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Biomedical subjects

R D Cohen

Publications and source records attributed to R D Cohen.

At least 109 records · Page 6Linked to original sources

Enhanced carrier-mediated lactate entry into isolated hepatocytes from starved and diabetic rats.

Hepatic plasma membrane lactate transport was studied in isolated hepatocytes prepared from fed, starved, and streptozotocin diabetic rats. Carrier-mediated lactate entry was determined using the lactate transport inhibitors alpha-cyano-3-hydroxycinnamate and D-3-hydroxybutyrate and was significantly greater in hepatocytes from starved compared to fed rats and in hepatocytes from diabetic fed compared to fed rats. The saturable component of lactate entry which corresponds to carrier-mediated transport was higher in the starved than in the fed state with results from diabetic fed being intermediate between the two. Insulin treatment prevented the increment in carrier-mediated lactate transport observed in hepatocytes from diabetic fed rats. The data indicate that hepatic plasma membrane lactate transport is increased under conditions of starvation and diabetes mellitus. This may partly explain the increased gluconeogenic flux under these conditions.

Animals↗

The contraindications for blind esophageal bouginage for coin ingestion in children.

Per oral bouginage of the esophagus for coin lodgement in children is a safe and simple mode of therapy. However, our experience with chronically ingested coins, multiple coins ingestion, and ingestion with preexisting esophageal pathology illustrate the potential hazards of such a practice. Intramural perforation, subacute mediastinitis, tracheoesophageal fistula, and long-term residual injury to the esophagus hallmark such cases. We believe that only acutely ingested coins, and only a single coin, can be treated safely by means of "blind" bouginage, provided that no preexisting esophageal disease is present.

Child, Preschool↗

The decline in ischemic heart disease mortality: prospective evidence from the Alameda County Study.

The contribution of secular changes in the distribution of ischemic heart disease risk factors and medical care utilization to the decline in ischemic heart disease mortality was investigated using data collected on the nine-year ischemic heart disease mortality experience of two cohorts selected to be representative of Alameda County, California, in 1965 and 1974. With adjustment for age, sex, race, and baseline ischemic heart disease conditions and symptoms, there was a 45% decline in the nine-year odds of ischemic heart disease mortality between the two cohorts (1965/1974, odds ratio (OR) = 1.82, p = 0.0001). Further adjustment for cohort differences in the following ischemic heart disease risk factors did not explain the decline: smoking status, leisure-time physical activity, self-assessed physical activity, alcohol consumption, body mass index, or social network participation; neither did adjustment for measures of education, utilization of preventive medical care, availability of a regular physician or clinic, health insurance coverage, number of physician visits during the last 12 months, or occupation. There was no change in the estimated ischemic heart disease decline when all adjustment variables were included in a logistic model (1965/1974, OR = 1.81, p = 0.0002). These variables do not appear to explain the large decline in nine-year ischemic heart disease mortality between these two cohorts.

Adult↗

Did early detection and treatment contribute to the decline in ischemic heart disease mortality? Prospective evidence from the Alameda County Study.

In a previous study, the authors reported a 45 per cent decline in ischemic heart disease mortality between cohorts selected to be representative of Alameda County, California, in 1965 and 1974. The decline could not be explained by baseline differences in the distribution of many of the known ischemic heart disease risk factors available for analysis in this cohort. This study reports the results of further analyses which evaluated the hypothesis that early detection and improved treatment contributed to the decline. In multiple logistic analyses adjusted for age, sex, and race, those who reported heart trouble at baseline had an ischemic heart disease mortality decline 2.5 times greater than those who did not (p = 0.01). Those who used preventive health services had an ischemic heart disease mortality decline 2.2 times greater than those who did not (p = 0.03). These interactions were independent of each other and were not explained by adjustment for physical activity, smoking, social connections, or body mass index. There was an increase in the prevalence of self-reported heart trouble between 1965 and 1974, especially among younger age groups. These results are consistent with the hypothesis that early detection and treatment contributed to the decline in ischemic heart disease mortality observed in the Alameda County Study.

Age Factors↗

Social connections and mortality from all causes and from cardiovascular disease: prospective evidence from eastern Finland.

The association between an a priori measure of social connections and five-year mortality from all causes, cardiovascular diseases (International Classification of Diseases, Eighth Revision (ICD-8) codes 390-458), and ischemic heart disease (ICD-8 codes 410-414) was studied in 13,301 men and women from eastern Finland who were first interviewed in 1972 or 1977. For men, there was a graded association between extent of social connections and mortality. In multivariate models with adjustment for age, smoking, serum cholesterol, mean weighted blood pressure, measures of prevalent illness, and other possible confounders, men who were in the two lowest quintiles of the social connections scale were at increased risk compared with those in the highest quintile (odds ratio (OR)all cause = 1.54, 95% confidence interval (CI) = 1.21-1.95; ORcardiovascular disease = 1.54, 95% CI = 1.11-2.13; ORischemic heart disease = 1.34, 95% CI = 0.94-1.90). No strong or consistent association was found for women. The association for men was modified by levels of blood pressure with the effect of low social connections greater at higher levels of blood pressure. In three separate analyses, there was no evidence for confounding or effect modification due to prevalent illness at baseline.

