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Biomedical subjects

Richard Cohen

Publications and source records attributed to Richard Cohen.

14 recordsLinked to original sources

Neonatal streptozotocin-induced glucose intolerance: different consequences in Lyon normotensive and hypertensive rats.

BACKGROUND: Lyon hypertensive (LH) rats exhibit a mild hypertension associated with excessive body weight, spontaneous hyperlipidemia, elevated insulin/glucose ratio and exaggerated urinary protein excretion. AIMS: We aimed to develop, in LH rats and their normotensive control (LL) rats, a moderate non-insulin-dependent diabetic model to study the different consequences on metabolic and renal functions. METHODS: Non-insulin-dependent diabetes was induced by intraperitoneal injection of streptozotocin (STZ) at 2 days of age (50, 75 or 100 mg/kg for LH and 75, 100 or 125 mg/kg for LL rats). The evolution, with age, of glycemia, glucose tolerance (glucose 2 g/kg by gavage), blood pressure, plasma lipids and urinary protein and albumin excretions were studied in control and STZ-treated LH and LL rats. RESULTS: Although fasting glycemia was not significantly changed, the neonatal administration of STZ increased non-fasting glycemia and induced a marked glucose intolerance that were comparable between LH rats receiving 75 mg/kg and LL rats receiving 100 mg/kg of STZ. Interestingly, in treated LH rats only, the impaired glucose tolerance was accompanied by further metabolic and renal dysfunctions characterized by additional increases in plasma cholesterol (+28%) and triglycerides (+105%) and accelerated progression of proteinuria (+36%) and albuminuria (+48%). CONCLUSIONS: These observations indicate that susceptibility to diabetic metabolic disorders and renal diseases may be linked to the genetic predisposition to hypertension. This new model offers a reasonable reflection of the human situation, where hypertension and non-insulin-dependent diabetes often coincide, suitable for molecular, biochemical and pharmacological investigations.

Animals↗

Hyperglycosylated ferritin in sera of HIV-1-infected patients treated with highly active antiretroviral therapy.

A study was conducted to determine the relationship between ferritin and glycosylated isoforms of ferritin and insulin resistance in 69 HIV-infected men receiving HAART. Ferritin levels were significantly correlated with aspartate aminotransferase, alanine aminotransferase, bilirubin and with insulin resistance. The ferritin isoelectric focusing patterns of five insulin-resistant HIV-infected patients under HAART showed large amounts of hyperglycosylated isoforms, which was not found in 56 control subjects and 46 untreated HIV-1-infected patients.

Adult↗

Interaction of fish oil and a glucocorticoid on metabolic responses to an oral glucose load in healthy human subjects.

Compared with saturated fat, n-3 long-chain PUFA-rich fish oil improves insulin sensitivity in rats. We studied whether n-3 long-chain PUFA could prevent insulin resistance induced by dexamethasone (a glucocorticoid) in healthy human volunteers. A group of eight subjects was studied twice after a 2 d dexamethasone treatment, before and after a 3-week supplementation with fish oil (providing daily doses of 1.1 g 20 : 5n-3 and 0.7 g 22 : 6n-3). The subjects were studied during the basal state and over the 6 h following an oral glucose load (1 g/kg). Plasma glucose fluxes were traced with [6,6-2H2]glucose and [13C]glucose (naturally 13C-enriched corn glucose). Substrate oxidation was obtained from indirect calorimetry. Following fish oil supplementation, plasma glucose fluxes and substrate oxidation were maintained despite a 17 % reduction (P<0.05) in the area under the curve of plasma insulin response, suggesting an insulin-sensitizing effect.

Administration, Oral↗

An update on master's degrees in medical education.

