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Biomedical subjects

R P Sherwin

Publications and source records attributed to R P Sherwin.

At least 19 recordsLinked to original sources

Air pollution: the pathobiologic issues.

In defining the adverse effects of ambient levels of ozone on the human lung, research has tended to emphasize direct cause and effect responses. However, disease is generally multicausative and the lung has relatively few ways to respond to injury. Moreover, all adult lungs have some disease. Thus, pathogenesis is more appropriately addressed by asking "What role does the agent in question play in the causation, promotion, facilitation, and/or exacerbation of disease that is present?" Our recent studies of the lungs of 107 ostensibly healthy youths between 14 and 25 years of age (violent death cases in Los Angeles County) add suggestive evidence to epidemiologic and experimental data indicating that air pollution is adversely affecting the human lung. We found 80% of the youths with some degree of presumably subclinical Centriacinar Region disease and, in 27%, the Centriacinar Region disease was severe and extensive. Centriacinar Region disease has been linked to infectious organisms, cigarette smoke, ozone, mineral dusts, and other noxious agents. Recently, a mild form of Centriacinar Region disease has been produced in primates exposed to a level of ozone (0.15 ppm) that is frequently exceeded in Los Angeles. Since there is suggestive evidence that air pollution in Los Angeles increases the rate of decline of lung function, we suspect that there has also been an increase in the rate of structural decline, manifest in part by accentuated Centriacinar Region disease. The health significance of Centriacinar Region disease is just beginning to be appreciated. At the very least, reserve depletion reflected in the Centriacinar Region disease implies some reduction in lung performance and some increase in susceptibility to disease in general. At worst, the unexpected severity of the Centriacinar Region disease may be a bellwether for an impending rise in clinically manifested lung disease for the general population. An urgent research need is the monitoring of health through inventories of the functional and structural units of the human lung, with special emphasis on subpopulations of cell societies of the lung. The feasibility of applying image analysis for large volume objective quantitations has been demonstrated and should be implemented. Multicity studies, in cooperation with Offices of the Medical Examiner-Coroner and autopsy services in general, can help meet the critical need for increased sensitivity in the monitoring of the public health in a changing environment.

Air Pollutants

Latex condom deterioration accelerated by environmental factors: I. Ozone.

Commercial non-lubricated latex condoms were unpackaged and exposed in an environmental chamber to ozone levels (0.3 ppm) commonly present in urban smog conditions. Deterioration was observed by scanning electron microscopy after 18 hours exposure. Loss of mechanical strength was quantitated by measurement of the air pressures necessary to burst the condom and volumes at burst. After 24 hours exposure to ozone the latex surface was covered with craters and after 48 hours the pressure required to burst the condom was 44% that of control samples. Data suggest the need for study of the effectiveness of lubrication and packaging in protecting condoms from environmental factors which may accelerate deterioration.

Contraceptive Devices, Male

Acute and chronic pericholangiolitis in association with multifocal hepatic lymphangiomatosis.

Multifocal, lymphangiomatous lesions were found in the right lobe of the liver of a 9-year-old girl who died seven days after head trauma. We believe the lesions represent a cystic and pseudoneoplastic dilatation of liver lymphatics secondary to a posttraumatic complication, acute and chronic inflammation primarily of small bile ducts, and canaliculi (pericholangiolitis). The findings provide new evidence that inflammation and fluid overload, in the absence of a congenital malformation, are cardinal factors in the pathogenesis of some forms of lymphangiomatosis.

Bile Canaliculi

Desquamative interstitial pneumonia in an infant. Mimicry of sudden infant death syndrome.

A 15-week-old infant girl, without a prior history of overt illness, was found dead while sleeping between her two parents. The gross examination at autopsy showed only congested lungs, and the initial diagnosis was sudden infant death (SID). On microscopic examination, a desquamative interstitial pneumonia (DIP) was observed. The widespread, patchy intraalveolar histiocytic desquamation was associated with lymphocytic infiltration of bronchiolar and aveolar walls, which together provided convincing evidence that an interstitial pneumonitis was the cause of death. A viral etiology seems most likely in view of the accompanying chronic inflammation of bronchial submucosal glands.

Cause of Death

The effect of ozone and simulated high altitude on murine lung elastin: quantitation by image analysis.

