N/H VOLUME 79
. Number 4

Journal of the December, 1989

WASHINGTON
ACADEMY .- SCIENCES

ISSN 0043-0439

Issued Quarterly
at Washington, D.C.

CONTENTS

Introduction:

KINGSLEY M. STEVENS

Articles:

WILLIAM S. ZIRKER, “Why Geriatrics?”

KINGSLEY M. STEVENS, LINDA O’CONNOR,, et al., ““Where Technology

KINGSLEY M. STEVENS, “Antibiotics and the Older Patient”’

SAUL KAMEN and PAUL KORNFELD, “Dental Developments Over the
EaStEtiey eats Which Affect the Geriatric Patient” {...2...2..02.0ce.+ 6.

KINGSLEY M. STEVENS, “Some Social, Scientific and Technologic Changes
in Medicine from 1935 to the Present”

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Introduction

The demographic changes in the United States with its increase in people
over age 65, both in absolute numbers and as a percentage of the population,
has great importance to many aspects of American life. Before World War II
the major changes which increased longevity were better sanitation and public
health measures. Since World War II the changes have been largely the effects
of new treatments of individual patients. In this issue we consider changes
over the past 50 years which have increased both longevity and the quality of
life for older people. As could be anticipated, new problems arise from suc-
cesses, and some of these will be addressed. Since most readers will now or
later fall into the category of older patients, the subject matter crosses all
specialties of the Washington Academy of Sciences.

Kingsley M. Stevens
Guest Editor

Journal of the Washington Academy of Sciences,
Volume 79, Number 4, Pages 147-152, December 1989

Why Geriatrics?
William S. Zirker

Geriatric Medicine Section
Veterans Administration Medical Center, Northport, New York

and

Department of Medicine
State University of New York at Stony Brook

ABSTRACT

Americans are growing increasingly older. Over the next 50 years we expect a significant
growth in the segment of the population over age 65. This will present unprecedented
challenges to our social, economic and health care institutions. Geriatrics, a relatively
new field in American medicine, focuses on the health problems of the elderly.

While the maximum human life span of some 100 years has not changed
over the course of time, it is quite clear that the number of individuals living
into old age has increased dramatically. During the twentieth century alone
the average life expectancy of Americans has gone from 47 years in 1900 to
73 years in 1980.' Environmental, social and medical advances in such areas
as sanitation, nutrition, health behaviors, infant mortality, antibiotics, surgical
techniques and cardiac care are known to have contributed to this remarkable
increase in life expectancy. Demographic data show that by 1990, 32 million
Americans, or 12.7% of the population will be 65 years of age and older. By
the year 2030 the expectation is that approximately 20% of American pop-
ulation will be 65 and over.?”

Among our aging population, the group over 85 years old is proportionately
increasing at the greatest rate. Currently there are some 2.7 million people
over the age of 85 and this group is predicted to double in size by the end of
the century. Since the 1960’s there has been a strong downward trend in the
mortality rates for the very elderly in western society. Between 1933 and 1966,
the death rate in the U.S. for those over 85 years old had declined only 10%.
In contrast, the death rate for this group declined 26% between 1966 and
1977. It appears that reductions in the risk of dying from heart diseases and
stroke may account for a substantial part of this change. If current trends
continue, by the year 2050 half of all American may live to age 85.*

147

148 WILLIAM S. ZIRKER

While the majority of older Americans enjoy relatively good health and
independence, they clearly have a much higher incidence of disease and dis-
ability. Heart disease, stroke, arthritis, cancer, diabetes and obstructive lung
disease are all for the most part diseases of the elderly. In a health survey
performed in the city of Uppsala, Sweden by Waern,° the prevalence of varieus
diseases for 50 versus 60 year old men revealed 5 times more circulatory
diseases, 10 times more musculoskeletal disorders, 8 times more diabetes,
respiratory diseases and cancer, 4 times as many nervous diseases and twice
the number of mental disorders among the older as compared to the younger
age group. The incidence of dementia, depression, hip and vertebral fracture
rates, urinary incontinence, and malnutrition all increase significantly with
age. Along with this high incidence of disease comes a high incidence of
disability and the need for more medical, nursing, rehabilitative, home care
and nursing home care. A number of health surveys have estimated the prev-
alence of disability to be from 3% to 18% of people between the ages of 65
to 74 years old, and from 6% to 50% of those above the age of 75.° Currently
there are more nursing home beds than acute hospital beds, and those over
65 years old have a 20% chance of being admitted to a nursing home during
the remainder of their life time.

With this weight of disease and disability it is easy to see why the elderly
consume more health care services than their numbers alone suggest. Pres-
ently, the 12% of the population over the age of 65 utilizes 40% of all acute
hospital beds, 25% of prescription drugs, and accounts for 30% of the nation’s
health care expenditures and half of all federal health dollars.’ By the end of
the century half of all health care encounters will be with patients 65 and over.

These overwhelming demographic changes challenging our health, social,
economic and political institutions have been referred to as the “geriatric
imperative”. Given this imperative one would have expected the American
academic medical community to have championed the cause of geriatrics and
gerontology, and to have produced a large cadre of clinicians and researchers
interested in geriatrics. In spite of the need this has not happened, and for
most medical students and postgraduate physicians in training there is little if
any formal training in geriatrics. This is particularly ironic since it was Ignatz
Nascher, an American pathologist, who is credited with coining the term
geriatrics in his 1914 text book Geriatrics: The Diseases of Old Age and Their
Treatment. But today, some 75 years later, the study of geriatrics is still new
to American medicine.

In Great Britain the importance of geriatrics has been formalized by it’s
recognition as a medical specialty. There are established academic depart-
ments in half of the medical schools, formal curricula in 93% ,* postgraduate
specialty training in geriatrics, hospitals specializing in the care of the elderly,
and certification and consultant status for physicians trained in geriatrics.

Geriatrics developed in Great Britain in the 1930’s when Dr. Marjory War-
ren and several other physicians began to take an active interest in the patients
on the long term care wards of the hospitals. They came to appreciate that
there was much to learn from these chronically ill and frail elderly patients
whose problems had been viewed as beyond the scope of medical practice.
These were patients with severe strokes, dementias, neurological disorders,

WHY GERIATRICS? 149

and other chronic disabling diseases who had often been viewed as medical
failures. It was from this attempt to uncover previously overlooked medical
problems and to find practical approaches to dealing with the disabilities
imposed by chronic diseases that the field of geriatrics grew in the United
Kingdom.

In the United States modern academic medicine has concerned itself largely
with basic science research and technological development. We have been
fascinated by high technology topics such as lasers, coronary by-pass surgery,
magnetic resonance imaging, monoclonal antibodies, and gene splicing.
It is only in recent years that American medicine has begun to address
geriatrics.

In reaction to the demographics of aging it has been the political and social
leaders, and a few evangelical senior academic physicians who have pushed
for the academic medical community to take an interest in aging.

One of the most important events in the development of American geriatrics
was the passage of the 1974 Research on Aging Act authorizing the estab-
lishment of the National Institute of Aging as one of the National Institutes
of Health. The NIA has become a leader in the effort to get geriatrics into
the mainstream of American medicine. During the past decade there has been
significant growth in geriatrics. A number of medical schools and hospitals
have established divisions of geriatrics with clinical and research faculty, and
fellowship training programs. In 1988 the first examination for special com-
petency in geriatrics was given jointly by the American Board of Internal
Medicine and the American Board of Family Medicine. The vast majority of
those taking the exam were practicing physicians without formal training in
geriatrics.

Kane’, in a 1980 Rand Corporation study of geriatric manpower needs,
estimated that in order to have enough geriatricians just for academic positions
and as consultants in practice, we would currently need about 8000 specialty
trained physicians. Several surveys of physician members of the American
Geriatrics Society and the Gerontological Society of America have estimated
the number of physicians who consider themselves geriatricians to be in the
range of 750 to 1200, and only a quarter of these could be considered as full
time academic faculty. In 1987 there were 66 geriatric medicine fellowship
programs graduating approximately 100 trained geriatricians per year.* It is
clear that these numbers fall far short of what is needed if geriatrics is to be
established as significant presence in American medicine. The training of
geriatricians has been severely limited by program funding, number of pro-
grams, availability of faculty and dearth of qualified applicants. The problem
of recruiting physicians to train in geriatrics is difficult because of a lack of
exposure to formal geriatrics during medical school and residency, negative
steroetype images of the elderly, and comparatively low Medicare reimburse-
ment for the time consuming physician visits which are typically needed in
evaluating elderly patients.

The argument has been made that since physicians (especially internists)
who treat adults treat a large number of elderly patients, there is no need for
geriatrics as a specialty area. But just as there are significant anatomic, phys-
iologic and clinical differences between children and adults, there are signif-

150 WILLIAM S. ZIRKER

icant differences between 40 year old and 80 year old.” Important physiologic
and functional changes occur in most organ systems with aging. While it has
often been difficult for researchers studying the biology of aging to differentiate
normal age related changes from disease related changes, a number of sig-
nificant age related changes have been identified. The heart and lungs are two
organs systems which illustrate age related changes and their clinical signifi-
cance.

In the heart there are sclerotic and calcific changes which occur principally
in the high wear areas of the aortic and mitral valves. These may lead to aortic
stenosis and mitral insufficiency. Calcification also occurs in the electrical
conduction system of the heart and may lead to abnormalities in heart rhythm.
The pacemaker cells of the heart are reduced both in number and rate of
firing and there is slowed conduction through the heart’s electrical conduction
system. There is a reduction in response to adrenergic stimulation. Although
it is unclear whether this reduced response is because of a decline in the
number or function of the receptors, the result is seen in the increased sen-
sitivity of elderly individuals to antagonist medications such as beta-adrenergic
blockers and channel blockers. Physiologically healthy older people have been
found to have decreases in maximum stroke volume, cardiac output, oxygen
uptake, and maximum heart rate in response to exercise.

The respiratory system shows some of the greatest age related changes. The
chest wall becomes increasingly more rigid and less compliant. The lungs lose
elasticity and there are fewer alveoli to effect gas exchange which results both
in ventilation perfusion mismatching and reduced gas diffusing capacity. While
total lung capacity remains relatively constant with age, residual lung volume
increases and there are marked decreases in airflow rates which become most
prominent in response to exercise. Lung defenses are also altered by reduced
cough force, impairments in mucocillary cleaning of the upper airways, and
the response of macrophages, lymphocytes and neutrophils to bacteria and
other antigens. The result of these changes, compounded in many cases by
smoking and environmental pollutants, leads to the increased incidence of
pneumonia and chronic obstruction pulmonary disease in the elderly. How-
ever, in spite of this decreasing respiratory capability, training and conditioning
can result in high levels of fitness.

While research into the biology and physiology of aging is key to the future
development of geriatrics and gerontology as a discipline and scientific data
base, it has been in the clinical arena that geriatrics has been most active and
faces it’s greatest challenges. The elderly and the frail elderly in particular
have their own set of rather unique problems which are rarely well addressed
by the mainstream of medicine. In addition to the high incidence of the diseases
mentioned above, there is a high incidence of gait disorders, falls, urinary
incontinence, dementia, depression, delirium, hearing and visual loss, skin
pressure ulcers, osteoporosis, adverse drug reactions, excessive medication
use, psycho-social dysfunction and ethical treatment dilemmas. A number of
these problems are frequently overlooked, and for many there is no clear and
effective therapy.

WHY GERIATRICS? 151

Urinary incontinence serves as a good example of such a problem. It is a
major health problem of the elderly estimated to affect 10 million American
adults and conservatively costing 10 billion of dollars per year"! in home,
hospital and nursing home expenses. It is a disruptive disorder which can lead
to urosepsis, falls, rashes, skin breakdown, social isolation, embarrassment,
loss of independence and often to nursing home placement. Although several
studies have demonstrated that combined medical and behavioral therapy
predicated on specific diagnosis can be effective in yielding a number of pa-
tients either continent or substantially drier, most patients receive no system-
atic evaluation. In a 1987 study of incontinent health related nursing home
patients, Zirker’* found that although these patients had been incontinent an
average of two years, only 16% had ever received a systematic evaluation to
diagnose the problem. After medical and functional assessments, half of the
patients were clinically improved using behavioral techniques and drug ther-
apy. However, in order to carry out such a program the combined efforts of
physicians, nurses, social workers, and physical therapists were required.

In an attempt to deal with such complex problems and disabilities, geriatrics
has recognized the need to go beyond the traditional medical model of disease.
For many chronic diseases such as diabetes and stroke, it is the resulting
disability, rather than the disease itself, which diminishes the quality of life.
While organ damage cannot usually be reversed, the functional disabilities
and quality of life can frequently be improved through physical therapies and
nursing care. Geriatrics has employed batteries of cognitive and functional
assessment tools, and interdisciplinary teams of health professionals to eval-
uate and coordinate the care of frail elderly patients. It is from this perspective
that the concept of geriatric assessment teams and geriatric evaluation units
for both inpatients and outpatients has grown. The Veterans Administra-
tion has been a leader in geriatrics and has established many such units.
The purposes of these units is to evaluate frail elderly patients, uncover prev-
iously overlooked diagnoses, dementias and psychiatric disorders, provide
medical, nursing and rehabilitative care, and coordinate services so that,
whenever possible, patients could return home. Although the goals and
basis for such units appears to be sound, their cost effectiveness remains to
be proven.

Conclusion

To provide good quality care for frail elderly patients is clearly an expensive
and very labor intensive activity. From the demographics of aging it is obvious
that there will be increasing need for hospital, nursing home, outpatient and
home care services. Given the “geriatric imperative’, it is logical to develop
geriatrics into a field of medicine capable of producing researchers, teachers
and clinicians, who can provide the leadership needed to meet this challenge.

152

11.

12;

WILLIAM S. ZIRKER

References Cited

. Rowe, J. W., R. W. Besidine. 1982. Health and Disease in Old Age. Little, Brown, and Company,

Boston.

. U.S. Bureau of Census, July 1977. Series P-25, No. 704.
. Office of Technology Assessment. June 1985. Technology and aging in America. US Congress,

OTA-BA-264, Washington, D.C.

. Report of the Institute of Medicine. 1987. Academic geriatrics for the year 2000. J. Amer. Geriatrics

Soc. 35: 773-791.

. Waern U. 1978. Health and disease at the age of sixty. Uppsala Journal of Medical Sciences. 83: 153-

166.

. Bourliere, F. & J. Vallert-Massan. 1985. Epidemiology and ecology of aging. In Brocklehurst, J. C.

Textbook of Geriatric Medicine and Gerontology. Churchill Livingstone, Edinburgh. pp. 3-28.

. Gibson, R. M. & C. R. Fischer. December 1978. Age differences in health care spending, FY 1977.

HCFA Health Note.

. Barker, W. H. 1989. Adding Life to Years. The Johns Hopkins University Press, Baltimore. pp. 87-

100.

