscle-fiber may coalesce, or approach each other so closely that the intermediate light sub- stance becomes invisible. We may explain the beaded condition of the fibrilla either by saying that the living matter produces a solid square piece, — the sarcous element, — which above and below is hollowed out and incloses the interstitial liquid, or by saying that from both edges of the sarcous ele- ment connecting filaments run to the neighboring sarcous element. In a longitudinal section of a muscle-fiber, we not infrequently meet with oblong solid masses of a highly refracting nature, which are termed by the authors, the nuclei. That such formations are present, not only on the sur- face of the muscle-fiber, but also in its interior, is best demonstrated in trans- verse sections, where, in the center of the fiber, we almost invariably observe a more solid mass, with stellate offshoots which subdivide the muscle-fiber into smaller fields. The presence of these large bioplasson masses within the muscle-fiber has a close connection with the history of the development of the muscle. Similar formations do, however, occur in the muscles of mammals. I have especially observed globular or oblong bioplasson masses in the center of the muscle-fiber of the ox. In making transverse sections, these masses are very liable to fall out, or, perhaps, be drawn out by the razor, leaving an empty space behind. This gives the incorrect impression that the muscle- fiber is hollow in its center. Every muscle-fiber in mammals is known to be ensheathed in an extremely delicate, firm, so-called elastic or hyaline membrane — the sarcolemma. This layer is present around the muscle-fibers of the lobster also. The statement of E. Briicke, which has gained general assent, that the sarcous elements are possessed of a double refracting power, is, I am con- vinced, incorrect ; at least, my own observations on the muscle of the lobster with polarized light are not in accord with this view. I made a large number of observations on specimens prepared in different ways, and also with perfectly fresh specimens, moistened with a drop of the blood of the animal, and could only obtain the phenomena of polarization in specimens of some thickness. In every case when the specimen was very thin, and allowed the light to pass through it freely, there was no evidence of polarization. W. Kuhne (1864) failed to obtain polarization with the amoeba, and my observation with the muscle-fiber of the lobster coincides with his. It is Doyere's and Kiihne's discovery that the motor nerves, which control the action of the muscles, never enter the muscle fibers, but terminate on their surface, generally in the form of hills, the so-called motor Mils. I have observed similar formations in the muscle of the lobster, and, further, I have 278 MUSCLE-TISSUE. observed a direct connection of the bioplasson of the motor hill with the adjacent sarcous elements by many delicate grayish filaments of bioplasson Thus, it becomes intelligible that the influence of the motor nerve may be transmitted to a number of sarcous elements, from which it may spread toward the points of the fiber and produce contraction. As a result of these investigations, I am led to the conclusion that the striated muscle of the lobster is constructed on the same plan as the striated muscles of the highly developed mammals. It is a formation of living matter of a reticular structure, the points of intersection being the sarcous elements, the means of connection being delicate filaments extending in a longitudinal and transverse direction. IX. NEKVE-TISSUEJ NERVE-TISSUE is composed of living matter, seen either as an extremely delicate reticulum, or as apparently homo- geneous filaments — the axis-cylinders. The reticulum is of a uniform width, without well-marked points of intersection (see page 128, Figs. 42 and 43), as seen in the gray substance of the brain and the spinal cord. In the reticular bioplasson, formations are imbedded, which bear resemblance to nuclei, with distinct walls and larger branching bodies, usually nucleated and reticu- lar in structure — viz.: the ganglionic elements. From the retic- ulum of the gray substance, and also from that of ganglionic elements, somewhat thicker filaments emanate, — the axis-cylin- ders,— which are the essential part of the structure of nerves. The axis-cylinders, as a continuous formation, pervade all tissues of the body except the horny epidermal tissue, and serve for the transmission of either sensory impressions from the peri- phery to the center, or motor impulses from the center to the periphery. Nerve-tissue, as such, is destitute of blood- and lymph- vessels. * This chapter will be found more deficient in histological facts than, per- haps, any other of the book. The reason is that I have not as yet given very much time to the study of nerve-tissue, this being the most unsatisfactory and discouraging portion of histology. I prefer, therefore, to be incomplete in this matter until I am able to make positive assertions, based on personal observation, instead of relying too much on what others have said. The par- ticulars that I shall give concerning the architecture of the brain I have taken from the ingenious publications of Th. Meynert. 280 NERVE-TISSUE. It is only the accompanying and ensheathing connective tissue which carries vessels. In order to facilitate the study of the nervous system, it is convenient to subdivide it into three main portions, all of which form one continuous mass of tissue — i. e., the central portion, the conducting portion, and the terminal portion. 1. NERVE-CENTERS. In the brain and the spinal cord, it is only the gray sub- stance which can be called nerve-center, as the white substance is composed of conducting nerves. The ganglia of the sympathetic nerves may also be considered as central organs. (A)' Brain. According to Th. Meynert,* the gray substance of the brain may be divided into four groups : (a) The uppermost mass of gray matter, from which the entire white sub- stance of the brain takes its rise, is the superficial gray substance of the cerebral lobes — the cortex cerebri; (b) Collections of gray matter are the ganglia of the cerebrum — the corpus striatum, the three members of the lenticular nucleus, the thalamus opticus, and the corpora quadrigemina ; ( c) The tubular gray matter, which invests the cavities of the brain as a direct prolongation of the gray substance of the spinal cord, traceable through the fossa rhomboidalis, the aqueduct, the middle ventricle, into the tuber cinereum and the infundibulum ; (d) The gray substance of the cerebellum, arranged partly in layers, partly in central aggregations, and in connection with the gray formations of the caudex cerebri, which are traversed by the medullary substance of the cere- bellum. The gray masses are connected by means of fibrous tracts of the white substance. The gray cortex of the brain receives all the sensory impressions from the outer world, and from it arise the motor impulses, communicated to the motor nerves. The medullary or white substance of the large hemispheres of the brain — the corona radiata — furnishes the routes of this system of projections of the first order ; and, moreover, this system is connected by bundles of nerve-fibers with the cerebellum. The fibers of this projection system take mostly a radi- ating course ; additional formations of this system are the commissures in the corpus callosum, which connect the corresponding portions of the right and the left side, and the systems of association, which connect different regions of the cortex in one hemisphere. The ganglia of the cerebrum interrupt the projection system of the first order, and in them a reduction of the number of the fibers of this system * " A Manual of Histology," by S Strieker. American edition, 1872. NEEVE-TISSUE. 281 takes place. The bundles of nerve-fibers, leaving the ganglia and entering the central tubular gray investment of the brain, are considered as the pro- jection system of the second order. This system is composed of two portions. One for the impulse of voluntary muscle action, arises from the corpus striatum and the nucleus lenticularis, penetrating the pedunculus cruris cerebri ; the other portion is the route of reflex motion, and takes its origin from the thalamus opticus, the corpora quadrigemina, and the corp. genicula- tum internum, running into the tegmentum cruris cerebri. The tubular gray matter gives rise to the peripheral nerves, which are greatly increased in number, as compared with their reduction in the ganglia. The peripheral nerves represent the projection system of the third order. The accumulations of nerve elements in the tubular gray matter are termed its nuclei, and this gray matter itself lies bare on the base of the brain in the lamina perforata posterior and the infundibulum. The cerebellum is independent, to a certain degree, of the projection systems of the brain, though connected by the crura cerebelli with the cortex cerebri, and probably by the crura cerebelli ad pontem. It connects with the spinal cord through the fasciculi gracilis and cuneiformis and the restiform bodies. The medulla oblongata connects the brain with the spinal cord ; in this formation the projection system of the second order is reduced to its simplest form, as observed in the spinal cord. Both halves of the medulla oblongata are connected by the pyramidal decussations, and both contain a number of gray nuclei, the superior and inferior olivary bodies and the nucleus of the pyramis. The cortex of the brain has a common form of stratification, from which, however, deviations are found in the occipital extremity, in the cortex bound- ing the fossa Sylvii, in Ammon's horn, and in the olfactory bulb. There are five strata of the cortex cerebri in man, which are as follows : (a) The most superficial layer, which consists mostly of connective tissue, and of a few small ganglionic elements and delicate nerve-fibrillae ; (b) The second layer is marked by a large number of small, multipolar ganglionic elements ; (c) The third and broadest layer contains multipolar ganglionic elements, decidedly surpassing in size those of the second layer. Their shape is either pyramidal or fusiform, with the longitudinal direction vertical to the brain surface. Their upper projection divides into a delicate reticulum ; the lower passes without division toward the white substance ; (d) The fourth layer contains small globules, with very delicate offshoots : these, possibly, may be only connected with the sensory nerves ; (e) The fifth layer holds spindle-shaped ganglionic elements, which lie parallel to the surface of the brain, and have undivided offshoots. Meynert considers them to be the intercalated cells of the system of association. In the occipital extremity there are eight layers ; the third typical layer is wanting, but the granular formation is composed of three layers. In the cortex, bounding the fossa Sylvii, the fifth layer is markedly developed, pro- ducing the claustrum. The cortex of the Ammon's horn has no granular layer, while the motor elements of the second and third typical layers are very abundant. The cortex of the olfactory bulb in its upper portion is cov- ered with a white layer, and exhibits from below upward : a layer of non- medullated nerve-fibers, a layer of the glomeruli olfactorii, a layer of 282 NEEVE-TISSUE. spindle-shaped ganglionic elements, and a layer of granules, the fibers between which unite with those of the uppermost white medullary layer. The Origin of tlie Cerebral Nerves. As before stated, the tubular gray matter, which is located around the aquseductus Sylvii and extends backward, connecting with the floor of the fourth ventricle, gives rise to the cerebral nerves. In this gray matter we find groups of multipolar ganglionie elements, which are known to be the nuclei of the nerves. There are also exceptional formations found in the tracts along the anterior pair of the corpora quadri- gemina, which consist of very large globular ganglionie elements. These con- stitute the sensitive roots of the trigeminus. Similar formations are found in the anterior nucleus of the root of the auditory nerve. Brown and black pig- ment granules are present in the substantia ferruginea of the fossa rhomboid- alis and in the substantia nigra of the pedunculus cerebri. The nucleus of the hypoglossal nerve has very large ganglionie elements and a reticular forma- tion, produced by a close combination of layers of the gray and white sub- stance. In the medulla oblongata such formations occur : in the pyramis, in the fasciculi restiformis, gracilis, and cuneiformis. The olfactory nerve arises from the olfactory bulb ; its external and larger tract is connected with the gyms uncinatus or subiculum cornu Ammonis ; its internal tract connects with the frontal extremity of the gyrus fornicatus, and its middle tract with the head of the corpus striatum. The optic nerve very probably starts from several nuclei, one of which is, perhaps, the anterior pair of the corpora quadrigemina (Corp. bigem. super.). The motor oculi and troclilear nerve spring from a cylindrical group of ele- ments below the aquseductus Sylvii, near the median line. This nucleus, by means of nerve-bundles, is in connection with the corpus striatum and the corpus bigem. superius. The trigeminus nerve has several nuclei. The upper sensitive nucleus is composed of groups of ganglionie elements along the tegmentum of the ante- rior pair of the corpora quadrigemina ; the middle sensitive nucleus is located below the upper one ; the under sensitive nucleus exists in the medulla oblongata, and is traceable into the posterior column of the spinal cord. The motor root of this nerve has its nucleus in the fossa rhomboidalis, extending anteriorly to the aquseductus Sylvii. 'The abducent nerve originates from a nucleus in the anterior portion of the fossa rhomboidalis, and is in connection with the deeper situated nucleus of the facial nerve. The facial nerve originates from three roots arising from a nucleus in the depths of the floor of the fourth ventricle, where large ganglionie elements with bulky offshoots are seen. The auditory nerve has its nucleus in the floor of the fossa rhomboidalis, extending from the median line toward the pedunculi cerebelli, and gaining in thickness as it advances. The median portion is the inner acoustic nucleus, which may be divided into three parts. The broad outer portion has large pyramidal ganglionie elements. An anterior nucleus is located at the side of the peduDculus cerebelli. The glosso-pnaryngeal and vagus nerve arise from one common nucleus, the anterior portion of which, reaching the internal acoustic nucleus, belongs to the glosso-pharyngeal nerve, while the posterior portion, in the ala cinerea of the fossa rhomboidalis, constitutes the vagus. The spinal accessory nerve originates partly from the nucleus of the vagus, NERVE-TISSUE. 283 partly from a columnar formation, closely connected with the nucleus of the vagus and traceable into the anterior column of the spinal cord. The hypoglossal nerve has its nucleus in the posterior portion of the fossa rhomboidalis, close to the median line. There is also a direct passage of fibers from the crus cerebri into the hypoglossus by way of the raphe. (B) Gray Substance. The gray substance is the only nerve- tissue found in the brain of the lower vertebrates. Here, instead of ganglionic elements, nuclei are present, which, especially around the ventricles, collect in regular rows, representing in its simplest relations the bioplasson of the nervous center. (See Fig. 118.) The presence of connective tissue in the gray substance is unquestionable, as it is the carrier of the numerous blood-vessels of the gray substance. The finest ramifications of connective tissue, however, have not been discovered, but are still the sub- ject of animated controversy among histologists. It seems that the finest offshoots of the ganglionic elements, producing an extremely delicate reticulum, first discovered by T. Gerlacli, deserve to be classified among nervous structures, inasmuch as in this reticulum there is no indication of a basis-substance — an essential part of all varieties of connective tissue. It may be that connective and nervous tissue blend with each other so intimately that an accurate determination of either of them is impossible. The blood-vessels of the gray substance are characterized by the presence of a lymph-sheath. His was the first to draw atten- tion to this fact. According to him, each blood-vessel is en- sheathed by an adventitial coat of endothelial structure, and the space between the tube of the blood-vessel and the investing tube of the lymph-vessel varies greatly in width. Boll's view con- cerning the lymph-sheath is somewhat different. The cortex of the cerebellum is composed of three layers. The outermost is called the gray layer, and exhibits, with low powers of the microscope, a delicate granular appearance, which, with high powers, proves to be a reticulum, considered by histolo- gists to be a connective-tissue formation. Within the reticulum there are scanty, small, branching ganglionic elements 5 on the innermost portion we notice fibrous tracts, in a direction par- allel to the surface. The middle so-called cell-layer contains large, branching, and nucleated ganglionic elements, mostly pear- shaped, standing in a vertical or oblique direction to the surface. These bodies, in honor of their discoverer, are termed Purkinje's cells. From the outer pole of each corpuscle originates an offshoot, 284 NERVE-TISSUE. which freely bifurcates and sends its branches into the outer gray layer. From the inner pole arises an offshoot, which, without ramifications, traverses the granular layer and runs into the FIG. 118. — ANTERIOR LOBE OF THE BRAIN OF A TREE-FROG. SAGITTAL SECTION. /, investing sheath of connective tissue; R, rows of nuclei; V, ventricle, with endothel- ial investment ; N, bundle of medullated nerve-fibers. Magnified 50 diameters. white substance. The inner so-called granular layer is composed of heaps of small globular bodies, mostly of a high degree of NERVE-TISSUE. 285 refraction and similar to the bodies found in the granular layers of the retina. Their nature is unknown. The hypophysis cerebri exhibits two lobules, which are separated from each other by a number of venous blood-vessels. The posterior small portion is an elongation of the infundibulum, and probably belongs to the nervous struct- ures. The anterior large lobule is a glandular formation, and, as Von Mihal- kovits has demonstrated, was originally a club-like prolongation of the oral cavity of the embryo. The pineal gland is attached to the brain by means of connective tissue, and has no nerve elements in its interior. It is composed of alveoli, contain- ing corpuscles in a reticular arrangement. In the middle portions, the alve- oli are filled with the cerebral sand, consisting of globular or mulberry-like concretions, as a rule exhibiting a concentric striation. The organic material in these bodies is infiltrated with carbonate of lime and phosphate of magnesia. The gray substance of the spinal cord is in the center through- out the whole length of the cord, reaching the greatest size in the cervical and the lumbar portion, where the largest nerves for the extremities arise. The general form of the gray substance in tranverse section resembles a butterfly, the two anterior larger wings being distinguished from the posterior smaller ones by a shallow depression. Each half of the gray substance represents a column, and the two are connected by commissures travers- ing the so-called medullary cone or commissure leaf (Markblatt, Commissurenblatt). (See Fig. 119.) Each gray column exhibits a large anterior, or motor, horn, and a smaller posterior, or sensitive, horn. In the outer portion of the anterior horn we find very large motor ganglionic elements, varying greatly in size and shape in different portions of the spinal cord. In some portions of the posterior horn ganglionic elements are absent, and in their place accumulations of nuclei- like bodies are observed. The posterior horn, from its soft con- sistence, bears the unnecessary name, "gelatinous substance/' which name by some histologists is given to the commissural portions in the neighborhood of the central canal. The latter portion is also called the central ependyma thread, or the central gray nucleus. The central canal, a prolongation of the cerebral ventricles, is lined by a columnar endothelium, which in youth shows distinct cilia, while in older individuals the cilia are not so plainly marked. (C) Ganglionic Elements. The ganglionic nerve elements (" gan- glion cells ") are scattered throughout the gray substance of the 286 NERVE-TISSUE. brain and spinal cord j they vary greatly in size and shape. The smallest of these bodies are kindred to those formations of the gray substance considered as nuclei. Many of them are doubt- ful in their nature — f. i., the " cells of Deiters," which by some observers are considered as nervous, by others as connective- tissue, corpuscles. The larger ganglionic bodies exhibit a dis- tinct angular or fusiform shape, and give rise to nerve-fibers, therefore are real nerve-centers. The largest ganglionic elements are found in the lateral portion of the anterior or motor horn of the spinal cord. In the spinal cord, the groups of ganglionic elements are dis- Cc /sc FIG. 119. — SPINAL CORD OF FROG. TRANSVERSE SECTION. A F, anterior longitudinal fissure ; PF, posterior longitudinal fissure ; W, white substance ; A C, anterior commissure of the gray substance ; MO, anterior or motor horn of the gray col- umn, rich with ganglionic elements ; SC, posterior or sensitive horn ; CO, central canal ; PC, commissure layer, with fibers of the posterior commissure ; MR, anterior or motor roots; PR, posterior or sensitive roots of nerves; MN, intervertebral ganglion, the connection with PR broken ; V, pia mater, holding a blood-vessel. Magnified 50 diameters. tributed in the following way : In the anterior horn we notice three groups of ganglionic elements, not distinctly marked throughout the whole ; the largest group lies in the lateral por- tion ; a smaller group in the anterior portion, near the greatest protrusion of the anterior horn, and a third group, the smallest. NERVE-TISSUE. 287 near the median line. A fourth group of ganglionic elements, constituting the columns of Clarke, is found only in the thoracic portion of the spinal cord, in the foremost part of the posterior horn, near the posterior commissure. In the posterior horn the ganglionic elements are always small, scattered, and with com- paratively few offshoots. The illustration is taken from the third group of the anterior horn. (See Fig. 120.) The ganglionic elements are bioplasson formations, which, according to the number of offshoots, are termed unipolar, FIG. 120. — GANGLIONIC ELEMENTS FROM THE ANTERIOR OR MOTOR HORN OF THE SPINAL CORD OF A CHILD. U, unipolar ; JB, bipolar ; T, tripolar ; Q, quadripolar ganglionic element ; G, gray sub- stance, containing small, shining nuclei, and a number of axis-cylinders; CL, capillary blood-vessel, longitudinally, CT, capillary blood-vessel, transversely, cut, each surrounded by the lymph-sheath. Magnified 600 diameters. bipolar, tripolar, quadripolar, or multipolar. The number of offshoots is in close relation with the size of the corpuscle. A light space is often found around the ganglionic element j this is the so-called " periganglionic space," which, in all probability, is artificially produced by the shrinkage of the neighboring tissue. 288 NEEVE-TISSUE. The reticular structure of these bodies was first described by C. Frommann, in 1867. This reticulum is usually very distinct, especially when the formations of nuclei, nucleoli, and nucleolini (L. Mauthner) are well marked. The reticular structure is not peculiar to these bodies, but is one of the general features of all bioplasson. The offshoots of the ganglionic elements are of two kinds : the broad, so-called protoplasmic offshoots of Deiters, and the narrow, axis-cylinder offshoots. Of the former, we know that they connect neighboring elements and branch out into the gray substance, where they divide into an extremely delicate reticulum, first described by T. Gerlach. This author further asserts that the ganglionic elements of Clarke's columns, and perhaps those of the posterior horns also, have no other than branching offshoots. The narrow axis-cylinder offshoot takes a more or less straight course, and enters the white substance without ramifications, thus being a future nerve-fiber. Axis- cylinder offshoots arise also from the gray substance, without any connection with ganglionic elements. M. Schultze and others maintain that the axis-cylinder has a delicate fibrillated structure, and that the fibrillae spread in the body of the ganglionic element after the manner of a fan. This assertion is based upon observation of teased specimens, and should be cautiously received. I have often studied the brain structure of freshly killed rabbits, both with and without the addition of an indifferent liquid, and could never discover any fibrillated structure in the axis-cylinders. Both the broad axis-cylinders and the broad offshoots have a delicate reticular structure, like that seen in the ganglionic elements themselves. The finest axis-cylinders are apparently solid or slightly vacu- oled. In the gray substance, especially in young animals, many axis-cylinders exhibit varicose enlargements, which are consid- ered by histologists to be post-mortem appearances. This, again, is an, assertion which I must contradict, as I have fre- quently observed such enlargements in fresh specimens (see page 129, Fig. 43). I must also contradict the assertion of histologists that medullated nerve-fibers arise directly from ganglionic ele- ments. These bodies are present only in the gray matter, where no medullated nerve-fibers exist, but only bare axis-cylinders ; obviously, therefore, the axis-cylinder, emanating from the gan- glionic body, must run for a certain distance without a myeline investment. Very little is known regarding the course taken by the nerve- NERVE-TISSUE. 289 fibers within the gray substance of the spinal cord. The nerves of the anterior or motor roots originate from the motor ganglia ; FIG. 121. — ANTERIOR PORTION OF THE SPINAL CORD OF A CHILD. TRANSVERSE SECTION. F, anterior longitudinal fissure ; P, pia mater ; W, white substance, traversed by offshoots of the pia mater ; O, passage of the anterior or motor nerves through the white substance; G, gray substance, containing JV, ganglionic elements; C, central canal, containing granular coagulated cerebro-spinal liquid. Magnified 150 diameters. a small number of nerve-fibers reach the motor roots from the white substance. From the reticulum of Gerlach nerve-fibers 19 290 NER VE-TISSUE. arise which reach the opposite horns, partly through the anterior commissure, partly by running upward to the medulla oblongata, where they decussate. The posterior roots also arise from two bundles, one of which traverses the posterior commissure. Ac- cording to Grerlach, it is also probable that from the reticulum of the posterior horn nerve-fibers originate, which in this horn and in the white substance take a centripetal course. The structure of the posterior horn is considered to be mainly connective tissue, especially in its gelatinous portion. (D) The white substance of the spinal cord, as well as that of the cerebrum and cerebellum, is composed of medullated nerve- fibers, which in the spinal cord run in a longitudinal direction and furnish the outer investment with its nerve supply. This substance borders on the anterior and posterior longitudinal fissure, and is pierced by numerous offshoots of the pia mater, which divide and subdivide the nerve-bundles into larger and smaller groups. (See Fig. 121.) The anterior and posterior roots of the spinal nerves also pro- duce smaller fissures in the lateral portions of the white sub- stance, the sulcus lateralis anterior and posterior, by which the white substance is divided on either side into an anterior, a lat- eral, and a posterior cord. In the thoracic and cervical portions of the spinal cord the posterior part is again divided into halves, the middle division of which is termed the delicate cord, and the larger lateral portions the wedge-shaped cords. The medullated nerve-fibers of the white substance vary greatly in size. The coarser offshoots of the pia mater send lat- eral prolongations between the nerve-fibers, every one of which has a delicate investment of connective tissue — the perineurium internum or neuroglia. According to Gerlach, this connective tissue is rich in elastic substance, and furnished with small glob- ular or angular nuclei, but has a relatively scanty supply of blood-vessels. In transverse sections of the white substance, we especially recognize the medullated nerve-fibers by their graceful ensheath- ing reticulum of connective tissue and their central, bright axis- cylinder, which readily takes up the carmine stain. (See Fig. 122.) Each nerve-fiber is provided with a delicate outer investing membrane — the myeline sheath, or Schwann's sheath — which holds flat, oblong (in the transverse section spindle-shaped) nuclei. Former observers denied the existence of this sheath ; NEEVE-TISSUE. 291 but G-erlach concluded that it must be present, and I positively maintain its existence. The next layer is the myeline investment, which, in thin sections, is invariably destroyed. In its place, a delicate, knotty retictiliim is visible, to the existence of which Kiihne and Ewald* first drew attention. These observers claim that the reticulum in the myeline layer is horny or keratoid, because it resists digestion with pepsine and tripsine. They also traced in the gray substance a similarly resistant reticulum. In the meshes of this reticulum the myeline is contained. The mye- line investment in some nerves is very narrow, and in others completely wanting. The next layer is a delicate sheath — the FIG. 122.— WHITE SUBSTANCE OF THE SPINAL CORD OF A CHILD. TRANSVERSE SECTION. PE, connective-tissue offshoot of the pia mater — the external periueurium ; PI, lateral connective- tissue offshoots around the nerve-fibers — the internal perineurium; M, oozed-out myeline investment, with inclosing myeline sheath; A, axis-cylinder, with inclosing axis, cylinder sheath. Magnified 600 diameters. axis-cylinder slieatli, discovered by L. Mauthner — similar to the myeline sheath. The center is occupied by the bright, homo- geneous-looking, usually roundish axis-cylinder, from which delicate radiating spokes emanate and go to the axis-cylinder sheath. In longitudinal sections the axis-cylinder is plainly visible only where the investing sheaths are stripped off, but where the * Verhandlungen der Heidelberger Gesellschaft, 1876. 292 NERVE-TISSUE. sheaths are preserved and the myeline is absent, a faint trace only of the axis-cylinder is discerned. We recognize the myeline sheath with its oblong nuclei ; at pretty regular intervals it sends out transverse septa through the myeline investment, the signifi- cance of which will be spoken of later. The reticulum of the myeline sheath is very distinct where the myeline has oozed out. The axis-cylinder sheath can be recognized here and there, though it is often very diffi- cult to distinguish it from the stretched myeline sheath, which may lie close to the axis-cylinder. (See Fig. 123.) (E) The Connective-tissue Investments of the Brain and the Spinal Cord. The brain and spinal cord have three membraneous investments — the dura mater, the arach- noidea, and the pia mater. The spaces between these are filled with a varying amount of cerebro-spinal liquid. The space between the dura mater and the arachnoid is called the subdural space; that be- tween the arachnoid and the pia mater bears the name sub- arachnoidal space, and is tra- versed by trabeculae of con- nective tissue, uniting the membranes. In the spinal canal this space is subdivided into halves by the Lig. den- ticulatum, and contains the large blood-vessels at the base of the brain. A third space between the pia mater and the surface of the brain may be pro- duced artificially by the injection of liquids from without ; it is called the epicerebral space. The dura mater of the skull represents the periosteum of the cranial bones, while in the spinal canal there is a periosteal investment of the vertebrae, in addition to the dura mater. It is composed of very firm, dense interlacing fibers of connective tissue. Its outer layer is well provided with blood-vessels enter- FIG. 123. — WHITE SUBSTANCE OF THE SPINAL CORD OF THE HORSE. LON- GITUDINAL SECTION. A, axis-cylinder; AS, axis-cylinder sheath; N, nucleus of the myeline sheath ; MS, mye- line sheath, with oblong nuclei. Magnified 600 diameters. NEEVE-TISSUE. 293 ing the skull-bones j while the inner layer, that which alone forms the dura mater of the spinal cord, has a comparatively scanty supply of blood-vessels. The inner surface of this mem- brane is lined with a delicate layer of endothelia. The arachnoidea is composed of much more delicate bundles of connective tissue than the dura mater (see Fig. 55, page 160), and probably contains neither blood-vessels nor nerves. Both its surfaces are covered with endothelia. It sends numerous trabeculae in an oblique direction into : The pia mater, which is also constructed of delicate inter- lacing bundles of connective tissue and supplied with numerous blood- and lymph- vessels and nerves. The prolongations of the pia mater into the brain and spinal cord convey mainly capil- lary blood-vessels, as the division of the arteries into capillaries takes place before their entrance into the nerve-centers. The telae choroideae are freely vascularized formations of the pia mater ; their blood-vessels are coiled in bundles, and produce the lobules which are covered with large, partially ciliated, endothelia, often containing pigment and fat-granules. (F) The Ganglia. Nerves of the cerebro-spinal system are provided in certain localities with spindle-shaped, or globular or crescent-like, enlargements, the ganglia, which consist of an accumulation of ganglionic elements, greatly varying in size, and arranged either in rows or in clusters, which are more numerous at the periphery of the ganglion than at its center. The manner in which nerve-fibers are connected with the gan- glionic elements has not yet been elucidated. Each ganglion is ensheathed by a connective-tissue capsule, and divided by septa of connective tissue into smaller portions ; sometimes every single large ganglionic element is inclosed by a connective- tissue sheath, the connective tissue being always freely sup- plied with blood-vessels. The ganglia of the sympathetic nerve system contain smaller ganglionic elements and numerous globular bodies, exhibiting the features of lymph-corpuscles or nuclei rather than those of ganglionic elements. The ganglionic bodies are, as a rule, mul- tipolar. In those of the frog the central axis-cylinder was found to be surrounded by a delicate spiral fiber (Beale), which is also considered to be an offshoot of the ganglionic element. J. Arnold claims that the straight central fiber comes from the nucleolus of the ganglionic body, while the spiral fiber originates from its periphery. All these assertions have been contradicted, and need further proof before they can be received. 294 NERVE-TISSUE. 2. NERVES. Nerves are thread-like formations of bioplasson connecting the nerve-centers with the periphery of the body. They are of two kinds: first, those endowed with a myeline investment, FIG. 124. — BRANCH OF THE MOTOR OCULI NERVE OF MAN. L, longitudinal, T, transverse section of the bundle ; PE, external perineurium ; PI, internal perineurium; ML, myeline investment; A, axis-cylinder; M, transverse sections of muscle-fibers. Magnified 600 diameters. the medullated or white nerves; and secondly, those which are without a myeline investment, the non-medullated or gray nerves. NEEVE-TISSUE. 295 (a) Medullated Nerves. These compose the white substance of the brain and of the spinal cord, and all the nerves springing from the brain and the spinal cord, with the exception of the olfactory and auditory nerves. They invariably run their whole course without branching. The constituent parts of medullated nerves are best studied in specimens where, owing to a wavy course of the nerves, the razor in cutting produces alternately longitudinal and transverse sections. (See Fig. 124.) We see that each nerve-bundle is made up of a varying number of fibers. The bundle is surrounded by a somewhat broader layer of fibrous connective tissue, the external perineurium^ from which arise delicate membranes of connective tissue, ensheathing each single fiber j this formation has received the name of the internal perineurium. Both the external and internal perineurium are provided with a large number of blood-vessels. Next, there is a delicate hyaline layer with distinct nuclei, the myeline sheath, or sheath of Schwann. This sheath incloses a layer of a semi-fluid fatty substance, the myeline or nerve-fat, or the white substance of Schwann. At comparatively regular intervals the myeline investment is traversed, according to L. Ranvier, by transverse septa, which he found to be in connection with the axis-cylinder sheath (Mauthuer), and closely related to the development of the medullated nerves. The myeline investment is separated from the central axis-cylinder by a delicate hyaline sheath, the axis-cylinder sheath (Mauthner). This incloses the central axis- cylinder, which may be either round or oblong, and is the con- ducting part of the nerve-fiber. In transverse sections this is easily recognized from its bright, almost homogeneous, appear- ance, while in longitudinal sections it is invisible if the myeline be present, and only faintly visible if the myeline be absent. Not infrequently we find two axis-cylinders in one nerve-fiber. Together with the large medullated nerve-fibers in the same bundles there are sometimes found fibers without and also fibers with a very delicate myeline investment. The latter formations probably belong to the sympathetic system. The myeline is a fatty substance, diifering from ordinary fat, however, in both its optical and chemical characteristics. From the fact that a delicate reticulum is still preserved in the space between the sheaths of the myeline and that of the axis-cylinder (see Fig. 123), and from the fact that fat is a product of living matter, we may conclude that the myeline is, perhaps, produced from only a part of the living matter, while the other part 296 NEBVE-TISSUE. remains unchanged in the shape of a reticulum, or, still more probably, the myeline originates in a manner different from that of fat — viz., from the lifeless liquid contained in the meshes of bioplasson. In specimens of medullated nerve-fibers the myeline is often found exuded from the nerves in the form of numerous slightly refracting formations with a concentric striation, which is evidently caused by a slow oozing and aggregation of the myeline. (See Fig. 125.) FIG. 125. — MYELINE DROPS, OOZED OUT FROM THE OPTIC NERVE OF A BULL. N, bundle of medullated nerve-fibers ; M, myeline drops ; F, fat-granules. Magnified 400 diameters. By staining fresh medullated nerve-fibers with a solution of nitrate of sil- ver, the bundle was found to be covered by an endothelial coat. Each fiber exhibits a series of marks, which correspond to the " annular constriction " of Ranvier. The axis-cylinder at the point of constriction exhibits a number of dark brown transverse lines (Frommann). Between every two constrictions a transverse bar has been found, of a biconical shape, through the broadest portion of which the axis-cylinder passes. Ranvier concludes from these facts that each section of the nerve-fiber is a unit, a tubular cell, filled with myeline, like a fat-globule, which he terms the inter annular segment, with an oblong nucleus in its investing membrane. The axis-cylinder, according to this author, pierces a series of interannular segments without interruption ; while Engelmann, on the other hand, claims that each interannular con- striction corresponds to an interruption of the axis-cylinder. This latter NEEVE-TISSUE. 297 assertion is contrary to our ideas of nerve action and so is the assertion of other histologists, that the axis-cylinder is a fluid. In peripheral formations of connective tissue — f. i., in the female breast, the derma of the skin, etc. — we often encounter single medullated nerve-fibers, exhibiting the characteristic feat- ures just described. Their double contour is due to the presence of the myeline sheath, and not to the refraction of the myeliner for the double contour is visible even when the myeline is absent.. The fluted appearance of medullated nerve-fibers is partly due to FIG. 126. — MEDULLATED NERVE-FIBERS OF THE FEMALE BREAST. N, nerve-libers ; C, capillary blood-vessels ; F, fat-globule with vacuoles. Magnified 60G1 diameters. the presence of the oblong nuclei in the myeline sheath, and partly to constrictions along the course of the nerve-fiber, to the presence of which Remak, and recently Schmidt, drew attention,, the nature of which is not yet understood. All these features are marked characteristics of medullated nerve-fibers, in contra- distinction to those of capillary blood-vessels. (See Fig. 126.) In nerve-bundles no ramification of the fibers takes place, but. as they approach the periphery, either motor or sensitive, they branch very freely, and one fiber often splits into a number of slightly thinned branches. 298 NERVE-TISSUE. (J)) Non-medullated Nerves. These nerves have the appearance of being bare axis-cylinders, destitute of a myeline investment. There are comparatively broad so-called Remak's fibers (1838). in large numbers, in the sympathetic and in the cranial portions of the olfactory and auditory nerves. These fibers exhibit on their surface a number of oblong nuclei, and they have often a delicate sheath, kindred to the axis-cylinder sheath of medullated nerve-fibers, to which, probably, the nuclei belong. These nerves are described as indistinctly fibrillar in structure, and at certain intervals showing clusters of small, bead-like forma- tions, giving rise to the so-called necklace appearance. All nerves in the earliest stages of embryonal development are non- medullated. Besides these broad non-medullated nerve-fibers, there are others which are narrower, scattered throughout the gray sub- stance of the brain and of the spinal cord. They run in bundles with the medullated nerve-fibers, and also with nerves of the sympathetic system. Such fibers, which are bare axis-cylinders, represent the origin of all nerve-fibers, even of the medullated, in the gray substance. In many instances, the medullated fibers become again non-medullated upon approaching the periphery of the body. With high amplifications of the microscope, some of the larger non-medullated nerve-fibers show distinctly a delicate reticular structure. Others exhibit a number of minute vacuoles in their interior; still others, and these are the finest nerve-fibers, have a homogeneous appearance and give no evidence of structure. (See Fig. 127.) Many of the finest non-medullated nerve-fibers show oblong, varicose enlargements along their course, and bear the name of varicose nerve-fibers. The varicosities are certainly not post-mor- tem appearances, as they are visible in the perfectly fresh condi- tion of nerve-specimens, as stated above. 3. TERMINATIONS OF NERVES. The manner in which the ultimate nerve filaments terminate in the tissues and at the periphery of the body is known only in part. There are two varieties, either terminations of medul- lated nerves as such, or terminations of non-medullated nerves. The latter are either continuations of originally medullated NEEVE-TISSUE. 299 nerves, which have become destitute of their myeline investment upon approaching the periphery, or they are non-medullated? sympathetic nerve-fibers. (a) Termination of Medullated Nerve-fibers. The motor Mil of nerves controlling the action of muscles (see chapter on muscle tissue). The tactile corpuscles of Merlcel in the web of the feet of water-birds, in the trunk of the pig, etc. These are finely granu- lar, distinctly nucleated, globular bodies, into, which the axis- cylinder penetrates, and which are located in the upper layers of the derma or in the epithelium — f. i., in that of the external root- sheath of the tactile hairs. Sometimes two or more such corpus- cles are attached to the medullated nerve-fiber. The tactile corpuscles of Meissner or Wagner are present in the papillae of the derma of the skin, often below the level of the FIG. 127. — MEDULLATED AND NON-MEDULLATED NERVE-FIBERS FROM THE RETINA OF A BULL. Sl, myeline sheath, with oblong nuclei and Y#2) transverse septa. The myeline oozed out. N, non-medullatecl nerve-fibers, with varicose enlargements. Magnified 600 diameters. papillae, and especially numerous in the tips of the fingers and toes. These are ovoid or globular formations, with transverse or spiral striations and oblong nuclei arranged in the direction of the striations. One or more medullated nerve-fibers enter the corpuscle at one pole. Sometimes two or more such corpuscles are clustered together ; but the way in which the termination of the axis-cylinder is effected is unknown. The bulbs of Krause are found in the conjunctiva, in the mucous membrane of the floor of the mouth and of the lips, of the soft palate and the tongue, in the glans penis and in the cli- toris. They are ovoid or mulberry-shaped bodies, in which the 300 NERVE-TISSUE. axis-cylinder terminates as a knob. Longworth found them in some conjunctivas, but not in all, and saw their interiors filled with nucleated corpuscles. Waldeyer considers these bodies to be intermediate formations between the tactile and the Pacinian corpuscles. The corpuscles of Pacini (discovered by Vater in 1741) are found in the subcutaneous tissue of the nipple, the palm of the hand, and the labia majora, in the periosteum, the mesentery, especially along the branches of the sympathetic nerve, and in many other places. They are oval or pear-shaped bodies, com- posed of numerous concentric strata, exhibiting nuclei. The medullated nerve-fiber upon entering this body becomes destitute FIG. 128.— TERMINAL PLEXUS OF NON-MEDULLATED NERVES, BENEATH THE EPITHELIAL LAYER OF THE CORNEA OF A BULL. N, non-medullated nerve-fibers, partly with a delicate reticular, partly with a lumpy, structure ; G, ganglionic enlargement ; E, columnar epithelia, in top view. Magnified 600 diameters. of its myeline, and terminates in a knob or a chain of granules. Sometimes two nerve-fibers pass into the corpuscle. The signifi- cance of these formations is not understood. (I) Termination of Non-medullated Nerve-fibers. The most common termination of nerve filaments is a plexus, in which, as a rule, ganglionic elements are found as nodular points of inter- NERVE-TISSUE. 301 section. Such plexiform terminations are seen in different local- ities beneath the epithelia, in the submucous tissue, and in the connective tissue between the circular and longitudinal muscle- layers of the intestines. (See Fig. 128.) The plexus of Meissner is located in the submucous layer of the intestine, and exhibits distinct ganglionic enlargements (see chapter on alimentary canal). The plexus of Auerbach is found at the junction of the two muscle-layers of the intestine ; it contains nodular gan- glioiiic bodies with numerous nuclei (see chapter on alimentary canal). The axis-cylinders, near their terminations, divide into ex- tremely delicate axis-fibrillm (M. Schultze), which are slender, beaded filaments, representing the bioplasson reticulum in an elongated direction. Their course in the cornea has been accu- rately studied by W. Hassloch (see page 175, Fig. 67). They enter a cornea-corpuscle and inosculate with its bioplasson reticulum, evidently in the same manner in which they originate in the cen- tral ganglionic element. Many fibrillae simply pass through one corpuscle and enter another ; fibrillae have been also traced into the bioplasson reticulum of the basis-substance. Terminations of this kind are found in different connective-tissue formations ; they are not permanent, but may occur from a temporary enlargement and elongation of reticular fibrillae connecting with former nerves. As they are bioplasson formations, they may disappear by falling back into the reticulum. The finest plexiform terminations of axis-fibrillae are observed in the walls of capillary blood-vessels, particularly in the cement- substance between the endothelia (W. Tomsa and others). Such plexus formations were found in the epithelia by Pfliiger, Langer- haus, and others, and it is still an unsettled question whether the nerves terminate in the cement-substance between the epithelia, or penetrate the epithelial bodies themselves. Peculiar epithelial formations are the gustatory buds (Schwalbe) and the olfactory cells (M. Schultze), the connection of which with nerve-fibers, however, is still a disputed point. Very complicated formations are those of Corti's organ and of the retina. The plates, the " hair-cells," the rods and cones are well known, but how the nerves connect with these is unsettled. In the light of the bioplasson theory we may, at a time not far distant, hope for new discoveries and new views. 302 NERVE-TISSUE. DEVELOPMENT OF NERVOUS TISSUE. Very little is known in regard to the development of the nerve- centers and the nerves. All observers adhere to the idea that the nerve-centers are products of the outer or horny embryonal layer, the epiblast. According to general biological views, this cannot be correct. The nerves, being so closely allied to connective tissue, are offspring developments from the middle embryonal layer, the mesoblast. L. linger * maintains that the medullated nerve-fibers of the brain arise from radiating tracts, in which the cells are arranged in columns ; these columns first have a retic- ular appearance and an investing membrane. He claims that the reticulum of the myeline layer is produced earlier than the axis-cylinder ; that connective tissue and nerve- tissue may arise from one and the same cell, and that nerve-fibers or axis-cylinders may come from certain portions of the reticulum. FIG. 129. — BRAIN OF A HUMAN EMBRYO, FIVE WEEKS OLD. P, gray substance with numerous nuclei ; A, axis-cylinders ; C, capillary blood-vessels. Magnified 600 diameters. My own observations prove that the brain of a human embryo five weeks old is composed of a bioplasson reticulum, whose points of intersection with low powers appear to consist of gran- ules. In this reticular mass numerous nuclei are imbedded, and tracts of axis-cylinders laid before even a trace of a medullated nerve can be demonstrated. (See Fig. 129.) This shows that the development of the nerves can never be understood in accordance with the cell theory, inasmuch as there * " Untersuchungen iiber die Entwicklung der eentralen Nervengewebe." Sitzungsber. d. Wiener Akad. d. Wissensch, 1879. NERVE-TISSUE. 303: is nothing to support the assumption that nervous tissue origi- nates from " cells." Unquestionably, there are large masses of re- ticular bioplasson in which by a growth of living matter, chiefly in one direction, axis-fibrillae originate, while the medullary investment is a much later formation. At first there is no trace of ganglionic elements. We know that these elements make their appearance only after the third month of intrauterine life. The motor elements of the spinal cord particularly are first observed during the third and fourth months, corresponding to the time when the embryo begins to manifest signs of life. Further, the ganglionic elements cannot arise from cells, as they are no cells, but from portions of living matter arranged in clusters, in which all the plastids remain interconnected. This mode of development is indicated by the inflammatory changes of the ganglionic ele- ments, when they return to their embryonal condition. In the human embryo two months old, the intervertebral ganglion is composed of medullary tissue, with relatively large fields of myxomatous basis- substance. The nerves are non- medullated, which proves that the myeline investment must be formed at a later period than the axis-cylinder. (See Fig. 130.) For a successful investigation of the development of nerv- ous tissue the recognition of two points is, in my opinion, of fundamental importance: — viz. : first, that the nervous sys- tem is a formation originating in the middle embryonal layer j and second, that no isolated " cells" take part in the pro- duction of nervous tissue. With the knowledge of these facts, we can understand that in an elongated group of intercon- nected plastids the central portion may remain unchanged living matter, the axis-cylinder j while a more peripheral por- tion may become reticular (horny ?) and infiltrated with mye- line as a kind of basis-substance, and that the most peripheral portion, by a solidification of the bioplasson liquid, may be trans- formed into the myeline sheath with a nucleus, in about the same manner as a fat-globule arises from myxomatous connective tissue. METHODS FOR THE PREPARATION OF NERVE-TISSUE. Successful examination of the nerve-tissue depends on a suit- able mode of preservation. Teasing, tearing, pulling, and making specimens " half dry " are methods unworthy of being named. Small pieces of the brain or the spinal cord should be placed 304 NERVE-TISSUE. in a dark wine-yellow solution of bichromate of potash, or in Miiller's fluid. Either of these liquids should be greatly in excess compared with the bulk of the specimens. They will preserve the nerve-tissue, if changed every fourth or fifth day, or until the liquid remains clear. The hardening can be accom- plished afterward by alcohol or a very weak (one-fifth to one- tenth per cent.) solution of chromic acid. A slight excess of chromic acid will soon render the nerve-tissue brittle and not suitable for sections. JV" FIG. 130. — INTERVERTEBRAL GANGLION OF A HUMAN EMBRYO, EIGHT WEEKS OLD. G, partly solid, partly nucleated, plastids ; N, nerve-fibers, not yetmedullated ; M, delicate rayxomatous connective tissue ; B, capillary blood-vessel, cut transversely. Magnified 600 v FIG. 154.— LATERAL SURFACE OF THE CONDYLE OF THE FEMUR OF A GROWN CAT, ON THE SEVENTH DAY OF INFLAMMATION. FRESH SPECI- MEN. [PUBLISHED IN 1872.] H, hyaline cartilage in transition to F, fibrous cartilage ; C, greatly widened cavity, filled with inflammatory corpuscles; B, newly formed red blood-corpuscles, sprung from L, the bioplasson in a juvenile condition. Magnified 800 diameters. glistening, polyhedral fields of a brown color, which was more intense and wide-spread on the surface of the cartilage. Many of the cartilage corpuscles within the brown basis-substance 366 INFLAMMATION. contained granules and lumps of a blackish-brown color, which were most numerous at a certain distance away from the border of the wound. Extremely minute black granules also were found in the basis-substance. That these granules were animal char- coal could easily be determined by comparing them with the charred pastids attached to the surface of the wound, and with the eschar of the cartilage of other animals. But how did the charred granules penetrate the cartilage corpuscles ? There must have been either a carboiiification of certain parts of the cor- puscle and the basis-substance, or else the coal particles had been transported from the surface of the wound toward the periphery. The supposition of a partial carbonification was not sustained by experiments on other animals, — cats and rabbits, — and I never succeeded in producing brown granules in the corpuscles situated in the neighborhood of the burnt place of live or dead cartilage. The conclusion, therefore, became admissible that the coal particles realty were transmitted within the basis-substance by an active process of the cartilage corpuscles and their offshoots. Other experiments with powdered vegetable carbon and cin- nabar, forced into fresh wounds of the cartilage, did not yield satisfactory results. I succeeded but once in demonstrating the presence of cinnabar granules in a cartilage corpuscle inclosed by an uninjured basis-substance. Cinnabar granules, on the contrary, which I had injected into the jugular vein, I invariably succeeded in finding in the cartilage corpuscles, within the dis- trict of inflammation, both in inflammatory corpuscles, filling the enlarged cartilage cavities, and also in cartilage corpuscles, apparently unchanged. I can, therefore, corroborate the asser- tions made by Reitz and Hutob. In inflamed cartilage I have often seen red blood-corpuscles arising from both the corpuscles of cartilage and medulla. The insular and intravascular formation of red blood-corpuscles in some cases proved to be extremely active. After injuries inflicted on the lateral surface of the condyles, I observed enlarged fusiform cavities, which evidently had sprung from carti- lage, partly or totally filled with initial forms of red blood-corpuscles — the " haBmotoblasts " — as well as with fully developed corpuscles. Solid bioplas- son tracts sometimes directly connected the closed cavities of the above description, which were found in a large number, especially toward the ten- don-tissue ; they were sometimes hollow, and contained a single chain of red blood-corpuscles. The process of new formation of blood-vessels and blood proved to be identical with that noticed in inflamed bone-tissue, and for fur- ther particulars I refer to the article on inflammation of bone. INFLAMMATION. 