Abba I. Terr

Effects of Psychosocial Treatment in Prolonging Cancer Survival May Be Mediated by Neuroimmune Pathways

Abstract: Research has provided growing evidence of links between the social environment and cancer progression. Indeed, social support in the form of marriage, frequent daily contact with others, and the presence of a confidant may all have protective value against cancer progression. Furthermore, retrospective data suggest that major stressful life events are more prevalent in patients with relapse or malignancy, and thus may contribute to cancer morbidity. Initial studies of the effects of psychosocial intervention with cancer patients have provided some promising results. In three randomized prospective trials, protective effects of psychosocial interventions on cancer progression have been confirmed, while one matching and one randomized study showed no survivial effect after psychosocial treatment. Though more research is clearly needed in this area, this body of evidence suggests that psychosocial factors have potentially powerful modulating effects on the course of disease. Here we review evidence of one possible mechanism whereby psychosocial factors may influence disease‐resistance capabilities: the neuro‐immune connection. Suppressive effects of stress on immune function are well documented, and these effects have been shown to be modulated by social support. Thus, it is reasonable to hypothesize that supportive social relationships may buffer the effects of cancer‐related stress on immunity, and thereby facilitate the recovery of immune mechanisms that may be important for cancer resistance. Data addressing this hypothesis are reviewed.

Stachybotrys: relevance to human disease.

LEARNING OBJECTIVES Recent public concern about the danger of environmental fungi has focused attention on one particular mold, Stachybotrys. The purpose of this review is to examine and critique the published literature on Stachybotrys for objective scientific and clinical evidence of disease caused by the presence of this fungal organism in the environment. DATA SOURCES Data were obtained from all published research and reviews of Stachybotrys indexed in MEDLINE since 1966. STUDY SELECTION The publications used for this review were those that contained information about human health effects of this microorganism. The critique of these publications is the authors. RESULTS Stachybotrys is a minor component of the indoor mycoflora, found on certain building material surfaces in water-damaged buildings, but airborne spores are present in very low concentrations. Published reports fail to establish inhalation of Stachybotrys spores as a cause of human disease even in water-damaged buildings. A possible exception may be mycotoxin-caused pulmonary hemorrhage/hemosiderosis in infants, although scientific evidence to date is suggestive but not conclusive. Based on old reports ingestion of food prepared from Stachybotrys-contaminated grains may cause a toxic gastroenteropathy. No convincing cases of human allergic disease or infection from this mold have been published. CONCLUSIONS The current public concern for adverse health effects from inhalation of Stachybotrys spores in water-damaged buildings is not supported by published reports in the medical literature.

Trends in Asthma Therapy in the United States: 1965–1992

BACKGROUND Many recent studies indicate an increasing morbidity and mortality of asthma in the past two decades. This study uses data from the National Disease and Therapeutic Index (NDTI) to document and analyze trends in drug therapy for asthma in the United States from 1965 through 1992. METHODS The NDTI maintains a continuous rotating national sampling of approximately 1% of US physicians in office-based practice proportionately representative of practicing generalists and specialists who report issuance of drugs in treatment by diagnosis for all patient encounters for a period of two days every 3 months. Annual summaries of five demographic categories and 14 drug categories, characterizing the asthma patient-physician encounters as percent of visits for the 28-year period of 1965 through 1992 are analyzed and characterized. RESULTS Physician visits for asthma treatment have shifted somewhat from generalists to specialists in internal medicine and pediatrics. Allergists treat a significant proportion of the asthmatic population. Most patients are seen in the office. There has been no significant change in rates of inpatient visits. Age distribution of the population of patient visits for asthma has been stable, but there is a steady drop in ratio of males to females. Since the mid-1970s, inhaled adrenergic bronchodilator prescriptions have been issued at a markedly increasing rate. Concurrently, issuance of xanthines and oral adrenergic drugs also rose dramatically but then decreased beginning in the mid-1980s. Corticosteroids are used in 15% to 20% of visits, but only recently has the inhaled route of administration shown prominence. Allergen immunotherapy for asthma has decreased more than 10-fold. Cromolyn is prescribed infrequently. CONCLUSIONS Major changes have occurred in drug treatment by physicians for asthma in the US since 1965. Bronchodilating drugs predominate, and they are being prescribed in more effective forms at a generally increasing rate. Corticosteroid use has increased at a slower rate and in smaller proportion of patient-visits, while allergen immunotherapy has dramatically declined. The male-to-female ratio of asthmatic patients who visit doctors for treatment appears to be decreasing.

