Wadley Institutes of Molecular Medicine/Dallas, Texas
February 16-19, 1984
Faculty:
Kenneth A. Bonnet, Ph.D.
Department of Psychiatry
New York University School of Medicine
New York, New York 10016
Marvin Boris, M.D.
Stanley Weindorf, M.D.
Robert N. Corriel, M.D.
Laura S. Inselman, M.D.
Mark Schiff, M.D.
Joel R. Butler, Ph.D.
Melody J. Milam, M.S
and
Shere G. Wright, M.S.
E. J. Calabrese
University of Massachusetts
Amherst, MA 01003
Gary H. Campbell, DO
Department of Public Health and Preventive Medicine
Texas College of Osteopathic Medicine
D. D. Decker
University of Colorado
S. R. DiNardi
University of Massachusetts
Amherst, MA 01003
Dennis M. Driscoll
Texas A&M University
College Station, Texas
Robert T. Edgar
Human Ecology Research Foundation of the Southwest
Dallas, Texas
Trygg Engen
Brown University, Providence, Rhode Island, USA
and
The National Institute of Environmental Medicine
Stockholm, Sweden
Dr. Ronald Finn, M.D. FRCP
Consultant Physician
Royal Liverpool Hospital
Liverpool, England
Eduardo Gaitan, M.D.
and
Robert C. Cooksey, M.S.
University of Mississippi Medical School
and Veterans Administration Medical Center
Jackson, Mississippi 39216
Robert W. Gardner, Ph.D
Brigham Young University
John W. Gerrard, D.M.
University of Saskatchewan
Saskatoon, Canada
Jack D. Hackney, M.D.
Environmental Health Service
Rancho Los Amigos Hospital
University of Southern California School of Medicine
7601 East Imperial Highway
Downey, California 90242
Alfred R. Johnson, D.O.
Environmental Health Center-Dallas
Jozef J. Krop, M.D.
J. Swierczek, M.D., Ph.D.
C. Radulescu, Ph.D.
Franz Langmayr, Ph.D.
Institut für Baubiologie und kologie
Holzham 25
D 8201Neubeuern, West Germany
John L. Laseter, Ph.D.
Center for Bio-Organic Studies
University of New Orleans
New Orleans, Louisiana 70148
Stephen Levine, Ph.D.,
N.B. Holley
Biocurrents Research Development
944 Lake St.
San Francisco, CA 94118
Andrew A. Marino, Ph.D., J.D.
Department of Orthopaedic Surgery
Louisiana State University Medical Center
P. O. Box 33932
Shreveport, LA 71130-3932
Edward Joseph Masoro
University of Texas Health Science Center
San Antonio, Texas 78284
J. J. McGovern, Jr., M.D.
Brigham Young University
Provo, Utah
Ian C. Menzies, F.R.C. Psych.
Consultant Psychiatrist, Tayside Area
Child and Family Psychiatric Service
Royal Infirmary, Dundee, Scotland
Martin C. Moore-Ede.
Harvard Medical School
Department of Physiology and Biophysics
25 Shattuck Street
Boston, Massachusetts 02115
Jon B. Pangborn, Ph.D
Bionostics, Inc.
Cecil E. Pitard, M.D.
Clinical Associate Professor,
Otolaryngology,
University of Tennessee
Memorial Research Center and Hospital
2001 Laurel Avenue
Knoxville, Tennessee 37916
Doris J. Rapp, M.D.
State University of NY at Buffalo
3435 Main Street, Buffalo, NY 14214
Paul Ratner, M.D.
Scott Davis, M.D.
Maria Rodriguez, M.S., R.D.
Richard DeVillez, M.D.
W. T. Kniker, M.D.
San Antonio, Texas
W. J. Rea, M.D. F.A.C.S.
Environmental Health Center-Dallas
Dallas, Texas
James L. Repace
Environmental Protection Agency
Washington, D.C.
Sherry A. Rogers, M.D.
2800 W. Genesee Street
Syracuse, New York
Phyllis L. Saifer, M.D., M.P.H.
John D. Michael, M.D.
Scott D. Saifer, S.A.
Private Practice Clinical Ecology and Environmental Medicine
3031 Telegraph Avenue
Berkeley, California 94705
Douglas B. Seba, Ph.D.
Michael J. Suess
World Health Organization Regional Office for Europe
8, Scherfigsvej
2100 Copenhagen, Denmark
John G. Tew
Marie Kosco
and
Andras K. Szakal
Department of Microbiology and Immunology, and Anatomy
The Medical College of Virginia
Virginia Commonwealth University
Richmond, Virginia 23298
Faculty Abstracts:
Douglas B. Seba, Ph.D.
DIMENSIONS OF ENVIRONMENTAL POLLUTION
The health of the chemically sensitive patient is ecologically entwined
with his or her environment. This introductory paper will explore the general
state of the patient's environment. This will range from natural mutagens
to antibiotics and animal feed. General areas to be covered are air pollution,
water pollution, wildlife, soils, forests, living space and energy. Particular
attention will be devoted to the transport of airborne pesticides and indoor
air pollution including building types, air handling systems and personal
exposure to individual chemicals such as formaldehyde.
*******
Robert T. Edgar, Human Ecology Research Foundation of the Southwest, Dallas, Texas
HOW TO INTERPRET THE POLLUTANT STANDARDS INDEX
The pollutant standards index (PSI) is a method of reporting ambient
air quality across the United States on a uniform basis. The index is based
on five pollutants for which National Ambient Air Quality Standards have
been established. These pollutants are: Total suspended particulates (TSP),
sulfur dioxide (SO2), carbon monoxide (CO), ozone (O3)
and nitrogen dioxide (NO2). For each pollutant, a subindex is
calculated from a segmented linear function that transforms ambient concentrations
onto a scale extending from 0 through 500. One hundred corresponds to the
primary National Ambient Air Quality Standards and 500 corresponds to the
level which is expected to cause significant harm to the general population.
The PSI is chosen as the maximum of the calculated subindexes.
The main purpose of the PSI is to present urban air quality data from
across the nation on a consistent basis. However, the PSI for a particular
day does not indicate the level of air contaminants to which an individual
is exposed. The PSI can be interpreted as an indicator of meteorological
conditions with which either high or low levels of air contaminants can
occur.
An individual's exposure to outdoor ambient air pollutants depends primarily
upon his proximity to air contaminant sources and the prevailing meteorological
conditions. The gasoline motor vehicle is the major source of carbon monoxide
and nitrogen oxides in the United States. Coal combustion is the major
source of particulates and sulfur dioxide. Ozone is a photochemical oxidant
produced in the atmosphere by a mixture of nitrogen oxides, hydrocarbons,
and particulates along with sunlight. Therefore, the closer an individual
lives or works near a heavily traveled highway, the higher his exposure
will be to carbon monoxide and nitrogen oxides. Depending on wind speeds,
the highest concentration of ozone can occur many miles downwind from the
urban center.
Meteorological conditions such as wind speed and atmospheric stability
determine air contaminant concentrations downwind from a source. Inversions,
usually radiational and subsidence types, act as a lid on air contaminants
released into the air. Wind disperses pollutants with levels decreasing
exponentially from the source. Precipitation, such as rain and snow, can
remove some types of air contaminants from the atmosphere.
Since the PSI is based upon a small number of air quality monitors in an urban area, a high PSI level indicates that source levels along with meteorological conditions are favorable for the exposure of the population to high levels of air contaminants. However, since PSI levels are announced after the fact, their value as a warning to protect people from high levels of air contaminants can be questioned.
*******
John L. Laseter, Ph.D., Center for Bio-Organic Studies, University of New Orleans, New Orleans, Louisiana 70148
TRACE LEVELS OF ORGANIC CHEMICALS IN BODY TISSUES AND FLUIDS
At present there are a multitude of organic molecular species that result
from anthropogenic activities. These chemicals frequently become pollutants
of the work place and the environment. Some are biodegradable whereas others
appear as biorefractories. Humans, therefore, can receive a toxic insult
from either ingestion of contaminated food materials or absorption from
contaminated atmospheres.
Technology is now available that can quantitatively and qualitatively measure trace levels of toxic organics in body tissues and fluids. A number of examples of bioaccumulation in patients of these environmentally derived chemicals will be discussed. Specifically, chlorinated pesticides, chlorinated phenols, low molecular volatile organics, herbicides, and related chemicals will be presented along with their possible environmental origin.
*******
Dennis M. Driscoll, Texas A&M University, College Station, Texas
A PERSPECTIVE ON EMPIRICAL HUMAN BIOMETEOROLOGY
The atmospheric environment iminges upon man both directly and indirectly.
His health and well-being may be related to microorganisms and vectors
whose viability depends on the proper conditions of light, heat, and moisture.
Or, the interaction may be as direct as erythema produced by the absorption
of solar radiation.
Another perspective on the broad range of man-atmosphere interaction
is afforded by noting that cause and effect may be established or only
suspected. Quantitative Human Biometeorology deals with measurable changes
in man caused by measured environmental elements in a way that is understandable
from the physical, chemical, and biological viewpoints. That is, there
is an established physical transfer mechanism. Examples are solar radiation
effects, anoxia, and thermal stress leading to impairment of the cardiovascular
system. When possible, the effects have been reproduced in laboratories.
Qualitative Human Biometeorology describes those situations in which
there is little or no doubt about cause and effect, but the physical transfer
mechanism is not well established, and there are often mitigating circumstances.
Examples are allergies and the effects of air pollution and of air ionization.
In some cases there effects are reproducible in the laboratory.
Relationships which are only suspected - the third level of inquiry
into man-atmosphere interactions - are those deduced by association. There
is only circumstantial evidence that the atmosphere is causative; thus
the term Empirical Human Biometeorology. The evidence has accumulated from
a great number of studies which, largely on the basis of statistical or
graphical correlations, link weather to human response in general, and
to mortality and morbidity in particular. The weather features which have
been implicated as causative include fronts, especially cold fronts, certain
winds (Foehn, Sharov, Santa Ana), and rapidly changing weather. The conceptual
framework for most of this research has been weather types, certain associations
of weather elements which are geographically fixed with respect to an idealized
wave cyclone model.
It is particularly noteworthy that these findings are almost exclusively
European, and have been used there as the basis of medical-meteorological
forecasts. These are issued to doctors, clinics, and hospitals, and some
kinds of surgery are scheduled only when certain weather types are forecast.
There the focus is on biotropic weather factors and processes and the meteorotropic
diseases and their pathophysiology. This contrast sharply with the conduct
of human biometeorology in North America, the Commonwealth countries, the
Scandinavian countries, and Japan, where the focus has been on human environmental
physiology or climatic physiology. In these areas the main research topics
are thermoregulation, the physiology of acclimatization to heat, cold,
and mountain environments, comfort, working efficiency, and limits of tolerance.
Studies of weather emphasize meteorological extremes rather than fronts,
air masses, or special winds. Or, to express this contrast in terms of
the perspective cited above, European research is largely in Empirican
Human Biometeorology, while the remaining technologically advanced nations
emphasize Qualitative and Quantitative Human Biometeorology.
Even though weather factors have accounted for a small proportion of
the daily, seasonal, or regional variance of physiological functions, mortality
and morbidity, the associations have for the most part been shown to be
statistically significant, and have been replicated many times. They imply
that there is something about everyday weather - weather exclusive of events
known to be harmful such as floods, hurricanes, tornadoes, blizzards, acute
air pollution episodes, and excesses of temperature - that predisposes,
precipitates, or exacerbates pathological manifestations.
Why? What is the linking - the physical transfer - mechanism? The medical-meteorological
community, from Hippocrates to Petersen, Huntington, and Mills; to the
European investigators; to the contemporary researcher, armed as he is
with data hungry computers and the most sophisticated statistical techniques;
has amassed an enormous amount of empirical evidence suggesting cause and
effect. The fact that there is nothing in medical science to explain these
associations - to provide the linking mechanism - makes them both puzzling
and provocative.
