Section G

Cardiovascular

Chapter 42

Cardiovascular Disease in Response to Chemicals and Foods

William J. Rea and Ollie Dawkins Brown


Introduction
Agents affecting the cardiovascular system
Water
Food
Air
Electric phenomena
Mechanisms of environmentally induced vascular damage
Types of mechanism in vascular damage
Clinical manifestations of vascular injury
Diagnosis of vasculitis
Clinical Syndromes
Vasculitis
Recurrent phlebitis
Cardiac arrhythmias
Treatment
Avoidance
Nutrition
Drugs
Exercise
Conclusion
Appendix
Reaction to double-blind exposure to fumes of chemicals in ECU
References
 

INTRODUCTION

Environmental insults have long been known to influence man’s health. Even Hippocrates emphasized environmental effects (see Air, Water and Places in ref. [39]). Early environmental records indicate that excess heat and cold influence bodily functions with extreme exposure resulting in death. Present-day thought and technology have allowed us to substantiate and augment the view that health and disease are a function of how man deals with his environment. It has become evident that treatment and prevention of cardiovascular disease must not only encompass views on biological (pollen, bacteria, virus, fungus, parasites) but also chemical factors (organic and inorganic) and physical forces (weather, cyclic phenomena, sound and electromagnetic effects). AGENTS AFFECTING THE CARDIOVASCULAR SYSTEM

Chemical agents

While chemical incitants may trigger a maladaptation response in virtually any of the smooth muscle systems, those of the cardiovascular system appear to be the most susceptible (Lichtwitz in [37]). Recent literature has verified previous findings regarding the harmful effects of a variety of chemicals on the cardiovascular system as shown in Table 42.1.
Table 42.1

Chemical Agents Affecting the Cardiovascular System

 
Reference
 
Reference
Fluorocarbons
37, 86
Formaldehyde
72
Phenol
56
Chlorine 
21
Petroleum alcohol
98
Cigarette smoke
24
Glycerine
26
Chlorophenothane (DDT)
72
Hydralazine
84
Turpentine
72
Toluene
72
 
 

 
 
 

Physical agents

Physical agents such as heat, cold, weather changes, light, and cycles have for centuries been known to influence health. The increase in modern technology has augmented our environment with noise and with electric and electromagnetic fields. The induction of disease and the maintenance of cardiovascular health can be regarded as functions of how the individual manipulates the total load of these pollutants through his immune and biochemical detoxification mechanisms. Water Water usually contains minerals, organic chemicals, particulate matter, and radiation. Chemically contaminated water is a major component of the total environmental load. Most public water systems are loaded with organic and inorganic chemicals which may increase the body burden of some chemicals several-fold. These include trihalmethanes [97], pesticides [9,61,76,92], formaldehyde [55], solvents [55], oils [98], heavy metals [55], and other metals such as copper [55]. Public drinking water has been described by Laseter [46] and others [81] as containing most of the contents of an organic chemical laboratory.

Hard water. When water is ingested, all of its components must be metabolized, catabolized, or excreted. In developed nations, the prevalence of many chronic diseases, particularly cardiovascular diseases, can be associated with various water characteristics related to hardness. Those involved include coronary heart disease, hypertension, and stroke. The theorized protective agents found in hard water are calcium, magnesium, vanadium, lithium, chromium, and manganese [55]. Recent studies report fewer heart attacks, less coronary disease and lower mortality rates in patients with existing cardiovascular disease in areas where there is hard water [25].

Soft water. Suspected harmful agents include the metals cadmium, lead, copper, and zinc which tend to be found in higher concentrations in soft water as a result of its relative corrosiveness. Nitrates in water pose immediate threats to children under 3 months of age. Excessive levels have been known to react with hemoglobin in the blood to produce methemoglobinemia. Though barium occurs naturally in the environment, it can enter water supplies through industrial waste discharges. Barium can bring about an increase in blood pressure and even death [19]. Patients susceptible to water contaminants may exhibit multiple sensitivities and be especially sensitive to airborne chemicals [68].
 
 

Food There are at least three aspects of food to consider in evaluating a patient’s cardiovascular health. These are (a) food sensitivity, (b) additives (natural and manmade toxins), and (c) the nutritive quality. Food sensitivity Involvement of the cardiovascular system in food sensitivities has been reported by a number of researchers. It was first shown by Hare [36] in 1905. He recognized tachycardia and bradycardia in patients following ingestion of some foods. Since then a variety of cardiovascular disease states have been reported to be related to food, including increased heart rates, angina pectoris, arrhythmias, myocardial infarction, extrasystoles and atrial and ventricular fibrillation [37]. Other reports have found phlebitis and vasculitis to be triggered by foods [69,75,89]. Food additives The widespread contamination of food supplies is witnessed by the increasing use of food additives, preservatives, and dyes in the manufacturing and processing of commercially available food products. Urticarial reactions, vascular abnormalities and immunological changes as a function of exposure to a number of chemicals and food additives have been reported by a number of authors [6,8,35,41,48,54,71,73,97].

Food constituents. Intake of high fat plus sugar in combination with additive-rich food will damage blood vessels yielding plaque deposition with resultant arteriosclerosis. Many discussions appear in the literature on this subject and it will not be further discussed here.
 
 

Air The physical factors of the weather include not only heat and cold but humidity, barometric pressure, electromagnetic and electric fields, seasons and weather cycles as well. It has been estimated that 25-30% of the population are sensitive to weather changes [38]. Some authors have suggested that triggering of cardiovascular disease including myocardial infarction may be related to the weather [17,38]. Outdoor air pollution Outdoor air pollution has long been thought to enhance disease processes. Prior to the 19th century, air pollution as we know it was virtually unknown. The term ‘smog’ was first used in England to denote a combination of smoke and natural fog, which may produce ill-effects [32]. The term is now used in all industrialized countries but often denotes air pollution of vastly different compositions. For example, Los Angeles smog is largely composed of petrochemicals and their by-products [32], while in China it is composed mainly of coal effluent. According to Environmental Protection Agency studies [32], there has been no "fresh" air in the United States in 20 years! Contaminants involved in air pollution include inorganic chemicals (sulphur dioxide, carbon monoxide, nitrogen oxides, lead, etc.), organic chemicals (petroleum-derived hydrocarbons, etc.), particulates (pollen, molds, dust, car and factory emissions) and electromagnetic and electric emission [17].

London smog. A combination of weather inversions occurred in London during a four-day period in December 1952. The London-type smog of particulates, sulphur oxides, and fog caused approximately 4,000 deaths in the following week. Between 80-90% of the deaths were due to respiratory and cardiovascular disease which were mainly of a chronic nature. A majority of deaths occurred in people over the age of 65 years [93]. A similar incident occurred in Donora, Pennsylvania, A highly industrialized valley, during six-day period in October 1984. Out of a population of 44,000, 42% became ill and 18 deaths resulted [50]. This highlights the clinical effect of outdoor air pollution.

