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Biomedical subjects

E Chan

Publications and source records attributed to E Chan.

At least 109 records · Page 6Linked to original sources

Comparative study of isradipine and sodium nitroprusside in the control of hypertension in patients following coronary artery-bypass surgery.

Essential hypertension is a common occurrence after coronary artery bypass-graft surgery. CABG and may lead to postoperative complications. In an open randomized study, either isradipine or sodium nitroprusside was given by infusion to 27 postoperative CABG patients who had a mean arterial pressure (MAP) greater than 100 mmHg. Both agents were able to achieve reductions in MAP to 80-90 mmHg quickly and safely, although the effects of isradipine at the dosage used were apparent sooner and gave smoother control than with sodium nitroprusside. There were two non-responders with the latter agent. Systemic vascular resistance fell and cardiac output increased in patients in both treatment groups. Also, an increase in heart rate was observed with both agents, although this increase was smaller with isradipine. In conclusion, isradipine appears to be a useful agent in the treatment of hypertension following CABG surgery and may have some advantages over sodium nitroprusside.

Adolescent↗

Displacement of bilirubin from albumin by berberine.

A study was made of the effect of berberine, the major ingredient of the Chinese herb huanglian (coptis chinensis) reported to pose some risk for kernicterus among jaundiced newborn Chinese infants, on the protein binding of bilirubin, using the peroxidase kinetic method. Berberine was found in vitro, as to its displacing effect on a molar basis, to be about tenfold superior to phenylbutazone, a known potent displacer of bilirubin, and about hundredfold to papaverine, a berberine-type alkaloid. The chronic intraperitoneal administration of berberine (10 and 20 micrograms/g) daily for 1 week to adult rats (mixed breed of Wistar and Sprague-Dawley) resulted in a significant decrease in mean bilirubin serum protein binding, due to an in vivo displacement effect and a persistent elevation in steady-state serum concentrations of unbound and total bilirubin, possibly due to inhibition of metabolism. The use of the herb and other traditional Chinese medicines containing a high proportion of berberine is best avoided in jaundiced neonates and pregnant women.

Animals↗

The use of glipizide combined with intensive insulin treatment for the induction of remissions in new onset adult type I diabetes.

To determine if glipizide could enhance remission induction in new onset type 1 diabetes compared to intensive insulin treatment alone, 27 patients with type 1 diabetes were intensively treated in an open randomized trial with subcutaneous injections for one month. The insulin was randomly either discontinued (Group A) or the insulin discontinued and glipizide begun (Group B) Three patients in Group A (22%) and 7 in Group B (54%, p < .05) underwent insulin-free remissions for 10.3 +/- 4.4 and 8.7 +/- 2.6 months, respectively (p = NS). Mean blood glucose levels during insulin treatment were lower in patients entering remissions (94 +/- 3 mg/dl versus 102 +/- 5 mg/dl, p < 0.05). C-peptide levels were performed 0, 4, 8, and 24 weeks after insulin treatment. When all patients were examined, mean stimulated C-peptide levels at 4 weeks (0.58 +/- 0.09 pm/ml) were increased compared to time 0 (0.32 +/- 0.05 pm/ml, p < 0.02). Patients not entering remission had higher 4-week stimulated values (0.67 +/- 0.12 pm/ml) compared to time 0 values (0.29 +/- 0.06 pm/ml, p < .01), whereas remission patients' mean C-peptide levels remained similar at 0, 4, 8 and 24 weeks. These data indicate that a) insulin treatment plus glipizide induces higher rates of remission compared to intensive insulin treatment alone, b) the intensity of initial metabolic control may be an important determinant for remission induction, and c) endogenous insulin secretion is not associated with remission induction, suggesting that glipizide alters insulin sensitivity or is immunomodulatory in the context of new onset type 1 diabetes.

Adult↗

Intrauterine pressure wave characteristics of the upper and lower uterine segments in parturients with active-phase arrest.

