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NIH Clinical Center 



SUMMARY ANNUAL REPORT OF PROGRAM 
ACTIVITIES 

October 1, 1977 through September 30, 1978 



October 1, 1977 through September 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

OFFICE OF THE DIRECTOR 



CONTENTS 

General ^^_^ 

Mission of the Clinical Center .'.".*!!.'!.* *0D-1 

Leadership Changes nn i 

ACRf :;:;:::;;::;:::;;:;;:;:;;;odI2 

New Services qjj_2 

Office of the Assistant for Bioethics ...\..\\'...\ OD-3 

Medical Board -,_, , 

safety :::::..::::::::::::::::::::::::::::;:::oS: 

Associate Program qj5_5 

Medical Information System \\\ OD-7 

Research Accomplishments nn-7 

Yvr\ ' ••««.. uu— / 

Office of Clinical and Management Systems .' . OD-9 

Office of Clinical Reports and Inquiries WW .\. OD-12 

Professional Activities !!.*!!!.*!!.'!.'!.'!! !oD-24 

Bibliography .!.!!..!.!!..!!.!!!!!].. OD-25 

Normal Volunteer Program .*!.'!.*,"." OD-27 

Patient Activity Section !!!!.'.*!!!!!!.'.'!!.'! .'oD-35 

Anesthesiology Department .'.*.'!.'!.'!.'.'!.',*!.'.' OD-42 



i'lationa! In^titntes &f HsaM 
Bathesda, Marvtand 20014 



/9 7f 



October 1, 1977 through September 30, 1978 



PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

OFFICE OF THE DIRECTOR 

General 

The Clinical Center, celebrating its 25th Anniversary this past year, 
provided facilities, patient care, and support services for NIH physicians 
who conduct clinical research for eight of the eleven Institutes and the 
National Institute of Mental Health. With the exception of direct 
physician care, hospital services were provided by Clinical Center staff. 
Department members conducted research in their own specialties to develop 
and improve current technology to meet the needs of the clinical programs 
and collaborated with Institute scientists. Opportunities for advanced 
training were provided to young physicians, medical students, nursing 
students, and members of the paramedical professions. 

Mission of the Clinical Center 

(1) To ensure the highest possible level of medical care to each 
patient; 

(2) To provide optimal resources and facilities for clinical research; 

(3) To perform research on methods and systems involved in patient 
care and study; 

(4) To disseminate information to professionals and to the public 
relevant to clinical investigation; 

(5) To develop and maintain training programs in the techniques and 
ethics of biomedical research and clinical research; 

(6) To interact with scientists and physicians, nationally and inter- 
nationally, on mutual problems of clinical research, such as 
policy, education, ethics, and priorities. 

The Clinical Center was reviewed by a committee of the Joint Commission 

on Accreditation of Hospitals (JCAH) and awarded full two-year accreditation. 

The accreditation will be effective until October, 1979. 

Leadership Changes 

Dr. Jay Shapiro, formerly director of medical and educational affairs 
at the Greater Southeast Community Hospital, Washington, DC, joined 
the Clinical Center Executive Staff as Associate Director for Education 
and Training. He replaces Dr. Philippe V. Cardon, Jr., who will 
retire from that post at the end of September. 



Ambulatory Care Research Facility ^^ 

Stage I of ACRP construction, which included all subterranean structures, 
was completed on schedule this past year. In September nine hundred 
underground parking spaces were turned over to NIH. 

Stage II construction has begun. Included in this phase are the Departments 
of Nuclear Medicine, Radiology, Clinical Pathology, and Surgery (all to 
be located on the first two floors of the new building) and the 13-story ^ 
structure which will contain clinics and basic laboratories. 

The ACRF/CC Modernization Committee, representing the NIH community, continued 
to address programmatic, design and construction issues related to integrating 
the old and new facilities. 

During the fiscal year a number of construction and renovation projects 
were completed or undertaken. The 9-West NICHD patient care pediatric 
unit was finished and occupied in September; construction of the 9-bed 
medical intensive care unit commenced immediately thereafter. 

Design of the NCI 13 N/E unit was completed; construction will begin in 
January. Expansion of the 9-E patient care unit to include the North 
Corridor will make this 36-bed unit the largest in the hospital. 

Consolidation of the surgical programs onto the second floor has begun; 
the 2-West area (previously occupied by NIMH) is being renovated into |^ 
a heart surgical patient care unit. Design was completed by 6-D wing ^ 
(previously physician on-call rooms) , to accommodate the 2-West NIMH program. 

A number of hospital areas were closed and departments relocated to ac- 
commodate ACRF construction: the Employee Health Service moved from B- 
2 wing to Building 31; activities in the 2D north wing were relocated. 

New clinic facilities were built to accommodate expanding outpatient programs 
and to offset the loss of space caused by ACRE construction. The project 
includes the remodeling of NIMH facilities, the addition of satellite 
services in X-ray, clinical pathology, and nutrition, and a general expansion 
of examination and treatment rooms. 

Other projects completed this year include construction of a recovery 
room within the lOth-floor operating room, the conversion of the 9th-floor 
solarium into a 50-person conference room, and the activation of a trash 
chute system. 

NEV; SERVICES 



Installation of the Technicon Medical Information System (MIS) was 
completed in all inpatient units. This is a total hospital computer 
system through which all patient care related activities in the 
Clinical Center are initiated. The primary functions of the MIS 
are to accept physicians' orders, communicate the contents of those 



OD-2 



orders to all Clinical Center departments, and generate computer 
printed portions of the medical record such as X-ray reports, 
medications given and nursing notes. Users of MIS include physicians, 
nurses, and ancillary medical personnel. 

In June a major portion of the laboratory link directly connecting 
the MIS and the Honeywell system in the laboratory was installed. 
This new feature eliminates the need for laboratory request cards 
for inpatient test ordering and facilitates specimen collection 
accession. 

2) An ENT Consultation Service has been established in collaboration 
with the National Naval Medical Center. Dr. Fred Stucker, Chairman 

of the NNMC Department of Otolaryngology, has assigned senior residents 
to provide consultations to the CC. The agreement is of mutual benefit, 
with the Navy otolaryngologists receiving clinical experience and the 
CC having the benefit of in-house ENT consultations. 

3) Office space for an outpatient dietitian was allocated and this 
service was initiated on a full-time basis in December. The outpatient 
dietitian provides professional services to investigators developing 
outpatient studies involving counseling and collection of data. This 
service also provides continuity for follow-up in patient studies 
involving diet. 

Office of the Assistant for Bioethics to the Director, Clinical Center 

John C. Fletcher, Ph.D. began work in this new assignment September 5, 

1977. His responsibilities cover three major areas: 1) assistance to 

the Director with his review of protocols, 2) consultation with investigators, 

nurses, or units requesting help with ethical problems, 3) research on 

medical and research ethics. 

The Director asks for the view of the Assistant for Bioethics on aspects 

of protocols that he or one of the Associate Directors thinks presents 

an ethical problem. Most often the problem is in the consent document. 

Occasionally, the problem has to do with the objective of the research 

or the selection of subjects. From time to time conferences are held between 

the principal investigator(s) , the Director, and the Assistant for Bioethics 

to clarify issues and resolve differences. 

Requests for ethics consultation have come from units or investigators 
about the following types of problems: refusal of blood transfusion on 
grounds of religious principle, removal of desperately ill patient from a 
protocol, refusal of psychiatric patient to consent to a diagnostic prodedure, 
staff relations following an ethical dispute, dispute about the need for 
therapeutic abortion between a patient and members of staff, and various 
types of proxy consent issues. Dr. Fletcher also is teaching a bioethics 
course for members of the Administrative Council of the Clinical Center's 
Nursing Department. The objective of the course is to enable each 
participant to become a more effective ethics consultant in conflict situations. 



OD-3 



Other activities during the year include: (1) an orientation and training ^^ 
meeting for lay members of Clinical Research Subpanels, (2) a lecture to 
normal volunteers on the DREW policy for protection of hu m an subjects, (3) 
classes for trainees in supervision on ethical issues in supervision (4) 
a lecture in the STEP program on medical ethics on the development of 
bioethics since 1966, (5) the supervision of an intern in bioethics, 
Marian Secundy, M.S.W. 

Medical Board H^ 

The primary objective for the 1977-1978 Medical Board was to maintain and, 
where possible, increase the quality of care provided at the Clinical 
Center. Achieving high quality takes prospective action to establish 
standards, action on processes - to carry out policies, and retrospective 
outcome evaluation to see that compliance with standards have been achieved. 
These three ingredients were provided through actions of the Quality 
Assurance Committee and its subcommittees. 

The Clinical Associate Subcommittee administered its second annual 
survey. Questionnaires were sent to all Clinical Associates in an effort to 
"grade" the consultative and support services provided within the Clinical 
Center. Deficiencies uncovered in this manner received priority attention 
from the full Board and the hospital's administrative staff. Two changes 
resulting from these surveys included: a requirement that all consultations 
rendered by junior staff members be reviewed on a timely basis by a senior 
consultant, and the establishment of specialty consultation programs /clinics^k 
e.g., ENT. 

Medical staff accountability remained an important issue of discussion 
during the year. Attention was focused on the subject of clinical privilege 
delineation. In the previous year a program was established wherein 
the Clinical Director would grant specific privileges to those clinicians 
under his supervision. This year the Board considered and developed pertinent 
policy statements regarding those individuals with authority to perform 
surgical procedures in the operating rooms; the granting of specific 
privileges to non-physician/dentist health professionals who work independently 
with only general medical staff supervision (staff affiliates) ; and the 
periodic reappraisal of physician health status. 

The availability and accuracy of medical records is critical to the quality 
of medical care. The Medical Record Subcommittee was charged with developing 
a system to prevent record loss, make records available for research review 
and patient care emergencies, and at the same time to maintain confidentially^ 
of the information contained in the record. This was accomplished by ^P 
restricting the sign-out of records to those physicians participating in 
patient care and to limit the loan period to forty-eight (48) hours. After 
a brief trial period, it was found that most physicians could accomplish 
their record reviews within the specified time frames. Also, records were 
found to be available whenever an emergency admission was necessitated. 



OD-4 



The accuracy and timeliness of record completion was improved after it 
became mandatory for a senior investigator in addition to the clinical 
associate, to sign all discharge summaries.' 

Other areas of concern addressed by the Medical Board included the 
establishment of a "No Code" policy (orders not to attempt cardiac 
resuscitation), informed consent, compensation of injured research subjects, 
centralized medical record dictation, patient medication labeling, and the 
self -administration of medications. 

Safety 

Clinical Center Multi-Disciplinary Committee activity continues to develop 
and expand. A main event this year involved the development of a committee 
functional statement and its acceptance by both the Clinical Center 
Director and the Medical Board. 

Other noteworthy progress included: a) rewriting the Fire and Other Hazardous 
Emergency Booklet, 6) revision of the fire training program, c) development 
and distribution of a general evacuation diagram to each Building occupant, 
d) revision of the Master Disaster Plan and the Department plans, e) rewriting 
of a Building Evacuation Plan and submission for approval, f) preparation 
and acceptance of fire safety related policies, g) institution of a quarterly 
safety seminar program for all Building Occupants, h) assisting the Food 
and Drug Administration in the development of two medical devices standards 
i) participation in the review of two National Fire Protection Association 
Standards affecting patient care. 

A team safety inspection program has been implemented with the goal of 
assuring that structural safety features have been provided by renovated 
and/or newly construction facilities. 

Ongoing programs continue in: waste disposal, water supply, accident/incident 
reporting, emergency incident critiques, and corridor clean-up. 

Office of the Associate Director 

Philippe V. Cardon, M.D., Associate Director of the Clinical Center announced 
his plans for retirement as of September, 1978. Dr. Cardon' s successor, 
Dr. Jay Shapiro, assxamed the position of Acting Associate Director on April 1, 
1978. 

The activities of this office during 1978 centered on the following: 
Clinical Associate Program, Medical Student Electives, Continuing Medical 
Education, the Education Committee of the Medical Board, the MIS Program, 
and participation in other Clinical Center and NIH Activities. 

The Associate Program: There were 204 Clinical, A2 Research, and 3 Staff 
Associates at the Clinical Center during 1978. 



OD-5 



Mrs. Rachael Peabody conducted the application and selection process for 
Clinical Associates. 850 applications were sent to condidates, 203 were 
returned; of these, 141 were interviewed and 75 selected for appointment in 
1979 and 1980 through the NIH matching program. This number is exclusive 
of appointments made outside the formal matching process. The number of 
positions offered for 1979 were satisfactorily filled. Although this is 
the smallest number selected via the matching process in recent years, the 
positions available for 1979 were filled with trainees of outstanding ability. 
Institute staffs and the Education Committee have reviewed the implications o^f 
a diminished interest in research training and careers which is apparent 
nationally and reflected in recruiting for Clinical Associates. A reorganized 
recruiting effort is now being implemented, the major thrust of which will 
be to familiarize medical students and recent graduates with the variety of 
excellent training opportunities available at the NIH. 

Medical Student Electives: The Student Elective Program is assuming a more 
important role as a method for recruiting future Clinical Associates. 
During 1977-78 over 100 students participated in the follovring clinical 
electives: Computers (Dr. W. Mohler) , Endocrinology (Dr. B. Weintraub) , 
Genetics (Dr. J. Schulman) , Immunology (Dr. A. Steinberg), Nuclear Medicine 
(Dr. G. Johnston), Oncology-Hematology (Dr. H. Gralnick) , Psychopharmacology 
(Dr. M. Ebert) , and Surgical Oncology (Dr. S. Rosenberg). 

Two new electives were announced for 1979: Anesthesiology (Dr. K. Huttner) 
and P^diology (Dr. J. Doppman) . 

To strengthen the elective program new promotional flyers and a newly de- 
signed catalogue have been produced for mailing to second and third year 
medical students throughout the country. 

Continuing Medical Education: The Clinical Center-FAES Continuing Education 
program was surveyed by the AMA Liaison Committee on Continuing Education. 
34 courses were approved for credit, an additional 10 were subsequently 
approved by the Education Committee. Only 17 had been approved for Category 
1 credit in 1977. 

A report is not yet available from the AMA. Clinical Center-FAES Category 1 
programs have appeared in the Annual 1978-1979 AMA Continuing Education Guide, 

Clinical Directors have been asked to request approval for appropriate 
teaching sessions not now approved for Category 1 credit. There has been a 
good response to this request the result of which will be greater access to 
Category 1 programs for those staff requiring this for relicensure or member- 
ship in professional organizations. 

The Education Committee: The Associate Director serves as Executive Secretary 
for the Education Committee of the Medical Board. The Education Committee has 
reviewed the results of the Associate matching program for 1978 and has 
inititated revisions in the matching system to deal with difficulties encounter- 
ed by specific Institutes. In order to more effectively compete with other 
educational institutions, the Institutes will be free to interview and select^ 
Clinical Associates throughout the year except for the dates January 15 - 

OD-6 



March 30, during which time applications are being actively processed for 
the intramural match. Under unusual circumstances recruiting may also occur 
during that period. 

The Education Committee has also approved guidelines for advertising of 
associateships in medical journals and will monitor this process through its 
Subcommittee on Advertising. 

MIS Program: In view of the anticipated departure on sabbatical of the Deputy 
Director, CC, the Associate Director has actively participated in the activities 
of the MIS Executive Committee. Among various concerns of that group have 
been training exercises for Clinical Associates, the evaluation of the impact 
of this system on Clinical Associate research and patient care functions, and 
the implementation and on-going development of the computer system on the 
medical floors of the Clinical Center. 

During this year MIS became operational on all nursing units, as did the 
laboratory specimen pickup system. A laboratory reporting link and inclusion 
of the outpatient department in IHS are major projects scheduled for imple- 
mentation during late 1978 and early 1979. 

Participation in Other Clinical Center/NIH Activities: Dr. Cardon was course 
coordinator for the FAES-MED 610 course; approximately 80 physicians attended 
the 2 semester lecture series. Dr. Shapiro will coordinate the course for 
'78-' 79 academic year. 

Dr. Shapiro chairs the Clinical Center Surgical Administrative Committee. 
Dr. Cardon has participated as a member of the NIH-OMAR Committee, the Clinical 
Center Medical Board, NIH Clinical Trials Committee and the PHS Career 
Developm.ent Committee, the Career Development Coordinating Council, and the 
Surgeon General's Medical Review Board. 

Research Accomplishments 

Clinical Center investigators produced a number of notable research 
advances this past year. Some of these may soon affect national 
and global health care practices and policies. 

This has been a significant year in hepatitis research for Clinical Center 
Blood Bank investigators, with two studies achieving national prominence. 

The first study demonstrated in a chimpanzee model that while freezing and 
deglycerolization of human blood could render it free of hepatitis B surface 
antigen, it did not remove hepatitis B infectivity. Frozen deglycerolized 
red cells have many well-documented advantages; but their major potential 
advantages was their postulated ability to prevent human hepatitis. Their 
studies did not support this. 

Last year it was reported that a hitherto unknown form of hepatitis had 
been uncovered by scientists from the Clinical Center Blood Bank and NIAID. 



OD-7 



The non-A, non-B hepatitis was identified as being responsible for 80%-90% r~ 
of post-transfusion hepatitis occurring in patients receiving noncommercial v- 
blood from donors screened for the hepatitis B surface antigen. 

This year Clinical Center investigators, together with scientists from FDA's 

Bureau of Biologies demonstrated for the first time that a transmissible 

agent which can remain infectious over prolonged periods is responsible 

for non-A, non-B. It is hoped that these studies will lead to the visualization 

of virus material, to the development of a serologic test for non-A, non- 

B hepatitis, and ultimately to the elimination of post-transfusion hepatitis. '■- 

This past year Clinical Center scientists expanded their clinical evaluations 
of a new computer-based radiotracer imaging procedure called ECG-gated scinti- 
graphic angiocardiography which they developed in cooperation with MLBI 
and DCRT scientists. The procedure, which offers non- invasive visualization 
of the working heart, yields quantitative measures of left ventricular functions 
This technique is superior to the exercise electrocardiogram for detecting 
heart disease, particularly coronary artery disease. 

A Clinical Center worker has developed a simple device for concentrating 
parasite eggs, larvae, and protozoa from stool samples. A patent has been 
granted for the new device which consists of a tube divided into an upper and 
lower chamber by a filter. The stool sample is emulsified in the upper 
chamber where possible pathogens are killed. The emulsion is them filtered 
into the lower chamber and centrifuged. The resultant pellet contains the 
eggs and larvae and gives up to 300 times the yield of the direct wet mount 
method. The new device saves time, recovers more pathogens, and is safer '^ 
for technologists. 

A Rhesus monkey model has been successfully developed to examine the 
process of platelet aging. With this model it was shovm that young 
platelets are larger and denser on the average compared to old platelets. 
This observation was correlated with previous work from this laboratory 
which demonstrated that with aging various intrinsic platelet properties 
decrease. Although the specific factor which limits platelet life span 
has not been identified, we are now able to use these platelet age dependent 
properties to estimate mean platelet age. This technique is currently being 
applied to analyze the blood of patients who have too few platelets and 
to provide accurate information as to the cause of these disorders. This 
promises to be a powerful new tool in this area. 

Recent advances in the study of the factor Vlll/von Willebrand factor protein 
have shown that the penultimate galactose residue of the normal protein 
is necessary for the expression of the von Willebrand factor activity of , I 
the normal protein. Some patients with von Willebrand 's disease have a 
decreased galactose content of their protein. Other evidence of abnormalities 
and heterogeneity of the factor Vlll/von Willebrand factor protein in von 
Willebrand 's disease and hemophilia have been demonstrated by immunologic 
techniques and by identifying the protein molecules involved in platelet 
binding. These studies suggest a marked heterogeneity of the factor Vlll/von 
Willebrand factor protein and offer insights into the mechanisms of the 
hemostatic defects in hemophilia and von Willebrand 's disease. ,^ 



Clinical Center investigators, working in collaboration with scientists from 
New York University, have found a way to qualitatively improve red cell trans- ■- '- 
fusion. Red cells in a Shesua monkey, separated according to cell age and 
different age-dependent cohorts of cells, were transfused into these monkeys. 
Young cells showed improved survival after transfusion compared to the older 
cells. This may be a very aseful way to prepare cells for a transfusion 
regimen for patients requiring chronic transfusions. 

EEC 

The Clinical Center released its first Affirmative Action Plan for Employment 
Opportunity which received desk-to-desk distribution to all employees. The 
Director and the EEO Coordinator met with Heads of Departments in which 
minority and/or female employees are underrepresented. These meetings were 
designed to develop strategies to intensify affirmative action initiatives 
to increase the employment of minorities and/women in those occupational 
series in which they are underrepresented. 

The Clinical Center EEO Advisory Committee participated in a two day training 
session to familiarize its members with their responsibilities and to increase 
their understanding of the EEO Program in the federal sector. Clinical 
Center employees elected the following representatives and alternates to 
the Advisory Committee: Ms. Minnie Todd and Mr. Coleman Chandler, Nutrition 
Department; Mr. Frank Greenwell and Mr. George Gaskins, Fabric Care Department; 
Ms. Geri Mann and Ms. Mary Aber, Social Work, Rehabilitation and Spiritual 
Ministry Departments; Mr. Norman Turner and Mr. Andrew Tyler, Property Manage- 
ment Section; Ms. Rose Lawrence and Mr. Neil French, Diagnostic Radiology 
and Nuclear Medicine Departments; Ms. Patricia Seto and Mr. Joseph Middleton, 
Pharmacy Department; Mr. Thomas Bonnar and Ms. Cathy Hawkins, Outpatient 
Department . 

Ms. Elsilee Des Bordes, Nursing, and Chaplain Robert White, Spiritual Ministry 
were appointed to three year terms as EEO Counselors. 

EEO Awards were presented to Ms. Adrienne Hatchett, Personnel Specialist, 
Office of Administrative Management; Dr. Ronald J. Elin, Chief, Clinical 
Pathology Department; Mr. Walter E. Moten, Assistant Chief, Environmental^ 
Sanitation Control Department; and Ms. Jennie L. Mauck, Personnel Specialist, 
Office of Administrative Management. 

Office of Clinical and Management Systems 

I. Missions and Goals ; The mission of the Office of Clinical and Management 
Systems is to assist the staff of the Clinical Center by providing services 
of systems analysis, computer systems evaluation, and management engineering. 

The goals are fourfold: 

1) Coordinate the planning, development, inplementation, and operation 
of all computer and automated systems within the Clinical Center; 

2) Provide working liaison between the Clinical Center, the Division of 
Computer Research and Technology, and the various Institutes to assure 

CD- 9 



optimal and integrated clinical management and information systems; ^ 

3) Assist Clinical Center management in application of techniques of opera- 
tional planning; facility development; resource allocation, and program 
evaluation and review; and, 

4) Initiate and conduct research and education programs in clinical and 
management systems. 

II. Department Activities: 



^ 



A. Medical Information System: The largest portion of the Office's 
activities during this period involved the continuing implementation of 
the computerized Medical Information System (MIS) . The ten remaining in- 
patient nursing units were added to the system, bringing the implementation 
on inpatient services to the 100% mark. A new documentation and tracking 
scheme enabled the systems team to gather, process, and implement almost 
200 protocol and prestructured order sets in the system. More than 600 
change requests, reflecting user input on system problems and enhancements 
were processed to completion during this time. The level of physician 
participation in the system increased to the point where over 80% of physi- 
cians orders are entered directly into the system by physicians themselves. 
A new physician training package, involving self- instructional modules, 

was developed and put into use in time to train 94 new Clinical Associates 
and staff members in early July, usually involving no more than 4 classhours 
per physician for MIS training. A videotape explaining the MIS System 
and its use in the Clinical Center was developed by the OCAMS staff and t0 
Office of Clinical Reports and Inquiries and put into use for physician 
and CC staff orientation. Ordering of Radiation Oncology and Cytology 
consults was added to the system to add to the physician convenience in 
ordering these services. A new printout, depicting vital signs in a 
graphic form for use by the physician in evaluating trends of these para- 
meters was initiated on a daily basis. Major revisions were made to the 
system for ordering and charting intravenous fluids with additives. As 
the year was ending, the implementation of a link between the Honeywell 
Laboratory Computer and the MIS Computer was being completed. This link 
enables orders from the MIS System to produce accession documents for the 
laboratory to use in processing specimens. ^-Jhen laboratory test results 
are certified by the technologists, these results are electronically 
transmitted to the MIS System for retrieval by physicians at terminals 
throughout the hospital. This major system feature had been three years 
in development and marks a major milestone in the installation of a 
"total" computerized medical information system. 

(I 

B. Clinical Information Utility: The Clinical Information Utility, which - 

stores medical information at DCRT and retrieves it on request for medical 
researchers in the various Institutes, continued to serve the needs of 
the staff throughout the campus. The medications file was brought to 
completion and systems analysis began on inclusion of vital signs and 
consultation reports for retrieval purposes. 



OD-10 



C. Laboratory Computer System: The Chief, OGAMS, continued to serve as 
the Chief, Laboratory Computer Service, Clinical Pathology Department, per- 
mitting this office to support the Laboratory Computer Service, especially 
in matters pertaining to the Honeywell Laboratory Information System. Dur- 
ing the year, an interface was designed and implemented by OCAMS staff in 
conjunction with CP staff, to enable results from the 19-channel SMAC 
Analyzer to be transmitted electronically and automatically to the Honey- 
well Laboratory Computer. The OCAMS staff also participated extensively 
with the Clinical Pathology staff in systems design and modifications within 
the laboratory to maximize the effectiveness of the Honeywell/MIS informa- 
tion link. Also during the year, automatic transmission of Admission, 
Transfer, and Discharge data from the MIS computer to the Honeywell com- 
puter was installed. 

D. Workload Reporting System for Clinical Center Departments - (P^MS - 
Resource Monitoring System) : The RMS continues to serve the needs of the 
Clinical Center for budgetary planning. Reporting was changed to a 
quarterly basis during this year to synchronize the reporting periods for 
the RMS Report with those of the Manpower Management Program Report. 

E. Bed Allocation Committee: Members of the OCAMS staff continue their 
participation in the Clinical Center Bed Allocation Committee. A major 
reporting scheme was designed this year so that input from nursing units 
on beds occupied, beds available for loan to other Institutes, and nurs- 
ing manhours expended in patient care were forwarded for batch computer 
processing. From this data, detailed reports for staff allocation, utiliza- 
tion, and bed availability could be produced for analysis and management 
decision making. 

F. Material Handling: Responsibility for the planning of material handl- 
ing and materials management in the ACRF was shifted to the OCAMS staff. 
This activity has involved site visits to locations featuring automated 
material handling systems and integrated material management programs. 
This major portion of the ACPOF program requires Industrial Engineering 
and management surveys in an area which will prevade all aspects of build- 
ing operations in the 1980' s. 

G. Outside Activities: The Office continues to be a resource for the 
hospital community in fields of medical information systems, laboratory 
computer systems, and management information systems. Papers were pre- 
sented to the First Annual Symposium on Computer Applications in Medical 
Care of the Institute of Electronic and Electrical Engineers Computer 
Society, the Annual Joint Systems Conference of the Hospital Management 
Systems Society and the American Institute of Industrial Engineers Health 
Services Division, the Productivity in Radiology Systems Forum of the 
Center for Hospital Management Engineering, and the American Hospital As- 
sociation 8th Annual Institute on Computerized Hospital Information Sys- 
tems. In addition, the Chief, OCAJffi , was elected President of the MISA 
(Medical Information Systems Association) , a Users Group representing 
clients of the contractor providing us with the medical information sys- 
tem. Also, a staff member was elected Second Vice-Chairman of the Maryland 
Hospital Education Institute. Staff members also serve on various NIH 

OD-11 



and other agency cotninittees, including the American College of Surgeons t 
Patient Safety Project Connnittee, and a Data Processing Curriculum Develop- 
ment Coranlttee for the Health Record Technology School of the USPES. 

H. Staffing: The Office attempted to hire an additional Management Analyst 
during the year but was unsuccessful in obtaining a suitable candidate. 
The staff therefore remains at three full-time employees. The Clinical 
Pathology resident who had been serving the office in conjunction with 
laboratory related matters, phased into a full-time role in the Clinical f^. 
Pathology Department, thus, removing this resource from the office as well. 

III. Future Objectives : 

A. Foremost in the objectives for the coming year is the completion of the 
MIS installation in the Outpatient Services, thus making the system of 
service to the total hospital. In conjunction with this, a major goal is 
to complete the automation of the link between the Laboratory Information 
System and the MIS so that accessioning, as well as result reporting, are 
automatic. This should enhance the service to the medical staff as well 

as reduce manpower requirements in the Clinical Pathology Department. 

B. Another objective for the year will be to complete the Data Base 
Analyses for the Clinical Information Utility. 

C. The RMS System is in dire need of updating in several departments 
which have changed their operating modes, as well as in the constant work i 
area of all departments on the System. It is an objective for the coming * 
year to complete the constant work evaluations for all departments and do 
reevaluations in Clinical Pathology, Diagnostic Radiology, Pharmacy, and 
Nuclear Medicine, as staffing will allow. 

D. The Office expects to fill the position for I^nagement Analyst /Industrial 
Engineer at the GS 11/12 level to provide greater capability to handle 
projects involving departmental workload analysis and operations. 

E. A major thrust for the coming year will be the design and conduct 

of studies aimed at evaluation of the MIS as a tool in the Clinical Center 
patient care and research effort. These studies will be directed at deter- 
mining whether the operation the MIS System in its current off-site mode is 
optimum in terms of our data processing needs. Also, strong emphasis will 
be placed on evaluating MIS as to whether it has fulfilled its objective in 
the areas of optimizing patient care information, communications, and 
supporting the medical researcher in his work. , 

w 

Office of Clinical Reports and Inquiries 

Clinical Center information, publications, press, and public affairs 
activities are centered in the Office of Clinical Reports and Inquiries. 
The office is responsible for advising the Director and Executive Staff 
on ways to enhance the Clinical Center's public and professional image 
as a preeminent clinical research facility, and on the effective interpre-- 



OD-12 



tation and reporting of research findings produced within the Center. These 
findings are of interest and concern to many audiences, including Congress, 
the Department and other Government agencies, scientists, physicians, voluntary 
health agencies, and the general public. 

The Office initiates many programs and responds to Congressional and De- 
partmental, NIH, and internal and public requests. It keeps all Clinical 
Center personnel informed of hospital activities, provides all hospital 
departments with communications assistance, and supports the functions 
of the CC s hospital service departments to ensure the delivery of the 
highest quality of patient care. 

Staff Communications 

Physician Recruitment An aggressive national recruiting program to attract 
top candidates to the NIH medical elective and associate training programs 
was inaugurated this past year with the OCR&I and the Office of the Associate 
Director for Education and Training sharing the responsibility for this 
vitally important project. 

The plan calls for continuous exposure throughout the year using journal 
advertisements, direct mailings of brochures and flyers, and selective 
mailings of catalogs and other materials to key individuals and institutions 
who could disseminate this information or make it available to students. 

One of the first projects undertaken by OCR&I was the redesigning and 
rewriting of the associate catalogue and brochure. These efforts have 
produced readable and informative publications which students and advisors 
should find very helpful as guides to the training programs at the Clinical 
Center. The cover design of these publications has been adapted for use 
on posters and advertisements to call attention to a unified NIH training 
program. 

Unification is more than symbolic. The OCR&I and the Office of the Associate 
Director for Education and Training will be developing on a continuous 
basis generic promotional materials on all Institute programs. 

The OCR&I, Associate Director, and Clinical Center Education Committee 

will assist the Institutes in developing their own, more specific promotional 

materials and together with the Education Committee and its Advertising 

Subcommittee, will review materials for conformity and adherence to established 

guidelines. 

Department Pamphlets & Displays: Last year an extensive program of employee 
communications was undertaken to help promote a sense of unity essential 
to the smooth operation of the- hospital. This effort continues on several 
fronts and includes OCR&I 's efforts this past year to unify all Clinical 
Center publications and to establish a Clinical Center identity. A format 
has been developed and used already for several publications, including 
handbooks and brochures prepared for Clinical Center departments to acquaint 
personnel with special procedures relating to those departments. Publications 



OD-13 



were prepared for Office of Clinical and Management Systems, Social Work, ^ 
Training, Diagnostic Radiology, Normal Volunteers, Nursing, and Staff Physi-V 



Closeup : The employee newsletter Closeup appeared monthly and included 
feature articles on such topics as the CC Volunteers, the Center's 25th 
Anniversary celebration and profiles of the sixty-one individuals who have 
worked at the Center since it opened, and the Fabric Care Department Open 
House commemorating its new facilities. £ 

Director' s Newsletter ; The Information Office continued to coordinate 
preparation of Director's Update which the Clinical Center Director, Mortimer 
B. Lipsett, M.D. initiated last year as a newletter to communicate clinical 
information to over seven hundred physicians in the Clinical Center. 

MIS Videotape : This office also developed an educational videotape on 
the Medical Information System which briefly explained how the system works 
and its communication and research functions. The videotape is the first 
phase of a newly implemented educational approach to teaching physicians, 
nurses, and other CC personnel in the use of the computer system. The script 
was written in collaboration with the OCAMS and the MIS executive committee. 
Filming was coordinated by this office and OCAMS with the help of various 
CC departments. The film was completed by the NIH Audiovisual Section, 
TAS, and shown to the new group of Associates in mid- July. 

Patient Communications Program 

Last year's beginning efforts to develop a comprehensive information program 

for patients on hospital facilities and services resulted in the first 

edition of the Clinical Center Patient's Handbook and the development of 

the Patient's Bill of Rights as well as a document on the Privacy Act. 

Over the past year the OCR&I began to develop inserts for the handbook 

that would provide patients with individualized information about the specific 

nursing units and medical programs they will encounter. 

In addition, maps of various hospital services and a directory of often- 
used telephone numbers was prepared in insert-form. 

The OCR£(I, in anticipating its leadership role in the utilization of the 
newly installed closed circuit television system for patient and staff 
orientation, education, and recreation, began evaluating the needs of the 
Clinical Center departments and establishing a dialogue with departments 
to develop an operational plan. The OCR&I employed the services of Dr. 
Elmer Friman, Director of the Medical Educational Resources Program at T 
the Indiana University School of Medicine, Indianapolis, Indiana, to evaluate 
and critique the proposed television system and to make recommendations, 
to help ensure effective operation. Dr. Friman' s report which he made shortly 
before his untimely death indicated that the Clinical Center can proceed 
without much difficulty into effective programming. The televisions already 
are in place in all patient rooms and broadcast commercial stations. Installa- 
tion of relay equipment is expected in the early fall to permit broadcast 
over the closed channels. %, 

OD-14 



The OCR&I provides patient recruiting services to Clinical Center physicians 
needing patients for particular research studies. Twenty-one announcements 
of new protocols were sent to physicians throughout the Metropolitan area 
on a regular basis, notifying them of the latest NIH intramural clinical 
programs to which they may nominate patients. 

Clinical Reports and Scientific Publications 

The proceedings of 10 Combined Clinical Staff Conferences were edited by 
members of this office and by contract editors. These papers were prepared 
for publication in the Annals of Internal Medicine , and this office sent 
out approximately 28,000 notices to physicians on the availability of these 
papers in reprint form. Nearly 10,000 reprints were then sent to requesting 
physicians. These conferences and the proceedings are a primary means 
of sharing the most recent results, new techniques and findings, and experi- 
ments of NIH investigators with physicians and scientists throughout the 
nation and overseas. 

The office edited 129 professional papers prepared by CC staff for publica- 
tion in medical and scientific journals, and provided editorial services 
during manuscript preparation. 

Seven nursing conferences were presented this year by the Nursing Department. 
In addition to assisting in the preparation of programs, invitations, and 
publicity, the OCR&I prepared and printed conference proceedings to share 
nursing techniques developed at the Clinical Center with nurses throughout 
the Nation. 

Public Communications Program 

One of the missions of the Clinical Center is to disseminate information 
to professionals and to the public relevant to clinical investigation. 
The Center's unique status brings together leading researchers whose work 
at the frontiers of science produces many important advances in understanding 
the nature of diseases and in caring for patients. 

Medicine for the Layman : To disseminate some of this information to the 
public, the Clinical Center last year initiated a series of health seminars 
called " Medicine for the Layman." Leading NIH scientists presented timely 
and informative talks that covered normal body function and what can sometimes 
go wrong. 

The series was itself an experiment which proved to be highly popular among - 

many Greater Washington residents. Word of the series' success traveled 

surprisingly far with organizations from around the country requesting 
advice. 

This success prompted the OCR&I to develop a series of pamphlets and videotapes 
based on the lectures for national distribution. The series continues 
this fall with twelve additional topics. 



OD-15 



Public Inquiries : The OCR&I also receives numerous calls and letters asking 
about admission policies and/or information relating to diseases or health '' 
care. In addition, last year the hospital's preadmission functions were 
turned over to OCR&I. Approximately 320 patient referrals to the Clinical 
Center from private physicians were processed through this office. 

The office also answered approximately 200 Congressional and general inquiries 
by letter and telephone. 

Press ? Clinical Center Programs received extensive national attention ^ 
this past year. The OCH&I called a press conference in March to brief 
the press on recent findings by Dr. Harvey Alter (CC) and Dr. Edward Tabor 
CFDA) regarding non-A, non-B hepatitis. They demonstrated in chimpanzees, 
for the first time, that a transmissible agent was responsible for this 
form of hepatitis. The story received network television coverage as well 
as coverage by the wire services and major metropolitan newspapers. 

A program on NIH featuring the Clinical Center was filmed by WTOP for 
use on their network morning show, House Calls. Dr. Fredrickson was the 
special guest. 

Press and media activity was high for the Medicine for the Layman series. 
Lecture participants appeared on Channel 5's Panorama, WGMS Radio, and 
Channel 4's evening news. In addition*, many radio stations aired our prepared 
announcements and all television stations showed Public Service Announcement 
film spot. 



i. 



All newspapers in the area carried announcements about Medicine for the 
Layman and special mention of the series was made in the Washingtonian 
Magazine (as part of a feature article) and the Washington Post's "Try It" 
magazine section. 

Press interest in other Clinical Center activities, including care of the 
Sutherland family, remained high. 

Various Institutes called upon the OCR&I to assist them in press events 
of national importance. In addition, the OCR&I was on hand to help press 
at special functions, Including Secretary Califano's visits to NIH for 
Dr. Arthur C. Upton's appointment as Director of NCI and the celebration 
of the PHS's 180th Birthday. 

The OCR&I coordinated the Clinical Center's July 6th Anniversary celebration 
that featured a ceremony for employees at the Masur Auditorium. 

I 
Sixty-one employees received certificates and specially designed plaques 
in recognition of their long and devoted service. Also, an exhibit com- 
memorating twenty-five years of research for people was put on display 
for staff and visitors in the Clinical Center lobby. 



OD-16 



special Events 



The Special Events Staff planned, coordinated and directed 
specific programs for 65,031 visitors to the NIH in FY 1978. 
Included were 297 visitors from 44 foreign cotontries and 
2,374 domestic visitors. The Section consulted, planned and 
provided staff assistance for 264 scientific and administrative 
meetings attended by 62,360 visitors in the Jack Masur Auditorium. 



During the FY 1978, the Special Events Section engaged in the 
following: 

Scheduled 363 appointments with NIH researchers 

Arranged 246 film showings for 1,352 visitors 

Conducted 240 tours for 1,531 visitors 

Collected, assembled and distributed 9,738 publications 
to visitors 

Collected, assembled and distributed 49,050 publications 
for lecture series "Medicine for the Layman" 

Answered 1,501 public inquiries by letter and telephone 

Maintained the NIH Speakers Bureau and filled 28 requests 

Administered roster of individuals and called upon them to 
assist in interpreting for 29 foreign visitors and foreign 
born patients 

Maintained a current and comprehensive invitation list for 
all NIH Lectures, dedications and ceremonies 

As executive Secretary for NIH Lecture Committee, was 
responsible for administrative arrangements for 2 NIH 
Lectures, 2 q. Burroughs Mider Lectures and the R.E. Dyer 
Lecture 



OD-17 





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OD-20 



VISITORS DUniNG FISCAL YEAR 1978 - By Discipline 



A. Domestic 



2,374 



Laboratory Science .... 66 

Medical 319 

Paramedical 473 

Administrators 73 

Hospital Administrators . 32 

Teachers 76 

Graduate School 263 

College 418 

High School 88 



Layman 126 

Medical Educators .... 1 

Employees 398 

Science Writers 7 

Clergy 1 

Congressional Staff ... 12 
Asst. Sec. for Health . . 2 

Statesmen 17 

Military 1 

Interpreter 1 



Foreign - 297 



Laboratory Science . . . .145 

Medical 75 

Paramedical 24 

Administrators 5 

Hospital Administrators . 2 

Teachers 1 

Graduate School 11 

College 9 

High School 1 



Layman 7 

Medical Educators .... 1 

Engineers 8 

Press 1 

Minister of Health. ... 1 

Statesmen 5 

Interpreter 1 



OD-21 



Foreign Visitors by Country of Origin - Fiscal Year 1978 



Africa 1 

Algeria 2 

Argentina • ■• i 

Australia 5 

Austria 1 

Belguim ]_ 

Brazil 7 

China X6 

Canada 5 

Czechoslovakia 1 

Egypt 5 

England 5 

France 26 

Germany 3 

W. Germany 13 



Ghana 



Israel 



Poland 



3 



India n 

Iran 7 

Iraq I 



22 



Italy 3 

-Japan 62 

Kenya 2 

Korea 2 

Netherlands 3 

New Zealand 1 

Nigeria ]_ 

Peru I 

Philippines 4 



10 



Portugal I 

Surinam 1 

Scotland ]_ 

Spain 20 

Sweden 4 

Switzerland 4 

S. America -^ 

Syria 2 



Thailand 



Turkey 2. 

Uganda 2 

USSR TT 



Venezuela . 
Yugoslavia 



CD- 2 2 



NIH LECTURE SERIES 
Fiscal 1978 

The Special Events Section is responsible for administrative arrangements 
for the NIH Lecture Series. 

G. Burroughs Mider Lecture: November 2, 1977 Attendance: 83Q 

Philip Leder, M.D. 

Chief, Laboratory of Molecular Genetics 
National Institute of Child Health and 
Human Development 
National Institutes of Health 
Title: "A Close And Surprising Look At 
The Mammalian Genome" 

NIH Lecture: March 29, 1978 Attendance: 350 

Eric R. Kandel, M.D. 
Department of Physiology 
Columbia Univ. College of Physicians and 
Surgeons 

630 West 168th Street 
New York, New York 10032 
Title: "Cellular Insights Into Behavior 
And Learning" 

NIH Lecture: May 10, 1978 Attendance: 500 

Har Gobind Khorana, Ph.D. 
Professor of Chemistry and Biology 
Massachusetts Institute of Technology 
Cambridge, Massachusetts 

Title: "Total Synthesis of a Biologically 
Functional Gene" 

R.E. Dyer Lecture: May 31, 1978 Attendance: 300 

Robert M. Chanock, M.D. 

Chief, Laboratory of Infectious Diseases 
National Institute of Allergy and 
Infectious Diseases 
National Institutes of Health 
Title: "Influenza Virus - Recent Insights 
And Prospects For More Effective 
Control" 

G. Burroughs Mider Lecture: September 13, 1978 Attendance: 525 
Jesse Roth, M.D. 
Chief, Diabetes Branch 
National Institute of Arthritis, 
Metabolism, and Digestive Diseases 
National Institutes of Health 
Title: "Receptor Disorders in Man" 



OD-23 



Professional Activities £~ 

Dr. Llpsett was chosen President-Elect of the Endocrine Society and served 
as Secretary General, International Society of Endocrinology. He was 
appointed Chairman of the Endocrinology and Metabolism Advisory Committee, 
Food and Drug Administration. 

He served as Associate Editor of Cancer Research Editorial Board and is on 
the Board of Editors for Monographs on Endocrinology . a 

Dr. Lipsett spoke at the 6th Asia & Oceania Congress of Endocrinology 
Symposium on Andrology in Singapore, on "Testicular Function." He was asked 
to participate in the Smith-Kline and French Lectureships at the University 
of Texas Health Science Center and gave two lectures: "Ovary and Testis — 
Similarities of Functions 5c Diseases" and "The Physiologic Significance of 
the Metabolism of the Hormones." 

In addition, he presented lectures on "Hirsutism & Virilization" at the 
College of Physicians & Surgeons, Columbia University Annual Postgraduate 
Course in Obstetrics and Endocrinology; "Endocrine, and Paraneoplastic Syn- 
dromes" at the Mount Sinai School of Medicine Medical Oncology Course; 
"The Endocrine Function of the Human Testis" at Cook County Hospital Division 
of Endocrinology Seminars in Clinical Endocrinology, Chicago; "Considerations 
about Breast Cancer," Harbor General Hospital, UCLA School of Medicine. 



He also participated on the American College of Physicians Panel on Repro- 
ductive Endocrinology for the Internist, Boston, and participated as a 
member of the faculty for The Institute for Continuing Education for the 
program "Recent Advances in Endocrinology & Metabolism," in Nassau. 

Dr. Ross was the recipient of the Ashbel Smith Distinquished Alumnus Award, 
University of Texas Medical Branch, Galveston, Texas. He was appointed 
honorary fellow of the American Gynecological Society. 

Dr. Ross presented the First Carl Gemzell Lecture on "The Ovulatory Process 
in Women" at the Symposium on "New Leads on Contraception" in honor of the 
Five Hundredth Anniversary of the University of Uppsala, Sweden. He also 
presented the Fiftieth Charles Sumner Bacon Lecture, "Clinical Relevance of 
Structural Properties of HCG," University of Illinois, Chicago. Dr. Ross 
spoke at the VIII Meeting of the International Study Group for Steroid 
HorEones, presentisg a lecture on "Intraovarian Relationships and Steriod 
Secretion by the Ovary," Rome, Italy. As an invited speaker of the 
Spanish Endocrine Society, he presented a lecture on "Intraovarian Hormonal 
Control of Follicular Growth and Atresia," Barcelona, Spain. In addition. 
Dr. Ross was guest lecturer at the New York Obstetrical Societ]^ and South- 
western Gynecologic Assembly, Dallas Texas. 



• 



e 



OD-24 



Bibliography 

Bahr, J.M. , Ross, G.T., and Nalbandov, A.V.: Hormonal regulation of the 
development, maturation, and ovulation of the ovarian follicle. In Creep, 
R.O. (Pro j . Dir.): Frontiers in Reproduction and Fertility Control-A Review 
of the Reproductive Sciences and Contraceptive Development . Cambridge, 
the MIT Press, Pt.2, 1977, pp. 40-43. 

Cardon, P.V., Dommel, Jr., F.W., and Trumble, R.R. : Injuries to research 
subjects: a survey of investigators. N. Engl. J. Med . 295: 650-656, 1976. 

Hill, S.E.K. , and Lipsett, M.B.: A survey of cancer education: physicians' 
and dentists' needs and preferences. Ohio State Med J 73:701-704, 1977. 

Lipsett, M.B.: Effects of cancers of the endocrine and central nervous 
systems on nutritional status. Cancer Res . 37:2373-2376, 1977. 

Lipsett, M.B.: Estrogen use and cancer risk. JAMA 237:1112-1115, 1977. 

Lipsett, M.B.: Regulation of androgen secretion. In Martini, L. and 
Motta, M. (Eds.): Androgens and Antiandrogens . New York, Raven Press, 

1977, pp. 11-17. 

Lipsett, M.B., and Ross, G.T. : The Ovary. In Ingbar, S.H. (Ed.): The 
Year in Endocrinology. 1975-1976 . New York, Plenum Press, 1976, pp. 89-109. 

Lipsett, M.B.: Functional ovarian tumors. In Givens, J.R. (Ed.): Endocrine 
Causes of Menstrual Disorders . Chicago, Year Book Medical Publishers, Inc., 

1978, pp. 289-306. 

Lipsett, M.B.: Steroid hormones. In Yen, S.S.C. and Jaffee, R.B. (Eds.): 
Reproductive Endocrinology . Philadelphia, W.B. Saunders Co., 1978, pp. 80-92. 

Lipsett, M.B., and Ross, G.T.: The ovary. In Ingbar, S.H. (Ed.): The Year 
in Endocrinology. 1977 . New York, Plenum Publishing Corp., 1978, pp. 233-254. 

Macks, G.C.: Liability control: The next great management systems challenge 
for hospitals. In Cost Containment and Consumerism Within the Health Care 
Delivery System . Chicago, Center for Hospital Management Engineering, 1978, 
pp. 97-104. 

Ross, G.T.: Clinical relevance of research on the structure of human 
chorionic gonadotropin. Am. J. Obstet. Gynecol . 129: 795-808, 1977. 

Ross, G.T.: Disorders follicular maturation and atresia. In Givens, J.R. 
(Ed.): Endocrine Causes of Menstrual Disorders . Chicago, Year Book Medical 
Publishers, Inc., 1978, pp. 223-236. 

Ross, G.T.: Ovaries. In Rudolph, A.M. (Ed.): Pediatrics 16 . New York, 
Appleton-Century-Crofts, 1977, pp. 1726-1732. 



OD-25 



Ross, G.T.: Clinical infertility in women. Environmental Health Perspectivj 
Vol. 24, pp. 17-23, 1978. ^ 

Ross, G.T.: The First Carl Gemzell Lecture: Morphologic correlates of 
hormone frofiles in blood and antral fluid during avulatory cycles in women. 
Ups. J. Med. Sci . Suppl. 22: 7-15, 1978. 

Ross, G.T., and Lipsett, M.B. : Homologies of structure and function in mam- 
malian testes and ovaries. Int. J. Androl. Suppl. 2: 39-52, 1978. , 



m 



« 



OD-26 



Normal Volunteer Program 

The FY 1978 was a difficult period for the Normal Volunteer Program 
and staff because of the illness and retirement of the Chief. A new 
assistant to the Chief was appointed. During FY 1977 two important 
aspects of the program suffered. First, liaison with our sponsoring 
contractors was reduced. However, their cooperation and support was 
excellent and we have maintained a close rapport. Second, our day-to- 
day contact with the in-patient volunteers was minimal and there were 
minor volunteer problems but all the needs of our research investigators 
were met for the in-patient, out-patient and off-site studies. 

College student volunteers were well -motivated, intelligent, purposeful 
young people and honored their conmitments to our studies. We in turn 
have been able to locate each of them in a career assignment related 
to his/her academic or career goals. This is important as educational 
development opportunities are one of the main reasons why students 
join our program. The community groups sponsoring out-patient and 
off-site volunteers have been most cooperative and effective in finding 
the various types of volunteers requested by our investigators, 
recruiting and screening applicants and arranging for the various 
meetings or visits. 

Through the Assistant to the Director of the Clinical Center for 
Bio-ethics the NVP staff and normal volunteers completed an evaluation 
form for each study on which they participate, reflecting the volunteers' 
opinions of how completely they were informed of each study before 
consenting, the treatment they received by staff, and any problems or 
discrepancies they encountered. Seminars were also conducted on the 
history of bio-ethics, the responsibility of both investigators and 
volunteers for developing informed consent and the implications of 
this for the present and future. There is no question that the stress 
on informed consent and concern for ethical procedures has improved 
the quality of our program and the respect of our volunteers and 
sponsoring agencies. 

Dr. Philippe V. Cardon, Jr., Associate Director of the Clinical Center, 
supported the Normal Volunteer Program and staff through consultation, 
interviewing of volunteers and liaison with our contracting resources. 

IN-PATIENT PROGRAM : 

The overall in-patient program remained relatively consistent with 
past years, with about 50-65 volunteers in the Clinical Center at any 
one time, comprising about 15-20% of the in-patient census. There 
were fewer volunteers this year but the average stay was several days 
longer, 

NO. VOLS. TOTAL DAYS AVERAGE STAY 
(PRORATED MONTHLY) (PRORATED MONTHLY) PER VOLUNTEER 

1978 36.2 1,781.4 49.58 days 

1977 48.1 1,880.1 39.27 days 

- 11.9 -98.7 +10.31 days 

OD-27 



IN-PATIENT PROGRAM (Continued) : i^ 

This decrease in the in-patient number of volunteers and total days 
is due to the transfer in January 1978 of the administration of the 
volunteer program at the Phoenix Indian Medical Center, Phoenix, 
Arizona to the NIAMDD Research Unit. 

The cost of the in-patient volunteer program remains about the same as 

last year when considering the extended period for fiscal year 1977 * 

and the transfer of the Phoenix Indian Medical Center to NIAMDD ' 
Research Unit in Phoenix. 

FISCAL YEAR EXPENDITURES 

1978 $323,586.40 

1977 (15 months) 428,040.75 



■$104,454,35 



OUT-PATIENT AND OFF-SITE PROGRAM: 



This portion of the Normal Volunteer Program fluctuates from year to 
year, depending on the duration of project, and number of visits 
required and length of each visit. All requests for volunteers were 
met, but the number of visits and total hours decreased dramatically 
this year returning to the level of 1975. Note that though there 
were less Per Clinic Visits in 1978 than in 1975 and 1977, there was 
a considerable increase in total hours in 1978 in both Per Clinic and* 
Off -Site visits. 

PER CLINIC VISITS 

VISITS HOURS 



FY 1978 
FY 1977 
FY 1976 


(15 


mon 


2520 

ths) 4652 

2624 

OFF-SITE VISITS 

VISITS 


7695 
8290 
4620 

HOURS 


FY 1978 
FY 1977 
FY 1976 


(15 


mor 


435 

iths) 1481 

411 


793 

3050 

718 



NIMH and NCI continue to have the most Out-Patient Volunteer Visits 
and NIMH and NICHD the most Off-Site Volunteer Visits. For the cost 
of these programs and breakdown by Institute and sponsor see charts 
number 4 & 5. 



OD-28 



IV. VOLUNTEER RESOURCES : 

Our present college and university sponsoring agencies are actively 
recruiting for us as they feel our program is an educational and 
worthwhile program for their students. We will continue to investi- 
gate colleges, universities and other sponsoring institutions as 
possible sources of volunteers. 

V. SPECIAL INCIDENTS : 

No medical misadventures were reported this fiscal period, but there 
were problems which have caused frustrations for both the nursing 
staff and the volunteers. Attempts to remedy the situation are now 
being made. 

VI. CAREER DEVELOPMENT PROGRAM : 

This is a very important part of our program and has been most 
successful this year. The majority of the volunteers are pre-med, 
bio-chem, psychology and nursing students, and the opportunity to 
work in laboratories and gain some pre-professional experience under 
the guidance of our research investigators is one of the main reasons 
students join our program and that colleges and universities continue 
to support us and recruit volunteers for us. All volunteers this 
year without exception have taken advantage of this career development 
opportunity, and both the students and their respective colleges are 
enthusiastic and appreciative of the learning experience the students 
have received. 

Most preceptors who have worked with the volunteers were very pleased 
with these bright, well motivated, young people and continue to support 
our program. However, the volunteers understood the primary reason 
for being here at NIH was to willingly participate on bio-medical 
research studies and they honored that priority. 

VII. AGE RANGE : 

The age of volunteers during this fiscal period ranged from 9 years 
to 57 years, with an average age of 24.5 years. College age students, 
18-23 years, continue to constitute the largest and most important 
group of our in-patient program, comprising about 73.8% of the total 
group. 

VIII. SEX RATIO : 

The percentage of male and female volunteers is dictated primarily by 
the nature of the medical research studies. In past years rarely have 
we had enough men applying for the in-patient program to meet the needs 
of the researchers and have had to replace the men with women. This 
year we have had sufficient men and women applying to meet the investi- 
gators' needs resulting in 230 men and 204 women in-patient volunteers, 
or about 53% men and 47% women. 

on- 2 9 



CHART # 1 
TOTAL ESTIMATED* AMOUNT BY AGENCY FOR FISCAL YEAR 1978 
AGENCY AMOUNT 



California State University, Chico 
Church of the Brethren General Board 



.D.S. 



Church of Jesus Christ of L 

Church of Jesus Christ of L 

Church of Jesus Christ of L 

Davidson College 

Green Acres School 

Gustavus Adolphus College 

Indian Health Advisory Board 

Indiana State University, Terre Haute 

Kalamazoo College 

Keuka College 

Mental Health Association, Montgomery County 

Montgomery College 

Pennsylvania State University 

Phoenix Indian High School 

University of California, Davis 

University of California, Santa Cruz 

Warner Memorial Presbyterian Church 

Wittenberg University 



(Mormon), Gaithersburg Ward 
(Mormon), Kensington Ward 
(Mormon), Rock Creek Ward 



,489.00 
,049.00 
,564.25 
,583.15 
,409.75 
,943.00 
35.00 
,030.00 
,144.25 
,875.00 
,749.00 
,579.00 
,836.00 
,183.00 
,344.00 
,590.00 
,584.00 
,472.00 
527.75 
,728.00 



5379,916.15 



*July, August and September 1978 estimated 



OD-30 



CHART # 2 
TOTAL ESTIMATED* AMOUNT BY INSTITUTE FOR FISCAL YEAR 1978 
INSTITUTE AMOUNT 



NIAMDD $ 37,595.00 

NIAMDD/Phoenix 26,834.25 

NCI 18,753.50 

NICHD 44,586.00 

NIDR 2,409.50 

NEI 17,452.50 

NHLBI 74,789.10 

NIAID 57,076.00 

NIAID/CC 3,696.00 

NIMH 93,289.05 

NINCDS 3,425.25 

$379,916.15 



*July, August and September 1978 estimated 



OD-31 



CHART # 3 

NUMBER OF VOLUNTEERS, TOTAL DAYS & EXPENDITURES (In-Pat1enf 

October 1, 1977 - September 30, 1978 



INSTITUTE 

NIAMDD 

NIAMDD/Phoenix 

NCI 

NICHD 

NIDR 

NEI 

NHLBI 

NIAID 

NIMH 

NINCDS 



BY INSTITUTE 
VOLUNTEERS 

38 

42 

12 

41 


12 

86 

66 
123 

14 
434 



TOTAL DAYS 



AMOUNT 



2375 


$ 37,385.00 


2119 


26,724.00^ 


540 


9,933.00 


2478 


38,807.00 


1167 


16,519.00 


4710 


72,329.60 


4989 


60,722.00 


3995 


60,270.80 


46 


846.00 



21,519 



5323,586.40 



'Transferred effective January 



978 



AGENCY 



BY AGENCY 



VOLUNTEERS 



California State University Chico 30 

Church of the Brethren General Board 55 

Church of L.D.S., Kensington 12 

Church of L.D.S., Rock Creek 3 

Davidson College 13 

Gustavus Adolphus College 34 

Indian Health Advisory Board 39 

Indiana State University, Terre Haute 14 

Kalamazoo College 22 

Keuka College 25 

Mental Health Assoc, Montgomery County 81 

Pennsylvania State University 19 

Phoenix Indian High School 3 

University of California, Davis 53 

University of California, Santa Cruz 16 

Wittenberg University 15 

"434 

*July, August & September 1978 estimated 



TOTAL DAYS 


AMOUNT 


3490 


$ 55,489.00 


2270 


33,049.00 


61 


794.40 


6 


135.00 


644 


8,943.00 


2665 


38,030.00 


1861 


21,034.00 


813 


10,876.00 


1682 


23,749.00 


892 


14,579.00 


433 


6,090.00 


1237 


16,433.00 


258 


5,690.00 


3272 


58,584.00 


1146 


19,472.00 


789 


10,728.00 


21,519 


5323,586.40 



• 



OD-32 



CHART # 4 
ESTIMATED* OUT-PATIENT REPORT FOR PERIOD OCTOBER 1, 1978 - SEPTEMBER 30, 1978 

BY AGENCY 

AGENCY 

Church of L.D.S., Gaithersburg 

Church of L.D.S., Kensington 

Church of L.D.S., Rock Creek 

Mental Health Assoc, Montgomery County 

Montgomery College 

Warner Memorial 

Indian Health Advisory Board 



INSTITUTE 

NCI 

NICHD 

NIDR 

NEI 

NHLBI 

NIMH 

NINCDS 

NIAMDD/Phoenix 



TOTAL 


TOTAL 




VISITS 


HOURS 


AMOUNT 


339 


343 


$ 3,664.25 


128 


199 


1,623.75 


153 


270 


2,229.75 


)unty 1772 


6110 


42,663.00 


104 


673 


2,183.00 


17 


86 


527.75 


7 


14 


110.25 


2520 


7695 


$53,001.75 


BY INSTITUTE 






TOTAL 


TOTAL 




VISITS 


HOURS 


AMOUNT 


774 


891 


$ 8,820.50 


378 


379 


4,068.50 


167 


353 


2,745.25 


60 


183 


1,260.00 


10 


14 


127.50 


1025 


5467 


33,290.50 


99 


394 


2,579.25 


7 


14 


110.25 


2520 


7695 


$53,001.75 



''July, August, September 1978 estimated 



OD-33 



CHART # 5 
ESTIMATED* OFF SITE REPORT FOR PERIOD OCTOBER 



1978 - SEPTEMBER 30, 1978 



BY AGENCY 



AGENCY 



TOTAL VISITS TOTAL HOURS 



Church of L.D.S., Kensington 

Church of L.D.S., Rock Creek 

Green Acres School 

Mental Health Assoc, Montgomery County 



#Includes visit to contractor's resources 



33 

9 

1# 
392 
435 



33 
9 


751 
793 



AMOUNT 

$ 165.00 
45.0|P; 
35.00 
3,083.00 

$3,328.00 



INSTITUTE 

NIAMDD 

NICHD 

NIMH 



*July, August, September 1978 estimated 
#Inc1udes visit to contractor's resources 



BY INSTITUTE 






TOTAL VISITS 


TOTAL HOURS 


AMOUNT 


42 
301 

92# 
435 


42 
434 
317 
793 


$ 210.00 
1,904.00 
1,214.00 

$3,328.00 



OD-34 



PATIENT ACTIVITY SECTION 

I. MISSION AND GOALS 

The Patient Activity Section's primary mission is to provide a diversified, 
patient-centered program of therapeutic recreation activities and library ser- 
vices to all patients of the Clinical Center to in- and out-patients. Some 
of the goals of the program are: 

To eliminate boredom, and as a result, to help alleviate stress 
and anxiety 

To provide emotional and psychological support to the patient 
and his family 

To adapt leisure activities for the patient, based on his physical 
and emotional needs and on his individual research protocol 

To help the patient regain or reinforce his self-esteem 

To educate/re-educate the patient in the constructive use of his 
leisure, during hospitalization and after discharge 

All programs were organized, executed, and evaluated under the guidance 

of a professional staff of Therapeutic Recreation Specialists and Assistants. 

II. THERAPEUTIC RECREATION 
Programs 

Adult Recreation Referral Program 

Based upon a written referral from the attending physician, this 
program featured arts and crafts, and sports activities. This 
year, of the 3764 patients referred to this particular program, 2597 (approxi- 
mately 69%) participated. See Attachment //I, Item #1. 

As part of this program, 158 different patients were worked with on their 
vm.lt on a one-to-one basis. 

Adult Social Program 

This program featured seasonal events, dances, musical programs, trips, 
feature films, and many other appropriate social activities. This year, 
there were 229 social and _95 music and drama activities planned, with 13,475 
patient/family participants. 

As part of this program, recreation activities were offered for patients/ 
family members at the United Inn (SCAP) with 121 social and _60 craft activities, 
with 2054 patient /family participants. 



OD-35 



Children's Play Programs (All Institutes) 

A creative and diversified play program was offered to all child patients, 
siblings, and child visitors. This year, 990 different child patients 
and child visitors were involved in the program, including 102 different 
child patients required bedside visitations. See Attachment //I, Item #2. 

Institute Programs : Therapeutic Recreation activities geared to meet 
specific patient/institute needs. 

National Institute of Mental Health (2 West, 3 East & West, 

4 East & West) 

This year, 697 different patients were involved in this program. 

For a more detailed statistical breakdown, see Attachment #1, Item #3. 

National Cancer Institute 

Pediatric Oncology 

Unit 2 East/2B : This year, 621 different patients were involved in 
this particular program. 

GPD-West Clinic ; This year, _803 different patients and 144 siblings 
were active in this program. 

Special Unit Programs (10 East, 12 East & West, 13 East) 

This year, 2122 different patients were involved in these programs. 
For a mere detailed statistical breakdown, see Attachment #1, Item 
#4. 

NINCDS ; This year, 1035 different patients were involved in this 
program. 

III. 



r 



PATIENT'S LIBRARY 






Books 






Inventory 


6. 


,935 


New Acquisitions 




208 


Lost in Circulation 




50 


Circulation 






(Patients & Personnel) 


12, 


,073 


Via Library 


8, 


,871 


Via Bookcarts 


3 


,156 


Inter-library loan 




46 



Patients Contacted 

Visiting library 7,474 

Visited on unit 

(bookcart) 9,273 

OD-36 



Magazines 

Subscriptions 69 

Monthly 44 

Semi-monthly 2 

Bi-monthly 3 

Bi-weekly 4 

Weekly 15 

Quarterly 1 

Circulation 8,918 

Average monthly 743 

Newspapers 

Subcriptions 

Washington Post 23 

Wall Street Journal 1 

Christian Science Monitor 1 
Circulation 

(Washington Post) 2,400 

Reading Utilization (See Attachment #2) 

Lost books are few in comparison to circulation. Even with an 
average circulation of 1,005 books per month, we only lost an 
average of four books each month. 

Hyperactive Study : Mrs. Swim, Library Supervisor, was an integral 
part of the 2 West Mental Health inter-disciplinary team, giving the 
children on that unit extra reading time. She was required to evaluate 
the specific patient behavior in relation to the type or quality of 
drug intake. There was a total of 30 different children in this program 
for an average of three weeks length of stay. Mrs. Swim worked with 
two children per week for about 2-3 hours per week with each child. 

IV. MAJOR PROGRESS IN SERVICES/TRAINING/DEVELOPMENT 

Monthly Report 

Our means of reporting and recording statistics and programs was re-eval- 
uated and declared "outdated." As a result, a Section committee was 
formed to take a serious look at our Monthly Report to see what could be 
done to make it actually reflect what we do and how we do it. After 
a three month period of change, adjustment, and staff orientation, a new 
and more realistic means of reporting was established. 

Exhibit, Brochure and Color Slide Presentation 

With the help of the Clinical Center's Office of Clinical Reports 
and Inquiries, and the Design Graphics Section, DRS, a professional 
exhibit and accompanying brochure were put together to promote our 
Therapeutic Recreation Program. The exhibit is portable and has thus 



OD-37 



made the rounds at various state and local conferences and workshops; 
it was also set up at the 1977 Congress for Recreation and Parks, t 
Las Vegas, Nevada. The brochure has also been used in response to the 
many inquiries we get about our Therapeutic Recreation Program. 

A series of 87 color slides, depicting various aspects of our Therapeutic 
Recreation Program, was put together, along with appropriate taped music, 
to show at state and national meetings and conferences. It is hoped 
that this slide presentation will eventually be automated and tied into 
our Section's exhibit. ' 

Reorganization 

With the promotion of two of our ataff to supervisory positions, the 
organizational structure and lines of responsibility have drastically 
changed — all for the better. This was the first organizational "over- 
haul" this Section has had since its inception over 18 years ago. 
Also, one of our Therapists was promoted to the position of Supervisory 
Coordinator, Therapeutic Recreation Program, NIMH. As a result of 
these actions, the Section now runs with greater efficiency. 

Patient Review Conference 

As of June 1978, the Recreation Therapist on 10 East initiated a weekly 
Patient Review Conference , consisting of the various non-medical staff 
members on 10 East, i.e. Social Work, Chaplain's Office, Recreation 
Therapy, and Physical Therapy. Previously, each individual related his | 
specific experiences with patients and relatives to the Nursing Staff 
alone , with little or no sharing of this material amongst non-medical 
staff. As a result of the Patient Review Conference , the staff feels 
that this open communication has tied them closer together, and made 
them more aware of patient problems and needs. 

SACP (United Inn) 

Our satellite recreation program at the United Inn has completed its 
first full year. A part-time recreation worker has planned and executed 
recreation programs about 20 hours per week for the outpatients and their 
families. To date, programming has stressed social activities, trips, 
and some craft programs. Also, in cooperation with the restaurant staff 
of the United Inn, several "theme" dinners have been held with great 
popularity (Thanksgiving Buffet, Christmas Dinner, and Hawaiian Luau.) 
Our recreation program at the Motel has become an integral part of the 
success of the toal SACP concept. |p 

ACCH 

The National Conference of the Association for the Care of Children 

in Hospitals was held this June in Washington, DC. Several members 

of the Patient Activity Section, in cooperation with the Clinical Center 

Nursing Staff, helped in the presentation of the Clinical Center to 

conference delegates. Karen Hosty Steshko (Supervisor, Children's m^'; 

OD-38 



Recreation Program) , Lois Swim (Patient Librarian) , and Sue Maletic 
O'Connell and Joanie Vigersky (Therapeutic Recreation Specialists/ 
Pediatric Oncology) presented their programs, and helped conduct tours 
throughout the Clinical Center. 

Teen Group (Units 2 East/2B) 

During the past year, the Pediatric Oncology Unit has seen an increase 
in the number of teenage patients. In order to meet the social and 
psychological needs of these patients, a teen group has been developed. 
The group, coordinated by the Unit Therapeutic Recreation Specialist, 
and the Unit Social Worker, is run by the patients themselves, and in- 
cludes both inpatients and SACP patients. The weekly meeting is used as 
the patients wish, for either discussion, planning unit activities, or 
simply a chance for meeting with other patients. Unlike some teen groups 
throughout the country, the emphasis of this group is primarily social 
rather than primarily a discussion group. It is the belief of the 
coordinators that the atmosphere is of prime importance in promoting the 
group, and if the patients meet each other in a social situation and 
become comfortable with each other socially, discussion will inevitably 
follow. 

Charting/Documentation 

This year the decision was make to develop a medium for charting/ document- 
ing the Therapeutic Recreation Programs. This system increased communi- 
cations with other professionals. 

A Committee was organized to develop a consistent forum in which the 
Recreation Therapy staff could record their assessment, evaluation and 
plan concerning recreational needs when consulted by NIMH Medical and 
Nursing Staff, and recording this data in patient charts. It is realized, 
some units require more indepth analysis and planning than others; 
however, we feel all Recreation Therapists should begin their consultations 
using the same approach. 

Currently, the Docximentation Committee is designing a checklist 
consultation form for Physicians and Nursing Staff which will request 
Recreation Therapy evaluation of patient needs. At discharge it is 
planned that the Recreation Therapy staff will make recommendations for 
patients which will be based on patient progress while at NIH. These 
comments will also be written on a consult sheet under Nursing Notes. 

Patient Council (Units 5 East and 5 West) 

A Patient Council was formed in June 1977; the Council, a loosely structured 
group, meets weekly and has fostered many supportive relationships. 
The Council has been most successful in planning a variety of well received 
recreation activities, and has offered a media for ventilation, friendship 
and sharing. 



OD-39 



Student Fieldwork/Intemahip Program 



f 



We were involved in training students from various colleges and 
universities to help them meet their "final" majors doing their 
"therapeutic recreation fieldwork./ internship" with us. Three of the 
students were from the University of Maryland, and two were from 
Penn State. These students were oriented to our programs, as well as to 
other Clinical Center disciplines (OT, PT, Social Work, Nursing, etc.) 
Their stay with us lasted anywhere from ten to fiftenn weeks, depending ^ 
upon the particular school's curriculum requirement. ^. 

V. PROFESSIONAL INVOLVEMENT OUTSIDE OF CLINICAL CENTER 

Maryland Recreation & Parks Association 

Past-Chairman, Therapeutic Branch (Arnold Sperling) 

Executive Board Member, Therapeutic Branch (Axnold Sperling/ Sue O'Connell) 

Membership Chairman, Therapeutic Branch (Sue O'Connell) 

Chairman, Nominating Committee, Therapeutic Branch (Arnold Sperling) 

Member, Nominating Committee, MRPA (Arnold Sperling) 

National Recreation & Parks Association 

Program Committee member, Mid-Atlantic Forum on Innovative Programming, 

Valley Forge, PA. (Arnold Sperling) 
Steering Committee, Mid-Eastern Symposium on Therapeutic Recreation, 

Baltimore, MD (Arnold Sperling) 

Conferences/Meetings /Workshops 

1977 Congress on Recreation & Parks; Las Vegas, NE. 

(Otis Crutchfield) 
Mid-Atlantic Forum on Innovative Programming; Valley Forge, PA. 

(Arnold Sperling) 
Annual Conference, Society for the Advancement of Travel for 

the Handicapped; Orlando, Fl. (Cynthia Kauff) 
Annual State Conference on Recreation & Leisure Services; 

Ocean City, MD. (Arnold Sperling/Sally Hinson) 
Mid-Eastern Symposium on Therapeutic Recreation; Baltimore, MD. 

(Arnold Sperling/Jane Millman/Cindy Pregent/Sue O'Connell) 
Annual Conference, Association for the Care of Children in 

Hospitals; Washington, DC (Janis Partin/Karen Steshko/ 

Joan Vigersky/Sue O'Connell) 
Workshop - "Clinical Approaches by Adjunctive Therapies"; ^ 

Central 'Neuropsychiatric Hospital Association, Chestnut ^ 

Lodge, Rockville, MD (Cynthia Kauff /Sally Hinson) 

Other 

Session on "T'Jhat Makes Recreation Therapeutic"; 1978 Convention, 
Eastern District, American Association for Health, Physical 

Education and Recreation, Baltimore, MD. (Arnold Sperling, A 



OD-40 



Chairman; Interpreters : Karen Steshko, Cynthia Kauff, Sue O'Connell 
& Patti Tepsic) 

Session on "Consumer Advocacy - What Is It? Who Is It?"; Annual State 
Conference on Recreation & Leisure Services, Therapeutic Branch, MRPA; 
Ocean City, MD (Arnold Sperling, Chairman) 

VI. FUTURE OBJECTIVES 

Continued emphasis in working with "special" patients on a one-to-one 
basis 

Greater communication, both verbal and written, with other hospital 
disciplines and among our own staff 

Continued development of a standard means of patient documentation 
and evaluation 

Incorporation into the Clinical Center Medical Information System 

More involvement in the leisure counseling aspects of therapeutic 
recreation 



Attachment #1 
1. Adult Recreation Referral Program 



Number of Referrals 


Number of Responses 


NIAID 1045 


695 


NIAMDD 336 


214 


NCI 505 


334 


NHLBI 867 


684 


NINCDS 133 


106 


NEI 123 


48 


NIMH 187 


97 


NICHD 50 


36 


SACP 518 
Total 3764 


383 
Total 2597 


2. Children's Play Programs 




Patients 




NIAID 59 




NIAMDD 35 




NCI 179 




NHLBI 62 




NINCDS 9 




NEI 24 




NIMH 95 




NICHD 157 




SACP 94 
Total 714 




+276 child visitors 
Grand Total 990 




OD-41 





3. National Institute of Mental Health 



Unit 2 West 244 patients 




Units 3 East/West 237 




Units 4 East/West 216 




Total 697 




4. National Cancer Institute - Special Unit Program 




Unit 10 East 900 patients involved 




Unit 12 East 430 patients involved 




Unit 12 West 262 patients involved 




Unit 13 East 530 patients involved 




Total 2122 




Patient Library Reading Utilization 




Item Number on Hand Numb 


er Circulated 


Stereo Record Players 28 


209 


Stereo Records 600 


3107 


Talking Book Machines 6 


35 


Talking Books 53 


103 


Magnifying Glasses & Bed Specs 10 


11 


Bookracks 5 


14 


Earphones 7 


37 


Cassette Players 4 


79 


Cassettes 38 


113 


ANESTHESIOLOGY DEPARTMENT 





GENERAL 

I. Missions and Goals 

The Anesthesiology Department provides anesthesia and related 
support services to all patients of the Clinical Center in need 
of such support. These services include: 

A. Administration of anesthesia to patients undergoing surgical 
and diagnostic procedures requiring anesthesia or standby 
coverage. 

B. Provision of consultative services in anesthesia-related 
problems. 

C. Administration of pain relieving techniques to selected patients 
with acute and chronic pain syndromes. 

D. Provisions of readily available, specialized resuscitative 
techniques in cardiopulmonary, anaphylactic, or traumatic 
emergencies occurring within the Clinical Center. 



OD-42 



E. Provision of professional support and advice to other 
organizational units of the Institutes or the Clinical Center 
in their investigational programs, both to aid in those 
programs and to utilize opportunities for anesthesiological 
research. 

F. Initiation of primary clinical investigation when opportune 
and appropriate. 

G. Teaching of residents and medical students in the principles 
and clinical practice of anesthesiology. 

H. Participation in the continuing medical education program 
of the clinical center. 

II. Activities 

Anesthesiological services provided from 1 October 1977 through 
30 September 1978 included anesthesia and/or supportive treatment in 
1613 total instances, representing 1427 surgical operations, 162 
diagnostic procedures, and 24 miscellaneous services (consultations, 
nerve blocks, and resuscitations). 

In the past year staffing was provided in the Clinical Center basis for 
5 operating rooms, the hyperthermia project, consultative services and 
emergency procedures including the provision of 24 hour call coverage. 
In addition staffing was provided for the new recovery room facility 
which opened in April. 

Institute Procedures Percent 

NCI 851 53% 

NHLBI 392 25% 

NINCDS 127 8% 

NEI 16 1% 

NICHD 22 1% 

NIAMDD 123 8% 

NIAID 48 3% 

NIMH 10 1% 

III. Major progress in research, services, training, and development 

A. The hyperthermia program in treatment of selected cancer 
programs has progressed and matured. It continues with 
a resultant accumulation of data and experience. The following 
papers have been presented by the Anesthesiology Department 
representing the investgation thus far: 

The effect of ketamine on the ventilatory response to extreme 
hyperthermia in man. 



OD-43 



Evaluation of liquid crystal thermometry as a screening device 
for elevations of core body temperature. 

A rapid portable method for determining Pa02 on microsamples. 

B. A retrospective study of anesthesia methods for management 
of patients with asymmetric septal hypertrophy. 

C. Evaluation of preoperative factors as indicators of potential 
respiratory problems in myasthenic patients. 

The following statistics display the nature of the anesthesia procedures 
undertaken and reflect the complexity and protracted duration of many 
of the operations. 

Anesthesia time exceeded 



# 



3 hours in 773 instances 

5 hours in 447 instances 

6 hours in 306 instances 



(48% of all procedures) 
(28% of all procedures) 
(19% of all procedures) 



Surgical procedures classified as to type of surgery were as follows; 



1. Thoracic procedures 

A. Heart and great vessels 

(1) Open heart with extracorporeal circulation 222 

(2) Closed Heart 19 

B. Intrapleural 133 

C. Chest wall 53 



• 



2. Neurological 

A. Craniotomies 

B. Spinal cord operations 

C. Other 



3. General surgical 



A. 


Abdominal 


224 


B. 


Pelvic 


4 


C. 


Inguinal 


34 



262 (total) & 
including 



4. Urological procedures, including bladder 
and adrenal 

5. Perineal procedures 

A. Gynecologic operations 35 

B. Geni to-urinary procedures 40 

C. Others 13 

6. Face, head, and neck operations 

7. Eye, ear, nose, and throat 



44 



(total) & 
including 



116 
45 



OD-44 



8. Dental 5 

9. Orthopedic 39 
10. Miscellaneous 338 

TOTALS 1,427 

V. Future Objectives 

The principle objective of the Department continues to be the provision 

of appropriate anesthesia support to patients at the Clinical Center, 

with special attention to the better utilization of resources and the 
maintenance of high standard of patient care. 

In addition, departmental efforts will be focused on the following 
special areas of interest: 

1. The use of the pain control techniques on a formalized basis 
in diagnosis and treatment will continue while new techniques 
of pain control and study are explored and utilized. 