367 (C) Inflammation of Bone. Numerous experiments made during the years 1872 and 1873, on bones of dogs, cats, and rab- bits, for the purpose of artificially producing inflammation, enabled me to obtain a general view of the phenomena of oste- itis, from its incipient stage up to the eighth day. These are : first, the freeing of the bioplasson from its basis-substance ; and, secondly, the return of the bioplasson to the juvenile condition. In the earliest stages of the inflammation, twenty-six hours after the injury, also in the succeeding days, at the periphery of the inflamed district, a dissolution of the lime-salts of the basis- substance takes place in bay-lihe fields ; this destructive process, however, does not invariably invade the whole of the territory, but often only part. The decalcified basis-substance itself is next dissolved out, and in its place flat or globular bioplasson masses become visible, either single or coalesced into groups, exhibiting a number of nuclei, each of which corresponds to an original nucleus of a bone-cor- puscle. Within these coalesced groups, new nuclei originate, and the multinuclear body presents the appearance formerly known under the name of a "myeloplax." (See Fig. 155.) Such multinuclear bioplasson masses arise from one or sev- eral coalesced bone territories, and represent the bioplasson of the territory itself.* A multinuclear body, at the periphery of the inflammatory district, may at once lay the foundation for the new formation of a bone territory ; or it may, in the more central portions of the inflammatory district, divide into a number of corpuscles, each one of which is provided with a nucleus. The corpuscles, as well as the larger bioplasson layers, are separated from the neighbor- ing kindred formations by light, narrow rims, which are trav- ersed by transverse filaments. These filamentous formations are threads of living matter, by which all newly developed ele- ments are connected with each other and also with neighboring bone-corpuscles not yet set free. This series of changes may be observed in the middle of the bone-tissue, as well as at the borders of vascular canals. The dissolution of the decalcified basis-substance, as a rule, begins at * The multinuclear bodies are by no means formations confined exclusively to the medullary tissue of bone. They may appear wherever territories (units) existed before the infiltration with basis-substance took place, or where the basis-substance, either in normal or in morbid processes, is slowly being dissolved out, and thus the units of the tissue made free. 368 INFLAMMA TION. the border of the lacuna, therefore in the circumference of the uninfiltrated bioplasson body, — the bone-corpuscle, — and ad- vances outward toward the periphery of the territory. We can satisfy ourselves that it is not the central bone-corpuscle itself alone which enlarges, but that, after a wasting or dissolution of the basis- substance has taken place, leading to the freeing of the bioplasson, FIG. 155. — BAY-LIKE EXCAVATIONS, PRODUCED BY DISSOLUTION OF THE BASIS-SUBSTANCE, FROM THE TIBIA OF A DOG INJURED WITH RED-HOT IRON; EIGHTH DAY OF INFLAMMATION. CHROMIC ACID SPECIMEN. [PUBLISHED IN 1872.] B, unchanged bone-tissue, with C, the bone-corpuscles ; P, large nucleated bioplassou masses, filling the bays in connection with the unchanged bone, by means of delicate fila- ments. Magnified 800 diameters. the latter, which before the inflammation was seen only in the bone- corpuscle, becomes visible throughout the whole territory. The next step in these phenomena is that the bioplasson contained in i INFLAMMATION. 369 the former osseous basis-substance now divides into a number of flat, fusiform, nucleated bodies. As a matter of course, it is the reticular bioplasson within the basis- substance, and not the basis-substance itself, furnishing the material for these elements, which are not really newly formed bodies, but only made visible and re-arranged in new groupings. The final result of the melting or dissolution of the basis-sub- stance is the appearance of medullary spaces. They may arise from bone-corpuscles and their surrounding basis-substance, in- dependently of the vascular canals in the middle of the bone-tis- sue. This fact was known previously by Rokitansky. Medullary spaces may also have their origin in the borders of vascular canals, and the nearer the wound of the bone, the larger and the more irregularly excavated are the medullary spaces come from the vascular canals. They are always packed with globular or spindle-shaped corpuscles, while in their centers blood-vessels, containing blood-corpuscles, are found. Running from the widened vascular canals, now transformed into medullary spaces, are channels filled with medullary corpus- cles, which penetrate the interstices between the systems of lamellae. The spaces which arise in the vicinity of the bone-cor- puscles unite with those of the widened vascular canals and interstices ; and in intense inflammation, up to the eighth day, the formerly compact bone is transformed into a cancellous structure — i. e., only narrow trabeculae of unchanged bone are left, between which are large spaces containing medullary cor- puscles. In still more intense inflammation, especially that pro- duced by boring into the compact bone with a pointed hot iron, the bone-tissue in the district of inflammation around the wound is to a great extent transformed into medullary tissue, holding newly formed blood-vessels, and in this tissue, only very small, irregular islands of the former compact bone are found. Obvi- ously, the juvenile condition of the bone is reestablished by this process, even in its coarser anatomical relations. (See Fig. 156.) The elements which have newly appeared bear a close resem- blance, so far as their shapes are concerned, to those present in normal vascular canals, between the wall of the blood-vessel and the wall of bone. They are nothing more than medullary ele- ments in the stage of indifference — eventually osteoblasts. In slight degrees of inflammation, the medullarj^ elements, up to the eighth day, may, at the surface of the inflamed bone, again be transformed into the so-called " osteoid " tissue by infiltration 24 370 INFLAMMA TION. with lime-salts. In this way are originated new trabeculae, with a high degree of luster, between which, in irregularly arranged cavities, in part nucleated bioplasson bodies are left. In the reealcified basis-substance we can trace the former medullary corpuscles, as their general configuration is unaltered. The reticular structure of this basis-substance is distinctly visible without any re-agent, owing to the high degree of refraction of the fields, infiltrated with lime-salts. (See Fig. 157.) The second series of changes concerns the bioplasson itself : it returns in a relatively short time from the phase of advanced FIG. 156.— TRANSFORMATION OF COMPACT BONE INTO MEDULLARY TISSUED TIBIA OF A DOG, EIGHTH DAY OF INFLAMMATION. CHROMIC Aero SPECIMEN. H, widened Haversian canal ; C, projections of the compact bone, with considerably enlarged and apparently augmented bone-corpuscles; J, islands of bone; M, medullary tissue containing newly formed blood-vessels. Magnified 300 diameters. development into the juvenile condition. This occurs before any other change, and is quite constantly observed in the homogene- ous nucleus of plastids in the younger, and the nucleolus of those in older animals. The nucleus is transformed into a bright, yellowish body, which divides into several lumps. In the in- flamed district, beginning from the second and third day of inflammation, we meet with bone-corpuscles, containing divided nuclei, even in unchanged osseous lamellae INFLAMMA TION. 371 Rejuvenescence may involve either the larger portion of bone-corpuscles or the whole corpuscle, and these bodies are partially or totally transformed into yellowish, shining lumps, which I formerly considered hsematoblastic (see page 101). The dissolution of the basis-substance around the homogeneous lump takes place in the same manner, as described above. The return to the juvenile condition, however, may at a com- paratively early date invade not only the central bone-corpuscle, but also take place, to a greater or less extent, in the bioplasson, inclosed in the basis-substance. Some offshoots j_ _ of the bone-corpuscle may become |^%fl broader; in some of them even ®^^^lf^fe\^& rejuvenescence may occur, inde- prudently of the central bioplas- son body. Lastly, this change may affect the whole mass of bio- plasson present in a territory, as illustrated by Fig. 40, page 126. Here the retrogressive change in the bioplasson preceded the disso- lution of the basis-substance. The result of the recurrence to the juvenile stage of development is different, according to its degree. A number of bright, homogeneous lumps may arise from the bioplas- son of the bone-corpuscle, as well as from that of the basis-substance, and each lump, even the most mi- nute, is enabled to produce a new element. This new formation, traceable step by step in the me- dullary spaces, is due to the differentiation of compact bioplasson into a reticulum, therefore an advance toward a higher stage. Each lump, or each element, under these circumstances, remains, by means of delicate filaments, in living connection with all its neighbors. (See Fig. 158.) Should the division of young bioplasson into small lumps occur at a very early stage, and very rapidly, the formations which I have termed " haematoblasts " will be the result. Each haematoblast, by being severed from the neighboring elements. FIG. 157. — KECALCIFICATION OF THE MEDULLARY TISSUE OF A DOG'S TIBIA, INJURED WITH BED-HOT IRON, EIGHTH DAY OF INFLAMMATION. CHROMIC ACID SPECIMEN. [PUBLISHED IN 1873.] P, large, nucleated bioplasson bodies ; .B, calcified basis-substance, exhibiting a distinct reticular structure. Magnified 800 diameters. 372 INFLAMMA TION. and becoming dense at its periphery, may give rise to a colored blood-corpuscle. The newly formed blood-corpuscles either lie within and between other bioplasson bodies, or else they are inclosed by a shell of bioplasson which, by vacuolation, has FIG. 158. — FRACTURED FIBULA OF A GROWN DOG, LONGITUDINAL SEC- TION. FOURTH DAY OF INFLAMMATION. CHROMIC ACID SPECIMEN. [PUBLISHED IN 1873.] T, flat bioplasson bodies, iu the stage of indifference, blending with the basis-substance ; P, bioplasson bodies (medullary corpuscles), sprung from both the bone-corpuscle and the basis- substance ; S, bioplasson bodies, with numerous bright lumps ; JV, original bone-corpuscle, with enlarged nucleolus, and a partly solidified nucleus. Magnified 800 diameters. become hollow. This represents the first trace of blood-vessels which, from their earliest stage, hold red blood-corpuscles. The second series of changes in inflamed bone, described INFLAMMATION. 373 above, lead to formations, constantly met with in the immediate vicinity of the inflammatory district. A number of newly formed medullary spaces are filled with yellowish, shining ele- ments, which, in their form and the nature of the basis-substance surrounding them, are analogous to normal juvenile medullary corpuscles. In such spaces a more or less abundant new forma- tion of red blood-corpuscles, and also, though not constantly, of blood-vessels, is going on ; the spaces, as a rule, contain in their centers blood-corpuscles and blood-vessels, and at their periphery bioplasson bodies of varying size. Sometimes red blood-cor- puscles originate in multinuclear bioplasson masses, as I de- scribed in 1872. Finally, I emphasize that the living connection of the bioplasson bodies, except the hcematoblasts, is not interrupted in the non-puru- lent inflammation of bone. An isolation can be asserted to exist only in colored blood-corpuscles and in pus-corpuscles. The blood-cor- puscles float in a liquid whose origin is connected with a partial paling and waste of bioplasson. The formation of this liquid always occurs within the first vacuoles — i. e., the first vascular tubes, and both the liquid and the newly formed red blood-cor- puscles take part in the circulation as soon as the newly formed vessels join the older ones. It has been proved by Bustizky * that from the freed bioplasson in the process of inflammation of bone, pus-corpuscles also originate. New Formation of Blood-vessels in Inflamed Bone-tissued In bone in which inflammation is artificially induced, a very active new formation of blood-vessels takes place.f These are mostly capillaries arising from the elements of the decalcified, but not dissolved, bone-tissue, and in medullary spaces originating from the derivations of the bone-tissue — viz., the medullary corpuscles. * " Untersuchungen iiber Knocheneiterung." Wiener Mediz. Jahrbiicher, 1871. t "Ueber die Ruck- u. Neubildung von Blutgefassen im Knocheii u. Knorpel." Wiener Mediz. Jahrbiicher, 1873. t R. Volkmann (Langenbeck's Archiv f. Klinische Chirurgie, IV. Bd. 1863) describes a new formation of vascular canals in the compact substance of bone, occurring in so-called " vascular ostitis." What this author describes is not identical with what I have seen, for he maintains that in the formation of vascular canals the bone-corpuscles take only an accidental part, or do not participate in the least. How the vessels themselves are formed he does not say. H. Lessen (Virchow's Archiv, Bd. lvv 1872) attempts to demonstrate, in specimens obtained from dry bone, that the canalization of bone-tissue really starts from bone-corpuscles. 374 INFLAMMA TION. At the surface of the injured scapula of a dog, on the fourth day of inflammation, I met with well-marked features indicative of a new formation of blood-corpuscles and blood-vessels. (See Fig. 159.) I saw enlarged cavities in the basis-substance, deprived of lime-salts, containing a number of bright, yellowish, homogene- ous lumps and disks, which might be properly termed a haemato- blasts" (see page 100). Some of these lumps were vacuoled, FIG. 159.— SCAPULA PLATE OF A DOG, ON THE FOURTH DAY OF INFLAM- MATION. CHROMIC ACID SPECIMEN. [PUBLISHED IN 1873.] L, lumps of bioplasson in a cavity partly inclosed by an investment of bioplasson ; V, elon- gated and vacuoled bioplasson tube, traversed by septa and containing isolated lumps — the haematoblasts ; .Bi and B*, offshoots of the bioplasson tube, terminating blindly. Mag- nified 800 diameters. others vacuoled and elongated, and, again, others considerably enlarged by vacuolation. In all cavities produced by vacuolation, isolated haeinatoblasts in varying numbers could be seen beside a pale granular mass. By coalescence of vacuoled bioplasson bodies tubular formations originated, which were divided into a INFLAMMATION. 375 number of chambers by transverse or oblique septa, the remnants of the hollowed bodies. The septa eventually disappearing by liquefaction and wasting of the bioplasson, a common caliber i& established, irregularly bounded by flattened layers of unchanged bioplasson, exhibiting in their optical diameter a number of nodulations. This tube is in a direct communication with hol- low offshoots, exhibiting the same features, and terminating s either blindly or in cavities de- stitute of a bounding layer, but containing haematoblasts. In the scapula plate of a cat, on the third day of the artifi- cially induced inflammation, I observed solid bioplasson tracts, which arose from the border of a medullary space, ran along the lamellae, and connected several enlarged and homogeneous bone- corpuscles. Not infrequently the bone-corpuscle next to the me- dullary space was most enlarged, and appeared hollow, while the distant corpuscles of the chain were solid. I also observed fin- ished tubules, terminating in a solid point and traversed by transverse septa or their rem- nants, indicative of the origin of the tubule. Such tubules always contained a varying number of isolated solid bioplasson lumps, — the " haematoblasts, " — to- gether with finely granular, (See Fig. FIG. 160. — SCAPULA PLATE OF A CAT, ON THE THIRD DAY OF IN- FLAMMATION. CHROMIC ACID SPECIMEN. [PUBLISHED IN 1873.] Newly forming blood-vessel, terminating in a vacuoled plastid, L ; 8, remnant of a former septum ; H, lumps of bioplasson — the hsematoblasts — entangled in finely granular, coagulated albumen. Magnified 800 diameters. coagulated albumen. 160.) In many specimens obtained from inflamed bone, up to the fifth day of inflammation, I observed similar formations in the newly formed medullary spaces also. In all cases, first, solid 376 INFLAMMATION. bioplasson tracts were seen, which, by vacuolation, became hol- lowed, often exhibiting transverse septa, — the remnants of the walls of the vacuoles, — and containing haRmatoblasts. From the walls of these forming blood-vessels, solid buds or fusiform or club-shaped prolongations arose, which indicated the formation of new, collateral branches of blood-vessels. Not all the red blood-corpuscles found in medullary spaces were inclosed in blood-vessels, for I often met with blood-corpuscles, isolated or in groups, among the medullary elements which had sprung from inflamed bone-tissue, without a trace of an investing bioplasson layer. Such corpuscles evidently are never carried into the circu- lation, and I was unable to discover either their office or destiny. Often, multinuclear bioplasson masses were found, holding in their substance a varying number of red blood-corpuscles. Sev- eral times I observed an outer investment of spindle-shaped bod- ies, which surrounded the multinuclear masses. Sometimes the spindle-shaped bodies produced a well-marked, broad layer around these masses, which had been partly changed into a homo- geneous or finely granular, possibly liquid, substance. Along the investing layer, inside the caliber, wreaths of haematoblasts were seen. All these features indicated the formation of veins , but I was not able to determine that the investing spindles were muscle formations. That in inflamed tissues a new formation of arteries occurs I am certain from a specimen of Prof. Strieker's, who, in 1871, showed me an inflamed cornea — I cannot recall whether of a frog or a rabbit — in which a newly formed artery could be posi- tively diagnosticated. Conclusions arrived at in 1873. Inflammation was considered by humoral pathologists to consist essentially in a diseased con- dition of the blood and an exudation of its plasma ; while cell- ular pathologists located the disease predominantly in the " individuals," the "tissue-cells." The latter view, announced by Virchow, was the leading one up to our time. The presence of an exudation, the altered liquid of the blood, in the inflammatory process, needs to-day no special proof. It has never been doubted. The phenomena in the inflammation of bone could not be explained without the presence of a liquid which causes a dissolution first of the lime-salts and afterward of the glue-yielding basis-substance. Inflamed cartilage tissue like- wise furnishes important proofs of the presence of an exudation. The fact that injuries entirely confined to hyaline cartilage pro- INFLAMMATION. 377 duce trifling changes, while, if cartilage and bone be injured simultaneously, very marked changes occur at once in the car- tilage tissue, indicates a direct dependence of inflammatory changes on blood-vessels. The rapid deposition of lime-salts in the latter case can scarcely take place from any other source than from a liquid introduced into the cartilage corpuscles. Upon boring into the cartilage and the bone, lime-salts are deposited in the basis-substance of the cartilage, at the border of the perforation, in a zone which broadens as it approaches the bone. This proves that the aperture is inundated with a liquid, flowing from the blood-vessels of the injured bone, from which the living matter of the cartilage derives the lime, origi- nally kept in solution, ultimately to be deposited in the chondro- genous basis-substance. Neither the sum of facts so far known to occur in inflamma- tion of cartilage, nor the observations in keratitis, furnish any foundation for overthrowing the theory of exudation, and of the participation of the blood and the blood-vessels in the inflamma- tory process. As regards the changes of the assumed " individuals/' the u cells," this is a different matter. Strieker was the first who positively declared that the cells by inflammation are reduced to a juvenile condition, in which they are enabled to proliferate. This assertion was based upon the observation of the changes which take place in the " proto- plasmic body" — namely, its swelling, its becoming amoeboid, the formation of new nuclei and new corpuscles from the older ones, and also the wasting of the " intercellular substance." This view, with all that it involves, can be maintained, not only so far as the cells are concerned, but also for the inflamed tissue in general. Every tissue, by the inflammatory process, is reduced to the condition in which it existed in the first stage of its development — that is to say, to a condition corresponding to its. embryonal state. Thus bone-tissue, in inflammation, is dissolved into the ele- ments from which it originated. Through the dissolution of the basis-substance medullary spaces are formed in the bone, at cer- tain distances, which give to the inflamed bone of an animal, no matter how old, the appearances found in a newly born individ- ual. In addition to this, in inflammation the basis-substance loses its lamellated structure, and in part assumes a striated aspect, which again corresponds to the bone of a new-born 378 IN FLA MM A TION. animal. Finally, the medullary spaces are filled with elements identical to those from which bone-tissue originated. The same is the case with periosteum and cartilage. The periostea! ribbons, whose boundaries remain marked by un- changed " elastic fibers/' are dissolved and form rows and groups of globular and fusiform corpuscles, which correspond with the original formers of periosteum, not only as regards their shape, but in every particular. By inflammation cartilage is transformed into medullary elements, such as originally composed its tissue. The totality of the elements observed in the inflammatory process has been designated by the terms " inflammatory new formation," " granulation tissue/' and " suppuration. " Recently, every newly appearing element was termed simply a " pus-cor- puscle." My own observations prove that the newly appearing elements at first are nothing but the elements of the tissue themselves. The term "inflammatory new formation" is applicable only in the later stages of the inflammation, when really newly produced corpuscles have originated from the freed mass of living matter. The designation " granulation tissue " is scarcely tenable for the earliest stages of the inflammation, inasmuch as there is no new tissue produced, but only a formation analogous to that from which the inflamed tissue sprang — that is, a medullary tissue-formation for periosteum, cartilage, and bone. The general designation of " inflammatory new formation," applied to " suppuration" or u formation of pus-corpuscles," is decidedly incorrect. The results of my researches show that the newly appearing, as well as the newly formed, elements are con- nected uninterruptedly by filaments of living matter, both with each other and with the non-inflamed neighboring tissue. If in inflammation of a tissue single corpuscles become sepa- rated from their neighbors, and the so-called " migrating cells" are produced, their locomotion is evidently only a transient action. The newly formed red blood-corpuscles lying within their newly formed vessels, and which in a later stage join the older vessels, are really separated from the parent soil. Pus-corpuscles, on the contrary, are unquestionably isolated elements which are separated from each other by a liquid. Pus, however, is no tissue, and from it, so far as we know and it is generally admitted, new tissue will never arise. There is a marked difference, therefore, between those proc- esses which pathologists have termed "plastic inflammation," on INFLAMMATION. 379 the one hand, and " suppuratiee inflammation" on the other; al- though it may be granted that these processes depend only on different degrees of irritation. Let us consider the inflammatory changes of the living matter of the tissue-units. In inflammation, this matter is probably at first provided with a surplus of liquid nourishing material. The question whether this material is conveyed in spaces between the living matter and the basis-substance, or whether the liquid im- mediately enters the living matter, — i. e., is imbibed by it — cannot be answered by direct observation. This fact, nevertheless, is certain, that the surplus nourishing liquid shows its effects gen- erally in the youngest portion of the tissue-unit — viz.: in the nucleolus and the nucleus of the non-infiltrated corpuscle. This portion is usually the first to return to the juvenile condition ; it is divided into a number of particles, as has been stated by Virchow. The living matter inclosed in the basis substance, upon receiving the increased nourishing material, responds, as a rule, by a dissolution of its basis-substance. Next follows the reestab- lishment of the juvenile condition in a certain number of centers, each of which represents a nucleus or a nucleolus ; and thus the embryonal or juvenile stage of the tissue, as described above, is re-assumed. Nearer the inflammatory focus the recurrence of youth is established in a larger amount of living matter, which is transformed into compact masses. Each mass may divide, and each fraction may give rise to a new corpuscle. If the connec- tion between these corpuscles remains intact, medullary tissue is the result ; if, on the contrary, the connection is broken, the com- pact particles of living matter are hcematoMasts, and, eventually, red blood-corpuscles. The formation of new elements from larger masses of living matter, as can be directly proved, is accomplished in such a way that within these masses, at certain intervals, new boundaries arise, the so-called " marks of division," which depend upon the location of the compact centers. These boundaries are newly formed cement- or basis-substance, in which there are no reticular formations, but merely delicate spokes of living matter. Every newly formed inflammatory corpuscle corresponds to a central body, whose living matter retains its embryonal condition — viz. : to a nucleus or to several nucleoli. Lastly, if in many places the connection of living matter be broken, — i. e., the spokes uniting the single lumps be torn, — the 380 INFLAMMATION. lumps become unfit for producing new elements, and are sus- pended in a liquid, viz. : serum, derived from the blood which con- stitutes suppuration proper. Pus, as is known, is destined to perish. The facts above enumerated lead to the conclusion that a cellular pathology, according to the theory of Virchow, cannot be maintained, for in the tissues of the animal body there are no "individuals,77 no "cells," and consequently can be no isolated " cellular foci of disease." Tissues are composed of living matter and its derivations. In the center of the tissue-unit the living matter remains unchanged, while at the periphery the living matter is infiltrated with basis - substance. The continuity of living matter is nowhere inter- rupted ; the detrimental influence, therefore, which acts upon the central body will also directly or indirectly reach the whole tissue- unit, and vice versa.* The changes which occur in the inflammatory process consist, first, in a dissolution or liquefaction of the basis-substance, and, secondly, in an increased production of the living matter of its own kind. As I have previously demonstrated (see page 46), each lump of living matter, no matter how minute, is capable of producing its kind, consequently to grow and form a new element. This is true of isolated particles as well as of masses of living matter combined into tissues and organs. It yet remains to be proved whether or not certain "free" exudations of the animal body contain a number of extremely minute, isolated lumps, which have been torn from connection with the diseased tissues, and whether or not such lumps, under certain conditions, are still viable and endowed in any degree with the capacity for reproduction. Together with the emigra- tion of colorless blood-corpuscles, such lumps may, perhaps, be a source of the enormous new formation of pus-corpuscles. It is always only the living matter within a tissue which is subject to disturbances of nutrition, whether it is surrounded by an interstitial liquid or by an interstitial solid basis-substance. The non-living basis substance may undergo different changes, * Later researches have proved that the changes may take place under certain conditions, first in the tissue-unit, before any change in the plastid has yet occurred. Even a portion of the plastid may exhibit inflammatory changes, while the remaining portion continues in a nearly unchanged condi- tion. (See article " Caries of Teeth, especially of Cemeiitum.") INFLAMMATION. 381 "but it is living matter exclusively which is enabled to reproduce its kind, and therefore capable of producing the extensive new formations which give rise to new tissues, such as pseudo-mem- branes, callosities, vegetations, etc. It is not the cell and not the living portion of the cell which alone grows and proliferates j in the tissue, everything that is endowed with life can do so, consequently that portion of living matter which is inclosed by basis-substance also grows and pro- liferates. To this extent, made clear by observations and infer- ences, as far as connective tissue is concerned, we return to the stand-point of Eokitansky, inasmuch as we admit that the so- called " intercellular substances" are endowed with the capacity of growth. There is no reason, however, to speak hereafter of a humoral or solidar pathology, any more than of a cellular pathology. There exists but one pathology, and that is the pathology of living matter. That only which is alive can become the subject of disease. THE HEALING PROCESS OF FRACTURED BONES. In several of m'y publications, issued in 1873, and quoted in the foregoing articles, incidental references are made to the phenomena of the healing process in fractured bones, which I propose here to include in one article. Later writers on this subject* have advanced no new views, as they have not con- sidered the inflammatory process in the light of the bioplasson theory. My researches were made in the leg-bones of dogs, cats, and rabbits, which I fractured designedly while the animals were kept under anaesthesia. In all instances I produced a displace- ment of the broken ends, in order to induce a somewhat higher degree of inflammation — the covering skin always remaining intact. How the healing process of fractured bones progresses by primary intention — i. e., when the broken ends are in close contact, — is not known. All the numerous observations and con- clusions concerning healing by primary intention in the soft tissues require revision, as a thorough understanding of this process is possible only through a knowledge of the minute structure of the tissues involved. None of the authors have had * J. Hofmokl, "Ueber Callusbildung." Wiener Mediz. Jahrbiicher, 1874. Here an exhaustive account of the literature on this subject is found. 382 INFLAMMA TION. this knowledge, strange as it may appear. Through the kind- ness of Dr. J. Lewis Smith, of New York City, I obtained two fractured arm-bones of children, one of fourteen days', the other of about four weeks', standing. I learned from these specimens that the process of healing is in human bones identical with that observed in animals. Upon fracturing the bones of an animal, hemorrhage is pro- duced, on account of the rupture of blood-vessels in surrounding tissues, as well as those of the bone ; the initial swelling of the tissues around the place of injury is known to surgeons to be due to the extravasation of blood. The subsequent fate of the extravated blood-corpuscles we do not know ; what we call " absorption " of the blood is merely an expression of ignorance. In the first few days following the injury inflammation sets in, varying in intensity with the degree of displacement of the ends of the fractured bone, and the general constitution of the animal operated upon. The inflammatory process is most active in the tissues which have the most abundant vascular supply — i. e.y the outer layer of the periosteum and the ruptured muscles, while it is less marked in the central medullary tissue of the bone, and still less in its compact portions. The result of the inflammation, as described in former arti- cles, is that the involved tissues, and mainly the periosteum, break down into medullary corpuscles, the same formation which originally contributed to produce the periosteal tissue. By an outgrowth of living matter, new medullary or inflammatory elements are afterward produced, all of which remaining in uninterrupted connection represent the inflammatory new forma- tion. The compact bone-tissue, in the immediate vicinity of the fracture, is also melted out, and on the eighth day we see medul- lary spaces, which are more or less numerous, and filled with medullary or inflammatory corpuscles. These corpuscles are con- nected with the inflammatory tissue arising from the periosteum and the central marrow. In the second week the inflammatory elements, being identi- cal with medullary or embryonal corpuscles, form a new tissue, in a manner already dwelt upon in the chapter on formation of connective tissue. The result of tissue formation in this case is again identical with that observed in the earliest stages of embryonal life — i. e., the medullary tissue is transformed into cartilage. Cartilage tissue appears after fractures, both of the human and animal bones, and constitutes the provisional callus of 1NFLAMMA TION. 383 Dupuytren. Whether such a provisional or cartilaginous callus is ever formed, when the broken bone-ends are closely fitting and the periosteum but slightly injured, has not been determined. This much is certain, however, that when a deviation of the bone-ends has occurred, the formation of provisional callus is invariably present. The manner in which the inflammatory corpuscles are trans- formed into cartilage (see page 212) is briefly as follows : FIG. 101. — CARTILAGINOUS CALLUS OF THE BROKEN TIBIA OF AN OLD CAT, FOURTEENTH DAY AFTER FRACTURE. CHROMIC ACID SPECIMEN. [PUBLISHED IN 1873.] B, slightly striated basis-substance ; 7, plastids in the stage of indifference, shortly before the formation of basis-substance ; V, capillary blood-vessel in the middle of a medul- lary space. Magnified 800 diameters. At the places most distant from the blood-vessels, the greater part of which are newly formed, the originally globular cor- puscles become elongated, and the nuclei of many of them dis- appear. This is caused by the splitting of the solid bioplasson of the nuclei into a reticulum, and the passing into the uniformly 384 INFLAMMATION. " granular " stage of indifference. Usually such a change occurs without a preceding coalescence of corpuscles into territories. Many of the indifferent corpuscles become infiltrated with basis- substance j but we do not know whether this is of a gelatinous or chondrogenous character. Some, however, remain free from infiltration, at least in their central portions, and in this condition constitute the cartilage corpuscles which are found lying at nearly regular intervals throughout the newly formed basis- substance. In the second week after the injury, we invariably encounter nests of inflammatory corpuscles lying around a cen- tral blood-vessel. The corpuscles nearest the vessel are more globular, while the more distant ones are elongated and fusiform ; we are able to trace all the stages of transition, from a uniformly reticular bioplasson into an apparently structureless basis-sub- stance. (See Fig. 161.) In the above-mentioned groups or nests of inflammatory ele- ments we observe the transformation of capillary blood-vessels into solid cords, and subsequently the division of these into smaller medullary corpuscles, which in turn also share in the production of cartilage. This process is similar to the transmu- tation in advancing age of capillaries into tissue. The newly formed basis-substance of the provisional callus is in part hyaline and in part striated. The striations are produced either by the preservation of the boundary lines of the former fusiform, indifferent elements, or by a splitting of these elements into small spindles, within the territory, before the infiltration with basis-substance had taken place. We notice bioplasson bodies at regular intervals, which in this stage deserve the name of cartilage corpuscles ; they vary greatly both in size and ap- pearance. In some cavities of the basis-substance we encounter large, pale, nucleated plastids ; in others, smaller, shining lumps, usually with vacuoles ; and in other cavities plastids are found which are composed of a varying number of lumps of different size. Lastly, very small cavities are seen in the basis-substance, containing only a single yellowish, bright lump. All plastids, whatever may be their size and shape, exhibit a distinct reticular bioplasson structure, whenever they are nucleated ; all granules and lumps contained in a plastid are likewise interconnected, and from all plastids, without exception, delicate radiating spokes arise, which penetrate the surrounding narrow rim, and are lost in the basis-substance. (See Fig. 162.) The newly formed cartilage of the provisional callus corre- INFLAMMA TION. 385 spends in its structure with normal hyaline or striated cartilage. A striking difference, however, is displayed in the tissue of the provisional callus by the large amount of bioplasson it contains. The coarse granulation of even the nucleated plastids j the masses of bioplasson lumps lying in the cavities j the presence of single compact and vacuoled lumps in many of the cavities are all unquestionably due to the great augmentation of living matter pro- duced by the inflammatory process. Such irregular formations are never met with in normal hyaline or stri- ated cartilage. They can be ex- plained only by the different phases of development which the bioplasson lumps undergo. (See page 46.) That the newly formed cartilage has really to a great extent sprung from former periosteal tissue is proved by the presence of unchanged elastic fibers. The cartilage tissue is traversed by a varying number of single, sometimes bifurcating, straight, glistening fibers, which either divide the tissue into more or less regular rhomboidal fields, or are scattered through it without uni- formity. There is scarcely any doubt that these elastic fibers originally belonged to the periosteal tissue, and remained unaltered by the in- flammatory process. They also con- tinue unchanged even after calcifi- cation of the cartilaginous tissue has taken place — nay, even after this tissue has retrogressed to the medullary state, the fibers often traversing the newly formed medullary spaces without any apparent regularity. In the third week after the fracture, a calcareous deposition takes place in the tissue of the provisional callus. Its extent varies greatly in different individuals, and sometimes it is very scanty, though never entirely wanting. In the fractured humerus of a child, during the fourth week after the injury, the calcifica- 25 FIG. 1 62. — CARTILAGINOUS CAL- LUS, FOURTEEN DAYS AFTER THE SUBCUTANEOUS FRACT- URE OF THE TIBIA OF AN OLD CAT. CHROMIC ACID SPECIMEN. [PUBLISHED IN 1873.] a, plastic! with several formations like nuclei; ft, vacuoled, shining plas- tid ; c, plastid, composed of numerous small, bright granules and lumps; d, minute bioplasson lump in a cavity of basis-substance. Magnified 800 diam- eters. 386 INFLAMMATION. tion had pervaded a large amount of the newly formed cartilage, while in other places the formation of medullary spaces and of trabeculae of bone was observed — the latter, however, only on a small scale. Simultaneously with the deposition of lime-salts, and often independently of it, a peculiar change is observed, at nearly reg- ular intervals, in certain points of the cartilage tissue — viz. : the formation of red blood-corpuscles, of blood-vessels, and also of medullary tissue. Those portions of the cartilage tissue which exhibit, in the basis-substance, at an earlier stage, the greatest number of small bioplasson lumps, and which have, to all appear- ance, sprung from former capillary blood-vessels, show the most marked new formations of blood and blood-vessels. Nests of medullary or indifferent corpuscles, or multinuclear bioplasson masses, are found, exhibiting an active outgrowth of living matter. This divides into small lumps, which subsequently imbibe haemoglobin, and constitute, first, haematoblasts and, later, red blood-corpuscles (see page 98). The peripheral portions of the plastids, or the multinuclear masses, are changed into flat, thickened layers of bioplasson, which lay the foundation of the walls of blood-vessels. Such a wall, in the optical section, exhib- its slight fusiform thickenings, indicating, perhaps, the future nuclei of the endothelia. Club- and rosette-shaped formations of this kind are at first connected with older blood-vessels by means of solid, bright cords of living matter, which, after they are hol- lowed out, establish a communication between the newly formed blood-vessels and the older ones. (See Fig. 163.) Together with the appearance of blood-corpuscles and blood- vessels, and the deposition of lime-salts in the basis-substance of the cartilage (uosteoid tissue" of authors), the new formation of medullary spaces is inaugurated. Around the newly formed blood-vessels, or independently of them, the cartilage tissue breaks down into medullary elements, solely in consequence of a dissolution or liquefaction of the basis-substance. The newly appearing medullary corpuscles are the same which, at an earlier date in the healing process of the fracture, produced the cartilage tissue. By a continuous dissolution of the calcified basis-substance, the medullary spaces are enlarged and the medullary cor- puscles augmented by a growth of living matter. In the cen- tral portions of the medullary space the corpuscles produce new blood-vessels, if such had not previously formed. The INFLA MM A TION. 387 process is exactly like that of the normal dissolution of carti- lage, which leads to the new formation of medullary tissue, and subsequently of bone. Meanwhile, at the fractured surfaces of the bone, similar medullary spaces have formed in consequence of the dissolution of the basis-substance of the bone and an increase of its bioplas- son material. The connection of the irregular, bay-like medul- lary spaces of the bone with those of the adjacent calcined cartilage can be traced directly. From the medullary tissue, which is the offspring of the FIG. 163. — CARTILAGINOUS CALLUS, EIGHTEEN DAYS AFTER THE SUBCU- TANEOUS FRACTURE OF THE TIBIA OF A CAT. CHROMIC ACID SPECIMEN. [PUBLISHED IN 1873.] C', cartilage corpuscles in a striated basis-substance; M, elongated medullary plastids, tending toward the formation of basis-substance, or resulting from a dissolution of basis-sub- stance ; -B', Ift, club-like spaces, lined by a continuous bioplasson layer, containing haemato- blasts and red blood-corpuscles. Magnified 800 diameters. inflamed periosteum, bone-tissue arises, in exactly the same man- ner as in the normal development of bone (see page 247). This bone-tissue establishes the formation termed definitive callus (Du- puytren). The trabeculae of bone in children and animals begin to appear in the fourth week after the fracture ; these at first are r 388 INFLAMMA TION. very irregular formations, exhibiting an indistinctly striated, cal- cined basis-substance and very large and irregular bone-corpus- cles. The medullary spaces are filled with medullary corpuscles, and contain, in their centers, newly formed blood-vessels, which are smaller the nearer they approach the compact structure of FIG. 164. — EXOSTOSIS AFTER PERIOSTITIS OF THE TIBIA OF A DOG IN THE FIFTH WEEK OF INFLAMMATION; IDENTICAL IN STRUCTURE WITH THE DEFINITIVE CALLUS. CHROMIC ACID SPECIMEN. C, superficial compact layer, with H8, the Haversian systems, and SS, newly formed medullary spaces ; H, vascular canals, widened into medullary spaces, S ; T, trabeculae of newly formed bone, with large and irregular bone-corpuscles, inclosing large medullary spaces, MS. Magnified 200 diameters. the injured bone. Unquestionably, also, the injured muscle-tis- sue shares in the formation of both the provisional and the defin- itive callus, always through the intermediate stages of medullary INFLAMMATION. 389 tissue. The newly formed trabeculae of bone are in every respect identical to those observed after plastic periostitis, and in this sit- uation termed "exostoses" and " osteophytes." (See Fig. 164.) The connection between the old and the new bone is estab- lished at the fractured surfaces by direct inosculation. At the surface of the compact bone, however, bay-like excavations are often wanting, and the newly formed bone may be attached to the old bone without the latter exhibiting any marked inflamma- tory changes. This occurrence has misled some authors into the belief that the newly formed bone is simply in apposition to the compact structure of the old bone, without being directly connected with it. Such views must be the result of the study of dry specimens, for in all other preparations there is no diffi- culty in ascertaining a direct union of the newly formed bone- corpuscles with the old ones by means of anastomosing offshoots. The originally irregular and bulky new formation of bone, gradually — viz. : after several months — is transformed into a more regular osseous structure. This can be explained by the supposition of repeated dissolution and new formation of bone- tissue only. After the lapse of several years the bony cicatrix becomes so perfect, and even supplied with a central marrow- space, in continuity with the old one, that, were it not for the deviation of the fractured ends, no trace of the former accident could be discovered. My researches may be summed up in the following state- ments : (1) The injury done to the bone and the adjacent soft tissues by the fracture leads to an inflammation, which is most intense in the most vascularized tissue — viz., in the periosteum j (2) The inflammatory new formation results in the produc- tion of a medullary or inflammatory tissue, from which arises cartilage tissue, representing the formation termed a provisional callus " ; (3) The cartilage tissue at certain regular intervals, which depend upon the new formation of blood-vessels, is broken down into- a freely vascularized medullary tissue ; (4) The medullary tissue, which has sprung from the former cartilage, produces bone, first in the form of irregular trabeculae, constituting the formation termed " definitive callus » ; (5) The formation of the definitive callus is in all essentials like the formation of bone in the process of normal ossification from cartilage and periosteum. 390 INFLAMMATION. NECROSIS. BY C. F. W. BODECKER, OF NEW YORK.* The successful study of the elements of bone-tissue depends very much upon the method employed. The proper examination of bone-tissue origi- nated in the second, third, and fourth decade of this century, and was pursued by Howship, J. Miiller, Henle, and others ; all of whom resorted to dry bone, which they divided into thin slabs by the use of the saw, after which these were ground thin by a variety of devices, reducing each specimen to semi- transparency. Observations made in this way resulted in the theory of canaliculi bearing a solution of lime-salts. In 1850 and 1853, Rodolph Virchow and F. C. Bonders applied the cell doctrine of Schwann to the explanation of bone-tissue. They sometimes used dry and sometimes fresh bone in their investigations, macerating it in dilute hydrochloric acid, where- by they liberated the elements of the structure more or less distinctly. The bodies so isolated presented, sometimes, nucleated structures connected together by branches ; at other times, completely isolated bodies consisting of a central mass with projecting processes, and to these they gave the name bone-cells. Bonders drew attention to the fact that bone-tissue had spaces filled by cell-like structures similar to those of other kinds of connective tissue. E. Neumann, in 1863, asserted that the so-called bone-cells were not the cells designated by Schwann, but spaces with offshoots having a more densely calcified wall than the other basis-substance, and thus better able to withstand the re-action of solvents. These bone-cells are no other than the lacunaa, and their offshoots, the canaliculi. Inasmuch as the dry method of examination of bone-tissue prevailed up to the introduction of the wet method, by Heinrich Miiller, in 1856, it is not surprising that it is fre- quently persisted in to this day. The nearer to the living state the examina- tions can be made, the more instructive and definite will the observation be. Hence the dry method is fast falling into disuse among those making histo- logical researches. In 1871, E. Lang introduced the examination of living bone under the microscope upon the heated stage, by which he noticed amoeboid motion in bone-corpuscles. By this management the lacunas were proved to contain protoplasm, but the nature of the contents of canaliculi he said nothing about. The method of examining bone-structure introduced by H. Miiller — viz., to decalcify bone by the use of a solution of chromic acid — is to be preferred. In this way bones are decalcified in a short time, and without considerable change. For thin bones, two or three weeks are sufficient to soften them enough to produce sections of any degree of thinness by the .use of the razor. Such sections may be stained by placing them in a solution of chloride of gold, of one-half per cent, in strength. An examination of such preparations will show that, within the lacunas of the bone, nucleated bodies are to be seen, with finely granular offshoots extending into the larger canal- *iculi, where they are lost to sight. From the surface of the bioplassoi> body in the direction of the basis-substance many conical processes protrude toward the small canaliculi, with which they blend. In 1872, C. Heitzmami described and illustrated a bone-corpuscle from bone in the early stage of inflammation [see page 126, Fig. 40, of this book]. This figure shows very * Abstract from " Necrosis," by C. F. W. Bodecker, D. D. S., M. D. S., New York. " Dental Cosmos," Philadelphia, 1878. In order to establish uniformity throughout the book , the term " protoplasm " is changed into that of " bioplasson." INFLAMMA TION. 391 plainly the shining, nearly homogeneous-looking bone-corpuscle, with off- shoots in every direction, filling the whole caliber of the canaliculi. It solves the question of the contents of the canaliculi in bone by direct observation. The living matter in bone behaves precisely as in other tissues under the influence of the inflammatory process — that is to say, the central mass becomes a shining and nearly homogeneous lump, the offshoots from which occupy the whole caliber of the canaiiculi, and by this the analogy of bone to all other varieties of connective tissue is established. That is to say, here, as elsewhere, the living part of the bioplasson forms a continuous net-work throughout the whole animal body, in the meshes of which a more or less fluid basis-substance is found, differing in its chemical properties in different situations, which in bone is glue-giving, and infiltrated with lime-salts. I have followed the methods, in my examination of bone tissue, as above described. This enabled me, by the use of the razor, to obtain sections fit to be examined by an immersion lens magnifying 800 to 1000 diameters. I noticed that the canaliculi could be plainly seen in sections, the basis-substance of which had retained a small quan- tity of lime-salts ; in completely de- calcified specimens they are very faintly discernible. According to my experience, it is better to stain the sections witn a solution of chlo- ride of gold of the half of one per cent., whereby a better view of both bioplasson and basis-substance is obtained. Another good way is to stain the sections with carmine and hgematoxylon. The results of my observations with high magnifying powers are that bone- tissue presents faint parallel lines, dividing it into the so-called lamellae, within which we find the bone-corpuscles, the shapes of which vary according to the direction of the cut and of the lamellae. As bone-corpuscles are flattened lenticular bodies, we will recognize them in this shape in the front view only. Longitudinal sections through these bodies give a spindle-shaped outline, small when cut near the boundary, broad when cut through the middle line of the lentil. A cross-section through a bone-corpuscle shows a somewhat irregular body. A cross-section from the compact bone of a lower jaw presents invariably bone-corpuscles in all three varieties. (See Fig. 165.) We see large spaces, showing a number of ray-shaped offshoots. Besides these coarse offshoots, innumerable extremely fine light ones are present. The larger as well as the smaller all communicate with each other, forming a deli- cate net-work through the whole of the basis-substance. Within the lacunas are present " protoplasmic " bodies. We observe, in the centers, shining oblong nuclei and nucleoli. Around the nuclei we see a narrow seam, trav- FIG. 165. — NORMAL BONE-TISSUE OF THE LOWER JAW OF A MAN, AGED THIRTY YEARS. CHROMIC ACID SPECIMEN, STAINED WITH CHLORIDE OF GOLD. Three bone-corpuscles, pi, with an oblong nucleus ; PZ, with a globular nucleus, both ex- hibiting indistinct nucleoli ; PS, with a small, compact nucleus. Magnified 1000 diameters. 