Dependence of alignment direction on magnitude of strain in esophageal smooth muscle cells.

The response of cells in vitro to mechanical forces has been the subject of much research using devices to exert controlled mechanical stimulation on cultured cells or isolated tissue. In this study, esophageal smooth muscle cells were seeded on flexible polyurethane membranes to form a confluent cell layer. The cells were then subjected to uniform cyclic stretch of varying magnitudes at a frequency of approximately five cycles per minute in a custom made mechatronic bioreactor, providing similar strains experienced in the in vivo mechanical environment of the esophagus. The results show that the orientation response is dependent on the magnitude of cyclic stretch applied. Smooth muscle cells showed parallel alignment to the force direction at low cyclic strains (2%) compared to the hill-valley morphology of static controls. At higher strains (5% and 10% magnitude), the cells exhibited a consistent alignment perpendicular to the strain. To our knowledge, this is the first time that the alignment direction's dependence on strain magnitude has been demonstrated. MTS analysis indicated that cell metabolism was reduced when mechanical strain was applied, and proliferation was inhibited by mechanical strain. Protein expression indicates a decrease in smooth muscle alpha-actin, indicative of changes in cell phenotype, an increase in vimentin, which is associated with increased cell motility, and an increase in desmin, indicating differentiation in stimulated cells.

Measurement of beryllium in lung tissue of a chronic beryllium disease case and cases with sarcoidosis.

BACKGROUND: The clinical features of chronic beryllium disease (CBD) are similar to many other chronic lung diseases. In particular, it may be difficult to distinguish it from pulmonary sarcoidosis since the two conditions may be very alike in clinical, pathological and radiological features. Aim To determine if the amount of beryllium found in the lungs could be used to differentiate CBD from sarcoidosis and controls. METHODS: Analyses for beryllium in the autopsied lung tissues of 29 cases and controls were carried out. The cases included one CBD, three confirmed sarcoidosis and 25 controls. Blocks of formalin-fixed tissues were analysed by an atomic absorption spectrophotometer equipped with a graphite furnace. A method for analysis of beryllium in air was modified to permit tissue analysis. RESULTS: The CBD case had a much higher average beryllium level, but some individual results were similar to controls and patients with sarcoidosis. CONCLUSION: The CBD case had beryllium levels within the range of values reported in the literature. The differentiation between CBD and sarcoidosis could not be made with reasonable assurance based only on the analytic result. Occupational history is very important in making a diagnosis of CBD, along with the analysis of tissues. Tissue analysis helped confirm the diagnosis of compensatable CBD in this particular case.

Tentative explanatory variable of lung dust concentration in gold miners exposed to crystalline silica.

INTRODUCTION: The first objective of the study was to investigate the relationships between quantitative lung mineral dust burdens, dust exposure history, and pathological fibrosis grading in silicotic workers. The second objective was to evaluate the association between particle size parameters, concentration of retained silica particles and the severity of the silicosis. Sixty-seven paraffin-embedded lung tissue samples of silicotic patients were analyzed. The cases of silicosis included 39 non-lung cancer patients and 28 patients with lung cancer. All of the cases were gold miners in the Province of Ontario, Canada. MATERIAL AND METHODS: Particles, both angular and fibrous, were extracted from lung parenchyma by a bleach digestion method, mounted on copper microscopic grids by a carbon replica technique, and analyzed by transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS). Quartz concentration was also determined by X-ray diffraction (XRD) on a silver membrane filter after the extraction from the lung parenchyma. RESULTS: Total particles, silica, clay, and quartz also increase in concentration with increased age at death, although the trends are not statistically significant. Quartz concentration has a statistically significant correlation with the silicosis severity score (r = +0.45, p < 0.001), with the geometric mean concentration increasing from 2.24 micrograms/mg in the group having silicosis severity score less than 1 to 4.80 micrograms/mg in group with highest score. Quartz concentration is the only significant explanatory variable of the silicosis severity with a regression coefficient of +0.41 (p < 0.001). CONCLUSION: Among several dust exposure variables extracted from the work history of the miners, the calendar year of first exposure was the primary significant determinant of lung retained total particles, silica, and clay minerals, except for quartz. A statistically significant linear relationship between lung quartz concentration and silicosis severity in the gold miners was observed (p < 0.001). Among the several types of lung particles detected, quartz was the only significant determinant of the silicosis severity in the gold miners in this study and vice versa, although it explained only 20% of the variation in the severity. This study suggested no significant linear relationship between the duration of dust exposure and the lung burden of any particle types in the gold miners.

Angular and fibrous particles in lung in relation to silica-induced diseases.