The implications of findings in Empirical Human Biometeorology should
be pursued to some conclusion, and not left unresolved. Are these relationships
real or spurious? Are they not meteorological at all, but due to other
factors which are coincident in time with weather? It is time to redirect
attention for purely statistical studies - of which there is now a surfeit
- to those which attempt to provide a firmer etiological basis for these
weather-human response links. Empirical Human Biometeorology must be advanced
from this very rudimentary stage of research to a higher level - to qualitative
or even quantitative human biometeorology.
*******
Dr. Michael J. Suess, World Health Organization Regional Office for Europe, 8, Scherfigsvej; 2100 Copenhagen, Denmark
EXPOSURE AND HEALTH EFFECTS OF INDOOR AIR POLLUTANTS
There have been many reports of serious impacts on human health due
to indoor exposure to formaldehyde, to carbon monoxide and other products
of unvented combustion, to a variety of organic chemicals from consumer
products, and to radioactive pollutants namely, radon and daughters. The
as yet inadequately evaluated chronic exposures to imprecisely determined
concentrations of the pollutants known to be released indoors is a matter
of considerable public health concern. Consequently, the WHO Regional Office
for Europe has undertaken to follow-up this subject through a series of
working groups, each concentrating on a different aspect.
The second Group, meeting in 1982, reviewed current knowledge about
the sources of a number of the more important indoor pollutants and considered
the concentrations at which they have been reported. A summary of the current
levels of knowledge about population exposure, sources, distribution, effectiveness
of presently used measurement techniques, and the adequacy of available
monitoring data for estimating population exposure are presented in Table
1.
Also considered were the concentrations at which the pollutants have
been reported, and the respective adverse health effects to be expected
were identified. In general, it was found that the instrumentation available
for measuring exposure was usually of acceptable quality, but that the
monitoring data and knowledge about the distribution of sources and concentrations
were inadequate or marginal. It was noted that the types of adverse health
effect to be expected were largely known, but that in many cases knowledge
of exposure-effect relationships were inadequate, especially with regard
to delayed effects of chronic exposures.
It was concluded that current knowledge did not yet allow quantitative
assessments of public health impact. With this understanding, and subject
to modification in the light of improved knowledge, estimates were prepared
for most of the pollutants, of concentrations below which it was felt no
unacceptable adverse health effects would occur and above which serious
concern about adverse health effects was to be expected in an indoor environment.
| Table 1. Current levels of knowledge about
population exposure |
||||||
|
Pollutant |
People
with low exposure |
People
with high exposure |
Sources |
Distri- bution |
Instrumen- tation |
Indoor/
personal monitoring |
| Tobacco smoke (passive smoking) |
most |
some |
+ |
± |
±* |
± |
| NO2 | some | some | ± | 0 | + | ± |
| CO | most | few | ± | 0 | + | ± |
| Radon and
daughters |
most |
few |
± |
0 |
+ |
0 |
| Formaldehyde | most | few | ± | ± | + | ± |
| SO2 | few | few | ± | ± | + | 0 |
| CO2 | most | few | + | ± | + | + |
| CO3 | few | few | ± | + | + | ± |
| Asbestos | few | few | 0 | 0 | ± | 0 |
| Mineral fibres | few | few | 0 | 0 | ± | 0 |
| Organics | most | some | ± | 0 | ± | 0 |
| Allergens | most | some | 0 | 0 | ± | + |
| *For respirable particulates 0=inadequate ± = marginal + = adequate | ||||||
*******
James L. Repace, Environmental Protection Agency, Washington, D.C.
TOBACCO SMOKE AND NONSMOKERS
Objective: To explore the factors affecting the concentration of tobacco
smoke in occupied spaces; determine their implications for the health of
exposed nonsmokers.
Method or Approach: An indoor air pollution model has been developed,
verified experimentally, which can be used to accurately predict levels
of RSP and carbon monoxide from cigarette smoke in occupied spaces given
the smoker density and the effective ventilation rate. This model was found
to accurately predict the experimental chamber measurements of Leaderer,
from 4 to 16 cigarettes per hour over effective ventilation rates ranging
from 2.2 to 13.6 air changes per hour.
Results to Date: Experimental observations on levels of respirable particles
in public buildings where tobacco is smoked conclusively demonstrate that
tobacco smoke inflicts substantial air pollution burdens on nonsmokers,
far in excess of those encountered in smoke-free indoor environments, outdoors,
and in vehicles on busy commuter highways. Some nonsmokers could absorb
quantities of tobacco smoke comparable to those of low-tar cigarette smokers
and these effects might very well be observable epidemiologically, since
the doses absorbed by low-tar cigarette smokers appear to be similar to
the doses absorbed by high-tar cigarette smokers who do not inhale. High-tar
smokers who do not inhale appear to suffer from fourfold to eightfold the
lung cancer risk of nonsmokers. Thus, based on modeled dose, there is reason
to believe that some nonsmokers are at risk of the diseases of smoking
from breathing ambient concentrations of smoke. After a series of experiments
involving cigarettes, a pipe, and cigars, it is concluded that indoor air
pollution from tobacco smoke cannot be adequately controlled by standard
ventilation rates set by the American Society of Heating, Refrigerating,
and Air-Conditioning Engineers under ASH-RAE Standards 62-73, 90-75, or
62-1981. These standards are based upon design occupancy and their inadequacy
appears to be due to the large source strengths of smoking materials, indicating
that the appropriate control measures lie not in uneconomical increases
in ventilation rates, but rather strategies designed to separate smokers
from non-smokers physically, by regulating side stream emissions from smoking
materials, or by encouraging smokers to quit. Further experiments have
shown that so-called low-tar cigarettes (less than 1 mg) have side stream
emissions which are 80 percent of those of 1977 cigarettes (about 17 mg)
and 40 percent of those of 1959 cigarettes (about 29 mg). This model, based
on 1977 cigarette emissions, should continue to be useful as the tar level
of U.S. cigarettes declines, and with appropriate scaling, can be used
to estimate exposures of populations in the past.
Project Dates: April 1977 - continuing.
*******
Franz Langmayr, Ph.D., Institut für Baubiologie und kologie, Holzham 25, D 8201Neubeuern, West Germany
THE PRINCIPLES OF BIO-ARCHITECTURE
Bio-architecture (in German Baubiologie) deals with the construction
and the remodeling of dwelling places in order for them to be most conducive
to human health. Since we dwell in buildings for maybe 90% of our time
this is a most important aspect of environmental health.
Our emphasis is on the whollistic overall view of the many different
aspects to be considered in this respect.
Following we give a list of 25 main principles:
In toxicology e.g. we know a lot about the immediate response of the
body to large doses of poisons. But we know very little about its response
to small doses when administered regularly for many years. And the same
applies to all kinds of technical electrical and magnetic fields, unnatural
lighting and other factors. Though especially the long-term aspect is essential
concerning ones dwelling place. Bio-architecture has great positive aspects.
"Bio-architectural" home owners report considerable decrease in their susceptibility
to disease as well as increase in their feeling of well-being and efficiency.
*******
John W. Gerrard, D.M., University of Saskatchewan, Saskatoon, Canada
ENVIRONMENTAL ILLNESSES
Illness Induced by Urea Formaldehyde Foam Insulation
W.C., age 43, a farmer and his wife D. age 41, were symptom free until
June of 1978 when UFFI was installed in their propane-heated home. Both
W. and D. then developed headaches, depression, forgetfulness, inability
to concentrate and nasal stuffiness, D. also bloating and impaired hearing.
Both also developed sensitivities to food. Both recovered when living away
from home, symptoms returning as soon as they lived in the house.
May 1983 - UFFI removed, but when it was removed chemicals were used
to caulk leaks around the windows, these chemicals precipitated symptoms.
Energy-Efficient Homes
M.P., an RN, age 27, was symptom free when, in Dec. 1981, she moved
with her husband, an engineer, into an energy-efficient home. Two months
later she began to experience spells of vertigo and tachycardia which increased
in frequency and severity. Feb. 1983 she moved out of her own home into
a safe house, and her symptoms began to clear. Fifteen months after moving
into the energy-efficient home formaldehyde levels in the house were 0.28
parts/million.
Restoration of Home After a Fire
D.B. age 37, a worker at a local pulp mill, his wife E., age 36, and
their sons Curtis, age 14, and Cory, age 12, were well and symptom free
when, on December 7, 1982 their home was damaged by fire. The house was
boarded up, dried out by propane and repaired. The family moved back into
the house on February 29, 1983. Two to three weeks later D. and E., both
developed headaches, nasal stuffiness, itchiness of eyes and lassitude.
Both had to give up work. Their two sons developed existaxes, headaches,
an inability to concentrate and think clearly, and their marks at school
fell.
When their home was repaired it was sprayed heavily with chemicals to
counteract the effect of smoke. Wall-to-wall carpets were installed as
well as new furniture. Formaldehyde levels - basement 0.142 ppm. living
room 0.26 ppm, kitchen 0.23 ppm.
Illness Induced by Occupation, House Painting, and Energy-Efficient
Home
W.E. was born in 1942. At age 26 he went to Senegal as a missionary.
Soon after arriving, he became paralyzed from the waist down, recovering
gradually during the next six months. Following this illness he began to
complain of headaches and sinus problems, he also had a nervous breakdown.
1972 - age 30, painted during the summer, and drove school bus during
the winter. He noted when he painted houses the exposure to certain paints
made him ill.
1979 - he moved in the fall into a new energy-efficient home heated
by propane, and began to paint during the winter, becoming ill after spraying
a building with Alkyd taking three weeks to recover. He found that exposure
to oil-base paints was followed by insomnia. During the winter his behavior
became unpredictable and his speech incoherent. He was admitted to a psychiatric
ward, recovered, was able to paint during the summer, but became ill each
winter. Exposure to his paints and confinement to his house results in
confusion, depression and incoherence.
*******
Sherry A. Rogers, M.D., 2800 W. Genesee Street, Syracuse, New York
RAPID, MARKED CLEARING OF DIVERSE RECALCITRANT CONDITIONS COINCIDENT
WITH ADMINISTRATION OF MOLD EXTRACTS AND FOOD AVOIDANCE
In previous publications we have shown that there are many more fungi
prevalent than we were previously aware of. Now we needed to determine
whether these fungi can cause disease. We needed to determine whether people
react to them and upon receiving them if their symptoms could be improved
and last, whether discontinuing the injections could cause a recurrence
of the symptoms. This is not easy to evaluate because mold allergy is rarely
an isolated event, rather, the total antigenic load must be dealt with.
Sixteen fungi were selected and added to our pollens, four mold, dust,
and mite tests. It was winter season. Not only were positive test results
obtained to the fungi, but coincident, dramatic improvement of various
recalcitrant conditions occurred within two months, (and in some cases
within weeks) of administration of these fungal antigens. Dietary manipulation
was essential in most for optimum improvement. Coincident with stopping
injections, or discontinuing the diet, the conditions would recur.
Before-and-after photos of patients will be shown.
Patient #1 had an IgE of 33,000 with extremely severe total body eczema.
He had sought treatment at the Massachusetts General Hospital and from
innumerable dermatologist and allergists in three states. His skin started
clearing with the second and third injections and was totally clear in
two weeks. After four months of treatment, his IgE was 8,000 I.U. At six
months, it was 4,000. Single blind saline substitution of his injection
6 months later caused recurrence within two weeks.
Patient #2 had severe acne conglobata which resulted in keloid formation.
He had consulted seven dermatologists in three states with no improvement.
Patient #3 had severe adult facial eczematous dermatitis.
Patient #4 had unbearable total body pruritis and pruritic vasculitis
of the ankles
Patient #5 had idiopathic fluid retention of hands, face and feet, unresponsive
to diuretics, often making her unrecognizable to friends. She had consulted
internists and endocrinologists.
Patient #6 had hyperactivity and at the age of eight years old was on
six amphetamines a day by the Medical Center Pediatric Neurology Department.
He was still dangerously uncontrollable and unteachable and it took three
adults to hold him down during attacks.
All patients were markedly clear within less than two months (many were
clear within two weeks) and had been failures with other methods. Either
single-blind substitution of injections with normal saline, or dietary
indiscretion could cause recurrence of the conditions.