. Kane, R., D. Solomon, J. Beck, E. Keeler, & R. Kane. 1980. The future need for geriatric manpower

in the United States. N Engl J Med 302: 1327-1332.

. Beck, J. C. 1985. Development of pediatrics and family practice from a historical perspective: lesions

for geriatrics. J. Amer. Geriatrics Soc. Vol 33, No. 10:727-729.

National Institutes of Health. 1988. Consensus Development Statement, Urinary incontinence in adults.
Vol. 7, No. 5.

Zirker, W. S., R. Kennedy, K. Freeman. 1988. Evaluating and treating urinary incontinence in the
nursing home. Proceedings of the American Geriatric Society/ American Federation of Aging Research
Annual Meeting, Anaheim, CA.

Journal of the Washington Academy of Sciences,
Volume 79, Number 4, Pages 153-158, December 1989

Where Technology Fails

Kingsley M. Stevens, Linda O’Connor, Barbara Cartabuke-Mule,
Louise Hueppe, Sue Carlson, Madeline Fox and the Staff
of the 9A Hospice

Veterans Administration Medical Center,
Northport, New York 11768

ABSTRACT

While medical science has made amazing progress over the past half-century, clinical
applications have fully solved only a small number of diseases. Hence blind application
of all of our technology not only will not halt these diseases but will produce many
complications, medical and otherwise. In our society, the individual patient should make
his own informed decisions on how much technology is appropriate for him. These de-
cisions are needed for specific medical situations and for more general areas such as ““Do
not resuscitate orders” and “‘hospice”’ care.

One hundred and forty years ago, a prominent Boston physician vividly
presented a central concept for geriatrics. His presentation was non-medical,
but highly appropriate. Oliver Wendell Holmes, in ““The Deacon’s Master-
piece” or ““The One-Hoss Shay,” described a chaise which lasted without
repairs for 100 years to the day, then disintegrated. One section goes like this:

Now in building of chaises, I tell you what,
There is always somewhere a weakest spot,
In hub, tire, felloe, in spring or thill,

In panel, or crossbar, or floor or sill,

In screw, bolt, thoroughbrace, lurking still,
Find it somewhere you must and will,
Above or below, or within or without,

And that’s the reason, beyond a doubt,

A chaise breaks down, but doesn’t wear out.

This is certainly the way to live in old age! Holmes picked a time span for
the chaise of 100 years, the actual life span attained by a few people, so the
analogy as an ideal is realistic and probably intentional. It has often been
stated that an objective in geriatric care is to “‘add life to the years, not years
to the life.”” This emphasizes the concept of functional ability even though it
may be at the expense of a longer life span.

153

154 KINGSLEY M. STEVENS ET AL

The objective of the deacon, so well carried out, was to have the chaise
remain integrally sound for a long time and then collapse in toto. No one is
really expecting medical technology to provide people with functional integrity
for 100 years and then suddenly die. The preceding papers have briefly de-
scribed ways in which medical and dental programs have helped older people
approach this goal. The key to this progress has been technology and Jennett
has written a good overview of high technology.' If the advances enabling
patients to retain or regain full function had kept pace with the advancing
longevity, the impact of technology would be overwhelmingly beneficial. This
has not happened. Technology is much more successful at making precise
diagnoses and at keeping people alive than in restoring them to full function.
Consider those polar extremes. At one end are the prosthetic devices such as
eyeglasses and contact lenses. They are tremendously effective and enable
users to be almost 100% functionally effective in vision. However, they do
not cure the visual defect and they are a nuisance. The decision on the benefit
is clear; the technology should be, and is, extensively used. At the other
extreme is the demented patient who has had several strokes and is kept alive
for years on respirator, feeding tube and antibiotics. The technology is “‘ef-
fective” but of negative value. Hence this technology should not be used, but
itis used. The United States leads the world in the percentage of its population
who are over age 85. While many of this group are highly functional, far too
large a number lead a vegetative existence due to technology. These examples
are extremes and most technological applications will not offer such clear
choices.

The development and application of medical technology follows a certain
sequence. First, the question is raised as to whether a certain procedure or
effect can be carried out. Research and development follow which provide
a “‘yes” answer. Once available to physicians, the approach is “Since it is
available, it may be desirable to use it.”’ Soon this changes to “If it can be
done, it should be done.”’ Usage expands and, all too soon, the stage of the
technological imperative has arrived which says, “If it can be done, it MUST
be done.”’ There are, of course, clear medical contraindications to diagnostic
and therapeutic interventions. Yet the overwhelming pressure is toward the
technological imperative. To some degree, it comes from patients and families.
But in the United States the major players are the medical profession, which
is extremely technologically oriented, and the legal profession, which often
appears ready to turn any omission of a diagnostic or treatment procedure
into a malpractice claim. Hence in this country, medical care runs largely on
the technological imperative.

Application of technology will increase longevity and American courts have
often ruled that length of life is vastly more important than any other consid-
eration. The desires of the spouse and other family members are usually
ignored by courts; the only person who can say “‘no”’ is the patient. Court
rulings throughout the United States in both state and federal courts have
established the right of a competent patient to accept or refuse any type of
treatment or life support system. This position is basically sound, but often a
formerly competent person is not competent when the decision concerning

WHERE TECHNOLOGY FAILS 155

his care must be made. Emphasis on self-determination then turns from an
asset to a liability, since many courts will not accept “‘substituted judgment”’
by the patient’s representative.” In operational terms, this means that even if
you felt very strongly that you did not want to exist in a severely disabled
state, you might well be forced by law to exist in that state for many years.

The answer to this problem is by writing a “‘living will” or “‘advance direc-
tive” which specifies in reasonable detail what you do or do not want and
under what circumstances. Since certain states refuse to accept tube feedings
as a medical treatment, it is very important to specify that you refuse forced
feeding by tubes or intravenous methods under certain circumstances. How-
ever, no advance directive can be both broad enough yet contain enough
specifics to cover the large range of actual situations which may arise. Hence
you should also complete a form often titled “‘Durable power of attorney for
designation of health care agent.’ The individual(s) so designated will make
specific medical decisions consistent with the general provisions of your ad-
vance directive. Both documents should have witnesses and be notarized.
Neither of these documents are fully accepted by all states. Irrespective of
their “official”? status, they demonstrate clearly that you have considered this
problem and reached definite conclusions and that the individual selected to
make decisions knows of your wishes and expects decisions to be made along
the lines you determined when competent.’

Important as they are, such advance planning does not in itself resolve
ongoing medical decisions which we all face in varying degrees. The pervasive
technological imperative will be urging us on. How does one make a logical
decision? As a scientist, the reader knows that the way to make medical
decisions is to obtain the needed facts and be able to interpret them. Faith in
technology often dominates the facts on technology: Consider the facts about
cardiopulmonary resuscitation (CPR) and do not resuscitate orders (DNR).

The application of effective CPR using electrical defibrillation began in 1962
with patients who had acute heart attacks who were on EKG monitors. Many
had episodes of cardiac arythymmias, some of which were ventricular fibril-
lation producing cardiac arrest. These patients were essentially dead, but about
half of them resumed cardiac function following CPR. Since the patients were
constantly monitored, CPR began within seconds of the arrest. Here we have
the original technological advance with appropriate application under specific
conditions. Its application under these circumstances quickly spread. Soon it
was being used on non-monitored cardiac patients as well; then on non-cardiac
patients. Malpractice suits soon emerged when patients died from any cause
and were not given CPR; this vastly increased the numbers of patients who
received CPR. By the 1980s most patients who had a cardiac arrest when in
a hospital received CPR unless they specifically requested a DNR order. The
technology of CPR had clearly reached the state of the technological imper-
ative. It could be done and it was done. That was not the end. In New York
State, the legislature passed a DNR law so that doctors could be absolved
from liability if they withheld CPR under defined conditions. These were
highly defined conditions: The order could only be written for terminal pa-
tients, it had to be reviewed every three days and there were other strictures.

156 KINGSLEY M. STEVENS ET AL

Since the law specified what was required so as not to be liable, it in effect
also specified that if the doctor did not provide CPR when a DNR order was
not in place, then he may be liable. Hence since 1988, a technological medical
procedure has been demanded by state law.

State laws may require other technological procedures such as immunization
against certain diseases before entering grade school. The above terse history
covering 26 years would certainly imply that CPR was an extremely valuable
technology which should be widely utilized. But how effective is CPR? For
the type of patients for which it was developed, about 30% of those receiving
CPR leave the hospital alive. For other groups, the results are much less
successful. Many will have cardiac function partially restored but few will
leave the hospital alive. The time lapse from cardiac arrest to defibrillation
is extremely important, with much higher survivals when the time is less than
three minutes. Patients who have sepsis, pneumonia, cancer and renal failure
have almost no survivors from CPR and older patients, as a group, fare very
poorly.** The facts on CPR today are that most patients receiving CPR attain
only added misery. The rigidity of legal requirements makes it very difficult
to apply this valuable technology as it should be applied.

An escape from the technological imperative can be by use of palliative and
“hospice” type programs. The shift in emphasis is to couple length of life
more closely with the quality of life. The technological imperative, in practice
if not in theory, almost invariably comes out favoring length of life over quality
of life, so leads to frenetic activity to the very end. This does not happen in
the hospice type programs in the United States.

The need for an “escape hatch” from current mainstream medical practice
is due to society’s views on two subjects: Liability litigation and refusal to
accept death. True malpractice certainly exists, but the number of malpractice
suits filed in the U.S. is totally out of line with actual malpractice. These
charges are so frequent that a doctor is almost forced to act as though every
episode of illness he treats must be treated as though he will be sued. A
malpractice lawyer might claim this is as it should be. It is not. This approach
is incredibly expensive for society. At the individual level, each patient is
forced to undergo all that technology can muster, often repetitively. American
views on death set the stage for the American scene. Our society does not
accept death as part of the natural order. Our society also has great faith in
technology (even though society is not infrequently very anti-scientific!) The
combination demands that medicine see death as the ultimate enemy and
technology the way to defeat death. Given American views on litigation and
death, it is small wonder that physicians as a group do everything possible to
extend life, no matter what. Many social trends have shaped this view toward
death. Low death rates, most people dying in hospitals and widely scattered
families, all make death unfamiliar to Americans. In addition, Americans
traditionally take the view that everything can be improved, so everything
should be tried to forestall death. Yet in 1989, as it has for billions of years,
death comes to every living organism.

The need for a haven from the dominant societal pressure for frenetic
activity to the very end is all too real. That need has not been adequately met

WHERE TECHNOLOGY FAILS 157

but the hospice concept of care is spreading and there are now about 2,000
hospice programs in the U.S. The patient accepts that there is no more specific
treatment which might cure or arrest his progressive disease. The patient
desires to be free of pain and have his other symptoms controlled so that he
can continue to maintain maximum independence and maximum social inter-
actions until he dies. These goals are surprisingly hard to meet in both acute
hospitals and nursing homes. For most hospice programs, the patients is not
expected to survive over six months. Because of the nature of the disease,
cancer patients make up the large majority of hospice patients. But certain
patients with advanced heart, lung or liver disease, and those with advanced
AIDS are also appropriate.

The term “‘hospice” as used in medieval Europe often referred to rest houses
supported by religious groups where pilgrims, en route to an important reli-
gious site, could find food, lodging, rest and some nursing care. Refreshed
and remotivated, the pilgrims continued their journey. Today, as then, the
hospice is a way-station, a place of rest and relaxation for the sick as they
travel to the end of their personal journey. The involvement of third-party
payers had led to rigid definitions of their requirements for a hospice. It is
ironic that both federal and state regulations define hospices as being primarily
an “‘at home” function, while in the original definition the pilgrim was far
from home. Since hospice care is a concept of care, the term is appropriate
whether the care is given primarily in the home or in a hospital or other
institution. Home-based programs utilize many community volunteers which
enhances this type of hospice program and the home model is the ideal type.
The National Hospice Organization (U.S.) has prepared this definition:

Hospice is a medically directed, nurse coordinated program providing a
continuum of home and inpatient care for the terminally ill patient and
family. It employs an interdisciplinary team acting under the direction of an
autonomous hospice administration. The program provides palliative and
supportive care to meet the special needs arising out of the physical, emo-
tional, spiritual, social and economic stresses which are experienced during
the final stages of illness and during dying and bereavement.

Since death is the expected outcome for hospice patients, the staff does not
view death as representing failure. The staff is well satisfied if they can provide
a good quality of life leading to an easy death. If the person can come to
terms with his death and find renewed support from family members, some
previously alienated, so much the better. The team spends much time with
family members to reach the objectives. The nurse, especially, must play
multiple roles. She or he needs to know current technical options, although
the nurse may not apply many of them. The nurse needs to understand the
steps of adjusting to death and dying and interact with the patient as he works
his way through the process. Team members need time to listen and talk with
the patient far more than happens for most patients today. ‘Standard pro-
tocols” are often inappropriate for hospice patients and nurse and physician
must be ingenious and flexible in developing individual solutions to promote
physical and emotional comfort. All this should be done with the patient

158 KINGSLEY M. STEVENS ET AL

actively participating in decision making. A sense of humor is especially helpful
in hospice-type programs. These programs can lead to surprisingly contented
patients despite their destructive diseases; visitors to our hospice often com-
ment on the cheerful appearance of our patients.

Conclusions:

Il

is;

Medical technology has two sides. While designed to decrease disability and suf-
fering, at times technology increases both of these.

The technological imperative is prevalent in this country and often inappropriate.
Some of its negative effects can be countered by the preparation of “‘living wills”
and ‘durable power of attorney” documents.

. For many terminally ill patients, a hospice-type setting will provide superior care

to an acute hospital.

References Cited

. Jennett, B. 1986. High Technology Medicine. Oxford University Press, Oxford.
. NY. State Court of Appeals. 1988. Matter of Westchester County Medical Center (O’Connor), 72 N.Y

2d 517, October 14.

. Society for the Right to Die. The Physician and the Hopelessly Ill Patient, New York, and the 1988

Supplement.

. Peatfield, R. C., R. W. Sillett, D. Taylor and M. W. McNicol. 1977. Survival after cardiac arrest in the

hospital. Lancet 1: 1223-1225.

. Bedell, S. E., T. L. Delbanco, E. F. Cook and F. H. Epstein. 1983. Survival after cardiopulmonary

resuscitation in the hospital. New Eng. J. Med. 309: 569-575.

. Rozenbaum, E. A. and L. Shenkman. 1988. Predicting outcome of inhospital cardiopulmonary resus-

citation. Crit. Care Med. 16: 583-586

. Taffet, G. E., T. A. Teasdale and R. J. Luchi. 1988. Inhospital cardiopulmonary resuscitation. J. Amer.

Med. Assoc. 260: 2069-2072.