Indoor air pollution Historically, contaminated indoor air began with the soot on the ceilings of prehistoric caves resulting from open fires. Home air was very bad for health during the times of the great plagues and tuberculosis outbreaks. Changes in cleanliness in the home resulted in the virtual elimination of many diseases such as tuberculosis. More recently, the use of rapidly disintegrating synthetic materials, fossil fuels and pesticides, coupled with the sealing of buildings in an attempt to conserve fuel by prevention of heat loss, led to A new type of indoor pollution.

Electrical phenomena can also contribute to indoor air pollution. Sources of indoor electric fields include most electrical appliances ranging from electric blankets (250 V/m) to light bulbs (2 V/m) [5].

Time spend indoors. Typically, people spend more than 90% of their time indoors. Some contaminants have been found to be in higher concentrations indoors than outdoors. Indoor contaminants which have been found to be associated with health include aeroallergens, microorganisms, asbestos fibers, formaldehyde, pesticides, nitrogen dioxide, carbon monoxide, radon decay products, and tobacco smoke.
 
 

Electrical phenomena Although not strictly within the remit of this chapter, there seems little doubt that electromagnetic fields (EMF) can have clinical effects, and that EMF may contribute to the overall environmental load. This, in turn, may make patients more susceptible to chemicals in foods. Electrical fields Some natural areas of the earth have higher levels of EMF than others. These are found over water veins and geological faults. There are increased areas found radiating from the poles and widening over the equator [5].

High frequency emitters in the United States consist of the whole of the EMF spectrum including AM radio band (0.535–1.604 MHz) and FM and TV band (54–806 MHz). Low-frequency electromagnetic exposures emanate from the electrical power systems (60 Hz in the US, 50 Hz in Europe and the USSR). The main sources of indoor electromagnetic fields include hair dryers (10-25 gauss), electric shavers (5-10 gauss) and televisions (1-5 gauss) [5]. However, environmental exposures are very small compared with the 10-1V/m across a live cell membrane [5].

Clinical effects of electromagnetic fields Cardiovascular effects. Animals exposed to EMF may exhibit significant changes in electrocardiograms [7], sinus arrhythmia [7] and brachycardia [22,67]. Alterations in heart function such as falling arterial pressure [67] and increased heart rate [30] have been noted in humans. Both short- and long-term hypotensive effects have been reported [51] along with decreases in efficient cardiac output [23]. Autonomic nervous system dysfunction was reported in individuals who were continuously exposed to higher levels of EMF, whereas very low frequency exposures were found to cause neurovascular instability in some individuals [80].

Hematological effects. Changes in the cellular composition of blood of a variety of laboratory animals exposed to EMF have been shown. Changes in number of red and white blood cells have been noted and the changes were found to be dependent on time and the magnitude of the EMF. A variety of other changes in hematological parameters in response to EMF have been reported and are discussed elsewhere [34,43,45,50,80]. These include changes in iron metabolism, fibrinolytic activity and coagulation [45].

Charged electrical conditions Negative ions have been shown to affect the carbon dioxide combining power of plasma and to increase blood pH [95,96]. Stimulation of heart rate and cortical alpha-rhythm [20,79] with decreases in alpha-frequency have been seen in humans exposed to air ions of either polarity. Increases in blood pressure and 17-ketosteroids under positive ionization have been noted accompanied by cholesterol decreases. Tchijevsky [87] and Vasiliev [91] proposed as a mechanism the penetration of charged particles through the alveolar wall into the blood vessels where the charges are transferred to blood cells and colloids. MECHANISMS OF ENVIRONMENTALLY INDUCED VASCULAR DAMAGE There are probably numerous ways that environmental pollutants trigger vascular responses while disturbing the immune and biological detoxification systems. Effects on vessel walls As the pollutants enter the body, they may create free radicals [52]. These may be O-, OH+, lipid peroxide or others and may damage mitochondrial and cellular membranes of the vascular tree causing vessel leakage.

According to Zeek [99], vessel wall damage may be mild with leak of fluid, but as it progresses the leaks get larger allowing red blood cells to migrate. With severe damage to the wall, clotting may occur giving distal peripheral tissue damage.

Attempts at healing may occur in various ways leading to granulomatous or fibrous scar formation. Triggering agents may be infectious (bacteria, virus, fungi, parasitic), chemical (sulphur dioxide, phenol, hydrocarbon), [65,70] nutritional [70] or traumatic (physical environmental agents, as discussed above). Effect on the clotting system Countless medical and surgical procedures have been associated with chemically triggered reactions. Nickel sensitivity has been reported secondary to the use of skin clips, and in a patient with a nickel steel heart valve who developed valve thrombosis. All synthetic heart valves and artificial hearts and lungs are known to be able to trigger the clotting mechanism. Hemolysis has been associated with necrotizing dermatitis, and this can occur after exposure to the epoxy resin in needles and polyvinyl chloride tubing. Effect on cells Some chemicals like dichlorodiphenyltrichloroethane (DDT) suppress the mast cells so thoroughly that anaphylaxis is less likely to occur [28,29].

Cadmium can suppress the mononuclear phagocyte system [3]. Ozone can cause lipid plastic parathyroiditis with leukocytic infiltration and capillary proliferation [83]. Some substances such as phenol have an affinity for the cardiovascular system [56]. Yervick [98] demonstrated cardiovascular changes in sea animals exposed to oil spills. Chloracne perivasculitis lesions have been produced in monkeys fed a pesticide, Arochlor 1248 (polychlorinated biphenyl).
 
 

Types of mechanisms in vascular damage

Immune mediated

The intrinsic mechanisms by which blood vessels are damaged can be mediated either via the immune system or via the nonimmune biological detoxification system The immune hypersensitivity responses in the vessel wall can be any of four types and frequently can be a combination of types.

Type I hypersensitivity is mediated through the IgE mechanism on the vessel wall. The classic examples are angioedema, urticaria and anaphylaxis due to sensitivity to pollen, dust, mold or food [89].

Type II cytotoxic damage may occur with direct injury to the cell. A clinical example of this is seen with exposures to mercury [31], although this might be directly toxic rather than antibody mediated.

Type III immune complex syndromes include lupus vasculitis. Numerous chemicals including procaine amide [78] and chlorothiazide [78] are known to trigger the autoantibody reactions of lupus. Other chemicals such as vinyl chloride [47] will produce microaneurysms.