A discussion will follow of how the fungi were chosen, tested, and given;
and how the study could be improved if patients were willing to be part
of a study where they might receive placebo.
*******
Dr. Ronald Finn, M.D. FRCP Consultant Physician, Royal Liverpool Hospital, Liverpool, England
PHARMACOLOGICAL ASPECTS OF FOOD INTOLERANCE
Diet is the most important environmental factor affecting man. This
was recognized from very early times and manipulation of the diet was a
major weapon in treating disease. Indeed before the introduction of potent
modern drugs, diet was the only effective therapeutic method available
to physicians, hence the importance given to fasting in religious practice,
because the functions of the physician and priest were combined. The availability
of modern drugs led to a decline in interest in diet, but this trend is
now being reversed, and modern practice should be to combine diet and drug
therapy in the management and prevention of disease.
The purpose of this presentation is to present a classification of food
intolerance and to emphasize the importance of recognizing pharmacological
reactions in clinical practice.
Psychological Reactions include anorexia nervosa and bulimia and are readily distinguished from organic reactions.
Enzyme Defects include lactose intolerance and avoidance of the relevant food is clinically effective.
Toxic Reactions The use of synthetic chemical additives such as preservatives, colouring and tasting agents, can cause symptoms in sensitive subjects, and the use of toxic chemicals such as DDT in agriculture can lead to serious problems particularly in the chemically sensitive subject.
Pharmacological Reactions are particularly important in clinical practice and produce recognizable clinical syndromes. These will be discussed in detail and include caffeine effects such as a) palpitations and paroxysmal tachycardia, b) indigestion and vomiting, c) anaemia and 3) anxiety states. The recognition and management of these syndromes will be described. Other pharmacological reactions include the production of headaches by amines, and the long-term effects of excessive salt intake which can lead to hypertension in susceptible subjects.
Food Allergy is an important cause of disease in susceptible
subjects. IgE reactions occur rapidly and are easily recognized by the
patient. The more common slow reactions, possibly initiated by immune complexes
are responsible for a much wider range of symptoms and are more difficult
to identify. Immunological reactions to food are, however, very common
and most individuals have IgG antibodies to common foods, and the relevance
of these findings will be discussed.
*******
W. J. Rea, M.D. F.A.C.S., Dallas, Texas
THE EFFECTS OF POLLUTANTS ON THE NON-IMMUNE SYSTEM OF THE LUNG AND
CARDIOVASCULAR SYSTEM
The effects of inorganic and organic chemical pollutants on the non-immune
system of the lung and cardiovascular systems are rapidly becoming recognized.
Recent evidence incriminates ozone, nitrous oxide, and phenols. Mild to
moderate exposure of these pollutants cause acute toxicological tolerance
or a dysfunction to occur in the pulmonary vascular systems.
This adaption is characterized pathologically by damage to the Type
I ciliated epithelial cells with replacement by Type II ciliated epithelial
cells, interstitial cells, and fibroblasts. This change in cellular make-up
allows for return of pulmonary function to control levels, but the lung
will have long term damage with repeated episodes.
Metabolic changes occur with mitrochondrial damage from the generation
of free radicals. Glucose, lipid, and protein metabolism are altered, and
RNA and DNA changes occur. Many enzyme systems like the monamine oxidase,
cytochrome P-450, and glucose-6-phosphate-dehydrogenase systems are changed.
Resultant metabolic dysfunctions and limitations in the detoxification
of aromatic hydrocarbons occur. The glutathione system is also effected
thereby altering sulfhydral reduction mechanisms.
*******
Stephen Levine, Ph.D., N.B. Holley, Biocurrents Research Development, 944 Lake St., San Francisco, CA 94118
FREE RADICAL PATHOLOGY, ENVIRONMENTAL CHEMICAL TOXICITY, AND CHEMICAL
HYPERSENSITIVITY
According to the Second Law of Thermodynamics, all physical or chemical
changes tend to proceed irreversibly toward a decrease in utilizable energy
and an increase in entropy (disorder). These changes equilibrate when the
entropy is the maximum possible under existing conditions.* This law must
be consistent with the degeneration that occurs in disease, as viewed from
the atomic, molecular or supramolecular level. The dynamic progression
from health (low entropy) towards death and decay (increasing entropy)
underlies all disease processes, whether induced by environmental chemicals,
infection or emotional stress. These degenerative processes are initiated
through lipid peroxidation, free radical damage, the consequent release
of inflammatory mediators, and immune suppression. The immune system is
a delicate redox system, which when functioning optimally retards entropic
decay.
Most research on chemical hypersensitivity has been directed only at
the symptoms produced by these chemicals. If we can understand the biochemical
mechanisms that underlie this disease, then protective and therapeutic
modalities should become evident.
Many symptoms in ecological illness are consistent with deterioration
in the antioxidant defense system. This system is composed of enzymes and
the very antioxidant nutrients that are most required for immune defense
(vitamins A, C and E, Ze, and Se). Effectiveness of antioxidants resides
in their electron-rich chemistry. Toxic chemicals either themselves cause
oxidant damage, or are metabolized to free radical toxins in vivo,
their toxicity resulting from their reactivity as oxidants or reductants.
When a nonradical molecule loses an electron it becomes unstable, since
electrons like to group in pairs. Chemicals are constantly losing and gaining
electrons in normal cellular energetics, which is naturally regulated by
cellular redox balance and the antioxidant system. In abnormal (stressed)
metabolism, the balance is shifted towards an increase in single electron
transfer (electron leakage) leading to increased production of radical
species. If each radical species is not stabilized with the addition of
an electron (supplied by antioxidant molecules) then an electron will be
taken from a cellular molecule, often an unsaturated lipid from a cellular
membrane, resulting in membrane damage, release of inflammatory prostaglandin-leukotriene
agents via membrane peroxidation, formation of (-)foreign(-) antigenic
(haptenic) complexes due to covalent modification of tissue macromolecules,
and ultimately cell death and necrosis.
Imagine a fire burning in a fireplace. The fire represents normal metabolism,
the burning fuel producing energy for bodily functions. Sparks flying from
the fire represent the free radicals, which are unstable products of incomplete
burning of the fuel. Unrestrained, the sparks can react with other material
and damage one's home, even to the point of destroying it. With a screen
in front of the fire, the sparks are prevented from doing harm. This is
a purposefully simplistic image of antioxidant function. Antioxidants can
neutralize the dangerous free radical byproducts from the metabolism of
foods, environmental chemicals or drugs. Oxidant stress can locally exhaust
or overwhelm the antioxidant defense capability to neutralize free radicals.
Reserve antioxidant defenses can be mobilized, as occurs in the lung. However
prolonged (chronic) oxidant stress will eventually lead to systemic exhaustion
and inflammatory or autoimmune degeneration.
A particularly important antioxidant enzyme, glutathione peroxidase,
detoxifies peroxides, using reduced glutathione and selenium as cofactors.
A recent clinical study demonstrated that petrochemically sensitive patients
improve with the use of Se. Dr. A. Zamm found three basic responses to
treatment with Se as selenite. One group improved slowly, over a two month
period. Another group benefitted immediately, within days. The third group
initially reacted unfavorably to the Se preparation, but eventually did
improve. Those most sensitive patients were started with minute doses,
and the doses gradually increased. The improvements in chemical tolerance
with Se is a full-spectrum one, supporting my hypothesis that environmental
chemicals are consistently toxic to biological systems via redox mechanisms.
Selenium is known to modulate the adaptive responses of the antioxidant
enzymes, which then provide increased protection against transient increases
in oxidant stress.
Selenium has also been proven effective in the treatment of Candida
albicans (yeast) infections. Selenium-deficient neutrophils can phagocytize
yeast cells, but are unable to kill them. Clinically, supplying Se along
with the nystatin antibiotic often assists patients in recovering from
yeast infections. Our antioxidant defenses also determine our cellular
immune capability. Ascorbate and vitamin E improve immune function, by
protecting phagocyte cell membranes against damage from the very oxidants
that these cells produce to kill pathogens.
The themes underlying degenerative disease are consistently those of
oxidant stress, free radical attack, lipid peroxidation with consequent
inflammation, and hapten formation leading to immune dysregulation. Individual
cases will vary, but degenerative disease processes must inevitably follow
upon universal laws established by the electrochemical nature of physical
reality. The present extensive use of (-)anti-inflammatory(-) drugs and
(-)antidepressants(-) may be largely replaced by the use of nutritional
factors which approach the problem at a more primary level. Clearly this
approach to healing or slowing oxidative degeneration will position nutritional
medicine as a primary treatment modality.
*Lehninger AL, Principles of Biochemistry, 1982, P. 362.
*******
Jon B. Pangborn, Ph.D. Bionostics, Inc.
METABOLIC ASPECTS OF CHEMICAL SENSITIVITIES
Many intolerances that individuals present to environmental chemicals
and to various foods can be linked to dysfunctions in the individual's
metabolism. Such dysfunctions can be identified through laboratory tests
and measurements of essential nutrient and metabolite concentrations in
body tissues and fluids: blood cell and hair minerals analyses, functional
enzyme tests using erythrocytes, urine and plasma amino acids, etc.
Sensitivity to ammonia, amines and to high-protein foods follows from
limited capacity for ammonia detoxification and may involve limited or
subnormal liver urea cycle capacity. Catabolism of amino acids from dietary
protein can be disordered in numerous ways; impaired amino group transfer
due to subnormal coenzyme activity of pyridoxal phosphate or to subnormal
levels of a-ketoglutarate, the primary amino group receptor in human metabolism,
are not uncommon. Activity of pyridoxal phosphate can be affected by enzyme
assimilation of zinc as well as by intake of precursor vitamin B6. Alpha-ketoglutarate
formation in the tricarboxylic acid cycle (citric acid cycle) is strongly
dependent upon enzymes that depend on manganese and magnesium for their
catalytic activity.
Sensitivity to alcohol and to aldehydes may occur if the enzyme aldehyde
dehydrogenase is weak. This FAD-linked metabolism enzyme normally oxidizes
acetaldehyde (from the essential amino acid threonine) to acetic acid.
This enzyme uses niacin in the form of NAD as a cofactor, and the enzyme
protein contains iron and molybdenum which must be adequate for proper
enzyme activity. The enzyme alcohol (ethanol) dehydrogenase is activated
by zinc; it forms acetaldehyde from ethanol. Weakness is aldehyde dehydrogenase
automatically leads to alcohol intolerance as well as to intolerance of
acetaldehyde, formaldehyde, and other aldehydes such as are present in
glues, resins, and building insulation material.
The metabolism of the nutritionally essential amino acid methionine
is notoriously sensitive to coenzyme activity of pyridoxal phosphate and
to other factors which may impair its enzymatic steps. Taurine is an extremely
important metabolite of methionine or cystine, and impaired metabolism
of methionine tends to lower taurine levels. A low methionine/cystine diet
or incomplete digestive proteolysis or malabsorption can cause reduced
levels of taurine. Disordered rental transport also can lead to subnormal
taurine in liver cells. Inflammation of the epithelial tissue in kidney
tubules and hyperaminoacidurias in general (renal acidosis) also appears
to affect renal conservation of taurine (clinical observation).
When taurine is low, extreme sensitivities to environmental chemicals
can develop. Taurine mediates the chemical oxidation sequence initiated
with respiratory burst in phagocytes for microbicidal activity. When taurine
levels are low, this immune system chemistry is unregulated with respect
to scavenging OCI and formation of aldehydes. Also possible when taurine
is low are the following degenerative chemistries: formation of nitriles
from chloramines, oxidation of methionine to methionine sulfoxide in chemotactic
peptides (inactivation of methionine enkephalin?), and oxidation of mercaptans
to sulfur acids.
Taurine is a key component of bile acid (with glycine). If bile synthesis
is disordered, then it is also possible that assimilation of vitamins A
and E (and other lipid-soluble vitamins) is disordered since the intestinal
absorption of lipid-soluble vitamins is bile sensitive. Assimilation of
essential and dietary fatty acids also may be affected. Low taurine can
also be coincident with electrolyte mineral imbalances at the cellular
level.