. Murphy, D. J., A. M. Murray, B. E. Robinson and E. W. Campion. 1989. Outcomes of cardiopulmonary

resuscitation in the elderly. Ann. Int. Med. 111: 199-205.

Journal of the Washington Academy of Sciences,
Volume 79, Number 4, Pages 159-169, December 1989

Antibiotics and the Older Patient

Kingsley M. Stevens

Geriatrics Section, Medical Service,
VA Medical Center, Northport, N.Y. 11768

and

Dept. of Medicine,
State University of New York at Stony Brook

ABSTRACT

Effective antibiotics were introduced in 1935 and the field has expanded steadily since
then. Their application has influenced almost every aspect of medicine, either directly or
indirectly. Because of this pervasive aspect, antibiotics have been the most important
single determinant of improved medical care for older patients over the past half century.
In the 1980s, the bacteria causing most infections in hospitalized patients are not classical
pathogens but normal flora growing in abnormal locations. This had led to widespread
use of antibiotics active against many species of normal flora; this extensive usage has led
to the emergence of many resistant strains of bacteria. Approaches to lessen damage to
normal flora and also decrease the development of resistant microbes are presented.

Use of Antibiotics

Statistics on the causes of death in the United States are available over the
1900-1985 period.'* These data are not directly comparable over time due to
changes in classification, changing age distribution and improved diagnostics.
Despite these factors, the major trends are clear. It will be a surprise for many
to find that not only today, but even in 1900, the largest cause of death was
cardiovascular. After that, however, the 1900 picture was dominated by in-
fectious deaths: Pneumonia, influenza, tuberculosis, enteric infections, diph-
theria, measles. By 1935 the frequencies of all these diseases had fallen,
especially the enteric infections. Although the death rate for syphilis had not
changed greatly from 1900, in 1935 it was among the top ten causes of death.

In 1985 the overall death rate was 874/100,000 population. Heart disease
accounted for 37%, cancer for 22%, stroke for 7% and chronic obstructive
lung disease for 4%. The only infectious disease producing more than 1% of

159

160 KINGSLEY M. STEVENS

deaths was pneumonia, listed at 3%.* From these mortality data, it would
appear that bacterial infections are not now a major problem as causes of
death. The amounts of antibiotics used today are immense and at great cost.
What have antibiotics done, how are they being used today and what appears
ahead?

Social changes, better hygiene and sanitary engineering were the major
causes of decreases in tuberculosis and enteric infections produced by Sal-
monella and Shigella species. However, antibiotics have effectively treated
most of those cases which did develop. Antibiotics have been highly effective
against pneumococcal pneumonia, streptococcal infections, gonorrhea, men-
ingitis and syphilis. They have cured innumerable cases of bacterial infections
of the lungs, bladder and other internal organs. Antiseptic technics made
major surgery possible and remain a critical requirement. Nevertheless, an-
tibiotics have also greatly increased the ability to carry out surgery on patients
formerly considered at too high risk. They have also provided effective treat-
ment of local and systemic infections which occur following surgery.

Drug treatment of rickettsial infections such as typhus and Rocky Mountain
Spotted Fever works well but drug treatment for viral infections is still prim-
itive. However, antibiotics have played a major role in the development of
viral vaccines. The major technical problem for such development was ob-
taining large supplies of purified virus. Some viruses, such as influenza virus,
could be grown in adequate quantities in chick embryos although purification
remained a problem. But most viruses required the development of tissue
culture technics. These were begun by Alexis Carrel before World War I and
were successful at the laboratory level because of his extreme methods of
maintaining sterile conditions. However, commercial development was im-
possible without antibiotics. Addition of antibiotics to the medium prevented
destruction of the tissue culture cells by the ubiquitous contaminants. This
led directly to viral vaccines, both killed and attenuated.

When organ transplantation began, there was need to depress the immune
system to prevent rejection of the transplant unless it was from an identical
twin. We now have very effective immunosuppressive drugs, but they could
not be used if antibiotics were not available. Chemotherapy of most forms of
cancer is widely used in the United States. Since these drugs almost invariable
depress host responses to infections, their use also depends on antibiotics.

The Antibiotics

We have presented the successes of antibiotics without any consideration
of their history, how they act and how the bacteria react. The word “antibiotic”’
is defined as ‘“‘a substance produced by a microorganism and able in dilute
solution to inhibit or kill another microorganism.” It is now over a half century
since the first really satisfactory antimicrobial drug was introduced. That was
in 1935 and the drug was an azo dye named Prontosil. The azo dyes containing
a sulfa nucleus were developed by the I.G. Farbenindustrie as dyes which
bound very tightly to the proteins of wool and silk. Their synthesis began in
1909 and soon afterwards it was suggested that these dyes might also bind

ANTIBIOTICS AND THE OLDER PATIENT 161

tightly to bacterial proteins and thereby inactivate them. Twenty-five years
passed before Domagk demonstrated that mice would be protected from ex-
perimental streptococcal infections with Prontosil. Soon after, French workers
found that in mice and other mammals the azo bond was cleaved and the
active agent was sulfanilamide, shown below:

ANS COO

We now know that the mode of action of sulfa drugs is not by binding of
bacterial proteins but by competitive inhibition of para-amino benzoic acid
(PABA), shown below:

EN 0) -se.NE,

PABA is one of three major precursors of the vitamin folic acid. Sulfa drugs
inhibit those microbes which must synthesize folic acid as they have no trans-
port mechanism whereby extracellular folic acid could be taken into the cell.

The first true antibiotic was penicillin and its history is well known. Although
Fleming described its antibacterial effects in 1929, the instability of penicillin
and the small amounts produced delayed commercial production until these
problems were solved by British and American teams in World War II. The
toxicity of penicillin G is so low that the lethal effect of huge doses is due to
the cation in the salt, potassium or sodium. This pharmacological inertness
for mammalian cells reflects penicillin action on cell walls, which mammalian
cells lack.

Since the “‘antibiotic era’”’ began, between 5,000 and 10,000 natural anti-
biotics have been described and between 50,000 and 100,000 semi-synthetic
analogues have been made! Yet fewer than 150 antibiotics are available com-
mercially in the United States. In 1986, 29 of these were naturally occuring
with the remainder being either partially or totally synthesized.’ Antibiotics
can be grouped by mode of action, shown in Table 1:

Table 1.—Major antibacterial agents.
Mode of action Examples
Inhibition of cell wall synthesis All penicillins

All cephalosporins
Vancomycin

Inhibition of nucleic acid synthesis Quinolones
(e.g. nalidixic acid, ciprofloxacin)
Inhibitors of ribosome function Streptomycin
Gentamicin

Tetracycline

Erythromycin
Inhibitors of folate metabolism Sulfa drugs

Trimethoprin

162 KINGSLEY M. STEVENS

The penicillins and the cephalosporins have been the least toxic of the
antibiotics and they share a B-lactam ring, the active group, which is labeled
‘‘A”’ in the structural formulae.

General Formulae

Penicillin Cephalosporin
S
KH Ras aa
COOH N R
ah)
COOH

These two groups of antibiotics, plus new groups called the carbapenems
and the monobactams, comprise the B-lactam antibiotics. The B-lactams dom-
inate development work in antibiotics. Cephalosporins have greater changes
in activity than penicillins when side chains are modified. The mode of action
of all B-lactam antibiotics is the same. The bacterial cell wall is synthesized
by enzymes on the cell membrane. The B-lactam ring, on interacting with a
specific bacterial membrane bound peptidase, opens at the site of the arrow
and binds to the enzyme, inactivating the enzyme and thereby halting cell
wall synthesis.‘

Bacterial Infections Today

The general concept of a bacterial infection in 1935 was that you “caught
it” from another person, as occurs today with such minor virus infections as
colds or a major one such as AIDS. Pneumococcal pneumonia, streptococcal
sore throats, scarlet fever, diphtheria, whooping cough, gonorrhea, syphilis
and local infections with Staphylococcus aureus followed this pattern. These
still occur, but in much smaller numbers, and in 1989, the bacteria we deal
with in hospitals are primarily the opportunistic normal flora of man. Normal
flora are those species found on skin and in the respiratory, digestive systems
and the genital tract in a high percentage of normal people. These bacteria
rarely produce disease in people without risk factors. Yet these- bacteria now
comprise the vast majority of isolations from hospitalized patients who,
through debilitation or various treatments, become at high risk for infection.
Many of the strains are not “‘caught”’ from another person; they are from the
normal flora of the infected patient, with the bacteria now growing in an
abnormal site. The bacterial groups and culture sites appear in Table 2.

ANTIBIOTICS AND THE OLDER PATIENT 163

Table 2.— Bacterial isolations in the clinical microbiology laboratory at the Northport VA Medical Center
during 1988.

No. of Normal
Bacterial Type isolates location Cultured from
Enteric bacteria 2484 Colon
Pseudomonas sp. 520 urine >sputum>wounds/abcesses
Escherichia coli 503 4 urine >wounds/abscesses>blood
Enterococci 490 t ‘ 4 :
Proteus sp. 279 i ‘ " >sputum
Other gram-neg bacilli 692 : f , r
Staphylococcus aureus 685 Nose wounds/abscesses>sputum>nose
Staphylococcus 314 Skin blood>urine>wounds/ abscesses
coagulase negative
8-streptococci 158 Upper resp. tract wounds/abscesses>sputum>throat
Pneumococcus 72 i sputum>blood
Hemophilus sp. 71 f sputum>throat

The isolates were predominantly normal enteric bacteria found in other lo-
cations. Staphylococcus aureus has always been a prominent pathogen? es-
pecially of wounds and abscesses. The Staphylococcus coagulase-negative
group primarily represent S. epidermidis, the universally abundant normal
skin microbe. But it also includes S. saprophyticus, found in bladder infections
and other newly defined species.° In the past, blood cultures which grew out
S. epidermidis usually represented contamination from the skin. In contrast,
many positive blood cultures today represent true bacteremias by this orga-
nism.’ This marked change in pathogenicity is due to two factors. Staphylo-
coccus epidermidis colonizes foreign bodies very effectively, rarely establishing
itself internally without a foreign body as a primary site. The number of foreign
bodies used today is extensive: Permanent ones, such as prosthetic joints and
heart valves, vascular grafts, pacemakers, cerebrospinal fluid shunts, perito-
neal dialysis catheters, and temporary intravascular catheters which now con-
stitute almost routine care.” The other major change is that S. epidermidis,
formerly sensitive to penicillin and many other antibiotics is now often resistent
to not only penicillin but to many other antibiotics also.° This brings us to the
problem of antibiotic resistance.

Antibiotic Resistance

Microbial resistance was first noted in 1913 when Paul Ehrlich reported that
certain strains of trypanosomes were not killed by usually lethal concentrations
of a dye, and these strains did not take up the dye. Biochemical studies on
the basis of antibiotic resistance began with penicillin, with the penicillin-
destroying enzyme, penicillinase, being described even before penicillin was
used clinically!® Strains of $. aureus produced this enzyme which was later
shown to cleave the B-lactam ring. Beta-lactamases have been isolated from
many species but none from pneumococci or B-hemolytic streptococci, which
therefore remain highly sensitive to penicillin. For S. aureus, however, pen-

164 KINGSLEY M. STEVENS

icillinase production has become the normal with 93% of our hospital strains
doing so and 83% of community strains.’

By altering side chains near the active site of the B-lactam ring, penicillins
resistant to penicillinase action have been produced. The first commercially
successful one was methicillin, marketed in 1960. But even before being used,
methicillin-resistant Staphylococcus aureus (MRSA) strains had been found.’
These MRSA strains were first noted in England and spread rapidly in Europe
with 34% of strains being MRSA in Denmark in 1968. However, by 1980,
the percentage of such strains in Denmark had fallen to 2%" and fell to <1%
in 1986."' Australian hospitals reached peak MRSA values of about 35% in
1982,’* which figure was not attained in Italy until 1987.'* Emergence of MRSA
strains began in the U.S. in 1967 with waxing and waning in different areas.
In our hospital, the percentage of MRSA strains stayed between 10 and 20%
from 1981 through 1987. In 1988 there was an abrupt rise to 42% which
in 1989 is beginning to fall. The actual 1988 percentage of resistant strains
was probably nearer 35%, the maximum figure found elsewhere, since the
42% figure included large numbers of cultures taken specifically to trace the
spread of MRSA. Epidemic strains have been described'* and such sud-
den fluctuations probably reflect introduction of such strains. As others have
found'*!° these MRSA strains are often multiply resistant. Our 1988 results
showed the following percentages of MRSA strains resistant to: Cephalothin
42%, clindamycin 41%, erythromycin 48% and gentamicin 35%. Very little
resistance was found to the heavily restricted drugs chloramphenicol (3%)
and vancomycin (0%) or to the new drug ciprofloxacin (3%). The older
trimethoprim/sulfamethoxazole combination showed 20% resistant strains.
These drugs represent all major modes of action (Table 1). Hence, many
different biochemical changes, directed by DNA, have taken place in these
resistant bacteria. Many of these mechanisms have not been thoroughly
worked out but Neu* presents much current information.

As noted earlier, S. epidermidis has developed multiple resistance, overall
more so than S. aureus.°? Our 1988 figures confirm this, with 70% of S.
epidermidis isolates from foreign body sources being resistant to oxacillin
(methicillin equivalent), 70% to cephalothin, 58% to clindamycin, 68% to
erythromycin and 57% to gentamicin. Aside from vancomycin, the S. epi-
dermidis are much more often resistant to those antibiotics now most often
active against S. aureaus: Chloramphenicol with 22% of S. epidermidis isolates
resistant vs 3% S. aureus, ciprofloxacin, 12% vs 3%, trimethoprim/sulfa-
methoxazole, 51% vs 20%. The primary drug used to treat these multiply
resistant staphylococci of both species is vancomycin. This antibiotic was 1so-
lated 30 years ago but has been little used due to toxicity and cost. Although
vancomycin inhibits cell wall synthesis, it does so by direct attachment to a
cell wall chain during synthesis, preventing completion of the chain.'’ Recently
a strain of S$. epidermidis has shown vancomycin resistance.'* To date, no
strains of S. aureus are vancomycin resistant’ but it is probably only a matter
of time before some appear.

Bacterial resistance to antibiotics is genetically determined but through two
mechanisms. Chromosomal mutations are the normal genetic mechanism for

ANTIBIOTICS AND THE OLDER PATIENT 165

all types of cells, including bacteria. But much of bacterial resistance is trans-
mitted by DNA outside the chromosome in particles called plasmids. Spread
by this mechanism can be much more rapid than by chromosomal mutation
since the plasmids can be taken up by other bacteria, sometimes even of
different species. Although spread by plasmids is more rapid than through
chromosomal transmission, it is less stable. Bacteria contain a chromosome
but lack a nuclear membrane. Hence incorporation of information from cy-
toplasmic DNA into the genome is not infrequent. In the staphylococci, the
production of penicillinase was originally plasmid directed but it is now in-
corporated in the genome of most strains. Methicillin resistance was also
plasmid linked, but it too appears incorporated into the genome in certain
strains} )°.?

