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Mesothelioma is a "new" malignant disease strongly associated with exposure to amphibole asbestos exposure (amosite and crocidolite) environmentally and in the work place. Nonetheless, in recent years, we have learned that many cases of mesothelioma are idiopathic, while some are caused by therapeutic irradiation or chronic inflammation in body cavities. This paper reviews the key epidemiological features of the malignancy in the context of the biological and mineralogical factors that influence mesothelioma development. These tumors challenge the diagnostic pathologist's acumen, the epidemiologist's skill in devising meaningful and definitive studies, the industrial hygienist's knowledge of environmental hazards in diverse occupational settings, and the clinician's skill in managing an intrepid and uniformly fatal malignancy.

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We present a new approach to the analysis of the conformational and the motional properties of an oligosaccharide, methyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside. The approach relies on an order matrix analysis of residual dipolar couplings in the solution state. By combining a number of different types of couplings, (1)D(CH), (2)D(CH), and D(HH), an order matrix is solved for each ring of the trimannoside. The resulting order parameters indicate the internal motion at the alpha (1,3) linkage to be limited, while significant motion is suggested at the alpha (1,6) linkage. Two structures for the trimannoside were determined by aligning the order tensor principal axes obtained from two different orienting media, bicelles and phage. The very similar conformations at the alpha (1,3) linkage of these two structures confirm that the internal motion at the alpha (1,3) linkage is small and the conformation is a good representation of a single preferred structure. The different conformations at the alpha (1,6) linkage suggest that the motional amplitudes are large and the conformations must be viewed as virtual conformers. Compared with traditional NMR methods, data acquisition is easy and data analysis is straightforward.

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The purpose of this study was to compare postabortion health services utilization of hospital abortion patients with community clinic abortion patients using administrative databases. The study was a retrospective cohort study. The study group consisted of patients with induced abortions (n = 41,039) performed in hospitals or community clinics recorded in the 1995 Ontario Health Insurance Plan claims (OHIP) database. An age-matched cohort of 39,220 women who did not undergo induced abortions was selected from the same data source to serve as controls. The main outcome measures were health services utilization indicators constructed from OHIP data within 3 months postabortion from office consultations, emergency room consultations, and hospital admissions. Hospitalization indicators were constructed from Canadian Institute for Health Information hospital discharge data within 3 months postabortion and included data on hospitalizations for infection, certain surgical events, or psychiatric problems. Postabortion health services utilization and hospitalization were higher in the patient population, regardless of service location, than in the age-matched cohort. Within the abortion patient population, hospital day-surgery patients had higher rates of postabortion utilization and hospitalization than did community clinic patients. Multivariate analysis revealed that hospital day surgery patients had a higher risk of subsequent post-abortion hospitalizations for infections (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.23-2.28), surgical events (OR 1.70, 95% CI 1.30-3.24) and psychiatric problems (OR 2.65, 95% CI 1.77-3.98) than community clinic patients. The rates of postabortion health services utilization and risk of hospitalization were lower in community clinic abortion patients than in hospital day-surgery patients. However, it is not possible to fully control for important confounding variables when using these administrative data.

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The objective of this research was to examine the performance of a brief patient survey about quality of care received in community-based diagnostic and therapeutic facilities. The survey was administered to patients in 44 facilities that were also scheduled for a formal external assessment. The response rate was 53%. Patients generally rated their care positively; 18.5% of patients rated at least 1 item as fair or poor. The amount of information received about risks and complications was rated least favorably; concern and caring shown by staff was rated most favorably. The 10 items which patients rated regarding aspects of quality formed an internally consistent scale (alpha = .93). Patients' ratings were not useful predictors of assessor ratings. Although patients' ratings cannot substitute for expert on-site assessments, they are an important part of a quality management program. The patient survey provides additional, complementary information about components of quality care that are important to them.

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Interest in improving the speed of DNA analysis via capillary electrophoresis has led to efforts to integrate DNA amplification into microfabricated devices. This has been difficult to achieve since the thermocycling required for effective polymerase chain reaction (PCR) is dependent on an effective contact between the heating source and the PCR mixture vessel. We describe a noncontact method for rapid and effective thermocycling of PCR mixtures in electrophoretic chip-like glass chambers. The thermocycling is mediated through the use of a tungsten lamp as an inexpensive infrared radiation source, with cooling effected with a solenoid-gated compressed air source. With temperature ramping between 94 and 55 degrees C executed in glass microchambers as rapidly as 10 degrees C/s (heating) and 20 degrees C/s (cooling), cycle times as fast as 17 s could be achieved. Successful genomic DNA amplification was carried out with primers specific for the beta-chain of the T-cell receptor, and detectable product could be generated in a fraction of the time required with commercial PCR instrumentation. The noncontact-mediated thermocycling format was not found to be restricted to single DNA fragment amplification. Application of the thermocycling approach to both quantitative competitive PCR (simultaneous amplification of target and competitor DNA) and cycle sequencing reactions (simultaneous amplification of dideoxy terminated fragments) was successful. This sets the stage for implementing DNA thermocycling into a variety of microfabricated formats for rapid PCR fragment identification and DNA sequencing.