392 INFLAMMATION. ersed by numerous very fine threads, which are cone-shaped. Their bases are directed toward the nucleus, from the periphery of which they arise, while their points are in connection with the nearest granules of the protoplasm. Within the corpuscle there are finer and coarser granules, all being connected with each other by very fine threads. The seam around the nucleus, as well as the spaces between the meshes of the threads, are observable, being much lighter than the latter. From the periphery of the bioplasson body numerous thick offshoots enter the larger canaliculi, which sometimes can be followed up until they commu- nicate with the bioplasson of other large neighboring canaliculi. Besides these, many very fine offshoots run from the periphery of the bioplasson, con- tained in the larger canaliculi towards the basis-substance. Some of them can be seen to enter the fine canaliculi, but their course cannot be distinctly fol- lowed. My preparations show a much finer net-work within the basis-substance than Heitzmann's figure, before alluded to. Though I am not able to distinctly demonstrate the presence of living matter in the finest canaliculi, yet, as we find it in all other kinds of connective tissue, I am justified in assuming it. In normal bone, the lacunae and canaliculi are not entirely filled by the living mat- ter. On the periphery of each corpuscle we see a distinct light seam, traversed by the offshoots, which, in a cross section, only show the bioplasson in the center of the canaliculis, hence leaving sufficient space for the nutrient circulation. It is impossible to study the differences between necrotic and normal bone if the specimens be prepared from dry osseous tissue. I have made microscopical' examinations of necrotic bone from the lower Jaw, and from another piece from an upper jaw removed by Dr. Frank Abbott. The methods employed were exactly the same as before described from nor- mal bone. In both cases the necrotic sequestra, as soon as they had been taken from the mouth, were placed into the solution of chromic acid, and cut in due time. As these pieces were small, I imbedded them in a mixture of paraffine and wax (after the extraction of the water by treatment with alcohol for twenty-four hours), whereby I was enabled to obtain extremely thin sec- tions, some of which I stained with chloride of gold, some with haematoxylon, and some I mounted unstained. The results of these examinations were as follows : The outer surface of the necrotic bone, which, to the naked eye, looked rough and eaten out, when brought under the microscope showed bay-like excavations, known formerly as " Howship's lacunce," in which there was visible a granular mass mixed with pus-corpuscles. In the middle of the bone I found all the Haversian canals more or less enlarged, some showing the bay- like excavations. The contents of the Haversian canals were everywhere the same — a conglomerate mass of darkly shaded granules, which I was unable to stain with carmine. These masses are the same that we see in decomposi- tion of organic matter — "micrococci." Here and there some medullary cor- puscles and multinuclear bodies were recognizable. I did not see blood-vessels in any of the Haversian canals. In the necrotic bone I found the traces of former osteitis. The enlargement of the Haversian canals and lacunae are direct proofs of this ; the dissolving out of the basis-substance "on the per- iphery may, on the contrary, have been due to chemical changes, produced by infiltrations from the neighboring inflamed tissues. The Haversian systems and concentric lamellae were unchanged. The lacunae and canaliculi were yet preserved. In the necrotic preparation from the lower jaw I observed many INFLAMMATION. 393 lacunas in which the bioplasson body, with its net-work, was yet distinguish- able, especially where the sequestrum had been attached to the periosteum, I found, also, in the preparation from the upper jaw, some comparatively unchanged bone-corpuscles."* But the majority of the bone-corpuscles, and especially in the neighborhood of the Haversian canals, were either empty or their bioplasson bodies were shriveled up (probably the remains of the living matter), only showing a few coarse granules. (See Fig. 166.) No signs of fatty degeneration could be seen, for the granules were stained violet by chloride of gold. Many lacunse showed no structure at all, the con- tents looking rather like a mass of coagulated albumen. In none of these lacunae was the characteristic struct- ure of bioplasson recognizable. To sum up my observations, I found : First. The lacuna? contain a bioplas- son body, with a distinctly visible net- like arrangement, to be regarded as the living matter proper. Second. The basis -substance is pierced by numerous coarse and fine canaliculi, communicating with each FIG. 166. — NECROTIC BONE-TISSUE OP THE LOWER JAW OF A WOMAN, AGED THIRTY-EIGHT YEARS. CHROMIC ACID SPECIMEN, STAINED WITH CHLORIDE OF GOLD. oilier, as well as with the lacunae. Third. The bioplasson bodies, which do not quite fill the lacunce, send off- shoots of the living substance into the canaliculi, but can only be seen in the coarser ones. Fourth. In necrotic bone, traces of former osteitis are visible, but no blood-vessels present in the Haversian canals? which are filled with micrococci. Fifth. In necrotic bone, most of the lacuna! contain no bioplasson, but either a coarsely granular or a structureless mass — remnants of the living matter and coagulated albumen. Three lacunae : LI, with two clusters of a granular mass; L*, with scanty granules ; LS, with a nearly homogeneous mass. Magnified 1000 diameters. RACHITIS AND OSTEOMALACIA. During the years of 1872 and 1873, I made a number of experiments, for the purpose of elucidating the causes of rachitis and osteomalacia. The results of these tedious and expensive experiments I published in 1873, in the form of a provisional communication.t * An important feature is not mentioned in this article — viz. : that even in apparently unchanged bone-corpuscles the nuclei were jagged, as if shriveled, this sufficiently indicating death of bioplasson.— ED. t Anzeiger der Akademie d. Wissensch. in Wien, 19 Juni, 1873 ; und Vortrag in der Ge- sellschaft d. Aerzte in Wien, October, 1873. 394 INFLAMMATION. Marchand, Ragsky, Lehman, Simon, and others, found free lactic acid in the urine of persons affected with either rachitis or osteomalacia. C. Schmidt discovered lactic acid in the liquid of malacic shaft-bones which had been transformed into globular cysts. Based upon these researches I commenced, in April, 1872, a series of experiments on the influence of internal administra- tion and subcutaneous injection of lactic acid on the bones of living animals. These experiments were continued till the end of October, 1873, and were made on five dogs, seven cats, two rabbits, and one squirrel. The result was that in dogs and cats, in the second week of the administration of lactic acid, no matter whether introduced with the food or by subcutaneous injection, the quantity of lime-salts given with food being simultaneously reduced, swell- ings appeared in the epiphyses of the shaft-bones of the extremi- ties, and at the insertions of the rib-bones into their cartilages. The enlargement of the epiphyses and the ribs increased con- tinually up to the fourth and fifth week, and at the same time curvatures of the bones of the extremities were noticed. Catarrhal inflammation of the conjunctiva, the bronchi, the stomach, and the intestines, emaciation and twitching of the extremities, were the concomitant symptoms. The microscopical examination of the epiphyses demonstrated the identity of this pathological process with that seen in the epiphyses of rachitic children. On continuing the administration of lactic acid, the enlarge- ment of the epiphyses of the long-bones decreased, and the shafts themselves became, to a certain degree, less curved, while catarrhal inflammations of the mucous membranes occurred repeatedly. After four or five months, softening of the shaft- bones set in to such a degree as to render the bones as pliable as willow-boughs. The microscopical examination of the bones, after administration of lactic acid, continued for four to eleven months, showed a condition of things identical to that seen in human beings, dead of osteomalacia. In the three herbivorous animals no swelling of the epiphyses was observable. One rabbit died in the third month, the other in the fifth month, of the administration of lactic acid, both having symptoms of inanition. In the bones of these animals there were no marked signs of rachitis or malacia. The squirrel, on the con- trary, which died after thirteen months' treatment with lactic acid, exhibited, in a high degree, the characteristics of osteomalacia. INFLAMMATION. 395 Frony these experiments it follows that we are able to produce artificially in carnivorous animals, by continued administration of lactic acid, first, rachitis, and afterward osteomalacia ; while in herbivora the same agent produces osteomalacia without a prelimi- nary rachitic stage. Thus, the identity of these forms of disease is demonstrated, and the differences in their course depend mainly upon the differ- ence in the age of the animals in which the solution of the lime- salts is produced. In October, 1873, I exhibited to the Society of Physicians, in Vienna, a female foetus of seven months, which had died immedi- ately after birth. The mother of this foetus had been employed by me for months to feed the animals with lactic acid. In this foetus the symptoms of congenital rachitis were in the highest degree marked, to such an extent that the skull-bones were entirely absent, the cartilages of the ribs and the extremities showed only scanty depositions of lime-salts, but numerous breaches in the continuity; and throughout the body of the other- wise well-developed foetus there could be found no trace of bone- tissue. Feeding with lactic acid was repeated by E. Heiss,* on a dog one year and six months old, with only negative result. The age of dogs and cats in which rachitis can be induced is between the first and six months of life — at the period, therefore, when the skeleton is developing from the cartilage and the periosteum. After this stage of development is passed, the symptoms of osteo- malacia will be produced, and with greater certainty, toward the end of the first year of the animal's life. The experiments of Heiss rest on mistaken grounds. Age is an essential factor in the production of either of these diseases in human beings. Rickets occurs only in children between the first and the fifth years of life, this corresponding with the age of the above-named animals. Osteomalacia is exclusively a disease of adults. Rachitis (Rickets}. This disease of early childhood in its clin- ical features has been well known for over two centuries. Whistler t was the first to describe it, and from the title of his book the name of " English disease "was adopted by the German physicians. Next followed G. Glisson,t who made use of the name " rhachitis." Simon, § according to Marchand and Lehman, found lactic acid in the urine * "Zeitschr. f. Biologic," Bd. xii. t " De Morbo Puerorum Auglorum," 1645. Rare book. t "Tractatus de Rhaehitide," 1659. § Lehrbnch d. Med. Chemie., 1842. Bd. ii., p. 203. 396 INFLAMMATION. of rachitic children. He says that such children void urine which sometimes is very rich in lactic, also in oxalic, acid, and that it contains four times as much phosphate of lime as the normal urine of children. Rickets may be caused by the formation of lactic acid in the digestive tracts ; certainly this acid is not dis- posed of in the blood, in which only a small portion of the nitrogenous mate- rial is transformed into urea. In osteomalacia of adults, the lactic acid in the urine is considerably augmented, as well as the uric acid. In rickets, the lactic acid dissolves the phosphate of lime of the bones, and these become pli- able ; while, in osteomalacia, even the organic portion of the bone is in part absorbed. G. O. Rees* gives a thorough chemical analysis of the earthy phosphates in "Mollities ossium." He found the resorption of the phosphates to be different in different bones, and in the softened bones, on an average, he found only 78 per cent, of the normal 86 per cent, of phosphate of lime. The absorption, he says, affects the carbonate less than it does the phosphate of lime. Chossat t observed the absorption of lime-salts in pigeons which had been fed exclusively on wheat. The " rarefaction/' of bone corresponds more closely with osteomalacia than it does with rickets. Diarrhoea was a concomitant symptom of this disease. Sam. Solly | distinguishes two varieties of softening of bone. Osteomalacia, he says, has also been observed in animals by Spooner, especially in dogs, with post-mortem results identical with those found in man. Sometimes the disease is confined to single bones. C. Schmidt § found the lactic acid by combining it with zinc, in the acid liquid of cysts into which the malacic bones were transformed, and he thought that the lactic acid was of local origin. Ernst V. Bibra || observed, in accordance with the experiments of Chossat, that by withdrawing the lime- salts from fowls the lime-depositions in the egg-shell disappeared, and finally the fowls ceased laying eggs altogether. The bones of chickens showed a decrease of about 10 per cent, of the inorganic substances and a decrease of 6 to 10 per cent, of the phosphate of lime; while the carbonate of lime and phosphate of magnesia were only a little lessened, and the alkalies and the fat not at all. V. Bibra found no lactic acid in fresh bones ; no consideration is given to this acid in his chemical analyses. J. Schlossberger f obtained the following results : In the normal occipital bone the percentage of inorganic material never falls below 60 per cent. In craniotabes the percentage sinks to 51-53 per cent., and in the spongy and thickened portions to 43-48 per cent. Carbonate of lime is either decreased or normal. GuSrin1 says that if young animals are given other food than milk, dis- turbances of nutrition, especially of the bones, will follow. He took pups of the same litter, and fed some with exclusively animal and others with mixed vegetable food (bread and milk). The latter remained healthy j the former * Guy's Hosp. Reports, viii., p. 191. Schmidt's Jahrb., 1841. t Comptes rendus. Tom. xiv., p. 451-454. t Med.-Chir. Transactions, xxvii. 2d Ser., ix., 1844. § Annales de Chem. et Pharm., Ixi., 3, 1847. || " Chem. Untersuch. iiber die Knochen u. Zalme des Menschen u. der Wirbelthiere." Schweinfurt, 1844. U " Chemische Untersuchungen iiber d. erweichten Kinderschadel." R. u. W. Arch. viii. Schmidt's Jahrb., 1849, Bd. Ixii., p. 277. i Gazette des Hopitaux, xxxvii., 1848. INFLAMMATION. 397 » at first grew rapidly, but soon diarrhoaa set in, they emaciated and became rachitic. The bones became so soft that the animals walked on their femurs and humeri, which were very much curved. The main cause of rachitis, according to this author, is animal food, given too early. Or. Wegener * made experiments on fowls and calves, producing rachitic changes by the administration of small doses of phosphorus, continued for months. He found the epiphyseal cartilage considerably dissolved out, and also in a high degree of hypergemia. The histology of rachitic bones has been studied by many excellent observers, such as H. Meyer, R. Virchow, H. Miiller, A. Kolliker, C. Wedl, Steudener, and others. H. Meyer t especially comes to the conclusion that : (1) osteomalacia is osteoporosis; (2) rachitis originates from universal peri- ostitis ; (3) osteomalacia and rachitis are the consequences of one and the same disease. We know that, in the normal process of ossification, both car- tilage and periosteum are reduced to a juvenile condition, giving rise to medullary tissue. Simultaneously, also, new red blood- corpuscles and blood-vessels are formed. In rickets, all this is going on in a more rapid manner, but the new formation of bone from the medullary tissue is very scanty or entirely absent. In sagittal sections of the epiphyseal ends of rachitic bones we notice an intensely yellowish-red zone on a level with the portions in which the formation of medullary tissue from carti- lage is going on, and we see that this portion is considerably thickened, constituting the characteristic rachitic swelling of the shaft-bones. Under the microscope we find, at the level men- tioned above, large cartilage corpuscles containing a far greater amount of bioplasson than normal. The calcification of cartilage is scanty and in irregular patches, or sometimes completely wanting. The large, irregular, newly formed medullary spaces abound in hollow, club-shaped formations — the future capillaries — which contain numerous haematoblasts and red blood-corpus- cles. At the peripheral portions of the epiphyseal cartilage a new formation of vascularized cartilage, instead of bone, can be traced, while the newly formed trabeculae of bone are scanty, irregular in shape, holding large bone-corpuscles and territories with distinct boundary lines. Similar features are observed at the points of junction of hyaline cartilage and bone in rachitic ribs. Here, too, the new formation of cartilage is proceeding from medullary tissue on a large scale, mostly in groups, repre- senting the territories. The cartilage is dissolved out, leaving a * Virchow'sArchiv, Bd.lvi. t "Zur Lehre von den Knochenkrankeiten." Henle u. Pfeiffer's Zeitschr., iii., 1853. 398 INFLAMMA TION. medullary tissue freely supplied with blood-vessels of considera- ble caliber, venous and capillary chiefly ; but the production of bone from this vascularized tissue is extremely scanty and with- out uniformity. (See Fig. 167.) At the peripheral portions of the shaft-bones we find, between the thin cortical bone-tissue and the fibrous portion of the perios- teum, a broad layer of medullary tissue, which is sometimes arranged in patches. The blood supply of this medullary tissue is so great as to give the appearance of a hemorrhage to the MS MossENGCoN.Y, FIG. 167. — RACHITIS. RIB OF A CHILD, IN TRANVERSE SECTION. CHROMIC ACID SPECIMEN. C, cartilage corpuscles, arranged in territories ; MS, medullary space, sprung from carti- lage tissue ; M, medullary tissue with very large blood-vessels, BV, and a scanty new forma- tion of bone-tissue, B. Magnified 200 diameters. naked eye. The bone generally remains in the stage of cancel- lous structure, with large, irregular medullary spaces. The flat skull-bones, being developed from fibrous connective tissue, exhibit similar features — the so-called craniotabes. In some places medullary tissue is formed, leading to a reproduction of fibrous connective tissue, instead of bone j or already formed bone, through the intermediate medullary stage, passes into a INFLAMMATION. 399 new formation of fibrous connective tissue, resulting in thinning of the bone. In other places the exuberant growth of medullary tissue causes a broadening of the diameter of the bone, with a scanty trabecular new formation of bone-tissue. Both the medul- lary and the newly formed connective tissue are supplied with a considerably larger amount of blood-vessels than is seen in the normal condition. The pathological condition is that of a plastic inflammation, in accordance with the views expressed by Virchow, and there is good reason to consider the process of rachitis as an inflammation. By feeding pups and kittens with lactic acid, rickets was induced, exhibiting in the osseous system features identical to those observed in rachitic children. Osteomalacia. This rare form of disease, which is always accompanied by intense pains, usually attacks the vertebral col- umn and the pelvic bones, though there are cases on record in which the whole skeleton was rendered as pliable as wax. Under the microscope we see a decalcification of fully formed bone-structure, usually of the compact portions, advancing in a way similar to the inflammatory process. The bone-tissue is transformed into medullary tissue, which in some places is distin- guished by a large quantity of blood-vessels. My researches enable me to state that the ultimate productions from medullary tissue are of two kinds : either colloid globules or simply fibrous connective tissue. In a femur of a woman who, during pregnancy, was attacked with osteomalacia, and died of the disease, the compact portion of the bone was reduced to the thinness of a pasteboard, and was very pliable. The central marrow space was filled with a smeary, grayish yellow mass, which, under the microscope, proved to be colloid — viz. : consisted of globular or irregularly shaped corpuscles of a luster similar to fat, but not yielding to the re-agents which dissolve fat. They resisted even the action of strong alkalies and acids which destroyed the bone-tissue proper,, and assumed a dark purplish violet color upon being stained with chloride of gold. (Fat is unaffected by chloride of gold.) Within the globules radiating bodies were often seen, somewhat similar to the needle-shaped crystals of the so-called margaric acid. Between the globules scanty fibrous connective tissue with a few blood-vessels was noticeable. The origin of the colloid corpuscles could be traced in the thin compact shell of the femur, in which the lamellae were much . 400 INFLAMMA TION. more marked than normal, evidently due to a dissolution of the lime-salts during life. Numerous medullary spaces, containing a varying number of colloid corpuscles, traversed the bone. Some of these bodies exhibited faint traces of the medullary cor- puscles which composed them ; others, in the initial stage of the colloid metamorphosis, were distinctly seen, consisting of medul- lary corpuscles, so that each colloid body might be considered as having originated from a group of coalesced medullary cor- puscles. In some places long rows of colloid corpuscles were noticeable, each of which re- sembled a territory with a condensed, peripheral colloid frame, and a central body, somewhat like a bone-corpus- cle. (See Fig. 168.) In the rib-bone of another woman, dead of osteomalacia, I found very large medullary spaces, which were filled partly with medullary and partly with fibrous tissue, and contained also a number of yellow-brown pigment clusters. These spaces were very vascular. In this case no colloid corpuscles could be detected. In dogs and cats, whose bones were artificially brought into the condition of osteomal- acia, all features described J5, bone-corpuscle ; L, distinctly marked la- mellae ; C, colloid corpuscles, arranged in a row. Magnified 500 diameters. FIG. 168. — OSTEOMALACIA. FEMUR OF A WOMAN; LONGITUDINAL SECTION. CHROMIC ACID SPECIMEN. above as occurring in the mal- acic femur of the woman were present, and especially the col- loid globules. These closely resemble fat-globules, but, never- theless, were an entirely different substance, as they did not yield to strong alkalies and acids, not even after being boiled with them. Chloride of gold stained them a dark purplish-violet color. The bones of the squirrel, which had been fed for thirteen months with lactic acid, had compact portions as thin as paper. They were, to a great extent, transformed into medullary and fibrous tissue; they contained a large number of blood-vessels INFLAMMATION. 401 and pigment clusters, but no colloid corpuscles. The resem- blance the case bore to the second case of malacic ribs was very striking. In conclusion, I wish to say a few words as to the withholding of lime food in the animals experimented upon. It was, in fact, only a reduction, but not by any means an entire cutting off of the lime supply. The dogs and cats were fed with fresh boiled meat, with fat, with milk and white bread ; but no bones were given. The desire of all these animals for lime food, during the treatment with lactic acid, was evident. The cats and dogs rushed for egg-shells, whenever they came within their reach ; the squirrel scraped off the kalsomining from the wall so eagerly that its cage had to be removed from the wall, though its food was that suitable for squirrels. In a dog, in which osteomalacia had been induced, I produced a subcuta- neous fracture of the leg-bones. When the animal was killed, seven weeks after the fracture, the callus exhibited a marked cartilaginous new formation, but with only a scanty deposition of lime-salts and very limited new formation of bone near the injured bone-tissue. As in the above-named period the fractured bones of normal dogs invariably exhibited the formation of a defined cancellous bone-callus, in the dog treated with lactic acid the forma- tion of a bone-callus was obviously prevented. As to the case of the seven months fostus, completely destitute of bones, born of a woman who for months during her pregnancy had fed the animals with lactic acid, I wish to state that this woman must certainly have inhaled the vapors of lactic acid, more particularly if poured into the warm soup destined for the animals. The woman was otherwise healthy, and remained so after delivery ; nevertheless, it must be mentioned that, several years previously, she had given birth to a child which in early childhood was slightly rachitic. The seven months foetus died of cerebral hemorrhage, which had evidently taken place during delivery, as the protecting skull-bones were absent. 2. INFLAMMATION OF MUSCLE. TRICHINOSIS. t In 1868,* I published a series of observations and experiments leading to the conclusion that the villi of the small intestine had, at their points, perforations which opened directly into the cen- tral lymph-vessel of the villus. The existence of these openings could not, however, be positively proved. If these were really an anatomical condition, we could easily understand how the embryo trichinae are transported from the cavity of the small intestine, first into the chylif erous duct and afterward into the vascular system. The trichinae could be carried with the blood, and fixed * "Zur Kenntniss der Diinndarmzotten." Sitzungsber. d. Wiener Aka- demie d. Wissensch., Iviii., Bd. 1868. 26 402 INFLAMMATION. as emboli in the tissue of striped muscles, at the points where the arteries merge into capillaries, which, owing to their rectangular division (see page 274, fig. 117), would retain the worms. Muscles which have a continuous motion and a markedly rectangular division of their blood-vessels — f. i., the diaphragm — would be the first to be invaded by the parasites, while muscles without this rectangular arrangement of the vessels — f. i., the heart — would not be apt to become trichinosed. The theory that the trichina embryos perforate the walls of the intestine, and thence migrate into the muscles, is highly improbable, as these parasites have no apparatus for perforating tissues. At the time before mentioned, I made in the Vienna Veterinary School a number of experiments for the purpose of observing trichinae in the chyliferous system of the intestine. I fed Guinea pigs with fresh trichinosed muscle ; but these experiments proved to be failures, as the animals became so rapidly affected after a few days that all of them died, and I looked in vain for embryonal trichinae in the villosities of their small intestines. As soon as the embryos of trichinae reach the muscle an inflammation of this tissue (myosibis) sets in, which I have studied in all its phases. As to inflammatory changes of smooth muscle, we know,, through the researches of Durante and others, that the spindles divide into rows of inflammatory corpuscles, which at first retain the general shape of the original muscle-spindles. Later, the cor- puscles break apart in the same way as those sprung from con- nective tissue. Inflammation of the striped muscles has, since 1851, often been the subject of microscopic researches. Some observers have asserted that only the nuclei of the muscle-fibers participate in the inflammatory new formation j others, that both the nuclei and the contractile substance proliferate ; again, others have denied any participation of nuclei or contractile substance, believing that both perish, and that the whole inflammatory new formation is due only to an emigration of colorless blood-corpuscles. Colberg especially, in 1864 asserted that in trichinosed muscles an increase of the nuclei occurs. Spina, one of the recent writers on the inflammation of muscle, based his views upon researches made in the frog's tongue, which he had artificially inflamed; he claims that the nuclei become much augmented, and that the contractile INFLAMMA TION. 403 substance itself breaks up into pus-corpuscles, and that from solid caky masses, the product of the inflamed muscle tissue — red blood-corpuscles arise.* The invasion of muscle-tissue is immediately followed by an inflammatory process, visible first in the perimysium. (See Fig. 169.) The perimysium becomes thickened and more or less crowded with inflammatory cor- puscles. The basis-substance is liquefied, the tissue reduced to its juvenile condition, and the newly appearing medullary cor- puscles by increase of their liv- ing matter become augmented in the same manner in which fibrous connective tissue in gen- eral is affected by the inflamma- tory process. (See page 356.) The muscle-fibers in the ear- liest stages of inflammation are unaltered, but very soon a marked change takes place in certain portions, depending upon the location and number of the parasites. The process may attack single muscle-fibers in such a way that almost un- changed fibers lie close to those exhibiting highly advanced al- terations in their texture ; or even a single fiber may be normal in parts, and in parts FIG. invaded by the inflammatory process. The first noticeable change consists in an enlargement of the sarcous elements and a destruction of their regular arrange- ment, together with the appearance of a larger number of bodies, usually termed the nuclei of the muscle-fiber. These formations * Arnold Spina. " Untersuchungen iiber die entziindl. Veranderungeu d. quergestreifteri Muskelfasern." Wiener Mediz. JahrMcher, 1878. In this essay a full account of the literature of this subject is found. 169.— STRIPED MUSCLE FROM THE LEG OF A MAN, RECENTLY INVADED BY TRICHINAE. F, trichina in front view ; S, trichina in side view. Magnified 200 diameters. 404 INFLAMMATION. being present in the middle of every muscle-fiber as well as at its periphery, in both situations clusters of nuclei are found, some of which have originated from former nuclei, while others are newly formed. A division and multiplication of the nuclei is inferred from the fact that we frequently find clusters of nuclei, exhibiting cleavage, or marks of division. The next change is that, by an increase of the bioplasson of the sarcous elements, solid lumps arise, which in turn are split into a reticulum and become nucleated, by the usual process of formation of reticular from solid bioplasson. Thus medullary or inflamma- tory corpuscles become visible, arranged in clusters, which are unquestionably identical with those embryonal formations from which the striated muscle-tissue is developed. Instead of clus- ters of medullary corpuscles, sometimes multinuclear bioplasson masses are observed. These clusters are separated from each other by rims broader than those between the single medullary elements ; but all of these and all of the clusters remain uninter- ruptedly connected by means of delicate bioplasson filaments which traverse the interlyingjight rims. (See Fig. 170.) The clusters are arranged in rows, indicating that at first the sarcolemma remains unaltered. Afterward, however, it becomes liquefied, and the inflammatory corpuscles sprung from the muscle-tissue commingle with those produced by the peri- mysium, and in this manner more or less extensive masses of inflammatory corpuscles are formed, which are bounded by relatively little changed muscle-fibers. A second change of the muscle-tissue consists in an enormous increase of the bioplasson of the sarcous elements, which, by confluence, produce irregular, caky, and globular masses of a high degree of luster, apparently destitute of structure and closely resembling fat. Former observers mistook these formations for the result of a degenerative process. According to Spina's view, which is undoubtedly correct, they are the products of a progress- ive inflammatory change of the contractile muscle-tissue. These formations are not soluble in turpentine, therefore are not fat j they are readily stained with chloride of gold, but not with carmine. Evidently, they are solid lumps of bioplasson in a juvenile condition, which, in 1872, I termed " haamatoblastic." From them originate, by division, a number of small solid parti- cles, each of which gives rise to a new inflammatory element, or, should the lumps break apart and become isolated, to red blood- corpuscles. Such corpuscles are often found in clusters within INFLAMMA TION. 405 the unbroken sarcolemma sheath, which plainly 'demonstrates that they are not the result of hemorrhage. After the inflammation abates, the medullary corpuscles give rise to a more or less extensive new formation of connective tis- sue, constituting a cicatrix in the middle of the muscle. Clusters of medullary corpuscles may again proceed to the forming of FIG. 170. — INFLAMMATORY CHANGES OF MUSCLE-TISSUE AFTER RECENT INVASION OF TRICHINA. FROM THE LEG OF A MAN. PM, inflamed perimysium; P, initial inflammatory change of muscle; /, high degree of inflammatory change ; L, homogeneous caky, and F, globular, masses of solid bioplasson ; 6', capillary blood-vessel, with enlarged eudothelia. Magnified 600 diameters. striated muscle-tissue, as was first maintained by C. O. Weber. If, on the contrary, the filaments connecting the inflammatory corpuscles break, pus-corpuscles will be produced, and by their 406 INFLAMMATION. presence establish an intramuscular abscess. I have observed this result after amputation of the tongue, for cancer, with the galvano-cautery. The cicatrix may, under certain conditions, become trans- formed into bone; and regular bone-plates are sometimes met with in muscle-tissue, which, for a long period of time, was exposed to irritation. If, from the very beginning, the inflammatory process is con- fined to the perimysium, a hyperplasia of connective tissue will ensue, which is often mistaken for genuine hyperplasia of the muscle-tissue itself. In trichinosis, one of the re- sults of the plastic inflamma- tion is the formation of a hya- line capsule around the parasite, provided that the life of the patient is sufficiently prolonged for such a comparatively favor- able termination. How the cap- r sule is formed I cannot say from direct observation. In old cases of trichinosis we find in the mid- dle of the capsule one, sometimes two, worms, coiled up with the well-known two and a half turns, shriveled and evidently saturat- ed with lime-salts. (See Fig. 171.) The space between the tri- china and its capsule is filled with a granular deposit of lime- salts. Such depositions are fre- quently met with at the poles of the capsule, and sometimes they have a peculiar stratified appear- ance. In the vicinity of an en- cysted trichina we always find cicatricial fibrous connective tissue replacing the muscle fibers which were destroyed by the former inflammatory process, and the cicatrix, as a rule, con- tains a varying number of fat-globules. FIG. 171. — ENCYSTED TRICHINA IN THE PECTORAL MUSCLE OF A MAN. T, shriveled trichina, surrounded by a gran- ular calcareous mass and inclosed by a hya- line capsule, C; JC, knob-like deposition of lime-salts at one pole of the capsule; F, vacu- oled fat-globules. Magnified 200 diameters. INFLAMMATION. 407 3. INFLAMMATION OF NERVE-TISSUE. Inflammation of nerve-tissue is characterized by occurrences very similar to those observed in inflammation of connective tissue. All varieties of nerve-tissue — the gray substance, the ganglionic elements, the medullated and non-medullated nerve- fibers — first break down into medullary corpuscles, identical with those which in embryonal development took part in the produc- tion of nerve-tissue. The first step of the inflammatory changes in nerves, as in muscle-tissue, always starts in the supporting and accompanying connective tissue, which, being the carrier of blood-vessels, reacts most promptly to the irritation. Next follows the proliferation of inflammatory corpuscles arising from the nervous tissue, and the sum of the inflammatory new formation, so long as the continuity of the corpuscles remains unbroken, results in the production of a dense, indistinctly fibrous connective tissue, establishing the condition of sclerosis in the tissues of the nerve- centers. Later, shrinkage of the newly formed connective tissue causes retractions on the surface of the brain, which process H. Kundrat terms porencephalitis. Should the inflammatory corpuscles break apart in the early stages of inflammation, the result will be a complete destruction of the tissue involved — L e., the formation of an abscess. The wall of the abscess, again, may be built up by newly formed connective tissue. Such a combination of a formative and destructive inflammatory process is well illustrated by the fol- lowing article : MICROSCOPICAL STUDIES ON ABSCESS OF THE BRAIN. BY H. G. BEYER, M. D., P. A. SURGEON U. S. NAVY.* The subject of my studies is a brain, the history of which is published in the Transactions of the New York Pathological Society, vol. i., edited by JohnC. Peters, M.D. At a meeting of this society, held on January 13, 1875, Dr. J. Lewis Smith presented a specimen with the history, which is briefly as follows : " Maggie, aged two years and six months, seemed in good health, was plump and well developed. On the evening of December 5th, she ate her supper as usual, and was placed in her crib, apparently in perfect health. At 3 A. M. she was found in severe general ecclampsia. The general spasmodic * "Journal of Nervous and Mental Disease," July. 1880. The essay is here reprinted in abstract. The term " protoplasm " is changed into that of " bioplasson." 408 INFLAMMATION. movements continued with more or less violence till 1.30 P. M., and in the muscles of the neck somewhat longer. "At about 6 P. M., I found her lying quiet, rather stupid, but easily aroused. Her vision was evidently good, and she was conscious ; the pupils responded to light, and the direction of the eyes was normal ; pulse 104 ; no cough ; respiration and temperature normal. There was no apparent loss of motion of the muscles of the face, but the right arm and legs were paralyzed, though the palsy was not complete. The great toe flexed on tickling the sole of the foot, but the foot itself showed little or no motion ; but on attempt- ing to flex the leg, which was extended, some rigidity of the muscles was observed. At times, the patient produced slight movement of the thigh upon the trunk. I think, during the two or three days succeeding the convulsions, sensation in the right limbs was not entirely lost, though greatly enfeebled. Subsequently paralysis in the right limbs, both of the nerves of sensation and motion, became nearly or quite complete, and continued so until death. Nevertheless, tickling of the sole of the foot caused some movements of the great toe. On the left side, -sensation and motion were perfect. "December 9th. Has vomited to-day for first time ; apparently sees well, and the appearance of the eyes is normal ; has no retraction of the head or rigidity of the muscles of the neck, nor along the spine ; pulse 96 ; tempera- ture normal ; lies quiet with eyes shut ; is stupid and not particularly fretful when aroused ; her bowels moved regularly. "December llth. Continued to vomit at intervals; pulse 68. " December 16th. Pulse 80, temperature 100; vomited once yesterday, not to-day ; lies in a constant doze. " December 18th. Moans at times, as if in pain; pulse 180, temperature 100° F. "December 19th. Pulse 180, temperature 103°; there is convergent strabismus, and her eyes have a wild, almost insane, look ; but she can see, and grasped, hurriedly, a percussion hammer presented towards her. Para- lysis of nerves of motion and sensation in the right extremities nearly com- plete ; slight movement could still be induced in the great toe by titillation ; the vomiting has ceased ; tongue covered with a thick fur ; movements of the bowels pretty regular; has a slight cough, such as is common in cerebral disease. " December 22d. Lies quietly on her side in perpetual slumber, with eyes constantly shut ; pulse 118, temperature 101^°; the bowels still moved nearly normally. The pupils, when exposed to the light, were seen to oscillate, but are constantly more dilated than in health ; the urine passes freely. Has, at intervals, circumscribed flushing of the features. " December 24th. Pulse intermittent ; pupils dilated. "December 25th. Died in profound stupor to-day, having lived nineteen days from the commencement of the malady. "Autopsy. On removing the calvarium and dura mater, which presented no unusual appearance, the vessels of the pia mater were found rather more injected than common. The cerebro-spinal fluid was scanty, and the surface of the brain rather dry. The vertex of the left hemisphere was unusually prominent, rising perhaps half an inch higher than that of the opposite side. At the highest point, which was about one inch and a half from the median line, was a circular yellowish spot upon the surface of the brain, about one and a half inches in diameter. Pressure upon the spot, made lightly, com- INFLAMMATION. 409 municated the sensation of a large cavity underneath, filled with liquid, and approaching to within two or three lines of the surface. There was no adhesion or exudation at that point ; and the surface of the brain appeared entirely normal, except slight cloudiness of the pia mater at the base of the brain, a little posterior to the optic commissure. The incised surface of the brain, at a distance from the abscess, showed no increase of vascularity. The right hemisphere appeared in every way normal, except that its lateral ventri- cle was filled with pus, but not distended. "On the left side, occupying the center of the hemisphere, was an abscess as large as the fist of a child of two years, extending from within two to three lines of the vertex, where its site corresponded with the yellow spot on the surface of the brain, to the roof of the lateral ventricle. Through this roof the abscess had burst, filling and distending the ventricle with pus, and thence making its way into the lateral ventricle of the right hemisphere. The whole amount of pus contained in the abscess and the two ventricles was perhaps two ounces. " The walls of the left lateral ventricles were much softened, the upper part of the corpus striatum and thalamus opticus being nearly diffluent. The walls of the right lateral ventricle were slightly softened, but to a less depth. The parietes of the abscess, which extended from the roof of the ventricle to the vertex, as already stated, were indurated to the depth of one and a half lines, except at the base of the abscess, which corresponded with the roof of the ventricle, where softening had occurred. The spinal cord, so far as it could be examined from the cranial cavity, had the usual vascularity, but was slightly softened. " The cause of the encephalitis from which the abscess resulted was obscure. The inflammation, so far as could be ascertained, was idiopathic. There was no history of otitis, which is one of the most frequent causes of cerebral abscess ; nor of heart disease so as to produce embolism. It seems probable, since there was no fever till about the fourth day after the convul- sions, that an abscess had primarily occurred in the hemisphere between the roof of the ventricle and the vertex — possibly some weeks previously. The bursting of this into the lateral ventricle, and the constitutional disturbance, inflammation, and softening to which these would inevitably give rise, affords sufficient explanation of the history of the case, after the commencement of the convulsions." * The specimen was kept in a very dilute solution of chromic acid for several months, after which time it was hardened in alcohol and imbedded in a mix- ture of paraffine and wax, whereby care was taken to enclose mainly the wall of the abscess and its immediate surroundings. Previous to the beginning of my studies, a certain number of sections had been made of the wall of the abscess itself, as well as from other parts of the brain, such as the cere- brum, the cerebellum, the medulla oblongata, and the gray matter. These sections everywhere had been found holding a large number of so-called amy- laceous corpuscles, exhibiting all the characteristic chemical and morpholog- ical features of these formations. No other changes could be traced out, nor did the blood-vessels show any anomalous conditions, excepting the capil- laries, which were found dilated and choked with blood-corpuscles within the inflammatory focus, as well as in its neighborhood. I made a number of sections, both from the wall of the abscess and the surrounding portion of the brain, which sections embraced the gray matter of 410 INFLAMMA TION. the corpus striatum, thalamus options, the cortex of the left hemisphere, also the white substance of the same, which, as is evident from the history, was the seat of the abscess. The specimens thus obtained were stained, partly with an ammoniacal solution of carmine, partly, after thorough washing out with distilled water, with a one-half per cent, solution of chloride of gold. The different sections were mounted in glycerine, diluted with distilled water — this method of mounting, as experience teaches, being far superior to the method of mounting in Canada balsam or dammar varnish. While glycerine-mounted specimens, if taken from properly hardened material, keep almost any length of time, never losing their sharp and definite outlines of detail, Canada balsam •specimens, on the contrary, very soon become so transparent that their minute details are completely lost to sight, and only the coarser formations remain distinguishable. Canada balsam specimens, therefore, are fit for lower powers of the microscope only; they are worthless for a power exceeding 400 diameters, or for any power intended to give a display of the m-M FIG. 172. — WALL OF AN ABSCESS OF THE BRAIN. TRANSVERSE SECTION. F, layer of fibrous connective tissue with scanty blood-vessels, bounding the abscess ; M, layer of myxomatous connective tissue, with numerous capillary blood-vessels ; W, white substance of the brain, with numerous large blood-vessels. Magnified 200 diameters. more minute anatomical features. Our lack of knowledge of the minute pathological anatomy of the central nervous organization is mainly due to the method of mounting in Canada balsam. The subject of these investigations will be treated under the four follow- ing heads, namely : Inflammatory changes of — (1) Wall of abscess; (2) white substance; (3) non-medullated nerve- fibers ; (4) gray substance. (1) Wall of Abscess. Transverse sections through the wall of the abscess, which in different places varied in width from one to two millimeters, exhib- INFLAMMA TION. 411 ited the following characteristic features. (See Fig. 172.) A layer of fibrous connective tissue forms the boundary of the abscess, its innermost portion presenting a somewhat jagged appearance, due to a number of attached pus- corpuscles. The bundles of connective tissue in this situation were partly infiltrated with, partly transformed into, pus-corpuscles, and were arranged in the shape of rows, between which a scanty basis-substance was traceable. In their general direction, these rows corresponded to that of the bundles in the subjacent tissue stratum, which was built up by dense bundles of fibrous connective tissue in a more or less parallel course, and with but few decus- sations inclosing narrow, oblong spaces. These connective-tissue fibers held a large number of small spindle-shaped and a somewhat larger number of globular bioplas- son bodies, the former representing what has been termed connective- tissue corpuscles, the latter in- flammatory elements. The meshes between the bundles contained granular layers of bioplasson, with a number of inflammatory elements, and also a moderate amount of capillary blood-vessels. In this layer, all stages of newly developing connective tissue could be observed ; clusters of medullary or inflammatory elements ; clus- ters in which these elements had already assumed an oblong or spindle shape ; delicate spindles, closely packed together and trans- formed into basis-substance, with a relatively small number of bio- plasson bodies left. Beneath the above described layer of fibrous connective tissue, the so-called membrana pyogena of the older writers, there followed a broad layer of connective tissue, exhibiting all the characteristics of the variety termed myxomatous. The connective-tissue bundles, while dense in the innermost layer, had become loose in the myxomatous portion, changing to a more or less vertical course, and inclosing large meshes of a homogeneous basis-substance. The coarser bundles formed strings, which by inosculating with each other produced a reticulum, built up almost exclusively by spindle- shaped elements, partly transformed into basis-substance. Within the meshes of this reticulum is contained a very delicate fibrous connective tissue, with numerous, mainly spindle-shaped, bioplasson bodies ; large fields of the meshes hold an almost homogeneous or very slightly gran- ular basis-substance. (See Fig. 173.) A number of capillary blood-vessels of a considerable size, and partly filled with red blood-corpuscles, were also met with. The endothelia of these capillaries were very large, and found FIG. 173. — WALL OF AN ABSCESS OF THE BRAIN. TRANSVERSE SECTION. F, layer of fibrous connective tissue ; V, nests of medullary elements, apparently produced by the proliferation of the endothelia of former blood- vessels ; M, myxomatous portion, in the meshes of which numerous medullary elements are im- bedded, either in a delicate fibrous reticulum, or in a light, homogeneous basis-substance. Magni- fied 500 diameters. 412 INFLAMMATION. to take up the carmine stain much more readily than endothelia under normal conditions. Around the wreath formed by these endothelia, in many instances, a light space was present, which space was enclosed by a collection of spin- dle-shaped bodies — the peri vascular sheath. Outside of this myxomatous layer of connective tissue, in the wall of the abscess, is seen the white sub- stance, bounding the layer of connective tissue in a very nearly straight line, and considerably altered in structure, as will presently be described. In addition to the above-described changes within the wall of the abscess, one of the most striking phenomena exhibited in some of my specimens is the retro- grade movement of already newly formed capillary blood-vessels into their embryonal state — namely, the dissolution of their walls into medullary or embryonal or indifferent elements, resulting in the formation of solid connective-tissue bundles. (2) White Substance. The white substance around the abscess, as mentioned above, was in the condition of softening, and, even after careful preservation of the specimen, difficult to cut. With lower powers of the microscope, in the immediate vicinity of the abscess, the capillary blood-vessels of the white substance were seen to be considerably dilated and en- gorged with blood-corpuscles. The perivas- cular space, in many instances, was also dilated, and filled with a finely granular, evi- dently serous or albuminouS) exudation. The changes in the nerve-tissue were best marked on the periphery of the blood-vessels. The nerve-fibers had lost their myeline-sheath to a considerable degree, and their axis-cylind- FIG. 174. -Axis - CYLINDERS FROM THE BOUNDARY BE- TWEEN THE GRAY AND A\ rosary-like, A*, club-shaped, the breaking apart of the axis-cylin- layer of a faintly reticular bioplasson, which der; .zv, nucleus of the gray substance again was bounded by a thin homogeneous OT granular sheath. Owing to a want of di- rect observation I am not enabled to tell what really had become of the myeline. It is, however, very probable that during the initial stages of the inflammatory process the myeline is dissolved out. In many places the white substance was transformed into a finely granular mass, in which bioplasson bodies, so-called medullary elements, could be traced out, alternating with groups of shining homogeneous granules and relatively little changed nerve-fibers. Higher powers of the microscope gave a complete series of the changes of the axis-cylinders, which had led to the formation of medullary elements. (See Fig. 174.) First, the axis-cylinders exhibited delicate nodular enlarge- ments and, at certain irregular intervals, a more regular rosary-like arrange- ment. In certain districts the axis-cylinder was transformed into a relatively coarse, shining, beaded fiber, also presenting a great many club-like enlarge- ments. Next, some of the granules alongside the axis-cylinders appeared enlarged, and were provided with delicate vacuoles ; and, lastly, the axis- INFLAMMATION. 413 cylinders were transformed into a chain of pale "bioplasson bodies, the so- called medullary or inflammatory elements. Within the inflamed portion of the white substance were observed numer- ous varicosities, each of which was in direct connection with an axis-cylinder. In many instances, the interior of these varicosities could be made out to be of a delicate reticular structure ; they were invariably bounded by a dense and homogeneous layer, continuous with the axis-cylinder. All the forma- tions of the above description were uninterruptedly connected with each other by extremely delicate threads. In some places small abscesses had formed outside the wall of the main abscess ; these abscesses were detected only with the microscope. In such localities the medullary elements had assumed a more uniform size, a some- what coarser granulation, and, having also lost their mutual connections, they were transformed into pus-corpuscles. As a matter of course, that portion of the white substance which had undergone such a change into pus-corpuscles was devoid of blood-vessels. The manner in which blood-vessels are lost, shortly before the tissues break down and are transformed into pus, was easily traceable in the neighborhood of such small abscesses. The endothelia of both the blood-vessel and the perivascular sheath became considerably enlarged, coarsely granular, or were supplied with at least several large shining granules, which might justifiably be considered as newly formed nuclei. By a process of splitting of the enlarged endothelia into medullary elements, the caliber of the blood-vessel, as well as of the ,perivascular sheath, became obstructed, and thus, what formerly had been a capillary, now was seen to have become transformed into a row of medullary elements. These at first remained in connection with each other by means of delicate processes, traversing the newly formed cement-substance, afterward broke apart and became pus-corpuscles, in shape and size fully identical with those sprung from other portions of the inflamed tissue. The above-mentioned varicosities of the nerve-fibers, by different authors are considered as post-mortem changes, and due to an irregular coagulation of the myeline. The varicosities which I have described here have nothing to do with myeline, but are formations of the axis-cylinders themselves, and due to structural changes in the substance of these axis-cylinders proper — viz., enlargement of the thread, exhibiting the ordinary structure of bio- plasson, and in close connection with the inflammatory changes of the nerve- fibers in general. These changes in the axis-cylinders can be understood only if we look upon the latter as formations of living matter. In the inflammatory process, the granules of living matter in bioplasson bodies increase in size, some- times to such an extent that the body is transformed into a shining, homo- geneous lump, which readily divides into smaller particles, each of which in turn may become a medullary element. The axis-cylinders, being formations of living matter, also become coarsely granular, beaded, or rosary-like, and each one of these granular enlargements may give rise to a new medullary element, eventually a pus-corpuscle. In this manner we understand the formation of rows of medullary elements and of pus in the middle of the white substance of the brain. Ever since J. Cohnheim asserted that the main, if not the only, source of inflammatory elements and pus-corpuscles are the emigrated colorless blood- corpuscles, some authors had entirely overlooked the changes taking place 414 INFLAMMATION. in the constituent elements of an inflamed tissue. Nobody, nowadays, is intending to deny the emigration of colorless blood-corpuscles from capillary blood-vessels and small veins during the inflammatory process. Specimens obtained from the brain under consideration, by the immediate transportation of softened parts of the white and gray substance under the microscope, plainly demonstrated the existence of such a process. Along the wall of an enormously enlarged and engorged blood-vessel were seen colorless blood- corpuscles of a club shape, with one blunt extremity still in the caliber of the blood-vessel, with a thin pedicle still embedded in its wall, with the other blunt extremity protruding outside the periphery of the blood-vessel. Not infrequently a colorless blood-corpuscle was seen to be attached to the wall of the vessel by means of a slender pedicle, the main mass of the corpuscle being outside the wall of the blood-vessel or within the lumen of the peri vascular space. There cannot be any doubt that the emigrated colorless blood-cor- puscles share in the formation of pus-corpuscles, yet I lay stress upon the fact that the main source of inflammatory elements and pus-corpuscles must be looked for in the living substance of the inflamed tissue itself. More espe- cially in the white substance of the brain under consideration, all the stages were traceable, from the granular enlargement of the living matter of an axis- cylinder up to the complete development and formation of inflammatory ele- ments and pus-corpuscles therefrom. ' (3) Non-medullated Nerve-fibers. A certain portion of my specimens, which was taken from the vicinity of the abscess, exhibited a large number of non- medullated nerve-fibers in bundles cut longitudinally and transversely. In the longitudinal bundles, the gray nerve-fibers were so closely packed together that but a very faint striation could be traced out. In the midst of such bundles there were numerous nests of medullary elements, of a prevailing oblong shape, and independent of any blood-vessels. Around these nests the following changes in the non-medullated nerve-fibers could be made out : First, the nerve-fibers had assumed a beaded or rosary -like appearance ; next, they had become spindle-shaped and coarsely granular ; after this, evidently from an increase in the size of the granules, the nerve-fibers had been transformed into an oblong cluster of bioplasson, within which, through the formation of a separating cement-substance, medullary elements made their appearance, in clusters, still retaining their spindle shapes. Lastly, a number of such spindle-shaped nests had coalesced, and rows and clusters of medullary ele- ments could be seen, separated from each other only by a small number of unchanged non-medullated nerve-fibers. Wherever such a transformation of nerve-fibers into clusters of medullary elements had taken place in a larger district, the result was the formation of an inflammatory nest, in which' the elements were connected with each other by delicate threads. I have not seen an abscess in the middle of non-medul- lated nerve-fibers, but it is obvious from what I said before, that through the breaking apart of these medullary elements, as yet connected by delicate threads, pus-corpuscles may arise. I claim, basing myself upon direct observation, that inflammatory foci, with crowded inflammatory elements, can arise from direct changes of the bare axis-cylinders constituting non-medullated nerve-fibers, independently of either blood-vessels or emigration of colorless blood-corpuscles. (4) Gray Substance. In the vicinity of the abscess of the brain, I have met with a number of changes in the gray substance. First, the points of inter- INFLAMMATION. 