Resistance to penicillin and ampicillin is present in about 90% of both
staphylococcal species in our hospital isolates. Since antibacterial agents active
against penicillinase producing staphylococci are very widely used in hospitals,
why have the methicillin resistant strains of $. aureus peaked at about 35%
and those of S. epidermidis at 70%? To answer this, we must first address
another question: Do MRSA strains produce more or less severe disease than
methicillin-sensitive strains (MSSA)? No study presents MRSA as producing
more severe disease but several reports claim that MRSA and MSSA are
equally virulent.'*'*!° Clinical studies of such infections cannot have controls,
so animal studies are important. The best such study was by Peacock et al’
who isolated two MSSA and one MRSA strain from patients and determined
relative virulence for them plus an American Type Culture Collection standard
strain. Using both intravenous and intraperitoneal injections into mice, they
found no marked differences amongst the strains. Despite this, most reports
and reviews consider MRSA and other resistant bacteria less virulent than
sensitive strains.”'’?! Relative frequencies of MRSA compared to MSSA
strains in specific infections also support the greater virulence of the sensitive
strains: The ratio of MSSA/MRSA in 39 cases of complications of bacteremia
was 12:1,” the ratio in 22 cases of bacteremia in AIDS patients was 11:1,”
in 400 cases of S. aureus bacteremia the ratio was 133:1!** Even when MRSA
cases are specifically reported, the number are small: A pediatric study cov-
ering seven years recorded only 20 cases, primarily from intravascular
catheters’® as is found with the normally non-pathogenic S. epidermidis. A
report on MRSA in pulmonary cases presented only nine cases.”

The reason that multiply resistant bacteria have not more extensively re-
placed sensitive bacteria and are, overall, of lower virulence, appears due to
the fact that they do not grow as well.*'*?!“° The acquisition and maintenance
of resistance factors will increase the energy requirements of the bacterial cell
compared to the “‘wild”’ (sensitive) type. Hence, unless the selective pressure
of the specific antibiotic is constantly present, the plasmid or the chromosomal
mutation will be lost'’’’ as the sensitive type is subjected to positive selection
by its faster growth rate.

Production of bacteria resistant to most antibiotics is fairly easy in the
laboratory by growing the bacteria in increasing concentrations of the anti-
biotic. Under such circumstances, the bacterium is grown in its ideal medium

166 KINGSLEY M. STEVENS

with the only restraining influence being the antibiotic. The selective condi-
tions in clinical situations are very different. The antibiotic concentration is
widely variable in place and time. Perhaps more importantly, the many host
resistance factors and the geneal biochemical mileau of the host will often
select positively for the sensitive strain while the antibiotic is selecting posi-
tively for the resistant strain. Particularly if isolates from a large number of
hospitals are pooled, it may appear that there is almost no increased resistance
from the use of antibiotics.** Due to the factors noted in this and the preceding
paragraph, resistant strains are always in a state of flux. It is clear that clinical
use of antibiotics does increase resistance.*”? Our hospital laboratory followed
resistances of three species to three different B-lactam antibiotics over the
1981-1988 period. S. aureus tested against oxacillin showed 8% resistant
strains in 1981 which rose to 17% in 1982. It remained between 10 and 20%
until 1988 when it rose to 42%. Escherichia coli in 1981 had 20% of strains
resistant to ampicillin. This rose to 50% in 1984 but fell to 30% in 1986 and
has remained there. Pseudomonas sp tested against ceftaxime had only 8%
resistant strains in 1981 which showed little increase through 1983. The figure
then began to rise so that in 1988, 66% of strains were resistant.

As was noted earlier, methicillin-resistant $. aureus peak at about 35% of
the total strains while S. epidermidis reaches about 70%. This large difference
probably reflects the additive effects of two factors. Since S. epidermidis col-
onizes everyone, staff and patients alike, the pool for new mutants and plas-
mids is much greater. The vast quantities of antibiotics used in most hospitals
ensure that all people spending long hours on a hospital unit will have much
skin exposure to antibiotics. In addition, the skin has fewer immune systems
at work than the wounds and abcesses where S. aureus abounds.

Antibiotics and the Older Patient

Although this heading is the title of the article, so far we have dealt with
general features of antibiotics, microbes and patients without regard to age.
In actual clinical practice, patients over age 65 largely determine the course
of events in antibiotic use. Not only are their numbers rapidly increasing but
they are the group with repeated hospitalizations. Catheters, especially urinary
catheters, are much more frequently used in this group. They populate the
nursing homes which are rife with resistant bacteria.“” Carcinomas are more
frequent over age 65 and most types increase linearly with age.

The medical-pharmaceutical complex is at war with the normal flora of man.
The resources on both sides are formidable. The result is an antibiotic race
which is certainly advantageous to the antibiotic manufacturers. The three
synergistic weapons of the bacteria are their universal presence, their genetic
variability’? and their incredible growth rates. Common gram-positive and
gram-negative bacteria can replicate as rapidly as every 20 minutes in standard
media in vitro. This means that in 12 hours a single bactertum could produce
10" progeny!

ANTIBIOTICS AND THE OLDER PATIENT 167

Physicians tend to treat defined infections and most often use “broad spec-
trum” antibiotics; not infrequently two or even three at the same time. Al-
though each is chosen for a specific “‘coverage,”’ nonetheless all have wide
spectra. Hence, with such treatment, almost all of the hundreds of billions of
bacteria which constitute the normal flora of that patient—dozens of spe-
cies—are subjected to selection for resistance to each of the antibiotics. Med-
icine uses many foreign body devices which in themselves turn normal flora

into pathogens. Increasing resistance develops in certain bacterial groups. A
- manufacturer introduces a new antibiotic highly active against these resistant
organisms. Sales soar due to extensive use which occurs despite attempts to
restrict use. Since resistant strains grow more slowly, they are also less sus-
ceptible to bacteriolytic antibiotics, thereby often requiring longer to clear.
This increases the number of mutants to the new drug. A prime example of
such indolent growth was that of a vancomycin resistant S. epidermidis, grow-
ing intraperitoneally, which persisted for 14 weeks! without either killing the
patient or disappearing.’®

A Modus vivendi—Is It Possible?

While “‘classical’’ bacterial infections still exist and are treated effectively
with antibiotics, most bacterial infections seen in hospitals today are produced
by common bacteria which were infrequent opportunistic pathogens when
antibiotic use began half-century ago. When a classical contagious bacterial
disease is under treatment, the objective is to eradicate the alien invader. But
if that bacterium is part of the host’s common normal flora, it can only be
eliminated on a transient basis and then from ‘‘abnormal”’ sites where it nor-
mally does not grow. From the preceding sections and other sources, we
develop the following principles regarding bacterial resistance to antibiotics:

1. The normal flora in a healthy individual represents a stable but dynamic equilibrium
and should be altered as little as possible.

2. The indigenous antibiotic resistances of the normal flora are their most stable form.

3. Foreign bodies of all kinds increase the invasive potential of normal flora.

4. Contact between a specific antibiotic and a sensitive population of bacterial cells
will promote proliferation of those bacterial cells resistant to the antibiotic.

5. Such induced resistant strains will tend to regain their native sensitivities if left
unexposed to antibiotics over several generations.

6. The dosage of an antibiotic and its length of use will directly correlate with selection
of resistant strains of bacteria which are not the target strain of the treatment
program. (E.g.: A patient has a symptomatic urinary tract infection and the or-
ganism and sensitivities are known. Dosage with an appropriate antibiotic could
vary from 500 mg every 12 hours for five days to 1 g every eight hours for ten
days. For this and other situations, the higher dosage schedule would make it less
likely that the targeted bacterium would develop resistance and more likely that
the infection would be completely cleared. But that same higher dosage and longer
time would produce a larger antibiotic gradient and longer time of exposure to
every bacterium in his body, wherever located.)

168 KINGSLEY M. STEVENS

. In the hospital setting, antibiotics are not given only to the patient. The greater

the use, the greater the distribution of antibiotics throughout the unit at low levels
to staff and other patients by air and hand spread.

From these principles, one may formulate principles of antibiotic use de-

signed to diminish emergence of antibiotic resistance:

lf

Do not use antibiotics at all unless the need is clear. This has too many aspects to
discuss here. A main point is that.a “‘positive’’ bacterial culture, per se, is not an
indication to administer antibiotics.

Foreign bodies should be used as sparingly as possible and removed as soon as
possible. This includes simple devices used to give intravenous fluids and urinary
catheters.

. When antibiotics are used, it must be realized that multiple antibiotics, high dosages

and long courses are the most effective way to increase resistant strains of all types.
Adherence to good handwashing practices and to standard aseptic technics to
prevent spread of resistant strains is extremely important.

. Unless restricted antibiotics are really tightly restricted, a major purpose of re-

striction, i.e., to keep them highly effective, will always be lost.

Conclusions

In this article, the major emphasis has been on the development of resistance

by the normal flora to antibiotics. Antibiotics have indeed been a great boon.
However, their continued effectiveness will depend heavily upon more judi-
cious usage.

Acknowledgement

The data on Northport VA Medical Center bacterial isolations was gener-

ously provided by the Clinical Microbiology Laboratory (Dr. C. Saceanu,
Director). Typing was provided by Angela R. Wright.

References Cited

. Bureau of the Census. 1975. Historical Statistics of the United States, Colonial Times to 1970. Part

1. Bicentennial Edition, U.S. Gov’t Printing Office, Washington, D.C. p. 58.

. Hoffman, M. S. (ed). 1986. The World Almanac and Book of Facts 1987. Pharos Books, New York.

peene

. Mitscher, L. A. 1987. Chemistry of newer antibiotics directed toward overcoming bacterial resistance.

Bull. N.Y. Acad. Med. 63: 269-294.

. Neu, H. C. 1987. The biochemical basis of antimicrobial and bacterial resistance. Bull. N.Y. Acad.

Med. 63: 295-317.

. Sheagren, J. N. 1984. Staphylococcus aureus: the persistent pathogen. New Eng. J. Med. 310: 1368-

1373, 1437-1442.

. Christensen, G. D. 1987. The confusing and tenacious coagulase-negative staphylococci. Adv. Int.

Med. 32: 177-192.

. Christensen, G. D. 1987. The coagulase-negative staphylococci: little brother grows up. J. Amer. Ger.

Soc. 35: 469-471.

. Abraham, E. P. and E. Chain. 1940. An enzyme from bacteria able to destroy penicillin. Nature 146:

837.

. Eykyn, S. J. 1988. Staphylococcal sepsis. Lancet 1: 100-103.

10.

11.
12.
15:

14.

iS.
16.
ij.
18.
19.
20.
21.
22.

25.

24.
fas)
26.
27.
28.
28:

30.

ANTIBIOTICS AND THE OLDER PATIENT 169

Rosendal, K., O. Jessen, V. Faber and M. W. Bentzon. 1983. Frequency, phage types and antibiotic
resistance of Staphylococcus aureus isolated from blood cultures in Denmark, 1975-1981. Scand. J.
Infect. Dis. Suppl. 41: 19-26.

Ipsen, T. and B. Gahrn-Hansen. 1988. Occurence of methicillin resistant S. aureus in a department
of orthopaedic surgery. Europ. J. Clin. Microbiol. Infec. Dis. 7: 400-403.

Pavillard, R., K. Harvey, D. Douglas et al. 1982. Epidemic of hospital-acquired infection due to
MRSA in major Victorian Hospitals. Med. J. Australia 1: 451-455.

Schito, G. C. and P. E. Varaldo. Trends in the antibiotic resistance of clinical staphylococcal strains
in Italy. 1988. J. Antimicrob. Chemotherapy 21: Suppl C, 67-78.

Peacock, J. E., Jr., D. R. Moorman, R. P. Wenzel and G. L. Mandell. 1981. Methicillin-resistant S.
aureus: microbial characteristics, antibiotic susceptibility and assessment of virulence of an epidemic
strain. J. Infect. Dis. 144: 575-582.

Cookson, B. D., and I. Phillips. 1988. Epidemic methicillin res istant Staphylococcus aureus. J. An-
timicrob. Chemotherapy 21: Suppl C, 57-65.

Ribner, B.S. 1987. Endemic, multiply resistant Staphylococcus aureus in a pediatric population. Clinical
description and rash factor. Amer. J. Dis. Child. 141: 1183-1187.

Barna, J. C. J. and D. H. Williams. 1984. The structure and mode of action of glycopeptide antibiotics
of the vancomycin group. Ann. Rev. Microbiol. 38: 339-357.
Schalbe, R. S., J. T. Stapleton and P. H. Gilligan. 1987. Emergence of vancomycin resistance in
coagulase-negative staphylococcus. New Eng. J. Med. 316: 927-931.

Lacey, R. N. 1984. Evolution of microorganisms and antibiotic resistance. Lancet 2: 1022-1025.
Datta, N. & M. E. Nugent. 1983. Bacterial variation. In Topley & Wilson’s Principles of Bacteriology,
Virology and Immunity. Edited by Wilson, G. & Dick, H.M. 7th Ed., Vol. 1, pp. 163-171. Williams
& Wilkins, Baltimore.

Krasinski, K. M. 1987. Virulence vs resistance. Bull. N.Y. Acad. Med. 63: 237-252.

Libman, H. & R. D. Arbeit. 1984. Complications associated with Staphylococcus aureus bacteremia.
Ar ch. Int. Med. 144: 541-545.

Jacobson, M. A., H. Gellermann & H. Chamber. 1988. Staphylococcus aureus bacteremia and recurrent
staphylococcal infections in patients with AIDS and AIDS-related complex. Amer. J. Med. 85: 172-
173:

Gransden, W. R., S. J. Ekykn & I. Phillips. 1984. Staphylococcus aureus bacteraemia: 400 episodes
in St. Thomas’s hospital. Brit. Med. J. 288: 300-303.

Cafferkey, M. T., E. Abrahamson, A. Bloom & C. T. Keane. 1988. Pulmonary infections due to
methicillin-resistant S. aureus. Scand. J. Infect. Dis. 20: 297-301.

Sabath, L. D. 1987. Some historical aspects of bacterial resistance. Bull. N.Y. Acad. Med. 63: 330-
336.

Todd, E. W., G. S. Turner & L. G. H. Drew. 1945. The temporary nature of “‘fastness” of staphylococci
to penicillin. Brit. Med. J. 1: 111-113.

Barry, A. L. & R. N. Jones. 1987. Bacterial antibiotic resistance before and after clinical application
in the United States. Bull. N.Y. Acad. med. 63: 217-230.

McGowan, J. E., Jr. 1987. Is antimicrobial resistance in hospital microorganisms related to antibiotic
use? Bull. N.Y. Acad. Med. 63: 253-268.