2. The department will continue to be active in the provision of 
approved techniques in cardiopulmonary resuscitation and in the 
education and orientation of Clinical Center employees in these 
techniques at the appropriate level. 

3. Close liaison with Dr. Byron McLees and the Intensive Care 
team will be maintained with the aim of improving patient 
coverage in this area and identifying mutual avenues of 
interest. 

4. Efforts will be made to utilize the resources of the 
new Surgical Recovery Room, to provide intensive 
support to Clinical Center patients surgical and 
non-surgical, where such support is indicated. 

5. Continuing attention will be given to enhancing the 
academic area of the department. This will include 
participation in the medical student elective program 
of the Clinical Center. 



OD-45 



f 



« 



SMITHSONIAN SCIENCE INFORMATION cXCHANGE 
PROJECT NUMBER (Oo NOT use this space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE Of 

INTRAHUfiAL RESEARCH PROJECT 



PROJECT NUMBER 



Z01CL07001-01 



PERIOD "^vp^^^^ ^^ ^g^g _ 3gp^g^(3g^ 3Q^ ^973 



TITLE OF.i-ROJECT (gO characters .or lessj . ^ ^ ., ~ 

Elucidation of Basic ITecnamsms of Taste Transduction by Studying the Effectjs 
of Topically Applied Neuropharmacological ly Active Drugs on Taste Acuity 
in Normal Human Beings. 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS ANO ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



P. Kapp 

C. F. Mattern * 

R. 0. Wolf 

J. Weiffenbach 

J. F. Bosma 

* Study Chairman 



Attending Anesthesiologist 

Assistant Chief, LVD 

Senior Investigator 

Senior Investigator 

Chief, Oral Pharyngeal 
Development Section 



Anesthesiology, CC 

NIAID 

CID, NIDR 

CID, NIDR 

CEB, NIDR 



COOPERATING UNITS (if any) 

NIAID, NIDR 



LAB/BRANCH 



Anesthesiology Section 



INSTITUTE ANO LOCATION 

CC, NIH, Bethesda 



TOTAL MANYEARS: 



PROFESSIONAL: 



CHECK APPROPRIATE 80X(ES) 
tlr(a) HUMAN SUBJECTS 



(b) HUMAN TISSUES 



D (c) NEITHER 



D (^0 MINORS n (a2) 1 NTERV I EWS~^-- 



SUMMARY OF WORK (200 w,rts or less^- underlme keywords J, . , . , , . 

This Study wi 1 I test the working %pothesis that acetylcholine is present 
in the taste pore and is important in taste transduction . The pore is 
accessible to topically applied substances and taste tests are available 
to evaluate the effect of a competitive inhibitor of acetylcholine. 
In view of the fact that potent neuromuscular blocking agents will be 
instilled in the oral cavity, participation of the Anesthesiology Section 
is particularly important should there be rapid absorption or inadvertent 
reaction. 



Anesthesiology Section 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 
Individual Project Report 
October 1, 1977 - September 30, 1978 

Project Title: Elucidation of Basic Mechanisms of Taste Transduction 
by Studying the Effects of Topically Applied Neuro- 
pharmacologically Active Drugs on Taste Acuity in 
Normal Human Beings 

Project Serial Number: Z01CL07001-01 

Principal Investigator: Carl F. Mattern, M.D. Assistant Chief 
LVD, NIAID 

Other: Philip Kapp, Anesthesiology Section, CC 
R. 0. Wolf, D.D.S., CID, NIDR 
J. Weiffenbach, Ph.D., CID, NIDR 
J.F. Bosma, M.D., CEB, NIDR 

Cooperating Units: CC, NIAID, NIDR 

Man Years: Total : 

Professional: 
Other: 

Project Description 

Objective : 

T'riis study will test the working hypothesis that acetylcholine is 
present in the taste pore and is important in taste transduction. 

Major Findings : 

Too early in the study to report any major findings 

Significance in Biiomedial Research : 

If indeed potent neuromuscular blocking agents interfere with 
acetylcholine in taste transduction by topical application, 
further insight into the mechanisms and disorders of taste will 
be gained. 



6 



Proposed Course: 

Plan is to continue applying neuropharmacologically active substances 
topically to the taste pores in escalating doses. 

Honors and Awards 

None 

Publications 

None 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE U.S. DEPARTMENT OF 
PROJECT NUMBER (Oo NOT use this space) HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 
NOTICE OF 
INTRAMURAL RESEARCH PROJECT 



PERIOD COVERED 



PROJECT NUMBER 



Z01CL070O2-O1 



October 1. 1977 - September 30, 1978 



TITLE OF PROJECT (30 characters or less) 

Phase I Clinical Trial of Whole Body Hyperthermia 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



D. E. Lees 
J. M. Bulf 

J. Whang-Peng 

W. Schuette 

E. R. Atkinson 

*Study Chairman 



Attending Anesthesiologist Anesthesiology, CC 



Senior Investigator 

Senior Investigator 

Electrical Engineer 

Physical Sciences Project 
Officer 



COP, OCT, NCI 

OCT, NCI 

ACE, BEIB, DPS 

OCT, NCI 



COOPERATING UNITS (if any) 

NCI, DPS, 



LAB/BRANCH 



Anesthesiology Section 



INSTITUTE AND LOCATION 

CC, NIH, Bethesda 



TOTAL MANYEARS: 



PROFESSIONAL: 



CHECK APPROPRIATE BOX(£S) 
i (a) HUMAN SUBJECTS 

D (al) MINORS D (a2) INTERVIEWS 



n (b) HUMAN TISSUES 



D (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

The purpose of this study is to assess the physiological effects of whole 
body hyperthermia in patients with advanced malignant disease unresponsive 
tu conventional therapy. Concurrently, the toxicity of this procedure will 
be evaluated as well as tumor response after 4 hours at 41.8° C. 

The eventual goal of this study is to determine the feasibility of 
using whole body hyperthermia as an adjuvant to conventional modes 
of cancer therapy. 



Anesthesiology Section 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 
Individual Project Report 
October 1, 1977 - September 30, 1978 

Project Title: Phase I Clinical Trial of Whole Body Hyperthermia 

Project Serial Number: Z01CL07002-01 

Principal Investigator: Joan Bull, M.D., OCT, NCI 

Other: David Eric Lees, M.D., Anesthesiology Section, CC 
William Schuette, B.E.E., ACE, BEIB, DRS 
Jacquelyn Whang-Peng, M.D., OCT, NCI 
E. Ronald Atkinson, Ph.D., DCT, NCI 

Cooperating Units: CC, NCI, DRS 

Total 
Profei 
Other: 



Man Years: Total : 

Professional 



Project Description 



Objective: 



The purpose of this study is to assess the physiological effects of 
whole body hyperthermia in patients with metastatic cancer unresponsive 
to conventional therany. Concurrently, tumor response and toxicity 
at 41.8 C will be evaluated. 

Methods Employed : 

Hyperthermia is induced by means of a high-flow, heated-water 
perfusion suit that was designed specifically for this project. 
Cardiovascular performance is studied by repeated Swan-Ganz 
heart catheterization and percutaneous arterial cannulation. 

Major Findings : 

Subjects with advanced metastatic tolerate the physiological 
extreme of 41.8 C with minimum morbidity from either the 
means of inducing hyperthermia or from the anesthesia. 
Cardiovascular oerformance appears to be the major factor in 
determining whether a patient is a candidate for the new 
form of treatment. 

Significance in Biomedical Research : 

This project provides the base for the expansion of this mode of 
therapy into combinations with other conventional modes of theraoy, 
such as chemotherapy or radiation. In addition, it has provided 
information of clinical usefulness to the anesthesiologist in the 



areas of thermometry, regional blood flow and distribution of 
anesthetic agents under hyperthermic conditions. 

Proposed Course : 

The study has been completed 

Honors and Awards : 

None 

Publications and Presentations: 

Publications : 

Bull JM, Lees DE, Schuette W, Whang-Peng J, Smith R, Bynum G, 
Atkinson ER, Gottdiener JS, Gralnick H, Shawker T, DeVita VT: 
Whole Body Hyperthermia - A Phase I Trial of a Potential Adjuvant 
to Chemotherapy. In Press, Annals of Internal Medicine 

Lees DE, Schuette W, Bull J, Whang-Peng J, Atkinson ER, 
Macnamara TE: An Evaluation of Liquid Crystal Thermometry as 
a Screening Device for Intraooerative Hyperthermia. 
In Press, Anesthesia and Analgesia. . .Current Researches 

Lees DE, Kim YD, Bull J, Schuette W, Whang-Peng J: 
Inadverent Hyperthermia under Anesthesia (letter) 
Anesthesiology (In press ) 

Presentations by Members of the Anesthesiology Section, CC 

Lees, D.E., An Evaluation of Liquid Crystal Thermometry as a 
Screening Devices for Elevations of Core Body Temperature. 
Presented at the 52nd Congress of the International Anesthesia 
Research Society in San Francisco, March 1978 

Lees, D.E., The Effect of Ketamine on the Ventilatory Response 
to Extreme Hyperthermia in Man. Presented at the annual 
meeting of the American Society of Anesthesioloaist, New Orleans, 
October 1977 

Kim, Y.D., Hyperthermic Potentiation of the Alpha-Adrenergic 
Blockade Induce by Droperidol. To be presented at the annual 
meeting of the American Society of Anesthesiologist in Chicago, 
October 1978 

Kim, Y.D., Hemodynamic and Blood Gas Changes with Whole Body 
Hyperthermia. To be presented at the annual meeting of the 
American Society of Anesthesiologists in Chicago, 1978 



Lees, D.E., Innovar Modification of the Ventilatory Response 

to Extreme Hyperthermia in Man. To be presented at the annual 

meeting of the American Society of Anesthesiologist in Chicago, 
October 1978 

Lees, D.E., Ascultatory Confirmation of Esophageal Temperature 
Probe Placement. To be presented at the annual meeting of th3 
American Society of Anesthesiologists in Chicago, October 1978 

Lees, D.E., Exhibit: The Anesthetic Management of Whole Body 
Hyperthermia for the Treatment of Cancer. Exhibit to be 
displayed at the annual meeting of the American Society of 
Anesthesiologist in Chicago, October 1978 



€> 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Do NOT use this space) 



U.S. DEPARTMENT OF 
HEALTH, EDUCATION, AND WELFARE 
PUBLIC HEALTH SERVICE 
NOTICE OF 
INTRAHURAL RESEARCH PROJECT 



PROJECT NUMBER 



Z01CL07003 -01 



PERIOD ^c^ovE^R^ED^ 1, 1977-September 30. 1978 



TiTLt OF P«^o^J|CT jao^characurs jr (|JJjg^^,^g^^- g + Methyl CCNU ip Malignant Melanoma 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



D. E, Lees 
J. M. Bull* 

J. Whang-Peng 

W. Schuette 

E. R. Atkinson 



Attending Anesthesiologist 

Senior Investigator and 
Study Chairman* 

Senior Investigator 

Electrical Engineer 

Physical Sciences Project 
Officer 



Anesthesiology, CC 
COP, OCT, NCI 

OCT, NCI 

ACE, BEIB, DRS 

OCT, NCI 



COOPERATING UNITS (if any) 

NCI, DRS 



.AB/BRANCH 



Anesthesiology Section 



NSTITUTE AND LOCATION 

CC, NIH, Bethesda 



TOTAL MANYEARS: 



PROFESSIONAL: 



CHECK APPROPRIATE BOX(ES) 
^ (a) HUMAN SUBJECTS 



□ (b) HUMAN TISSUES 



□ (c) NEITHER 



n(ai) 



(a2) INTERVIEWS 



SUMMARY OF WORK (200 words or less - underline keywords) 

This study builds on the experience gained with whole body hyperthermia 
phase I protocol that was completed by the same group. This new protocol 
combining whole body hyperthermia with chemotherapy in the treatment of 
malignant melanoma is designed to evaluate the combination versus heat 
alone in metastatic melanoma. as well as to evaluate the toxicity of the 
combination. 

The exposure to hyperthermia is for two hours at 41.8 C every six 
weeks. With each treatment the dose of Methyl CCNU is escalated. 



i 



Anesthesiology Section 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 
Individual Project Report 
October 1, 1977 - September 30, 1978 

Project Title: A Phase I-II Trial of Hyperthermia + Methyl CCNU in 
Malignant Melanoma 

Project Serial Number: Z01CL07003-01 

Principal Investigator: Joan M, Bull, M.D. 

Other: David Eric Lees, M.D., Anesthesiology Section, CC 
William Schuette, B.E.E., ACE, BEIB, DRS 
Jacqueline Whang-Peng, M.D., OCT, NCI 
E. Ronald Atkinson, Ph.D., DCT, NCI 

Cooperating Units: CC, NCI, DRS 

Man Years: Total : 

Professional: 
Other: 



Project Description 



Objective : 



The objective of this study is te determine the toxicity and 
effective dosage of Methyl CCNU in combination with whole body 
hyperthermia. 

Methods Employed : 

Hyperthermia is induced by means of a high-flow, heated water 
perfusion suit, which elevates the patient's temperature to 
41.8 C over a period of approximately two hours. Once the 
temperature is attained, a dose of Methyl CCNU is administered 
and the heat is maintained for two additioncil hours. 

Major Findings : 

It is too early in the study to report any major findings. No 
serious complications have developed with this study, however, 
and the risk does not appear to be any greater than that of just 
whole body hyperthermia alone. 



Significance in Biomedical Research : 

This combined therapy, utilizing both hyperthermia and chemotherapy, 
may offer a better response rate than conventional modes of therapy, 
with little of no increase in toxicity. 

Proposed Course : 

Study will continue to define effective dose of drug in combination 
with heat. 

Honors and Awards : 

None 

Publications: 

None 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Oo NOT use this space) 



0,3. DEPARTMENT OF 
HEALTH, EDUCATION, AND WELFARE 
PUBLIC HEALTH SERVICE 
NOTICE Of 
INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 



Z01CL0700A-01 



"tt'cffir 1, 1977 - September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Pilot Study Examining The Effect of Whole Body Hyperthermia Combined with 
Adriamycin in Patients with Metastatic Sarcoma and Other Cancers 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



D. E. Lees 
J. M. B-Jll* 
J. Whang-Peng 
W. Schuette 

E. R. Atkinson 

*Study Chairman 



Attending Anesthesiologist 

Senior Investigator 

Senior Investigator 

Electrical Engineer 

Physical Sciences Project 
Officer 



Anesthesiology, CC 
COP, OCT, NCI 
OCT, NCI 
ACE, BEIB, DRS 
OCT, NCI 



COOPERATING UNITS (if any) 
NCI, DRS 



lab/branch 



SECTION 

Anesthesiology Section 



NSTITUTE AND LOCATION 

CC, NIH, Bethesda 



TOTAL MANYEARS: 



[PROFESSIONAL: 



CHECK APPROPRIATE BOX(ES) 
^(a) HUMAN SUBJECTS 

(al) MINORS □ (a2) INTERVIEWS" 



n (b) HUMAN TISSUES 



Q (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

This protocol expands on the experience gained with whole body hyperthermia 
alone in the treatment of metastatic cancer . This study is designed 
to evaluate the efficacy and toxicity of combj^ning iricreasing doses of 
adriamycin with whole body hyperthermia, "~ 

Adriamycin is known to have cumulative cardiotoxicity, but nothing is 
known of the toxicity of the drug in combination with heat, so this 
will be an area of particular interest to the Anesthesiology Section. 



Anesthesiology Section 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 
Individual Project Report 
October 1, 1977 - September 30, 1978 

Project Title: Pilot Study E:xamining the Effect of Whole Body 

Hyperthermia Combined with Adriamycin in Patients with 
Metastatic Sarcomas and Other Cancers 

Project Serial Number: Z01CL07004-01 

Principal Investigator: Joan M. Bull, M.D. 

Other: David Eric Lees, M.D,, Anesthesiology Section, CC 
William Schuette, B.E.E., ACE, BEIB, DRS 
Jacquelyn Whang-Peng, M.D., OCT, NCI 
E. Ronald Atkinson, Ph.D., DCT, NCI 
Rosalie Smith, R.N., CC 

Cooperating Unit: CC, NCI, DRS 

Man Years: Total : 

Professional : 



Other: 



Project Description 



Objective: 



This study is designed to evaluated the effeicacy and toxicity of 
adriamycin in combination with whole body hyperthermia. This 
protocol builds on the experience the group gathered with whole 
body hyperthermia alone in patients with advanced metastatic cancer. 

Methods Employed : 

Hyperthermia is induced by means of a high-flow, heated -water 
perfusion suit which elevateds the patient's temperature to 41.8 C 
over a period of approximately two hours. Once at that temoerature 
the adriamycin is then administered intravenously. 

M ajor Findings : 

While the study is not complete, minimal problems above those 
encountered with whole body hyperthermia alone have been seen. 
To date, doses of adriamycin of 50 mg/m have been well tolerated. 



i 



Significance in Biomedical Research : 

Hyperthermia alone has been reported by other investigators to 
be effective against sarcomas alone and adriamycin by itself 
also is effective. By combining the two modes of therapy, an 
enhanced tumoricidal effect is hoped for with no more than additive 
toxicities from the two modes of therapy. 

Proposed Course : 

When an optimum dose of adriamycin is arrived at and toxicity defined, 
expansion into phase III trials will then be possible. 

Honors and Awards : 

None 

Publications : 

Lees DE, Kim YD, Bull J, Schuette W, Whang-Peng J, Smith R: 
Hyperthermia Potentiates Adriamycin Cardiotoxicity. In press, 
Journal of the American Medical Association (JAMA) 



«• 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Oo NOT use this space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

MOT ICE OF 

INTRAMURAL RESEARCH FItOJECT 



PERIOD COVERED 

October 1, 1977 - September 30, 1978 



PROJECT NUMBER 



:01C]i37005 -01 



TITLE OF PROJECT (30 characters or less) ~~~~ " 

Prevention of Post-Thoracotomy Pain by Bupivicaine (Marcaine) 
Nerve Block Anesthesia 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



P. Kapp 

A, Dwyer 

E. A. Weltering'' 
M. W. Flye 

B. McLees 
*Study Chairman 



Attending Anesthesiologist 

Staff Radiologist 

Clinical Associate 

Senior Investigator 

Chief, Critical Care Medicine 



Anesthesiology, CC 

Radiology, CC 

Surgery Branch, OCT, NCI 

Surgery Branch, OCT, NCI 

CC 



COOPERATING UNITS (if any) 
NCI, CC, 



LAB/BRANCH 



Anesthesiology Section 



CHECK APPROPRIATE 80X(ES) 
§^(a) HUMAN SUBJECTS 

q (al) MINORS Q (a2) INI 



INSTITUIE^AN 



ttr^^rfe°e\hesda 



TOTAL MANYEARS: 



PROFESSIONAL: 



D (b) HUMAN TISSUES 



n (=) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) ' ~~ 

Intercostal nerve block after thoracotomy has been used to give objective 
improvement in patient's postoperative pulmonary functions and subjective 
pain- The use of intercostal nerve blocks via- intermittent catheter infusi on 
for a protracted period of time has not been studied. This method may 
be safer and more effective than repeated percutaneous blocks and can 
eliminate the hazards associated with systemic analgesics, such as narcotics 
Marcaine, in usual doses, has little or no systemic effects and therefore 
may offer distinct advantages. 



Anesthesiology Section 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 
Individual Project Report 
October 1, 1977 - September 30, 1978 

Project Title: Prevention of Post-Thoracotomy Pain by Bupivicaine 
(Marcaine) Nerve Block Anesthesia 

Project Serial Number: Z0107005-01 

Principal Investigator: Eugene Woltering, Surgery Branch, OCT, NCI 

Other: Philip Kapp, M.D., Anesthesiology, CC 

A. Dwyer, M.D., Radiology, CC 

B. McLees, M.D,, Critical Care Meqiicine 

M. W. Flye, M.D., Surgery Branch, OCT, NCI 

Cooperating Units: CC, NCI 

Man Years: Total: 

Professional : 
Other: 

Project Description 
Objective: 

Study will evaluate a new method of delivering postoperative analgesia 
to patients with thoracotomies. 

Methods Employed : 

Intermittent catheter infusions post-surgery, bedside pulmonary 
functions before and after surgery, quantitative pain assessment 
techniques 

Major Findings : 

Too early in study to report any major findings. Toxicity,::however, 
has not been a problem. 

Significance in Biomedical Research : 

Intermittent catheter infusion offers the possibility of better 
postoperative analgesia over an extended period and avoids the 
problems associated with repeated percutaneous nerve blocks or 
systemic analgesic agents, such as narcotics. 



Proposed Course : 

Completion of study as outlined in the orotocol 

Honors and Awards : 

None 

Publications : 

None 



October 1, 1977 through September 30, 1978 

PUBLIC HEALTH SERVICE: NATIONAL INSTITUTES OF HEALTH 

SUMMARY OF ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

BLOOD BANK DEPARTMENT: 

CONTENTS 

I Missions and Goals BB- 1 

II Department Activities BB- 2 

A. Service Responsibilities BB- 2 

B. Department Organization BB- 4 

C. Donor Program BB- 4 

D. Laboratory Service BB- 4 

E. Professional Activities BB- 5 

F. Honors and Awards BB- 7 

III Major Progress BB- 7 

A. Progress in Research BB- 7 

1. Hepatitis BB- 7 

2. Immunohematology BB- 9 

B. Progress in Training and Development BB-10 

IV Futiire Objectives BB-12 

V Blood Bank Department Organizational Chart BB-14 

VI Publications BB-15 

VII Protocols on Ongoing Research Projects BB-17 

1. 51 Cr RBC Survival as a Measure of Transfusion BB-17 
Compatibility. 

2, Use of Hepatitis B Immune Globulin Following Acci- BB-21 
dental Exposure to HBsAg Positive Sertim. 



3 . Role of Hem agglutinating and IgE Penicillin Antibody in 
Donor Blood. 

4. Prospective Study of Post -transfusion Hepatitis in Open BB-27 
Heart Surgery. 

5. Chronic Sequelae of Non- A, Non-B Hepatitis. BB-31 

6. The Duffy Blood Group Determinant and Susceptibility to BB-34 
Malaria. 

7. Chido (Ch^) Antibody Production Induced by Cancer Immuno- BB-37 
therapy. 

8. Mechanism of Vertical Transmission of Hepatitis B Virus. BB-40 

9. Transmission of Non-A, Non-B Hepatitis in Chimpanzees. BB-43 

10. Evaluation of Anti-Core Antibody and Serum Transami- BB-46 
nase as Indicators of the Infectivity of HBsAg-Negative 

Donors. 

11. Identification of the Non-A, Non-B Hepatitis Agent and BB-49 
the Development of Serologic Markers. 

12. Hepatitis B Vaccine Trial Among Renal Dialysis Patients. BB-52 

13. Evaluation of the Hepatitis Risk of Hospitalized Patients BB-55 
londergoing invasive procedures, but not receiving blood 
transfusion. 

14. Alterations in Whole Blood Oxygen Affinity Following BB-58 
Transfusion. 

15. Identification of Bacterial Organisms with Kell-like Speci- BB-61 
ficity. 

16. Blood Group Substances in Malignant and Benign Breast BB-64 
Cyst Fluids . 

17. Frozen Red Cells in the Prevention of Non-A/Non B Hepa- BB-67 
titis . 

18. Hypothesis of X-linkage in Bi-polar and Uni-polar Affective BB-70 
Disease. 



October 1. 1977, through September 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY OF ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

BLOOD BANK DEPARTMENT 



I. BLOOD BANK MISSIONS AND GOALS 

The NIH Clinical Center Blood Bank is first and foremost a service organi- 
zation, thus it provides safe and effective blood and components to CC pa- 
tients. However, the department's missions and goals extend into teaching 
the disciplines of blood banking, and immuno hematology, plus conducting 
developmental research. 

The primary mission of the Blood Bank Department remains service to Clin- 
ical Center patients. The Blood Bank processes all blood and blood products 
transfused to NIH inpatients and outpatients. More than half of the blood 
transfused is obtained from NIH volunteer donors phlebotomized in this de- 
partment; the remainder is obtained from cooperating centers in the Ameri- 
can Red Cross and the American Association of Blood Banks. Blood obtained 
from outside the NIH is also processed and crossmatched in the Blood Bank 
laboratories to assure safe and effective blood and components. 

This department makes maximal use of a relatively small nimiber of blood 
donors. Donors are registered in a computer file and recruited to fill spe- 
cific patient requirements. In addition, donated blood is separated into com- 
ponents whenever possible to maximize the use of each unit. We are further 
increasing our collection of com.ponents by emphasizing both manual and 
automated cell separation techniques. 

The service mission of the Blood Bank includes provision of consultation and 
blood products to all the NIH Institutes and to the community when necessary. 
We have cooperative agreements with the American Red Cross, the American 
Association of Blood Banks, and other groups involved in providing blood, es- 
pecially those in the Washington Metropolitan region. We maintain a sophis- 
ticated referral laboratory for this area as well as for more distant parts of 
the United States; we attempt to provide answers and, frequently, compatible 
blood. We work closely with the Red Cross in the collection of blood, with 
joint blood drives, and in husbanding of blood resources in the commimity. 
The Blood Bank provides pheresis of patients and normal donors to supply nu- 
merous blood samples and components to clinical and laboratory scientists at 
NTH; this latter service is limited only bv the demands of patient related ac- 
tivities. Through our "blood assurance" program we guarantee the blood 
needs of NIH employees and their families (both locally and throughout the 
U. S.). 

The second mission of the Blood Bank is teaching. We provide a varied edu- 
cational experience to physicians enrolled in our 1-2 year blood bank train- 

BB-1 



ing program, one of the few American Medical Association approved pro- 
grams in the country. In addition, physicians from the Clinical Center Clin-x- 
ical Pathology Department, the Georgetown University Pathology Department^ 
and Hematology Divisions at local m.edical schools participate in training ex- 
periences of varying length. Medical students may also spend elective time 
in our department. Blood Bank technologists obtain a year of graduate train- 
ing in our AABB approved Specialist in Blood Banking (SBB) program which 
qualifies them for subspecialty certification. Student laboratory technicians ■ 
from Montgomery Community College receive their blood bank practical ex- 
perience in our laboratory. We have an active in-service education program 
for our staff and for other Clinical Center employees. Members of this De- 
partnaent also teach and provide consultation for local hospitals, universities, 
and military facilities as well as for organizations all over the country. 

Research is the third component of the Blood Bank mission. Our applied re- 
search is directed toward improved therapeutic techniques for transfusion, 
phlebotomy, and pheresis; production of superior blood products; and reso- 
lution of difficult clinical problems, as they present to our service and refer- 
ence laboratories. The CCBB has gained an international reputation for its 
contributions in the prevention of viral hepatitis, especially after transfusions, 
and the elucidation of problems in immunohematology. 

Departmental goals for the coming year relate to all three areas. 

Service - in the past year we have expanded our blood donor base by 10% and 
hope to add an additional 10% in the coming year. We expect to add more 
joint, mobile blood drives at off campus NIH buildings mth the American Red^ 
Cross. We plan to enlarge our hemotherapy services; we established auto- 
mated pheresis and cell separation this past year and hope to offer a full 
range of pheresis services in the coming year. 

Teaching - our training programs continue to attract more applicants than 
we can accommodate. We begin the year with an excellent group of students 
and residents as well as a redesigned curriculimi for the SBB program 

Research - we intend to further our research program by intensifjdng inves- 
tigations of the problems of chronic transfusion and the significance of peni- 
cillin antibodies in blood. 

II. DEPARTMENT ACTIVITIES 

Service Responsibilities 

The Blood Bank Department's major service goal remains the provision of 
safe and effective blood and blood products. More than 7600 units of whole 
blood and red cells were transfused during the past year. Approxiinately 51% 
was drawn in our own blood bank ^Arith the remainder being supplied primarily 
by the Washington Regional Blood Program, of the Red Cross. This repre- 
sents a 2% increase in both transfusion and collection. Blood Bank physi- 
cians continued their clinical consulting role and evaluated 75 suspected 
transfusion reactions, 66% of which were, in fact, transfusion related. In 



BB-2 



addition. Blood Bank physicians assumed the responsibility of evaluating 
platelet transfusion reactions and assisted patient care physicians in manag- 
ing niimerous immunohematologic problems. The first known instance of 
plasma exchange to remiove a cold agglutinin from a patient schedtxLed 
for heart surgery under hypothermia was successfully carried out under 
Blood Bank supervision. 

The Blood Bank continued to prepare fresh frozen plasma and cryoprecipita- 
ted antihemophilic factor for congenital and acquired bleeding disorders. 
While these components are primarily for Clinical Center inpatients, we fre- 
quently provide for home therapy of, e.g. , hemophiliacs. To provide suf- 
ficient coagulation components factor Vin commercial concentrate was again 
acquired by contracts; we obtain this concentrate by direct purchase as well 
as in exchange for our plasma. 

Therapeutic procedures have increased in the past year: m.ore than 20 
phlebotomies have been performed on patients with polycythemia and hemo- 
chromatosis. The cell separator (Haemonetics Model 30) which became fully 
operational in the past year was used for exchange transfusion in sickle cell 
anemia, exchange transfusion in autoimmune hemolytic anemia, and removal 
of cryoglobulins in patients with primary cryoglobvilinemia. This capability 
and our emphasis on therapeutic pheresis brought BBD personnel to the pa- 
tient's bedsicfe., The cell separator was also extensively used for plasma and 
component preparation for patient and research use. In the face of great 
demand, the use of this instrument was limited only by the number of our 
nursing personnel. 

The Plateletpheresis Center, in its fifth year on an NCI contract, continued 
to function at close to maximum capacity. It routinely prepared approxi- 
mately 1100 units of platelets per month and continued to enlarge its list of 
HLA typed, potential donors. The Blood Bank monitored its performance 
and functioned as its primary backup for Clinical Center platelet needs. 
Dr. Holland continued as the Project Officer for this facility. 

The Blood Bank, in general, met increasing requests for blood products 
from the NIH "research community. " We performed an average of 41 man- 
ual plasmapheresis procedures and fifteen machine phereses per month for 
research purposes. Approximately 330 blood samples a month were dra-^m 
in the Blood Bank for NIH laboratory studies. In addition, we occasionally 
provided blood products for other government facilities such as the provis- 
ion of 16 units of serum drawn in specially designed polyethylene tubing, in 
order to remain free of the polychlorinated biphenol compounds found in vir- 
tually all plastic and rubber products; this serum was used by NIEHS for en- 
vironmental research and could not be obtained readily from an3/ other U.S. 
source. The pro-rision of specialized research blood and blood products has 
been limited at times by lack of space and personnel since pro-nsion of ther- 
apeutic products for patients always takes precedence over other demands. 



5-3 



Department Organization ^ 

The Blood Bank Organizational Chart is on page BB-14, Ms. Mary Gustafson 
was appointed technical supervisor for the service laboratory upon the resig- 
nation of the chief technologist. Ms. Sandra Maytag, a prior graduate of our 
SBB program, returned to the CCBB to assume the newly created position of 
assistant technical supervisor. Dr. Ronnie J. Garner has been acting super- 
to the Recruiting Unit of the Blood Services Section. 

Donor Program 

The Blood Bank continued its policy of using all volunteer blood and received 
a certificate from the American Association of Blood Banks attesting to the 
all volunteer blood program. The current donor rolls are now at 2 443, an 
all time high. Active recruitment of new blood donors continued. Joint mo- 
bile operations with the Red Cross were extended from the Westwood, the 
Landow, the Blair, and the Federal Buildings, producing 312 additional units 
of blood, as well as new donors for the Blood Bank computer files. There 
has been increased publicity about the NIH Blood Bank and the need for new 
blood donors in the NIH Record and the Clinical Center Closeup . A biiilding 
to building drive was instituted to familiarize potential donors with Blood 
Bank procedures and its blood needs. One new promotional item, a tennis 
ball size Nerf ball given to each volunteer donor during May, 1978 to squeeze 
during the phlebotomy, was extremely successful, A one month survey of 
NIH blood donors showed that almost every donor was pleased with the NIH 
Blood Bank. m 

Through the Blood Assurance Program, one of the most liberal assurance 
plans in the country, approximately 500 units of blood were supplied for NIH 
employees and their relatives over the past year. 

Laboratory Service 

The Blood Bank Laboratory is divided into Compatibility Testing and Donor 
Processing areas. It is staffed for a minimum of 76 hours a week but pro- 
vides 24 hour coverage, seven days a week via an "on call" system utilizing 
regular personnel. During the past year the laboratory staff determined 
the blood group and type of 3, 683 new patients and performed 4, 971 direct 
Coomb's tests, 5, 997 patient screening tests for irregular antibodies, and 
13, 734 crossmatches. These procedures make up the bulk of our routine 
laboratory work. 

The routine work of our staff is far from "routine, " however. Our patient 
population differs from that of most general and even university hospitals. 
The nature of the illnesses and number of blood transfusions predispose our 
patients to difficult and unusual transfusion problems. For example, patients 
with five or more unexpected antibodies in their serum were encoiintered. 
5lCr red cell survival studies were necessary in a number of patients with 
compatibility problems and were invaluable in several cases. Two patients 
with transfusion reactions but iwith no serologic evidence of incompatibility 
were found to have greatly reduced in vivo red cell survivals. Red cell A^ 



antibodies of low thermal amplitude are generally not considered to be sig- 
nificant when choosing appropriate blood for transfusion. However, the in- 
creased niomber of cardiac by-pass operations performed with hypothermia 
has given us the opportunity to observe the effects of these antibodies during 
hypothermia. Several antibodies were identified and confirmed by special- 
ized tests. 

Professional Activities 



The professional staff has continued to participate actively in a wide variety 
of local, national, and international meetings and programs during the past 
year. 

Dr. Paiol Holland was a speaker and workshop moderator at the International 
Hepatitis Symposium in San Francisco and a participant in the 3rd Interna- 
tional Congress of Immunology, Sydney, Australia; he was the moderator 
of the USA-USSR joint meeting on transfusion related hepatitis (and coordin- 
ator of a joint seroepidemiologic swrvej of blood donors in both countries), 
the chairman of the NHLBI Policy Board for the Transfusion Transmitted 
Viruses Study, and a speaker at the American Gastroenterological Society's 
Postgraduate Course in Las Vegas. He continued as a member of the clini- 
cal faculty of the George Washington, Georgetown, and Uniformed Services 
medical schools, and was course director of the NIH FAES sponsored Immu- 
nology #508, Immunohematology and Blood Transfusion. He lectured widely 
at area medical schools and hospitals, and served on the Technical Manual 
Committee of the American Association of Blood Banks, the American Red 
Cross Research Review Committee, and various standing and ad hoc com- 
mittees at NIH. 

Dr. Harvey J. Alter was chairman of the Scientific Working Group of the 
NIH Viral Hepatitis Coordinating Committee, speaker at the symposium. 
Advances in Immunohematology and Blood Transfusion at the University of 
Minnesota Medical School, and speaker and workshop co-chairman at the 
International Hepatitis Symposium in San Francisco. He was a member of 
the Medical Advisory Committee of the American Red Cross, member of the 
Scientific Program Committee of the American Association of Blood Banks, 
and chairman of a technical session at the AABB Annual Meeting. Dr. Alter 
was the author of several scientific papers, including a widely publicized 
work demonstrating the transmissibility of non-A, non-B hepatitis. He is 
clinical associate professor of medicine at Georgetown University Hospital, 
made numerous presentations to NIH groups and area hospitals, and was a 
faculty member of the FAES coxirse Immunology #508. 

Dr. Harvey G. Klein continued as consultant to the Johns Hopkins Hospital 
in the hematolo.gy clinic and was a speaker at hematology grand rounds. He 
lectured at the Baltimore -Washington Blood Study Group. Dr. Klein pre- 
sented a paper on the clinical effect of two dosage regimens of hepatitis B 
immune serum globulin at the International Symposium on Hepatitis in San 
Francisco. He spoke to the Clinical Pathology and Blood Bank departments 
at the ?/Iassachusetts General Hospital and was a member of the NIH Hemo- 
philia Review Committee, MCHS, HSA, and clinical consultant ^Arith the Clin- 



BB-5 



ical Hematology Service, NHLBI. He attended the annual meetings of the 
American Society of Hematology and the American College of Physicians. # 
He was a faculty member in Immunology #508, in the Nursing Department's 
blood transfusion course and in the Uniformed Services Medical School's 
pathology course. 

Dr. Richard J. Davey is clinical assistant professor of medicine at George- _ 
town University Hospital; he served as attending physician for the Department 
of Medicine, as instructor for the second year medical school course in hem- 
atology, and as a speaker at the Georgetown hematology conference. He 
spoke at grand rounds at the D. C. General Hospital, and to the Blood Bank 
and Clinical Pathology departments, Massachusetts General Hospital, Boston, 
Massachusetts and attended the annual meeting of the American College of 
Physicians in Boston and the International Transfusion Congress in Paris. 
He was a member of the NTH Clinical Center Education Coordinating Commit- 
tee and coordinator of educational activities in the CCBB. He was a faculty 
participant in the USUHS pathology course. Immunology course #508, and the 
Nursing Department's blood transfusion course. 

Ms. Mary McGinniss served on the Scientific Section Coordinating Commit- 
tee, the Scientific Program Committee, and the Standards Committee for the 
American Association of Blood Banks. At the AABB annual meeting Ms. 
McGinniss received the Ivor Dunsford Award for distinguished accomplish- 
ments in immunohematology and spoke on her research linking malaria to 
the Duffy blood group system. Ms. McGinniss conducted numerous teaching 
sessions in immunohematology throughout the year, was a fac-ulty member % 
of Inmnunology course #508, participated in the Georgetown Hematology con- 
ference, and NIH Clinical Pathology Department conferences. Ms. McGinniss 
was an invited guest speaker at the International Transfusion Congress in 
Paris, and also at the annual convention of the Canadian Society of Labora- 
tory Technologists in Winnipeg, Canada. 

Laboratory supervisor Ms. Mary Gustafson organized a successful poster 
presentation on the Chido blood group at the AABB Annual Meeting at Atlanta. 
She served on the advisory committee for the Montgomery College MLT pro- 
gram and as preceptor for their blood bank rotations at NIH, Ms. Gustafson 
continued as Education Coordinator for the SBB students and joined the pre- 
sent faculty of Immunology #508 during its second semester. 

Blood Bank fellow Dr. Ronnie J, Garner successfuly com.pleted board exami- 
nations in anatomic and clinical pathology. He attended a symposium on 
advances in immunohematology at the University of Minnesota and the AABB 
annual meeting in Atlanta- He was a faculty participant in Inamunology course 
#508 and in the nurses' blood transfusion course. He developed expertise in 
automated pheresis techniques by participating in the pheresis program at the 
U.S. Naval Medical Center. 



BB=6 



NIH Honors and Awards 

Ms. Mary H. McGinniss and Ms. Marie Moroney received Length of Service 
Awards for 20 years of government service, and Ms. Mary Ann Tourault re- 
ceived a Ten Year Award. 

Ms. Elsie Yanchtdis received the NIH Merit Award for her outstanding work 
in blood banking and received a Quality Increase Award. 

Mr. Jimmie Driscoll received the Special Act of Service Award for his parti- 
cipation in the Joint Clinical Center Blood Bank and American National Red 
Cross Blood Drives. 

Ms. Susan Eberhard, Ms. Debra Leach, Ms. Le nit a Hudson, and Mr. Dana 
James received Cash Awards for their outstanding work performance during 
the summer. 

The Blood Bank as a whole was recognized in two additional ways this 
past year. In the annual Clinical Associate Survey, the Blood Bank ranked 
first of the eleven supportive clinical services rated. For the second year 
in a row the Clinical Pathology Resident Staff ranked the Blood Bank first 
among their four rotations. 

III. MAJOR PROGRESS 

Progress in Research 

Hepatitis 

This has been a significant year in hepatitis research for the Immunology 
Section of the Blood Bank under the direction of Dr. Harvey Alter. Two 
studies have achieved national prominence. The first, published in the New 
England Journal of Medicine , demonstrated in a chimpanzee model that while 
freezing and deglycerolization of human blood could render it free of hepatitis 
B surface antigen, it did not remove hepatitis B infectivity. Frozen degly- 
cerolized red cells have many, well -documented advantages; but their major, 
potential advantage was their postulated ability to prevent human hepatitis; 
our studies do not support this. New studies are underway to determine if 
frozen and deglycerolized red cells afford a protective effect against the now 
more prevalent non-A, non-B hepatitis virus. 

The second major study completed this year relates to the postulated non-A, 
non-B hepatitis virus. Our ongoing study of posttransfusion hepatitis (see 
below) reveals that 90% of transfusion- related hepatitis is serologically un- 
related to the hepatitis A (infectious) or hepatitis B (serum) hepatitis viruses. 
This has led to the hypothesis that there is at least one additional, previously 
unrecognized, human hepatitis virus. However, no virus particle has been 
observed, no serologic test has been developed, no growth in tissue culture 
has been achieved, and, until owe study, there had been no transmission to 
an anim.al model. Using serum or plasma obtained from patients with acute 
or chronic non-A, non-B hepatitis, we were able to transmit non-A, non-B 



BB-' 



hepatitis to 5 of 5 experimentally inoculated chimps. This documented that 
non-A, non-B hepatitis was due to a transmissible agent, and that this agent f"" 
could remain infectious over a prolonged period of time, thereby establish- 
ing the existence of a chronic asymptomatic carrier state for non-A, non-B 
just as there is for hepatitis virus B. 

The most recent phase of our ongoing study of posttransfusion hepatitis a- 
mong open heart surgery patients now has 377 patients who have completed 
9 months of follow-up. Of these patients, 30 (7. 7*7c) have developed hepatitis 
of which 2 7 (90<7c) had neither type A nor type B disease. Among the non-A, 
non-B cases, approximately 2/3 are anicteric and only mildly symptomatic. 
Despite the relative benignity of the acute course, this is a significant entity 
since approximately 45% of the 26 patients have had transaminase elevations 
for longer than a year; 7 of 8 biopsied show histologic changes of chronic 
active hepatitis. We are continuing to observe the long term sequelae of the 
entity. C3f interest is the fact that similar chronic hepatitic disease is being 
observed in non-A, non-B infected chimpanzees. A new aspect of our heart 
studies this year has been the addition of a non-transfused control group. 
This control population was added because we have no serologic markers for 
the non-A, non-B virus, and because in cases of mild enzyme elevation it is 
difficult to assess if the hepatic inflanamiation is of viral, toxic, or cardio- 
genic origin. In addition, in cases of suspected viral origin, we wanted to 
ascertain if this was piorely the result of transfusion or if it could derive 
from procedures such as cardiac catheterization or was merely because of 
the hospital environment. We are thus prospectively following all patients 
who -undergo cardiac catheterization in whom surgery and transfusion are 
not contemplated in the next six months. We have currently enrolled ap- t 
proximately 60 control patients, one of whom has developed mild transient 
hepatitic enzyme elevations. We anticipate that in the next year we will have 
sufficient control patients to make statistical comparisons with our trans- 
fused cardiac surgery population. 

We completed two aspects of our studies of Hepatitis B Immune Globulin 
(HBIG) this year. The first, headed by Dr. Harvey Klein, demonstrated 
that a two dose regimen of HBIG was superior to a single injection schedule, 
even though they both involved the same total dose of globulin. The second 
was a collaborative study with the VA Cooperative Group. This study clearly 
demonstrated the efficacy of HBIG as compared with immune serum globulin 
(ISG) and also clearly showed that blood containing the e antigen was highly 
infectious as compared with blood which lacked this antigen. 

We have continued to participate in a large multi -hospital study of hepatitis B 
in renal dialysis centers which will serve as a baseline for subsequent hepa- 
titis B vaccine trials in these same units. It is anticipated that the hepatitis 
B vaccine will be ready for clinical trial in the Spring of 1979. 

Our studies of non-A, non-B hepatitis in humans and chim.panzees will re- 
main our main area of emphasis over the next year. The most pressing need 
is to develop serologic test for this viral agent or agents. Our attempts 
thus far have been unsuccessful. This year, in collaboration with Drs. John 
Gerin and Robert Purcell, we prepared pellets from acute phase, non-A, 



BB-8 



non-B sera by ultracentrifugation and reacted these against a series of con- 
valescent phase sera in a solid phase radioimmunoassay. 

The results were disappointing, but we are now going to repeat the study us- 
ing sera from heavily transfused hemophiliac and thalassemic patients as 
the potential source of antibody. We may also try to obtain viral antigen by 
partial hepatectomy of a chronically infected chimpanzee. Other collabora- 
tive efforts towards developing a test are being done in association with 
Abbott and Pfizer laboratories using a radioimmunoassay and ELISA test re- 
spectively. 

Further studies in chimpanzees will follow the natural course of their chronic 
non-A, non-B hepatitis and then to initiate cross -challenge experiments to 
determine if more than one non-A, non-B agent exists. These studies will 
also include homologous challenge in an attempt to boost antibody levels. 

Other current studies can be briefly summarized as follows: (1) an evalua- 
tion of the efficacy of testing for anti-core antibodies as a means to detect 
HBsAg -negative carriers of the hepatitis B virus; (2) an evaluation of the 
role of fetal antigens, e.g. CEA, in relation to non-A, non-B hepatitis (3) 
an evaluation of the role of immune complexes, as measured by the sensi- 
tive RAJI cell assay, in relation to non-A, non-B hepatitis (4) an evaluation 
of the usefiilness of testing donors for SGPT as a means to decrease the 
transmission of non-A, non-B hepatitis until such time as a serologic test 
is developed (5) the establishment of a pedigreed large volume panel of in- 
fectious material containing the non-A, non-B agent. We currently have in 
excess of 25 plasmapheresis units of proven infectious or potentially infect- 
ious material. One such unit is being vialed in multiple dilutions to serve 
as a reference reagent. 

Imm unohe m at ol o gy 

The Immunohematology Laboratory, under the direction of research biolo- 
gist Mary H, McGinniss, continues to serve as a major reference center 
for problems in transfusion-related immunohematology. Between 5 and 8 
cases monthly are referred to this laboratory from local and distant hospital 
laboratories, with the vast majority of these referred problems being satis- 
factorily resolved. 

The long term study by Ms. McGinniss concerning the loss of normal red 
cell antigens of the ABO, I and Lewis systems has culminated in a paper en- 
titled "Multiple Red Cell Antigen Loss in Acute Granulocytic Leukemia" 
which will appear in the journal Cancer . Further evaluation of one of the af- 
fected patients revealed the gain of a Kell-like antigen during apparent sepsis 
with bacteremia. Thus, a study has been initiated to determine the influence 
of certain bacterial organisms on either the acquisition of Kell-like antigen 
on red blood cells or the induction of IgM, transient anti-Kell in infected pa- 
tients. This study is being conducted with the help of the Microbiology 
section of the Clinical Pathology Department and is a follow-up of an original 
observation by Ms. McGinniss. 



33-9 



The long term study of the passive transfer of IgE penicillin antibody present 
in donor plasma continues with a new and more intensive protocol. Work is r 
continuing on the RAST test for determining the presence of IgE penicillin 
antibody. 

Ms. McGinniss and Dr. Louis H, Miller of NIAID continue to study rare red 
cells which may delineate the red cell antigen involved in the life cycle of P. _ 
falciparum . The antigen may be part of the MNS system. 

A study defining the possible relationship between bi -polar manic depressive 
disease and the X sex chromosome, using the Xg blood group as a marker, 
will be concluded in June '78. This study involved collaboration with the 
National Institute of Mental Health. 

During 1iie past year increased emphasis has been placed on the rapid se- 
quence "HZr red cell survival technique as a research tool. Dr. Richard 
Davey has used red cell survival studies to identify clinically significant red 
cell alloantibodies which were unable to be detected by standard in- vitro labo- 
ratory techniques. Certain of these antibodies had caused severe transfusion 
reactions in blood recipients. Identification of the antibodies through the 
51Cr survival studies allows transfusions to be given with relative safety to 
these patients in the future. On occasion red cell alloantibodies can be easily 
detected in - vitro , but their in-vivo significance remains unclear. Drs. Davey 
and Garner are currently studying a group of patients with the anti-Lewis^ 
antibody with chromium labeled cells to determine the clinical potency of this 
commonly encountered antibody. Studies of two families with unusual red 
cell antibodies are progressing. Several members of one family have sickle-' 
cell anemia, while the siblings of the other family have an unusual hypo- 
chromic, microcytic anemia. 

Dr. Davey also supervised a trial of a new therapeutic regimen for the pro- 
phylaxis of high altitude mountain sickness and high altitude pulmonary e- 
dema. A group of moixntain climbers ascending to high altitude in the 
Himalayas were given acetazolamide prophylaxis and compared to a control 
group who did not take the drug. The results confirmed previously reported 
observations of the efficacy of acetazolamide prophylaxis during rapid ascent 
to a high altitude. 

Progress in Training and Development 

Mastery of blood banking and immixnohematology requires extensive training 
in those fields. The Clinical Center Blood Bank considers the education of 
physicians, ntirses, and technologists in these disciplines one of its primary 
responsibilities and goals. 

The training of physicians was expanded this past year through the initiation 
of a fully A. M. A. accredited fellowship program in blood banking. The first 
blood bank fellow. Dr. Ronnie Joe Garner, completed one year of extensive 
training in all aspects of the specialty and accepted a position as blood bank 
director at Presbyterian Hospital, Albuquerque, New 3/Iexico. He success- 
fully passed the board examination in Blood Banking. The second blood bank ^ 

BB-10 



fellow. Dr. Jory Braun, came from the Hematology Service, Beth Israel 
Hospital, Boston, for subspecialization in blood banking. It is anticipated 
that the fellowship program will continue to grow in both clinical exposure 
and research opportunities in the forthcoming years. We have numerous, 
qualified applicants for our one opening a year. 

The Blood Bank participates in the training of the Clinical Pathology resi- 
dents at the Clinical Center. Four first-year residents participated in a 
highly successful, modular training program covering all major aspects of 
blood banking during an 11 week rotation. Four residents and hematology 
fellows from Georgetown and George Washington University Hospitals also 
participated in this program during the past year. A measure of the effect- 
iveness of this training program is the first place rating given to the Blood 
Bank by the Clinical Pathology residents for the second year in a row. One 
second year Clinical Pathology resident spent a six month rotation in the 
Blood Bank to further his training in immunohematology and his research 
project while another began a one year elective for the same purpose. 

Advanced training in blood banking technology is another area of emphasis 
at the CCBB. We completed the first year of a completely revised training 
program for two employee-students in the Specialist in Blood Banking (SBB) 
school at N.I.H. The new program employs teaching by objectives and a 
specific, modular curriculum under the direction of the Blood Bank senior 
staff. Both students and faculty expressed satisfaction with the new format. 
Blood Bank personnel also participated in the medical laboratory technician 
(MLT) training program at Montgomery Community College, giving lectures 
at the Rockville campus and providing laboratory rotations for four students. 

The training of nvimerous Clinical Center nurses in the theory and technique 
of blood transfusion and component therapy continued. Several times during 
the year blood bank senior staff taught the course. 

The Blood Bank conducted an extensive series of weekly "in-house" confer- 
ences designed to maintain and upgrade the professional competence of the 
entire departmental staff. These conferences included residents' rounds, a 
journal club, a clinical -laboratory correlation conference, and a Friday noon 
lecture. The weekly Blood Bank lecture featured talks by internationally rec- 
ognized scientists, research presentations by NTH workers, and reports on 
meetings attended by the Blood Bank staff. On the average, four hours a 
week are devoted to teaching activities by and for the staff of the Blood Bank 
and interested individuals at NIH. 

Community teaching activities included fioll senior staff participation in the 
FAES course Immunology #508, Immunohematology and Blood Transfusion 
which was taught both Spring and Fall Semesters. In addition, the full-time 
blood bank physician staff held faculty positions at Georgetown, Johns Hop- 
kins, and George Washington University Hospitals and the Uniformed Ser- 
vices University for the Health Sciences, 



BB-11 



IV. FUTURE OBJECTIVES: 

The Blood Bank staff views its present patient care, teaching and research ^ 
activities in the context of several future objectives and goals. Many of 
these future objectives center around the projected major increase in the 
Blood Bank's space and staff when the AmbiiLatory Care Research Facility 
is completed in the next few years. 

The Blood Bank plans to strengthen its ability to provide optimal support for 
patient care in the future. A primary objective related to this goal is to ex- 
pand our base of blood donors on the NIH campus. Eventually we hope to be- 
come completely self-reliant in terms of Clinical Center blood requirements 
through increased donor recruiting efforts at all NIH buildings. There also 
will be an increased emphasis on frozen red cells for patient care needs. 
Use of frozen red cells would allow greater blood inventory control, as well 
as the selection of the best available red cell product for the patient, autolo- 
gous blood. In addition, specialized patient care needs such as plasmapher- 
esis and exchange transfusion can be more easily met through projected in- 
creased use of automated blood processors such as the Haemonetics Model 
30. We plan to acquire another m.achine, a continuous flow cell separator, 
to give more flexibility in producing products and carrying out therapeutic 
pheresis. 

Continued progress in research is of primary importance to the Blood Bank. 
A major research goal is the development and expansion of automated phere- 
sis techniques in blood banking. The Haemonetics Model 30 blood processing 
machine has been used for prophylactic and therapeutic whole blood and m"' 

plasma exchange transfusion in selected patients. It is planned to expand the ^- 
role of these machines in the treatment of hemoglobinopathies such as sickle 
cell anemia and thalassemia. 

With the projected eventual increase in Blood Bank space, it is anticipated 
that the plateletpheresis operation will come under direct Blood Bank control. 
This will open up research opportunities relating to platelet transfusion. 

Research in immunohematology will continue through investigation of new 
suspending media for conducting antibody identification tests, and further 
exploration of the relationship of red cell antigens to disease. The use of 
radiolabeled red cells as a tool in the evaluation of unusual antigen-antibody 
systems will continue on an expanded basis. 

Research in hepatitis will also continue, based on the Blood Bank's solid 
record of achievement in this field. Further studies of non-A, non-B hepa- 
titis especially to develop a test to identify carriers will be carried out. 

Continued growth in the Blood Bank's teaching program is another primary 
objective for the future. The recently developed core curricula for the fel- 
lowship and SBB programs will be revised and modified on an annual basis. 
Emphasis will continue to be placed on teaching immunohematology at area 
medical schools and at the FAES evening program. It is anticipated that 
both the fellowship and SBB programs will expand when increased space and 
staff become available. ii, 

BB-12 



The Blood Bank staff views the future with optimism and excitement. With 
increased space and staff, we plan to reach the patient care, teaching and 
research goals we have established- 



BB-13 



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BB-14 



PUBLICATIONS 

1. Alter, H. J, : How frequent is posttransfusion hepatitis after the intro- 
duction of 3rd generation donor screening for hepatitis B ? What is its 
probable nature? Vox Sang . 32: 346-364, 1977. 

2. Alter, H. J. , Purcell, R.H,, Feinstone, S.N,, Holland, P.V, and 
Morrow, A. G. : Non-A, non-B hepatitis: A review and interim report 
of an ongoing prospective study, in Viral Hepatitis , In Press, 

3. Alter, H. J. , Purcell, R.H,, HoHand, P.V. and Popper, H, : Trans- 
missible Agent in "non-A, non-B" hepatitis. Lancet 1: 45 9-463, 1978. 

4. Alter, H. J. , Tabor, E,, Meryman, H.T., Hoofnagle, J. H. , Kahn, 
R.A., Holland, P.V,, Gerety, R.J,, and Barker, L, F. : Transmission 
of Hepatitis B Virus Infection by Transfusion of Frozen- Deglycerolized 
Red Blood Cells. New Engl, J, Med , 298: #12, 637-642, 1978. 

5. Courouce, A, M. and Holland, P, V. : Workshop on HBsAg and its sub- 
types, in Viral Hepatitis , In Press. 

6. Davey, R. J. , Esposito, D.J,, Jacobson, R, J, , Corn, M, : Partial 
exchange transfusion as treatment for hemoglobin SC disease in preg- 
nancy. Arch. Internal. Med . 138: 937-939, 1978. 

7. Davey, R. J. , O'Gara, C. . and McGinniss, M. H. : The saline agglut- 
inating phenomenon. Vox Sang . , In Press. 

8. Davey, R. J. , TouraiiLt, M.A,, Holland, P. V, : The clinical significance 
of anti-H in an individual with the O (Bombay) phenotype. Transfusion , 
In Press. 

9. Holland, P.V.: Discussion of paper bv Dr. M. Goldfield entitled, 
"Control of Posttransfusion Hepatitis. ' in Viral Hepatitis , In Press. 

10. Hollinger, B, and Alter, H, J, : Workshop on non-A, non-B hepatitis. 
in Viral Hepatitis , In Press. 

11. Klein, H.G., Alter, H. J. , and Holland, P. V. : Postexposure immuno- 
globulin prophylaxis of hepatitis B: A comparison of two dosage 
schedules, in Viral Hepatitis , In Press, 

12. Kolins, J,, HoUand, P, V. , and McGinniss, M. H. : Multiple red cell 
antigen loss in acute granulocytic leukemia. Cancer , In Press. 

13. Mason, S.J,, Miller, L,H, , Shiroishi, T,, Dvorak, J. A. , and 
McGinniss, M,H, : The Duffy blood group system and susceptibility to 
Plasmodium knowlesi malaria, Brit, J. Haem. 36: 327-335, 1977. 



BB-15 



14. MUler, L.H.. McGiimiss, M.tL. , Holland, P. V. . and Sigmon, P.: 

The Duffy group phenotype in iVmerican Blacks infected with Plasmodiumf ' 
v ivax in Vietnam. Amer. J. of Tropical Medicine & Hygiene , In Press. " 

15. Moraczewska, Z. , Madalinski, K. , and Holland, P. V. : Simultaneous 
Presence in Serum of HBsAg and Anti-HBs of Different 
Specificities. Intervirology 9: 189-192, 1978. 

16. Keys, L. L. , Purcell, R.H., Holland, P.V. and Alter, H. J. : The Rela- 
tionship between hepatitis B virus infection and hepatic cell carcinoma 
in Mozambique. Trop. Geogr. Med . 29:251-256, 1977. 

17. Seeff, L.B., Wright, E.G., Zimmerman. H.J,, Alter, H.J,, Dietz, 
A. A., Felsher, B.F., Finkelstein, J. D. , Garcia-Pont, P., Gerin, 
J. L. , Greenlee, H. B., Hamilton, J., HoUand, P.V. , Kaplan, P.M., 
Kiernan, T., Koff, R. S., Leevy, C.M., McAuliffe. V. J. , Nath, N. , 
PurceU, R.H., Schiff, E.R. , Schwartz, C.C., Tamburro, C.H., 
Vlahcevic, Z. , Zemel, R. , and Zimmon, D.S.: Type B Hepatitis after 
needle -stick exposure: Prevention with Hepatitis B immune globulin. 
Ann. Int. Med . 88: 285-293, 1978. 

18. Weiss, G.B., Nienhuis, A.W., Mcintosh, C.L. and Klein, H.G.: 
Traumatic Cardiac Hemol37tic Anemia as a Late Complication of a 
Starr-Edwards Mitral Valve Prosthesis. Arch^ Intern. Med . , 

In Press. 

19. Whitney, R.A. , Ganaway, J. R. , Allen, A.M., Alter, H. J. , Purcell, f 
R. H, , and Holland, P. V. : Failure to transmit human viral hepatitis 
types A and B to the congenitally athvmic nude mouse. Lab. Animal 

Sci. 27: #6, 1031, 1977. ' 



€ 



BB-16 



SMITHSO^ilAM SCIENCE IMFORMATION cXCMAMGEl U.S. DEPARTMENT OF 
PROJECT NUMBER (Oo NOT use this space) IHEALTH, EDUCATION, AiND WELFARE 

I PUBLIC HEALTH SERVICE 
NOTICE Of 
INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl-CL-02001-03 BB 



PERIOD COVERED 

October I, 1977 



September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Cr RBC Survival as a Measure of Transfusion Compatibility 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND 
PROFESSIONAL PERSONHEL ENGAGED ON THE PROJECT 



TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 



Principal Investigator: 



Richard Davey, M. D. , 
Bank Department, CC 



Senior Investigator, Blood 



Other: Paul V. Holland, M. D. , Chief, Blood Bank Department, CC 

Harvey J. Alter, M. D, , Chief, Immunology Section, Blood Bank, CC 



COOPERATING UNITS (if any) 


LA3/ BRANCH 

Blood Bank Department 


SECTION 

Immunology 


INSTITUTE AND LOCATIOi'i 

Clinical Center, Building lOA/Room 1E33. 


NIH, 


Bethesda, Maryland 20014 


TOTAL MANYEARS: 

1 


PROFESSIONAL: 
1 


OTHER: 


CHECK APPROPRIATE BOX(ES) 
n (a) HUMAN SUBJECTS □ (b) HUMAN TISSUES 

D (al) MINORS □ (a?) INTERVIEWS ~~^ 




D (c) NEITHER 



SUMMARY OF V.'ORK (200 words or less - underline keywords) 

The inability to find compatible blood for transfusion is not an uncommon oc- 
currence. A procedure has been developed whereby a small amount of ^-^Cr 
labeled donor red cells which are incompatible by in - vitro techniques are 
transfused into the potential recipient and the in- vivo survival of the trans- 
fused cells determined. Survival characteristics of these cells allow decisions 
to be made with greater certainty regarding the safety of standard transfusions. 

In the patients studied thus far, two cases of the rare " saline auto -agglutinating 
phenomenon " have been shown to have no significance clinically when appropri- 
ate precautions are taken. In addition the suspected incompatibility of group 
O red cells with a rare "Bombay O" recipient has been documented. In other 
instances "incompatible" blood for important surgery has been able to be re- 
leased, whereas previously it would have been difficult to predict the relative 
hazard of transfusing such blood. Studies of rare or poorly defined red cell 
antibodies are progressing. 

It is anticipated that further patients ^will continue to be included in this study 
when in- vitro crossmatch incompatibility is encountered. 

PHS-D040 3-q_l^ 



ZOl-CL-02001-03 BB 
Blood Bank Departm 
Clinical Center 
Bethesda, Maryland 



Blood Bank Department ^ 

Clinical Center * 



PHS-NIH 

Individual Project Report 

October 1, 1977 - September 3 0, 1978 

Project Title: A Rapid Technique for Determining In - Vivo Red Cell Survival 
in Patients Demonstrating In - Vitro Incompatibility with all 
Donor Red Cells 

Previous Serial Number: ZOl-CL-02001 -02 BB 

Principal Investigator: Richard J. Davey, M, D. 

Other: Paul V. Holland, M. D, 
Harvey J, Alter, M, D. 

Cooperating Units: None 

Man Years: Total: 1 

Professional: 1 



Project Description 



Objectives : 



A. To evaluate in detail a procedure for the rapid determination of the sur- 
vival in- vlvo of chromium (51Cr) labeled red blood cells (RBC's) and 

to determine this procedure's clinical significance in predicting trans- 
fusion safety in patients for whom compatible blood cannot be found by 
in - vitro techniques . 

B, To utilize this rapid 51 Cr survival procedure to clarify the clinical 
significance of certain specific rare red cell antibodies (e.g. anti-H 
in Bombay O, anti-Chido). 

Methods Employed : 

A small sample (1.0 - 2.0 ml) of test red cell suspension is labeled with 
20 u Ci of 51 Cr, washed, and infused into the patient. Serial blood samples 
are subsequently drawn and the survival characteristics of the infused cells 
determined by measuring the radioactivity of each sample. 



BB-18 



Major Findings : 

Since approval of this study the following observations have been made. 

A. Two unusual cases of "saline agglutinating phenomenon" have been docu- 
mented and described. Patients with this phenomenon have a serum 
factor which agglutinates all red cells which have been washed in saline, 
thus complicating laboratory crossmatching efforts and rendering the in- 
fusion of saline containing fluids potentially hazardous. Survival studies 
using cells washed in various media permitted a decision to be made 
which resulted in a safe open-heart surgical procedure being done on one 
patient . 

B. People with the rare inherited blood group called "Bombay O" have in 
their serum an antibody which reacts in -vitro against all normal ABO 
blood groups. The clinical significance of this antibody was investigated 
through 51cr survival studies in a person with the "Bombay O" blood 
group. It was determined that the antibody was strongly active in - vivo 
and that "Bombay O" people can safely receive blood only from other 
"Bombay O" donors. 

C. Patients who required transfusion with panagglutinating antibodies and 
with antibodies against high incidence or poorly described RBC antigens 
were studied. The clinical significance of each patient's antibodies was 
determined by a "^Cr survival study, with decisions made as to the rel- 
ative safety of transfusion. 

D. A series of patients with the commonly encountered alio -antibody, anti- 
Lewis ° are being studied. The in-vivo potency of this antibody has 
never been clearly defined. If it proves to be of little in- vivo signifi- 
cance, transfusion of patients with the antibody will be considerably 
easier. 

E. Two patients with delayed hemolytic transfusion reactions but without 
serologic evidence of incompatibility were found to have shortened 
51Cr rbc survival of the implicated units. 

Significance to Biomedical Research and the Program of the Institute 

The primary goal of the Clinical Center Blood Bank is to provide safe blood 
products to Clinical Center patients. This ^\2r red cell survival procedure 
provides a valuable tool in defining the relative safety of transfusion in 
patients for whom compatible blood cannot be found by in- vitro techniques. 
If this procedure continues to prove its significant clinfcal value, it is hoped 
that it will become a widely used blood bank service. 

Proposed Course : 

Continued use of ^Icr survival technique in appropriate patients. 



3B-19 



Publications: 

Significance of Anti-H in the Bombay (Ov^) Patient, Transfusion {In Press). 
The Saline Agglutinating Phenomenon. Vox Sang (in press). 



BB-20 



Z01-CL-02002-03-BB 
Blood Bank Department 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1977 - September 30, 1978 

Project Title: Comparison of single dose and divided dose administration 
schedules of Hepatitis B immune globulin: Efficacy in pre- 
venting hepatitis B following accidental exposure (needle 
stick). 

Previous Serial Number: Z01-CL-02002-02-BB 

Principal Investigator: Harvey G. Klein, M.D, 

Other: Harvey J, Alter, M. D. 
Paul V. Holland, M. D. 
David DeMets, Ph.D. 

Cooperating Umts: NHLBI 

Man Years: Total: 2 

Professional: 1 
Other: 1 

Project Description 

Objectives : 

To determine whether a single injection of hepatitis B immune globtdin (HBIG) 
is as effective as a divided dose injection schedxole in preventing hepatitis B 
caused by accidental exposure. 

Methods Employed : 

Exposed individuals are referred by telephone to the Clinical Center Blood 
Bank. The purpose of the study is explained and a telephone questionnaire 
is used to determine eligibility for study. 

Individuals who qualify are required to send blood specimens to the Blood 
Bank to assure exposure to an infectious source and susceptibility of the 
individual. Simultaneously, the individual is supplied with an informed 
consent form which further explains the purpose of the study. 

Individuals who enter the study are randomized in a double blinded fashion 
to the single injection or divided dose schedule. Each receives the same 
total dose of HBIG. Serial blood samples are mailed and a follow-up 
clinical symptom questionnaire must be completed at month six and month 
12. 

BB^2 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE; 
PROJECT NUMBER vOo NOT use this space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl-CL-02002-03 BB 



PERIOD COVERED 

October 1, 1977 - September 30, 1978 



TITLE OF PROJECT (30 characters or less) 

Use of Hepatitis B Immune GlobtiLin Following Accidental Exposure to HBV 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Principal Investigator: Harvey G. Klein, M. D. , Chief, Blood Services 
Section, Blood Bank Department, CC 

Other: Harvey J. Alter, M, D. , Chief, Immunology Section, Blood Bank, CC 
Paul V. Holland, M. D. , Chief, Blood Bank, CC 

David DeMets, Ph.D., Biometrics Researcher, National Heart, Lung, 
and Blood Institute 



COOPERATING UNITS (if 

NHLBI 



LAB/BRANCH 

Blood Bank Department 



SECTION 

Immunology Section 



NSTITUTE AND LOCATION 

Clinical Center. Bids 



lOA/Room 1E33. NIH. Bethesda, Maryland 20014 



TOTAL MANYEARS: 



PROFESSIONAL: 



CHECK APPROPRIATE BOX(ES) 
n (a) HUMAN SUBJECTS 



n (b) HUMAN TISSUES 



n (c) NEITHER 



n (a1 ) MINORS 



{a2) INTERVIEWS 



SUMMARY OF WORK (200 words or less - underline keywords) 

Two recently reported, randomized, double blinded trials have dem.onstrated 
jthe efficacy of high titer hepatitis B immune globulin (HBIG ) in affording tem- 
porary passive immunity to individuals accidentally exposed to low doses of 
HBs A g - po s iti ve material. In both studies, a 5 ml injection of HBIG was given 

ithin one week of exposure and a second injection one month later. This 

osage schedule was chosen arbitrarily. 

single dose schedtile of HBIG has proven efficacious in prophylaxis of 
jpouses exposed to hepatitis B. However, these two dosage schedules, single 
Injection and divided injections, have never been compared in a controlled 
study. This study plans to enroll 300 individuals accidentally exposed to 
lepatitis B positive m.aterials for development of hepatitis . Candidates will 
)e randomized in a double blinded fashion and treated with the same dose of M 
[BIG in either a single or double injection. Two hundred and ninety- six 
individuals have been enrolled to date. Samples are collected at monthly 
Intervals, following exposure, for six months and at 9 and 12 months. 



PHS-6040 
(Rev. 10-76) 



3B^1 



Major Findings : 

This study was initiated eighteen months ago. Two hiindred and ninety-six 
individuals have been entered and 171 have completed the 12 month follow- 
up- The two injection regimen patient group experienced less hepatitis 
than the single injection group. We are in the final stages of the follow- 
up period. 

Significance to Biomedical Research and Programs of the Institute 

The Clinical Center Blood Bank has had a longstanding interest in the pro- 
blem of hepatitis caused by blood and blood products. This study should 
(1) add fxirther information about the natural history of hepatitis following 
HBIG administration (2) answer the question of whether a single injection 
is as effective as a divided dose schedule, a question of great practical 
importance and (3) provide valuable serum samples for studying other 
markers of hepatitis and hepatitis infectivity. 

Proposed Course : The study should be completed within one year. 

Publications : 

1. Klein, H. G. , Alter, H.J. and Holland P. V. : Postexposure immuno- 
globulin prophylaxis of hepatitis B; a comparison of two dosage schedules. 
Proceedings of the Second UCSF Symposi\mi on Viral Hepatitis {In Press). 



BB-23 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (,Do MOT use this space) 



U.S. OEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 1 

NOTICE OF 

INTRAHURAL RESEARCH PROJECT 



PROJECT NUMBER 



ZOl-CL-02003-04 BB 



PERIOD COVERED 

October 1, 1977 - September 30, 1978 



TITLE OF PROJECT (.30 characters or less) 

"Role of Hemagglutinating and IgE Penicillin i^ntibody in Donor Blood' 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Principal Investigator: Richard J. Davey, M. D. 

Senior Investigator, Clinical Center Blood Bank 

Mary H, McGinniss AB(ASCP)SBB 

Research Biologist, Clinical Center Blood Bank 

Other: Harvey J. Alter, M. D. , Chief, Immunology Section 
Clinical Center Blood Bank 



COOPERATING UNITS (if any) 



LAB/BRANCH 

Blood Bank Department 



SECTION 

Immunology 



INSTITUTE AND LOCATION 

Clinical Center. Bldg. lOA. Room 1E33, NIH, Bethesda, 



Md. 20014 



TOTAL MANYEARS: 



0.5 



PROFESSIONAL: 



0.5 



CHECK APPROPRIATE BOX(ES) 
n (a) HUMAN SUBJECTS 



D (al) MINORS □ (a2) INTERVIEWS 



(b) HUMAN TISSUES 



(c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

Several years ago it was reported by us that some patients on penicillin ther- 
apy, when transfused with donor blood containing hemaggiutina!ting penicillin 
antibody, suffered an untoward reaction similar to anaphylajcis or serum sick- 
ness. We are attempting to establish a prospective, control study to deter- 
mine if passively transferred antipenicillin antibody can induce allergic mani- 
festations in patients who are receiving penicillin or penicillin derivatives as 
part of their therapy. Donors will be screened for a history of penicillin hy- 
persensiti^/ity and their blood will be tested for anti-pencillin antibodies by 
hemagglutination and radioimmunoassay techniques. Recipients of blood from 
donors with a history of penicillin hypersensitivity will be followed for un- 
toward reactions following penicillin therapy and will also be tested for IgG 
and IgE anti -penicillin antibodies. Appropriate controls will be similarly fol- 
lowed. , 



BB-2^ 



PHS-6040 
(Rev. 10-76) 



Serial No. ZOl-CL-02003-04 BB 
Blood Bank Department 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1977 - September 30, 1978 

Project Title: Passive Transfer of Penicillin Hypersensitivity in 
Transfused Blood 

Previous Serial Number: ZOl-CL-02003-03 BB 

Principal Investigt at or: Richard J. Davey, M. D. 

Mary H. McGinniss, AB(ASCP)SBB 

Other Investigators: Harvey J. Alter, M,D. 

Cooperating Units: Inside NIH 
None 

Outside NIH 
None 

Man Years: Total: 0.5 

Professional: 0,5 

Project Description 

Objectives : 

A. To study the incidence and type of untoward reaction patients on penicil- 
lin therapy may experience when transfused with blood from a donor 
having a history of penicillin allergy and/or hem agglutinating or IgE 
penicillin antibody. 

B. To gather data on the momber of NIH donors having these types of anti- 
bodies and to do a statistical analysis on the data. 

Methods Employed : 

1. All donors will be questioned regarding a history of Penicillin allergy. 
Those with such history will be divided into those with anaphylactic re- 
actions and those with just rash. The next consecutive donor after the 
donor giving a positive history of penicillin allergy will serve as a con- 
trol. 

2. An aliquot of serum will be obtained from both allergic and control pa- 
tients and the aliquot tested for IgM, IgG (hemagglutination) and IgE 
(RAST) anti-penicillin antibody. 



3. Recipients of blood from allergic and control patients will be followed for^ 
untoward reactions occurring within 48 hours of transfusion. Such reac-^ 
tions will be correlated with whether or not the recipient is being treated 
with penicillin or a penicillin derivative. 

4. Pre and post transfusion samples will be obtained from those recipients 
who received blood from a donor with detectable anti penicillin antibody - 
to determine if passive transfer can be documented. 

Major Findings : 

In 1971, at the American Association of Blood Banks meeting, we reported 
findings in three patients on penicillin suffering untoward reactions which 
retrospectively could only be attributed to the passive infusion of penicillin 
antibody in donor blood. This was the impetus for the present study. 

In the original study, of 29 patients who received a unit(s) of blood known to 
contain hemagglutinating penicillin antibody, three (10%) had untoward reac- 
tions of the serum sickness variety which could not be attributed to any other 
factor. 

Subsequently 9 new cases of possible urticarial or serum sickness type of 
reactions following blood transfusion to patients receiving penicillin have 
been observed. A causal relation between donor anti -penicillin antibody 
and recipient reaction has, however, been difficult to document because the 
radioimmunoassay for IgE anti -penicillin antibodies is not working optim- g 
ally. 

Significance to Biomedical Research and the Program of the Institute : 

A. Identification of another possible cause of untoward reaction of blood 
transfusion. 

B. If it can be shown that some penicillin reactions in patients are due to 
passive transfer of anti -penicillin antibody, then such patients will not 
need to be restricted from future penicillin therapy. 

C. Similary if it can be shown that such a mechanism for penicillin reactions 
exists, then patients being treated with penicillin will have to receive 
blood from donors without a history of penicillin allergy and /or without 
demonstratable anti -penicillin antibodies. 

Proposed Course : 

Setting up a working radioimmunoassay test for detecting IgE penicillin anti- 
body, continued testing of new NIH donors for hemagglutinating penicillin 
antibody and monitoring of patient's response to such transfusions. 

Publications: None 



BB-2 6 



SMITHSONIAN SCIENCE 



PROJECT NUMBER 



NFORMATICN EXCHANGE 
Do NOT use this space) 



U.S. DEPARTMENT OF 



NOTICE OF 
INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl-CL-02005-09 BB 



PERIOD COVERED 

October 1, 1977 



September 30, 1978 



TLE OF PROJECT (80 characters or less) 

Prospective Study of Post -transfusion Hepatitis in Open Heart Surgery 
Patients 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



Principal Investigator: 



Harvey J. Alter. M.D., Chief, 
Clinical Center Blood Bank 



Immunology Section, 



Other: Paul V. Holland, M.D,, Chief, Clinical Center Blood Bank 

Robert H, Ptircell, M. D, , Head, Hepatitis Virus Section, LID, NIAID 



COOPERATING UNITS (if any) 

NIAID, NHLBI 



LAB/BRANCH 

Blood Bank Department 



SECT 1 ON 

Immunology Section 



INSTITUTE AND LOCATION 

Clinical Center, Bldg. lOA/Room 1E33, NIH, Bethesda, Maryland 20014 



"OTAL MANYEARS: 



12 



PROFESSIONAL: 



CHECK APPROPRIATE BOX(ES) 
(a) HUMAN SUBJECTS 

D (al) MINORS a (a2) INTERVIEWS" 



□ (b) HUMAN TISSUES 



D (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

To prospectively follow all adtilt patients undergoing open heart surgery for 
the development of post -transfusion hepatitis and by appropriate serologic 
tests to determine the causative agents. Primarily interested in investigating 
the incidence of " non-A, non-B " hepatitis and to see if there are any epidemi- 
ologic or serologic clues to its prevention. This study will also compare the 
clinical course of the various forms of PTH and determine the frequency 
with which chronic hepatitis develops. 



33-27 



Serial No. ZOl-CL-02005-09 BB 
Blood Bank Department 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 
Individual Project Report 
October 1, 1977 - September 30, 1978 

Project Title: Prospective Study of Posttransfusion Hepatitis (PTH) in Open 
Heart Stirgery Patients 

Previous Serial Number: ZOl-CL-02005-08 BB 

Principal Investigator: Harvey J. Alter, M.D. 

Other Investigators: Robert Purcell, M. D. 
Paul V. Holland, M.D. 

Cooperating Units: Inside NIH 

mATD, NHLBI 

Outside NIH 
None 

Man Years: Total: 12 

Professional: 4 
Other: 8 

Project Description 

Objectives : 

1. To prospectively follow all adult patients undergoing open heart surgery 
at NIH for evidences of PTH. 

2. To determine the relative occurrences of type B, type A and type non-A, 
non-B hepatitis. 

3. To determine the effectiveness of various tests for HBsAg for screening 
blood donors. 

4. To compare the clinical course of the various forms of PTH and to deter - 
m.ine the frequency with which chronic hepatitis develops. 

5. To develop improved screening m.ethods for type B and type non-B hepa- 
titis. 

Methods: 



1 . All adult patients undergoing open heart surgery are followed for six to 

c SGF 

BB-28 



nine months with serial tests for SGPT, HBsAg and anti-HBs. ^, 



2. Cases of hepatitis are additionally tested for serologic response to CMV, 
EBV and the hepatitis A virus; if type B disease, they are tested for anti- 
core antibody, e_ antigen, DNA polymerase and are subtyped. 

3, Donors are tested by the most sensitive methods for HBsAg currently 
available. In addition donors will be tested for SGPT to see if this relates 
to recipient hepatitis. 

Major findings : Studies to date have demonstrated: 

1. The increased risk of blood containing HBsAg. 

2. A 90% reduction in hepatitis by exclusion of commercial and HBsAg posi- 
tive donors. 

3. The superiority of RIA over CEP as a donor screening method. 

4. The fact that approximately 90% of PTH is now due to a previously unrec- 
ognized virus (or viruses) ciorrently termed "non-A, non-B. " 

5. That the type A hepatitis virus is almost never implicated in PTH: neither 
have the CMV or EBV been implicated in our cases. 