Hence and individual's tolerance for ingestion of exogenous chemicals
as well as his tolerance for foods strongly depends upon the state of his
metabolism. Metabolic weaknesses can lead to a great variety of intolerances.
Bolstering metabolism weaknesses must join avoidance strategies, diet rotation,
and neutralizing doses in combating allergic-like sensitivities or maladaptive
reactions to chemical substances.
*******
Kenneth A. Bonnet, Ph.D., Department of Psychiatry, New York University School of Medicine, New York, New York 10016
A GENERAL MODEL FOR BIOCHEMICAL AND ANATOMICAL SUBSTRATES OF HIGH
SENSITIVITY TO ENVIRONMENTAL SUBSTANCES
The unusual sensitivity of many individuals to environmental agents
often results in presenting symptoms that include features suggesting central
nervous system mediation. A difficulty has been the diversity of agents
that can result in these symptoms, and the variation of the symptoms themselves.
We have studied a number of unique cases of such heightened sensitivity
and have been able to conduct biochemical, neurological and computerized
electroencephalography studies of each case under controlled circumstances.
It has become evident that many of the symptoms so often encountered in
these individuals clinically are mediated by anterior ventral forebrain
structures that have greater accessability to blood-borne and airborne
substances than does the remainder of the central nervous system. Moreover,
the biochemical neurotransmitter systems in these specific areas are also
affected by certain foodstuffs that occur in the common diet. Amino acids
can increase the available pools of certain neurotransmitters. Sugars can
seriously reduce the release rate of certain neurotransmitters. In addition,
certain synthetic agents can gain rapid access to central nervous sites
to perturb metabolism and neurotransmitter or neuro peptide activity.
We have studied several cases with computerized EEG before challenge,
during challenge (on a double blind basis) with a known offending agent,
and carried out behavioral analysis at each point. These cases provide
confirmation, along with on-line biochemical studies of plasma, of the
model presented that can account for the locus and biochemical substrate
for many types of chemical hypersensitivity syndromes encountered clinically.
*******
Martin C. Moore-Ede., Harvard Medical School, Department of Physiology and Biophysic, 25 Shattuck Street, Boston, Massachusetts 02115
THE TWENTY-FOUR HOUR SOCIETY: CONFLICTS BETWEEN ENVIRONMENTAL AND
BIOLOGICAL TIME
The last 100 years-a mere instant on an evolutionary time scale-have
seen a fundamental change in the world we live in. Throughout the millions
of years of evolution on this steadily-rotating planet, humans have been
exposed to a regular 24-hourly cycle of day and night. But in 1882 Thomas
Edison unlocked a Pandora's box with his invention of electric light. It
not only became a personal choice whether to sleep during the night or
the day, but the creation of that option demanded, by 1984, that 21 million
Americans work the "graveyard" (night) or evening shifts in order to maintain
the services that a 24-hour-a-day society demands. The problem was further
compounded by the introduction of the jet airplane in the 1950s which now
whisks hundreds of millions of passengers each year across time zones so
that their bodies are confronted with day when it ought to be night.
Modern man readily becomes out-of-synch with his environment because
he is equipped with circadian (approximately 24-hour) clocks within the
brain which govern rhythms of sleep and wakefulness, alertness, performance,
and virtually every aspect of our physiology and behavior. These internal
clocks, designed for the highly predictable world of our origins, adjust
only slowly to changes in the timing of light and dark. The result is that
after rapid travel across time zones, or rotation onto a new shift, people
are forced to work at a biological time of day when their bodies are geared
for sleep. Alertness is low, reaction time is reduced, productivity is
seriously decreased, and errors are more likely to be made and accidents
to occur. The consequences can be enormous-the Three Mile Island nuclear
power plant accident happened at 4 a.m. with a crew that had just rotated
onto the night shift; truck drivers have single vehicle accidents eight
times more frequently at 5 a.m.; airline pilots fall asleep in the cockpit
and overshoot the airport.
The consequences are not confined to increased risk of accidents or
to sleep loss and insomnia, although 80-90% of shift workers have serious
problems with chronic sleep deprivation. The risk of heart disease and
the incidence of stomach ulcers and digestive problems are far higher in
rotating shift workers. Animal studies also suggest that life expectancy
may be reduced by 5-20%.
Yet this is the way that modern society is developing. Each year an
additional ½-1% of the working population is being switched to shift
work schedules. One out of every four working men and one out of every
six working women now alternate work between day and night. The major TV
networks adopted 24-hour-a-day programming during the past year, and five
million TV sets are turned on between 2 a.m. and 5 a.m. each day. With
increasing automation in industry, and the enormous capital costs of industrial
plants, the trend is to require increasing numbers of people to work when
their bodies are geared for sleep.
Recent biomedical research has established that there are biological
clock (circadian pacemakers) located in the hypothalamus which time our
sleep-wake cycle, hormonal patterns, and when we feel alert or drowsy.
These clocks have a natural day length, depending on the species, that
is either shorter or longer than 24 hours (e.g. 23 hours in mice and 25
hours in humans). To keep in synch with dawn and dusk, these clocks are
reset each day by light falling on the eyes, and the information is relayed
via a retino-hypothalamic tract to the pacemakers in the brain. The apparent
locus of a circadian pacemaker in the human brain was only located three
years ago, but many secrets have already been unlocked as to how the clocks
work and how they may be reset.
The property of these clocks which made them so well suited to the highly
predictable environment of our origins is that they are hard to shift by
more than an hour a day. However, this is the root cause of the problem
that humans have in adjusting to the schedules of modern society. Many
of the people who staff our hospital, fly our planes, or work in our industries
and power plants have their body times perpetually out-of-synch with their
imposed schedules of work and rest.
In the past few years research in circadian physiology has started to
provide some practical solutions. We have shown that when the shift work
schedules at an industrial plant were scientifically revised to facilitate
the adjustment of the workers' biological clocks to changes between shifts,
20-30% increases in productivity, a 39% reduction in personnel turnover,
an 87% increase in satisfaction with the schedules, and a 27% reduction
in health complaints were achieved. At the same time, new techniques for
correcting certain forms of sleep disorders have been developed that are
based on circadian principles. Furthermore, in the laboratory certain pharmacological
agents have been shown to be effective in resetting biological clocks and
might, in the future, be useful in correcting disparities between body
time and the work-rest schedule. Thus biomedical science at last seems
ready to tackle a 100-year old problem.
REFERENCES:
1. M.C. Moore-Ede, F.M. Sulzman, C.A. Fuller. The Clocks That Time Us: Physiology of the Circadian Timing System. Cambridge, MA: Harvard U. Press, 1982.
2. M.C. Moore-Ede, C.A. Czeisler, G. S. Richardson. Circadian timekeeping in health and disease. NEJM 309 (8 & 9): 469-476 and 530-536, 1983.
3. C.A. Czeisler,, M. C. Moore-Ede, R. M. Coleman. Rotating shift work schedules that disrupt sleep are improved by applying circadian principles. Science 217: 460-463, 1982.
4. M.C. Moore-Ede. What hath night to do with sleep? Nat. Hist. 91:
22-24, '82.
*******
Andrew A. Marino, Ph.D., J.D., Department of Orthopaedic Surgery, Louisiana State University Medical Center, P. O. Box 33932, Shreveport, LA 71130-3932
HEALTH ASPECTS OF ENVIRONMENTAL ELECTROMAGNETISM
Consideration of the role of electrical forces in biological systems
began with a move away from a purely chemical view of life, and towards
one that emphasized electron dynamics and the electrical properties of
biological tissue. Studies of the physiological role of the body's intrinsic
electrical signals led to experiments on the therapeutic effects of artificial
signals. A variety of devices are now available for treating bone nonunions,
and intense efforts have begun to exploit other potential applications
of electromagnetic therapy. These efforts include the areas of soft tissue
growth, wound healing, infection control, and the diagnosis and treatment
of cancer. Preceding this developmental period of bioelectricity, electricity
itself had become firmly established in society. There was a proliferation
of transmitter towers, high-voltage lines, and the innumerable devices
they serve, and it resulted in environmental levels of electromagnetic
energy comparable to those being studied in the laboratory and applied
clinically. The actual extent of the health consequences attendant uncontrolled
environmental exposure to electromagnetic energy are presently only dimly
perceivable; the existence of such consequences is no longer in serious
doubt.
The first transmission line was built in 1882, and five years later
the first transmitter-receiver system was successfully operated. From this
beginning came our modern electrical power and communications systems.
Traditional engineering concepts, at least in the United States, sanctioned
only two electrical bioeffects, namely heating and shock. They became the
sole design criteria with regard to possible side-effects. The rule developed
that electromagnetic energy could be beamed through the environment or
directed along high-voltage lines at any intensity level up to that which
produced heating or shock..
It is convenient to divide environmental electromagnetic energy into
the power and broadcast regions. The power system operates at a single
frequency of 60 hertz and includes all transmission lines and line-powered
devices. The Broadcast frequencies are characterized by wireless energy
transmission and include radio, TV, radar, and microwave ovens. The traditionally-recognized
electrical bioeffects can occur only above 10,000 micro watts (to be read
"micro watts per square centimeter") or, at the power frequency, if one
touches an energized wire. Thus, in all American jurisdictions and in the
military, electrical sources are considered safe with regard to side-effects
if these precautions are followed.
In the USSR regulation of environmental electromagnetic energy followed
a much different course. Soviet scientific literature contains many reports
of biological effects below 10,000 micro watts, and, many reports of biological
effects due to power-frequency electric and magnetic fields - effects associated
with merely being in the vicinity of high-voltage lines. Based on
these studies, national exposure standards were adopted; the standard at
broadcast frequencies is 1 micro watt.
What are some typical levels of environmental electromagnetic energy
in the United States? Mount Wilson is a high point where many commercial
broadcast installations have been build to serve Los Angeles. A level of
1,000 micro watts was measured by the Environmental Protection Agency in
the Mount Wilson post office. There is a similar transmitter concentration
near most other U.S. Urban areas. The elevation necessary for efficient
energy transmission is frequently attained by mounting transmitters on
tall buildings. This can produce high levels in nearby buildings. About
2 million Americans are exposed daily to environmental electromagnetic
energy above the USSR safety levels.
There have been many studies - mostly Soviet - describing non-thermal
biological effects due to broadcast-frequency radiation (Figure 1). Many
studies have also shown the existence of biological effects of electrical
and magnetic fields such as arise from the electrical power system. Several
such studies are shown in relation to the fields produced by a typical
high-voltage line (Figure 2). Beischer, at the Naval Aerospace Medical
Research Laboratory, found that one day's exposure to a 1-gauss magnetic
field caused elevated serum triglyceride levels in humans. We found that
electric fields of 3,500-15,000 volts per meter altered the growth rate
and mortality of mice. Wertheimer, of the University of Colorado, found
an association between child cancer and transmission lines. These studies
used fields which exist within the first 100 feet of a high-voltage line.
The remaining five studies used field intensities which exist at the indicated
distances from a typical 765 kV line. Lott, of North Texas State University,
found altered EEGs in rats after 90 minutes' exposure. Wever, of the Max
Planck Institute, found that weak electric fields altered human circadian
rhythms after several weeks. Noval, of Temple University, found that 30
days' exposure to an electric field equivalent to that at 2,000 feet from
the line produced stunted growth in rats. There are many other similar
reports of biological effects.
Electromagnetic energy does not act only on a single target organ. There
is a clear pattern in the literature indicating that electromagnetic energy
is a biological stressor - that it places a nonspecific physiological demand
on the exposed organism. When the organism's capacity to resist has been
exceeded, a clinical sign - an effect - is manifested whose nature depends
in part on the predisposition of the exposed subject. It follows, therefore
that the exposure of substantial part of the population in an uncontrolled,
random, and essentially involuntary manner amounts to a significant public-health
(and ethical) problem.