Weinstein, R. A. 1987. Resistant bacteria and infection control in the nursing home and hospital. Bull.
N.Y. Acad. Med. 63: 337-344.

Journal of the Washington Academy of Sciences,
Volume 79, Number 4, Pages 170-179, December 1989

Dental Developments Over the
Past Fifty Years Which Affect the
Geriatric Patient

Saul Kamen
Parker Jewish Geriatric Institute, New Hyde Park, New York 11040
and
Paul Kornfeld

VA Medical Center, Northport, New York 11768

ABSTRACT

In the past half-century dentistry has changed from a narrow emphasis on the mechanics
of restoration of the dentition to the interrelationship between medical problems and oral
health. At the same time, the demographic imperatives of an aging population have given
rise to a new subdiscipline of the profession—geriatric dentistry, which may be defined
as oral health care for elderly persons, usually with multiple medical disorders, poly-
pharmaceutical regimens, and/or psychosocial problems which render them more vul-
nerable to dental intervention. This chapter will explore the impact of medical develop-
ments since World War II on the clinical management of geriatric dental patients.
Concomitantly it will describe refinements in our understanding of the normal and path-
ological effects of aging on the hard and soft tissues of the mouth. New technology with
special implications for geriatric oral rehabilitation, and which are relevant to total health
care, will be delineated. All of these factors have produced significant changes in the
epidemiology of dental disease in the elderly and have given us new insights into the
maintenance and preservation of the oral health of the elderly.

Introduction

Although dentists have always treated older patients, qualitative and quan-
titative changes in the past half century have resulted in the emergence of a
new subdiscipline of the profession—geriatric dentistry. This may be defined
as the delivery of oral health services to elderly patients, usually with at least
one major chronic disorder, frequently on polypharmaceutical regimens, and

170

DENTAL DEVELOPMENTS WHICH AFFECT THE GERIATRIC PATIENT 171

often with psychosocial problems, all of which render them more vulnerable
to stress in the environment.

With some exceptions the life span of patients with major diseases which
influence dental care has been increased, primarily because of effective med-
ical treatment. Thus, although degenerative disease of the cardiovascular sys-
tem is still the number one cause of death in the elderly (40% of all deaths
beyond 55 years), there has been a dramatic reduction in fatalities due to
ischemic heart disease in the past two decades. This is true for both sexes and
for whites and nonwhites over 65 years of age, and is demonstrated by the
fact that for white males in the 65—74 year cohort the mortality rate has fallen
from 2119 per 100,000 individuals in 1968 to 1642 per 100,000 in 1977.' This
decline in cardiovascular mortality is attributed to changes in lifestyle as well
as newer pharmacologic agents and surgical interventions.* This trend, of
course, is good news to potential victims of heart disease, but it also increases
the number of elderly patients at higher risk for dental treatment because of
pre-existing cardiac deficits and valvular heart prostheses who will require
antimicrobial prophylaxis prior to invasive procedures.

The Changing Epidemiology of Dental Disorders

A dramatic change in the oral health status of the U.S. population in the
past fifty years is demonstrated in a definitive epidemiological study reported
by the National Institute of Dental Research (NIDR) in 1986. It must be
contrasted with the fact that in the early 1940’s, ten percent of potential recruits
for the army in World War II were rejected because they could not meet the
requirement that they must have at least six opposing natural teeth in occlu-
sion. The NIDR study, entitled, ““The National Survey of Oral Health in U.S.
Employed Adults and Seniors: 1985-1986,” reported on the dental status of
21,000 adults ranging in age from 18 to 103 years—this sample being statis-
tically significant for 105 million people. It revealed an almost complete ab-
sence of edentulism (the loss of all teeth) in persons less than 40 years of age.
Additional findings were that only 4% of working adults under 65 years of
age were completely edentulous, and half of them had lost at most a single
tooth. This is indeed a tangible reflection of the benefits of dental research
in the prevention of dental disease and clinical practice in the past half century.

The survey, however, did not paint the same optimistic picture for many
older Americans who grew up before World War II and did not benefit from
programs of prevention. The 1985 study compared 16,000 working adults
under 65 years of age with 5,000 older patients in senior citizen centers and
other ambulatory elder care agencies. In the latter group, 42% are still ed-
entulous, a disturbing fact despite a reduction of 10% from previous studies
conducted in the early 1970’s. And although both groups demonstrate coronal
decay, i.e., occlusal or interproximal lesions, the older age group has three
times a higher incidence of cervical caries—decay occurring at the junction
of the crown and the gingiva (also called root surface caries) than the younger
group. Both groups showed a significant prevalance of periodontal disease—

172 SAUL KAMEN AND PAUL KORNFELD

inflammatory processes of the gingiva and supporting structures of the teeth,
with increasing severity in the older age group. Parenthetically, another NIDR
survey of children’s oral health in 1986-1987 brought the good news of a
dramatic decline in the caries rate in school children aged 5-17, a further sign
that Americans, in general, are experiencing better dental health than did
their predecessors in the first half of this century.’

Much of the progress reflected in these epidemiological statistics is a result
_of the changing focus in dental science from a narrow emphasis on the me-
chanical restoration of carious lesions and treatment of gum disease to a broad
understanding of the interrelationship between oral disease and the total health
status of the patient. While this is true for individuals of any age, it is partic-
ularly applicable to the elderly, who are more vulnerable to pathological effects
of aging on the hard and soft tissues of the mouth, as well as normal age-
related changes which result in regressive physiological decrements in function.
Research in aging in the past 40 years, furthermore has given us a new un-
derstanding of the impact of immunity and endocrine gland function on the
oral tissues, and the reciprocal relationship between oral health and systemic
disorders common in the elderly.

Salivary Function

Salivary function is too often ignored or underestimated as a factor in health
and comfort particularly in older people. On a cellular and tissue level it
involves the parotid, submandibular, and sublingual glands, as well as acinar
glands in the palatal and pharyngeal mucosa. Whole saliva and its enzymes
play essential roles in the following respects:

—a necessary lubricant for the mastication and swallowing of food
—a diluent for the taste sensations of sweet, bitter, salt, and sour

—comfort or discomfort, depending on the degree of dysfunction

—a natural detergent mechanism for the prevention of decay

—in remineralization of incipient carious lesions

—a liquid film essential for the retention of dentures

Xerostomia, dry mouth, impacts on all of these functions in varying degrees,
and results from four possible etiological factors: 1) anticholinergic medica-
tions, 2) chemotherapy, 3) radiation, 4) benign and malignant obstructions of
the salivary ducts. It has been estimated that 80-90% of drugs prescribed for
the elderly may have a xerostomic side effect.

We have recently refined our knowledge about the effects of aging on
salivary flow based on the results of a study of this oral function in the Bal-
timore VA Longitudinal Aging Investigation.* This study concluded that in a
large group of healthy, aging male veterans there was no significant reduction
in the quantity of salivary production. The universal application of this con-
clusion, however, is difficult to accept, for two reasons: 1) the study excluded
females, who are certainly more numerous and typical of the geriatric pop-
ulation, and 2) 81% of those over 65 years of age have at least one major

DENTAL DEVELOPMENTS WHICH AFFECT THE GERIATRIC PATIENT 173

chronic disorder, and a huge number of drugs consumed by the elderly have
known xerostomic (i.e., mouth-drying) side effects. In our experience, the
loss of intracellular water previously alluded to is implemented by the xeros-
tomic side effects to produce varying degrees of diminution of saliva and
mucous.”

The diagnosis of xerostomia is essentially made on a clinical base. There
are some sophisticated laboratory tests which can be utilized to confirm the
diagnosis, but these are usually employed to verify suspicion of an underlying
systemic disorder, such as Sjégren disease. When the physician or dentist
establishes a positive diagnosis, however, it is incumbent on the professional
to alert the patient and prescribe appropriate therapy, as follows:

—increase intake of water in the diet, e.g. soups

—change drugs to those with least anticholinergic side effects

—counsel patient in oral hygiene procedures, including fluoride dentifrices,
fluoridated mouth washes, and topical fluoride gels. This is best accom-
plished by the dental professional

—artificial saliva substitutes. These are now commercially manufactured
and available as over-the-counter items

—in extreme cases pilocarpine has been shown to oppose anticholinergic
drug effects and may be prescribed in slow-release capsule form. This
drug has possible adverse side effects when the patient is taking certain
drugs

—a 10 percent mixture of glycerin in distilled water, to be used as a mouth
wash.

Salivary gland dysfunction can result in significant morbidity and should not
be casually dismissed as a normal age-caused event. It should be carefully
evaluated and vigorously treated by the physician and/or the dentist.

Burning-mouth syndrome is a pathologic entity well recognized by oral
pathologists and frequently defies treatment. It occurs most commonly in post-
menopausal females and is considered to have a strong psychogenic component
in addition to causing glossodynia and glossopyrexia. Other etiologic factors
that have been implicated include estrogen imbalance, xerostomia, iron de-
ficiency, and malnutrition. The chief complaint is pain, either of the tongue
or in a more generalized pattern. The differential diagnosis should rule out
vitamin deficiency, (particularly B,,), iron deficiency anemia, pernicious ane-
mia, SjOgren syndrome, Mikulicz disease, and Plummer-Vinson syndrome.
Depression can also be a contributory factor, with the mouth as a focus of
somatization of a depressed mental affect.

Treatment consists first in the elimination of frank pathologic factors such
as concomitant lichen planus or candidiasis. Palliative agents include the use
of an artifiical saliva, now available as an over-the-counter oral rinse; a mouth-
wash consisting of equal parts of elixir of Benadryl® with Kaopectate®, with
instructions to expectorate after swishing over the tissues for one minute every

174 SAUL KAMEN AND PAUL KORNFELD

four hours and, for recalcitrant cases, 2% viscous xylocaine applied topically
every four hours.

The Impact of Oral Health on the Management of Geriatric Patients

The past fifty years have taught us that the impact of oral health on the
clinical management of geriatric patients can seriously compromise progress
and alter prognosis. Thus, poor masticatory function may thwart efforts to
provide nutritional support for the victim of a stroke, while noncompliance
with recommendations for antibiotic prophylaxis of the cardiac patient has
been identified as the chief etiologic factor in subacute bacterial endocarditis
following dental intervention. Because the vast majority of geriatric patients
have at least one major chronic disorder, the medical-dental interactions in
their care by both physicians and dentists demand scrupulous attention to the
effects of aging on oral function. As ever-increasing numbers of elderly are
integrated into dental practice, the physician will be called on more frequently
for advice on such diverse aspects of care as the drug profile of the patient
and possible contraindications for certain dental procedures; the use of sed-
ative agents to minimize stress or manage the patients with depression or
dementia, and management of the patient with iatrogenic oral manifestations.

Lessons from the research in the past two decades into dental diseases in
the elderly demonstrate many common denominators between medical and
oral conditions. The major medical-dental interactions in the compromised
older patient are described in Table I, as follows:

Table 1. Medical-Dental Interactions in the Elderly

Medical

Conditions Symptoms Dental Aspects Medical-Dental Interactions

Cardiovascular
disorders

Dyspnea; cyanosis; edema of Minimize apprehension and Consult with doctor regarding

Hypertension

extremities; tachycardia; bra-
dycardia; fatigue; nausea;
vomiting; anxiety; syncope;
thromboses.

Malignant: seizures; retinal

hemorrhages; papilledema;
proteinuria and renal failure.

Essential: Tachycardia; in-

creased cardiac output; head-
ache; sweating; nausea; anxi-
ety; glycosuria; left

ventricular failure; atheroma.

stress; avoid postural hypo-
tension; short appointments
preferable; defer elective
treatment for 6 months fol-
lowing acute myocardial in-
farction.

Patients are prone to stress and

anxiety; for diastolic pressure
over 110 do elective proce-
dures only; can tolerate ele-
vation of pressure better than
depression; avoid postural
hypotension; excessive post-
surgical bleeding possible.

antibiotic prophylaxis, sed-
atives, potentiated rauwol-
fia alkaloids, phenothia-
zines, and antihypertensive
drugs; epinephrine con-
traindicated in patients re-
ceiving monoamine oxidase
(MAO) inhibitors; long-
term digitalis therapy
makes patient prone to
nausea and vomiting; ob-
serve American Heart As-
sociation recommendations
for standard and special
regimens. *

For patients on reserpine
MAO inhibitors used a-
stimulators (e.g., Neo-Cob-
efrin) rather than epineph-
rine; barbiturates increase
CNS pressure; depression
may be secondary to neu-
roleptics; xerostomia a side
effect of drugs such as
methyldopa.

DENTAL DEVELOPMENTS WHICH AFFECT THE GERIATRIC PATIENT 175

Table 1.

(Continued )

Medical
Conditions

Symptoms

Dental Aspects

Medical-Dental Interactions

Cerebrovascular

accident
(CVA)

Diabetes
mellitus

Parkinsonism

Osteoporosis

Paget’s disease

SjOgren’s
syndrome

Carotid (anterior circulation):
contralateral weakness, dys-
phasia, apraxia, and confu-
sion, with dominant hemi-
sphere involvement; transient
ipsilateral monocular blind-
ness; homonymous visual
field defects; ipsilateral
throbbing headache.

Vertebral-basilar (posterior cir-
culation): dysarthria and dys-
phagia; vertigo, tinnitus, and
deafness; unilateral or bilat-
eral sensory-motor defects;
general imbalance with uni-
lateral limb ataxia; visual
field defects.

Glycosuria, polyuria, polydip-
sia; retinopathy; peripheral
vascular changes; periodontal
disease; ketosis and hyper-
glycemia (“‘brittle” diabetic).

Involuntary tremors; progres-
sive rigidity of extremities;
“cog-wheel” effect; masklike
facies; dysphasia, ptyalism.

Loss of 40% of mineral content
of bone; loss of bony matrix,
thin cortex, and large medul-
lary canals in x-rays.

Acromegaly: ‘‘woolly” appear-
ance of bone in skull x-rays;
high serum alkaline phospha-
tase.

Keratoconjunctivitis sicca; par-
otitis; buccopharyngolaryngi-
tis sicca; arthritis; xerosto-
mia.

Circumoral and neuromuscular
imbalance; dysphasia;
aphasia; adverse effect on
dentures; drooling; flexion of
the neck causes management
problems; hemiparesis leads
to poor oral hygiene.

Periodontal disease; lowered re-
sistance to infection; delayed
healing; prone to stress;
prone to irritations (as with
dentures); schedule patient in
AM following usual insulin
dose for routine care.

Bruxism; tongue thrust drool-
ing; slurred speech; problems
in deglutition and swallowing;
stress increases symptoms.

Loss of alveolar bone and loss
of teeth have been suggested.

Progressive enlargement of
maxilla and mandible; “‘flar-
ing” of teeth; dentures be-
come unstable.

