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The quality of indoor air and its potential to adversely impact human health is a significant public health concern. In the 1980s, this concern was focused on the availability of a safe and comfortable environment in which to live and work [1]. After the oil embargo in 1973, homes and commercial buildings were constructed with a view of conserving energy. Homes were insulated tightly, and commercial buildings were constructed as hermetically sealed units that were dependent on the rate of fresh outside air that was drawn into the system. Building managers became aware of the minimal amount of outside fresh air that was required to ventilate the building in an effort to conserve the energy to heat and cool the building. Distinctions between building-related disease (eg, hypersensitivity pneumonitis, humidifier fever, Legionnaire’s pneumonitis) and the symptoms of sick building syndrome were discussed frequently in the medical literature [2,3]. In the 1990s, there was a surge of juridic and media attention that sought to link sick building syndrome with a controversial and unscientific symptom complex of multiple chemical sensitivity (idiopathic chemical intolerance) [4]. In 1994, a series of events took place that shifted the paradigm from generic sick building syndrome to a toxic mold threat. In Cleveland, Ohio, 10 infants became seriously ill with pulmonary hemosiderosis and hemorrhage, 2 of whom died. The Centers for Disease Control and Prevention initially concluded that there was a causal link between inhalation of Stachybotrys atra mycotoxin and this cluster of cases [5]. Subsequent events have led to assertions related to the adverse health effects of toxic mold or fatal mold in various buildings [6]. New markets have been developed to conduct testing for the presence of indoor molds and to remediate mold damage. There also has been a proliferation of juristic activities in the United States related to mold-induced health effects [7]. In Western Europe

Learning Objectives This overview discusses the respiratory complications of indoor air pollution, emphasizing the most common pollutants that individuals are likely to encounter outside the workplace. Data Sources Data were obtained from a review of the recent literature. Study Selection The expert opinion of the author was used to select and synthesize relevant data on this multifaceted subject. Results There have been a number of studies documenting an association between exposure to indoor allergens and development of both sensitization and asthma in children. In addition to classic allergens, chemical indoor air pollution may also exert an adverse effect on both the upper and lower respiratory tract by a variety of nonimmunologic, irritative mechanisms. Conclusions Our understanding of the adverse effects of indoor air pollution on health and comfort has broadened in recent years. It has supplied a credible framework for developing and implementing a variety of control strategies.

Reactive airways dysfunction syndrome (RADS) is defined as the sudden onset of asthma following a high level exposure to a corrosive gas, vapor, or fume. This variant of occupational asthma continues to generate controversy regarding the criteria for its diagnosis. There is also some disagreement as to the likely prognosis with this disorder. Currently, the diagnosis requires the assumption of normal premorbid pulmonary physiology and absence of bronchial hyperreactivity. Criteria for the diagnosis of RADS are discussed with a proposal for both major and minor criteria to increase the confidence of an accurate diagnosis. The pathology of RADS involves a primarily lymphocytic inflammatory response with some evidence of subepithelial thickening and fibrosis. Most patients with this condition who survive the short-term exposure to a toxicant recover completely without significant clinical or physiologic sequelae. The issue of low-level RADs remains controversial and problematic as a tenable diagnosis, and will require further careful investigation to evaluate the premise that chronic, low-level toxicants are capable of leading to such a condition. More likely, most of the cases which have been reported represent preexisting asthma and/or expressions of an atopic predisposition.

