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 author's. 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.

Differential representations of memory T cell subsets are characteristic of polarized immunity in leprosy and atopic diseases.

We identified functionally polarized subsets of CD4 memory T cells on the basis of the expression of CD11a, CD45RA and CD62L. Within the several phenotypically distinct subsets of CD4 memory cells are two that, upon stimulation, produce primarily IL-4 (MT(2), CD45RA(-)CD62L(+)CD11a(dim)) or primarily IFN-gamma (MT(1), CD45RA(-)CD62L(-)CD11a(bright)). In addition, four other phenotypically distinct subsets of CD4 cells have unique cytokine profiles. To determine the clinical relevance of the representation of these cell types, we analyzed blood from patients with the chronic diseases leprosy and atopy. These diseases are characterized as immunologically polarized, since T cell responses in affected individuals are often strongly biased towards T(h)1 (dominated by IFN-gamma production) or T(h)2 (IL-4 production). We show here that this polarization reflects homeostatic or differentiation mechanisms affecting the representation of the functionally distinct subsets of memory CD4 T cells, MT(1) and MT(2). Significantly, the representation of the MT(1) and MT(2) subsets differs dramatically between subjects with tuberculoid leprosy (a T(h)1 disease), or lepromatous leprosy or atopic disease (T(h)2 diseases). However, there was no difference in the cytokine profiles of these or any of the other finely resolved CD4 subsets, when compared between individuals across all disease states. Thus, it is the representation of these subsets in peripheral blood that is diagnostic of the polarized state of the immune system.

Asthma and reproductive medicine.

Asthma is a common disease affecting approximately 5 percent of the population and is a major cause of disability. Research interest in the condition is high because of frequent reports that the incidence, prevalence, severity, and mortality rates have been rising in recent years. Although the etiology remains elusive, knowledge about its pathophysiology is extensive and detailed, which in turn has spawned an impressive array of effective and safe drugs to prevent and treat acute exacerbations. Pharmacotherapy is enhanced by appropriate environmental control measures and immunotherapy for the significant number of asthmatics with an allergic component to their disease. The pregnant asthmatic may pose special requirements for the small minority with severe corticosteroid-dependent disease or those subject to frequent attacks. However, the great majority of asthmatic women need not face much risk of adverse effects on the course of the pregnancy or significant fetal or perinatal abnormalities, as long as appropriate preventive measures and monitoring are taken.

Effects of psychosocial treatment in prolonging cancer survival may be mediated by neuroimmune pathways.

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 survival 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 neuroimmune 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.

Assessing the role of the biomaterial Aquavene in patient reactions to Landmark midline catheters.

Landmark midline catheters (Menlo Care, Inc., Palo Alto, CA) provide peripheral venous access for the infusion of medications or fluids. They are constructed of an inner layer of polyurethane and an outer layer of the biomaterial Aquavene, a blend of polyurethane and polyethylene oxide to which butylated hyroxyanisole (BHA), butylated hydroxytoluene (BHT), and triallyl-s-triazine trione (TTT) are added. Once inside the vein, the Aquavene material becomes hydrated and the catheter swells resulting in minimal trauma to the vein. It is well recognized that some patients experience reactions to catheterization. Recent reports of hypersensitivity-like reactions in some patients catheterized with Landmark catheters have prompted the manufacturer to reexamine biocompatibility data and clinical data to assess whether Aquavene was the source of the patient responses. None of the biocompatibility studies provided by Menlo Care in support of U.S. registration and marketing of Aquavene-based catheters demonstrated any tendency for Aquavene or material extracted from Aquavene to invoke an immunological or toxicological response. Examination of potential catheter residuals revealed that significant amounts of BHA and BHT were unlikely to be released from the catheters during expected use. The amounts of polyethylene oxide and TTT expected to be released during the first few minutes after catheter insertion (when most of the patient reactions were reported) are almost 92,500 and 270,000 times lower, respectively, than nontoxic animal exposures. These analyses do not support chemically mediated toxicity as an explanation for the adverse events experienced by some patients. A review of the postmarket surveillance data on Aquavene-based catheters revealed that the reported events were not consistent with a hypersensitivity (immunogenic) response to the biomaterial. The rare reported adverse events tend to occur quickly, most often after flushing of the catheter, and resolve quickly, even when the catheter remains in place. Determining the frequency and severity of adverse events reported in association with the use of Landmark catheters will ultimately require a controlled prospective study, preferably one with a concurrent control group using alternative products.

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.

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 sensitivity syndrome: a clinical perspective. I. Case definition, theories of pathogenesis, and research needs.

Multiple chemical sensitivity syndrome (MCS) does not appear to fit established principles of toxicology. Yet social, political, and economic forces are demanding that MCS be defined medically, even though to date scientific studies have not identified pathogenic mechanisms for the condition or any objective diagnostic criteria. Consequently, a working definition of MCS can rely only on an individual's subjective symptoms of distress and attribution to environmental exposures rather than currently measurable objective evidence of disease. Nevertheless, patients labeled with MCS are clearly distressed and many are functionally disabled. In this review, four theories of causation are explored: (1) MCS is a purely biologic/physical or psychophysiologic reaction to low-level chemical exposures. (2) MCS symptoms may be elicited by low-level environmental chemical exposures, but the sensitivity is initiated by psychologic stress. (3) MCS is a misdiagnosis and chemical exposure is not the cause. The symptoms may be due to misdiagnosed physical or psychologic illness. (4) MCS is an illness belief system manifest by culturally shaped illness behavior. Areas for further research regarding the etiologies of MCS are suggested. Recognizing that the cause of the syndrome may be multifactorial, strategies are proposed for clinical evaluation and management in Part II of this manuscript using a biopsychosocial model of illness.

Multiple chemical sensitivity syndrome: a clinical perspective. II. Evaluation, diagnostic testing, treatment, and social considerations.

Multiple chemical sensitivity syndrome (MCS) does not appear to fit established principles of toxicology. Social, political, and economic forces are demanding that MCS be defined medically, even though scientific studies have failed as yet to identify pathogenic mechanisms for the condition or any objective diagnostic criteria. Consequently, a working definition of MCS can only rely on a person's subjective symptoms of distress and attribution to environmental exposures rather than currently measurable objective evidence of disease. Nevertheless, patients labeled with MCS are clearly distressed and many are functionally disabled. Without reconciling the different theories of etiology of MCS discussed in Part I of this report, and recognizing that the cause of the syndrome may be multifactorial, strategies are proposed for clinical evaluation and management of patients with MCS using a biopsychosocial model of illness. The social implications of this illness are also discussed.

Guidelines for the clinical evaluation of occupational asthma due to high molecular weight (HMW) allergens. Report of the Subcommittee on the Clinical Evaluation of Occupational Asthma due to HMW Allergens.

Sensitization to HMW allergens is a relatively common immunopathogenic factor in occupational asthma. The mechanism of sensitization is an IgE-mediated, type I reaction. High molecular weight allergen refers to proteins and polymers of organic compounds over 5 kd and usually in the 20 to 50 kd range. In most cases diagnosis requires: 1. A high index of suspicion of job-related asthma. 2. Exposure to HMW compounds and clinical findings associated with such an exposure. 3. Confirmation of sensitization by appropriate in vitro or in vivo tests. 4. Confirmation of a pathogenic role by physiologic measurements in either a natural setting or during laboratory-controlled challenges.