Figure 1 and Figure 2 (Not Displayed)
*******
Jack D. Hackney, M.D., Environmental Health Service, Rancho Los Amigos Hospital, University of Southern California School of Medicine, 7601 East Imperial Highway, Downey, California 90242
RESPIRATORY EFFECTS OF SULFUR DIOXIDE AIR POLLUTION IN ASTHMATICS
This presentation discusses effects of sulfur dioxide (SO2)
inhalation in asthmatics, and strategies for personal protection against
such exposure. It emphasizes results of laboratory studies of human volunteers
exposed to controlled environments containing SO2. Epidemiologic
studies often have shown associations between elevated ambient levels of
SO2 and/or particulate matter, and increased rates of illness
or premature death. Since SO2 and particulates may be closely
associated in the atmosphere, it is often difficult to separate their effects
epidemiologically. This is not a problem in controlled studies of human
volunteers, which have been applied to SO2 alone, various particulate
species alone, and gas-particulate combinations.
A number of such controlled studies of SO2 during the1960's
and '70's indicated that increased airway resistance and symptoms of irritation
could occur with exposure, but only at concentrations of 1ppm or higher
(above the common ambient range) in most subjects. However, in 1980, asthmatic
subjects were reported to be consistently and markedly more reactive to
SO2 than similarly exposed healthy subjects. Subsequently, statistically
significant increases in airway resistance were reported in a group of
moderately exercising asthmatics exposed to as little as 0.25 ppm for 10
minutes.
The first SO2 exposures of asthmatics in our laboratory failed
to show significant effects at 0.25 or 0.50 ppm. This inconsistency with
previous findings most likely related to differences in the mode of breathing
during exposure. Mouthpiece breathing, as employed originally by other
researchers, typically produces more severe responses than natural unencumbered
breathing, as employed by our group. The difference is at least partly
explainable in terms of the high solubility of SO2 in aqueous
media. Natural breathing occurs at least partly through the nose, even
during heavy exercise. The moist surfaces of the nasal cavity scrub SO2
effectively, reducing the dose to the bronchial passages where constriction
occurs. But with sufficiently heavy exercise, we found that even natural
breathing of SO2 can cause some asthmatics to experience symptoms
and increased airway resistance at concentrations at least as low as 0.4
ppm. The effects develop in less than 5 minutes. Their severity appears
to depend on the dose rate of SO2 (concentration times the subject's
ventilation rate), rather than on the total dose. In most asthmatic subjects,
the effects disappear in less than 1 hr with rest, even if SO2
exposure continues. Many asthmatics experience symptoms and airway constriction
with exercise even in very clean air, so care must be taken to differentiate
the effect attributable to exercise from that attributable to SO2.
Also, cold or dry air can aggravate the exercise-induced effect and may
enhance the SO2 response. This is being studied currently.
Recent controlled SO2 exposure studies leave little doubt
that respiratory effects can occur at concentrations within the possible
ambient range, in a particular small segment of the population-asthmatics
who exercise heavily. Whether these "positive" findings have any connection
with earlier "positive" epidemiologic findings (not related specifically
to exercising asthmatics) is not yet clear.
Advice about personal protection against impending SO2 exposure
should of course be tailored to individual patients, but the following
general recommendations have wide usefulness. First, minimize the need
for extra ventilation; there is an approximately proportional increase
in ventilation with increased exercise. Second, minimize mouth breathing;
mouth breathing is generally less efficient in scrubbing water-soluble
pollutants than nose breathing. Third, stay indoors, but avoid indoor pollutants,
including SO2 producing heating fuels. Fourth, if air purification
devices are available, use them.
In summary, recent information from controlled human studies has focused
public health concern on short-term peak SO2 exposures in exercising
asthmatics. Lung function decrement or symptoms or both can result, but
more attention is needed in assessing the medical importance of these effects.
Possible exacerbation of effects by coincidental cold or dry air is being
studied. By using certain avoidance strategies and personal protective
devices, irritation and broncho spasm from SO2 exposure can
be minimized.
*******
Alfred R. Johnson, D.O., Environmental Health Center-Dallas
WATER CONTAMINANTS
Water quality is a persistent problem causing a growing concern by the
public and health care professionals. Newer techniques now enable measurement
of organic chemicals. Analysis by gas chromotography and mass spectrometer
have yielded clues to contaminants and naturally occurring substances.
Many compounds once thought safe - especially synthetic organic chemicals
can have substantial health risks and effects. "Spring" and bottled water
companies have grown dramatically in recent years.
Individuals with hypersensitivity are having more difficulty in finding
water they can tolerate. Special attention to the source, handling and
treatment and packaging is mandatory. Individual challenges to specific
waters are then necessary to determine acceptance.
*******
Phyllis L. Saifer, M.D., M.P.H., John D. Michael, M.D., and Scott D. Saifer, S.A., Private Practice Clinical Ecology and Environmental Medicine, 3031 Telegraph Avenue, Berkeley, California 94705
"AUTOIMMUNE ENDOCRINOPATHY IN ENVIRONMENTAL DISEASE"
There exists an autoimmune condition consisting in polyendocrinopathy,
Candida susceptibility and allergies resulting from immune dysregulation.
A higher incidence of cancer is expected in this group because of the immune
dysregulation, and, other autoimmune phenomena like lupus and rheumatoid
arthritis also occur more frequently in these patients. The most common
form we see in our environmental practice is thyroiditis followed by what
we think to be oophoritis and then diabetes. We have not seen adrenalitis
or para thyroiditis. Just recently we have been given access to measurement
of the ovarian antibodies by which we hope to confirm the diagnosis of
oophoritis. Other autoimmune measures which are available include ANA titers,
antiparietal cell antibodies, anti-muscle antibodies, parathyroid antibodies
and adrenal antibodies. We suspect a specific 'T' suppressor cell defect
because total 'T' cells are normal. This syndrome is hereditary and as
such must have a trigger. We recognize chemical exposures, viruses, Candida,
radiation, physical and emotional trauma, mis-nutrition and perhaps others
as the environmental insults that trigger a disease waiting to happen.
Chemical overload, childbirth and Candida are the most common initiating
events noted in our office.
Thyroiditis: We suspected autoimmune endocrinopathy from the
following history, symptoms and signs:
It is terribly important to recognize this syndrome of immune dysregulation,
endocrine disease, Candida and allergies in order to be forewarned of the
increased possibility of cancer, and, in order to provide maximal and optimum
medical care of the endocrine disease as well as the allergic problems.
Failure to consider each component of the syndrome lessens the patient's
chance for full control and recovery. Treatment of the endocrine component
is the keystone in recovery for a number of patients. Best results are
achieved when all the factors are balanced and treated.
*******
Eduardo Gaitan, M.D. and Robert C. Cooksey, M.S., University of Mississippi Medical School and Veterans Administration Medical Center, Jackson, Mississippi 39216
EFFECTS OF ENVIRONMENTAL POLLUTANTS ON THE THYROID.
Several organic compounds, naturally occurring and anthropogenic, can
alter thyroid gland structure and function by acting directly on the gland
or indirectly by affecting its regulatory mechanisms and/or the peripheral
metabolism and excretion of thyroid hormones. The gland may increase in
size becoming a goiter, but thyroid hormone secretion, depending on dietary
iodine intake or presence of underlying thyroid disease, may remain adequate
or become insufficient inducing hypothyroidism.
A. Resorcinol and Humic Substances - In the 1950's the goitrogenic
effect of resorcinol was demonstrated when patients applying resorcinol
ointments for the treatment of varicose ulcers developed goiters. Subsequently,
investigators confirmed both the in vivo and in vitro antithyroid
effect of resorcinol and several other parent phenolic and phenolic-carboxylic
compounds. Concomitantly, it was shown that these antithyroid compounds
are in fact degradation monomeric products of humic substances.
Humic Substances (HS) are the principal organic components of soils
and waters. HS are high molecular weight complex polymeric organic compounds.
HS are also important constituents of coals, shales and other carbonaceous
sedimentary rocks. At the heart of the process of humification are the
production and polymerization of phenolic and carboxylic benzene-rings.
Up to 70% of flavonoid HS may be made up of these subunits. This in itself
is sufficient reason to question and investigate a relationship between
the phenolic derivatives of humic substances and thyroid disease.
However, the need for such investigation has become more imperative,
particularly in the U.S., since the limited supply of natural gas and petroleum
has focused increased attention on development and expansion of processes
for the conversion of coal to liquid and gaseous fuels. Phenols are the
major organic pollutants in aqueous effluents from coal-conversion processes.
Coal-conversion waste waters contain in addition to phenolics, thiocyanate
and disulfides, also known to possess antithyroid and goitrogenic properties.
Resorcinol and other antithyroid phenolic pollutants comprise as much as
5 g/liter in aqueous effluent form a bench-scale coal-liquefaction unit.
Besides other toxic effects of phenols, we must add at present, their potential
for a deleterious effect on the thyroid, reinforcing the need for their
removal if coal-conversion processes are to be environmentally acceptable.
B. PCBs, PBBs and Other Organochlorines - Polychlorinated Biphenyls
(PCBs) have been of national concern since 1971, but the risk to human
health from chronic exposure to these toxic substances is still uncertain,
due to imperfection and limitations of risk assessment techniques. The
uncertainty extends to the potential harmful effects of PCBs and polybrominated
biphenyls (PBBs) on the thyroid. Other organochlorines (pp'-DDT, pp'-DDE
and Dieldrin), heavily used as insecticides and resistant to environmental
degradation, are known to cause marked alterations in thyroid gland structure
and function of birds. However, the impact of these pollutants on the human
thyroid is unknown.
C. Phtalates - Phthalate esters are among the priority pollutants
listed by the U.S. Environmental Protection Agency. Like resorcinol and
organic disulfides, phthalates have been frequently identified as water
pollutants in the U.S., as well as in the water supply of an endemic goiter
district in western Colombia. Phthalates undergo degradation by bacteria
with production of di hydroxybenzoic acid (DHBA) known to possess antithyroid
properties. Fish actively concentrate and metabolize phthalates. Whether
these abundant pollutants exert deleterious effects on the thyroid of human
and other animal species has not been investigated.
D. 2,4-Dinitrophenol - DNP is an insecticide, herbicide and fungicide
which causes toxicity by the uncoupling of oxidative phosphorylation. Decrease
of serum thyroid hormones concentration occurs after the administration
of DNP in man. DNP inhibits pituitary-thyroid regulation and accelerates
peripheral metabolism of thyroid hormones in the rat. The public health
impact on the thyroid of this toxic pollutant is unknown.
Lack of quantitative assessments of the thyroid risk from exposure to
the environmental pollutants precludes valid risk/benefit analysis of their
health and social impact versus the cost to remove them from the environment.
It is on the basis of such data that policy decisions should be made concerning
the need to develop cost/effective techniques for the removal or inactivation
of the offensive agents. At present, medical treatments for the individual
but not measures for prevention and control at community level, are applied
in the United States.
*******
Edward Joseph Masoro, University of Texas Health Science Center, San Antonio, Texas 78284
NUTRITION AND AGING
Although it is often claimed that nutrition influences the aging process,
the only unequivocal evidence supporting this view is the action of food
restriction on laboratory rodents. It was in 1935 that McCay and his colleagues
first described the increase in length of life when weaning rats were food
restricted throughout post-weaning life. This basic finding has been repeatedly
confirmed and the general conclusions that can be drawn from these subsequent
studies are the following: 1) Food restriction extends the life span of
rodents; 2) food restriction retards age-related physiological deterioration
in rodents; 3) food restriction retards age-related disease processes in
rodents.
Our recent research on the male Fischer 344 rat has provided some further
understanding of this phenomenon. Food restriction started in early adult
life was found to be just as effective in extending life span as food restriction
started soon after weaning. On the other hand, food restriction limited
to the childhood and adolescent period of life was much less effective.
Restriction of protein but not calories from six weeks of age on increased
the median length of life, but did not influence life span. Age-related
physiological deterioration was markedly retarded by food restriction started
soon after weaning or started in early adult life but not by food restriction
limited to childhood and adolescence or by protein restriction without
caloric restriction.