Xerostomia; glosspyrexia
(“burning mouth” syn-
drome); increased incidence
of cervical caries; dysgeusia.

*Recommendations of the American Heart Association, Circulation, July, 1984.
From: Kamen, S: Current concepts in geriatric dentistry. In (Levine et al, eds. Current Treatment in Dental Practice.
W. B. Saunder Co. 1986), p. 394.

Inplantology in Geriatric Dentistry

Anticoagulant therapy in-
creases clotting time, af-
fecting oral surgery; pa-
tients are prone to stress;
monitor epinephrine in lo-
cal anesthetics; Demerol
(meperidine) increases in-
tracranial pressure; moni-
tor PT and PTT prior to
invasive dental procedures
if patient is on anticoagu-
lants.

Consult with dentist regard-
ing dose and type of insu-
lin; corticosteroids can
cause hyperglycemia; sug-
gest antibiotic prophylaxis
prior to oral surgery for
“brittle” diabetic.

Use of epinephrine in anes-
thetic agents may increase
stress; extrapyramidal reac-
tions to L-dopa lead to oro-
facial dyskinesia; atropine
causes increases in L-dopa
effect.

Potential benefits of fluoride
supplementation.

Patients often require psy-
chotherapy. in additon to
palliative treatment; if on
steroids will be more prone
to stress, periodontal dis-
ease, and delayed healing.

A major advance in the management of the atrophic mandible, a crippling
problem in the prosthetic rehabilitation of elderly patients, is the new tech-
nology of ridge augmentation inspired by developments in orthopedic surgery
in the past 20 years. Three methods have now been employed by oral surgeons
with varying degrees of success. The introduction of titanium subperiosteal
implants since the mid 1960’s was a great stride forward in meeting the chal-
lenge of the severely resorbed dental arch, but may be contraindicated in

176 SAUL KAMEN AND PAUL KORNFELD

patients with systemic disorders such as diabetes. A more recent innovation
is the use of hydroxylapatite, an artificial bony material which has been em-
ployed along with hip grafts to reconstruct the alveolar ridge. Most promising
however, is the result of a splendid collaboration between the Swedish or-
thopedist, Per-Ingvar Brannemark, and American oral surgeons in the de-
velopment of the osseo-integrated implant, a precisely engineered titanium
implant which is biocompatible with bone and has an excellent track record
of success for the past 20 years. This striking development is a testimonial to
a scientific accomplishment which is particularly beneficial to edentulous ger-
iatric patients.

One of the more recent developments in implantology particularly appro-
priate for relatively healthy elderly patients is the use of surgical alloys (ti-
tanium, titanium alloy and cobalt-chrome molybdenum alloy) coated with a
biocompatible hydroxylapatite (HA). This material has a strong degree of
adherence to the underlying metal over an extended period of time, and has
attractive properties for applications in prosthodontic and orthopedic den-
tistry. This has been demonstrated in both animals and humans to be a viable
materials system for biological fixation because the osteophyilic type surface
of the HA increases the rate of bony adaptation.°’ In humans, a three year
clinical follow-up of four hundred fifty seven HA coated implants placed in
130 patients for prosthetic restorations noted that osseous biointegration was
achieved in as early as eight weeks.*®

One of the promising developments in periodontal and prosthodontic re-
habilitation is the utilization of a new polymer called HTR (hard tissue
replacement) as a synthetic bone substitute. This material is a nonresorb-
able, microporous, synthetic bone grafting agent that combines a poly-
methylmethylacrylate core with a polyhydroxylethylmethacralate (poly-
hema) coating which produces a biocompatible composite without the ad-
dition of catalyst inducers or impurities. This HTR polymer is premixed
and packaged in a sterile unit ready to use.? The material has been
employed in periodontal surgery where it has proven successful in the
repair of osseous deficits and intrabony pockets, and in alveolar ridge re-
construction, in which it acts as a vehicle for a bone-inductive substance
that remodels the mandible by converting connective tissue to alveolar
bone se

Kamen has conducted histological in vitro studies which demonstrate the
kinetics and morphology of the attachment of human gingival fibroblasts to
HTR® polymer. Although he cautions against the interpolation of in vitro
findings to in vivo situations, he is quite optimistic that this material augments
connective tissue repair, promotes wound healing, and will be a valuable
addition to the armamentarium of periodontal and prosthodontic rehabilita-
tion.”

A major consideration in implantology, which has not as yet been adequately
addressed, is the feasibility of the use of these new materials in geriatric
patients with various disorders, and particularly the interface of artificial bone
substitutes with osseous tissue in patients with osteoporosis.

DENTAL DEVELOPMENTS WHICH AFFECT THE GERIATRIC PATIENT 177

Oral Rehabilitation

In the early 1970’s the use of polymethylmethylacrylate resins as an esthetic
material for the repair of carious lesions was dramatically enhanced by the
technique of acid etching of the enamel surface.'’ The teeth are cleaned with
flour of pumice, isolated with a rubber dam, and an unbuffered solution of
phosphoric acid is applied for one (1) minute. This procedure results in mi-
croporosities of the enamel surface which mechanically interlock with bis-
GMA composite resin tags. Retention of the restorative material is aided by
the use of a bonding agent—an unfilled resin of low viscosity which readily
penetrates the microscopic irregularities, and then chemically bonds with a
filled resin. An ultraviolet photocure unit (white light) is utilized to polymerize
the resin restorative materials, and offers the clinician adequate working time
for placement, contouring and polishing. Because people are living to an older
age and are retaining their natural teeth these esthetic materials are constantly
being perfected and are in ever increasing demand. Thus, a new resin called
a glass ionomer cement which bonds to dentin has been found to be more
appropriate for the common carious lesion affecting adult teeth-root surface
decay. Both erosion and carious defects are now restored with the glass io-
nomer cements. The advantages of these materials are their esthetic and
cosmetic appearance, superior retention, slow release of fluorides and pro-
tection against marginal leakage. Their durability remains to be tested in the
years ahead."

The therapeutic effect of fluorides on root and coronal caries in older adults
has been well documented in several studies. Banting and Stamm have com-
pared root caries prevalence in adults in fluoridated and nonfluoridated com-
munities in Canada, and confirm a dramatic reduction in carious lesions in
the fluoride protected subjects.’ Of even greater significance in geriatric oral
rehabilitation is the report of Nyvad and Fyerskov that incipient and active
root surface cavities can be arrested and rendered inactive with rigorous oral
hygiene utilizing fluoridated dentifrices and mouth washes.'*'’ The author
routinely recommends to his geriatric patients the daily application of a stan-
nous fluoride gel before retiring. In view of the technical difficulties in re-
pairing root surface caries the employment of preventive measures such as
these are certainly merited.

The beneficial effects of a sodium fluoride dentifrice was demonstrated in
a carefully controlled study of 810 subjects 54 years of age and older who
were living in 43 communities in Iowa without a fluoridated water supply.
The test dentifrice contained 1,100 ppm F as sodium fluoride, compared with
<1 ppm F in the control group. After one year there was a 41% reduction in
coronal caries and a 67% decrease in root surface caries.'®

The prime etiological factor in periodontal disease is the deposition of
plaque, an invisible film consisting of microorganism in a substrate of mucous
and carbohydrates, which results in a concatenation of events including gin-
givitis, gingival recession, pocket formation, 1.e., loss of gingival attachment,
and the loss of the supporting bony matrix of the tooth. Basic periodontal

178 SAUL KAMEN AND PAUL KORNFELD

therapy therefore, requires the elimination of infection and inflammation by
controlling caries and removing plaque on the coronal and root surfaces of
the teeth by scaling and root planing. Residual bony defects are then surgically
treated with the synthetic bone substitute.

Treatment of the Terminal Dentition

It has been estimated that 42 percent of all individuals over 65 years of age
in the U.S. are completely edentulous, 1.e., have lost all of their natural teeth.
Previously it was common practice to remove any remaining roots and tooth
fragments prior to fabrication of dentures. This often resulted in additional
atrophy and resorption of the alveolar ridges. It is now generally accepted
that the retention of these remnants preserves the integrity of the maxilla and
mandible, and aids in the function and stability of prosthetic appliances.” The
methods employed to retain these roots, and sometimes to bury them beneath
the alveolar mucosa, are highly technical and beyond the scope of this review,
but to a great extent have revolutionized prosthodontic rehabilitation, espe-
cially for the geriatric patient. The appliances constructed over these modified
roots are called overdentures, and have enormous advantages in maximizing
comfort and function.”” A sophisticated array of attachments, bars, and other
devices attached to the roots further enhance the stability of the overdenture,
and are increasingly being utilized by dental geriatricians. It is incumbent on
the patient to practice meticulous hygiene of these appliances and the physician
should reinforce the dentist’s instructions towards this goal. Desjardins has
stated that ‘“‘successful rehabilitation must also incorporate preventive and
maintenance care. To achieve a rehabilitation that cannot be maintained, and
which encourages development of additional disease, defies the goals and
objectives of the dental professions.”!

Conclusions

The experience of the past several decades posits that poor oral health can
have a domino effect on the total health status of the elderly patient, dimin-
ishing the quality of life and leading to metabolic imbalance, malnutrition,
anorexia, and cachexia. Thus, dental disease per se can significantly influence
the multiplicity of chronic illnesses that characterize the elderly, while at the
same time the medical disorders complicate the dental treatment. Although
today’s elderly are healthier than in the past, the very fact that they are living
well into their 80’s and 90’s means that they become more vulnerable to a
variety of chronic illnesses, including cardiovascular conditions, neurologic
disorders, metabolic deficiencies, Alzheimer disease, and other types of men-
tal impairment. These elderly patients are at high risk for dental intervention,
and the gerodontist will frequently consult the physician to discuss clinical
management.

DENTAL DEVELOPMENTS WHICH AFFECT THE GERIATRIC PATIENT 179

Acknowledgment

The authors wish to acknowledge, with appreciation, the technical assistance

of Kathryn Sisley in the preparation of this manuscript.

References

. Levy, R. I. and Feinlieb, M. 1980. Risk Factors for coronary artery disease and their management in

heart disease, in Textbook of Cardiovascular Medicine (E. Braunwald, ed.), W. B. Sauders Co.,
Philadelphia, pp. 1246-1278.

. Duthie, E. H. and Keelan, M. H. Geriatric Cardiology and Blood Pressure in Contemporary Geriatric

Medicine (S. Gambert, ed.) Plenum Medical Publishers, New York, 1986, pp. 1, 2.

. NIDR: 40 years of progress. Jour. Amer. Dent. Assn., vol. 116, June 1988.
. Baum, B. J. and Bodner, L. 1983. Aging and oral motor function: Evidence for altered function

among older persons. J. Dent. Res. 62:2-16.

. Kamen, S. 1983, Oral care of the geriatric patient, in: Care of the Geriatric Patient, 6th ed. (F. V.

Steinberg, ed.), C. V. Mosby Company, St. Louis, pp. 388-405.

. Kay, J. F.; Jarcho, M.; Logan, G.; and Lin, S. T. The structure and properties of HA coatings on

metal. Trans. 12th Ann. Mtg. Soc. Biomaterials, 13, 1986.

. Cook, S. D.; Kay, J. F.; Thomas, K. A.; Anderson, R. C.; Hardin, A. F.; Reynolds, M. C.; and

Jarcho, M. Variables affecting the interface strength of HA coated implant surfaces. Trans. 12th Ann.
Mtg. Soc. Biomaterials, 14, 1986.

. Kent, J. M.; Block, M. S.; and Misek, D. S. Three year clinical results with HA coated dental implants.

Proc. World Biomaterials Congress, Kyoto, Japan, April, 1988.

. Ashman, A. The introduction and history of HTR® polymer. Compendium, Supplement No. 10, 1988,

S- 318, 319.

. Murray, V. K. Clinical applications of HTR® polymer in periodontal surgery. Compendium, Supple-
p Pp P Pp pp

ment No. 10, S. 347.

. Boyne, P. J. Bone induction and the use of HTR® polymer as a vehicle for osseous inductor materials.

Compendium, Supplement No. 10, 1988, S. 341.

. Kamen, P. Attachment of oral fibroblasts to HTR® polymer. Compendium, Supplement No. 10, 1988,

S. 350—352.

. Jorgensen, K. D. and Shimokobe, H. Adaptation of resinous restorative materials to acid etched

enamel surfaces. Scand. J. Dent. Res. 83-31, 1975.

. Wenner, K. K.; Fairhurst, C. W.; Morris, C. F.; Hawkins, I. K.; and Ringle, R. D. Microleakage of

root restorations, J.A.D.A., Vol. 117, December 1988, p. 825.

. Stamm, J. V. and Banting, D. W. Comparison of root caries prevalence in adults with life long residence

in fluoridated and nonfluoridated communities. J. Dent. Research 59:405, abstract no. 552, 1980.

. Nyvad, R. and Fyjerskov, O. Active root surface caries converted into inactive caries as a response

to oral hygiene. Scand. J. Dent. Res. 94:281—284, 1986.

. Fyerskov, O. and Nyvad, R. Geriatric oral rehabilitation, In: L6e, H. and Pedersen, P. H. Geriatric

Dentistry, C. V. Mosby, St. Louis, 1988.

. Jensen, M.E. and Kohout, F. The effect of a fluoridated dentifrice on root and coronal caries in an

older adult population. J.A.D.A., Vol. 117, December 1988, p. 829, 830.

. Crum, R. J. Oral perception and proprioception—a review of the literature and its significance to

prosthodontics. J. Prosth. Dent. 1972; 28:215-230.

. Brower, A. A. and Morrow, R. M. Overdentures, 2nd ed., C. V. Mosby Co., St. Louis, 1980.
. Desjardins, R. P. Oral rehabilitation. (In: Levine, et al, eds. Current Treatment in Dental Practice.

W. B. Saunders, Co. Philadelphia, 1986) p. 57.

Journal of the Washington Academy of Sciences,
Volume 79, Number 4, Pages 180-191, December 1989

Some Social, Scientific and
Technologic Changes in Medicine
from 1935 to the Present

Kingsley M. Stevens

Geriatrics Section, Medical Service, Veterans Administration Medical
Center, Northport, N.Y. 11768

and

Department of Medicine, State University of New York
at Stony Brook

ABSTRACT

Changes in the prevention and treatment since 1935 of the major causes of death and
disability in older people are discussed. Today, these major diseases are not infectious
diseases but chronic degenerative diseases and cancer. For individual patients, there have
been major improvements in several areas. Yet for society as a whole, the prevalence of
these diseases has greatly increased.