OBJECTIVE: To determine the gradient of pressure between the upper and the lower uterine segments of parturients with non-progressing labor and to see whether the gradient correlates with subsequent successful oxytocin augmentation. METHODS: Fifteen women with active-phase arrest of labor were monitored with two intrauterine pressure transducers before and after oxytocin augmentation. Seven parturients without arrest of labor were evaluated for comparison. One intrauterine pressure transducer was inserted into the upper and one into the lower uterine segment of each subject. Overall, 444 contractions were assessed using the mean active pressure method. RESULTS: A total of 16 patients delivered vaginally. Nine received oxytocin augmentation, and all had significantly higher pressure in the upper segment than in the lower both before and after oxytocin (P < .001). Six women delivered by cesarean had a reversed gradient of uterine activity, with the lower segment contracting significantly more strongly than the upper uterine segment both before (P = .002) and after oxytocin (P = .001). CONCLUSION: Pressure gradients between the upper and lower uterine segments in the active phase might predict the likelihood of success of oxytocin augmentation.

Case-Control Studies↗

In situ islet T cell receptor variable region gene usage in the nonobese diabetic mouse.

Several features of the genetics and immunopathology of diabetes in the nonobese diabetic (NOD) mouse, which spontaneously develops type I diabetes, are shared with the human disease. Immunohistochemical studies support the concept that T lymphocytes are the major components of inflammatory cells in the pancreatic islets and these cells may play a critical role in the destruction of the beta cells leading to diabetes. Therefore, we examined whether particular TCR-beta variable region genes were utilized by in situ islet T cells at different stages (4 - 5, 7, 14 - 15 and 16 weeks of age) of the disease process. Dot-blot hybridization was performed using RNA prepared from isolated islets, thymus, spleen, peripheral blood leukocytes and axillary lymph nodes of 10 to 15 mice pooled for each data point. Ten different TCR V-beta probes were used for the analyses. Limited usage of islet V-beta genes was observed only at the early prediabetic stage (4 - 5 weeks old) of the disease. At later stages of the disease (7 - 16 weeks old), no preferential usage of TCR genes was observed in the islets compared to those of peripheral lymphoid organs. These data suggest that only certain types of T cells bearing particular TCR V-beta genes may be responsible for initiating and perpetuating infiltration of immune cells into the islets and these particular T cells are only identified at the very early stages of the autoimmune process.

Animals↗

Quantitative analyses comparing all major spleen cell phenotypes in BB and normal rats: autoimmune imbalance and double negative T cells associated with resistant, prone and diabetic animals.

The BB rat is a model of spontaneous autoimmune diabetes. To characterize quantitatively all known immune cell subsets involved in disease pathogenesis, FACS analysis of spleen cells was performed in diabetes-prone (DP) and acutely diabetic (D) BB rats and compared with diabetes-resistant (DR) BB and normal Wistar-Furth (WF) strains. We observed increased percentages of splenic NK cells in DP and D animals compared with DR rats using an NK-specific monoclonal antibody. We found increased proportions of splenic macrophages in the T-lymphopenic DP and D rats and low macrophage contents in DR spleens compared with WF spleens. We observed that percentages of the CD4-CD8- T cell receptor alpha/beta+ (double-negative) T cell subset were strikingly increased in the lymphopenic DP and D animals, compared with DR animals. We observed increased percentages of activated splenic CD5+ T cells expressing the IL-2 receptor and MHC class II antigen in DP and D rats compared with DR animals. Our studies suggest that (a) splenic NK cells and macrophages quantitatively appear to be involved in the pathogenesis of diabetes; (b) double-negative T cells escape from the T cell depletion process; (c) a marked increase of activated splenic T cells suggests diabetes is associated with general T cell activation processes; and (d) an altered balance among the different immune cell subsets may in part explain the pathogenesis of diabetes, since marked relative changes are observed when comparing the DR strain to the DP strain in both the prediabetic and diabetic stages.

Animals↗

Fatal Legionella maceachernii pneumonia in Canada.

A case of pneumonia and acute tubular necrosis was caused by an initially unknown species of Legionella. The organism was later identified as Legionella maceachernii by a combination of cultural, biochemical, and serological methods along with a gas-liquid chromatographic profile.

Canada↗

Long term radiological effects of short term exposure to amosite asbestos among factory workers.