Four subgroups of a colony of 50 mice were housed in environmental chambers supplied by particle- and pollutant-filtered air. The animals were exposed to 0.35 ppm ozone and/or simulated high altitude (380 mm Hg) for four weeks, with exposure 4 1/2 hours/day and 5 days/week. Lung elastin area and alveolar wall area were quantitated by computer assisted image analysis of paraffin embedded sections stained with aldehyde fuchsin and metanil yellow. Compared to the controls, the combination of ozone and simulated high altitude resulted in a 54.5% increase in lung elastin area (p less than 0.005), and simulated high altitude by itself increased elastin area by 19.6% (p less than 0.05). Simulated high altitude with and without ozone exposure also increased alveolar wall area (24.8%, p less than 0.01; and 9.7%, NS, respectively). Ozone exposure alone had a reverse effect: a 16.1% decrease in elastin area (p less than 0.1), and a 6.5% decrease in alveolar wall area (NS). Since an intact lung scaffolding is required for full restoration of injured alveolar epithelium and since intact lung elastin is critical for proper lung compliance, the results suggest that ozone exposure at high altitude is most likely to have an adverse effect on lung structure and function.

Altitude

Recent trends in mesothelioma incidence in the United States.

Mesothelioma incidence rates based on data from population-based cancer registries in New York State (exclusive of New York City), Los Angeles County, California, and the SEER Program of the National Cancer Institute were analyzed for trends, using original cancer registry diagnoses. Results indicate a significant increase in incidence during 1973-80 for pleural mesothelioma among white males older than 55 at time of diagnosis but not for other age-race-sex-site subgroups. A histopathologic review of New York State and Los Angeles County cases by two independent pathologists, expert in the diagnosis of mesothelioma, lowered the overall estimates but a significant upward trend remained. The observed trend does not appear to be related to changes in diagnostic practice. The results of a five-member panel of expert pathologists will be published in a separate methodology paper.

Adolescent

Effect of 0.3 ppm ozone exposure on type II cells and alveolar walls of newborn mice: an image-analysis quantitation.

Newborn Swiss-Webster mice were exposed to intermittent 0.3 ppm ozone (O3) for 6 wk, and the lungs of 137 exposed and 138 control animals (275 of the 301 in the colony) were suitable for computer-assisted image-analysis quantitation. Data were obtained on numbers and areas of lactate dehydrogenase stained type II cells, and also area, perimeters, and linear intercepts of the alveolar wall. As noted in an earlier study of adult mice, ozone exposure increased all cell and wall measurements. In contrast to the adult animal findings, there was a greater increase in mean type II cell area (p = 0.07) than in numbers of type II cells, with the latter increase falling short of statistical significance. The increase in cell area at the expense of cell number may largely be due to cell pairing or multicell clustering, events that would mask type II cell hyperplasia. Ozone effects on the type II cell population implicate damage to the type I alveolar lining cells. Moreover, the increases in alveolar wall measurements that were found in both the adult and developing mouse lung imply an alteration of the lung scaffolding, and this raises the question of impaired regeneration of the epithelial lining.

Age Factors

Malignant mesothelioma: incidence, asbestos exposure, and reclassification of histopathology.

The Los Angeles County Cancer Surveillance Program abstracts records on almost all cases of cancer occurring in the county. In a study of those cases of pleural and peritoneal malignant mesothelioma (MM) that occurred from 1972 to 1979 occupational histories were obtained during interviews, and histopathology of the tumours was reviewed and classified by a member of a mesothelioma reference panel who was unaware of the exposure histories. About half the cases reviewed had likely exposure to asbestos at work. The greatest proportion of cases designated as MM by the pathologist occurred among individuals likely to have had the heaviest exposure of asbestos (42%). No upward trend of incidence over time was apparent among cases designated as MM. The age adjusted incidence rates for designated MM were lower than in other studies. The well recognised interobserver variability in diagnosing MM apparently produces raised estimates of incidence and an overestimate of trends of incidence. The interobserver variability may result from different awareness of MM occurrence, a lack of precise histopathological criteria for the diagnosis, or the influence of a history of exposure to asbestos on the interpretation. A history of exposure to asbestos may bias interpretation of histopathology and should not be used to make the histological diagnosis.

Asbestos

Histological types of malignant mesothelioma and asbestos exposure.

The Los Angeles County Cancer Surveillance Program abstracts hospital pathology records on almost all cases of cancer occurring in the county. Those cases of pleural and peritoneal mesothelioma that occurred between 1972 and 1978 were identified. Occupational histories were obtained from interviews, and the histopathology of the tumours was reviewed by a member of a mesothelioma reference panel who was unaware of the exposure histories. The relation of asbestos exposure to the three histological types of mesothelioma (epithelial, mesenchymal, and mixed) was studied among the 29 cases for whom occupational histories were available and who were also considered to have histopathology consistent with mesothelioma. The proportion of cases exposed to asbestos was high for both the epithelial (11/17, 65%) and mixed histological types (6/11, 55%). The single case of mesothelioma classified as a mesenchymal type was also exposed to asbestos. Cases who had worked in shipyards were represented in each of the three groups. In cases who had worked in asbestos production and manufacture an exclusively epithelial type of tumour was observed. In cases who had worked as insulators or in heating trades the histological type was predominantly (3/4) mixed. These data do not support the hypothesis that any specific histological type of mesothelioma is especially related to asbestos exposure.

