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Biomedical subjects

R D Cohen

Publications and source records attributed to R D Cohen.

At least 19 recordsLinked to original sources
PubMed1992

Protective factors and social risk factors for hospitalization and mortality among young men.

The association between presumed protective factors and social risk factors for hospitalization and mortality was studied during a 14-year follow-up period in a cohort of 8,168 Swedish men aged 18-20 years at baseline. Using Cox regression analysis, the authors found that five protective factors (high social class, home well-being, school well-being, good emotional control, and self-perceived good health) were associated with lower risks of hospitalization and death. Four social risk factors (contact with police or child welfare authorities, running away from home, having divorced parents, and ever using narcotics) were significantly associated with increased risk of hospitalization and mortality. The relative hazard decreased with the number of protective factors and increased with the number of social risk factors, almost linearly. The relative hazard was 0.24 for hospitalization among those with six protective factors and 0.24 for mortality for those with five or six protective factors. The relative hazard for hospitalization was 3.09 among those with five social risk factors compared with those with none, while for mortality the relative hazard among those with four or five social risk factors was 5.74 compared with those with none. While these results indicate strong cumulative effects for both the social risk factors and the protective factors, the associations of individual factors with the two outcome measures were generally reduced in models which simultaneously adjusted for all factors, which presumably indicates collinearity among the factors. There was only limited support for a buffering, or interacting, effect between the risk factors and the protective factors.

Adolescent↗
PubMed1992

Effects of D-3-hydroxybutyrate and acetoacetate on lactate removal in isolated perfused livers from starved and fed rats.

We examined the influence of nutritional state on the role of the hepatic plasma membrane lactate transporter in determining overall hepatic lactate disposal. The effects of infusion of sodium D-3-hydroxybutyrate (DOHB) on lactate uptake were studied in perfused livers from fed or starved rats. In livers from starved rats, DOHB (15 to 20 mmol/L) inhibited lactate removal by approximately 45%. This effect was associated with a decrease in intracellular lactate concentration, with cell pH remaining unchanged. Inhibition was maximal when perfusate lactate was less than 1.6 mmol/L, and was undetectable at concentrations exceeding 2.5 mmol/L. A similar degree of inhibition was observed with infusion of acetoacetate. These observations add to the evidence that the inhibition of lactate removal by DOHB seen in livers from starved animals is mediated through an effect on the hepatocyte lactate transporter. At similar low levels of perfusate lactate, DOHB infusion produced a decrease in output of lactate from livers obtained from fed animals. When such livers were subjected to prolonged preperfusion, lactate removal, rather than output, was observed; in these livers DOHB stimulated lactate removal, an effect directionally opposite to that observed in livers from starved animals. These data confirm that hepatic lactate transport is a limiting factor for lactate utilization in intact livers from starved rats; in contrast, lactate utilization in livers from fed animals is limited at a step subsequent to plasma membrane transport, ie, possibly pyruvate transport into mitochondria.

3-Hydroxybutyric Acid↗
PubMed1992

The dynamics of disability and functional change in an elderly cohort: results from the Alameda County Study.

OBJECTIVE: To examine changes in functional status over time by age, gender, and ethnicity in a representative sample of older persons. DESIGN: Six-year prospective cohort study. SETTING: Alameda County, California. PARTICIPANTS: 508 persons 65 years old and older at baseline in 1984. MAIN OUTCOME MEASURES: Activities of daily living (ADL) dependence, mobility impairment, and functioning on an 18-item scale. RESULTS: The prevalence of ADL dependence and mobility impairment at baseline increased with age, while function decreased. Particularly striking differences occurred for those 80 and older. Changes in function over the 6-year follow-up showed a similar pattern. While death rates for males were higher, females had poorer initial functioning, and surviving females declined more than surviving males. The incidence of ADL dependence and mobility impairment during follow-up was similar for males and females, although females survived longer with incident disability than did males. Blacks had poorer baseline functioning, more ADL dependence and mobility impairment, and declined more than non-Blacks during follow-up. Some of the baseline difference in function between Blacks and non-Blacks was due to higher rates of chronic illness and co-morbidity. In spite of the general downward trend in functioning over the 6 years, 13% of the males and 20% of the females improved. CONCLUSION: Age-related changes in function for older persons are complex and result in much heterogeneity. Clarifying the reasons for such heterogeneity is an important and challenging area of research.

Activities of Daily Living↗
PubMed1992

Hepatic glutamine metabolism and acid-base regulation.