415 section of the living matter were enlarged, wherefrom resulted a coarse granulation of the gray substance. In many places, with the highest powers of the microscope, the points of intersection of the reticulum were clustered together to such an extent that lightly granular, nearly homogeneous, groups appeared, each of which was surrounded by a light rim. Owing to an aug- mented afflux of nourishing material, the formations of living matter had evidently very much increased in size, and by approaching each other pro- duced densely granular or homogeneous lumps of living matter, with the appearance of indifferent or medullary elements. In certain places, the whole mass of the gray substance had been transformed into such medullary cor- puscles, between which bundles of non-medullated nerve-fibers and blood- vessels, mainly capillary in nature, were still recognizable. The nerve-fibers traversing the gray substance were mostly increased in size, and transformed into beaded fibers or chains of small homogeneous lumps. The blood-vessels, besides being completely obstructed with red blood-corpuscles, exhibited changes in their endothelial walls identical with those described above in connection with the white substance. The nuclei of the gray substance were mostly very coarsely granular ; the nucleoli especially had increased in size, and looked as if split up into a num- ber of coarse granules. More especially in the carmine-stained specimens I often observed larger spaces, identical with the periganglionic space, either empty or holding extremely delicate granules. These spaces, so-called vacuoles, very probably had formed by an accumulation of a serous exudation around the nuclei, by which either a certain amount of the surrounding gray substance was pushed in a peripheral direction, or a certain amount of living matter destroyed. The fine granules within the above spaces, consequently, were either coagulated albumen or remnants of the former reticulum of living matter. New formation of nuclei in the inflamed gray substance is of very common occurrence. Within the spaces just described I sometimes saw one large and two or three small nuclei, which, being in contact with their flattened sur- faces, looking toward each other, allow of the conclusion that they had origi- nated by a process of division of the original single nucleus. New formation of nuclei, doubtless, takes place independently of former nuclei in the gray substance. I have seen repeatedly clusters of bioplasson near the wall of the abscess, with irregular outlines and holding a large num- ber of oblong nuclei. Such multi-nuclear masses are evidently produced by the confluence of bioplasson bodies (emigrated colorless corpuscles — Ziegler),. or by the formation of territories previous to their division into inflammatory elements. The ganglionic elements within the inflamed brain-tissue exhibit a series of changes of great interest. Nearest to the abscess a number of ganglionic elements had swelled and been transformed into almost homogeneous, indis- tinctly granular bodies, still characterized by the presence of offshoots and a deep carmine stain. No doubt, the swelling of these elements is due to an inundation with exudation, which leads to a stretching and breaking apart of the reticulum of living matter therein. The capillaries of regions where such swelled ganglionic elements are numerous are considerably dilated, their endothelial coat is partly thinned, partly thickened, by endogenous new growth, and their perivascular sheath enormously widened. In this space I have seen faint granules and pale gran- 416 INFLAMMA TION. ular bioplasson "bodies of the size of colorless blood-corpuscles, indicating that immigration of such corpuscles had taken place. In other portions of the gray substance a marked proliferation of the gang- lionic bodies can be observed. There are bodies with enlarged and beaded nucleoli, bodies with two or three isolated nucleoli, bodies with two or three coarsely granular nuclei, sprung from a division of the original nucleus, as is proved by the presence of facets, where the nuclei lay against one another. (See Fig. 175.) Many ganglionic elements are transformed into coarsely granular, nearly homogeneous, lumps, and split into smaller lumps, varying in number from two to seven or eight. The clusters of bioplasson bodies are grouped together in such a way as to retain the general shape of the ganglionic body, considerably enlarged. The offshoots of these elements are in many instances still recognizable as being either enlarged and coarsely granular or broken apart into rows of bioplas- son bodies. As to the origin of medullary elements within the ganglionic bodies, I can state positively that they have originated by a process FIG. 175.— INFLAMMATORY CHANGES OF of endogenous growth from the THE GANGLIONIC ELEMENTS OF THE bioplasson of the ganglionic bodies GRAY SUBSTANCE OF THE BRAIN. themselves. First, the living mat- ter was increased, hence we explain the coarsely granular and homo- geneous looks of such an element ; next, marks of division had formed by the division of living matter into angular lumps, closely packed to- gether so as to flatten each other, and separated by a thin layer of fluid, which everywhere was traversed by delicate conical offshoots, uninterruptedly con- necting all newly formed lumps with each other. Some of these lumps, apparently, had further advanced in development than others ; while some looked still shining and homogeneous, others were already coarsely granular, and presented a marked formation of a nucleus and a nucleolus. Again, all these formations, granules, nucleolus, and inclosing shells are united by delicate threads. Lastly, the whole ganglionic element and its offshoots had broken apart into medullary or indifferent corpuscles, which, so long as they remain united to one another by delicate threads of living matter, represent an indifferent, medullary, or inflammatory tissue, identical with that arisen from the gray and white substance of the brain. If, on the contrary, the uniting offshoots be torn, the isolated medullary elements will produce pus-corpuscles, and an accumulation of such corpuscles gives rise to what is called an abscess. In the pus taken from the abscess of the brain under consideration, besides pus- corpuscles, a large number of bioplasson bodies were found suspended in the fluid, in size considerably exceeding that of ordinary pus-corpuscles. 6ri, coarse granules and new nuclei in the body of the ganglionic element ; (?*, splitting of the ganglionic element on its peripheral portion ; G3, the whole body transformed into medullary ele- ments : A, axis-cylinder exhibiting the same change. Magnified 600 diameters. INFLAMMATION. 417 These large bodies exhibited all stages of endogenous formations and prolif- erations of living matter, sufficiently indicating their origin from the gang- lionic elements of the gray substance of the brain. The literature on the subject of my studies is extremely sterile. No exact observations, at least to my knowledge, have as yet been made on acute encephalitis and suppuration of the brain substance. Only one point has so far been called attention to, and this is the proliferation of the ganglionic bodies of the gray substance. Th. Meynert * first noticed a proliferation of the nucleoli and nuclei of ganglion elements. E. Fleischl t found a division of ganglionic bodies, though not in a strictly inflammatory process, but in a brain involved in the formation of a tumor. A. R. Robinson \ produced inflamma- tion in the ganglia of the sympathetic nerve around the aorta of the frog, and observed a division of the ganglionic elements from the formation of a furrow on the surface to the complete division into small particles. The division may involve only a part of a ganglionic body, the rest remaining normal, or it may invade the whole. Analogous transformations were also observed in the elongations of the ganglion cells. Andrea Cecchirelli § produced traumatic lesions in the large hemispheres of the brain of a chicken and of rabbits. He saw enlarged and granular " gang- lion cells " within the inflammatory focus, and came to the conclusion that the nuclei had increased in number and that the whole " ganglion cell," by divi- sion, had been transformed into smaller elements. The results of my own observations can be summed up in the following points : ( 1 ) The gray substance of the brain, by the inflammatory process, is trans- formed into inflammatory or medullary elements, in the production of which the nuclei and ganglionic bodies also share. Non-medullated nerve-fibers, through an increase of living matter in the axis-cylinders, are likewise transformed into medullary elements. The same results are produced in inflammation of the white substance of the brain, after the dissolution of the myeline. (2) The medullary elements, sprung from the gray or the white substance of the brain, are transformed into connective tissue, either myxomatous or fibrous, and thus the wall of an abscess in the brain is the result of the reduc- tion of the brain tissue first into medullary corpuscles, next into myxoma- tous, and lastly into fibrous connective tissue. (3) Medullary elements, irrespective of which particular nerve-element they had originated, when broken apart, constitute pus-corpuscles, and, therefore, the contents of an abscess of the brain. In the fluid of the abscess clusters of bioplasson bodies are seen, proving a transformation of ganglionic elements into pus-corpuscles by a process of endogenous new formation and subsequent division of living matter. All the stages of this process are observable within the ganglionic bodies of the inflamed gray substance itself. (4) The endothelia of the blood-vessels become enlarged, coarsely granu- lar, and proliferating in the process of inflammation of the brain-tissue. New blood-vessels are formed in the wall of the abscess. A consolidation of the * " Vierteljahrschrift fur Psychiatric," 1867. 1 " Med. Jahrbiicher," 1872. t " Ueber die eutziiiidlichen Veranderungen der Ganglionzellen des Sympathicus," Med. Jahrbiicher, 1873. § "Ein Beitrag zur Kenntniss der entziindlichen Verauderungen des Gehirnes," Med. Jahrbiicher, 1874. 27 418 INFLAMMATION. blood-vessels, on the contrary, and a breaking up of their endothelia into medullary elements, afterward pus-corpuscles, takes place whenever the tissue is destroyed by suppuration. Pus is mainly a product of the inflamed tissue itself, and not of emigration of colorless blood-corpuscles. 4. INFLAMMATION OF EPITHELIA AND ENDOTHELIA. Epithelia and endothelia, being formations of living matter, respond in a very active manner to irritation. The changes of this tissue are not primary, as the inflammation invariably starts from the subjacent vascularized connective tissue. Even in mild cases of inflammation in connective tissue, the presence of an exudate can be demonstrated, which constitutes the condition known as "oedema." The surplus nourishing material is carried into the epithelia and endothelia from the blood-vessels, even though the irritating agent should be brought in direct contact with the epithelial or endothelial investment. The inflammatory changes in this tissue, as in every other, consist in an increase of the living matter j the elements become what is termed " coarsely granular," or assume the " condition of cloudy swelling." If the inclosing shell of cement-substance is not immediately liquefied, a marked endogenous new formation of corpuscles takes place, resulting in the appearance of the so-called u mother cells" — i. e., bioplasson bodies, containing a varying number of inflammatory elements, in all stages of development. We can trace the new formation of these elements from the coarse granules to the large homogeneous lumps, and, finally, to the nucleated plastids (see page 46). If, on the contrary, the cement- substance is liquefied in the early stages of inflammation, the living matter herein present — i. e., the connecting filaments (" thorns v) — is enlarged, and shares in the new formation in the same manner, as observed within the epithelial or endothelial elements. First, a number of these elements coalesce, and form large clusters of bioplasson, containing a varying number of nuclei and a large quantity of coarse granules, which, passing through the phases of bioplasson development, result in the production of inflammatory corpuscles. The final result of the inflammation is different, according to the plastic or formative, or the suppurative nature of the inflammatory process. In plastic inflammation, the newly formed medullary or in- flammatory corpuscles remain interconnected, and, becoming fusiform, give rise to new formation of connective tissue. The " cirr- INFLAMMA TION. 419 hotic" condition of the kidneys and the liver, f. i., is caused by the transformation of the epithelia into connective tissue, through the intermediate stage of medullary tissue. In suppura- tive inflammation, on the contrary, the connection of the medul- lary elements, which originated in the enlarged epithelia and endothelia, is broken, and the medullary plastids, now termed pus-corpuscles, are freed either by active emigration or by the contraction of the bioplasson of the parent body, which remains FIG. 176. — BEGINNING OF THE PUSTULAR STAGE IN ILEMORRHAGIC SMALL-POX. J), formation of homogeneous lumps from the bioplasson of the cuboidal epithelia ; E, homogeneous and vacuoled lumps suspended in a finely granular, albuminous liquid. C (left), ledges of former cement-substance, the bioplasson of which has considerably increased in bulk ; C (right), deepest layers of epithelia, compressed and rendered spindle-shaped, also with commencing increase of bioplasson. O, papillary layer, flattened and in the condition of redematous swelling. Magnified 600 diameters. comparatively little changed. The parent body itself, after the evacuation of the pus-corpuscles, presents a fenestrated appear- ance, with a varying number of vacuoles, indicating the location of the pus-corpuscles, or an apparently empty shell, pierced by delicate septa. All these formations are easily traced in the vesicular and pustular stages of small-pox. (See Fig. 176.) Surface epithelia, if present in a single layer, are readily cast 420 INFLAMMATION. off from the underlying membraneous connective tissue, and in the secretions are found to exhibit different degrees of an endo- genous new formation of bioplasson. In the case of stratified epithelia, the outermost are shed off without marked changes, their bioplasson being lost in a horny metamorphosis. Some- times the nuclei in these epithelia are seen to be homogeneous or coarsely granular, indicating that these formations are still endowed with a certain degree of vitality. The cuboidal epithelia of the middle, and the columnar epithelia of the deepest, layer show, in the most marked manner, the inflammatory changes described above. Whether or not lost epithelia can be replaced by a new forma- tion arising from the subjacent connective tissue is still an unset- tled question, notwithstanding the numerous experiments which have been made. It is also unknown how the new formation of epithelia proceeds from former epithelia, although it probably takes place in the same manner, as will be described later on, in the article by L. Elsberg on papilloma — viz., from wedge-shaped bioplasson masses, springing from coalescence and growth of the inter-epithelial connecting filaments (" prickles"), imbedded in the cement-substance. That such a new formation is actually and rapidly going on is illustrated by the catarrhal inflammation of mucous membranes, in which great quantities of epithelia are lost, and again replaced after the inflammation has subsided. The cast-off epithelia of single layers are probably never completely restored. A third series of changes of epithelia is observed in fibrinous or croupous inflammation. Here the epithelia are imbedded in? and saturated with, the exudate, and are either completely destroyed or only their nuclei are left. Such a destruction of epi- thelia takes place in the croupous inflammation of mucous mem- branes ( Wagner) and in the croupous inflammation of the kidneys. The production of tubular casts in the latter disease is largely due to a degenerative metamorphosis of the epithelial elements of the uriniferous tubules. Cornil and Ranvier were the first who maintained that in inflammation the endothelia are enlarged, and their nuclei divide and become the source from which pus-corpuscles are formed. The inflammatory changes of the endothelia of the peritoneum (omentum) have been studied most accurately by H. Kundrat. He noticed first a loss of the cement-substance, in place of which scattered globular bodies were seen. Next, enlargement and INFLAMMATION. 421 division of the nucleoli and the nuclei of the endothelia followed. In recent peritonitis he found large multinuclear bodies, which greatly surpassed in size single endothelia, and in purulent peri- tonitis a marked new formation of inflammatory corpuscles, aris- ing from the endothelia and leading to the formation of pus- corpuscles ; but, probably, not all of these corpuscles are offspring of endothelia. Kundrat was the first to maintain that from the endothelia of the peritoneum, in chronic, plastic peritonitis, con- nective tissue arises, which leads to the formation of vegetations ; and that this process takes place in two ways : either the endo- thelia themselves become spindle-shaped, elongated, and trans- formed into fibrillae, or uniformly nucleated protoplasmic layers, sprung from the endothelia, become directly fibrillated. The inflammatory changes of the endothelia of Mood-vessels were studied by Virchow, Waldeyer, Ranvier, Thiersch, Durante, and others. Swelling of the endothelia, division of their nuclei, and new formation of inflammatory corpuscles from endothelia, have been proved to occur beyond any doubt. By some observers a direct transformation of endothelia into connective tissue is maintained. The occlusion of ligated vessels is mainly due to a' proliferation of the innermost endothelia, and the vascularization of the thrombus is proved to start in the inflamed intima, and to proceed also from the adventitia and media. This is contrary to the views of C. O. Weber, who held that the coagulated blood of the thrombus itself becomes organized and vascularized. The coagulation of the blood was found to be caused by the inflam- mation of the endothelia. In the foregoing article on encephalitis, by Beyer, repeated allusion is made to the inflammatory changes, both progressive and regressive, that take place in the endothelia of capillaries. From what I have observed, I can confidently state that the endo- thelia of the capillaries participate in the inflammatory process in a very active manner. In the earliest stages of inflammation the endothelia become at first enlarged and coarsely granular, in consequence of which the caliber of the vessel is considerably narrowed. Next, the endothelia enter the juvenile stage of bio- plasson by becoming homogeneous, and through their confluence render the formerly hollow bioplasson a solid, homogeneous cord, in which afterward a differentiation into medullary or inflamma- tory corpuscles takes place. Such corpuscles may sometimes spring directly from the capillary endothelia, without previous solidification of the blood-vessel. The result is, that in acute inflam- 422 INFLAMMATION. mation a large number of capillary blood-vessels are destroyed — i. e., transformed into the inflammatory new formation. Should the inflammatory corpuscles separate and produce pus, a permanent destruction of the vessels ensues. If, on the contrary, the in- flammation should not pass the stage of tissue-formation, — i. e., become plastic and formative, — an active new formation of blood- vessels in the middle of the inflamed tissue will follow, independ- ently of the former and older blood-vessels, and to an extent far exceeding the former vascularity. Most of these newly formed blood-vessels contain newly formed red blood-corpuscles. The manner of new formation of blood and blood-vessels is dwelt upon on page 373. Should new formation of blood-vessels in an inflamed tissue not take place, the tissue will represent what is termed a " tubercle,7' and undergo different secondary changes. The endogenous new formation of elements within the epi- thelia was first maintained by Remak in physiological, and after- ward by Buhl, Rindfleisch, and others in pathological, conditions, and its existence thoroughly proved by L. Oser. In opposition to the view that the corpuscles visible in the endothelia had immigrated from without, Oser demonstrated the origin of in- flammatory corpuscles within the epithelia. My own researches fully corroborate the statements of Oser. VARIETIES OF INFLAMMATION. From my statements it follows that I consider the presence of blood-vessels to be a requisite for the production of an inflam- matory process. As only connective tissue is supplied with blood-vessels, it necessarily follows that the primary seat of inflammation must always be in the connective tissue, and that the structural changes of muscles, nerves, and epithelia are sec- ondary to, though, perhaps, almost simultaneous with, those of the connective tissue. An independent inflammation of epithelia never occurs. I, therefore, consider the terms of " interstitial,7' " parenchymatous," etc., inflammation as superfluous, except for clinical purposes. Emigration of colorless blood-corpuscles unquestionably oc- curs, even in the earliest stages of inflammation, probably pre- ceding structural tissue changes. Such an emigration may also participate in the formation of pus-corpuscles, so long as the blood-vessels are not destroyed. The principal change, however, INFLAMMATION. 423 more particularly concerns the invaded tissues themselves. They are first reduced to their juvenile condition; their medullary elements, by endogenous or exogenous new formation or simple division, give rise to a new formation of inflammatory corpus- cles. If these remain interconnected, a new formation of tissues, in most instances, and most predominantly of connective tissue, takes place; thus, "hypertrophy" or " hyperplasia " is estab- lished. If, on the contrary, the inflammatory corpuscles become separated, pus-corpuscles arise from the inflamed tissue, either forming an abscess or leading to pyorrhoea or empyema. The question, how many of the pus-corpuscles owe their origin to emigration of colorless blood-corpuscles, cannot be answered positively. Considering both the nature of the exudation and the tissue changes, there is no good reason to abandon the old terminology of "humoral pathology " for the designation of different forms of inflammation — such as catarrhal, croupous, etc. These, it is true, differ only in degree, but the names, having been once adopted, may be used, as heretofore. (a) Catarrhal inflammation consists of a serous exudation, a partial reduction of the connective tissue into its juvenile con- dition, an increased secretion, proliferation, and shedding of the epithelia. In acute catarrhal inflammation the predominant feat- ures are the serous exudation, the augmented secretion, and shed- ding of the epithelia from the free surfaces and in glandular organs ; there is, in addition, a hyperaemia of the subjacent con- nective tissue. In subacute or chronic catarrhal inflammation the augmented secretion and shedding of the epithelia persists, and the subjacent connective tissue is hypertrophied, with a more or less new formation of blood-vessels, or, on the contrary, reduced in bulk — atrophy. In closed or occluded glandular cavities the epithelia are transformed into medullary 'corpuscles, from which new connective tissue arises — cirrhosis. (~b) Croupous inflammation consists of a fibrinous exudation and a partial reduction of the connective tissue into its juvenile condition, while the epithelia, by their imbibition of the fibrinous exudate, are destroyed. In acute croupous inflammation the exu- date is sometimes fibrinous, sometimes modified albuminous. On free mucous surfaces and in glandular organs the epithelia are destroyed ; these, with intense hyperasmia, haemorrhage, and inflammation of the connective tissue, are the main symptoms. In subacute or chronic croupous inflammation the exudation is 424 INFLAMMATION. modified, often containing the so-called colloid or waxy material. The subjacent tissue is hypertrophied, and, in certain districts, the epithelia are completely destroyed and a profuse new forma- tion of fibrous connective tissue is produced. This condition is called atrophy. Diphtheritic inflammation consists of a fibrinous exudate in the substance of the connective tissue, with an isolation of portions of this tissue, and their subsequent death — viz. : putrefaction and throwing off of the so-called mem- brane. Organisms of decomposition, micrococci and bacteria, are secondary products of putrefaction. For a long time the difference between croupous and diphtheritic inflammation was held to be that in the former the exudate forms on the surface, in the latter in the substance of the tissue itself ; but they are, in essential points, identical processes. (c) Suppurative inflammation consists of an albuminous exu- dation, a complete breaking down of the connective, muscle-, or nerve-tissues, and of all blood-vessels, into pus-corpuscles, also a new formation of these corpuscles from epithelia. Acute suppur- ative inflammation results in the formation of an abscess in the middle of the tissue, or a flow of pus from free surfaces, — the so-called pyorrhoea, or an accumulation of pus in closed cavities — the so-called empyema. Blennorrhoea and intense catarrhal inflammation blend with suppuration, and may be either acute or chronic. Chronic suppurative inflammation is characterized by intense hyperplasia of the connective tissue, together with per- sistent augmented secretion and a partial destruction of blood- vessels and tissues — the ulcer ation. The healing process of wounds by suppuration is accompanied by an active outgrowth of freely vascularized, newly formed, connective tissue, which is at first of the myxomatous variety, and is termed granulation tissue. How much pus is produced by emigration of colorless blood-corpuscles in blennorrhoea, pyorrhosa, and in healing and granulating wounds, we are unable to say. The originally myxomatous tissue of granulating wounds is changed into fibrous connective tissue ; the at first numerous blood-vessels are, to a great extent, also transformed into fibrous tissue, and these processes terminate finally in a scar, cicatrix. If the inflammatory new formation be not supplied with newly formed blood-vessels it is called a tubercle, and the totality of the avascular new formation represents the tuberculous mass, which, by the breaking and the shrinkage of the inflammatory corpuscles, becomes " cheesy." Tubercle, therefore, with some reason, may be termed a dry abscess. No allusion is made in this chapter to the parasitic origin of the inflam- matory process, especially the germ theory, as applied to inflammation. Unquestionably, organisms of decomposition, if brought into the interior of a living tissue, or, perhaps, even only in contact with it, will excite inflamma- INFLAMMATION. 425 tion or necrosis. But how much is true of the " specificity " of such low organ- isms, as regards malarial fever, recurrent fever, typhoid fever, syphilis, leprosy, diphtheria, etc., is a question which to-day cannot be positively answered, as the sources of mistake, both in experimental and microscopical research, are too many and too little undej? our control. What the infecting germs of measles, scarlet-fever, and small-pox are, we do not know. Secondary Changes. Among the disturbances of nutrition, partly considered as inflammatory, partly unknown in their origin, three deserve mentioning — namely, the fatty, the pig- mentary, and the waxy degeneration. Fatty Degeneration. As mentioned before (see page 155), the fat-granules are directly produced from granules of bioplasson. Every living tissue, in a physiological or pathological process, may exhibit fat-granules, both in its free bioplasson bodies and in the interstitial substances. In this latter, situation, also, the fat originates from the bioplasson formations. In the myxoma- tous and fibrous variety of connective tissue the fat is a normal product, at least to a certain degree ; cartilage corpuscles often exhibit fat granules and globules, even in middle-aged individ- uals. In chronic inflammation of cartilage and bone, especially in their ulcerative destruction, in caries, fat-granules are very common occurrences in the plastids. In muscles, fat-granules arise from a direct transformation of the sarcous elements : in paralyzed and atrophied muscles, from want of exercise; in typhoid fever ; in the muscle of the heart, either as an independ- ent pathological process, or in connection with hypertrophy. In higher degrees of fatty degeneration of the muscle of the heart, nearly the whole organ, but principally the left ventricular wall assumes a yellow color, and the tissue becomes quite brit- tle. Most of the sarcous elements have been converted into fat-granules, which slightly exceed the original sarcous elements in size j they still remain interconnected, however, by delicate filaments. In the ganglionic elements of nerve-tissue, fat-gran- ules are often met with ; this always indicates a disturbance in the intellectual, sensitive, or motor centers. I have seen fatty degeneration of the axis-cylinders of nerves, resected for the relief of neuralgia, caused by the so-called perineuritis — i. e., chronic inflammation of the external and internal perineurium. In epithelia and endothelia fatty degeneration also occurs, reach- ing its highest degree in the epithelia of the liver. Wedl has demonstrated fatty degeneration even in the cement-substance of epithelia perfectly healthy. A rare and sometimes intra- 426 INFLAMMA TION. uterine process is the fatty and pigmentary degeneration of the covering endothelia of the heart, probably caused by pericarditis. (See Fig. 177.) Tissues in fatty degeneration are often subject to calcareous depositions, both processes being indicative of a lowered nutri- tion of the bioplasson, the causes of which are not clearly under- stood. Pigmentary degeneration is closely allied to fatty degeneration. Even under normal conditions fat-globules may contain a diffuse or granular coloring matter, and fatty and pigment degenerations are often found combined. "We have no chemical analysis of the pigment; but its source is un- questionably the coloring matter of the blood. Extravasated blood, after a while, produces rhomboidal or needle-shaped crystals of haema- toidine, which are in color dark reddish-brown. (See chapter on urine.) If the coloring matter be imbibed by living plastids, pig- ment-granules of a rust-brown or brownish black color will be seen in these bodies. The rusty color of the tissue, sometimes seen abounding in old, healed apo- plectic focus in the brain, is due to the presence of pigment-gran- ules. Rokitansky maintained, in 1846, that in melanotic cancer the pigment is supplied by the blood, which originates in the mother cells. My own researches, made especially in the boundaries of melanotic myeloma of the choroid invading the vitreous body, demonstrate that the sources of the pigment are the haemato- blasts — i. e., lumps of living matter, saturated with coloring matter (haemoglobin ?) of the blood. The points of intersection of the bioplasson reticulum within these plastids are enlarged, and assume a dark yellow or brown tint, remaining, however, in con- nection with the reticulum. By coalescence of the granules pig- FIG. 177. — FATTY AND PIGMENT- ARY DEGENERATION OF THE PERICARDIAL ENDOTHELIUM OF THE HEART OF A CHILD. F, endothelia, exhibiting the begin- ning of fatty change of the granules of bioplasson; P, endothelia, with pigment granules in their interior. Magnified 600 diameters. INFLAMMATION. 427 ment-clusters originate, which may still remain connected with the unchanged Moplasson ; and if the granules are present in large numbers they may conceal the nucleus of the plastid, which, as a rule, both in physiological and pathological pigment formations, remains unchanged. (See Fig. 177.) All varieties of tissues may become the seat of pigmentary degeneration, and it is evident, par- ticularly in melanotic cancer, that both the connective tissue and the newly formed epithelial plastids are more or less abundantly supplied with granules and clusters of coloring matter. Bust- brown pigmentation is sometimes observed in the sarcous elements of striated muscles, in the gray substance, and the ganglionic cor- puscles of the nerve-centers, independently of former haemorrhage. The fact that it is the living matter itself which is transformed into pigment, facilitates the understanding of the very rapid disappearance of pigment — f. i., from the epithelia of the skin and the medullary tissue of the hair-bulb. Waxy degeneration. In chronic ailments, such as syphilis, pro- fuse suppuration, caries of bone, etc., and in the placenta even in apparently healthy women, a peculiar change of the tissues, called waxy, takes place, which leads to an increase of bulk, a paling of their color, due to compression and obliteration of blood-vessels, and an increase of weight and consistence. There is a general appearance of the tissue similar to that of wax or lard ; hence the term " lardaceous," which is also used to designate this change. Unquestionably, this degeneration is due to a chemical change of the plasma of blood, as it is sometimes found in hagmorrhagic clots, independent of, or combined with, analogous tissue changes. What this change really consists in we do not know, and it is a mere hypothesis of Dickinson's to call the waxy substance " de- alkalized fibrine." The appearance of waxy degeneration varies in different tissues and organs. The chemical reactions are not always the same ; neither are the stainings with carmine and ani- line colors always productive of the same results. The myxom- atous variety of connective tissue is not infrequently the seat of waxy degeneration. (See article on waxy degeneration of the placenta.) In certain diseases the medullary tissue of bone is invaded by this change, which leads to the formation of globules termed " colloid corpuscles," which are remarkably unresponsive to the usually destructive action of acids and alka- lies. (See article on osteomalacia.) In the myxomatous tissue of the thymus body such homogeneous or concentrically^ striated 428 INFLAMMA TION. corpuscles are, as a rule, found after the involution of the organ. Among the blood-vessels, the arteries of the spleen are often seen in waxy degeneration before the other constituent parts are attacked. (See Fig. 178.) The degeneration starts in the smooth muscle-fibers of the middle coat 5 these are enlarged, transformed into a homogeneous mass, in which no trace of structure or of nuclei can be recognized. In the kidneys, the waxy change is sometimes observed in the walls of the capillaries sooner than in the arteries. In the liver, waxy degeneration takes place independently of the blood-vessels. Muscle-tissue is often subject to this degeneration, especially FIG. 178. — WAXY DEGENERATION OF AN ARTERY OF THE SPLEEN OF A MAN AFFECTED WITH SYPHILIS. H, endothelial coat of artery ; Jf, muscle-coat of artery, in waxy degeneration ; B, bundles of smooth muscle-fibers accompanying the artery ; D, lymph-corpuscles in the myxomatous reticulum. Magnified 600 diameters. the muscle of the heart, predominantly the wall of the left ven- tricle, by which this structure is enlarged, rendered friable, and of a peculiar lardaceous luster. Waxy degeneration is often found in nerve-tissue, both in the gray substance and the ganglionic elements, in connection with similar changes in the walls of the blood-vessels, and also without INFLAMMA TION. 429 any such changes. For particulars I refer to the two following articles. Epithelia and endothelia are likewise subject to this degeneration — f. i., in the liver, the kidneys. The epithelia of the lungs sometimes give rise to homogeneous or concentrically stri- ated colloid corpuscles, and such are sometimes observed in the epithelia of the prostate gland. The concentric colloid corpus- cles of the latter organ may become the seat of calcareous depo- sitions, and are sometimes voided with the urine. They are not of uncommon occurrence. (See chapter on urine.) Peculiar, but certainly kindred, formations are the colloid corpuscles of the nervous system. Usually they exhibit a concentric striation; sometimes two or more such concentrically striated corpuscles may be surrounded by a common homogeneous or striated layer. (See Fig. 179.) Virchow, by mistake, termed FIG. 179.— COLLOID OR AMYLACEOUS CORPUSCLES OF THE ARACHNOID OF THE SPINAL CORD OF AN ADULT. A, concentrically striated amyloid corpiiscle ; O, group of medullary corpuscles in colloid degeneration ; L, medullary corpuscles in the beginning of colloid degeneration. Magnified 600 diameters. them " amylaceous" corpuscles. In the arachnoid of a man whose brain, crowded with these corpuscles, was in the condition of the so-called " gray atrophy/' I could trace the origin of these formations from medullary elements, which had arisen in the fibrous tissue of the arachnoid in consequence, evidently, of a 430 INFLAMMATION. slight inflammatory process. The medullary corpuscles, being infiltrated with the colloid material, either remained in irregular groups, or, becoming elongated, gave rise to the concentrically striated corpuscles, in a way similar to that in which the territo- ries of connective tissue are formed. In the center, sometimes an unchanged plastid is seen, or a larger homogeneous mass, or a shallow depression, termed an umbilicus. WAXY DEGENERATION OP THE CEREBELLUM. BY J. BAXTER EMERSON.* Mr. B. was the youngest of a family of seven children. His mother died of acute encephalitis, terminating in abscess ; a maternal uncle and aunt both showed symptoms of dementia late in life. One of his sisters has suffered for several years with hysteria ; a second sister has at the present time posterior spinal sclerosis. When about fifteen years old, he was thrown from a car- riage, and received a severe scalp wound on the posterior part of his head, from which he seemed to recover. His habits were regular. He was much troubled with naso-pharyngeal catarrh. At the age of twenty-eight he lost all his property, which worried him excessively; soon he found that he was losing flesh and strength, that his appetite was poor and his digestion bad ; he also had the tendency to fall when walking or on turning suddenly. His brother noticed that he became slower in his work. In January, 1874, the above symptoms returned; he began to stammer, and would often forget localities and names. These symptoms were intermittent in character ; at times he was apparently well. In September, 1874, he was married, and, while on his wedding trip, his wife noticed that if he endeavored to walk down a flight of steps, he would become pale and complain of vertigo. Shortly afterward he was attacked with most intense pain in the head, accompanied with great irritability, photophobia, and inability to stand alone. These acute symptoms lasted several days, and for several weeks he had to be led to prevent his falling. About a month later he had a second similar attack, this time losing the power of speech and being " delirious." Later, he complained of "pain in the forehead," numbness of the extremities, occasional twitching of the muscles, and he was unable to walk without assistance. On two occa- sions he asserted that he was blind, which assertion he persisted in for two days. He was exceedingly childish in his actions. Toward the latter part of the summer of 1876, he became violent, his hallucinations and delusions being of an exalted character. On October 5, 1876, I found his left pupil dilated, the tongue tremulous, the power of coordinating the muscles much impaired, those of the left side more so than the right ; the left biceps permanently contracted, so as to keep the fore-arm at an angle of about one hundred and thirty-five degrees with the axis of the arm; contractile power of the muscles on the right side more marked than on the left ; an almost incessant movement of either the fore-arm and hand, or grinding of the teeth ; partial anaesthesia of the left side ; aphasia of both varieties, but principally amnesic ; hallucinations and delu- sions of a very exalted character, seeming to dwell principally on financial * Abstract of the paper "Peri-encephalitis," by J. Baxter Emerson, M. D., New- York. Journal of Nervous and Mental Disease. Chicago, April, 1880. INFLAMMA TION. 431 subjects ; emotions not under control ; sense of decency lost ; using the most obscene language; responding to calls of nature regardless of surrounding circumstances ; dementia very marked, at times so violent as to necessitate restraint; insomnia. On November 14, 1876, he had an attack, with the following symptoms : Complete left hemiplegia and hemianaesthesia ; complete aphasia ; congestion of head and neck ; extremities cold, especially the left ; head drawn to the right, and fixed ; both eyeballs drawn to the right ; left pupil widely dilated ; conscious, with sense of sight and hearing intact ; facial muscles slightly par- alyzed on the right side ; those of deglutition interfered with ; respiration irregular and sighing in character; pulse 84, irregular and intermittent; temperature 100°. Soon after, the muscles of the paralyzed side began to twitch, first in the extremities, gradually extending to the trunk, until, finally, all the muscles of the left side were in a constant state of spasmodic contraction. The next morning the symptoms were all gone, except slight paralysis and aphasia, and the patient apparently better than before the attack. These attacks, of varying intensity, occurred about once a month during the remainder of the patient's life. Dementia became more marked. He persisted in keeping up the movements of his right fore-arm and the grinding of his teeth to the last ; consequently, their muscles retained the normal size, while all others underwent atrophy from disuse ; but to the day of his death he was able to walk with assistance. His urine was normal to the last, but he had retention for five days previous to his death, which occurred May 13, 1879, from exhaustion. A post-mortem examination gave the following results : Body much ema- ciated ; ulcer, the size of a dime, on sacrum. Dura mater much thickened throughout its whole extent, adherent to the pia mater in spots, and firmly adherent along sup. long, sinus and in the temporal regions, much more so on the left side than on the right. The pia mater was much thickened and con- gested, and had numerous haemorrhages, from the size of a pin's head to that of a split pea, imbedded in its structure. These were principally on the left side, all confined to the upper surface. The pia mater was adherent to the base of the skull and the brain, in spots. The brain was much congested, weight 40 oz. The convolutions on the right side seemed deeper, and the gray matter thicker than on the left. The white substance was slightly darker than normal, and much congested. The consistency of the whole normal, and all other parts negative. A large portion of both hemispheres was removed and placed in Mutter's fluid, then in a weak solution of chromic acid, until it was sufficiently hard for section, after which it was kept in dilute alcohol. The pia mater was composed principally of bundles of decussating fibers of connective tissue, coarser than normal, traversed by dilated and enlarged blood-vessels, distended with blood, and around many of them were bundles of spindles and inflammatory elements. This condition of connective tissue is characteristic of an inflammatory process of chronic nature, which process led to the formation of new connective tissue, while an acute recurrence of the same process has given rise to a new formatibn of inflammatory ele- ments. The dura mater was found structurally in the same condition as the pia mater, but had no haemorrhages in it. A vertical section through either hemisphere of the cerebellum with a low power of the microscope gave the following appearance : The blood-vessels 432 INFLAMMATION. could be traced from the pia mater, especially in the sulci between the con- volutions, through the external gray and granular layers into the white sub- stance, profusely branching and ramifying, and almost invariably engorged with blood. In numerous places there were ramifications closely resembling those of the capillaries, with sharp, well-defined, fluting outlines, colorless, and of a high refractive power. Such groups were found principally in the granular layer, but extended somewhat into the contiguous layers. There were also numerous isolated, highly refracting bodies, scattered throughout the whole cerebellum, but mainly in the granular layer. With a higher power of the microscope, peculiar changes of the capillaries were shown, first described by C. Wedl — namely, the capillaries were transformed into either single or double rows of brilliant, colorless globules, or completely trans- formed into a glistening rod-like mass, with fluting outlines, and numerous, partly, pedunculated, buds. The large isolated bodies had all the character- istics of the corpora amylacea — namely, they were concentrically striated and umbilicated. In some instances, the umbilicus was found in direct union with capillaries, which had undergone the above described changes. Excep- tionally, I found the " cells of Purkinje," with their offshoots, presenting the same glistening, highly refractive, appearance as the capillaries and corpora- amylacea. Some of the latter looked as if they were composed of a number of shining globules, closely packed together, the outlines of the globules being just traceable within the clusters. I used the following re-agents: Carmine (both ammonia and alum solu- tions), which stained the tissues, but left the globules colorless. Iodine (both tincture and aqueous solution, both with and without sulphuric acid) ; the result was unsatisfactory, for only once, after the use of the aqueous solution, did I perceive any change in the globular bodies, and then the pale blue tint was very indistinct, and only a few of the bodies affected. Hcematoxylon pro- duced a distinct violet upon the tissues and the blood-vessels, while the glob- ules were little affected, if any, by it. Chloride of gold (one-half per cent, solution) made the outlines more distinct, but did not change the color of the globules. Violet methylaniline stained the granular layer a deep blue, the external gray layers and the white substance a dirty grayish-blue ; the blood-vessels both in the normal and pathological condition were unaffected. Fuchsine produced a pink stain in the gray layers ; the globular bodies and blood-vessels were untouched. Osmic acid (one per cent, solution) pro- duced a marked brown discoloration on the globules, but by no means as deep as that we are accustomed to see on fat-globules. Picro-indigo gave the blood-vessels and globules a bright green color, while the surrounding tissues were of a much paler tint of green. In unstained specimens, the refractive power of the globules and corpora, amylacea was so characteristic as to allow of no diagnosis, except calcareous degeneration of capillaries, of corpora amylacea, and exceptionally of " cells of Purkinje." In the whole list of my re-agents there was nothing found con- tradictory to this, though, I must admit, very little to confirm it. The capil- lary blood-vessels in several instances showed rows of calcareous globules on both walls, while in the center a row of blood-corpuscles was still recognizable in that portion of the capillary nearest the pia mater, while the central end of the capillary was completely filled with the shining globules. The change, therefore, which led to the formation of these globules must have taken place in the walls of the capillaries, and in turn has led to the consolidation of the entire blood-vessel. INFLAMMATION. 433 The highest powers of the microscope (1200 diameters) showed in many capillaries of the cerebellum an enlargement of the endothelia, with a coarser granulization therein, and a splitting of the original endothelia into coarsely granular clusters. The peri vascular sheaths in some instances were consider- ably dilated and sometimes filled with globular elements, slightly increased in refractive power. From the above facts it would seem that the shining globular bodies are products of the endothelia, which first become inflamed, then proliferate, and the inflammatory elements thus formed become infil- trated with lime-salts. Concerning the formation of the corpora amylacea, we at present know nothing. The gray layers of the cerebellum with a high power of the microscope showed a reticular structure. The white substance of the cerebellum was composed almost exclusively of nerve-fibers with numerous varicosities, and a reticular structure was seen in the nerve-fiber as well as in the varicosities. On broken ends of nerves, I could trace several sheath-like layers, composed of a row of spindles, bounding the swollen pear- shaped ends of the nerve-fiber, while the center of the so formed body showed a delicate reticular structure. Such formations, we know, never are seen so long as myeline is present. It therefore follows that either the myeline has oozed out after death, or has been absorbed during life, perhaps in the same manner that adipose tissue disappears in wasting diseases. The boundary layer of the nerve-fiber in all instances was shining and homogeneous, thus representing a complete sheath. There is no reason, therefore, to my mind, for denying the existence of a sheath in the nerves of the white substance of the cerebellum, and I may also add cerebrum, for they were both similar in this case. The gray substance of the cerebrum was similar in structure to that of the cerebellum. The calcareous corpora amylacea were less frequently, and the calcareous globules exceptionally, found. The blood-vessels were, as a rule, distended with blood. The perivascular sheaths were, in some instances, dilated. Several specimens showed a fatty degeneration of the blood-vessels and of the ganglionic bodies, both demonstrated by their refraction and by the action on them of osmic acid, which produced a black stain. The fat- granules were arranged in the ganglionic bodies in a crescent shape, the con- vexity being on one side of the ganglion, and the concavity toward the nucleus. In the cerebrum I frequently found empty spaces, as they were found also in the cerebellum — so-called vacuoles. * Most of the vacuoles had in their interior a pale nucleus, and their origin must be attributed to an accumulation of fluid around the nucleus after death, or to a hydropic destruc- tion of the ganglionic elements, due to serous exudation. The latter view is corroborated by similar formations around the blood-vessels, where not only lymph-sheaths were found dilated, containing bioplasson elements, but there was also a large space around the lymph-sheath. Several ganglionic bodies with partly fatty degeneration also showed closed empty spaces on the periphery. The diagnosis, as obtained from the microscope, in this case is chronic pachy-meningitis, meningitis, and encephalitis, terminating in atrophy. * Later observations in the gray substance of the brain and the spinal cord, which were invaded by atrophy, due to chronic encephalitis and myelitis, demonstrated that the bioplasson reticulum was more or less rarifled — viz. : its meshes enlarged. There is a gradual transition of enlarged mesh-spaces to still larger spaces, termed vacuoles. I am unable to say what becomes of the bioplasson in such a wasting process.— ED. 28 434 INFLAMMATION. WAXY DEGENERATION OF THE BRAIN. BY JOHN A. EOCKWELL, M. D.* The pathology of the central nervous system has as yet been very little elucidated, for the simple reason that its minute anatomy has not as yet been fully understood. The reticulum in the gray substance, first described by J. Gerlach, and by L. Mauthner, twenty years ago, has been considered to be nervous in nature, as both observers saw this reticulum in direct communication with axis-cylin- ders. Quite recently, however, this assertion has been contradicted by S. Strieker and L. Unger, who claim that the reticulum is an elongation of the pia mater, and therefore of connective-tissue nature. So far as my experience goes, I must coincide with the views held by Gerlach and Mauthner. I invari- ably succeeded in staining the reticulum. of the gray substance violet with a solution of chloride of gold, the same as the nuclei which are scattered throughout the gray matter, and the ganglionic elements, whose nervous nature cannot be questioned. Moreover, I saw the reticulum in connection with axis-cylinders, which we also know to be positively nervous elements. It seems to me that the question, What is connective tissue, and what is nervous structure in the gray substance ? will never be definitely answered, as the connective-tissue offshoots of the pia mater, upon reaching the finest ramifications, lose their basis-substance and become bioplasson in nature, the same as the nervous structure itself. C. Wedl was the first to maintain that a waxy degeneration may invade the capillary blood-vessels, resulting in the formation of shining, homogeneous cords, ramifying like blood-vessels and freely supplied with pedunculated, bud-like, stratified projections. The amylaceous corpuscles have, for a long time, been known to occur in the gray substance of the central nervous system, where they represent bright, stratified, apparently structureless masses, containing sometimes in their cen- tral portion an unaltered plastid. Such corpuscles are so common, both in the gray substance of the brain and the spinal cord, and in the arachnoid of each, that some histologists have asserted that they were normal formations. They occur either singly or in double or multiple formations, clustered and partly coalesced. Their designation, " amylaceous," originated with Virchow, who, upon applying iodine and dilute sulphuric acid, could in some instances pro- duce a bluish tinge of these corpuscles. Upon the authority of Virchow the name " amylaceous corpuscles" has been accepted, although the bluish color after treatment with iodine — which feature reminded Virchow of starch cor- puscles of plants — by later observers could not, or only in a very slight degree, be produced. Evidently, the bluish color, wherever it occurs, is noth- ing but the complementary color of these highly refracting bodies to the yel- low-brown neighborhood after the application of iodine. I consider this re-agent of no value. What the intimate nature of the amylaceous corpuscles, or the waxy degeneration in general, is, we do not know. This much is certain, that the formation of these corpuscles, as well as the waxy degeneration itself, is closely connected with chemical alteration of the plasma of the blood, inas- much as in almost all instances the waxy change is known to first invade the blood-vessels. In the spleen and the kidneys the muscle-coat of the small * Abstract of the paper, by John A. Rockwell, "A Contribution to the Pathology of the Brain." The New England Medical Gazette, March, 1882. INFLAMMATION. 