Adult↗

Femoral hernias in children. An infrequent problem.

Femoral hernias in children are uncommon and many surgeons have had little exposure to their clinical manifestations. A ten-year survey of our experience with groin hernias in children showed only six children with this condition, which represents 0.12% of this entire population. Definite preoperative diagnosis was made in only two patients, while in the other patients this condition was suspected during herniorrhaphy. Preoperative diagnosis is possible if the bulge appears in a location inferior and lateral to that of the commonly occurring indirect hernia. Any child with early recurrence of a groin swelling after what seems to be an adequate inguinal herniorrhaphy should be suspected of having a femoral hernia.

Age Factors↗

Alcohol consumption and mortality in Alameda County.

The association between level of alcohol consumption and 15-year mortality, focusing particularly on the possible protective effect of light drinking compared to abstention, was studied in a representative population sample of 6928 residents of Alameda County, California. Because abstainers differ from light, moderate and heavy drinkers on a number of demographic, physical, and psychosocial characteristics, the role of these as confounders of the alcohol/mortality association was examined. Using multiple logistic models, the mortality experience of abstainers, moderate drinkers, heavy drinkers and very heavy drinkers was compared with that of light drinkers. Among men only, very heavy drinkers were at significantly greater risk of death from all causes than were light drinkers (OR = 2.5, p less than 0.01). Neither abstainers nor other drinkers were at significantly higher risk of death from ischemic heart disease than were light drinkers. This pattern of results persisted with adjustment for 11 covariates of alcohol consumption in addition to age.

Adult↗

NMR as a metabolic tool.

We have briefly reviewed the broad range of applications of NMR spectroscopy to metabolism in tissues and biological fluids. Most of these studies are in the exploratory stage, though the potential of NMR for non-invasive and non-destructive monitoring of certain important substrates and reaction pathways is considerable. The limitations of the technique lie in its relative insensitivity and the rather restricted range of substances that it can detect, as well as the current expense. So far, the main clinically useful applications have been in the diagnosis and monitoring of treatment of certain inborn errors of metabolism, namely those that result in altered energy of pH states or the abnormal accumulation of significant amounts of metabolites in body fluids. It might be expected that as localization techniques improve, clinically useful information will be obtained in a wide range of ischaemic or hypoxic states, e.g. stroke and myocardial infarction. The possibility of producing a detailed spatial image of metabolite concentrations (e.g. ATP), in the way that NMR imaging techniques currently do using features of the water proton resonance, is attractive and the initial results are very encouraging (Bogusky et al, 1986; Bailes et al, 1987; Blackledge et al, 1987).

Animals↗

Mortality among the elderly in the Alameda County Study: behavioral and demographic risk factors.

We studied the association between behavioral and demographic risk factors and 17-year mortality in members of the Alameda County (California) Study who were 60-94 years of age at baseline. In this age group, increased risk of death is associated with being male, smoking, having little leisure-time physical activity, deviating from moderate weight relative to height, and not regularly eating breakfast. These increased risks were independent of age, race, socioeconomic position (SEP), other behavioral risk factors, and baseline physical health status. Further examination of the group aged 70 or more revealed the same patterns of heightened risk.

Aged↗

Carrier-mediated efflux of ketone bodies in isolated rat hepatocytes.

The rate of efflux of ketone bodies has been studied in isolated hepatocytes prepared from starved rats and preloaded with D-3-[14C]hydroxybutyrate. Efflux of ketone bodies was temperature-dependent, saturable and inhibited by alpha-cyano-3-hydroxycinnamate and phloretin. The rate of efflux was also reduced by 6 mmol/l lactate and pyruvate added to the external medium. Under conditions of simulated metabolic acidosis in the hepatocyte suspension medium, ketone body efflux rate was reduced. The experimental data suggest that hepatic plasma membrane ketone body transit is carrier-mediated.

3-Hydroxybutyric Acid↗

Amiodarone pulmonary toxicity: functional and ultrastructural evaluation.

Pulmonary function, chest radiographic appearances, and the cellular composition of bronchoalveolar lavage fluid were assessed in 13 patients who were receiving amiodarone treatment. Eight of the patients had developed clinical and radiological evidence of lung disease and five were symptom free. The proportions of lymphocytes (mean 8.6 (SD 6.9)) and neutrophils (mean 3.4 (3.3)) obtained by bronchoalveolar lavage were similar in patients with and without lung complications. Electron microscopic examination of alveolar macrophages showed intralysosomal inclusion bodies in all subjects, regardless of clinical state. There was no significant difference in the mean number of inclusion bodies per macrophage transection between those with and those without lung disease. The differential cell count in bronchoalveolar lavage fluid and the presence of macrophage inclusion bodies were therefore not useful as markers of disease activity. Among those who developed clinical and radiological evidence of lung disease, the cumulative drug dose per kilogram of body weight and the duration of treatment (mean 16.5 (SD 9.0) months) were significantly correlated with the degree of lung restriction as measured by total lung capacity and forced vital capacity. It is concluded that, while the severity of the restrictive pulmonary defect that is induced by amiodarone is largely dose related, the development of lung toxicity is to some extent idiosyncratic.