Type IV cell-mediated immunity occurs with sensitization and stimulation of T lymphocytes. Numerous chemicals such as phenol, pesticides, organohalides, and some metals will also alter immune responses possibly triggering lymphokines giving a Type IV reaction [94]. Clinical examples are polyarteritis nodosa, hypersensitivity angiitis, Henoch Schönlein purpura and Wegener’s granulomatosis [69]. Nonimmune mechanisms: mediators Nonimmune triggering of the vessel wall may also occur. Complement may be triggered directly via the alternative pathway by molds, foods, or toxic chemicals [73]. Mediators like kinins and prostaglandins may also be directly triggered. Interestingly, in addition to allergic responses, pollens have been shown to have toxic substances which will trigger hemolysis and other responses [27]. Endocrine effects in the vascular system Estrogen has long been known to have a mildly suppressive effect on the cardiovascular system. The late onset of arteriosclerosis in females with the onset of menopause is commonly observed. A study by Couch and Wortman [13] supports this observation in that they found a significantly greater number of occurrences of migraine in pathologically anovulatory females (polycystic ovary, galactorrhea, amenorrhea) compared with pregnant women or women taking the contraceptive pill. It was suggested that this might also be due to hypothalmic problems [13]. Excess estrogen has been shown to have an adverse effect on vessel walls giving rise to venous inflammation which results in thrombophlebitis and pulmonary emboli [13]. Neurogenic vascular responses to external stimuli When A noxious stimuli are first detected there is a retrograde impulse to the dorsal nerve root ganglia through the afferent fibers of peripheral nerves (slow C or rapid delta A), or the gastrointestinal plexus. The sensory neurotransmitter, substance P, will cause immediate vasodilatation and increased permeability of the microcirculation in the area of the nerve and activate the non-IgE-mediated release of histamine via the mast cells. In addition, the release of leukotactic factors and leukotrienes is stimulated. Somatostatin is released in other cells of the dorsal root, but can also be released from the central nervous system and the pancreas. The relationship between somatostatin and substance P is complicated and both have effects on other cell interactions. Clinical manifestations of vascular injury Vascular injury gives rise to a variety of clinical manifestations depending on the types of vessels involved (vein, capillary, large or small artery) and the intensity and duration of the insult. Hypersensitivity vasculitis The hypersensitivity vasculitides are a group of disorders characterized by small vessel inflammation. Manifestations are often mild and self-limited. Although any organ can be involved, the most common is the skin, lesions being found on the buttocks, ankles, and legs. Causes for some of these have now been found. Theorell [89] showed occurrences of purpura and other signs of vasculitis after challenge with molds, cedar, and some foods. We have observed such vascular lesions after challenge with phenol, formaldehyde, and beef Hypersensitivity vasculitis is a diverse group of disorders including serum sickness reactions, Henoch-Schönlein purpura, essential mixed cryoglobulinemia and the connective tissue diseases particularly rheumatoid and lupus vasculitis [40].

Foreign serum proteins can cause serum sickness reactions and similar reactions may occur after use of penicillin [85], sulphonamides [77], streptomycin [11], thiouracils [11], and hydencompounds [11]. We have seen a case of Henoch-Schönlein purpura triggered by pollen, dust, molds, foods, and chemicals.

Periarteritis nodosa (PAN) Periarteritis nodosa generally follows a prodromal fever with arthralgia and malaise; it may manifest itself as acute gastrointestinal distress, myocardial infarction, neuritis, muscle pain, and/or gangrene of the extremities. It generally presents in the muscular arteries involving all three layers of the arterial wall and adjacent veins and is usually segmental.

Biopsy. Biopsy of skin, subcutaneous nodules or smooth muscle reveals acute healing vasculitis without giant cells. The infiltrative process involves polymorphonuclear leukocytes, eosinophils, and edema followed by fibrinoid necrosis. The areas of fibrinoid necrosis are subsequently replaced by fibroblasts and scar tissue is formed.

Systemic lupus erythematosus Apparently, many foreign substances can trigger a systemic lupus erythematosus-like syndrome. Chemical triggering of lupus has been well-established in the literature [88]. The following case report is an example of a patient whose symptoms were environmentally induced (Table 42.2).
Table 42.2

Case Report of A Patient with Systemic Lupus Erythematosus

Patient: 36-year-old white female
Symptoms: Vomiting, migraine, bruising, petechiae, peripheral edema
 
Patient
Control
Laboratory: Sedimentation rate

Total complement CH50

C-reactive protein

Total eosinophil count

Antinuclear antibody

LE test

48

181%

Positive

325

+

+

10 ± 10 mm/h

100 ± 20%

Negative

125 ± 75% m3

Triggering Molds

agents: Chemicals—phenol, formaldehyde, pesticides, chlorine, petroleum alcohol

Discharge Improving. Clear of symptoms without medication on discharge.

status:

Follow-up: Long-term follow-up (5 years)—Doing well without medications.

Occasional mild symptoms following acute exposures.


  Case study 1. A 36-year-old, white female had developed recurrent bouts of vomiting at the age of 5; these gave way to migraine at the age of 11 and the latter persisted. At the age of 16 she developed a polyarthritis, and a diagnosis of system lupus erythematosus (SLE) was made. Her disease progressed over the next several years, with further involvement of the gastrointestinal, genitourinary, respiratory, and vascular systems. Spontaneous bruising and petechiae occurred, together with peripheral edema. She was eventually placed on cortisone and cytotoxic drugs. Antinuclear antibodies and LE preparations were positive on numerous occasions. She was placed in the environmental control unit, and all medications were discontinued. The stiffness and swelling of her joints gradually disappeared. Her sedimentation rate fell from 63 to 15 mm. This was the lowest it had been for many years. The circumference of her fingers diminished by 1.5-2 cm while fasting, reflecting the massive decrease of edema. She was able to open and close her hands for the first time in many years. Challenges with 20 out of 30 different foods precipitated a return of her symptoms. The inhalation of chemicals such as perfume, phenol, and natural gas also triggered symptoms. She has done well without medications on an avoidance programme for several years. Wegener’s granulomatosis PAN is closely related to Wegener’s granulomatosis, which is characterized by necrotizing granulomas in the respiratory tract and vasculitis of the medium-size arteries, veins, arterioles, and venules. The onset may be acute or chronic. Though pathologically well defined, the etiology of the disease is still obscure. Recent studies indicate that is worthwhile looking for incitants. Rheumatoid vasculitis Diseases such as rheumatoid arthritis exhibit a variety of vascular manifestations and biopsy evidence of vasculitis. Although the etiology of this disease is generally not known, evidence of immune changes in patients with rheumatoid arthritis following food and chemical challenges has been found out. Two controlled series have been reported defining triggering agents in rheumatoid arthritis [44, 58] and a recent report has clearly shown the efficacy of diet in rheumatoid arthritis [15]. Eosinophilic vasculitis Eosinophilic vasculitis has now been reported in some disease processes, i.e., eosinophilic granulomas and Goodpasture’s syndrome. Lymphocytic vascular inflammation has been seen in some infectious diseases [58] and other syndromes [44]. Diagnosis of vasculitis A variety of laboratory tests can be performed with the most relevant ones being indicated by clinical experience. Angiograms should be carried out to rule out fixed lesions as required. Frequently, spasm will be seen if the larger vessels are involved. If skin lesions are present, biopsies may show either necrotizing vasculitis with polymorphonuclear leukocyte infiltration or non-necrotizing lesions with eosinophils and/or lymphocytes around or in the vessel wall. However, only active lesions are likely to be positive when biopsy of the petechiae and bruises is done.