435 arterioles is, as a rule, the first to exhibit the waxy change. In the "brain, the capillaries are unquestionably the first invaded formations, as recently proved again by J. Baxter Emerson. The case from which my specimen has come was one for two years under the observation of Dr. E. H. Linnell, of Norwich, Conn.* " Mr. T , aged sixty-three, of nervous temperament and thin habit, first consulted me," says Dr. Linnell, "for failing vision, in November, 1879. His vocation had been that of a photographer, until ill health obliged him to relinquish it. Inquiry elicited the following facts: For the past eight or nine years he had been subject to frequent attacks of neuralgia, affecting his head and limbs ; he had been habitually constipated ; his urine had been somewhat increased in quantity, light-colored, and passed frequently; and for four years he had had paralysis agitans, affecting his right arm and leg, but more markedly the arm. This tremor developed gradually, and was attended with partial anaesthesia, denoted by numbness and tingling sensations in the affected limbs, and by general debility. In other respects he enjoyed good health until the fall of 1879. During the night of September 27th, of that year, he had a sudden severe attack of pain in the head, extending from vertex to chin, accompanied by total blindness, and followed by vertigo, nausea, and slow pulse. After twenty-four hours the intensity of symptoms was moderated, and his sight began very gradually to be restored, but was never fully recovered. He continued to suffer with neuralgic headache and vertigo, and his gait became halting and uncertain. His mental faculties, however, remained unimpaired, and the paralysis agitans, or the difficulty of locomotion, did not increase. When I first saw him, VOU = fft, refraction Em. He had, however, left-sided binocular hemianopsia. ... In the latter part of April, 1880, he had another sudden attack of complete blindness. This attack was unattended by pain, and was of shorter duration than the first. During the following year his sight seemed to fail gradually, until he could with difficulty distinguish large objects. He complained much of diz- ziness, but suffered less pain ; walking became more fatiguing, the right leg seeming heavy, and as if too long. He retained the use of all his faculties, and could converse intelligently, although his mind seemed to lose some of its natural vigor. In the latter part of June, 1881, he was suddenly seized with a general tremor of the whole body, afterwards becoming more pronounced upon the right side. This was not attended with pain, and he apparently recovered from the effects of it ; but had a similar seizure July 2, accompan- ied with constriction of the post-cervical muscles. The rigidity increased, he soon became unconscious, and was apparently entirely blind. After a few hours he partly regained consciousness, and had perception of light. From July 4 to 8, he seemed to improve somewhat. From this time he gradually failed, both in intellect and strength, until he became comatose, in which con- dition he remained for several days, and died July 19. " Autopsy gave the following result : The dura mater was so firmly adher- ent that the calvarium could not be removed without cutting; and in so doing, several ounces of dark fluid blood escaped from the sinuses. Both the dura mater and the arachnoid appeared healthy. The pia mater was much injected, the veins being distended with dark blood. The entire weight of the brain was two pounds, fifteen and one-half ounces. The cortical substance of the cerebrum was of normal consistence ; but upon section of the right hemi- * Published in the "Archives of Ophthalmology," vol. x., No. 4, December, 1881. 436 INFLAMMATION. sphere, a large and firm coagulum was found in the medullary substance. It was nearly circular, and measured, approximately, four centimeters in diam- eter and two and one-half centimeters in thickness. It was situated a little anterior to the center of the hemisphere, and did not anywhere encroach upon the cortical substance. The contiguous brain substance was softened for a thickness of about two lines, but the clot was removed almost entire, and there was no serum, pus, or other indication of inflammation or of extensive degeneration. No pathological changes could be discovered in the left hemi- sphere. The fluid in the ventricles was not appreciably increased in amount, although there was more serum upon the left than upon the right side. The velum interpositum and choroid plexuses of the ventricles were highly vascu- lar, the veins being turgid and swollen, and this was more marked upon the left side. The tubercula quadragemina were manifestly degenerated, and presented the appearance described as white softening. This condition was much more evident upon the left side, but it was not limited to these bodies, It also extended laterally and anteriorly, involving the corpora geniculata, the posterior and inferior portions of the optic thalamus on the left side, and also, to some extent, the floor of the fourth ventricle. A portion of the left optic tract and the adjacent under surface of the thalamus was removed for micro- scopical examination. This was so soft as to require very careful handling to prevent crushing." Dr. Linnell kindly sent me a portion of the under surface of the left optic thalamus, which came to me preserved in alcohol. The specimen exhibited a grayish-yellow discoloration, as if fatty. It was placed in a one-fifth per cent, solution of chromic acid, and after a few days was sufficiently hard to be sliced with a razor. The sections were mounted in glycerine, and even those which went through the treatment with alcohol and oil of cloves were again introduced into water and mounted in dilute glycerine. Incidentally, I wish to say that, for three years, I have been pursuing microscopical studies in the laboratory of Dr. C. Heitzmann, and by repeated trials have become convinced that the mounting of specimens in glycerine is far superior to mounting in Canada balsam or Damar varnish. Comparative mountings in these liquids, especially for specimens of the nervous centers, have resulted in the conviction that the balsam or varnish mounting ought to be wholly abandoned. Unquestionably one, if not the main, reason why our knowledge as to the pathology of the brain and the spinal cord has progressed so slowly for the past twenty years is the mounting in balsam. By this method, the specimens in a short time clear up to such an extent that the minutest details fade, and the specimens become unfit for research with high amplifications of the microscope (800 to 1200 diameters), which are the only possible means of revealing the minutest normal, as well as pathological, features. All the specimens obtained exhibited a peculiar change of the gray sub- stance. This consisted in the presence of homogeneous, grayish fields of greatly varying size and configuration, mostly with fluted outlines, scattered throughout the gray substance. With lower powers of the microscope, I was satisfied that these shining fields either accompanied capillary blood-vessels, or were distributed without any regularity in the gray substance, or, lastly, represented more or less straight tracts in closely lying parallel or in diverg- ing fan-shaped courses, in the direction of the axis-cylinders. The latter feat- ure was especially pronounced in the neighborhood of the optic tract. (See Fig. 180.) INFLAMMA TION. 437 •JV The shining fields are doubtless in close relation to the capillary blood- vessels, inasmuch as they appeared, by the side of the capillaries, as if in the perivascular space, without at first invading the endothelial coat itself. With advancing degeneration in the neighborhood of the blood-vessels, they also became destroyed to such an extent that the direction of the glistening tracts was the only indication of the course of the former capillaries ; though, also, in such tracts, occasionally, a small portion of the original capillary was found imbedded. The numerous straight tracts following the course of the axis- cylinders were evidently due to a degeneration upon a large scale. Owing to the tolerably high degree of refraction of these fields, my first impression was that a fatty degeneration of the gray substance had taken place. The treatment of the specimens, however, with strong alcohol and oil of cloves at once revealed the fact that these formations could not be fat, for they were not perceptibly altered by those re-agents. A second full proof of their not being fat was the treatment with a one per cent, solution of osmic acid, which we know to be the most trustworthy re-agent for fat, and which should stain the fat black. No such thing occurred in my specimens. The next question was, could the waxy nature of these fields be proved by the application of different re- agents ? To answer this question I applied the fol- lowing re-agents : Carmine, iodine, hsematoxylon, fuch- sine, violet methyl-aniline, picro-indigo, and chloride of gold. Among those, picro- indigo was the only one which, in Emerson's case, yielded a positive result, where the waxy blood-vessels and globules were rendered by it a bright green. In my case no one of these re-agents, not even the picro-indigo, yielded positive results, as all the hyaline fields remained unchanged in their color. Nevertheless, I am satis- fied that this change is ma- terially a form of waxy de- generation, somewhat different from the degeneration in Emerson's case, but kindred to the waxy degeneration which J. B. Greene * described in the pla- centa as the most common cause of abortion and premature birth. * " American Journal of Obstetrics and Diseases of Women and Children," vol. xiii., No. 2, April, 1880. W* FIG. 180. — WAXY DEGENERATION OF THE GRAY SUBSTANCE OF THE THALAMUS OPTICUS. V, capillary blood- vessel, containing a granular mass, compressed at its upper portion, surrounded by a layer of the waxy mass ; G, gray substance, the meshes of the bioplasson enlarged by the waxy material, which col- lects into branching, irregularly contoured, shining fields, Wi, W*; N, nucleus of the gray substance; a part of the periphery, surrounded by a waxy mass. Magnified 800 diameters. 438 INFLAMMATION. This certainty as to the nature of this degeneration could be obtained by a study with high amplifications of the microscope, such as 1000 to 1200 diameters. The best specimens for the study with such high powers I obtained by the treatment with a one-half per cent, solution of chloride of gold, in which solution the specimens were placed for one hour and twenty minutes, after having been thoroughly soaked in distilled water. By this, the blood- vessels were rendered dark blue violet, and the gray substance, with its nuclei, purple, while the shining fields remained unaffected. Here I could see the first change into the shining, homogeneous mass before mentioned, at the periphery of the capillary blood-vessels, and in the mesh spaces of the bioplasson reticulum. By the transformation of the liquid contents of a mesh space into a semi-solid shining mass, the space became enlarged, and the neighboring reticulum was pushed apart. By coalescence of neighboring shining formations, larger clusters with fluting outlines originated, in the middle of which often a faint trace of bioplasson was recognizable in the shape of a few delicate granules and their connecting filaments. Whether or not the reticulum of the bioplasson within the homogeneous masses was destroyed, I am unable to say. Not quite infrequently I met with small clusters of the homogeneous mass around nuclei of the gray substance, as if ensheathing them. In the further progress of the degeneration, a great many capillaries became destroyed ; probably first by pressure, and later by trans- formation. These blood-vessels, free of the change just described, looked, especially in their transverse sections, as if compressed and engorged with blood-corpuscles. My researches prove that there are waxy degenerations going on in the brain-tissue kindred to the waxy degeneration in other organs, such as the spleen, the liver, the kidneys, and the placenta. The intimate reason of this degeneration is not known, nor do we understand its intimate chemical con- struction. One thing is certainly of interest in the case examined — namely, that the blood-vessels being destroyed to great extent by waxy degeneration, the circulation of the blood in the brain is interfered with, and an encephal- itic process may in consequence ensue ; or the walls of the blood-vessels, being rendered brittle by the waxy degeneration, may give way the same as in fatty degeneration, and give rise to cerebral haamorrhage. XII. TUBERCULOSIS.* MY views on the subject of tuberculosis are based on exami- nations of two hundred corpses in which tuberculosis existed. In a number of these cases death had resulted from other diseases, and tuberculosis was a secondary condition.! A recapitulation of the literature of this subject is found in the excellent book of L. Waldenburg.| Nobody who, to-day, undertakes to discuss the question of the formation of tubercle would be allowed to dwell only upon the theory of tubercle. On the contrary, he would be bound to con- sider the former views, and to present the anatomical facts, in order to demonstrate the admissibility of separating the tuber- culous granulation from tuberculous infiltration. This cannot be accomplished simply by a description. Rokitansky has settled the descriptive part in such a manner that scarcely anything is left to be said. The views brought forward here are based entirely upon my own observation j they, to some extent, must be eclectic and polemical. An answer to the question what the * Translated from "Ueber Tuberkelbildung." Wiener Med. JahrMcher, 1874. tlwas able to perform the post-mortem examinations in the dead-house of the Wieden-hospital in Vienna, thanks to the kindness of the curator, Dr. Quiquerez. After the publication of my essay, I made one hundred more examinations of tuberculous bodies, the sum total being, therefore, three hundred. tuDie Tuberculose, die Lungenschwindsucht, und Scrofulose." Berlin, 1869. 440 TUBERCULOSIS. nature of tubercle really is can be given only after an accurate examination of facts. Tuberculosis of the Lungs. In order to properly group the dif- ferent phenomena of tuberculosis of the lungs, it will be of advantage to first illustrate its four principal varieties. " Chronic tuberculosis n comprises a tolerably well-defined group, which may be called " localized tuberculosis/7 as " chronic" is an expression mostly clinical. This form appears most fre- quently in the apices of the lungs, simultaneously in both, although this is not without exceptions. As it is never fatal, per se, we are rarely able to study it as a disease by itself. We meet with it, as an intercurrent condition, in the bodies of individuals dead of other diseases. We find, imbedded in the lung-tissue, nodules of about the size of a millet- or hemp-seed, which have a gray or grayish-yel- low color, are homogeneous, and of soft, or moderately firm, con- sistency ; or we see nodes, the size of a lentil or an almond, distinctly marked from the surrounding tissue. These are cir- cumscribed infiltrations, which, in transverse section, appear al- most dry, homogeneous, and of a yellowish-red or yellowish-gray color, which are in firm connection with the adjacent structures, and not yielding juice or tissue-particles on being scraped with the knife. Or, lastly, we find nodules or infiltrations of the size before described, whose centers are usually soft and friable, which can be mashed with the fingers, and from which the scraping- knife can reduce crumbs and brittle particles. In the apices, in some cases, nodules are the only formations present, and these may be found either isolated or conglomerated into groups ; in other cases we encounter only nodes, and therefore infiltrations. Not infrequently we see in the same apex a varying number of both nodules and nodes. All subsequent changes of these formations relate chiefly to the healing process; for, provided that no recurrences take place, localized tuberculosis of the lungs, as a rule, terminates in a cure. The healing process may be accomplished in two ways. Either it may start in the nodule or the infiltration while they are still in connection with the lung structure, and they themselves rep- resent a tissue, though a morbid one. Or the healing process may start after the nodule or the infiltration have been trans- formed into a brittle, friable mass, and therefore have ceased to be a tissue. TUBERCULOSIS. 441 In the first case, the tubercle is transformed into a semi-trans- parent or white, consistent, cartilage-like mass (the fibrous tuber- cle of Virchow), which must be regarded as dense callous con- nective tissue 5 or the nodule changes into a firm, dark, pigmented, homogeneous, sometimes stratified, mass — that is, it becomes horny or obsolete. These hard nodules, attaining sometimes the size of a sugar-pea, are often found scattered in the lungs. If, on the contrary, the disintegration of the tissue has once commenced, the crumbling mass becomes a foreign body, both as regards the surrounding tissue and the whole organism. Here, as around every foreign body, inflammation sets in, and the tissue around it is transformed into a firm connective-tissue cap- sule, of varying diameter. The encysted product of tubercle becomes a viscid, fatty, sometimes pigmented, paste $ or lime- salts are deposited in it, which results in its being transformed into a dry, cement-like mass. Finally, it becomes calcified, and is termed a calcareous concretion. The tissue in the neighborhood of the diseased focus behaves differently, according to whether originally only discrete or con- glomerated, and closely lying foci were present. The surround- ings of a horny nodule are found to be lung-tissue, which is radiatingly contracted, but otherwise normal, and from which the hard mass can be easily dug out. The structures in the neighborhood of a callous capsule, on the contrary, are firmly concreted with it, so that the capsule cannot be separated from the inclosing tissue. If from the very beginning, in a circumscribed district of lung-tissue, numerous nodules and infiltrations are present, and the lung- tissue itself is in the condition of a chronic inflamma- tion, the transformation into a hard, consistent callosity takes place, more or less extensively, usually in the apices of the lungs. The .tissue is indurated, and, as it is almost constantly provided with an abundant supply of dark pigment, the callosity appears of a slate-color, or even black. This is the pigmentary induration of Virchow, the cirrhosis of Corrigan and Buhl. In the indurated lung-tissue are found all the before-men- tioned methods by which tubercle is healed — viz. : the white, almost cartilaginous, nodule, the size of a hemp-seed ; the gray or black node of a concentric striation ; the cement-like or cal- cified mass, directly imbedded in the callosity. Observation, therefore, teaches that a genetic separation of the tuberculous nodule from the tuberculous infiltration is not admis- 442 TUBERCULOSIS. sible ; that the later metamorphoses depend materially upon the circumstance whether or not the nodule or node remained a tissue ; and, further, that the possibility of a focus becoming callous depends greatly upon its size ; and, lastly, that the solidification of the lung- tissue may take place either by the formation of a capsule, or as a diffuse induration, and any of these are secondary occurrences. A second group, found most frequently in bodies of persons who died of tuberculosis, is called subacute tuberculosis. As the term " subacute " is mostly a clinical expression, we might term this from the disseminated or dispersed tuberculosis. Its charac- teristic feature is, that new tuberculous nodules and infiltrations are produced in comparatively short space of time, in consequence of repeated recurrences. If the ulcerative destruction has not reached a high degree, we find almost constantly the first form of tuberculosis, as a general thing, in the apices of the lungs. Upon examining an apex, not too much destroyed, we notice that, while the horny and calcareous nodules remain unchanged, the capsule originally inclosing a friable product has undergone marked alterations. In the transverse section of the callosity constituting the cap- sule we find gray, grayish-yellow, or yellow nodules, the size of a poppy- or hemp-seed j the inner surface of the capsule is lined 'with a firmly attached, grayish-yellow, layer, resembling croup- ous formations. After the removal of this, the intensely red- dened capsular wall is seen dotted with the before described nodules. Many of these are in a process of softening, or disin- tegration into a cheesy, friable mass. When numerous nodules were originally formed in the cal- losity, the inflammation accompanying the disintegration evi- dently leads to suppuration, local mortification, and ulceration of the capsule. The bordering formation of new callous tissue in the inflamed lung-tissue is scanty. Here and there a new rudimentary capsule may appear ; or it altogether may be absent where the disease is of rapid course, and then we find lung- tissue, which is eroded, uneven, sinuous, and studded with granu- lations. Consequently, we meet with transitions from an acute inflammation of the capsule of a tuberculous focus to its sup- puration, and to a partial new formation of a thin, so-called pyogenous membrane, and, finally, to an ulcerative destruction of the lung-tissue. Simultaneously an exudation takes place into the cavity, and the crumbly contents are saturated with the liquid. Should sup- TUBERCULOSIS. 443 puration ensue on the inner surface of the capsule, which is freely vascularized, the pus mingles with the former contents, and a thin, serous pus results, which contains a number of friable particles. This is the so-called tuberculous pus. At length the entire mass becomes softened, and the formation of a cavity fol- lows, which is inclosed by a capsule and is therefore a closed abscess. The cavity may be completely surrounded by lung-tis- sue, thus producing the so-called parenchymatous cavity. If a cavity arises from a bronchus by a formation of tubercles in its- mucous lining, or if perforation takes place into one or more bronchi, a bronchial cavity is formed, which result must follow after a certain size of the cavity is reached. By this means, the expectoration of the contents becomes possible, and, also, the access of atmospheric air to the contents of the cavity. The walls between two or more cavities may be perforated by ulcerations, due to a continuous or repeated formation of tuber- cles. Lastly, a cavity may arise from the confluence of a number of cavities, of sizes varying from that of a walnut to that of the fist of a child or the fist of a man, the walls being formed by lung-tissue, which is partly callous, partly sinuous and corroded. I would mention, incidentally, that not infrequently the cav- ity is traversed by firm cords of different sizes, and the walls thickly set with such formations. These are the remains of the former blood-vessels of the lung, which, by thickening of their adventitial coat, have become callous, and resisted the process of ulceration. Sometimes, as is well known, a tuberculous nod- ule, imbedded in the adventitia, may disintegrate before oblit- eration of the vessel, and, in consequence of the ulcerative destruction of the wall, a profuse or fatal haemorrhage may ensue. Finally, it. may happen, perhaps, under the influence of the penetrating air, that a rapid ulcerative destruction invades large portions of the wall of the cavity, which becomes necrosed and, together with the neighboring tissue, passes into gangrene. Then we find the cavity bordered by lung-tissue, of a grayish or brownish-green color, eroded and containing irregular sinuses, while its contents are an offensive, putrescent ichor, mixed with blood, pus-flakes, and cheesy crumbs. These characteristics cor- respond to the tuberculous phthisis of Laennec. This term may be employed if we understand by it the ulcerative destruction of the lung-tissue, and if, by the addition of " tuberculous/7 we designate the nature of the destruction. -444 TUBERCULOSIS. In addition to the above-described changes taking place in the neighborhood of the encysted or disintegrated foci, morbid processes occur in the rest of the lung-tissue, most intense, as a rule, in the upper lobes, while the lower lobes are comparatively little affected. In more or less extensive districts, isolated nod- ules, the size of a poppy- or millet- or hemp-seed, are observed ; first as gray, gelatinous dots in the lung-tissue, this being satur- ated with a viscid, albuminous exudation. Starting from their -centers, the nodules then assume a grayish-yellow color, after- ward become yellow, and are finally transformed into a cheesy, crumbly mass, before a capsule or callosity has formed in the vicinity. While the old nodules take part in this metamorphosis, fresh gray ones arise, so that we often find in the same lung all transitions, from the gray to the yellow, and disintegrated tuberculous nodule. Sometimes the nodules are grouped around a bronchus in a wreath-like arrangement (Peribronchitis nodosa, Buhl), or they may appear first at the periphery of a lobule which is in the condition of a flabby, red, or grayish-red hepatization. They may also fill the whole lobule, retaining their nodular form as long as no disintegration has taken place. Sometimes only scattered nodules are met with in the diseased lung; sometimes nodules are combined with infiltrations; and sometimes only infiltrations present themselves, which consist of grayish-yellow, firm, half -dry foci, ranging in size from that of a lentil to that of a hazel-nut, such as I have described as occurring in chronic tuberculosis. The infiltrations become disintegrated into a friable, crumbly mass. This disintegration always starts from the centers of the diseased parts. The view held by older pathologists, and also by Virchow, is that the softening is a chemical process, occur- ring, perhaps, independently of any imbibition of water from without. This idea of a melting process taking place, as it were, in the own liquid, follows from the belief that the infiltration from its very outset appears of a certain size, and retains this size until " melted'7 or transformed to " softened cheese." A different explanation may be obtained if we remember the fact that the node at its periphery continues enlarging, and that the oldest focus of disease is to be looked for at the place where the soften- ing starts. The tuberculous mass, therefore, may have become soft by liquid derived from the inflamed neighboring parts before peripheral new production has occurred, which still exists in the •" cheesy " stage. TUBERCULOSIS. 445 Softened infiltrations are usually bounded by thin, yellow, sinuous layers of tissue. In the vicinity the lung usually ap- pears in the state of flabby, red hepatization, saturated with a viscid exudate, and at other times it is moderately indurated. The softening of the infiltrations also terminates in the forma- tion of cavities, and the ulcerative destruction of the lungs. This variety of tuberculous phthisis differs from that described before only in form and acuity, but not in any essential point, nor in its terminations. Sometimes, scattered or clustered nodules and infiltrations fill a district or the larger portion of a lobe so entirely that this becomes rigid, fragile, and, in part, atelectatic. In such cases, we may speak of a pneumoniform, subacute tuberculosis, whose features are sufficiently marked to distinguish it from catarrhal or " desquamative" pneumonia. If a group of nodules, or an infiltration lying close to the pleura, is. disintegrated, and the pleura destroyed by ulceration, perforation into the pectoral cavity may follow. This is the most common cause of pneumo- and pyo-pneumothorax, which not infrequently accompany tuber- culosis of the lungs. In looking over the second form of tuberculosis of the lungsf we again are satisfied that there is no essential difference between a nodule and an infiltration ; that either may be transformed into a crumbly mass and become softened. The next step — i. e., ulcera- tion of the lung-tissue — is different only in its acuteness ; that isr according to whether a number of scattered nodules are breaking down at different times, or whether an infiltration is continually softened and simultaneously increases in size at its periphery. The surrounding lung-tissue, in all forms of softening and local necrosis, is evidently involved only in a secondary manner, therefore is in a " re-active," acute, or chronic inflammation. The third form of tuberculosis of the lungs is comparatively rare ; it is called tuberculous pneumonia, pneumonia tuber culisans. In the description of subacute tuberculosis, I have already men- tioned that lobules, in flabby hepatization, are sometimes the points where tuberculous nodules or infiltrations are formed. Should this grayish-red or gray hepatization involve a number of lobules, or nearly the whole of a lobe, the features of lobular pneumonia arise. It becomes tuberculous by the appearance of gray and grayish-yellow nodules, or of gray and grayish-yellow infiltration, either in the neighborhood of bronchi or at the periphery of the lobules, or scattered throughout them. In the 446 TUBEBCULOSIS. initial stages of the disease the infiltrations are not sharply marked from the surrounding hepatized lung-tissue. Sometimes they have the appearance of being composed of numerous con- glomerated particles the size of a pin's point. At other times we find a lobe, or the larger portion of a wing, in the condition of lobar pneumonia, consequently en- larged, heavy, dense, rigid; and without air — i. e.f in a grayish- red or gray hepatization ; and if the inflammation has invaded a pigmented lung, it has the aspect of granite. In genuine croupous pneumonia the section looks finely gran- ular, owing to the filling of the alveoli j if the inflammation has attacked a coarsely spaced, atrophic lung, it is filled with coarser, yellow exudation plugs. In tuberculous pneumonia, on the con- trary, we find, usually, in the vicinity of the finer bronchi, groups of moderately firm, grayish-yellow nodules, in varying numbers, imbedded in the hepatized tissue. I have observed this form several times, generally in the lower lobes, after capital opera- tions— f. i., amputations in individuals who, by previous sup- purative processes, had become broken down. In a third instance we find the whole wing in brown-red hepatization, its tissue without air, firmly indurated with a slight serous infiltration, and pervaded by numerous nodules the size of hemp-seed, or nodes from the sizes of a lentil to that of a hazel- nut ; these are mostly softened. Such a lung exhibits an aspect similar to that of porphyry. If the indurated tissue of the wing is profusely pigmented, the pigmentary induration, therefore, has invaded the whole wing, we find in it scattered nodules, usually of a size not exceeding that of a millet- or hemp-seed, which may be both obsolete and calcareous, or gray, grayish-yellow, and soft. Here, too, the characteristics of pneumonia are marked and have led to a condensation, hypertrophy, callosity, and pigmentary induration. Still the nature of the process is sufficiently apparent by the presence of the nodules and infiltrations. Finally, we find in the indurated tissue of red- brown hepatiza- tion of which only little is left, firm, grayish-yellow, half -dry infiltrations, partly softened, about the size of a pea, hazel-nut, or perhaps as large as a walnut, which are closely packed together or confluent. An entire lobe, or wing, with the exception of scanty remains of red-brown, hepatized lung-tissue, may be per- vaded by this " cheesy" infiltration, which on being scraped yields only a small amount of a cloudy liquid. Such an infiltra- tion renders the diseased tissue friable and brittle. Only the TUBERCULOSIS. 447 pigment indicates the otherwise unrecognizable lung-tissue (Rokitansky). One of the cases which I observed deserves mentioning, because it will be of value in supporting the theory of tuberculosis, to be dwelt upon later. A strong boy, eet. 15, was taken to the hospital with the symptoms of typhoid fever. Soon pneumonia of the right lung was diagnosticated. Two months afterward the patient died, with symptoms of a clinically diagnosticated tuber- culous pneumonia. In autopsy I found the right wing pervaded by " cheesy" infiltrations to such a degree that the tissue was atelectatic and firm ; the left lung at its apex contained an infiltration the size of a child's fist. The infiltra- tions in both apices were softened, and in the right apex showed a number of cavities of different sizes, but not very large. No traces of any previous chronic tuberculosis could be discovered. The spleen, the small intestines, and the mesenteric lymph-ganglia had the same appearance as seen in typhoid fever after the healing process had been going on for a few weeks. Here, therefore, under the influence of marasmus after typhoid fever, an original, clinically well-marked genuine pneumonia was changed into a tuberculous pneumonia. The nodules and infiltrations, through their peculiarities, may be at once recognized as tuberculous, because they are markedly different from analogous nodular infiltrations of the lungs, as observed in carcinomatosis and pycemia. The distinguishing features are: the white color, the scanty vascularization, the wreath-like arrange- ment around the pulmonary vessels in carcinomatosis j the yellow color, the softness, the partial disintegration to pus or ichor, the purple color, and sometimes the dark red hepatization of the neighboring parts in pyaemic infarctions. A fourth form of tuberculosis of the lungs is known by the name of the acute or miliary tuberculosis (Bayle). Here we find both lungs diseased nearly simultaneously, and to nearly the same extent. They are enlarged, heavy, profusely supplied with blood, and saturated with a viscid, cloudy exudate. In the apices we encounter chronic and sometimes even healed tuberculosis 5 in other cases, no trace of this condition. The whole hyperasmic lung-tissue is pervaded in nearly uniform distribution by more or less densely arranged gray, or grayish-yellow, soft, translucent, opaque nodules, the size of poppy-, millet-, or hemp-seed. In several cases, the largest and most numerous of these nodules were found in the upper lobes ; comparatively few nodules of the millet-seed size in the right middle lobe, and but very few gray nodules the size of a poppy-seed (submiliary) in the lower lobes. All cases of this variety exhibited in the meninges, the liver, the spleen, the kidneys, and the peritoneum the same morbid condi- tions in different combinations. 448 TUBERCULOSIS. Beyond this stage no changes are observed, for this form of the disease, as" a rule, terminates fatally, with symptoms similar to those of typhoid fever. This form is the rarest. It differs from nodular tuberculosis, termed subacute, only in the simultaneous appearance of tubercle nodules in different organs and the acute- ness of its course. I can corroborate, from my own careful researches, the statement of Buhl that in ten per cent, of the cases dead of this variety of tuberculosis no trace of cheesy focus can be found. Tuberculosis of the Serous and Mucous Membranes. Under this head I shall only take into consideration tuberculosis of the pleura and the peritoneum, as these have supplied me with the most abundant material for observation. In the pleura, we find tuberculosis is always combined with the chronic or subacute form of the disease in the lungs, and in the peritoneum also, though here not so constantly, it is found secondary to tuberculosis of other organs. This form of disease has features corresponding with those of chronic tuberculosis of the lungs, and may be considered as chronic tuberculosis of the pleura and the peritoneum. The pleura of one pectoral cavity, and the parietal peritoneum in its whole extent, may be considerably thickened, and trans- formed into a white, firm, and dense callosity. I have seen the peritoneum in the pubic region as thick as the width of the little finger. These callosities were either formed by the costal, dia- phragmatic, and the pulmonary pleura, or, as is sometimes the case, mostly by the costal pleura alone. In the abdominal cavity the thickened parietal layer was concreted with the visceral layer by means of thin, pseudo-membraneous cords and plates. In the callosity I found abundant foci, from the size of a hemp-seed to that of a hazel-nut, containing a crumbly mass. In the pleura I met even with cavities, ranging from the size of a Imzel-nut to that of a pigeon's-egg, which were filled with a mixture of pus and cheesy particles. I could trace all transitions in consistence and liquefaction, from cheese to pus. I have several times en- countered such foci between the basis of the lung and the dia- phragma, and also at the anterior border of the lung, with perforations outward, between the third and the fourth rib. I have also observed this condition at the posterior border of the lung, in the niche formed by the union of the vertebrae and ribs, with caries of single ribs. In the peritoneum I have observed such cavities perforating into the abdominal space, with subse- TUBERCULOSIS. 449 quent ulceration of the pseudo-membraneous adhesions, between the parietal and visceral layer, and a final perforation of the intestine from without inward. That tuberculous nodules of the peritoneum, however, may heal up in the same way as those of the lungs is proved by cases in which the small intestines are found massed together and thickened, and at the periphery surrounded by a thick, pseudo- membraneous capsule. Upon detaching the firmly agglutinated loops, the visceral peritoneum was found strewn with nodules, either isolated or in groups, of the size of a millet- or hemp-seed. They were colorless, half translucent, and sometimes transparent, having a vesicular appearance j or they were white, firm, fibrous, even cartilaginous, while many of the nodules and clusters were surrounded by a narrow area of dark brown or gray pigment. I have sometimes found, in the peritoneum, a second form of tuberculosis, of a subacute character — i. #., a miliary tubercu- losis— with repeated recurrences. The conditions were the fol- lowing: after opening the abdominal cavity, which was filled with a serous or haBmorrhagic exudation, I saw in both peritoneal layers, besides firm nodules encircled by pigment, others which were of a grayish-yellow or yellow color, surrounded by an injected or haemorrhagic area, and still other nodules which were gray or grayish-yellow in color, tolerably soft, easily mashed, and imbedded in the cloudy, swelled peritoneum. Scarcely a doubt could arise that, in such cases, the " fibrous " and pigmentary nodules were the oldest, or they might even be healed, judging from their analogy to the " obsolete" or " cartilaginous " nodules of the lung, and also from the fact that pigment can form only after a certain length of time. That, however, repeated recur- rences had taken place was proved by the presence of tubercu- lous nodules in their different stages, such as we have become acquainted with through the researches of Laennec. A third form is the acute, miliary tuberculosis of the pleura and the peritoneum, which is always combined with tuberculosis of other organs. We find the pleura and the peritoneum thick- ened by pseudo-membraneous layers and pervaded by innumera- ble tubercles, which, in some parts, are isolated and in others coalesced. Some of these are mere dots, the size of a pin's point, and others are as large as a millet- or hemp-seed. All of them show a nearly uniform grayish-yellow or yellow color. Pseudo- membraneous callosities of varying thickness may be throughout crowded with yellow tubercles, which have, to a great extent, 29 450 TUBERCULOSIS. become confluent, and in some localities are packed together without a trace of separating tissue. The same condition may be observed in the omentum after it has grown together into a firm, bulky mass. Sometimes there are present simultaneously recent, cobweb-like, freely vascularized pseudo-membranes, which may be crowded with submiliary gray tubercle granules, not surpassing in size a pin's point. Of the mucous membranes I shall consider only the mucosa of the larynx, the intestine, the uterus, and its tubes. The differ- ent forms of tubercle cannot be traced in mucous membranes, because the nodules and infiltrations lie near the surface and rapidly soften, disintegrate, and lead to ulcerative destruction of the mucosa. Doubts have been raised (Rheiner) whether or not the ulcers in the posterior wall of the larynx, which are so often combined with tuberculosis of the lungs, are really tuberculous in nature. As is well known, they are either f ollicular or cleft-like, either shallow and superficial, or sinuous ulcers, which, penetrating into the depth, sometimes cause necrosis of the cartilages of the larynx. All doubts regarding the tuberculous nature of these ulcers will disappear if we see — though not in many instances, it is true — in the mucosa of the larynx, at the borders and the basis of the ulcers, yellow, flat infiltrations, the size of millet- or hemp-seed. The mucosa of the lower ileum, the cwcum, the ascending and transverse colon, offer a good chance to study, macroscopically, the genesis and the course of tuberculosis. Not infrequently we see intestines in which there are all transitions, from minute, follicular nodules and superficial ulcers, springing from them to an ulceration, extending over several square inches in circum- ference, the so-called tuberculous phthisis of the intestine. The formation of tubercles, and the consequent ulceration, is sometimes chronic and sometimes acute in its course (Eoki- tansky). I would mention here that the deepening and spreading of the ulcers is due to a continuous new formation of tuberculous nodules, which are seen as flat, grayish-yellow, and yellow forma- tions, the size of hemp-seeds, imbedded in the inflamed tissue. In the chronic course of tubercle formation a thickening of the mucosa and of the sub-peritoneal tissue takes place, in the neigh- borhood and at the base of the ulcer. The ileo-coecal valve may remain as a ledge-like projection, of several lines in thickness, of considerable density, and undermined by a number of sinu- ous ulcers, emptying above and below the valve. ! TUBERCULOSIS. 451 When the ulceration penetrates the sub-peritoneal tissue, a circumscribed peritonitis always follows, corresponding in extent to the size of the ulcer. This peritonitis is decidedly marked by nodules, which are either discrete or grouped together in clus- ters, of a yellow or grayish-yellow color, and are imbedded in the tissue of the peritoneum, which is swelled, opaque, and often considerably injected and ecchymosed. Such an acute localized formation of tubercles, accompanied by considerable hyperaBmia of the peritoneum, may give rise either to a peritonitis confined to the hypogastrium, or to a general purulent peritonitis. Fi- nally, if in the peritoneum tubercle, in circumscribed places, is softened and disintegrated, and if no protecting pseudo-membrane has been previously formed, a perforation of the wall of the intes- tine will take place, with an escape of the contents into the abdominal cavity, and a general purulent peritonitis will set in, with a rapidly fatal termination. Tuberculosis of the mucosa of the uterus and the tubes exhibits similar characteristics. Here, too, the primary tuberculous formation appears as flat, gray, or grayish-yellow granulations, which are only exceptionally found in the mucosa of the fundus uteri and that of the swelled and winding tubes. I encountered most frequently ulcerative destruc- tion of the mucosa to a considerable extent. These ulcers were shallow, and were defined by abrupt, sinuous, and irregularly eroded borders. Upon removing the cheesy, crumbly, and some- times almost as if croupous, formation from the surface of the mucosa, flat, grayish-yellow infiltrations about the size of hemp- seed became at once visible. Real nodules are of as rare an occurrence in this situation as in the mucosa of the larynx ; for the prominence, which is the essential feature of a nodule, is wanting. Tuberculosis and Scrofulosis of the Lymph-ganglia. O. Schiip- pel* has arrived at results widely different from those of Virchow. He admits the fact that there exists such a thing as primary tuberculosis of the lymph-ganglia, and that this may arise and terminate as a purely local disease. He describes the tubercles of the ganglia as " globular, tolerably well-marked nodules of not more than O. 3 mm. diameter, which are invariably and exclu- sively located in the vascularized follicles of the ganglion." Schiippel also considers only the nodules to be tubercles, and, in his opinion, scrofulosis is nothing more than a miliary tuber- culosis of the inflamed hyperplastic ganglion. This conception I cannot accept as correct. True, sometimes we meet with * " Untersuchungen liber Lymphdriisen — Tubereulose," 1871. 452 TUBERCULOSIS. nodules — i. e., prominent formations of a size varying from that of a pin's point to that of a hemp-seed — in ganglia which are swelled, softened, and grayish-red. More commonly, however, such nodules are wanting, and the diseased ganglion exhibits a grayish-yellow discoloration, either throughout the transverse section or only in a portion of it, and in the latter case the dis- coloration is sharply marked from the gray-red, vascularized portion of the ganglion. If a discoloration is observed in a sub- miliary spot the size of a pin's prick or of a poppy-seed with- out a protrusion, what reason have we for calling it a " nodule "J? Would it not be more correct to name such a condition an " infil- tration'7! If we observe whitish-yellow submiliary spots on a grayish-yellow basis, are we authorized in calling only the whitish- yellow parts tubercles? And, lastly, if the whole ganglion has become homogeneous, grayish-yellow, half-dry and friable, where are the tubercles? I should say that here, as in every other tissue, a sharp dis- tinction between the tuberculous nodule and the tuberculous infil- tration leads to confusion and error, and I should prefer insisting upon the genetic identity of both these forms, also in the lymph- ganglia. I, however, agree with Schiippel in the view that the tubercle is formed from an inflammatory new formation, and that scrofulosis and tuberculosis are identical. If we should place before a person a lymph-ganglion in " cheesy" metamorphosis, without telling him from what part of the body it came and what were the concomitant phenomena, would he be able to decide whether this ganglion was scrof- ulous or tuberculous, or whether it came from the region of typhoid or cancerous disease ? I should certainly think not. The feature common to all is the grayish-yellow infiltration, the u cheese " of Virchow. Later stages of disintegration, softening, suppuration, or calcification are also identical. Nevertheless, Virchow considered it necessary to separate " scrofulosis" from " tuberculosis." To what the " cheesy" degeneration is due I will demonstrate later. Here I only wish to maintain that there is no one in- variable anatomical sign which would entitle us to call a given ganglion either scrofulous or tuberculous. Schiippel, however, deserves credit for having demonstrated, by the means of micro- scopic research, that the theory of "hyperplasia" and "hetero- plasia" is not tenable, especially so far as tuberculosis of the lymph-ganglia is concerned. TUBERCULOSIS. • 453 Finally, I would draw attention to the fact that the ganglion in grayish-yellow or cheesy infiltration may become softened and suppurate. This process starts from certain centers, and results in the formation of a " scrofulous n abscess. In an abscess of this kind, the thin pus mixed with cheesy crumbs is so charac- teristic that the experienced surgeon Schuh at once made the diagnosis of " scrofulosis " in an apparently well-nourished indi- vidual, when upon incision the abscess yielded pus of the above description. On the other hand, the softened infiltration may become fatty and encysted, or calcified, and in the latter case the whole lymph-ganglion in time is transformed to a calcareous mass the size of a hazel-nut, such as we sometimes find in the mesentery. Tuberculosis of the Kidneys — Concomitant Nephritis. Before entering upon the description of my researches concerning tuber- culosis of the kidneys, I would remark that the kidneys here con- sidered were not primarily affected by tuberculosis, but the same pathological condition existed in other organs, notably in the lungs. Not infrequently we meet, both in the pyramids and in the cortical portion, with single, white, almost cartilaginous infiltra- tions, of sizes varying from that of a millet- up to that of a hemp- seed, which are surrounded by unchanged kidney-tissue, and, in accordance with analogous occurrences before described, might be considered as healed tubercles. Whether or not the firm, yel- lowish-white, callous nodes, the size of a lentil or a pea, are tuber- culous formations is doubtful, for we also see such nodes in the kidneys of non-tuberculous individuals. They might be, with equal reason, considered healed infarctions, more particularly if any evidences of healed endocarditis are found. Chronic and Subacute Tuberculosis of the Kidneys I have encountered much less frequently than other forms of the disease. I have occasionally seen small, yellow, friable infiltra- tions in the swelled, cloudy, partly ecchymosed cortex, in the neighborhood of which wreath-like or discrete infiltrations, the size of a millet- or hemp-seed, were found. I concluded, from similar occurrences in the lungs, that the larger infiltrations were the oldest, the smaller ones of a later date, without maintaining, however, that the former originated from the latter. In chronic tuberculosis of the kidneys, tuberculous phthisis may arise from confluence of a number of foci, which, though a simultaneous cal- 454 TUBERCULOSIS. lous condensation of the bordering connective tissue takes place, may become softened and produce cavities (Eokitansky). Lastly, acute miliary tuberculosis of the Mdneys is observed as infiltrations, not exceeding the size of a millet-seed, which, as a rule, are most abundant in the cortical substance, and present, in a comparatively small amount, in the pyramids. Such formations are either scattered or, in part, clustered together, with simulta- neous miliary tuberculosis of the lungs, the peritoneum, and the liver. This form of tuberculosis of the kidneys I have seen but twice. Here I wish to draw attention to the nephritis which accom- panies both the tuberculosis of the kidneys and that of other organs. Usually, many different forms of nephritis are classed under the head of " Bright's disease/' and Rokitansky especially distinguishes an acute and a chronic form. I wish briefly to state that, in these two varieties of Rokitansky, I recognize two kinds of inflammation of the kidneys, readily distinguishable as diseases sui generis. What Rokitansky describes as acute "Bright's disease" should be designated croupous nephritis, a characteristic of which, in addition to the inflammatory swelling and redness or hyperaBinia, is a diffused exudation. Rokitansky' s chronic form of " Bright's disease," on the contrary, must be con- sidered an interstitial, catarrhal, or desqiiamative nephritis. In croupous nephritis tubular casts appear in the urine, and large quantities of albumen, and the casts are recognizable even after waxy degeneration of the kidneys has ensued. In catarrhal nephritis, on the contrary, there is albumen in the urine in a comparatively small quantity, the tubular casts are missing, and only desquamated epithelia of the urinif erous tubules are found. It is obvious that these forms of inflammation are different only in degree and not in acuteness. Gatarrhal nephritis may also appear in an acute form and be followed by acute recurrences, in which, as a rule, the urine becomes more albuminous. The characteristic pathological sign of catarrhal or interstitial nephritis is the striation of the sometimes slightly, sometimes considerably, swelled cortical substance. The striation is most marked on the boundary line between the cortical and pyramidal substances. The seat of the disease is evidently the connective tissue between the urinif erous tubules, while the exudation into the tubules leads only to a desquamation of the epithelia, but not to formations similar to those of croup of mucous membranes. In acute catarrhal nephritis and in its acute recurrences there TUBERCULOSIS. 