Adult↗

Measurement of intracellular pH with microelectrodes in rat kidney in vivo.

The construction of two types of double-barreled microelectrodes of sufficiently small tip size to record cytosolic pH (pHc) in renal tubular epithelial cells is described. Mean pHc in control anesthetized rats was 7.10 and mean basolateral membrane potential (Em) was -51.8 mV. These results suggest that hydrogen ions are actively extruded from either or both poles of the proximal tubular cell but that bicarbonate exit across the basolateral membrane is passive. In animals treated with acetazolamide, pHc was significantly elevated (mean 7.35) but Em was unchanged, suggesting that proton extrusion continues but that the rate of reaction of OH- with CO2 is diminished due to carbonic anhydrase inhibition. A pH higher than that of arterial blood was obtained from sites presumed to be in the interstitium. The evidence for the various assignments of microelectrode tip position is discussed.

Acetazolamide↗

Inhibition of lactate removal by ketone bodies in rat liver. Evidence for a quantitatively important role of the plasma membrane lactate transporter in lactate metabolism.

We studied the effect of DL-3-hydroxybutyrate and acetoacetate on lactate transport into isolated hepatocytes and on lactate removal in the isolated perfused rat liver. Ketone bodies inhibited lactate transport into isolated hepatocytes (maximum, 35% at concentrations of 10-20 mM). Lactate removal and glucose production by perfused livers were examined before and after the introduction of a constant infusion of hydroxybutyrate, acetoacetate, or appropriate control into the portal venous limb. Lactate removal was significantly inhibited within 10 s of the appearance of increasing concentrations of ketone bodies in the effluent. Corresponding decreases in glucose production were observed. The dependence of inhibition on D-3-hydroxybutyrate concentration was documented in isolated perfused livers (maximum inhibition of lactate removal, 58% at 14 mM). This phenomenon could be a factor in the development of lactic acidosis accompanying ketoacidosis, and indicates that plasma membrane lactate transport may determine the rate of hepatic lactate removal.

3-Hydroxybutyric Acid↗

Neuropsychological effects of short-term discontinuation of oxygen therapy. Observations in patients with chronic hypoxemia who are receiving long-term oxygen therapy.

Twelve patients receiving long-term oxygen therapy were assessed for possible detrimental neuropsychological effects of short-term withdrawal of oxygen. Patients served as their own controls and received either their usual oxygen prescriptions or room air, through nasal prongs, over four-hour periods on two successive days. A battery of neuropsychological tests assessing memory and learning, sustained concentration, and motor and visuomotor speed were administered. In the room-air condition, the mean arterial oxygen partial pressure fell from 86.1 +/- 25.7 to 59.1 +/- 11.7 mm Hg, and the mean oxygen saturation fell from 94.7% +/- 3.2% to 89.9% +/- 5.3%, but the mean carbon dioxide partial pressure did not change significantly. No significant differences in neuropsychological test scores were found between the two conditions, suggesting that four hours of mild hypoxemia causes no significant deficits in cognition in patients receiving long-term oxygen therapy. Paradoxically, low-order inverse correlations were found between arterial oxygen partial pressures and results of visuomotor speed and memory tests, suggesting that an improvement in performance may have taken place during oxygen withdrawal.

Aged↗

Effect of chlorthalidone on zinc levels, testosterone, and sexual function in man.

This study was designed to test the hypothesis that chlorthalidone, a diuretic used to treat hypertension, depletes body zinc enough to interfere with testosterone production and thereby cause sexual dysfunction. Serum and hair zinc, serum testosterone, and sexual function were measured in 19 middle-aged hypertensive men who had been taking chlorthalidone in average daily doses of between 11 and 50 mg per day for at least 6 months, and a control group of 31 unmedicated middle-aged normotensive men. Although the medicated group had a higher incidence of sexual dysfunction (42% as compared to 16% in the control group), use of chlorthalidone did not significantly affect serum testosterone levels. When other variables were controlled for, medicated men had significantly higher serum zinc levels, and men on the highest dosage of chlorthalidone had higher hair zinc levels than all other men. There was no significant correlation between hair zinc, serum zinc, testosterone, and sexual function. Serum zinc decreased significantly with age (p = 0.043) and with ethanol intake after controlling for age (p = 0.032). Sexual dysfunction occurred more often in older men (p = 0.002). In the unmedicated controls, prevalence of dysfunction increased slightly with increasing serum potassium levels.

Adult↗