Switching of hepatic nitrogen disposal from urea synthesis to glutamine production has been proposed as a mechanism for countering acidosis, with glutamine synthesis providing a route for the detoxification of ammonium not incorporated into urea. Isolated livers from starved rats were perfused with ammonium (0.8 mM); increasing perfusate lactate concentration 0-2 mM raised glutamine synthesis threefold whilst increasing perfusate glucose concentration 0-20 mM did not. This was true under normal and acidotic conditions. In the presence of both substrates plus either 14C-glucose or 14C-lactate, the mean specific activity of glutamine synthesised was greater for 14C-lactate. Thus, the preferred substrate for hepatic glutamine synthesis is lactate, a proton neutral reaction. Perfusion with lactate and glutamine over the pH range 6.9-7.5 with or without the glutamine synthase inhibitor L-methionine-s-sulphoxime showed that the switch in acidosis to net glutamine production is entirely due to inhibition of glutamine removal by periportal hepatocytes.

Acidosis↗
PubMed1991

Substrate and pH effects on glutamine synthesis in rat liver. Consequences for acid-base regulation.

Switching in acidosis of hepatic nitrogen disposal from urea synthesis to NH4+ and net glutamine production was demonstrated in the isolated perfused livers of starved male Wistar rats. Lactate was preferred to glucose as the substrate for the carbon skeleton of glutamine synthesized over the pH range 6.9-7.5. This is necessary if the switch away from a proton-producing process (ureagenesis) in acidosis is to constitute an acid-base regulating system intrinsic to the liver. Glutamine balance shifted with pH from marked net uptake to small net output under acidotic conditions (pH 7.5-6.9), an effect due solely to a decrease in glutamine uptake. NH4+ uptake by the liver had a linear relationship with pH, being markedly decreased in acidosis because glutamine synthesis was insufficient to compensate for the decreased incorporation into urea. Animals rendered chronically acidotic showed a lower central venous plasma urea concentration and a raised NH4+ concentration, but their livers synthesized no more glutamine when perfused at an acidotic pH than did normal livers. We conclude that perivenous hepatocytes may not be efficient scavengers of NH4+ ions, which must be partly disposed of elsewhere by non-proton-generating pathways if inhibition of ureagenesis is to represent a hepatic acid-base regulating system.

Acid-Base Equilibrium↗
PubMed1991

Change in alcohol consumption and risk of death from all causes and from ischaemic heart disease.

OBJECTIVE: To examine the association between alcohol consumption and mortality from all causes and from ischaemic heart disease with a focus on differentiating between long term abstainers and more recent non-drinkers. DESIGN: Cohort study of changes in alcohol consumption from 1965 to 1974 and mortality from all causes and ischaemic heart disease during 1974-84. SETTING: Population based study of adult residents of Alameda County, California. SUBJECTS: 2225 women and 1845 men aged 35 and over in 1965. MAIN OUTCOME MEASURES: Alcohol consumption in 1964 and 1974 and mortality from all causes and from ischaemic heart disease during 1974-84. RESULTS: There was a significantly higher risk of death from all causes and from ischaemic heart disease in women who gave up drinking between 1965 and 1974 than in women who continued to drink (relative risk 1.72, 95% confidence interval 1.11 to 2.66, and 2.75, 1.44 to 5.23, for all causes and ischaemic heart disease respectively). A significant increase in risk was not seen in men who gave up drinking (1.32, 0.87 to 2.01, and 0.95, 0.41 to 2.20, respectively). Among men, long term abstainers compared with drinkers were at increased risk of death from all causes and from ischaemic heart disease, though the associations were not significant (1.40, 0.98 to 2.00, and 1.40, 0.76 to 2.58, for all causes and ischaemic heart disease respectively). CONCLUSION: Some of the increased risk of death from all causes and from ischaemic heart disease associated with not drinking in women seems to be accounted for by higher risks among those who gave up drinking. Men who are long term abstainers may also be at an increased risk of death. The heterogeneity of the non-drinking group should be considered when comparisons are made with drinkers.

Adult↗
PubMed1991

Physical activity and depression: evidence from the Alameda County Study.

The relation between level of physical activity and risk of subsequent depression was examined using three waves of data from the Alameda County Study. Among subjects who were not depressed at baseline, those who reported a low activity level were at significantly greater risk for depression at the 1974 follow-up than were those who reported high levels of activity at baseline. Adjustments for physical health, socioeconomic status, life events, social supports, and other health habits did not affect the association appreciably. Associations between 1965-1974 changes in activity level and depression in the 1983 follow-up suggest that the risk of depression can be altered by changes in exercise habits, although these associations were not statistically significant after adjustment for covariates. These results provide somewhat stronger evidence for an activity-depression link than do previous studies, and they argue for the inclusion of exercise programs as part of community mental health programs, as well as for further studies that focus on the relation between life-style and mental health.