455 are gray striation s, alternating with the dark brownish-red hyperaemic kidney-tissue and the engorged blood-vessels. In the chronic form of this disease, on the contrary, the striation is of a grayish-yellow color, and there is no hyperaemia whatever of the kidney-tissue. One of the reasons which led to the statement that these two varieties are different morbid conditions, was the difference observed in the appearance of the consecutive atrophy. After croupous nephritis this appears on the surface of the kidneys as a coarse lobulation, with the formation of irregular elevations and depressions of the cortical substance ; while after catarrhal nephritis there is only a more or less uniform granulation and shallow furrowing of the surface. The most striking proof is furnished by kidneys which were in both poles in part attacked by catarrhal and in part by croupous nephritis. The parts in catarrhal inflammation exhibit fine granulation on the surface and corresponding grayish-yellow striation of the nearly uni- formly reduced cortical layer. In the portion attacked by croupous inflammation the surface is coarsely lobular, and a grayish-yellow infiltration prevails in both the irregularly atrophied cortical and the reduced pyramidal layers. In the highest degrees of atrophy after catarrhal nephritis the kidney is uniformly reduced to a half, a third, or even less, its original size, yet still there is an indication of the striation of the narrowed cortex, which blends, almost without a boundary line, with the striated pyramids. The granulation of the surface is very marked. After croupous nephritis in the highest degrees of atrophy there are large nodes, separated from each other by deep furrows, with an almost complete destruction of the cortical sub- tance, and also a marked reduction of the pyramids, which are pushed apart. In addition, there is a considerable amount of fat at the periphery, and also at the hilus of the kidney, and a more or less marked secondary waxy degeneration of the kidney- tissue, which in some places may be reduced to a diameter of not more than four to five lines. In both forms of nephritis, however, fatty and waxy degenera- tion occur. Fatty degeneration in either produces a diffuse yel- low discoloration of the kidney, and for the recognition of the original morbid process the increased volume of the organ and the aspect of its surface are decisive. I have observed high degree of waxy degeneration after both kinds of nephritis, but so far as my subjects of observation admit of a conclusion, I 456 TUBERCULOSIS. should say this condition was less frequent after catarrhal than after croupous nephritis. In the first instance, the waxy degeneration invades a pale or dark-brownish-red kidney, or it may be confined to the pyramidal substance only j while in the last instance the lardaceous appearance is uniformly distributed throughout the organ. Out of two hundred cases of tuberculosis of different organs I found croupous nephritis only seven times. In bodies, on the contrary, in which tuberculosis was the cause of death, I have never failed in finding catarrhal nephritis. I am far from connecting nephritis in causal relation with the tuberculosis of other organs. Catarrhal nephritis almost invariably accompanies all severe acute and chronic diseases — f . i., croupous pneumonia, typhoid fever, small- pox, pyaemia, chronic suppurative processes, etc. Besides, both forms of nephritis may appear primarily with the well-known symptoms, and in their severest forms lead to a fatal termination. THEORY OF TUBERCULOSIS. Anatomical Signs of the Tubercle. We must examine the char- acteristics of the morbid process which are concerned in the formation of tubercle : the features which are observed by the naked eye, those brought to light by the microscope, and those inferred from the views taken by different pathologists. In this way we may obtain a definition of the tubercle. What are the characteristic features of tubercle ? Is it the nodular shape 1 Certainly not. We know of a num- ber of diseases of the skin which are characterized by nodules, such as lichen, milium, acne, etc., and all follicular furuncles are at first nodular. We know that in catarrhal inflammation of the mucous membranes nodular follicular swellings occur, which dis- appear as soon as the inflammation subsides. Occasionally we find, in corpses where there is no sign of tuberculosis, nodules the size of a pin's point or a poppy-seed, in the peritoneal cover- ing of the liver and spleen, and sometimes, also, in the pleura. These are very firm, transparent, without an injected area, and are located on slightly cloudy or unchanged bases. Their origin is apparent to any one who has seen acute pleuritis, especially in the neighborhood of peripheral pyaemic infarctions of the lung, and acute peritonitis in its earliest stages — f. i., in puer- peral process. Further, we often encounter, chiefly at the free TUBERCULOSIS. 457 border of the bicuspid valve, nodules the size of a millet- or hemp-seed ; these are sometimes pedunculated, and are papillary vegetations from former endocarditis. Lastly, a number of tumors, fibroma, papilloma, sarcoma, and cancer appear, first as a nodule. Who would think of designating such nodules tuber- cles, although they are in reality " tubercwla" f Is it the form of an infiltration ? We have no better grounds for that. The swelled patches and solitary follicles of the mu- cosa of the intestines, the enlarged bronchial and mesenteric lymph-ganglia in typhoid fever, pygemic infarctions of the lungs, etc., furnish examples of circumscribed infiltrations j in croupous pneumonia and in croupous nephritis we have specimens of dif- fuse infiltrations, and such infiltrations, it is 'obvious, have noth- ing in common with tuberculosis. We, therefore, look in vain for the shape to distinctly charac-1 terize the disease termed tuberculosis. Not only tuberculosis, but any product of inflammation, may appear at one time as a nodule, at (finer times as an infiltration. Let us search further for a pathological feature peculiar to this disease. Is it the cheesy metamorphosis ? We know, on the one hand, that tuberculous nodules dp not always pass on to this meta- morphosis, as is demonstrated by the isolated '"fibrous "tubercles of serous membranes, whose cure is made manifest by the pig- mentary area and by the obsolete nodes of the lungs, which, as mentioned before, sometimes attain the size of a sugar-pea. We know, on the other hand, that the tissues of cancer, of typhoid lymph-ganglia, nay, pus itself, may undergo a cheesy metamor- phosis. Virchow announced that a tissue might, under some con- ditions, become caseous, as it might under other conditions enter calcareous, fatty degeneration or become putrescent. According to his view, there is a hyperplasia which terminates into a cas- eous condition (scrofule of a lymph-ganglion) and a hetero- plasia which also terminates in the same caseous change (tubercle, cancer). This " cheesy" change, therefore, cannot be an essential feature of tubercle. Is it the heteroplasia ? In Virchow's classification the miliary tubercles belong to the lymphatic tumors ; they are adenoid — i. e., gland-like new formations and heteroplastic productions — which means that they originate " in places in which they do not belong." I cannot think that Virchow intended this for a serious definition. We know perfectly well that any inflammatory new formation, without exception, any " accumulation of cells/7 may 458 TUBEBCULOSIS. be of a "lymphoid" character, — f. i., the granulations of a wound, and very likely every disease does originate in a place where it does not belong. Besides, Schiippel (I. c.) has demonstrated that the view of a " heteroplastic " origin of the tubercles of the lymph-ganglia is not tenable. More recently, efforts have been made to locate the essential sign of the tubercle in its multinuclear elements — Rokitansky's mother-cells. In this view, the presence of a central " multinu- clear cell " would be sufficient to stigmatize all the surrounding " lymphoid" new formation as tuberculous. We know that the so-called " giant-cells " occur, not only in normal medullary tissue of bone and in inflamed tissues, such as cornea, cartilage, bone, but also in a number of tumors (sarcomata), so that it is impossi- ble to consider them as definite characteristics of the formation Af tubercle. They are no more specific for this disease than are the "tubercle-cells" of Lebert. Neither are we justified in claiming that the minute size of the elements, their transient nature, their "low vitality,"* are characteristic. The so-called " small-cellular" sarcomata and can- cers in disintegration exhibit elements which are certainly still less stable than those of the tubercle. Besides, we find in the tubercle the large, so-called epitheloid, and also the very large multinuclear elements. This much is certain, that all previous definitions of tubercle lack clearness. I again return to the question, what are the •essential characteristics of tubercle ? Beyond doubt (and on this point all observers are agreed) the tubercle is a new formation — i. e.f a new product "in a place where it does not belong." It, however, has a peculiarity known to all accurate observers. It contains no blood-vessels. Tubercle, therefore, is an avascular new formation. Origin of Tubercle. As early as 1816 Broussais maintained that the tubercle, or rather the "tuberculous matter,7' was a product of inflammation. Much discussion followed this assertion, but all was to no purpose, since nobody then knew what inflam- mation really was. Most later observers have considered the pneumonic form of tuberculosis of the lungs as inflammatory in nature, and even Virchow cannot be suspected, having considered every tuberculosis due to inflammation. While Broussais took "irritation" and " inflammation " for one and the same process, Virchow, in a logical manner, sepa- rated them. He says : " Primary tuberculosis of the lymph-glands TUBERCULOSIS. 459 is primary only as tuberculosis, but not as a process of irrita- tion, whose irritating agency is generally carried in from an atrium." This ingenious remark shows that the irritating agency is to be considered as the cause — the irritative process, on the contrary, as the result. The difference between the " irritation7' of Broussais and the " irritative process " of Virchow is obvious. The history of the theory of inflammation elucidates the meaning of the process un der consideration. Humoral pathology placed it almost exclusively in the blood-vessels and in the diseased blood. Cellular pathology, on the contrary, set aside the blood- vessels and everything arising from the blood, and 'sought for the essentials in a disease of the tissue, in the inflammatory new formation. To the irritating agency at first the blood-vessels only responded ; later, only the cells of the tissue. S. Strieker, in 1870, in opposition to these views, urged the importance of the blood and the blood-vessels as factors in giving rise to the inflammatory process j and he demonstrated that the Mood- vessels take an essential part in the production of tissue changes. Since then, somewhat more has been added. It is proved through my own researches that, besides the exudation and the new formation of living matte?, the new formation of Mood and blood-vessels is an essential feature of traumatic inflammation. I have shown that the process of inflammation first causes a liberation of the living matter, which before was infiltrated with basis-substance; that the inflamed tissue first returns to its juvenile or embryonal condition, and that it splits up in the primordial elements from which it originated. The " inflam- matory cell-infiltration," therefore, must be regarded only as the representative of an early normal condition. A real " inflamma- tory new formation n does not take place till later, when the living matter is newly formed and the elements divide in boundaries, depending upon the more compact centers, the nucleoli and the nuclei. Rokitansky, in 1854, ascertained that the " tissue-cells" are not by any means the only starting-points of inflammatory new formation, but in the outgrowth of connective tissue the " inter- cellular substance" also participates actively. I demonstrated in 1873 that the basis-substance of all varieties of connective tissue is abundantly supplied with living matter, and that after a dis- solution or liquefaction of the glue-yielding basis-substance the living matter is productive as well as the cells. I have therefore 460 TUBEBCULOSIS, supported the views held by Kokitansky, in opposition to the plasma theory of Schwann and the cell-proliferation of Virchow. The substratum of the inflammatory new formation, the out- growth of connective tissue, is the whole of the living matter of a living tissue. This process, as before mentioned, is constantly accompanied by a new formation of red blood-corpuscles and also of blood- vessels, due to a new formation of living matter. This occurs in all tissues formed from the middle germinal layer, which from their very origin are supplied with blood and blood-vessels. The result 'of these processes is the formation of a new tissue, which simultaneously becomes vascularized, such as granulations, vegetations, pseudo-membranes, etc. Virchow is satisfied in the belief that a " tissue " is a mere accumulation of " cells " ; while I have proved that we are justified in applying the term " tissue " only when the elements are in a continuous living connection. Isolation of the elements produces pus; pus is not a tissue, and not endowed with the capacity for forming a tissue. The fact has been known a long time that inflammation may exhibit marked differences, both in its course and in its termina- tions. " Acute" and " chronic," "sthenic" and "asthenic," " plas- tic" and " suppurative" inflammation are expressions common to all clinicians. One of the most striking differences in the course of inflammation was based upon the circumstance that, in some instances, the disturbance is mainly confined to the vascular sys- tem, in others it mainly appears in the inflamed tissue itself. One of the main supports of the theory of the cellular pathology was that the phenomena of vascular disturbance, nay, the blood-ves- sels themselves, might be absent, — f. L, in the cornea or the car- tilage,— and, notwithstanding, the tissue could become inflamed. A new formation of " cells," even suppuration, might occur in such tissues, these results being sufficient for the diagnosis of an inflamed tissue. The essential feature of inflammation was the new formation of " cells." To-day, things are different. With us, a new formation of " cells "means a new formation of living matter, and we are satisfied that blood and blood-vessels are requisite to set up an inflammation. We know, besides, that in inflammation a number of blood-vessels perish, their hollow bio- plasson becomes solid and is immediately appropriated for the new formation of tissue; while a simultaneous formation of blood-vessels is going on by the hollowing and vacuolation of originally solid cords of living matter. TUBERCULOSIS. 461 One fact only remains to be considered — namely, that on the one hand the phenomena in the vascular system, under certain circumstances, may be slightly marked, and on the other hand the new formation of living matter may be comparatively so scanty that in the inflamed district a new formation of blood- vessels is completely absent. With this knowledge we may undertake to analyze tubercle — it is immaterial whether in the form of a nodule or an infiltration. Tubercle arises in vascularized tissues only. The inflammatory phenomena in the vascular system in the initial stage of forming nodules are not marked to the naked eye, but are rather more distinct in the formation of an infiltration. Tubercle, for the cellular pathologist, is a tissue composed of pro- liferated and divided "cells" ; with us, it is bioplasson freed from basis-substance, with a scanty new formation of living matter. This explains the gray color and the softness of a fresh tubercle nodule. Tubercle, furthermore, is a tissue which is connected with the mother-tissue, and in which all elements are in a living union, established by the connecting filaments. Tubercle is composed mostly of small elements, as there are only small centers of living matter — viz. : small nuclei and nucleoli. Finally, tubercle is avascular ; in other words, in the produc- tion of the tissue of the tubercle the new formation of blood-ves- sels is wanting. Tubercle may therefore be defined as an inflammatory new formation, a tissue arising from an inflammation, ivith a scanty new formation of living matter and without any neiv formation of blood-vessels. Further Changes of Tubercle. In our conception, all later meta- morphoses of the tubercle become easily understood. So long as tubercle is a tissue, in spite of the lack of blood-vessels, it may give rise to new basis-substance ; and if it has not exceeded a certain size, it then becomes fibrous or cartilaginous. This proc- ess leads to a healing of tubercle and to its obsolescence, while, as the residuum remains an indurated nodule, a granulation (in the sense of Bayle), a papillary vegetation. My views regarding the curability of miliary tubercle fully coincide with those of Empis and Waldenburg. Far more frequently a shrinkage of the bioplasson, an absorp- tion of the liquid, a so-called cheesy degeneration occurs, which is 462 TUBERCULOSIS. due to the lack of blood-vessels, therefore to an insufficient sup- ply of nourishing material. In this condition the infiltration may persist as a tissue for quite a time. It is only after the shriveled, and in part fatty, elements are disconnected from the mother-tissue, and from each other, that the crumbly and friable mass becomes a foreign body, like pus. It then is subject either to being encysted or to softening, to liquefaction from without, and to necrosis. The first process is the result of an inflamma- tion of the surrounding vascularized tissue, leading principally to a new formation of callosities ; the second process is due to an inflammation of the surrounding tissue, leading mainly to an exudation and suppuration. In consequence of the suppuration at the inner surface of the inflamed capsule serous pus arises, mingled with crumbs, and a cavity filled with pus — an abscess — is formed. The softened mass may become innocuous by a process of fatty and calcareous metamorphosis, and, as such, will not excite a new inflammation. The " caseous metamorphosis " of Virchow, therefore, is due to a shrinkage, a desiccation of the new formation, which is inflam- matory in the tubercle, in consequence of the absence of nourishing Hood-vessels. The softening of the " cheese," on the contrary, as has been already maintained by Lombard and Andral, is invari- ably due to a hyperaemia or inflammation of the vascularized neighboring tissue, and to a stagnation in its blood-vessels, which is frequently accompanied by haemorrhages and followed by the formation of pigment. In this manner, the tubercle is removed from the group of the lymphomatous new formations and the tuber- cular product deprived of all specificity. Comparison with Suppuration. It only remains to draw the parallels between tuberculization and suppuration, as these proc- esses are evidently kindred to each other. Reinhardt, who con- sidered the tubercle as an inflammatory product, arising from an exudate (1847), declared the yellow tuberculous matter to be meta- morphosed pus. This conception has nothing in common with our ideas. That pus may become " cheesy," in consequence of an absorption of its liquid portions, and that pus-corpuscles under these circumstances may be 'transformed into tubercle corpuscles, — a process which Andral has termed tuberculization of pus, — is unreservedly admitted. But this does not by any means prove that suppuration and tuberculization are identical processes. In suppuration there is also a stage in which the diseased tissue, TUBERCULOSIS. 463 though infiltrated with pus, is still a tissue. The comparison with pysemic infarctions of the lung, as alluded to before, proves this statement to be correct. The differences, however, are sharply defined. The firm, brittle, half -dry tuberculous infiltration grows gradually, — i. e., in peripheral recurrences, therefore in a chronic manner, — and may remain for months in the tissue stage before it becomes softened and disintegrated. In suppuration, on the con- trary, the whole process runs an acute course, being limited to a few days. Eight days after an injury which was immediately followed by purulent phlebitis, numerous suppurating pyaemic infarctions or abscesses may be found in the lungs, and the more recent infarctions appear as soft, moist, yellow infiltrations. In the production of pus within the inflammatory district, the new formation of blood and blood-vessels is likewise absent, and the living matter of older blood-vessels breaks down into the inflam- matory new formation. Nevertheless, the result is strikingly different from tuberculosis. I recall the purple inflammatory area at the boundary and the dark red hepatization in the vicinity of an infarction of the lung, before alluded to. Such an inflammatory area is constantly present around every acute abscess. The tissue in purulent infil- tration is evidently richly supplied with liquid — i. e., an exuda- tion from without. When the separation of the elements follows, they are suspended in a comparatively large amount of liquid, the serum of pus. Then the result is the same as in the soft- ening and suppuration in the formation of tubercle, namely, an abscess, though in the latter instance this result only is reached by slow process. The abscess in the former instance is u acute? containing thick, genuine pus — the " good, laudable, and healthy pus" of the surgeons ; in the latter instance it is "chronic" " scrof- ulous" inclosing serous pus mingled with tuberculous matter. In the former case the process is accomplished within a few days ; in the latter it is extended over months and years. By inspissation of genuine pus and the shrinkage of the pus- corpuscles the same condition will result as after incapsulation of a softened tuberculous focus — viz. : a fatty, viscid paste, a cement-like mass, a calcareous concretion. Such a termination of suppuration is well known, especially in peripsoitic abscesses. If, on the contrary, an inundation of the inspissated pus takes place by exudation from without, in consequence of new inflam- mation, we find pus with " cheesy " crumbs, which is not materi- 464 TUBERCULOSIS. ally different from tuberculous pus. The course and the termination may be identical with that of an acute abscess after the softened tubercle has become encysted. Tuberculous and Scrofulous Diathesis. In conclusion, I wish to make a few remarks on the scrofulous diathesis of the tissues. This, according to Virchow, consists in a " feeble resistance on the part of tissues against disturbances, and a lowered capacity for equalizing disturbances ; in an increased vulnerability of the parts, with a greater persistence of the disturbances." The latter conditions are the consequence of a certain " pathological consti- tution/7 which consists in a " weakness of single parts or regions and an especial weakness in their lymphatic organs," and we must understand by this "a certain incompleteness in the arrange- ment of the glands." Here we have the results of exact cellular- pathological research, and these results show what an important advance the cellular theory of tissue diathesis involves, in com- parison with the old humoral theory of the blood krases. The swelling of the gland is originally of an irritative, inflam- matory, and hyperplastic nature j but under the influence of a certain " incompleteness in the arrangement of the glands," of a certain "diathesis," it undergoes further regressive metamor- phoses, and among these the " cheesy " is the most common. According to Virchow, the same holds good for the heteroplastic new formation of tubercle proper. In opposition to these assertions, it seems to be of advantage not to abandon the ground furnished by the above enumerated facts. Let us say : in the inflammatory new formation, which is the substratum, not only of scrofulosis of the lymph-ganglia, but also of tubercle, the old blood-vessels perish in the production of a new tissue, and no new formation of blood-vessels takes place. The succeeding step will be the shrinkage of the living matter, under certain circumstances the softening of the same, etc. Let us say, further : certain organisms have not the capacity for producing in a morbid condition, especially in the inflammatory process, abundant living matter, and we have before us the "scrofulous and tuberculous diathesis." But we do not need such a thing as a " diathesis," for we only maintain what direct observation proves. The scanty production of living matter first causes a deficiency in the new formation of blood and blood-ves- sels ; this influences the shrinkage of the inflammatory product ; this in turn causes the disintegration, and finally the softening TUBERCULOSIS. 465 "by inflammation of the surrounding tissue, etc. Then the circle is rounded, and scrofulosis and tuberculosis are identical, according to the ideas of Laennec and Rokitansky. Why, in certain organisms, are the tissues so easily inflamed? Virchow says : "It is remarkable that the disposition for tuber- culosis is always associated with a disposition for inflammation.77 Here again a factor, the "disposition" is introduced, which ought to explain so much, and in reality does explain nothing. Let us say: we do not know why inflammatory processes occur, with much frequency, in certain organisms. Let us fur- ther acknowledge that we do not know why inflammation ever arises spontaneously ; in saying this, we speak the simple truth. Then we are at liberty to analyze critically all experiments which have been committed, since Villemin7s time, for the pur- pose of artificially producing tuberculosis in animals by inocula- tion and infection • but what would we gain ? It would be folly to fight against observers — not to use a harsher expression — who, even in our day, insist upon the infectiousness of cheese, and assert that not every kind of cheese is equally infectious. Wal- denburg, one of the soundest experimenters, came to the conclu- sion that tuberculosis, by which he, in agreement with Virchow, obviously refers only to miliary tuberculosis, is due to the taking into the circulation finely distributed corpuscular elements. These, according to his view, would be deposited in numerous scattered foci in various organs, with the formation of nodules. Inspis- sated, cheesy pus, and caseous tissue of the lymph-ganglia, he says, are most generally the subjects of absorption. With him, too, miliary tuberculosis is a disease of absorption, for he agrees with the idea of Buhl, that miliary tuberculosis depends upon preexisting cheesy foci — in the face of the fact that Buhl himself admitted that in ten per cent, of the cases of miliary tuberculosis, he was unable to discover any cheesy foci whatever. What is the real gain from all this? Many experimenters have succeeded in inducing an inflammation, every one in his own way, perhaps through embolism, perhaps by a diiferent process. All of them have produced "miliary tubercles,77 — that is, circum- scribed inflammatory products in circumscribed inflammatory foci, — and it may be admitted that all this was brought about by embolism. The inflammatory products, however, did not proceed to vascularization, but shriveled up and became "cheesy,77 there- fore tuberculous. This was not due to the skill of the experi- menters, for the reason that the cause of such a result lay in the 30 466 TUBERCULOSIS. organisms which were used for the experiment. That such a metamorphosis is easily produced in rabbits and guinea-pigs is a fact which has been well known for a long time. I abstain from drawing conclusions concerning the therapy of tubercle. For in the question of tubercle it is doubtless Vir- chow's greatest merit that he has accurately denned the aims of therapy, namely : . " the removal of the disposition and the avoid- ance of all obnoxious irritation." To my assertions made in 1874 I have but little to add. Since that time I have examined with the microscope a large number of different organs affected with tuberculosis, and have no alter- ation to make in my previous statements. More than this, I have become acquainted with the anatomical features characteristic of tuberculosis, recognizable not only in single pus-corpuscles, but, from the peculiar aspect of the colorless blood-corpuscles, in every fresh drop of blood. (See page 58.) There is a want of living matter, and to this deficiency can be traced all the features observed in scrofulous and tuberculous individuals. This involves the peculiarity that such persons are easily attacked by inflammation in general, and especially by " catarrhal n inflammation of the mucous membranes. This in- cludes also an incapacity for reproducing blood-vessels destroyed in the inflammatory new formation of medullary elements. Blood- vessels being at first solid, bulky cords of bioplasson, which in a latter stage are hollowed out, cannot be reproduced in certain inflamed districts, and by this fact a clear understanding of the puzzle termed tuberculosis is made evident to our minds. Dyscra- sia, diathesis, disposition, and kindred expressions, filling medical literature and representing medical wisdom, deserve to be aban- doned. For we have something positive, something that every one can comprehend ; we have facts replacing all former vague ideas expressed by a fanciful nomenclature. Scrofulosis and tuberculosis are constitutional diseases. Want of living matter causes these and many kindred diseases, as, f. i., caries of the bones, lupus, etc. Unfortunately, I have not yet learned how to improve a person's constitution, how to increase his living matter. Could we but do that, we might also extinguish forever the misery produced by these constitutional diseases which sweep away thousands of victims. Generations are sacri- ficed to an irrational mode of living, to an irrational waste of living matter, in excesses of all kinds. TUBEECULOSIS. 467 As to more recent researches, I merely allude to the modern views, which decidedly favor the parasitic origin of tuberculosis. This, it is said, is a contagious, an infectious disease, depending on the presence of a certain inoculable parasite. One claims that a certain disposition is required for the reception of the parasite j another says that every one of us is tuberculous, only in some there is no manifestation of the disease, etc. Tuber- culosis seems a regular witches7 caldron for the brewing of absurd theories. A simple wound is sufficient to render a rabbit, a guinea- pig, a dog, etc., tuberculous, if these animals are kept in cellars, in cages, and poorly fed. Even a lion will die of tuberculosis under these circumstances. On the contrary, none of these animals will ever become tuberculous if left in freedom, and simply allowed to enjoy fresh air, proper food, and to live in a climate suitable for their organizations. XIII. TUMOKS.^ DEFINITION. Tumors are morbid outgrowths of living tis- sues. An exact definition is impossible; and Virchowt himself has said : "If we were to torture a person to the last degree of endurance, he would still be unable to tell what tumors really are." The same author extends the limits of these forma- tions to such a degree that he speaks of " tumors of extravasation and of retention" — that is, tumors which have arisen from a col- lection of extravasated blood, or an exudate, or physiological secretions. He furthermore dwells upon " granulation tumors," which, in the present view, are considered products of inflamma- tion. We shall confine the idea of tumors to those formations only which, by pathologists, are termed " neoplasma " or " pseudo- plasma," which originate without marked inflammatory symp- toms, and terminate without a typical end; while the inflammatory process is completed by the production of a cicatrix. The best definition is undoubtedly that of A. Liicke, who says : " A tumor is a growth produced ~by new formation of tissue, without a physio- logical termination." * This chapter aims to present the outlines of oncology only. Since the establishment of my laboratory in New-York, over seven years ago, I have been generously supplied with specimens of tumors by a large number of physicians. I desire to return my thanks to them, and must specially mention by name Dr. H. B. Sands, for his kindness in this and other respects in sup- port of my laboratory. t " Die krankhaften Geschwiilste." Berlin, 1863-67. The most exhaust- ive treaty on tumors, but unfortunately not completed. TUMORS. 469 Origin. All tumors originate from indifferent or medullary elements, in nearly the same manner as that by which physiolog- ical tissues are produced. No tissue can increase or pass into another, except through the intervening stage of medullary tis- sue, and no tumor arises from a normal tissue without the latter first passing through the same intervening stage. Virchow maintained that the new formation of a tissue — the hyperplasia — is either homologous (homoeo-plastic, Lobstein) or heterologous (heteroplastic, Lobstein) ; the former meaning a new formation of a tissue, identical or similar to the parent-tissue ; the latter a tissue differing in type from the parent-tissue. This idea cannot be carried out, as every new formation is at first heterologous — i. e.j medullary tissue. The reason why a tissue sometimes produces a tumor is not understood. This, at least in some instances, appears to be due to a long continued irritation, or to an injury. But in many instances no such cause can be traced 5 neither are we able to explain why the reaction following irritation is, in some individ- uals, an acute or chronic inflammation only, and in others the production of a tumor in addition. Tumors are tissues which, so long as they are in connection with the living organism, are living themselves — i. e., pervaded by a delicate reticulum of living matter in the same manner as physiological tissues. The type of a tumor is usually that of a physiological tissue ; in other words, there is no tissue constitut- ing a tumor which differs materially from the normal tissues. A difference, however, in many instances, is established, for the reason that the tissue of a tumor remains in an embryonal or medullary condition, without passing on to a more fully devel- oped type, — f. i., in myeloma, — or else the combination of the tis- sues is different from that which we know to be a physiological type — f. i., in cancer. It is an easy matter to explain the cause of the formation of a tumor by the terms "general diathesis," or "general or local disposition." Is there any- thing satisfactory in such an assumption ? Is it not more correct to honestly admit that we do not know the real etiology of a tumor ? An apparent progress was made by Thiersch (1865) and by Waldeyer (1868), who claimed that the epithelia of cancer arise invariably from genu- ine preexisting epithelia, and that, therefore, cancer can originate only in tis- sues which are offspring of the upper and under germinal layer, and in a physiological condition are constructed of epithelia. These assertions in turn have been disproved by both clinical and microscopical observation. A tumor once formed may gradually involve its neighborhood and grow at the 470 TUMORS. expense of the surrounding tissue ; it then bears the name of a malignant tumor. We do not know where this capacity for infecting is located. Malig- nant tumors have the property of producing their own kind in internal organs, mostly in the lungs and the liver, although often their origin was far from these organs. The inference is that particles of the tumor are carried as emboli by the vascular system of these organs, and being fixed there, owing to the narrow capillaries, increase and involve the tissue in which they are lodged. Cohnheim and Maas * have attempted experimentally to prove the presence of embolisms by transferring pieces, freshly cut from the periosteum of a dog, into the jugular vein of the same animal. Between the tenth and sixteenth day after the experiment they found the periosteal pieces embolized in the lungs, and exhibiting all the features characteristic of a new formation of bone-tissue. In animals which were killed after the twentieth day they found the pieces of periosteum shriveled, and no trace of ossification or of a neighboring inflammation. The above-named observers claim that their experiments prove the possibility of proliferation of cancer emboli, and, as they were not successful with scraps of periosteum, they concluded that indi- viduals with generalized tumors lack the capacity of removing useless mate- rial from the organism. S. Strieker t analyzes these results, and gives the following summary : (a) Question: Are emboli of tumors capable of growing into tumors? (b) Experi- ment: Emboli of periosteum have perished, (c) Conclusion: Emboli of tumors, therefore, do not perish. Repeated experiments have been made to infect dogs, by transferring particles of freshly extirpated malignant tumors of man, by inoculation, or by injection into the vascular system. C. O. Weber and B. v. Langenbeck have reported positive results. But as these results are so few in comparison with the failures of many other experimenters, and, in addition to this, dogs are known to be frequently subject to malignant growths, the conclusions derived from such experiments must be received with caution. Composition and Localization. In the composition of tumors connective tissue always enters, this structure being the carrier of blood-vessels. The character of the tumor depends greatly upon the amount of connective tissue present, its stage of develop- ment, and its combination with other varieties of tissue, such as muscles, nerves, and epithelia. There is a class of tumors which are composed entirely of connective tissue and its derivations, and exhibit a simple type of construction ; by Virchow these are termed simple Mstoid tumors. Another class shows combinations of several tissues, imitating, to some extent, the structure of cer- tain organs of the body, and Virchow proposes for their designa- tion the name organoid tumors. In a third variety of tumors the structures of different organs are incompletely represented, and such growths are called by Virchow teratoid tumors. Lastly, * Virchow's Archiv. Bd. Ixx. t " Vorlesungen iiber allg. u. exper. Pathologic." Wien, 1878. TUMORS. 471 several types of tumors may be combined into what Virchow designates tumors of combination. Tumors may be localized, that is, confined to the production of a single growth in the body ; or, in other instances, several or a number of tumors may appear. In the latter case, all tumors may be produced by the same tissue system j or an originally solitary tumor may become multiple by what is called infection. Infection with the formation of multiple tumors may again be local if the tumors are near each other; or general, if the multiplication is brought about by the infection of different, usually internal, organs, distant from the original seat of the disease. In myeloma the infection is primarily car- ried by the blood-vessels; in cancers almost always by the lymphatic system. Benignity and malignity. For a number of years tumors have been divided, according to their clinical features, into benign and malignant. This designation is based upon the nature of the tumors, as well as their clinical course. Nobody doubts that a tumor as such can never be altogether benign, as it always expresses a morbid condition, and tumors of a so-called benign character may produce distressing and even fatal results by pres- sure and tension, atropy of organs, or disturbance of their func- tion. But it is of great importance to preserve the clinical nomenclature, so much the more from the fact that the patho- logical and microscopical features fully agree with the clinical observation. Benign tumors are those which appear in most instances as single growths ; if multiple, they arise in the same tissue system ; for instance, many chondromata are found in the osseous sys- tem, many lipomata in the subcutaneous tissue, many fibromata in the skin. They remain local during their entire course, are not infectious, and do harm only by disfigurement, ulceration, pressure, and tension. Such tumors are either composed of simple tissues or combinations imitating the structure of the normal organs. Malignant tumors are those which, though appearing originally as single tumors, subsequently, by local infection or by " metas- tasis,"— i. e., transportation into other organs, — become multiple, therefore they are also called infectious tumors. Sooner or later, but invariably, they lead to general disturbances, to a breaking down of the constitution, and to a fatal termination, either by exhaustion, by haemorrhage, or by interference with the function of important internal organs, such as lungs, liver, kidneys, etc. 472 TUMOES. DuHons tumors are those which at the outset exhibit a benign type, but spontaneously, or by improper or incomplete surgical interference, gradually assume the characteristics of malignant tumors 5 or, being from the first in a moderate degree malignant, gradually become infectious, and multiply both locally and in the internal organs. The peculiar wasting of the body, the depreciation of the con- stitution, the so-called "dyserasia," or "cachexia," which by former surgeons was considered as the primary cause of the for- mation of malignant tumors, to-day is regarded as of secondary origin. In former times, cancer was considered as the result of a certain dyscrasia; to-day, surgeons are satisfied that tumors of this kind are the results of a local or general disposition. These expressions, as a matter of course, explain nothing. (a) Clinical and pathological features. The clinical differences between benign and malignant tumors are not distinctly marked in all cases, but the degree of malignity can usually be determined. Pain in benign tumors is only exceptional, and if present it is due to pressure and tension, or a transient inflammation, and not lasting. Fibroma and cavernous angioma are sometimes painful ; neuroma is, as a rule, painful in a high degree. Malignant tumors are from the first painful, or become so in their course ; the more intense the pain the greater, as a general thing, is their malignity. Especially painful are malignant tumors growing in locali- ties which are abundantly supplied with nerves — f. i., the socket of the eye, the parotid region, the tongue, etc. The boundary in benign tumors is, in most cases, sharply defined to the sight or touch, and the tumor has a certain degree of movability, owing frequently to the presence of an ensheathing capsule. Malignant tumors usually appear as an infiltration, without sharp boundaries separating them from the neighboring tissues. It is only exceptional that a malignant tumor is sharply marked. Growth in benign tumors, as a rule, is decidedly slower than in malignant. It takes a number of years for a fibroma to attain the size of a man's fist, while malignant tumors often reach the same size in a few months or years. Scirrhus or hard cancer is an exception ; it arises frequently with an apparent diminution of the bulk of the organ invaded, — f. i., the female breast, — and during a number of years shows only a limited growth ; while, on the other hand, some benign tumors (for instance, the so-called cysto-sarcoma or myxo- adenoma of the female breast) may increase with great rapidity. The integument in benign tumors remains movable and pliable even after the tumor has reached considerable size. It is only after inflammation has been induced by pressure that a fixation of the skin occurs. Malignant tumors, though growing beneath the skin, very soon invade that structure and render it immovable before any considerable distension has taken place. There is an exception to this rule when an aponeurotic or serous layer intervenes between the tumor and the skin. TUMOES. 473 The number. Benign tumors are often Dingle; sometimes, however, they may appear in large numbers, — f. i., fibroma, chondroma, lipoma, papilloma, — always growing from the same parent-tissue. Malignant tumors usually soon multiply, either in their immediate neighborhood, or as a secondary process in different localities, or in different systems and organs of the body. Excep- tionally, very large and rapidly growing cancer and, as a rule, flat cancer (epithelioma, rodent ulcer) of the face remain single. Ulceration. Benign tumors ulcerate only in consequence of local irrita- tion, by friction of clothing, pressure, their own weight, etc. Vascular tumors (angioma) occasionally break open and ulcerate spontaneously. Malignant tumors (myeloma) often, cancer always, ulcerate, after having attained a certain and usually limited size, if situated on the surface of the body or in a cavity in direct connection with the surface. In organs of the large cavities of the body a partial disintegration or softening of malignant tumors may occur, as a process kindred to ulceration. The ulcerating surface in benign tumors is smooth or covered with granula- tions, and discharges " healthy " pus ; the same feature is exhibited by the ulcers of myeloma whenever such an ulceration occurs. Cancers, upon break- ing open, present an irregularly deepened, often crateriform ulcer, with a rough, corroded base, lacking uniform granulation, and with jagged, abrupt borders, discharging a scanty, ichorous pus. The tissues in the neighborhood of a cancerous ulcer are invariably hard, almost cartilaginous, to the touch, this being one of the most important diagnostic features. After the formation of an ulcer benign tumors may swell slightly, without, however, exhibiting any sign of more rapid growth, unless changing into a malignant type. Malignant tumors, after ulceration, invariably grow more rapidly. The same is the case after poulticing, irritation with local remedies, or injuries done through mistaken diagnosis with the trocar or lancet. The exu- berant growth of ulcerating malignant tumors takes the form of irregular vegetations, advancing toward the place of the least resistance, outward, therefore in tumors of the surface of the body. Only flat cancer (rodent ulcer) penetrates from the surface into the depth of the part affected without produc- ing vegetations. The lymphatic ganglia in the range of benign tumors swell only when they are the seat of inflammation, in what is termed a consensual manner ; similar swelling of the lymphatic ganglia may also occur in the earliest stages of development of myeloma and cancer. After the removal of the tumor the lymph-ganglia return to their normal condition. A real infiltration of the lymph-ganglion with its transformation into the tissue of the tumor, is excep- tional in myeloma, but is the rule in cancer. Pain and fixation of the swelled lymph-ganglion are the clinical signs of its invasion by the morbid growth. This happens the more surely after ulceration has started in the original tumor. Recurrence after extirpation is exceptional with benign tumors, though in some fibromata of the skin this occurs even after all diseased portions of the neighboring tissue have been carefully removed. Local reappearance is the rule with malignant tumors, with myeloma as well as cancer, and the recur- rence usually takes place within the first two years after extirpation. The second tumor may appear either locally — *. e., in the cicatrix after the operation — or in its neighborhood, indicating either that the " roots "of the disease had been left behind, or that at the time of the operation the infection 474 TUMORS. was present at some distant points not perceptible to clinical observation. Every recurrent tumor, as a rule, takes on a more malignant type than the preceding. Recurrence in internal organs after extirpation is considered to be due to the fact that the tissues were already affected with the disease at the time of the operation. A multiplication of benign tumors never occurs in internal organs, and what was formerly considered a multiplication of chondroma, admits of a different interpretation. A multiplicity of malignant tumors, both myeloma and cancer, is often observed. Very probably this is due to a transportation of tissue particles from the tumor, either directly into the vascular system (in myeloma) or through the lymphatics and from them to the vascular system (in cancer). These particles produce emboli in places where most numerous and narrowest capillaries are found — i. e., in the lungs and the liver. A sat- isfactory proof of the presence of such emboli has not as yet been obtained, neither do we understand why the embolized particles should infect the neigh- boring parts and transform the normal tissues into a formation like them- selves. Such secondary tumors are sometimes present in enormous quantities, exhibiting the structure of the primary tumor. Not infrequently, however, secondary tumors, after cancer, do not show a trace of the characteristic epi- thelial structure of cancer, but that of myeloma. (~b) Histological Features. The examination of a tumor with the microscope is of the utmost importance, as, in many instances, it is only by an examination of this kind that a correct diagnosis of the nature of the tumor can be obtained. In 1879 * I made the following statements : " I fully concur with Prof. Liicke, of Strassburg, in the opin- ion that every practitioner should be acquainted with the minute structure of tumors. Such knowledge would enable him to give a more correct diagnosis and prognosis than is the case at present. Very often we can decide the future of the patient through microscopical examination of tumors, either after extir- pation or before it, when small parts of the tumor are removed for diagnostic purposes. "We know that there exists a series of tumors — the benign — which do not materially interfere with the health of the patient. Such tumors are either formations of connective tissue, with fully developed basis-substance in its four principal varie- ties— viz.: myxomatous, fibrous, cartilaginous, or osseous; myx- oma, fibroma, chondroma, and osteoma. Or they may be composed of imitations of the fully developed tissues, sprung from the middle germinal layer of the embryo, such as angioma; lipoma, neuroma, myoma. Or, lastly, they may be combinations " The Aid which Medical Diagnosis receives from Recent Discoveries in Microscopy." Archives of Medicine, vol. i., February, 1879. TUMORS. 475 of epithelial and connective tissue, such as papilloma and ade- noma. u Another series of tumors, on the contrary, — called malig- nant,— have a deleterious influence upon the constitution of the patient. They grow rapidly, are painful, liable to ulceration, recur very often after extirpation, and produce secondary tumors in internal organs. For the differentiation of these growths we are greatly indebted to R. Virchow. He first cleared up the fact that some of these tumors are formations of connective tissue in its undeveloped embryonal or medullary condition, for which he used the rather unsuitable denomination i sarcoma'; while others are combinations of epithelium and connective tissue — the so-called cancer forms. A third variety of tumors exhibits intermediate stages between these two kinds, and they represent what is termed, in a popular expression, suspicious tumors, such as myxo-, fibro-, chondro-, osteo-sarcoma, etc. These, upon their first appearance, do not impair the constitution of the patient ; but gradually, or after repeated extirpations, or rather trials of extirpation, become decidedly malignant. " The study of the minute anatomy of tumors, in its present condition, is as yet far from being satisfactory. Still, if the ques- tion should be raised, whether microscopy has advanced so far as to give a thorough decision of the benign, suspicious, or malignant nature of a tumor, the answer, doubtless, will be a hearty yes, it has. " There are but very few points worthy of consideration as to the nature of a tumor. The more of a basis-substance of the above description is present, the smaller, therefore, the amount of free bio- plasson bodies, the surer it is that the new growth is of a benign nature. On the contrary, the smaller the amount of basis-substance, the larger the relative number of bioplasson bodies, the more cer- tainly does the tumor belong to a malignant type. The very worst tumors — glio-sarcoma, round-cell-sarcoma, and medullary cancer — exhibit a trifling amount of fibrous connective tissue. The difference mentioned, namely, is true, not only for sarcoma, but also for cancer. The more the connective tissue prevails, in comparison with the epithelial formations, the less malignant is its course, the more we are entitled to term it a l scirrhus ' ; while in the fast-growing and rapidly killing medullary cancers, the frame of connective tissue bearing the blood-vessels is very small, and the epithelia are ill-developed — viz. : remain in their medullary or embryonal condition. 476 TUMORS. " Combinations of fully developed basis-substance, with partial retention of the embryonal character, are by no means rare ; they involve what is termed the suspicious nature of the tumor. These tumors allow of a prognosis of recurrence after extirpation, or of a gradual change for the worse, when the surgeon, judging from the appearances to the naked eye, has not the slightest idea of the threatening danger. The inflammatory process in even benign tumors may mislead the microscopist in exceptional instances, and it is only by a thorough examination of different parts of a tumor that a correct decision as to its nature can be obtained. The presence of inflammatory elements within the connective-tissue frame of cancer is well known to be decisive of its malignant nature, and the circumstance that such elements are often found on the surface of an extirpated cancer-tumor indicates, on the one hand, that recurrence will rapidly ensue, on the other hand, that such elements play an important part in the new growth of epithelia, characteristic of cancer." Secondary Changes. The tissues of tumors are subject to the same pathological changes which we observe in physiological tissues. These changes sometimes deprive a malignant tumor of its malignity, either in part or altogether, and they may occasion- ally result in a spontaneous cure of either benign or malignant tumors. Inflammation ensues spontaneously, and after irritation or mechanical injuries from without. The inflammatory process is different here in its results, though not in its aspect, from the rapid new formation of tissue in malignant tumors. It some- times leads to a formation of an abscess in the depth of the tumor, and may terminate, as in physiological tissues, in the pro- duction of a cicatrix. It sometimes causes ulceration — i. e., a slow necrosis of the superficial layers — or gangrene, with a partial or complete destruction of the tumor. Gangrene may ensue from the weight of a pedunculated tumor, from pressure, traction, etc. Hemorrhage occurs most frequently in tumors which are abundantly supplied with blood-vessels, or where the blood-ves- sels are dilated. It may lead to the formation of encysted extra- vasations in the middle of the tumor, — the so-called blood-cysts, — from the walls of which again a new growth of the tissue of the tumor may arise. Haemorrhage often causes pigmentation of the tumors. Gangrene is sometimes produced after haemorrhage by complete destruction of the tissue, and in this way a cure may follow. TUMORS. 477 Fatty degeneration is often met with, especially in malignant tumors, and, if a larger portion be invaded, results in the forma- tion of the " reticulum " of older pathologists. Fatty degenera- tion rarely appears throughout the entire tumor, but if this happens, subsequent calcification and ossification ensue, rendering the growth harmless. Cheesy metamorphosis is sometimes ob- served with the production of a yellow, friable, half -dry, shriveled mass, as seen in tubercle ; this process is, as a rule, limited, and has no influence upon the further growth of the tumor. Mucous and colloid degeneration is a rather common occur- rence, especially in adenoma antJiy pd/LKeu tOgei er. tudinally, interlacing with similar bundles at right Between the Spindles We angles, D-, O, bundles cut obliquely, and F, bundles „ T f, . cut transversely. Magnified 100 diameters. find finely granular bio- plasson and plastids, mostly reduced to the size of nuclei. The light interstices between the spindles are always traversed by extremely delicate transverse filaments, which interconnect the bioplasson formations contained in the glue-yielding basis-sub- stance. Similar filaments connect the bioplasson formations FIG. 184. — FIBROMA OF THE VAGINA. 484 TUMORS. with the spindles. An oblique section of a bundle is obviously marked by short spindles ; while the transverse section of the bundle exhibits circular formations, which are surrounded by a reticulum of bioplasson or of cement-substance. Where capil- lary blood-vessels traverse the tissue, the spindles are seen di- rectly connected with the endothelial wall by means of delicate filaments. (See Fig. 185.) The varieties of fibroma are : (a) Loose fibrous connective tissue, composed of delicate bun- dles of fibrillae (see page 159), builds up fibrous tumors of a FIG. 185. — FIBROMA OF VAGINA. L, connective-tissue fibers composed of spindles, cut longitudinally ; O, oblique sections of spindles ; T, transverse sections of spindles ; C, capillary blood-vessel. Magnified 100O diameters. moderate degree of consistency, while the vascular supply is not abundant. They occur usually as sessile tumors of the skin, with a smooth or lobulated surface, and, if piginented, bear the name of moles (naevus or melanoma). They are frequently found on the mucous membranes, especially of the posterior nares, the pharynx and larynx, and the uterus. Polypous, pediculated tumors- of the uterus are often constructed of delicate fibrous connective tissue, which in this situation is sometimes abundantly supplied with blood-vessels. This variety blends with the next. (bj Myxo-fibroma or soft fibroma, which may be considered as an intermediate stage between myxoma and fibroma. The myx- TUMORS. 