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Industrial hygienists (IHs) are called upon to investigate exposures to mold in indoor environments, both residential and commercial. Because exposure standards for molds or mycotoxins do not exist, it is important for the industrial hygienist to have a broad knowledge of the potential for exposure and health effects associated with mold in the indoor environment. This review focuses on the toxic effects of molds associated with the production of mycotoxins, and the putative association between health effects due to mycotoxin exposure in the indoor environment. This article contains background information on molds and mycotoxins, and a brief summary and review of animal exposure studies, case reports, and epidemiological studies from the primary literature concerning inhalation of mycotoxins or potentially toxin-producing molds. The relevance of the findings in the reviewed articles to exposures to mold in indoor, non-agricultural environments is discussed. Although evidence was found of a relationship between high levels of inhalation exposure or direct contact to mycotoxin-containing molds or mycotoxins, and demonstrable effects in animals and health effects in humans, the current literature does not provide compelling evidence that exposure at levels expected in most mold-contaminated indoor environments is likely to result in measurable health effects. Even though there is general agreement that active mold growth in indoor environments is unsanitary and must be corrected, the point at which mold contamination becomes a threat to health is unknown. Research and systematic field investigation are needed to provide an understanding of the health implications of mycotoxin exposures in indoor environments.

Trichloroethylene has been identified by the Agency for Toxic Substances and Disease Registry as being among the most prevalent constituents found at contaminated sites. Residents living near TCE-contaminated sites often request neuropsychological evaluations, primarily in the context of litigation. Evidence for usually reversible central nervous system effects associated with acute, high-level exposure to trichloroethylene is unequivocal; however, evidence for permanent encephalopathic effects associated with chronic, low-level exposure has not been established. This paper reviews the toxicological and neuropsychological evidence underlying the TCE encephalopathy issue. Standard approaches to causation assessment are discussed and applied to the relevant scientific data regarding chronic low-level exposure. Trichloroethylene

The multiple chemical sensitivity (MCS) phenomenon can cause significant dysfunction and symptomatology and presents a difficult challenge for patient management. Central to the MCS debate is whether this phenomenon results from a primary emotional response to perceived chemical exposures or from pathological interactions between chemicals and biological systems. Those who believe the latter argue that toxic interactions result in physiological impairment and that subsequent emotional problems derive from such impairment. Distinguishing between psychogenic (emotional) or a toxicodynamic (chemical toxicity) origin is essential to the medical management of an MCS patient. A psychogenic basis requires treatment with appropriate behavioral therapies; in contrast, a belief in a strictly toxicodynamic etiology argues for avoidance and often precludes treatments that address the psychological responses. Current scientific evidence strongly suggests that behavioral or psychogenic explanations predominate for reported MCS symptoms. Acceptance of a purely toxic origination (i.e., pathological abnormalities result from a low level chemical exposure) defies known toxicological and medical principles; whereas psychogenic explanations are consistent with these principles. Because symptoms are the end points of many diseases with many causes, both physical and emotional, modern medicine is charged with and expected to consider both when treating MCS patients. The argument can be made that insufficient information exists about the causal nature of many diseases, and future research may provide support for a strict toxicodynamic cause. However, the practice of medicine must be based upon current knowledge, not future possibilities. Proper care of MCS patients requires identifying the existence of both psychological and organic pathological dysfunction. The rejection of a psychological aspect of the MCS phenomenon and appropriate behavioral treatments is both illogical and detrimental to MCS sufferers.

Clinical practice always necessitates proper diagnosis and correct treatment. For most clinical fields, determining the cause of the illness is irrelevant to the intervention. An oncologist, for example, has no need to explore the “cause” of the patient’s lymphoma. Allergists, by contrast, have tools and the need to examine the relevant allergen which is the putative “cause” of the patient’s allergic symptomatology. In the context of a legal claim, the “cause” of the symptoms or disorder is central, because it determines financial responsibility. However, in the case of an allergic disorder and identified allergen, a claim requires more. Whose allergen? Where did it come from? These are crucial questions that must be answered. This paper explores the approaches to causal assessment which are important for the clinical allergist as he/she navigates the interface between clinical practice and legal proceedings. Its purpose is to help the allergist understand that interface, and to be prepared to enter an unfamiliar legal arena.