The people of the United States are enamored with drugs. They consume between 2 and 10 times more prescription and over-the-counter drugs than any comparable population anywhere in the world. 40 The average hospitalized patient is prescribed between 6 and 13 drugs, 15 and the country's aging population is frequently treated with multiple medications for a variety of ailments. 5 More than 1.6 billion prescriptions for some 30,000 different drugs are written each year in the United States. 17 Approximately 200 new pharmaceuticals are approved annually by the Food and Drug Administration (FDA). This figure does not include consumption of the more than 450 herbal products on the market today (i.e., approximately 8 to 10 billion herbal capsules are produced on a daily basis). Americans are spending more than $3 billion a year on herbal products, and their popularity has grown faster than American scientists can research them or the FDA can regulate them. The goal of physician-prescribed medication is to achieve an optimal therapeutic outcome. This goal has been defined as "the right drug for the right patient at the right time." 10 An optimal therapeutic outcome also implies the absence of any drug-related problems. 21 The latter is defined as an event or circumstance involving a patient's medications that actually or potentially interferes with the achievement of an optimal outcome. 21 It goes without saying that drug-related problems are frequent outcomes of medical management because medications are dispensed by an imperfect process, and few available therapeutic agents have no undesirable effects. Seven general categories of drug-related problems have been identified 43 : •Failure to start a drug for an indicated medical problem •Administration of a drug in the absence of a valid indication •Administration of an inappropriate drug for an indicated medical problem •Development of a de novo medical problem or worsening of an existent health problem because of a failure to administrate an indicated drug •Administration of an ineffective dose of an appropriate drug •Administration of an overdose of an appropriate drug •Undesirable or unexpected effect of an appropriate drug This article focuses on the issues principally related to adverse drug reactions and their potential medical and legal implications.

With an increasing proportion of individuals surviving until the seventh or eighth decade of life, diagnosis and treatment of elderly patients has become commonplace. Chronic airways obstruction is very prevalent in adults, and because asthma may not develop until later age and is frequently accompanied or obscured by other complications, it often goes unrecognized. Failure to diagnose asthma in a timely fashion unnecessarily increases the socioeconomic burden of asthma. In a recent survey to assess the functional status of a population 65 years of age or more, asthmatic patients had more problems with activities of daily living and a greater assessment of poor health, in comparison with a control group matched for age and sex. 36 Asthma very definitely changes the quality of life of many patients in this age group. Asthma may be a continuum of disease from childhood to adulthood, but asthma in the elderly may present unique diagnostic and therapeutic challenges to the clinician. In contrast to the younger asthma patient, the elderly asthma patient is more likely to have other illnesses and associated therapies that must be considered and managed. A clinical understanding of disease–disease, disease–drug, and drug–drug interactions between asthma and other associated illnesses is imperative. 3 This article focuses on the major diseases, drugs, and drug interactions that challenge us when treating asthma in the older patient (Table 1).

As summarized in Table 1, the literature consistently supports the hypothesis that allergic asthmatic patients have seasonal BHR changes that parallel allergen exposure. These seasonal changes appear to be preventable by treatment with corticosteroids (systemic, inhaled, or nasal), disodium cromoglycate, and immunotherapy. Studies have almost exclusively focused on pollens, though similar limited data exist for dust mites. Though the dust mite is a perennial allergen, mite levels are well known to fluctuate with seasonal temperature and humidity trends (44-46), and therefore, seasonal BHR variation in mite-sensitive asthmatic patients is not surprising. Allergenic mold species have not been studied in this regard. In allergic rhinitis patients, the data are less consistent (see Table 2). However, the studies that failed to identify a seasonal BHR difference were either small or had other design limitations. The seasonal changes identified by the larger analyses were similar to those identified for asthmatic patients. Thus, although confirmatory studies would be helpful, it seems likely that in the absence of clinical asthma, allergic rhinitis patients with baseline BHR have allergen-related seasonal changes in BHR. The BHR effects of seasonal changes in air pollution and viral URIs are not known, since they have not yet been directly studied. However, interesting recent reports have identified possible synergistic effects of air pollution exposure on BHR and allergic responses. Similarly, the availability of new viral identification techniques has resulted in the discovery that viral infection may be more prevalent during clinical asthma exacerbation than previously realized. Therefore, air pollution and viral infections may well influence BHR seasonally, and (along with allergens) may contribute to seasonal asthma morbidity and mortality peaks. The mechanism(s) underlying seasonal BHR changes is (are) not known. One plausible possibility with regard to allergen-driven BHR changes involves a type I hypersensitivity late-phase reaction. Characterized by recruitment of eosinophils, lymphocytes, and other cells that are central components of allergic inflammation and are not normally found in the lower airways, this reversible inflammatory process could in turn act, presumably via chemical mediators, on the airway smooth muscle. This may cause bronchoconstriction, but may also increase responsiveness to bronchoconstrictive stimuli independent of bronchoconstriction. This explanation for seasonal BHR changes is supported by findings of blood eosinophil (31,47) and BAL eosinophilic cationic protein (31) level changes that parallel BHR. Prevention of seasonal BHR changes using anti-inflammatory medications (32,33,35) also supports this hypothesis (30) however, and the complex potential interactions between infectious agents and air pollutants on seasonal BHR changes have yet to be studied directly. Therefore, although BHR indeed may predictably vary season to season in allergic individuals, additional investigation is needed to better characterize the reasons for this phenomenon. Further insight in this area may help address the reasons why there are often seasonal epidemics in asthma morbidity and mortality.