485 omatous character is caused by the reticular arrangement of the usually delicate bundles of connective-tissue fibers, which at the same time inclose in their meshes -a gelatinous, apparently homo- geneous, myxomatous basis-substance, with single plastids, hav- ing the appearance of nuclei. The fibrous character is produced first by the circumstance that the reticulum is composed of a number of fibrillae, in the midst of which delicate rod-like or spindle-shaped plastids are found, and secondly, by an inter- lacing of dense bundles with bundles which are loose and deli- cate. (See Fig. 186.) Tumors of this kind often exhibit a transition from the myxomatous to the fibrous structure; in addition to this they I FIG. 186. — MYXO-FIBROMA, GROWN BENEATH THE SCAPULA OF A WOMAN. Bundles of fibrous connective tissue in a reticular arrangement. The spaces contain either bundles, O, in an oblique or a transverse section, or a mucoid basis-substance, holding mostly central plastids, P. Magnified 600 diameters. sometimes abound in fat-globules, thus assuming the character of lipoma. Myxo-fibroma is a common tumor in the skin and the mucous membranes. Bulky, folded masses of the skin, occurring in the face, on the chest, and the posterior aspect of the body, the so-called leontiasis, belong to this class. It is of somewhat rarer occurrence in the female breast, in internal organs, and as a periosteal growth. 486 TUMORS. (c) Dense, interlacing bundles of fibers (see page 162) are found in firm, almost cartilaginous tumors of the skin ; if pediculated, they are termed fibroma molluscum. They develop in middle and advanced age, sometimes in large numbers all over the skin, and some of them may reach a considerable size — viz., that of a man's fist, or even that of a man's head. Tumors of this variety may be painful, like neuroma. In some individuals, especially of the colored races, there exists a peculiar liability to the formation of fibrous tumors. Around the auricles of the ear, in females, they are usually caused by the piercing for ear- rings. Such tumors are also remarkable for their disposition to recur after extirpation, though, as a rule, the recurrent tumors grow slowly, and retain their benign character. (dj Scar-shaped fibroma, Moid is a flat, radiating, freely vas- cularized fibroma of the skin, usually painful. It grows slowly, and attracts the neighboring skin in folds. It may grow from a scar, produced by previous operations with the knife, or by caustics, or independently of any previous cicatrix. It is also characterized by an extreme proneness to recurrence. Accord- ing to J. C. Warren, the cheloid is composed of more regular bundles of fibrous connective tissue than the original scar. Combinations. Fibrous connective tissue, combined with smooth muscle-tissue, is of common occurrence in the uterus and its appendages. Sometimes smooth muscles are so abundantly pre- vailing in the composition of the tumor that it deserves the name of fibro-myoma, or myo-fibroma. These tumors will be con- sidered in connection with myoma. Fibrous tumors, growing from the mucosa of the neck or the body of the uterus, may sometimes also exhibit an enormous new formation of tubular glands; a tumor of this construction must be considered as adenoma. Fibrous tumors of both the uterus and the ovaries not infrequently are supplied with a large number of blood- vessels, and then may be styled fibro-angioma. Sometimes fibrous tumors are the seat of partial depositions of lime -salts, — calcified fibroma, — and, especially those grown from the periosteum, may be partly transformed into bone — osteo-fibroma. 3. CHONDROMA. CARTILAGINOUS TUMOR. Chondroma is a dense, firm tumor, composed of cartilage, either hyaline, fibrous, or reticular, or these varieties mixed. The fibrous portions sometimes produce trabeculae, which carry TUMOES. 487 the blood-vessels and inclose portions of the hyaline cartilage structure. Cartilaginous tumors are comparatively rare. They grow both from the soft tissues and from bone, and are more common in the latter situation than in the former. There are many transitions from myxomatous and fibrous into cartilaginous con- nective tissue, and the diagnosis often rests only on the large size and the regular arrangement of the plastids, termed cartilage corpuscles. Chondroma is a benign tumor which may appear multiple in the same kind of tissue, but, as a rule, it does not infect the neighboring parts. In very exceptional cases, however, true chondroma attains the capacity not only to infect its neighborhood, but also to produce secondary tumors in the lungs, never surpassing, however, the size of a walnut. Virchow enumerates six cases of this kind. Pathologists have described under the head of " chondroma " soft tumors, rich in " cells," which were imbedded in a scanty, gelatinous basis-substance. Tumors of this kind were termed villous chondroma and mucous chondroma; they may grow into the blood-vessels and produce embolic metastases. Obviously, tumors of this description, though resembling chondroma under the microscope, are not cartilaginous tumors, but either myxo-myeloma or chondro-myeloma, both being of a malignant type. If firm, genuine cartilag- inous tumors are found in different localities of the body and in the lungs, also, there is no necessity for concluding that the latter are secondary formations. For the lungs hold in the walls of the bronchi enough hyaline cartilage to give rise under certain conditions (the chondromatous dyscrasia or diathesis of some writers) to primary cartilaginous tumors. Chondroma of the "hyaline" variety is constructed like physiological " hyaline " cartilage, the difference, at least in many cases, being that in chondroma the plastids are of large size, vary greatly in shapes, and are irregularly distributed. Besides, the elements of chondroma are more coarsely granular — i. e., contain more living matter than is found in normal cartilage. The gold stain reveals the reticulum in the basis-substance, just as in normal cartilage. (See Fig. 187.) Cartilaginous new formation is found either throughout the whole tumor, or in combinations with myxomatous, fibrous, or bone-tissue; and sometimes, also, with myeloma, myoma, and cancer. The latter combinations represent Virchow's group of teratoid tumors — i. e., undeveloped remnants of all varieties of tissues in one tumor. This condition is probably due to an un- developed organism, being inclosed in a fully developed one — foetus in fcetu. Formations of this kind are met with mostly in the so-called dermoid cysts of the ovaries and the testes, although 488 TUMOES. they have been found in other organs. I am indebted to Dr. Clinton Wagner for a specimen of an almost perfectly developed auricle of an ear, attached to the soft palate. Cartilaginous tumors grown in glandular organs not infrequently exhibit partial mucoid degeneration and secondary formation of cysts — cysto-cliondroma. Sometimes there is a calcareous deposition in the tissue of chondroma and a combination of cartilagin- ous with bony tissue — osteo- cJiondroma; or, as mention- ed before, a combination of chondroma with myeloma — cJiondro - myeloma. This was the condition of a tum- or the size of a child's skull, grown in the testis, and from which Fig. 187 is taken. Among the soft tissues, chondroma is known to occur primarily in the par- otid and the submaxillary gland, in the female breast, in the periosteum of the phalanges, in the testes, and in the lungs. It causes only local disturbances ; occa- sionally, however, by sup- puration and ulcerative destruction it may become rather serious. In bones, chondroma originates either from the surface (perios- teum) or from the cancellous portion, the diploe of skull-bones and the central medullary space of shaft-bones. The most com- mon places for chondroma to appear are the phalanges and meta- carpal bones of the fingers, more rarely those of the toes j next, the epiphyses of the shaft-bones, the carpal and tarsal bones, the ribs, the sternum, and very rarely the pelvis and skull-bones, the upper maxillary bone, and the socket of the eye. The simulta- neous growth of a number of cartilaginous tumors in several of the above enumerated localities has also been observed. What pathologists describe as central chondroma, arising from the medulla of the shaft-bones, in many instances probably was, judging from the clinical phenomena and the multiplication in the lungs, myxo- and chondro-myeloma, but not pure chondroma. FIG. 187. — CHONDROMA OF TESTICLE. P, plastids, mostly nucleated and coarsely gran ular ; _B, finely granular, so-called " hyaline substance. Magnified 600 diameters. TUMOES. 4. OSTEOMA. OSSEOUS TUMOR. 489 Osteoma is a solid tumor, composed of bone-tissue, and grow- ing without symptoms of inflammation, in contradistinction to the exostosis or the osteophytes, which are products of osteitis and periostitis. Corresponding to the two principal varieties of bone-tissue (see page 223), we have two kinds of osteoma : (a) Cancellous or EpipJiyseal or Spongy Osteoma. This occurs on the epiphyseal ends of shaft-bones, closely connected with the cancellous portion ; it is found only in youth, and is never a primary formation after the thirtieth year of life. Such tumors lie beneath the covering periosteum, and at their free surfaces FIG. 188. — CANCELLOUS OR EPIPHYSEAL OSTEOMA, FROM THE SECOND PHALANX OF THE THUMB. J1, trabeculae of bone-tissue, indistinctly lamellated; M, large and irregular medullary spaces, containing blood-vessels and medullary tissue. (The latter shriveled, owing to the circumstance that the specimen was brought for examination in a half-dry condition.) Mag- nified 100 diameters. are usually lobular. They are either inclosed by a thin layer of compact bone-tissue or by a layer of hyaline cartilage. They are composed of indistinctly lamellated trabeculas of bone, contain, ing regularly developed bone-corpuscles, and inclosing medullary spaces, which vary greatly in size and are filled with medullary tissue and blood-vessels. (See Fig. 188.) Formations closely allied to cancellous osteoma are the pro- cessus supracondijloidei, which Hyrtl first described as congenital 490 TUMORS. formations 5 they occur at the articular ends, mostly, of the humerus and the femur, analogous to the processus trochleares of some animals. To these may be added the bony formations at the points of insertion of the tendons, muscles, and aponeur- oses, which Virchow termed exostoses apophyticce. They are either directly connected with the bone, or take rise independ- ently of it (so-called tendon bones). These bony structures orig- inate, unconnected with inflammation, perhaps on account of an excess of lime-salts in the organism. Maslowsky has succeeded in producing calcareous deposition and ossification in the mus- cles of animals, in the vascular system of which, for a certain length of time, he had injected lactate of lime. Bony formations in the dura mater, the muscles, and the lungs are products of inflammation. (~b) Compact or eburneal osteoma is a rare tumor; it occurs on the bones of the face, the skull, the scapula, the pelvis, and the phalanges; its favorite locality is the frontal bone. It has a smooth or slightly nodulated surface, and very rarely attains any considerable size. It is composed of a more or less regularly lamellated bone-tissue, imitating in its structure the outer per- ipheral layer of compact bone, and is scantily supplied with medullary spaces. These, on the surface of the tumor, are, as a rule, large, and contain several blood-vessels; while the main mass shows only irregular Haver sian canals, which contain one capillary blood-vessel. Toward the point of attachment the com- pact bone formation usually blends with the cancellous structure. (See Fig. 189.) The cement-layer of the roots of teeth not infrequently develops into compact osteoma, which sometimes reaches a considerable bulk. Tumors of the dentine are entirely dif- ferent formations ; for their designation Virchow has pro- posed the term odontoma. These are composed of dentine, with irregularly arranged dentinal canaliculi, similar to formations of secondary dentine and the so-called pulp-stones. (See chapter on teeth.) Bone-tissue is often found combined with other varieties of tumors, such as fibroma, chondroma, myeloma, and it is asserted that it also unites with cancer and forms the " malignant oste- oid" of Joh. Miiller. The terms employed to designate tumors of these varieties are osteo-fibroma, osteo-chondroma, and osteo- myeloma. In all these instances the bone-tissue is unquestiona- bly a secondary formation. TUMOES. 491 Psammoma is the term applied by Virehow to a class of tumors character- ized by the presence of peculiar corpuscles, which usually exhibit a distinct concentric striation, or appear as nodular or rod-like masses. Virehow main- tains that these tumors may be either homologous (benign) or heterologous (malignant) — i. e., represent transitions into sarcoma. Virehow proposes to call the corpuscles arenoid — that is, sand-like ; they are a normal feature in the anterior portion of the glandula pinealis, where they form the acervulus cerebri. Besides, they are met with in the cerebral and spinal dura mater, especially in the Pacchionian bodies, and in the arachnoid. They are amy- laceous corpuscles, infiltrated with lime-salts, although Virehow insists upon their being different from the corpora amylacea on account of the blue stain of the latter, shown when treated with iodine. Such corpuscles were found also in enlarged hyperplastic lymph-ganglia. The tumors containing them occur both in the brain-tissue and in its investing membranes, especially the dura mater, in the optic nerve and its investments, and in the retina. (See Fig. 190.) FIG. 189. — COMPACT OR EBURNEAL OSTEOMA, FROM THE FRONTAL BONE OF A MAN. L, lamellate*! bone-tissue, pierced by medullary spaces, M, which toward the periphery of the tumor are large and contain several blood-vessels ; while in the more central portions of the tumor the medullary spaces are reduced to irregular Haversian canals. Magnified 100 diameters. The term "psammoma," applied to a tumor, is obviously superfluous, for the arenoid corpuscles do not determine the nature of the tumor, which may be a myxoma, a fibroma, an angioma, or a myeloma, consequently widely dif- fering in pathological features. The arenoid corpuscles are secondary and incidental formations in these tumors. The same holds good for pig- mented tumors, which occur in rare cases in the pia mater, and are termed 492 TUMOES. melanoma. The presence of pigment alone is not sufficient to characterize the nature of the tumor. There is, however, no objection to calling a tumor which contains sand-like bodies an " arenoid fibroma, angioma," etc., and a tumor which contains pigment granules a " melanotic fibroma, myeloma," etc. 5. MYELOMA OB SARCOMA. The special character of this group of tumors was first determined by Virchow. He considers the structure to be con- nective tissue in an embryonal or medullary condition, without any epithelial elements, and thus sharply marked from cancer. All later researches have corroborated Virchow's views. We FIG. 190. — ARENOID MYXOMA (PSAMMOMA, VIRCHOW) OF THE DURA MATER. T, trabeculse of fibrous connective tissue, holding partly sessile, partly pediculated, arenoid corpuscles, A, or elongated calcareous formations, C. Magnified 50 diameters. define sarcomata as Virchow defined them — that is, connective- tissue tumors, in which very little or no basis-substance is developed. We object, however, to the word " sarcoma," as this means fleshy tumor, and would substitute for it the old term "myeloma," — viz., medullary tumor, — as this accords better with the histological features. Virchow divided sarcomata into the following varieties: (a) net-ceil sarcoma; (~b) spindle-cell sarcoma; (c) round-cell TUMORS. 493 sarcoma ; (d) giant-cell sarcoma, and (e) melanotic sarcoma. Billroth added another variety, the alveolar sarcoma. In ana- lyzing the different varieties of myeloma, we are satisfied that there are but two principal forms, which I propose to term (a) globo-myeloma, corresponding to Virchow's round-cell sar- coma j and (~b) spindle-myeloma, corresponding to Virchow's spindle-cell sarcoma. Both varieties are sometimes found in one tumor. (A) Globo-myeloma is composed of medullary tissue, with globular elements. (See page 147.) These contain single or double nuclei, or they are divided into smaller plastids, evidently in the mode of growth and multipli- cation of the elements. Tum- ors of this kind, as a rule, are of a grayish-red or grayish- yellow color, containing a com- paratively small number of blood-vessels. Its sub-varieties are: (a) Globo-myeloma, composed of large plastids (large round- cell sarcoma). These are sepa- rated from each other, either by a narrow rim of cement-sub- stance or by a delicate fibrous reticulum 5 all elements, how- ever, are connected by means of FIG. delicate filaments. The nuclei are large, and contain several coarse granules — nucleoli. (See Fig. 191.) fbj Globo-myeloma, composed of small plastids (small round- cell sarcoma), the structure closely resembling the so-called adenoid or lymph-tissue. A deli- cate fibrous reticulum holds varying numbers of plastids, which are mostly solid, having the appearance of lymph-corpuscles, some being surrounded by a finely granular bioplasson. This form represents the a lymphoma " or " lympho-sarcoma " of authors. (See Fig. 192.) (c) Glioma or glio-sarcoma. Virchow applies the term " gli- oma" to tumors arising from the connective-tissue formations 191. — GLOBO-MYELOMA, COM- POSED OF LARGE PLASTIDS. FROM THE INTERMUSCULAR TISSUE OF THE FOREARM OF A WOMAN. The globular, slightly flattened corpuscles are separated from each other by a scanty basis- or cement-substance. C1, solid cord, indicating a new formation or a retrogression of a blood-vessel; (72, fully developed capil- lary blood-vessel. Magnified 600 diameters. 494 TUMORS. of the central nervous system and the retina, without reference to their intimate histological structure. Kecently, efforts have been made to remove glioma from the group of myeloma. Clin- ical observation shows the extreme malignity of many of these tumors ; microscopic examination shows their close relationship to myeloma, and that a varying amount of fibrous connective tissue may enter into their construction. Glioma is composed of elements closely resembling those found in the cortex cerebri and cerebelli, and those of the granular layers of the retina. These elements exhibit comparatively large nuclei, around which is a scanty rim of granular bioplasson. In rapidly growing tumors the elements exhibit distinct proliferation, and in many instances flatten each other. Between FIG. 192. — GLOBO-MYELOMA, COMPOSED OF SMALL PLASTIDS. FROM THE TESTICLE OF AN ADULT. T, transverse section of a seminiferous tubule, toward the epididymis ; S, myeloma of the type of lymph-tissue (adenoid tissue) ; TS, transition of the epithelia into myeloma tissue. (For high amplification of the same tumor, see Fig. 206.) Magnified 200 diameters. them we see a delicate layer of cement-substance, traversed by the connecting filaments. In the cement-substance homogeneous plastids occur, indicating either development of glioma- or spindle- shaped elements, which latter belong to the connective-tissue frame. (See Fig. 193.) (B) Spindle-myeloma is composed of medullary tissue with spindle-shaped elements. The difference between physiological TUMORS. 495 CF- medullary and myelomatous tissue is that, as a rule, in the latter the bundles of the spindles are interlacing — i. e., course in differ- ent directions, like interlacing fibrous connective tissue. Some- times, however, the bundles take an almost parallel course, and can be separated into radiating groups of spindles, the fascicular spindle-myeloma (fascicular spindle-cell sarcoma of Virchow, fas- cicular cancer of older patho- logists). The sub-varieties of spindle-myeloma are : (a) Spindle-myeloma, com- posed of large plastids. These are separated from each other by a light rim of cement-sub- stance or a delicate fibrous re- ticulum, most distinct in trans- verse sections of the bundles. The nuclei of the spindles, as a rule, are seen as homogen- eous and shining lumps, often exhibiting marks of division and multiplication. Between the nucleated spindles there are fusiform fields, containing a finely granular or homogen- eous mass; this indicates an approach to basis-substance. (See Fig. 194.) (~b) Spindle-myeloma, composed of small plastids, either interlac- ing or taking an exclusively parallel course. In many instances this tissue bears a close resemblance to non-medullated nerve-fibers. Evidently, tumors composed of such delicate spindles are often mistaken for true new formations of nerve-fibers, a neuroma. This variety of myeloma is not of infrequent occurrence in the choroid, and often contains clusters of pigment which previously belonged to the choroid or to the layer of pigmented endothelium of the retina. Such pigment clusters, however, unless present in a large number, will not justify a diagnosis of a melanotic mye- loma. (See Fig. 195.) (c) Spindle-net myeloma (net-cell sarcoma of Virchow). In this variety spindles of varying sizes branch at acute angles, unite and form a reticulum. The meshes of the reticulum are elongated, and hold a slight amount of basis-substance and globular or FlG. 193. — GrLIOMA FROM THE ORBIT. RECURRENT TUMOR AFTER THE ENUCLEATION OF THE EYEBALL FOR GLIOMA OF THE RETINA. M, glioma element with several nuclei ; MS, group of glioma elements, sprung from divi- sion ; GC, fully developed glioma element ; CF, spindle-shaped fibers between the groups of glioma elements ; E, capillary blood-vessel. Magnified 600 diameters. 496 TUMORS. oblong plastids, which are apparently isolated. The more nearly the reticulum approaches to a circular arrangement, and the smaller its composing spindles, the more closely allied is this variety to that of myxo-myeloma. Finally, all distinguishing marks are lost, and spindle-net my- eloma and myxo-myeloma blend with each other. (See Fig. 196.) The " giant-cell sarcoma" of Virchow cannot be considered as a tumor sui generis, for the so- called " giant-cells v never consti- tute the entire mass of the tumor. They are intermixed with fibrous FIG. 194. — SPINDLE-MYELOMA, COM- POSED OF LARGE PLASTIDS. FROM THE OMENTUM OF A WOMAN. L, nucleated spindles cut longitudinally ; O, spindles cut obliquely ; F, spindles cut transversely. Magnified 600 diameters. connective tissue, as well as with fibro-myeloma, and are more numerous and better de- veloped the greater the amount of basis-substance contained in the surrounding tissue. As, in our view, the multinuclear plas- tids arise from a fusion of me- dullary elements, whenever there is a tendency to form ter- ritories, usually of cartilage and bone, it will be understood from this fact that the malignity of these .tumors is very slight. Their favorite site of growth is the periosteum, especially the periosteum of the jaw-bones (so-called lt epulis "), and a perma- nent cure will ensue if the tumor is thoroughly extirpated. I have examined several globo- and spindle-myelomata which had grown from the maxillary bones, where very little basis-substance FIG. 195. — SPINDLE - MYELOMA, COMPOSED OF SMALL PLASTIDS. FROM THE CHOROID OF AN ADULT. L, nucleated spindles cut longitudin- ally ; O, spindles cut obliquely ; P, pig- ment clusters from theformerpigmented endothelium of the retina. Magnified 600 diameters. TUMOES. 497 could be found ; therefore, they were decidedly malignant. In tumors of this sort the multinuclear plastids were always scanty and imperfectly developed — i. e., composed only of clusters of medullary corpuscles. The comparatively benign type of " epulis," however, is more common than the malignant. (See Fig. 197.) Any myeloma, including the alveolar myeloma, may be the seat of a more or less abundant formation of pigment, and is then termed melanotic myeloma. The pigment, therefore, is merely an inci- dental feature of myeloma, but it is known to increase greatly the malignancy of the tumor. The origin of the pigment was FIG. 196. — SPINDLE-NET MYELOMA, FROM THE SUBCUTANEOUS TISSUE OF THE LEG OF A MAN. S, nucleated spindles branching and uniting ; the meshes contain a finely granular myxom- atous basis-substance, and G, apparently isolated globular or oblong plastids. Magnified 600 diameters. formerly attributed to extravasated blood. I have ascertained that in such tumors a very profuse new formation of living matter takes place, which causes the production of numerous haematoblasts, — i. e., solid lumps of living matter, — which in their earlier stages of formation, for reasons unknown, are supplied with the coloring matter of the blood. (See page 98.) From 32 498 TUMORS. these haematoblasts, before their development into red blood- corpuscles, arise the pigment clusters. The process can be best studied at the border of melanotic myeloma of the choroid in the region of the vitreous body. Here the haematoblasts originate in the middle of the vitreous body, being characterized by a globular shape, luster, distinct yellow color, and their small size, as com- pared with fully developed red blood-corpuscles, for which they often are taken. How far the haematoblasts participate in the new formation of the my- eloma elements I was unable to ascertain ; but unquestion- ably they are the source of pigment in melanotic myelo- ma. (See Fig. 198.) Combinations of Myeloma. ^Myeloma may combine with any variety of connective tis- sue- and epithelial tumors, which means that a portion of the tumor possesses fully developed basis -substance, while another portion has but little or lacks it entirely. A tumor with originally well- FIG. 197.-FIBRO-MYELOMA, WITH MUL- developed basis - substance TINUCLEAR PLASTIDS. FROM THE in i •, LOWER JAW OF A YOUNG MAN. ma^ gradually change its character, and in the por- tions of later growth be with- out basis-substance. With this failure in the production of basis-substance a more rapid growth of the tumor ensues, and it assumes a more malignant type. As before mentioned, such tumors are clinically considered "dubious" in their nature, although some of them are either of a marked malignant char- acter, or become so in a relatively short time. According to our nomenclature, the various combinations of these tumors are termed as follows : (a) Mbro-myeloma, the "fibroplastic" tumor, or " recurrent fibroma" of older pathologists. It consists of bundles of fibrous connective tissue, between which are large numbers of usually globular elements ; or the tumor originates from fibrous tissue, — M, group of medullary corpuscles approach- ing the stage of indifference ; G, multinuclear plastid, so-called giant-cell. Magnified 600 diameters. TUMOES. 499 f. i., the derma of the skin, — and by degrees entirely replaces it. The fibrous structure of such tumors is sometimes very faintly marked ; but their comparatively slight degree of malignity is recognized by the presence of a finely granular basis-sub- stance between the homogeneous plastids, which, of the size of nuclei, are scattered at regular intervals. Sometimes these tumors are lobate or nodular, and covered with a richly pig- mented rete mucosum (mole, naevus). With advancing age or FIG. 198. — MELANOTIC GLOBO- AND SPINDLE-MYELOMA OF THE CHOROID. L, group of globular pigmented plastids ; f, delicate fibrous connective tissue at the periphery of the tumor; Jf, haematoblasts ; P, pigment cluster ; V, vitreous body. Magnified 600 diameters. improper treatment they readily assume the character of malig- nant myeloma. (See Fig. 199.) fb) Myxo-myeloma is constructed on the plan of myxomatous tissue — i. e.j a delicate fibrous reticulum contains in its meshes plastids in different stages of development; but they are^far 500 TUMOES. more numerous than in simple myxomatous tissue. Myxoma- tous tumors, especially the so-called polypoid tumors, often exhibit some of the features of this type, indicating a rapid growth of the tumor and its liability to recur after extirpation. If the reticulum is very delicate, and the inclosed plastids very small, not exceeding in size the lymph-corpus- cles, the type of a lympho-myeloma (small globo-myeloma) is established, which growth is of intense malignity. Myxo-myeloma, therefore, blends with the spindle-net myeloma, as well as with the lympho-myeloma. (See Fig. 200.) (c) Chondro-myeloma differs from chondroma in the softness of its basis- substance, while the plastids may FIG. 199. — GLOBO-MYELOMA, WITH A MARKED FORMATION OF BASIS-SUBSTANCE. FROM THE ABDOMINAL WALL OF AN ADULT. C, capillary blood-vessel in trans- verse section ; A, artery in transverse section. Magnified 600 diameters. exhibit the size and shape of cartilage corpuscles. Many of the so-called " ma- lignant chondromata" prob- ably are chondro-myeloma, and I know this mistake to have been made by good pathologists. The term ' i chondro - myeloma " may also be applied to tumors which, in a tissue showing all the features of globo-myeloma, contain islands of well- developed cartilaginous tissue. (d) Osteo-myeloma is a term used for the designation of myelomatous tumors growing in the middle of the bone, or of FIG. 200. — MYXO-MYELOMA. RECURRENT PHARYNGEAL POLYPUS. B, portion of myxomatous structure ; P, portion of myelomatous structure ; V, large capillary blood- vessel. Magnified 600 diameters. TUMORS. 501 tumors in which within myeloma-tissue new formation of bone has taken place. The error resulting from such a nomenclature is not great, as in many instances it is impossible to decide whether the bone-tissue in the tumor is a remnant of the former physiological bone, or whether it is newly formed. A great irregularity in the size and the arrangement of the bone-cor- puscles will favor the view of the bone being newly formed, FlG. 201. — OSTEO-MYXO-MYELOMA, FROM THE HlP-BONE OF A GIRL. T, trabeculse of newly formed bone, with large and irregular bone-corpuscles ; M , myx- oniatous tissue, changing to myeloma ; C, plastids, infiltrated with lime-salts. Magnified 400 diameters. and this view is strengthened if we are able to trace the new for- mation of bone through all its stages, from the first infiltration of plastids with lime-salts up to the appearance of trabeculae. Besides, it is granted that the myeloma tissue (myxo- or fibro- 502 TUMORS. myeloma) is not of a very malignant type where bone-tissue is formed, though it is possible for the tumor to change to a more malignant form. Myeloma, with numerous globular or spindle- shaped elements, is, as a rule, deficient in new formation of bone. The tumor the size of a child's head, from which Fig. 201 is taken, for a number of years grew slowly, though steadily, while later it increased rapidly to a fatal termination. The combinations of myeloma tissue with other varieties of tissue (lipoma, angioma, myoma, neuroma, and adenoma) will be considered in the articles treating of these tumors. Here I only mention that, according to Virchow, there also exists a combination of cancer with myeloma — a view which I, from a large number of observations, can corroborate. Alveolar myeloma (Billroth) is of a dubious nature. Most pathologists regard it as cancer, .but it seems more correct to class it among the myelomata j for it shows all the clinical and pathological features of such tumors — nay, it appears occasionally as a secondary tumor after primary myeloma. A delicate frame of connective tissue forms the alveoli, which are filled with glob- ular, oblong, or irregular and usually nucleated plastids, very loosely connected with one another — so loosely, that in sections the alveoli appear incompletely filled. The plastids never reach the size and the polyhedral shape of epithelia, so characteristic of cancer 5 those nearest to the connective-tissue frame are pear- shaped, being attached to the frame by a slender pedicle. I have seen this variety of tumor in the groin, in the testis, the omentum, and the liver ; in both the last-named positions the tumors were secondary, and that of the liver was of a pronounced melanotic type. Perhaps this tumor represents a transition of myeloma into cancer, a transition which in the opposite way — cancer to myeloma — is of more common occurrence. (See Fig. 202.) Myeloma is a malignant tumor, and any portion of the con- nective tissue of the body may serve as its starting-point. In fact, this tumor has been observed in all parts and all organs of the body, except in horny tissue. Contrary to cancer, it is often a growth of childhood and youth, and may occur at any age. Its malignity is intensified when the constituent elements are small, the blood-vessels abundant, and the basis-substance scanty. The presence of pigment, both in the fibrous and medullary portions of the tumor, greatly increases its malignant character. Not infrequently local irritation, particularly injuries of all kinds, can be traced as the exciting cause of myeloma. TUMORS. 503 The clinical diagnosis, in many instances, is possible when there is a rapid growth and local multiplication ; often, however, the tumor has all the appearances of a benign growth, while microscopic examination reveals its malignant nature. An error in diagnosis may occur owing to the circumstance that myeloma, upon approaching the surface, as a rule does not cause ulcera- tion of the skin, neither are the neighboring lymphatics enlarged or painful. Sometimes myeloma appears in great numbers, almost simultaneously in different parts of the body, and tumors, which already have reached a certain size, may gradually disappear and return again. Local recurrence after extirpation is a common FIG. 202. — ALVEOLAR MYELOMA, FROM THE MESENTERY OF A YOUNG MAN. F, frame composed of a delicate fibrous connective tissue, carrying blood-vessels, inclos- ing alveoli ; the latter contain C, the spindle-, pear-, or irregularly shaped plastids. Mag- nified 600 diameters. feature ; and so is multiplication, especially in the lungs, which are sometimes found crowded with whitish, slightly vascularized, tumors, the size of a poppy -seed, a hazel-nut, or a walnut. The same may be found in the pleura and the peritoneum. Mel- anotic myeloma selects the subcutaneous tissue, mostly of the 504 TUMORS. hands and the feet, as a point of departure, from which it gradu- ally invades large portions of the surface of the body, in some cases so rapidly that inflammatory symptoms are observed with the formation of every new nodule. In such cases, the secondary tumors in internal organs are either white or pigmented. The patients die showing the symptoms of exhaustion (cachexia, marasmus) or of septicaemia, in consequence of extensive gan- grene of the tumors. Mucous or colloid degeneration may also occur, and this change renders the tumor much less malignant. In the growth of myeloma, muscle- and nerve-tissue are trans- formed into medullary tissue. If the tumor has originated in a glandular organ, the epithelia are also converted into medullary plastids, and glands are either completely destroyed or partly enlarged, and even newly formed. In the latter cases, peculiar cauliflower-like vegetations are produced within the gland, owing to the encroachment of the myeloma tissue. Under these condi- tions, cysts are very common occurrences — f. i., in cysto-mye- loma of the female breast or the ovary. THE CHANGES OF EPITHELIA PRODUCED BY GROWTH OF MYELOMA. BY RUDOLPH TAUSZKY, OF NEW YORK.* It is known that myelomatous growths, which have originated either in the cutaneous or subcutaneous tissue, and also those which appear in tissues more deeply situated, as they approach the surface, sometimes produce ulcer- ative processes in the integument. This always becomes attenuated before the ulcerative process, often accompanied with inflammatory symptoms, begins. After a certain time a loss of substance is observed at the most prominent point of the tumor, which gradually enlarges ; and at its base the tumor is seen as a reddish, slightly nodular, or even smooth mass. The ulcer produces, as a rule, a relatively small quantity of pus. Clinically, this is a valuable diagnostic symptom of myeloma. Cancer invariably gives rise to an uJcerative process in the skin, and the ulcers thus produced present uneven, nodular, and irregularly granulating surfaces, yielding pus or ichor. The question now arises: What histological changes take place in the wasting process of the epidermis ? Of course, with the customary expression of "fading or dying" of the epithelium only a clinical fact is recognized, and the cause must be sought for in anatomical changes. At the same time, the question may be answered : What changes does the epithelium of glandular organs undergo when myeloma appears in them ? The literature of the morbid growths under consideration gives no satisfac- tory explanation of the question. I therefore examined a number of myelo- * Abstract from Dr, Rud, Tauszky's essay : " Ueber die durch Sarcomwucherung be- dingten Veranderungen des Epithels." Sitzunsber. d. Kais. Akademie d. Wissensch. in Wien. Bd. Ixxiii. The term " sarcoma" is changed into "myeloma," and that of "protoplasm " into "bioplasson." TUMOES. 505 mata of the skin and glandular organs, with special reference to the behavior of the epithelium. My specimens were: (1) A myeloma about the size of a child's fist, which was extirpated from the abdominal wall of a man fifty-five years of age ; ( 2 ) myeloma growths of the size of walnuts, which appeared in the right groin of a man sixty-nine years of age, and which, after repeated extirpa- tions, were followed by numerous secondary myeloma nodules in the lungs ; (3) a myeloma of the testis of a man, aged forty-eight years, nearly the size of a child's head; (4) a myeloma of the submaxillary gland, of a man aged FlG. 203. — FlBRO-MYELOMA FROM THE ABDOMINAL WALL OF AN ADULT. P, papillae, cut transversely; D, derma of skin, with commencing transformation into- myeloma ; B. blood-vessel ; R, rete mucosum. Magnified 200 diameters. seventy-two years, as large as a chicken's egg; (5) myeloma nodules from the liver of a man, aged fifty-nine, which occurred as a secondary growth after extirpation of a tumor of the eyeball, simultaneously with nodules in the omentum, the mesentery, and the walls of the small intestines. Among 506 TUMORS. these were represented the varieties called ' ' round-cell sarcoma " ; " spindle-" combined with " round-cell sarcoma" and " alveolar sarcoma." The changes in the epithelium, which are induced "by the growth of mye- lomatous tumors, may be divided into two groups. The first embraces the purely inflammatory process; the second includes changes that lead to the production of myeloma elements from epithelium. No distinct boundary can be drawn between these two groups ; for the changes observed in inflamma- tion are like those accompanying the growth of tumors, inasmuch as in both instances new formation of living matter and production of new elements results. Inflammatory changes. Specimens of the tumor (1) taken from the integu- ment near the ulceration show, with low power, that the epidermal layer was thinned in several places. (See Tig. 203.) We could see that the pigmented layer which constitutes the border nearest the connective tissue is in a con- FlG. 204. — FlBRO-MYELOMA FROM THE ABDOMINAL WALL OF AN ADULT. D, bundles of connective tissue of derma in transformation to bioplasson; V, blood- vessel ; P\ transformation of pigmented epithelia into non-pigmented plastids; f2, epithelia breaking down into pigmented lumps. Magnified 800 diameters. dition of moderate " cell-infiltration " — that is, inflammation. The pigmented epithelium is arranged irregularly, and is deficient in many places. Higher amplification proves that the epithelium along the connective tissue is broken up into elements, which do not differ from those which originate in connect- ive tissue ; only the pigment is a reminder of their origin, but the pigment in this situation also gradually decreases as the inflammatory changes proceed toward the epithelium. We meet with dispersed pigment granules, or groups of such granules, apparently remnants of former epithelium, though the larger TUMORS. . 507 mass of pigment has disappeared, perhaps by interference with the nutrition of the granules themselves, which have not yet been entirely deprived of vitality. Thus the epithelium containing pigment is changed directly into indifferent bioplasson bodies, from which, in turn, new elements arise. A real new formation has as yet not taken place, but out of specific elements indifferent ones have been produced by the formation of new separating lines of cement- substance. (See Fig. 204.) Of particular interest is the condition of the hair-follicles and sweat-glands which are imbedded in the tumor. Many hair-follicles, still holding hairs, presented no material change ; in others, the hair was wanting and the con- nective tissue of the follicle was transformed, in part at least, into the tissue of the tumor. The elements of the outer root-sheath were divided into FIG. 205.— SURFACE OF A MYELOMA IN THE EIGHT GROIN OF AN ADULT. M, partial wasting of cement-substance ; P, thickened spokes (prickles) ; Si, spindle- shaped plastids replacing the cement-substance ; S2, transition of the spindles into the frame of the myeloma tissue. Magnified 600 diameters. glistening, brownish-yellow lumps, whose groupings indicated their origin from epithelia. All these bodies were interconnected by fine filaments. The ducts of the sweat-glands remained unaffected in most instances; but the glands presented a conglomeration of bright-yellowish bodies, which by their clustered arrangement indicated their origin from glandular epithelia. In many tubules seen in transverse sections the central caliber was absent, and in some places the bounding (structureless) layer of connective tissue was also gone, and the tissue of the tumor came in direct contact with the changed epithelia. 508 TUMOES. The skin covering the tumor (2) gave no evidence of ulceration, but was merely stretched, attenuated, and reddened. In vertical sections peculiar changes were noticed in the epidermal layer, which was reduced to a few layers of epithelia of the rete mucosum. Near the surface several epithelia were found coalesced, owing to the entire disappearance of the separating cement- substance. The "prickles" traversing the lines of cement-substance were well marked, even enlarged into oblong or square granules. In other places, instead of these granules, spindle-shaped or oblong bodies were seen, repre- FIG. 206.— GLOBO-MYELOMA, COMPOSED OF SMALL PLASTIDS. VERSE SECTION OF A SEMINIFEROUS TUBULE. TRANS- E, unchanged columnar epithelia; ES, commencing transformation of epithelia into myeloma elements ; 8, completed .transformation of epithelia into myeloma elements ; L, caliber of the seminiferous tubule. (For low amplification of the same tumor see Fig. 192.) Magnified 800 diameters. senting what Biesiadecki termed " migrating cells." Careful observation, however, revealed that all of these bodies were connected with the neighbor- ing epithelial elements by means of delicate filaments. Such formations were particularly numerous along the border separating the epithelia from the TUMORS. 509 myeloma-tissue, and many of the spindle-shaped bodies merged into the fibers separating the groups of myeloma elements. Here, therefore, a new forma- tion had arisen mainly from the " prickles," while a direct transformation of epithelia into myeloma elements could not be demonstrated. (See Fig. 205.) Transformation of epithelium into myeloma elements. The tumor of the testis(3) clearly exhibited the changes of the epithelia of the seminiferous tubules caused by the growth of the myeloma. Even low powers of the microscope demonstrated that the myeloma tissue had in numerous places pushed apart the seminiferous tubules, which in other places were entirely lost. In a number of specimens, not only the boundary layer of the tubules — to- ward the epididymis — was found to have disappeared, but the glandular epithe- lium itself presented, in part at least, features identical to those of the tumor. (See Fig. 193.) Higher amplifications explained satisfactorily this peculiar condition. The epithelium, in a transverse section of the tubule, appeared in part to be well preserved, while in another portion of the same tubule some of the epithelia exhibited coarse granules and solid lumps the size of nuclei. A striking feature was that in one epithelium an unchanged portion was found, and another portion was in the condition above described. Finally, there were portions in which the epithelium was replaced by myeloma tissue, in which its gradual stages could be traced. The increase of the living matter first gave rise to the formation of coarse granules and new nuclei ; next, new boundary lines originated within the epithelia, dividing them into elements which bore no resemblance to the epithelia. Finally, the newly formed elements were partly infiltrated with basis-substance, the perinuclear form of which is characteristic of embryonal and lymph-tissue, as well as of certain so-called " small-cellular" varieties of myeloma. (See Fig. 206.) The result of these changes is a real and complete transformation of the epithe- lia into myeloma tissue. Here and there I met in this tissue groups composed of 6-12 epithelia, which in all evidence were remnants of former glands or ducts, but not a glandular new formation. In all specimens of this tumor the spindle-shaped bodies which sprung from the cement-substance were in dis- tinct connection with the reticulum of the myeloma tissue ; and all. forma- tions of living matter (granules, nucleoli, nuclei, spindles, and trabeculse) were interconnected by delicate filaments. Even in the perinuclear, mucoid basis-substance, in some places the bioplasson reticulum could be seen without the aid of re-agents. In the case (5)1 obtained a distinct view of the changes of the liver-epithelia in growth of myeloma. Low powers of the microscope proved that the newly formed myeloma nodules were separated from the surrounding liver-tissue by a tolerably thick capsule of connective tissue. Inside the capsule was a mye- loma of alveolar structure j outside of it tracts of liver-epithelia were com- pressed, spindle-shaped, and running in a direction parallel to the surface of the capsule. In some places the boundary line between myeloma and liver- tissue was not sharply marked, but merely indicated by delicate bundles of connective tissue. Probably, these were the myeloma nodules of later periods. (See Fig. 207.) Here, in some places, the tracts of the liver- epithelia were well preserved, while in other parts the epithelium was broken up into globular or irregularly shaped bodies, which could only have origi- nated from the living matter in the epithelium. These bodies presented all the stages of transformation into myeloma tissue ; for, upon approaching the myeloma nodule, they were seen in groups, which, by virtue of their shape, 510 TUMOES. must be pronounced myelomatous alveolar formations, separated from each other by scanty connective tissue. Here, also, the endogenous production of living matter in liver-epithelia had led to the formation of myeloma tissue. The brownish color of the liver epithelium gradually faded into the grayish- yellow of the myeloma nodules. In like manner, the gradual transformation was indicated by the degree of carmine-staining, which had no effect upon unchanged liver epithelium, but became more intense with the deviation of the newly formed tissue from normal type of epithelium. I can add that the myeloma of the submaxillary gland (4) presented, in some portions, analogous appearances. In this tumor, too, the transforma- tion of the epithelium of the acini of the salivary gland could be traced, step by step. My researches, in brief, gave the following results : The myeloma growth, in its progress toward the epidermis, produces a change in the living portion of the epithelium similar to that which is observed in the superficial inflammatory processes of the skin. The cement-substance is dissolved ; multinuclear bioplasson bodies arise, and in them new lines of division originate, producing indifferent elements, resembling those which spring from connective tissue. New elements are also produced by a new formation of living matter, both within the epithelia and in their cement-substance investment ; in the latter situation, of course, from the filaments or "prickles" of living matter. Such a new formation FIG. 207. — SECONDARY MYELOMA OF THE LIVER. C, connective tissue which separates the myeloma nodule from the liver-tissue ; E, little changed liver-epithelia within the myeloma nodule ; S, new formation of myeloma elements from liver-epithelia ; P, remnants of portal vessels. Magnified 600 diameters. occurs in the epithelia of the external root-sheath and of the sweat-glands. The attenuation of the epidermis is evidently caused by a gradual transformation of the epithelia of the rete mucosum into myeloma tissue. In myelomata of glandular organs, — salivary glands, testes, liver, — the new formation of bioplasson starts in the epithelia with the appearance of new marks of division, and newly formed mye- loma elements. The living matter of epithelium is directly converted into myeloma tissue, with a partial or complete destruction of the epithelia. TUMORS. 511 6. LIPOMA. FATTY TUMOR. Lipoma is composed of fat-tissue, exhibiting a lobular struct- ure and traversed by septa of connective tissue, which carries the blood-vessels. In the so-called soft, fatty tumors the con- nective tissue is scanty and the fat of a more oily nature, while in tumors termed fibrous lipoma (formerly called steatoma) the frame attains considerable development and the fat is more solid. The fat-globules resemble those of normal fat-tissue, and like these sometimes contain needle-shaped crystals of "margaric acid.7' (See Fig. 208.) Lipoma appears as a tumor sui generis in the subcutaneous, submucous, and subserous tissues, rarely in glandular organs. FIG. 208. — LIPOMA, FROM THE SHOULDER OF A MAN. V, capillary blood-vessel in the frame of connective tissue ; F, fat-globules, pierced by vacuoles, the latter being caused by preservation in chromic acid. Magnified 400 diameters. In the subcutaneous tissue it occurs usually on the posterior aspect of the body, and produces single globular, highly elastic tumors, the surface of which appears to be lobulated to the touch, and which, in different localities, have different degrees of con- sistency. The tumor is usually quite movable, and sometimes is very loosely attached to the body, pendent like a bag. The covering integument is either unchanged or it is thickened and pigmented, but may, as a rule, be raised in folds; it becomes 512 TUMORS. attached to the tumor only after injuries from without — f. i., friction of the clothing or long-continued pressure. Under these circumstances ulceration even may be produced, which is char- acterized by the offensive odor of discharge. In the subcutaneous tissue both solitary and multiple fatty tumors occur $ they may be circumscribed or diffused. Pedun- culated and diffused fatty tumors are exceptional ; the latter are of a softer consistency, and are attached to the skin by means of dense, fibrous connective tissue. Lipoma is painful only when nerve branches are involved in the growth, and disturbance of functions is caused only by its size and weight. The growth is slow but almost indefinite, as there have been observed fatty tumors of twenty to thirty pounds. The larger the tumor the more marked is its lobular structure. Not infrequently calcareous deposition is found in the connective-tissue frame, and occasionally, though rarely, ossification. Lipoma occurs combined with : Hypertrophy of a finger, a toe, or the entire hand or foot ; Myxoma, fibroma, and myxo-fibroma, producing tumors of the skin, termed " naevus lipomatodes " ; Cavernous angioma (Billroth), when especially the veins are ectatic in a high degree ; Myeloma, usually myxo-myeloma of the subcutaneous tissue. Peculiar branching growths of serous membranes, especially of the knee-joint, which consist of delicate papillary vegetations of connective tissue, whose meshes contain fat-tissue, are con- sidered as formations of lipoma (1. arborescens). Localized, diffuse new formation of fat occurs in the female breast, which, on one or on both sides, may reach an enormous size and weight. 7. ANGIOMA. VASCULAR OR ERECTILE TUMOR. The characteristic feature of angioma is an abundant supply of blood-vessels — arterial, venous, or capillary. This causes its erectility — i. e., its swelling on a spontaneous engorgement of the vessels. Such tumors yield readily to pressure, but as soon as the pressure is removed they refill. In former times many of these tumors were termed " teleangiectasis," as they were thought to be due to a mere dilatation of the vessels ; now we are ac- TUMORS. 513 quainted with the fact that the blood-vessels are really new formations. We can distinguish three varieties of angioma, according to the nature and distribution of the blood-vessels — simple, lobular, and cavernous angioma. (a) Simple angioma is, to a great extent, composed of newly formed capillary blood-vessels, between which, in more or less uniform distribution, is a varying amount of fibrous or homo- geneous connective tissue. The coat of the blood-vessels is com- posed of very large nucleated, sometimes stratified, endothe- lia j numerous tracts are solid, and composed entirely of en- dothelia (endothelioma). Both in the endothelia and the con- nective-tissue frame there are indications of a new forma- tion of red blood-corpuscles, through- the intermediate stage of haematoblasts. (See Fig. 209.) (~b) Lobular angioma is composed of coils of large capillary blood-vessels, held together by delicate fibrous tissue, while between the coils FIG. 209.— SIMPLE ANGIOMA, FROM this tissue is somewhat denser. The lobate structure is some- ,• -I -i , ,-1 -i -i L, longitudinal section of a capillary; S, Times marKea IO tne naxea soli(1 cor(1 of eudothelia; F, frame of a nearly eye. In Sections, the blood- homogeneous connective tissue. Magnified , . . ,7 ., T T 600 diameters. vessels are cut in longitudinal, oblique, and transverse directions, and are found either empty or filled with blood. The capillaries are connected with large arteries or large veins, and the blood in the angioma may be clinically recognized as being of either venous or arterial char- acter. (See Fig. 210.) (c) Cavernous angioma is constructed on the plan of cavern- ous tissue — i. e., composed of venous sinuses, which lie close to each other, separated only by walls of fibrous tissue, in which are capillary blood-vessels, and sometimes bundles of smooth muscle-fibers. The cavernous sinuses -are filled with blood-corpuscles, and the blood has in its clinical aspect a venous THE SKIN" OF THE FOREHEAD OF A CHILD. 33 514 TUMOES. character — i. e., is dark purple or bluish-red. The sinuses are lined with a delicate layer of endothelia. (See Fig. 211.) Angioma is a common type of tumors, and in most instances is congenital. The simple and lobular angioma is located either in the tissue of the derma of the skin or in the subcutaneous tissue, and is in the latter situation abundantly supplied with fat-globules. These tumors may occupy large districts in the face (the so-called " fire-mole/7 naevus vasculosus), or they may appear in a number of smaller spots or elevations in different parts of the skin. They may either remain stationary or grad- ually increase in extent. Spontaneous cure is not an infrequent FIG. 210. — LOBULAR ANGIOMA, FROM THE ORBIT OF A CHILD. LL, lobules composed of coils of large capillary blood-vessels; I, interstitial dense abrous connective tissue. Magnified 350 diameters. occurrence. The lobular angioma is, as a rule, more deeply situated than simple angioma 5 the tumor is to the naked eye marked by shallow, irregular nodulations of the surface. Upon invading the derma, the thinned skin covering it becomes im- movable, and sometimes spontaneous ulceration takes place, though the haemorrhage is rarely profuse. Cavernous angioma is somewhat rarer, and appears either as a sharply circum- TUMORS. 