The phenomenon of multiple chemical sensitivities is a peculiar manifestation of our technophobic and chemophobic society. It has been rejected as an established organic disease by the American Academy of Allergy and Immunology, the American Medical Association, the California Medical Association, the American College of Physicians, and the International Society of Regulatory Toxicology and Pharmacology. It may be the only ailment in existence in which the patient defines both the cause and the manifestations of his own condition. Despite this, it has achieved credibility in workmen?s compensation claims, tort liability, and regulatory actions, all of which are briefly reviewed.

There is no uniformity in the suggested guidelines for acceptable levels of fungi in indoor ambient air. Thus, health professionals have no way to determine what levels of fungi may pose a threat to human health. The authors reviewed the published literature to identify data reported for noncomplaint structures, that is, structures in which occupants did not have health concerns associated with the quality of the indoor air. For both commercial and residential structures, fungal concentrations detected were often higher than currently suggested guidance values. The average indoor air concentration in 149 noncomplaint commercial buildings was 233 colony forming units (CFU) per cubic meter, whereas outdoor ambient air levels averaged 983 CFU/m(3). Total indoor spore counts ranged from 610 to 1040 spores/m(3) in three commercial buildings. Outdoor total spore counts associated with these buildings ranged from 400 to 80,000 spores/m(3). The average indoor concentration reported for 820 noncomplaint residential structures was 1252 CFU/m(3) with an average outdoor level of 1524 CFU/m(3). Total spore counts detected indoors at 85 residential structures ranged from 68 to 2307 spores/m(3). Outdoor spore levels associated with these structures ranged from 400 to 80,000 spores/m(3). A large proportion of both commercial and residential noncomplaint structures have indoor ambient air fungal concentrations above 500 CFU/m(3), a level often advocated as requiring remediation in structures when occupants complain of nonspecific adverse health symptoms.

The fundamental issue in the multiple chemical sensitivity (MCS) debate is whether this phenomenon is primarily a psychogenic or toxicodynamic disorder, that is, whether symptoms are due to an emotional response to perceived chemical toxicity or to a pathological interaction between chemical agents and organ systems. The distinction between psychogenic or toxicodynamic is essential to the medical management of an MCS patient. A behavioral origin leads to a behavioral therapy, whereas a toxicodynamic etiology may necessitate avoidance and exposure control methodologies. Regulatory, legislative, judicial, and occupational control responses are also dependent upon the critical distinction between psychogenic and organic etiologies. If people are being poisoned by low levels of chemicals, one set of responses follows. If, on the other hand, MCS sufferers are symptomatic for emotional reasons, the response is different. Everything that is known about MCS to date strongly suggests behavioral and psychogenic explanations for symptoms. The premature use of the term multiple chemical sensitivities has hampered effective exploration of and response to this phenomenon, because it suggests, to the lay person, a physiological explanation. It is time that this disorder be properly characterized so that sufferers receive the care they need and so that new "victims" are not recruited.

To the Editor. —The articles by Dr Haley et al 1-3 are fraught with design and interpretive problems. Unique symptom complexes, neurologic syndromes, and toxicologic end points, contrary to established criteria, form the bases of these studies. The clinical data presented 2 provide little evidence from which to conclude that these patients had any neuropathic processes. The authors point out that comprehensive evaluations found that the findings were "nonspecific and not sufficient to diagnose any known syndrome." Importantly, the authors fail to explain what these subtle, neurophysiological findings have to do with the symptoms. In addition, the problems with interpretation of neurologic testing are extensive. For instance, only 5 veterans (2 with "confusion ataxia" and 3 with "arthro-myo-neuropathy") had peripheral neurophysiological tests (nerve conduction studies, electromyography, single fiber electromyography, and quantitative sensory tests). The only abnormality detected was "borderline abnormal motor nerve conduction in the lower extremity in 2" (from syndrome 3) and