Challenge tests. Challenge tests should be done to define triggering agents. These may be done via oral, inhaled, and/or interdermal routes. Care should be taken to do challenge tests under steady-state environmental conditions in order to reduce variability.

Environmental control unit. The use of an environmental control unit with its reduction of pollutants in air, food, and water can lead to the most precise diagnosis and treatment for the environmental aspects of cardiovascular diseases, and is particularly useful for the severely compromised patient. Since these units are not commonly available, controlled areas in hospitals and offices may have to be used as a less satisfactory substitute. An improvement on reduction of the total load with deterioration on subsequent challenge is the key to diagnosing triggering agents of cardiovascular disease.
 
 

CLINICAL SYNDROMES

Vasculitis

Small vessel vasculitis

Rea et al. [17] described a group of patients with multisystem involvement distinguished by a wide variety of symptoms. All evidenced frequent peripheral vasospasms, spontaneous cutaneous bruising, and/or petechiae and peripheral edema.

Following challenge, most patients produced a sequential progression of symptoms of color change of the hands, feet, nose, and skin, followed by pulse alteration, periorbital and peripheral edema, petechiae, and/or spontaneous bruising. Biopsies showed perivascular lymphocytic infiltrates.

Large vessel vasculitis Large vessel involvement associated with sensitivities has also been reported [18,33]. Rea detailed the case of a 65-ear-old female who exhibited large-vessel involvement. She was found to be sensitive to ten foods and three synthetic chemicals. All appeared to trigger spasm of her femoral arteries [74].

Large vessel vasculitis may ultimately have more devastating results than other vascular disorders since the blood supply to major organs is affected. Organ ischemia and/or necrosis may result in severe disability or even death. The author has now seen five patients with spastic carotid phenomena resulting in transient cerebrovascular accidents.

Case study 2. One patient with large-vessel involvement was a 42-year-old surgeon who developed involuntary arm movements, accompanied by asthma-like symptoms, spontaneous bruising, petechiae and acneiform lesions [33]. A carotid arteriogram revealed a decrease in left carotid and left intracerebral flow due to arterial spasm. Double-blind challenges with foods and synthetic chemicals revealed the following sequence of events: (a) immediate right-sided peripheral cyanosis, (b) tenderness in left neck, © decrease of superficial temporal pulse, (d) loss of use of right arm and hand followed by (e) severe digital edema accompanied by very foggy thinking and memory loss.

Vasculitis: Raynaud’s disease? Raynaud’s disease refers to any localized peripheral digital vascular spasm or collapse of unknown etiology. It may lead to gangrene [74].

Triggering agents can be identified and culprits include both foods and chemicals. One patient’s symptoms could be reproduced by challenge with multiple foods and five inhaled chemicals. Follow-up over an 8-year period showed total clearing of the problem with exacerbations occurring only when massive exposures occurred.

Recurrent phlebitis Conner (in [37]) noted two patients whose phlebitis was triggered by fish and citrus fruits. Others have identified numerous triggering agents including foods, chemicals and inhalants. It has become apparent that, in many patients, phlebitis is only part of a more generalized and severe vasculitis [74]. A study of 10 patients (see Table 42.4) treated in an environmental control unit (ECU) shows that symptoms can generally be reproduced following the relevant challenge and that treatment is effective both in the short-term and the long-term. The treated group showed a remarkable improvement in walking distance and exercise on a stationary bicycles (Tables 42.3 and 42.4). These results have both clinical and important financial implications, since all 10 of the treated patients were able to return to work whereas only 1 out of the 10 patients with triggering agents not defined was able to do so.
Table 42.3

Thrombophlebitis: Associated Signs and Symptoms and Results of Challenge Studies in 10 Patients in an Environmental Control Unit

Associated Signs and Symptoms Offending Agents Phlebitis Reproduced
1. Diarrhea, pulse increase (30 beats/min), nasal congestion, bigeminy, multifocal premature ventricular contractions Beef, chicken, cigarette smoke, shrimp, pork, gas heat, ingested chemicals Pork, shrimp, inhaled chemicals
2. Vomiting, pulse increase Wheat, rice, inhaled chemicals No
3. Wheezing, rhinorrhea, red nose, nasal stuffiness, tender muscles, cystitis Corn, cane sugar, eggs, inhaled chemicals Corn, eggs, inhaled chemicals
4. Peripheral pulse from 1+, tachypnea, shortness of breath, cyanosis, belching Beef, potatoes, corn, ingested chemicals Beef, corn, inhaled chemicals
5. Edema (generalized), tender muscles, colitis, dizziness Pork, pork fumes, ingested chemicals, inhaled chemicals  
6. Syncope, wheezing, muscle tenderness, hives, paroxysmal atrial tachycardia Legumes, seafood, cane sugar, wheat, chicken, cigarette smoke, inhaled chemicals Cigarette smoke, ingested chemicals, inhaled chemicals, seafood
7. GI bloat, belching, premature ventricular contractions, ventricular tachycardia Beef, chicken, lettuce, ingested chemicals, inhaled chemicals Wheat potatoes
8. Decrease in pulse left arm only, left neck and arm tenderness, tender over arm veins Turkey, chicken, peas, beef, cigarette smoke, inhaled chemicals No
9. Dyspnea, wheezing, eyes watering, hoarse, pulse increase (50 beats/min) Coffee, peanut butter, cane sugar, chemicals Apple, corn, wheat, inhaled chemicals
10. Cystitis, diarrhea, skin rash, itching, dyspnea, pulse increase Corn, wheat, beef, eggs, inhaled chemicals Chicken, beef, inhaled chemicals
Table 42.4

Results of Thrombophlebitis Treated in an Environmental Control Unit

 
Exercise
 
Phlebitis
Before Treatment
After Treatment
 
Cleared
Reproduced
Times walking around a 10 x 10 ft room
Exercycle miles at 150 kpm resistance
Walking round a 10 x 10 ft room
Exercyle miles 150 kpm resistance
ECU
10
8
0.5
0
36.6
2.85
Control
0
10 (continued)
2.1
0
3.1
0

 

Cardiac arrhythmias

Food and chemical inhalation and ingestion can cause cardiac arrhythmias or coronary spasm [82,86]. The causal role of coffee and cigarettes in the triggering of atrial arrhythmias is well-known. Pollutants can also harm the heart [73].