Chest radiographs were read from a sub-cohort of 386 factory workers with short term exposure to amosite asbestos (median exposure six months) and long follow up (median 25 years). Prevalence of abnormality was determined independently by two readers from the first film available after 20 years from first employment. Serial films were obtainable for 238 men (median interval from first to last film: nine years). Progression was classified with a direct progression scoring scale. Individual dust exposure estimates were derived from dust counts from two similar plants. With as little as one month or less of employment, about 20% of the films showed parenchymal abnormality and about a third showed pleural abnormality. Those in the lowest cumulative exposure stratum (less than 5 fibre-years/ml) were similarly found to have high rates of abnormality. Dose-response relations were present in the data of both readers. Smokers had higher rates of parenchymal abnormality. On multivariate analysis, cumulative exposure was the exposure variable most closely related to parenchymal abnormality, and time from first employment was the variable most closely related to pleural abnormality. Progression (including first attacks) 20 or more years after ceasing employment occurred and was more common for pleural than for parenchymal abnormality. It is concluded that with exposure to high concentrations to amosite such as existed in this factory and with follow up for at least 20 years, (1) exposure for as little as a month was sufficient to produce radiological signs of parenchymal and pleural fibrosis, (2) no cumulative exposure threshold for parenchymal and pleural fibrosis was detectable, and (3) parenchymal and pleural progression were still detectable >/= 20 years after the end of exposure.

Asbestos↗

Relationship of pulmonary function to radiographic interstitial fibrosis in 2,611 long-term asbestos insulators. An assessment of the International Labour Office profusion score.

Radiographic evidence of interstitial fibrosis (IF) secondary to asbestos inhalation (using the International Labour Office [ILO] profusion of small irregular opacities) was compared with FVC as an independent indicator of IF. In addition, spirometric indices of airflow (FEV1/FVC and FET25-75%) were correlated with the radiographic profusion score. A study of 2,611 long-term insulators was well designed for these analyses since all subjects were from the same trade, there were sufficient (n = 515) nonsmokers to assess the effects of asbestos exposure in the absence of smoking, most (60%, n = 1,557) of the workers had parenchymal abnormalities (scores greater than or equal to 1/0), and there was a greater prevalence of high scores than in other published series (347 workers or 13.3% had scores greater than or equal to 2/1). Looking at all subjects, the FVC decreased as profusion score increased. The FVC was abnormal (88.0% of predicted) even when the profusion score was clearly normal (0/0). The FVC was lower at any score in smokers and in workers with pleural thickening (more so with diffuse thickening). There was, however, no difference in FVC between intermediate scores 0/1 versus 1/0 and 1/2 versus 2/1. Airflow increased with greater profusion, tending to overcome a decrease seen at lesser profusion scores. These results provide a greater understanding of the relationships among profusion scores, smoking, pleural diseases, and pulmonary function.

Asbestosis↗

Spontaneous and stimulated growth hormone release in adolescents with type I diabetes mellitus: effects of metabolic control.

Abnormalities in GH release have been found in adults with poorly controlled type I diabetes mellitus. During puberty, circulating GH concentrations transiently increase. To investigate in pubertal diabetic adolescents, the physiological relationship between metabolic control and GH release, we compared spontaneous and GH-releasing hormone (GHRH)-stimulated GH release in six pubertal subjects during poor (study A) and improved (study B) metabolic control. The subjects included two females and four males (mean age +/- SE, 15.5 +/- 1 yr; duration of diabetes, 8.6 +/- 0.9 yr; Tanner stages II-V). Serum samples for glucose and GH determinations were obtained at 20-min intervals over a 24-h period. Significant pulses of GH release were identified using a pulse detection algorithm (Cluster). Fourier expansion time series was used to document the occurrence of significant periodicities in the GH concentration-time data series. All subjects received 1.0 microgram/kg GHRH-44, iv, at 0800 h on the day after the 24-h monitoring for GH. After GHRH administration, samples were taken for glucose and GH determinations over 90 min. The overall mean glucose level (+/- SE) during the 24-h monitoring was 11.5 +/- 0.2 mmol/L during study A and 7.2 +/- 0.2 during study B (P = 0.0001). During the 4 weeks of improved control, glycated hemoglobin fell from 13.9 +/- 1.4% to 11.7 +/- 0.8% (mean +/- SE; P < 0.025). All subjects had significant pulses of GH release during poor or improved metabolic control. Relative to that at night, the daytime pulse frequency was higher in study A (P < 0.025). The overnight pulse frequency increased during study B (P < 0.01). Other pulse parameters, including maximal and incremental pulse amplitudes, pulse width, and interpulse valley mean, did not change during improved control. The mean +/- SE 24-h GH concentration was 4.1 +/- 0.7 micrograms/L during study A and 4.3 +/- 0.8 during study B. The amplitude of the circadian GH rhythm was not different by Fourier analysis. The overall mean glucose +/- SE after GHRH administration was 15.3 +/- 0.2 mmol/L in study A and 6.8 +/- 0.1 in study B. In spite of the marked hyperglycemia during study A, the GH responses were similar during studies A and B. Maximal GH levels were obtained at 15-30 min (mean +/- SE) and were 36.0 +/- 16.9 micrograms/L in study A and 38.7 +/- 18.9 in study B.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Quantitative and functional analyses of spleen and in situ islet immune cells before and after diabetes onset in the NOD mouse.