Tainted Truth is a well-researched, if confusing, expose of science-for-hire. No bodies of data escape the author's probing. Opinion polls, advertising statistics, studies designed to promote legislation, data for the courtroom, and biomedical research deserve equal skepticism when they are bought and paid for by self-interested parties. The intensity of Crossen's research and her style bespeak her background as a writer and editor for the Wall Street Journal . The reader is propelled from one situation to another in a manner more appropriate to journalistic reporting than to a research treatise. Crossen demonstrates certain inconsistencies, which detract from her message. An exploration of the oat bran cholesterol-lowering controversy concludes that Quaker Oats bought the results. She criticizes the Quaker-sponsored meta-analysis that was used to add power to the supportive studies. However, in the case of passive smoking, she praises the Environmental Protection Agency's estimates of lung cancer, failing to note that

Today’s newest growth industry-environmental health litigation-is straining our court system’s search for the truth. The newness of the subject matter has spawned an abundance of inexpert experts coming before courts which are unprepared to discern valuable from misleading testimony. As a result, scientifically worthless testimony, misleading rather than helpful to the triers of fact, abounds. Here we will consider the proper role of modern science in the assessment of environmentally caused illnesses. We will see how offhanded, nonscientific testimony is often admitted in violation of Federal Rules of Evidence against such admissions. Finally, I shall present recommendations to permit the courts to assess the methodology employed, and hence, the admissibility, of evidence presented by medical expert witnesses in these proceedings.

Dalal, Fram R. (University of Pennsylvania, Philadelphia), Ronald E. Gots, and Joseph S. Gots . Mechanism of adenine inhibition in adenine-sensitive mutants of Salmonella typhimurium . J. Bacteriol. 91: 507–513. 1966.—The inhibition of growth of Salmonella typhimurium by adenine was studied with three adenine-sensitive mutants. These mutants were acutely sensitive to inhibition by adenine, were prototrophic in their growth requirements, and represented mutational events in three different genetic loci. In all cases, inhibition by adenine was relieved noncompetitively by thiamine (or its pyrimidine moiety), pantothenate (or its pantoyl moiety), and methionine alone or, more efficiently, in the presence of lysine. Kinetics of reversal indicated that adenine inhibited the synthesis of the reversing agents, probably at the level of a common factor required for their syntheses, such as the folic acid coenzymes. Support for this inference has been found by the facts that one of the mutants was identified as a partial auxotroph for p -aminobenzoic acid, and sulfadiazine could sensitize the wild type to acute inhibition by adenine.

These studies were designed to examine the functional relationship between respiring rat liver mitochondria and bound hexokinase. Kinetic studies were peformed varying either exogenously supplied ATP or ATP synthesized endogenously by respiring mitochondria and varied concentrations of ADP. Michaelis-Menten constants and maximum velocities were determined at two, five, and ten minutes after initiating the reactions. The K m 's and Vmax's were invariant with respect to added ATP, but the apparent K m 's varied considerably when endogenous substrate was utilized. At two minutes, the K m for endogenous ATP was 25% of the K m for provided ATP, but, by ten minutes, it had reached 70%. The Vmax's varied far less markedly. This is a clear demonstration of preferential utilization of mitochondrial ATP by bound hexokinase.

A patient with the preoperative diagnosis of indeterminate pulmonary nodule which proved at operation to be a single left pulmonary vein has been presented. No resection was performed and delayed postoperative pulmonary angiography confirmed the operative diagnosis. We discuss differential diagnosis and a retrospective analysis of how unnecessary thoracotomy might have been avoided.

The hexokinase-acceptor theory of insulin action is described and evidence for its validity is discussed. The theory states that insulin acts by connecting hexokinase to mitochondria. The close association of this particular enzyme to specific energy generating sites stimulates energy generation by the process known as respiratory control. The ADP generated when mitochondrial ATP is utilized by hexokinase to phosphorylate glucose acts as a stimulus — substrate — for further ATP generation by the Krebs cycle. The close proximity of the enzymes to the sites of energy generation makes the process of energy generation more efficient, providing more energy for anabolic reactions, all of which are stimulated by insulin. The lack of insulin effect on brain results from the fact that hexokinase in brain is tightly bound to mitochondria. On the other hand, the requirement of glucose for energy production in brain is evidence for the functional significance of this binding of hexokinase. The insulin-like effect of exercise in the diabetic is seen in the light of this theory as an acceptor effect of creatine liberated by muscle contraction.