Chronic nephropathy and cardiomyopathy are major disease processes occurring
in the male Fischer 344 rat. Food restriction started soon after weaning
or started in adult life markedly retarded the progression of these disease
processes and protein restriction without caloric restriction was also
quite effective in this regard. Food restriction started soon after weaning
or in early adult life also markedly delayed the occurrence of neoplastic
disease, but protein restriction without caloric restriction did not.
Although these findings clearly show that food restriction slows the
aging process, they provide no insight on the mechanism of this anti-aging
action. However, over the years, several hypotheses have been proposed
in regard to mechanism; four of these have been seriously received by the
scientific community.
Is the anti-aging action of food restriction also true of other mammalian
species including humans? There are no hard data which can be brought to
bear on this question. Nor is it likely that such data will be obtained
in the near future because the resources needed to explore this question
in long-lived species make the execution of such studies unlikely. However,
it seems likely that this highly reproducible effect involving a spectrum
of rodent species (rat, mouse, hamster) will be true of most if not all
mammalian species. This is not meant to imply that such a manipulation
would extend the human life span past the 100- to 115-year range that we
have come to accept as the human life span. Indeed, it seems likely that
of the many billions of people who have lived, some have had dietary regimens
similar to the life-prolonging ones given to rats and that it is this group
of people which have yielded those who have lived to the 100- to 115-year
human life span.
*******
Robert W. Gardner, Ph.D., Brigham Young University
AROMATIC COMPOUNDS - A NEW DIMENSION IN TREATING ENVIRONMENTAL DISEASES
Flavanoids, gallo-tannins, and many other aromatic compounds have been
identified as toxins inasmuch as they have inhibitory effects on enzyme
systems. For example, rutin (quercetin) and gallic acid inhibit the enzyme
catechol O-methyl-transferase which catabolizes circulating epinephrine.
The result is elevated levels of epinephrine with associated symptomologies.
Inhibitors of monoamine oxidase enzymes have likewise been identified in
foodstuffs, pollens, perfumes, air pollutants, etc. These chemicals prolong
the life of such monoamines as dopamine, noradrenaline, and serotonin.
Elevated levels of neurotransmitters may also occur as a result of ingestion,
or inhalation, of their precursors, or enzyme co-factors needed in their
synthesis. There is likewise evidence that steroids of both endogenous
or exogenous origin may have detrimental side effects on both females and
males. A successful treatment regimen has been developed which includes
systematic challenge of the patient with the chemicals identified as causative
agents until tolerance has developed to that chemical and others of like
structure.
*******
J. J. McGovern, Jr., M.D., R. W. Gardner, Ph.D., Brigham Young University, Provo, Utah
MODULATION OF NEUROPSYCHIATRIC RESPONSES USING SUBLINGUAL NEUROTRANSMITTERS
Abstract
A growing body of neurochemical evidence suggests that the ingestion
of large doses of phenyl food constituents which serve as neurotransmitter
precursors, affect the rate at which neurons synthesize and release
specific neurotransmitters in normal subjects, thereby affecting behavior
and other processes controlled by the brain (1)
We showed in short term controlled clinical studies that the neurotransmitter
molecule itself (dopamine, norepinephrine) administered in nanogram
doses abolished purposeless behavior in children with Attention Deficit
Disorder (A.D.D.).(2)
In the present study we assessed the behavioral and neuromuscular effect of the administration of the neurotransmitters dopamine, norepinephrine, serotonin and histamine administered sublingually in nanogram amounts in 28 patients with clinical disorders thought to be related to alterations in either neurotransmitter
synthesis, transport, release or receptor-site responsiveness. These
include four patients each with schizophrenia, mild Parkinson's disease,
myasthenia gravis, narcolepsy, multiple sclerosis and eight patients with
catalepsy. These patients also demonstrated cutaneous hypersensitivity
(reaginic) to pollens, dust, molds and food allergenic extracts; in addition
they demonstrated abnormal reduction in the levels of T suppressor lymphocytes
suggesting the presence of an impairment in immune regulation. We found
in this study using scores for the Profile of Mood State (P.O.M.S.) That
the administration of serotonin, compared to placebos, significantly increased
subjective fatigue and objective sleepiness; histamine consistently provoked
anger, hostility and confusion whereas norepinephrine administration was
repeatedly associated with elevated levels of tension-anxiety or depression-despair.
Using neurological measures we found that the sublingual administration
of histamine, compared to placebos, consistently reversed the narcoleptic
state and increased muscle strength in patients with myasthenia gravis.
Dopamine administration, compared to placebos, reliably reduced the tremor
in mild Parkinson's disease; decreased cutaneous anesthesia and increased
deep tendon reflexes and muscle strength in catalepsy; norepinephrine and
dopamine were significantly superior to placebos but indistinguishable
from each other in modifying distorted ideation in patients with schizophrenia.
The neurochemical rationale underlying the potential therapeutic use of
these agents will be discussed.
_________________
(1)Wurtman, R. J., Behavioral Effects on Nutrients, Lancet, May 21, 1983, pp. 1145-1147
(2) McGovern, Jr., J.J., Gardner, R. W., Painter, B. S. Rapp, D. J.,
Natural Food borne Aromatics Induce Behavioral Disturbances in Children
with Hyperkinesis, International Journal Biosocial Research, Vol. 4, pp.
40-42, 1983.
*******
Paul Ratner, M.D., Scott Davis, M.D., Maria Rodriguez, M.S., R.D., Richard DeVillez, M.D., and W. T. Kniker, M.D., San Antonio, Texas
FOOD ALLERGY AND DIETARY MANIPULATION IN ATOPIC ECZEMA
We have completed a long term study on the incidence of food allergy
in chronic eczema and the efficacy of dietary manipulation. After a baseline
week all 30 subjects went on an elemental diet, Vivonex (V), for 3-12 days.
Eighteen (60%) responded to (V) with improvement in eczema and a decrease
in severity (p<.001) and frequency (p<.005) as compared to non-responders.
Responses to V occurred in 12/16 (75%) children and 6/14 (43%) adults.
In the next month responders were challenged with 50+ foods so that a rotary
diet of "safe" foods could be established. On the diet some improvements
of eczema continued. Open or double blind challenge with "unsafe" foods
caused immediate or delayed flaring of eczema and occasional diarrhea,
asthma, rhinitis or edema. Food intolerance appears to play a major role
in eczema; immunologic factors such as food specific IgE and IgG4,
as well as immune complexes are being evaluated.
*******
Gary H. Campbell, DO, Department of Public Health and Preventive Medicine, Texas College of Osteopathic Medicine
OSTEOPATHY AND ECOLOGY: THE NEUROL CONNECTION
The osteopathic and ecological physicians have recognized the importance
of the autonomic nervous system's relationship to the state of a patient's
health. The ecologic physician recognizes the integration of the autonomic
nervous system with the immune system. A competent immune and autonomic
nervous system is essential for optimal health.
Early contributors to scientific literature, including Cannon and Selye,
describe the physiologic autonomic response of the human to a stressful
event. Continuously applied stressors have levels that do not cause mortality
lead to chronic unwellness and malaise. These stressors include allergy,
hypersensitivity, toxicity, dietary inadequacy, inappropriate exercise,
and the osteopathic concept of somatic dysfunction. The ability of an organism
to deal with these stressors is primarily genetically mediated.
Any type or combination of stressors, be it physical, psychological
or structural, leads to tissue dysfunction if severe or prolonged.
The final target of the autonomic and immune system commonly includes
the smooth muscle of the vasculature in the organ system that is involved.
This effect is as apparent in the vasculature of the central nervous system
as it is peripherally. Vessel spasm commonly associated with vasculitis
or sympathetic autonomic input is a recurrent presenting complaint to the
osteopathic and ecologic physician. Vascular spasm can be due to a singular
environmental cause or through complex humoral neuronal interaction initiated
by structural dysfunction and segmentally activated by the spine. A combination
of environmental and structural triggers may cause marked vascular reaction
readily evaluated by palpatory changes, including changes in temperature,
tissue texture, edema, and tenderness.
The ability to diagnose the segmental relationships by tactile skills
allows the physician to determine visceral and somatic interrelationships.
For example, the gastrointestinal reaction may be readily defined through
palpation of the parathoracic tissues from the 5th to the 10th
thoracic segments. These tissue changes allow the physician to determine
quantitatively the condition of the visceral target. Furthermore, many
painful syndromes associated with ecological triggers are often complicated
by structural disorders. Significant symptomatic relief may follow appropriately
applied physical therapy and/or manipulative therapy to the stressed areas.
The ecologically-oriented physician may overlook the structural relationships
of a stressed organ system. Likewise, the osteopathic physician often does
not recognize that an allergic or hypersensitivity reaction may be an important
factor in the patient's musculoskeletal complaints. It is important to
understand the ecologic and somatic interrelationships so the physician
can apply both principles to insure an optimal outcome for the patient.
To apply only one of these techniques is similar to rowing a boat with
only one oar. One may get to where one wants, but the route is often erratic
and prolonged.
*******
S. R. DiNardi, University of Massachusetts, Amherst, MA 01003, E. J. Calabrese, University of Massachusetts, Amherst, MA 01003, D. D. Decker, University of Colorado
ANALYSIS OF CHLOROFORM AND OTHER TRIHALOMETHANES IN THE RESIDENTIAL
ENVIRONMENT
Based on risk assessment models, the U.S. EPA has established maximum
contaminant levels for several trihalomethanes in water, the most common
being chloroform. The risk assessment model assumes that the only exposure
to the contaminated water is by ingestion. This study reports on the effects
of inhalation as an exposure route using an experimental shower chamber
connected to a municipal water supply containing 80 to 135 ug/1 of chloroform.
A sampling and analytical method was developed to quantify the levels of
chloroform stripped from the heated water used in the test shower. The
air sampling train contained a sodium hydroxide desiccant and a charcoal
tube. The charcoal was desorbed in trimethylpentane and analyzed for chloroform
in the 1 ug/1 range by electron capture gas chromatography.
*******
Edward J. Calabrese, Ph.D. and Salvatore R. DiNardi, Ph.D., Division
of Public Health, University of Massachusetts, Amherst, MA 01003
The study was designed to assess whether ascorbic acid supplementation
of up to 1000 mg/day would affect blood lead levels. Non-occupationally
exposed healthy adult human male volunteers were randomly divided into
three study groups according to the degree of daily ascorbic acid supplementation:
control, 500mg, and 1000 mg. The subjects had their baseline blood lead
levels taken prior to the start of the study and then on monthly intervals
over the next three months. The findings revealed that the ascorbic acid
supplementation had no significant affect on the blood lead levels.
*******
Doris J. Rapp, M.D., State University of NY at Buffalo, 3435 Main Street, Buffalo, NY 14214
ENVIRONMENTALLY-TRIGGERED MUSCLE PAIN
A 37-year old white female with a strongly positive family and personal
history of allergy was initially seen because of recurrent classical, perennial,
nasal symptoms evident since age 13. She had chronic idiopathic pruritis
noted particularly in the flexures of her extremities. She had had daily
headaches, abdominal pain, nausea, abdominal distension, and diarrhea for
many years. She had periods of extreme hyperactivity, irritability, depression,
and emotional lability, as well as severe episodes of fatigue which interfered
with her ability to care for her home or her family. She had muscle aches
affecting her neck, shoulders, and back which were so severe at times that
they totally incapacitated her. She would spend weeks in traction in the
hospital. All three of her children have classical evidence of the allergic-tension-fatigue
syndrome.
On physical examination, she had mild hypertension, moderate obesity,
marked scoliosis, and the deep tendon reflexes on the right were greater
than those on the left.
Exposure to offending foods or chemicals caused reactions which usually
occurred within 3-6 hours. She would develop progressively more incapacitating
muscle spasms, headaches, intestinal complaints, and depression which usually
caused her to be confined to bed. A detailed history frequently would reveal
the specific offenders. With appropriate testing, we could exacerbate individual
symptoms with one dilution and then relieve her medical complaints with
the appropriate neutralizing dose of the antigen. She consistently showed
little change to placebo injections given prior to or during antigen testing.