Cytofluorometric analysis using specific monoclonal antibodies directed against the T cell antigens Thy-1.2, CD4, CD8, CD4V beta(8.1 + 8.2 + 8.3), and the antigen Mac-1 expressed by mature macrophages and NK cells were used to characterize and quantify the phenotypes of (1) unfractionated and Percoll gradient fractionated in situ islet immune cells isolated from prediabetic and diabetic female NOD mouse spleens. We found in prediabetic female mice that the majority (approximately 70%) of the in situ islet immune cells were Thy-1.2 positive T cells. CD4 positive T cells (approximately 40%) were the most abundant phenotype together with double negative T cells (approximately 20%). The percentage of CD8 positive T cells were approximately 10%, and only approximately 4% of the immune cells were Mac-1 positive. The percentages of CD4V beta (8.1 + 8.2 + 8.3) positive and double negative T cells in diabetic spleens were significantly higher in comparison to prediabetic spleens. In C57B1/6J control nondiabetic mice the percentage of double negative T cells in the spleens was significantly 4-fold lower when compared to diabetic NOD spleens. The specific cytolytic activity mediated by in situ islet immune cells against 51Cr-labeled dispersed syngeneic single-cell islet cells at an effector to target ratio of 20 was twenty- to thirty-fold higher than that mediated by prediabetic splenic lymphoid cells. It is concluded that prediabetic NOD mouse in situ islet immune cells are mostly CD4 positive and double negative T cells, and that CD4 and CD8 positive T cells in the intra-islet infiltrate warrants further evaluation as potential effector T cells in target beta-cell destruction.

Animals↗

Completeness of case ascertainment of the State Cancer Registry.

The authors evaluated the ability of the New Jersey State Cancer Registry to detect known cancer cases during an investigation of a cancer cluster occurring in professional football players. The Registry was found to be a valuable tool for the detection of cancer cases for New Jersey residents.

Adult↗

Molecular structure of rat hepatic 3 alpha-hydroxysteroid dehydrogenase. A member of the oxidoreductase gene family.

3-alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) (EC 1.1.1.50) is an important multifunctional oxidoreductase capable of metabolizing steroid hormones, polycyclic aromatic hydrocarbons, and prostaglandins. 3 alpha-HSD is also required for bile acid synthesis and has been suggested to play an important role in net bile acid transport across the hepatocyte (Stolz, A., Takikawa, H., Ookhtens, M., and Kaplowitz, N. (1989) Annu. Rev. Physiol. 51, 166-177). In order to characterize molecular forms and begin to determine its regulation, we now report the nucleotide sequence, tissue distribution, and homology to other members of the oxidoreductase superfamily. Rat hepatic 3 alpha-HSD cDNA encodes for a 322-amino acid protein with a predicted molecular weight of 37,022 expressed in a 2.4-kilobase (kb) message size. Northern blot analysis of total RNA revealed equivalent steady-state levels in liver and intestine in male rats with lower levels of expression in the colon and minimal expression in stomach, lung, and testis. Female liver contained approximately 2-3-fold greater steady-state levels of mRNA as compared to the male liver with equivalent intestinal expression. Two hybridizing bands, 2.4 and 1.4 kb, were identified in total RNA from the ovary. 3 alpha-HSD exhibits 75% amino acid sequence homology with bovine lung prostaglandin F synthetase and 50% homology with human aldose reductases. Amino acid sequence analysis with short chain alcohol dehydrogenases identified a possible NADP(H) cofactor-binding site at the amino terminus. The significant homology of 3 alpha-HSD with both prostaglandin F synthetase and aldose reductases suggest a subdivision of monomeric, NADPH reductases within the larger oxidoreductases superfamily.