Details of 12 patients and their cardiovascular response to chemical exposure are shown in Table 42.5.

Table 42.5

Reaction to double-blind exposure to fumes of chemicals (1-15 minute exposure) (ambient dose) in environmental control unit

Patient
Saline control (3 challenges)
Petroleum alcohol <0.5 ppm
Phenol <0.002 ppm
Chlorine <0.33 ppm
(Mixture) pesticides <0.134 ppm
Pine-scented floor wash
Formal-dehyde <0.2 ppm
Arrhythmia spectrum
1
-
+
+
+
+
+
+
Sinus tachycardia

(above 130/min)

10
2
-
+
+
+
-
+
+
Sinus bradycardia

(below 45/min)

10
3
-
-
+
+
+
+
-
Sinus arrhythmia
11
4
-
-
+
+
-
+
+
Atrial fibrillation (PAT)
4
5
-
+
+
+
+
+
-
Coronary sinus rhythm
12
6
-
+
+
+
+
+
-
1 AV block
8
7
-
+
+
-
-
+
+
PVC
8
8
-
+
+
+
+
+
+
Ventricular tachycardia
2
9
-
+
+
+
+
-
-
   
10
-
+
+
+
+
+
+
   
11
2-,1+
-
-
-
-
-
-
   
12
-
-
-
-
-
-
-
   

 
 
  Case study 3. An undertaker had a myocardial infarct at the age of 35 and a quadruple bypass operation oat the age of 37. This did not clear his recurrent chest pain and ventricular arrhythmias, and he was refractory to medication. In addition, this patient had recurrent sinusitis, bronchitis, and gastrointestinal upsets. After 5 days in the ECU he became symptom-free, in sinus rhythm and on no medication. Following the ambient dose bronchial challenge with formaldehyde (<0.2 ppm), the patient sequentially developed rhinorrhea, sinus pain, coughing, chest pain, and ventricular ectopic beats. He continued to run his business in an office distant to the mortuary.

Case study 4. A 45-year-old, white male had a 6-month history of uncontrollable bradycardia-tachycardia syndrome with associated irritable bowel syndrome. Following challenge with phenol, he developed bradycardia and then sinus arrest. On another occasion he responded to a natural gas exposure with a tachycardia of over 200 beats/min for over an hour.
 
 

TREATMENT Systematic avoidance treatment for inflammatory vascular disease can now be used in addition to drug therapy. The two should go hand in hand, but avoidance with removal of triggering agents should be emphasized. This has been the cornerstone of treatment of infectious disease and applies as well to other noninfectious inflammatory diseases.

The best mode of treatment and prevention of most cardiovascular disease is avoidance of incitants and replacement of nutrients.

Avoidance

Acute reactions

Acute reactions triggered by a sudden exposure can best be treated by avoidance or removal of the offending substance(s). This can be done by placing the individual in a less polluted office, room at home, or hospital. If the toxin is ingested, treatment should be given as outlined in Table 42.5. Rapid institution of these procedures within the first 1-2 hours after exposure will usually stop an acute reaction and allow the patient to return to his basal state. This regime may be effective up to 24 hours after an acute exposure.
Table 42.5

Treatment of Acute Reactions

Laxative
Oxygen 40-100% for 2 hours
Sodium bicarbonate, 50 mEq i.v.
Vitamin C 7.5-15 g i.v.oral to GI tolerance (oral 2 tsp.)

 

Chronic inflammatory vascular disease

The treatment of recurrent inflammatory vascular disease (whether it be phlebitis, arthritis or vasculitis) again involves avoidance of as many triggering agents as possible. This can be done by drinking less-polluted water (spring, distilled, charcoal-filtered), and eating less-contaminated food (less additives, preservatives, pesticides, etc.). If a patient has a food sensitivity (usually non-IgE-mediated), avoidance of those foods is necessary. Injection therapy is usually needed. An oasis in the home For severely affected patients an oasis should be created in the bedroom removing all possible pollutants including pesticides, fossil fuels, carpets, toxic mattresses, formaldehyde-saturated plywood, particle board, etc., synthetic and dry-cleaned clothes and curtains. Some severely ill patients may have to change jobs or areas of work. Complete cessation of smoking in the home is mandatory. Nutrition

Nutritional deficiencies

Correction of nutritional deficiencies is important when trying to correct vascular damage.

Vitamin C. Vitamin C can be depleted with chemical exposures particularly to substances like benzene [1,42], carbon monoxide [10], ethanol, smoking [2], nitrous compounds [94], vinyl chloride [94], heavy metals [94], and pesticides [46]. Amorphous ground substance of the vessel wall is somewhat dependent on vitamin C. Vitamin C supplements can be used not only to strengthen the blood vessel wall but also as a free radical scavenger and antioxidant [60]. Usually a dose of 1-10 g per day of powdered vitamin C has been used in patients with vascular dysfunction. One must be careful of the source since many individuals become intolerant of the food of origin, such as corn, sago palm, potato, and carrot.

Vitamin A. ß-Carotene (precursor of vitamin A) is used as a potent antioxidant and has been shown to positively affect free radical activity. Up to 5,000 units daily has been used in our center without side-effects. The patients with vascular acne-like lesions sometimes will respond to vitamin A-cis-retinoic acid. Care has to be taken in order to avoid multiple potential side-effects [63]. Careful monitoring of vitamin A compounds should be carried out to avoid liver damage. Vitamin A has been shown to blunt the effects of radiation, probably through its free radical scavenger effect [66]. It should not be taken for a long period of time without attempting to find the triggering agents.

Vitamin D. Vitamin D is needed to help regulate calcium metabolism. Those who live in northern climates have more difficulty generating vitamin D due to less exposure time to the sun. It has been shown that those persons living where oxidant pollutant levels are high may have a concomitant decrease in vitamin D accumulations by as much as 15% over a 25-year period. Pasteurization also eliminates vitamin D. Supplementation must be carefully monitored in order to avoid toxicity. The safest therapy is exposure to sunlight [62].

Vitamin E. Vitamin E has been used in some vascular patients. It has been shown to be an effective antipollutant. From 400 to 1,400 units has been used [16].