INTRODUCTION: The lung concentration of angular and fibrous particles was measured in cases of lung fibrosis only, in cases of lung fibrosis and lung cancer, and in cases of lung cancer only. These patients worked in different trades (mining, foundries, construction and were not a homogeneous group of exposed workers. MATERIAL AND METHODS: Particles, both angular and fibrous, were extracted from lung parenchyma by a bleach digestion method, mounted on copper microscopic grids by a carbon replica technique, and analyzed by transmission electron microscopy (TEM) and energy-dispersive spectroscopy (EDS). The quartz concentration was also determined by X-ray diffraction (XRD) on a silver membrane filter after extraction from the lung parenchyma. RESULTS: (1) Lung cancer and lung fibrosis cases retained more metal-rich particles (P = 0.02) and more angular particles of all sorts (P = 0.009) than did lung fibrosis cases only, and the differences were statistically significant. (2) However, more quartz was retained in the lungs in lung fibrosis cases than in lung fibrosis or lung cancer cases, but the difference in the concentrations was not statistically significant. (3) More ferruginous bodies were retained in the lungs in lung cancer and lung fibrosis cases than in cases of lung fibrosis only, and the difference in the concentrations was statistically significant (P = 0.02). CONCLUSION: Results obtained from lung tissue must always be interpreted cautiously. However, these results are consistent with the hypothesis that workers in some trades such as foundries were exposed not only to quartz but also to asbestos, ceramic fibers, metal-rich non fibrous particles, and other likely carcinogenic chemicals. The wide range of particle types identified in the lungs of these workers illustrates the complexity of trying to determine disease origins in these work environments. Epidemiology studies have to control for the exposure to these carcinogens as well as for smoking habits.

Angular and fibrous particles in lung are markers of job categories.

INTRODUCTION: The lung concentration of angular and fibrous particles has been measured when cases are stratified into their job categories; 21 miners (metallic mines such as gold, zinc and copper), 18 iron foundrymen, 22 non-iron foundrymen, four welders, three sand-blast workers, four construction workers, three technicians and professionals, seven workers in other trades excluding welding. Twelve asbestos miners representing a positive exposure to asbestos and 20 people representing a background population were added to the previous groups. MATERIAL AND METHODS: Particles, both angular and fibrous, were extracted from lung parenchyma by a bleach digestion method, mounted on copper microscopic grids by a carbon replica technique and analyzed by transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS). Quartz concentration was also determined by X-ray diffraction (XRD) on a silver membrane filter after the extraction from the lung parenchyma. RESULTS: (1) The highest concentrations of quartz were found in mines (metallic mines), iron foundrymen and sand-blast workers. Notable amounts quartz were found in welders and professionals. (2) The highest concentrations of short fibres were found in non-iron foundrymen, asbestos miners and construction workers. (3) The highest concentrations of long fibres were found in non-iron foundry men and asbestos miners. (4) The highest concentrations of ferruginous bodies were found in non-iron foundrymen and asbestos miners. (5) The non-iron foundrymen were exposed to ceramic fibres and asbestos fibres. CONCLUSION: The results of the study may not be representative of the broad spectrum of workers in the industrial activities in which they have been involved. However, the detailed composition of the retained particles of our workers is explained both qualitatively and quantitatively by their work histories. Finally, the broad range of particle types identified in the lungs of these workers illustrate the complexity or trying to determine disease origins in these occupational settings.

Mortality from lung cancer in Ontario uranium miners.

Mortality from lung cancer was greater in Ontario uranium miners than in the general male population of Ontario (observed = 152, expected = 67.6, standardised mortality ratio 225, 95% confidence interval 191-264). Part of the excess of lung cancer may be because the proportion of men who are smokers or have smoked is greater in uranium miners than in Ontario men. Smoking does not explain the whole excess. Mortality from lung cancer in Ontario uranium miners is clearly related to exposure to short lived radon progeny. The excess relative risk of lung cancer from the same degree of exposure to short lived radon progeny is greatest five to 14 years after exposure and less subsequently. It is greater in men under the age of 55 years and less in older men. Part of the excess of lung cancer mortality in Ontario uranium miners is probably also due to exposure to arsenic that occurred earlier in gold mines. In Ontario uranium miners, the lung cancer mortality from exposure to arsenic increases as the intensity of exposure to short lived radon progeny increases. This finding is consistent with the hypothesis that the risk of lung cancer from exposure to arsenic is enhanced by exposure to other carcinogens. In Ontario uranium miners, the proportion of lung cancers that are small cell carcinomas is greater than in the general population. The proportion of small cell carcinomas is especially great five to 14 years after exposure to short lived radon progeny and in men who die from lung cancer at younger ages.

Mortality from stomach cancer in Ontario miners.