Multiple Chemical Sensitivities

Multiple chemical sensitivities has been proposed as a name of a new disease in which the affected patient has adverse reactions when exposed to numerous items encountered under ordinary, daily conditions. The items, referred to as chemicals, include organic solvents, pesticides, paints, new carpets, household detergents, new clothing, building construction materials, and many others. Reactions consist of subjective symptoms without accompanying physical signs or biochemical abnormalities. Patients have many and varied symptoms, but the ones they report most frequently include fatigue, malaise, headache, lack of concentration, memory loss, and spaciness. Many of these patients report similar intolerances to many foods and almost all drugs. In a few cases, the onset of illness appears to coincide with a reported single high-dose exposure to a specific chemical, usually in the workplace. This subgroup of patients has been particularly perplexing to specialists in occupational medicine [1]. Multiple chemical sensitivities was first proposed as a new disease in the 1950s, at which time it was called environmental illness [2]. For many years, proponents of the existence of environmental illness, or multiple chemical sensitivities, have theorized that the disease results from an immunologic dysfunction caused by inhalation of fumes from various chemicals. The chemically induced toxic damage to the immune system is postulated to then lead to sensitivities to other chemicals [3]. Recently, a neurologic dysfunction theory has emerged as an alternative explanation of multiple chemical sensitivities [4]. This theory proposes that inhaled chemical molecules travel along the olfactory nerve to the forebrain, the hypothalamus, and other parts of the limbic system. The many symptoms and alterations in mood and thought processes that these patients experience are thought to be of neurotoxic origin, and reactions to other chemicals are explained on the basis of kindling. The phenomenon of multiple chemical sensitivities as a disease has generated widespread skepticism among clinicians who encounter patients with this diagnosis [5]. Seasoned internists, other primary care physicians, and specialists recognize in these patients an all-too-familiar pattern of over-utilization of medical diagnostic facilities because of many longstanding unexplained symptoms. The only thing that distinguishes environmental illness or multiple chemical sensitivities from this pattern is the attribution of symptoms to environmental exposures. A series of clinical investigations of patients with multiple chemical sensitivities, including the one by Simon and colleagues [6] in this issue of Annals, now provides a reasonably coherent medical picture of the multiple chemical sensitivities phenomenon. Immunologically, these patients are functionally intact [7]. As a group they display no deficiency or excess in their ability to mount appropriate immune responses, nor do they suffer an excess prevalence of unusual or opportunistic infections, allergic reactions, autoimmune disease, or cancer [8]. Because of the absence of consistent physical, biochemical, or immunologic abnormalities, most studies have focused attention on a possible psychiatric cause. Although selection bias and small numbers of patients suggest the need for some caution in interpreting these studies, it is clear that diagnosable psychiatric illness is common in patients with this disorder [9-12]. Early studies suggested that the multiple chemical sensitivities entity was merely undiagnosed somatoform illness [9, 13]. Later reports, however, documented that anxiety, depression, panic disorder, schizophrenia, and affective disorders, with or without somatization, could be diagnosed in most patients [10-12]. Does this mean that common everyday environmental chemicals cause a group of disparate mental illnesses? Probably not; psychological testing of patients with multiple chemical sensitivities, as reported by Simon and colleagues and others, reveals a substantial number with preexisting diagnosable psychiatric illness. Other investigations that analyzed the previous medical records of these patients point strongly to a much higher prevalence of preexisting psychiatric illness compared with that uncovered by current psychological tests [14]. The temporal association of symptoms with chemical exposure rests solely on patient reports. In most cases, awareness of an odor is the triggering factor. An odorant-induced learned response has been proposed to account for an expanding range of chemical sensitivities [15]. Thus, a pattern of increasing intolerance to common, familiar, and formerly innocuous environmental exposures, coupled with the iatrogenic suggestion of a serious underlying lack of immunologic protection, readily explains the anxiety, depression, fear, and frank panic experienced by patients with a diagnosis of multiple chemical sensitivities. The immunotoxic concept, however, can be acceptable to individuals with either a susceptible personality type or a preexisting psychiatric illness who then perceive their environment as physically harmful to them. The perception is reinforced by frequent media reporting of pollution incidents and environmental disasters and by inappropriate avoidance therapy prescribed by certain environmental physicians. These physicians typically recommend a variety of therapies of unproven worth [16, 17]. Central to their goal of preventing multiple environmental sensitivities are chemical avoidance strategies, often reaching extremes of social isolation and restrictive diets [18]. Detoxification franchises are appearing that offer a program of niacin-induced flushing followed by exercise and sauna combined with high-dose vitamin and fatty acid ingestion promoted as a means of ridding the body of foreign chemicals [19]. Vitamins, minerals, diets, intravenous globulin, and other medications are prescribed allegedly to enhance immunologic function. No clinical trials assessing safety or efficacy exist to support these measures. In fact, some evidence exists that patients worsen with such a treatment regimen [8]. Avoidance therapy, rotation diets, sauna detoxification, and various maneuvers to boost the immune system serve merely to reinforce a counterproductive behavior pattern. Investigation of multiple chemical sensitivities by proven methods of clinical science is a daunting endeavor. Clearly, more work needs to be done, but the existing data provide clinicians with a reasonable framework for dealing with these challenging patients who are disabled by factors that cause them no physical illness or physiologic impairment. The task is made all the more difficult by their mistrust of and hostility toward the medical profession in general. It is not necessary to offer advice to treat patients with multiple chemical sensitivities with sympathy and understanding, because compassion and respect should not be withheld from any class of patients. Scheduling regular visits, making extra time available for these visits, and establishing short-term, modest, workable goals aimed at reducing disability rather than focusing on specific symptoms is helpful. The temptation to order still another test when the going is rough should be resisted. Antidepressant medication and psychotherapy are rational approaches to current depression and anxiety, although these patients usually reject psychiatric intervention, which they often express in symptomatic intolerance to even low doses of antidepressant medications. Beyond these general suggestions, firm recommendations for specific treatment modalities must await results of definitive clinical trials. Based on the current knowledge of multiple chemical sensitivities, behavior modification therapy seems to be a good place to start.