Calcium. Calcium is clearly one mineral that is necessary for membrane stability and thus vascular wall tone. It is also a cofactor in many metabolic steps. Calcium level has been found to be inversely proportional to radiostrontium, thus it would be of use in protecting a patient against this pollutant. One to three grams of calcium have been given daily to patients with vascular disease without problems. Many forms have been used due to the patient’s sensitivity. These are calcium plus magnesium, calcium chloride, calcium gluconate plus calcium carbonate. The complications of excess calcium ingestion are well-known.

Magnesium. Magnesium is a membrane stabilizer. It is complexed with ATP and ADP and therefore is a mandatory cofactor for all kinases and other enzymes with nucleotides as a substrate or product cytosol. Intravenous challenge is necessary occasionally to correct a total body deficiency. Magnesium is an integral factor for vascular membrane function. Up to 500 mg may be used. A combination of calcium and magnesium in a 2 or 3 to 1 ratio may be necessary [64].

Zinc. Zinc is needed for wound healing. Zinc supplements are capable of reducing lipid peroxidation. Because of this, zinc loading has been found to stabilize cell membranes. It has reduced the damage induced by carbon tetrachloride in animals. Zinc also catalyzes many other metabolic reactions in the body. Up to 45 mg of elemental zinc has been used in patients with vascular disease without problems [63].

Selenium. Selenium has immune stimulating properties. It enhances the capacity of PHA to increase blastogenic transformation of lymphocytes [53,59]. Up to 300 µg of selenium has been given safely. It is necessary for many biochemical detoxification reactions [59]. Care should be taken to avoid overdose since severe toxic symptoms of weakness and muscle pain may occur [53].

Drugs Prednisone (10 mg four times daily) may be given and usually will diminish reactivity in some patients by the anti-inflammatory and immunosuppressive properties. Just as often prednisone will aggravate the problem making the patient much worse. The complications of long-term use of prednisone are well-known and will not be discussed here.

Cytotoxic agents have been used in some patients with leukocytoclastic vasculitis. Cyclophosphamide has been used but may not induce a significant long-term remission since the patient is well into fixed end-stage disease at this point.

Immunostimulants such as transfer factor have been used by a few groups. We have a small group of patients who appeared to respond to biweekly injections of transfer factor. However, no patient was totally cleared of his vascular malady. Levamisole and thymosin have been suggested as immune stimulants. No reports, however, were found in the literature of their use in vascular disease. Exercise Exercise as a treatment for cardiovascular disease is like a double-edged sword. When used early in the preventive and treatment cycle, it may well blunt reactions and exclude incitants from harming the vessel wall. When it is used later in the disease process the vasculitis patient responds just as in exercise-induced asthma. We have seen many patients attempting to exercise in a late stage of vascular disease only to be incapacitated with muscular aches, dizziness, and weakness. It is well-known that marathon runners who ignore their cardiac signs and symptoms can die suddenly. Clearly, exercise in moderation appears to help strengthen the cardiac muscle in other patients. CONCLUSION The prospect for the future is very bright. A concept and method has now been established for the scientific definition of chemical and food triggering agents for inflammatory cardiovascular diseases including spastic vascular phenomena such as migraines and other vascular headaches, angina due to coronary spasm, Raynaud’s disease, etc., many autoimmune vasculitides, i.e., lupus, rheumatoid and other early collagen vasculitis, in addition to small and large vessel vasculitis with Henoch-Schönlein purpura, etc., cardiac arrhythmias and nontraumatic phlebitis. Thee are now many articles in the scientific literature supporting the view that cardiovascular diseases can be caused by reactions to food and environmental irritants. REFERENCES 1. Askari, E.M, and J. Galiks. DDT and immunological responses. I. Altered histamine levels and anaphylactic shock in guinea pigs. Arch Environ Health 26(6):309-19, 1979.

2. Astaldi, G., D. Karanoic, P.P. Vettori, et al. Phytochemagglutinin (PHA) stimulation of peripheral-blood lymphocytes and stem cell. Biol Ist Seroten Milanesi 53:599, 1974.

3. Barnes, D.W., and A.E. Munson. Cadmium-induced suppression of cellular immunity in mice. Toxicol Appl Pharmacol 45(1):350, 1978.

4. Bass, H.N., and B.F. Hildreth. Paroxysmal atrial fibrillation and exposure to smoke. Lancet i:1036, 1979.

5. Becker, R.O., and A.A. Marino. Electromagnetism and life. Albany: State University of New York Press, 1982.

6. Bell, I., and D. King Psychological and physiological research relevant to clinical ecology: An overview of the recent literature. Clin Ecology 1(1):np, 1982.

7. Blanchi, D., L. Cedrini, F. Ceria, et al. Exposure of mammals to strong 50-Hz electric fields. Arch Fisiol 70:33, 1980.

8. Bjorkner, BH. Sensitization capacity of acrylated prepolymers in ultraviolet curing inks tested in the guinea pig. Acta Derm Venereol (Stockh) 61(1):7-10, 1981.

9. Bunter, R.G., J. H. Carroll, and J.C. Randolph. Water in the urban environment: Real Estate Lakes. US Dept of Interior/Geological Survey, 11-19, 49. Pestic Monit J 14(3):102-7, 1980.

10. Calabrese, E.J. Pollutants and high risk groups: The increased human susceptibility to environmental and occupational pollutants. New York: John Wiley and Sons, 1978.

11. Cluff, L.E. Serum sickness and related disorders. In Harrison’s Principles of Internal Medicine. Ed. M.M. Wintrobe, G.W. Thorn, and R.D. Adams, et al. 374-6. New York: McGraw-Hill, 1970.

12. Collman, J.D. Diseases of the peripheral vessels. In Textbook of Medicine, 14th ed. Ed. P.B. Beeson, and W. McDermott, 1076.. Philadelphia, PA: W.B. Saunders, 1975.

13. Couch, J.R., and J. Wortman. Anovulatory states as a factor in occurrence of migraine. Paper presented at The Migraine Trust, Fifth International Symposium, Sept. 1984.

14. Crapo, J.D., K. Sjostiam, and R.T. Drew. Tolerance and cross-tolerance using NO2 and O2. I. Toxicology and biochemistry. Appl Physiol 44:364, 1978.

15. Darlington, L.G., N.W. Ramsey, and J.R. Mansfield. Placebo-controlled, blind study of dieatry manipulation therapy in rheumatoid arthritis. Lancet i:236-8, 1986.

16. Davis, A. Let’s Get Well. 41-2. New York: Harcourt, Brace, and World, 1965. 17. De Pasquale, N.P, and G.E. Burch. The seasonal incidence of myocardial infarction in New Orleans. Am J. Med Sci 242:468-78. 18. Dickey, J.W., Jr. Drifting hematomas. Surg Gynecol Obstet 148:209, 1979.