In the preceding article, we discussed antibiotics as the single most im-
portant medical advance since 1935. In this article, we will address some of
the many other changes which have occurred. For non-medical readers, a few
definitions are required. The “mortality rate” refers to the number of deaths
due to a certain cause per 100,000 population per year. When comparisons
are made where the demography may vary, it is necessary to correct for age.
For example, both heart disease and cancer are strongly correlated with age.
In 1935, the average age of the U.S. population was considerably younger
than in 1985. Uncorrected mortality rates for these diseases would therefore
show marked increases in 1985 compared with 1935 solely on the basis of the
demographic change. ‘‘Morbidity” refers to illness from a disease or other
cause. “Incidence”? means the number of cases recorded for the first time
during a given year while ‘‘prevalence”’ refers to the number of people ill with
a given disease during a year span. If a person developed chronic heart disease
in 1965 and died from it in 1985, he would be counted in the “incidence”’
statistics for 1965, in the ‘‘prevalence”’ statistics in each of the 20 years. He
would be recorded also in the morbidity statistics for each year and in the
mortality statistics for 1985.

180

CHANGES IN MEDICINE FROM 1935 TO THE PRESENT 181

The diseases discussed represent the major causes of death and disability
in 1985. Hence, many well-known diseases are not discussed or even men-
tioned; this does not imply that important new treatment methods have not
emerged for them over the half-century.

Tobacco Usage

From a medical viewpoint, the most important social change since 1935 has
been the shift in public support for smoking cigarettes. In America, this habit
became prominent among the military during World War I. It spread rapidly
among men and more slowly among women and by the early 1950s over 60%
of men were smokers. But in 1939, Oschner, an American thoracic surgeon,
reported that most of the patients with lung cancer which he saw were heavy
smokers of cigarettes. By 1964, enough data had accumulated on the multiple
adverse health effects of smoking for the Surgeon General of the Public Health
Service to issue his now famous first report on ““Smoking and Health.” Smok-
ing is far and away the most important preventable cause of serious disease
in the United States. In 1985, the overall mortality rate was 874 per 100,000
population. Of this total, 130 are estimated to be due to tobacco use. The
range by states is from 176 in the prominent tobacco state of Kentucky to a
low of 45 in the state of Utah with its large population of non-smoking Mor-
mans. Of the many effects of smoking,the most prominent are lung damage.
Almost every patient developing lung cancer receives extensive treatment with
all the types of treatment which offer any hope—surgery, radiation, chemo-
therapy with multiple drugs. Despite such intensive, high technology treat-
ments, five years after diagnosis 87% of lung cancer patients are dead. Lung
cancer usually develops in patients with chronic obstructive lung disease
(COPD), which includes emphysema and is almost totally due to smoking.
The morbidity for this disease is extreme and goes on for years. Development
of more effective broncho dilating drugs and antibiotics and the extensive
home use of oxygen as compressed oxygen or as oxygen concentrators of room
air has ameliorated the symptoms of COPD without reversing the pathology.
The only bright light in this bleak picture is that since about 1955 there has
been a gradual decrease in cigarette use which from 1974 through 1985 has
been an almost linear decline. The 1985 smoking rates for men was 33.5%
and for women 27.6%. Soon women will outnumber men as smokers. People
aged 65 in 1985 would have been age 35 in 1955 so their smoking patterns
were well-established long before the dangers of tobacco to health became
defined. However, many of the effects are reversible and a great many of this
age cohort and older have stopped. This change in smoking patterns must
rank second to antibiotic development as a major determinant of the health
of the older patient.

Heart Disease

Diseases of the heart lead the list of causes of death producing over a third
of all deaths in 1985. In 1935, rheumatic heart disease and syphilitic heart
disease were frequent causes of death but they have been vanquished by

182 KINGSLEY M. STEVENS

penicillin and today coronary artery disease is the dominant cause with ath-
erosclerosis being the underlying pathology. The past 50 years have seen
advances in the treatment or prevention of heart disease from multiple ap-
proaches: Prevention, medical treatments, surgical treatments, even after-
death treatments with cardiac resuscitation! Prevention has focused on three
approaches: Decrease in smoking, decrease in cholesterol and fat intake and
an increase in exercise. In our frequently lethargic society, it is very encour-
aging that every one of these has shown marked improvement at the society
level, even though many persons have not changed their patterns at all. We
now have more effective and less toxic drugs to reduce cholesterol and/or
lipid levels if dietary changes are insufficient.

Coronary Artery Disease

Atherosclerosis causes mortality and morbidity through myocardial infarc-
tions, cardiac arrhythmias, congestive heart failure and angina pectoris. In
the preceding paragraph we noted preventive measures relating to smoking,
exercise and types of foods. Another preventive measure is the use of aspirin
in low dose to prevent repeated heart attacks by decreasing platelet agglutin-
ation. Diabetes is another risk factor for atherosclerosis and better diabetic
control has helped.

Surgical treatment of heart disease (open heart surgery) has had superb
media coverage and coronary by-pass grafts using vein grafts from the patient
(CABG) has had great success in relieving symptoms, especially angina, and
lesser success in prolonging life. While heart transplants are no longer a rare
surgical procedure, there are many complications and they have little impact
on the overall picture. Mechanical hearts are entirely experimental and will
remain so for a long time.

The drama of cardiac surgery has tended to obscure the amazing advances
in the drug treatments of heart disease over the half-century. In 1935, the
powdered leaf of the foxglove, which contained digitalis, was still the most
commonly used medication. The purified glycosides, digitoxin and the shorter
acting digoxin, were purified in 1925 and 1930 respectively but were not widely
used for about 20 years. Digitalis had been introduced in the treatment of
congestive heart failure (dropsy) by William Withering in 1785. When I was
in medical school in the mid-1940s, I was taught that digitalis, unlike most
drugs, had an “all or none” effect. This meant that blood levels just below
toxic were required and indicated use of the long acting digitoxin to keep the
level more constant. There was no assay method for serum digitoxin then
available, nor was hemodialysis available. As a result, digitoxin toxicity was
rather frequent, especially in older people. When radioisotopes became avail-
able, the development of radioimmunoassay methods became possible. This
was particularly valuable for measuring substances such as digitoxin which
have very low serum concentrations. Using this technic, it was soon demon-
strated that digitalis preparations behaved just like other drugs; they did not
have an “all or none” pattern but the usual dose-response effect. This led
quickly to dropping digitoxin and using digoxin, the shorter-acting and there-

CHANGES IN MEDICINE FROM 1935 TO THE PRESENT 183

fore safer drug. This story illustrates what the results can be when well-
established principles appear inconsistent with clinical experience and the
clinical results are used to justify the practice. In the mid-1940s, the principle
in pharmacology of a dose-response curve was well-established. Both the
glycosides were then available, but the more toxic was deliberately selected
based on inadequately controlled clinical studies. After 200 years, the digitalis
glycosides remain the best cardiotonic drugs but the safety of their use has
greatly increased. Digitalis is also less needed than in 1935 because of new
drugs with different actions which are also needed in the treatment of conges-
tive heart failure (CHF). The most important are the oral diuretics.

In 1935, there were no good diuretics for chronic use; the mercurial diuretics
were effective but required injection and were often toxic if renal insufficiency
was present. In the early 1950s, when penicillin was still expensive, one of
the pharmaceutical companies set out to find a drug which would decrease
the renal tubular secretion of penicillin and therefore maintain higher serum
levels. A chemical which did this effectively in man was found (probenecid),
but very shortly the price of penicillin fell steeply, making the product of less
value. However, probenecid also increased uric acid loss so was useful in the
treatment of gout and the company decided to continue its renal program.
One of the chemicals synthesized for the program was found to have marked
diuretic and hypotensive effects. This was chlorothiazide, the first of the ef-
fective oral diuretics and still today, as hydrochlorothiazide, a very useful drug
in treating both congestive heart failure and hypertension. However, the type
of diuretic most often used today in treating CHF is a “loop” diuretic, such
as furosemide. These drugs very effectively reduce the reabsorption of sodium
and chloride in the renal loop of Henle.

Angina Pectoris

This is the most frequent cause of chronic disability in patients with coronary
artery disease. Since pain is the symptom which most often causes people to
visit doctors, angina causes many Office visits. Yet in 1935, the only really
useful drug was sublingual nitroglycerin. Synthesized in 1846, its medical use
began over a century ago. The very major effect of nitroglycerin on the history
of science began in 1862 when Alfred Nobel patented dynamite, which in-
corporates nitroglycerin with diatomaceous earth and a small amount of so-
dium carbonate. In a very real sense, nitroglycerin was the founder of the
Nobel Prizes! Although sublingual nitroglycerin is very effective in the pre-
vention and treatment of acute anginal attacks, it is very short-acting. Much
effort has been made to prepare oral nitrates which could be used on a con-
tinuing basis to prevent anginal attacks. Several preparations have been used
extensively but have not been highly effective. Today we use nitrates delivered
through the skin rather than orally. However, we also have other effective
anti-anginal drugs. The B-adrenergic blocking agent propranolol was the first
of these. This drug has almost the reverse effect of digitalis in that it decreases
the force of cardiac contraction. The cause of pain in coronary artery disease
is oxygen lack, produced when the ratio of oxygen demand to oxygen supply

184 KINGSLEY M. STEVENS

is too low. Propranolol, by decreasing myocardial contraction, decreases ox-
ygen demand and hence decreases anginal attacks. The effect lasts for several
hours and newer preparations are effective for even longer periods. Just when
the “beta blockers” were well established, a whole new group of cardiac
regulating drugs appeared: The calcium channel blocking agents. The bio-
chemistry of muscle contraction requires that the calcium concentration inside
the muscle fiber be increased. Calcium ions enter the fiber through tiny chan-
nels. These new drugs, e.g., nifedipine, diltiazem, verapamil, inhibit this
Ca** increase, thereby decreasing contractility with decreased oxygen de-
mand. Using combinations of old and new cardiac drugs, many patients with
coronary artery disease can be treated as effectively medically as surgically.
There is now enough data to separate fairly well those patients who will do
well on a medical regime from those who will benefit more from a coronary
artery by-pass procedure.

Hypertension

Although hypertension is found in all ages, it is most frequent over age 65
with about one third of all people in the U.S. over 65 having some degree of
hypertension. The most important sequellae are congestive heart failure and
strokes, although many cases of kidney failure are also due to long-standing
hypertension. In 1935, there was no satisfactory drug treatment. It was not
until almost 25 years later that the effective combination of a thiazide diuretic
coupled with a specific anti-hypertensive drug such as methyldopa became
available. Today there are almost too many antihypertensive medications! The
reason there are so many is two-fold. Some patients have very resistant hy-
pertension so are on multiple drugs and even then may not be controlled. The
“ideal” drug for hypertension is one of the hardest assignments possible for
the drug industry. None of the medications “‘cure” hypertension so long-term
treatment is the norm, even though remissions occur. But high blood pressure
itself causes symptoms in only a small fraction of all people with hypertension.
Therefore, for most Americans under treatment for hypertension, the “‘symp-
toms” of their disease are actually the side effects of the antihypertensive
drugs. This makes long-term compliance extremely difficult. So the quest
continues for an oral drug, taken once or twice daily, that will have almost
no side effects. Despite all these problems, the treatment has vastly improved
since 1935 and is being used by millions of patients. It has decreased mortality
rates from strokes and congestive heart failure.

The most specific, and therefore one of the least toxic, antihypertensive
agents are the angiotensin-converting enzyme (ACE) inhibitors. The back-
ground for these goes back over half a century. In 1934, Goldblatt showed
that chronic renal ischemia would produce persistent hypertension. He felt
that both experimental and clinical hypertension were produced by increased
secretion of a renal enzyme, renin. He tried to inhibit renin but could not
develop a suitable method. While the ‘‘Goldblatt kidney” remained a standard
method of producing experimental hypertension, anti-renin studies were not
pursued. Many years passed before the renin-angiotensin-aldosterone system
was worked out. Briefly stated, renin acts on a serum globulin to produce a

CHANGES IN MEDICINE FROM 1935 TO THE PRESENT 185

decapeptide, angiotensin I, which is not active. A serum enzyme converts the
decapeptide to an octapeptide, angiotensin II, which is a potent vasoconstrictor
thereby raising blood pressure. Angiotensin II also stimulates the adrenal
gland to secrete the mineral-corticoid hormone aldosterone which increases
blood volume and enhances the hypertensive state. One way to block the
effects of increased renin would be by blocking the conversion of angiotensin
I to angiotensin II. Some snake venoms contain toxic peptides which may
produce shock. In 1965, Ferreira isolated a mixture of peptides from the venom
of a Brazilian snake, and in 1967, Ng and Vane found that one of these peptides
blocked conversion of angiotensin I to angiotensin II. By 1971, Ondetti et al
had synthesized the nonapeptide. Laragh and his colleagues demonstrated
that the peptide did, indeed, decrease blood pressure in patients with elevated
renin levels. However, it required intravenous injection so had minimal market
potential. Hence Cushman and Ondetti set about developing a peptide-like
product that would be an ACE inhibitor when taken orally. This they achieved
and captopril was patented in 1977. A decade later we have even more specific
ACE inhibitors. Furthermore, they are often effective even when renin levels
are low, which somewhat confuses the tidy theoretical development of these
important drugs.

Cardiovascular Disease Today

In the preceding pages we have presented the many ways in which we have
improved the prevention and treatment of cardiovascular diseases. In the
1950s, a longitudinal study of cardiovascular diseases was set up in Fra-
mingham, Mass. This is known as the Framingham Study and many people,
originally without any evidence of cardiovascular disease, have been followed
until death or for over 30 years. Over these 30 years, there has indeed been
a fall in the cardiovascular mortality rate of the study population as has also
occurred nationally. But there has been no decline in the incidence of car-
diovascular disease. Hence, we have not yet reached either true prevention
or cure with these many advances, but have made the diseases milder. If the
mortality rate has fallen but the incidence has not, it must follow that the
prevalence of cardiovascular disease has actually increased.

Cancer

Cancer was the second largest cause of death in both 1935 and 1985. How-
ever, instead of declining, the overall rate almost doubled. The most spec-
tacular change was for lung cancer in men, climbing from 7 in 1935 to 74 in
1985. In a reverse trend, stomach cancer fell from 38 to 9. In women, these
values were from 3 to 27 and 28 to 4 for lung and stomach respectively. In
men, cancer of the colon and rectum and of the prostate rose slightly between
1935 and 1945, then leveled off and have remained between 20 and 30 ever
since. Women showed the same initial rise in colon and rectal cancer as men
but this has fallen from a high of 27 in 1947 to 18 in 1985. Uterine cancer
(cervical and endometrial) has fallen from 30 in 1935 to 7 in 1985. Breast
cancer, the most frequent cause of cancer deaths in women from 1933 to 1988

186 KINGSLEY M. STEVENS

(when overtaken by lung cancer), has shown no meaningful change, being 27
in 1935 and 28 in 1985 with only minor variations during the half-century
between. Hence at the statistical level of mortality rates, the only good news
for the major types of carcinoma is for cancer of the stomach and uterus.
Results have been somewhat better for the leukemia/lymphoma malignancies,
especially for Hodgkins Disease where a significant percentage of true cures
have been achieved with aggressive radiation therapy and/or chemotherapy.