6. That non-A, non-B hepatitis is generally less acutely severe than type-B 
but that it tends to frequently become chronic. 

Significance to Biomedical Research and the program of the Clinical Center : 

These studies have been instrumental in establishing many key points con- 
cerning the frequency, etiology and prevention of PTH at the Clinical Center 
and across the United States. 

Proposed Course : See objectives and methods. 

Publications : 

Holland, P.V., Alter, H. J. , Purcell, R.H., Walsh, J.H., Morrow, A.G., 
and Schmidt, P. J. : The infectivity of blood containing the Australia antigen. 
In Prier, J.E. and Friedman, H, (Eds.): Australia Antigen Baltimore, 
University Park Press, 1973, pp. 205-211. 

Alter, H.J., Holland, P. V, , Purcell, R.H., Lander, J. J. , Feinstone, S. M. , 
Morrow, A.G. , and Schmidt, P. J. : Posttransfusion hepatitis after exclusion 
of the commercial and hepatitis B antigen positive donor, Ann. Int. Med . 77: 
691-699, 1972. 

Feinstone, S. M. , Kapikian, A.Z., Purcell, R.H., Alter, H. J. , and Holland, 
P. V. : Transfusion-associated hepatitis not due to viral hepatitis type A or B. 
N. Eng. J. Med . 292: 767-770, 1975. 



BB-29 



Alter, H. J. , Holland, P, V. , and Purcell, R. H. : The emerging pattern of 
post -transfusion hepatitis. Am. J. Med. Sci . 270:329-334, 1975. ^ 

Alter, H.J., Purcell, R. H. , Holland, P.V., Feinstone, S. M. , Morrow, 
A. G. , Moritsugu, Y. : Clinical and Serological Analysis of Transfusion- 
Associated Hepatitis. Lancet 2: 838-481 1975. 

Alter, H.J., Purcell, R. H. , Feinstone, S.N. , Holland, P.V. Morrow, 
A, G. : Non-A, Non-B Hepatitis: A review and interim report of an ongoing 
prospective study. Proc . of the Second UCF Symposium on Viral Hepatitis 
(In Press). 



BB-3 



SMITHSONIAN SCICfJGE INFORMATION EXCHANGE 
"ROJcCT NUMBER (Oo MOT use this space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl-CL-02010-04 BB 



PERIOD COVERED 

October 1, 



1977 - September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Chronic Sequelae of Non-A, Non-B Hepatitis 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Principal Investigator: Marvin Berman, M.D., Clinical Associate, NIAMDD 

Other: Harvey J. Alter, M. D. , Chief, Immunology Section, Blood Bank, CC 
Robert Purcell, M.D., Head Hepatitis Virus Section, LID, NIAID 
Anthony Jones, M.D., Chief, Section on Diseases of the Liver, DDB, 
NIAMDD 



COOPERATING UNITS (if any) 

NIAID, NIAMDD 



LAB/ BRANCH 

Blood Bank Department 



EOT ION 

Immunology Section 



INSTITUTE AND LOCATIOM 



Clinical Center, Bldg. lOA/Room 1E33, NIH, Bethesda. Maryland 20014 



TOTAL MANYEARS: 



PROFESSIONAL: 



CHECK APPROPRIATE BOX(ES) 

□ (a) HUMAN SUBJECTS 

□ (al) MINORS (a2) INTERVIEWS' 



n (b) HUMAN TISSUES 



□ (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

Patients identified as having non-A, non-B hepatitis will be followed as long 
as possible. Liver biopsy wiU be obtained when the SGPT is elevated for 
more than 6 months and then as indicated thereafter. Biopsy material wiU 
be saved for fluorescent studies when reagents for non-A, non-B hepatitis 
becom.e available. 

All patients developing non-A, non-B hepatitis following open heart surgery 
will be followed with serial studies of SGPT to determine the mcidence 
of chronic liver disease and to compare this incidence with those having type 
B hepatitis. 



3B-31 



Serial No, ZOl-CL-02010-04 BB 
Blood Bank Department ^ 

Clinical Center ^ 

Bethesda, Maryland 

PHS-NIH 
Individual Project Report 
October 1, 1977 - September 3 0, 1978 

Project Title: Chronic Sequelae of Non-A, Non-B Hepatitis 

Previous Serial Number: ZOl-CL-02010-03 BB 

Principal Investigator: Marvin Be rm an, M.D. 

Other: H. Alter, M.D. 

R. PurceU, M.D. 
A. Jones, M.D, 

Cooperating Units: Inside NIH 

NIAID, NIAMDD 

Outside NIH 
None 

Man Years: Total: 2 

Professional: 2 M 

Project Description 

Objectives : 

1. To establish long-term follow-up of patients identified as having non-A, 
non-B hepatitis in post -transfusion hepatitis (PTH) studies conducted at 
NIH since 1970. 

2. To determine by SGPT the frequency of chronic hepatitis. 

3. To determine by liver biopsy the histologic pattern of non-A, non-B hepa- 
titis and to save biopsy specimens for future immunofluore scent studies 
when reagents become available for non-A, non-B hepatitis. 

Methods Employed : See objectives 

Major Findings : 

Chronic hepatitis frequently follows acute non-A, non-B hepatitis and in the 
patients thus far biopsied the histologic picture is sim.ilar to chronic type B 
hepatitis, showing features of either chronic persistent or chronic active 
hepatitis . 



Significance to Biomedical Research and the Program of the Clinical Center : 

Non-A, non-B hepatitis now accounts for 80'7c to 90% of PTH and is thus a 
major transfusion hazard. WhHe it tends to be less acutely severe than type 
B hepatitis, preliminary evidence suggests that it progresses to chronic hepa- 
titis with considerable frequency. Very little is known about this disease and 
it is imperative that clinical and serologic studies be undertaken. It is possible 
that a high percentage of chronic active hepatitis and cryptogenic cirrhosis 
represent the chronic sequelae of a previously unrecognized case of anicteric 
non-A, non-B hepatitis. 

Proposed Course ; See objectives 

Publications: None 



-33 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE U.S. OEPARTMEfJT OF 
PROJECT NUMBER (Do NOT use this space) HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 
NOTICE OF 
INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 

Z01-CL-02011-04-BB 



PERIOD COVERED 

October 1, 1976 to June 30, 1977 



TITLE OF PROJECT (80 characters 



less) 



The Droffy Blood Group Determinant and Susceptibility to Malaria 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

: Principal Investigator: Louis H. Miller, M.D,, Head Malaria Section, LPD, 
NIAID 

(pther: Mary McGinniss, AB(ASCP)SBB, Research Biologist, Clinical 
Center Blood Bank 
Paul V. Holland, M. D. , Chief, Clinical Center Blood Bank 



COOPERATING UNITS (if any) 

Laboratory Parasitic Diseases, NIAID 



lab/branch 
Blood Bank Department 



SECTION 

ImmLinology Section 



NSTITUTE AND LOCATION 

Clinical Center, Bldg. lOA, Room IE 33, NIH, Bethesda, Maryland 20014 



rOTAL MANYEARS: 

2 



CHECK APPROPRIATE BOX(ES) 
n (a) HUMAN SUBJECTS 



n (al) MINORS □ (a2) INTERVIEWS 



□ (b) HUMAN TISSUES 



□ (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

Working with an in vitro model for invasion of red cells by malaria mero - 
: :oites , this study has demonstrated that human red cells lacking the Duffy a 



$.nd b antigens are resistant to invasion. This corresponds well with epi' 



demiologic studies which show that approximately 707c of West African and 
American blacks are resistant to Vivax malari a. A similar proportion of 
toese blacks are Duffy a and b negative whereas the Duffy negative genotype 
Is extremely rare in other racial groups. The close association between the 
Duffy negative genotype and resistance to Vivax malaria has also been con- 
firmed by retrospective analysis of 11 volunteers experimentally inoculated 
with P. Vivax. xA. retrospective study of U.S. servicemen who contracted 
ijnalaria in South East Asia has been completed and confirmed again our 
original hypothesis. A second study conducted by CDC in Honduras has also 
been completed and is another in- vivo study in-proof. 



3B-3U 



PHS-6040 
(Rev. 10-76) 



Serial No. Z01-CL-02011-04-BB 
Blood Bank Department 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 
Individual Project Report 
October 1, 1977 - September 30, 1978 

Project Title: The Duffy Blood Group Determinant and Susceptibility to 
Malaria 

Previous Serial Number: Z01-CL-02011-03-BB 

Principal Investigator: Louis H. Miller, M.D. 

Other: Mary H. McGinniss, AB(ASCP)SBB 
Paul V. Holland, M. D. 

Cooperating Units: Lab. Parasitic Disease, NIAID 

Man Years: Total: 2 

Professional: 2 

Project Description 

Objectives : 

A. To use a red cell culture technique to determ.ine if invasion of erythro- 
cytes by Plasmodium falciparum is dependent upon antigenic determin- 
ants on the erythrocyte membrane similar to that found for Vivax ma- 
laria. 

B. To characterize the antigens involved and determine the sequence of 
events when malarial invasion occurs. 

C. To determine if RBC antigens are involved in other, less known forms 
of malaria and other parasitic diseases using the RBC as part of its 
life cycle. 

Methods Employed : 

1. P. falciparum merozoites are added to RBC in culture and the degree 

of RBC invasion is observed microscopically. The degree of invasion of 
RBC with differing phenotypes is compared. 

2 . When a specific antigen is identified as being involved in the attachment 
or invasion by malaria parasites (as in (1)), attempts are made to block 
or destroy that site with specific antibody or enzyme treatment. 

3. Blood samples from donors of rare MNS system phenotypes are being 
collected to test with P. falciparum parasites. 



BB-3 5 



Major Findings ; 

Thus far one cell among many tested was not invaded normally by P. falci - 
parum parasites. This is a very rare cell known as En(a-). This cell lacks 
sialic acid and therefore M and N antigens. This cell is also Wr(b-) which 
is a universal antigen. One person who is En(a+) is Wr(b-). We have made 
plans to secure these rare cells and other cells having low levels of sialic 
acid to see if low invasion by P. falciparum parasites is due to lack of sialic 
acid, or the lack of the En^ or Wr ^ antigens. 

Significance to Biomedical Research and the Program of the Institute : 

A. Elucidation of the mechanisms of red cell invasion by _P. falciparum . 

B. Increased knowledge of erythrocyte polymorphisms. 

C- Accumulation of data which could culminate in a vaccine or other immuno- 
logic means of malaria prevention. 

Publications 

1. Miller, L. H. , Mason, S,J. , Clyde, D.F., and ^IcGinniss, M. H. : The 
resistance factor to Plasmodium vivax in blacks. N, Eng, J. Med. 
295: 302-304, 1976. 

2. MHler, L. H. , Haynes, J. D. , McAuliffe, F. M. , Shiroishi, T. , Durochei^ 
J. R., and McGinniss, M.H. : Evidence for differences in erythrocjrte ff^ 
surface receptors for the malarial parasites, Plasmodium falciparum 

and Plasmodium knowlesi, J. Exp. Med. 146:277-281, 1977. 

3. MHler, L.H., McGinniss, M. H. , HOlland, P.V., and Sigmon, P.: 

The Duffy-Group Phenotype in American Blacks Infected with Plasmodium 
vivax in Vietnam. Am. J. of Trop. Med. and Hyg. (In Press for Nov. 
1978). 

4. Spencer, H. C. , Miller, L. H. , Collins, W.E., Knud-Hansen, C. , 
McGinniss, M. H. , Shiroishi, T., Labos, R. A., and F el dm an, R. A. 
The Duffy blood group and resistance to Plasmodium vivax in Hondxiras 
(In Press). 



m 



BB-36 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Do NOT use this space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAHURAL RESEARCH PROJECT 



project number 

ZOI-Cl-02012-02 BB 



PERIOD COVERED 

October 1, 1977 - September 30, 1978 



TITLE OF PROJECT (80 characters 



less) 



Chido (Ch^) Antibody Production Induced by Cancer Immxmotherapy 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Principal Investigator: Mary L. Gustaison, MS, MT{ASCP)SBB 

Technical Supervisor, Clinical Center Blood Bank 

Other: Ritchard G. Cable, M. D. , Medical Director, Syracuse Regional 
Red Cross Blood Program, Syracuse, New York 
Edwin J. Matthews, Ph.D., Investigator, Litton Bionetics, Inc., 
Rockville, Maryland 

Lloyd L. Lauer, M.S., Research Technician, Litton Bionetics, 
Inc., Rockville, Maryland 



COOPERATING UNITS (if any) 

NCI, Litton Bionetics 



LAB/BRANCH 

Blood Bank Department 



SECTION 

Blood Services Section 



INSTITUTE AND LOCATION 

Clinical Center, Bethesda, Maryland 20014 



TOTAL MANYEARS: 

0.5 



PROFESSIONAL: 

0.5 



CHECK APPROPRIATE BOX(ES) 
G (a) HUMAN SUBJECTS 

□ (a1 ) MINORS "J (a2) INTERVIEWS 



□ (b) HUMAN TISSUES 



□ (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

On routine testing, it was discovered that two patients with malignant mela - 
noma had developed the red blood cell antibody. anti-Chido(Ch^) , following the 
initiation of cancer immunotherapy in the treatment of their disease. We are 
currently testing the Cha antigen status of the remaining persons in this protocol 
to see if the number varies from the statistical norms of 98% Ch^ positive, Wej 
are attempting to test the Ch^ antigen status of three cell lines of neuramini d ase 
treated and untreated cultured melanoma cells used for injection in this protocc|»l 
to determine if these cells can be responsible for inducing antibody production. 



33-3: 



Serial No. ZOl-CL-02012-01 BB 
Blood Bank Department tf 

Clinical Center 
Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1976 - September 30, 1977 

Project Title: "Chido(Ch^) Antibody Production Induced by Cancer 
Immunothe r apy 

Previous Serial Number: ZOl-CL-02012-01 -BB 

Principal Investigator: Maxy L, Gustafson, MS, MT(ASCP)SBB 

Other Investigators: Rite hard G. Cable, M.D, 
Edwin J. Matthews, Ph.D. 
Lloyd L. Lauer, M.S. 

Cooperating Umts: Inside NIH 
NCI 

Outside NIH 

Litton Bionetics, Inc. 

Man Years: Total: 0.5 W 

Professional: 0. 5 
Other: 

Project Description 

Objectives : 

To determine the Ch antigen status of the cell lines used in the treatment 
of persons with malignant melanoma to determine whether these cells are 
responsible for inducing antibody production. 

Methods Employed : 

Ch antigen status of individuals is determined by a serum agglutination inhi- 
bition procedure. Absorption-elution techniques will be employed in the ex- 
perimental testing for the Ch ^antigen on the neuraminadase treated and un- 
treated melanoma cells from culture. 



Major Findings : 

To date, one other person on the melanoma therapy protocol appears to be 
Ch^ negative. 

t 



BB-38 



Significance to Biomedical Research and the Program of the Institute : 

This may demonstrate the first evidence of red blood cell antibody produc- 
tion following treatment of cancer immunotherapy. 

Proposed Course : 

See objectives and methods. 

Publications : 

Gustafson, M. , Cable, R. G. , Matthews, E.J., Lauer, L.L., Holland, 
P. V. : Anti-Chido Following Cancer Immunotherapy. Abstract Book, 
30th Annual AABB Meeting, Atlanta, 1977. 



BB-39 



;MITHSONlAn SfMENCe I ivFORMAT 1 GfJ EXCHANGE 
'ROJECT MUMBEH (Oo NOT use this space) 



I U.S. OEPARTMENT OF 
HEALTi;, EDUCATIOM, AMD WELFARE 
PUBLIC HEALTH SERVICE 
NOTICE OF 
INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl-CL-02013-02 BB 



PERIOD COVERED 

October 1, 1977 - September 30, 1978 



TITLE OF PROJECT (30 characters or less) 

Mechanism of Vertical Transmission of Hepatitis B Virus 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES Of PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



Principal Investigator: George Grady, M. D. 



Others: Harvey J. Alter, M.D., Chief, 
Department, Clinical Center 



Immunology Section, Blood Bank 



COOPERATING UNITS (if any) 

Mass. Department of Public Health 



LAB/BRANCH 

Blood Bank Department 



SECTION 

Immunology Section 



INSTITUTE AND LOCATION 

Clinical Center, Bldg. lOA/Room 1E33, NIH, Bethesda, Maryland 20014 



■QTAL .VIANYEARS: 



PROFESSIONAL: 



0.5 



0.5 



CHECK APPROPRIATE 80X(ES) 
n (a) KUIMH SUBJECTS 



n (b) HUMAN TISSUES 



D (c) NEITHER 



D (al) MINORS □ (a2) 



INTERVIEWS 
-ds or less 



SUMMARY OF WORK (200 words or less - underline keywords) 

Maternal -fetal transmission is felt to be responsible for a large number of 
chronic carriers of HBsAg. The mechanism by which the virus is trans- 
mitted from mother to infant, is however, unclear with the three main pos- 
sibilities being: (1) transplacental transmission prior to birth (2) swallowing 
of maternal blood at the time of delivery (3) post partum transmission via 
breast feeding or maternal handling. 

We will attempt to sort these possibilities by delivering the infants of HBsAg- 
positive chimpanzees by Caesarian section and by having the infant reared 
separate from the HBsAg -positive mother. 



33-1+0 



Serial No. ZOl-CL-02013-02 BB 
Blood Bank Department 
Clinical Center 
Bethesda, Maryland 

NIH-PHS 

Individual Project Report 

October 1. 1977 - September 30, 1978 

Project Title: Mechanism of Vertical Transmission of Hepatitis B Virus 

Previous Serial Number: ZOl-CL-02013-01 BB 

Principal Investigator: George Grady, M. D. 

Other: Harvey J. Alter, M. D, , CCBBD 

Cooperating Units: Massachusetts Dept. of Public Health 

Man Years: Total: 1 

Professional: 0.5 
Other: 0.5 

Project Description 

1. To see if maternal -fetal hepatitis transmission occurs despite the ab- 
sence of any post-partiom contact between mother and infant. 

2. To see if the possibility of blood ingestion by the fetus can be avoided 
by bloodless Caesarian section and to see what impact this has on 
maternal -fetal transmission. 

3. To see if prepartum transmission can be documented by the presence 
of HBsAg in cord blood or by the presence of hepatitis related antigens 
in fetal liver tissue obtained at the time of delivery. 

Methods : 

1. Chronic HBsAg carrier chimpanzees will be housed and bred in the lab- 
oratory for Experimental Medicine and Surgery (LEMSIP). The carriers 
employed will be e_ antigen positive to document their potential infectivity. 

2. Chimps will be delivered by a traumatic and bloodless Caesarian 
section as possible. 

3. At birth, samples will be obtained for HBsAg and e antigen testing from 
maternal blood, cord blood, fetal venous blood and amniotic fluid. A 
liver biopsy will also be obtained from the fetus and stained by fluo- 
rescent techniques for the presence of HBcAg and HBsAg. 

4. The fetus will have no contact -with the HBsAg -positive mother after 
delivery and will be followed for the development of type B hepatitis. 

BB-I4I 



Major Findings : 

The first infant so studied developed type B hepatitis 7 weeks after delivery. 
This rules out post-partum contact as the cause of hepatitis transmission, 
but does not distinguish the other possibilities because the Caesarian section 
was not entirely bloodless. Against transplacental transmission, was the 
finding of HBsAg -negative cord blood and fetal venous blood. However, liver 
biopsy was not performed at the time of birth. 

Significance to Biomedical Research and the Program of the Clinical Center : 

It has been estimated that maternal -fetal transmission of hepatitis B may be 
the major cause for the development of the HBsAg carrier state. Through- 
out the world this is probably a far more significant route of transmission 
than blood transfusion. Any studies which elucidate the mechanism of such 
transmission may help in its prevention. It has already been proposed that 
mothers who are HBsAg-positive be delivered by Caesarian section. These 
studies may shed light on the rationale for such an approach. 

Proposed Course ; 

The carrier mother whose fetus has already been followed will be inpregnated 
as soon as possible and the second fetus delivered by a more meticulous C- 
section and also biopsied at the time of delivery. 



BB-li2 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Do NOT use this space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl-CL-02014-02 BB 



PERIOD COVERED 

October 1, 1977 - September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Transmission of Non-A, Non-B Hepatitis to Chimpanzees 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 



Principal Investigator: 



Harvey J. Alter, M.D., 
Blood Bank Department, 



Chief, Immunology Section, 
CC 



Other: Robert Purcell, M.D., 
Paul V. Holland, M.D. 



NLAID 
. CCBBD 



COOPERATING UNITS (i 

NLAID 



LAB/BRANCH 

Blood Bank Department 



SECTION 

Immunology Section 



INSTITUTE AND LOCATION 

Clinical Center. Bldg. lOA/Room 1E33. NIH. Bethesda. Maryland 20014 



TOTAL MANYEARS: 



PROFESSIONAL: 



CHECK APPROPRIATE 80X(£S) 
D (a) HUMAN SUBJECTS 

□ (al) MINORS □ (a2) INTERVIEWS 



□ (b) HUMAN TISSUES 



(c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

Eighty-Ninety percent post -transfusion hepatitis now appears related to a 
third human hepatitis ' virus tentatively termed " non-A, non-B . " There 
are several pieces of evidence to suggest this is a virus but to date this 
agent has not been observed, has not had an identifiable antigenic marker , 
has not been grown in culture and has not been transmitted to animals . 
This study will attempt to identify bloods with a high probability of containing 
virus and will then attempt chimpanzee inoculation. 



3B-43 



?HS-b040 
(Rev. 10-76) 



Serial No. ZOl-CL-02014-02 BB 
Blood Bank Department ^ 

Clinical Center 
Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1977 - September 30, 1978 

Project Title: Transmission of Non-A, Non-B Hepatitis to Chimpanzees 

Previous Serial Number: ZOl -CL-02014-01 BB 

Principal Investigator: Harvey J. Alter, M.D. 

Other: Robert Pur cell, NIAID 

Paul V. Holland, CCBBD 

Cooperating Units: NIAID 

Man Years: Total: 2 

Professional: 1 
Other: 1 

Project Description 

Objectives : % 

1. To prove that non-A, non-B hepatitis is due to a transmissable agent. 

2. To transmit this agent from human blood to chimpanzees and if success- 
ful from chimpanzee to chimpanzee. 

3. To obtain plasmapheresis units from infected chimpanzees to aid in char- 
acterization of the virus and development of serologic tests. 

4. To determine if more than one agent of non-A, non-B hepatitis exists. 
Methods : 

1. Potentially infectious sera will be obtained from patients with acute and 
chronic non-A, non-B hepatitis and from donors implicated in such trans- 
mission. 

2. Depending on the volume of sample available, either 1 ml or 75 ml will 
be inoculated into chimpanzees and the animals followed for six months 
for evidence of enzyme (SGOT/SGPT) elevations. 

3. Animals with elevated SGOT/SGPT will be plasmapheresed and have 
liver biopsies. Biopsy material will be observed for evidence of hepatitis, 
but will also be frozen for subsequent immunofluorescent tests should ^ 
they becom.e available, ^ 

BB-kh 



4. Acute phase plasma from reactive chimps will be administered to addition- 
al additional animals in an attempt to demonstrate serial passage. 

5. Infected chimps will be rechallenged with the same inociiL\im to boost anti- 
body response - 

6. Following 5, chimpanzees will be cross challenged to determine by cross 
immtinity if there is more than one agent of non-A, non-B hepatitis. 

7. Partial hepatectomy may be performed in infected chimps to serve as a 
source of non-A, non-B antigen. 

Major Findings : 

Sera were obtained from four patients with well documented non-A/non-B 
hepatitis and from one donor implicated in non-A/non-B transmission. These 
were inoculated into five chimpanzees and all five showed biochemical and 
histologic evidence of acute hepatitis. This study demonstrated two major 
points: (1) non-A/non-B hepatitis is due to a transmissible agent (2) there is 
a chronic carrier state in humans for the non-A, non-B agent(s) just as 
there is for the type B agent. The later is based on the fact that transmission 
occurred following inoculation of plasma obtained from patients with chronic 
as well as acute non-A/non-B hepatitis. 

Proposed Course : 

We will now observe these infected chimpanzees to see if they develope 
chronic hepatitis and if not will proceed with booster and cross-challenge 
studies as above. 

Publications : 

1. Alter, H.J,, Purcell, R. H. , Holland, P.V. and Popper, H. : Trans- 
missible agent in "non-A, non-B" hepatitis. Lancet 1: 459-463, 1978. 



■^5 



;XCHANG£| U.S. DEPARTMENT OF 

space) IHEALTH, EDUCATlUr;, AND iVELFARE 
PUBLIC HEALTH SERVICE 
NOTICE OF 
INTRAaURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl-CL-02016-02 BB 



PERIOD COVERED 

October 1, 1977 - September 3 0, 1978 



TITLE CF PROJECT (30 characters or less) 

Evaluation of Anti-Core Antibody and Serum Transaminase as Indicators 
of the Infectivity of HBsAg-Negative Donors 



NAMES, LASCRATORY AND INSTITUTE AFFILIATIONS, AND TlTLi 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



S OF PRINCIPAL INVESTIGATORS AND ALL OTHER 



Principal Invest 



^ator: Harvey J. Alter, M.D., 
Blood Bank Department, 



Chief, Immunology Section, 
Clinical Center 



Other: Paul V, Holland, xM.D., Chief, Blood Bank Department, CC 
Deloris Koziol, Medical Research Technologist, Blood Bank 
Department, Clinical Center 



COOPERATING UNITS (if any) 



lab/shanch 

Blood Bank Department 



SECTio;-; 

Immunology Section 



INSTITUTE AND LOCATION 

Clinical Center, Bldg. lOA/Room 1E33, NIH, Bethesda, Maryland 20014 



TOTAL MANYEARS: 



1.5 



PROFESSIONAL: 



0.5 



CHECK APPROPRIATE B0X(E3) 
D (a) HUMAN SUBJECTS 

D (al) MINORS □ (a2) INTERVIEWS^ 



n (b) HUMAN 



D (c) NEITHER 



SUMMARY OF WORK (2C0 words or less - underlir.e keywords) 

Despite sensitive radioimmunoassay tests for HBsAg applied to all donor blood, 
some type B hepatitis continues to occur following transfusion. It has pre- 
viously been suggested that HBsAg negative individuals who have anti-core 
antibody may transmit the hepatitis B virus. The availability of a new sensitive 
radioimmunoassay for anti-core antibody allows this postulate to be tested in 
our prospectively followed, open heart surgery patients. Similarly, we can 
ascertain if chronic carriers of non-A, non-B hepatitis have elevated serum 
transaminase; and. if so, whether this could be employed to screen donors and 



'educe the frequency of post -transfusion hepatitis due to this agent. 



3B-4 6 



Serial No. ZOl-CL-02016-02 BB 
Blood BaJik Department 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1977 - September 30, 1978 

Project Title: Evaluation of Anti-Core Antibody and Serum Transaminase as 
Indicators of the Infectivity of HBsAg -Negative Donors 

Previous Serial Number: ZOl-CL-02016-01 BB 

Principal Investigator: Harvey J. Alter, M.D. 

Other: Paul V. Holland, M. D. 

Deloris Koziol, Medical Research Technologist 

Cooperating Units: None 

Man Years: Total: 1.5 

Professional: 0.5 
Other: 1 



Project Description 



Objectives : 



1. To determine if HBsAg-negative donors who have anti-core antibody are 
more likely to transmit type B hepatitis then those who lack anti-core 
antibody. 

2. To determine if donors with elevated SGPT are more likely to transm^it 
non-A, non-B hepatitis than donors with normal SGPT and to ascertain 
if this would be a practical way to screen for chronic carriers of this 
presTxmed virus. 

Methods : 

1. We have now prospectively followed over 400 patients to determine if 
they developed post -transfusion hepatitis and, if so, by what etiologic 
agent. All donors to type B and non-A, non-B hepatitis cases will be 
tested for anti-core antibody as will the donors to at least 30 patients 
who did not develope hepatitis (approximately 500 donors in all). Data 
will be analyzed to see if there is any positive correlation between the 
presence of anti-core antibody in the donor and hepatitis in the recipient. 

2. All donors to open heart surgery patients will be tested for SGPT. These 
tests will be performed in a sample obtained at the time of donation but. 



BB-U7 



will not be tested until approximately three days after transfusion. The 
results of transaminase tests will not be known at the time of transfusion^ 
but recipients will be followed prospectively for the development of hepa- 
titis. Data will be analyzed to see if there is a positive correlation be- 
tween the presence of elevated donor transaminase and the development 
of recipient hepatitis. 

3. When an elevated transaminase is found (initially tested under contract 
by Bionetics Lab), the same sample will be retested by the Clincial 
Chemistry lab at NIH, If the elevated value is confirmed, the donor 
will be recalled and at least two units of plasma obtained by plasma- 
pheresis for subsequent study should hepatitis develop in the recipient. 

Major Findings : None to date 

Significance to Biomedical Research and the Program of the Clinical Centei 

Any test system which could reliably detect carriers of hepatitis B who are 
below the detectability range of RIA tests for HBsAg or which woiild detect 
chronic carriers of non-A, non-B virus would have major impact on the in- 
cidence of post -transfusion hepatitis. 



3B-1+3 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl-CL-02017-02 BB 



PERIOD COVERED 

October 1, 1977 to September 30, 



1978 



TITLE OF PROJECT (80 characters or less) 

Identification of the Non-A, Non-B Hepatitis Agent and the Development 
of Serologic Markers 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Principal Investigator: Harvey J. Alter, M. D. , CCBBD 

Others: Robert Purcell, NIAID 

Stephen Feinstone, NIAID 

John Gerin, Molecular Anatomy Program 



COOPERATING UNITS (if any) 

Laboratory Infectious Disease, NIAID 
Molecular Anatomy Program, AEC 



LAB/BRANCH 

Blood Bank Department 



SECTION 

ImmTinology Section 



INSTITUTE AND LOCATION 

Clinical Center, Building 10A/1E33, Bethesda, Maryland 20014 



"OTAL MANYEARS: 



PROFESSIONAL: 



lOTHER; 

1 



CHECK APPROPRIATE BOX(ES) 
n (a) HUMAN SUBJECTS 

D (al) MINORS D (a2) INTERVIEWS' 



□ (b) HUMAN TISSUES 



D (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

Plasma units derived from: either donors implicated in non-A, non-B 
hepatitis or patients with acute or chronic non-A, non-B hepatitis will be 
ultracentrifuged. The pellet derived by ultr ac entrifugation will be reacted 
against a radiolabelled IgG fraction obtained from patients convalescent 
from non-A, non-B hepatitis in a solid phase radioimmunoassay system. 



^B-^Q 



Z01-CL-02017-02-BB 

Blood Bank Department ^ 

Clinical Center 

Bethesda, Maryland 

PHS-NIH 
Individual Project Report 
October 1, 1977 - September 30, 1978. 

Project Title: Identification of the Non-A, Non-B Hepatitis Agent and the 
Development of Serologic Markers 

Previous Serial Number: ZOl-CL-02017-Ol-BB 

Principal Investigator: Harvey J. Alter, M. D. 

Others: Robert Purcell, NIAID 

Stephen Feinstone, NIAID 

John Gerin, Molecular Anatomy Program 

Cooperating Units: NIAID, Molecular Anatomy Program, AEC 

Man Years: Total: 2 

Professional: 1 
Other: 1 

Project Desciption ^ 

Objectives : 

1- To obtain a large quantity of non-A, non-B viral antigen. 

2. To establish a sensitive detection system for this presumed viral agent. 

Methods : 

1. Sem.i-purify non-A, non-B viral antigen by tiltracentrifugation of plasma 
units, clinically presumed to carry this agent. 

2. Prepare radiolabelled IgG from plasma of persons who have recovered 
from non-A, non-B hepatitis in the hopes that they contain specific 
antibody. 

3. React the antigen and antibody in a solid phase radioimmunoassay system. 

4. If an assay can be developed, the antigen pellet will be further purified by 
Cesium chloride and sucrose gradients. 

Major Findings : None to date 

Proposed Course: See objectives and methods 



BB-50 



Significance to Biomedical Research and the Program of the Clinical 
Center 

The development of a detection system for non-A, non-B viral agent(s) 
woiiLd be highly significant in that none are currently available and in 
that this agent(s) currently is responsible for over 80% of post -transfu- 
sion hepatitis and probably responsible for a great deal of chronic active 
hepatitis. 



-51 



PROJECT NUMBER (Do NOT use this space) 



PERIOD COVERED 

October 1. 1977 - September 30, 1978 



TITLE OF PROJECT (30 cnaracters or less) 

Hepatitis B Vaccine Trial Among Renal Dialysis Patients 



U.S. DEPARTMENT OF PROJECT MUMBER 
HEALTH, EDUCATION, AND WELFARE 
PUBLIC HEALTH SERVICE 
NOTICE OF 
INTRAMURAL RESEARCH PROJECT 



ZO1-CL-02018-02-BB 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Principal Investigator: Wolf Szmuness, M. D. , Chief, Epidemiology, 
New York Blood Center 

Other: Cladd Stevens, M. D. , NYBC 
Edward Harley, NYBC 
Harvey J. Alter, M. D. , CCBB 



COOPERATING UNITS (if any) 

New York Blood Center 



lab/branch 

Blood Bank Department 



SECTION 

Immunology Section 



NSTITUTE AND LOCATION 

Clinical Center, Building 10A/1E33, NIH, Bethesda, Maryland 20014 



TOTAL MANYEARS: 



PROFESSIONAL: 



CHECK APPROPRIATE BOX(ES) 
G (a) HUMAN SUBJECTS 

n (al) MINORS □ (a2) INTERVIEWS 



□ (b) HUMAN TISSUES 



(c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

A two part study is being undertaJcen to evaluate a hepatitis B vaccine being 
produced by NIAID. In the first phase baseline seroepidemiologic data 
will be obtained in 10 dialysis units in NYC and the Metropolitan Washington 
Renal Dialysis Unit. When the hepatitis B vaccine is available (approximately 
Spring of 1979) a prospective, controlled, randomized double blind trial of its 
efficacy will be undertaken in these same dialysis units. 



BB-52 



Serial No. ZO1-CL-02018-02-BB 
Blood Bank Department 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 
Individual Project Report 
October 1, 1977 - September 30, 1978 

Project Title: Hepatitis B Vaccine Trial Among Renal Dialysis Patients 

Previous Serial Number: ZOl-CL-02018-Ol-BB 

Principal: Investigator: Wolf Szmuness, M, D. 

Other: Cladd Stewvens, M. D. , NYBC 
Edward Harley, NYBC 
Harvey J. Alter, M. D. , CCDBB 

Cooperating Units: New York Blood Center 

May Years: Total: 6 

Professional: 2 
Other: 4 



Project De script! 



Objectives ; 
1. 



To obtain baseline incidence figures on hepatitis B and non-A, non-B 
among a large number of nenal dialysis patients and staff. 

To try to assess patterns of hepatitis spread in these units based on 
serologic and epidemiologic parameters. 

To evaluate the effectiveness of a hepatitis B vaccine in reducing the 
frequency of type B hepatitis among patients and staff. 



Methods : 



Patients and staff in multiple dialysis untis will be monitored monthly 
for evaluation of SGPT and appearance of HBsAg and anti-HBs. More 
frequent sampling and additional tests such as those for subtyping, e 
antigen and anti-core antibody will be employed when a positive result 
is obtained. 

When the hepatitis B vaccine is ready for clinical trials, patients and 
staff of these dialysis units will be randomly assigned to receive hepa- 
titis B vaccine or placebo and the effectiveness of each assessed over 
a one year period in each individual. The hepatitis B vaccine will be 
prepared from a ptirified preparation of 20 nm HBs-Ag-containing par- 

3B-5 3 



tides which have been formulin treated and which have already been 
shown to be non -infectious, but immunogenic in chimpanzees. Patients 
and staff will be monitored as above. 

3. Other potential methods of decreasing the risk of hepatitis will also be 
employed including the administration of HBIG to those accidentally in- 
oculated with HBsAg -positive material and the isolation of positive pa- 
tients as recommended by the CDC. 

4. All serologic and epidemiologic data will be computerized. 

Major Findings : 

Study is just in preliminary phase and sufficient data have not been accumu- 
lated for analysis. 

Significance to Biomedical Research and the Program of the Clinical 
Center ^ 

Dialysis patients and staff remain a very high risk popiilation for hepatitis B 
and represent one of the few US populations in whch a hepatitis vaccine can 
be clinically evaluated. If the vaccine proves effective, it will have vast im- 
plications, not only for dialysis patients and staff, but also for patients and 
staff in institutions, for medical personnel in general, for inner city and sex- 
ually promiscuous populations, and for many foreign populations where hepa- 
titis B frequencies are extremely high. 

Proposed Course : See methods and objectives. 

Public ations : None 



BB-51+ 



SMITHSOfJIAIJ SCIENCE IflFORMATlOM EXCHANGE 
PROJECT NUMBER (Oo NOT use this space) 



U.S. OEPArtTMENT OF 
HEALTH, EOUCATIOfJ, AND WELFARE 
PUBLIC HEALTH SERVICE 
HOT ice OF 
INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl-CL-02019-02 BB 



PERIOD COVERED 

October 1, 1977 - September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Evaluation of the hepatitis risk of hospitalized patients undergoing 
invasive procedures, but not receiving blood transfusion 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Principle Investigator: Harvey J. Alter, M.D., Chief, ImmTonology Section, 
Blood Bank Department, Clinical Center 

Other: Paxil V. Holland, M. D. , Chief, Blood Bank Department, CC 

Robert H. Purcell, M. D. , Head, Hepatitis Virus Section, LID, NIAID 



COOPERATING UNITS (if any) 

NIAID. NHLBI 



las/branch 

Blood Bank Department, Clinical Center 



SECTION 

Immunology Section 



INSTITUTE AND LOCATION 

Clinical Center, Building lOA/Room 1E3.3, NIH, Bethesda. Maryland 20014 



TOTAL MANYEARS: 
3:5 



PROFESSIONAL: OTHER: 

0.5 3 



CHECK APPROPRIATE B0X(ES; 
n (a) HUMAN SUBJECTS D (b) HUMAN TISSUES □ (c) NEITHER 

□ (al) MINORS (a2) INTERVIEWS ';~ 



SUMMARY OF WORK (200 words or less - underline keywords) 

This is a new study which will serve to supplement and control project ZOl- 
CL-02005-07 BB, Cardiac patients will be enrolled if they undergo closed 
mitral com.m.issurotomy or cardiac catheterization but do not receive blood. 



They will then be followed prospectively for 6 months and hepatitis rates 
compared with patients undergoing open heart surgery. This should provide 
data on the relative risk of hepatitis between transfusion exposure and ex- 
posure to a hospital environment and the types of hepatitis associated with 
each. 



BB-5 5 



Serial No. ZOl-CL-02019-02 BB 
Blood Bank Department i^ 

Clinical Center ^ 

Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1977 - September 30, 1978 

Project Title: Evaluation of the hepatitis risk of hospitalized patients under- 
going invasive procedures, but not receiving blood transfusion 

Previous Serial Number: ZOl -CL-02019-01 BB 

Principal Investigator: Harvey J. Alter, M,D. 

Other: Paul V. Holland, M. D, 

Robert H. Purcell, M. D. 

Cooperating Umts: NIAID, NHLBI 

Man Years: Total: 3.5 

Professional: 0,5 
Other: 3 



Project Description 



Objectives : 



1. To determine if there is a viral hepatitis risk which accompanies hospital- 
ization and invasive procedures such as closed mitral commisSTxrotomy 
and cardiac catheterization, 

2. To compare this hepatitis risk with patients with similar cardiac lesions 
who reqmre transfusion as part of corrective surgical procedures for 
their cardiac lesion. 

3. To determine the type of viral hepatitis in each group (i. e, B versus 
non-A, non-B) and thus to establish the absolute incidence of non-A, 
non-B hepatitis related to blood transfusion. 

Methods : 

1. All patients undergoing closed mitral commissurotomy or cardiac cathe- 
terization (with or without coronary angiogram) will be foHowed for six 
months with serial tests for SGPT, HBsAg and anti-HBs. 

2. Cases who develope hepatitis will be additionally tested for serologic re- 
sponses to CMV, EBV and the hepatitis A virus; if type B disease, they 
will be additionally tested for anti-core antibody, e_ antigen and will be 
subtype d. 

V. 

BB-5 6 



Major Findings ; Study just beginning but 60 subjects enrolled to date. 

Significance to Biomedical Research and the Program of the Clinical Center ; 

This study will serve as a control for project no. ZOl-CL-02005-09 BB and 
will define the baseline hepatitis incidence which accompanies hospitalization 
and invasive procedures not accompanied by blood transfusion. 

Proposed Course ; See objectives and methods 

Publications: None 



BB-57 



SMITHSONIAN SCIEMCE IhFORMATION EXCHANGE 
IpROJEGT WUdiBER (Do NOT use this space) 



U.S. DEPARTMENT OF 
iEALTH. EDUCATION, AND v.'ELfARE 

pOdlic health service 

NOTICE OF 
INTRAaURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl-CL -02020-02 BB 



PERIOD COVERED 

October 1. 1977 - September 30, 1978 



TITLE OF PROJECT (30 characters or less) 

Alterations in Whole Blood Oxygen Affinity Following Transfusion 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Principal Investigator: Harvey G. Klein, M. D. , Chief, Blood Services 
Section, Blood Bank Department, CC 

Other: Robert M. Winslow, M. D. , Senior Investigator, National Heart 
Lung and Blood Institute 



COPERATiNG UNITS (if any) 

f^HLBI 



LAB/ BRANCH 

Blood Bank Department 



SECTION 

Blood Services Section 



INSTITUTE AND LOCATION 

Clinical Center, Bldg. lOA/Room 1E33, NIH, Bethesda, Maryland 20014 



■OTAL MANYEARS: 



PROFESSIONAL: 



CHECK APPROPRIATE 30X(E3) 
n (a) HUMAN SUBJECTS 

D (al) MINORS n (a2) INTERVIEWS" 



a (b) HUMAN TISSUES 



Q (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

It has been widely reported that whole blood oxygen affinity varies in different di 
sease states characterized by anemia . The fact that whole blood oxygen affinity 
is reduced in persons with sickle cell anemia has been known for many years. A 
recent report indicates that non -transfused children with homozygous B thalas- 
semia may have a paradoxical increase in anemia. There is very little quantita- 
tive information concerning serial changes in whole blood O2 affinity post -trans- 
fusion in those disease states which require transfusion of red cells. It is quite 
possible that post -transfusion changes in Oj affinity actually result in a more_ 
severe functional anemia despite the -hemoglobin elevation. If the red cell miliei; 
is important, as the report concerning thalassemia major suggests, whole blood 
O 2 affinity post -transfusion may differ significantly in such different disease 
states as thalassemia, sickle cell anemia , aplastic anemia and myeloid meta - 
plasia . In this study, whole blood Op affinity will be measured in patients who -^h 
quire transfusion (1) prior to transfusion (2) daily for 5 days (3) weekly thereai^. f 
for three weeks. Whole blood oxygen affinity of the transfused blood will be meaj- 
sured as well. A quantitative estimate of the percent of transfused cells remainj 
ing in each sample ^NJll be "derived by differential agglutination (Ashby technique )|. 

PHS-oOiO ^^ ^n 



Serial No. ZOl-CL-02020-02 BB 
Blood Baxik Department 
Clinical Center 
Bethesda, Maryland 

PHS-NTB 

Individual Project Report 

October 1, 1977 - September 30, 1978 

Project Title: Alterations in Whole Blood Oxygen Affinity Following 
Transfusion 

Previous Serial Number: ZOl-CL-02020-01 BB 

Principal Investigator: Harvey G. Klein, M.D, 

Other: Robert M. Winslow, M. D. 

Cooperating Units: NHLBI 

Man Years: Total: 2 

Professional: 1 
Other: 1 

Project Description 
Objectives : 

1. Determine what alterations occur in whole blood oxygen affinity and 2, 3 
DPG following transfusion. 

2. Determine whether any changes in oxygen affinity^ occur in the transfused 
red cells which might suggest an influence of the "disease milieu. 

3. Determine whether such changes vary according to the blood product 
transfused (fresh blood, bank blood, frozen blood). 

4. Follow these alterations as the transfused red cells are eliminated from 
the recipient's circxilation. 

Methods Employed : 

This study will be carried out over a two year period. Patients who require 
transfusion on the Molecular Hematology Service will be studied. The studies 
will initially be confined to patients with thalassemia, sickle cell anemia and 
aplastic anemia. Initially patients of blood group A, B, or AB will receive 
group O ("universal donor ) packed red cells. A five cc pretransfusion speci- 
men as well as a five cc aliquot from the transfused cells will be obtained for 
measurements of whole blood oxygen affinity and 2, 3 DPG levels. Whole blood 
O- affinity will be measured by the technique of Rossi-Bernardi. A one hour 
post -transfusion specimen, daily specimen for five days and weekly specimens 
for three weeks will be drawn. Percent of transfused cells remaining will be 

BB-59 



measured by differential agglutination {Ashby technique) and correlated with 
changes in Opaffinity. Additionally the recipient's cells will be lysed in- ^ 

vitro by use of an anti-A or anti-B hemolysin. This will permit separation y 
of transfused from recipient cells in the post -transfusion specimen. Oxygen 
affinity can then be determined directly on the remaining transfused cells and . 
on the whole blood. These determinations permit calculation of O2 affinity of 
the lysed recipient cells. In this way it should be possible to determine 
whether specific changes occur in the transfused cell population post -trans- 
fusion and what component is the major influence in changes in whole blood 
O 2 affinity. 

A second series of studies using ABO identical transfusions of red cells and 
whole blood can be carried out if donor and recipient are not identical for a 
minor blood group. This is necessary to permit separation of donor from 
recipient cells following transfusion. For these studies, differences in the 
presence of red cell M antigen will be used to distinguish donor from recip- 
ient cells. This antigen was chosen because of its low antigenicity, rarity 
of clinical importance of anti-M isoantibodies, and presence of an anti-M 
reagent potent enough to effect the required separation. 

Major Findings : 

This project has been underway for less than one year. Three patients have 
been scheduled to date. It is too early to draw firm conclusions. 

Significance to Biochemical Research andthe Program of the Clinical Center 

This project has practical importance in the management of blood resources 
and the transfusion approach for chronic anemia. Results of these studies 
should indicate the physiologic changes that result in different anemia states 
when various red cell preparations are transfused. 

Proposed Course : 

This study should have its initial phase completed within one year. 

Publications: None 



(T 



SMITHSOMIAH SCIENCE Iflf-ORMAT 
PROJECT NUMBER (Oo NOT use t 



EXCHANGE 
space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATIOM, AND WELFARE 

PUBLIC HEALTH CERVICE 

NOTICE Of 

INTRAUURAL RESEARCH PROJECT 



PERIOD COVERED 

October 1, 1977 - September 30, 1978 



TITLE OF PROJECT (80 characters or less) . . 

Identification of Bacterial Organisms with Kell-like Specificity 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Principal Investigators: Mary H. McGinniss, AB(ASCP)SBB 
Research Biologist 
Paul V. Holland, M. D. , CCBBD Chief 

Other: James D. MacLowry, M.D. CC, CP, Deputy Chief 



COOPERATING UNITS (if any) 

Clinical Pathology 



lab/branch 
Microbiology 



INSTITUTE AMD LOCATION 

Clinical Center, Building 10 



TOTAL MANYEARS: 



PROFESSIONAL: 
1 



CHECK APPROPRIATE 80X(ES) 
□ (a) HUMAN SUBJECTS 

□ (al) MINORS a (a2) INTERVIEWS" 



(b) HUMAN TISSUES 



(c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

The red cells of patients with positive blood cultures are being analyzed 
for acquisition of a non-genetic ally determined Kell antigen. 

Patients with a serologically determined saline anti-Kell are being monitored 



for infection. 



Bacterial filtrates are being analyzed for inhibitory property for anti -Kell 
and ability to confer Kell -like antigens on Kell negative red cells. 



33-^1 



Serial No. ZOl-CL-02022-01 BB 
Blood Bank Depajrtment 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1977 - September 30, 1978 

Project Title: Identification of bacterial orgamsms with Kell-like specificity 

Previous Serial Number: None 

Principal Investigators: Mary H, McGinniss, AB(ASCP)SBB 
Patil V. Holland, M. D. 

Other: James D, MacLowry, M.D, 

Cooperating Units: Inside NIH 

Microbiology Service, Clin. Path. Dept. , CC 

Outside NTH 
None 

Man Years: Total: 1 

Professional: 1 

Project Description 

Objectives : 

A. To identify bacteria with Kell antigen-like specificity. 

B. To identify the etiology of persistent IgM anti-Kell in patients. 

C. To search for acquisition of Kell-like antigen in septicemic patients. 
Methods Employed : 

1. Bacterial cultures, whole and sonicated, plus their filtrates are 
being analyzed for their ability to inhibit anti-Kell antibodies and 
adsorb to Kell -negative human red blood cells. The former will 
involve inhibition of anti-Kell in a hemagglutination reaction and 
the latter serologic testing for an acquired Kell antigen. 

2. Patients with bacterially proven sepsis will have their red cells 
tested for the presence of Kell antigen. If positive, followup 
studies will be begun to determine if this antigen is present on 
the patient's red cells by genetic or acquired means. 



Major Findings : 

Thus far, one patient apparently developed an acqtdred Kell antigen 
while septic. One patient has been described in the literature who 
developed a transient anti-Kell while septic with an E. coli bacteremia. 

Significance to Biomedical Research and the Program of the Institute : 

A, Elucidation of mechanisms by which patients develop antibodies 
to red cell antigens which may restrict the availability of cross- 
match compatible blood. 

B. Understanding of red cell antigens in health and disease whereby 
these genetically controlled characteristics may be lost or 
acquired in certain clinical situations. 

Public ations : None 



IMITHSOt'ilAN SCIEiJCE I MFORMAT I ON EXCHANGE 
■ROJECT NUMBER (Oo NOT use this space) 



U.S. OEPARTMEfJT OF 

HEALTH, EDUCATION, AfJO WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRADURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl-CL-02023-01 BB 



PERIOD COVERED 

October 1, 1977 



September 30, 1978 



■|TL£ OF PROJECT (30 characters or less) 

Blood Group Substances in Malignant and Benign Breast Cyst Fluids 



MAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Principal Investigator: Mary H, McGinniss AB(ASCP)SBB 

Research Biologist Clinical Center Blood Bank 

Other: Ernest V. DeMoss, M, D. , Surgical Branch, NCI 

David Zopf, M. D. , Anatomic Pathology, NCI and CC 



COOPERATING UNITS (i 

NCI 



LAB/SRANCH 

Surgical Branch, NCI and Anatomic Pathology, Dept. 



of CC 



INSTITUTE AND LOCATICn 

Clinical Center, Bldg. 10, NC I 



TOTAL MANYEASS: 



PROFESSIONAL: 



CHECK APPROPRIATE BOX(ES) 
G (a) HUMAN SUBJECTS 

D (al) MINORS n {a2] INTERVIEWS" 



□ (b) HUMAN TISSUES 



D (c) NEITHt 



SUMMARY OF WORK (200 'words or less - underline keywords) 

Breast cyst fluids are being analyzed for the presence of soluble blood 
group substances , both serologically and biochemically. These data will 
be correlated, at a later date, with breast cyst fluid analysis for malignancy . 
If a consistent difference is noted between malignant and non-malignant 
cyst fluids, it may serve as a marker for patients at risk. 



<:il 



3B-0 



Serial No. ZOl-CL-02023-01 BB 
Blood Bank Department 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 
Individual Project Report 
October 1, 1977 - September 30, 1978 

Project Title: Blood Group Substances in Malignant and Benign Breast 
Cyst Fluids 

Previous Serial Number: None 

Principal Investigator: Mary H. McGinniss, AB(ASCP)SBB 

Other Investigators: Ernest V. DeMoss, M. D, 
David Zopf, M. D. 

Cooperating Units: Inside NIH 

nCi 

Outside NIH 
None 

Man Years: Total: 1.0 

Pr of e s sional : 1.0 
Other: 

Project Description 
Objectives : 

A. To delineate any differences in soluble blood substances found in breast 
cyst fluid from malignant tissue as opposed to benign tissue. 

B. To test the accuracy of anti-T titers to predict breast malignancy as op- 
posed to benign breast cysts. 

Methods Employed : 

1. Breast cyst fliiids, supplied by Dr. DeMoss of the NCI surgical branch, ^ 
will be tested, using an inhibition test for the presence or absence of Le , 

Le^, A, B, H, M, N and T soluble substances. 

2. These same fluids will be analyzed biochemically for Lewis substances 
by Dr. Zopf of the Anatomic Pathology Department. 

3. Blood serum from the patients will be tested for atypical red cell anti- 
bodies and anti-T titer. 



BB-65 



4. Saliva from these patients will be tested for secretor status (ABH) and ^^ 
Lewis substance. W, 

5. Red cells will be used for a complete red cell phenotype. 
Major Findings : None as yet 

Significance to Biomedical Research and the Program of the Institute : 

A. If a consistent difference is noted between malignant and nonmalignant 
cyst fluids, it may serve as a marker for patients at risk. 

B. Anti-T titers could become part of a breast cancer work -up. 

Proposed Course : 

To analyze as stated above 50-100 patients who are admitted for aspiration 
of breast cyst fluid. 

Public ations : None 



ROJiiCT iii;,V,r>i:R (Uo COT use tins opaccj 



HtALTli, EDUCATICt;, ACO WiirAf! 
PUBLIC HlALTH StiiVICE 
flOTlCt: Or 
INTRAHURAL RESEAnCH PfJOJECT 



ZOl-CL-02024-Ol-BB 



>ER100 COVEKEO 

October 1, 1977 - September 30, 1978 



riTLE OF FI^OJCCT (80 characters or less) 

Frozen Red Cells in Prevention of Non-A/Non-B Hepatitis 



tUMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVEc 
PROFESS lOWAL PERSONNEL ENGAGED ON THE PROJECT 

Principal Investigator: Harvey J. Alter, M.D., CCBB 

Other: Robert Gerety, BOB, FDA 

Leonard Seeff. VA. Wash,, D.C. 
George Grady, State Lab, Boston, Mass. 



IGATORS AHO ALL OTHER 



COOPERATING UfllTS (if any) 

V A Hospital, Washington, D. C, 
State Lab, Boston, Mass. 



LAB/BRAuCH 

Blood Bank Department, Clinical Center 



SECTION 

Immunology Section 



ciSicai'Centerl Building 10A/1E33, NIH, Bethesda, Maryland 20014 



PROFESSIC.'IAL 



CHECK APPROPRIATE eOx(ES) 
□ (a) HUMAN SUBJECTS 

[j (at) MINORS □ (a2) I fITERV I Ews" 



D (b) HUMAO TISSUES 



□ (c) NEITHER 



SUMMARY OF V.'CHK (200 ^.-ords or less - underline keywords) 

It has been suggested in the literature, but never conclusively documented 
that frozen-deglycerolized red cells (FDRC) could prevent post -transfusion 
hepatitis (PTH). In a recent experiment, we showed in a chimpanzee model 
that FRBC did not prevent the development of type-B PTH. Since 80-90% of 
PTH is now due to the non-A/non-B agent or agents it seems appropriate to 
determine if FRBC play any role in the prevention of this disease . Such a 
study has now become feasible because of the recent transmissions of non-A/ 
non-B hepatitis to chimpanzees. In this study, we will utilize a human plasma 
pool shown to be infectious in chimpanzees, admix with RBC shown to be non- 
infectious and then subject this reconstituted unit of whole blood to freezing 
and deglycerolization. The final product will be tested for infectivity in 
additional chimpanzees. 



Serial No. ZOl -CL-02024-01 -BB ^ 
Blood Bank Department f 

Clinical Center 
Bethesda, Maryland 

PHS-Nm 

Individual Project Report 

October 1, 1977 - September 30, 1978 

Project Title: Frozen Red Cells in Prevention of Non-A/Non-B Hepatiits 

Previous Serial No. None, 

Principal Investigator: Harvey J. Alter, M. D. 

Other: Robert Gerety, BOB, FDA 

Leonard Seeff. M. D. , VA, Washington, D.C. 
George Grady, M. D. , State Lab, Boston, Mass. 

Project Description 

1. To produce reconstituted units of whole blood known to contain an infec- 
tious inoculum of the non-A/non-B hepatitis agent. A pretested infec- 
tious plasma pool will be utilized to insure uniform infectivlty. 

2. Units will be sujected to a standout method of freezing and deglycero- m 
lization. f 

3. Frozen and deglycerolized cells and appropriate controls will be inocu- 
lated into chimpanzees who will be followed for biochemical and histologic 
evidences of viral hepatitis. 

Methods: 



1. A large volume of infectious plasma will be obtained by plasmapheresis 
from a donor know to transmit non-A/non-B hepatitis. 

2. Freezing and deglycerolization will be performed by a standard proce- 
dure for human use employing the IBM red cell washer. 

3. Chimpanzees will be transfused with frozen deglycerolized cells and 
followed with weekly SGOT/SGPT. Biopsies and plasmaphersis units 
will be obtained when indicated. 

4. Chimpanzees who do not become infected will be tested for acceptibility 
to the non-A/non-B agent by subsequent inoculation with the untreated 
infectious plasma pool. 

Major Findings : None to date 

Proposed Course : See Objectives /^ 

BB-68 



Significance to Biomedical Research and the Program of the Institute 

There is considerable uncontrolled data in the literature to suggest that 
FRBC prevent PTH. If true, this woxold provide a means of preventing 
PTH irrespective of our ability to detect virus in the donor. However, 
a previous chimpanzee study in our laboratory demonstrated that FRBC 
did not prevent type B PTH. Since 80-90% of posttransfusion hepatitis 
is now classified as non-A/non-B, it is important to establish if freezing 
and deglycerolization might prevent this form of hepatitis. 



BB-69 



project' NUMBER (Oo NOT use this space)" 



U.S. OEPARTKEWT OF 

HEALTH, EDUCATiCM, AtJD WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT MUMBER 

Z01-MH0083-04 AP 



PERIOD COVERED 

October 1, 1977 - September 30, 1978 



TL£ OF PROJECT (80 characters or less) 

hypothesis of X-linkage in Bi-polar and Uni -polar Affective Disease 



NVESTIGATORS ANO ALL OTHER 



NAMES, LABORATORY AMD INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Principal Investigator: Elliot Gershon, M. D. . NIMH AP Branch 

Dther: Mary H. McGinniss, AB(ASCP)SBB, Research Biologist 
Clinical Center Blood Bank 



COOPERATING UNITS (if any) 

Ulinical Center Blood Bank 



LAS/BRAIiCH 

NIMH AP Branch 



SECTION 

Effective Disorders 



IMSTITUTE AND LOCATION 

NIMH Clinical Center Building 10, Room 3N218 



TOTAL MANYEARS: 



PROFESSIONAL: 



CHECK APPROPRIATE 30X(E3) 
n (a) HUMAN SUBJECTS 

D (a!) MIIJORS n (a2) INTERVIEWS" 



D (b) HUMAN TISSUES 



D (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

[t has been reported that one form of affective disease (manic-depressive 
disease) may be carried on the X chromosome . Phenotypes , including X£ 
typing, have been done on 200 patients representing a mixture of bipolar 
and unipolar diagnoses and 951 family members. This study is targeted 
to end June 1, 1978. Statistical data on Xg and the incidence of other 
blood group antigens are now being compiled. 



3B-70 



Serial No. Z01-^IH0083-04 AP 
Blood Bank Department 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1977 - September 30, 1978 

Project Title: Hypothesis of X-linkage in Bi-polar and Uni-polar Affective 
Disease 

Previous Serial Number: ZOl -MH0083-03 AP 

Principal Investigator: Elliot Gershon, M. D. 

Other: Mary H. McGinniss, AB(ASCP)SBB 

Man Years: Total: 2 

Professional: 1 
Other: 1 

Project Description 

Objectives : 

A. To confirm or reject previously published claim that a gene involved 
in one form of manic depressive disease may be carried on the X sex 
chromosome. 

B. By statistical analysis to see if any correlation exists between manic 
depressive disease and any of the commonly known red cell antigens. 

Methods Employed : 

1. Mental health evaluations and complete red cell phenotyping including 
Xg typing. 

Major Findings : 

Six informative pedigrees were found. The reported linkage of Bi-polar 
major affective illness to known X-chromosomal markers, using the Xg 
blood group, could not be confirmed. 

Significance to Biomedical Research and the Program of the Institute : 

See objectives 

Publications : 

"Studies of Xg and Bi-polar illness linkage'' to be presented at the Annual 
APA meeting. May 1978 and paper entitled "A Failure to Replicate Link- 
age Between the Xg Blood Group and Bi-polar Illness, '' Gershon, E. S. , 
Leckman, J.F., McGinniss, M.H., and Tar gum, S.D. is in preparation. 

3B-71 



i I 



October 1, 1977, through Septemhier 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

CLINICAL PATHOLOGY DEPARTMENT 



CONTENTS 

I. Departmental Missions and Goals CP-1 

II . Department Activities. CP-1 

A. Service Productivity CP-1 

B . Personnel CP-1 

C . Presentations CP-2 

D. Formal Training Courses Completed by Staff CP-2 

III. Major Progress 

A. Service 

Office of the Chief CP-2 

Clinical Chemistry Service., CP-2 

Hematology Service . .CP-4 

Laboratory Computer Service , CP-4 

Microbiology Service CP-5 

B. Research and Development 

Office of the Chief CP-6 

Clinical Chemistry Service CP-6 

Hematology Service. . CP-7 

Laboratory Computer Service , CP-9 

Microbiology Service. CP-9 

C. Training 

Office of the Chief.,,.,.,.. CP-10 

Clinical Chemistry Service, CP-11 

Hematology Service. ...,,., CP-11 

Laboratory Computer Service CP-11 

Microbiology Service. CP-11 

IV. Future Objectives 

Clinical Chemistry Service , CP-12 

Hematology Service CP-12 

Microbiology Service , CP-13 

V. Publications CP-14 

VI . Intramural Project Reports CP-19 



October 1, 1977, throug?i September 30, 1978 



PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 
CLINICAL CENTER 



CLINICAL PATHOLOGY DEPARTMENT 

I. DEPARTMENT MISSIONS AND GOALS 



1. To provide the optiEum laboratory medicine support to patient- 
care physicians and their patients within the Clinical Center. 

2. To act as a consultant to patient-care physicians regarding 
the interpretation of laboratory data and patient care 
problems in hematology. 

3. To educate and train clinical pathology residents, clinical 
associates and visitors in the discipline of laboratory 
medicine. 

4. To conduct a program of research and development in the area 
of laboratory medicine. 

II. DEPARTMENT ACTIVITIES 

A. Service Productivity 

Using the Resource Monitoring System established last year, 
the Clinical Pathology Department performed 1,433,954 tests during 
FY-1978, which represents an 11.6% increase over FY-1977. The 
average monthly workload index likewise increased from BP in 
FY-1977 to 96 for FY-1978. 

The Hematology Service has continued its role as the major hemato- 
logy consultants to physicians and patients in the Clinical Center. 
This year, the Hematology Service has implemented a Hematology Out- 
patient Clinic which meets on Wednesday mornings in the hast Wmq AFU. 
The number of outpatient visits for this year has been over 3?5. The 
Hematology Service has interpreted over 3,000 bone marrow biopsies, 
clot sections, iron stains and aspirate smears of patients ii: the 
Clinical Center. Tn addition, approximately 200 bone marrovv ppeci- 
mens have been sent for consultation from various surrounding in- 
stitutions. 

B. Personnel 

Three staff physicians and one Staff Fellow joined tne Hematology 
Service this year. 



C. Presentations 

Fifty-eight members of the Clinical Pathology Department made 
74 formal presentations at universities and various national and inter- 
national meetings. 

D. Formal Training Courses Completed by Staff 

Sixteen Commissioned Officers participated in 26 formal training 
courses . 

Seventy-four Civil Service employees participated in 130 formal 
training courses. 

III. Major Progress 

A. Service 

The Phlebotomy and Urine Collection Team under the Office of the 
Chief is now fully staffed and covers both in and outpatients . With 
the interface of computers in full force, the Phlebotomy Team is very 
much involved with the computer-generated blood drawing work lists and 
labels, and accessioning specimens. All blood cultures, gentamicin 
levels, and timed test specimens are also a function of the Phlebotomy 
Team. Limited services for sterile clean catch urines are offered on 
both in and outpatients, which has resulted in better specimens for 
analysis and a decrease in the contamination rate. 

A new guide, "The Clinical Pathology and Blood Bank Guide" to 
help patient care physicians make best use of laboratory services was 
coordinated by the Office of the Chief. It was distributed to patient- 
care physicians in November 1977, and contains a master table of all 
laboratory tests available at NIH whether performed by the Clinical 
Pathology Department, Blood Bank Department, or via contract. 

An on-site inspection of the Clinical Pathology Department was 
conducted by the College of American Pathologists in May 1978. The 
few deficiencies that were noted by the inspection team have been cor- 
rected, and the laboratory has been accredited for a tv\70 year period. 

The Clinical Chemistry Service continued to review, update and 
rewrite routine analytical procedures. New procedures for amylase, 
gastric analysis, phosphorus, creatinine (microchemistry ) , blood 
gases, urinalysis and several serum enzymes have been developed to 
replace or supplement previously existing methods. 

An extensive evaluation of automated systems for determining serum 
electrolytes resulted in the purchase of a new fully automated four- 
channel electrolyte analyzer which greatly improves the efficiency and 
turnaround time for STAT electrolyte requests . 



The SMAC analyzer has been expanded to its full capacity of 20 
channels and interfaces directly with the laboratory computer system, 
so that test results are rapidly and efficiently transferred to the 
computer, making them available for patient care in a much shorter 
time; this system now operates daring the evening hours so that 
test requests received in the late morning and during the afternoon 
can be completed and reported the same day . The Clinical Chemistry 
Service initiated and coordinated a hospital-wide change to evacuated 
blood collection tubes which allows the use of a serum separator tiibe 
with a higher yield of serum in less time and fewer steps. The result 
is faster turnaround time for test results and lower requirements for 
phlebotomy . 

The electrowriter system for reporting STAT test results was 
expanded to cover 7 more patient care stations. 

In collaboration with BEIB, an automated mechanical evacuated 
blood tube stopper remover was developed, and a patent applied for. 

Serum Cortisol determinations have been introduced into routine 
use in the laboratory. 

Renovation of several modules of the service laboratory was com- 
pleted including a .new microchemistry laboratory allowing this ser- 
vice to be moved from its distant location on the 10th floor down 
to join the rest of the laboratory on the 4th floor. 

Twelve additional tests were added to the list of tests which 
are performed STAT by the Chemistry service 24 hours a day, 7 days 
a week. This was done to facilitate the ordering of STAT tests via 
the MIS computer system and to facilitate laboratory analyses on 
critically ill patients. 

The Chemistry Service achieved coverage of the laboratory by a 
technologist or technician 24 hours a day, 7 days a week. This insures 
that fully trained individuals are now performing or supervising the 
performance of all assays within the Chemistry Service. 

An on-line computer link was established between Bioscience 
Laboratories, a major contract laboratory for the Department, and the 
Honeywell Computer system. Bioscience Laboratories are now able to 
enter directly into the Honeywell system the results of those tests 
which are contracted for by the Chemistry Service. These results may 
be certified by Bioscience, with saving of time for the Chemistry 
Service. Senior staff of the Chemistry Service and Clinical Pathology 
residents, using an out-of-range list generated by the Loneywell com- 
puter system, review al] results from the Chemistry Service and Bio- 
science Laboratories before printing patient reports. This review sys- 
tem has reduced the number of clerical and computer errors which might 
otherwise have appeared in patient reports. 



The Chemistry Service designed a series of screens and four 
panels to facilitate ordering tests from the Chemistry Service 
through the MIS computer system. 

During eight months of this fiscal year, the Hematology Service 
has undergone a major laboratory renovation to make better use of 
available space for the clinical hematology evaluation of patients 
in the Clinical Center. 

The Hematology Serv.i ce implemented a new program in the Outpatient 
Department which utilizes whole blood for over 90% of all Outpatient 
hematology determinations and reduced the large number of finger 
punctures for hematologic determinations with a saving of technolo- 
gist time. In addition, the use of whole blood allows greater ac- 
curacy in analytical determinations, ana results can be returned to 
patient-care areas more quickly. 

All Outpatient hematology samples are now being treated as 
STAT's, and results are back to the patient area in less than one 
hour. In addition, the Hematology Service has developed a new 
filing system for test results which allows rapid retrieval of 
in- and outparients ' laboratory data for the previous 24 hours, 
whether the blood is from fingersticks or whole blood. 

The Hematology laboratory is now staffed 24 hours a day, 7 days 
a week by technicians or technologists. This insures the presence 
of a professional person with high professional competence in the labo- 
ratory to perform and evaluate analytical procedures in hematology for 
Clinical Center patients. 

During this year, the Hematology Service established the 
position of Quality Control Supervisor who is responsible for the 
overall, day-to-day quality control of all analytical systems, 
control samples, and sporadic checks of the Hematology Service. 
Three new quality control programs have been implemented to: 
1) insure the proper operation of the Coulter Model S, 2) to insure 
accurate platelet counts, and 3) to insure quality control of co- 
agulation tests and reagents. 

The Hematology Service is evaluating the efficacy of two new 
radioimmunoassays. One radioimmunoassay allows determination of 
vitamin B and folate levels simultaneously in a single tube; the 
second radioimmunoassay is a quantitative, direct measurement of 
beta thromboglobulin to identify a platelet antigen. This antigen 
appears only in human plasma after platelet release reaction has 
occurred and is a more sensitive indicator of intravasciilar co- 
agulation and other platelet reactions which frequently occur in 
Clinical Center patients. 

The requesting and reporting of laboratory results has been im- 
proved by the Laboratory Computer Service by establishing a computer- 
to-computer link between the Clinical Pathology Department Honeywell 



laboratory computer system and the Clinical Center Technicon M'S 
computer. Laboratory results may now be retrieved throughout the 
hospital on MIS terminals. STAT results are printed imrr.odia tely 
and automatically on the nursing units. Equipment and programs 
have been provided to record and analyze quality control data for 
the SMAC multichannel analyzer. Enhancements to the Honeywell 
system's hardware and software have increased the speed and respon- 
siveness of the system and provided more flexibility in its opera- 
tion. The SMAC multichannel analyzer has been interfaced to the 
Honeywell system eliminating the manual entry? of several thousand 
test results each week. 

The Microbiology Service implemented tho MIC 2000 to perform 
antibiotic sensitivity tests which produces the microdilution plates 
and not only saves considerable time but allows at least 20 dit 
antibiotics to be tested simultaneously. The MIC 2000 also provides 
qualitative interpretation of the data. 

The API 20E biochemical system has been extended to the diagnosis 
of many of the nonf ermentative gram negative rods which permits more 
rapid diagnosis of many of these difficult organisms with no sacrifice 
in accuracy over the previous much more laborious method. 

Use of the API-20 Anaerobic Strip has expedited the identifi- 
cation of alpha hemolytic and nonhemolytic streptococci. The 
Microbiology Service continues to speciate such streptococci when 
isolated from blood or other sterile fluid sites. Fermentation 
patterns are available in one day as opposed to the usual seven 
day readings that are sometimes necessary by standard tube techniques. 
Information from these identifications will provide increased knowledge 
on the frequency and type of infections caused by the different indivi- 
dual species. 

A new more rapid bioassay for determination of antibiotic serum 
levels, particularly gentamicin, has been implemented. This method 
allows a determination of the antibiotic in approximately 6 hours which 
means that the value can be available for adjusting the next dose of 
antibiotic to be given. As a consequence of this new method, the 
requests for antibiotic levels increased markedly this year. 

A penicillinase assay system was evaluated and then modified for 
routine laboratory use. This assay is now being used primarily as a 
rapid means (usually less than 1 hour) of detecting penicillinase pro- 
duction for S. aureus , S. epidermidis . Neisseria, and Haemophilus. 

Additional modifications were made to improve the laboratory 
Anaerobic Glove Box. Plexiglass viewing areas have significantly im- 
proved technologists' ability to examine culture plates. 

The Microbiology Service, in cooperation with the Infections 
Control Committee, investigated contaminated Operating Room lubricating 



solutions which revealed inadequate sterilization of spigots in the 
solution vats as the probable source. Following our recommendation, 
vats without spigots are being installed. 

This Service continued bacteriophage typing of Staphylococcus 
aureus for epidemiological purposes because of the spread within the 
hospital of Staphylococcus aureus , phage pattern 94/96. Serotyping of 
Pseudomonas aureginosa is becoming more useful as an epidemiological 
tool. This laboratory is a typing reference laboratory since the 
CDC NO LONGER PROVIDES THIS SERVICE. 

A new stool concentrating procedure, developed in this laboratory 
for parasitologic evaluation, has been put into routine use. This tech- 
nique permits rapid concentration of ova from small amounts of stool 
and is equal to or superior to traditional, more laborious methods. 

An extensive array of microbiology ordering screens have been de- 
signed for the Technicon Medical Information Service to facilitate se- 
lection of appropriate diagnostic procedures by the patient care 
physicians. 

B. Research and Development. 

The Office of the Chief distributed a 14-page Pathology Question- 
naire which evaluated the relationships between space, personnel, and 
test volume to over 100 academic pathology departments in the United 
States. Fifty departments completed the questionnaire. The data have 
defined mathematical relationships between space, personnel, test volume, 
publications, and budget that will be valuable to this Department and 
other pathology departments in the country. 

A variety of instruments were evaluated by the Clinical Chemistry 
Service including a Beckman BUN/glucose analyzer, a Beckman creatinine 
analyzer, Technicon BGII blood gas analyzers, Technicon Statlytes analy- 
zer, the Photovolt PVA4 electrolyte analyzer, the Micromedics MARC4 
gamma counter, and the Beckman Inimunochemistry Analyzer. A number of 
analytical methods v;ere either upgraded or added to the laboratory 
service as indicated under Major Progress above. 

Work on biomedical applications on microcalorimetry continued, with 
particular emphasis on analysis of amylase activity and cholesterol. 

Collaborative studies with NIILBI on the association between 
platelet function and atherogenesis have focused on the effect of 
vitamin E. In addition, work on biochemical markers of in vitro platelet 
function shows that LDH and phosphorus are more reliable than pH or 



Radioimmunoassays for the determination of creatine kinase iso- 
enzymes had previously been developed by Clinical Chemistry and are now 



being applied in studies of patients following cardiac surgery, with 
myocardial infarction, and schizophrenia. Further optimization 
of these RIA's is being studied. 

A method for measurement of ascorbic acid levels in serum and 
leukocytes is under development as part of a study of lipoprotein and 
ascorbic acid levels in patients on chronic hemodialysis. 

A method for measuring serum concentrations of gentamicin by 
high pressure liquid chromatography is being developed. In conjunction 
with Bio-Science and the Neurology Service at NIH, the effect of certain 
drugs used for the treatment of Parkinson's Disease on 24- hour urine 
vanilmandelic acid excretions was studied. 

An investigation of the use of a nephelometric technique to analyze 
low levels of pyrogens using lysate of amebocytes from Limulus poly- 
phemus was initiated, and the specificity of the limulus amebocyte 
lysate test was evaluated in collaboration with the Hematology Service. 

In collaboration with the investigators in NIAMDD, a study was 
begun to evaluate drug interference on determination of uric acid 
performed by a specific uricase method and by a method that involves 
measuring reducing substances. 

The Hematology Service has undertaken studies in conjunction with 
the Medical Neurology Branch, NINCDS, and the Pediatric Oncology Branch, 
NCI, to determine the effect of plasmapheresis and plasma exchange by 
automated techniques on coagulation. Patients had samples taken prior 
to, immediately after and 24 hours after the plasma exchange. Coagula- 
tion studies were performed on patients' blood as well as on specimens 
taken from the automated system. These studies are being performed in 
conjunction with determinations of IgG, cholesterol, triglyceride, serum 
protein and trace metals. Initial studies suggest that patients re- 
ceiving plasma exchange are anticoagulated at the end of the procedure 
and that there is a significant drop in various coagulation proteins 
related to the plasmapheresis technique itself. 

Studies were undertaken with the NCI to determine the effect of 
hyperthermia with and without chemotherapy on the hemostatic system on 
patients with neoplasms which have been unresponsive to other chemo- 
therapy. The effect of graded prolonged hyperthermia and the effect of 
hyperthermia and chemotherapy have been investigated to determine if 
subclinical or clinical intravascular coagulation occurs in these 
patients. 

Studies on human platelets with tlie NINCDS and NIMH have continued 
to determine whether platelet heterogeneity is due to aging in the peri- 
pheral circulation. A successful in-vivo model in rhesus monkeys has 
been developed and in-vitro biochemical parameters associated with 
platelet aging in normal individuals and patients with disease states 



have been measured. These studies may make it possible to develop non- 
invasive procedures to determine mean platelet age and will be useful 
in identifying those patients with a thrombocy tolytic state versus those 
with hypoproliferative states resulting in thrombocytopenia. 

The carbohydrate content of the human factor Vlll/von Willebrand 
factor protein has been characterized, and the key carbohydrate in- 
volved in the interaction of platelets, ristocetin, and factor Vlll/von 
Willebrand factor protein has been identified. The von Willebrand' s 
disease factor Vlll/von Willebrand factor protein reveals that there ^s 
decreased carbohydrate content. These studies and the structure-function 
relationships of the von Willebrand' s disease factor Vlll/von Willebrand 
factor protein are useful in understanding the role of this protein in 
platelet-vessel wall interactions and may explain some of the clinical 
and laboratory findings in patients with von Willebrand' s disease. 

In association with the National Naval Medical Center, the effect of 
canine factor VII I/von Willebrand factor protein in blood flow after 
induced cerebral ischemia has been studied. These studies may elucidate 
the role of the von Willebrand factor in transient ischemic attacks 
or in strokes in man. 

The factor Vlll/von Willebrand factor protein has been investigated 
in a variety of therapeutic concentrates to ascertain which form of con- 
centrate might be most useful in the treatment of hemophilia and/or 
von Willebrand' s disease. 

Work has continued in the area of acquired dysfibrinogenemia , and 
it has been shown that patients with hepatoma and acquired dysfibrino- 
genemia not only have an increased sialic acid content of their fibrino- 
gen, but also have increased neutral sugars and hexosamine content. 

Collaborative morphology studies with NCI and the USUHS determined 
terminal transferase by both biochemical and immunologic methods in the 
cells of patients with a variety of hematologic diseases. This has been 
a useful technique in trying to differentiate myeloid from lymphoid or 
undifferentiated types of blast cells in leukemias and lymphomas. 

A collaborative study with the NIAID was undertaken to investigate 
the clinical pathological correlations of morphology and the course of 
the disease in hypereosinophilic syndromes. 

Participatioft in the French, American, and British working group on 
leukemia has continued with a meeting to re-evaluate the classification 
of acute leukemia and to prepare new guidelines for this classification 
and other hematologic malignancies. 

A joint venture with the Johns Hopkins School of Medicine, the 
University of Indiana, and NICHD was undertaken to investigate the effect 
of vitamin E on red cell survival. Reports that patients with chronic 
hemolysis treated with large doses of vitamin E have had an improvement 



(i.e., prolongation of their red cell survival as well as other hema- 
tologic parameters) , suggest a simple, non-invasive v.ay to improve ti:e 
hemoglobin content and reduce transfusion requirements in these 
patients. 

A combined study with the New York University School of Medicine 
revealed a way to qualitatively improve red cell transfusion. Red cells 
in rhesus monkeys separated according to cell age and different age- 
dependent cohorts of cells were retrans fused into those monkeys. 
This study demonstrRted that young cells have improved survival after 
transfusion compared to the older cells. This may be a very useful way 
to prepare cells for a transfusion regimen for patients who require 
chronic transfusions. 