Planning and implementing educational programs in medicine optimally requires a background in educational theory and practice. An avenue of training open to such practitioners is a master's degree in medical education. A single 1998 report lists the programs known at that time and information about them remains scarce. The authors have re-examined all current programs offering master's degrees in medical or health sciences education in the English-speaking world, including the Netherlands. The authors contacted the programs identified in the 1998 report to establish how many were still in operation. The search was extended using Pubmed and other search engines. A further verification targeted a selected sample of 10 prominent US medical schools. Twenty-one currently operating programs were identified: six in the US, eight in the UK, three in Canada, three in Australia and one in Holland. Seven of nine original master's programs were still in existence. URLs, website and other logistical information about each program are tabled. A master's degree in medical or health sciences education is the most specific method for medical faculty to obtain a credentialed grounding in educational theory and practice. The authors provide up-to-date contact information for current programs and summarize other related essential logistical data.

Curriculum↗

Results of surgical removal of the pouch after failed restorative proctocolectomy.

PURPOSE: Restorative proctocolectomy is the elective surgical procedure of choice for ulcerative colitis and familial adenomatous polyposis. Most patients have a satisfactory outcome, but at ten years 15 percent or more will have failed, needing indefinite defunctioning or excision of the pouch. There is little information on the morbidity of pouch excision. The study was designed to present the early results of surgical removal of the pouch after failed restorative proctocolectomy with reference to the indications and intermediate complications, particularly of the perineal wound. METHODS: Between 1977 and 2002, 996 patients underwent a restorative proctocolectomy at our hospital and 245 patients were referred for potential salvage. The pouch was excised in 58 and 10 patients respectively. There were 40 females and 28 males (median age, 34 (14-65) years) including 47 with ulcerative colitis, 10 with Crohn's disease, and 11 with familial adenomatous polyposis. The median follow-up was 79 (range, 3-312) months from excision. RESULTS: There was one (1.4 percent) postoperative death. The overall morbidity rate was 62.3 percent (immediate 30 days (25 percent), late (53.7 percent)). Thirty-six patients (53.7 percent) were readmitted on 67 occasions for a late complication. The risk of readmission from the time of pouch excision was 38 and 58 percent at one and five years, respectively. Surgical treatment was required during 48 of these readmissions. A persistent perineal sinus was the most common late complication. The perineal wound was not healed at 6 months in 27 patients (40 percent) and at 12 months in 7 patients (10 percent). No factor, including age at the time of pouch excision, gender, indication for excision, or final histologic diagnosis, was associated with an unhealed perineal wound. Two males (7 percent) had impotence. One female suffered from short-bowel syndrome with the need of permanent parenteral nutrition. The median overall hospital stay for all admissions was 20 (range, 8-220) days. CONCLUSIONS: Pouch excision is associated with high morbidity. Perineal wound-delayed healing is the commonest late complication and often requires further surgery.

Adenomatous Polyposis Coli↗

MRI of fistula in ano: inter- and intraobserver agreement and effects of directed education.

OBJECTIVE: Preoperative MRI of fistula in ano is becoming more common. This prospective study aimed to determine if a significant difference occurred in interpretation between one expert and one novice observer and to assess inter- and intraobserver agreement after both observers underwent a period of directed education. SUBJECTS AND METHODS. An outcome-derived reference standard was defined in 100 patients with suspected fistula in ano via a combination of preoperative MRI, surgical findings, and clinical outcome. The performances of a single expert and a single novice interpreter were compared with this reference standard both before and after a period of directed education, and inter- and intraobserver agreement was determined. RESULTS: Initially the expert correctly classified significantly more fistulas than the novice (85% vs 63%, p = 0.024), but after directed education there was no significant difference, with good agreement for both the classification of the primary track (kappa = 0.71) and identification of extensions (k = 0.61). Intraobserver agreement was very good for the expert (kappa = 0.92) and novice (kappa = 0.88) for classification of the primary track and good (kappa = 0.64 and 0.74, respectively) for identification of extensions. CONCLUSION: The diagnostic accuracy for fistula in ano classification using MRI was significantly higher for one expert than for one novice, though this was rectified by a short period of directed education.