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Free-standing health care facilities now deliver many diagnostic and therapeutic services formerly provided only in hospitals. The financial arrangements available to these facilities differ according to whether the services are uninsured or insured. For an uninsured service, such as cosmetic surgery, the patient pays a fee directly to the service provider. For an insured service, such as cataract surgery, the provincial government uses tax revenues to fund the facility by paying it a facility fee and remunerates the physician who provided the service with a professional fee. No comprehensive, proactive quality assurance efforts have been implemented for either these facilities or the clinical practice provided within them. A pilot study involving therapeutic facilities in Ontario has suggested that a large-scale quality improvement effort could be undertaken in these facilities and rigorously evaluated.

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A primary cardiac spindle cell tumor with immunoreactivity for keratin proteins is reported. Cytogenetic analysis of the tumor demonstrated a translocation (X;18), an aberration almost exclusively reported in synovial sarcomas. Postmortem examination revealed amphibole asbestos within the lungs and diaphragmatic pleural plaques indicative of asbestos exposure. These findings raise questions about the possible causation of this tumor.

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Seventeen cases of "talc pneumoconiosis" were examined pathologically and mineralogically to ascertain whether a true talc pneumoconiosis existed and also to compare these results in primary, secondary, and tertiary exposures. Mineralogic analyses were performed on wet tissue or tissue blocks by a variety of techniques, including analytical transmission electron microscopy and x-ray diffraction. Overall, the pathologic appearance of the tissues was similar in primary, secondary, and tertiary exposures, although ferruginous bodies and foreign body giant cells were not always present in cases caused by secondary exposures. Mixed dust fibrotic lesions were found in two cases in which there were substantial quantities of quartz present. There was great variation in the minerals found within the lung tissues. Several cases showed significant quantities of mica and kaolin in addition to talc. One case consisted predominantly of mica and in fact could be regarded as "mica pneumoconiosis"; this diagnosis was correctly attributed because of the mineralogic findings. Tremolite fibers were found in only two cases. Substantial quantities of crocidolite and amosite fibers were found in one case. This study shows that "talcosis" frequently represents disease associated with a variety of minerals and that talc is a common denominator. It shows also the usefulness of lung dust mineral analysis, particularly in secondary industries, for evaluating the cause of a pathologic reaction when exposures are especially complex.

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Slate is a metamorphic rock comprising silica, aluminum silicates, and small amounts of chlorite, hematite, magnetite, and various carbonates. In the United States slate is quarried in Virginia, Pennsylvania, New York, and Vermont. Workers are exposed during mining and processing of the slate and in crushing mills that prepare gravel. We have conducted detailed mineralogic and pathologic studies on the lungs of 12 workers who developed a pneumoconiosis while employed in the quarries of west central Vermont and adjacent areas of New York. Perivascular and peribronchial lesions accompanied by interstitial fibrosis and macules were scattered diffusely in the lungs. The lesions were associated with a variable number of silicotic nodules. Scanning electron microscopy combined with energy-dispersive x-ray spectrometry demonstrated aluminum and silicon-containing particles with variable cationic constituents and silicon alone in a pattern typical of free crystalline quartz. By x-ray diffraction analysis the majority of the mineral particulates were free crystalline quartz and muscovite, an aluminum silicate in the mica group of minerals. Slateworkers are exposed to respirable airborne dust that has the capacity to produce a pneumoconiosis that differs from classic silicosis.

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Murine cytomegalovirus causes diffuse myocardial lesions in immunologically intact young adult male BALB/cBy mice. The cardiac changes develop in and around the small penetrating blood vessels of the heart where perivascular and interstitial infiltrates of macrophages and lymphocytes accumulate. Focal lesions of the coronary vessels and the endocardium also appear. When infected mice are depleted of CD4+ T lymphocytes, myocardial lesions fail to develop even though virus replication in the heart is enhanced. Contrary wise, when CD4+ cells are adoptively transferred into infected, thymectomized, irradiated, bone marrow-repleted mice, focal perivascular necrotizing lesions of the heart develop. Depletion of CD8+ T lymphocytes fails to influence virus replication and the development of cardiac lesions. Endothelial and endocardial cells appear to be major sites of virus replication in the heart. Delayed hypersensitivity is hypothesized to be the mechanism of cardiac injury in this model system.