The Laboratory Computer Service collaborated with the Microbiology 
Service in the mathematical analysis of light scattering patterns of 
bacteria exposed to antimicrobial agents and in computerized monitoring 
of impedence changes in bacterial cultures from Clinical Center patients. 

With the cooperation of investigators overseas and at Children's 
Hospital, the laboratory profiles of malnourished children in Zaire are 
being studied. 

Empirical Bayesian methods are being applied to serial clinical 
laboratory results to interpret the relation between screening and 
follow-up tests. 

The Laboratory Computer Service assisted the Clinical Chemistry 
Service to evaluate additional tests for the SMAC multichannel bio- 
chemical analyzer, in determining clinical reference ranges for high- 
volimie tests, and in the statistical analysis of instrument comparison 



The Laboratory Computer Service is evaluating the use of statisti- 
cal analyses of patient results to monitor laboratory performance. 

Programs to facilitate the real-time interpretation of SMAC quality 
assurance specimens are under development. Analysis of variance tech- 
niques are being used to investigate the lot-to-lot variation in results 
obtained with commercial radioimmunoassay kits. 

The Microbiology Service continued studies on the distribution and 
occurrence of new species of a resistant Corynebacterium species which 
has been causing infections in severely compromised patients both here 
and in other hospitals. 

A more accurate, more rapid and simpler method for identification 
of Neisseria species is being evaluated. Appropriate technical modifi- 
cations are being made and it will soon be in routine use. 



The occult blood test which uses a potential carcinogen, benzidine, 
for its major reaction is being evaluated for the possibility of si±)- 
stituting the non- carcinogen, tetramethyl-benzidine . 

Evaluation continues with the Differential III, a laser light 
scattering instrument, on the problem of rapid determination of anti- 
biotic synergy with Group D Streptococci. 

A trial comparison of blood culture techniques is in progress. 
One is the conventional culture of whole blood, and the other is the 
culture of filtered preparation of blood which has been lysed by a 
solution which is non-injurious to bacteria. The lysed blood 
technique has many theoretical advantages and has been markedly 
superior in the recovery of Gram-positive cocci from blood. 

Work continues on the detection of positive blood cultures by a 
computerized impedance instrument, based on lowering of impedance when 
bacterial growth occurs in the blood culture medium. This means of 
growth detection has many potential advantages . 

An accidental discovery made during the blood lysis - filtration 
culture study was the observation that bacteria were quantitatively 
removed from suspension by filters with pore sizes up to thirty times 
larger than the bacterial cell. The nature of the attraction is not 
yet well understood but is being actively studied. 

Work continues on Blastocystis hominis , an anaerobic intestinal 
protozoan of man. A single cell contains hundreds of mitochondria 
whose function in a strictly anaerobic cell is being investigated. 

C. Training. 

Four first year residents entered the Clinical Pathology Depart- 
ment residency training program. They joined three second-year 
residents in the program. Each rotation of the first year residency 
training program was evaluated by the residents using an evaluation 
sheet developed by the Office of the Chief . All comments and evalua- 
tions were transmitted to the Chiefs of the Services. Changes in the 
program and rotation were made where indicated by the residents' 
appraisal. 

The senior staff and the residents continued weekly Clinical 
Pathology Rounds in which interesting patients, laboratory problems, 
and original research were presented and discussed. These rounds are 
approved by the American Medical Association for Category I Continuing 
Medical Education credit. 

The second-year residents, while on the Resident-Consultant rota- 
tion, chose the following management- laboratory problems to evaluate: 
The use of contract laboratories, audit of the laboratory computer 
service, defining references for tests provided by the Hematology Service, 



and an evaluation of the need for an Immunology Service. Each of these 
projects was a significant contribution to the department. 

Two separate lecture series were provided by the senior staff of 
the Clinical Chemistry Service for technologists and clinical patholo- 
by residents. A two-semester course describing current methodology 
and instrumentation of the Clinical Chemistry Service and the clinical 
value and interpretation of tests performed by the Chemistry Service 
was offered. This course was approved for PACE and ACCENT Continuing 
Education credit. This course for residents was approved by the 
American Medical Association for Category I Continuing Education 
Credit. 

The Hematology Service had two guest workers during the year from 
local medical schools who spent 3 to 6 months in the Hematology Service 
learning bone marrow interpretation, assisting patient consultation, and 
improving their understanding and facility with coagulation procedures. 

The Hematology Service continued to coordinate the Hematology- 
Oncology Clinical Elective and its direction and teaching of this 
elective. Twelve medical students took their rotations in the Hematology 
Service from September 1977 through May 1978. A senior staff advisor 
supervised all consultations by these students and insured that they were 
able to perform bone marrow aspirations and biopsies, and also assisted 
them in interpretation of peripheral blood smears and bone marrow 
material. 

The senior staff, residents, and medical students of the Hematology 
Service met at least twice weekly to have rounds related to patients 
with hematologic problems. In addition, several guest physicians from 
other institutes as well as some from outside the NIH attended these 
rounds on a regular basis. 

A member of the Hematology Service presented the board review 
course in hematology to the FAES . A member of the Hematology Service 
participated in the American College of Physicians' Self-Assessment 
Recertification Examination course given in Washington, D.C. 

During the summer, three part-time employees were directed in 
hematologic research by individual advisors who formulated research 
projects for these employees. 

The Laboratory Computer Service conducted a three-week training 

course on medical computing. In addition, personnel from other 

services were trained to use the NIH computer facilities for data 
processing . 

In the Microbiology Service two Infections Disease Fellows from 
Walter Reed Army Medical Center and one Infections Disease Fellow from 
the Bethesda Naval Hospital, spent one month, learning diagnostic 
bacteriology. Also, a Clinical Pathology Resident from the Bethesda 



Naval Hospital spent two months in the service learning more advanced 
techniques. A number of medical students on their Infections Disease 
Elective and Clinical Associates from LCI, NIAID, spent varying 
periods of time learning fundamentals of bacteriology. 

The senior staff continued the biweekly lecture series on 
Fundamental Microbiology which is given for the residents of the 
Clinical Pathology Department and other interested individuals in this 
area. 

Weekly conferences were held with the technologists to discuss cur- 
rent interesting clinical cases and changes in techniques. 

A PACE approved course in continuing education for medical techno- 
logists on Antibiotic Sensitivity Testing was given by the Senior Staff 
and was taken and passed by 18 technologists. 

Three senior staff members were awarded specialty boards in Medical 
Microbiology by the American Board of Pathology, and three senior staff 
members were made Diplomates of the American Board of Medical Micro- 
biology after taking competitive examinations. 

FUTURE OBJECTIVES. 

The Clinical Chemistry Service will maintain the highest standards 
of quality while simultaneously increasing efficiency and output, as 
well as expanding the services offered to Clinical Center patient-care 
personnel. Through research and development and the use of new tech- 
nology as it enters the market place, we hope to increase the accuracy 
and specificity of our tests, and to investigate the clinical appli- 
cability of new areas of testing. 

Therapeutic drug monitoring and trace metal analysis/toxicology 
will receive particular emphasis in the near future. Work on immuno- 
logical approaches to measuring specific markers of tissue pathology 
(such as the work on creatine kinase isoenzymes) will continue and be 
expanded to include other types of markers which may be even more 
specific and sensitive. 

The Hematology Service plans to evaluate automated coagulation 
load. Research in the Hematology Service will continue, and we will 
introduce tests to better understand the structure-function relation- 
ships of platelets and coagulation proteins. More sensitive and pre- 
dictive tests for bleeding, thrombosis and platelet survival, quali- 
tative and quantitative abnormalities of platelets and coagulation 
proteins are being developed. 

Training and clinical consultation will be important Hematology 
Service goals so as to improve the care of individual patients in the 



Clinical Center, improve the concepts and design of the piotocols in- 
volved in the diseases studied in the Clinical Center and, in an over- 
all aspect, help to upgrade general medical care of patients in the 
Clinical Center. 

The Microbiology Servi ce hopes that enough information can be de- 
rived from the experimental blood culturing procedure to discontinue 
parallel operation and institute this new procedure as a routine. 

The new senior staff niember will have as a primary area of respon- 
sibility, the evaluation of immunologic procedures for bacterial diag- 
nosis. It is hoped that some of these approaches will lead to more 
rapid bacterial diagnosis utilizing immunologic methods. 

We have begun an evaluation of high pressure gas chromatography and 
radiometric enzymatic assays of serimi antibiotic levels to increase speed 
and accuracy and possibly to replace our present bioassay. 

The evaluation of the laser light scattering instrument should be 
completed this coming year which will allow us to more rapidly predict 
antibiotic susceptibility and bactericidal activity. 

An evaluation of the Dynatech MIC-2000 Automatic Inoculator is 
planned for the near future. This instrument may considerably facili- 
tate the inoculation of the Microtiter plates used in antimicrobial 
sensitivity determinations. 

A clinical and bacteriologic report is planned regarding several 
patients v/ith central nervous system tumors who have been infected 
with the usually non-pathogenic organisms Propionibacterium acnes . 



V. PUBLICATIONS 

Adornato, B. T. , Corash, L. , and King, E. S.: Erythrocyte survival in 
Duchenne muscular dystrophy. Neurology 27: 1019-1022, 1977. 

Bennett, J. E. and Jennings, A. E. : Factors influencing susceptibility 
of Nocardia species to trimethoprim- sulfamethoxazole. Antimicrob. Ag. 
Chemother. 13: 624-627, 1978. 

Blitzer, B. L. , Waggoner, J. G., Jones, E. A., Gralnick, H. R. , Towne, D. , 
Butler, J., Weiss, V., Kopin, I. J., Walters, I., Teychenne, P. F., 
Goodman, D. G. and Berk, P. D.: A model of fulminant hepatic failure in 
the rabbit. Gastroenterology 74: 664-671, 1978. 

Coller, B. S., Frank, R. , Milton, R. and Gralnick, H. R. : Plasma cofactors 
of platelet function: Correlation with diabetic retinopathy and hemoglobin 
;: 311-316, 1978. 

Corash, L. , Shafer, B. and Perlow, M. : Heterogeneity of human whole blood 
platelet subpopulations . II. Use of a sub-himian primate model to analyze 
the relationship between density and platelet age. Blood . (in press) . 

Costa, J. L., Stark, H. , Shafer, B., Corash, L., Smith, M.A. and Murphy, 
D. L. : Maximal packet size for serotonin in storage vesicles of intact 
human platelets. Biochem. Biophys. Res. Comm. (in press). 

Dinarello, C. A., Elin, R. J., Chedid, L. and Wolff, S. M. : The pyrogenici- 
ty of synthetic adjuvants. J. Infect. Pis. (in press). 

Donlon, J. A., Jaffe, E. S. and Braylan, R. C: Terminal deoxynucleotidyl 
transferase activity in malignant lymphomas. N. Engl. J. Med. 297: 461-464, 



Elin, R. J. : A program for residency training in clinical pathology. 
Am. J. Clin. Path, (in press) . 

Elin, R. J.: Role of magnesium in membranes; erythrocyte and platelet 
function and stability. In Cantin, M. (Ed.): Proceedings of the Second 
International Symposium on Magnesium . Spectrum Publications, New York, 
(in press) . 

Elin, R. J.: Nonspecific resistance. In Dick, George. Immunology of 
Infectious Diseases. Livingston Co., London, (in press). 

Elin, R. J. and Ailing, D. W. : Survival of normal and magnesium-deficient 
erythrocytes in rats: effect of magnesium-deficient diet vs. splenectomy. 
J. Lab. Clin. Med. 91: 666-672, 1978. 

Elin, R. J., Knowles, R. , Barth, W. F. and Wolff, S. M.: Lack of specificity 
of the limulus lysate test in the diagnosis of pyogenic arthritis. The J. 
of Infect. Pis. 137: 507-513, 1978. 



Elin, R. J. and Tan, H. K. : Formation of plaques on erythrocyte membranes 
from rats with magnesiiom deficiency. In Cantin, M. (ed. ) : Proceedings of 
the Second International Symposium on Magensium . Spectrum Publications, 
New York. (in press) . 

Elin, R. J. and Wolff, S. M. : Bacterial endotoxins. In Laskin, A. I. and 
Lechevalier, H. A. (eds.): C RC Handbook of Microbiology . Cleveland, Ohio, 
CRC Press. (in press) . 

Gill, V. J. and MacLowry, J. D. : Antibiotic susceptibilities of commonly 
encountered anaerobic bacteria. Handbook Series in Clinical Laboratory 
Science , Clinical Microbiology , Vol. II, Seligson, D., (ed.), CRC Press, 
Cleveland, Ohio, pages 281-292, 1977. 

Gralnick, H. J.: Factor Vlll/von Willebrand factor protein: Galactose-A 
cryptic determinant of von Willebrand factor activity. J. Clin. Invest. 
62:496-499, August 1978. 

Gralnick, H. R. : Intravascular coagulation. 1. Differential diagnosis and 
conditioning mechanisms, and 2. Underlying conditions and therapy. 
Postgraduate Medicine 62: 68-87, 1977. 

Gralnick, H. R. , Galton, D. A. G. , Catovsky, D. , Sultan, C, and Bennett, 
J.: Classification of acute leukemia. Ann. Int. Med. 87: 740-753, 1977. 

Gralnick, H. R. , Givelber, H. and Abrams , E.: Dysf ibrinogenemia associated 
with hepatoma: A carbohydrate abnormality. N. Engl. J. Med. 299:221-226, 
August 3, 1978. 

Jaffe, R. , Schmid, A. and MacLowry, J.: Effect of ascorbic acid on detection 
of blood in urine. Am. J. Clin. Path , (in press). 

Jaffe, R. M. and Zierdt, W. : An occult blood test procedure not subject to 
inhibition by reducing substances. J. Lab. Clin. Med, (in press). 

MacLowry, J.D.: Criteria for obtaining proper cultures and serum antibiotic 
levels. Journal of Saint Barnabas Medical Center . Pages 1-9, August 1977. 

MacLowry, J.D.: How you will recognize the lab of the future when you see 
it in use now. Laboratory World . Pages 100-108, April 1978. 

MacLowry, J.D.: Nonspecific expressions of bacterial pathogenicity. CRC 
Forum. In Bacteriolo gy, (in press). 

MacLowry, J.D. and Robertson, E. A.: Applications of computers and computer 
diagnostic models in the clinical microbiology laboratory. In Mechanizing 
Microbiology . Sharpe, A. M. and Clark, D. S. (eds.) pages 293-318, 1978. 
Charles C. Thomas, publishers, Springfield, Illinois. 

MacLowry, J.D., Robertson, E. A. and Elin, R. J.: The place of the computer 
in diagnostic medical bacteriology. In Progress in Clinical Pathology . 7: 
pages 49-70, 1977. Grune & Stratton, Inc. , New York. 

cp-15 



MacLowry, J.D., Robertson, E. A., Friedman, R. B. and McDonald, C.J.: 
Antibiotic Susceptibilities of Commonly encountered aerobic and facultative- 
ly anaerobic bacteria. In CRC Handbook Series in Clinical Laboratory Science . 
Clinical Microbiology . Vol. II, Seligson, D. (ed.) CRC Press. Cleveland, 
Ohio, pages 251-280, 1977. 

McAdairi, K. P. W. J., Elin, R. J., Sipe, J. D. and Wolff, S. M. : Changes in 
human serum amyloid A and C-reactive protein following etiocholanolone 
induced inflammation. J. Clin. Invest. 61: 390, 394, 1978. 

McMaster, P. R. B., Robertson, E. A., Witebsky, F. G. and MacLowry, J.D.: 
Evaluation of a dispensing instrument (Dynatech MIC-2000) for preparing 
microtiter antibiotic plates and testing their potency during storage. 
Antimierob. Agents. Chemother. 13: 842-844, 1978. 



Miller, L. H. , Neva, F. A. and Gill, F.: Failure of chloroquin in human 
babesiosis (Babesia microti) - case report and chemotherapeutic trial in 
hamsters. Ann. Int. Med. 83: pages 200-202, 1978. 

Mundy, G. R. , Rick. M.E., Turcotte , B. A. and Kowalski , M.A.: Hypercalcemia 
in lymphosarcoina cell leukemia. Am. J. Med. (in press) . 

Murphy, D. C, Costa, J. L., Shafer, B. and Corash, L. : Monoamine oxidase 
activity in different density gradient fractions of human platelets. 
Psy chopharmacology . (in press) . 

Nishi, H. and Young, D. S. : A flexible reaction rate analytical system 

for the rapid determination of IgA, IgG and IgM concentration. In 

Automated Immunoanalysis , Part 2, Ritchie, R. F. (ed.) Marcel Dekker, Inc. 
New York, Pages 353-373, 1978. 

Norton, J. A., Shulman, N. R. , Corash, L., Smith, R. L. , Au, F. and 
Rosenberg, S. A. : Severe thrombocytopenia following intralesional BCG 
Therapy. Cancer 41: 820-826, 1978. 

Papadopoulos, N. M. : Hyperliproteinemia phenotype determination by agarose 
gel elctrophoresis. Clin. Chem. 24: 227, 1978. 

Papadopoulos, N. M.: Clinical application of lactate dehydrogenase iso- 
enzymes. Ann. o f Clin, and Lab. Sci. 7: 506, 1977. 

Piomelli, S., Seaman, C, Reibm.an, J., Tytun , A., Graziono, J., Tabachnik, 
N. and Corash, L.: Separation of younger red cells with improved "in vivo" 
survival: A new approach to chronic transfusion therapy. Proc. Natl. Acad. 
Sci . (in press) . 



(*- 



Pitas, R. E., Nelson, G. J., Jaffe, R. M. and Mahley, R. S.: ;n5,lS- 
Tetracosadienoic Acid Content of Sphingolipids from Platelets aid Erythro- 
cytes of animals Fed Diets High in Saturated or Polyunsaturated Fats. 
Lipids , (in press) . 

Pizzo, P. A., Ladisch, S. K. and Vvitebsky, F. G.: Alpha hemolytic 
streptococci: Clinical significance in cancer patients. Med. Ped. Oncology , 
(in press) . 

Rehak, N. N. and Young, D. S.: Applications of calorimetry in the clinical 
laboratory. C lin. Chem. , 1978 (in press) . 

Rick, M. E. and Hoyer, L. W. : Thrombin activation of factor VIII. 
II. A comparison of purified factor VIII and the low molecular weight 
factor VIII procoagulant. Brit. J. Haematol . 38: 107-119, 1978. 

Robertson, E. A., Sliva, C. A. and Young, D. S.: Values for uric acid in 
patients' sera as measured with SMAC (phosphotungstate) and AutoAnalyzer 
(uricase) . Clin. Chem. 24: 173, 1978. 

Robertson, E. A.: The role of computers in laboratory medicine: clerks, 
tools, or consul Lants? Proceedings: The First Annual Symposium on Computer 
Application in Medical Care . pages 6-7, 1977. 

Robertson, E. A. and Young, D. C: Evaluation of SMAC performance by 
analysis of variance of quality control data. Advances in Automated Analysis . 
Vol. 1. Tarrytown, N. Y. : Mediad, Inc. pages 204-210, 1977. 

Spielberg, S. P., Garrick, M.D. , Corash, L. M., Butler, J. D., Tietze, F., 
Rodgers, L. and Schulman, J.: Biochemical heterogeneity in human glutathi- 
one sythetase deficiency. J. Clin. Invest. 61; 1417-1421, 1978. 

Spiro, T. , Jaffe, R. M. , Holland, P. V., and Alter, H. J.: A study of street 
heroin lots for the presence of the hepatitis-B surface antigen. Drug and 
Alcohol Dependence . (in press) . 

Sweet, J. B., Gill, V. J., Chusid, M. J. and Elin, R. J.: Nitroblue tetra- 
zolium and limulus assays for bacteremia after dental extraction. J. Amer. 
Dent. Assn. 96: 276-281, 1978. 

Tan, H. K., Harrison, M. and Corash, L.: Demonstration of the outer sur- 
face of freeze etched normal human platelets: Correlation with buoyant 
density. Brit. J. Haematol, (in press). 

Van Steirteghem, A., Robertson, E. A. and Young, D. S . : Variance components 
of serum constituents in healthy individuals. Clin. Chem. 24: 212-222, 1978. 

Van Steirteghem, A., Robertson, E. A. and Young, D. S.: Influence of large 
doses of ascorbic acid on laboratory tests. C lin. Chem. 24: 54-57, 1978. 



CP-17 



Van Steirteghem, A. C, Zweig, M. H. and Schechter, A. H. : Radioimmunoassay 
of creatine kinase isoenzymes in human serum: Isoenzyme MM. Clin. Chem. 
24: 414-421, 1978. 

Voss, S. R. and MacLowry, J. D.: Antimicrobial levels in various body fluids 
in the normal individual. Handbook Series in Clinical Laboratory Science, 
Clinical Microbiology, Vol. II, Seligson, D. (ed.d.) CRC Press, Cleveland, 
Ohio, pages 293-322, 1977. 

Young, N. A., Kwon-Chung, K. J., Kubota, T. T., Jennings, A. E. and Fisher, 
R. I.: Disseminated infection by Fusarium moniliforme during treatment 
for malignant lymphoma. J. Clin. Microbiol, (in press) . 

Yutaka, H., Homma, J. Y. and Zierdt, C. H. : Serotyping of Pseudomonas 
aeruginosa from patients with cystic fibrosis of the pancreas. Jap. Jr. 
Exper. Med. 47: 249-254, 1977. 

Zierdt, C. H.: Blastocystis hominis, an intenstinal protozoan parasite of 
man. The Pub. Health Lab, (in press) . 

Zierdt, C. H. : Systems for typing Pseudomonas aeruginosa . Chapter 11 in 
Non-fermentative Gram Negative Bacteria in Clinical Microbiology . G. L. 
Gilardi (Ed. ) . CRC Press, Inc. (in press) . 

Zierdt, W. : A simple device for concentration of parasite eggs, larvae, 
and protozoa. Amer. J. Clin. Path. (in press) . 

Zierdt, W. : A stool concentrating device. U. S. Patent Office #726218. 
Granted. Nov., 1977. 

Zweig, M. H. and Van Steirteghem, A. C: Immunochemical determinations of 
enzymes as tissue markers: Specific applications to the isoenzymes of 
creatine kinase in human serum. In Clinical Immunochemistry . Natelson, S. 
(ed.) 1978 (in press) . 

Zweig, M. H., Van Steirteghem, A. C. and Schechter, A. N.: Radioimir.unoassay 
of creatine kinase isoenzymes in human serum: Isoenzyme BB. Clin. Chem. 
24: 422-428, 1978. 



SMITiioOiil a;, OoIl:,GL It.KUHMATlUN EXCHANGE 
PROJECT NUMBER (Do NOT use this apace) 



U.S. DEPARTMENT OF PROJECT NUMBER 

HEALT.I, EDUCATION, AND WELFARE ' 
■'UBLIC liEALTH SERVICE "i 

NOTICE OF zoi CC 10001-04 CP 

INTHAMURAL RESEARCH PROJECT 



PERIOD COVERED 

October 1, 1977 to September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Analytical Methodology: Development and Interpretation Application 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



PI: 



R. J. Elin, Chief, Clinical Chemistry Service 



CP CC 



OTHERS: M. Green, Staff Chemist CP CC 

R. M. Jaffe, Staff Physician CP CC 

E. A. Robertson, Assistant Chief, Laboratory Computer Serv. CP CC 

M. H. Zweig, Asst. Chief, Clinical Chemistry Service CP CC 



COOPERATING UNITS (if any) 



LAB/E 



Clinical Pathology Department 



Clinical Chemistry Service 



NSTITUTE AND LOCATION 

Clinical Center, NIH, Bethesda, Maryland 



TOTAL MANYEARS: 



PROFESSIONAL: 
3 



CHECK APPROPRIATE BOX(ES) 
Q (a) HUMAN SUBJECTS 

D (al) MINORS □ (a2) INTERVIEWS 



D(t 



□ (c) NEITHER 



SUMMARY OF WORK (200 words or le 



keywords ) 



Analytical methods in use in clinical laboratories have been evaluated 
New methods and instrumentation have been studied and effects of drugs on 
test values determined. Continued work with automatic interpretation of 
e ffects of drugs has shown that is possible to assist physicians in 
understanding influence of drug therapy in changing laboratory test values . 



PHS-6040 
(Rev. 10-76) 



Project No. ZOl CC 10001-04 CP 

1. Clinical Pathology Department 

2. Clinical Chemistry Service 

3. Bethesda, Maryland 
PHS-NIH 

Individual Project Report 
October 1, 1977 to September 30, 1978 

Project Title: Analytical Methodology: uevelopment and Interpretative 
Application 

Previous Serial Number: ZOl-CC-OOOOl-03-CP 

Principal Investigator: Ronald J. Elin 



Other Investigators: 


Maurice Green 




Russell M. Jaffa 




E. Arthur Robertson 




Mark H. Zweig 


Man Years : 




Total 8 




Professional 


3 


Other 


5 



Project Description 
Objectives 

1. To upgrade the quality of clinical laboratory data within NIH and 
elsewhere . 

2. To facilitate the correct interpretation of laboratory data. 
Methods employed : 

1. Reference methods have been developed against which other methods can 
be compared. These methods are well characterized with respect to 
accuracy, precision, sensitivity and specificity. 

2. Data bases have been developed in a computer file to list effects of 
drugs on laboratory tests, conversion factors from traditional to 

SI units, and centers where unusual clinical laboratory tests are 
performed throughout the country. 

Major findings : 

Deficiencies in analytical methods have been identified and alternative 
methods studied in depth. By appropriate selection of method it is possible 
to avoid erroneous answers due to nonspecif icity of the procedures. Drugs 
have been added to serum to their therapeutic concentration and effects 
observed on many different procedures on several different analyzers. 

CP-20 



Project No. ZOl CC 10001-04 CP 

Significance : 

This work has upgraded the quality of some tests in this laboratory and 
has the potential for doing the same thing in other laboratories when the 
same methods are used. By alerting physicians to drugs as a possible cause 
of abnormal data it has been possible to explain the cause of the unusual 
values and to prevent extensive and unnecessary workups of patients. 

Proposed course : 

Continued development and evaluation of methods will be undertaken. 

Publications : 

Forman, D.T. and Young, D.3. Drug interference in laboratory testing. 
An. Clin, Lab. Sci. 6, 263-271, 1976. 

Forman, D.T. and Young, D.S. Drug interference in laboratory testing 
in Clinical Chemxstry, Forman, D. R. and Mattoon, R. W. eds. American 
Chemical Society, Washington, D. C. pp 271-284, 1976. 

Jaffe, R. M. A test for occult blood. US patent serial no. 498-109. 

Jaffe, R. , Schmid, A. and MacLowry, J. : Effect of ascorbic acid on 
detection of blood in urine. Am. J. Clin. Path, (in press) . 

McClean, S. W. , Young, D. S. and Yonekawa, W. Anticonvulsants in 
serum, determined with a fully mechanized enzyme analyzer. Clin. Chem. 
23, 116-118, 1977. 

Robertson, E. A., Sliva, C. A. and Young, D. S.: Values for uric acid 
in patients' sera as measured with SMAC (phosphotungstate) and AutoAnalyzer 
(uricase) . Clin. Chem. 24, 173, 1978. 

Robertson, E. A. and Young, D. C: Evaluation of SI^C performance by 
analysis of variance of quality control data. Advances in Automated Analysis 
Vol. 1, Tarrytown, N. Y. : Mediad, Inc., pages 204-210, 1977. 

Rodbard, D. and McClean, S. W. Automated computer analysis for 
enzyme-multiplied immunological techniques. Clin. Chem. 23, 112-115, 1977. 

Young, D.S. and Panek, E. Effects of drugs on the analytical pro- 
cedure of a multitest analyzer in Drug interferences and drug measurement in 
Clinical Chemistry. Siest, G., and Young, D. S. eds. Karger, Basel, 
pp 10-20, 1975. 



'Si'.ilTHSUMAN bCltf.Cu INFORMATION EXCHAfiGE 
PROJECT NUMBER (Oo NOT use this space) 



j.s. oepai.tmlMT of 

HEALIH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

iNl.tAMURAL RESEARCH PROJECT 



PROJECT NUMBER 



Zol-CL-10004-03 



PERIOD COVERE 



October 1, 1977 to September 30, 1978 



ITLE OF PROJECT (80 characters or less) 

Radioimmunoassay of creatine kinase 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Dr. Mark H. Zweig, Staff Physician and Asst. Chief, Clinical Chemistry 
Service, CP, CC 

Dr. Sharon McClean, Chemist, CP, CC 



COOPERATING UNITS (if any)_ ^r. Andre Van Steirteghem, Brussels, 
Feld and David Witte, Univ. of Iov7a; Dr. Bruce Adornato, 
.Silverman, Good Samaritan Hospital, Los Angeles 



Belgium; Drs. Ronald 
NINCDS; Dr. Lawrence 



lab/branch 
Clinical Pathology Department 



SECTION 

Clinical Chemistry 



INSTITUTE AND LOCATION 
CC, NIH, Bethesda 



TOTAL MANYEARS: 
1.5 



PROFESSIONAL: 
0.5 



CHECK APPROPRIATE BOX(ES) 
G (a) HUMAN SUBJECTS 

J (al) MINORS □ (a2) INTERVIEWS 



(b) HUMAN TISSUES 



D (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 
Previously, we developed radioimmunoassays for the MM and M isoenzymes of 
creatine kinase in human serum. Currently we are investigating the clinical 
usefulness of these assays by measuring isoenzyme levels in serum and cerebro- 
spinal fluid from patients with schizophrenia , in the serum of patients with 
neuromuscular diseases , prostatic and other cancers , myocardial injury, and 
in the serum of patients undergoing cardiac surgery. The assay for the BE 
isoenzyme seems particularly useful. Elevations in CK-BB occur in neuro- 
muscular diseases, myocardial infarction , prostatic and several other cancers, 
as well as following cardiac surgery . 



PH S-6040 
(Rev. tO-76) 



_t 



Project NO. ZOl CC-10004-03 CP 

1. Clinical Pathology Department 

2. Clinical Chemistry Service 

3. Bethesda, Maryland 



PHS-NIH 

Individual Project Report 

Octber 1, 1977 to September 30, 1978 

Project Title: Radioimmunoassay of Creatine Kinase 

Previous Serial No.: ZOl-CC-0004-02 

Principal Investigator: Dr. Mark Zweig 

Other Investigator: Dr. Sharon McClean 

Cooperating Units: Dr. Andre Van Steirteghem, Vrije Universiteit , 
Brussels, Belgium; Drs. Ronald Feld and David 
Witte, Dept. of Pathology, University of lowa; 
Dr. Bruce Adornato, NINCDS; Dr. Lawrence 
Silverman, Good Samaritan Hospital, Los Angeles 

Man Years: Total 1.5 

Professional 0.5 
Other 1 . 



Project No. ZOl CL-10004-03 

1. Clinical Pathology Department 

2. Clinical Chemistry Service 

3. Bethesda, Maryland 



PHS-NIH 

Individual Project Report 

October 1, 197? to September 30, 1978 



Project Title: Radioimmunoassay of Creatine Kinase 

Previous Serial No.: ZOl-CC-0004-02 

Principal Investigator: Dr. Mark Zweig 

Other Investigator: Dr. Sharon McClean 

Cooperating Units: Dr. Andre Van Steirteghem, Vrije Universiteit , 
Brussels, Belgium; Drs. Ronald Feld and David 
Witte, Dept. of Pathology, University of Iowa; 
Dr. Bruce Adornato, NINCDS; Dr. Lawrence 
Silverman, Good Samaritan Hospital, Los Angeles 

Man Years: Total 1.5 

Professional 0.5 
Other 1.0 



ZOl CL-10004-03 



Proposed Course 

Studies of CK-BB in serum of patients with myocardial infarction 
and after cardiac surgery will continue, to better define the appli- 
cations of the test in patient management. Examination of patients 
with cancer will continue to determine what role, if any, CK-BB might 
have in the staging of various cancers. 

Publications 



1. Van Steirteghem, A. C, Zweig, M. H., and Schechter, A. N., 
Radioimmunoassay of creatine kinase isoenzymes in human serum: 
Isoenzyme MM. Clm. Chem. 24, 4-4-421 (1978). 

2. Zweig, M. H. , Van Steirteghem, A. C, and Schechter, A. N., 
Radioimmunoassay of creatine kinase isoenzyme in human serum: 
Isoenzyme BR. Clin. Chem. 24, 422-428 (1978) 



CP-25) 



SMITHSONIAN SCIEMCE INFORMATION EXCHANGE 
PROJECT NUMBER (Oo NOT use this space) 



S. DEPARTMENT OF 

HEALTi!, EDUCATION, AND WELFARE 

•UBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEAf.CH PROJECT 



JPROJECT NUMBER 

I ZOl CL-10005-04 



PERIOD COVERED 



July 1, 1977 to September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Development of a Nephelometric Procedure for the Quantitation of Pyrogens 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

H. Harold Nishi, CC, CPD - Research Biochemist, Principal Investigator 



COOPERATING UNITS (if any) 

None 



LAB/BRANCH 

Clinical Pathology Department 



m^ 



Clinical Chemistry Service 



NSTITUTE AND LOCATION 

Clinical Center, NIH, Bethesda, Maryland 20014 



■OTAL MANYEARS: 
1.0 



PROFESSIONAL: 
0.5 



CHECK APPROPRIATE BOx(ES) 
[J (a) HUMAN SUBJECTS 

□ (al) MINORS □ (a2) INTERVIEWS 



D (b) HUMAN TISSUES 



(c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

Limulus lysate, an aqueous extract of the amebocytes obtained from the 
blood of the horseshoe crab, Limulus polyphemus , gels when mixed with endo- 
toxins (pyrogens) of gram-negative bacteria. The Limulus gelation test is 
used as a method for detecting pyrogens in parenteral pharmaceuticals. Al- 
though the test will normally detect low levels of endotoxins, there is a 
border-line region in the gelation process where the analyst must rely 
heavily on visual judgment. 

In this project nephelometry is used to measure the rate of precipitin- 
like formation resulting from the reaction of Limulus lysate with endotoxins 
from gram-negative bacteria. The nephelometric approach indicates the de- 
tection and quantitation of pyrogen from E. coli in the pg/ml level. 

Evaluation of the new procedure indicates the possible use of this method 
for the quantitation of endotoxins for diagnostic care of NIH patients. 



PHS-6040 
(Rev. 10^76) 



., ^- ^ -r ^ . T, u r, .. ZOl CL-10005-04 
Notice of Intramural Research Project 



SUMMARY OF WORK (continued) 



Studies are continuing to finalize the nephelometric procedure 
for endotoxin quantitation and to define the rate of reaction of endo- 
toxin and lysat'^ of Limulus with a mathematical model. 



Serial No. ZOl CL-10005-04 

1. Clinical Center, Clinical Pathology 
Department 

2. Clinical Chemistry Service 

3. Bethesda, Maryland 



PHS-NIH 
Individual Project Report 
July 1, 1977 through September 30, 



Previous Serial Number: Z01-0005-03-CP 

Principal Investigator: H. Harold Nishi 

Other Investigator: None 

Cooperating Units: Inside NIH 

Man Years: 

Total: 1.0 

Professicrial: .5 

Other : . 5 



Project Description 



@ 



Objective 



The object of this research project is to develop a sensitive assay pro- 
cedure for the quantitation of pyrogens (endotoxins of gram-negative bacteria) 
using lysate of amebocytes of Limulus polyphemus . 

Method Employed: 

Nephelometry is used to measure the rate of precipitin-like formation 
resulting from the reaction of specific proteins (s) found in the lysate of 
Limulus polyphemus amebocytes with endotoxins from gram-negative bacteria. 

Major Findings : 

Preliminary studies showed that E. coli. endotoxin reacted with the 
lysate of L. polyphemus amebocytes to form fine precipitin-like particles in 
the presence of large quantities of pyrogen-frce water. Nephelometric 
measurements indicated that the rate of formation of these particles was a 
function of endotoxin concentration. Our present findings indicate that the 
detection and quantitation of pg/ml of endotoxin in fluids are possible by 
nephelometric measurements. 



ZOl CL-10005-04 



Significance : 

Based on the aggregate of our experience and the knowl'sdge gained from 
our studies, we believe that the nephelometric assay of endotoxin using 
lysate of L. polyphemus emebocytes will provide a simple reliable system 
for the quantitation of endotoxin for diagnostic care of NIH patients. 

Proposed Course : 

1. To continue the development and perfection of nephelometric 
procedure for endotoxin quantitation. 

2. To define the rate of reaction of pyrogens and lysate of Limulus 
with a mathematical model. 

3. To install the endotoxin assay procedure in our routine clinical 
chemistry service for use in NIH patient-care work. 

Honors and Awards : 

None 

Publications : 

Nishi, H. H. A flexible Reaction Rate Analytical System for the Rapid 
Determination of IgA, IgG, and IgM Concentrations. In "Automated 
Immunoanalysis, Part 2" (Ritchie, Ed.), Chapter 17. pages 353, Marcel 
Dekker, Inc. New York, N. Y. , 1978. 



SMITHSONIAN SCltWCE KIFORMATION EXCHANGE! M.S. DEPARTMENT OF 

PROJECT NUMBER (Oo NOT use this space) HEALTH, EDUCATION, AND WELFARE 

riJBLIC HLALTH SERVICE 
NOTICE OF 
INTtlAWURAL RESEAr.CH PROJECT 



PROJECT NUMBER 

Zol CL-10006-02 



TITLE OF PROJECT (80 characters or less) 

Use of Laser Light Scattering for Rapid Determination of Potential 
Antibiotic Synergy 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PRUJECT 

Dr. James D. MacLowry , Chief, Microbiology Service 

Dr. E. Arthur Robertson, Asst. Chief, Laboratory Computer Service 



COOPERATING UNITS (if any) 
None 



lab/branch 
Clinical Pathology Department 



SECTION 

Microbiology Service, Laboratory Computer Service 



INSTIIUT.E AND LOCATION 

Clinical Center, National Institutes of 



Health, Bethesda, Maryland 20014 



TOTAL MANYEARS: 

1.5 



PROFESSIONAL: lOTHERi 



CHECK APPROPRIATE 80X(ES) 

n (a) HUMAN SUBJECTS Q (b) HUMAN TISSUES □ (c) NEITHER 

[] (al) MINORS D (a2) INTERVIEWS 



SUMMARY OF WORK (200 words or less - underline keywords) 

The Differential III laser light scattering instrument is being evaluated 
for its potential usefulness for rapidly determining antibiotic synergy . 



PHS-6040 
(Rev. 10r76) 



Project No. ZOl CL-10006-02 

Project Title: Use of Laser Light Scattering for Rapid Determination of 
Potential Antibiotic Synergy 

Previous Serial No.: ZOl CC 0006-01 CP 

Principal Investigator: Dr. James D. MacLowry 

Other Investigator: Dr. E. Arthur Robertson 

Cooperating Units; None 



Man Years: Total 1.5 

Professional .2 
Other 1.3 



Ri 



5) 



Project No. Zol CL-10006-02 
Project Description 

Objectives 

Evaluation of a prototype light scattering instrument, the Differential III 
for its potential use in clinical microbiology. 

Methods Employed : 

Antibiotic combinations are being evaluated with a novel laser light 
scattering instrument to detect changes in bacterial growth. An updated 
more rapid instrument is in the initial phases of evaluation. 

Major Findings : 

The laser light scattering technique is very sensitive to the presence of 
and shape of particles. It has been necessary to capture the output of 
the instrument for computer analysis to detect significant changes. 

Significance to Biomedical Research and the Program of the Institute : 

If this instrument and method can be made to work in a consistent fashion, 
it is possible that there will be a number of applications in clinical 
microbiology which would be useful. Specifically the ability to rapidly 
assay serum bactericidal activity and antibiotic bacteriocidal activity 
would be very useful if they can be done in a reasonable time frame with 
minimal cost. 

Proposed Course : 

Evaluation will continue until instrument has been adequately evaluated. 

Honors and Awards : 

None 

Publications : 

None 



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PROJECT NUMBER (Do NOT use this space) 



li.S. DEPARTMENT OF PROJECT "■: "PER 

HEALTH, EDUCATION, AND WELFARE ' 
PUBLIC HtALTM SERVICE "; 

NOTICE OF Zol Ci.-10008- 

INTRAMURAL REEEATXH PROJECT 



PERIOD COVERED 

October 1, 1977 to September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Evaluation of Some Aspects of Dynatech Mic-200i 
95 Channel Dispenser 



NAMES, LABORATORY Af^O INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAl I 'iVESTIGATOTS AND ALL 0'": rt 
PROfESSIONAL PERSONNEL ENGAGED ON THE PROJEOT 

Dr. Philip R. B. McMaster, Residen" Physician,- Clinical Pa'-i.oloqy Dent. , CC 

Dr. Frank G. Witebsky, Asst. Chipf, ..licrobiol. gy Service, CPD, CC 

Dr. James D. MacLowry, Chief, Microbiology Service, CPD, CC 

Dr. E. Arthur Robertson, Asst. Chief, Laboratory Computer Service, CPD, CC 



COOPERATING UNITS (it any) 

None 



lab/branch 

Clinical Pathology Department 



SECTION "^ 

Microbiology Service and Laboratory Computer Service 



NSTITUTE AND LOCATION 



Clinical Center, National Institutes of Health, Bethesda, Md. 



■OTAL MANYEARS: 

0.1 



PROFESSIONAL: OTHER: 

0.1 0.0 



CHECK APPROPRIATE BOX(ES) " 

n (a) HUMAN SUBJECTS Q (b) HUMAN TISSUES ^ (c) NtlTHER 

□ (al) MINORS n (a2) INTERVIEWS 



SUMMARY OF WORK (200 words or less - underline keywords) '. 

The Dynatech MIC-2000 96 channel dispenser (manufactured by Cooke 
Laboratory Products, 900 Slaters Lane, Alexandria, Va. .^2314), an 
instrument comprising part of the Dynatech MIC-2000 Sysrex, for' 
antimicrobial susceptibility testing of bacteria, was evaluated to deter- 
mine the accuracy and reproducibility of the amount of fluid it dispensed. 
Also, a battery of antimicrobial agents was dispensed and stored at 
-20 C and -70 C; these antimicrobials were subsequently examined at 
intervals to determine their potency. 

A battery of clinically relevant antimicrobic concrntrat ions was 
selected for sensitivity testing, and a new i.terpr^-t 1^..,. code was created 
to facilitate interpretation of susceptibility data. 



Project No. ZOl CL-10008-02 



Project Title: Evaluation of Some Aspects of Dynatech MIC-2000 96 
Channel Dispenser 

Previous Serial No. : ZOl CC 0008-01 CP 

Principal Investigator: Dr. Philip R. B. McMaster 

Other Investigators: Dr. Frank G. Witebsky 
Dr. James D. MacLowry 
Dr. E. Arthur Robertson 

Cooperating Units : None 

Man Years: Total 0.1 

Professional 0.1 
Other . 



ZOl CL-10008-02 
Project Description 

Objectives : 

The DynatGch MIC 2000 96 channel dispenser was evaluaLed to dt termxne 
accuracy and reproducibility of the voliJines it dispensed into each of the 
96 wellr of a microdilution plate. In addition, a battery of antimicrobial 
agents was dispensed, frozen, and stored at -20 C and -70 C; these 
antimicrobials were subsequently examined at intervals to determine their 
pott ncy. 

Methods Employed : 

Disposable capillary pipettes were used to measure the volumes 
dispensed; it was determined that the volumes could be assessed 
accurately by measuring the length of the column of fluid in the pipette. 
Antimicrobial potency was determined by removing a certain amount of 
antimicrobial solution from the wells of the microdilution plates, placing 
the solution on a filter paper disc and measuring the zone of inhibition 
of growth of Staphylococcus aureus . 

Major Findings: 

Accuracy of repetitively dispensed volume was found to be 
satisfactory. The antimicrobiol agents tested were found to retain their 
potency for at least 2 weeks at -20 C and 4 months at -70 C. 

Significance to Biomedical Research and the Program of the Institute : 

The instrument was found to function satisfactorily with respect to the 
parameters evaluated. It has been incorporated for use in routine sensitivity 
testing. Only one array of antimicrobials now needs to be employed, instead 
of several different arrays previously required. The incorporation of our 
interpretive code has facilitated the use of sensitivity data by patient care 
physicians. 

Proposed Course : 

The project has been completed. A manuscript reporting the results of 
the instrument evaluation has been published, and another manuscript discussing 
the rationale of our use of the instrument, together with the interpretive code 
currently employed, is in preparation . 

Publications : 



McMaster, P. R, B., Robertson, E. A., Witebsky, F. G., and MacLowry, J. D. 
Evaluation of a Dispensing Instrument (Dynatech MIC 2000) for Preparing 
Microtiter Antibiotic Plates and Testing Their Potency During Storage. 
Antimicrob Aq. Chemother. 13: 842-844, 1978. 



iOI use this space) 



''■ "-"rlfs. DEPARTMENT OF 
HEALTfl, EDUCATION, AND WELFARE 
lilBLlC HlALTH SERVICE 
NOTICE OF 
INTRAMURAL RESEAHCH PROJECT 



PROJECT NUMBER 
ZZol CL-10009-03 



PERIOD COVERED 



October 1977 to September 30, 1978 



TITLE OF PROoEoT (80 characters or less) 

Blastocystis hominis. Structure, and Physiology 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCipAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Dr. Charles H. Zierdt, Microbiologist, Microbiology Service, CPD, CC 



COOPERATj^^(j^^NITS (if any) 



LAB/BRANCH 

Clinical Pathology Department 



SECTION 

Microbiology Service 



NSTITUTE AND LOCATION 
Clinical Center, 



National Institutes of Health, Bethesda, Maryland 20014 



OTAL MANYEARS: 
0.1 



PROFESSIONAL: 
0.05 



CHECK APPROPRIATE BOx(ES) 
D (a) HUMAN SUBJECTS 

g (al) MINORS n (a2) INTERVIEWS 



n (b) HUMAN TISSUES 



(c) NEITHER 



SUMMARY OF WORK (200 words or less - ynderline keywords) 

Blastocystis hominis , A protozoan parasite of the human gastrointestinal 
tract and an organism implicated in the causation of human diarrhea , is 
being studied in terms of its morphology, physiology, and sensitivity to 
metronidazole, enteroviof orm and similar drugs. This sporozoan may contain 
hundreds of mitochondria, although it is a strict anaerobe. Whether these 
are anaerobic mitochondria, and their enzyme activity are subjects of the 
study. 



Project No. ZOl CL-10009-04 

1. Clinical Pathology 1 lei^artnief 

2. Microbiologi" Service 

3. Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1977 to September 30, 1978 

Project Title: BlastocvFtis hommis, Structure, and Physiology 

Previous Serial No.: ZOl CC 0009-03 CP 

Principal Investigator: Dr. Charles H. Zierdt 

Other Investigator: None 

Cooperating Units: None 

Man Years: Total 0.1 

Professional 0.05 
Othei 0.05 

Project Description 

Objectives : 

Continuing study of Blastocystis hominis , newly designed protozoan 
parasite of man. 

Methods Employed : 

Study of diarrhea caused by B. hominis , and the ultrastructure , physiology 
and life cycle of this organism. 

Honors and Awards : None 

Publications : 

Phillips, B. P. and Zierdt, C. H.: Bias ;_ jcysti s hominis : Pathogen --C 
Potential in Human Patients and in Cotcbiotes . Lx i ^erimental 
Parasitology . 39^: 358-364, 1976. 

Zierdt, C. H. and Tan, H. K. : Ultrastructure and Light Microscope 
/Appearance of Blastocystis hominis in a Patient with Enteric Disease. 
Z. Parasitenk. 5^: 277-283, 1976. 

Zierdt, C. H.: Blastocystis hominis , an intestinal protozoan parasite 
of man. The Public Health Lab. (in print) 1978. 



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PROJECT NUMBER (Do NOT 



this space) 



U.S.- DEPARTMENT OF PROJECT NUMBER 

HEALTH, EDUCATION, AND WELFARE ' i nm n m rP 

PUBLIC HEALTH SERVICE "i ZOl CL 10010-OJ CP 

NOTICE OF 
INTRAMURAL RESEARCH PROJECT 



<&>' 



PERIOD COVERED 

October 1, 1977 through September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Effect of Magnesium Deficiency on Erythrocyte Structure and Function 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



PI: Dr. Ronald J. Elin, Chief, Clin. Path. Dept. CP CC 

OTHER: Dr. Laurence Corash, Asst. Chief, Hematology Serv. CP CC 



COOPERATING UNITS (if any) 

None 



lab/branch 

Clinical Pathology Department 



# 



SECTION 

Hematology Service 



NSTITUTE AND LOCATION 

CC, NIH, Bethesda, Maryland 20014 



TOTAL MANYEARS: 
1.5 



CHECK APPROPRIATE BOX(ES) 
D (a) HUMAN SUBJECTS 

D (al) MINORS D (a2) INTERVIEWS 



D (b) HUMAN TISSUES 



B (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

Magnesiijm deficiency in experimental animals produces an anemia and a 
shortened erythrocyte survival . Experimental animals with severe mag- 
nesium deficiency produce erythrocytes with normal magnesium content, 
enzyme concentrations and structure. However, once this erythrocyte i£ 
subjected to an environment deficient in magnesium (plasma) structural 
and biochemical abnormalities occur which lead to the shortened 
erythrocyte survival . 



PHS-6040 
(Rev. 10-76) 



mmm 



Project No. ZOl CC 10010-03 CP 

1. Clinical Pathology Dept. 

2. Hematology Service 

3. Bethesda, Maryland 
PHS-NIH 

Individual Project Report 
October 1, 1977 through September 30, 1978 

Project Title: Effect of Magnesium Deficiency on Erythrocyte Structure 
and Function 

Previous Serial Number: ZOl CC 10010-02 CP 

Principal Investigator: Dr. Ronald J. Elin 
Other Investigator: Dr. Laurence Corash 

Man Years: 

Total: 1.5 
Professional: 0.5 
Other: 1.0 

Project Description 



Objectives : 

Define and characterize membrane abnormalities associated with deficiency of 
magensium. Determine the effect of magnesium deficiency on erythro- 
poiesis. 

Methods Employed : 

The erythrocyte specimen was prepared by freeze-fracture and etching. The 
etched surface was coated with carbon and platinum. The specimen was then 
studied using an electron microscope. Erythrocytes from magnesium-deficient 
rats were separated on the basis of age using a stractan gradient. The 
magnesium concentration ana pyrophosphata;'e activity were determined for 
each population of erythrocytes using standard techniques. 

Major Findings : 

The erythrocytes from magnesium-deficient rats develop membrane altera- 
tions in the form of a plaque. These plaques were present on erythro= 
cyte ghosts prepared by osmotic lysis. The membrane piques were un- 
altered by incubating the cells in normal concentrations of magnesium. 
Erythropoiesis in magnesium-deficient rats is normal since reticulocytes 
and very young erythrocytes have a normal magnesium content, and normal 
concentration of erythrocyte pyrophosphatase and have a normal membrane 
surface. More mature erythrocytes show a decreased magnesium content, de- 
creased erythrocyte pyrophosphatase activity and the development of mem- 
brane abnormalities in the form of plaques. In addition, the examination 
of the bone marrow of these animals shows normal erythroid precursors and 
an increase! myeloid component. 

CP-39 



ZOl CC 10010-03-CP 



Significance to Biomedical Research and the Program of the Department : 

This is the first membrane abnormality of erythrocytes in experimental 
animals that is related to an abnormality in mineral metabolism. Magnesium 
has been clearly established as an essential element for biochemical 
processes involving energy production. In this study, magnesium has 
been shown to be important for normal membrane structures. This is part 
of a series of studies by the Department to define factors which influence 
erythrocyte survival and function. The structural and biochemical 
abnormalities of erythrocytes in magnesium deficiency occur after the 
cell has entered the vascular space. Thus, the bone marrow is able to 
produce a normal cell but an environment deficient in magnesium produces 
erythrocyte abnormalities. 



Proposed Course : 

This project will now be extended to study factor of erythropoiesis that 
enable the synthesis of a relatively normal cell in magnesium deficiency. 

Honors and Awards : 

None 

Publications : 

Elin, R. J. and Tan, H. K. : Formation of plaques on erythrocyte membranes 
from rats with magnesium deficiency. Blood. 49: 657, 1977. 



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IpROJECT NUWGtR (Oo NOT use this space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJiCT NUMBER 



ZOl CL 10012-10 



PERIOD COVERED 



October 1, 1977 through September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Investigation of Hemorrhagic and Thrombic Disorders in Man 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



PI: Dr. Harvey R. Gralnick 



Chief, Hematologv Service 



COOPERATING UNITS (if a-.y) 



lab/branch 

Clinical Pathology Dept., Clinical Center 


SECTION 

Hematology Service 


INSTITUTE AND LOCATION 

CP, CC, NIH, Bethesda, Maryland 20014 


TOTAL MANYEARS: 

10.0 


PROFESSIONAL: 
5.0 


OTHER: 

5.0 . 



|CHECK APPROPRIATE BOX(ES) 
S (a) HUMAN SUBJECTS 

B (al) MINORS n (a2) INTERVIEWS 



(b) HUMAN 



□ (c) NEITHER 



SUMMARY OF WORK (200 words or less - underli 



keywords) 



Investigation of congenital and acquired hemorrhagic and thrombotic 
disorders in man to elucidate the clinical entities and to investigate the 
molecular basis for the defects. This has involved purification of coagu - 
lation proteins , immunologic investigation of coagulation protoins and 
inhibitors, and defining the role of these proteins in normal hemostasis 
and abnormal hemostasis. 



PhS-6040 
(Rev. 10-76) 



Project No. Zol CL-10012-10 

PHS-NIH 

Individual Project REport 

October 1, 177 through September 30, 1978 

Project Title: Investigation of Hemorrhagic and Thrombic Disorders in Man 

Previous Serial Number: Zol CC 00012-09 CP 

Principal Investigator: Dr. Harvey R. Gralnick 

Man Years: 

Total 10 . 

Professional: 5.0 
Other : 5.0 

Project Description 

Objectives : 

Define and characterize normal and abnormal coagulation proteins, inhibitors, 
and cof actors associated with clinical disorders of hemostasis. 

Methods Employed : 

Purification and isolation of various coagulation proteins, determination of 
functional defects, and molecular characterization of the defect. In addition 
multiple immunologic techniques are utilized for elucidation of abnormal 
proteins. 

Major Findings : 

Three families with congenital dysf ibrinogenemia have been fully described 
and elucidated. These families have defects in the conversion of fibrinogen 
to fibrin which interferes with normal hemostasis in two of the three 
families. The abnormalities vary in each family and in some families have 
been related to the release of f ibrinopeptides and in others to polymerization 
of fibrin monomers. Studies of the pathological aspects of fibrinogen have 
indicated the importance of fibrinogen in maintenance of normal hemostasis. 
In particular, defects were observed in immunologic techniques, clotting 
techniques, and in the ability of fibrinogen to cross-link. In one family, 
the abnormal fibrinogen also had a markedly shortened intravascular survival. 

Significance to Biomedical Research and the Program of the Department : 

These studies elucidate some of the molecular defects associated with obnor- 
mal hemostasis and thrombosis and have allowed a greater understanding of the 
pathophysiology of blood coagulation. Not only have individual patients 
benefited from the elucidation of these defects in proper therapy but our 
greater understanding of blood coagulation in general has developed. This is 
part of a series of studies by this service to define the factors associated 
with hemorrhage and thrombosis in man. 



Project No. ZOl CL-10012-10 



Proposed Course : 

This project will be extended to study other coagulation states and thrombotic 
states. 

Honors and Awards : 

None 

Publications : 

1. Gralnick, H. , Abrell, E., and Bagley, J.: Heparin Treatment for 
Hemorrhagic Diathesis of Acute Promyelocytic Leukemia. Am. J. Med. 52_: 
167, 1972. 

2. Gralnick, H., Gxvelber, H., Shainoff, J., and Finlayson, J.: Fibrinogen 
Bethesda:. A congenital Dysf ibrinogenemia with Impaired Fibrinopeptide 
Release. J. Clxn. Invest. 5£: 1819, 1971. 

3. Gralnick, H. and Abrell, E.: Studies of the Procoagulant and Fibrinolytic 
Activity of PromyeJ ocytes in Acute Promyelocytic Leukemia. Brit. J. 
Haematol. Z4: 89, 1973. 

4. Gralnick, H. and Finlayson, J.: Congenital Dysf ibrinogenemias . Ann. Int. 
Med. 77_: 471, 1972. 

5. Gralnick, H., Marchesi, S. and Givelber, V . : Intravascular Coagulation in 
Acute Leukemia. Blood 40: 709, 1972. 

6. Gralnick, H., Givelber, H., and Finlayson, J.: A New Congenital Abnormal- 
ity of Fibrinogen: Fibrinogen Bethesda II. Thromb. Diath. Haemorrh. 29^: 
562, 1973. 

7. Gralnick, H. and Tan, H.: Acute Promyelocytic Leukemia: A Model for 
Understanding the Role of the Malignant Cell in Hemostasis. Hum. Pathol. 
5_: 661, 1974. 

8. Fratantoni, J., lollet, R., and Gralnick, li . : Hepar in-induced Thrombo- 
cytopenia: Confirmation of Diagnosis with In Vitro Methods. Blood 45: 
395, 1975. 

9. Gralnick, H. and Saltan, C: Acute Promyelocytic Leukemia: Haemorrhagic 
Manifestation and Morijho]oaic Criteria. Brit. J. Haematol. 2_9: 273, 1975. 

10. Grcipp, P. and Gralnick, H.: Platelet to Leukocyte Adherence Phenomena 
Associated with Thrombocytopenj a . Blood 47: 513, 1976. 



Project No. ZOl CL-10012-10 



Hoover, Jr., H. C. , Ketcham, A. S., Millar, R. C, and Gralnick, H. R. : 
Osteosarcoma: Improved Survival with Anticoagulation and Ttoiputation. 
Cancer. In press. 

Horvath, A. and Gralnick, H. R. : The I Fibrinogen Euglobulin Lysis 
Test. Am. J. Clin. Path. In press. 

Spellman, Jr., G. G. , Macoviak, J. A., and Gralnick, H. R. : Comparison 
of Polymerization of Ancrod and Thrombin Mono'-.iers. Blood 50^: 619, 1977. 

Gralnick, H. R. : Intravascular Coagulation. 1. Differential Diagnosis 
and Conditioning Mechanisms, and 2. Underlying Conditions and Therapy. 
Postgraduate Medicine 62_: 69, 1977. 

Gralnick, H. R. , Givelber, H., and Abrmas, E.: Dysf ibrinogenemia 
Associated with Hepatoma: A Carbohydrate Abnormality. N. Engl. J. Med. 
In press. 



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PROJECT NUMBER (Oo NOT use this space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT MUMBER 
ZOl CL-10013- 



PERIOD COVERED 



October 1, 1977 through September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Chemical and Structural Studies on the Human Factor Vlll/vcn Willebrand 
Factor Protein 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



PI: Harvev R- Gralnick, M.D. 



Chief, Hematology Service CP CC 



COOPERATING UNITS (if any) ' 
Barry S. Coller, M.D., Div. of Hematology, School of Medicine, State Univ. of NY 
at Stony Brook, Stony Brook, N.Y. 
Yvette Sultan, M.D., Dept. of Hematology, Hopital Saint-Louis, Paris, France 



LAB/BRANCH 

Clinical Pathology Dept. 



Clinical Center 



SECTION 
Hematology Service 



NSTlTUTE AND LOCATION 

CP, CC, NIH, Bethesda, Maryland 20014 



TOTAL MANYEARS: 



CHECK APPROPRIATE BOX(ES) 
B (a) HUMAN SUBJECTS 

a (al) MINORS 3 (a2) INTERVIEWS 



S (b) HUMAN TISSUES 



n (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

The long-range purpose of this project is to initially s^-udy the immunologic 
aspects of the factor Vlll/von Willebrand factor protein and then to study 
the biochemistry and structure of this protein in man. The topics of present 
interest are: (1) the defect of the factor Vlll/von Willebrand factor protein 
in hemophilia A , (2) the defect of the factor Vlll/von willebrand factor 
protein in von Willebrand's disease , {^) the importance of carbohydrate con- 
tent in biological functions , (4) the lelationship of carbohydrate content 
to atherosclerosis, (5) the mechanism, of thrombin activation , and (6) biochem- 
ical characterization of the biologically active sites of the factor Vlll/von 
Willebrand factor protein. 



Project No. ZOl CL-10013-10 

PHS-NIH 

Individual Project Report 

October 1, 1977 through September 30, 1978 

Project Title: Chemical and Structural Studies on the Human Factor Vlll/von 
Willebrand Factor Protein 

Previous Serial Number: Zol CC 00013-10 

Principal Investigator: Dr. Harvey R. Gralnick 

Other Investigators: Dr. Barry S. Coller 
Dr. Yvette Sultan 



Years: 


Total 11.0 




Professional: 5.5 




Other: 5.5 




Project Description 



Objectives : 

Define and characterize the normal factor Vlll/von Willebrand factor protein, 
to elucidate the defects of the protein in hemophilia and von Willebrand' s 
disease and then to ascertain its role in atherosclerosis. 

Methods Employed : 

This has been accomplished by limited alpha chymotrypsin of cryo- 
precipitate or other concentrates of factor VIII followed by gel chromato- 
graphy on Sepharose 4B. 

Major Finding s: 

Individuals with hemophilia A have a protein identical to normal in all 
respects except that it lacks clot-promoting activity while in von 
Willebrand 's disease it has been found that the protein is quite hetero- 
geneous. In some patients there is a complete absence of the protein with 
all its associated biological functions (quantitative defect) while in other 
patients there is a qualitative defect where the protein is present in normal 
amounts; however, it is deficient in biological activity. A major finding 
has been that the carbohydrate moiety of the factor Vlll/von Willebrand 
factor protein is most important in its interaction with the platelets and 
vessel wall and may play an important role in the maintenance of normal 
hemostasis and propagation of atherosclerosis. 



Project No. ZOl CL-10013-10 

Significance to BiomeJicai Research and the Program of the Department : 

These studies further our long-term project of investigating hemorrhagic and 
thrombotic clinical disorders. The finding of the importance of carbohydrate 
in the interaction of platelets with vessel wall or with each other may not 
only be of major significance in the understanding of von Willebrard's 
disease but may be equally important in understanding the propagation of 
atherosclerosis . 

Proposed Course : 

This project will be continued in its present phase with greater emphasis 
placed on the contribution of carbohydrates to platelet/platelet and 
platelet/vessel wall interaction. In addition, studies are underway to 
localize the sites on the factor Vlll/von Willebrand factor protein which are 
involved in these interactions. Modification of these sites will be attempted 
in an effort to reproduce in vitro a von Willebrand 's disease-like state. 

Honors and Awards : 



1976 Fight for Sight Award for "von Willebrand Factor and Effect on 

Platelet Aggregation of Plasma from Diabetics with REtinopathy . " Association 

for Research in Vision and Ophthalmology, Inc. 

Fublications : 

1. Gralnick, H., Abrell, E., and Bagley, J.: Immunologic Studies of Factor 
VIII (Antihemophiliac Globulin) in Hemophilia A. Nature 230 : 9, 1971. 

2. Marches!, S., Shulman, N., and Gralnick, H.: Studies on the Purification 
and Characterization of Human Factor VIII. J. Clin. Invest. 5_1: 2151, 1972. 

3. Gralnick, H. , Coller, B., and Marchesi, S.: Immunological Studies of 
Factor VIII in Haemophilia and von Willebrand 's Disease. Nature New 
Eiology 244: 281, 1973. 

4. Gralnick, H., Coller, B., and Marchesi, S.: Studies of the Human Factor 
Vlll/von Willebrand Factor Protein. I. Comparison of the Protein I'ound 
in Normal, von Willebrand 's Disease and Hemophilia A. Thromb. Res. 6: 
93, 1975. 

5. Gralnick H. , Marchesi, S., and Coller, B.: Theoretical Approach to 
Molecular Biology of Factor VIII; Heterogeneity of the Molecule. Ann. 
NY Acad. Sci. 24o : 373, 1975. 

6. Coller, B., Hirschman, R. , and Gralnick, H.: Studies cf the Factor VIII/ 
von Willebrand '^actor Antigen or; the Platelet Surface. Thromb. REs. 6: 
469, 1975. 



Project No. ZOl CL-10013-10 

7. Gralnick, H. and Coller, B.: Studies on the Factor Vlll/von Willebrand 
Factor Protein. II. Identification and Characterization of the von 
Willebrand Protein. Blood 4£: 417, 1975. 

8. Gralnick, H., Coller, B., and Sultan, Y.: Studies of the Human Factor 
Vlll/von Willebrand Factor Protein. III. Qualitative Defect in von 
Willebrand' s Disease. J. Clin. Invest. 56^: 814, 1975. 

9. Gralnick, H., Coller, B., and Sultan, Y.: Carbohydrate Deficiency of 
the Factor Viii/von Willebrand Factor Protein in von Willebrand 's 
Disease Variants. Science 192 : 56, 1976. 

10. Gralnick, H. and Coller, B. : Molecular Defects in Hemophilia A and 
von Willebrand' s Disease. Lancet, April 17, 1976. 

11. Coller, B., Franza, Jr., B., and Gralnick, H.: The pH Dependence of 
Quantitative Ristocetin Aggregation: Theoretical and Practical 
Implications. A New Device for Maintenance of Platelet-Rich Plasma pH. 
Blood 47^: 841, 1976. 

12. Gralnick, H. R. , Sultan, Y. , and Coller, B. S.: von Willebrand's 
Disease Combined Qualitative and Quantitative Abnormalities. N. Engl. 
J. Med. 296: 1024, 1977. 

13. Gralnick, H. R. , Coller, B. S., Shulamn, N. R. , Andersen, J. C, and 
Hilgartner, M. : Factor VIII. Ann. Int. Med. 86: 598, 1977. 

14. Coller, B. S. and Gralnick, H. R. : Studies on the Mechanism of 
Ristocetin-Induced Platelet Agglutination: Effects of Structureal 
Modification of Ristocetin and Vancomycin. J. Clin. Invest. 60: 302, 
1977. 

15. Gralnick, H. R. : Factor Vlll/von Willebrand Factor Protein: Galactose- 
A cryptic Determinant of von Willebrand Factor Activity. J. Clin. 
Invest. In press. 



ISMlTHSONIAtl SGlttMUt I .1 'n:. . , i oN tXGHAijGE 
PROJECT NUMBER (Do NOT use this space) 



U.S. DEPARTMENT OF PROJECT NUMBER 

HEALTH, EDUCATION, AND WELFARE ' ZOl CL-10016-02 

PUBLIC HEALTH SERVICE "] 

NOTICE OF 
INTRAMURAL RESEARCH PROJECT 



PERIOD COVERED 

October 1, 1977 through September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Qualitative Improvement of Blood Transfusion Using Young Cell Cohorts 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

PI: Laurence Corayh, H.D. Assistant Chief Hematology Service 

CP CC 



COOPERATING UNI'lS (i^ ^'^■y) 

S. Piomelli, Dept. of Pediatrics, New York University £^chooi of Medicine 
New York, New York 10016 



lab/branch 

Clinical Pathology Department 



SECTION 

Hematology Service 



INSTITUTE A.\D LOCATION 

CP, CC, NTH, Bethesda, Maryland 2001 



TOTAL MANYEARS: | PROFESSI ONAL: iGTh 
0.8 ! 0.^ i 



CHECK APPROPRIATE BOx(ES) 

3 (a) HUMAN SUBJECTS S (b) HUMAN TISSUES □ (c) NEITHER 

D (al) MINORS □ (a2) INTERVIEWS 



SUMMARY OF WORK (200 words or less - underline keywords) 

The purpose of this study is to demonstrate that S tractan separated young red 



blood cells can be transfused into autologous non-human pr±mate donors and 
that these cells have an improved survival compared to whole blood. Prelimin-j 
ary studies have shown that young red cells ■ rom rabbits can be isolated and | 
transfused by this method. These cells demonstrate a markedly improved survi-j 
val compared to unf ractionated whole blood. The rhesus moji'-'ey model has been '■ 
developed and demonstrates that young r^d cells can be isolated by this method 
and have improved post transfusion survival. P solid phase radioimmunoassay , 
was developed to look for antigalactan antibodies in treated animals and in | 
untreated normal human subje^-ts of all ages. The eventual goal of this pro- 
ject will be to explore the use of this system for human transfusion, thus 
reducing the transfused iron load in patients with chronic anemias . : 



Project No. ZOl CL-10016-02 



PHS-NIH 

Individual Project Report 

October 1, 1977 through September 30, 1978 



Project Title: Qualitative Improvement of Blood Transfusion Using Young 
Cell Cohorts 

Previous Serial Number: ZOl CC 00016-01 CP 

Principal Investigator: Dr. Laurence Corash 

Other Investigators: None 

Man Years : „ , ^ ^ „ 

Total: 0.8 

Professional: 0.5 

Other : . 3 

Project Description 

Objectives : 

1. Development of a rhesus monkey model to examine the survival of Stractan 
separated age dependent red cell cohorts. 

2. To determine if naturally occurring arabino-galactan antibodies exist 

in humans and rhesus monkeys and to determine if they develop in animals 
after exposure to arabino-galactan treated cells. 

Methods : 

Age dependent red cell cohorts were obtained with arabino-galactan density 
gradients. REd cell life span is measured with radiochromium or radioactive 
cyanate . Radioimmunoassay using an iodinated myeloma protein with anti- 
arabino-galactan specificity. 

Major Findings : 

Young red cells from rabbits have an improved survival compared to old red 
cells when transfused in autologous donors. Experiments in the rhesus model 
were similar. 

Significance : 

This technology may provide a means for qualitatively improved red cell 
transfusion, thus limiting iron overload in patients with chronic transfusion 
requirements. 



Project No. ZOl CL-10016-02 



Awards and Honors : 

NIH Grant HL 19946-1. "Reducticn of Iron Overload in Thalassemia" 

Publications : 

1. Corash, L. , Piomelli, S., Seaman, C, Comisa, C: High RE^^lutirn 
Separation of Blood Cell Types by Density Gradient Centrif ugatic . . 
Blood 42_: 1006, 1973. 

2. Corash, L., Piomelli, S., Chen, H., Seaman, C, Gross, E.: Separation 
of ERythrocytes According to Age on a Simplified Density Gradient. J. 
Lab. Clin. Med. 84: 147-151, 1974. 

3. Corash, L., Seaman, C, Comisa, C, Reibman, J. R. , Piomelli, S.: 
Separation of RBC ' s with Improved Survival from Normal Flood. Ped. Res. 



Corash, L., Seaman, C, Reibman, J., Tytun-, A., Piomelli, S.: 
Qualitatively Improved Blood Cell Transfusion: A New Approach to 
Therapy of Chronic Anemias. 16th Meeting, Int. Soc. Hem., Kyoto, Japan, 
1976. 

Piomelli, S., Seaman, C, REibman, J., Tytun, A., Graziano, J., 
Tabachnik, N., Corash, L. : Separation of Younger Red Cells with 
Improved "In Vivo" Survival: A New Approach to Chronic Transfusion 
Therapy. Proc. Natl. Acad. Sci., 1978, in press. 



■3CMA:. oCit',G£ !;,FCnMATIG\ cXCh^NGc U.:.. GLPARTi'.Lfv , Cr ! PROJECT ^;UWB£S 
-:G1 .NjMBER (Oo not use this soace; mcALTH, EUJCATIOtJ, ;;.D UtLFARE - 
PUBLIC i-.tALTH oERVlCE I 
• NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



ZOl CL 



=ERICD COVERED 

. ctcber 1)77 - roj- teni:.,er :_, 1978 
"tTtIe of PROTeTt (bo characters oTlTI^ ) ^. ~ 

.'-:esista:'!t Ccrynebacr:t-r lum - Further Characterization and Identification 
of Normal Habitat. 



I.H.'tS, LASORATCRY AND KiSTIfUTE AFF IL i ATiON5, AND TiTLEB OF PRINCIPAL INVESTIGATORS At.G All i 
PRCFlSSICNAL personnel engaged on THE PROJECT 

.\?r. Voe J. Gill, Su :ervi~or'.' ■licroLiologist , Microbiology Servir^, C 

:.r. Frank Witebskv, Ass't c;-.-.ef, Microbioloay Service, CPD, CC 

Dr. Philip A. Pizzo, Senicr Investigator, Feaiatric Oncology Branch, 
Division of Cancer Treatment. 



.PEriATF'.G J.',iT3 (if ar.y; 

, cdiatric vDncology Branch, \"CI 



lical i-atholocv DecartiTn.-nT 



r'lcrobioicgy Service 

■rTTTuTi~ANirro'c~AY"i'oy, 



'linical Center, National Institutes of Health, Bethe^da, Md . 



KR0FESSI3NAL: 
0.5 



C-.CK APrROPP.iTE SOX(ES) 

1 ;a) i^LMArj Subjects z. (o< ^'mau tissues j^ (c) neither 

. .. i .i; ;,li:.CRS -: (a2, .■,T£RVIE..S 

.^VMAR" OF WORK (200 .eras or less - 'jraerline keywords) 



An a ntibiotic-resist ar.t Corynebacterium sp. has tjen isolsred -.vith I 

increasing freruencv frcm -4p--erely iTPmuncsurpressed pa tieiits at the Clinical ! 

Center and now also at other Cancer hospitals. Isolates c^f thi.= cr-anism | 
continue to be ::ollected and further characterized since this C-rynebacterium 

seems to be an un-narr.ed ;;pe;;3es with little infcrmation currentl" available ' 

^.s to It;- free-uency and distribution. Use cf a seli.H-tivs mcdiu- nas helped j 

us to gather more information about the organism. < 



Project No. ZOl CL-10019-02 



Project Title: Resistant Corynebacterium - Further Characterization and 
Identification of Normal Habitat 

Previous Serial No.: ZOl CC 00019-01 CP 

Principal Investiqator : Dr. Vee J. Gill 

Other Investigators: Dr. Frank Witebsky 
Dr. Philip A. Pizzo 

Cooperating Units: Pediatric Oncology Branch, NCI 

Man Years : Total 1 . 

Professional 0.5 
Other 0.5 



Project No. ZOl CL-10019-02 



Project Description 



Objectives : 

Further characterize with respect to biochemical characteristics and 
antibiotic sensitivity patterns, a resistant corynebacterium species. 

Determine the normal habitat of this organism. 

Determine the types of patients and predisposing characteristics to 
colonization and infection with this organism. 

Methods Employed : 

Organisms isolated from a variety of clinical specimens and found to 
be this antibiotic-resistant Corynebacterium species are evaluated for 
their biochemical characteristics and specific antimicrobial sensitivity 
pattern by in vitro testing procedures. A Culture medium selective for 
this organism has been devised to aid in isolation, thus allowing us to 
screen numerous specimens as well as do survey cultures on normal volun- 
teers and patients to define the organism's normal habitat. 

Major Findings : 

These antibiotic-resistant Corynebacteria are biochemically homogeneous 
in their reactions, indicating that they probably represent a single species. 

There is some variability in their antibiotic resistance patterns 
mainly with tetracycline, erythromycin and gentamicin. They are con- 
sistently sensitive to vancomycin which is used for treatment when necessary. 

The organism probably resides as part of the skin flora of hospital 
patients particularly in the axilla and groin. It was difficult to find 
in non-hospitalized individuals. 

Significance to Biomedical Research and the Program of the Institute : 

This organism can be a significant pathogen, particularly in compromised 
hosts. Further characterization of the species and its ecology is important 
for understanding the pathogenesis of and selecting appropriate treat- 
ment for, disease caused by this organism. 

The project will be continued to further define the characteristics of 
the organism and its normal habitat. 

Publications : 



CP-54) 



ISMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Oo NOT use this space) 



,S, DEPARTMENT OF | PROJECT NUMBER 

, EDUCATION, AND WELFARE 
JBLIC HEALTH SERVICE 
NOTICE OF 
INTRAMURAL RESEARCH PROJECT 



HEALTH, EDUCATION AND WELFARE ' n nmi o-> I 

pflBLIC HEALTH SERVICE 1 ZOl CL-10021-C2 ' 

NOTICE OF 



PERIOD COVERED 

October 1, 1977 - September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Mycologic Sensitivity Testing 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 

PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Ms. Anne E. Jennings, Medical Technologist, Microbiology Service, CFD, CC 
Dr. John E. Bennett, Head Clinical Mycology Section, Laboratory of Clinical 
Investigation, NIAID 



COOPERATING UNITS (if any) ' 

Clinical Mycology Section, LCI, NIAID 



lab/branch 

Clinical Pathology Department 



SECTION 

Microbiology Service 



NSTITUTE AND LOCATION 

Clinical Center, National Institutes of Health, Bethesda, Md. 20014 



TOTAL MANYEARS: 



PROFESSIONAL: 



|CHECK APPROPRIATE BOX(ES) 

h (a) HUMAN SUBJECTS □ (b) HUMAN TISSUES (c) NEITHER 

[] (al) MINORS [] (a2) INTERVI EWS 

SUMMARY OF WORK (200 words or less - underline keywords) 

Antimicrobiolsensitivity testing of yeasts is being done with 5- 
f luorocytosLne ant imicrobiol sensitivity testing of molds is being done 
with Miconazole, 5-f luorocytosine , and amphotericin B; antimicrobiol 
sensitivity testing of Nccardia is being done- with Sulfadiazine, Tri- 
methoprim, Minocydine, Ampicillin, Rifampin, Erythromycin. 



PhS-6040 
(Rev. 10-76) 



Project No. ZOl Cl-10021-02 

1. Clinical Pathology Department 

2. Microbiology Service 

3. Bethesda, Maryland 
PHS-NIH 

Individual Project Report 

October 1, 1977 to September 30, 1978 

Project Title: Mycologic Sensitivity Testing 

Previous Serial No.: ZOl CC 00021-01 CP 

Principal Investigator: Ms. Anne E. Jennings 

Other Investigator: Dr. John Bennett 

Cooperating Unit: Clinical Mycology Section, LCI, NIAID 

Man Years: Total 0.1 

Professional 0.1 
Other 0.0 

Project Description 

Obj ectives : 

Determination of antimicrobial sensitivity of species of pathogenic 
yeasts to 5-f luorocytosine and species of molds to Miconazole, 5- 
fluorocytosine, and amphotericin B. 

Methods Employed : 

In vitro determination of antimicrobial sensitivity testing was performed 
using test tube serial dilution technique involving use of roller drum 
for yeasts and molds. The susceptibility of the various Nocardin sp. was 
determined by the use of the agar dilution technique. 

Major Findings : 

Most of the molds and yeasts examined proved to be susceptible to the 
antimicrobials tested. The sensitivity of the Nocardin isolates varies 
significantly among the different antimicrobials tested. 

Honors and Awards : 

None . 

Publications : 

Bennett, John E., and Jennings, Anne E.: "Factors Influencing Susceptibility 
of Nocardin species to Trimethoprim-Sulfamethoxazole Antimicrobials 
agents and Chemotherapy." 13: 624-627. 

Young, N. A., Kwon-Chung, Kubota, Jennings, A. E., and Fisher, R. I. 
"Disseminated Infection by Fusarium Moniliform During Treatment for 
Malignant Lymphoma." Journal of Clinical Microbiology. In Press. 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Do NOT use this space) 



•KS. DEPARTMENT CF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 



ZOl CL-n022-03 



PERIOD COVERED 



October 1, 1977 - September 30, 1978 



TLE OF PROJECT (80 characters or less) 

Detection of Bacteremia using an electrical impedance detec-^ion system 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL 
PROFESSIONAL PERSONNEL ENGAGED CN THE PROJECT 



Charles H. Zierdt, Microbiology 

James D. MacLowry, Chief, Microbiology Service 

Edward Hall, Engineer, B.E.I.B. 