The spectrum of vasculitis is extremely diverse and frequently confusing. Several of the vasculitis variants can present with respiratory symptoms that may masquerade as common allergic disorders. The clinician who is faced with seemingly new and isolated respiratory tract symptoms may be lulled into a diagnosis of either an infectious or allergic disorder. Persistence of the condition despite what appears to be appropriate therapy should prompt the allergist/immunologist to consider alternative diagnoses with similar presentations. Among the more likely possibilities are the granulomatous vasculidites known for their prominent respiratory tract manifestations. The immunopathogenesis of these diverse conditions has been elucidated in the past several years, facilitating a description of how cross-regulating mechanisms allow a shift from Type 1 to Type 2 cytokine production, or vice versa. This helps to explain why there are so many apparent similarities in these seemingly divergent disease processes. 19 It is now established that the CD4 Th-2 type cell is associated with mast cell and eosinophil growth and differentiation as well as IgE production by B cells in the induction of allergic inflammation. The associated CD4 Th-2 cytokine profile comprises IL-4, -5, -10 and -13, and the responsible stimulus is either an allergen or a helminth. On the other hand, disorders with a Th-1 profile appear to act in concert with activated macrophages to provide a cytokine cascade composed of IL-1 and IL-2, interferon gamma, and tumor necrosis factor. The stimulating antigen includes bacteria, viruses and mycobacteria. This article focuses on those vasculitic disorders that appear to have a Th-1 cytokine profile in which the final inflammatory result is frequently an epithelial cell granuloma such as that seen in sarcoidosis, Wegener's granulomatosis, Churg-Strauss syndrome, and several collagen vascular disorders with prominent vasculitic manifestations. These disorders have been generically referred to as the respiratory vasculidites . It is possible that future research will permit an even better understanding of the regulating mechanisms that shift the immune response along one cytokine path or another. It is also possible that some of these disorders have elements of both cytokine profiles, explaining some of their confusing similarities.

Occupational rhinitis is a common but generally underreported entity. Although it may occur alone, it is frequently associated with occupational asthma. Occupational asthma may have one of several presentations that are difficult to distinguish from non-work conditions. The respiratory tract acts as the final common pathway for all inhaled environmental pollutants, whether encountered in the home or at work. More than 200 chemicals have been incriminated as a cause of work-related asthma. It is said that about 2% of the 10 million Americans who have asthma acquired it as a result of some chemical irritant or immunogen in their work environment. A number of predisposing factors facilitate the development of work-related asthma. These include industrial conditions, climatic factors, atopic predisposition, smoking, recreational drug use, viral infection, nonspecific bronchial hyperreactivity, and a variety of miscellaneous factors. Pathogenetically, occupational asthma may be immunologic or nonimmunologic in nature. The immunologic variants involve sensitization to a variety of large-molecular-weight constituents. The major nonimmune variant is referred to as inflammatory bronchoconstriction or reactive airways dysfunction syndrome (RADS). There are well-defined criteria for the diagnosis of immunologic and nonimmunologic asthma. The several clinical variations of occupational asthma can be difficult to distinguish from nonindustrial disorders. The most common presentation in practice involves the worker with preexistent asthma who has been adversely affected by work exposures. Occasionally these industrial exposures precipitate permanent impairment. It is clear, however, that occupational asthma is not a single, simple, or homogeneous entity, even when a single specific causal factor can be identified in the workplace. Therefore the physician must be aware of the patient's entire medical history and the precise occupational exposures and must have convincing physiologic evidence that demonstrates a cause-and-effect relationship before making a definitive diagnosis of work-related asthma. Once the diagnosis is established, the worker should be removed from the work-place. If the diagnosis is made in a timely fashion, the patient should experience a significant improvement. The major factor in determining a poor prognosis in occupational asthma is the duration of exposure before the diagnosis is established. Prevention of the disorder is the best therapeutic intervention.