An excess of mortality from stomach cancer has been found in Ontario gold miners (observed (obs) 104, standardised mortality ratio (SMR) 152, 95% confidence interval (95% CI) 125-185) and no excess of stomach cancer could be detected in other miners in Ontario (obs 74, SMR 102, 95% CI 80-128). The excess of stomach cancer appeared five to 19 years after the miners began gold mining in Ontario. In that interval, similar patterns of excess mortality from stomach cancer were found in miners born in north America (obs 14, SMR 268, CI 147-450) and in miners born outside north America (obs 12, SMR 280, 95% CI 145-489). Twenty or more years after the miners began mining gold, an excess of mortality from stomach cancer was found in gold miners born outside of north American (obs 41, SMR 160, 95% CI 115-218) but not in gold miners born in north America (obs 37, SMR 113, 95% CI 80-156). The excess of stomach cancer in gold miners under the age of 60 (obs 45, SMR 167, 95% CI 122-223) seems larger than the excess in gold miners between the ages of 60 and 74 (obs 59, SMR 143, 95% CI 109-184). Exposures to arsenic, chromium, mineral fibre, diesel emissions, and aluminium powder were considered as possible explanations of the excess of stomach cancer in Ontario gold miners. Exposure to diesel emissions and aluminium powder was rejected as gold miners and uranium miners were exposed to both agents but an excess of stomach cancer was noted only in gold miners. The association between the excess of stomach cancer and the time since the miner began mining gold suggested that duration of exposure to dust in gold mines ought to be weighted according to the time since the exposure to dust occurred and that an appropriate time weighting function would be one in the interval five to 19 years after each year of exposure to dust and zero otherwise. A statistically significant association between the relative risk of mortality from stomach cancer and the time weighted duration of exposure to dust in gold mines was found in miners under the age of 60. Time weighted indices of exposure to chromium and arsenic were formed for each gold miner by time weighting the product of the duration of exposure to dust in a gold mine and the percentages of arsenic and chromium in rocks in that gold mine. Exposure to mineral fibre was measured in terms of the time weighted duration of employment in those gold mines that contain mineral fibre. A statistically significant association between the excess of stomach cancer in gold miners under the age of 60 and the time weighted index of exposure to chromium occurred and not association was found between the excess of stomach cancer and either the time weighted duration of employment in mines containing mineral fibre. The excess of stomach cancer in gold miners under the age of 60 was better associated with the time weighted index of exposure to chromium than to the time weighted duration of exposure to dust in gold mines. Although the number of cases of gastric cancer that were classified according to the system of Lauren was small, the data suggest that for miners under the age of 60, exposure to chromium is associated with the development of the intestinal rather than the diffuse type of gastric cancer.

Carcinoma of the lung in Ontario gold miners: possible aetiological factors.

A cohort of 54,128 men who worked in Ontario mines was observed for mortality between 1955 and 1986. Most of these men worked in nickel, gold, or uranium mines; a few worked in silver, iron, lead/zinc, or other ore mines. If mortality that occurred after a man had started to mine uranium was excluded, an excess of carcinoma of the lung was found among the 13,603 Ontario gold miners in the study (standardised mortality ratio (SMR) 129, 95% confidence interval (95% CI) 115-145) and in men who began to mine nickel before 1936 (SMR 141, 95% CI 105-184). The excess mortality from lung cancer in the gold miners was confined to men who began gold mining before 1946. No increase in the mortality from carcinoma of the lung was evident in men who began mining gold after the end of 1945, in men who began mining nickel after 1936, or in men who mined ores other than gold, nickel, and uranium. In the gold mines each year of employment before the end of 1945 was associated with a 6.5% increase in mortality from lung cancer 20 or more years after the miner began working the mines (95% CI 1.6-11.4%); each year of employment before the end of 1945 in mines in which the host rock contained 0.1% arsenic was associated with a 3.1% increase in lung cancer 20 years or more after exposure began (95% CI 1.1-5.1%); and each working level month of exposure to radon decay products was associated with a 1.2% increase in mortality from lung cancer five or more years after exposure began (95% CI 0.02-2.4%). A comparison of two models shows that the excess of lung cancer mortality in Ontario gold miners is associated with exposure to high dust concentrations before 1946, with exposure to arsenic before 1946, and with exposure to radon decay products. No association between the increased incidence of carcinoma of the lung in Ontario gold miners and exposure to mineral fibre could be detected. It is concluded that the excess of carcinoma of the lung in Ontario gold miners is probably due to exposure to arsenic and radon decay products.

Ultrastructure of poorly differentiated diffuse epithelial mesotheliomas.