E. Arthur Robertson, Asst. Chief, Laboratory Computer Service 

Robert Harshman, Computer Programmer, Laboratory Computer Service 



COOPERATING UNITS (if any), 

Bioinedical Engineering and Instrumentation Branch, DRS , 



lab/branch 

Clinical Pathology Department 



SECTION 

Microbiology Service, Laboratory Computer Service, B.E.I.B. 



iSTITUTt AND LOCATION ^ ^„„-, . 

Clinical Center, National Institutes of Health, Bethesda, Maryland 20014 



TOTAL MANYEARS: 



PROFESSIONAL: 



CHECK APPROPRIATE BOX(ES) 
C (a) HUMAN SUBJECTS 

,al) MINORS 0, (a2) INTERVIEWS 



H (b) HUMAN TISSUES 



D (c) NEITHER 



SUMMARY OF WORK (200 words or le 



underline keywords) 



A prototype instrument has been constructed and improved which allows 
the monitoring of blood cultures with an electrical imp'jdance detect' r. 
This transmits data to a computer, which analyzes impedance change over a 
time period, stores the data, and makes the decision when a culture is 
positive. This is transm.itted to a display screen in ^hc laboratory. A 
new instrument handling 60 cultures has been constructed. 



PHS-6040 
(Rev. 10-76) 



(, 



Project No. ZOl CL-100022-03 



Project Title: Detection of Bacteremia Using an Electrical Impedance 
Detection System 

Previous Serial No.: ZOl CC-00022-03 CP 

Principal Investigator: Dr. Charles H. Zierdt 

Other Investigators: Dr. James D. MacLowry 

Mr. Edward Hall 

Dr. E. Arthur Robertson 

Mr. Robert Harshman 

Cooperating Unit: Biomedical Engineering and Instrumentation Branch, 
DRS, NIH 

Man Years: Total 1.0 

Professional 0.5 
Other . 5 



(r 



Project No. ZOl-CL-10022-03 



Project Description 



Objective : 

An attempt is being made to more rapidly detect positive clinical blood 
cultures in an automated fashion. 

Methods Employed : 

A prototype impedance detector has been developed and connected to a 
dedicated computer m the laboratory. This represents a novel approach 
to detection of bacterial cultures by using a very minimum amount of human 
intervention. The blood has been lysed and filtered before presentation 
to the detector to increase bacterial yield. 

Major Findings : 

Blood cultures are detected more rapidly and fewer colony forming units can 
be detected than by conventional methods. 

Significance to Biomedical Research and the Program of the Institute: 

This methodology may enable a routine diagnostic laboratory to detect 
bacteremia more rapidly than with conventional means. 

Proposed Course : 

We will continue toevaluate patient specimens in parallel with our 
traditional method to confirm the initial observations with this method. 

Honors and Awards : 

None 

Fublicati on s : 

1. Zierdt, C. H., Kagan, R. L. and MacLowry, J. D. : Development of Lysis- 
Filtration Blood rulture Technique. J. Clin. Microbiol. 5^: 46-50, 1977. 

2. Kagan, R. L., Scnuette, W. H., Zierdt, C. H. and MacLowry, J. D.: 

Rapid Automated Diagnosis of Bacteremia by Impedance Detection. J. Clin. 
Microbiol. 5: 51-57, 1977. 



CP-59) 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE U.S. DEPARTMENT OF 
PROJECT NUMBER (Do NOT use this space) HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 
NOTICE OF 
INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 
ZOl CL-10023-02 



=ERIOD COVERED 



October 1, 1977 - September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Cell Wall Deficient Streptococci Causing Disease in Man 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



Dr. Charles H- Zierdt, Microbiollgist: , Microbiology Service, CPD, CC 



COOPERATING UNITS (.i 
None 



LAS/BRANCH 

Clinical Pathology Department 



SECTION 

Microbiology Service 



NSTITUTE AND LOCATION 

Clinical Cente 



r. National Institutes of Health, Bethesda, Md. 20014 



■OTAL MANYEARS: 



PROFESSIONAL: 



CHECK APPROPRIATE BOX(ES) 
D (a) HUMAN SUBJECTS 

|[] (al) MINORS □ (a2) INTERVIEWS 



n (b) HUMAN TISSUES 



CI (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

A collection of cell wall deficient. Gram variable, pleomorphic 
organisms has been collected from cases of endocarditis, urethritis, 
fever of undetenpined origin, brain abscess, and other deep abscesses. 
Two strains of this collection have recently reverted to definitive 
parent forms, both of which are Streptococcus sanguis . This data is 
being prepared for publication. The strains have been well documented 
through ultrastructure , guanine-cytosine base ratios , acrylamide gel 
protein patterns , fatty acid profiles via gas liquid chromatography , 
morphological and biochemical characteristics. 



PHS-6040 
(Rev. 10-76) 



Project No. ZOl CL-1002:-.- J2 

1. Clinical Pathology Departmeiit 

2. Microbiology Service 

3. Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1977 to September 30, i978 

Project Title: Cell W^ll Deficient Streptococci Causinq Disease in Man 

Previous Serial No. : ZOl CC 00023-01 CP 

Principal Investigator: Dr. Charles H. Zierdt 

Other Investigator: None 

Cooperating Units: None 

Man Years: Total .05 

Professional .05 
Other 0.0 

Project Description 

Objectives : 

In-depth study of this group of pathogenic bacteria. 

Methods Employed : 

Electron microscopy, guanine-cytosine base ratios, acrylamide gel p;atterns, 
and gas-liquid chromatography have been used for the characterization of 
these organisms. 

Significance to Biomedical Research and Lhe Program of the Institute: 

These organisms have been implicated in a number of infectious disease 
processes in man. 

Proposed Course : 

On completion of the studies of the organisms, the data has been prepared 
for publication. 

Honors and Awards : 

None 

Publications : Now in publication. 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Do NOT use this space) 



U.S. DEPARTMENT OF TpROJECT NUMBER 
HEALTH, EDUCATION, AND WELFARE ' 

PUBLIC HlALTH SERVICE | „^ -,„„„-.^ on 

NOTICE OF ZOl CL-100024-20 

INTRAMURAL RESEAMH PROJECT 



PERIOD COVERED 

October 1, 1977 - September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Analysis of 20 years of Staphylococcus aureus Bacteria Phage Typing 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Dr. Charles H. Zierdt, Microbiologist 

Dr. James D. MacLowry, Chief, Microbiology Service 

Dr. E. Arthur Robertson, Asst. Chief, Laboratory Computer Services 



COOPERATING UNITS (if any) 
None 



lab/branch 

Clinical Pathology Department 



-^ 



SECTION 

Microbiology Service, Laboratory Computer Service 



NSTITUT£,AND.LOC, 



Clinical Center, National Institutes of Health, Bethesda, Maryland 



>THER: ^ 



CHECK APPROPRIATE BOX(ES) 
G (a) HUMAN SUBJECTS Q (b) HUMAN TISSUES □ (c) NEITHER 

n (al) MINORS D (a2) INTERVIEWS 



SUMMARY OF WORK (200 words or less - underline keywords) 

Analysis of the phage typing data to date reveals: 1. That the 
"major" epidemic strains of S. aureus increased in the early 1960 's 
to high levels and declined in the mid-1960' s, not to reappear. . 
2. The world-wide epidemic strain 80/81 appeared in the Clinical Center 
in March of 1959, immediately spreading through the hospital and via 
employees, to their families. It disappeared from the Clinical Center 
in 1965, and has not reappeared. 3. At present there are in the 
Clinical Center no "epidemic types." 4. Phage typing patterns are 
less clearcut, particularly in the mixing of reactions of phage and 
from lytic groups I, II, III, and Miscellaneous. 



Project NO. ZOl CL-100024-20 

1. Clinical Pathology Department 

2. Clinical Chemistry Service 

3. Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1977 to September 30, 1978 

Project Title: Analysis of 20 years of Staphylococcus aureus Bacteria 
Phage Typing 

Previous Serial No.: ZOl CC 00023-01 CP 

Principal Investigator: Dr. Charles H. Zierdt 

Other Investigators: Dr. James D. MacLowry 

Dr. E. Arthur Robertson 

Cooperating Units: None 

Man Years: Total 1.0 

Professional 0.5 
Other . 5 

Project Description 

Objectives: 

Statistical analysis of 22,000 bacteriophage typed Staphylococcus aureas 
strains, from Clinical Center patients, 1957 to 1977. 

Methods Employed : 

Reconstruct the epidemiology of Staphylococcus aureus infections in the 
Clinical Center over the past 20 years using the central DCRT computer 
facilities. 

Honors and Awards : 



None 

Publi cations : 

In preparation. 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Oo NOT use this space) 



U.S. DEPARTMENT OF | PROJECT NUMBER 

HEALTH, EDUCATION AND WELFARE.^ mmc: no 

PUBLIC HEALTH SERVICE ZOl CL-10025-02 

NOTICE OF 
INTRAMURAL RESEARCH PROJECT 



PERIOD COVERED 



July 1, 1977 - Sept. 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Clinical Laboratory Applications of Microcalorimetry 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OiHER 
PROFESSIONAL PERSONNEL ENGAGED CN THE PROJECT 

N. N. Rehak, Ph.D., CC, CCS, CPD 



COOPERATING UNITS (if any) 
None 



lab/branch 

Clinical Pathology Department 



SECTION 

Clinical Chemistry Service 



INSTITUTE AND LOCATION 

Clinical Center, NIH, Bethesda, Md . 20014 



rOTAL MANYEARS: 

0.6 



PROFESSIONAL: 

0. 



OTHER: 

0.2- 



CHECK APPROPRIATE BOX(ES) 
G (a) HUMAN SUBJECTS □ (b) HUMAN TISSUES □ (c) NEITHER 

n (al) MINORS □ (a2) INTERVIEWS 



SUMMARY OF WORK (200 words or less - underline keywords) 

Two different calorimeters have been used to study various biological 
phenomena in body fluids. Measurements have been made of bilirubin binding 
to albumin and the heat output from washed erythrocytes has also been studied 
Measurements of chymotrypsin , trypsin and pepsin activity in gastrointestinal 
secretions have been made. Differentiation of lactate dehydrogenase isoenzymes 
by calorimetry has been accomplished. Studies are continuing on the measure 
ment of free and total cholesterol using specific enzymes. 



PHS-6040 
(Rev. 10-76) 



Project NO. ZOl CL-10025-02 

1. Clinical Pathology Dep,-rtment 

2. Clinical Chemistry Service 

3. Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

July 1, 1977 through September 30, 1978 

Previous Serial NumbGr: ZOl-CC 0002-01 CP 

Principal Investigator: N. N. Rehak, Ph.D. 

Other Investigator: None 

Cooperating Units: None 

Man Years : 

Total: 0.6 
Professional 0.4 
Other : 0.2 

Project Description 
Objective 

To determine the feasibility of calorimetry as a technique in clinical 
laboratory. 

Methods Employ ed 

Calorimetric assays of body fluids components were compared aaainst 
conventional routine methods used in clinical laboratory. 

Major Findings 

Sensitivity and precision of calorimetric methods was found to be 
comparable to that of the proposed reference methods of clinical assa^'s 
Furthermore, the limitations of the routine spectrophotometric method-, due 
to interfering substances are avoided with the use of calorimetric trchnique . 

Significance 

The accuracy and simplicity of calorim etric mea?urnm-n^s mdi nt^ the 
possible ai plication of this technique m the developme^.t of reference 
mr-tl.od for Clinical Chemistry. 



Project NO.ZOl CL-1002:'-02 



Proposed Course 

Calorimetric evaluation of clinical assays based on an antigen- 
antibody reaction, which will enable further development of calorimetric 
antibody-specific assays. 

Honors and Awards 



Publications : 

Rehak, N. N. and Young, D. S.: Prospective applications of 
calorimetry in the clinical laboratory. Clin. Chem. 24: 1307, 197J 



( I 



l:.i.t|THSO;MAN science INFORMArlUN tXCIIA^lGE 
|(-'!?UJECT :UMB£R (Oo NOT u-e this sr^ce) 



U.S. DtrARTMENT OF 

HEALTH, EDUC-TICN, AKD WELFARl 

"iJBLlC ii'^ALTH CERV!i:E 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUnlBER 
ZOl CL-10027-01 



' period'covered 

October 1, 1977 through September 30, 1978 

TiTlTf of' PR0Jl.Ct"I80 l:Tiara(rie7Tor lesr.) 

Platelet Serotonin Metabolism 



ti'Ur% LABORATORY AND IMSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
ROFESGIONAL PERSONNEL ENGAGED ON THE PROJECT 

ri: Laurence Corash, M.D., Assistant i.'hief. Hematology Service, CF 

CC 

Other: J. Costa, M.D., Stafi Physician, LCS, NIMH 



COOPERATING UNITJ 



-AB/BRA;iCH 



Clinical Pathology Department ! 

Hematology Service , 



INSTITUTE AND LOCATION 

CP, CC, MIH, Bethesda, Md. 20014 

Frcfessi oijalV Tot h 

0.1 



Ci.ECK APPROPRIATE B0X(E3) 
<^. (a) HUMAN SUBJECTS EJ (b) HUMAN TISSUES [J (c) NFIT'^ER 

:J (5l) MINORS n (a2) l.'.TERVItvJS 



rjMMARY OF WORK (200 wrrdr or Ic s - underline keyword:,) 

Serotoiii:) is a vdso-aciivc amine which is hignly concL:ntrated in the blood 
platelet. Release of serotonin in response to platelet activating stimuli 
mav pl-y a mle in many pathologic £;tates . '^he absence of platelet serotonin 
is associates with severe platelet dysfunctio n and a hemorrhagic diathesis. 
We have modifitd :i sensitive assay to accurately measure platelet endoqenoud 
serotonin coritent in normal subjects and patients. Young, l .eav^y plate^lots 
contain four tim s the serotonin of old, light platelets . Thus, platelet 
serotonin cont"n+- miy be a useful reanr to measure i'late let turnove--- rates . 
Isola* ici. of aije dependent platelet cohorts permits the study of serotonin 
uptake, content and release in a variety of pathologic states. 



Project NO. ZOl CL-10027-01 



PHS-NIH 

Individual Project Report 

October 1, 1977 through September 30, 1978 



Project Title: Platelet Serotonin Metabolism 

Previous Serial Number: ZOl CC 00014-01 CP 

Principal Investigator: Dr. Laurence Corash 

Other Investigators: Dr. J. Costa 

Man Years : 

Total: 0.3 

Professional: 0.1 

Other : 0.2 

Project Description 
Objectives : 

1. Measurement of platelet endogenous serotonin content. 

2. Quantification of serotonin storage sites and transport rates in age 
dependent platelet cohorts. 

Methods Employed : 

Platelets were isolated by use of arabino-galactan gradients. Serotonin 
transport was measured by rapid uptake of radioactive serotonin and formal- 
dehyde fixation. Serotonin content was measured by a specific double iso- 
tope dilution assay. 

Major Findings : 

1. Serotonin storage sites, platelet dense bodies, are distributed in an age 
dependent fashion among platelets. 

2. The rate of transport is equal in young and old platelets. 

3. Young platelets contain four time the serotonin content of old platelets. 
This is due to a decreased number of storage sites. 

Significance : 

Platelet serotonin is important for normal platelet function and may play a 
role in pathologic states that involve the platelet release reaction. The 
methodologies developed in this study serve to better understand these 
disorders. 



Project NO. ZOl CL-10027-01 



Awards and Honors : 



Publications : 

1. Corash, L. , Costa, J., Tan, H. , Shafer, B., Fauci, A. S., Wolff, S. M.: 
5 -Hydroxy tryptamine Metabolism, Alpha Granule Release and Life Span of 
Chediak-Higashi Syndrome Platelets. Clin. Res. 25_: 337A, 1977. 

2. Costa, J. L., Stark, H., Shafer, B., Corash, L. , Smith, M. A., Murphy, 
D. L. : Maximal Packet Size for Serotonin in Storage Vesicles of Intact 
Human Platelets. Biochem. Biophys. Res. Comm. ., 1978, in press. 



ailTHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Oo NOT use this space) 



U.S. DEPARTMENT OF 



NOTICE OF 
INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 
ZOl CL-10028-01 



PERIOD COVERED 

October 1, 1977 through September 30, 1978 



TITLE OF PROJECT (80 characters or less) 
Platelet Aging 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



PI: Dr. Laurence M. Corash 
Other: Dr, Henry K. Tan 

Dr. Mark Perlow 

Dr. Jon Costa 

Dr. Dennis Murphy 



Assistant Chief, Hematology Service CP, CC 

Palomar Memorial Hospital, California 

Staff Fellow M SMRC 

Staff Physician, Lab. of Neuropharmacology 
NIMH 

Chief, Lab. of Neuropharmacology NIMH 



COOPERATING UNITS (if any) 



Hematology Service 



INSTITUTE AND LOCATION 

CP , CC, NIH, Bethesda, Maryland 20014 



TOTAL MANYEARS: 



PROFESSIONAL: 



CHECK APPROPRIATE BOX(ES) 
U (x) HUMAN SUBJECTS 



(b) HUMAN TISSUES 



D (c) NEITHER 



G (al) MINORS □ (a2 ) INTERVIE WS 

SUMMARY OF WORK (200 words or less - underline keywords) 

Blood platelets have a finite life span in the peripheral circulation and under 
normal steady state conditions are removed by a discrete aging process. Earlier 
studies had suggested that there were structural, metabolic, and functional 
differences between young and old platelets. Existing methods to isolate 
platelets for study were inadequate. An efficient method to quantitatively 
isolate pure blood platelets has been developed in this laboratory. Experi- 
ments have shown that there is a strong relationship between platelet density 
and platelet structure, metabolism and function . Use of a non-human primate 
inode_l has shown that these density dependent characteristics do correlate with 
platelet age. Thus, it is now possible to isolate age dependent platelet co- 
horts and to measure age dependent parameters of pure whole blood platelets. 
These techniques provide a means to analyze mechanisms of platelet aging to 
estimate platelet turnover rates , and to isolate platelets of improved quality 



PHS-C040 
(Rev. 10-76) 



Project NO. ZOl CL-10028-01 

PHS-NIH 

Individual Project Report 

October 1, 977 through September 30, 1978 

Project Title: Platelet Aginq 

Previous Serial No.: ZOl CC 00011-04 CP 

Principal Investigator: Dr. Laurence M. Corash 

Other Investigators: Dr. Henry K. Tan 

Dr. Mark Perlow 

Dr. Jon Costa 

Dr. Dennis Murphy 

Man Years: 

Total: 1.0 

Professional: 0.5 

Other : 0.5 

Project Description 
Objectives : 

1. Isolation of pure whole blood platelets which are structurally and 
functionally intact. 

2. Correlation of platelet density with structure, metabolism and function. 

3. Development of a sub-human primate model to prove that platelet density 
is an age dependent parameter. 

4. Evaluation of platelet size, serotonin content and glycolytic rate as a 
means to estimate platelet turnover rate m patients with various plate- 
let disorders. 

Methods Emp loyed : 

Platelets were isolated from whole blood and separated into density de- 
pendent cohorts by use of isosmolar arabino-galactan discontinuous grad- 
ients and ultra-centrifugation. Cell volume distribution was m-asured 
with an electronic particle counter equipped with a logarithmic amplifier 
and d small computer. Platelet ultrastructure was viewed with transmission 
elertron-microscopy. Platelet function was evaluated by aggregation to 
standard platelet stimulating agents. A sensitive double isotopic radio- 
active assay v/as adopted to measure endogenous serotonin content. The rhesus 
monkey model was developed to isolate density dependent platelet cohorts 
which were labelled and radiochromium and reinfused into donor animals to 
measure cohort life span. 



CP-71 



Project No. ZOl CL-10028-01 
Major Findings : 

1. Pure whole blood platelets in high yield can be isolated by this technique. 

2. Traditional isolation methods are biased in favor of smaller, lighter 
platelets. 

3. Platelets can be effectively isolated from plasma proteins and then be 
reconstituted to a functional state with autologous plasma. 

4. There is a significant correlation between platelet density and cell 
volume, structure and organelle content. 

5. A well defined range of platelet size distribution exists and was defined 
for a large population of normal subjects. 

6. Simultaneous platelet size determination and standard radiochromium 
platelet survivals were performed in patients. There is a strong 
correlation between decreased platelet life span and increased platelet 
volume . 

7. The rhesus monkey model has shown that heavy platelets have a longer 
survival than do light platelets. Introduction of a heavy platelet co- 
hort label into the bottom of a gradient results in progressive migration I 
of the label up through the gradient, thus clearly demonstrating that 
heavy platelets become light platelets. 

8. Heavy platelets contain four times the serotonin content of light 
platelets, thus serving as a useful age dependent marker. 

Significan ce : 

Earlier techniques have not been able to efficiently isolate whole blood 
platelets. This method removes all plasma proteins from platelets which was 
not possible by earlier methods. For the first time age dependent platelet 
cohorts from a total whole blood platelet population can be isolated. Sub- 
sequent study of these cell cohorts will permit evaluation of aging effect 
on platelets in disease. This method will also provide diagnostic informa- 
tion to discriminate diseases with increased platelet destruction from 
diseases with failure of platelet production. It will also facilitate studies 
to determine if platelet disorders are due to a qualitative protein defect 
or a quantitative protein defect. This study provides a new method to explore 
platelet aging. 

Proposed Course : 

The project is now being extended to apply the method to patients with 
platelet disorders. The animal model will be manipulated to perform i£ vivo 
experiments which cannot be performed in patients. 



Project No. ZOl CL-10028--01 

Honors and Awards : 
None 

Publications: 

1. Corash, L. , Gralnick, H. R. : High Yield Quantitative Isolation of 
Human Platelets from V7hole Blood. Blood 44: 91':', 1974. 

2. Corash, L. , Tan, H., Gralnick, H.: Heterogeneity of Human Whole Blood 
Platelet Subpopulations . I. Relationship Between Buoyant Density, 
Cell Volume, and Ultrastructure . Blood 49^: 71-87, 1977. 

3. Corash, L., Shafer, B., Weinberg, D. , Steinfeld, M. B.: Platelet Sizing 
of Whole Blood Total Platelet Populations. Platelet Function Testing. 
Day, H. J., Holmsen, H. and Zucker, M. B. (eds.). Dept . HEW Publication, 
NIH 78-1087, pp. 315-322 and pp. 733-737, 1976. 

4. Anderson, J., Gralnick, H., Corash, L.: Partial Characteriiiat-ion of 
Platelet .'Associated Factor VIII. Circulation 54: 11-115, 1976. 

5. Corash, L. , Costa, J., TAn, H., Shafer, B., Fauci, A. S . ,. Wolff, £. M. : 
5-Hydroxytryptamine Metabolism, Alpha Granule Release, and Life Span of 
Chediak-Higashi Syndrome Platelets. Clin. Res. 25^: 337A, 1977. 

6. Norton, J. A., Shulman, N. R. , Corash, L. , Smith, R. L., Au , F., Rosenberg, 
S. A.: Severe Thrombocytopenia Following Intralesional BCG Theraj-iy. 
Cancer 41: 820-826, 1978. 

7. Murphy, D. L. , Costa, J. L., Shafer, B., Corash, L.: Monoamine Oxidase 
Activity in Different Density Gradient ' Fractions of Human Platelets. 
Pschopharmacology, 1978, in press. 

8. Goldstein, R. E., Corash, L., Capurro, N. L., Anderson, J. C, Epstein, 

S. E.: Decrease in Platelet Survival and Enhancement of Syir.pathetically 
Mediated Reflex Rises in Heart Rate after Abrupt Withdrawal of 
Propranolol. Clin. Res. 26: 235A, 1978. 

9. Corash, L., Costa, J. L., Shafer, B., Pettigrew, K. , liUrphy, D.: Platelet 
Organelle Content: Biochemical Activity and KElationship to Platelet 
aging. Clin. Res. 26_: 345A, 1978. 

10. Corash, L. , Shafer, B., Perlow, M.; Platelet Heterogeneity: RElation- 
phip Between Buoyant Density and C.^11 Age. Clm. Res. 26: 345A, 1978. 

11. Corash, L. , Shafer, B., Perlow, M. : Heterogeneity of Human Whole Blood 
Platelet Subpopulations. IT. Use of a Sub-Human Primato Model to 
Analyze the Relationship Between Density and Platelet Age. Blood, 
1978, in press. 



Project No. ZOl CL-10028-01 



12. Tan, H. K. , Harrison, M. , Corash, L. : Demonstration of the Outer 

Surface of Freeze Etched Normal Platelets: Correlation with Buoyant 
Density. Brit. J. Haematol., 1978, in press. 



(C 



U.;--. OLTARTMENT OF 

HEALTH, EDUCATION, AND WiILFARE 

PUBLIC :'£ALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl CL-10029-01 



PERIOD COVERED 



October 1, 1977 through September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Protective Effect of Vitamin E on Oxidative Related Hemolysis 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



ITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 



Joseph Schulman, M.D. 
Laurence Corash, M.D. 
Stephen Spielberg, M.D. 



Lawri-nce Boxer, M.D. 



Chief, Medical Genetics Section, NICHD 
Asst. Chief, Hematology Service, CP , CC 
Asst. Prof. , Dept. of Pharmacology 
Johns Hopkins Medical School 
Baltimore, Maryland 
Assoc. Prof., Dept. of Pediatrics 
Univiversity of Indiana School of 
Medicine, Indianapolis, Indiana 



COOPERATING UNITS (if any) 



Johns Hopkins University Medical School 
University of Indiana School of Medicine 



lab/branch 



Clinical Pathology Department 



Hematology Service 



INSTITUTE AND LOCATION 

CP, CC, NIH, Bethesda, Md. 20014 



TOTAL MANYEARS: 

0.4 



PROFESSIONAL: 



CHECK APPROPRIATE BOX(ES) 
Sc] (a) HUMAN SUBJECTS 

y (al) ;,'INORS n (a2) INTERVI 



S (b) HUMAN TISSUES 



U (c) NEITHER 



SUMMARY UF iJORK (200 words or less - up-^Tline keywords) 

Patients with c hronic hemolysis due to defect:., m production of reduced 
g] n tathione or reduced nucleotides are being treated with large doses of 
vi tamin E . It is postulated that vitamin F can act as a free radical scavenger 
and provide a partial protective effect against oxidative related hemolysis in 
'his qrcup of patients. Re d cell su rvival pro- and post-therapy, as well as 
rour.ine hematologic parameters and riinical course, are being monitored to 
evaluate the efficacy of this therapeutic approach. 



Project NO. ZOl CL-10029-01 

PHS-NIH 

Individual Project Report 

October 1, 1977 through September 30, 1978 

Project Title: Protective Effect of Vitamin E on Oxidative Related Hemolysis 

Principal Investigator: Dr. Laurence M. Corash 

Other Investigators: Dr. Joseph Schulman 

Dr. Stephen Spielberg 
Dr. Lawrence Boxer 



Man Years : 






Totat: 0.4 




Professional: 0.4 




Other : 




Project Description 


Objectives: 





To determine if oral high dose Vitamin E therapy can increase red cell 
survival in patients with defects in reduced nucleotide or reduced 
glutathione production disorders. 

Methods Employed : 

Routine hematologic studies are used to assess clinical status. Red cell 
survival studies are performed using autologous radiochromated red cells. 
Clinical status and red cell survival are measured before and after three 
months of therapy. 

Major Findings: 

One patient with severe chronic hemolysis due to G6PD deficiency showed 
improvement with therapy. A second patient with glutathione synthetase 
deficiency was also improved with Vitamin E therapy. Thirty-eight 
patients with G6PD deficiency of the mediteranean type were entered into 
a cooperative study with this laboratory and Dr. C. Barthocas, Athens, 
Greece. Pre-therapy studies have been completed and the patients are now 
on therapy. 

Significance : 

Severe hemolysis due to oxidative stress occurs in patients with red cell 
deficiencies of reduced nucleotides or glutathione. These hemolytic crises 
may result in death or contribute to associated disorders. Eighty million 
people are affected by G6PD deficiency. High dose Vitamin E therapy may 
offer a protective effect to these patients against oxidative stresses 
with subsequent hemolysis. The ultimate goal of this therapy will be to 
reduce both mortality and morbidity. 



Project NO. ZOl CL-10029-01 



^ropi 



osed Course; 



Studies in severly affected patients with chronic hemolysis will be 
extended. The Greek study in patients with episodic hemolysis will be 
completed and if warranted a large scale multi center trail will be 
initiated. 

Publications : 

1. Spielberg, S. P., Garrick, M.D., Corash, L. M. , Butler, J. D., Tietze, F. 
Rodgers, L. , Schulman, J.: Biochemical Heterogeneity in Human Glutathione 
Sythetase Deficiency. J. Clin. Invest., 61_: 1978. 



lOM EXCHANGE 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AMD WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



'ROJEGT NUMBER 
ZOl CL-10030-01 



PERIOD COVERED 



October 1, 1977 through September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Terminal Deoxynucleotidyl Transferase Assays and Disease Correlations. 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



PI: 

Other : 



Jerome A. Donlon 
Harvey R. Gralnick 
Fred Bollum 
Ted Keneklis 
Elaine Jaffe 
David Poplack 



Resident, Clinical Pathology Dept. 
Chief, Hematology Service, CP, CC 
Chairman, Biochemistry Dept., USUHS 
Fellow, Biochemistry Dept., USUHS 
Staff, Anatomical Path., NCI 
Staff, Pediatric Oncology, NCI 



COOPERATING UNITS (if any) 

Dept. of Biochemistry, USUHS 
Dept. of Anatomic Pathology, NCI 
Pediatric Oncology Branch, NCI 



LAB/BRANCH 



Clinical Pathology Department, Clinical Center 



Hematology Service 



INSTITUTE AND LOCATION 

CP, CC, NIH, Bethesda, Maryland 20014 



rOTAL MANYEARS: 



PROFESSIONAL: 



CHECK APPROPRIATE BOX(ES) 
□ (a) HUMAN SUBJECTS 



D (al) MINORS Q (a2) INTERVIEWS 



a (b) HUMAN TISSUES 



D (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

The presence of terminal transferase (TDT) enzyme is determined by an 
indirect fluorescent antibody assay on slide specimens from peripheral blood 
smears, bone marrow aspirate smears , cytocentrifuge preparations and frozen 
tissue sections . This approach is rapid, sensitive and utilizes a minimum 
of tissue material. The presence of terminal transferase is consistently 
demonstrated in normal thymus tissue, ALL at diagnosis and relapse, CML- 
Lymphoblast phase , and in Lymphoblastic lymphoma tissue. Normal lymphoid 
tissue, ALL in remission, AML, CML, other lymphomas and tumors as well as 
normal bone marrows do not demonstrate appreciable levels of TDT. 
Correlation of the immunoassay and enzyme activity assay is good. Currently 
immunohistochemical procedures are being evaluated to enhance the 
sensitivity and localization of TDT in tissues. Correlations of TDT activity 
with morphology, histochemistry, chemotherapy, and clinical course is also 
underway. 



PHS-6040 
(Rev. 10-76) 



%t 



Project NO. ZOl CL-10030-01 



PHS-NIH 

Individual Project Report 

October 1, 1977 through September 30, 1978 



Project Title: Terminal Deoxynucleotidyl Transferase Assays and Disease 
Correlations 

Principal Investigator: Dr. Jerome A. Donlon 

Man Years : 



Total : 


0.7 


Professional : 


0.5 


Other : 


0.2 



Project Description 
Objectives : 

1. Determine the clinical relevance of a TDT positive assay. 

2. Develop Immunohistochemical (PAP) procedures for TDT assays in tissue 
sections. 

3. Build a data base of diagnoses, morphology, histochemistry, clinical 
course. 

Methods Employed : 

1 . Indirect fluorescent antibody procedure for TDT assay in peripheral 
smears, bone marrow smears, cytocentrifuge preparations, and tissue 
sections. 

2. Enzyme activity assay for TDT in cell suspensions. 

3. Immunohistochemical procedures (PAP). 

Major Findings : 

The fluorescent antibody procedure correlates with the enzyme activity 
assay in demonstrating the presence of TDT in specimens. Positive reactions 
are found in normal thymus tissue, ALL at diagnosis and in relapse, CML — 
lymphoblastic phase and in lymphoblastic lymphoma tissue. 



Project NO. ZOl CL-10030-01 



Significance to Biomedical Research and the Program of the Department : 

TDT as a biochemical marker may be helpful in the diagnostic classification 
of leukemias and lymphomas. It can help to differentiate lymphoblastic 
from myeloblastic crisis of CML. Additional correlations may be found 
which would indicate that TDT could predict a disease prognosis or response 
to chemotherapy. 

Honors and Awards : 

None 

Publications : 

Donlon, J. A., Jaffa, E. S., and Braylan, R. C: Terminal Deoxynucleotidyl 
Transferase Activity in Malignant Lymphomas. New England J.- of Med. 297 : 
461-464, 1977. 



r 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Do NOT use this space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC I'EALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



ROJECT NUMBER 
ZOl CL-10031-01 



PERIOD COVERED 



October 1, 1977 through September 30, 1978 



TITLE OF PROJECT (80 characters or less) 
A Clinico-pathologic study of the Hypereosinophilic syndrome 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

PI: Dr. Morris A. Flaiam Clinical Associate, Hematology Service 



Other: Dr. Harvey R. Gralnick 
Dr. Anthony Fauci 
Dr. Robert Schooley 



Chief, Hematology Service, CC CP 

Staff, Laboratory Clinical Investigation 

Chief, Clinical Associate NIAID 



COOPERATING UNITS (i 



LAB/BRANCH 

Clinical Pathology Dept., Clinical Center 



SECTION 

Hematology Service 



INSTITUTE AND LOCATION 
CP, CC, NIH, Bethesda, Maryland 20014 



TOTAL MANYEARS: 



PROFESSIONAL: 



CHECK APPROPRIATE BOX(ES) 
n (a) HUMAN SUBJECTS 



3(b) HUMAN TISSUES 



n (c) NEITHER 



D (a1 



INORS □ (a2) INTERVIEWS 



SUMMARY OF WORK (200 words or less - underline keywords) 

The bone marrows of patients seen at the Clinical Center with Hyper- 
eosinophilic Syndrome were reviewed. This was done in an attempt to 
correlate the bone marrows and other hematologic parameters with the 
patient's clinical course and response to therapy . 



PHS-6040 
(Rev. 10-76) 



Project NO. ZOl CL-10031-01 



PHS-NIH 

Individual Project Report 

October 1, 977 through September 30, 1978 

Project Title: A Clinico-pathologic study of the Hypereosinophilis Syndrome 

Principal Investigator: Dr. Morris A Flaum 

Man Years : 

Total : 2 

Professional : 2 
Other : 

Project Description 

Objectives : 

To determine whether hematologic manifestations of the hypereosinophilic 
syndrome can be used to correlate with 1) the clinical course of the 
patient and, 2) response to therapy. 

Methods Employed : 

The bone marrows of 30 patients were reviewed microscopically. The clinico- 
pathologic correlation has not as yet been completed. 

Significance : 

The significance of this study lies primarily in the fact that hypereosino- 
philic syndrome appears to be a spectrum of disease. It is hoped that in 
the initial evaluation, the patient's prognosis and response to therapy 
may be able to be determined. 

Proposed Course : 

Further studies on subsets of patients with hypereosinophilic syndrome will 
be pursued. 

Honors and Awards : 

None 

Publications: 



SMITHSOMAN SCIE.'.CE I ;JFQRMATI O.'J EXCHANGE 
PROJECT NUMBER (Do NOT use this trace) 



U.S. DEPART.VE.'JT OF 

HEALTH, EDUCATIC;,, AND »ELFARE 

PUBLIC HEALTH CERVICt 

NOTICE Of 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl Cl-10032-01 



PERIOD COVERED 



October 1, 1977 through September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

The Role of Factor VIII in von Willebrand Factor Activity. 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



PI: Dr. Morris A. Flaum 
Other: Dr. Harvey R. Gralnick 



Clinical Associate, Hematology Service 
Chief, Hematology Service CP CC 



COOPERATING UNITS (if any) 



LAB/BRANCH 

Clinical Pathology Dept., Clinical Center 



SECTION 

Hematology Service 



INSTITUTE AND LOCATION 

CP, CC, NIH, Bethesda, Maryland 20014 



TOTAL MANYEARS: 



PROFESSIONAL: 
1.5 



CHECK APPROPRIATE BOX(ES) 
D (a) HUMAN SUBJECTS 

D (al) MINORS n (a2) INTERVIEWS 



n (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

The role of factor VIII in von Willebrand factor activity is being pursued 
by using a factor VIII antibody as a probe. The antibody, produced in 
goats is pre-incubated with fresh or formalinized platelets and von 
Willebrand Factor activity is then determined by the usual methods. The 
antibody has been demonstrated to inhibit factor VIII in coag- 
ulation studies. 



PHS-6040 
(Rev. 10-76) 



ZOl CL-10032-01 

PHS-NIH 

Individual Project Report 

October 1, 1977 through September 30, 1978 

Project Title: The Role of Factor VIII in von Willebrand Factor Activity 

Principal Investigator: Dr. Morris A. Flaum 



Man Years : 



Objectives : 



Total: 1.5 

Professional: 1.5 
Other : 



Project Description 



To determine the role of platelet membrane-bound factor VIII in the von 
Willebrand factor activity. 

Methods Employed 

The role of factor VIII in von Willebrand factor activity is being pursued 
by using a factor VIII antibody as a probe. The antibody, produced in goats, 
is preincubated with fresh or formalinized platelets and von Willebrand 
factor activity is then determined by the usual methods. The antibody has 
been demonstrated to inhibit factor VIII activity in coagulation studies. 
Adherance of the antibody to platelet membrane factor VIII is confirmed by 
immunofluorescence microscopy. 

Major Findings : 

Preliminary findings suggest that the factor VIII antibody does not inhibit 
von Willebrand factor activity after pre-incubation with platelets. Pre- 
liminary studies also suggest that the antibody is in fact reacting with plate- 
let membrane bound factor VIII. 

Significance : 

The role of platelet membrane bound factor VIII is unknown. Clarification 
of its role will increase understanding of platelet function in hemostasis. 
This may lead to new insights of the interaction of platelets with the 



Froiect h.o. ZOl CL-10fi':!2-C: 

coagulation sequence and platelet dysfunction m the von Wiilebrand disease. 

Proposed Course: 

Further studies to clarify the functional significance of platelet mambrane 
bound factor VIII will be pursued . 

Ho rorL. and Av.'ards : 

None ■ 

Publicat ions : 



u.:. 'jU ■(.:■•£;. t of 

HEALTh, EDUC.\TICf.., A'.D «tLFARE 

FUBLIC i'tALTH oERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



Tf^ 



ZOl CL 10033-01 



\^ 



I PERIOD COVERED 

[_ October 1. 



1977 through September 30, 1978 



TITLE OF PROJECT (80 characters or less) 



The Effect of Plasmaphoresis on Coagulat] 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

PI: Dr, Morris A. Flaum 

Other: Dr. Harvey R. Gralnick 

Dr. Richard Cuneo 

Dr. W. King Engel 

Dr. Frederick Applebaum 



.ES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 

Clinical Associate, Hematology Service 
Chief, Hematology Service, CP CC 
Clinical Associate, Neurology NINCDS 
Staff, Neurology Branch NINCDS 
Staff, Pediatric Oncology NCI 



COOPERATING UNITS (if any) 



LAB/BRANCH 



(t 



Clinical Pathology Dept. , Clinical Center 



Hematology Service 



NSTITUTE AND LOCATION 

CP, CC. NIH, Bethesda, Maryland 20014 



OTAL MANYEARS: 

j^ 

CHECK APPROPRIATE BOX(£SJ 
Q: (a) HUMAN SUBJECTS 



D (al ) MINO RS D (a2) INTERVIEWS 
SUMMARY OF nCnK (2 



PROFESSIONAL! 
.75 



.75 



(b) HUMAN 1 ISSUES 



D (c) NEITHER 



words or less - underline keywords) 

The effect of plasmaphoresis on coagulation was determined by sampling 
patients prior to, Immediately after, and 24 hours after, plasmaphoresis. 
Coagulation studies were then performed on these specimens as well as the 
patient's plasma. In conjunction with this study, a second study was 
performed to determine the effect of plasmaphoresis on immunoglobulins, 
cholesterol, triglyceride, serum proteins, trace elements. 



r'' S-bO-'.O 
(Rev. iO-76) 



Project No. ZOl CL 10033-01 



PHS-NIH 
Individual Project Report 
October 1, 1977 through September 30, 1978 



Project Title: The Effect of Plasmaphoresis on Coagulation 
Principal Investigator: Dr. Morris A. Flaum 
Man Years: 



Total: 


1.5 


Professional: 


.75 


Other 


.75 



Project Descr iption 

Objectives: 

To determine the effect of plasmaphoresis on coagulation factors. 

Methods Employed : 

Patients were sampled prior to, immediately after, and 24 hours after 
plasmaphoresis. Routine coagulation studies wore than performed on 
these specimens as well as on the plasma removed. Special studies included 
anti-thrombin III levels and fibrinogen levels by Clauss, Ratnof f-Menzie 
and immunologic methods, clotting factor assays, factor VIII antigen levels, 
and von Willebrand factor activity. The- effect of plasma exchange on 
immunoglobulin levels, triglyceride, cholesterol, serum proteins, and trace 
elements vjas also determined. 

Ma jor Fin d ings : 

The specimens are being analyzed at this time. Preliminary data reveals 
that the patients are anti-coagulated at the end of plasma exchange and 
rt'tnrn to normal by 24 hours. 

is ignji f icance : 

Plasma exchange is a nt^w modality c.f therapy x^ith possible application to 
multiple disorders. It's effecc on .nans hoir.costa^is is unknown. This 
study will aJlow us to gain insight into the effect of plasma exchange on 
coagulation. 



Project No. ZOl CL 10033-01 (f' 



Proposed Course : 

Further studies on the effect of plasma exchange will be pursued, 



Honors and Awards : 
None 

Publications : 
NONE 



CP-38 



■■iTi-'Oi.iA;. GCiti.CL I!;for;/ati>j:. i>.ChA'.Z:., u.:. ^ . •■^■■cM Or ,.jJ:_t ..ui, 

iiabJi-CT ;iU.V3ER tDo NOT use this srace) HEALT", EDUC'TICf., A.'.D „CLFAht ! 
I FlIBLIC KlALTH :lRVICE j 

I I INTRAMURAL RESEARCH PROJECT ZOl CL 10034-01 

I PERIOD COVERED 

October 1, 197/ through September 30, 1978 

tTtLE^f"" PROJECT (80 characters or less) 

Thrombin Activation of Factor VIII 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



Dr. Margaret E. Rick Staff Physician CP CC 



any) 



LAB/BRA. Cr 

Clinical Pathology Dept., Clinical Center 



SECTION 

Hematology Service 



NSTITUTE AND LOCATION 

CP, CC, NIH, Bethesda, Maryland 20014 



TOTAL MANYEARS: PROFESSIONAL: CTHER: 

15 0.75 0.75 



CHtCK APPROPRIATE BOX(ES) 
;j (a) HUMAN SUBJECTS 11(b) HUMAN TISSUES M (c) NtiTHER 

□ (al) MINORS D ( a2) INTERVIEWS 

SUMMARY OF WORK (200 words or less - underline keywordr) 

This investigation seeks to characteriz the inter action of the factor VIII 
comple x with thrombin , in particular the biochemical mechanism by which 
thrombin activates factor VITI rrocoagu lanu '^rivity and rubsequently in- 
activates the activity. ' An understanding of the r egulatory role of this 
interactio: in norml hemoj-tacis ^^ill lead to c better understanding of 
the basic hemostatic process and oi the functional defects in the factor 
VIII deficiency diseases (H emophilia A ans von Will ebrand's Disease ) as 
well as in pafhologic th rombotic sta tes. 



Project No. ZOl CL 10034-01 " 

1. Clinical Pathology Department 

2. Hematology Service 

3. Bethesda, Maryland 



PHS-NIH 

Individual Project Report 

October 1, 1977 through September 30, 1978 

Project Title: Thrombin Activation of Factor VIII 

Prlnicpal Investigation: Dr. Margaret E. Rick 

Man Years: ^ -, , ,- 

Total: 1.5 

Professional: 0.75 

Other: 0.75 



Project Description 



Objectives : 



To characterize the biochemical interaction of thrombin and factor VIII a||^ 
relate this to the functional changes in factor VIII procoagulant activity 

Methods Employed : 

Purified human factor VIII is obtained by differential PEG precipitation of 
factor VIII concentrates followed by agarose gel filtration. A low molecular 
weight factor VIII procoagulant is obtained by gel filtration of purified 
factor VIII with buffers containing 0.24 M CaCl2. Thrombin interaction with 
the factor VIII preparations is assessed with factor VIII procoagulant assays. 
Inhibitors of thrombin (hirudin, DEP, heparin) are employed in studying 
various aspects of the interaction. 

Major Fi ndings: 

The reaction patterns of thrombin with purified factor VIII and the calcium 
dissociated low molecular weight factor VIII are similar, demonstrating an 
initial increase in factor VIII activity followed by a decay of procoagu- 
lant activity. The extent of activation which is observed in the initial 
phase decreases with lower temperatures and with lower thrombin concen- 
trations. A pseudo-first order relationships is demonstrated for the acti- 
vation phase. The labile factor VIII procoagulant activity produced by 
thrombin action cannot be stabilized by the addition of inhibitors of throm- 
bin and thus appears to be intrinsically labile. 



Project No. ZOl CL 10034-01 



Signiricance to Bi om edical Research and the P i ogram of t h e Department : 

The goal of this research is to gain a better understanding of the function 
of factor VIII in normal hemcstasis, in factor VIII deficiency diseases, and 
in pathologic thrombotic states. The important regulatory role of thrombin 
in factor VIII function will lead to a better understanding of regulation in 
normal nemostasxs and may allow therapeutic manipulation by pharmacolOf^-'c 
agents in thrombotic diseases. 

H^3n ors and Awards: 

None 

Publications: 



1. Rick, M.E., and Hoyer , L.W.: Immunologic Studies of Antihemophilic 
Factor (AHF, Factor VIII). V, Immunologic Properties of AHF Sub- 
units Produced by Salt Dissociation. 

2. Rick, M.E., and Hoyer, L.W.: Thrombin Activation of Low Molecular 
Weight Antihemophilic Factor (Factor VIII). Nature 252:404, 1974. 

3. Rick, M.E., and Hoyer L.W : Interaction of thrombin and factor VIII; 

I. The Role oL Proceas. Inhibitors. Br. J. Haematol. 36:585-597, 1977, 

4. Mundy G.R. Rirk, M.E., Turcotte, B.A., Kowalski, M.A. ; Hypercalcemia 
in LyT.phosarcoma Cell Leukemia. Am . J . Med . (in press) 



PROJECT NUMBER (Do NOT 



SWI'tHSONIAN science information EXCllANGi|~ U.S. Dt 



SERVICE 
NOTICE OF 
INTRAMURAL RESEARCH PROJECT 



ROJEGT NUMBER 
ZOl CL 10035-01 



PERIOD COVERED 



TITLE OF PROJECT (80 ch; 



^b-^Sp-pJiBinhftr 30 , 132R. 



;ters or less) 



Factor VIII Interaction with other Coagulation Factors 



NAMES, LABORATORY AND INSTITUTE AFF I LI AT I ONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



PI: Dr. Margaret E. Rick 



Staff Physician 



COOPERATING UNITS (if any) 



lab/branch 
Clinical Pathology Dept. 



Clinical Center 



SECTION 
Hematology Service 



INSTITUTE AND LOCATION 
CP, CC, NIH, Bethesda, 



Maryland 20014 



rOTAL MANYEARS: 
0.5 



PROFESSIONAL: 
0.25 



CHECK APPROPRIATE BOX(ES) 
LJ (a) HUMAN SUBJECTS 

U (al) MINORS L, (a2) INTERVIEWS 



(b) HUMAN TISSUES 



(c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

This project seeks to investigate the int erartion of factor VIII with other 
coagulation factors, particularly with factor XI , calcium , and phospholipid 
in the quaternary comple x formed by these factors. The importance of 
proteolytic activation of factor VTII prior to its participation in the 
complex will be assessed, and the nonfunctional factor VIII molecule present 
in patients with Hemoph ilia A will be studied to determine whether it can 
participate in the quaternary complex. 



PH S-6040 
(Rev. 10-76) 



f 



Project No. ZOl CL 10035-01 

1. Clinical Pathology Department 

2. Hematology Service 

3. Bethesda, Maryland 

PHS-NIH 
Individual Project Report 
October 1, 1977 through September 30, 19d78 
Project Title: Factor VIII Interaction with other Coagulation Factors 

Principal Investigator: Dr. Margaret E. Rick 

Man Years: Total 0.5 

Professional 0.25 
Other 0.25 



Project Description 



Objectives : 



To characterize the interaction of factor IX with factor VIII and the low 
molecular weight factor VIII procoagulant, aisessing any "activation" of 
factor procoagulant activity by factor IX and developing an affinity 
reagent to study components of the quaternary complex (factor VIII, factor 
IX , calcium, phospholipid) . 

Methods Employed : 

Purified human factor VIII is obtained by differential PEG precipitation of 
factor VIII concentrates followed by agarose gel filtration. A low 
molecular weight factor VIII procoagulant is obtained by gel filtration of 
purified factor VIII wuth buffers containing 0.24 M CaCl . Factor IX is 
purified by barium citrate adsorption and elution, ion exchange chromato- 
graphy, and affinity chromatography. Activation of factor VIII is assessed 
by procoagulant assay and the quaternary complex will be assessed using 
solid phase factor IX as an affinity reagent. 

Major Findings : 

Preliminary studies indicate that factor IX does not activate factor VIII 
in a purified system. ^ 



Project No. ZOl CL 10035-01 



Significance to Biomedical Research and the Program of the Department 

The goal of this research is to gain a better understanding of the function 
of factor VIII in normal hemostasis and in the factor VIII deficiency 
diseases (Hemophilia A and von Willebrand's Disease). The role of the 
respective components within the quaternary complex will provide insights 
into the normal function of factor VIII and the possible mechanism of 
dysfunction in the factor VIII deficiency diseases. 

Honors and Awards : 

None 

Publications: 



IsMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Oo NOT use this space) 



^J.S. DEPARTMENT OF 

HEALTH, tOUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 



ZOl CL 10036-01 



PERIOD COVERED 

October 1, 1977 through September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Evaluation of the Limulus Lysate Test 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Principal Investigator: Ronald J. Elin, Chief, Clinical Pathol. Dept. , CC 

Others Harold Nishi, Senior Staff, Chemistry Service, CPD,CC 



COOPERATING UNITS (if any)^ 

None 



lab/branch 

Clinical Pathology Department 



SECTION 

Clinical Chemistry Service 



NSTITUTE AND LOCATION ^ , 

National Institutes of Health, Bethesda, Maryland 20014 



OTAL MANYEARS: 

1 



CHECK APPROPRInTE BOX(ES) 
[i(a) HUMAN SUBJECTS 

D (al) MINORS D (a2) INTERVIEWS 



HUMAN TISSUES 



D (c) NEITHER 



SUMMARY OF WORK (200 worts or less - underline keyworts) 

The limulus test was found to be nonspecific in attempting to determine 
pyogenic arthritis in humans. A very significant correlation was found 
between a positive limulus test and an elevated neutrophil count. It may be 
that neutrophils or a product of neutrophils can cause a positive limulus 
test. Thrombin, esterase and poly I ' poly C were found to cause a positive 
limulus assay. A nephelometric method for performing the limulus assay is 
being studied. 



PHS-6040 
(Rev. 10-76) 



Project No. ZOl CL 10036-01 

1. Clinical Pathology Department 

2. Clinical Chemistry Service 

3. Bethesda, Maryland 



PHS-NIH 

Individual Project Report 

October 1, 1977 to September 30, 1978 

Project Title: Evaluation of the Limulus Lysate Test 

Previous Serial No. : None 

Principal Investigator: Dr. Ronald J. Elin 

Other Investigator: Mr. Harold Nishi 

Cooperating Units : None 

Man Years: Total 1.0 

Professional 0.25 
Other 0.7 5 



Z 01 CL 10036-01 
Project Description 

Objectives : 

To determine the specificity, clinical utility and optimiiin method for per- 
formance of the limulus assay. 

Methods Employ ed: 

The limulus assay was performed by mixing lysate with the test material and 
determining if gelation occurred. The assay wa.s also performed using a 
nephelometer. 

Major Findings : 

The limulus assay is not specific for detecting pyrogenic arthritis using 
joint fluid. The highest correlation was found between an elevated 
neutrophil count and positive limulus test. 

Significance : 

The liT.ulus test is not recommended for the detection of pyrogenic arthritis 
using joint fluid from human subjects. 

Honors and Awards : 

None 

Publications : 

Elin, R. J., Knowles, R. , Barth, W. F., and Wolff, S. M. : Lack of 
specificity of the limulus lysate test in the diagnosis of pyrogenic 
arthritis. J. Infect. Dis. 137: 507-513, 1978. 



U.S. DEPARTMENT OF 

HEALTH, EDUCATiON. AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl CL 10037-01 



PERIOD COVERED 
October 1977 - September 30, 1978 



TITLE OF PROuECT (80 characters or less) 

Adherence of bacteria, blood cells and other particles to large porosity 
membrane filters. 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 



Dr. Charles H. Zierdt, Microbiologist, Microbiology Service, CPD, CC 



COOPERATING UNITS (jf any) 

None 



lab/branch 
Clinical Pathology Department 



SECTION 
Microbiology Service 



NSTITUTE AND LOCATION 
ri in1 nal C pnter, 



National Institutes of Health, Bethesda, Md. 



TOTAL MANYEARS: 
1.0 



PROFESSIONAL: 
0.5 



OTHER: 
0.5 



CHECK APPROPRIATE BOx(ES) 
'J (a) HUMAN SUBJECTS 

D (ap MINORS □ (a2) INTERVIEWS 



n (fa) HUMAN TISSUES 



@(c) 



SUMMARY OF WORK 200 w(jrds or less - underline .keywords K , .-, , ^ ■ loocoTn 

Membrane filters with pore sizds mufch larger chan bacteria, 1,2,3,5,8,10, 

and 14 micra diameter, will effectively remove those bacteria from filtered 
suspensions. The phenomenon depends on surface charge, intrinsic to membrane 
filters and probably a by-product of the manufacturing process. Membrane 
filters of any m.aterial possess the charged surfaces, but cellulose and 
cellolose acetate polymers have more than polycarbonate filters, and thereby 
are more attractive to bacteria. Gram-posicive organisms are attracted more 
than Gram-negative. Nylon, Teflon, and vinal membrane filters are far less 
"magnetic." Bacteria continue to attach to a membrane until the surface 
charges are neutralized. For a 47 mm diameter cellulosic filter, roughly 1 x 
10 bacterial cells are required to "saturate" the filter on continued filtra- 
tion. Then a much larger percent of the bacteria pass through the filtrate, 
but never 100% and eventually they pile up on the filter sufficiently to slow 
filtration by blocking the pores. Only a small percent of the adherent bac- 
teria can be removed by back-washing the filter. No method for quantitativj 
removal that is harmless to bacteria has yet been devised. 
CP-98 
"■^-604 



"m 



Project No. ZOl CL 10037-01 

1. Clinical Pathology Department 

2. Microbiology Service 

3. Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1977 to September 30, 1978 

Project Title: Adherence of Bacteria, Blood Cells and Other Particles to 
Large Porosity Membrane Filters 

Previous Serial No. : None 

Principal Investigator: Dr. Charles H. Zierdt 

Otiier Investigator: None 

Cooperating Units: None 

Man Years: Total 1.0 

Professional 0.5 
Other 0.5 

Project Description 

Objectives : 

To work out the basics of the phenomenon described, to attempt to develop 
ways of reversing the phenomenon (getting particles backoff the filters), 
and to report this in an appropriate journal (Science) . 

Methods Employ ed 

The usual filtration techniques, with appropriate commercial filters apparatus 
and membranes- The use of various tween compounds (non- ionic) to effect 
detaclimcnt of adherent particles. 

H ones an d Awards: 

None 

P ublications . 

Zxerdt, C. H. : Blastocystis hominis, an intestinal protozoan parasite of 
man. The Public Health Lab. (in print) 1978. 



NIAN SCItNCt INFORMATION EXCriANG 
NUMBER (Do NOT use this spacs) 



U.S. DEPARTMENT OF 



PROJECT NUMBER 



NOTICE OF 201 CL 10038-01 

INipAftSURAL RESEARCH PROJECT 



PERIOD COVERED 
October 1, 1977 - September 30, 1978 



TITLE OF PROJECT (80 characters or less) 
Identification of alpha hemolytic and non-hemolytic Streptococci 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Dr. Vee J. Gill, Supervisory Microbiologist, Microbiology Service, CPD, CC 



COOPERATING UNITa (if any) 



LAB/BRANCH 








# 


SECTION ' 
Microbiolocrv Service 


INSTITUTE AND LOCATION 


Bethesda, 


Maryland 


20014 




TOTAL MANYEARS: 
1 


PROFESSIONAL! 

,75 


OTHER! 


.25 









CHECK APPROPRIATE BOX(£S) 
D (a) HUMAN SUBJECTS 

D (al) MINORS D (a2) INTERVIEWS 



D (b) HUMAN TISSUES 



D (c) NEITHER 



SUMMARY OF WORK (200 words or less 



derline keywords) 



Group D. Streptococci and alpha hemolytic and non-hemolytic 
Streptococci isolated from blood and other sterile fluid sties from 
Clinical Center patients are being collected and speciated. Speciation 
of these Streptococci will define which species are of greater significance 
in infection of compromised hosts. 



PHS-6040 
(Rev. 10-76) 



Project No. ZOl CL 10038-01 

1. Clinical Pathology Department 

2. Microbiology Service 

3. Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1977 to September 30, 1978 

Project Title: Identification of Alpha Hemolytic and Non-hemolytic 
Streptococci 

Previous Serial No. : None 

Principal Investigator: Dr. Vee J. Gill 

Other Investigator: None 

Cooperating Units: None 

Man Years: Total 1-0 

Professional 0.75 
Other 0.25 



ZOl CL 10038-01 

Project Description 

Objectives : 

To define the fole of different species of Group D, alpha, and non-hemolytic 
streptococci as infecting agents of compromised hosts. 

Methods: 



Alpha and non-hemolytic streptococci isolated from blood or other sterile 
fluids are evaluated for their biochemical and antibiotic sensitivity 
characteristics. Identification has been facilitated by adapting a 
miniaturized biochemical evaluation strip (ana - API) for more rapid 
results. 

Major Findings: 

Most' isolates can be identified as one of the 15 recognized species of 
Group D, alpha or non-hemolytic streptococci. Amongst Group D Streptococci, 
the fact that S. faecium represents 30% of presumptive Group D isolates is 
unexpected. The species seen most frequently amongst alpha and non-hemolytic 
are S. mitis (27), S. intermedium (20), and S. Sanguis II (21). This 
distribution differs from that seen in studies of the various species in cases 
of endocarditis, and also organisms referred to CDC. ^^ 

Significance : 

Sepsis and other serious infection with gram positive organisms seem to be 
increasing in importance in patients at the Clinical Center. Knowledge of 
the specific species involved is necessary in order to understand the 
pathogenesis of these infections. 

Proposed Course : 

Project will be continued further to define the roles of the various species 
of streptococci as pathogens m compromised hosts. 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Do NOT use this space; 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEAF-CH PROJECT 



PROJECT NUMBER 



ZOl CL 10039-01 



PERIOD COVERED 
July 1977 - Septembar 30, 1978 



TITLE OF PROJECT (60 characters or less) 
Development of a Biological Titration Microcalorimeter 



NAMES, LABORATORY AND IIJSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PifiSONNEL ENGAGED ON THE PROJECT 

1) Russell M. Jaffe (P.I.) 

2) Ted Jensen, Ph.D. 
Brigham Young University 
Prove, UT 

3) Mark Holmes 
NIH/University of Maryland 
College Park, MD 

4) Phil Chang 

■University of California, davis 
S^n nieun, CA 



COOPERATING UNITS (if 



lab/branch 

Cliniral Pathology/ Department 



SECTION 
Clinical Chemistry Service 



INSTITUTE AND LOCATION 
Clinical Csnter, Biii 1 



dmg ] 
I PROFES! 

J O. 



TOTAL MANYEARS: 
1.3 



I PROFESSIONAL: 
A 



lOTHER: 
J Q.^ 



CHECK APPROPRIATE BOX(ES) 
D (a) HUMAN SUBJECTS 

G (al) iVIMOrt^ [_, (a2) I.\TERV1EI-, 



13(h) HUMAN TISSUES 



n (c) NEITHER 



SU.VMARY OF WORK (200 wcrds 



underli 



Drds) 



1,-ont-inued development of a biological titration microcalorimetry resulted 
in the first SGC-et -jf ul the rmorh -mica 1 analysis of amylase enzymatic digestion 
of starch (its sul:;stratc ) , as well as differentiation of nonspecific glucose 
c" Nation from starch digestion. The results suggest that a sensitive and 
Cf-'. cific assay i^ available for lot- to- lot characterization of starch (and 
similar amylase substrate) 



I In addition, ;: ^ system was ■ -^ uograirimed to allov; autonomous micro- 

; processn control. Further, mM .doioyic and system improvements allow 

I S'^nsitivity improvement to a :^ev=l of ,) ir.icrocalories/second within iC seconds 

1 at- a precision of + j% of C.V. 



d040 

. 10-7d) 



Project No. ZOl CL 10039-01 

1. Clinical Pathology Department 

2. Clinical Chemistry Service 

3. Bethesda, Maryland 

PHS-NIH 
Individual Project Report 
July 1977 to September 30, 1978 

Project Title: Development of a Biological Titration Microcalorimeter 

Previous Serial No. : None 

Principal Investigator: Russell M. Jaffe, M.D., Ph.D. 

Other Investigators: Ted Hensen, Ph.D. 
Mark Holmes 



Phil Chang 



Cooperating Units: None 



Man Years: Total 1.3 

Professional 0.4 
Other 0.9 



ZOl CL 10039-01 
Project Description 
Objectives : 

1. To apply thermochemical techniques tC' biologic systems for non- 
invasive intracellular metabolic studies. 

2. To develop reference thermochemical methods for clinical labora- 
tories. 

3. To optimize analytic techniques in thermochemistry. 

4. To understand mechanisms of protein-protein and protein- 
carbohydrate interaction, especially membrane receptors and 
antigen- antibody interaction. 

Methods Employed : 

1. Serum, plasma, or cells are obtained from hum.an and animal sources. 

2. Pill if led proteins are obtained from collaborating laboratories. 

3. Correlative analytic methods are used to confirm observations, 
where appropriate. 

Major Findings : 

A. Analytical 

1. Calorimetric determination of some serum enzyme is 
possible, especially serum amylase and glucose. 

2. Precise calculation of bind:ng constants and specific 
heats is possible, especially those of proteins (e.g., 
serum albumin). 

b. Methodological 

1. Proper comparison of control titrations allows unique 
evaluation of coupled reaction steps that are inseparable 
by othe'- methods (such as coupled action of glucose 
oxidase-catalase) . 

2. Data collection and syntem control is possible by automatic 
means, especially use of microprocessors. 

S ignific ance 

We believe thermochemistry can be usefully applied to clinical chemical 
problems both for refence procedures and standardization of laboratory 



ZOl CL 10039-01 



reagents. The calorimeter also provides a useful service to many research- 
oriented aspects of biochemistry. 

Proposed Course 

Studies of amylase enzyme are continuing to specify both its funda- 
mental mechanism of action and its clinical applic£ibility . 

Studies of protein-substrate/ligand/receptor/cofactor will commence, 
to supplement work in progress. 

Studies of specific heat of certain cell proteins may aid in elucida- 
tion of bioelectronic activity of some reactions under study by others. 

Publications 



1. Non-invasive study of tissue culture cells and cellular com- 
ponents of whole blood may further specify the kinetics of some metabolic 
processes. In preparation. 



(«^ 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Oo NOT use this space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEAnCH PROJECT 



j PROJECT NL 



:;oi CL 10040-01 



PERIOD COVERED 
July 1977 - September 30. 197£ 



TITLE OF PROJECT (80 characters or less) 
Role of Platelets in Atherogenesis in Dogs and Pigs 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



1) Russell Jaffa, (P. I. ) 

NIH, CCS, CPD, CC 10/4n-309 
Bethesda, Maryland 

2) Donald Fry, M.D. 

Chief, LEA, NHLBI 10/5N-204 
Bethesda, Maryland 

3) Robert Mahley, M.D., Ph.D. 
LEA, NHLBI, 10/5N-204 
Bethesda, Maryland 



4) Lynne Huffman 
Meloy Laboratories 
Springfield, VA 

5) Robert Pitas, Ph.D. 
Meloy Laboratories 
Springfield, VA 



COOPERATING UNITS (if any) 



lab/branch 
Clini cai — Pathology nppr 



SECTION 
Clinica l Chemistry Service 



NSTITUTE AND LOCATION 
Clinical Center. Ridr 



"OTAL MANYEARS: 
2.8 



PROFESSIONAL: 
1 . 4 



CHECK APPROPRIATE BOX(£S) 
D (a) HUMAN SUBJECTS 

(ai) Mii\ORS □ (a2) INTERVIEWS 



n (b) HUMAN TISSUES 



)g{c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 



A relationship between IN VITRO platelet responsiveness and athero- 
genesis is shown in foxhound dogs and Hormel miniature swme. In the presence 
of significant hyperlipidemia (Choi 1200; tgy >600, both ADP and collagen 
induced platelet aqgregation are affected. A general relationship between 
disease severity and platelet sensitivity is being further investigated. 
After months on experimental diet, platelet survi val decreases (only) in 
animals rendered athero sclerotic . Significant changes in platelet fatty acid 
composition (see Pitas, et al. Lipids, in press) are associated with 
functional changes. Dose- response platelet aggregavity is necessary to 
detect the functional change. 



CP-107 



PriS-6040 
(Rev. 10-76) 



ZOl CL 10040-01 

Project Title: Role of Platelets in Atherogenesis in Dogs and Pigs 

Previous Serial No. : None 

Principal Investigator: Russell Jaffa, M.D., Ph.D. 

Other Investigators; Russell Jaffe, M.D., Ph.D. 
Donald Fry, M.D. 
Robert Mahley, M.D., Ph.D. 
Lynne Huffman 
Robert Pitas, Ph.D. 

Cooperating Units: None 

Man Years: Total 2.8 

Professional 1.4 
Other 1.4 



ZOl CL 10040-01 
Pioject Description 
Objectives : 

1. To elucidate the relationship between platelet function and 
athtrogenesis. 

2. To study and evaluate the effect of controlled aietary lipit 
intake on platelet function in dogs and pic.s. 

3. To develop methodologies of high specifxcity in coagulation 
studies related to the model. 

Methods Employed 

1. Platelet aggregation, dose- response titiation 

2. Platelet survival 

3. Fibrinogen survival 

4. Platelet coagulant activity 

5. Arachidonic acid metabolism 
Major Findings 

1. Severe hyperlipidemia induces increased sensitivity of platelets to 
aggregating stimulae. 

2. Atherogenesis is associated with shortening of platelet survival. 

3. Dog platelets produce arachidonic acid metabolites similar to human 
platelets. 

4. Dose-response platelet aggregation is reliable and reproducible. 

Significance 

We believe that the long suspected association between platelet function 
and atherogenesis has been established and confirmed in our animal (dog and 
pig) studies, currently in their third year. 

Proposed Course 

Examine the role of specific dietary fats and nutritive supplements on 
platelet function and atiierosclerotic lesions m bJo'". v..'ssels. 

Publications : In preparation. 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
IpROJECT number (Do NOT use this space) 



U.S. DEPARTMENT OF PROJECT NUMBER 

HEALTH, EDUCATION, AND WELFARE ' 

PUBLIC HEALTH SERVICE 1 „., „, 

NOTICE OF ZOl CL 10041-01 

INTRAMURAL RESEARCH PROJECT 



PERIOD COVERED 



July 1977 - Septeiriber 30, 1978 




TITLE OF PROJECT (80 characters or less) 




Platelet preservation: biochemical correlates 


NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 


OF PRINCIPAL INVESTIGATORS AND ALL OTHER 


1) Russell Jaffe 4) 
NIH, CCS, CPD, CC 10/4N-309 
Bethesda, MD 


Mark Franczak 

U. of Maryland/NIH 10/4N-309 

Bethesda, MD 


2) Paul V. Holland 5) 
Chief, Blood Bank Dept.,CC lO/lE-50 

Bethesda, MD 


Wanda Chappel 

Blood Bank Dept. , CC lO/lE-50 

Bethesda, MD 


3) Rita Hofberg 

CCS, CPD: CC 10/4N-309 




Bethesda, MD 




COOPERATING UNITS (if any) ' 


lab/branch 

Clinical Pathology Department 


e 


SECTION 

Clinical Chemistry Service 


INSTITUTE AND LOCATION 
Clinical Center, Bldg. 10 


TOTAL MANYEARS: 
3.4 


PROFESSIONAL: 
1.4 


lOTHERs 

2.0 


CHECK APPROPRIATE BOX(ES) 




n (a) HUMAN SUBJECTS 


□ (b) HUMAN TISSUES 


D (c) NEITHER 



:D(al) 



n (a2) INTERVIEWS 



SUMMARY OF WORK (200 words or less - underline keywords) 

Continuing investigation into biochemical correlates and predictors of 
IM VITRO platelet preservation for transfusion confirms our earlier obser- 
vation that pH does NOT predict IN VITRO platelet viability. Neither lipid 
nor selective amino acid feeding improves biochemical stability. A relation- 
ship is observed between glucose metabolism and lactate production; between 
phosphorolvsis and platelet viability, between LDH release and platelet 
viability; between donor dietary state and platelet viability and between 
qas exchange and platelet viability. Further, osmotic stress (present in 
all available transfusions models) is a reason for short IN VITRO platelet 
viability for transfusion, FINALLY, 25 detrees C appears to be superior to 
4 degrees C for platelet storage. 



ZOl CL 10041-01 

Project Title: Platelet preservation: biochemical correlates 

Previous Serial No. : None 

Principal Investigator: Russell Jaffe, I»1.D., Ph.n. 

Other Investigators: Paul V. Holland 
Rita Hofberg 
Mark Franczak 
Wanda Chappel 

Cooperating Units: None 

Man Years Total 3.4 

Professional 1.4 
Other 2.0 



ZOl CL 10041-01 
Project Description 
Objectives : 

1. Determine biochemical predictors in IN VITRO platelet viability 
for transfusion. 

2. Extend platelet concentrate shelf life. 

Methods Employed 

1. Blood gas analyses 

2. Enzyme determinations 

3. Lipid analyses 

4. Platelet counts 

5 . Liposome adducts 

6. Glucose analysis 

7. Lactic acid analysis 

8. Osmolality analysis 

9. pH analysis 



Major Findings 



pH is a codependent factor and does not predict IN VITRO survival. 

LDH release predicts IN VITRO viability 

Amino acid supplementation does not enhance survival 

Lipid supplementation does not enhance survival 

Isomolar conditions improve viability 

Donot dietary state correlates with IN VITRO survival 

25 C storage is superior to 4 C storage 

Phosphorolysis correlates with loss of cell viability 



Significance 

Prolongation of platelet storage by at least 100% is possible based 
on our observations. An easy and widely available enzyme assay may be the 
best available predictor of transfusion viability. 

Proposed Course 

Do prospective clinical trial to test the hypothesis formulated con- 
cerning predictable prolongation of platelet shelf life. 

Publications 



In preparation 



SMITHSONIAN SCIENCE INFORMATION tXCHANGE 
PROJECT NUMBER (Do NOT use this space) 



U.S. DEPARTMENT OF 



PROJECT NUMBER 



HEALTH, EDUCATION, AND WELFARE ' 
PUBLIC HEALTH SERVICE "i 

NOTICE OF I ''01 CT iro42-o: 

INTRAMURAL RESEARCH PROJECT | 



PERIOD COVERED 



July 1977 - September 30, 1978 



TITLE OF PROJECT (80 characters or less) 
Cryoglobulin and cryof ibrinogen detection in plasma 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



1) Dr. Russell Jaffc 

NIH, CCS, CPD, CC 10/4n_309 
Bethesda, MD 



2) Miss Theresa Wilson 

NIH, CCS, CPD, CC 10/4N-309 



COOPERATING UNITS (if any) 



LAB/BRANCH 

Clinical Pathnlngy nepartment 
SECTION 

Clinical Chemist r y Service 



INSTITUTE AND LOCATION 

Clin i ca l Cent 



Rld g 



fOTAL MANYEARS: 
2.1 



PROFESSIONAL: 
LJ 



1.0 



CHECK APPROPRIATE BOX(ES) 
□ (a) HUMAN SUBJECTS 

n (al) MINORS n (a2) INTERVIEWS 



B{(b) HUMAN TISSUES 



n (c) NEITHER 



SUMMARY OF WORK (200 words or U 



underline keywords) 



Simultaneous detection of cryoglobulins and cryofibrinogen s in human 
plasma is confirmed in over 600 clinical chemistry specimens. Results are 
similar in carefully prepared s erum c.nd citrated plasma. The latter method 
is technically superior and easiei. Positive assays are confirmed by 
electrophoresis of plasma supernatanv kept at 4 C at all times (control) 
and plasma supernatant rewarmed to 37 C after being preci].- itated at 4 C (test) 

we find 30° of patitntr w: th lupus erythematosa'^ , rheumatoid arthritis , 
myelonas, dysproteiremiao , c-lmically significant urticarias to be positive 
foL cryoglobulins. In our asymptorat ^ c (c:ri<-rol) population, we find 8% 
positive specimens. Cryofibrinogens are exceedingly rare. 



PHS-6040 



ZOl CL 10042-01 

Project Title: Cryoglobulin and cryof ibrinogen detection in plasma 

Previous Serival No.: None 

Principal Investigator: Dr. Russell Jaffa 

Other Investigators: Miss Theresa Wilson 

Cooperating Units : None 

Man Years: Total 2.1 

Professional 1.1 
Other 1.0 



i' 



ZOl CL 10042-01 
Project Description 
Objectives 

1. To apply a new and reliable methodology to assay of cryoglobulins 

2. To apply an improved procedure for detection of cryof ibrinogens 

3. To apply a single approach to simultaneous analysis of all 
cryoproteins 

Methods Employed 

1. Plasma is analyzed from human source 

2. Microzone electrophoresis is performed for confirmation of results. 
Manor -Findings 

1. A clinically applicable technique for cryoprotein identification 
yields results comparable to research-laboratory methods. 

2. In asymptomatic populations, 8% of specimens are positive. 

3. In patients with arthritis, lupus, urticaria, dysproteinemias, and 
myelomas over 30% of specimens are positive. 

4. Results on plasma and serum are sim.ilar 

5. Occasional ono-globulin migrating cryoproteins are detected 

Si gnificance 

An easy, r.-^'liable, controllable assay for cryoproteins is undergoing 
further clinical trial. It may be helpful in the clinical management of 
patients with cold sensitivity or undergoing therapy which might effect 
protein synthesis. 

Pij pose ^ Course 

Continue^ cl:nical evaluation. Apply methodology to cold agglutinin 
testing in mi cr.^biology and blood bank laboratories. 

Publi cations 

In or^"oara"ion 



October 1, 1977 through September 30, 1978 



PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 
SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 
CRITICAL CARE MEDICINE DEPARTMENT 



Department Missions and Goals CCM-i 

Department Activities CCM-1 

Clinical Consultative Service CCM-1 

Critical Care Unit CCM-2 

Physiological Monitoring Section CCM-2 

Respiratory Therapy Section CCM-2 

Major Progress in Research, Training and Development CCM-2 

Table I and II CCM-4 



CCM-i 



I Department Missions and Goals 

The Department of Critical Care Medicine was established in November 
1977, to care for critically ill patients throughout the Clinical 
Center who have potentially reversible medical problems. Critical 
care medicine may be defined as the observation, diagnosis, treatment, 
and rehabilitation of patients with overt or potential failure of vital 
functions . 

The need for critical care medicine services has been stimulated by the 
gradual extension of clinical investigation to patients who are 
critically ill with potentially reversible medical problems. 

The Department is responsible for the respiratory therapy and physio- 
logical monitoring services because of their frequent utilization by 
critically ill patients. It is currently composed of the following 
administrative sections: 

1. Clinical consultative services 

2. Critical care unit 

3. Physiological monitoring 

4. Respiratory therapy 

The function of the Department is to (a) provide optimal care for 
Clinical Center patients who may benefit from careful nursing observation 
to those patients requiring the application of one or more major life 
support systems, (b) work to improve both understanding and prevention 
of acute problems which frequently necessitate the need for critical 
care and (c) develop the best possible equipment, techniques, and 
systems for the management of the critically ill. 

The activities of the Department have been directed principally towards: 

1. Organizing and developing a department capable of providing 
a full spectrum of critical care services to the Clinical 
Center . 

2. Designing, organizing, and constructing a critical care unit 
which will be readily accessible and easily utilized by any 
Clinical Center physician. 

3. Developing a consultative service to assist in the management 
and care of critically ill patients throughout the hospital. 

4. Developing and presenting an educational program for technicians, 
nurses, and physicians interested in critical care medicine. 

II Department Activities 

A. Clinical Consultative Service. Since its formulation the Department 
has provided consultative service directed toward all aspects of 
the management of the critically ill patient. Detailed assistance 



in the evaluation of patients and institution of respiratory and 
hemodynamic life support systems have been provided; patients 
have been followed throughout the duration of that phase of their 
illness requiring life support measures. The consultative service 
is available on a twenty-four hour a day basis, seven days a week. 

B. Critical Care Unit . The planning and design of a critical care unit, 
which will occupy the 10-D wing has been completed and construct- 
ion has commenced. Basic medical equipment has been ordered in- 
cluding an automated data collection system designed to facilitate 
hour to hour and day to day management of the patients and, in 
addition, to provide for the storage of archival data to facilitate 
subsequent clinical investigation, A vascular research console has 
been designed to facilitate the detailed assessment of the hemo- 
dynamic status of patients and to permit vascular diagnostic 
studies to be performed on critically ill patients. 

The Chief Technician for the Critical Care Unit has joined the 
Department, and recruitment of additional technical staff is 
currently underway. Protocols for the management of common medical 
problems anticipated in the unit have been written and developed. 

C. Physiological Monitoring Section . This section supplies, operates, 
and maintains physiological monitoring equipment utilized through- 
out the hospital. This includes the telementry of ECG signals, 

and the measurement of respiratory and vascular parameters both at . 
the bedside and within the recovery room and intensive care units 
throughout the Clinical Center. This service is provided from 
7 AM until 12:30 AM, Monday through Friday, and on an On Call 
basis at all other times. Four full-time permanent technicians 
provide this service. A summary of the services provided is 
listed in Table I. 

D. Respiratory Therapy Section . This section provides a full spectrum 
of respiratory therapy services (intermittent, positive pressure 
breathing, ultrasonic nebulization, incentive spirometry, oxygen 
therapy, chest physiotherapy, and mechanical ventilation), for all 
Clinical Center patients. This section also provides, as an adjunct 
service, blood gas determinations for the Anesthesiology Recovery 
Room and for one of the research projects sponsored by the National 
Cancer Institute. Respiratory therapy services are available on a 
twenty-four hour day basis, and the staff coverage is provided by 
eleven full-time technicians and one part-time technician. A 
siimmary of this section's activities is presented in Table II. 

Ill Major Progress in Research, Training and Development 

With the invaluable assistance of the Laboratory of Computer Sciences 
of the Division of Computer Resources and Technology, an automated 
data collection system is being designed and programmed to provide real 
time to collect all data for flow sheet generation. These Protocols || 



CCM-2 



are being developed, written and debugged prior to the opening of the 
unit in late 1978 which emphasize management of specific problems 
likely to be encountered within the Critical Care Unit. 