The effects of dietary manipulations on autoimmune disease are understood poorly. In this article, we detail our experience with a human subject who developed autoimmune hemolytic anemia while participating in a research study that required the ingestion of alfalfa seeds. Subsequent experimental studies in primates ingesting alfalfa sprout seeds and L-canavanine (a prominent amino acid constituent of alfalfa) is presented. The results of these studies indicate a potential toxic and immunoregulatory role of L-canavanine in the induction of a systemic lupus-like disease in primates.

A diversity of airborne dusts, gases, fumes, and vapors can induce dose-related respiratory symptoms in individuals exposed in the workplace. These agents can cause annoyance reactions, irritational effects, sensitization, or the induction of corrosive changes in the respiratory tract, depending on their composition, concentration, and duration of exposure. The prevalence of occupational asthma (OA) ranges from 9% to 15% of the asthmatic population. Factors that might influence the development of OA include the work environment, climatic conditions, genetic proclivities, tobacco and recreational drug use, respiratory infection, bronchial hyperresponsiveness, and endotoxin exposure. Pathogenetically, new-onset OA can be allergic or nonallergic in origin. The allergic variants are usually caused by high-molecular-weight allergens, such as grain dust and animal or fish protein. Selected low-molecular-weight agents are also capable of inducing allergic OA. Symptoms ensue after a latent period of months to years. Nonallergic OA can be precipitated by a brief high-level exposure to a potent irritant. Symptoms occur immediately or within a few hours of the exposure. Once the diagnosis of allergic OA is established, the worker should be removed from further exposure in the workplace. In nonallergic OA the worker can return to work if the exposure was clearly a nonrecurring event. If the diagnosis is made in a timely fashion, most workers experience improvement. Prevention is the best therapeutic intervention.

Background: Three well-accepted mechanisms of mold-induced disease exist: allergy, infection, and oral toxicosis. Epidemiologic studies suggest a fourth category described as a transient aeroirritation effect. Toxic mold syndrome or inhalational toxicity continues to cause public concern despite a lack of scientific evidence that supports its existence. Objectives: To conduct a retrospective review of 50 cases of purported mold-induced toxic effects and identify unrecognized conditions that could explain presenting symptoms; to characterize a subgroup with a symptom complex suggestive of an aeroirritation-mediated mechanism and compare this group to other diagnostic categories, such as sick building syndrome and idiopathic chemical intolerance; and to discuss the evolution of toxic mold syndrome from a clinical perspective. Methods: Eighty-two consecutive medical evaluations were analyzed of which 50 met inclusion criteria. These cases were critically reviewed and underwent data extraction of 23 variables, including demographic data, patient symptoms, laboratory, imaging, and pulmonary function test results, and an evaluation of medical diagnoses supported by medical record review, examination, and/or test results. Results: Upper respiratory tract, lower respiratory tract, systemic, and neurocognitive symptoms were reported in 80%, 94%, 74%, and 84% of patients, respectively. Thirty patients had evidence of non–mold-related conditions that explained their presenting complaints. Two patients had evidence of allergy to mold allergens, whereas 1 patient exhibited mold-induced psychosis best described as toxic agoraphobia. Seventeen patients displayed a symptom complex that could be postulated to be caused by a transient mold-induced aeroirritation. Conclusion: The clinical presentation of patients with perceived mold-induced toxic effects is characterized by a disparate constellation of symptoms. Close scrutiny revealed a number of preexisting diagnoses that could plausibly explain presenting symptoms. The pathogenesis of aeroirritation implies completely transient symptoms linked to exposures at the incriminated site. Toxic mold syndrome represents the furtive evolution of aeroirritation from a transient to permanent symptom complex in patients with a psychogenic predisposition. In this respect, the core symptoms of toxic mold syndrome and their gradual transition to chronic symptoms related to nonspecific environmental fragrances and irritants appear to mimic what has been observed with other pseudodiagnostic categories, such as sick building syndrome and idiopathic chemical intolerance. Ann Allergy Asthma Immunol. 2005;95:239–246.