Adult↗

Osteoporosis and health-related quality-of-life outcomes in the Alameda County Study population.

INTRODUCTION: The objective of this study was to identify physical and mental outcomes of osteoporosis that affect quality of life in women. METHODS: Data were from the Alameda County Study, a longitudinal study of health and mortality that since 1965 has followed a cohort of 6,928 American persons aged 16 to 94 years at baseline. Subjects for this analysis were women who survived until at least 1994 (N = 1,171). The variables analyzed as possible outcomes of osteoporosis included measures of physical health, quality of life, and mental health. Sequential logistic regression models were run, and associations were presented as odds ratios. RESULTS: After controlling for age, ethnicity, education, financial strain, and physical activity, subjects with osteoporosis in 1994 were more likely to report the following outcomes in 1999: frailty, difficulty with balance, weakness, problems with activities of daily living, fair/poor perceived health, never going out for entertainment, and not enjoying free time much. When controlling for chronic medical conditions, the odds ratios were reduced, but remained significant for difficulty with balance and weakness (odds ratio = 2.48) and problems with activities of daily living (odds ratio = 2.80). CONCLUSION: From this study, it appears that people with osteoporosis are at higher risk of developing problems with physical frailty and difficulties with activities of daily living, and may be at risk for reduced quality of life in terms of going out for entertainment and enjoying free time. Therefore, care should be taken to maintain the quality of life for people with osteoporosis by helping them to keep as physically functional as possible.

Adolescent↗

Socioeconomic gradients in health status over 29 years of follow-up after midlife: the Alameda county study.

Socioeconomic status is well known to be associated with inverse gradients in a wide range of health outcomes. Very little is known about the precise shape of these relationships and how they evolve through the life-course, although recent work has suggested steep non-linearities for mortality in samples of the entire population that include the very poor. We investigate the shape of gradients, against baseline family income, in gender-specific prevalence rates for seven self-reported health outcomes commonly used on surveys, in a cohort of 1190 men and 1302 women representative of Alameda County, California, aged 40-59 in 1965. Over 29 years of follow-up, four different prevalence-income gradients among surviving subjects are examined as this cohort has aged, in 1965, 1974, 1983 and 1994. Virtually all the gradients are inverse, although there is no simple pattern of shape, or evolution of shape over time, across health outcomes. However, there is a consistent trend for male gradients to be distinctly more non-linear than female gradients, such that the poorest men show disproportionately higher rates of ill health, based on generalized linear piecewise regression models, comparing the low versus high-income slopes of the gradients. However, sub-analyses of only those long-lived cohort members, who survived through all follow-ups, largely abolished the non-linearities in the male prevalence curves (except for "self-assessed health status" and "depression"), making them much more like female curves. This suggests that for all of these common forms of morbidity, the excess prevalence among very low income males was associated with elevated mortality. Confirmation of this observation must await richer data on other aspects of socioeconomic status in comparable cohorts, analyzed with similar methods.

Activities of Daily Living↗

Fish-oil supplementation reduces stimulation of plasma glucose fluxes during exercise in untrained males.