Training of critical care technicians, nurses and physicians interested 
in critical care medicine has been instituted through formal courses 
offered by FAES . 

Research activities will not be instituted until all sections of the 
Department are organized, intergrated, and functioning. 

Recruitment of three senior physicians with major interests in critical 
care medicine will be initiated now that a target date for opening of 
the Critical Care Medicine Unit has been formalized. 



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1 

I 
October 1, 1977 through September 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

DIAGNOSTIC RADIOLOGY DEPARTMENT 

CONTENTS 

Department Missions and Goals DR-l 

Departmental Activities DR-1 

Major Projects and Research DR-5 

Problems .• DR- 

Summary of Departmental Activities DR-7 

Publications DR-8 



Project Reports: 

1 .Development and Clinical Evaluation of Ultrasonic Signal . . . .DR-12 

2. Evaluation of CT Body Scanning in Oncologic Patients DR-14 

3. Evaluation of Contrast Agents for Transcatheter Organ Ablation. .DR-15 

4. Evaluation of Serial Hepatic Scans in Patients with Primary and 

Secondary Hemochromatosis DR-18 

5. Development of an Opaque Agent for Opacification of the Liver on 
Computed Tomography DR-20 

6. IV Hepatosplenography DR-22 



DR-i 



r 







October 1, 1977 through September 30, 1978 



PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

DIAGNOSTIC RADIOLOGY DEPARTMENT 

DEPARTMENTAL MISSIONS AND GOALS 

In addition to providing radiologic service to the patients of the Clinical 
Center, we have changed departmental emphasis in the past year. 1) Continued 
efforts to encourage research activity in the department - efforts which have 
been rewarded by increased independent and collaborative research productivity. 

2) We have sought a satisfactory balance between our clinical, research 
and teaching activities. Interdepartmental clinical radiographic conferences 
have improved the quality of patient care by developing a clinical team 
more responsive to patient needs and more understanding of the diagnostic 
modalities offered by a modern radiologic department. Teaching and 
clinical conferences have proven too successful - we are unable to 

fulfill all requests for radiologist participation in such activities. 

3) In keeping with the President's directive about radiation exposure 
levels, we have hired a department physicist whose efforts are in part 
directed toward the development of radiographic examination techniques 
which minimize xray exposures delivered to patients and staff. Emphasis is 
being placed on realistic control of diagnostic xray exposure, in the 
department in our discussions with clinicians. 4) We are attempting to in- 
crease department administration, efficiency and responsiveness. The 
office of the Director of the Clinical Center is assisting. Emphasis is 
being placed on the investigation, development, perfection, and use of 
interventional radiographic techniques. Radiographically directed and 
controlled local administration of chemotherapeutic agents, use of 
temporary or permanent vaso occlusive techniques, superselective vascular 
samplings and directed percutaneous biopsies have gained support from 

the physicians of the Clinical Center. 

DEPARTMENTAL ACTIVITIES 

Though the number of conventional x-rays produced by the department from 1977 
to June 1978 decreased slightly (3%) in comparison to last year, the 
total number of diagnostic examinations performed remained the same. 
The workload mix in the department is changing somewhat with increasing 
demands being placed on us to perform examinations which are expensive 
in terms of equipment, personnel and time required. Increases in the 
number of special procedures (+5%), computerized tomographic examinations 
of the head (+7%), ultrasonic studies (+10%), computerized tomographic 
examinations of the body (+113%) have been observed. (See the accompanying 
table of Summary of Departmental Activity, DR-8). 



DR-1 



Computed Tomography 

I I i 

Acceptance of CT scanning techniques is reflected in the fact that from July 
1977 - June 1978 we performed a total of 4,484 scans as compared to 3,454 the 
previous year. The zenith of our CT head scanning program has been passed and 
we anticipate that next year's annual report will reflect a slight to 
moderate decrease in the number of head scans reported. Until recently we 
provided scanning services to metropolitan area DOD medical facilities. 
As both WRAMC and USNMC have recently completed installation of CT 
scanners, the benefits to us of such referrals which supplemented the 
rather select NIH patient load with patients with a normal mix of neurologic 
disorders, will cease. We are considering to offer our head scanning capabili- 
ty to other governmental institutions in the area, in hopes of maintaining a 
challenging and instructive mix of neuropathology. We will try to continue 
scanning adequate numbers of patients with diverse abnormalities. 

Some growth in the number of CT body scans is to be anticipated. The I 
growth will be limited in that we have been working the body scanner very close 
to its capacity. Further increases in our patient load will require acquisition 
of newer scanning units which provide shorter scanning and data processing times 
The explosion of technologic development which followed the introduction 
of CT scanning has quieted. Because manufacturers have en-countered serious 
design and physical limitations to further improvements, we may 
observe a more sedate pace of development in the future. We welcome this slower 
pace of technologic development, as long as deliberate evaluation of the 
commercially available scanners is done. Acquisition costs of $6-800,000 ar^ 
sufficiently high to preclude the panic buying observed during the embryonic J' 
stages of CT development. 

The Director of the Clinical Center has been apprised of our CT needs; 
i.e., decreasing patient demand for head scans and continued increase in 
the requirements for body scanning. Guided by this fact, we have planned 
to replace the dedicated head scanner with a high speed universal scanner 
which will meet anticipated Clinical Center requirements for CT. Though 
the existing CT equipment fulfills our immediate needs, the changing 
pattern of these needs demands a change in our scanning capacity. 

The CT scanners in the Department of Diagnostic Radiology require the 
full time of 2 radiologists, 4 technicians, one appointment file clerk 
and the part time energies of our physicist. Maintanence costs were 
$71,000 this year, an increase over last year's expenditure. Warranty 
periods have expired on the equipment and contract costs for maintanence 
have increased. 

Ultrasound 

Unexpectedly, the number of ultrasonic examinations has shown further , 

increase (10% over last year) though the space dedicated to this function 

is small and congested. In addition to increasing its patient load the I 

ultrasound section of the Diagnostic Radiology Department has continued 

yery actively in research and development of new techniques and equipment. | u 



DR-2 



In cooperation with the National Bureau of Standards the development of 
the real-time sector scanner has been completed but the unit is now 
being modified by the addition of a digital scan converter to improve 
scan images. A portable real-time scanner has been perfected which 
permits us for the first time to scan the "jery ill on their wards - 
heretofore patients had to be transported to the Diagnostic Radiology 
Department for such examinations. The Sonochromatoscope (tissue signature 
scanner) demands more professional and technician research time for its 
development but it shows promise of being able to deliver numerical 
readouts of data which will permit differentiation of normal and abnormal 
tissues. The ultrasonic facility requires the full time of two radiologists, 
two technicians, and an appointment file clerk. 

We have assumed the responsibilities for CT and ultrasonic scanning with no 
increase in professional or technical staff. 

Special X-Ray Procedures 

There has been a further increase in the number of CT head exams performed 
synchronous with a continuing decrease in the number of special neuro- 
diagnostic procedures (PEGs and cerebral angiograms). Most of this 
change is explained by the profound decrease in the number of NINCDS 
patients admitted who require special x-ray studies. 

Head Cerebral 
Dates CT Angios Pneumos 

7/1/74 - 6/30/75 - 135 52 

7/1/75 - 6/30/76 1877 94 13 

7/1/76 - 6/30/77 2750 67 9 

7/1/77 - 6/30/78 2936 72 6 

We may well observe a striking reversal of this trend next year after the 
arrival at the Clinical Center of the new neurosurgical staff. In spite of the 
paucity of neuroradiologic procedures there has been a slight increase in 
the numbers of special procedures in the past year (713 to 745). With each year 
a greater proportion of these examinations require multiple selective 
and superselective catheterizations, therapeutic embolization or fluoros- 
copically directed chemotherapeutic infusions. Some of these procedures 
may last 2 1/2-3 hours and require the presence of at least one radi- 
ologist, two technicians and two nurses. The demands made on the department 
by such examinations can in no way be equated with the special procedures we 
performed several years ago. 

Research Facility 

The activity of the radiophic research facility is not accurately reflected 
by the statistics which reveal a 9% decrease in the number of exams 



DR-3 



performed this year as compared to last. Larger proportions of the 
studies performed in the research labs involve the use of physiologic #lj" 
monitoring equipment, ancillary CT scanning, and biochemical assays - ^ ' 
information not revealed by data which indicates a 9% decrease in activity. 
A significant proportion of the departmental publications evolved from 
the work performed in this cramped and inadequate area. Two fulltime 
technicians work with a rotating group of radiologists to maintain the 
research facility. 

Teaching and Education 

Our teaching and educational conferences have been so well received that 
we are unaole to meet the requests for further increases in the number of such 
activities. We average more than two interdepartmental conferences each 
day. Members of the staff continue to give teaching sessions at D.C. 
General Hospital, USNMC, GWU Hospital and the AFIP. Students from the 
USUHS third year class are rotating through our department on a regular 
basis for clinical experience. The ultrasound section of the Diagnostic 
Radiology Department hosted a national ultrasound meeting at the NIH 
which was attended by 225 registrees and a large number of the NIH 
staff. Weekly x-ray technician's meetings have been added to the educa- 
tional agenda to help fulfill the technicians' desire for a program of 
continuing education. 

Hours of Coverage 

Responding to the needs of the patient care staff of the Clinical Center r"]| 
we began providing longer hours of clerk coverage in the X-Ray film 
library. During the year in-house technician coverage of the department 
has been increased twice. We now supply 24 hr/day in-house technician 
coverage, without increase in the total number of technicians employed. 

Equipment Acquisition 

Save for the new ultrasonic scanner, no major capital equipment was 
acquired in the past year. There has been additional modernization of 
the CT body scanner which further improves image quality and speed of 
data processing. Moderate expenditure for film processors, rapid filming 
devices and physiologic monitoring equipment was made. Purchase of a 
universal CT scanner has been deferred until this coming fiscal year 
pending demonstration by the manufacturer that the new equipment will 
meet our demands. Our continuing deferral of major purchases is inten- 
tional and is designed to permit acquisition of the most modern machinery 
possible for installation in the new department. We anticipate moving 
\/ery little, if any, of our current equipment into the ACRF. Such a 
decision, of course, requires the commitment of very large sums of money 
for major capital purchases prior to opening the new department. 



^R-4^ 



MAJOR PROJECTS AND RESEARCH 

Listed below are the major research projects now under investigation in 
the department. The appended description of the projects are adequate 
and require no summation. (See Project Reports, pp DR12-DR23). 



1. Evaluation of Contrast Agents for Transcatheter Organ Ablation 

2. Development and Clinical Evaluation of Ultrasonic Signal 

3. Evaluation of CT Body Scanning in Oncologic Patients 

4. Evaluation of Serial Hepatic Scans in Patients with Primary and 
Secondary Hemochromatosis 

5. Development of an Opaque Agent for Opacification of the Liver 
on CT 

6. IV Hepatosplenography 



DR-5 



PROBLEMS 

^ t' 

The problem areas of the department, which are the same as last year, con- 
tinue to grow. 

1. SPACE for patient waiting has become totally inadequate. Our halls 
are choked with patients, on occasion the mix may include members of 
Congress, ambulatory outpatients, and acutely ill or even moribund 
stretcher patients. The area dedicated to patient waiting has pro- 
gressively decreased over the past 25 years as our work load has in- 
creased. 

The same observation must be made regarding work areas for our physi- 
cians - the departmental MD staff has more than doubled since the late 
1950's without any increase in office space. Some physicians are now 
forced to work in converted janitorial closets. 

For over a year we have been awaiting the installation of the 
automated chest unit and diagnostic table in the Out Patient Depart- 
ment (the equipment is gathering dust in storage). The benefits 
to be derived from these units to the physicians in the OPD 
have been detailed in past reports. An estimated 35% decrease 
in elevator traffic between the first and sixth floors can be 
anticipated when the installation is complete. Upon ompletion 
of the OPD some space in the department will become avail ble to 
permit for the absolutely essential expansion of our ultraound arei ) 



2. PHYSICIAN RECRUITMENT AND STAFF RETENTION have become progressively 
more difficult problems. We can no longer offer salaries even 
closely competitive to those paid by major universities. There is 
a total disarray of the pay scales for federal physicians: 
contracts are offered to radiologists by Army hospitals for $97,000 
+/per annum and at the same time that fully trained board certified 
radiologists are asked to enter the Public Health Service at $32,000. 
Contract physicians now staff the radiology department at WRAMC, 
perhaps the finest military hospital in the world, at salary levels 
of approximately $100, 000. To have any chance of recruiting and re- 
taining staff we must have funding adequate to maintain a stimula- 
ting clinical and research environment. Funds for meetings and con- 
tinuing education courses must be generous. 

3. RESEARCH FACILITY INADEQUACY has been noted for the past several 
years in the 1977 annual report we said, "Last year the inadequate 
research facilities available to the staff were decried. The avail- 
able research area has been further significantly erroded by the 
loss of animal holding space - animal subjects must now be housed in 
the research area - an unconscionable situation in an institution 
devoted and dedicated to fostering superior research." 

These remarks need re-emphasis, y^ 



DR-6 



SUMMARY OF DEPARTMENTAL ACTIVITIES 



7/\ne-e/2Qni 7/1/77-6/30/78 % change 



#MDs 


13 


13 





#Technicians 


26 


24-26 


to -8% 


#Other Staff 


23 


26 


+13% 


#X-ray Exams 


47284 


45906 


-3% 


#Department Diagnostic Exams 


53746 


53515 





#Specials 


713 


745 


+5% 


#CT Head 


2750 


2936 


+7% 


#CT Body 


704 


1548" 


+113% 


#Lntrasound Exams 


1560 


1708 


+10% 


#Animal Research Exams 


735 


672 


-9% 


#Publi cations 


40 


m 


+30% 



DR-7 



PUBLICATIONS: 

f 
Alderson PO, Doppman JL, Diamond SS, Mendenhall KG, Barron EL and Girton 
M: Ventilation Perfusion Lung Imaging and Selective Pulmonary Angiography 
in Animals with Experimental Pulmonary Embolism. J Nucl Med 19: 164- 
171, 1978 

Bagley DH, Felix EL, Sindelar WF, Doppman JL, and Ketcham AS: Barium 
Enema, Proctosigmoidoscopy and Upper Gastrointestinal Series in the 
Preoperative Evaluation of the Cancer Patient. Cancer 39: 1743-1747, 
1977 

Bagley DH, Sindelar WF, Felix EL, Doppman JL and Ketcham AS: Excretory 
Urography in Evaluation of the Surgical Patient. Surg Oncol 10: 59-65, 
1978 

Brennan MF, Doppman JL, Marx SJ, Spiegel AM, Brown EM and Aurbach 6D: ^.^ 
Reoperative Parathyroid Surgery for Persistent Hyperparathyroidism ^r 
Surgery 83: 669-576,1978 ^p 

Brennan MF, Brown EM, Marx SJ, Spiegel AM, Broadus AE, Doppman JL, 
Weber, Bruce and Aurbach GD: Parathyroid Autotransplantatfon with 
Adenomatous Parathyroid Tissue: A Source of Recurrent Hyperparathyroidism. 
Ann Surg . In Press 

Brereton HD, 0"Donnell JF, Kent CH, Mathews M, Dunnick NR and Johnson i 
RE: Spinal Meningeal Carcinomatosis in Small Cell Carcinoma of the Lung. 
Ann Int Med 88: 517-519,1978 

Broughton WL, Gee W, Doppman JL and Ommaya A: Nonpulsatile Exophthalmos 
in Carotid-Cavernous Sinus Fistula, J Ped Ophthalmology 14: 221-227, 
Jul/Aug 1977 

Chang AE, Schanner EG, Conkle DM, Flye WM, Doppman JL and Rosenbweg SA: 
Evaluation of Computed Tomography in the Detection of Pulmonary Metastases. 
Cancer In Press 

Doppman JL, Girton M and Kahn ER: Proximal vs Peripheral Hepatic Artery 
Embolization: Experimental Study in Monkeys. Radiol In Press 

Doppman JL, Dunnick NR, Girton M and Fauci AS: Bile Duct Cysts Secondary 
to Liver Infarcts: Experimental Production by Small Vessel Hepatic 
Artery Occlusion and Clinical Correlation. Radiol In Press 

Doppman JL, Brown EM, Brennan MF, Spiegel AM, Marx SJ and Aurbach GD: 
Deliberate Angiographic Staining of Parathyroid Adenomas. Radiol In Press 

Doppman JL: " Embolization of Arteriovenous Malformations": Spinal Angiomas , 
New York, Springer-Verlag, 1978, pp - In Press 



DR-i 



Doppman JL: "Islet Cell Tumors" and "Medullary Carcinoma of the Thyroid 

and Multiple Endocrine Adenomatosis II and III" in SURGICAL RADIOLOGY 

edited by Drs Teplick and Haskin, W.B. Saunders Company, 1978 pp In 
Press 

Doppman JL, Aven W, Bowman RL, Wood L and Girton M: Hypol - A Rapidly 
Polymerizing Polyurethane for Transcatheter Embolization. Cardiovascular Radiol 
1: 109-116, 1978 

Doppman JL, Brennan MF and Brown EM: Tracheal Overlap: Arteriographic 

Sign of Parathyroid Adenomas in Posterior Superior Mediastinum. Am J Roentgenol 

130: 1197-1199, 1978 

Dunnick NR: "Radiographic Evaluation" in PRINCIPLES AND MANAGEMENT OF 
UROLOGIC CANCER edited by Javadpour, Nasser, Williams & Wilkins publishers 
1978 pp In Press 

Dunnick NR, Anderson Tom: Distant Metastases to Bone from Carcinoma of 
the Bladder. Am J Roentgenol In Press 

Dunnick NR and Harwick A: Lymphography in Patients Following Leg Amputation. ^'■ 
Radiol In Press 

Dunnick NR, Horvath K, Head GL and Bender RA: Lymphography in Unresectable 
Adenocarcinoma of the Endocrine Pancreas, Lymphology In Press 

Dunnick NR, Doppman JL and Brereton HD: Balloon Occlusion of Segmental 
Hepatic Arteries for Control of Biopsy Induced Hemobilia. JAMA 238: 
2524-2526, Dec 5, 1977 

Dunnick NR, Schaner EG and Doppman JL: Detection of Subcutaneous 
Metastases by CT. J Comput Assisted Tomogr 2: 275-279, 1978 

Dunnick WR, Schuette WH and Shawker TH: Ultrasonic Demonstration of 
Thrombus in the Common Carotid Artery. J Clinical Ultrasound In Press 

Dunnick NR, Wixson D, Doppman JL, Bokinski G and Javadpour Nasser: 
Metastatic Hypernephroma to the Remaining Kidney 14 years after Nephrectomy: 
Report of 2 Cases. Am J Roentgenol In Press 

Dunnick NR, Schaner EG, Doppman Jl, Strott CA, Gill JR and Javadpour, 
Nasser: CT in Adrenal Tumors. Am J Roentgenol In Press 

Dunnick NR, Head GL, Peck GL and Yoder FW: Basal Cell Nevus Syndrome: 
Radiographic Manifestations including Cystlike Lesions of the Phanges. 
Radiol In Press 

Dwyer A: The Displaced Crus : A Sign for Distinguishing Between Pleural 
Fluid and Ascites on Computed Tomography. J Comput Assisted Tomogr 



DR-9 



Fauci AS, Doppman JL and Wolff S: Cyclophosphamide - Induced Remissions . 
in Advanced Polyarteritis Nodosa. Am J Med 64: 890-894,1978 I f 

Geelhoed GW and Doppman JL: Embolization of Ectopic Parathyroid Adenomas. 
A Percutaneous Treatment of Hyperparathyroidism. The Am Sug 44: 71-80, 1978 

Grimes G, Vermesss M, Gallelli JF, Girton M and Chatterji: Formulation 
and Evaluation of Ethiodized Oil Emulsion for Intravenous Hepatography. 
J of Pharmaceutical Sciences In Press 

Kalman MA: Radiographic Soft Tissue Shadows in the Pelvis: Another 
Look. Am J Roentgenol 130: 493-498, 1978 

Kollarits CR, Moss ML, Cogan DG, Doppman JL, Di Chiro G, Curler GB, Marx 
SJ and Spiegel AM: Sceral Calcifications in Hyperparathyroidism. 
Demonstration by Computed Tomography. J Comput Tomog 1 : 500-504, 1977 

Maguire R, Fauci AS, Doppman JL and Wolff SM: Unusual Radiographic 
Features of Wegener's Granulomatosis. Am J Roentgenol 130: 233-238, 
1978 

Mills SR, Doppman JL and Kahn ER: Metastatic Islet Cell Carcinoma to z' 
the Liver Visualized only after Intra Arterial Epine;phrine. Am J ■' 

Roentgenol In Press i> 

Mills SR, Doppman JL, Head GL, Javadpour Nasser, Brennan MF and Chu EW: . :, ^ 
Transcatheter Brush Biopsy of- Intravenous Tumor Thrombi. Radiol 127: * i' f 
667-670, 1978 



Popovsky MA, Costa JC and Doppman JL: Myenburg's Complex of the 

Liv:er and Bile Cysts as a Consequence of Hepatic Ischemia. Human Pathology 

In Press 

Javadpour N, Doppman JL, Bergman SM Anderson T: Correlation of 
Computerized Tomography (CT) and Serum Tumor Markers in Metastatic 
Retroperitoneal Testicular Tumor. J Comput Assisted Tomogr 2: 176- 
180, 1978 

Schaner EG, Horvath K, Balow J and Doppman JL: Computed Tomography in 
the Evaluation of Renal, Adrenal and Retroperitoneal Hemorrhage. 
Excerpta Medica In Press 

Schaner EG, Dunnick NR, Doppman JL, Strott CA, Gill JR and Javadpour N: 
Low Mu Adrenal Cortical Tumors - A Pitfall in CT Diagnosis: A report of 
four cases. J Comput Assisted Tomogr 2: 11-15, 1978 

Schanner EG, Head GL, Kalman MA, Dunnick NR and Doppman JL: Whole Body 
Computed Tomography in the Diagnosis of Abdominal and Thoracic Malignancy: 
Review of 600 Cases. Cancer Treatment Reports 61 : 1537-1560, 1977 



DR-TO 



V 



( II 



Shawker TH, Schuette WH and Whitehouse Wm: An Ultrasonic Real-Time 
Sector Scanner for the Assessment of Early Fetal Development. 
Proceedings of Second International Workshop on Diagnostic Ultrasound 
Imaging , Cairo, Apr 1978 

Shawker TH: Changes in Normal Anatomical Structures due to the Growth 
and Spread of Abdominal Malignancies. Proceedings of Second International 
Workshop on Diagnostic Ultrasound Imaging , Cairo, Apr 1978 

Shawker TH, Schuette WH and Whitehous Wm: Real-Time Sector Scanning of 
Common Abdominal Disease. Proceedings of Second International Workshop on 
Ultrasound Imaging , Cairo, Apr 1978 

Shawker TH, Schuette WH and Whitehouse Wm: Ultrasound Evaluation of the 

Upper Abdomen with the Real-Time Sector Scanner Ultrasound in Med 4: 101-109, 

1978 

Shawker TH and Steinfeld AD: Ultrasound Evaluation of the Pulsatile 
Abdominal Mass. JAMA 239: 419-422, Jan 30, 1978 

Schuette WH, Shawker TH and Whitehous Wm: Television Synchronization 
of a Real-Time Ultrasonic Sector Scanner. J Clin Ultraound In Press 

Spiegel AM, Doppman JL, Marx SJ, Brennan MF, Brown EM, Downs RW, Gardner GD, 
Attie M and Aurbach GD: Preoperative Localization of Abnormal Parathyroid 
Neck Massages vs Arteriography and Selective Venous Sampling. Ann Int Med 
In Press 

Vermess M, Haynes BF, Fauci AF and Wolff SM: Orbital Manifestations of 
Wegener's Granulomatosis on Computerized Tomography, J Comput Assisted 
Tomogr 2: 45-48, 1978 

Vermess M, Adamson RA, Doppman JL and Girton M: Computed Tomographic 
Demonstration of Hepatic Tumor with the Aid of Intravenous lodinated Fat 
Emulsion: An Experimental Study. Radiol 125: 711-715, 1977 

Von Hoff DD, and Dunnick NR: The Case of the Triangular Foreign Body. 
JAMA In Press 

Wood JH, Doppman JL, Lightfoote WE, Girton M and Ommaya AJ : Role of 
Vascular Proliferation on Angiographic Appearance and Encapsulation of 
Experimental Traumatic and Metastatic Brain Abscesses. J Neurosurg 48: 
264-273, 1978 

Weingrad DW, Doppman JL and Chretien PB: Post-Traumatic Pelvic Arteriovenous 
Fistula with Progressive Paraplegia: Treatment by Combined Surgical/Embolic 
Approach. Surgery In Press 

Wright S, Girton M, Doppman JL, Pevsner P, Catravas GN, Williams 0, Fouts T and 
Dillard D: An Experimental Cerebral Biobonded Arteriovenous Fistual 
Model in Primates. Stroke In Press 



DR-1^ 



r J 



July 1, 1977 through June 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

ENVIRONMENTAL SANITATION CONTROL DEPARTMENT 

CONTENTS 

Missions and Goals ES-1 

Department Activities ES-1 

Major Progress in Research, Services, Training and Development ES-3 

Future Objectives Directed Toward Meeting Goals ES-4 

Table 

1. Formal Training - Classroom ES-5 

2. Positions Filled by Recruitment ES-7 

3. Number of Separations, Resignations, etc ES-8 

4. Reasons for Personnel Leaving ES-9 



(I 



CI 



o 



July 1, 1977 through June 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

ENVIRONMENTAL SANITATION CONTROL DEPARTMENT 

MISSIONS AND GOALS 

The primary objectives of the Environmental Sanitation Control Department 
during the year were to: 

1. Provide the safest possible sanitary environment for the Institutes 
and services in the Clinical Center. 

2. Provide a dependable, efficient, elevator service responsive to the 
requirements of patients, emergencies, staff, and visitors. 

3. Study the Department's manpower requirements and formalize its work and 
personnel procedures. 

4. Orient, train and supervise its personnel so that they are proficient 
in carrying out the program objectives. 

5; Test various products and equipment in order to utilize the most modern 
housekeeping practices. 

6. Cope with day-to-day environmental problems within the Clinical Center 
and study the total environmental problems within the Clinical Center as 
they relate to an institutional setting. 

7. Develop an objective evaluation of the housekeeping program. 
DEPARTMENT ACTIVITIES 

Employee turnover continues to be low. Thirty-four new employees entered 
on duty and thirty-two left. Table 4 shows that 6 resigned, 1 transferred, 
10 retired, 14 were terminated and 1 deceased. 

Individual employees and groups received 24 letters of appreciation or 
commendation from building tenants for services rendered. 

The Department coordinated the selection, procurement, and installation of 
approximately 2,277 yards of carpeting during the year. This includes 
replacing 677 yards of existing carpeting. We have been able to find 12 
carpet qualities within GSA Contract Schedules that meet DHEW standards. 



Operator-controlled passenger elevator service was extended to 7:00 PM on 
the "D" wing elevators. This was made necessary because of changing traf 
patterns within the building that resulted from ACRF (construction. 



A procedure for providing special elevator service on elevator 15 was 
developed in cooperation with Surgical Nursing Service. Change was needed 
because the regular passenger elevator is not large enough to accomodate 
the patient, bed, and surgical support team. The new procedure has worked 
well . 

All ESCD employees received copies of the newly revised "Negotiated 
Agreement beteen National Institutes of Health and Washington Area Metal 
Trades Councel . " 



V 



iMAJOR PROGRESS IN RESEARCH, SERV ICE S, TRAINING AND DEVELOPMENT 

Construction of the ACRE and building renovations continued to present the 
Department with its greatest challange. In addition to uncounted minor 
projects, during the year, there were several major projects affecting all 
areas of the building. While renovations are in progress the natural re- 
action is to throw in the dust towel and give up on housekeeping until 
conditions settle and housekeeping can be handled in a normal routine 
fashion. 

However, renovation creates conditions which call for an actual intensifica- 
tion of housekeeping activities. There is a very real problem of maintenance 
becoming considerable more difficult, both from a psychological and a prac- 
tical performance standpoint, while at the same time it becomes more import- 
ant. 

The Department experienced minimal inconvenience because of a emergency 
shortage created by a breakdown at Washington Suburban Sanitary Commission 
facilities during the first week of July. Normal cleaning activities were 
uninterrupted in patient care units. No wet cleaning was done in non- 
patient units. Preparations were made to provide emergency water in G.I. 
cans to each nursing unit if it was required. 

Construction of the ACRE created many novel problems for the ESCD: areas 
adjacent to the construction had to be protected from contamination by the 
soils and waste material produced in renovation; floors became badly damaged 
by scratching or abrading, tracking in of particles of concrete, metal chips, 
splinters, mud, etc; air-borne waste particles and dust could damage office 
equipment and mechanical systems. Comfort became an important factor since 
people react to unpleasant conditions caused by excessive dust and soil. 

Infection control became more difficult. The basic housekeeping principle 
during ACRE Construction renovation has been isolation: the remodeling 
work and its by-products have been completely isolated from the portion 
of the building not involved. Some of the more effective steps in this 
direction are containment barriers around the work area, mats and runners 
in connectiong areas to entrap as much soil and dirt as possible and restirc" 
tion of sightseers walking through the area and tracking soil back intib 
other areas . 

Night Service Section began implementing a new system for cleaning in 
laboratory and office areas. This system, called "team" or "squad" cleaning 
replaces a system of area responsibility which had been in use, with minor 
modifications since the Clinical Center opened. 

In squad cleaning, teams are formed to perform certain cleaning tasks such 
as waste pick up, mopping, etc., on several floors. The objectives of the 
new system are 1) to equalize work loads, 2) to assure all essential cleaning 
is completed nightly, and 3) to promote team work and overall effectiveness 
of the Section. 



The emergency assistance program for the Department operated satisfactorily 
during the year. Elevator Operators and others were briefed several times ^^ :|| 
on emergency procedures. Water pick-up equipment was renovated and replaced 
during the year and operated in a very satisfactory manner. The following 
emergencies were encountered during the year: 



Floods 

Fires 

Acid Spills 

Others 



52 calls for 189 1/4 staff-hours 

3 calls for 1 1/2 staff -hours 

3 calls for 6 1/4 staff -hours 

89 calls for 59 staff-hours 



Four cleaning products were evaluated. Two were quaternary ammonium 
germicidal -detergents and the others were a general purpose detergent and 
an acid bowl -cleaning material. Both germicidal -detergents were found to 
be excellent cleaners. The general purpose detergent was found satisfactory 
but no significant improvement over our present product. The acid bowl- 
cleaning material was considered too hazardous for general use. 

Vestal Gloss Builder and Floor Finish were evaluated. Both products were 
found to be satisfactory. 

There were two equipment demonstrations, the ultra high speed floor polisher 
and the advanced floor scrubber. The polisher was '^ery good but did not 
offer the versatility of the 2-speed floor polisher we have recently been 
procuring. The scrubber was versatile and safe. 

FUTURE OBJECTIVES DIRECTED TOWARD MEETING GOALS | 

1. Implement new solid waste handling system based on reactivation of 
existing Clinical Center trash chutes. 

2. Complete refresher training and certification in basic work procedures 
for all Department supervisors, leaders, and employees. 

3. Support and encourage upward mobility for employees so that they may 
work at their fullest potential. 

4. Continue to study the feasibility of phasing out manual passenger 
elevator service and converting to automatic passenger elevators. 

5. Continue program of replacement of Clinical Center personal lockers. 

6. Publish new cleaning procedures in "Clinical Center Cleaning Procedure 
Manual," and revise 25% of Programmed Work Plans. 

7. Continue to test new products and equipment. 

8. Coordinate selection of textiles and fabrics for draperies, furniture, 
and wall and floor coverings within the Clinical Center. 



TABLE 1 

ENVIRONMENTAL SANITATION CONTROL DEPARTMENT 

July 1, 1977 through June 30, 1978" 

GOVERNMENT STAFF HOURS 

Supervisory Training I 240 

Motivational Dynamics 192 

Human Relations 240 
Civil Service 

EEO Training 32 

Advanced EEO Training 24 

The Role of Supervisors and Managers 8 

Civil Service Interview 12 

Employee Assistant Program 20 

Educational Program 235 

Adult Education 640 

AA School 86 

Cardiac Pluminary Resucitation 72 

Spot Light on Safety 48 

Letter Writing 32 

Travel Procedures 12 

Performance Appraisals 40 

Basic Concepts of Mathematics 16 

Composition on Basic Reading 10 

Mental and Physical Health 18 

Organization and Administration on Aging 18 

2-Day Seminar on Retirement Planning 16 



Table 1 continued 

NON-GOVERNMENT 

Engineers Service Incorporated 
5-Day Housekeeping Seminar 
3-Day Housekeeping Work Shop 
2-Day Seminar-Housekeeping Management 

Upward Mobility College 

Institutes on Hospital Housekeeping 

*How to Mini Ban-Clinic Clean System 

*Federal Personnel Procedures 

WITHIN DEPARTMENT 
Procedures and Orientation 
All Employee Training 



♦Attended course on employee non-duty time 



TOTAL 



2,031 



TOTAL 



1,626 
355 



TOTAL 
GRAND TOTAL 



185 



1,981 
4,197 



TABLE 2 

POSITIONS FILLED BY RECRUITMENT 

ENVIRONMENTAL SANITATION CONTROL DEPARTMENT 

JULY 1, 1977 through JUNE 30, 1978 





MONTH 


GENERAL 
SCHEDULE 


OTHER 
WAGE BOARD 


WG-03 


WG-02 


WG-01 


TOTAL 
















July 




1 




1 




2 


August 








4 




4 


September 








3 




3 


October 








1 




1 


November 








9 


1 


10 


December 








5 




5 


January 










1 


1 


February 








2 




2 


March 








3 




3 


April 








1 




1 


May 















June 








2 




2 


SUB-TOTAL 




1 




31 


2 


34 



*Total includes 12 700-hour appointments and 15 NTE 1-year appointments 



TABLE 3 
NUMBER OF SEPERATIONS, RESIGNATIONS, ETC., BY MONTH & GRADE 
ENVIRONMENTAL SANITATION CONTROL DEPARTMENT 

JULY 1, 1977 through JUNE 30, 1978 





MONTH 


WAGE 
SUPERVISOR 


WAGE 
LEADER 


WG-03 


WG-02 


WG-01 


TOTAL 
















July 






2 






2 


August 






1 


3 




4 


September 








4 




4 


October 


1 






2 




3 


November 






2 


1 




3 


December 






1 






1 


January 


1 






1 




2 


February 




1 




3 




4 


March 






1 


3 




4 


April 















May 






1 


1 




2 


June 






1 


3 




4 


SUB-TOTAL 


2 


1 


9 


20 





32 



*Total includes 5 700-hour appointments and 5 1-year appointments 



TABLE 4 
REASONS FOR PERSONNEL LEAVING 
ENVIRONMENTAL SANITATION CONTROL DEPARTMENT 

JULY 1, 1977 through JUNE 30, 1978 



RESIGNATIONS 


TRANSFERES 


RETIREMENTS 


TERMINATIONS 


DECEASED 












Resgined when 
faced with possible 
disciplinary action 

2 


Improve 

career 

opportunities 


Retirement 
disability 

4 


Separation 
during 

probationary 
period ^ 


1 


To accept non- 
government position 

2 


Transportation 


Retirement 
optional 

6 


Termination 
of temporary 
appointment 

2 




Moving away 

1 


Higher Salary 
1 




Expiration 
of temporary 
appointment 
8 




Health 






Abandonment 
of position 
2 




Transportation 










Personal 

1 


- 








SUB-TOTALS 

6 


1 


10 


14 


1 



TOTAL - 32 



October 1, 1977 through September 30/ 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

FABRIC CARE DEPARTMENT 



TABLE OF CONTENTS 

PAGE 

I. MISSION AND GOALS FC-1 

II. ACTIVITIES FC-2 

III. FUTURE OBJECTIVES FC-3 



October 1, 1977 through September 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

FABRIC CARE DEPARTMENT 

I. MISSION AND GOALS 

The primary objectives of the Fabric Care Department during 
Fiscal Year 1978 were to: 

1. Provide quality fabric care services at the most 
reasonable cost consistent with the needs of patient 
care and research in the Clinical Center and other 
N.I.H. installations on the Bethesda campus, the 
Poolsville animal farm, the Landau, Westwood, Auburn 
buildings, the Baltimore Cancer Research Center, and 
St. Elizabeth's Hospital. 

2. Study manpower requirements in an effort to reduce 
authorized permanent full-time staff by two positions. 

3. Continue to improve the quality of sejrvice to the 
N.I.H. community. 

4. Reduce budgeted overtime usage by 12%. 

5. Provide technical and administrative training for new 
assistant. 

6. Establish a two to three year plan for replacing 
several key employees who are nearing retirement. 

7. Draft Employee Handbook for Fabric Care employees. 

8. Complete and publish Fabric Care Procedural Manual to 
be made available to the N.I.H. community. 



FC-1 



II. ACTIVITIES 

A. Production 

Laundry Operations: 

Pounds Washed and Finished 1,712,675 

Pounds Dyed 4 0,475 

Dry Cleaning Operation: 

Pounds Dry Cleaned and Finished 111,500 

New Linen Stores: 

Items Issued 43,100 

Items Repaired 10,022 

Items Altered 28,800 

New Items Fabricated 1,258 

Opening Inventory 138,244 

Purchases 904,315 

Cost of Goods Sold 856,723 

Stock Write Off 279 

Closing Inventory 186,133 

1. The Department was able to meet the normal demand 
for service with no major problems or additional 
staff during the Fiscal Year. 

2. Selected and ordered a new flatwork ironer 
complete with primary and cross folders. 

3. Redesigned Building Services Area. 

4. The Environmental Ssfety Branch, Biological 
Control Section, DRS, was requested to make an 
Environmental and Safety Survey of the Fabric 
Care facility. 

B. Personnel 

1. Selected a Laundry Manager's training course for 
Assistant Chief of the Department. 

2. Four employees attended Basic Adult Education 
Classes - (624 Man Hours) . 

3. The Department sponsored seven (7) job related 
training sessions - (374 Man Hours) . 

4. One employee attended Upward Mobility College - 

(62 Man Hours) . 

FC-2 



5. Provided training and work experience for eight (8) 
Stay-in-School and four (4) Suinirier-Aid employees. 

6. One supervisor attended the N.I.H. seminar on 
Problem Employees - (40 Man Hours) . 

7. One supervisor attended the C.C. Advanced 
Supervisory Course - (40 Man Hours) . 

8. Assistant Chief of the Department attended the Zero 
Base Budget Course and a one day seminar on 
Infectious Control in the Laundry - (48 Man Hours) . 

9. The Chief of the Department attended the 38th 
Annual Educational Conference of the National 
Association of Institutional Laundry Managers 
in Denver, Colorado, and was selected National 
Laundry Manager for 19 78. 

10. Three employees of the Department were honored at 
the Twenty-Fifth Anniversary of the Clinical Center. 

11. The Department provided a work therapy program for 
one Clinical Center patient - (32 Man Hours) . 

12. Two employees were retired on disability. 

13. No major personnel problems. 
III. FUTURE OBJECTIVES 

1. Renovate the Dry Cleaning Plant in accordance with 
Environmental Health and Safety Standards. 

2. Install new flatwork ironer complete with primary 
and cross folders. 

3. Reduce budgeted overtime by 15%. 

4. Continue to review manpower requirements in an 
effort to keep the number of permanent, full-time 
positions to at least three positions below 
authorized N.I.H. ceiling. 

5. Provide in-service training for all employees. 

6. Continue to improve the quality of service to the 
N.I.H. community at a reasonable cost. 

7. Complete the two to three year plan for replacing 
key personnel nearing retirement. 



FC-3 



October 1, 1977 through September 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

MEDICAL RECORD DEPARTMENT 

CONTENTS 

Department Missions and Goals MR-1 

Activities MR-1 

Progress MR-2 

Future Objectives MR-5 



MR-i 



« 



October 1, 1977 through September 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

MEDICAL RECORD DEPARTMENT 

DEPARTMENT MISSIONS AND GOALS 

The Clinical Center Medical Record Department maintains a medical record for 
every registered Clinical Center patient. The prime objective of the Medical 
Record Department is to insure that each medical record is complete, accurate, 
safeguarded, and available to authorized personnel. To this end systems are 
maintained which provide: 1) immediate access to and release of medical 
records and/or microfilm and information to authorized users; 2) a computer- 
ized listing of each patient by diagnosis and operation; 3) an analysis by 
Institute of discharged inpatients; k) a systematic arrangement of reports 
within the medical record; 5) transcribed medical reports and communication 
with referring physicians, 

ACTIVITIES AND PROGRESS 

Education and Training 

Two Medical Record Department employees successfully passed the National 
Registration Examination for medical record administrators. 

Two student affiliates from the Department of Medical Record Administration, 
College of St. Scholastica, Duluth, Minnesota, received orientation in the 
Medical Record Department, February 13 - 2k, 1978. In addition, they toured 
various Clinical Center departments, attended committee meetings and visited 
other educational organizations in the area. 

Several employees were honored at the awards ceremony in September 1978 as 
recipients of individual awards. 

The following is a breakdown of classes, seminars and meetings attended by 
personnel : 

2 Medical Record Administrators Motivational Dynamics 48 hrs. 

2 Files Supervisors " " " 

1 Administrative Technician " " " " 

1 Supv. Clerk DMT " " " 

1 Supv. Clerk " " " 

1 Files Section Supv. T & A Refresher 2 hrs. 

2 Medical Record Administrators Insp. & Quality Control 8 hrs. 
1 Files Section Supv. " " " " 

1 File Clerk Upward Mobility 48 hrs. 

MR-1 



3 Medical Record Administrators 
1 Supv. Clerk DMT 

1 Secretary DMT 

5 Medical Record Administrators 

2 File Clerks 

3 Supervisors 

1 Medical Record Administrator 

2 Supervisors 
1 File Clerk 

1 Clerk 



Record of Cal 1 



Communications Worksliop 



Card iopulmi nary 
Resusci tation 



Release of Contract Facts 
Under Freedom of Informa- 
tion Act 



EEO Advisor Committee 
Training Session 



2 hrs. 
II 

II 

7 hrs. 

8 hrs. 

k hrs. 

1 1 
16 hrs. 



Activities and Progress 

Major organizational changes were approved by the Director, CC. These changes 
involved: 1) Creating a section for Coding and Retrieval, 2) Abolishing the 
Transcribing Section and incorporating its functions with the Record Process- 
ing Section. 

All departmental positions were audited and position descriptions updated 
by the Personnel Management Specialist to coincide with the Factor Evalua- 
tion System. 

An Access Policy book, an authority-source for the Medical Record Department 
employees, was compiled by the Chief, Medical Record Department. The Access 
book outlines requirements for release of medical records and reports to 
authorized users. The Access Policy book was approved by Medical Record 
Executive Committee May 1978 and Office of the Director, CC. 

The Chief, Medical Record Department is a member of the MIS outpatient work- 
group. The work-group, the service departments of the Clinical Center, will 
plan and implement the conversion from a manual to the Medical Information 
System (MIS) for outpatients. 

REMAC Information Corporation, Ga i thersburg , Md. was awarded a one-year nego- 
tiated microfilm contract with a 2-year hard option renewal to microfilm 
62,000 medical records. As a result, the purchase of the required equipment 
was made, system procedures written, policy for the disposal of the original 
medical record established, and off-site underground storage location for the 
security roll selected. 

Two significant policy changes occurred: 1) discharged medical records are 
returned from nursing units to the Medical Record Department the day of dis- 
charge. Studies proved that holding the charts for a longer period did not 
improve dictation time significantly; 2) completed medical records are 



MR-2 



charged out to authorized users for ^8 hours. Non-compliance of the loan 
period results in 30 day restriction whereby the user is required to come |^ 
to the Medical Record Department for review of medical records. 

Site visits were made by the Chief, Medical Record Department and representa- 
tives from the Office of the Director to various installation sites to observe 
dictation and automatic tracking equipment. As a result, the Lanier centra- 
lized dictating system was selected for use at the Clinical Center. Installa- 
tion occurred in June, a flyer distributed and orientation sessions scheduled. 
This has facilitated dictation of the records by physicians. 



MR-3 



WORK PRODUCTION STATISTICS 

October 1, 1977 to September 30, 1978 - Actual 
July 1, 1978 to September 30, 1978^ - Projected 



Column A Column B Column C 
10-1-77/6-30-78 7-1-78/9-30-78 TOTAL 
(Actual) (Projected) 



Medicolegal Section 
Total number of requests 
Average requests per day 



5,110 
27 



,918 
30 



,028 
29 



I I . Record Processing Section 

Incomplete records as of 5-31-78 1 
Incomplete records as of 9-30-78 



051 



598 



825 



III. Files Section - Record Circulation 

Complete Records 16,013 

Clinics & Admissions ^0,553 

Incomplete Records (delinquent) 1,528 



A, 970 

5,109 

598 



20,983 

55,662 

2,126 



I v. Transcribing Section 
Belts received 
Bel ts Transcribed " 



10,i»99 
10,3^*7 



3,978 
^,127 



1^,477 
14,474 



" Belts transcribed figures are greater than belts received due to belts 
remaining at beginning of the month. 



MR-4 



PROBLEMS 

1. Inability to recruit permanent full-time employees for the Microfilm ^ 
project, thereby resulting in the use of temporary part-time high school 
and college students. 

2. The number of delinquent medical records exceed JCAH's recommendation 
number significantly despite revocation of admitting privileges for 
attending physicians, 

OBJECTIVES 

1. Continue participation with MIS Outpatient Workgroup to develop a single 
integrated medical record system. 

2. Preliminary planning to convert coding classification ICDA-8 to ICD-9 
to Include attending workshops and utilizing conversion tapes in con- 
junction with DCRT. 

3. Implement automated tracking systems designed for collecting and report- 
ing delinquent medical record control. 

k. Physical reorganization in the Record Processing Section. Utilize work 
modules to allow more work area for the clerks while physically occupy- 
ing less floor space. Consequently, more room will be provided for the 
physicians who must review and/or dictate clinical reports and allow 
for an efficient workflow. li 



MR-5 



October I, 1977 through September 30, 1978 

PUBLIC HEALTH. SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMJIARY ANNUAL REPORT OF PROGRAM ACTIVITIES 

CLINICAL CENTER 

DEPARTMENT OF NUCLEAR MEDICINE 

CONTENTS 

Department Missions and Goals NM-1 

Department Activities NM-2 

Major Progress in Research, Services, Training 

and Development NM-4 

Future Objectives Toward Meeting Goals NM-5 

Research Projects 

The Metabolism of Zn-65 and Zn-69m in Patients with and without 
Taste Abnormalities NM-7 

Studies of Copper Metabolism in Man using Cu-67 and Cu-64 NM-10 

EGG-Gated Scintigraphic Angiocardiography '. . .NM-14 

TABLES 

I. Comparison of Whole Body Measurements for Fiscal 

Years 1977 and 1978 NM-15 

II. Percentage of Whole Body Counts by Institutes NM-15 

III. Eleven Year Record of Whole Body Measurements NM-16 

IV. Other Analysis Related to Whole Body Metabolism Studies .NM-17 

V. Radiopharmaceutical Section Statistical Data NTi-18 

VI. Radionuclides and Products Received, Registered, and 
Formulated - FY 1978 NM-19 

VII. Diagnostic Nuclear Medicine Section Patient Visits by 
Fiscal Year NM-21 



GRAPHS 



Growth of Clinical Center Nuclear Medicine Service to 

NIH Patients NM-22 



NM-i 



October 1, 1977 through September 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 
SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 
DEPARTMENT OF NUCLEAR MEDICINE 

DEPARTMENT MISSIONS AND GOALS 

Applied Physics Section 

The Applied Physics Section performs two basic functions: 1) to supply 
technical and professional assistance to the Department of Nuclear 
Medicine and other investigators in the resolution of selected 
diagnostic and experimental problems requiring Nuclear Medicine 
technology and 2) to independently develop novel diagnostic procedures, 
from concept through hardware, aimed at resolving selected problems of 
medical diagnosis. 

Diagnostic Imaging Section 

This section serves the clinical research goals of the NIH through the 
in vivo diagnostic use of radioactive pharmaceuticals to evaluate 
diseases that are under study in the Clinical Center in- and 
outpatients. This information helps physicians to choose and assess 
therapy. Major goals are to improve existing techniques and to develop 
new techniques that have minimal morbidity for the patient. 

Radiopharmaceutical Section 

The major responsibilities of the Radiopharmaceutical Section are to aid 
dosing patients with radionuclides and quality control for the 
Diagnostic Imaging Section. Services consist of the procurement, 
receipt, registration, formulation, and development of all 
radiopharmaceuticals intended for use in Clinical Center patients. 
Quality control consists of assaying, radio- chemical and radionuclide 
purity checks, pH determination, particle sizing, and a host of other 
considerations necessary to establish the pharmaceutical quality of the 
products . 



NM-1 



Whole Body Counter Section 

The Whole Bodv Counter Section orovides the Clinical Center and the NIH 
communitv with direct quantitative measurements of uptake and retention 
of biologically active materials and trace elements labelled with 
gamma-ray emitting radionuclides, and evaluation of the amount and 
identity of unknown radionuclides in the human bodv. It also helps 
investigators who desire to design special counting systems to measure 
biological samnles containing radionuclides. 



DEPARITIENT ACTIVITIES 

A pplied Phys i cs Sect ion 

In accord with its mission, the APS intensified its collaborative 
efforts with NHLBI/CB, DCRT/LAS, and DCRT/CSL during FY 1978 in the 
pursuit of non-invasive methods for detecting and diagnosing cardiac 
disease. 

Equipment 

Imagine equipment, work space, and expendables were provided "by M/CC 
and DCRT. Radiopharmaceuticals were provided by the Radiopharmacy 
Section/NM. 



D iagnostic Imaging Section 

The components necessary to achieve the above mission require continued 
upgrading. The field of Nuclear Medicine is fast changing and requires 
a constant refreshment of departmental physician and technician 
knowledge. Electronic equipment is costly and is under continual 
development by private industry. Medical diagnostic capability can be 
improved and maintained only if a program of continued, well chosen 
acquisition of newly created electronic devices is followed. Equipment 
was improved through the acquisition of two large f ield-of-view gamma 
cameras provided in FY 1978 budget. New devices (computerized axial 
tomograph) CAT units utilizing either single photon gamma emissions or 
positron emissions are now being introduced into nuclear medicine 
clinics throughout the world. Thus far NIH has not purchased such a 
unit but is involved in the evaluation of a single photon CAT unit. 



Patient visits decreased 10% in FY 1978 compared with a 26% increase in 
FY 1977. Please see updated graph titled "Growth of Clinical Center 
Nuclear Medicine Service" (page 22) . 



NM-2 



Radiopharmaceu tic al Section 

Eighty-nine percent of the Section's work was to service the Diagnostic 
Imaging Section because a new agent introduced In January allowed more 
doses per preparation. The decrease in the number of unit doses 
prepared was also due to a decrease in the number of brain scans and 
Galllum-67 scans. A radiopharmaclst continued to be involved in the 
dosing area for approximately 30 manhours per week. The future workload 
can be anticipated to be proportional to that of the Diagnostic Imaging 
Section in regards to its usage of radionuclide products. 

The 12% actual decrease in radiopharmaceutical expenditures is 
attributable to the procurement of a particularly expensive 
radiopharmaceutical (Thallium-201) by the National Heart, Lung, and 
Blood Institute since February and the decrease in cost of the new bone 
imaging agent mentioned previously and also a lesser usage and decrease 
in cost of Ga-67. 

The dose dispensing area was relocated within the Diagnostic Imaging 
Section and the radiopharmaclst effectively controlled and dispensed 
radio- pharmaceuticals and insured the practice of good radiation safety 
principles. 



Whole Body Counter Section 

During FY 1978 the Whole Body Counter Section continued routine thyroid 
uptake measurements, a function previously handled by the Diagnostic 
Section. Use of a highly shielded counting chamber and multi-channel 
analyzer allowed a marked reduction in activity given each patient per 
thyroid uptake from 8 to 15 uCi to less than 0.5 uCl. The data from the 
first year's results are being correlated with the data of the 
endocrinologists who made the initial patient referrals to obtain a 
distribution curve of thyroid uptake vs. thyroid function. 

In order to inform the NIH community of the availabilitv and usefulness 
of services offered by the Whole Body Counter Section, a short 
illustrated pamphlet was prepared for distribution to incoming 
associates and all BIDs involved in human studies with gamma-ray 
emitting radionuclides. This 'Whole Body Counter Handbook' DHEW 
Publication No. (NIH)78-348, is now being distributed. 

The Section acquired a triple "diskette" data storage device for our 
Wang 2200 data processing system and a magnetic tape interface between 
our Packard Instrument Company model 5220 "autogamma" well counter and 
the 2200 system for automated data collection and computerized records. 
These computer systems now give us the capability of "instant" program 
or data storage and retrieval. Data from samples counted in the well 
counter can now be submitted directly into the computer for analysis. 



NM-3 



During FY 1978 the Section published results of the 5-year zinc metabolism 
study on oral and intravenously administered ZN-69m and Zn-65. The 
clinical phase of this study was completed in 1977. Together, these 
studies represent the largest and most detailed investigations of zinc 
metabolism ever done with radionuclides as well as the first studies to 
involve oral and intravenous administration of zinc radionuclides to the 
same human subjects in order to investigate the effects of route of entry 
on metabolism. Publication of these results is expected by the end of FY 
1978. 

MAJOR PROGRESS IN RESEARCH, TRAINING AND DEVELOPMENT 

Applied Physics Section 

Four major objectives were realized in the APS during FY 1978 in 
collaboration with other NIH organizations: (1) APS technical and 
scientific support of an expanded, large scale clinical evaluation of 
gated-cardiac Islood pool imaging at rest and during bicycle exercise was 
intensified, (CB/NHLBI,APS) ; (2) the real-time scintigraphic imaging system 
used in these studies was extensively modified (software and hardware) to 
further increase the clinical utility of the system, (APS); (3) 
investigations were undertaken of (a) automated data reduction methods for 
cardiac studies, (LAS/DCRT,APS) ; (b) minimum frame rate requirements for 
accurate measurements of LV function during exercise, (APS); (c) the 
effects of other perturbing factors on these measurements, (APS); (4) a 
portable non-imaging probe system was completed and is now being modified 
to perform special measurement tasks, (CSL/DCRT,APS) ; (5) preliminary 
investigations of the computer requirements for several new tomographic and 
conventional imaging devices scheduled for acquisition by the DNM were 
completed , (APS , CSL/DCRT) . 



Diagnostic Imaging Section 

Two new forms of computerized axial tomography have appeared in the 
specialty Nuclear Medicine. One of these devices is a first of its kind 
and is under evaluation in the Diagnostic Imaging Section. The other 
device is on order, at the request of NINCDS, and should arrive by January 
1979. These units utilize emitted gamma rays from radiopharmaceuticals 
administered to the patient and they promise major research advances. 

Gated cardiac blood pool studies are being utilized to further characterize 
a variety of cardiac disorders and to assess the results of therapy. (See 
Applied Physics Section) . 

Gated pulmonary studies have been further refined and a cooperative effort 
continues with DCRT and NHLBI-Pulmonary Branch. 



NM-4 



Ra diophar maceutical Sectio n 

Research efforts consisted of the labelling of lymphocytes with In-111 
and collaborative work with a guest worker chemist in analyzing the 
labelled composition of Tc-99m HSA and developing a labelling technique 
for Cr-51 HSA. 

A total of 19 different radionuclides were received which constituted 59 
different product formulations (see Table VI) . Products not previously 
received and/or formulated were Technetium- 9 9m Methylene Diphosphonate, 
Technetium-99m Glucoheptonate, and Indium-Ill lymphocytes. 

The Radiopharmacy also provided a preceptorship to the Duquesne 
University School of Pharmacy Controlled Internship Program and, in 
addition, trained 3 Pharmacy students within the COSTEP. Lectures and 
consultative functions were also rendered to paramedical personnel 
regarding various aspects of Radiopharmacy. 



Whol e Body Counter Section 

During FY 1978, there was increase in the number of research and 
diagnostic studies requested of the Section. In part this ■was due to 
the thyroid uptake studies which totaled 712 patient visits in FY 1978, 
the first full year the VJhole Body Counter Section has done these 
studies. The Section emphasized medical research measurements for the 
past seven years, and will continue to do so during FY 1970. 

FUTURE OBJECTIVES TOWARD MEETING GOALS: 



Applied Physics Section 

Clinical Studies with the real-time cardiac imaging system will 
continue. Refinements of this system through appropriate software and 
hardware changes will also be continued. 

The portable probe system will be exploited in intervention studies in 
the Catheterization Laboratory and elsewhere. Investigations of the 
accuracy, precision, and assumptions underlying the scintigraphic method 
will be continued. Investigations of tomographic imaging systems will 
be pursued. 



NM-5 



Diagnostic Imaging Section 

Computerized axial tomography utilizing emission energy (E-CAT) should 
commence in FY 1979. The positron E-CAT promises to provide a totally 
new approach to actually being able to see the metabolism of various 
labelled compounds in vivo. For example, the brain will be seen as it 
metabolizes glucose. A radiochemist will ioin this department in order 
to prepare new labelled compounds. These compounds will be labelled 
with radioactive elements that are cyclotron generated and will 
introduce a whole new approach to the study of the metabolism of the 
human body. Much of this work will be in cooperation with NINCDS. To 
support this effort a radio- chemistry laboratory is to be set up. 



Radiopharmaceutical Section 

The future objectives of the Section are to continue to collaborate with 
the service and research efforts of the Diagnostic Imaging Section and 
other Clinical Center investigators with involvement in the formulation, 
development, and quality control of all radiopharmaceutical products 
intended for patient administration. 

The projected utilization of positron emitting radionuclides 'will 
involve the radiopharmacy in new aspects pertaining to the chemistry and 
pharmaceu- tical control assurances of the labelled products. 



Whole Body Counter Section 

The main future objective of the Whole Body Counter Section is to 
acquaint the investigators at NIH who are involved with human metabolism 
and human nutrition with the unique capabilities of our services. The 
Section will review protocols on file that relate to radioisotope use in 
humans and contact those investigators who could conceivably use our 
facility. We feel it is necessary to have the most people benefiting 
from our capabilities as is physically possible. 



NM-6 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Do NOT use this space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAHURAL RESEARCH PROJECT 



PROJECT NUMBER 
ZOl CL 00009-04 



PERIOD COVERED 

October 1, 1977 through September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

The Metabolism of ZN-65 and Zn-69m in Patients with and without Taste 

Abnormalities. 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



Principal Investigator; 
Other Investigators: 



Gerald S. Johnston M. 
Roger L. Aamodt PH.D. 
Fredrick Bartter M.D. 
Robert I. Henkin M.D. 



INVESTIGATORS AND ALL OTHER 

D. CC:NM 

CC:NM:WBC 
NHLBI:IR 

Georgetown University 
Medical Center 



COOPERATING UNITS (if any) 

Georgetown University Medical Center, Washington, D.C. 



LAB/BRANCH 

Department of Nuclear Medicine 



SECTION 

Whole Body Counter Section 



INSTITUTE AND LOCATION 

Clinical Center, NIH, 



Bethesda, Maryland 20014 



•OTAL MANYEARS: 
1 



PROFESSIONAL: 

.25 



.75 



CHECK APPROPRIATE BOX(ES) 
3 (a) HUMAN SUBJECTS 

□ (al) MINORS □ (a2) INTERVIEWS 



D (b) HUMAN TISSUES 



n (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

Patients with idiopathic hypogeusia show a loss of taste acuity following 
infection or surgery. Both of these processes are associated with increased 
excretion of zinc in the urine and decreased serum zinc concentration. This 
study is designed to investigate zinc metabolism in these patients and to 
compare them to patients with hypogeusia following head trauma, patients 
without hypogeusia, but with other unrelated diseases and patients with 
terminal diseases. Measurements after administration of Zn-65 of Zn-69m 
will include whole body counting , partial body gamma-ray measurements, 
and measurements of gamma-ray activity in blood, urine and stool. 



101 CL 00009-04 NM 
Project Description 



Objectives : 



A. To study the metabolism of zinc in patients with taste and smell 
dysfunction in order to identify those who exhibit abnormal absorption, 
distribution, retention or kinetics. 

B. To determine the effects of zinc ion therapy on the metabolic 
parameters discussed above. 

Methods Employed : 

Following oral administration of 10 uCi of Zn-65, the NIH Whole Body 
Counter and probe systems will be used to measure Zn-55 in the total 
body and selected tissues for a period of 300 days. Patients will be 
given a placebo during this period. For a subsequent 300 day period 
patients will received 100 mg/day of Zn++ orally and measurements will 
be continued for another 300 days. Blood and excreta samples will 
also be collected and Zn-65 activity determined by gamma-ray 
spectroscopy. During both phases of the study, measurements of taste 
and smell acuity (threshold and forced scaling for each sensory 
modality) will be made. 

Findings : 

A. The absorption patterns of 63 unselected, untreated patients have 
been characterized and found to have a much wider than expected range 
(20-90%). Little data had been previously available for zinc 
absorption by humans. 

B. Retention of Zn-65 was generally found to agree with previously 
reported values following intravenous administration with the 
exception of one patient with congenital hypogeusia who exhibited a 
markedly shortened half-time (143 days). 

C. Administration of ZnS04 (100 mg/day) to patients who had 
previously been given Zn-65 resulted, in most cases, in a marked 
change in their retention of the radionuclide. This finding is 
important both in terms of the physiology of zinc in man, but also 
for its implications to the treatment of humans with high body burdens 
of zinc radionuclides. 



ZOl CL 00009-04 NM 



Significance of the Research Program ; 

Studies of zinc metabolism in patients with taste and smell 
dysfunction are a small part of an interdisciplinary program 
which attempt clinical, metabolic, and pathophysiological 
abnormalities in these patients. Beyond this, zinc is an essential 
trace metal, the importance of which is just being recognized. 
These studies will contribute to knowledge about zinc metabolism 
and may provide insights into ways of increasing absorption in 
people with absorption difficulties and removing radioactive 
Zn-65 following accidental uptake in order to reduce the 
radiation dose. 

Proposed Course ; 

Patient studies with Zn-65 have now been completed. The continuation 
of these studies will involve data analysis and preparation of data 
for publication. Dr. Mones Berman (C, LTB) is assisting with analysis 
of data from Zn-69m studies, and is expected to also contribute to 
data analysis of Zn-65 studies. 

Honors and Awards ; 

None. 

Publications; 

None. 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Do NOT use this space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 



ZOl CL 00011-04 NM 



PERIOD, COVERED 

October I, 



1977 through September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Studies of Copper Metabolism in Man using Cu-67 and Cu-64. 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

Principal Investigator: E. Anthony Jones M.D. NIAMDD:DI 

Other Investigators: Paul D, Berk M.D. NIAMDD:DI 

John M. Vierling M.D. NIAMDD:DI 

Roger L. Aamodt Ph.D. CC:NM 



COOPERATING UNITS (if any) 

NIAMDD 



lab/branch 

Department of Nuclear Medicine 



SECTION 

Whole Body Counter Section 



INSTITUTE AND LOCATION 

Clinical Center, NIH, Bethesda, Maryland 20014 



TOTAL MANYEARS: 
1 



PROFESSIONAL: 

0.2 



0.8 



CHECK APPROPRIATE BOX(ES) 
[^ (a) HUMAN SUBJECTS 

D (al) MINORS n (a2) INTERVIEWS 



n (b) HUMAN TISSUES 



D (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

Copper, although present in the body in small amounts, is essential for life. 
In certain diseases, copper metabolism is abnormal; however, the mechanisms 
of copper homeostasis are poorly understood. An important potential cause 
of abnormal copper metabolism is defective absorption. It is possible that 
increased copper absorption may contribute to the increased hepatic copper 
which occurs in Wilson's disease and chronic cholestasis. Alternatively, 
copper absorption may be impaired in diseases of the small intestine, such 
as adult celiac disease. Studies of copper absorption and metabolism are 
being conducted using the NIH whole body counter systems using simultaneous 
oral administration of Cu-64 and intravenous administration of Cu-67. In- 
vivo gamma-ray measurements of the liver and thigh areas, total body retention , 
and activity in blood and excreta will provide information about absorption 
and retention of copper in normal subjects and in patients with disorders of I 
copper metabolism. It is hoped that such studies will provide insights into 
the normal metabolism of copper on the mechanisms of abnormal copper 
metabolism which result in disease. 



ZOl CL 00011-04 NM 
P roject Description 



Objectives: 



A. To evaluate quantitatively the metabolism of copper in health and 
specific diseases associated with abnormalities of copper metabolism. 

B. The ultimate goals include a comprehensive understanding of normal 
copper metabolism, and an evaluation of the significance of specific 
abnormalities of copper metabolism in patients with hepatolenticular 
degeneration and their relatives and patients with primary biliary 
cirrhosis and other disease states. 

Methods Employed : 

A. Studies using Cu-67 alone. After the intravenous injection of Cu-67 
serial measurements are made of whole body radioactivity (using a whole 
body counter), hepatic radioactivity (using a scintillation probe), 

and radioactivity in whole blood, red cells, plasma, ceruloplasmin, urine 
and feces. With the exception of hepatic radioactivity, these measure- 
ments are made for a period of 13 days. Plasma ceruloplasmin-bound Cu-67 
determination involves the removal of non-ceruloplasmin-bound Cu67 from 
plasma samples by passage of these samples down small columns of activated 
charcoal. Plasma non-ceruloplasmin-bound Cu-67 are determined by 
subtracting radioactivity in ceruloplasmin from that in whole plasma. 
The curves of total body, hepatic, whole blood, red cell, plasma 
ceruloplasmin and plasma non-ceruloplasmin radioactivity are defined 
and the total excretion of radioactivity in urine and feces calculated. 

B. Studies using Cu-67 and Cu-64. Studies are also being conducted in 
which Cu-67 is being administered by intravenous injection and Cu-64 is 
being administered simultaneously by mouth. The subsequent protocol is 
the same as for studies using Cu-67 alone except that both Cu-67 and 
Cu-54 radioactivity are measured in all experimental specimens. In 
measuring Cu-67 and Cu-64 simultaneously an appropriate correction is 
made for the radioactivity due to Cu-64 which cannot be excluded when 
measuring Cu-67. The plasma disappearance curve of non-ceruloplasmin- 
bound Cu-64 curve for losses employing deconvolution and integration 
procedures on a digital computer. This enables the total Cu-64 which 
passes from the gut lumen to the plasma to be calculated. This quantity 
less the amount of the administered Cu-64 which does not appear in feces 
gives an estimate of the biliary secretion of Cu-64 and hence of the 
enterohepatic circulation of this metal. 



ZOl CL 00011-04 m 



Findings : 

A. The ranges of whole body Cu-67 retention for normals and homozygotes 
and heterozygotes for hepatolenticular degeneration have been defined. 

B. There was appreciable incorporation of Cu-67 into ceruloplasmin in 
normals and a similar degree of incorporation in heterozygotes for hepato- 
lenticular degeneration. In contrast, incorporation of Cu-57 into 
ceruloplasmin in homozygotes for hepatolenticular degeneration was 
minimal . 

C. After administering Cu-67 intravenously and Cu-64 orally to normal 
volunteers, plasma curves of non-ceruloplasmin-bound Cu-67 and Cu-64 
have been defined and the feasibility of studying the enterohepatic 
circulation of copper using these two isotopes has been established. 

Significance of the Research Program : 

In certain disease states marked variation in the copper content of plasma 
and various organs are known to occur. However, the mechanisms by which 
copper hemeostasis is maintained in health and disturbed in disease are 
poorly understood. Increasing attention has been focused on copper 
metabolism in hepatolenticular degradation since the refutation of the 
concept that low ceruloplasmin concentration is primarily responsible for 
manifestations of the disease. Recent work has been demonstrated diffuse 
deposition of copper in the liver in primary biliary cirrhosis raising 
the possibility that abnormal copper metabolism may contribute to the 
pathogenesis of this disease, the etiology of which is at present unknown. 

An important potential cause of deranged copper metabolism is a defect in 
the intestinal absorption of the metal. For example, it is possible that 
increased copper absorption may contribute to the increased hepatic copper 
which occurs in hepatolenticular degeneration and chronic cholestasis. 
Alternatively, copper absorption may be impaired in diseases of the small 
intestinal mucosa. Lack of reliable methods, variability in hepatic copper 
uptake and the presence of an enterohepatic circulation for copper have 
hitherto prevented acquisition of reliable data on absorption. 

Using the double radionuclid technique outlined, it is possible to quanti- 
tate the intestinal absorption and biliary secretion of copper in human 
subjects and hence to determine whether there is a derangement of 
intestinal absorption or biliary secretion of copper in specific disease 
states. 



II CL 00011-04 NM 



Proposed Course : 

Patient studies with Cu-64 and Cu-67 are now essentially complete. 
Continuation of these studies will involve preparation and analysis 
of data and kinetics analysis. 

Honors and Awards : 

None. 

Publications : 

"Incorporation of Radiocopper Into Ceruloplasmin in Normal Subjects 
and in Patients with Primary Biliary Cirrhosis and Wilson's Disease". 
John M. Vierling, M.D., Richard Schrager, M.A., Warren F. Rumble, B.A. 
Roger Aamodt, PhD., Marvin Berman, M.D., and E. Anthony Jones, M.D., 
M.R.C.P. Gastroenterology 74: 652-660, 1978 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE 
PROJECT NUMBER (Do NOT use this space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl CL 00007-03 NM 



PERIOD COVERED 



TITLE OF PROJECT (30 characters or less) 

ECG-Gated Scintigraphic Angiocardiography 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 



PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



PI: 



J. 


S. 


Borer 


s. 


L. 


Bacharach 


M. 


V. 


Green 



OTHER: K. M. Kent 

. J. J. Bailey 

M. A. Douglas 

H. G. Ostrow 



Senior Investigator 
Physicist 

Chief, Applied Physics 
Section 

Senior Investigator 
Head, MAS 
Programmer 
Engineer 



CB 


NHLBI 


NM 


CC 


NM CC 


CB 


NHLBI 


LAS 


DCRT 


LAS 


DCRT 


CSL 


DCRT 



COOPERATING UNITS (I 

CB NHLBI 
LAS DCRT 
CSL DCRT 



any) 



lab/branch 
Department of Nuclear Medicine, CC 



SECTION 

Applied Physics Section 



INSTITUTE AND LOCATION 

Clinical Center, 



NIH,Bethesda, Maryland 20014 



TOTAL MANYEARS: 



PROFESSIONAL: 



CHECK APPROPRIATE BOX(ES) 
n (a) HUMAN SUBJECTS 

D (al) MINORS □ (a2) INTERVIEWS 



n (b) HUMAN TISSUES 



n (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

High temporal resolution ECG-gated scintigraphic angiocardiography 
(radionuclide cineangiography) is a computer-based, radiotracer imaging 
procedure that allows non-invasive visualization of the chambers of the 
working heart, at rest, during bicycle exercise, during therapeutic 
intervention, etc. The procedure yields quantitative measures of left 
ventricular function such as ejection fraction, peak ejection rate, etc. 
Work is continuing to assess the accuracy of these data in man and to 
establish findings for the method in selected disease categories. 
Variations of this technique are being explored and will result in an 
inexpensive, portable device capable of continuous real-time measurement 
of left ventricular function. 



ZOl CL 00007-03 NM 
Project Description 



Objectives ; 

To continue to validate, develop and exploit ECG-gated scintigraphy 
(radionuclide cineangiography) in the detection and evaluation of 
cardiac disease in man. 

Methods Employed ; 

A variety of comparative clinical studies were continued during FY78 
(CB/APS) under the rest-exercise imaging protocol. Among these were; 
(1) studies designed to compare the sensitivity and specificity of 
radionuclide cineangiography with other established diagnostic pro- 
cedures (ECG-stress testing, Th^^-*- myocardial perfusion imaging) 
in the detection of coronary artery disease, (2) pre- vs. post- 
operative evaluation of the effects of surgical therapy on the 
exercise response of the left ventricle (cononary artery bypass 
grafting, myectomy and myotomy in IHSS, aortic valve replacement) 
and (3) investigation of the ventricular rest-exercise response to 
various medications (nitroglycerin, propranolol). During FY78 more 
than 500 patients were studied by the APS technical staff in these 
investigations . 

Technical support of these efforts was continued throughout FY78. The 
prototype real-time cardiac imaging used in these studies was totally 
revised to eliminate certain deficiencies noted in the operation of 
the prototype system (APS) . 

Investigation of automated data reduction techniques (LAS/APS) was 
also initiated during this period. Incorporation of algorithms found 
suitable in these studies into the real-time system should substantially 
reduce "turnaround" time and eliminate inter-observer errors. 

Basic investigations into the accuracy and precision of radionuclide 
cineangiography were also continued (APS) . Minimum framing rate 
requirements were established as a function of intervention (e.g., 
rest-exercise) and of disease category, for precise determination of 
left ventricular ejection fraction and peak ejection rate. 

The final design for a microprocessor-based, non-imaging portable probe 
system was established (CSL) . The device was assembled and is now 
undergoing final testing in the DNM. Additional software and minor 
hardware changes are being instituted that will permit the system to 
be used in any of three measurement modes; (1) as a bedside monitor 
of left ventricular function, (2) as a real-time pressure-volume loop 
generator in the catheterization laboratory and (3) as a beat-by-beat 
monitor of left ventricular function. 



,Z01 CL 00007-03 NM 



Findings : 

During FY78, a sufficient number of patients were studied to establish the 
comparative sensitivity and specificity of radionuclide cineangiography 
in the detection of coronary artery disease. In this regard radionuclide 
cineangiography was found to be superior to stress electrocardiography 
and probably superior to Th myocardial perfusion imaging. 

Similarly, earlier findings were confirmed in a larger patient population 
subject to coronary artery bypass operation. This therapy appears to 
produce an improvement in left ventricular function during exercise in 
most patients (rather than merely relieving symptoms). Other clinical 
results are detailed in the references. 

Continued refinement of the real-time imaging system has markedly enhanced, 
the clinical utility of the system. Preliminary findings with several 
early image processing algorithms has demonstrated the feasibility of 
this approach. Finally, the probe system will be immediately employed 
in the catheterization laboratory and in other validation and human 
studies which exploit the advantages of this system. 

Significance of the Research Program : 

Radionuclide cineangiography is demonstrably useful in the detection and 
in the management of patients with cardiac disease. This procedure requires 
only an intravenous injection of radiotracer and is otherwise utterly 
non- invasive. It is rapid, safe and can be repeated under varying circum- 
stances such as exercise, medication, etc., for period of hours, without 
further tracer administration. This characteristic also makes the 
technique suitable for continuous LV function monitoring. This application 
is being exploited through development of a portable probe system which 
will be employed in special measurement situations. 

Proposed Course : 

Continuation of the work. 

Honors and Awards : 

None. 

Publications: 



Borer, J. S., Bacharach, S. L., Green, M. V., Kent, K. M. , Epstein, S. E., 

Johnston, G. S. : Computer-based radionuclide cineangiography during 

exercise. Nuclear Cardiology : Selected Computer Aspects. Society of 

Nuclear Medicine, 475 Park Avenue, South, N. Y. , N. Y 10016, 1978, pp. 1-11. ^ 



•ZOl CL 00007-03 NM 



Green, M. V., Bacharach, S. L., Douglas, M. A., Borer, J. S., 
Johnston, G. S. : Sources of virtural background in multi-image blood 
pool studies. Nuclear Cardiology ; Selected Computer Aspects. Society 
of Nuclear Medicine, 475 Park Avenue, South, N. Y. , N. Y. 10016, 1978, 
pp. 97-106. 

Douglas, M. A., Green, M. V. : A system for computer generation of left 
ventricular masks for use in computerized ECG-gated radionuclide 
angiocardiography. Nuclear Cardiology ; Selected Computer Aspects. 
Society of Nuclear Medicine, 475 Park Avenue, South, N. Y., N. Y. 10016, 
1978, pp. 119-128. 

Borer, J. S. Bacharach, S. L. , Green, M. V., Kent, K. M. , Johnston, G. S., 
Epstein, S. E. ; Effect of nitroglycerin on exercise-induced abnormalities 
of left ventricular regional function and ejection fraction in coronary 
artery disease. Circulation 57: 314-320, 1978. 

Kent, K. M. , Borer, J. S. , Green, M. V., Bacharach, S. L. , Mcintosh, C. L. , 
Conkle, D. M. , Epstein, S. E. : Effect of coronary revascularization on 
left ventricular function during exercise. New England Journal of Medicine 
298 (26); 1434-1439, 1978. 



TABLE I 

Comparison of W!iole Pjody I'.easuronr^n ts 

for Fiscal Years in77 and n7r 

Isotope IT 77 illj 



Aesearch Studies 

Ca-t;7 

Ga-G7 

Zn-65 

Cu-67 

Cu-Gi+ 

Cr-51 

K-kO 

1-131 

1-123 

Fe-5g 

Personnel Monitoring Studies 






27 


n 


15 


ni 


1 


15 7 





115 


,"> 


lU 


122 


26 


55 


gno 


15n 





"1 


22 


n 


t+C5 


17CT 



i-125,131 lieft 171C 

l/hole 3ody C32 7"! 

i:^"r 2!^::^ 



Fiscal Year 197G values estimated from 10/77 t'lrou'^'i "/7, 
plus schs'w'uled increases, expressed as yearly rp.tes. 



TABLE II 
Percentc3,:^e of Wfiole Body Counts by Institut'^s 



FY 1977 FYIT 7 ; 



57. S 

3.0 

13. n 

5.C 
13.7 

0.9 
103. T 



DRS 


sn.tt 


CC 


0.1+ 


NCI 





NHLRI 


15. c 


NIAiMDD 


20. G 


NIA 


0^ 




100.0 



Fiscal year 1973 values estlnated fron 10/77 through r;/7o 
plus scheduled Increases expressed as nercenta^e of yearly 
rates. 



c t: 
s: c 




TABLE IV 
Otlier Analysis Related to Whole Hody I'etabolisn Studies 

FY 1977 PLJJiJL* 



Excreta Studies 








Cr-51 







■'^n 


Cu-67 




90 


n 


Cu-64 




_16 









126 


uc 


31ood Studies 








Samples Taken 




247 


23 


Red Cel 1 VJashi 


ngs 


Ihl 


_1G 






1+8 3 


5G 


Blood Counts 








Za-hl 







2 8 


CU-G7 




273 


n 


CU-6I+ 




192 





Zn-55 




328 









798 


7 2 


Tissue Sample Counti 


BS 





Sr-G5,Ce-lit4 

Yb-169,Sc-ltG 5336 3033 

Dose Cal ibrat ions 

1-131 568 370 



Fiscal Year 1973 values estimated from 10/77 throu-h "/!'. 
plus scheduled Increases expressed as yearly rates. 