19. Environmental Protection Agency (EPA). Is your drinking water safe?

20. Erban, L. A study of biochemical and haematological changes under the application of ionized air. Int J Bioclimatol Biometeorol 3(vi):np, 1958. 21. Finn, R. Food allergy. Lancet ii:249, 1979. 22. Fischer, G., R. Waibel, and T. Richter. Influence of line-frequency electric fields on the heart rate of rats. Zentralbl Bakteriol Mikrobiol Hyg [B] 162:374, 1976.

23. Fischer, G., R. Waibel, and T. Richter. Influence of line-frequency electric fields on the heart rate of rats. Zbl Bakt Hyg, I. Abt Orig B 162:374, 1976.

24. Fisher, S.A. Dermatitis due to the presence of formaldehyde in certain sodium lauryl sulfate (SLS) solutions. Cutis 27(4):360-2, 366, 1981.

25. Fourth International Symposium on Magnesium and American College of Nutrition 26th Annual Meeting. 4(3):303-404, 1985.

26. Fregert, S. Irritant dermatitis from phenol-formaldehyde resin powder.Contact Dermatitis 6(7):493, 1980.

27. Freed, D.J.L., C.H. Buckley, Y. Tsiviori, et al. Non-allergenic haemolysis in grass pollens and housedust mites. Allergy 38:477-86, 1983.

28. Gabliks, J., E.M. Askari, and N. Yolen. DDT and immunological responses. I. Serum antibodies and anphylactic shock in guinea pigs. Arch Environ Health 26(6):305-8, 1975.

29. Gabliks, J., T. Al-Tubaidy, and E. Askari. DDT and immunological responses. III. Reduced anaphylaxis and mast cell population in rats fed DDT. Arch Environ Health 30(2):81-4, 1975.

30. Gann, D. Final report, Electic Power Research Institute Project RP 98-02. Palo Alto, CA. 31. Gaworski, C.L., and R. P. Sharma. The effects of heavy metals on (3H) thymidine uptake in lymphocytes. Toxicol Appl Pharmacol 46(2):305-13, 1978.

32. Gilpin, A. Air Pollution, 2nd ed. St. Lucia, Queensland: University of Queensland Press, 1978.

33. Grant, E.C. Oral contraceptives, smoking, migraine, and food allergy. Lancet ii:381-9, 1968.

34. Groza, P., E. Nicolescu, D. Laz’ar, et al. The influence of magnetic fields on some humoral parameters and on resistance to hyperthermia in rats. Physiologie 19(1):15-24, 1982.

35. Hanington, E. Diet and migraine. J Hum Nutr 34:175-80, 1978.

36. Hare, F. The Food Factor in Disease. Chapter 10. London: Longmans, 1905.

37. Harkavy, J. Vascular Allergy and Its Systemic Manifestations. Washington: Butterworths, 1963.

38. Heyter, H.E., H.C. Teng, and W. B. Barris. The increased frequency of acute myocardial infarction during summer months in warm climates. Am Heart J 45:741, 1953.

39. Hippocrates. On the theory and practice of medicine. Np: Citadel Press, 1964.

40. Katz, P. Hypersensitivity vasculitis. AFP 26(1):171-5, 1982.

41. Kleibel, K., and M. Rackova. Cutaneous allergic reactions to dithiocarbonates. Contact Dermatitis 6(5):348-9, 1980.

42. Kollwe, L.D. Altered immune response by environmental contaminants. International Symposium on Pathobiology of Environmental Pollutants: Animal Models and Wildlife as Monitors, CPI (59), Reg No. A7722, 1977.

43. Korobetson, M.A., and B.U. Malenuik. Glucocorticoids and the blood anticoagulation system under the effect of SHF-range electromagnetic waves. Kosm Biol Aviakosm Med 1213:60-3, 1978.

44. Kroker, G.F., R. M. Stroud, R. Narshall, et al. Fasting and rheumatoid arthritis: A multi-center study. Clin Ecology 2(3):137-44, 1978.

45. Kuksinsky, Vye. Coagulative properties of blood and tissue of the cardiovascular system following exposure to an electromagnetic field. JPRS 71595:1, 1978.

46. Laseter, J.L., I.R. DeLeon, W.J. Rea, and J.R. Butler. Chlorinated hydrocarbon pesticides in environmentally sensitive patients. Arch Clin Ecol 2(1):np, 1983.

47. Lelbach, W.K., and H. J. Marsteller. Vinyl chloride associated disease. Ergeb Inn Med Kinderheilkd 47:1-100, 1981.

48. Lindemayer, H., and J. Schmidt. Intolerance to acetylsalicylic acid and food additives in patients uffering from recurrent urticaria. Wien Klin Wochenschr 91(24):817-22. 1979.

49. McMillan, R. Environmental thrombocytopenic purpura. J Am Med Assoc 2(22):2432-5, 1979.

50. Marino, A.A., T.J. Berger, J.T. Mithcell, et al. Electric field effects in selected biologic systems. Ann NY Acad Sci 238:436, 1974.

51. Markov, V.V. The effects of continuous and intermittent microwave radiation on weight and atrial pressure of animals in chronic experiemnts. JPRS 63321:95.

52. Mustafa, M.G., and D.F. Tierney. Biochemical and metabolic changes in the lung with oxygen, ozone, and nitrogen dioxide toxicity. Am Rev Respir Dis 118:1061-90, 1978.

53. Martin, J., and J. Spallholz. Proceedings of the Symposium on Selenium-Tellurium in the Environment. 204-25. Pittsburg, PA: Industrial Health Foundation, 1976.

54. Monroe, E.W., C.I. Schulz, J.C. Maize, and R.E. Jordan. Vasculitis in chronic urticaria: An imunopathologic study. J Invest Dermatol 76(2):103-7, 1981.

55. National Research Council: Water hardness and health. In Drinking Water and Health. 439-47. New York: National Academy of Sciences, 1977.

56. Nour-Elden, R. Uptake of phenol by vascular and brain tissue. Microvasc Res 2:224, 1970. 57. Olsen, T. Peripheral vascular diseases, necrotizing vasculitis and vascular-related disease. In Dermatology, Vol. 1, 2nd ed. Ed. S.L.Moschella and H. J. Hurley. Philadelphia, PA, 1985.

58. Parish, W.R. Studies on vasclitis, immunoglobulins, b1C, C-reactive proteins and bacterial antigens in cutaneous vasculitis lesions. Clin Allergy 1:97-110, 1971.