515 scribed, as if encysted, or as a diffuse tumor in the subcutaneous tissue, in muscles beneath the covering fasciae, in the liver, the spleen, and the kidneys. It grows very slowly, and is often painful. The pain may be continuous or be due to pressure from without, and by rupture it may produce a dangerous haemorrhage. Cavernous angioma reaches its highest develop- ment on the extremities, on single fingers, or as numerous scat- tered nodules, combined with considerable hyperplasia of the derma. Occasionally, though rarely, angioma involves mucous, membranes. Several cases of angioma in the larynx have been reported. In rare cases, all the soft tissues of an extremity are transformed into the cavernous structure, with a gradual wasting FIG. 211.— CAVERNOUS ANGIOMA, FROM THE BASIS OF A POLYPUS GROWN AT THE BORDER OF THE POSTERIOR NARES OF A CHILD. T, trabeculse of fibrous connective tissue, holding capillary blood-vessels ; E, endothelial lining of the cavernous spaces ; B, red blood-corpuscles. Magnified 700 diameters. of the bone. Primary tumors of this kind, grown from the peri- osteum, and which gradually transform the bone into their own tissue, the so-called " pulsating bone-tumors," are rare. Angioma combines with myxoma, fibroma, lipoma, and adenoma. Angioma may be composed of lymph-vessels, and is then termed lymph-angioma. There are two varieties : the simple lymph-angi- , composed of dense fibrous connective tissue, containing a 516 TUMORS. varying number of lymph-vessels (Hebra), and the cavernous fympli- angioma, composed of a large number of sinuous lymph- vessels and a comparatively scanty amount of connective tissue. Simple lymph-angioma is not of rare occurrence in the tissue of the skinr and usually appears in the form of numerous hard, compressible tumors the size of a lentil or of a hazel-nut. Cavernous lymph- angioma is rare, and, as a rule, deeply situated in the subcu- taneous or subfacial tissue, producing sometimes very large tumors. Ulceration of these tumors occasionally takes place, with a continuous oozing of lymph. (See Fig. 212.) In macro- FIG. 212. — CAVERNOUS LYMPH-ANGIOMA, FROM THE LATERAL REGION OF THE NECK OF AN ADULT. C, frame of connective tissue, of a homogeneous, waxy appearance and a high refractive power ; .F, irregular reticulum of coagulated fibrine ; L, lymph-corpuscle. Magnified 50O diameters. glossa, — the congenital enlargement of the tongue, of mainly its anterior portions, — the mass consists of a fibrous connective tissue with numerous sinuous lymph- vessels, and is, therefore, cavernous lymph-angioma (Virchow). In some cases, cavernous blood- angioma was observed. No new formation of striped muscles was found in the tumor. TUMORS. 517 Attention has recently been drawn to tumors which, in addition to well- developed fibrous connective tissue, contain tracts or alveoli filled with finely granular polyhedral nucleated plastids, resembling the endothelia of blood- vessels. Tumors of this structure are termed endothelioma, and, as a matter of course, are of a benign character. I have seen such formations in a sebaceous adeno-fibroma of the scalp, in a lipo-fibroma of the skin of the face, and in a tumor of the choroid the size of a sugar-pea. Endothelia are in their structure identical with the medullary corpuscles, representing the stage of indifference from which connective tissue and its derivations arise. In the first instance, the endothelial tracts were like blood-vessels, but without per- foration ; such tracts were also observed in the angioma of the skin of the forehead of a child, illustrated in Fig. 209. In the second case, fat-globules were found in the midst of the endothelia, and the conception was admissible that fat originated from the endothelia, there representing an intermediate stage. In the third case, alveoli were present, closely resembling cancer nests. The differential diagnosis in such a case rests upon the regular arrange- ment of the alveoli ; the lobular structure of the tumor ; the fully developed fibrous connective-tissue frame, which is of a nearly uniform width and scantily supplied with blood-vessels ; the fine granulation of the plastids and their pale, finely granular nuclei. In such cases a positive differentiation between endo- thelioma and epithelioma (cancer) seems difficult, if not impossible ; though the clinical course of the benign endothelioma is altogether different from cancer. 8. MYOMA. MUSCLE TUMOR. Tumors composed exclusively of striated muscles do not occur ; striped muscle-fibers are constituents of tumors, appear- ing occasionally in the testis and the ovary, which also contain remnants of other tissues, such as cartilage, bone, teeth, and hairs. These are the so-called " dermoid cysts" — teratoid and combination tumors. On the contrary, tumors composed of smooth muscle-fibers are of frequent occurrence, always com- bined, however, with fibrous connective tissue, constituting, therefore, myo-fibroma or fibro-myoma. The organ which is the most frequent site of tumors of this sort is the uterus, in middle and advanced age, especially in the colored races. Myo-fibroma of the uterus appears either beneath the mucous layer, in the middle of the wall, or at the periphery of the uterus (submucous, intraparietal, and subserous myo-fibroma), and in almost every instance more or less smooth muscle-fibers are found mixed with the connective tissue. The latter tissue carries the blood-vessels, which vary greatly in amount and sometimes are so abundant as to justify a diagnosis of angio-myoma. Fibrous tumors of the ovaries which I have examined exhibited the same features. A subserous myo-fibroma of the uterus, under the microscope, gave the appearances illustrated in Fig. 213. 518 TUMORS. The bundles of smooth muscles are either scattered irregu- larly throughout the tumor, always interlacing in different direc- tions, as shown by sections, or there is a lobular structure when nodules containing many smooth muscles, but little connective tissue, are separated from each other by comparatively . broad layers of fibrous connective tissue. In bundles of smooth mus- cle-fibers, cut longitudinally, the muscle nature of the fibers is often unrecognizable, as they blend with those of connective tis- sue, while in transverse sections of the bundles all doubts of the FIG. 213. — MYO-FIBROMA OF THE UTERUS. L, bundles of smooth muscle-fibers cut longitudinally ; F, bundles of smooth muscle- fibers cut transversely; A, artery with a very broad muscle-coat; V, vein. Magnified 200 diameters. muscle nature of the fibers are removed, owing to the presence of abundant bioplasson and rod-like nuclei within the spindles, separated from one another by a delicate fibrous perimysium. One of the most striking features, in some cases, is the heavy muscle-coat surrounding the arteries. (See Fig. 214.) TUMORS. 519 Myo-fibroma of the uterus is prone to fatty and calcareous degeneration j the former invades both the plastids of the con- nective tissue and the muscles, the latter only the connective- tissue frame. Moreover, there are cases on record where an original myo-fibroma has changed into a malignant myeloma, or even into cancer. Myoma is a tumor of rare occurrence in the skin (growing in the neighborhood of the nipple and in the scrotum), somewhat less rare in the wall of the ossophagus, the stomach, the intes- FIG. 214. — MYO-FIBROMA OP THE UTERUS. L, longitudinal bundles of smooth muscle-fibers, not distinguishable from fibrous connect- ive tissue ; F, bundles of smooth muscle-fibers, cut transversely ; A, artery with a heavy muscle-coat. Magnified 500 diameters. tines, in the wall of the urinary bladder, and in the prostate (in the latter, hyperplastic myoma — Virchow). 9. NEUROMA. NERVE TUMOR. The term " neuroma " can be properly applied only to tumors which consist entirely, or at least partially, of newly formed medullated or non-medullated nerve-fibers j but it is doubtful 520 TUMOES. whether such formations ever occur. Tumors containing nerves have been observed most frequently on the spinal nerves, less frequently on the sympathetic, and least frequently on the cere- bral nerves. No positive proof has been given, however, that the great quantities of nerves in these tumors are really newly formed. If the internal perineurium — of course connective tis- sue only — be augmented, the innumerable nerve-fibers are pushed apart and may make the impression of constituting a true neuroma. Giinsburg, Wedl, and others have demonstrated that, in the nodular nerve-growths developed after the amputa- tion of a limb, large numbers of the bundles of nerve-fibers, both of the medullated and non-medullated varieties, were newly formed. There are recorded cases in which one nerve produced a number of tumors, which gave the formation a rosary-like appearance $ in other cases, on a number of nerves in different localities, tumors were found, and it is asserted that in such nod- ules newly formed nerves were present in a large number (mye- linic neuroma of Virchow). Some congenital tumors in the sacral region have been found to contain a large number of medullated nerves. Virchow observed teratoid tumors, composed of nerve-tissue, resembling the gray substance of the brain. Of still more doubtful occurrence are the tumors composed of non-medullated nerve-fibers, — the amyelinic neuroma of Yir- chow, — who describes a case of recurrent ulcerative, and conse- quently malignant, neuroma (" neuromatous diathesis")- Even with our modern methods of investigation a positive proof of the presence of non-medullated nerve-fibers is not easily obtained, and many authors have doubted the existence of true amyelinic neuromata. Most of the nerve tumors have proved to consist, in addition to a varying number of nerve-fibers, of the myxomatous and fibrous varieties of connective tissue. Instead of using the term " spurious neuroma," we shall designate such tumors as myxoma or fibroma growing from a nerve, or if the tumor contains a large number of nerve-fibers, we may term it neuro-myxoma, or neuro- fibroma. Most of the so-called " painful tubercles " of the skin also belong to this class. (See Fig. 215.) Sometimes myeloma develops on or in a nerve, and, in accordance with our terminology, such a tumor would be called neuro-myeloma. The nerve-fibers, however, in the advancing growth of the tumor are soon destroyed and transformed into myeloma tissue. TUMOMS. 521 The most important clinical sign of neuroma is its painf ulness, which bears no relation to its size. Small tumors the size of a lentil are sometimes extremely painful, while large ones, the size of a man's fist, cause little or no pain. This difference in the amount of pain depends, doubtless, upon the fact that the nerve- fibers in some tumors are quickly destroyed or transformed into the tissue of the tumor. 10. PAPILLOMA. WARTY TUMOR. Warty tumors are combinations of connective and epithelial tissue j the former produces the finger-like, papillary elevations, the latter furnishes the outer investment. The connective tissue FIG. 215. — NEURO-FIBROMA OF THE SKIN ABOVE THE PATELLA OF A WOMAN. N, remnants of medullated nerve-fibers, with fluted outlines ; M, myeline drops, sepa- rated from one another ; V, capillary blood-vessel. Magnified 600 diameters. is in its structure either fibrous or myxomatous, or a combination of both, and, as a rule, supplied with numerous blood-vessels, some of which are very large. Sometimes papillomatous growths exhibit the structure of myeloma, either from the beginning or after, by repeated trials of extirpation, considerable irritation has 522 TUMORS. been set up. Under these circumstances, an originally benign papilloma may pass into a myeloma, or a secondary change into cancer may take place, both rendering the tumor malignant. According to the nature of the connective tissue and the amount of covering epithelium, we distingiiish a horny and a myxoma- tous papilloma as primary tumors. (a) Horny papilloma is composed of highly vascularized fibrous connective tissue, producing branched, finger-like pro- longations, and is covered by a stratified epithelial layer, usually of considerable breadth. The deepest layers of the epithelia con- tain a varying amount of pigment. (See Fig. 216.) FIG. 216. — PAPILLOMA OF THE LARYNX. E, heavy epithelial cover; P, papillary prolongations of connective tissue ; V, wide blood- vessels. Magnified 50 diameters. Warty tumors are of frequent occurrence on the skin, partic- ularly of the fingers, and are often caused by a continued local irritation of the part. They usually appear at the time of puberty, and disappear spontaneously. They attain the largest size in the region of the genitals, and are called in this situation warty condylomata, their growth being always due to the local irritation produced by the blennorrhoic secretion. They have nothing in common with syphilis. Warty tumors are also of frequent occurrence in the mucous membranes, especially of the TUMORS. 523 larynx. The horns and claws of the skin of the face and the scalp of elderly persons are papillomatous tumors with very long- and thin papillae. Warty tumors are known to be difficult to cure, and with advancing age sometimes to change into cancer. (I) Myxomatous papilloma occurs rarely on the skin, but more frequently on mucous membranes. Such tumors consist of a soft myxomatous connective tissue, always rich in blood-vessels, and covered either with a comparatively thin layer of stratified epithelia, or with a single layer of columnar epithelium. (See Fig. 217.) FIG. 217. — PAPILLOMA OF THE MUCOSA OF THE UTERUS. P1, papilla covered by a single layer of columnar epithelia ; PZ, epithelial layer in top- view ; pz, papiUa deprived of its epithelial cover. Magnified 600 diameters. To this class belong the papillomatous tumors, so-called " carun- eulae," of the female urethra, which are often extremely painful and cause serious haemorrhages. They appear as dendritical, scarlet, sessile vegetations, usually at the external orifice of the urethra. They occur, but are rare, in the mucosa of the uterus and of the bladder. Liicke first drew attention to the fact that the formerly so-called " papillary cancer77 of the bladder is originally a benign papilloma, which in a secondary change may take on the charac- 524 TUMORS. ter of myeloma or cancer. This fact was recently corroborated by the accurate investigations of A. W. Stein. Papilloma of the uterus may cast off portions of its substance with the menstrual discharges. This occurred in the case of the woman who passed the shreds illustrated in Fig. 217. Shreds of tissue may also be passed with the urine, if papilloma of the bladder be present. Papillary tumors combined with adenoma sometimes appear in other mucous membranes, and they are always more difficult to eradicate and more prone to change into a malignant type than simple myxo-adenoma. MICROSCOPICAL STUDY OF PAPILLOMA OF THE LARYNX. BY Louis ELSBERG, M. D., NEW-YORK.* All other laryngeal tumors together occur less frequently than papillo- mata. Of three hundred and ten cases of intralaryngeal morbid growths that have come under my observation, I believe one hundred and sixty-three to have been papillomatous, although the diagnosis, many times, was made clinically only — *. e., without microscopical examination. The tumor, the size of a coffee-bean, which is the subject of my study, was removed by evulsion from the anterior portion of the vocal band of a woman thirty-six years old. In sections examined with low powers of the microscope a central mass of connective tissue is seen, abundantly provided with large blood-vessels, mainly veins and capillaries, some choked with blood. Taper- ing prolongations extend from this mass outward toward the periphery of the tumor and the papillae, and terminate in a large number of minute, finger-like ramifications. The central mass, with its prolongations, is invested with a thick stratified epithelium, the lowest portion of which — i. e., the one nearest the connective tissue — is a row of columnar epithelia, the main mass cuboidal, and the peripheral portion flattened epithelia. The latter exhibit in some places irregular erosions, which produce a rather jagged outline. Corresponding to the papillae, the epithelial layers form rounded protrusions, the valleys between the papillae representing the main mass of epithelial structure. Higher powers of the microscope (500-600 diameters) show the fibrous con- nective tissue in the central portion of the tumor to be made up of interwoven, longitudinal, and transverse delicate bundles of fibers, the relatively thinner bundles being nearer the periphery. Most of the papillae contain predominantly the variety of connective tissue called myxomatous. Within the connective- tissue bundles are seen numerous plastids, either single or in chains, either roundish or oblong and fusiform, which are the so-called connective-tissue corpuscles. In the myxomatous portion the fibers are more delicate than in the fibrous, and are in many instances arranged in the shape of a delicate net-work, at the nodes of which small, oblong nuclei are met with, while the meshes contain either a finely granular basis-substance or globular plastids of varying size. The blood-vessels, which, as before mentioned, are very numer- ous and very large, wind their way between the bundles, and some of them * Abstract from the author's essay, " Archives of Laryngology," vol. i., 1880. TUMORS. 525 have a very narrow but distinct muscular coat. The endothelial coat of the capillaries is well developed; at some places the endothelia are clustered together, with marks of division within the cluster, pointing to a proliferation of the endothelial wall. Most of the capillaries are surrounded by a some- what denser fibrous connective tissue, even in the myxomatous portion of the tumor. This layer of fibrous tissue constitutes an adventitia of the capillary blood-vessels more distinct than is ordinarily met with in normal tissues. The boundary-line between connective tissue and epithelium at many places in the various specimens is sharply defined by a narrow zone of dense fibers, identical with what has been termed the basement membrane ; at other places, on the contrary, such a bounding zone is absent, and there is a gradual transition of connective tissue into epithelium. In the latter cases the epi- thelial bodies send offshoots into the reticular portion of the myxomatous tis- sue, and it is impossible to tell where one terminates and the other begins. Where a bounding layer of connective tissue exists, the columnar epithelia are well defined ; where such a zone is absent they are ill defined, several rows being sometimes piled up, each epithelium of a more or less fusiform shape and very narrow. Surrounding each individual epithelial body, whether spindle-shaped or well defined, and separating each from all the others, there are very narrow light rims, pierced by extremely delicate threads. The main mass of epithelium consists of cuboidal elements, which are polyhedral and separated from each other by a light rim, — the so-called cement-substance, — traversed by a large number of delicate threads or " thorns." Whenever the razor has reached the surface of a cuboidal element in front section, the epi- thelium looks as if studded with short hairs or thorns. The cuboidal epithelia nearest the outer limit exhibit the cement-substance and the thorns less markedly, and in the layer of flattened epithelium at the periphery, cement- substance and thorns are scarcely recognizable. Most of the cuboidal epithelia hold in their interior a nucleus, the aspect of which is, however, various. Not infrequently an epithelium has two nuclei, of which one is finely, the other coarsely, granular, or both may be coarsely granular, differing from each other only in size and in the number of granules they contain. Occasionally a nucleus constitutes an almost homogeneous shining mass ; and, again, a mass split up into two or three relatively large lumps or clusters of granules. Around compact nuclei a broad light rim is sometimes visible, evidently a vacuole — i. e., a closed space filled with a liquid. Large vacuoles in the centers of some epithelia are seen perfectly empty, presumably because the nucleus that was in them has fallen out, or been dragged out by the razor. Instead of the so-called thorns seen in cement-substance, frequently slender spindles are wedged in between two epithelia of a higher refracting power than the latter. Or a shining spindle-shaped corpuscle lies close against one wall of an epithelial body, while the cement-substance at the opposite side of • the spindle is slightly distended, and pierced by thorns running at right angles to the spindle. In other instances, the thorns between two epithelial walls seem to have run together into an almost square or oblong homogeneous shining rod ; the cement-substance, more or less broadened, surrounding the rod on one or both sides and being pierced with other slender thorns. Again, compact club-like or pear-shaped shining bodies, or a number of granules in clusters of either a pear- or spindle-shape, are seen in the considerably dis- tended cement-substance between two epithelia. These masses sometimes 526 TUMORS. reach, and sometimes surpass, in size that of large epithelial nuclei. Lastly, pale or coarsely granular bodies are seen wedged in between two or three neighboring epithelia, smaller in size than the latter, some being devoid of, and some possessing, oblong nuclei. These various formations in the cement- substance are found in large numbers in the vicinity of the papillse. They occur in the cement-substance of columnar as well as in that of cuboidal epi- thelia. Very near the periphery of the tumor they are scanty, but absolutely absent in the outermost layer of flat epithelium only. With the highest powers of the microscope (1200 diameters) the fibrous portion of the connective tissue is seen to be composed of extremely delicate spindles, which are separated from each other by very narrow light rims, analogous to those which we are accustomed to see in epithelial formations. By closely watching these light rims we certainly detect in them slender threads, analogous to the thorns long known to exist in the cement-substance of epithelium. The spindles themselves, representing what we call basis- substance of connective tissue, are by no means homogeneous. In the thin- nest layers of the bundles in the central portion of the tumor they exhibit a delicate but distinct net-work, the threads of which are grayish, the carmine coloring being confined to the meshes. Interspersed between the spindles is seen a large number of multi-caudate corpuscles of reticular structure, the peripheral sprouts of which tend toward the spindles and inosculate with the net-work of the basis-substance. The peripheral portion of the connective tissue is, as has already been stated, of a prevailing myxomatous structure. Here the spindles constituting the basis-substance, instead of being packed together to form bundles, are associated in the shape of a coarse reticulum, holding numerous small corpus- cles, mainly at the points of intersection ; but the larger meshes encircled by the spindles also contain a number of similar corpuscles or else a light, so-called myxomatous, basis-substance. High powers of the microscope reveal a delicate net-work structure in the inside fields of the myxomatous basis- substance, as well as in the encircling spindles, and this net-work is in unin- terrupted connection with the corpuscles at the junction of the spindles and those contained in some of the meshes. The most peripheral portion of the connective tissue is inx connection with the epithelium. Where a sharp line of demarcation exists, the highest powers of the microscope reveal a single layer of connective-tissue spindles, serving as a basis for the epithelia to rest on. This terminal stratum is in close connection with the subjacent reticulum of myxomatous tissue and with the capillary blood-vessels nearest the periphery. The blood-vessels not infrequently approach the stratum so near that only a very narrow light rim is left between their wall and the epithelium, and this rim is invariably tra- versed by delicate grayish filaments. On the opposite side the stratum is in close contact with the peripheral threads of the net-work of fully developed columnar epithelia. In the case of not fully developed epithelial elements, as intimate a connection is established by shining homogeneous spindle-shaped prolongations, which go from the terminal stratum into the epithelial layer as either an irregular reticulum or rows of filaments, arranged in a more or less regularly vertical direction around a reticulated corpuscle, containing in its interior one or more small, reticulated bodies of the aspect of nuclei. Thus, such a reticulated corpuscle — *. e., a not yet fully developed epithelium — is inclosed in the spindle in a similar manner to that in which the cement-sub- TUMORS. 527 stance surrounds fully developed epithelia. The difference is that the spin- dles are homogeneous and shining, of the same refracting power as the granules and threads of living matter, while the cement-substance is a pale layer without any refracting power. Evidently, the spindles are compact masses of living matter from which future epithelia arise, while the cement- substance proper is a lifeless, horny material, containing only very little liv- ing matter in the shape of the minute thorns that traverse it. Where there is no sharp demarcation between connective tissue and epi- thelium, even the highest powers of the microscope fail to demonstrate where one terminates and the other begins. Only the presence of capillary blood- FIG. 218.— PAPILLA, WITH SURROUNDING EPITHELIUM. OBLIQUE SECTION. a, bundle of fibrous connective tissue ; &, plastid between the spindles ; c, myxomatous connective tissue ; d, capillary blood-vessel cut across ; e, layer of connective tissue at the base of the epithelia; /, spindle-shaped prolongations of the layer e, insinuated between the epithelia; g, columnar epithelium; li, medullary tissue, transition of connective tissue into epithelium. Magnified 1200 diameters. vessels furnishes some guidance for the determination of what is connective tissue. (See Fig. 218.) In the lower strata of epithelia we most frequently meet with the appearances in the cement-substance already described. The high power 528 TUMORS. reveals in the cement-substance masses of living matter which tend unques- tionably toward the formation of new epithelial bodies. The initial stage of such formation is a growth and confluence of the thorns into rods or spindle- shaped masses, which remain in connection with the neighboring epithelia by means of delicate threads. Such a change in the bulk of the living matter is possible only after the liquefaction of the horny cement-substance. An increase in the bulk of the thorns is invariably accompanied with a widening of the space occupied by the cement-substance. Of course, the larger the formations of living matter between the epithelia become, the larger must become the space in which they are located ; and this enlargement often leads to the produc- tion of bay-like excavations along the walls of contiguous epithelia. Such excavations sometimes hold irregular clusters of bodies, which in their optical behavior are identical with the nuclei of epithelia generally. The preliminary stage in the development of a new epithelial body is completed by the appear- ance of a coarsely granular plastid, between the old finely granular epithelia and the appearance of lines of new cement-substance around the newly formed body. Changes similar to those that go on in the cement-substance also occur in the interior of the nuclei. Nuclei of a dumb-bell shape, or two nuclei within one epithelial body, have long been known as common features in epithelia. They certainly seem to point to a multiplication of nuclei, but I am unable to say whether they have anything to do with new formation of epithelia or not. (See Fig. 219.) As an addendum I may state that I have found, in microscopical sections made from a papilloma of the penis, a so-called venereal wart, the same characteristic features that I have described as belonging to papilloma of the larynx. A. Biesiadecki was the first to draw attention to the presence of shining, spindle-shaped bodies within the cement-substance of inflamed (eczematous) skin, in which an active new growth of epithelia takes place ; but he claimed that these spindle-shaped bodies came from the connective tissue. The most recent writer, E. Klein, holds a similar opinion, for he describes and figures in his "Atlas of Histology," in the cement-substance of epithelium from the tail of a tadpole, what he calls " branched cells" of connective tissue, which "are seen to extend with their processes amongst the epithelial cells." My observed series disproves, of course, any such opinion. What I have proved in regard to the new formation of epithelia is that : (1) Epithelium multiplies from medullary elements not distinguishable from those that form connective tissue at the boundary between these two tissues; (2) epithelium multiplies from the new growth of medullary elements which originate in the living matter — the so-called thorns — within the cement-substance. 11. ADENOMA. GLANDULAR TUMOR. Adenoma is composed of a myxomatous or fibrous connective tissue, containing newly formed glands of either the acinous or tubular varieties. Blood-vessels are found only in the connective- tissue portions. The most characteristic feature of the glands is the central caliber, which is invariably found in both the acinous TUMORS. 529 and tubular formations. Acinous glands, as a rule, are lined by cuboidal or short columnar epithelia, which are often stratified j while tubular glands are lined by columnar epithelia, which are sometimes ciliated. The regularity in the arrangement of the epithelia, their fine and uniform granulation, and the compara- tively fine granulations of the nuclei, are, in many instances at least, distinguishing points for the diagnosis of an adenoma under the microscope. FIG. 219. — CUBOIDAL EPITHELIA, FROM THE NEIGHBORHOOD OF THE COLUMNAR EPITHELIA. a, nucleus surrounded by a light space, a sc-called vacuole ; b, empty vacuole, nucleus dropped out; c, epithelium with two nuclei; d, epithelium with a bright, homogeneous nucleus; e, "thorns," or filaments of living matter in the cement substance; /, thorns in- creased in size ; g, enlarged thorns, united into a shining, spindle-shaped body ; h, pear-shaped body between epithelia; i, rows of lumps and rods ; fc, medullary elements ; I, newly formed epithelium wedged in between the old. Magnified 1200 diameters. Adenoma is a common tumor, and occurs most frequently in the following localities : In the skin glandular new formations are observed, starting from the sebaceous glands as sebaceous cysts, as molluscum seba- 34 530 TUMOES. ceum, and as milium. In some instances the epithelia are trans- formed into large, shining, sometimes stratified, colloid corpuscles, which were erroneously thought to be the infectious material of the so-called mottuscum contagiosum, when a number of smaller tumors form around a large adenoma. In milium the sebaceous mass is inspissated, and by deposition of lime-salts is trans- formed into cretaceous material. Tumors of this kind are often inclosed by a thick fibrous connective-tissue capsule ; they are liable to become inflamed and ulcerated or to enter the cystic degeneration. In mucous membranes, most of the myxomatous sessile or pedunculated so-called polypous tumors are adenomatous (Bill- roth), and deserve the name myxo-adenoma. They occur in the mucosa of the nasal cavities, the throat, the larynx, the tympa- num, the rectum, and the uterus. In children, polypi occur most frequently in the rectum, while in middle-aged persons they are more commonly found in other localities. Their size varies greatly. Those of the rectum sometimes grow to be as large as a chicken's egg 5 those of the uterus reach a still larger size. Ex- ceptionally a marked papillary character is observed on the sur- face. Eectal polypi show a distinct tubular structure in the newly formed glands. Ciliated epithelia occur both on the sur- face of the tumor and in the ducts of the glands, especially in polypi of the nasal, laryngeal, and aural regions. Those of the uterus also exhibit ciliated columnar epithelium, and are found both in the mucosa of the cervical canal and in that of the uterine cavity proper. In the latter situation they are often combined with the lymphoid variety of myxomatous connective tissue, re- presenting a benign type of tumors, though sometimes occupying quite extensive tracts of the mucosa. A larger number of medullary elements in the myxomatous connective tissue indicates a more rapid growth and greater proneriess to recurrence after extirpation. Exceptionally a trans- formation into myeloma and cancer takes place, particularly after repeated attempts at eradication. In the female breast, adenoma of the acinous variety is also of common occurrence, combined with myxoma or fibroma. Sometimes the tumor is circumscribed and sharply defined from the surrounding tissue ; at other times the growth invades one or both mammary glands almost uniformly, which results in the formation of very bulky tumors. If the connective tissue is pro- fusely provided with medullary elements, the growth becomes TUMORS. 531 an adeno -myeloma, which is often combined with cystic forma- tions, and this condition was called cysto-sarcoma mammce. In such tumors, well-marked cauliflower-like vegetations protrude into the calibers of the newly formed dilated and folded glandular spaces. These vegetations were erroneously supposed to be intraglandular ; but they are obviously produced by an outgrowth of the connect- ive, tissue lying behind the glandular wall, which is usually ex- tremely vascular, and pushes and folds the wall into peculiarly complicated prolongations. Adeno-myeloma of the breast some- times breaks open and ulcerates, and the vascularized vegetations may bulge out from the ulcer, with a simultaneous rapid growth of the tumor. Nevertheless, this variety of tumor is known to be comparatively benign, and to admit of a permanent cure by extirpation. In the thyroid body adenoma often occurs, producing the disease termed goitre. Either the alveoli, containing lymph-cor- puscles and colloid material, are uniformly dilated — the so-called parenchymatous goitre — or some of the alveoli, still lined by the original embryonal epithelia, may become cystic and, in addi- tion, be provided with numerous vascularized vegetations on the inner surface of the cyst — cystic goitre. From the alveoli can- cer may also develop as a primary or secondary tumor. The majority of cysts are secondary formations of adenoma. We sometimes observe cystic spaces in polypoid tumors, and can trace the gradual transformation of the glandular epithelia into a mucous, colloid, or serous mass. As an intervening stage, a sort of myxomatous tissue is observed -arising from medullary corpuscles, into which the epithelia change before their liquefac- tion. The closed cavity of the original alveolus is gradually dis- tended and becomes a cyst, the inside wall of which is lined by flat epithelia. (See Fig. 220.) The sebaceous cysts and milium in the skin are invariably pre- ceded by a stage of adenoma. In the subcutaneous tissue other cysts may arise independently of epithelial growth — f. i., the meUceris, a cyst with honey-like contents ; the hygromata, cysts of the bursce mucosw; and the so-called ganglia, cysts of the sheaths of tendons. The cause of the appearance of cysts in such cases as these is not known. Obviously, the cystic formations which spring from an accumulation of blood, due to an extravasation, cannot be considered as tumors in the strictest sense of the word. Unquestionably, epithelial growth produces the so-called der- moid cysts, which are very probably caused by anomalous forma- 532 TUMOES. tions in embryonal development — the formation of an imperfect foetus in one perfectly developed, or intrauterine isolation by constriction of parts of the embryonal body. These cysts contain, besides epidermal tissue, hair-pouches, hairs, and also sebaceous and sudoriparous glands, cartilage, bone, and teeth. Such tumors were observed in the subcutaneous tissue, concreted with the periosteum, in the orbit and its vicinity, in the testes and the ovaries, rarely in other organs. Dermoid cysts have also been observed in the lateral regions of the neck, and, as has been FIG. 220. — FORMATION OF CYSTS IN MYXO-ADENOMA. NASAL POLYPUS. M, myxomatous connective tissue ; G, mucoid degeneration of the epithelia of an aciuous gland — a future cyst. Magnified 400 diameters. suggested by Roser, are due probably to an imperfect retro- gression of the gill canals of the embryo. Some of the cysts, occurring at the base of the oral cavity beneath the tongue, and termed ranulce, are considered dermoid cysts, especially TUMORS. 533 when their contents are dry epidermal or fatty, sebaceous masses. Cysts of the internal female genital organs are of frequent occurrence, usually found in the ovaries, and presenting either simple cysts inclosed by a comparatively thick capsule, or the so-called parenchymatous cysts, which are combined with ade- noma or cancer (cysto-adenoma, cysto-carcinoma). The latter varieties are rare in comparison with simple cysts. They are composed of one sac only, or of a number of partly closed, partly confluent, cavities — the so-called multilocular cysts. Their con- tents are either a serous or a viscid colloid liquid, with a varying amount of blood. By a gradual change in the coloring matter of the blood the contents show varying shades of brown. An admixture of pus renders the liquid cloudy, and by decomposi- tion it becomes offensive and ichorous. Whenever pus-corpuscles are present, as a general thing, we find large, coarsely granular bodies, — the so-called gorged corpuscles, — which, perhaps, are epithelia in fatty degeneration; while red blood-corpuscles, swelled, and robbed of their coloring matter, appear as pale bod- ies, containing only few granules ; these are the so-called Drys- dale's corpuscles, which are not characteristic, by any means, of the contents of an ovarian cyst. Cysts of the broad ligament also can be traced back to their epithelial origin from the paro- varies ; these single cysts almost always have very thin walls and serous contents, without any combination with solid tumors. In ovarian cysts the origin of the closed sacs from previous glandular formations, in most instances, can be easily traced. Usually, cysts originate in organs containing epithelia, — f . L, the liver, the kidneys, — though here the cysts are, in the majority of the cases, produced by an inflammatory process. The medullary corpuscles springing from the former epithelia are specially endowed with the capacity of mucoid or colloid degeneration and the formation of secondary cysts. 12. CARCINOMA. CANCER, Carcinoma is composed of connective tissue and epithelium, the latter being arranged without regularity in the form of alveoli, cords, pegs, or nests ; they are without glandular struct- ure, and they show no regular central caliber. Cancer as a primary tumor exhibits the following varieties : 534 TUMORS. (a) In the variety termed scirrhus, or hard cancer, the con- nective tissue is comparatively abundant and well developed, either of loose, fibrous structure or compact, almost homogene- ous. The epithelia are small, and arranged in narrow alveoli or in tracts, irregularly distributed throughout the connective tissue. (See Fig. 221.) The connective tissue is fully developed, but scantily sup- plied with blood-vessels. The small, polyhedral epithelia are separated from each other by light, narrow rims of cement- substance, but interconnected by conical filaments, in the same way as normal epithelia. The epithelia are clustered together in small, irregular masses, and between the clusters and the adja- cent connective tissue, in preserved specimens, a narrow space is FIG. 221. — SCIRRHUS, OR HARD CANCER OF THE FEMALE BREAST. N, alveolus, filled with epithelia; CF, connective-tissue frame, with (CC) clusters of plastids, the connective-tissue corpuscles ; PP, rows of epithelia, probably sprung from con- nective tissue. Magnified 600 diameters. often observed, containing granular matter or mucous globules, which are considered to be the offspring of endothelia, lining the inner surface of the connective-tissue cavity. This variety is the least malignant and the slowest in its growth. It appears most frequently as a primary tumor in the female breast, at the side of the nipple, often retracting the nipple and producing folds in the skin. The comparative TUMOES. 535 density of its structure, an occasional darting, lancinating pain, especially at night, are its characteristic features. This tumor may exist for eight or ten years without any rapid increase in size, and without producing much discomfort to the patient. But after a certain time, almost invariably, the growth becomes more rapid, the pain more intense, and these changes mark the transformation of the tumor into medullary cancer, with a rapid unfavorable course and termination. Cb) In the variety called epithelioma, the epithelia are found lying in the connective-tissue frame as solid pegs or tracts or nests, in the centers of which a concentric arrangement is ob- served. The most central portions of the epithelia often undergo fatty degeneration, and produce shining, irregular masses of fat, the so-called cancer-pearls. The connective tissue is either of the myxomatous or fibrous variety, supplied with a moderate amount of blood-vessels, and either exhibiting fully developed basis-sub- stance or a varying number of medullary or inflammatory cor- puscles, replacing the basis-substance. (See Fig. 222.) This tumor is of common occurrence in the skin and the mucous membranes. Some of its varieties are comparatively slightly malignant ; for instance, the so-called flat cancer (rodent ulcer) of the skin of the face, whose cancerous nature was recog- nized thirty-five years ago by F. Schuh. The flat cancer produces shallow ulcers, without marked vegetations ; the ulcer gradually penetrates into the depth of the tissues, and destroys them, including cartilage and bone. Though, owing to the presence of the small epithelial nests, the cancerous nature of this tumor cannot be doubted, it never produces secondary tumors in inter- nal organs, but after a number of years kills by exhaustion. The nodular form of epithelioma is most frequently observed on the lips, the tongue, the anus, the external genitals, and the vaginal portion of the uterus. It is rarer in the skin of the extremities, the mucosa of the larynx, and the oesophagus. Sometimes the papillary (cauliflower) character of the epi- thelioma is marked, especially in the skin of the face, at the vaginal portion of the uterus, and in the mucosa of the bladder. As before mentioned, it is highly probable that such so-called papillary cancers have started as papilloma, and have gradually changed into cancer. None of the sub-varieties of epithe- lioma, though easily infecting the neighboring lymph-ganglia, are particularly prone to produce secondary tumors in internal organs. , 536 TUMORS. (c) The variety called medullary cancer is the most malignant. It shows the following features : The epithelia are very large and irregular in shape ; sometimes they are of a polyhedral form and partly nucleated, sometimes homogeneous and shining. They exhibit endogenous multipli- cation in the shape of so-called mother cells, and also multiplica- tion .effected through wedges which spring from the living matter FIG. 222. — EPITHELIOMA OF THE PREPUCE. E, epithelial pegs ; N, epithelial nests, with a concentric arrangement of the epithelia in the centers of the pegs and nests ; P, so-called cancer-pearl in the center of the nests and pegs; C, connective tissue, crowded with medullary or inflammatory corpuscles. Magnified 200 diameters. in the cement-substance. The connective tissue is scanty ; it is fibrous in character, and incloses large and small groups of epi- thelia in closed alveoli. (See Fig. 223.) The characteristic feature of what we call medullary cancer TUMORS. 537 is, therefore, the large number of epithelial formations in com- parison with the connective tissue, the coarse granulation of the epithelia giving them the appearance of bright, homogeneous lumps — i. e., solid masses of living matter, indicating an active morbid growth of epithelia. The compact lumps of bioplasson often appear as medullary corpuscles ; the more rapid the growth of the tumor, the greater is the increase of the corpuscles and the more malignant the type of the growth. In the worst tumors of this kind, we can barely trace under the microscope fully developed, nucleated, polyhedral epithelia, arranged in nests ; the main mass of the tissue is constructed of elements closely z-f FIG. 223.— MEDULLARY CANCER OF THE PAROTID GLAND. E, regularly developed, polyhedral, nucleated epithelia, which at H, by increase of their living matter, have become shining and homogeneous ; M, medullary corpuscles in a space inclosed by living matter (so-called mother-cell) : L, vacuolation of epithelia; F, scanty con- nective-tissue frame. Magnified 600 diameters. crowded together, exhibiting all the features of medullary cor- puscles, and rendering the tumor a myeloma rather than a cancer. Transition of cancer into myeloma under these circum- stances is often observed. An originally well-developed scirrhus may gradually assume the character of a medullary cancer, and this the features of myeloma, In the clinical variety of carcinoma 538 TUMORS. termed lenticular cancer (cancer en cuirasse, Velpeau), which starts from a cancer nodule of the breast, and in a comparatively short time invades all the soft tissues of the pectoral wall, the shoulders, the upper extremities, we look in vain for the epithe- lial cancer-nests, the main bulk of the tumor being constructed like a very malignant globo-myeloma. Secondary tumors in internal organs, chiefly the lungs and the liver, often exhibit no distinct epithelial nests, but only the structure of globo- myeloma. Medullary cancer may appear primarily in any organ or tissue of the body, although unquestionably, in the majority of cases, it starts from organs which contain epithelial formations as anatomical constituents, and are, therefore, glandular. The localities where primary cancer most frequently develops are : the female breast, the cervical portion of the uterus, and the stomach. According to Virchow the order in which the organs are invaded by malignant growth in general is the following : Stomach in 34.9 per cent. ; uterus, vagina, etc., in 18.5 per cent. ; large intestine and rectum in 8.1 per cent. ; liver in 7.5 per cent. ; face, lips in 4.9 per cent. ; female breast in 4.3 per cent, of the cases ; the sum total being 78.2 per cent, of fatal cases caused by malignant tumors. The classification of cancers is, as here shown, a simple matter,, but some pathologists are anxious to construct a large number of species and sub- varieties of cancer, with corresponding Greek and Latin denominations. The term "plexiform" is suitable for the designation of epithelial tracts branching and connect- ing within the connective tissue. It may be stated as a general rule that the larger the amount of connective tissue in a certain bulk of the tumor, and the smaller the number of epithelial nests, the harder will be its consistency and the less its malig- nancy. On the contrary, the smaller the amount of connective tissue, the larger the number of epithelial nests, the greater will be its malignancy. Myxomatous connective tissue between the epithelial nests necessarily lessens the consistency of the tumor without increasing its malignancy. An important point for the determination of the degree of the malignancy of cancer is the presence of small, shining, globu- lar elements in the connective tissue. Larger numbers of these formations invariably indicate a rapid growth of the tumor, and if occurring in a very large number they render the tumor a myeloma. This condition is only found in the worst types of TUMORS. 539 medullary cancer. The pathological significance of these ele- ments differs according to the views of different authors. Those who believe the cancer epithelia to be an offspring of physiologi- cal epithelia, and consider them to have a certain specificity and independence of connective tissue (Thiersch, Billroth, Waldeyer. and others), assume that the medullary corpuscles in the cancer frame are due to an inflammation reactive upon the growth of the epithelia. While Virchow, who maintains a formation of cancer epithelia-from connective tissue, considers these corpuscles as products of the " connective-tissue cells." The following article treats this subject more in detail. THE ORIGIN OF THE CARCINOMA ELEMENTS. BY E. W. HOEBER, M. D., NEW-YORK.* Regarding the origin of the cancer elements, pathologists nowadays hold two essentially different views. Virchow first announced that " connective- tissue corpuscles " might change into epithelial bodies ; while Thiersch, Wal- deyer, and others maintained the view that epithelium is endowed with the property of an independent development ; epithelia of pathological formation, therefore, must always be the offspring of normal epithelia. The followers of the latter view seek support in the history of development, and avail them- selves of the theory of the germinal layers, as established by Remak, for the explanation of pathological occurrences. To-day, arguments of this kind are of little value. The assertions of the independent action of the germinal lay- ers fall to the ground in face of the fact that, before the appearance of such layers, the germ is entirely composed of elements destitute of any peculiar character, and it is not till later that special formations arise from these elements. We know that in inflammation the tissue returns to a juvenile condition, and breaks down into the elements from which it had sprung. Elements pro- duce their own kind only when in the embryonal condition. All observers, notwithstanding our limited knowledge as to the cause of the growth of tumors, are agreed that the parent tissue, in which a primary new formation originates, also returns to a juvenile stage or stage of indifference, in which it is capable of producing new elements. These, in further development, give rise to the characteristic tissue forms, which are mainly of two kinds : vascu- larized connective tissue and a vascular epithelium. It has been maintained that the epithelia are always offsprings of the upper and under germinal layer, while endothelia originate from the middle germinal layer, especially from the connective tissue. But even this apparently sharp distinction between epithelia and endothelia will lose its point if we take into considera- tion the fact that both epithelia and connective tissue originate from elements which are morphologically identical. Koster has attempted to explain the development of cancers from endo- * Abstract of the author's essay, " Ueber die erste Entwickluug der Krebselemente." Sitzungsber. d. Kais. Akademie d. Wissensch., 1875. 540 TUMORS. thelia of the lymph-vessels, without, however, throwing light upon this ques- tion. Recently, also, A. Classen has endeavored to include the " migrating cells " in the production of cancer, forgetting, evidently, the fact that "migrating cells " are always elements in the stage of indifference ; that epi- thelia, if fully developed, are not possessed of the capacity of migration, and that no proof has yet been furnished of a new formation of tissue from wan- dering corpuscles. The subjects of my researches were cancers which had been removed from the right parotid region, from the skin of the face, from the female breast, and from the liver. The characteristic feature common to all cancers is the FIG. 224. — CANCER OF THE SKIN OF THE PAROTID REGION. CE, large, nucleated cancer epithelia, partly separated from each other by elastic libers, E; C, unchanged fibrous connective tissue of the derma of the skin. Magnified 600 diameters. epithelial new formation, the epithelial bodies, however, varying greatly in size. The largest I saw were in the cancer of the parotid region. (See Fig. 224.) The cancer epithelia represented polygonal bodies, separated from each other by narrow rims of cement-substance having a ledge-like appearance and traversed by delicate spokes. Sometimes I saw the peg-like or alveolar for- TUMORS. 541 mations, filled with a continuous layer of bioplasson, with nuclei imbedded at regular intervals. In such layers — analogous to the so-called myeloplaxes — the cement-substance was partly or totally absent. A striking feature was that, in tumors of slow growth, the epithelia were small and their granules and lumps of bioplasson minute ; while in cancers of rapid growth the epithe- lia contained coarse granules and large nucleoli. In the cancer of the liver, which had increased rather rapidly, the epithelia exhibited a very coarse granulation, and both within and between them were seen numerous lumps of a homogeneous appearance, without a reticular structure. Many of these lumps in the alveoli had no similarity whatever with true epithelial bodies. The second constituent part of the cancer tumors — i. e., the connective tissue — especially in those of comparatively rapid growth, exhibited the so- called " small cellular infiltration." (See Fig. 225.) ,1 FIG. 225. — CANCER OF THE SKIN OF THE PAROTID REGION. A, alveolus filled with epithelia; L, so-called "small cellular" infiltration of the con- nective tissue ; E, formations within the connective tissue resembling epithelia ; V, blood- vessel in transverse section. Magnified 600 diameters. Examination with the highest powers of the microscope proved that this in- filtration consisted of an accumulation of bright, globular homogeneous lumps, on an average not reaching the size of red blood-corpuscles. Each lump was almost constantly surrounded by a layer of bioplasson, whose granules .were connected with the lumps by means of radiating filaments. The lumps assumed a violet stain after treatment with chloride of gold. They exhibited all phases of development, from compact masses to those which were pierced with vacuoles, and finally tp those showing nuclei, which were inclosed by a thin shell and contained one or two nucleoli. Evidently these were bioplasson 542 TUMORS. formations in a stage of indifference, furnishing the material for specific formations. Now, what is the source of these bodies ? We observe that they appear first in rhomboidal fields, corresponding with the territories of connective tissue. At first one or two lumps only are visible in a territory ; later the whole terri- tory is transformed into a coarsely granular bioplasson mass, which contains a varying number of globular formations. In a still more advanced stage the territory is composed of polygonal plastids. Sometimes we see the connective tissue between two alveoli filled with flat elements, some of which contain large nucleoli. In such places it is apparent that a morphological difference FIG. 226. — CANCER OF THE SKIN OF THE PAROTID KEGION. C, connective tissue ; HE, epithelia, either arranged in closed alveoli or lying in the interalveolar connective tissue. Magnified 600 diameters. does not exist between the elements occupying the alveoli and those which lie without much regularity in the neighboring connective tissue. (See Fig. 226.) In specimens from a so-called flat cancer of the skin of the face, I observed that the connective tissue of the papillae in some places was almost completely transformed into elements having the appearance of epithelia, and to such TUMORS. 543 an extent had this change progressed that only a delicate layer of fibrous con- nective tissue was left around the considerably dilated blood-vessels. Sometimes we see in the connective tissue, besides the regular alveolar formations, spindle-shaped groups composed of small epithelial elements ; many of these groups prove to be on all sides inclosed by connective tissue. Furthermore, epithelial formations occur which are traversed by a branching, shining, elastic reticulum, as illustrated in Fig. 224. The elastic fibers are arranged in such a way that the boundaries of the former territories of con- nective tissue still remain recognizable, while in some places the elastic retic- ulum replaces the epithelial cement-substance. Finally, I would draw attention to rather common formations of the tran- sition of indifferent bioplasson masses into distinct epithelial bodies. On the FIG. 227.— CANCER OF THE LIVER. L, bioplasson lump in the middle of a rhomb of basis-substance of connective tissue