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Murine cytomegalovirus infects a variety of organs after inoculation into adult male mice. We have established a model of myocarditis in which focal lesions from adjacent to virus-infected endothelial cells. The development of the myocarditis is mediated by CD4+ helper T cells. The lesions fail to develop when these cells are eliminated from the animal by administration of a specific monoclonal antibody. Alternatively, repletion of thymectomized, irradiated and bone-marrow reconstituted animals with CD4+ cells results in myocarditis. The evidence, although incomplete, suggests that a delayed hypersensitivity response is the pathogenetic mechanism involved.

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EMC-M virus causes a monophasic paralytic syndrome characterized by encephalitic lesions in the brain and patchy demyelinating lesions in the spinal cord and nerve roots of BALB/c mice. Since the replication of EMC virus in vitro is inhibited by tumor necrosis factor (TNF)-alpha we have studied the effect of in vivo administration of this cytokine on the acute disease. Our studies show that periodic administration of TNF-alpha to animals infected with EMC-M reduces viral titers in the brain, and decreases the degree of clinical paralysis and the severity of the inflammatory lesions in the brain.

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Infection of female BALB/c mice with encephalomyocarditis virus results in the development of a paralytic syndrome in 7 to 10 days postinoculation. Previous studies had suggested the involvement of an immune component in the development of central nervous system pathology. We have examined the effects of T-cell depletion on the development of polioencephalitis (neuronal necrosis and inflammation of the brain and brain stem) and the relative contribution of the CD4+ and CD8+ subsets following the establishment of viremia. We show that monoclonal antibody depletion of T cells is effective in the reduction of polioencephalitis when given prior to viral inoculation. However, administration of the antibodies 12 h or more after viral inoculation failed to alter the development of polioencephalitis or encephalomyelitis. We conclude that T cells are involved in the development of central nervous system disease during the initial stages of infection but are not responsible for the later progression of disease.

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The E variant of encephalomyocarditis (EMC) virus causes an encephalomyelitis and coagulative necrosis of the pancreas and parotid glands in some but not all strains of inbred and outbred mice. In other models of disease caused by picornaviruses, depletion of specific lymphocyte subsets abrogates the development of tissue lesions. In this study, severe encephalomyelitis and acinar pancreatitis and parotitis developed in adult male A/J mice infected with 100 PFU of EMC virus. Depletion of the CD4+ subset of T lymphocytes in vivo with a monoclonal antibody (MAb) prior to EMC virus inoculation protects mice from developing encephalomyelitis, pancreatitis, and parotitis. This effect is also seen when animals are treated with anti-CD4 and anti-CD8 in combination, but the anti-CD8 MAb alone does not ameliorate the disease. Overall, concentrations of virus in tissues from anti-CD4-treated animals are lower than in immunologically intact control mice. Small-plaque variants of virus were also recovered from the tissues in some animals in this group. CD4+ lymphocytes are involved in the expression of EMC virus-induced pancreatitis and parotitis in A/J mice. This specific subset of T cells would appear to influence EMC viral tropism or replication in various organs.

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The lungs of 42 smokers and 13 nonsmoking males of various ages who died suddenly and unexpectedly were examined grossly using Gough-Wentworth whole-lung sections and by microscopic planimetry to assess the severity and prevalence of emphysema. The bronchioles in representative histologic sections were evaluated for inflammation and epithelial metaplasia as well as for fibrosis and muscular hypertrophy. Postmortem interviews with next of kin established a history of cigarette smoking and excluded possible occupational exposures to toxic or particulate inhalants. Emphysematous changes were not prominent in members of the study group, but they tended to be more severe in smokers (p = 0.059) and increased in severity with age (p less than 0.001). Inflammatory changes (so-called smoker's bronchiolitis) were evident in smokers of all ages, although they were significantly less prominent in the lungs of older smokers. On the other hand, respiratory and membranous bronchiolar wall fibrosis was increasingly evident in older smokers (p less than 0.05). Muscular hypertrophy in the bronchiolar walls was significantly greater in smokers, but a change with age was not observed. These findings strongly suggest that bronchiolar fibrosis is associated with chronic cigarette use. These lesions occur independently of emphysema and may account for some of the subtle physiologic alterations observed in smokers.

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