These studies examined the functional relationship between rat hepatic mitochondria and associated hexokinase (ATP: d -hexose-6-phosphotransferase, 2.7.1.1) to determine whether the binding of hexokinase to mitochondria might provide a privileged interaction with sites of ATP production. Initial kinetic analysis followed the sequential flow of phosphate through ATP generated by the mitochondria into glucose-6-phosphate catalyzed by the bound hexokinase. Kinetics were compared with an identical bound hexokinase-mitochondrial system using externally supplied ATP. The hexokinase had lower apparent Km values for ATP generated in the mitochondria from supplied ADP than for ATP provided. Respiratory inhibitors blocked both the ADP- and ATP-mediated reactions. Tracer studies further documented that the mitochondrial hexokinase initially and preferentially utilized the internally generated nucleotide. These studies demonstrate that the active site of bound hexokinase is relatively inaccessible to extramitochondrial ATP. They provide evidence that bound hexokinase can sequentially accept mitochondrially generated ATP in a kinetically advantageous way. Finally, they support the assumption that mitochondrial binding of this acceptor enzyme may play a propitious role in cellular energy economy.

The migration of intestinal epithelial cells from the crypt area to the villus tip is associated with progressive differentiation of these cells. The distribution of (Na+K+) stimulated adenosinetriphosphatase ((Na+K+)-ATPase; EC 3.6.1.3) along the intestinal villus may have functional as well as developmental implications. To define this distribution, rat jejunal and ileal segments were incubated in vitro with a citrate solution that dissociates epithelial cells sequentially from villus tip to crypt area. ATPase activity in cell collections from villus tips and crypt areas were compared. The specific activity of (Na+K+)-ATPase was higher in the villus tip than in the crypt cells of both jejunum and ileum. Crypt cell (Na+K+)-ATPase activity in the jejunum and ileum were similar. Thus, (Na+K+)-ATPase activity of villus tip cells in the jejunum was greater than in the ileum. There was no difference in villus tip and crypt cell Mg2+-ATPase activity in either jejunum or ileum. The steep gradient for (Na+K+)-ATPase along the intestinal villus may signify an improtant difference in Na+ transport between the villus tip and crypt area. The higher level of (Na+K+)-ATPase activity in the jejunal villi is consistent with the more important role of the jejunum in Na+ and substrate-linked Na+ transport.

This report describes the twenty-first case of intrahepatic cystic dilatation of the biliary tree and the first with an associated choledochal cyst. The age, incidence, and clinical manifestations of this disease are extremely varied and the prognosis, although unpredictable, has generally been unfavorable. Although this disease appears to be quite uncommon, it is likely that it will be seen more frequently as awareness of its existence is more widely disseminated. One should consider this diagnosis in cases of repeated jaundice or cholangitis when extrahepatic obstruction cannot be identified.

A batch chromatographic method for the determination of hexokinase employing trace-labelled glucose and resin chromatography is described. Markedly enhanced sensitivity compared with the standard spectrophotometric assay is shown. Its greater reliability and use for particulate-tissue preparations is discussed.

Complications following ilesostomy are not uncommon. Fluid and electrolyte imbalance, skin excoriation and breakdown, stenosis of the stoma and mechanical small bowel obstruction are the usual problems which may occur. Recently, a new complication following total colectomy and ileostomy has been recognized. Uric acid urolithiasis, usually associated with gout, leukemia or polycythemia, has been found in a significant number of patients after total colectomy. 1 Prospective studies report this complication in 9% to 13% of all patients with established ileostomies. 2,3 Loss of fluid and electrolytes from the gastrointestinal tract may contribute to this unusually high incidence of uric acid lithiasis, but confirming clinical data is lacking. The purpose of this study is to determine alterations in uric acid excretion in patients with established ileostomies and uric acid calculi. Based on these findings, methods of prevention and management of this complication will be discussed. Patients Three patients with established ileostomies