Five-year survival rates have shown modest improvement for the major
cancers. Data covering the 1960-1984 period show the percentage of cancer
patients surviving five years rising from 39 to 50% for all types of cancer (for
whites). Colon cancer rose from 43 to 53%, lung cancer from 8 to 13%, breast
cancer from 63 to 75%, prostate cancer from 50 to 73%. Since survival time
begins when the tumor was diagnosed, these figures measure improved di-
agnostic methods at least as much as improved treatment.

Huge amounts of resources have been put into cancer research and treat-
ment and we know much more about carcinogenesis at the cellular level than
in 1935. Yet we understand little about cancer in man and, overall, treatments
have made little progress. The development of genetic engineering has made
the production of such natural products as interferon possible but interferon
has had only limited success in cancer treatment. Demographic studies show
large differences in cancer incidence by country. For example, breast cancer
is almost six times as frequent in England and Wales as in Japan and prostate
cancer is five times as frequent in the U.S. as in Japan. Yet stomach cancer
is almost eight times as frequent in Japan as in the U.S. The causes of these
large differences have not been determined. Difficulties in identifying causes
is shown by the history of cigarette smoking as a cause of lung cancer. This
year marked the 25th anniversary of the first Surgeon General’s Report on
Smoking and Health in 1964. It should be appreciated that the first good
studies showing a correlation between lung cancer and cigarette smoking were
reported in 1939 by Muller in Germany and Ochsner and DeBakey in the
U.S., exactly 25 years before that first Surgeon General’s Report. For gas-
trointestinal cancer, the major focus today is on dietary differences in various
groups. Despite multiple theories, the major factors responsible for breast
cancer and prostate cancer remain undetermined. Even when a general etiol-
ogy has been established, the specific etiology can be extremely difficult to
identify. Cigarette smoking has been known to cause lung cancer for 50 years
and literally thousands of studies of the effects of ingredients of cigarette
smoke have been made. Yet today, there is no firm evidence identifying a
specific chemical compound as the major cause of lung cancer from cigarette
smoking. Hence, we may expect that the much less well defined ingredients
of “diet”? will be even more difficult to unravel.

Diabetes

Insulin was first used in 1922 and crystallized in 1926 so its use in diabetics
was well-established in 1935. The reported death rates for diabetes in 1935
and 1985 were not very different, but such rates cannot be accurate because

CHANGES IN MEDICINE FROM 1935 TO THE PRESENT 187

diabetes is a major risk factor for heart disease and is the chief cause of end
stage renal disease. Our supportive systems are so much better that the number
of deaths from ketoacidosis must be much lower. Despite this, diabetes in
1985 is a much more common disease than in 1935. Today the insulin is a true
human insulin produced either by a genetically engineered bacterium or by
chemical modification. Almost more amazing is how satisfactory pork and
beef insulins were over a sixty-year period. Since these are foreign proteins,
they did produce antibodies which at times required increases in insulin doses.
But only rarely did patients become totally resistant to insulin. Foreign proteins
can produce anaphylactic shock and severe kidney damage but both were rare
with these foreign insulins. The reason must lie in the small differences be-
tween human, beef and pork insulins. Insulin has a molecular weight of six
thousand and has A and B chains joined by disulfide linkages. Pork insulin
differs from beef insulin by two amino acids sequences while pork insulin
differs from human insulin by only one amino acid sequence, clearly dem-
onstrating that humans are more closely related to pigs than to cattle! Since
the difference between human and pork insulin is the C-terminal amino acid,
chemical replacement of the alanine with threonine produces a human insulin.
Alanine is an aliphatic amino acid with a single methyl side chain. In general,
antigenicity in proteins correlates with the complexity of the amino acid side
chains and aromatic radicals are much more antigenic than aliphatic radicals.
Hence, only if pork insulin had a C-terminal glycine instead of alanine could
it be less antigenic in man.

The antimicrobial era was introduced with the sulfonamides in 1935. Even
though true antibiotics became the dominant antimicrobial drugs, work on
finding better sulfonamides continued and lead to the sulfonylureas in 1957.
These drugs, e.g., tolbutamide and chlorpropamide, have no antibacterial
action but lower blood sugar and are effective orally. Recently 100-fold more
potent oral drugs have been introduced. These oral antidiabetic drugs have
been extremely useful in diabetic treatment, but have not replaced insulin for
severe diabetics. In fact, insulin today is given at more frequent intervals than
even a few years ago to better control fluctuations in blood glucose.

In 1935, monitoring of blood glucose at home was done by quantitative
measurements of urine glucose. This method revealed pooled blood glucose
levels over a previous time period but did not measure low levels at all since
the renal threshhold for glucose is in the range of 180 mg%. Today, urine
monitoring is little used with microamounts of blood from fingersticks pro-
viding quantitative blood glucose levels measured in simple machines. Various
attempts to provide implanted insulin pumps and continuous glucose moni-
toring for automated insulin delivery have not yet been perfected but progress
is expected.

Diabetes and its many complications remains a leading cause of death and
disability. Even if automatic infusion pumps improve and become widely
available, they will remain cumbersome and have problems. Research efforts
on the etiology of diabetes give hope that some diabetes may be preventable.
For now, the goal of the diabetic must be to follow a carefully controlled diet
with appropriate drug dosage which keeps glucose levels at near normal levels
but does not subject the patient to severe hypoglycemic episodes.

188 KINGSLEY M. STEVENS

Arthritis

So far, we have dealt with diseases which have high mortality rates. These
same diseases also produce a great deal of morbidity, i.e., discomfort or
disability or both. Of those diseases which produce high morbidity rates but
low mortality rates, arthritis is dominant. In a survey of people over age 65,
almost half reported arthritic symptoms. The actual prevalence of arthritic
changes must be even higher, since x-rays taken for other purposes frequently
show severe arthritic changes in patients asymptomatic for arthritis. Arthritis
is a generic term and has many varieties but two types account for most cases:
Rheumatoid arthritis (RA) and osteoarthritis (OA), also known as degen-
erative joint disease (DJD). Although OA is far more common, RA has been
the subject of much more research. This reflects both the severe crippling
effects of RA and its intriguing immunological factors. Most patients with RA
have a serum factor termed ‘“‘rheumatoid factor” which is an antibody against
denatured antibody of the IgG type. Arthritis attacks joints, but the bone
itself is only secondarily affected. In OA, the primary tissue response is in
cartilage, while in RA it is the synovium which lines the joint.

Soon after cortisone became available in the late 1940s, it was shown to
produce dramatic improvement in certain patients severely crippled with RA.
However, the side effects of chronic steroid use can be severe and improve-
ment was often not maintained. Aspirin was widely used and was effective in
RA but required continued use of large doses. Hence, pharmaceutical com-
panies searched for a drug which would be more effective than aspirin but
less toxic than steroids. The first product was indomethacin, introduced in
1962. This group of drugs carries the acronym of NSAID, for “non-steroidal
anti-inflammatory drugs” and many different products with slightly different
characteristics are now available. RA is a severe inflammatory disease and
these drugs were developed for RA. At the time, OA was felt to be non-
inflammatory, and the British therefore use the term “‘osteoarthosis” instead
of ‘“‘osteoarthritis” which does carry a connotation of inflammation. Since OA
is much more common than RA, the NSAID drugs were promptly tried in
OA and found to be very helpful. Following this therapeutic finding, it has
been shown experimentally that inflammation is indeed an important part of
OA.

Despite these drugs and others used in arthritis, both RA and OA can
progress to make joints non-functional. For such patients, the major advance
has been in orthopedics, with the development of total joint replacements.
Particularly successful has been hip replacement which has made a great many
patients crippled with-arthritis once again ambulatory.

Yet arthritis remains the major cause of morbidity for people over age 65
and much more basic and applied research is required.

Mental Illness

Another area with high morbidity but low mortality is that of diseases
affecting the brain. The original hope that psychotherapy would resolve such

CHANGES IN MEDICINE FROM 1935 TO THE PRESENT 189

functional diseases as schizophrenia and manic-depressive (bipolar affective)
disorders has not been borne out and these diseases are now known to be
heavily dependent upon genetic factors. Chlorpromazine was introduced in
France in 1952 and this group of drugs has had a dramatic effect on the
treatment of schizophrenia. Their extensive use has led to large scale dis-
charges of schizophrenics from mental hospitals. It should be realized that the
drugs do not cure the disease and rarely completely normalize the altered
thought processes. Also in the early 1950s, the simple chemical lithium car-
bonate was shown to be effective in control of manic symptoms. A few years
later an analogue of chlorpromazine was shown to be effective in depressed
patients while ineffective in agitated schizophrenics. The dibenzazepine nu-
cleus of this drug, imipramine, differs from the phenothiazine nucleus of
chlorpromazine in the linkage between the two benzene rings. Imipramine
and related compounds are used with good results in most cases of bipolar
depressed states but are of lesser values in depressions of other types.

Non-psychotic mental illnesses vastly outnumber schizophrenia and manic-
depressive disorders. Depression, anxiety, stress syndromes and substance
abuse with their myriad permutations and combinations permeate our society.
Primary physicians dispense huge quantities of the benzodiazepines typified
by diazepam (Valium). Psychiatrists couple more judicious drug use with
psychotherapy while new professional groups, e.g., clinical psychologists, use
only psychotherapy to aid patients coping with these problems. Perhaps the
greatest change since 1935 is the acceptance of the frequent need for profes-
sional help to resolve problems in which emotion and mood are paramount.
Although there are no good statistics, it appears that there has been a major
increase in depression, anxiety and stress syndromes since 1935 and there
certainly has been a huge increase in substance abuse. Many cases of these
disorders stem, at least in part, from our social organization, and since pre-
vention is certainly more effective and desirable than treatment, psycho-
therapy and medical treatment cannot be expected to have much effect on
the incidence of these problems.

In the older age group which we are primarily addressing, the most prom-
inent mental illness is dementia. The most frequent types, Alzheimer’s Disease
and multi-infarct dementia, are not only untreatable but are devastating for
both patient and caretaker. Multi-infarct dementia is due to strokes which are
highly correlated with hypertension. Hence, we have some preventive mea-
sures for it, but not for Alzheimer’s Disease. Both types of dementia are
highly correlated with age so our aging society will show increasing incidence.
Even more important, however, is the increase in prevalence. This is due in
large part to application of all our modern technology to prolonging the lives
of severely demented patients. It is very effective in that goal, which coincides
with prolonging the suffering of their caretakers. Not only routine technologies
but cardiac surgery, repair of asymptomatic aortic aneurysms, full treatment
programs for cancer, continuing hemodialysis are applied alike to demented
and undemented patients. While research in dementia must be vigorously
pursued, there is no possibility that research will resolve the increasing problem
of dementia in the foreseeable future.

190 KINGSLEY M. STEVENS

Hearing Loss

About 30% of people over age 65 have a symptomatic degree of hearing
loss. We now know that high noise levels have a cumulative effect over the
years on auditory acuity and much more stringent ear protection is required
in the workplace. At the same time, young people have vastly increased noise
levels in their recreational activities! The chief change in hearing aids has been
miniturization. Eyeglasses require only periodic changes in refractive pre-
scription done at periods of years, while hearing aids require ongoing ad-
justments in the volume control. This poses a particular problem in just that
population who need them most. Older people have more arthritis and less
ability to make rapid and fine adjustments of those tiny volume controls.
Putting in batteries and turning them on and off are major problems for
millions of users. Hearing loss isolates people from other people and is a major
cause of depression and withdrawal. We do not realize how often we repeat
or emphasize a point in ordinary conversation. Our superb memory often
reflects not such good memory but the repeated input of the item. The person
who is hard of hearing has much trouble getting the message once, much less
multiple times. A great many older people are thought to show senile memory
loss when the real problem is only hearing loss. All hearing cannot be helped
by hearing aids, but there is no question that the technology in use today is
very unsatisfactory for millions of users and potential users.

Chronic Sinusitis

When a sample of the general population over age 65 was asked about
chronic diseases which affected them, the top four were, in descending order
of frequency, arthritis (50%), hypertension (39%), hearing impairment (30%),
and heart condition (26%). The fifth most frequent, at 15%, was chronic
sinusitis. This definition includes patients with chronic nasal congestion and
post-nasal drip who do not show evidence of chronic sinusitis by x-ray. This
entity does not produce severe morbidity for most but it is certainly uncom-
fortable and a nuisance. The etiology is poorly defined but allergy, low-grade
bacterial infection coupled with structural features of the anterior skull which
alter drainage patterns are probably important. Vasoconstrictor drugs may
give transient relief but have long-term bad effects and indeed can worsen the
symptoms. Antibacterial therapy can be very helpful but again only transiently.
Nasal instillation of steroids can be helpful for some. Various surgical pro-
cedures have never become established as very helpful. Hence, chronic sin-
usitis remains an unexpected but major cause of morbidity and deserves further
study.

Vision Loss

About 10% of people over age 65 have significant uncorrected vision loss.
The major causes are cataracts, diabetic retinopathy and glaucoma. The treat-
ment of cataracts has vastly improved since 1935. At that time, patients spent

CHANGES IN MEDICINE FROM 1935 TO THE PRESENT 191

two weeks in the hospital and were subsequently fitted with very thick glass
lenses which at best produced distortion in size. Today the surgery is usually
done on an out-patient basis and an intraocular lens implanted. Subsequent
fitting of eyeglasses is no different from routine refraction. Diabetic retinop-
athy has been improved by laser treatment and has been very valuable for
individual patients. However, there are more diabetics, they live longer and
the development of retinopathy requires many years in the diabetic state.
Therefore, there are many more cases of vision loss from diabetes which is
today the chief cause of blindness in the United States.

Conclusions

Since 1935 there has been a tremendous increase in biomedical knowledge
and many new drugs and surgical procedures have brought a better life to
older patients with a wide variety of ailments. However, a viewpoint expressed
by Rene Dubos should be kept in mind. In the early 1960s, the University of
Kentucky opened a new medical center complete with schools in all the major
health sciences and a university hospital. Dubos, an eminent microbiologist
at the Rockefeller University, was the major speaker at the dedication cer-
emonies. To the governor, senators, officials from HEW and the university,
faculty and general audience, Dubos noted that everyone in the audience
expected that this new and expensive medical center would decrease the prev-
alence of disease in the Commonwealth of Kentucky. It would not do so,
declared Dubos. All the effort would only change the pattern and mix of the
diseases which presented, but would not decrease the overall prevalence of
disease. Twenty-five years later, he appears to have been correct.

Acknowledgment
I thank Mrs. Angela Wright for her typing.

References are available from the author on request.

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ra BMT Le COCA WU ASTIN PRO 3 oo ai thc eee anain Ae ace ih derad'ae © eww ee eters Austin B. Williams
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