Her typical reaction, unless she arrived crying in severe pain, was
that after antigen testing, her normal humor vanished. She would stare
into space. She quickly would be placed in a bed and frequently became
unconscious. Her fists usually were tightly clenched and her right leg
was flexed. As her symptoms worsened, her pulse usually increased. When
the neutralizing dose was approached, her eyes would slowly open, she'd
begin to speak, and her hands would relax. When the neutralizing dose was
found, she could extend her right leg without back pain. Usually her original
symptoms would subside to various degrees during testing. Her symptoms
often improved 50-100% by the time the testing was completed.
A brief movie demonstrating her typical reactions will be shown and
her laboratory findings will be discussed. In this movie, you will see
her enter the office with assistance, in tears, and barely able to walk
or talk. She had been exposed to a number of chemicals when Christmas shopping
several days before and had been so ill that she could not stand until
the day she came to the office. We tested her for formaldehyde and the
numerous symptoms of which she complained began to recede. We then tested
her for hydrocarbons and after a brief exacerbation of symptoms, she improved
to a greater degree. When she left the office, she is visible humorous,
able to speak, and able to walk on her own. Her improvement is approximately
50-60%.
I have an additional 3-minute movie of the same woman showing severe
TMJ pain due to banana and relieved with the correct dilution of banana.
| TYPICAL BLOOD FINDINGS: | ||||||||
|
Serotonin (N=50-200 ng/ml, CV=17.6) |
Sed Rates (N=0-20) |
|||||||
| Pre | Peak | Post | Pre | Peak | Post | |||
| 1st Sugar | 60 | 80 | 60 | 3rd Sugar | 32 | 22 | 23 | |
| 2nd Sugar | 40 | 150 | 130 | Rice | 23 | 15 | 3 | |
| 3rd Sugar | 191 | 190 | 227 | White fish | 33 | 16 | 30 | |
| Cherry | 30 | 50 | 45 | Lobster | 22 | 21 | 25 | |
| Control | 80 | 65 | 80 | |||||
| C3 (N=70-176 mg%, CV=6.3) | ||||||||
| Pre | Peak | Post | ||||||
| 1st Sugar | 210 | 120 | 195 | |||||
| 2nd Sugar | 170 | 160 | 170 | |||||
| 3rd Sugar | 150 | 150 | 160 | |||||
| Cherry | 159 | 135 | 99 | |||||
| Control | 170 | 160 | 180 | |||||
*******
Marvin Boris, M.D., Stanley Weindorf, M.D., Robert N. Corriel, M.D., Laura S. Inselman, M.D., and Mark Schiff, M.D.
ANTIGEN INDUCED ASTHMA ATTENUATED BY NEUTRALIZATION THERAPY*
ABSTRACT: The effect of neutralization therapy on animal antigen-induced
broncho spasm was evaluated with pulmonary function testing in double-blind
study on 19 subjects with a history of wheezing to animal dander. The 9
males and 10 females were challenged with inhaled animal antigen to determine
the dose causing a 20% decrease of FEV1. The neutralizing dose
was determined by the five fold serial dilution skin technique. On two
subsequent days, one week apart, the specific antigen neutralizing dose
or placebo was injected. Twenty minutes later, broncho provocation was
performed with the dose causing the 20% decrease of FEV1. The
FEV1 decreased 31.8% from baseline in the controls, 27.4% post
placebo, and 10.7% post neutralization injection (p<0.01). The FVC,
FEF25-75, and PEF had similar responses. These results indicate
a dimuntion in animal dander induced broncho spasm with neutralization
therapy and may have a therapeutic implication in wheezing resulting from
animal dander exposure.
*******
John G. Tew, Marie Kosco and Andras K. Szakal, Department of Microbiology and Immunology, and Anatomy, The Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298
THE ROLE OF FOLLICULAR DENDRITIC CELLS IN THE LONG TERM MAINTENANCE
AND REGULATION OF THE HUMORAL IMMUNE RESPONSE
The mechanism responsible for the long-term maintenance and regulation
of immune responses are clearly of major significance. For example, in
many allergic states we are attempting to modulate responses many weeks
to years after they were initially induced. If immunological intervention
is to be successful in these diseases, it is important that we understand
how immune responses are maintained and regulated. Nevertheless, the vast
majority of research has been directed toward understanding the induction
of immune responses rather than toward understanding mechanisms responsible
for long term maintenance of a specific response. Consequently, our understanding
of the mechanisms responsible for maintenance of immune responses and our
ability to manipulate an immune response during the maintenance phase is
limited.
Our work has been primarily directed toward understanding the mechanisms
responsible for the long term maintenance and regulation of the humoral
immune response. Specific antibody is maintained in vivo for months
or years. It is catabolized at a reasonably constant rate but it is produced
in a cyclical fashion. The regulatory mechanisms responsible for this cyclical
production of antibody appear to include an antibody feedback system and
unique cells which trap and retain antigens in vivo for months or
years. Since these special antigen-retaining cells are restricted to lymphoid
follicles and since they are dendritic in shape, they are referred to as
follicular dendritic cells (FDCs). Lymphoid tissues containing antigen
bearing FDCs have been studied in organ cultures as well as in cell cultures.
In the absence of specific antibody in the cultures the lymphoid cells
spontaneously begin to produce antibody specific for the antigen retained
on the FDCs. This production is inhibitable by the addition of specific
antibody and the nature of this antibody feedback system has been studied.
Since FDCs appear to play a major role in the maintenance of antibody
production, we have recently devised techniques for isolating FDCs and
a number of cytological features of these cells have been determined. Most
FDCs floated on a BSA column at the low density of 1.065 gm/cc. This procedure
provided a means for substantially enriching for FDCs since up to 5% of
the cells floating on BSA were FDCs and this contrast with a concentration
of less than 1% FDCs in normal lymphoid cell suspensions. Once fixed with
glutaraldehyde and stained, FDCs had a characteristic acidophilic cytoplasm
and a euchromatic nucleus with marginated chromatin. Under Normarski optics
and by scanning electron microscopy, FDCs appeared to possess one or two
distinct cell bodies (soma). From one pole of these somata numerous dendritic
like cell processes radiated. In whole mount preparations, FDCs had the
appearance of "sun bursts." The slightly ovoid somata tended to vary between
4 to 6 um in diameter. The dendritic processes were thicker near the soma
(0.2-0.3 um) but distally became thinner (0.1 um) with or without branching.
Some of the longer processes measured over 60 um in length. Unlike macrophages
FDCs were nonadherent, nonphagocytic, esterase negative to weakly positive,
and lacked macrophage surface markers like Mac 1. However, like macrophages
they were Fc positive, Ia positive, and were positive for the common leukocyte
antigen. One objective of future work will be to determine if the ability
of an animal to maintain an immune response can be reduced or eliminated
by selectively damaging antigen bearing FDCs. Work toward developing an
FDC specific monoclonal antibody which may service this purpose is in progress.
*******
Cecil E. Pitard, M.D., Clinical Associate Professor, Otolaryngology, University of Tennessee Memorial Research Center and Hospital, 2001 Laurel Avenue, Knoxville, Tennessee 37916
COMBINED IMMUNOLOGIC - PHARMACOLOGIC (CIP) AGENTS THAT MAY BE USEFUL
IN THE MANAGEMENT OF MALIGNANT DISEASE
There is sufficient information concerning the host defense system,
and the abnormal physiology of malignant cells to indicate there are some
points at which malignant cells should be vulnerable to a combination of
well researched legal, safe, low cost, non toxic and universally available
medications.
This paper discusses some of these points, and some agents which meet
the criteria of being well researched, legal, safe, abundant, low cost
and universally available. It suggests one such combination, and presents
case reports.
It is an appeal to the members of this group to apply their unique expertise
and knowledge to this field.
It is a call for more workers.
*******
J. Krop, M.D., J. Swierczek, M.D., Ph.D., C. Radulescu, Ph.D.
"THE APPLICATION OF OPIATE RECEPTOR ANTAGONIST IN THE MANAGEMENT
OF A UNIVERSAL REACTOR" (Case Presentation)
ABSTRACT
Addiction phenomenon, very well recognized in patients with environmentally
induced illness, is poorly understood. With the discovery of the opiate
receptors, it has been hypothesized that addiction might be related to
endogenous morphine-like substances (enkephalins and endorphins) which
action can be effectively blocked by naloxone.
We would like to report a patient who from an ecological point of view
is an universal reactor. This was a 33 year old woman (W.W.) who for many
years presented psychiatric manifestations and a variety of symptoms from
CNS, GI tract and respiratory tract. On many occasions her complaints were
induced by food allergens, antibiotics, a majority of drugs and chemicals
such as SEA, formaldehyde, TS, perfumes and inhalants; mostly molds and
Candida. She was tested for different antigens to find a proper neutralizing
dose. The testing usually provoked such sever reactions that the procedure
for testing one antigen usually lasted between seven to ten hours without
any apparent neutralizing effect. The neutralizing dose very often was
not possible to establish and other measures such as oxygen, intravenous
Natrium Bicarbonate, Vitamin C IV, Calcium Gluconate, and adrenalin only
partially relieved the symptoms.
During the last ecological testing in the office, the patient was re-tested
for mold mix (Bencard) because the previous neutralizing dose was no longer
effective. During the test she produced the usual severe symptomatology.
The best dose was #9 but it was not completely effective and appeared vague.
After seven hours of testing, the patient remained un-neutralized and appeared
to have many symptoms, the majority of which resembled an overdose of morphine.
The symptoms are as follows: clammy hands, tahycardia; 120-130 beats per
minutes, hot and cold flushes, severe cough with broncho spasms, uncontrollable
sneezing, itchy eyes, ear pressure and pain, headache, dizziness and nausea,
mental cloudiness, mood changes ranging from severe depression to extreme
highs and uncontrollable laughing, tiredness, abdominal pain, back pain
in the right lumbar area, muscular and joint pains, generalized muscular
tremors, severe grand mal seizures, generalized muscular spasms and hypocalcemic
posturing of hands.
We decided to apply opiate receptor antagonist in an attempt to neutralize
nonspecifically the symptoms. Naloxone was injected S.Q. at 0.4 mg. Three
minutes after the injection all symptoms had disappeared completely. She
was free of all symptoms for one and one half hours and returned to her
apartment which is heavy in mold content. Four hours later she became symptomatic
again. The next dose of Naloxone was injected resulting in complete disappearance
of her symptoms as after the first injection.
*******
Joel R. Butler, Ph.D., Melody J. Milam, M.S. and Shere G. Wright, M.S.
THE CHEMICAL EFFECT: ACTIVATOR OF THE PSYCHOTIC PROCESS
The concept of functional psychosis denotes no known or demonstrable
physical or organic base as a prerequisite for that diagnosis. Psychological
profiles of environmentally sensitive patients very often reveal what appear
to be active psychotic processes during the reactive phases of the disease.
While medical diagnostic techniques fail to expose presence of lesions
in these patients, our studies indicate that a diagnosis such as toxic
brain syndrome or organic brain syndrome (unknown eitology) could be applicable.
Results of extensive psychological testing yield symptom patterns traditionally
labeled as "schizophrenic or affective" psychosis related to an ecological
patient population. Also, comparisons of a group of environmental patients
with a group of orthopedic patients show the environmental patients scoring
significantly higher on measures of those symptoms. This syndrome manifests
in a pathological level of alienation from self and from others. Preoccupation
with physical malfunction is prevalent as well as withdrawal from family
and friends. Emotions tend to be flattened, ideation irrational, and patients
tend to regress into states of pronounced dependency and immaturity, feeling
a loss of impulse control and a sense of emotional, cognitive and perceptual
distortion. Symptom formation often varies with chemical precipitant. Reduction
of total stress load has been most effective in helping these individuals
to regain physical and emotional stability, and remission or partial remission
of symptoms usually occurs consistent with avoidance of specific chemicals
identified as incitants.