Background Psyllium use has increased significantly in the United States in part due to its lipid-lowering property. The increased prevalence of consumption has led to its recognition as an emerging food allergen. Objectives To report the case of a 42-year-old woman who experienced fatal anaphylaxis after ingesting a psyllium-based product and to review the literature. Methods The MEDLINE database was searched for articles from 1966 to 2002 using the keywords psyllium or ispaghula and each of the following: allergy, hypersensitivity, anaphylaxis, and asthma . Both English and non-English articles were included. Results Psyllium hypersensitivity has been well described in health care workers and pharmaceutical plant employees. Clinical manifestations of allergy range from upper respiratory tract symptoms on inhalation to anaphylaxis on ingestion. The prevalence of sensitization varies between these 2 groups. The allergenic epitope is not known. Conclusions We present a case of psyllium hypersensitivity that resulted in death. There is a clear association between atopy and psyllium allergy. The case underscores the fact that even nonprescription "natural" products can be harmful to people with allergies.

Objective To review the available literature on the subject of fungi (molds) and their potential impact on health and to segregate information that has scientific validity from information that is yet unproved and controversial. Data Sources This review represents a synthesis of the available literature in this area with the authors' collective experience with many patients presenting with complaints of mold-related illness. Study Selection Pertinent scientific investigation on toxic mold issues and previously published reviews on this and related subjects that met the educational objectives were critically reviewed. Results Indoor mold growth is variable, and its discovery in a building does not necessarily mean occupants have been exposed. Human response to fungal antigens may induce IgE or IgG antibodies that connote prior exposure but not necessarily a symptomatic state. Mold-related disease has been discussed in the framework of noncontroversial and controversial disorders. Conclusions When mold-related symptoms occur, they are likely the result of transient irritation, allergy, or infection. Building-related illness due to mycotoxicosis has never been proved in the medical literature. Prompt remediation of water-damaged material and infrastructure repair should be the primary response to fungal contamination in buildings.

Fungal contamination in buildings can vary greatly, and their presence in a dwelling does not necessarily constitute exposure. Measurement of mold spores and fragments varies depending on the methodology and instruments used. Meaningful comparison of data is rarely possible. The presence of a specific immune response to a fungal antigen only connotes that exposure to one or more related species has occurred, but not that there is a symptomatic clinical state. The response of individuals to indoor bioaerosols is complex and depends on age, gender, state of health, genetic makeup, and degree and time of bioaerosol exposure. In general, mold contamination in buildings is associated with incursion of water or moisture, which should be remedied as efficiently as possible. When disease occurs, it more likely is related to transient annoyance or irritational reactions. Allergic symptoms may be related to mold proliferation in the home environment. Because molds are encountered both indoors and outdoors, it is difficult to determine where the sensitivity initially arose and if the response is solely provoked by either an indoor or outdoor source. As an indoor allergen, mold is considered to be an infrequent participant in the induction of allergic disease when compared with housedust mites, animal dander, and cockroach allergens. Infection in healthy individuals is rare and usually is caused by an outdoor source. Building-related disease caused by mycotoxicosis has not been proved in the medical literature.