3-Hydroxysteroid Dehydrogenases↗

Radiographic abnormalities in asbestos insulators: effects of duration from onset of exposure and smoking. Relationships of dyspnea with parenchymal and pleural fibrosis.

Chest radiographs and spirometry were evaluated in 2,907 active and retired asbestos insulators; most (86.8%) had greater than or equal to 30 years from onset of asbestos exposure. Testing was performed in 19 cities in the United States during 1981-1983. Complete demographic, smoking, clinical, and radiologic data were obtained for 2,790 workers. This is the largest single group of insulators that has been studied. Five hundred forty-eight (19.7%) had never smoked cigarettes, 942 (33.9%) were current cigarette smokers, and 1,300 (46.6%) were ex-smokers. Only 439 (15.7%) workers had no radiographic evidence of asbestos-related disease (normal chest X-ray); 668 (23.9%) had pleural fibrosis only, 325 (11.6%) had parenchymal fibrosis alone, and 1,358 (48.7%) had both parenchymal and pleural fibrosis. The prevalence of radiographic parenchymal changes increased significantly (p less than .001) from 38.6% (DURONSET less than 30 years) to 70% (greater than or equal to 40 years). For pleural changes the comparative prevalences were 55% and 82%. Those with no history of cigarette smoking were more likely to have normal films than those with a history of smoking (19.2% versus 14.4% for current smokers and 15.2% among ex-smokers), and were less likely to have parenchymal fibrosis (44.5% versus 69.7% for current smokers and 60.2% of ex-smokers). Dyspnea, MRC grade 3 and higher, was more prevalent when pleural fibrosis was associated with interstitial pulmonary fibrosis (at all profusion levels of small opacities) than when pleural fibrosis was absent. Logistic regression analysis of factors contributing to such dyspnea showed that the presence of combined parenchymal and pleural abnormalities was a significant explanatory variable, in addition to age, smoking, and body mass (Quetelet index); the presence of parenchymal changes only or of pleural changes only, as factors contributing to dyspnea, did not reach the level of statistical significance in the regression analysis. The results of these examinations show that pleural fibrosis is a frequent finding in asbestos-exposed groups with long-term follow-up and that its functional significance is not negligible. The contribution of cigarette smoking to prevalence and severity of interstitial fibrosis is an additional reason for smoking cessation among asbestos-exposed individuals.

Adult↗

Pulmonary function and pleural fibrosis: quantitative relationships with an integrative index of pleural abnormalities.

Pleural fibrosis due to asbestos exposure was fully appreciated considerably later than pulmonary interstitial fibrosis due to similar exposure. This is well exemplified by the fact that pleura face on was included in the International Labour Office's International Classification of Radiographs of Pneumoconioses only in the last revision of the Classification. The functional relevance of pleural fibrosis, in particular circumscribed pleural fibrosis, has remained controversial. Since pleural fibrosis can occur at various sites (diaphragmatic plaques, chest wall in profile and face on, mediastinal) and can be of different thickness and extent, a comprehensive integrative assessment of pleural fibrosis was undertaken in order to permit a quantitative study of relationships between pleural fibrosis and pulmonary function. This approach was used for chest X-ray films of 1,584 asbestos insulation workers examined (1981-1983); 1,185 (75%) had pleural fibrosis. The distribution pattern of the integrative pleural index was found to be different in the subgroup with circumscribed (n = 975) from that with diffuse (n = 197) pleural fibrosis, with a higher profusion of high INDEX values in the latter. Stepwise regression analysis indicated that there was a significant inverse relationship between forced vital capacity (FVC) and the integrative index of pleural fibrosis in the subgroup with circumscribed pleural fibrosis. In the subgroup with diffuse pleural fibrosis, the obliteration of costophrenic angle(s), even with pleural fibrosis of limited extent, resulted in marked decrement in FVC% predicted; higher values of INDEX did not result in additional significant reductions of FVC. In those with both parenchymal and pleural abnormalities (n = 862) the pleural index was found to make a significant contribution, independent of that of parenchymal abnormalities, to decrements of FVC. Since pleural fibrosis has gradually become the predominant radiologically detectable abnormality in asbestos exposed workers, establishing its quantifiable functional relevance is useful.

Adult↗