*******
Trygg Engen, Brown University, Providence, Rhode Island, USA, and the National Institute of Environmental Medicine, Stockholm, Sweden
MEASURING DEFICITS IN ODOR PERCEPTION
No generally accepted protocol for measuring odor deficits exists. The
traditional approach to the problem is essentially a taxonomic description
of various forms of anosmia but without a clear connection between methods,
symptoms, and causes. The present paper will suggest that one can now begin
to establish such a rational based on contemporary psychophysics and research
on human and animal neurophysiology. While the usual sensory evaluation
is largely limited to so-called thresholds, it is proposed that four categories
of perceptual abilities can be considered: (1) sensitivity (detection of
low odorant concentrations); (2) capacity and tolerance (analogous to pitch
and loudness perception, respectively); (3) scaling (variation in perception
as a function of variation in odorant concentration); and (4) quality discrimination
and veridicality (perception of differences between molecules and ability
to identify odorant by name). The last task may be the most important in
real life, but all four categories must be considered for a complete assessment.
All are defined psycho physically and, whenever possible, illustrated with
clinical cases, such as odor deficits in workers in some occupations who
have been overexposed to certain chemicals. The discussion also includes
malingering and other response problems such as being able to identify
odors.
*******
Ian C. Menzies, F.R.C. Psych., Consultant Psychiatrist, Tayside Area, Child and Family Psychiatric Service, Royal Infirmary, Dundee, Scotland
AN ECOLOGIC APPROACH IN CHILD AND FAMILY PSYCHIATRY
A wide range of longstanding patterns of symptoms may result from individual
sensitivity to substances in the environment such as foods, chemicals,
dusts and pollens.
The assessment and treatment techniques of clinical ecologists are at
last attracting increasing interest within the United Kingdom National
Health Service although progress is still unacceptably slow.
Behaviorally disturbed and learning disordered children are common.
Their numbers may be increasing and certainly they make great demands on
parental understanding and courage as well as on professional judgement
and time.
Case studies will be presented which suggest that the difficulties encountered
by a significant number of such children have much to do with idiosyncratic
responses to foods, "additives" and contaminants in air and water.
Many show "sensitivity" features and exhibit remarkably similar clinical
pictures. At least one natural parent is often also affected and a transgenerational
history of allergy or migraine is frequently present. The onset of these
children's disorders can be related to stress such as the birth of a sibling,
death or other significant loss, or viral or other infection. Substantial
and lasting improvements often take place as a result of relatively simple
environmental manipulation.
These findings have far-reaching implications for the assessment and
management of disturbed, delinquent and learning disordered children and
their families. Further research is urgently required and certainly much
more attention should now be paid to the role of biological and environmental
factors in the development of children's problems.
Case 1> Patient admitted was a 20 y/o, w/f to Chicago CECU on
an emergency basis by ambulance from a physician's office on 1/9/82 in
Status Epilepticus. Symptom started January 1979 with headache and hand
tremors with first grand mal one week following treatment by dilantin for
headache. Her apparent sensitivity extended beyond the dust, molds and
pollens with hay fever symptoms to include foods and chemicals. Seen by
several neurologists and medical centers with negative reports. Diagnosed
as hysteria or in more recent terminology, somatization disorder. She was
told two years on psychotherapy would cure her. Massive medications including
Tegretol, Phenobarb, Dilantin and Mycelin which were given without seizure
control only worsened her condition. On one ER visit she experienced a
cardiac arrest secondary to massive anti-seizure medications. She found
better control after management by another ecologist along with a series
of homeopathic remedies and cranial manipulations. Six weeks before admission
to our facility, headaches began again following the placement of an acrylic
crown. The immediate causative agent was thought to be ingestion of oranges.
She had a history of irregular periods and was on therapy for a yeast vaginitis.
Physical Exam was unremarkable except an eczema of hands and feet.
This patient was admitted six times to our unit with Rx by dimethyl
glycine giving some control of her seizures during her later hospitalizations.
Her last two hospitalizations included surgery with removal of gall bladder,
appendix and right ovary. The ovary contained a dermoid cyst.
This patient shows no food or chemical sensitivities; today is symptom
free and living a completely normal life.
Case 2> Patient is a 26 y/o, w/f admitted to Chicago CECU, 3/31/83
for recurrent abdominal pain, nausea and vomiting. She had two laparotomies,
one in July, 1982 and the second in November, 1982 and on each occasion,
non-specific lymph adenitis was found. Abdominal pain and fatigue started
April, 1982. Hx of reaction to phenergen with a marked reduction of her
white count. She was also sensitive to Zoma, Talwin and Xylocaine. She
also complained of muscle joint pains.
Physical exam was not significantly abnormal except for wheezing in
the right middle and lower lung and the presence of laparotomy and appendectomy
scars.
This patient was followed conservatively and her pneumonitis cleared.
She did not react to test waters, carbon filters, commercial foods or test
chemicals. She did react rather severely to asparagus, pork, eggs, peanuts
and turkey requiring morphine to control her abdominal pain. Orange had
a lesser reaction. Candida antigen challenge produced abdominal pain, great
fatigue and depression. Ragweed, lambs quarters, grass and birch produced
positive skin wheels.
This case demonstrated the acuteness of some food reactions in selected
patients. These reactions were so severe as to produce two laparotomies
in six months in this case.
Case 3> Patient is a 36 year old white female admitted to CECU
via stretcher with seizure-like activities, having passed out in x-ray.
Developmental history uneventful, except for eneuresis until after starting
school. She became very fatigued as menarch, which occurred at twelve years
of age. History of frequent infections and antibiotic usage. In August
of 1977, a day following a bee sting, she experienced anxiety, depression,
jerking all over, convulsive-like episodes, chest pain, palpitations and
a feeling like she was going to die. She was aware of activities going
on around her, but could not respond. She was told it was nerves. Told
by a chiropractor it was hypoglycemia and treatment seemed to help for
a while but symptoms returned. Again a medical work-up was done and again
told it was psychosomatic. Her symptoms developed into crisis proportion
April, 1982, with personality changes, unable to cope with children, she
might meet husband with a kiss or screaming and yelling. Her husband was
convinced she as a schizophrenic. She was referred to an orthomolecular
psychiatrist. Patient was fasted and placed on food rotation diet and did
better for a while. Began combining her foods and started deteriorating.
She became much more reactive to chemicals and lost her "safe" foods.
Some constipation, vaginal yeast infections, severe leg aching at night.
Lives in a nine year old double-wide mobile home. Physical exam revealed
no significant abnormality.
After five days of fasting and bowel cleaning, this patient was cleared
100% of symptoms. A safe water and filter were found. The most reactive
foods were pork, rabbit, corn, eggs, peaches and cauliflower, lamb, tuna,
pear, and soybeans. Lesser reactive foods were trout, carrots, shrimp and
peas. Organic food symptoms included abdominal cramping, constipation,
headache, confusion, fatigue and sore throats. She reacted to her first
of six scheduled commercial foods with crying, lisping and confusion. Patient
reacted on sublingual challenges to cotton, natural gas, newsprint, tobacco,
formaldehyde, chlorine, phenol, fuel oil, synthetic ethanol and Candida.
Symptoms included fainting spells, blurred vision, headache, difficulty
breathing, confusion, morbid thoughts, feeling drunk, backache, chest,
jaw and shoulder pains. There was no reaction to auto exhaust.
Skin test for estrogen produced confusion and fatigue. She reacted to
Nilstat until a dot dose was utilized. She was treated for dust, molds
and mites sensitivity, Nystatin powder and vaginal tablets, Vitamin C,
calcium carbonate, Pan 5 enzyme and a rotary diet of her safe foods. Cotton,
Candida, Estrogen and her most positive chemicals were prescribed as treatment
doses.
This patient did well after discharge and by six months felt sufficiently
improved, went off of her rotation diet, chemical treatment doses and returned
to her previous living habits without apparent return of symptoms after
one year.
This case is unique and unusual by having such a complete healing in
so short a time.
Case 4> This patient is a 52 year old white male admitted to
the CECU of Chicago for evaluation and treatment of severe Rheumatoid Arthritis
requiring large doses of analgesics.
Past history indicated ulcerative colitis developed at eleven years
of age. A colectomy with ileostomy was performed in 1966 followed shortly
thereafter with rheumatoid arthritis affecting most joints, especially
his hands and knees. His diet consisted almost exclusively of animal protein,
very little fruit and vegetables, as he was conditioned that the roughage
would be detrimental to the ileostomy.
In June, 1983, he was hospitalized because of a bowel obstruction caused
by an adhesion. Shortly thereafter, his arthritis became much worse and
unmanageable except on large doses of steroids.
In the CECU, he was fasted 5 ½ days with modest improvement of
symptoms. A pulse-taper treatment of prednisone during this time was required
to quiet a knee that flared with redness, swelling and severe pain. He
required almost nightly doses of narcotics for pain.
Any attempt to feed him after the fast produced severe abdominal pain
and vomiting, and even drinking water was a problem. Our differential diagnosis
was bowel obstruction from further adhesions, a food reaction or withdrawal
from the addictive narcotics. The latter was favored. After five days,
G. I. tract was not a major problem. Switching from Demerol-Phenergen to
M. S. was very helpful. Liquified foods were given orally initially and
gradually thickened to semi-solid, and finally administered whole.
This patient owned a beef ranch and ate a considerable amount of beef.
Beef challenge produced a marked reaction and this made him a real believer.
Corn also reacted strongly. He did not react to chemicals or Candida.
The important aspect of this case is the D/D of the reaction G. I. after
the fast and the necessity to retrain him to eating a range of foods which
he had been conditioned to believe that he never would be able to eat again.
Case 5> 33 year old female was admitted to the CECU for evaluation
and treatment of severe bronchial asthma that began in childhood to 18
years of age, usually provoked by respiratory infections, for which she
was treated with antibiotics. For 15 years no asthma attack occurred, although
she experienced severe ragweed hay fever. At age 31, following two successful
pregnancies, and six months following an abortion, she started a full-fledge
attack of wheezing and coughing - her asthma was back. She was in and out
of the hospital three times and Emergency Rooms innumerable times for epinephrine.
She had been on many drugs, over the counter and prescribed. Prednisone
treatment was variable from 60 mgm. daily to 15 mgm every other day in
the past ten months. Some food cravings, binge eating were present plus
an acute sense of smell, especially to natural gas. She also complained
of anxiety, depression, irritability, loss of memory at times, and a short
attention span.
Except for a 3 cm. thyroid nodule in the right lobe, tendency for keloid
formation and some wheezing, no significantly abnormality was found on
physical exam. This patient had marked reactions to corn, wheat, shrimp,
chicken, eggs, lamb, carrots, oranges and beef. Some of the reactions including
wheezing, coughing, nasal congestion, headaches, joint pains, fatigue,
sleepiness and insomnia. Chemical challenges showed reactions to commercial
foods, synthetic ethanol, auto exhaust, phenol, tobacco smoke, glycerin
and natural gas. Candida was also positive, all with treatment doses found.
The diluent, normal saline, was without reaction. Also, dust, mites and
molds were reactive with a treatment dose established.
Her second admission to the CECU was February 24, 1982, with a history
of nausea, fear, paranoia, hallucination, lightheadedness, and on two mgm.
Prednisone daily. She was eating organic food as prescribed by her initial
hospitalization, but was found not to be rotating her food as previously
instructed. Nilstat powder ingestion also provoked paranoia and hallucinations.
This patient was fasted three days as she was phasing in and out of
psychosis, requiring restraints. As this patient cleared her symptoms of
psychosis, her asthma symptoms, which were not present on admission, started
reappearing. The most severe food reactions were milk, kiwi, yeast, apples,
filberts, brazil nuts and halibut. Corn, wheat, shrimp, egg, lamb, orange
and beef were not tested on the second hospitalization. Reaction to foods
included aggression, tension, fears, depression, loss of emotional control,
loss of concentration and loss of touch with reality.
She was discharged with her asthma back, but without psychosis. This case clearly fulfilled the history noted previously in the literature of an alternation b