A diversity of airborne dusts, gases, fumes, and vapors can cause dose-related symptoms in individuals exposed in the workplace. More than 250 chemicals have been incriminated as a cause of occupational asthma (OA). The prevalence of OA ranges from 2% to 6% of the asthmatic population. Predisposing factors facilitating the development of OA include the work environment, climatic conditions, genetic proclivities, tobacco and recreational drug use, respiratory infection, and bronchial hyperresponsiveness. Pathogenetically, new-onset OA may be immunologic or nonimmunologic in origin. The immunologic variants are usually caused by high molecular-weight allergens such as grain dust and animal or fish protein. Symptoms ensue after a latent period of months to years. Nonimmunologic OA can be precipitated by a brief, high-level exposure to a potent irritant. Symptoms occur immediately or within a few hours of the exposure. In either instance, once the diagnosis is established, the worker should be removed from the workplace. If the diagnosis is made in a timely fashion, most workers experience improvement. Prevention is the best therapeutic intervention.

Bronchial hyperreactivity is defined as an increased sensitivity to bronchoconstrictor stimuli. It is regarded as the physiological hallmark of bronchial asthma. It is usually associated with a positive family history of asthma, atopy, and evaluated total serum immunoglobulin E. Its prevalence in the normal population ranges from 10 to 20%; it increases with age and is significantly associated with both allergic rhinitis and atopic dermatitis. The relationship between bronchial hyperreactivity and respiratory symptoms may be weak. Bronchial hyperreactivity varies in severity with allergen exposure, viral infection, exposure to pollutants, environmental avoidance measures, anti-inflammatory therapy, and immunotherapy.

Anaphylaxis is a severe life-threatening systemic reaction that offers many challenges to the clinician. The incidence of anaphylaxis is significant in the general population and an important cause of morbidity and mortality. While the most common causes of anaphylaxis include drugs, foods, and venoms, other important etiologies must be considered. The etiology of anaphylaxis is classically based on IgE mediated hypersensitivity but multiple mechanisms may be involved. The clinical presentation of anaphylaxis may be extremely variable with a broad differential diagnosis which will be outlined. Although the diagnosis of anaphylaxis can many times be based on a careful history and physical examination, there are laboratory and skin tests which may be helpful in establishing a diagnosis in some cases. The cornerstone of treatment of anaphylaxis remains epinephrine. Other supportive therapies will be discussed.

Objective Reading this article will acquaint the reader with possible outcomes associated with the diagnosis of “sick building syndrome.” The definition, epidemiology, and precipitating events of this symptom complex are distinguished from other defined building-related illnesses. Data source The author's experience with many patients presenting with this diagnostic label and selected studies on indoor pollution and “sick building syndrome” are carefully reviewed. Study selection Pertinent scientific investigations on “sick building syndrome” and previously published reviews on this and related subjects that met the educational objectives were critically reviewed. Results “Sick building syndrome” is a pseudodiagnosis composed of nonspecific, transient symptoms without proven biologic markers. Its application in the clinical setting invites frequent subsequent linkage to other similar vague diagnoses associated with chronic debility and lack of therapeutic intervention. Conclusion The reader is encouraged to avoid the use of this term in favor of a simpler, descriptive diagnosis (eg, transient office-related annoyance and /or irritation) or if this seems inadequate, adoption of the diagnostic label of “idiopathic building intolerance.”

To determine the effects of phenytoin on serum immunoglobulins, complement, and antinuclear antibody conversion, a prospective, five-year longitudinal study was undertaken in 118 patients. Three major diagnostic groups were evaluated: 27 patients with idiopathic epilepsy, 50 with secondary epilepsy, and 41 with neuropathic syndromes without epilepsy. In addition, 83 normal volunteers were studied in a similar manner. Evaluations were performed prior to administration of phenytoin and at six-month intervals thereafter. Prior to treatment, patients with idiopathic epilepsy had a higher than expected incidence (13.5 percent, p less than 0.01) of low serum IgA (less than 61 mg/dl). Patients with secondary epilepsy and neuropathic disorders without epilepsy had a greater than expected incidence (9.2 percent, p less than 0.01; and 12 percent, p less than 0.01, respectively) of high serum IgA (greater than 417 mg/dl). Phenytoin treatment was associated with further decreases in serum IgA in patients with idiopathic epilepsy (p = 0.063) and secondary epilepsy (p = 0.008). Total serum IgE concentrations also decreased significantly in all patient categories during treatment with phenytoin. Minor decreases in serum IgG and IgM were noted, but serum IgD and complement remained unaffected. Antinuclear antibodies were observed with essentially the same frequency (10 percent) before and after phenytoin therapy.