In differentiating diffuse epithelial mesothelioma from metastatic adenocarcinoma in pleural and peritoneal biopsies, the number and form of microvilli and the amount and distribution of tonofilaments are thought to be the most useful criteria. This report details 5 cases of diffuse epithelial mesothelioma in which the characteristic fine structural features of neoplastic mesothelial cells were markedly modified. The majority or all tumor cells were poorly differentiated in electron micrographs, particularly with reduced prominence or absence of intermediate filaments, desmosomes, intracytoplasmic lumina, and microvilli. Immunohistochemistry revealed the absence of carcinoembryonic antigen and the presence of cytokeratin in all cases. Comparison with a better differentiated case suggests cytologic details that are useful in distinguishing the poorly differentiated type of epithelial mesotheliomas from adenocarcinoma. These include a mosaic pattern of closely associated tumor cells with a few long, narrow cytoplasmic processes lying parallel to adjacent plasma membranes, abundant cytoplasm with limited organelles usually having a polar arrangement, and nuclei with markedly disaggregated chromatin and prominent nucleolonemal-type nuclei.

Ultrastructural aspects of the histogenesis of diffuse and localized mesothelioma.

During an ultrastructural review of 30 diffuse and 10 localized mesotheliomas, it was apparent that some micrographs showed various stages in the developmental processes involved in the formation of histological patterns in diffuse mesotheliomas and a histogenetic link between diffuse and localized mesotheliomas. Cells in the stromal or sarcomatous regions of diffuse mesothelioma often show varying degrees of mesothelial differentiation and a gradual transition to cells with typical mesothelial characteristics that organize into structures recapitulating the surface layer of serosal membranes. Tumor cells in localized mesotheliomas had many similarities to the "stromal" cells in the diffuse counterpart including intercellular junctions, rare microvilli and occasional foci of basal lamina. It is postulated that diffuse and localized mesotheliomas share a common histogenetic origin as a result of neoplastic induction of specialized submesothelial cells. In this concept, tumor cells in diffuse mesotheliomas reflect stages in the differentiation and organization of normal serosal membranes and localized mesotheliomas mirror the earliest phases of this process.

Formation of intrahepatic portosystemic shunts using a balloon dilatation catheter: preliminary clinical experience.

Six patients with advanced cirrhosis and portal hypertension had life-threatening upper gastrointestinal hemorrhage from esophageal varices. The varices were obliterated angiographically, using the transjugular approach, after which an intrahepatic portosystemic shunt was created in each case by inflating the balloon of a Grüntzig dilatation catheter in the needle tract between the portal and hepatic veins. All of the patients were expected to succumb quickly to their severe liver disease and massive variceal bleeding, but three of the six survived the initial hemorrhage, and two of these were discharged from hospital. There was an initial reduction of portal venous pressure of 10-15 mm Hg in all patients. All six shunts were patent angiographically 12 hr after the procedure. Two patients had venograms 5 days later and both shunts were patent. All six patients died within 6 months, but in three of the four postmortem examinations the shunts were easily identified and shown to be patent, the last of these 6 weeks after the procedure. These findings suggest that the technique could be of therapeutic value in the management of patients with portal hypertension.

Histological staining for the diagnosis of mesothelioma.

The histological diagnosis of mesothelioma may be difficult, especially when only a small biopsy is available. The epithelial form of mesothelioma can closely resemble an adenocarcinoma, so much so that it is often difficult or impossible to distinguish between them by light microscopy. This paper examines the results of staining 30 cases of the epithelial form of mesothelioma by various techniques for mucus. The slides were evaluated according to the intensity and extent of staining, the color of the reaction, the location of the staining (intra- or extra-cellular), and the reproducibility and reliability of the technique.

Systemic infection with Alaria americana (Trematoda).

Alaria americana is a trematode, the adult of which is found in mammalian carnivores. The first case of disseminated human infection by the mesocercarial stage of this worm occurred in a 24-year-old man. The infection possibly was acquired by the eating of inadequately cooked frogs, which are intermediate hosts of the worm. The diagnosis was made during life by lung biopsy and confirmed at autopsy. The mesocercariae were present in the stomach wall, lymph nodes, liver, myocardium, pancreas and surrounding adipose tissue, spleen, kidney, lungs, brain and spinal cord. There was no host reaction to the parasites. Granulomas were present in the stomach wall, lymph nodes and liver, but the worms were not identified in them. Hypersensitivity vasculitis and a bleeding diathesis due to disseminated intravascular coagulation and a circulating anticoagulant caused his death 8 days after the onset of his illness.

Fatal human infection with mesocercariae of the trematode Alaria americana.

A fatal human infection with mesocercafiae of Alaria americana is described. Several thousand mesocercariae were estimated to be present in the peritoneal cavity, bronchial aspirate, brain, heart, kidney, liver, lungs, lymph nodes, pancreas, retroperitoneal adipose tissue, spinal cord, spleen, and stomach. Nine days from the onset of symptoms death resulted from asphyxiation due to extensive pulmonary hemorrhage probably caused by immun-mediated mechanisms. Circumstances suggest the victim probably ate inadequately cooked frog legs while hiking. Mesocercariae penetrated through the stomach wall and spread to the various organs both directly and via and circulatory system.