The present study examined the effects of a 3-week fish-oil supplementation (6 g/d) on the rate of plasma glucose disappearance (Rd glucose), hepatic glucose production (HGP), carbohydrate oxidation and lipid oxidation during exercise. Six untrained males (23+/-1 years; 67.6+/-2.7 kg) performed two 90 min cycling exercise sessions at 60 % of maximal O2 output separated by 20 d. During the 20 d before the first test, they ingested 6 g olive oil/d, then 6 g fish oil/d during the 20 d before the second test. Plasma glucose fluxes and lipolysis were traced using 6,6-[(2)H2]glucose and 1,1,2,3,3-[(2)H5]glycerol respectively. Substrates oxidation was obtained from indirect calorimetry. At rest HGP and the Rd glucose were similar after olive oil and fish oil (1.83 (SE 0.05) v. 1.67 (SE 0.11) mg/kg per min). During exercise, fish oil reduced the stimulation of both the Rd glucose (5.06 (SE 0.23) v. 6.37 (SE 0.12) mg/kg per min; P<0.05) and HGP (4.88 (SE 0.24) v. 5.91 (SE 0.21) mg/kg per min; P<0.05). Fish oil also reduced glucose metabolic clearance rate (6.93 (SE 0.29) v. 8.30 (SE 0.57) ml/min). Carbohydrate oxidation tended to be less stimulated by exercise after fish oil than after olive oil (12.09 (SE 0.60) v. 13.86 (se 1.11) mg/kg per min; NS). Lipid oxidation tended to be more stimulated by exercise after fish oil (7.34 (SE 0.45) v. 6.85 (SE 0.17) mg/kg per min; NS). Glycaemia, lactataemia, insulinaemia and glucagonaemia were similarly affected by exercise after fish oil and olive oil. Lipolysis at rest was similar after fish oil and olive oil (2.92 (SE 0.42) v. 2.94 (SE 0.28) micromol/kg per min) and similarly stimulated by exercise (6.42 (SE 0.75) v. 6.77 (SE 0.72) micromol/kg per min). It is concluded that fish oil reduced the Rd glucose by 26 % by reducing glucose metabolic clearance rate, possibly by facilitating fat oxidation, and reduced HGP by 21%, possibly by a feedback mechanism.

Adult↗

Baby Jane.

Explore the source record for details and available documents.

Congenital, Hereditary, and Neonatal Diseases and ↗

Peroxynitrite and vascular endothelial dysfunction in diabetes mellitus.

Macro and microvascular diseases are the principal causes of morbidity and mortality in patients with type I and II diabetes mellitus. Growing evidence implicates reactive nitrogen species (RNS), such as peroxynitrite (ONOO-), derived from nitric oxide (NO) and superoxide anion (O2*-), are important in diabetes. The mechanisms by which diabetes increases RNS, and those by which RNS modifies vascular function, are poorly understood. The authors recently discovered that physiologically relevant concentrations of ONOO- oxidize the zinc thiolate center in endothelial nitric oxide synthase (eNOS). In active eNOS dimers, a tetracoordinated zinc ion is held by four thiols, two from each 135-kDa monomer. Because it remains partially positively charged, the zinc thiolate center is subject to attack by the ONOO-. This oxidant disrupts the zinc thiolate center, releasing zinc, and oxidizing the thiols. Upon thiol reduction, eNOS dimers dissociate into monomers. This modification of eNOS results in reduced NO bioactivity and enhanced endothelial O2*- production, which reacts with NO, further generating ONOO- (eNOS uncoupling). In addition, the authors' studies also demonstrate that low concentrations of ONOO- selectively nitrate and inactivate prostacyclin synthase (PGIS), which not only eliminates the vasodilatory, growth-inhibiting, antithrombotic, and antiadhesive effects of prostacyclin (PGI2), but also increases release of the potent vasoconstrictor, prothrombotic, growth- and adhesion-promoting agents, prostaglandin H2 (PGH2) and thromboxane A2 (TxA2). In diabetic mice and rats, eNOS is uncoupled resulting in an increased tyrosine nitration of PGIS. The authors' studies indicate that in diabetes the synthetic enzymes of the two major endogenous vasodilators undergo oxidative inactivation by different mechanisms, which are, however, tightly interdependent.

Animals↗

Development of permissible exposure limits: the California experience.

The California OSHA Airborne Contaminant Advisory Committee reviewed several hundred substances and recommended occupational exposure limits with the intent of worker and employer protection. The model used offers important benefits. First, by allowing open meetings, the process was transparent, and input could be offered by concerned stakeholders. Second, the process was data-driven and, therefore, less susceptible to bias and error. Third, by incorporating members with backgrounds in toxicology, epidemiology, risk assessment, occupational medicine, and industrial hygiene, the process fostered a thorough and diverse assessment of substances.

Advisory Committees↗