Asbestos

Nitrogen dioxide exposure--influence on rat testes.

Prolonged intermittent exposure to subanesthetic concentrations of nitrous oxide (N2O) can impair spermatogenesis in the LEW/f mai rat. USP purity standards state that N2O used for medical purposes may contain other oxides of nitrogen such as NO and NO2 as impurities at concentrations up to one part per million (ppm) each. The question thus arises as to whether prolonged exposure to N2O may be associated with adverse health effects from oxides of nitrogen other than N2O, particularly NO2. NO2 has demonstrated biological toxicity at concentrations as low as 0.3 ppm. In this study, rats were exposed to filtered air with and without 1 ppm NO2 for 7 hr/day, 5 days/week, for 21 days. No gross or light microscopy abnormality was found in the testes of NO2-exposed rats. Serum vitamin B12 levels were within normal limits. The findings indicate that NO2 exposure under the test conditions does not in itself impair spermatogenesis or alter B12 levels.

Animals

Preface.

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Air Pollution

What is an adverse health effect?

Health is defined as homeostasis of the cellular ecology, and a state where there has not been an inordinate loss, reversible or irreversible, of the structural and/or functional reserves of the body. An adverse health effect is defined as the causation, promotion, facilitation and/or exacerbation of a structural and/or functional abnormality, with the implication that the abnormality produced has the potential of lowering the quality of life, contributing to a disabling illness, or leading to a premature death. Experimental animal studies indicate that poor air quality has the potential for serious adverse health effects through perturbations of the cellular ecology over long-term periods. Some of the most important concerns are inordinate depletions of lung reserves (in particular, emphysema), the facilitation of cancer metastasis to the lung, the facilitation of immunologic deficits with the concomitant expression of opportunistic organisms, and amplification of cardiovascular abnormalities (in particular, ischemic heart disease). It is argued that air quality standard setting should more strongly consider adverse health effects that are presently subclinical in nature in order to achieve early prevention instead of late correction.

Adolescent

When are electron microscopy, histoculture, and other procedures useful in the clinical evaluation of lung cancer?

The earlier pessimistic outlook on the prognosis of lung cancer has had two particularly adverse effects on progress in pathologic interpretation. There has been little incentive to resolve several basic problems, and little encouragement from clinical investigators to apply electron microscopy, tissue culture, immunopathologic tests, and biochemical assays. However, substantial advances in the clinical detection and management of lung cancer have renewed the clinician's interest in pathologic interpretation. In fact, the pathologist is under increasing pressure to narrow the gap between the diagnosis that routine laboratory examination provides and the more detailed and precise interpretation that can be obtained from a research facility. This report presents recommendations for improving the level of interpretation of the routine diagnostic work-up through modest investments in newer methods, and thorough special tissue processing in anticipation of a need for assistance from the research laboratory.

Carcinoma, Small Cell

Histoculture of human breast cancers.

Breast cancers from 53 patients were explanted in culture, and 39 with two-year or more follow-up and documentable tissue forms of cancer in culture (histoculture) are the subject of this report. Clinicopathologic findings have been correlated with dynamic aspects of the cancers in short-term histocultures, including cell cohesiveness, yield and survival time of the cancer cells in culture, emigration of macrophages from the explants, and the occurrence of special interactions of lymphocytes with cancer cells. The outstanding finding was the association of special lymphocyte-cancer cell interactions with a more favorable prognosis; six of seven patients (86%) with infiltrating ductal cancer showing lymphocyte congregation, emperiopolesis, or other special activity were tumor-free survivors. Additional findings were: 1) patients having four or fewer lymph nodes positive for cancer had a survival rate of 50%, but this fell to 20% when emigrating macrophages were not present in the cancer cultures; 2) eight of the 12 patients (67%) having discoid histoculture survival time of less than one week were tumor-free, as opposed to three of eight patients (27%) where tumor survival in vitro was greater than one week. The reverse was true for nondiscoid, poorly cohesive colonies of cancer; 3) the combination of tumor-negative lymph nodes and low in vitro cancer yield was associated with the best patient survival rate, 64%. However, the combination of negative nodes and high in vitro yield was linked to the worst patient survival (20%). Although the overall study does not permit definitive conclusions, there is an undeniable potential for the use of histocultures in the evaluation of human cancers. Expanded studies are warranted, including larger numbers of tumors and cultures, and longer patient follow-up periods.

Breast Neoplasms