Table V 
RadiopharTnaceutical Section Statistical Data 



*FY-77 



**FY-78 



Change 



Service Requests 3112 




2240 




- 10% 


V'ork Units 35562 




25350 




- 13% 


Unit Dose Requests 8782 




6500 




- 7% 


RPS Assays 5403 




4100 




- 5% 


Radionuclidic Purity Checks 638 




515 




+ 1% 


RPS Expenditures 156,419, 


.77 


109,527, 


.87 


- 12% 


* = FY-1977 - 15-month period 










** = FY-1978 - projected figure 











= % change based on difference to proportionate 12-inonth period in 

FY- 77 



Table VI 

Radionuclides and Products Received, Registered, and Formilated - FY-78 

H-3 - Aldosterone, [1 ,2,6,7-H-?(N)] 
Cholic Acid 

Hydrocortisone [1 ,2-H-3CN)] 
Maytansine 
Testosterone 
^'itamin A^ 

C-14 - A M S A 

Chenodeoxycholic Acid 
Dopamine 

P-32 - Chromic Phosphate 
Soditun Phosphate 

Ca-47 - Calciiim Chloride 

Cr-51 - Chromic Chloride 
Erythrocytes 
Human Serum Albtmin 
Sodium Chromate 

Co-57 - Cyanocobalamin Capsules 

Co-58 - Cyanocobalamin Capsules 

Fe-59 - Ferrous Citrate 
Plasma 

Callium Citrate 

Krypton Gas 

?1o-P9/Tc-99m Generator 

Antimony Sulfide Colloid 

Diethylenetriaminepentaacetic Acid 

Diphosphonate 

Macroaggregated Human Serum Albumin 

Methylene Diphosphonate 

Sodium Pertechnetate 

Stannous Glucoheptonate 

Stannous Human Serum Albumin 

Sulfur Colloid 

Diethylenetriaminepentaacetic Acid 

Indium Chloride 

Lymphocytes 



Page 2 - Radionuclides . . . (continued) 

14. 1-123 - Sodium Iodide Oral Solution 

Sodium-o- lodohippurate 

15. 1-125 - A-1 High Density Lipoprotein 

A-2 High Density Lipoprotein 

Fibrinogen 

Hemopexin 

Microaggregated Human Serum Albumin 

Porcine Insulin 

Pro-Insulin 

Thyroxine 

16. Xe-127 - Xenon Gas 

17. 1-131 - A-1 High Density Lipoprotein Chylomicrons 

A-2 High Density Lipoprotein 
Human Serum Albumin 
Liothyronine 
Porcine Pro-Insulin 
Sodium Iodide Oral Solution 
Sodium Iodide Uptake Solution 
Scdium-o- lodohippurate 
Sodium Rose Bengal 

18. Xe-133 - Xenon Gas 

Xenon in Saline 

Xenon Ventilation Study 

19. Tl-201 - Thallous Chloride 



TABLE VII 
Diagnostic Nuclear Medicine Section 
Patient Visits by Fiscal Year 

Date 1967 1968 1969 

Total 2568 

Yearly % Change 

Yearly % Change from 1967 

Date 1970 1971 1972 



3093 


1637 


20% 


47%* 


20% 


36%* 



Total 


2181 


2308 


2950 


Yearly % Change 


33%* 


0% 


28% 


Yearly % Change from 1967 


15%* 


7%* 


15% 



Date 1973 1974 1975 



Total 


4688 


7039 


7098 


Yearly % Change 


59% 


50% 


0% 


Yearly % Change from 1967 


82% 


174% 


176% 



Date 1976 1977 1978 



Total 


8054 


10056 


9074 


Yearly % Change 


13% 


25% 


10%^ 


Yearly % Change from 1967 


214% 


292% 


253% 



Decrease 



O -k 



PATIENT VISITS (1,000's) 




/^ October 1, 1977 through Sep'e^iber 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

NURSING DEPARTMENT 

CONTENTS 

Department Missions and Goals 1 

Department Activities 2 

Major Progress in Research, Services, Training and Development 3 

Publ ications 6 

Future Objectives Directed Toward Meeting Goals 9 



NR-i 



October 1, 1977 through Septemoer 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

NURSING DEPARTMENT 

I. Department Missions and Goals 

The Clinical Center Nursing Department exists to provide nursing services 
to patients and support to their families in a biomedical research envi- 
ronment. In addition to clearly identifiable and time-honored nursing 
practices, the Nursing Department assumes the responsibility for many ex- 
panding nursing activities recognized as physician services through the 
Joint Physician-Nurse Committee of the NIH Medical Board, i.e., the pro- 
fessional nurse's interdependent role is one of coordination and collab- 
oration in patient care. 

In order to achieve the departmental missions, the following goals have 
been identified and are being pursued: 

1. To maintain an environment that supports high morale and a com- 
mitted, caring performance by all members of the Nursing Department. 

2. To improve nursing services to patients and to eliminate thosenon- 
nursing activities that are inconsistent with the highest quality 
of nursing care. 

3. To provide, develop, and support the necessary nursing leadership 
to facilitate care. 

4. To evaluate and enhance the effectiveness of the nursing program 
and individual nursing practice. 

5. To identify and investigate areas of nursing research to improve 
nursing practice. 

6. To foster a climate where creative approaches and the spirit of 
inquiry prevail . 

7. To offer opportunities for students and other guests to share 
ideas and grow in the unique environment of the Clinical Center. 

8. To influence health care and nursing practices beyond the confines 
of the Clinical Center through active participation in professional 
and community affairs. 



NR-1 



Department Activities 

A. A major activity of the Department remains that of recruiting and 
retaining an adequate staff in numbers and competence to support the 
research activities of the Institutes. (Attachments I and II). In 
this complex situation the knowledge and skills required to perform 
competently are unique to each unit. Therefore, it becomes increas- 
ingly difficult to rotate nurses among program settings. The Admin- 
istrative Council of the Nursing Department has taken the position 
that "specialists" rather than "general ists" can make a maximally 
effective contribution in this Department. With a limited personnel 
ceiling to achieve the mission, nurses with higher educational attain- 
ment coupled with experience are better able to provide the required 
services 24 hours a day, 7 days a week. In addition, with the imple- 
mentation of the primary nursing system and its attractiveness to 
patients and staff, a majority of the staff must be registered pro- 
fessional nurses. 

B. The Clinical Center Nursing Staff participated in the PHS Nurse Staff- 
ing and Retention Survey. In our response to the report we proposed 
an implementation plan based on five major areas which require our 
attention: 

1. Programs in Continuing Education emphasizing the needs of the new 
graduate, management for new nurse managers, as well as first line 
supervisors and communications courses and workshops for the 
entire staff. 

2. Release time at the worksite for effective program planning, eval- 
uation and "think time" for the development and implementation of 
new and improved practices. 

3. Implementation of Sustained Administrative Support Services to 
free nurses from non-nursing activities through the unit manager 
concept. 

4. Improvement in the Rewards and Recognition Program creating 
additional awards to recognize special accomplishments in nursing. 

5. Improvement in the Physical Working Environment with the decora- 
tion and refurbishing of meeting rooms, lounges and principal 
work sites. 

C. The Nursing Department was the first to be reviewed by an outside Ad 
Hoc Advisory Committee. Our mission, organization, and patient care 
programs within the construct of the overriding research goal of the 
institution were reviewed with recommendations for further dialogue 
among CC management, nursing, and medical staff to effect agreed upon 
changes and future directions. The Committee reaffirmed the need for 
additional nurse staffing to accomplish the present mission, noting 
that the staff is being utilized maximally. 



NR-2 



D. The visit of the Joint Commission on Accreditation of Hospitals 
(JCAH) served as a reminder that nursing care standards with evi- 
dence of-well documented criteria to measure outcomes are required. 
Such a program of care requires continual staff commitment, support, 
and leadership in order to raise standards of care to even higher 
levels. We have activated a program to monitor our progress so as 
to be in compliance on the next visit two years hence when the re- 
vised nursing standards, which are more authoritative and rigorous, 
are used. 

E. The Nursing Department's Administrative Council, the policy making 
body in the Department, held a Retreat to review the two site visits 
and our response to the PHS Nurse Staffing and Retention Survey. 
Following the Retreat, the Chief Nurse informed all staff members 
that no new nursing programs were planned, and that those already in 
place would be strengthened. 

Major Progress in Research, Services, Training and Development 

A. Under the auspices of the Research Review Committee of the Nursing 
Department, for the first time this year, nursing research courses 
opened in the Foundation for Advanced Education in the Sciences 
(FAES). Three research proposals have been approved this year. 

1. Four nurses presented their study designs at the Ninth Annual 
Conference of Principal Investigators and Project Directors 
Involved in Research Facilitation which the Nursing Department 
hosted this year. Eighty-one participants engaged in the 2 1/2 
day meeting which included our well received Fourth Annual Nurs- 
ing Research Symposium on "Home Care: Preference or Priority." 
Ida Martinson, R.N., Ph.D., F.A.A.N., was the guest speaker 
while four Clinical Center nursing staff members served as 
panelists. 

2. Research in progress: 

Ms. Candyce Echelberger, Cancer Nursing Service, Pediatric 
Oncology - has developed a proposal to study the effect of body 
positioning on results of clinical therapeutic agents. 

Ms. Freddie Grice, Nursing Coordinator, and Ms. Emma Vogel , 
Assistant Coordinator, Outpatient Nursing Service - have imple- 
mented, "The Effects of Body Position on Nausea and Vomiting." 

Ms. Susan Hubbard, Cancer Nursing Service - continues to study 
patients during Phase I chemo-therapeutic drug trials . 

Ms. Deborah McGuire, Cancer Nursing Service ~ has developed a 
questionnaire for women at high risk for cancer of the breast 
because of family history. Her study will focus on two groups: 
one, eligible for teaching self breast examinations; the other, 
electing prophylactic mastectomy. 



NR-3 



Ms. Julianna Rugg, Mental Health Nursing Service - f' ' -eloping 
a module on "Teaching Empathy to Nurses." Her study will deter- 
mine if behavior is altered following classes. 

3. Kathleen McCormick, R.N., Ph.D., a clinical nurse specialist, 
joined our staff in May. She holds her doctorate in physiology 
with emphasis in cardiopulmonary physiology. She will assist 
staff members in developing their research and study design. 

She has presented a seminar on Hyperlipemia and Blood Coagulation 
to the Blood Bank staff. In addition, she makes patient care 
rounds with the Pulmonary Branch, NHLBI. 

4, Nurse membership has been established on the NINCDS Clinical 
Research Subpanel . 

Services to patients 

1. The first cycle of retrospective chart audits for 30 audit topics 
was completed and corrective action implemented. Nine additional 
audit topics have been developed and implemented (Attachment III). 
Seventeen others are being developed. 

2. The Nursing Department continues to implement the primary nursing 
system, a professional care model whereby individual nurses are 
accountable for selected patients. 

3. A new position has been classified which recognizes an accountable 
professional nurse who is more self-directed and assumes complete 
authority for nursing care to patients. The new position has been 
classified as a GS-10 in the 610 nurse series. Presently in the 
Nursing Department the RN staff are stratified as follows: 

GS-4 7 

GS-5 5 

GS-7 28 (3 When Actually Employed [WAE] or Part Time [PT]) 

GS-9 372 (64 WAE/PT) 

412 Total (67 WAE/PT) 

4. Stress of care providers is a major concern in our Nursing 
Department. A multidisciplinary initiative is being launched 
among Clinical Center departments that provide direct patient 
care services. In addition, the Administrative Council of the 
Nursing Department has formed a "stress group" and holds sessions 
weekly for discussion: Plans are being developed to focus on this 
topic at the Annual Program Meeting scheduled for the Fall. 

5. Chiefs for two major services, Cancer and Heart and Lung, have 
been selected. Six head nurses were selected this year as re- 
placements for those who have retired or been reassigned. This 
development is viewed as a positive force in the infusion of 
new ideas, as well as an authoritative collective for the im- 
provement of professional nursing practice. 



NR-4 



6. Nursing leadership, primarily through the Medical Information 
System (MIS) Cadre and the head nurses, has resulted in the full 
implementation of all nursing units on the system. We await the 
laboratory interface before initiating the refinement of nursing 
data. The MIS system has great potential for systematizing nurs- 
ing actions and their documentation; such an invaluable aid 
should result in improved nursing care to patients and greater 
satisfaction among care givers. 

7. Nine nursing staff members from NICHD Nursing Service have re- 
turned from a detail of one year at Naval Medical where oppor- 
tunities were afforded to keep their knowledge and skills in 
neonatal nursing current while construction proceeded in their 
program area at the Clinical Center. 

8. With the appointment of Dr. John Fletcher as Assistant for Bio- 
ethics to the Director of the Clinical Center, greater emphasis 
on bioethical questions and their resolution is apparent among 
the nursing staff. One response has been the contractual agree- 
ment between some members of the Nursing Department's Administra- 
tive Council and Dr. Fletcher to explore bioethical nursing/ 
patient concerns raised by the group. This study will include: 

a. Serious systematic study of bioethical issues and attention 
to the ways communications are carried out. 

b. Attempt to apply traditional ethics to current problems. 

c. Institui;ionalization of ethical concerns. 

9. Reorganization of the Nursing Department to maximize the delivery 
of quality nursing care to patients continues. Committee func- 
tions organized along the four tracts - administration, practice, 
education, and research, remain focused and productive. Position 
descriptions have been classified at the GS-13 level for Chiefs 
of Nursing Education, Nursing Practice, and Nursing Services 
Support. The position of Chief Nursing Education is being adver- 
tised and is expected to be filled this Fiscal Year. The position 
of Chief of Nursing Services Support, must await the advent of 
the unit manager system. An Operating Room Manager to administer 
the surgical suites will be recruited. This will result in abol- 
ishing the position, Chief, Surgical (O.R.) Nursing Service. 

10. The Medical Board voted unanimously to approve the recommendation 
of Proposal Number 10 submitted to the Joint Physician-Nurse Com- 
mittee to permit professional nurses to inject Marcaine into 
polyethylene catheters lying next to the intercostal nerves to 
produce a nerve block for control of post-thoracotomy pain. 

11. The Nursing Department has been well represented in extramural 
committee and professional society activities through partici- 
pation on the local, state and national level. Papers have been 
presented, some publications finalized with others in press. 

NR-5 



a) Publications include: 

Belling, D., Kelley, R., Simon, R. , "Use of the Swivel Adaptor 
Aperture During Suctioning to Prevent Hypoxemia in the 
Mechanically Ventilated Patient," Heart and Lung: The Journal 
of Critical Care , Vol. 7, No. 2, March-April, 1978, pp 320-322 

DeVita, V.T., and Hubbard, S.M., "Cancer" Merit Students 
Encyclopedia , Ed.Guerrier, J. P., McMillan Educational Corp., 
New York, Vol. 4, 1978, pp 153-157 

DeVita, V.T., and Hubbard, S.M., "Hodgkins Disease," Merit 
Students Encyclopedia , Ed. Guerrier, J. P., McMillan Educa- 
tional Corp., New York, Vol. 8, 1978, p 596 

DeVita, V.T., and Hubbard, S.M., "Leukemia," Merit Students 
Encyclopedia , Ed. Guerrier, J. P., McMillan Educational Corp., 
New York, Vol. 11, 1978,pp 90-91 

Fagin, CM., Nusbaum, J.G., "Parental Visiting Privileges in 
Pediatric Unit: A Survey," Journal of Nursing Administration , 
Vol. Ill, No. 3, March 1978 

Ferguson, V.D., Fletcher, J., "Letters to the Editor," 
Nursing Outlook , Vol. 26, No. 3, March 1978, pp 142-43 

Ferguson, V.D., "Primary Nursing - A Modality of Care for 
Today," Primary Nursing: One Nurse-One Client Planning Care 
Together , National League for Nursing, Pub. No. 52-1695, 

1977, pp 1-10 

Ferguson, V., "Meeting Patient Needs for Information - Impli- 
cations for Practice. " Proceedings of the Second Conference on 
Cancer Nursing , American Cancer Society, 1978,pp 107-111 

Hubbard, S.M., "Neoplastic Processes," Medical -Surgical 
Nursing:A Conceptual Approach , McGraw-Hill Book Co., New York, 

1978, Chapter Five, pp 123-161 

Hubbard, S.M., "Ovarian Carcinoma: An Overview of Current 
Concepts in Diagnosis and Management," Cancer Nursing , Vol. 1, 
No. 2, April 1978,pp 115-128 

Hubbard, S.M., "The Practice of Cancer Nursing," Proceedings 
of the Second Conference on Cancer Nursing , American Cancer 
Society, 1978, pp 23-29 

Johnson, B.L., Hubbard, S.M., "The Leukemias and Lymphomas," 
Medical -Surgical Nursing: A Conceptual Approach , McGraw-Hill 
Book Co., New York, 1978, Chapter Seven, pp 241-279 



NR-6 



Seipp, C.5 "Immunotherapy for Patients with Osteogenic 
Sarcoma: Approaches to an 'Out-Reach' Program," Oncology 
Nursing Forum Vol. 1-2, Winter-Spring 1978 

b) Significant speaking engagements included: 

1) Cancer Nursing Staff and Chief, Nursing Department - 
Third Annual Convention - Oncology Nursing Society 

2) Chief, Nursing Department - American Association for the 
Care of Children in Hospitals, Quad State Hospital Asso- 
ciation, University of Louisville, Syracuse University, 
Catholic University of America, George Mason University, 
Marymount College of Virginia, Virginia League for Nurs- 
ing, V.A. Hospital -Sal em, Prairie State College, Maryland 
Licensed Practical Nurses' Association, Inc., and Massa- 
chusetts General Hospital. Three Lectureships - 

Zula Mae Baber Bice Memorial Lecture - University of 
Virginia 

Kemble Lecture - University of North Carolina-Chapel 
Hill 

Fagan Health Care Lecture Series - Omaha, Nebraska 

3) Four staff members are scheduled to present papers at 
International cancer meetings - 2 in London and 2 in 
Buenos Aires. 

4) The Department has sponsored four seminars to be pre- 
sented at Chautauqua '78, a national continuing educa- 
tion symposium for registered nurses at Vail, Colorado. 

12. Criteria have been developed and plans made for Fiscal '79: for 
three new awards - The Nurse of the Year, Distinguished Nurse, 
and Recognition for Research Endeavors. 

13. Significant Awards: 

A. Ms. Vernice Ferguson, Chief, Nursing Department, received 

the DHEW Distinguished Service Award, the highest departmental 
honorary recognition conferred upon civilian employees. 

B. Ms. Alice Duncan, Chief, Cancer Nursing Service (Retired), 
received the PHS Commissioned Corps Meritorious Service Medal. 

C. Ms. Tanya T. Crow, Chief, Neurology Nursing Service, was the 
recipient of PHS Commissioned Corps Commendation Medal. 

D. Ms. Ruth Carlsen, Clinical Nurse Educator, Mental Health Nurs- 
ing Service, was the recipient of the NIH Merit Award. 

NR-7 



C. Training and Development 

1. Six nursing services held clinical conferences this year. 

a. The Parkinsonian Patient With Nursing Overview - Neurology 
Nursing Service 

b. The Care of the Patient with Idiopathic Hypertrophic 
Sub-Aortic Stenosis - Heart and Lung Nursing Service 

c. Health Education: An Essential Component of Health Care - 
Outpatient Nursing Service 

d. Preceptorship: Perspectives and Role Clarification - Mental 
Health Nursing Service 

e. The Nursing Process and MIS - MIS Cadre 

f. Taming Stress - Allergy and Infectious Diseases Nursing 
Service 

Monographs of these conferences will be forthcoming. It is of 
interest to note that at all recruitment efforts in the commun- 
ity, these monographs are in heavy demand. 

2. Two registered nurses have completed nurse practitioner programs 
this year. One of whom has received certification as a pediat- 
ric nurse practitioner from the Board of the National Association 
of Pediatric^ Nurse Associates .and Pediatric Nurse Practitioners. 

3. Ms. Roberta Seward, Clinical Nurse Expert, Cancer Nursing Service, 
has completed successfully the Enterostomal Therapy Program at 
Emory University and is now certified as an Enterostomal Therapist. 
An Ostomy Clinic, staffed by Ms. Seward with two physicians serv- 
ing as consultants, was established in May. 

4. Ms. Rosalie Smith, Clinical Nurse (Hyperthermia) is developing 
her new role as hyperthermia nurse in research trials. Her pri- 
mary goal is to define her role as it relates to all members of 
the mul tidisciplinary team and the patient population. 

5. Fourteen FAES courses were offered this year by the Nursing De- 
partment with total attendance of 152 students; 60 are Clinical 
Center staff members. 

6. Nursing Department staff members participated in a variety of ex- 
tramural educational offerings (Attachment IV). 

7. An internship program established this year has afforded 6 nurses 
an opportunity for 1 week to observe activities in the Central 
Nursing Office with the Chief Nurse as preceptor. Ten have 
applied for the coming year; 8 have been accepted. 



NR- 



8. The Head Nurse Group has made considerable progress in organizing 
their efforts in this critical leadership role, "'.... collective 
has stratified along the four tracts - administration, practice, 
research and education. 

9. Two nurses, one from England, the other from Holland, complete 
six months in the Foreign Exchange Nurse-Visitor Program co- 
sponsored by the Nursing Department and the National Cancer 
Institute. 

10. Graduate students from the University of Maryland and The CathoU; 
University of America have utilized the resources of the Clinics'* 
Center and the Nursing Department primarily while pursuing tr.eir 
practicum. They include: 

Catholic University - 5 masters level students in 
Community Health Nursing 

- 6 doctoral level students 

University of Maryland - 3 masters level students in 

Nursing Service Administration 

IV. Future Objectives Directed Toward Meeting Goals 

As a result of three significant external forces, the JCAH Visit, the 
Ad Hoc Advisory Committee and the PHS Nurse Staffing and Retention 
Survey, all of which reenforced our goal direction, the Nursing Depart- 
ment's Administrative Council determined its direction and program em- 
phasis. This counc^'T: 

1. Recognizes and accepts nursing as a freestanding profession 
with authority, autonomy and accountability for its pract'ce 
which is the "raison d'etre." 

2. Envisages nursing practice moving beyond sickness care t;' 
health promotion. Maximum use of closed circuit television 
for patient teaching and staff development is endorsed. 

3. Endorses heightened use of peer consultation within the 
Clinical Center and extramural consultations when indicated. 

4. Will continue to examine the role of new graduate nurses 
and develop responsive programs for their orientation to 
this complex research environment. 

5. Will urge a closer relationship with the Educational Services 
Officer to maximally utilize NIH resources in promoting 
multidisciplinary programs as we move toward a more collabora- 
tive role. 



NR-9 



6. Recognizes the need to examine the changing role of the 
head nurse. 

7. Is looking beyond JCAH and committed to the implementation 
of a multidisciplinary audit to ensure and enhance communi- 
cations with health care colleagues. 



NR-10 



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O -o 
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m yd 



STAFFING DATA - NURSING DEPARTMENT 



Total number of Positions 

Total number of positions filled 

Total number of vacancies 



July 1. 1977 



627 

618 

- 9 



June 30, 1978 



598 

605 

+ 7 



Administrative 

Total number of positions 

Total number of positions filled 

Total number of vacancies 

Clinical Instructors 

Total number of positions 

Total number of positions filled 

Total number of vacancies 

Nurse Clinicians 

Total number of positions 

Total number of positions filled 

Total number of vacancies 

Staff Nurse 

Total number of positions 

Total number of positions filled 

Total number of vacancies 

Practical Nurse 

Total number of positio"hs 

Total number of positions filled 

Total number of vacancies 

Technical Positions 

Total number- of positions 

Total number of positions filled 

Total number of vacancies 

Nursing Assistants 

Total number of positions 

Total number of positions filled 

Total number of vacancies 

Clerical 

Total number of positions 

Total number of positions filled 

Total number of vacancies 



343 

352 

+ 9 



88* 

84 
4 



341 
361 

■ 20 



67** 

74 

7 



*Includes 21 students in Stride Nursing Program at Marymount 
**Includes 10 students in Stride Nursing Program at Marymount 



AUDIT TOPIC 

First Cycle Completed for: 

WBC Donor 

Ca of Breast receiving chemotherapy 

Non-Hodgkins Lymphoma receiving chemotherapy 

Acute Lymphocytic Leukemia receiving chemotherapy 

Cardiac Catherization 

Melanoma with groin, axillary, neck dissection with or without wide 
excision and skin graft 

Wide excision of melanoma with split thickness skin graft with 

1) axillary node dissection 

2) superficial groin dissection 

3) superficial and deep groin dissection 

Hypertension 

Aortic Valve Replacement 

Non-Hodgkins Lymphoma 

Cerebral Seizures 

Regional Lymph Node Dissection 

Neuro-Psychiatric Disorder 
Huntington's Disease 
Pre-Senile Dementia 
Karsokoff's Psychosis 
Tardive Dyskinesia 
Gilles de la Tourette Syndrome 

Acute Lymphocytic Leukemia (2) 

Schizophrenia 

Asymmetric Septal Hypertrophy 

Manic Depressive Cyclical 

Unipolar Depression 



Attachment III 



2 - 



Systemic Lupus Erythegiatostis * - ";l .; ■ - . ^ 

Hyperparathyroidism 

Oat Cell Ca of Lung 

Pulmonary Fibrosis -; . 

Cystic Fibrosis 

Minimal Brain Dysfunction 

Childhood Minimal Brajn Dysfunction _ >■ 

Hyperkinesia 

Hyperactivity ^ 

Myasthenia Gravis 

Wiskott-Aldrich Syndrome 

Cryptococcal Meningitis 

Male Infertility 
Gynecomastia 
Varicocele 
Hypogonadism 
Azospermia 
Kalman's Syndrome 
Kleinfelter's Syndrome 
Testicular Biopsy 

Vitrectomy 

Prematurity/SGA 

(Failure to thrive) 

Developed and Implemented: 

Ewings Sarcoma 

Hypertension 

Surgical oncology patients receiving sigmoidoscopy for rectal Ca 

Thoracotomy 

Muscle biopsy for neuro muscular disease 

Hypogammaglobulinemia 

Growth hormone deficiency 

Intestinal lymphangiectasia 

Patients with diarrhea 



Attachment HI 



Nursing Department Staff in School 



Position 



Full Time 



Part Time 



Upward 
Stride Program Mobility 
Full Time Program 



NA 

Unit Clerk 

LPN 

Secretary 

Clerk Typist 

Patient Care Tech. 

Inhalation Therapy Tech, 

Total 



3* 



139 AA 

1 

6 



148 



5 *** 
3 **** 

3 AAA* 

5 AAAA 
8 AAAA 

2 AAAA 
"26" 



* 3 RNs fully funded by Nursing Department 
** 88 credit courses 

51 non credit courses of 40 hours or more 
*** B.S. Extended Program 
AAAA A.A.S. Program 



Attachment IV 



October 1, 1977, through September 30, 1978 



PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY OF ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

NUTRITION DEPARTMENT 



CONTENTS 

Department Mission and Goals Nt-1 

Department Activities Nt-2 

Major Progress in Research, Services, Training and Development Nt-2 

Future Objectives Directed Toward Meeting Goals Nt-4 

Problems Nt-4 



October 1, 1977, through September 30, 1978 



PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

NUTRITION DEPARTMENT 



I. DEPARTMENT MISSION AND GOALS 

The Nutrition Department of the Clinical Center makes a unique contri- 
bution to the development of valuable tools and techniques which have facili- 
tated the clinical research program of nine Institutes. Specifically, these 
tools and techniques are diets with meals served that not only meet the 
criteria of the various demands of research protocols in the clinical research 
programs at NIH but are also acceptable and enjoyable to patients. 

The Nutrition Department's opportunities for contributing to the 
clinical research program continue to grow along with the trend that recog- 
nizes nutrition as a significant factor in today's medicine. 

At the end of FY 1977 a major administrative decision was made to 
continue with decentralized food service rather than go into centralized tray 
service. In doing so, the Department is assured the ability to continue to ^ 
contribute in a major way to the clinical research program. By providing 
precise and complete data on patients' nutrient intake the Department assists 
the medical investigators in their work. Examples of some of the unique 
responsibilities assumed by the Nutrition Department are: 

1. Control of a single nutrient intake via food in varying amounts 
for an individual patient. 

2. Control of more than one nutrient intake via food for purposes 
of therapy or diagnosis for an individual patient. 

3. Control of nutrient and/or caloric intake for individuals who 

are placed on daily iso-nutrient or iso-caloric protocols or both. 

4. Control of group intakes qualitatively for control groups and 
therapy groups. 

5. Provision of diets for short-term studies or tests involving 
numerous controls. 

5. Measurement, where appropriate, of the daily nutrient intake of 
individual patients. 

7. Provision of constant diets for evaluation of balance studies from 
a Metabolic Kitchen Unit. W 



Nt-1 



In addition to these, the Department's goals include continued active 
participation in the Clinical Center Safety Program, the Clinical Center Equal 
Employment Opportunity Program, and the NIH Labor Management Relations 
Program. 

II. DEPARTMENT ACTIVITIES 

During the period October 1, 1977, through September 30, 1978, the 
Nutrition Department served a total of 336,410 meals. Fifty-six% of these 
meals were important to a research protocol, i.e., the protocols necessitated 
the control of nutrients, calories, fluid, and/or metabolic balance studies. 
To provide these services, 13 individual service units, a main kitchen, and a 
storeroom unit were staffed for the year and the 8th floor metabolic kitchen 
operated for 11 months. The Department was staffed with: 

22 Registered Dietitians 

1 WAE Registered Dietitian 

139 Full-time Nonprofessional Staff 

32 Part-time Nonprofessional Staff 
194 TOTAL 

III. MAJOR PROGRESS IN RESEARCH, SERVICES, TRAINING, AND DEVELOPMENT 

During this period, the average daily workload statistics indicated 
that 22 patients were on Category IV diets, 77 patients were classified as 
Category III, and 97 patients were classified as Category II. 

Category IV Required extensive professional time and care in 
planning diets which were an integral part of the 
research study. 

Category III Required professional staff to plan the diet order for 
the individual patient and to provide the physician 
with information to interpret his project. 

Category II Required professional staff to write the diet, or food 
service supervisor to adapt the food service to the 
patient. 

In addition, the Nutrition Department provided these additional 
services essential to successful medical research: 

1. Between 184-207 patients were on fluid intakes each day. 

2. Between 89-108 patients per day were on diets that required the accurate 
measurement of all food eaten. 



Nt-2 



3. Between 80-92 patients each day were on diets that required the checking 
back of each meal tray and replacement of the appropriate nutrient being ^ 
controlled by dietary intake. 

4. The Laminar Flow Unit served 16,184 meals during the year. Each tray 
served required a tremendous amount of staff time not only in planning 
the food that could be offered but also in preparation of each food item 
to meet the Clinical Center's standards of reverse isolation for Laminar 
Flow Units. 

Office space for an outpatient dietitian was allocated, and this 
service was initiated on a full-time basis on December 12, 1977. 

After close monitoring of the Technicon system, changes were 
recommended for new and improved Nutrition Department matrices. These changes 
were made and have appreciably improved service to both physicians and the 
Nutrition Department. 

Considerable emphasis was placed on training for all groups in the 
Department. Two meetings per month were held for the professional staff 
with recognized speakers invited for one of these meetings each month. In 
addition, training experiences were provided for appropriate staff members 
as a means of improving service and knowledge of recent advances in the area 
of nutrition. 

This year the Department sponsored staff in the following training 
programs: <^ 

4 - NIH Adult Education Program 

1 - NIH Upward Mobility College 

1 - Undergraduate degree program 

1 - Graduate degree program 

2 - Small Purchasing Procedures Class 

1 - Communications Workshop for Secretaries 

3 - Cardio-Pulmonary Resuscitation Class 

1 - Labor Relations Course for Supervisors and Managers 

8 - Leadership Training 

1 - Five day Workshop in Food Service Administration 

3 - Quad Hospital Association Meeting 

8 - National and Local Meetings j 



Nt-3 



Five Information Sessions were held for the entire Nutrition 
Department staff. The agenda for each session included a recent health 
film and a report from the Nutrition Department Representative to the 
Clinical Center EEO Advisory Conmittee. 

The Department sponsored two communication workshops to improve 
communications. The first was for dietetic assistants and metabolic cooks, 
and the second included Clinical Center dietitians, pharmacists, nurses, 
social workers, and medical records librarians. Fifty-nine Nutrition 
Department staff participated in these workshops. 

IV. FUTURE OBJECTIVES DIRECTED TOWARD MEETING GOALS 

During this next year the Nutrition Department expects to accomplish 
the following: 

1. Finish the remodeling of the main kitchen and re-establish quality 
controlled decentralized food service for the patients of the Clinical 
Center. 

2. Revise current diet instruction materials and procedures to provide a 
sound basis for diet instruction service in the new ACRE Building. 

3. Implement a re-negotiated agreement with AFGE, Lodge 2419. 

4. Re-establish an extensive in-service training program for nonprofessional 
staff. 

5. Conduct an administrative review of procedures and practices in the 
Department. To meet this goal, two experienced and highly respected 
chief dietitians were invited to consult with the Department during the 
week of June 12-16, 1978. Their review provided a basis for the senior 
staff to collectively establish goals to be accomplished during the 
period FY 1979 - FY 1984. 

V. PROBLEMS 

Many personnel problems continued to hinder adequate staffing coverage 
for some periods during this year. The Department experienced 1-2 employees 
on jury duty throughout the year and 1-2 employees on leave due to long-term 
illnesses. The initiation of 35 hour career part-time positions reduced 
turnover to some extent. 

Remodeling continued to require many adjustments for the Main Kitchen 
staff. With careful planning and supervision the Department continued to 
maintain its full food service with minimum inconvenience to the patients. 



Nt-4 



As a result of inflation, costs continued to spiral. The total 
expenditure for the Department for FY 1978 was as follows: 



Personnel $2,957,103 

Food 608,000 

Equipment and Supplies 134,000 
Training and Travel 4,528 

$3,703,631 



Nt-5 



October 1, 1977, through September 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

OFFICE OF OCCUPATIONAL MEDICINE 

Contents 

I Department Missions and Goals OOM- 1 

II Department Activities OOM- 1 

III Major Progress in Research, Services, Training, and Development. .OOM- 2 

IV Future Objectives Directed Toward Meeting Goals OOM- 4 



October 1, 1977, through September 30, 1978 
PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH ^ 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

OFFICE OF OCCUPATIONAL MEDICINE 

Department Missions and Goals 

The Office of Occupational Medicine through the Occupational Medical Service 
provides an extensive medical program for all employees of the National Insti- 
tutes of Health which includes all elements of the Federal Employee Occupational 
Health Program as specified by Executive and HEW Directives. 

The Occupational Medical Service is responsible for maintaining essential 
services and facilities to provide emergency treatment for on-the-job illness 
or injury of employees; provides health education and preventive medical pro- 
grams to make employees aware of the importance of maintaining good health; 
advises management and employees in resolving work related health problems; 
assists management in evaluating handicapped individuals in terms of specific 
job assignments; develops and executes a comprehensive mental health program 
for NTH, including alcoholism and drug abuse counseling; and develops medical 
surveillance programs designed to minimize environmental health hazards. 

The Occupational Medical Service's goal is to assure that employees are able 
to perform their duties without hazard to themselves or others; to offer job f6> 
assignments in relation to medical fitness; to provide preventive medical 
services to assist employees in meeting their health needs; to prevent adverse 
effects of hazards in the work environment; and to provide clinical consultation 
for occupational diseases for employees and Clinical Center patients at the 
request of Institute physicians. 

The Occupational Medical Service is administratively accountable to the Chief, 
Office of Occupational Medicine, CC, who also serves as the Occupational Health 
Officer, NIH. In carrying out its responsibilities, the Occupational Medical 
Service works closely with the Associate Director for Environmental Health and 
Safety, DRS , the Director, Office of Research Safety, NCI, and NIH Institute 
Clinical Directors. 

Department Activities 

National Health Services, Inc., was selected through competitive bidding as the 
contractor for provision of occupational medical services to NIH beginning 
October 1, 1977, National Health Services, Inc., as the incumbent, was able 
to begin new contract operations with a minimum of staff change and with no 
time lost for orientation and training of new staff personnel; thus continuity 
was achieved in the areas of health surveillance examinations, health education 
and uniphasic screening. 

Workload statistics have been prepared for October 1, 1977 through September 30. 
1978 using an estimated of average workload for the last quarter. There has (•^ 

OOM-1 



been a slight decrease in total visits for the one year period, with a decrease 
in visits for personal health problems and occupational injuries. 

The Occupational Medical Service facility underwent a major relocation which 
was conducted in a two-step move because of the expansion and remodeling of 
the Clinical Center with the addition of the Ambulatory Care Research Facility, 
On March 6, the Occupational Medical Service Health Unit in Bldg. 31 was closed 
for extensive remodeling to house the Bldg. 10 Health Unit. On June 23-24 the 
facility previously located in Bldg. 10 was relocated to Bldg. 31 and opened 
for patient care activities on June 26, 1978. This move necessitated careful 
planning and follow-through on support activities obtained from the Radiology 
and Clinical Pathology Departments in the Clinical Center. Patient care 
services to employees have been continued with a minimum of inconvenience in 
the new facility. Combination of facilities resulted in a reduction in staff 
of one Occupational Health nurse. In the total percent of workload, there is 
a significant increase in visits to the Employee Assistance Program, which has 
a new impetus during this program year. Percentage of total workload has in- 
creased from 6%-10%. 

The Employee Assistance Program, developed and expanded from the Alcoholism 
and Drug Abuse Program, was staffed during this reporting period by one psy- 
chiatrist working half-time and two full-time mental health counselors. The 
main thrust of the program during the first year was a concentrated effort to 
expand coverage to reach employees with mental health problems at all grade 
levels. To increase this coverage, the Occupational Medical Service psychiatric 
staff conducted three 10 hour seminars for senior supervisors entitled, "Under- 
standing Employee Problems" in conjunction with the Employee Relations and 
Recognitions Branch; the counseling staff presented details of the Employee 
Assistance Program to all Personnel Officers at NIH, the Administrative Officers 
Staff Meeting, and began individual meetings with Branch Chiefs of all Insti- 
tutes. As a result the workload of this program increased, and in the third 
quarter there was an increased percentage of referrals from GS Grades 9-12. 
It is felt that this represents moderate success in penetration for this 
important Employee Assistance Program. 

A Quality Assurance Inspection Survey was conducted May 16-17, 1978. A team 
of occupational medical physicians and nurses reviewed the NIH Occupational 
Medical Service program, facilities, and staffing. The findings of this panel 
were reviewed jointly by Clinical Center management and the contractor to 
improve areas of contract performance and services to the NIH employee popula- 
tion. 

Major Programs in Research, Service Training and Development 

Occupational Medical Service continued the expansion of surveillance examina- 
tions in patient care and research. The Occupational Medical Service worked 
closely with NIH Biohazards Committee and the Environmental Safety Branch, DRS, 
to continue the early identification of potential hazards. 

Significant effort was expended in continuing the periodic surveillance exami- 
nations for the National Cancer Institute laboratory personnel exposures to 
oncogenic viruses and chemical carcinogens. In addition, new medical protocols 

OQM-2 



for surveillance were developed and begun during this year for laboratory 
workers participating in recombinant DNA research at the P4 Containment Level, ^- 
employees exposed to chemical hazards (benzene and perchlorethylene) , and 
employees with a history of exposure to asbestos in their previous work assign- 
ments as well as past exposures at the NIH. 

In addition to the chemical environmental hazards eniimerated above, expanded 
surveillance examinations were conducted for clinical and laboratory workers 
exposed to tuberculosis and hepatitis. During this year a screening program 
for all female employees of the child bearing age for rubella was conducted. 
Approximately six hundred NIH employees participated i n this program, which 
is now ongoing and available to all female employees in the childbearing age. 

On January 16, following the recommendation of the Occupational Medical Service 
and the NIH Clinical Center, the Director, NIH, announced a High Blood Pressure 
Screening Program for all NIH employees to be conducted by the Occupational 
Medical Service. Pilot testing in the OMS clinic was completed in March and 
April with the official starting of the program in May 1978. 

This program offered screening, follow-up, monitoring, and education services 
at the work site for NIH employees. Working through an employee advisory 
committee. Occupational Medical Service coordinated the publicity and facilities 
for this intensive program. The HEW Interagency Technical Committee's working 
group on hypertension was consulted in the development of this program. On 
March 6-7, 1978, the Medical Director and Assistant Medical Director, Occupa- 
tional Medical Service, co-chaired the Interagency Technical Committee Confer- 
ence on High Blood Pressure Control in the Federal Work Setting, held in Wash- ^^ 
ington, D. C. This program was co-sponsored by the Occupational Medical Sectio., 
of the Civil Service Commission. 

During May and June screening programs were conducted in all off -campus rental 
facilities, shared laboratories, the Gerontology Research Center, U.S. Public 
Health Service Hospital, Baltimore, and the University of Maryland Hospital, 
Baltimore. This first phase of the program screened 2,906 employees and will 
continue in the Fall of this year with the completion of screening. This 
program will then be on-going through the Occupational Medical Service Units 
for all NIH employees. 

The Occupational Medical Service Health Education Program conducted for NIH 
employees completed a very successful year. In November and December, in 
cooperation with the Montgomery Police Department, several programs entitled 
"Sexual Assault Prevention" were presented. The first four scheduled presenta- 
tions were immediately filled, and the presentation was rescheduled in January 
and February for employee groups in outlying buildings and the NIH campus. In 
March the anti-smoking film "Smoking: How to Stop" was presented to NIH employees 
and employees in off-campus rental buildings. In April, with the Employee Recog- 
nitions Branch, OMS developed an all-employee notice and sponsored publication 
of a "Parents' Guide to Childhood Immunizations." This program alerted the 
employees to the importance of having their pre-school children fully immunized 
against childhood diseases. Both the anti-smoking and the childhood immuni- 
zations programs carried out HEW directives for employee exposure to these 
important preventive medical areas. /*»' 



OOM-3 



Future Objectives 

On March 2 the Occupational Medical Service Operations Research Advisory Com- 
mittee met to review specific goals with input from the NIH. Thirteen specific 
items were reviewed following preparation of proposed operations research pro- 
tocols. 

After consideration, the Committee selected five items for top priority to be 
reviewed as future objectives for Occupational Medical Service: 1) Expanding 
epidemiological opportunities in Occupational Medicine utilizing the stable 
employee population; 2) Refining health surveillance methodology as related to 
specific occupational disease hazards existing at NIH; 3) Continuing evaluation 
of the OMS Medical Records System to assure that specific occupational health 
needs of the NIH are being met; 4) Steps needed to improve liaison with the 
Environmental Health and Safety Branch, DRS, and other environmental health 
and safety programs at NIH to provide more complete health hazard exposure 
data basic to effective health surveillance; and 5) Basic to achievement of 
these objectives is a need for continued evaluation of the effectiveness of 
preventive medical programs provided by Occupational Medical Service to the 
NIH population. 



SELECTED WORKLOAD STATISTICS OCTOBER 1977 - SEPTEMBER 1978 



Average 



Occupational Injury 
Occupational Disease 
Preventive Medical Visits 
Personal Visits 
PHEAP 

(Public Health Employee 
Assistance Program) 

Total Visits 32,922 

*Includes 1,061 visits for alcohol and drug abuse 



Total 


Monthly 


Percent of 


Visits 


Frequency 


Workload 


2,920 


243 


9 


1,028 


85 


3 


18,162 


1,513 


55 


7,628 


635 


23 


3,184* 


265 


10 



2,741 



100 



• 



OOM-5 



October 1, 1977, through September 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

OUTPATIENT DEPARTMENT 

CONTENTS 

Program Ob j ectives OP- 1 

Departmental Activities OP-2 

Progress Achieved OP-2 

Other Activities OP-4 

Plans OP-4 



OP-i 



October 1, 1977, through September 30, 1978 



PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

OUTPATIENT DEPARTMENT 



PROGRAM OBJECTIVES 

The mission of the Outpatient Department is to assist the professional 
members of the Clinical Center staff to provide excellence in patient care, 
The Department's goal is to provide effective and convenient settings, 
expeditious and comprehensive seirvice to Clinical Center patients. 

The Outpatient Department is made up of six sections: Admissions; the 
Clinics; the Patient Travel Office; Special Ambulatory Care Program; Local 
Transportation; and the Messenger and Escort Service. Each Section provides 
special services to meet specific kinds of patient needs. 

The following are the individual objectives for each Section, which 
individually and collectively meet the overall objectives of the Department. 

Admissions - The objective of this Section is to admit both the inpatient 
and the outpatient in the most expeditious manner possible, ensuring that 
all information received and transcribed is accurate. 

The Clinics - This Section provides a setting in which physicians are able 
to conduct examinations and/or treatments of ambulatory patients on a timely 
basis, with assistance from other members of the Clinical Center staff. 

The Patient Travel Office - This Section provides and arranges transportation 
to and from the Clinical Center, taking into consideration the patients' 
medical and personal needs, comfort, and care with the least inconvenience 
to the patients. 

Special Ambulatory Care Program - The objective of this Program is to offer 
participating Institutes and physicians a method of treating ambulatory 
patients, not living within commuting distance, on an outpatient basis. The 
patients are housed in a nearby motel and provided transportation to and 
from the Clinical Center for treatment. 

Local Transportation - The objective of this Section is to provide essential 
transportation for patients when the patient cannot provide his own. This 
includes transportation to and from the air, train, or bus terminals, 
special car and driver service for debilitated patients, and ambulance 
service for those patients needing more technical care. 



Messenger and Escort Service - This Section's objective is to transport ^ 
patients and specimens expeditiously, always mindful of the necessary ^J 
safety measures to be taken during the transportation. 

DEPARTMENTAL ACTIVITIES 

These activities are designed to meet the overall objectives of the Department 
as well as those of the individual Sections to provide the support necessary 
for the highest quality patient care. 

1. To maintain the maximum productivity of the employees within the 
Department . 

2. To refine the centralized appointment system so that more of oiir patients 
are seen at an approved time rather than during a block of time. 

3. To continue to improve the supply system for the Clinics. 

4. To increase the number of patients preadmitted to the Clinical Center 
so that the patients are required to spend less time in the Admissions 
Office. 

5. To continue the reorganization of the Admissions Office. 

6. To train the staff in the art of public relations and other related 
courses. ^^ 

7. To continue to work with the architect in the design phase of the 
renovations for the Outpatient Department and to work with the contractor 
during the construction phase. 

8. To begin to reorganize the Patient Travel Office's procedures and 
policies to more effectively handle the ever-increasing load of patient and 
Clinical Center employee travel. 

9. To afford the Institute physicians detailed information on the Special 
Ambulatory Care Program, the Travel Section, and the Admissions Section. 

10. To effectively reduce the money spent on travel and the Special Ambulatory 
Care Program, without curtailing patient care. 

PROGRESS ACHIEVED 

1. Some of the training programs to improve the output of work of the 
various employees of the Department are: inservice training sessions, 
participative management, and individual counselling sessions. This process 
is an indefinite one, as it is difficult to place limitations on it if it is 
to be successful. 



2. The centralized appointment system has been implemented for all the 
Clinics now using the main Clinic. Currently we are refining individual 



OP- 2 



#: 



Clinics from block appointments to individual appointment times for the 
patients. There has been much success in switching the appointments for the 
Clinics from block times to individual times. Approximately 95% of the 
Clinics are utilizing individual times. 

3. The staff for the stocking program has been hired and have been cross- 
trained in all the Clinics. The program has been enlarged to encompass the 
handling of patients ' baggage (both inpatient and outpatient) . A list of 
supplies used by the Clinics has been given to Central Sterile Supply to 

be programmed for the Medical Information System. The policy and procedure 
manual has been completed as well as the quotas for each item used has been 
determined and labeled in the various rooms within the clinics. 

4. The number of preadmissions completed by the Admissions Office is 100% 
of the requests received by Admissions before the patient actually arrives 
at the Clinical Center. By pre-admitting the patient, we are able to make 
the patient record available to the physician to enter orders on the Medical 
Information System prior to the admission of the patient to the Clinical 
Center. 

5. The reorganization of the Admissions Office (to incorporate the functions 
of the Admissions Staff, Receptionists, Administrative Officers of the Day), 
has been completed. The policy and procedural manual has been developed 

and distributed to the staff and members of the Director's office of the 
Clinical Center. 

6. All the clerks in the Outpatient Department participated in a course in 
public relations and office procedures. Several employees of the Outpatient 
Department participated in a seminar on Death and Dying. 

7. The design phase of the Outpatient renovations was completed and the 
construction phase began in April. The completion of the job should be in 
January, 1979. At that time, several of the ancillary services will either 
be housed in the Clinic area permanently or else be a satellite unit of that 
particular department. 

8. Currently, a study is being completed of the Patient Travel Office. This 
is the first time that such a complete and detailed analysis of the Patient 
Travel Office has been done. The result of this project will be to initiate 
new procedures and policies within this office, as well as to ascertain 
whether monetary savings can be made through these new procedures. 

9. The physicians of the various institutes were oriented by the supervisors 
of the Special Ambulatory Care Program, Patient Travel, Admissions Section, 
and Clinics. This is an ongoing program for all new Clinical Center 
Associates. 

10. One of the measures taken to reduce the monies spent was to decrease the 
niamber of guardians (escorts) of patients transported to the Clinical Center 
and placed on the Special Ambulatory Care Program. In addition, other measures 
were taken to more strictly enforce Patient Travel and Special Ambulatory 
Care Program regulations. 



OTHER ACTIVITIES ^^ 

1. The Department is developing a packet to be mailed to the patients before 
their arrival. This packet would include: information about the Clinical 
Center; location of the NIH campus and the Clinical Center; list of local 
restaurants and motels; approximate charges for each, etc. 

2. The Outpatient staff has been working with the Technicon staff and the 
Office of Clinical and Management Systems to develop the Medical Information 
System procedures and its implementation in this Department. The Clinics 
began using the system in June and will continue to phase in the programs 
over the next several months. 

PLANS 

1. To further expand the duties and assignments of the Messenger and Escort 
Service. 

2. To continue to train employees of the Outpatient Department in public 
relations and other related areas. 

3. To continue to define and refine the Outpatient Department stocking 
program. 

4. To send the drivers of the Local Transportation Unit to Emergency 
Medical Technician courses. j, 

5. To develop a new system and procedures for the Local Transportation Unit. 



October 1, 1977, through Septeinber 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

OUTPATIENT DEPARTMENT 

CONTENTS 

Program Ob j ectives OP- 1 

Departmental Activities OP-2 

Progress Achieved OP-2 

Other Activities OP-4 

Plans OP-4 



OP-i 



October 1, 1977, through September 30, 1978 



PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

OUTPATIENT DEPARTMENT 



PROGRAM OBJECTIVES 

The mission of the Outpatient Department is to assist the professional 
members of the Clinical Center staff to provide excellence in patient care. 
The Department's goal is to provide effective and convenient settings, 
expeditious and comprehensive service to Clinical Center patients. 

The Outpatient Department is made up of six sections: Admissions; the 
Clinics; the Patient Travel Office; Special Ambulatory Care Program; Local 
Transportation; and the Messenger and Escort Service. Each Section provides 
special services to meet specific kinds of patient needs. 

The following are the individual objectives for each Section, which 
individually and collectively meet the overall objectives of the Department. 

Admissions - The objective of this Section is to admit both the inpatient 
and the outpatient in the most expeditious manner possible, ensuring that 
all information received and transcribed is accurate. 

The Clinics - This Section provides a setting in which physicians are able 
to conduct examinations and/or treatments of ambulatory patients on a timely 
basis, with assistance from other members of the Clinical Center staff. 

The Patient Travel Office - This Section provides and arranges transportation 
to and from the Clinical Center, taking into consideration the patients' 
medical and personal needs, comfort, and care with the least inconvenience 
to the patients. 

Special Ambulatory Care Program - The objective of this Program is to offer 
participating Institutes and physicians a method of treating ambulatory 
patients, not living within commuting distance, on an outpatient basis. The 
patients are housed in a nearby motel and provided transportation to and 
from the Clinical Center for treatment. 

Local Transportation - The objective of this Section is to provide essential 
transportation for patients when the patient cannot provide his own. This 
includes transportation to and from the air, train, or bus terminals, 
special car and driver service for debilitated patients, and ambulance 
service for those patients needing more technical care. 



Messenger and Escort Service - This Section's objective is to transport ^^ 
patients and specimens expeditiously, always mindful of the necessary ^J^' 
safety measures to be taken during the transportation. 

DEPARTMENTAL ACTIVITIES 

These activities are designed to meet the overall objectives of the Department 
as well as those of the individual Sections to provide the support necessary 
for the highest quality patient care. 

1. To maintain the maximum productivity of the employees within the 
Department . 

2. To refine the centralized appointment system so that more of our patients 
are seen at an approved time rather than during a block of time. 

3. To continue to improve the supply system for the Clinics. 

4. To increase the niomber of patients preadmitted to the Clinical Center 
so that the patients are required to spend less time in the Admissions 
Office. 

5. To continue the reorganization of the Admissions Office. 

6. To train the staff in the art of public relations and other related 
courses. ^ 

7. To continue to work with the architect in the design phase of the 
renovations for the Outpatient Department and to work with the contractor 
diiring the construction phase. 

8. To begin to reorganize the Patient Travel Office's procedures and 
policies to more effectively handle the ever-increasing load of patient and 
Clinical Center employee travel. 

9. To afford the Institute physicians detailed information on the Special 
Ambulatory Care Program, the Travel Section, and the Admissions Section. 

10. To effectively reduce the money spent on travel and the Special Ambulatory 
Care Program, without curtailing patient care. 

PROGRESS ACHIEVED 

1. Some of the training programs to improve the output of work of the 
various employees of the Department are: inservice training sessions, 
participative management, and individual counselling sessions. This process 
is an indefinite one, as it is difficult to place limitations on it if it is 
to be successful. 

2. The centralized appointment system has been implemented for all the 
Clinics now using the main Clinic. Currently we are refining individual ^ 



OP-2 



Clinics from block appointments to individual appointment times for the 
patients. There has been much success in switching the appointments for the 
Clinics from block times to individual times. Approximately 95% of the 
Clinics are utilizing individual times. 

3. The staff for the stocking program has been hired and have been cross- 
trained in all the Clinics. The program has been enlarged to encompass the 
handling of patients' baggage (both inpatient and outpatient). A list of 
supplies used by the Clinics has been given to Central Sterile Supply to 

be programmed for the Medical Information System. The policy and procedure 
manual has been completed as well as the quotas for each item used has been 
determined and labeled in the various rooms within the clinics. 

4. The number of preadmissions completed by the Admissions Office is 100% 
of the requests received by Admissions before the patient actually arrives 
at the Clinical Center. By pre-admitting the patient, we are able to make 
the patient record available to the physician to enter orders on the Medical 
Information System prior to the admission of the patient to the Clinical 
Center. 

5. The reorganization of the Admissions Office (to incorporate the fionctions 
of the Admissions Staff, Receptionists, Administrative Officers of the Day), 
has been completed. The policy and procedural manual has been developed 

and distributed to the staff and members of the Director's office of the 
Clinical Center. 

6. All the clerks in the Outpatient Department participated in a course in 
public relations and office procedures. Several employees of the Outpatient 
Department participated in a seminar on Death and Dying. 

7. The design phase of the Outpatient renovations was completed and the 
construction phase began in April. The completion of the job should be in 
January, 1979. At that time, several of the ancillary services will either 
be housed in the Clinic area permanently or else be a satellite unit of that 
particular department. 

8. Currently, a study is being completed of the Patient Travel Office. This 
is the first time that such a complete and detailed analysis of the Patient 
Travel Office has been done. The result of this project will be to initiate 
new procedures and policies within this office, as well as to ascertain 
whether monetary savings can be made through these new procedures. 

9. The physicians of the various institutes were oriented by the supervisors 
of the Special Ambulatory Care Program, Patient Travel, Admissions Section, 
and Clinics. This is an ongoing program for all new Clinical Center 
Associates. 

10. One of the measures taken to reduce the monies spent was to decrease the 
number of guardians (escorts) of patients transported to the Clinical Center 
and placed on the Special Ambulatory Care Program. In addition, other measures 
were taken to more strictly enforce Patient Travel and Special Ambulatory 
Care Program regulations. 

OP- 3 



OTHER ACTIVITIES . 

1. The Department is developing a packet to be mailed to the patients before 
their arrival. This packet would include: information about the Clinical 
Center; location of the NIH campus and the Clinical Center; list of local 
restaurants and motels; approximate charges for each, etc. 

2. The Outpatient staff has been working with the Technicon staff and the 
Office of Clinical and Management Systems to develop the Medical Information 
System procedures and its implementation in this Department. The Clinics 
began using the system in June and will continue to phase in the programs 
over the next several months. 

PLANS 



1. To further expand the duties and assignments of the Messenger and Escort 
Service. 

2. To continue to train employees of the Outpatient Department in public 
relations and other related areas. 

3. To continue to define and refine the Outpatient Department stocking 
program. 

4. To send the drivers of the Local Transportation Unit to Emergency 
Medical Technician courses. 

5. To develop a new system and procedures for the Local Transportation Unit. 



# 



October 1, 1977, through September 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

PHARMACY DEPARTMENT 

CONTENTS 

I, Mission and Goals Ph-1 

II. Department Activities Ph-2 

III. Major Progress in Services, Training, Development and 
Research 

Service Ph-2 

Training Ph-3 

Development Ph-4 

Research Ph-5 

IV. Future Objectives Ph-6 

Table I - Pharmacy Department Statistical Data Ph-8 

Publications Ph-9 

Intramural Project Reports 

Mechanism of Hydrolysis of Halogenated Nitrosoureas. . . Ph-10 

Preparation and Evaluation of Ethiodized Oil Emulsion 

for Intravenous Hepatography Ph-13 

Purity of Various Methotrexate Samples Ph-16 



Ph-i 



October 1, 1977, through September 30, 1978 



PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

PHARMACY DEPARTMENT 



I. MISSION AND GOAL 

The primary mission of the Clinical Center Pharmacy Department is to provide 
comprehensive, properly coordinated pharmaceutical services of the highest 
quality to the patients and staff of the Clinical Center. 

The department's goal is to meet the needs of the diagnostic and therapeutic 
Departments, the nursing service, the medical staff, and the hospital as a 
whole to ensure better patient care. 

To accomplish its mission and goal, the Pharmacy Department is also engaged 
in pharmaceutical development, training, and research. 

The Pharmacy Department consists of the Pharmacy, Pharmaceutical Develop- 
ment, Central Sterile Supply Services and the Office of the Chief. The 
Pharmacy Service interprets and transcribes medication orders, and monitors 
and dispenses all medications ordered for patients in the Clinical Center. 
This Service fulfills these responsibilities by dispensing doses (unit dose) 
to each patient individually packaged and labeled; it fills drug orders for 
patients on pass, discharged, and outpatients. This Service prepares all 
intravenous (13,000 per month) additive solutions ordered for inpatients and 
outpatients; it fills drug requisitions for clinics and other patient care 
areas not on unit dose system; it compounds and packages products not avail- 
able commercially and maintains all investigational drug dispensing records. 
The Pharmacy Service also provides drug information and clinical services 
for physicians and nurses. 

The Pharmaceutical Development Service (PDS) is responsible for the regis- 
tration and control of all investigational drugs used for patients in the 
Clinical Center. The PDS also develops, formulates, and assays many inves- 
tigational drug products used by physicians in their clinical research 
studies. The Service also supports physicians with such services as in 
vitro and in vivo drug identity and analyses, setting up single- and double- 
blind studies, maintaining disposition records, submitting manufacturing 
data in support of an IND to the FDA, and providing investigational drug 
information. 

Central Sterile Supply Ser-/ice provides clean and sterile supplies used in 
patient care. This Service decontaminates, processes, assembles, sterilizes, 
and issues a variety of packs, trays, sets, instruments, and utensils. It 
also procures, stocks, and issues many clean and sterile preprocessed dis- 
posable items to patient care areas and uses a 24-hour mobile exchange cart 

Ph-1 



delivery system to deliver these supplies. 

The Office of the Chief provides overall policy and direction to the serv- 
ices and centralized procurement of approximately $3,500,000 worth of drugs 
and sterile supplies. 

II. DEPARTMENT ACTIVITIES 

As seen in Table I, I.V. admixtures prepared by the Pharmacy Service in- 
creased from 140,930 to 155,041 (9%); outpatient prescriptions dispensed 
increased from 79,725 to 84,378 (5%), prescriptions mailed out increased 
from 1558 to 1983 (21%) . An additional 195 square feet of space in the 
outpatient prescription area was obtained by relocating the patient waiting 
area to the North Wing Clinic and replacing it with a small ante-room with 
dispensing and counseling windows. The entire outpatient area was sub- 
sequently redesigned for more efficient work flow and new modular shelving 
and cabinetry was obtained. 

The Unit Dose Dispensing and I.V. Additive Units are now staffed to provide 
full service from 7 a.m. to 11:30 p.m., 7 days a week. In addition, the on- 
call-sleep-in pharmacy OD was replaced by a night shift pharmacist from 11 
p.m. to 7:30 a.m., 7 days a week. 

As seen in Table I, although the total number of units formulated, developed, 
and issued by the Pharmaceutical Development Service decreased from 870,647 
to 786,249 (9-7%), the number of requests for service increased from 1,031 
to 1,121 (7.5%), and investigational drugs registered increased from 596 to 
628 (5.4%). 

As seen in Table I, requisitions filled by the Central Sterile Supply 
Ser^/ice increased 11% to 31,628, items issued increased 10% to 5,382,403, 
and trays and sets prepared increased 6% to 15,130. 

III. MAJOR PROGRESS IN SERVICES, TRAINING, DEVELOPMENT AND RESEARCH 

Service 

The Pharmacy Service completed the unit dose drug distribution system on all 
nursing units in the Clinical Center during FY 78. Nine additional nursing 
units (from the NCI, NICHD, and NET Nursing Services) were added to the 
system. This method of dispensing drugs to hospitalized patients has 
several distinct advantages: it provides patient safety, provides drug 
control, and saves nursing time. 

Since a large portion of medications dispensed and administered to patients 
in NCI are by infusion, pharmacists from the I.V. Admixture Unit were as- 
signed direct responsibility for both clinical and distributive functions on 
the NCI nursing units: these pharmacists, along with the other pharmacists 
from the Unit Dose Unit, continued to review all drug therapy for appropriate 
medication dosage and possible interactions, making daily visits to the 
nursing units to communicate with physicians and nurses, attend rounds, and 
provide drug information. 



Ph-2 



The I.V. Admixture Unit changed its preparation procedures in FY 1978 to 
better distribute workload, decrease space congestion, and reduce the nximber 
of returned solutions. I.V. admixtures are now prepared and delivered every 
12 hours instead of every 24 hours. This workload distribution better coin- 
cides with the increased hours of service (7 a.m. to 11:30 p.m.) provided by 
the I.V, Admixture Unit in FY 1978. 

Pharmacy continued to have representation on the Cardiopulmonary Resuscita- 
tion Subcommittee. Two CPR drug boxes were approved by the Committee for 
placement in the Dental Clinic and on the 7-East defibrillator cart, and all 
CPF carts and drug boxes located throughout the Clinical Center were in- 
spected. 

The Pharmacy and Therapeutics Subcommittee continued to advise the medical 
staff and to serve as an organizational line of communication between the 
medical staff and the Pharmacy Department on all matters related to the use 
of drugs. During the year, the Committee reviewed and recommended policies 
pertaining to medication counseling in the Clinical Center, self-administra- 
tion of drugs, reports of adverse drug reaction, medication incident report- 
ing, medications brought into the hospital by patients upon admission, and 
the use of commercially available personal medications by inpatients. 

Central Sterile Supply Service began utilizing the primary pharmacist on the 
nursing unit to be kept better informed of changes in clinical activities 
which may affect Central Sterile Supply Service, e.g., ordering of supplies, 
acquiring knowledge of infection problems, and protocol changes. 

Training 

The Pharmacy Department was involved in various training programs in FY 
1978: an agreement was reached with the Community College of Allegheny 
County, Pennsylvania, to participate in a six-week pharmacy technician 
extern program. Three students were trained throughout the Pharmacy Service, 
with emphasis on I.V. admixtures and unit dose distribution. As a result of 
this training two of the students were hired by the Pharmacy Department as 
pharmacy technicians. 

A structured externship program, designed to give the 2 undergraduate phar- 
macy students experience in the practice of hospital pharmacy, was continued 
with the University of Maryland School of Pharmacy. 

Three undergraduates were accepted from the Howard University School of 
Pharmacy's Government Work-Study Program. Two students in the program spent 
700 hours each in training in the Pharmacy Service, and one student spent 
900 hours in training in the Pharmaceutical Development Service. 

An I.V. technician training program consisting of lectures, audiovisual 
presentations, and practical demonstrations was developed and conducted 
for pharmacy technicians. The program was designed to provide pharmacy 
technicians with background knowledge and practical experience in the pre- 
paration of I.V. admixtures. Upon successful completion of this course, the 
technicians working in the I.V. Admixture Unit were more helpful to the 



^h-3 



professional personnel. 

The American Society of Hospital Pharmacists accredited the Pharmacy Depart- ^^ 
ment's residency program in hospital pharmacy for an additional 4 years. The 
Accreditation Committee strongly suggested that the Department increase the 
number of residents in the program because of the unique clinical research 
instruction available at the Clinical Center. 

As part of the requirement for the residency program, the resident undertook 
responsibility for reorganization of all drug information resources and 
services in the Pharmacy Department. Tais involved indexing and cataloging 
all pharmacy texts, journals, and files, and the set-up of the micro fiched 
Iowa Drug Information System. The resident then prepared a drug information 
procedure guide and developed and conducted a comprehensive training course 
for all pharmacists in the effective and efficient utilization of drug in- 
formation resources. 

Development 

To provide better pharmaceutical service to patients a uniform program of 
medication counseling for patients being discharged was implemented on most 
nursing units. Pharmacy, in cooperation with the medical and nursing staff, 
developed patient-oriented drug data sheets that are used in conjunction with 
pharmacist counseling. These sheets, written in layman's terms, provide the 
patient with basic information about each drug including dosage, importance 
of adherence to therapy, likely side effects, storage information, and other 
pertinent data. These patient data sheets reinforce the counseling of pa- ^ 
tients and will, we hope, increase patient compliance. Pharmacists review ^ 
and maintain the drug data sheets. 

Regular microbial surveillance of pharmacy prepared I.V. admixtures was 
initiated. The basic methodology and testing procedures were derived from a 
project completed in FY 1977 by the pharmacy resident. 

An expansion of the total parenteral nutrition (TPN) program throughout the 
Clinical Center resulted in a 42% (to 270/month) increase in the number of 
TPN solutions prepared by the I.V. Admixture Unit and had a great impact on 
the daily workload. Data for every patient on TPN was provided to Dr. M. 
Brennen, NCI, for subsequent entry into his own computer system. Pharmacy 
prepared chemotherapy flow sheets for each NCI protocol (used in the Clinical 
Center) to monitor more efficiently dosage and toxic effects of the cancer 
chemotherapy . 

Pharmacy and MIS staff jointly designed a system to generate, via the MIS 
system, I.V. admixture labels for individual orders and batch-processing. 

The Clinical Center MIS Executive Committee in conjunction with the Pharmacy 
Department monitored and facilitated the successful implementation of the MIS 
computer system for all inpatient services and required Pharmacy's constant 
support for all drug related problems. Tne Clinical Center Outpatient Imple- 
mentation Committee, in conjunction with the Pharmacy Department, planned and 
implemented the MIS computer system in the outpatient clinics. These re- ^ 



sponsibilities required Pharmacy's involvement in the design of common out- 
patient medication ordering paths and the redesign of many outpatient cancer 
chemotherapy protocols . 

The long-awaited renovation of the sterile room was finally completed in the 
Pharmaceutical Development Service. All air now entering the room is being 
filtered through a HEPA filter which removes 99.9% of the airborne particles 
0.3 microns or greater in size. This is a tremendous improvement in the air 
quality and overall environment in which sterile parenteral products are 
manufactured. 

Preclinical toxicology studies have been completed and an IND application 
submitted for an I.V. emulsion of ethiodized oil formulated and developed by 
PDS for intravenous hepatography of cancer patients in the Clinical Center. 
The product was formulated with special consideration to the particule size 
of the oil globule to afford some specificity regarding tissue. Studies 
indicated that oil globules between 2-3 microns in size had specific prefer- 
ence for the liver. 

The unit dose packaging was evaluated for moisture permeability and was 
found to be highly permeable, necessitating further protection for a number 
of moisture sensitive drugs. 

Central Sterile Supply Service was represented on the Hospital Infections 
Committee and has played an active role in the development of policy with 
reference to autoclaves and sterility. The Service also gained active mem- 
bership on the Fabric Care Committee. 

A program was undertaken to completely sanitize all of the supply carts in 
the Issue Area on a scheduled basis. The processing areas were redesigned 
to provide for better utilization of space. All storage rooms were com- 
pletely cleaned and reorganized. Additional space in a secured corridor was 
obtained for storage of supplies. 

A new inventory and supply system was established in conjunction with the 
reorganization of the storerooms which resulted in a significant reduction 
of certain items in inventory to approximately a three-weeks' supply. This 
has resulted in more responsive procurement actions, quicker turnover of 
inventory, and elimination of all supplies from public hallway areas. 

A new central sterile supply facility, to include a total surgical/CSS case 
cart system, decontamination, reprocessing, and distribution area to service 
the operating room, clinics, and inpatient areas was designed for the ACRF. 

A new decontamination facility was designed and procurement actions were 
completed to renovate the existing reprocessing area. The renovation will 
provide for a centralized decontamination facility to comply with JCAH 
recommendations and will update our current, aging equipment. 

Research 

The stability of Cis-Diamminedichloroplatinum (II) in aqueous solutions was 



Ph-5 



studied. The drug was found to be stable in normal saline for at least 24 
hours which meant that the drug could be mixed and added to infusion solu- , 
tions by the Pharmacy Department's Intravenous Admixture Unit saving physi- 
cian and nursing time and trouble of preparing it on the unit. 

The mechanism of hydrolysis of halogenated nitrosoureas, an important group 
of antineoplastic agents, was studied. On the basis of kinetic studies, a 
different mechanism for the hydrolysis was postulated which could be helpful 
in determining the mechanism of action of these drugs in the body. 

Various commercial and investigational methotrexate samples were studied to 
determine the purest drug for clinical use. Recommendations were made to the 
U.S. P. as to what specific material should be used as the U.S. P. reference 
standard methotrexate of choice. 

A cooperative pharmacokinetic study of misonidazole with the Radiation 
Oncology Branch, NCI, was undertaken in which pharmacy developed a high 
pressure liquid chromatography method for the analyses of plasma drug levels. 

IV. FUTURE OBJECTIVES 

The Pharmaceutical Development Service will further study the distribution of 
particles of drugs of specific size (1-5 micron diameter) in various tissues. 
It also will expand the pharmacokinetic program and clinical involvement in 
the design of protocols with reference to optimum drug delivery, assay, and 
stability. 

The Central Sterile Supply Service will a) develop a new item identification 
nomenclature system for cross referencing procurement actions and MIS order- 
ing information; b) will continue the surgical case cart/CSS planning process 
to include staffing/personnel, training, and communication with operating 
room personnel; c) will replace linen xvrrappers with non-woven paper wrappers 
for sterile surgical packs; d) will provide technical assistance to the 
Surgical Nursing Service so that both Services can establish a uniform 
quality control testing of supplies and batch identification system; e) will 
incorporate, as a result of the new decontamination facility, a new dress 
code for the processing areas. 

The Pharmacy Service will begin plans to develop and implement a satellite 
intravenous admixture unit in the outpatient clinic. 

This Service will organize and develop a comprehensive program to provide 
clinical pharmacy services to inpatients and outpatients. Strict guidelines 
would be developed governing functions, responsibilities, and parameters for 
evaluation. 

Direct resource monitoring of pharmacy services will be developed in the form 
of a monthly workload report. This report would replace the current product- 
oriented monthly report and will better reflect the patient-or ienced services 
provided by the Pharmacy Service. 

The Service will expand the use of the MIS computer for clinicallv-oriented | 



'h-6 



services such as maintenance of clinical information in important drugs, 
production of drug profiles for outpatients, and production and storage of 
patient-oriented drug data sheets which will be used in patient counseling. 



Ph-7 



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Ph-8 



PUBLICATIONS 

Chatterji, D.C. and Gallelli, J.F.: High-pressure liquid chromatographic 
analysis of methotrexate in presence of its degradation products. J. Pharm, 
Sci. 66: 1219-1222, 1977. 

Gallelli, J.F. and Chatterji, D.C: Purity of various methotrexate samples. 
Cancer Treatment Reports 62: 487-488, 1978. 

Chatterji, D.C. and Gallelli, J.F.: Thermal and photolytic decomposition 
of methotrexate in aqueous solutions. J. Pharm. Sci. 67: 526-531, 1978. 

Chatterji, D.C, Frazier, A.G., and Gallelli, J.F.: Identification and 
quantitation of impurities in methotrexate. J. Pharm. Sci. 67: 622-624, 
1978. 

Chatterji, D.C, Green, R. , and Gallelli, J.F.: Mechanism of hydrolysis 
of halogenated nitrosoureas. In press, J. Pharm. Sci. , 1978. 

Chatterji, D.C and Gallelli, J.F.: Stabilization of 5-azacytidine by 
bisulfite. In press, J. Pharm. Sci. . 1978. 



Ph-9 



SMITHSONIAN SCIpCE INFORMATION EXCHANGE 
PROJECT NUMBER (,Do NOT use this space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 



ZOl CL 05004-01 PHAR 



PERIOD COVERED 

October 1, 1977 - September 30. 197$ 



TITLE OF PROJECT (30 characters or less) 

Mechanism of Hydrolysis of Halogenated Nitrosoureas 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



D. C. Chatter ji 
R. F. Greene 
J. F. Gallelli 



Staff Fellow 
Staff Pharmacist 
Chief, Pharmacy Dept. 



Pharmacy, CC 
Pharmacy, CC 
Pharmacy, CC 



COOPERATING UNITS (if any) 



Pharmaceutical Development Service 



INSTITUTE AND LOCATION 
CC. NIH. Bethesda 



TOTAL MANYEARS: 
1 



I PROFESSIONAL: 



CHECK APPROPRIATE BOX(£S) 
n (a) HUMAN SUBJECTS 

□ (a1 ) MINORS n (a2) INTERVIEWS 



□ (b) HUMAN TISSUES 



n (c) NEITHER 



SUMMARY OF WORK (200 ..or 



le keywords) 



The mechanism of hydrolysis of halogenated nitrosoureas was studied to 
understand the possible active species at physiological pH . Evaluation 
was carried out from pH 1 to 9 to explain t,he conflicting reports 
in the literature. The findings of this study would be helpful in 
understanding the mechanism of action of halogenated nitrosoureas 
in the body. 



Ph-10 



Serial No. ZOl CL 05004-01 PHAR 
Pharmacy Department 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

Oct. 1, 1977 - Sept. 30, 1978 

Project Title: Mechanism of Hydrolysis of Halogenated Nitrosoureas 

Project Serial Number: ZOl CL 05004-01 PHAR 

Principal Investigator: Dulal C. Chatterji, Ph.D. 

Other: Raymond F. Greene, B.S., Pharmacy Department 

Joseph F. Gallelli, Ph.D., Pharmacy Department 

Cooperating Unit: None 

Man Years: Total: 1 

Professional: 1 
Other: None 

Project Description 

Objective : 

To stud^/ the mechanism of hydrolysis of various halogenated nitrosoureas. 

Methods Employed : 

UV spectrophotometry, chloride ion titration and fluoride ion measurement 
were used to follow the rate and extent of decomposition of various 
nitrosoureas. pH, buffer species and buffer concentration were varied. 

Major Findings : 

The mechanism of hydrolysis of chlorinated nitrosoureas at physiological 
pH involved water and hydroxide ion reactions, and major reactive 
intermediates were concluded to be 2-chloroethyi and vinyl cations. It 
was also concluded that when phosphate dianion was the nucleophile, 
2-chloroethyl cation acts as a bifunctional alkylating agent. 

Significance in 3iomedical Research : 

The mechanism developed in this project rationally explains the changes 
in decomposition product distribution at various pH and will have 
significance in determining the efficacy and toxicity of these drugs. 
The theory presented also suggests the pathway by which chlorinated 
nitrosoureas may act as bifunctional alkylating agents. 



Ph-11 



Proposed Course : 

Evaluate the bifunctional nature of halogenated nitrosoureas in greater 
detail. 

Honors and Awards : 

None 

Publications : 

Chatterji, D. C, Greene, R. F., and Gallelli, J. F., "Mechanism of 
Hydrolysis of Halogenated Nitrosoureas", In Press, J . Pharm. Sci . , (1978) 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE U.S. DEPARTMENT OF PROJECT MUM8ER 

PROJECT NUMBER (Oo NOT use this space) HEALTH, EDUCATION, AND WELFARE 

I PUBLIC HEALTH SERVICE 1 

NOTICE OF ! zoi CL 05005-01 PHAR 

INTRAMURAL RESEARCH PROJECT 



PERIOD COVERED 

October 1, 1977 - September 30, 1978 



TITLE OF PROJECT (30 characters or less) 

Preparation and Evaluation of Ethiodized Oil Emulsion for 

Intravenous Hepatography 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



George Grimes 
Michel Vermess 
J. F. Gallelli 
M. Girton 
D. C. Chatter ji 



Staff Pharmacist 
Assistant .Chief 
Chief, Pharmacy Dept, 

Staff Fellow 



Pharmacy, CC 
Diagnostic Radiology 
Pharmacy, CC 
Diagnostic Radiology 
Pharmacy, CC 



COOPERATING UNITS (if any) 



Diagnostic Radiology, Clinical Center 



lab/branch 



Pharmarpiifi ral Dpvplnnmpnt- Sprvirp, and niagnn.qrir IRprli nlngy Dppf 



NSTITUTE AND LOCATION 
CC . NTH 



OTAL VaNYEAR^ 



PROFESSIONAL: 



CHECK APPROPRIATE BOX(ES) 

□ (a) HUMAN SUBJECTS 

□ (al) MINORS □ (a2) INTERVIEWS 



□ (b) HUMAN TISSUES 



(c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 



An emulsion of ethiodized oil was formulated and evaluated for intravenous 
hepatography. It was concluded that the diameter of oil globules were 
very important in determining whether they opacified the liver. It 
appeared that the liver preferentially takes up oil globule between 2-3 u 
size. 



?h-13 



Serial No. ZOl CL 05005-01 PHAR 
Pharmacy Department 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

Oct. 1, 1977 - Sept. 30, 1978 

Project Title: Preparation and Evaluation of Ethiodized Oil Emulsions for 
Intravenous Hepatography 

Project Serial Number: ZOl CL 05005-01 PHAR 

Principal Investigator: Dulal C. Chatterji, Ph.D. 

Other: George Grimes, B.S., Pharmacy Department 

Michael Vermess, M.D., Diagnostic Radiology 
Joseph F. Gallelli, Ph.D., Pharmacy Department 
Mary Girton, R.T., Diagnostic Radiology 

Cooperating Units: Diagnostic Radiology, Clinical Center 

Man Years: Total: 1 

Professional: 1 
Other: None 

Project Description 

Objective : 

To develop an ethiodized oil emulsion suitable for intravenous hepatography. 

Methods Employed : 

Various emulsions prepared were evaluated for their globule size 
distribution using a Coulter Counter and simultaneously evaluated 
in rabbits and monkeys for liver opacification. Conventional X-ray 
and CT scans were used for iii vivo evaluation. 

Major Findings : 

The globule size preferentially opacifying the liver was in 2-3 p range. 
CT scans were able to get diagnostic images of the livers of monkeys at 
a dose of 0.2 ml/kg of emulsion compared Co 2 ml/kg needed by conventional 
X-ray. 

Significance to the Biomedical Research : 

Because of the smaller dose needed for CT scans, the emulsion would have 
potential use in diagnostic hepatography. The demonstration that one 
particular size range is preferentially absorbed in liver is significant. 



'h-14 



Proposed Course : 

Evaluate the emulsion developed in human subjects with liver cancer for 
diagnostic purposes. 