59. Passwaters, RA. Selenium as Food and Medicine. 88-95. New Canaan, CT: Keats Publishing, 1980.

60. Pauling, L. Vitamin C, Common Cold, and Flu. 191-3. San Francisco: WH Freeman, 1976.

61. Pestic Toxc Chem News 12(32): np, 1984. 62. Pfeiffer, C.C. Mental and Elemental Nutrients. 199-202. New Canaan, CT: Keats Publishing, 1975.

63. Pfeiffer, C.C. Mental and Elemental Nutrients. 190-99. New Canaan, CT: Keats Publishing, 1975.

64. Pfeiffer, C.C. Mental and Elemental Nutrients. 277-9. New Canaan, CT: Keats Publishing, 1975.

65. Pollutants. In Clean up Your Room: A Compendium on Indoor Pollution. CA: Dept. Of Consumer Affairs, 1982.

66. Primer on allergy and immunologic disease. J Am Med Assoc 248:20, 1982. 67. Prokhvatilo, YeV. Reduction of functional capacities of the heart following exposure to an electromagnetic field of industrial frequency. JPRS 70101: 76, 1977.

68. Randolph, TG. Human Ecology and Susceptibility to the Chemical Environment. Springfield, IL: Charles C. Thomas, 1962.

69. Rea, W.J. Environmentally triggered small vessel vasculitis. Ann Allergy 38:245-51, 1977. 70. Rea, W.J. Elimination of oral food challenge reaction by injection of food extracts: A double-blind evaluation. Arch Otolaryngol 110:248-52, 1977.

71. Rea, W.J. Recurrent environmentally triggered thrombophlebitis. Ann Allergy 47:338-44, 1981.

72. Rea, W.J., and M.J. Mitchell. Chemical sensitivity and the environment. Immunol Allergy Prac Sept./Oct. 21-31:np.

73. Rea, W.J., and C.W. Suits. Cardiovascular disease triggered by foods and chemicals. In Food Allergy: New Perspectives. Ed. J. W. Gerrard. Springfield, IL: Charles C. Thomas, 1980.

74. Rea, W.J., I.R. Bell, and R.E. Smiley. Large vessel vasculitis. In Allergy: Immunology and Medical Treatment. Ed. F. Johnson and J.T. Spence. Chicago: Symposia Specialist, 1975.

75. Rea, W.J., R.E. Smiley, R.E. Edgar, et al. Recurrent environmentally triggered thrombophlebitis: A five-year follow-up. Ann Allergy 47:338-44, 1981.

76. Rea, W.J., J.R. Butler, J.L. Laseter, and I.R. DeLeon. Pesticides and brain-function changes in a controlled environment. Arch Clin Ecol 2(3):145-50, 1984.

77. Read, H., S. Holt, E. Housley, et al. Raynaud’s phenomeonon induced by sulphasalzine. Postgrad Med 56:106-7, 1980.

78. Romaquera, C. and F. Grimalt. Sensitization to benzoyl peroxide, retinoic acid and carbon tetrachloride. Contact Dermatitis 6(6):422, 1980.

79. Silverman, D., and I.H. Kornblueh. Effect of artificial ionization of the air on the electro-encephalogram. Am J Phys Med 36:352-8, 1957.

80. Smith, C.W. Electromagnetic phenomena. In Living Biomedical Systems, Frontiers of Engineering and Computing. Health Care Sept.15-16, 1984.

81. Spalding, R.F., G.A. Junk, and J.J. Richard. Water: Pesticides in ground water beneath irrigated farmland in Nebraska. Pestic Monit J I(2):70-3, 1980.

82. Spizer, F.E., D.H. Wegerman, and A. Ramires. Palpitation rate associated with fluorocarbon exposure in a hospital setting. N Engl J Med 272:624, 1975.

83. Stokingert, H.E. Ozone toxicology: A review of research and industrial experience: 1954-1964. Arch Environ Health 10:np, 1965.

84. Suhonen, R. Contact allergy to dodeayl-di-(amino-ethyl)glyane (Desimex I). Contact Dermatitis 6(4):290-1, 1980.

85. Svedham, A., K. Alestis, and M. Jertborn. Phelbitis induced by parenteral treatment with fluxoxacillin and doxacillin: A double-blind study. Antimicrob Agents Chemother 18:349-52, 1980.

86. Taylor, G.S., and W.S. Hern. Cardiac arrhythmias due to aerosol propellents. J Am Med Assoc 219:8, 1970.

87. Tchijevsky, A.L. Die Wege des Eindringens von Luftionen in den organismus und die physiologische wirkung von luftionene. Acta Med Scand 83:219-72, 1934.

88. Tumulty, P.A. Systemic lupus erythematosus. In Harrison’s Principles of Internal Medicine. Ed. J.M. Wintrobe, G.W. Thorn, R.D. Adams, et al. 1962-7. New York McGraw-Hill, 1977.

89. Theorell, H., M. Blombock, C. Kockum. Demonstration of reactivity to airborne and food antigen in cutaneous vasculitis by variation in fibrino peptide and others, blood coagulation, fibrinolysis, and complement parameters. Thrombo Haemo Sts (Stattz) 36:593, 1976.

90. Titus, J.M., and H-S Kim. Blood vessels and lymphatics. In Anderson’s Pathology, Vol. 1, eth ed. ED. J.M. Kissane. 684-729. St Louis: CV Mosby, 1985.

91. Vasiliev, L.L. Theory and Practice of Aeroionotherapy. Leningrad: University of Leningrad Press, 1951.

92. What Everyone Should Know about the Quality of Drinking Water. Greenville, MA: Channing L. Better, 1977.

93. Whehner, A.P. Electro-aerosols, air ions, and physical medicine. Am J Phys Med 48(3):119-49, 1969.

94. Winslow, S.G. The Effects of Environmental Chemicals on the Immune System: A Selected Bibliography with Abstracts. 1-36. Oak Ridge, TN: Toxicology Information Response Center, Oak Ridge National Laboratory, 1981.

95. Worden, J.L. The effect of unipolar ionized air on the relative weights of selected organs of the golden haster. Sci Stud 15:71-82, 1953.

96. Worden, J.L. The effect of air ion concentrations and polarity on the CO2 capacity of mammalian blood plasma. Fed Proc 13:557, 1954.

97. Wuthrich, B., and L. Fabio. Acetylsalicylic acid and food intolerance in urticaria, bronchial asthma, and rhinoplathy. Schweiz Med Wochenschr 1(39):1445-50, 1981.

98. Yervick, P. Oil pollutants in marine life. Eighth Advanced Seminar, Society of Clinical Ecology, Instatape, Tape II.

99. Zeek, P.M. Periarteritis nodos and other forms of necrotizing angitis. N Engl J Med 248:764, 1953.