Multiple Chemical Sensitivity Multiorgan Dysesthesia, Multiple Symptom Complex, and Multiple Confusion: Problems in Diagnosing the Patient Presenting with Unexplained Multisystemic Symptoms

Patients are presenting in increasing numbers with multiorgan symptoms allegedly resulting from exposure to environmental chemicals. Among the symptoms expressed by patients with alleged multiple chemical sensitivities (MCS) are profound fatigue, mental confusion, myalgia, depression, anxiety, dizziness, headache, insomnia, loss of appetite, and numbness of the extremities, all in the absence of objective physical signs. Diagnostic criteria to assess the effects of environmental agents on organ systems are sorely needed because patients with MCS often have no tissue pathology or physiological abnormalities, but often do have diagnosable psychiatric illnesses. In treating patients with MCS, the physician should first perform a complete history and physical examination, including a comprehensive evaluation of chemical exposure. If the findings strongly suggest the presence of disease related to particular organ systems, further diagnostic evaluation should be undertaken. If abnormal findings are absent, psychiatric advice may be useful. The physician should keep an open mind about MCS but must also remember that a cause-effect relationship between exposure to multiple chemicals and symptoms has not been established.

IgE antibodies in tick bite-induced anaphylaxis.

The western black-legged tick, Ixodes pacificus, parasitizes reptiles, birds, and mammals throughout western North America.’ In California, it is the primary hector of Borrelia burgdorferi, the spirochete causing Lyme disease, and may also carry Francisella tularensis and a rickettsia of the spotted-fever group. 2-1 Toxic local reactions are common, but systemic IgE-mediated reactions have never been documented.* With the exception of the Australian paralysis tick, I. holocyclus, allergic reactions to tick bites have not been reported.6 We recently described a patient who had recurrent anaphylaxis after bites with I. pacijicus.’ The study in this article revealed that his serum contained IgG and IgE antibodies to tick extract and that his basophils released histamine on challenge with the extract. Tick extract was prepared from unfed female I. pacijicus by pestling in a pool of liquid nitrogen. The powder was suspended in a small volume of 0.1 mol/L of carbonate buffer, pH 9.6, and vortexed at 4” C for 48 hours. After centrifugation at 15,000 g for 15 minutes, the supematant was aspirated and stored at 80” C. The extract was diluted in phosphate-buffered saline to a concentration of 40 pg/ml. For SDS-PAGE, the extract was dialyzed for 48 hours at 4” C against PAGE-running buffer (0.025 mol/L of Tris, 0.192 mol/L of glycine, and 0.1% of SDS). SDS-PAGE, ELISA, and an immunoblotting assay for tick-specific IgE and IgG were performed as previously described.’ Basophil-enriched blood leukocyte HR was performed by monoclonal ELISA, as

Effect of total lymphoid irradiation on IgE antibody responses in rheumatoid arthritis and systemic lupus erythematosus

Thirteen patients with rheumatoid arthritis and four patients with systemic lupus erythematosus and nephritis were treated with total lymphoid irradiation because of severe disease refractory to other forms of treatment. Serum samples before and after irradiation were tested for changes in total serum IgE and for changes in specific IgE antibodies to ryegrass pollen, dust mite, cat dander, and Alternaria. There were no statistically significant changes in total or specific IgE from lymphoid irradiation in these patients. The therapy caused a significant decrease in circulating total lymphocyte and Leu-3 (helper/inducer) T-lymphocyte counts. Therefore, reduction in circulating levels of helper/inducer T cells does not appear to influence preexisting levels of IgE antibodies.