The pharmacokinetics and urinary excretion of intravenously administered 7-(2,3-dihydroxypropyl) theophylline (dyphylline), were studied in a 37-yr-old asthmatic woman with ethylene diamine sensitivity who manifested intolerance to intravenous aminophylline on three separate occasions. In this subject, intravenously administered dyphylline was tolerated very well and was effective in the subsequent management of acute bronchospastic episodes. Dyphylline was significantly concentrated in the urine. This, coupled with its rapid clearance, suggests potential clinical application in patients with hepatic dysfunction. Though aminophylline sensitivity is rare, ethylene diamine sensitivity should be considered in untoward reactions to this drug.

The allergist-immunologist is ideally trained to play a critical role in the recognition and evaluation of patients with building-related illness. The practitioners of this subspecialty should also take an active role in critical studies that will expand the knowledge base in this whole area, and collaborate as well with colleagues in toxicology and industrial hygiene to develop accurate and sensitive measures of implicated pollutants, irritants, and allergens. The role of multiple low level pollutants on healthy workers must be assessed in an objective fashion. Methods to evaluate and enforce regulations on building ventilation should be developed and widely applied. It is only in this fashion that an expanding population of office workers can be assured a suitable work environment as we emerge from the age of the industrial blue collar worker to the technical, office-based white collar worker.

Immunological function was evaluated in 9 patients who received oxisuran at a dose range of 5-90 mg/kg, for periods of 5-40 weeks. Bone marrow cytotoxicity and lymphopenia did not occur. Established humoral immunological reactions were unaffected by oxisuran. Only 6 of 19 previously positive skin tests reverted to negative. Primary cellular immune reactivity was markedly suppressed. Allogenic skin graft survival was prolonged to a mean of 30.7 days and only 2 of 9 patients were successfully sensitized to dinitrochlorobenzene and Keyhole limpet hemocyanin, respectively. Both IgG and IgM responses to primary typhoid immunization were inhibited. In vitro peripheral blood lymphocyte activity in phytohemagglutinin and mixed lymphocyte culture tests remained normal. These data suggest that oxisuran interferes with the afferent limb of the immune system and may thereby be clinically useful in human transplantation.

Serum samples serially obtained from 50 patients with systemic lupus erythematosus (SLE) were studied for antibody to deoxyribonucleic acid (DNA) and circulating DNA:anti-DNA complexes during the active and inactive phases of their disease. The patients were divided into four categories: Group I: six patients without clinical evidence of central nervous system (CNS) or renal involvement. Group II: three patients with CNS lupus. Group III: nine patients with normal urinalyses and glomerular filtration rates, but morphologic evidence of glomerular disease. Group IV: 32 patients with overt lupus nephritis. Elevated anti-DNA levels were observed in 16 of 18 patients (88 per cent) in groups I, II and III during active disease. This persisted in 14 (77 per cent) during remission. DNA:anti-DNA complexes were demonstrated in four of 18 (22 per cent) during active disease and disappeared in all but one patient with progressive disease. In 30 of the 32 patients (94 per cent) in group IV, DNA binding was increased during active disease; this persisted in 21 (70 per cent) despite remission. Complexes were observed in 25 of the patients in group IV (78 per cent) with active disease. In six of these patients, complexes have persisted; two have died, one has progressed to renal failure and the remaining three patients continue to manifest active disease. This study suggests that measurement of DNA:anti-DNA complexes provides a valuable additional index of disease activity and prognosis in SLE.