Honors and Awards : 

None 

Publication : 

Grimes, G. et_ al , "Preparation and Evaluation of Ethiodized Emulsion 
for Intravenous Hepatography", Accepted for Publication, J. Pharm. Sci . , 
(1978) 



Ph-15 



SMITHSONIAN SCIENCE INFORMATION EXCHANGE, 
PROJECT NUMBER (Oo NOT use this space) 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 



ZOl CL 05006-01 PHAR 



PERIOD COVERED 

October 1, 1977 - September 30, 1978 



TITLE OF PROJECT (80 characters or less) 

Purity of Various Methotrexate Samples 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



J. F. Gallelli 
D. C. Chatter ji 



Chief, Pharmacy Dept. 
Staff Fellow 



Pharmacy, CC 
Pharmacy, CC 



COOPERATING UNITS (i 



lab/branch 



INSTITUTE AND LOCATION 

CC. NIH. Bethesda 



TOTAL MANYEARS: 
(LJ. 



PROFESSIONAL; 

0.2 



CHECK APPROPRIATE 30X(£3) 
□ (a) HUMAN SUBJECTS 



n (b) HUMAN TISSUES 



(c) NEITHER 



(a1 ) MINORS 



(a2) 



SUMMARY OF WORK (200 '^ords or le 



underline keywords) 



A study was undertaken to evaluate various MIX samples available 
commercially (Lederle) or from NCI, along with some bulk powder 
sent to us by USP . It was concluded that the newer lots of MTX 
(after 1977) made by Monsanto for NCI is substantially purer than 
all other samples tested and should be the sample of choice for 
formulation and clinical use. 



Ph-16 



?hS-604Q 
(Rev. 10-76) 



Serial No. ZOl CL 05006-01 PHAR 
Pharmacy Department 
Clinical Center 
Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

Oct. 1, 1977 - Sept. 30, 1978 

Project Title: Purity of Various Methotrexate Samples 

Project Serial Number: ZOl CL 05006-01 PHAR 

Principal Investigator: Joseph F. Gallelli, Ph.D. 

Other: Dulal C. Chatterji, Ph.D. 

Cooperating Units: None 

Man Years: Total: 0.2 

Professional: 0.2 
Other: None 

Project .Description 

Objectives : 

To analyze and evaluate the purity of various Methotrexate samples. 

Methods Employed : 

Liquid chromatography on DEAE cellulose column using a gradient elution 
followed by UV spectroscopy of various Methotrexate peaks. 

Major Findings : 

More recent batches of MTX (after 1977) made by Monsanto for NCI were found 
to contain the least amount of impurities. 

Significance to the Biomedical Research : 

The project will help in selecting the bulk powder to be used for 
formulation of MTX. Administration of a purer MTX sample would allow 
the evaluation of MTX alone without interference from the effects of 
impurities . 

Proposed Course : 

None 



Ph-17 



Honors and Awards : 

None 

Publication : 

Gallelli, J. F. and Chatterji, D. C, "Purity of Some Methotrexate 
Samples", Cane. Treat. Rep . , 62 , 487-488 (1978) 



Ph-18 



October 1, 1977 through September 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRM-I ACTIVITIES 
CLINICAL CENTER 

REHABILITATION DEPARTMENT 



CONTENTS 

I. Departmental Missions S, Goals Rh-1 

II. Departmental Activities Rh-1 

III. Major Progress Rh-1 

IV. Future Objectives Rh-5 

Addendum I. Rehabilitation Department Staffing Pattern .... Rh-8 

Tables: 

1. Physical Therapy Service: Statistical Report FY 78. . . . Rh-9 

2. Physical Therapy Service: Comparative Statistics FY 74-78 . . Rh-10 

3. Occupational Therapy Service: Summary Report by Institutes of 
Number of Patients Treated, Number of Treatment Hours, FY 78. . Rh-11 

4. Occupational Therapy Service: Comparative Statistics, FY 78; 
Patient Treatments and Treatment Hours Rh-12 

5. Speech Therapy Service: Summary Report by Institute of 

Number of Patients Treated, Number of Hours, FY 78. . . . Rh-1 3 

6. Speech Therapy Service: Comparative Statistics, FY 78 . . . Rh-14 

7. Rehabilitation Department, Office of the Chief: Number of 

Patient Evaluations by Physiatrists, FY 74-78 Rh-15 

Intramural Research Projects: 

1. Correlation of Activity of Psoriatic Arthropathy with Psoriasis 

in Patients Receiving PUVA (Psoralen Ultraviolet A Therapy). . Rh-16 

2. Podiatric Evaluation and Treatment of Patients with Rheumatoid 
Arthritis Rh-19 

3. Study of Factors Accelerating Rehabilitation in Above-Knee 
Amputees with Sarcoma Rh-22 

4. Ribavirin Therapy of Patients with Systemic Lupus Erythematosus 

and Renal Disease: Phase I - Toxicity Study Rh-25 

5. Biofeedback in the Management of Raynaud's Phenomenon. . . . Rh-28 



Rh-i 



« 



October 1, 1977 through September 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

REHABILITATION DEPARTMENT 

I. Departmental Mission and Goals 

The primary mission of the Rehabilitation Department is to provide the 
highest quality physiatric evaluation and treatment, physical therapy, 
occupational therapy, and speech therapy for Clinical Center patients 
referred by Institute physicians. 

An equally important mission of the Department is to support efforts of 
and collaborate with Institute physicians engaged in research relevant to 
evaluation and treatment of patients with rehabilitation problems. 

A third mission is to initiate both clinical and basic research 
independent of the Institutes in the rehabilitation of mentally and 
physically handicapped individuals. 

A fourth mission is to advocate and defend the rights of handicapped 
persons, and to use educational, preventive measures, and to support legisla- 
tive efforts to accomplish this goal. 

II. Departmental Activities 

A. Staffing pattern is presented in Addendum I. 

B. Patient Care Statistics 

Patient care statistics are presented in detail in Tables 1-2 for 
Physical Therapy, 3-4 for Occupational Therapy, 5-6 for Speech 
Therapy, and Table 7 for Physiatrists . 

III . Major Progress 

A. Services 

1. Significant progress has been made by Occupational Therapy 
Service in establishing reliable and reproducible methods for 
evaluating function and impact of therapy on disability in 
three areas: 

(a) The arthritic hand assessment form has been completed. 

It has been in use this past year and has been tested for 
effectiveness in guiding and measuring treatment. At 
present, it is being used more frequently for pre- and 
postoperative measurements following joint replacement. 



(b) The occupational therapy physical disabilities program 
has developed an initial evaluation form for better 
defining patients' functional ability, and therefore 
better documentation of the effects of intervention. 
An OTR with extensive experience in treating patients 
with physical disabilities has joined the Rehabilitation 
staff as Special Consultant to Occupational Therapy 
Service. She is developing, coordinating and editing 
this evaluation. 

(c) The Occupational Therapy Task-Skills Assessment Form 
has been refined to document specific skills necessary 
for work. This is being applied to document change in 
work skills following intervention and to indicate 
specific areas of dysfunction to which GT treatment 
should be addressed. This assessment is being used by 
the OT Mental Health program where it is most efficacious 
in the treatment program for schizophrenia. 

2. Upper extremity prosthetic fitting and training has been 
added to the NCI Surgery/Rehabilitation Department treatment 
for patients with osteogenic sarcoma. Training in the use 
of the myoelectric arm as well as the standard prostheses 

is being offered NIH patients. 

3. The innovative use of new plastic materials is offered by the 
Department in a number of ways: 

[a) Vacuum- forming techniques are being used to provide 
custom-made lower extremity orthoses, including pediatric 
corrective inserts. 

(b) Prefabricated plastic quadrilateral sockets for above- 
knee amputees (AKA) are being used in their immediate 
postoperative management to provide early ambulation 
and easy access to visualization of the wound. 

4. An early postoperative dressing for patients with hip disartic- 
ulations and hemipelvectomies has been devised to provide a 
support for attaching an endoskeletal unit as a temporary 
pylon. This enables these patients to bear weight earlier 

and to provide a more symmetrical and comfortable sitting 
posture. 

5. Following an intensive in-service training session for the 
Rehabilitation Department staff, the Department is able to 
evaluate and counsel in a limited way physically handicapped 
patients with sexual dysfunction. Further, a psychologist 
with expertise in this area has been identified and provides 
consultative backup for sexual problems of the physically 
handicapped. 



6. Cognitively intact patients with progressive neurologic 
diseases who are unable to produce intelligible articulated 
speech are being trained to use various artificial voice 
systems. The speech pathologist has collaborated with the 
manufacturer of several devices and other N'lH staff to deter- 
mine modifications needed to best meet the needs of 
communicatively handicapped patients. 

7. Pre- and postoperative speech therapy is provided for selected 
NIDR patients with severe dental deformities and malocclusions 
who are part of a study of the effect of orthognathic surgery. 
The patients are trained to eliminate those incorrect lingual 
and mandibular movements which cause the dental deviance. 

Research 

1. The pilot work of Occupational Therapy Service on "Evaluation 
of Quality of Life for Patients with Soft Tissue Sarcoma 
Receiving Amputation Versus Limb-Sparing Local Tumor Resection" 
was completed. 

2. Summaries of advances in several areas of research are 
presented. They include: 

(a) Sixteen patients, 4 with primary and 12 with secondary 
Raynaud's phenomenon, who demonstrated white/blue/red 
color change when placed at 38 degrees Fahrenheit for 
3 minutes were selected for study. Each was randomly 
assigned to receive temperature biofeedback or relaxation 
techniques . 

(b) Rapid, effective rehabilitation of above-knee amputees 
is critical when lifespan is shortened. Rigid dressings 
have been shown to promote wound healing and shorten 
recovery time in amputees. Unanswered questions are: 

who can apply dressings, align pylons, and how soon should 
patients ambulate. We report a study attempting to answer 
these questions. 

(c) Seventeen patients with psoriasis and psoriatic arthritis 
receiving photocheraotherapy according to the Oral Meth- 
oxsalen Photocheraotherapy Cooperative Clinic Protocol 
(PUVA) have been followed to determine the effect of PUVA 
on skin and joint disease. 

(d) The patient with chest pain and normal coronary arteries, 
or one with heart disease whose chest pain seems dis- 
proportionate to disease severity, presents a diagnostic 
and therapeutic dilemma. We studied 12 patients with 
severe, often incapacitating, chest pain believed cardiac 
in origin. Subsequent evaluation, however, led to the 
diagnosis of chest wall syndrome (CWS) . 

Rh-3 



(e) The development of avascular necrosis of bone (ANB) is an 
increasingly frequent complication and major disability 
in patients with SLE. We have attempted to characterize 
the nature of and factors contributing to ANB. For this 
purpose, we have identified 40 patients with radiographic 
evidence of ANB selected from a population of 465 SLE 
patients and compared them with 31 SLE patients (NON-ANB) 
without xray evidence of ANB. 

(f) An investigation of the effects of dystonia on speech in 
one case of progressive supranuclear palsy appears to 
indicate the presence of abnormal and previously unreported 
displacements of the major laryngeal cartilages. The 
study has afforded criteria for description of the patterns 
and progression of the disease. The laryngeal performance 
of additional dystonic patients is currently under 

study. 

3. Other studies in progress which have not yielded adequate 
data to report are: 

(a) Review of Rehabilitation Problems of Patients with Ewing's 
Sarcoma, 

Cb) Evaluation of Patients Receiving Breast Reconstruction 
Following Mastectomy, 

(c) Pediatric Evaluation of Patients with Rheumatoid Arthritis. 

4. Publications: 

(a) Flexion-Adduction Movement Used to Reproduce Symptoms and 
to Relieve Pain in the Hip Joint: A Case Report, L.B. Smith 
Bulletin of the Orthopaedic Section , American Physical 
Therapy Association, Summer 1977, vol. 2, no. 2, pp 9-10. 

(b) Therapeutic Studies in NZB/NZW Fl Mice V. Comparison of 
Cyclophosphamide and Chlorambucil, Gerber, N.L., 
Powell, D., Steinberg, A.D., Arthritis d, Rheumatism , 
vol. 20, no. 6, 1977, pp 1263-1268. 

(c) The Hand in Mixed Connective Tissue Disease, Lewis, R., 
Adams, J. P., Gerber, N.L., et al . , Journal of Hand Surgery , 
vol. 3, no. 3, pp 217-222, 1978. 

(d) Study of the Multiple Factors in the Pathogenesis of 
Autoimmunity in New Zealand Mice, Steinberg, A.D., 
Klassen, L., Raveche, E.S., Gerber, N.L. et al . , Arthritis 
S Rheumatism , vol. 21, no. 5 supplement, June 1978, 



(e) Ribavirin Treatment in Murine Autoimmune Disease, 
Klassen, L.W., Williams, G.W., Reinertsen, J.L., 
Gerber, N.L., et al., in press. 

Training 

1. The core curriculum for the continuing education of the staff 
physical therapists is being implemented by therapists attend- 
ing training courses in prosthetics, orthotics, joint mobiliza- 
tion, transcutaneous nerve stimulation, and gait analysis. The 
department continues its weekly in-service training lectures. 

The core curriculum established for Occupational Therapy 
Service consists of: 

(a) Upper extremity prosthetics and orthotics, 

(b) Evaluation and treatment of the hand, 

(c) Sensory integration, 

(d) Group process, 

(e) Developmental disabilities; evaluation and treatment, 

(f) Biofeedback. 

2. Included in the in-service training was a series of six 
lectures by Dr. Wendy Schain on "Sexuality, The Disabled 
Population, and the Health Professional." 

3. A Speech Pathology Clinical Practicum for Graduate Students 
from Howard University has been established. Two graduate 
students have completed this training program which allows them 
to meet the national training requirements for certification 

in speech pathology. 

4. An Institute-wide Communicative Disorders Interest Group was 
organized by the speech pathologist. This group allows 
students and professional staff to exchange information on 
current research and theory in the field. 



IV Future Objectives 
A. Patient Care 



1. An ongoing program is evolving to evaluate the impact of 

Rehabilitation on disability. This is a previously unexplored 
area. Evaluation of treatment outcome continues to be an area 
in which great effort is to be expended. 



Rh-5 



2. Discharge planning is the natural consequence of in-depth 
studies of remaining or resultant dysfunction of NIH patients. 
Methods of communicating the rehabilitation needs to the primary 
referring physician of NIH patients whose rehabilitation 
programs need continuation beyond hospitalization are being 
developed. Ways to involve the allied health services in the 
patient's home community are being sought. 

3. The unique needs of the patient with progressive weakness is 
being studied to bring together research engineering and 
community services to support patients in interaction with their 
environment and independent functioning in their home 
communities. 

4. The expansion of the outpatient program through ARCF will 
necessitate a more versatile program to provide coverage for 
walk-in patients. To do this at current staffing levels, we 
plan to establish a more efficient triage system which will 
permit therapists to independently evaluate patients and initiate 
treatment plans in selected patients. 

Research 

1. To organize a cross-reference of federally funded rehabilitation 
oriented programs and rehabilitation research engineering 
programs so that this information can be assimilated into the 
Rehabilitation program for (a) patient treatment, and (b) patient 
referral to appropriate facilities near their home communities. 

2. Validation of recently generated functional assessment forms. 

3. A major effort is being made to evaluate the effects of long- 
term use of prostheses on amputees. Special emphasis will be 
placed on evaluation of spinal mechanics. Further effort 
will be directed at evaluating new techniques for applying 
immediate postoperative dressings and early pylons for patients 
receiving hemipelvectomy and hip disarticulation. 

4. Meticulous biomechanical evaluation of upper and lower extremity 
motion will be undertaken using force plates and vectors. 

5. Use of electromyography to study movement of selected velar, 
lingual, labial and facial muscles in patients with dysarthria. 

6. Use of EMG biofeedback techniques to train tongue and lip 
control in patients with myoclonus and dystonia. 

7. Application of ultrasound as a diagnostic technique in lingual 
movements will be initiated, cooperatively with Dr. Stephen 
Leighton of the Bioengineering Department. 



Rh-6 



8. Single case studies of the recovery of communicative 
function after surgical removal of cortical tissue. 

Miscellaneous 

1. Dissemination to other rehabilitation centers of audio- 
visual and other materials generated for educational 
purposes . 

2. Establishment of a professional consulting staff to 
provide guidance to the Rehabilitation Department in 
establishment of research and patient care programs. 



Addendum I Rehabilitation Department Staffing Pattern 

Office of the Chief 

Chief, Rehabilitation Department 1 

Assistant Chief 1* 

General Medical Officer 1 

Secretaries _3 (includes 1 part-time) 

6 

Physical Therapy Service 

Chief, Physical Therapy Service 1 

Assistant Chief 1 

Staff Physical Therapists 5 

Physical Therapy Assistants 2_ 

9 

Occupational Therapy Service 

Chief, Occupational Therapy Service 1 

Staff Occupational Therapists 6_ (includes 1 part-time) 

7 

Speech Therapy Service 

Speech Pathologist 1** 



Newly appointed 7/1/78 
Part-time 



Rh- 



PHYSICAL THERAPY SERVICE 

Table 1: STATISTICAL REPORT FISCAL YEAR 1978 
(October 1, 1977 to September 30, 1978) 



INSTITUTE 


Number of Different 
Patients Treated FY 78 


Niimber of Patient 
Visits FY 78 


IP 


OP 


IP 


OP 


NCI 

NEI 

NHBLI 

NIAID 

NIAMDD 

NICHD 

NIDR 

NIMH 

NINCDS 


560 

1 

109 

121 

205 

22 

2 

79 

627 


310 



38 

12 

171 

11 

2 

1 
86 


3100 

6 

734 

657 

1735 

213 

5 

166 

2953 


1320 

1 

378 

57 

1132 

12 

19 

2 

239 


TOTALS 


1726 


631 


9569 


3160 



Rh-9 



PHYSICAL THERAPY SERVICE 



Table 2: COMPARATIVE STATISTICS 
Fiscal Years 1974-1978 



Fiscal 
Year 


Number c 
Patients 


f Different 
Treated 


Number of Patient 
Visits 


1974 


IP 


OP 


IP 


OP 


1525 


551 


8397 


1174 


1975 


1694 


586 


12960 


2071 


1976 


2085 


796 


9016 


2155 


1977* 


2615 


966 


11513 


2621 


1978 


1726 


631 


9569 


3160 



*Figures for 1977 represent 15-month totals because 
transitional quarter is included in 1977 fiscal year. 



OCCUPATIONAL THERAPY SERVICE 



Table 3: SUMMARY REPORT BY INSTITUTES OF NUMBER OF PATIENTS TREATED, 
NUMBER OF TREATMENT HOURS" - FISCAL YEAR 1978 



INSTITUTES 


NUMBER OF DIFFEPxENT 
PATIENTS TREATED 




number of patient 
tpj:atments 




IP 


OP 




IP 


OP 


NCI 


149 


32 




559 


91 


NEI 


3 


1 




59 


1 


NHLBI 


11 


4 




56 


8 


NIAID 


33 


27 




208 


76 


NIAMDD 


124 


59 




439 


329 


NICHD 


35 


9 




227 


28 


NIDR 


3 


3 




14 


24 


NIMH 


522 


5 




10,012 


47 


NINCDS 


446 


30 




2,130 


57 














TOTALS 


1,326 


170 




13,704 


561 








_ 




i~. 



Estimates for July-Sept. 1978 



Rh-11 



OCCUPATIONAL THERAPY SERVICE 



Table ^■■. COMPARATIVE STATISTICS: FISCAL YEAR 1978 
PATIENT TREATMENTS AND TREATMENT HOURS" 



^iscal 
Years 


Nijunber of Different 
Patients Treated 


Niimber of Patient 
Treatments 




IP 


OP 


IP 


CP 


1974 


1,195 


444 


11,332 


250 


1975 


1,220 


359 


10,522 


358 


1976 


1,411 


235 


12,052 


599 


1977 


1,774 


294 


14,595 


519 


1978 


1,325 


153 


13,704 


509 













Estimates for July-Sept. 197 8 
1977 - represents 15-month due to transitional quarter, July-Sept. 



SPEECH THERAPY SERVICE 



Table 5: SUMMARY REPORT BY INSTITUTE OF NUMBER 

OF PATIENTS TREATED, Nm-BER OF TREATMENT HOURS'''' 



Fiscal Year 1978 



Institute 


Number of Different 
Patients Treated 


Number of Treatment 
Hours 




IP 


OP 


IP 


OP 


NCI 

NHBLI 

NIAID 

NIAMDD 

NICHD 

NIDR 

NIMH 

NINCDS 

NEI 

COURTESY 


23 
6 
33 
4 
7 
1 
5 
282 




51 
56 
23 

4 


76 


91 


10 


46 
12 
66 

7 
16 

2 

10 

464 






100 

110 

45 

8 


132 


182 


20 


TOTALS 


361 


311 


623 


597 



-Estimates for July, August, September 1978 



Rh-13 



SPEECH THERAPY SERVICE 

Table 6: COMPARATIVE STATISTICS 
Fiscal Year 1978 



Fiscal 
Year 


Number of Different 
Patient;^ Treated 


Number of Treatment 
Hours 




IP 


OP 


IP 


OP 


1977 


228 


143 


456 


286 


1978* 


361 


311 


623 


597 



"1978 figures reflect increase from 20 to 24 hours 
per week. 



REHABILITATION DEPARTMENT - OFFICE OF THE CHIEF 



Table 7: NUMBER OF PATIENT EVALUATIONS BY PHYSIATRISTS, 
FISCAL YEARS 1974-1978 



Fiscal 
Year 


Total 


1974 


839 


1975 


897 


1976 


848 


1977 


1525 (15 mos.) 


1978 (estimated J.A.S. ) 


2750 (12 mos. )" 



Additional physician added to staff 8/77. 



Rh-15 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTR SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 



ZOl CL 06 0001-2 REE4,B 



PERIOD COVERED 

November, 1976 through November, 1978 



riTLE OF PROJECT (80 characters or less) 

Correlation of Activity of Psoriatic Arthropathy 
Receiving PUVA (Psoralen Ultraviolet A Therapy) 



dth Psoriasis in Patients 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



INCIPAL INVESTIGATORS AND ALL OTHER 



Chief, Rehabilitation Department, CC 
Washington Hospital Center (off site) 



N.L. Gerber, M.D. 

Werner Barth, M.D 

John Decker, M.D., ARB, NIAMDD 

A. Eric Jones, M.D., Nuclear Medicine, CC 

T. Nigra, M.D., Washington Hospital Center 

Susan Perlman, M.D., Washington Hospital Center 



COOPERATING UNITS (if any) 

Washington Hospital Center, Rheumatology 5 Dermatology Section 
Nuclear Medicine 



lab/branch 

Arthritis § Rheumatism/Rehabilitation Department, CC 



INSTITUTE AND LOCATION 

NIAMDD/CC NTH, Bethesda, Maryland 20014 



■QTAL MANYEARS: 
1 



PROFESSIONAL: 

2/3 



CHECK APPROPRIATE BOx(ES) 
S (a) HUMAN SUBJECTS 

D (al) MINORS J (a2) INTERVIEWS 



□ (b) HUMAN TISSUES 



n (c) NEITHER 



SUMMARY OF WORK (200 words 



underline keywords) 



PUVA Therapy is recognized as an effective mode in treating psoriasis . 
It has no known anti -rheumatic properties. Approximately 15% of patients with 
psoriasis have an associated arthritis . This study monitors arthritis activity 
in patients with psoriatic arthritis during the course of PUVA Therapy, and 
correlates it with skin response to PUVA. Data shows two subpopulations of 
patients with arthritis: those with peripheral joint and those with axial 
involvement. The former group demonstrates a positive correlation between skin 
responsiveness and joint responsiveness. The latter group do not. The latter 
group has sacroilliitis and appears refractory to most forms of anti-inflamma- 
tory medication. 



CRh-16) 



PHS-6040 
(Rev. 10-76) 



( 

Project No. Zol CL 06 0001-2 REHAB 

1. Rehabilitation Department 

2. Clinical Center 

3. Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1977 through September 30, 1978 

Project Title: Correlation of Activity of Psoriatic Arthropathy with 

Psoriasis in Patients Receiving PUVA (Psoralen Ultraviolet A 
Therapy) 

Previous Serial Number: 76-CC-98 

Principal Investigator: N.L. Gerber, M.D. 

Cooperating Units: Washington Hospital Center, Department of Dermatology 
and Rheumatology 
Diagnostic Imaging Section, CC 

Man Years: Total - 2/3 

Professional - 1/3 per year 

Project Description 

Objectives : 

Patients with psoriasis and psoriatic arthritis receiving photochemotherapy 
according to the Oral Methoxsalen-Photochemotherapy Cooperative Clinical 
Protocol (PUVA) have been followed to determine the effect of PUVA on skin 
and joint disease, and to determine if a correlation exists between skin and 
joint activity. 

Materials and Methods: 



All were treated with PUVA until skin clearing (65-5) and were then placed 
on maintenance PUVA schedules. Assessment at regular intervals included % 
psoriatic skin, articular index of peripheral and root joints (AI) , visual 
analog scale, baseline x-rays and serial joint scans. 

Seventeen patients have been followed. They were later subdivided into 2 
groups: 11 with asymmetric seronegative peripheral arthritis (P) and 6 with 
active peripheral joint disease meeting New York Criteria for ankylosing 
spondylitis (S) . S and P subgroups have been followed for a mean of 63 
and 29 weeks, respectively. S had a higher initial AI (53 vs 37) and % skin 
involvement (55 vs 42%), longer duration of psoriasis (22 vs 16 yrs . ) . 
6/6 and 10/11 P cleared skin on PUVA. In contrast, mean % improvement in 
AI after initial skin clearing was only 25% for S vs 61% for P. After 
first skin clearing, there were 10 skin flares per 280 pt.-wks in S 
receiving maintenance PUVA vs 2 skin flares per 171 pt.-wks in P. For these 
two P patients, joint flares were temporally related to skin flares. S skin 
and joint activity appeared to vary independently. 

Rh-17 



Significance to Biomedical Research : 

These results suggest that there is a correlation between skin disease 
and joint disease in patients with psoriatic arthritis of the peripheral 
type. Patients with spondylitic psoriatic arthropathy are a different 
clinical subgroup, whose joint and skin activity vary independently. PUVA 
Therapy is of value for both skin and joint disease in patients with 
peripheral type psoriatic arthritis. 



Rh-18 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND '«(ELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 



ZOl CL 06 0002-i REHAB 



PERIOD COVERED 

June, 1977 through June, 1979 



TITLE OF PROJECT (80 characters or less) 

Podiatric Evaluation and Treatment of Patients with Rheumatoid Arthritis 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



N. L. Gerber, M.D., Chief, Rehabilitation Department, CC 
Joseph K. Reed, Jr., RPT, Physical Therapy Service, CC 



COOPERATING UNITS (if any) 



lab/branch 
Rehabilitation Department 



SECTION 

Physical Therapy Service 



NSTITUTE AND LOCATION 

CC, NIH, Bethesda, Maryland 20014 



TOTAL MANYEARS: 

1/5 



PROFESSIONA 

1/10 



OTHER: 

1/10 



CHECK APPROPRIATE BOX(ES) 
B (a) HUMAN SUBJECTS 

D (al) MINORS □ (a2) INTERVIEWS 



Q (b) HUMAN TISSUES 



n (c) NEITHER 



SUMMARY OF WORK (200 



bywords) 



Foot discomfort and deformity represent a significant disability to the 
patient with R.A. Corrective surgery is the usual end stage procedure. 
Advances in shoeing techniques permit conservative measures to be performed 
to provide comfort and increased stability to rheumatoids with painful feet. 
The study compares 2 treatments: insertion of soft insert s to provide comfort 
or insertion of a corrective appliance to control abnormal foot alignment. 
Of seven patients entered to date, none has come to surgery and one has been 
switched from conservative to corrective inserts. 



PHS-6040 
(Rev. 10-76) 



Project No. ZOl CL 06 0002-1 REHAB 

1. Rehabilitation Department 

2. Clinical Center 

3. Bethesda, Maryland 



PHS-NIH 

Individual Project Report 

October 1, 1977 through September 30, 1978 

Project Title: Pediatric Evaluation and Treatment of Patients with 
Rheumatoid Arthritis 

Previous Serial Number: 77-CC-A-132 

Principal Investigator: N. L. Gerber, M.D. 

Other: Joseph K. Reed, Jr., RPT 

Cooperating Units: none 

Man Years: Total - 1/5 
Professional - 1/5 



Project Description 



Obj ectives: 



To determine if conservative pediatric management of foot abnormalities 
in patients with early rheumatoid arthritis of the foot can preserve 
function, control pain, minimize deformity and delay surgery. Further, this 
study is designed to compare two conservative treatments. One is designed 
to provide comfort by inserting soft cushioning materials into shoes, 
thereby protecting primarily the soft tissues. The second is designed to 
correct any malalignment and preserve pediatric architecture and return 
weightbearing patterns to the most normal possible by inserting a custom- 
made orthosis. 

Materials and Methods : 

Careful physical examination is performed, including detailed magnification 
views of the feet and Harris pressure mats. Biomechanical assessment of 
gait patterns are also performed. Patients are re-evaluated for boney soft 
tissue or gait abnormalities at 3 monthly intervals. 

Major Findings : 

Nine patients have been entered into the study. One patient has failed to 
be adequately controlled using soft inserts. No patient has yet required 
surgical correction. 



Significance to Biomedical Research: 

This study will answer the question of whether surgery for control of the 
foot problems in R.A. can be delayed or averted using non-invasive technique. 
Further, it will provide valuable data on biomechanics of gait and indicates 
if restoration of normal architecture of the foot is of any benefit in delay- 
ing progressive deformity. 



Rh-21 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl CL 06 0003-2 REHAB 



PERIOD COVERED 

January, 1976 through February, 



1978 



riTLt OF PROJECT (30 characters or less) 

Study of Factors Accelerating Rehabilitation m Above-Knee Amputees with 
Sarcoma 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



ITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 



Naomi L. Gerber, M.D., Chief, Rehabilitation Department, CC 

William Thorpe, M.D., Surgery Branch, NCI 

Physical Therapy Service, Rehabilitation Department, CC 

Ivan Sabel, C. P., Capitol Orthopedics, Inc., Bethesda, Maryland 



COOPERATING UNITS (if any) 

Surgery Branch, NCI 



lab/branch 
Rehabilitation Department 



NSTITUTE AND LOCATION 

CC. NIH. Bethesda. Maryland 20014 



TOTAL MANYEARS: 



PROFESSIONAL: 
5 



OTHER: 
1/2 



CHECK APPROPRIATE BOx(ES) 
(a) HUMAN SUBJECTS 

n (al) MINORS [] (a2) INTERVIEWS 



n (b) HUMAN TISSUES 



n (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

This study evaluates the ability of physical therapists to apply rigid dress- 
ings intraoperatively to above-knee amputees (AKA) and compares it to that 
oT^rosthetists. Additionally, it is designed to evaluate if patients 
receiving a temporary pylon immediately postoperatively and who ambulate within 
24 hours of surgery accrue any benefit in earlier wound healing, better gait 
characteristics, to more rapid maturing of stump and earlier delivery of final 
prosthesis. The study reveals that physical therapists are as competent in 
applying rigid dressings as prosthetists . Patients receiving pylons and who 
are immediately ambulated have slightly more pain than those who are not 
ambulated until sutures are removed, but do not show any differences in time 
course of rehabilitation when compared to those ambulated later. 



Rh- 



PHS-6040 
(Rev. 10-76) 



Project No. ZOl CL 06 0003-1 REHAB ^ 

1. Rehabilitation Department 

2. Clinical Center 

3. Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1977 through September 30, 1978 

Project Title: Study of Factors Accelerating Rehabilitation in Above- 
Knee Amputees with Sarcoma 

Previous Serial Number: 

Principal Investigators: N. L. Gerber, M.D. 

William Thorpe, M.D. 

Others: Members of Physical Therapy Service, CC 

Ivan Sabel, CP, Capitol Orthopedics, Inc., Bethesda, MD 

Objectives: 

Rapid effective rehabilitation of AiCA's is critical when lifespan is shorten- 
ed. Rigid dressings have been shown to promote wound healing and shorten 
recovery time in amputees. Unanswered is who can apply dressings, align 
pylon, and how early should patients ambulate. We report a study attempting 
to answer these questions. (^ 

Materials and Methods: 



Twenty-four patients were randomized into 4 groups in a prospective trial. 
Group 1 (IT), casted by a physical therapist and Group 2 (IP) by a 
prosthetist, had pylon placed and ambulated within 24 hours of amputation. 
Group 3 casted by a therapist (ET) and Group 4 by a prosthetist (EP) had 
pylon placed and ambulated at time of suture removal. Each patient was 
carefully evaluated by physical therapist on a daily basis until discharge 
from hospital and then at 3 weekly intervals. Parameters followed were 
time to wound healing, gait characteristics, and time to delivery of final 
prosthesis. 

Major Findings : 

There were no significant differences among the groups with respect to 
age, sex, stump length, pre- or postoperative gait characteristics. Those 
patients who ambulated immediately had more stump pain and required more 
analgesia than those ambulating after suture removal. The time from 
surgery to prescription of final prosthesis was shorter in the group that 
ambulated immediately (not statistically significant) and was 40 days shorter 
than historical NIH controls. 



Rh-23 



S i gn ificance to Biomedical Research : 

This is the first randomised prospective study comparing immediate vs delayed 
ambulation in patients with AKA, and demonstrates the efficacy and safety 
of the procedure. It corroborates the safety of rigid dressings post- 
operatively and indicates that physical therapists can be trained to apply 
these as competently as prosthetists . 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

PCiBLIC HEALTH SERVICE 

NOTICE Of 

INTRAHURAL RESEARCH PROJECT 



PROJECT NUMBER 

ZOl CL 06 0004-1 REHAB 



PERIOD COVERED 

April, 1977 through April, 1978 



riTLE OF PROJECT (80 characters or less) 

Ribavirin Therapy of Patients with Systemic Lupus Erythematosus and Renal 
Disease: Phase I - Toxicity Study 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 

N. L. Gerber, M.D., Rehabilitation Department, CC 

Alfred Steinberg, M.D., ARB, NIAMDD 

John Decker, M.D., ARB, NIAMDD 

Gary Williams, M.D., ARB, NIAMDD 

Lynell Klassen, M.D., ARB, NIAMDD 

James Reinertsen, M.D., ARB, NIAMDD 



COOPERATING UNITS (if any) 



ARB, NIAMDD 



lab/branch 



Rehabilitation Department 



NSTITUTE AND LOCATION 

m N TH, Rethesd a. 



■OTAL MANYEARS: 



Maryland 20014 



PROFESSIONAL: 

1/IQ 



check APPROPRIATE BOx(ES) 
g (a) HUMAN SUBJECTS 

n (al) MINORS Q (a2) INTERVIEWS 



n (b) HUMAN TISSUES 



G (c) NEITHER 



SUMMARY OF WORK (200 word: 



•line keywords) 



(ith ribavirin, an anti-viral 



Five patients with systemic lupus were treated 
agent, shown to be effective in treatment of murine lupus. Patients were 
treated with 600 mgs . q.d., and were monitored for toxicity to hematopoietic, 
hepatic, renal, immune, cardiovascular systems. Simultaneously, patients 
were observed for indicators of SLE activity. Three patients completed the 
study. Of two patients who did not, one had Gilbert's disease and had an 
elevation of bilirubin, and one had marrow depression which was reversed 
when the ribavirin was discontinued. No patient flared SLE, and several 
patients demonstrated improvement in some parameters of renal function. 



Rh-25 



PHS-6040 
(Rev. 10-76) 



Project No. ZOl CL 06 0004-1 

1. Rehabilitation Department 

2. Clinical Center 

3. Bethesda, Maryland 

PHS-NIH 

Individual Project Report 

October 1, 1977 through September 30, 1978 

Project Title: Rivavirin Therapy of Patients with Systemic Lupus 

Erythematosus and Renal Disease: Phase I - Toxicity Study 

Previous Serial Number: 

Principal Investigator: M. L. Gerber, M.D. 

Cooperating Units: Arthritis 5 Rheumatism Branch, NIAMDD 

Man Years: Total - 2/5 
Professional - 1/10 

Project Description 

Objectives : 

Ribavirin is an anti-viral agent which has been demonstrated effective 
with prolonging life expectancy in NZB mice. Its effect seems to be on 
the immune system, with a decrease in production of autoantibodies and 
a delay in the onset of proteinuria. The drug has been shown to be safe 
in humans when given for acute viral illness and for short periods of time. 
This study is designed to determine its safety in patients with lupus. 

Materials and Methods : 

Five patients with SLE were given 600 mgs . ribavirin p.o., q.d. for 2 months. 
Patients had the following monitored: ECG, CBC, liver function tests, 
electrolytes, renal function, ANA, anti-DNA, C^, immunoglobulins, uric acid, 
bone marrow, stool, urine. 

Major Findings : 

Two patients had the drug discontinued; one with Gilbert's disease had an 
elevation of bilirubin and another had a suppression of bone marrow. The 
latter patient had had a long history of immunosuppressive drug administra- 
tion in the past and had a hypoplastic marrow before receiving drug. 

All patients demonstrated elevation of uric acid and reticulocytes. These 
were all reversible abnormalities and were unassociated with clinical 
problems. 

The study was not designed as a therapeutic study, but several patients 
demonstrated decreased protein in the urine and improved renal function 
while receiving drug. 



Significance to Biomedical Research : 

Adequate treatment for patients with SLE has not yet been achieved. 
Ribavirin, an effective agent in treating murine SLE, has been shown to have 
little toxicity in humans, and all abnormalities to date have been 
reversible. 

Proposed Course : 

We plan a Phase II, Therapeutic Study. 



U.S. DEPARTMEfJT OF 

HEALTH, EDUCATION, AND WELFARE 

PUBLIC HEALTH SERVICE 

NOTICE OF 

INTRAMURAL RESEARCH PROJECT 



^OJECT NUMBER 

ZOl CL 0005-1 REHAB 



PERIOD COVERED 

February, 1977 through October, 1978 



TITLE OF PROJECT (80 characters or less) 

Biofeedback in the Management of Raynaud's Phenomenon 



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER 
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT 



N. L. Gerber, M.D., Chief, Rehabilitation Department, CC 
Cynthia Smith, OTR, Occupational Therapy Service, CC 
Tim Reybum, OTR, Occupational Therapy Service, CC 
Andy Novick, RPT, Physical Therapy Service, CC 
Elaine Bardo, OTR, Occupational Therapy Service, CC 



COOPERATING UNITS (if any) 



SECTION 

Rehabilitation Department 



NSTITUTE AND LOCATION 

CC. NIH. Bethesda. Maryland 20014 



TOTAL MANYEARS: 
I 2/S 



PROFESSIONAL: 

1/10 



CHECK APPROPRIATE BOX(ES) 
Xl (a) HUMAN SUBJECTS 

□(al) MINORS n (a2) INTERVIEWS 



□ (b) HUMAN TISSUES 



□ (c) NEITHER 



SUMMARY OF WORK (200 words or less - underline keywords) 

Patients with primary or secondary Raynaud's phenomenon were randomized to 
receive relaxation training or temperature biofeedback in an attempt to 
relieve symptoms of" Raynaud's phenomenon and control the temperature of the 
distal digits. Patients were monitored for skin temperature during training 
sessions, and placed in a 38° F room with constant temperature monitoring. 
Post-training, patients were able to control temperature better and keep 
hands warmer in ambient outdoor temperature and in the cold room. Both 
groups of patients did equally well in terms of control of temperature and 
in areas of symptom control. 



PHS-6040 
(Rev. 10-76) 



Project No. ZOl CL 06 0005-1 REHAB 
1 .Rehabilitation Department 
2. Clinical Center 
3. Bathes da, Maryland 



PHS-NIH 

Individual Project Report 

October 1, 1977 through September 30, 1978 

Project Title: Biofeedback in the Management of Raynaud's Phenomen 

Previous Serial Number: 77-CC-22 

Principal Investigator: N. L. Gerber, M.D. 

Others: Cynthia B. Smith, OTR, Occupational Therapy Service, CC 
Tim Reybum, OTR, Occupational Therapy Service, CC 
Andy Novick, RPT, Physical Therapy Service 
Elaine Bardo, OTR, Occupational Therapy Service, CC 

Man Years: Total - 2/5 
Professional - 1/10 



Project Description 



Objectives: 



This study was designed to evaluate the efficacy of autogenic training 
in the management of Raynaud's phenomenon. Biofeedback has been 
demonstrated effective in control of cardiac arrhythmias, bowel incontinence 
and other autonomic functions. Its efficacy in management of Raynaud's 
remains unproven. 

Because little is known about the kinetics of response of skin temperature 
to cold, a further objective is to evaluate the normals response to 38 F 
cold and compare it to the Raynaud's patient. 

Materials and Methods : 

Sixteen patients, 4 with primary and 12 with secondary Raynaud's ^ 
phenomenon, who demonstrated white/blue/red color change when place at 38 F 
for 3 minutes, were selected for study. Each was randomly assigned to 
receive temperature biofeedback or relaxation techniques. All had 20 hours 
of training, kept accurate logs of their Raynaud's attacks, and were 
re-evaluated after training. 

Major Findings : 

All patients completed training. In the laboratory, 15 patients raised 
their skin temperature consistently during final 5 training sessions with 
an average increase of 6°F . Average digital temperature of 74 F increased 
from pre-training level of 77°F (68° - 87°) to 84 F (77° - 92^] post- 
training; and at 38 F for 3 minutes increased from 66 F to 71 F. 

Rh-29 



Post-training, 15 did not develop the 3-color change after 3 minutes at 
38°F. A significant change in kinetics of skin temperature at 38 F was 
noted. Prior to training, patients demonstrated a fall of 6 /IS sec, 
which plateaued at 66 after 45 seconds and post-training, a fall of 
1.0 /IS seconds which plateaued at 71 after 3 minutes. Post-training, 
patients felt improved and could do more activities in the cold. 

Significance to Biomedical Research : 

A better understanding of response to temperature has been learned for this 
study in both normals and patients with Raynaud's. Autogenic training is 
an easily learnable, useful therapeutic modality in management of Raynaud's 
phenomenon, and is capable of altering kinetics of digital temperature 
response to cold. Long term followup is pending. 

Proposed Course : 

To continue to add patients to the study to reach 35, and to have a year 
followup to learn if autogenic training provides lasting benefit. 



1. Civil Service desk auditing appeared to create rather than dispel the 
disparity in the grading system. Occupational Therapists with greater 
responsibility for impact on patient care and greater educational 
requirements for employment according to Civil Service criteria were 
rated GS-9, whereas 5 recreation therapists were rated GS-11. 
Supervisory responsibility was stated by Clinical Center Personnel 
Office to be the deciding difference. Although this is an inequity 
built into the "system" it should not be disregarded. Quality of work 
should be the guideline for Civil Service^ and professionals with such 
quality will disregard Civil Service due to these arbitrary decisions 
which, in essence, corrupt the intent of desk audit and revision. 

2. Communication with referring physicians is less than optimal. 

All too frequently patients are discharged before adequate treatment 
or evaluation can be completed. Also, discharge planning is infrequent- 
ly done. These deficits must be corrected in order to provide adequate 
care. 

3. Severe space restriction limits our activities both in patient care and 
research undertakings. 

4. The mechanism for admitting patients to the Rehabilitation Department 
is awkward and depends exclusively on accepting referrals. It is 
essential for Rehabilitation Department physicians to have autonomy in 
admitting patients. 



October 1, 1977 through Septeriber 30, 197i 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMVIARY OF ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

SOCIAL WORK DEPARTMENT 

CONTENTS 

I . Department Missions and Goals SW-1 

II . Departinent Activities SW-1 

Reorganization SW-1 

Staffing Patterns SW-2 

Administrative Conponents SW-2 

Intramural Activities SW-2 

III. Major Progress in Research, Services, Training and 

Developnent SV7-3 

Prospective Study and Evaluation J SW-3 

Progress in Training SW-4 

Staff Education SW-4 

Training Programs SW-4 

Social Group Work SW-5 

NIH Patient Rnergency Fund • SW-5 

Wig Contract SW-6 

Interment Allotments SlV-6 

On-Call Systan SW-6 

Ccsnmunity-Related Activities SW-7 

Patient Services SW-7 

IV. Future Objectives Directed Toward Meeting Goals SV7-8 

TABLES 

1. Inpatient Coverage by Percentage SW-10 

July 1977 through May 1978 

July 1976 through May 1977 

2. Number of Clients Provided with Social Work 

Services SW-11 

July 1977 through June 1978 

3. Group Activity Report SW-12 

October 1977 through June 1978 

4. NIH Patient Emergency Fund Expenditures SW-1 3 

October 1977 through Jione 1978 



October 1, 1977 through Septeinber 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY OF ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

SOCIAL lORK DEPARTMENT 

I. DEPAR»1ENT MJSSIONS AND GOALS 

The Social Work Department of the Clinical Center is responsible for 
providing comprehensive social services vdiich are implemented through 
individual social casework, social group work, social agency liaison work, 
and cross-discipline teainwork. The goals of these methods are (1) to modify 
or resolve personal difficulties and environmental conditions which interfere 
with patient- faitdly participation in bionedical research; (2) to promote 
patient-family capabilities for obtaining maximum benefit from hospital-based 
services; (3) to prevent patient- family psychosocial deterioration as 
precipitated by consexjuences of illness and disease; (4) to establish 
linkages for patient-family use of community and interagency entitlanents ; 

(5) to interact with multidiscipline teams for collaboration on the 
developaent of services, plans, activities which impact on the patients' 
understanding, expectations, and utilization of hospitalization purposes; 

(6) to develop and maintain training programs for social work students and 
to participate in programs for other health arena students; and (7) to 
develop social work research for the examination of methods and systems 
which are involved ip delivery of social services in the health arena. In 
summary, the overall mission of the Social Work Department is the provision 
of comprehensive social services to biomedical research patients and, 
simultaneously, the re-enforcement of rapport between the investigative/ 
therapeutic systems and the patient/family systems. 

II. DEPARTMENT ACTIVITIES 

Reorgani zat ion 

As determined in FY 1977, the Social Work Department's reorganization plans 
were accomplished. To show organizational changes and related policy 
adjusiirents, the department's Policy Manual was brought up-to-date in 
October 1977. The major reorganizational shift was from four Program 
Supervisors to two Program Supervisors and one Deputy Chief. Effective 
June 1977, the Program Supervision Units were assigned as follows: 
(1) Cancer; and Child Health and Human Development Social Work Sections; 
and (2) Heart, Lung and Blood; Neurological and Cortrounicative Disorders 
and Stroke; Eye; Allergy and Infectious Diseases; Arthritis, Metabolism and 
Digestive Diseases Social Work Sections. Effective January 30,1978, the 
Deputy Chief was instated. Early 1978, a new clinical social work position 
was created for the Cancer Social Work Section. 



SW-1 



staffing Patterns 

The department's professional positions were assigned as follows: Office 
of the Chief - 2; Cancer Social Itork Section - 7; Child Health and Human 
Developnent Social Work Section - 1 full-time and 1 part-time; Heart, Lung, 
and Blood Social Work Section - 4 full-time and 1 part-time; Allergy and 
Infectious Diseases/Arthritis, Metabolism and Digestive Diseases Social Work 
Sections - 2 full-time and 2 part-time; Neurological and Ccanraunicative 
Disorders and Stroke/Eye Social Work Sections - 2. Five Maryland University 
students worked in the department as Social Work Representatives. A sixth 
Representative, a graduate social worker, was anployed between sariesters. He 
was a candidate for a Master's degree fron the Graduate School of Public 
Administration, University of Arizona, Tuscon. 

Administrative Components 

In March 1978, the department's Administrative Committee was established to 
reenphasize the policy/managanent functions of the Chief, Deputy Chief, and 
Program Supervisors. To achieve managarient and coordination aims, this 
Ccmmittee shared departmental information, promoted program and staff 
developnent, and mplemented departmental policy changes and adjustments. 
Monthly staff meetings served as the vehicle for keeping the staff informed 
on administrative matters, internal issues, practice trends and resources, 
and relevant legislated social policy. 

In May 1978, the Administrative Ccmmittee established a six-msnber Performance 
Standards and Appraisal Committee for the purposes of (1) developing criteria 
and methods for evaluating social work practice in this setting; and 

(2) satisfying the need for objective ccsnpliance with the requirments of the 
annual Department of Health, Education, and Welfare Employee Appraisal. This 
Ccmmittee met on bi-monthly intervals. Periodically, this Ccmmittee had the 
duty to report progress to Monthly Staff Meetings. Objectives of the 
reporting process were (1) to increase staff awareness of professional 
accountability for performance in practice; (2) to prcmote professional growth 
by investment in formal and informal continued education opportunities; and 

(3) to institutionalize an evaluative attitude, departmental ly and individually. 

Intramural Activities 



The Social Work Department was well integrated into the Clinical Center's 
projects and committees . Social vrorkers were appointed to serve on 
Ccmmittees which included the Ccmmittee on Volunteer Workers, the Agenda 
Ccamiittee, the Quality Assurance Committee, the Research Protocol Ccmmittee, 
the Pediatric Policy Committee, the Equal Employment Opportunity Ccmmittee, 
the Architectural Barrier Committee, the Outpatient Department Housing 
Ccmmittee, and Recreation and Welfare Committee. 

Authorization of Contract Cab services for patients was formalized by use of 
a MIS transportation matrix in June 1978. Responsibility for authorizing cab 
services was assigned to the Social Work Department. In July 1978, social 
workers were assigned to participate in the orientation program for 
volunteers to provide th&a with information on the Clinical Center's systems 
and services. 

SW-2 



At tlie celebration of the Clinical Center's Twenty-Fifth Anniversay, the 
Social Work Department's Chief received recognition and award for 25 years 
of service to the Clinical Center and the department. 

III. MAJOR PROGRESS IN RESEARCH, SERVICES, TRAINING AND DEVELOPMENT 

The Program Supervisor, Cancer Social Work Section, participated in the 
developnent of a study of breast cancer patients for examination of the 
relative effects of treatnoent-oriented "educative" intervention introduced, 
previous to plastic surgery reconstruction. 

The clinical social worker. Arthritis and Rheumatism Section, was involved 
in data collection for a study on attitudes toward pregnancy as held by 
Systemic Lupus Erythematosis patients. 

Two Child Health and Human Developnent clinical social workers collaborated 
with a research team in an investigation of "parenting patterns, interactional 
patterns, age appropriate developnent, and ascribed characteristics." 

Workshops on Social Work Research Problansand Studies were organized in the 
Spring of 1978. To accomodate 14 interested social workers, two 8-week 
workshops were scheduled within the summer months (June, July, August) and 
within the fall months (October, November, December) . The stated aim of the 
workshop was to provide introductory fundamentals in support of declared 
interest in social work research problems and studies. The aim of this 
workshop was based on the premise that research-oriented social workers would 
enroll in university-based research courses for continued education credit 
and for the pragmatic purpose of applying the knowledge to practice. An 
additional aim-related pranise was that the department's workshops would 
enhance "consumerism," that is, pi±)lished social work research, in particular, 
would be read with greater interest, understanding, and appreciation. 

Prospective Study and Evaluation 

All direct practice clinical social workers, social work representatives, and 
Program Supervisors were coded into the Medical Information System (MIS) . 
The "computerized social work record" became available to all designated 
services from all professional members of the Social Work Sections. 

It is anticipated that the next major MTS project for the Social Work 
Department will be to develop data retrieval mechanisms for evaluation of the 
effectiveness of the computerized social work record in meeting requirements 
for ccmnunication, confidentiality, quality, accountability, coordination, 
ajid team planning. Additionally, data retrieval should serve department 
obligations and aims which concern social work research and study of social 
service delivery methods and systems and evaluation of practice performance. 

The six-member MIS Cadre, credited with the developnent of social work 
matrices, recognized the potential- for-publication in the pioneering 
experiences which sirrrounded the construction of the computerized social work 
record. During the past few months, manbers of the MIS Cadre have been 
analyzing and writing on the natiire and impact of the computerized social work 
record. 

S^V-3 



Progress in Training 

The department has an ongoing training affiliation with the School of Social 
Work and Ccmmunity Planning, University of Maryland, Baltiitore, Maryland. 
Four MSW degree candidates from this School canpleted their field work 
placonents in Decanber 1977. 

Expansion of the training affiliation was reccmmended by the Administrative 
CCTimittee to include the School of Social Work, Howard University, 
Washington, D. C. Effective Septonber 1978, students fron each of these 
Schools of Social Work were in practicum with Clinical Center social WDrkers. 
Four students received individual supervision from the department's four 
University-approved field instructors located in Cancer; Child Health and 
Human Development; and Heart, Lung and Blood Social Work Sections. 

Two University of Maryland students will complete their field experience in 
December 1978. Two Howard University students will be in practicum fron 
Septsnber 1978 to June 1979. 

By January 1979, seven field instructors should be affiliated with these 
Schools of Social Work. 

In the Fall of 1977, a carmittee of the department's field instructors 
prepared a Student Training Manual. The Manual was up-dated in August 1978, 
for use by the departnaent, the new field instructors, and new students. 

Staff Education 

Direct practice clinical social workers enrolled in "continued education" 
programs at local university affiliated hospitals, professional associations, 
and voluntary agencies. Subject matter for these programs included hospital 
management, human sexuality, and treatment methods for adolescent patients, 
obsessive-compulsive patients, and depressed patients. 

Under the leadership of the department's Staff Education Ccmmittee, the 
Journal Club contined to meet monthly. Two soninars were arranged: the first, on 
genetic counseling was led by Mrs. Joan Weiss, Clinical Social Worker in the 
Genetics Clinic at Johns Hopkins University; the second on social services in 
Great Britain, was led by Dr. Kathleen Jones, Social Scientist and Historian 
of the Mental Health Group, York University, England. 

The Staff Education Ccxnmittee, produced a major educational program "An 
Assembly on Human Sexuality for Health Professionals." This one-day assonbly 
held on September 20, 1978, was led by Robert C, Kolodny, M.D., Associate 
Director, Reproductive Biology Research Foundation, St. Louis, Missouri. 
Featured presentations were on the effects of illness and the effects of drug 
treatment on human sexuality. 

Training Programs 

Twenty-one clinical social workers enrolled in training/educational prograiris 
Among these p3X)grams were the Eleventh National Sex Institute, Symposium o-^ i 

SW-4 



Family Therapy Practice, Adolescent Psychiatry, Continuing Education Program 
at Georgetown University, American Association of Psychiatric Services for 
Children, National Association of Social Workers' Fifth Biannual Professional. 
Symposium, and Certificate Program in Family and Group Therapy at Smith' 
College, 

Social Group Work 

Between September 1975 and June 1978, the department retained the services 
of a Social Group V^fork Consiiltant. Within that period, approximately 20 groups 
were organized around disease entities and related psychosocial prohlanis.. 
Most of these groups met the criteria of the "open-end and continuous" 
format as opposed to the "closed and time-limited" format. Groups were 
CO- led by clinical social workers and occasionally were co-led by social 
workers with matibers fron other disciplines, such as, nursing, recreation 
therapy, and medicine. Major areas discussed included coping with the 
consequences of illness, the nature of disease entities, the utilization of 
social and health resources, and the purposes and methods of the hospital. 

Needs of patients and families were served by groups organized fron Cancer, 
Child Health and Human Developnent, Allergy and Infectious Diseases, 
Arthritis and Metabolic Diseases, and Neurology Social Work Sections, 
Service breakdown for FY 1978 showed NCI with seven groups " Special 
Ambulatory Care Patients (SACP) , Screening Clinic, Medicine Branch, Unit 
12-West patients. Unit 10-East parents. Unit 2-East parents, and Pediatric 
Oncology Teen Groups; NICHHD with one group - Unit 9-D parents; NIAMDD with 
the Lupus Rap Session; NIAID with two groups - Asthma Clinic Group and 
Chronic Disease Gixjup; NINCDS with two groups - Parkinson's Disease 
5-West Young People, Categorically, the social work group method served 
parents, adolescents, and marriage partners of both inpatients and 
outpatients. 

The Parkinson's Disease Group formally organized the Parkinsonian Society 
of Greater Washington in October 1977. 

NIH Patient Bnergency Fund 

Administered through the Social Work Sections and the Department, an array 
of services was available to Clinical Center patients. Patient Emergency 
Fund expenditures were for basic and miscellaneous necessities, local 
transpoirtation for patdents, room and board allowances for relatives, and 
special programs for patient attendance. The Fund has been kept viable by 
regular contributors and ingenious benefits. 

One special source of income was the annual gift fron NIH anployees at 
Christmas time under the "Davis Plan" v^ereby anployees donated to the 
Fund in lieu of sending Christmas cards to fellow employees. 

A second source of incone was the Annual Softball Game played this year 
between the NIH Gashouse Gang and the VJhite House Team on May 7, 1978, and 
won by the Gang. 



SW-5 



PATIENT ETffiRGENCY FUND BREAKDOWN ' 

Deposits Withdrawn Average Exp. Balance NCI OTHER 



July 1974-June 1975 


$38,100 


$52,600 


$124 


$18,400 


189 


236 


July 1975-June 1976 


$37,000 


$47,900 


$172 


$ 6,300 


169 


109 


July 1976-June 1977 


$49,000 


$45,500 


$150 


$10,000 


154 


152 


July 1977-June 1978 


$53,000 


$62,300 


$216 


$ 1,300 


145 


144 


Wig Contract 















Consistent with past utilization of this service, approxirtiately 308 wig 
requisitions (adult and child) were processed through the Social \<lork 
Departxtient. Wig contracts were let in the amount of $38,500 during the 
past 12 months. 

Interment Allotments 

Effective May 1977, the Social Work Department was assigned the decision- 
making responsibility for interment allotments. The chart, which follows, 
shows utilization frequencies of this resource. 

UTILIZATION FREQUENCIES - INTERMENT ALLOTMENTS 



Fiscal 
Year 


First 
Quarter 


Second 
Quarter 


Third 
Quarter 


Fourth 
Quarter 


Ttotal 


1977 
1978 


9 
12 


14 
12 


21 
9 


9 


53 
33 



On-Call Systgn 

Formalized in May 1977, the department's On-Call Systan was designed to 
provide social work coverage through week-day evenings, week-ends, and 
holidays. The following chart is a quarterly breakdown on the utilization 
of the On-Call Systan. 

UTILIZATION OF ON-CALL SYSTEr4 BY HOURS EFFECTIVE MAY 1, 1977 



Fiscal 
Year 


First 
Quarter 


Second 
Quarter 


Third 
Quarter 


Fourth 
Quarter 


Totals 


1977 
1978 


13hrs-33min 


25hrs-13min 


18hrs-5min 
4hrs-15min 


llhrs-3min 


29hrs-Smin 
42hrs-lmin 



SV>7-6 



Connunity-Related Activities 

Consistent with the record of past activities, the Clinical Center ' s 'social 
vvorkers continued to be involved in the activities of professional 
associations and volxmtary organizations. These social vrorkers were 
involved in leadership roles as chairpersons, in patient advocacy roles as 
project developers (turbans for patients suffering hair loss) , in organizer 
roles as participants in the 1978 founding of the Pediatric Oncology Social 
Work Association, and in public relations roles as writers of a brochiore on 
Clinical Center social work practice, and as contributors to the design of 
an exhibit for recruitment and general information purposes. 

Professional affiliations and patient service linkages were established and/or 
were ongoing with such organizations as the Amyotrophic Lateral Sclerosis 
Society of America, the D.C. Chapter of the Muscular Dystrophy Association, 
the Arthritis and Rheumatism Association of Metropolitan Washington, the 
American Cancer Society, and the Montgcmery County Chapter of the American 
Red Cross. 

Patient Services 



By providing carprehensive social services to the patient- family population, 
the Social Work Department carried out responsibilities to the Clinical 
Center's systans vvhich support the research mission and patient care standards. 

The following chart dononstrates an increase in social work coverage 
generated by the delivery of social services, which included social group 
work, individual social casework, liaison work, and interdisciplinary team 
vvork. Between May 1976 and May 1977, the increase was to 383 patients and 
between May 1977 and May 1978, the increase was to 666 patients. 



THREE- YEAR SIM4ARY OF PATIENTS SERVED 



Patient 


Patients 


Served 


Patients 


Served 


Patients 


Served 


Status 


July 1975 - 


- May 1976 


July 1976 - 


- May 1977 


July 1977 - 


- May 1978 




Number 


% of Total 


Number 


% of Total 


Number 


% of Total 


Preadmission 


144 


2.0 


109 


1.4 


91 


1.0 


Clinic 


487 


6.6 


587 


7.5 


1,014 


12.0 


Follow-Up 


1,548 


19.9 


1,593 


20.4 


1,422 


17.0 


Outpatients 
Total 


2,179 


28.5 


2,289 


29.3 


2,527 


30.0 


Inpatients 
Total 


5,240 


71.5 


5,513 


70.7 


5,941 


70.0 


GRAND TOTAL 


7,419 


100.00 


7,802 


100.0 


8,468 


100.0 



SW-7 



36^ 

of 348 patients who received social work intervention between July 1975 and W 
May 1978. Consistently within this three-year period, thirty percent of all 
delivered social services went to outpatients. Preadmission patients were 
those patients who were between acceptance for a project and admission to 
the Clinical Center. 

Social services to this group of patients alleviated problsns which anerged 
frcm language barriers, personal beliefs, status of physical mobility, 
guardianship, and interpersonal and relationship needs between relatives by 
birth or by marriage. Mobilized by Clinical Center social workers, county, 
state, federal, international and voluntary social/health agencies provided 
coordinated services on a case need basis. 

Clinic patients represented those patients who never had been an inpatient, 
and v*io were therefore unliJcely to have known a Clinical Center social worker. 
Over the past few years there was a trend to increase the number of outpatient 
clinics as well as patients. Presenting problans in this patient population 
were many faceted and included coping with illness in a new environment, 
resolving feelings about "unknown" aspects of an illness, and managing 
stressful situations in a large urban area. Clinical social workers 
established small groups for patients and their relatives to provide an 
opportunity for sharing conmon concerns, questions, and adaptations. Other 
purposes served by the social group work method included assessment of 
psychosocial functioning, provision of appropriate direct social services, 
and securing linkages with health and social agencies. ^ 

Follow-up patients were those v^o were formerly inpatients and most likely 
known to a Clinical Center social worker. Included among these patients were 
the Special ^^mbulatory Care Program patients (SACP) . For the past three 
years, ongoing weekly evening social work groups served SACP patients in 
the United Inn Motel and provided opportunities for these persons to reassess 
their social situation and their ability to cope with chronic stage illness. 

Inpatients received seventy percent of social work coverage. This coverage 
rate ranained steady over the past three years. Direct services, individual 
and group, were provided. Extensive collaboration with other disciplines 
was needed for comprehensive planning around individual patient requiranents . 
Supportive social and health agency sources were secured for patients and 
their dependents. 

IV. FUTURE OBJECTIVES DIRECTED TO^aZARD MEETING GOALS 

1. Maximized capacity for delivery of social services to Clinical Center 
patients v*io are in preadmission, clinic, and follow-up status. To a limited 
extent, this objective was managed by adjusting current staffing patterns. 
During FY 1977 - 29.3%, and during FY 1978 - 30% of patients provided social 
services were outpatients. These percentages were interpreted as being 
indicative of the need to expand Outpatient Department coverage through the 
development of appropriate programs and adequate staffing. 



SW- 



2. Developnent of a retrieval mechanism to assonble aggregate data fron 

the cxxnputerized social work record for the purposes of analyzing, eval'aating, 
and improving social service delivery in this setting. 

3. Continued improvanent and integration of the student training program. 
Realization of the objective is contingent upon staff participation in 
case finding and program developinent processes. 

4. Publish a professional paper on the pioneering work involved in the 
developnent and utilization of "the first" cotpiterized social work record. 



SIJ-9 



T/^BLE 1 
. INPATIENT COVERAGE BY PERCENTAGE' 
JULY 1977 through; MAY 1973- 



MST. 


INPATIENT 
CENSUS 


INPATIENTS ■ 
SERVED 




PERCENT 

COVERAGE 


■ TOTAL 
H0L1«-Sl« 


NCI 


3,426^ 


2,099 


.61.3 


14,050 


I'eLBI 


'1,850 ■■' 


1,396 


^ 75.5- 


11,180 


NIAID 


896 


695 


77.6 


3,744 


NIAlAlDD 


883 


673 


76.2 


3,900 


NINCDS 
NEI 


1,214 


713 


58.7 


4,160 


NICHHD 


340 


365 


93.2 


2,704 


TOTAL 


8,609 


5,941 


69.0 


39,838 



JULY 1976 through MAY 1977 






INST. 


INPATIEIW 
CENSUS 


INPATIENTS 
SERVED 


PERCENT 
COVERAGE 


TOTAL 
HOURS-SWD 


NCI 


2,987 


1,846 


61.8 




NtEBI 
NICHHD 


2,248 


1,743 


77.5 




NIAID 


904 


498 


55.1 




NIAtOD 


927 


710 


76.6 




NINCDS 
NEI 


1,237 


716 


57.9 




TOTAL 


8,303 


5,513 


66.4 





SlV-10 



TABI£ 2 
Number of Clients Provided with Social Work Services 









July 


1977 through June 1978 












PREADMISSION 


INPATIENT 


CLINIC 


FOUJJ,-lr-W 


DATIENT5 


TOTAL 

, FAMIL 

MEMBE 




Patient 


Family 
Meii±)er 




&M 


Patient 


fift& 


Patient 


mm 


S 


077 


5 




510 




223 




113 




851 














- 




311 




133 




44 




488 




VUG 


14 




553 




145 




102 




814 








2 




366 




91 




45 




504 




phPi' 


11 




519 




65 




113 




708 












323 




54 




55 




432 




JJI 


12 




530 




121 




104 




lei 








3 




305 




81 




52 




441 




\[0V 


6 




565 




71 




153 




795 








4 




350 




41 




71 




4fifi 




DEC 


3 




449 




58 




14Q 




6.5Q 








2 




272 




31 




62 




367 




1978 


13 




534 




82 




110 




739 








4 




350 




29 




52 




435 




BIB 


7 


h" 


590 




60 




142 




799 








5 




387 




31 




65 




488 




^_R 


4 




577 




59 




141 




781 








1 




365 




26 




60 




452 




^R 


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October 1, 1977 through September 30, 1978 



PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANMJAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

DEPARTMENT OF SPIRITUAL MINISTRY 



CONTENTS 

Overview SM-1 

Staff SM-1 

Chapel Service SM-2 

Chapel Services SM-2 

Pastoral Ministry to Patients and Their Families SM-3 

Work with Staff SM-5 

Research Committees SM-5 

EEO SM-5 

Education and Training SM-5 

Consultation SM-5 

Community Education SM-6 

Professional Meetings and Training SM-6 



SM-i 



October 1, 1977 through September 30, 1978 

PUBLIC HEALTH SERVICE, NATIONAL INSTITUTES OF HEALTH 

SUMMARY ANNUAL REPORT OF PROGRAM ACTIVITIES 
CLINICAL CENTER 

DEPARTMENT OF SPIRITUAL MINISTRY 



The basic task of the Department was to provide spiritual ministry to 
patients and their families who welcomed the ministrations of a clergy- 
man and to hold religious services in the hospital. It also included 
acting as liaison with religious groups not represented by the staff 
chaplains. Fundamental to this task was the bedside ministry to patients 
and family members and the religious services held in the fourteenth 
floor Chapel. Other tasks of the Department included consulting with 
fellow staff members of the Clinical Center, attending multidisciplinary 
conferences, membership on research committees, working with the N.I.H. 
EEO Council and EEO counseling, participating in educational and 
orientation seminars, lecturing, and consulting with other clergy and 
community groups. 

Statistics indicated the following average religious preferences of newly 
admitted patients: Jewish - 6%; Catholic - 24%; Protestant and others - 
70%. 

STAFF 

Chaplain LeRoy Kerney served as Chief of the Department and as a Protestant 
Chaplain. Chaplain Robert White and Chaplain William Payne were the other 
Protestant Chaplains. 

Father Eugene Linehan, S.J. served in the hospital on a five day basis 
with Father Michael Griffin and Father Vincent O'Brien serving on days 
not covered by Father Linehan. Assistance during the day was increased 
in the new contract to allow for several part-time priests or pastoral 
associates to bring an additional twenty hours a week of coverage to 
patients and their families. A small group of seminarians from the School 
of Theology, Catholic University, came for supervised training during the 
school year. 

Rabbi Joseph Levine served in the hospital on a half-time basis: Tuesdays, 
Thursdays, and Friday afternoon. He also served in a similar capacity 
at St. Elizabeth Hospital, Washington, D. C. He was available for 
emergencies at the Clinical Center through the paging system. 

SM-1 



CHAPEL SERVICE 



■Q 



Regular chapel services were held during the year for the major faith 
groups. Mrs. Frances Viernstein was our Sunday Chapel organist. These 
services were: 



Protestant : Sunday, 10:00 a.m. Holy Communion Service, the first 
Sunday of each month. 



Catholic; 



Sunday and weekdays, 11:15 a.m. Daily distribution 
of Communion to bedridden patients. 



Jewish : Friday, 4:30 p.m. 

In addition to the regular services, these special services were held: 

Protestant : World Wide Communion - 1st Sunday in October 
Thanksgiving Day Service 
Christmas Carol Service 
Christmas Day - bedside visitation 
Good Friday Service - (participation by Protestant 
and Catholic clergy and patients) 



Catholic: 



Jewish: 



Holy Days of Obligation Mass 
Special Blessing of Throats 
Distribution of Ashes - Ash Wednesday 



Rosh Hashana Sikkoth 
Yom Kippur Chanukah 
Memorial Services 



Purim Shavuoth 
Passover 



All three faiths extended the ministry of the chapel services by broadcasting 
the services through bedside speakers for those unable to go to the chapel 
and by visitation to bedridden patients. Appropriate sacraments were 
administered as desired. 

CHAPEL SERVICES 

The daily 11:15 Catholic Mass provided a great resource for both patients 
and staff. As the Out-Patient Clinic develops, so does the attendance 
at this service and supplies spiritual nourishment and the sense of 
community sorely needed for so many of these patients who are filled with 
the anxiety of treatment. Today's Liturgy is much richer in terms of 
Feast Days and the varied Bible Readings so that it contributes mightily 
to our Catholic Pastoral Care. 

One of the continuing highlights of ministry is the weekly Protestant worship 
in the chapel where the people are constantly reminded in a dramatic way 
that they are not merely individuals facing difficult and trying situations, 
but that they are indeed part of the family of God and the communion of 
saints. Week in and week out, those who attend show a desire and the 



SM-2 



willingness to share in the worship service and, although often they 
begin as strangers, there develops a sense of unity and fellowship and 
mutual concern that makes worship at the Clinical Center a refreshing and 
strengthening experience. 

The Passover Service this year consisted of an actual Seder meal for 
patients and family, and the Chanukah Service featuring the chorus from 
the Jewish Community Center. 

An Ecumenical Thanksgiving Service was held on Thanksgiving Day. This is 
the first time such a service was held in the Clinical Center. Patients 
and their families were given an opportunity to share with each other 
through a drawing or words their thoughts on this holiday. Several group 
photographs were taken and a print sent to each patient. 

A flower vase was given in memory of a Clinical Center nurse to be used 
in the 14th floor chapel and was dedicated on Good Friday. 

PASTORAL MINISTRY TO PATIENTS AITO THEIR FAMILIES 

The Department attempted, when possible, to have a staff member visit all 
patients prior to major surgery, patients who were on the seriously ill 
list, and families of patients who died. All Catholic patients were 
contacted through the sacramental ministry of the Catholic chaplain. The 
Jewish chaplain was able to see all the patients of the Jewish faith. Most 
of the Protestant patients were visited. Priority was given to visiting 
the terminally ill, the seriously ill, patients scheduled for surgery, 
referrals by staff, relatives and pastors, as well as direct patient 
requests. Clergymen from the community were called upon to minister to 
special patients, e.g., patients requesting special rites from clergymen 
of their own denominations. These included several Greek Orthodox priests 
who were routinely called to minister to the Greek-speaking patients. 

Pastoral problems which the chaplains encountered included: loneliness, 
grief, fear, guilt, anxiety, loss of spiritual meaning, boredom, identity 
crisis, and changes in body- image and body-function. Pastoral methods 
included pastoral conversations, pastoral counseling, sacraments, bless- 
ings, prayer, scripture, and worship. On occasion, the chaplains helped 
patients and their families resolve dilemmas of conscience, conflicts of 
values, and difficulties in accepting radical therapies. 

All members of the staff endeavored to be sensitive to the patient's own 
understanding of religion for himself, and, in turn, become a resource 
person for the patient to discover or rediscover his own spiritual 
strength. 

The complex work of a chaplain calls for familiarity with the medical 
situation, medical knowledge, sensitivity to emotional issues, and work 
with staff and family, and is illustrated by the following stories and 
reports. 



Sometimes a chaplain's ministry begins on an elevator. The look on a 
mental health patient's face alerted the chaplain that something was 
wrong. The two stepped off the elevator to check out the hunch. The 
patient was in a rage. He had spent the morning fighting with the staff. 
He had packed his bags and was checking out against medical advice. After 
he had "vented" a while, the chaplain asked him to re-examine his situation 
in the light of his own best interests, the impact on his family, and the 
real role of the staff in his situation. It took a while, about half a 
pack of partially smoked cigarettes, before some perspective emerged. 
Finally, the patient stood up, shook the chaplain's hand, and thanked him 
for taking time to notice that something was wrong and helping in the 
sorting out process. As he re-entered the nursing unit he said, "They 
couldn't force me to stay. I'll tell them I made up my own mind to come 
back after I talked it over with the chaplain man to man " . 

Patients who come to the out-patient clinics often develop very close 
relationships with each other even though they may not have been hospital- 
ized at the same time. This closeness also causes great concern when one 
of the group develops a complication from the disease or treatment, drops 
out of treatment, or dies. Chaplains have been assigned to meet with 
small groups of clinic patients as well as individual patients to help 
them talk about their concerns when this happens. 

Patients and their families often react to their illness and their life 
situation with anger, depression, and a reluctance to express their 
feelings toward staff. This is especially true while impatiently waiting 
for results from tests or the postponement of "bad news" by the medical 
staff. Chaplains are often involved in encouraging patients and their 
families to share their concerns with their doctors and in turn support 
the medical staff in open communication about their disease, treatment, 
and prognosis. 

What does one say, what does one do for a teen-age patient for whom 
nothing seemed to go right? The patient had undergone a radical amputation 
through the shoulder, several thoracotomies, and some extremely unpleasant 
and toxic chemotherapy. Almost daily visits, many discussions, and support 
in scripture and prayer helped the young man believe that his suffering 
and pain would have meaning and significance for others who might be helped 
as a result of his experience. At the end, just before he left for home, 
he asked the physician, "Will they be able to use my cornea and kidneys?" 
The patient's family, the doctor, and the chaplain all learned a very 
basic lesson about the meaning both of life and death from this young man. 

Pastoral Ministry statistics for two typical months follow : 

Protestant Catholic Jewish 

Admissions October 1977 385 (69%) 140 (25%) 34 (6%) 
May 1978 428 (71%) 141 (23%) 37 (6%) 

Discharges October 1977 356 (67%) 146 (27%) 32 (6%) 
May 1978 372 (67%) 148 (27%) 36 (6%) 



Pre- Ops 



WORK WITH STAFF 



October 1977 


62 (67%) 


25 (27%) 


6 (7%) 


May 1978 


71 (76%) 


14 (15%) 


8 (9%) 



Group seminars with staff members dealt with family, emotional, and treat- 
ment problems. Staff attended a number of weekly multidisciplinary 
meetings. 

Frequent, informal consultation with nurses, doctors, and social workers 
concerning a particular patient's progress and condition was helpful in 
carrying out an effective plan of pastoral care and visitation. 

RESEARCH COMMITTEES 

Chaplain Kerney was a member of the National Institute of Mental Health 
research review committee and of the National Institute of Neurological 
and Communicative Disorders and Stroke Research Review Committee. He 
also served on a human use committee of the Department of Defense to review 
a special project. 



Chaplain White was appointed to a two year term as an EEO Counselor and 
functioned as a member of the CC-EEO Advisory Council. 

EDUCATION AND TRAINING 

Chaplain Kerney was a resource leader in two sessions of the "Death and 
Dying Seminar" held by the Clinical Center Educational Services Office. 

Chaplain Kerney met with two groups of Social Workers and two groups of 
persons from Patient Activities for an orientation to the Spiritual 
Ministry Department. 

Chaplain Kerney presented his slide-sound show, "A Time to Heal" to a 
group of staff nurses and two groups of student nurses. 

Father Linehan was a member of a panel dealing with the emotional needs 
of cancer patients for student nurses in the Cancer Institute. 

Rabbi Levine participated in a panel discussion at the Clinical Center on 
"Some Perspectives on the Jewish Patient." 

CONSULTATION 

Chaplain Kerney met with a committee of Health Service Officers of the 
U. S. Public Health Service regarding Hospital Chaplaincy. 

Chaplain Kerney served on a certification review committee of the College 
of Chaplains of the American Protestant Hospital Assocxatxon. 



Chaplain Kerney was a member of the Clinical Pastoral Education Consultation 
Committee of Suburban Hospital, Bethesda, Maryland. 

Father Linehan was asked to be a consultant with the newly opened Hospice 
of Washington. He helped evaluate their guide lines for Spiritual Ministry. 
He will continue as consultant upon request. 

COMMUNITY EDUCATION 

Chaplain White lectured on Death and Dying in the Graduate School of 
Education, University of Maryland. 

Chaplain White led a workshop on "Pastoral Care of the Sick" for the 
Officers and Clergy of the National City Christian Church, Washington, D.C. 

Chaplain White spoke at the Concord-St. Andrew's Methodist Church, Bethesda, 
on "Pastoral Care of the Sick and Dying". 

Chaplain White was a panelist on Morning Break, WTOP-TV on the subject of 
"Terminal Illness, Death and Mourning". 

Chaplain White was a panelist on six of the Bauman TV Series programs on 
"Through Death to Life", on WJAL-TV. 

Rabbi Levine spoke to several local Jewish civic groups about the chaplaincy 
program at the Clinical Center. 

Rabbi Levine spoke to the Montgomery County Medical Society on "The Healing 
Team - Physicians and Clergy". 

Chaplain Kerney lectured on "Pastoral Care to Intensive Care Patients and 
their Families" at a workshop for Veterans Administration Chaplains, 
Washington, D.C. 

Chaplain Kerney and Rabbi Levine conducted an Ecumenical Worship Service 
at the Candlelighters National Parents Conference, Arlington, Virginia. 

PROFESSIONAL MEETINGS AND TRAINING 

Chaplain Kerney attended the annual meeting of the College of Chaplains, 
a division of the American Protestant Hospital Association, Dallas, Texas. 

Father Linehan received credit for ongoing education at the Fourth Institute 
on Theological Concerns of the Health Apostolate offered by the Catholic 
Hospital Association. He also finished a week's course in Catechesis 
offered the Pastors of the Maryland Province, Society of Jesus. 

Chaplain White was an elected commissioner to a Meeting of the Synod of 
the Piedmont, United Presbyterian Church. 

Chaplain White took three C.S.C. courses on Basic and Advanced EEO 
Counseling. 



SM-6 



Chaplain White took a CC EEO Advisory Connnittee sponsored course on EEO 
Operations. 

Chaplain White attended a Death and Dying Workshop, St. Francis Burial 
Society, Washington, D.C. 

Chaplain White attended the National Conference, Forum for Death Education 
and Counseling, Washington, D.C. 

Rabbi Levine attended The Annual Meeting of the Jewish Chaplaincy Committee 
of the Central Conference of American Rabbis in Toronto, Canada. 

Rabbi Levine attended the monthly meeting of the Washington Board of Rabbis 
and its annual retreat in Warrenton, Virginia. 

Chaplain Payne attended a conference/workshop on "Stress Without Distress" 
sponsored by the East West Academy of the Healing Arts, Washington, D.C. 



BBtliesda. Maryland 200t4 





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