Adult↗
PubMed1991

Correlation of nuclear morphometry and DNA ploidy in rectal cancer.

Several investigators have used morphometric measurements to determine differences in the nuclear size and shape of normal and neoplastic colorectal tissue. Changes in nuclear morphometric parameters have also been shown to correlate with prognosis in a variety of noncolorectal cancers. The association of nuclear morphometry with prognostic indicators in rectal cancer has not been well studied. Measurements of the nuclear area, perimeter, longest cord, and circularity factor from 39 primary rectal adenocarcinomas were compared with DNA content, degree of tumor differentiation, Dukes' class, and patient survival. Nuclear circularity was found to correlate with DNA ploidy. Nondiploid tumors with a DNA index greater than 1.3 had significantly more circular nuclei than tumors with diploid or near-diploid DNA content. There was no correlation between nuclear morphometry and Dukes' class or patient survival. Significant increases in DNA content of rectal cancers appear to be reflected by measurable changes in nuclear shape. Nuclear morphometric measurements may provide useful information in the study of the progression of neoplastic changes in colorectal cancer.

Actuarial Analysis↗
PubMed1991

The relationship between stressful life situations and changes in alcohol consumption in a general population sample.

Studies on the relationship between stressful life situations and alcohol consumption have almost exclusively been based on retrospective information from clinical populations. We conducted multiple regression analyses of the relationship between presumed stressful life conditions in 1965, life events during 1966-73 and psychosocial factors and amount of increase or decrease in alcohol consumption from 1965 to 1974 adjusting for age, alcohol consumption, education and health status in 1965. Data from surveys in 1965 and in 1974 in a general population sample of 4,864 subjects from Alameda County, California were used. The magnitude of the associations between the presumed stressful life situations and amount of change was generally low, although a few were statistically significant. However, among those aged 65 years and above, and especially among men, some of the associations were strong, but imprecise due to the low number of subjects in those ages. While a number of variables were associated with increase or decrease in alcohol consumption, the R2-values indicated that these variables explained little of the variation over time in alcohol consumption. Thus, people in general seem to cope with stressful life situations by means, other than a longstanding increase in alcohol consumption.

Adaptation, Psychological↗
PubMed1990

Hormonal modulation of hepatic plasma membrane lactate transport in cultured rat hepatocytes.

Hormonal modulation of hepatic plasma membrane lactate transport was studied in primary cultures of isolated hepatocytes from fed rats to examine the mechanism for the known enhancement of lactate transport in starvation and diabetes. Total cellular lactate entry was increased by 14% in the presence of dexamethasone; this was accounted for by an approximately 40% increase in the carrier-mediated component of entry with no effect on diffusion. A trend of similar magnitude was evident with glucagon. The effects of dexamethasone and glucagon on lactate transport constitute an additional potential mechanism for enhancement of gluconeogenesis by these hormones.

Animals↗
PubMed1990

Sex differences in time from self-reported heart trouble to heart disease death in the Alameda County Study. Significance of time dependence of risk variable effects.

In a previous analysis from the Alameda County Study, it was observed that although men had higher heart disease mortality rates than women, there was no male excess in the prevalence of self-reported heart disease morbidity at baseline or in new reports of morbidity 9 years past baseline. This apparent contradiction might occur because women report less severe heart disease than men. In the present study, this hypothesis was evaluated by examining whether self-reported heart trouble was more strongly associated with subsequent heart disease mortality for men than for women in a representative sample of the population of Alameda County, California, selected in 1965 and followed for mortality for 19 years (n = 3,742). In a time-dependent Cox model, self-reported heart trouble was a stronger predictor of heart disease mortality for men, but only during the early years of follow-up (p = 0.00). This effect was due to a shorter time to death for men who reported heart trouble. The relative hazard for men reporting heart trouble was 6.6 (95% confidence interval (CI) 3.7-11.6) at baseline, declining to 3.2 (95% CI 2.2-4.5) by 5 years past baseline and 1.5 (95% CI 0.9-2.5) by 10 years past baseline. Self-reported heart trouble was a consistent predictor of subsequent heart disease mortality for women over the 19-year follow-up period (relative hazard = 2.0, 95% CI 1.4-2.8). Sex differences in the prognosis of self-reported heart trouble were masked in non-time-dependent analyses. These results illustrate that consideration of time dependence may be required for meaningful analysis of long-term cohort studies. Possible explanations of the shorter time to death for men who reported heart trouble are discussed.

Adult↗
PubMed1989

Gluconeogenesis and the protection of hepatic intracellular pH during diabetic ketoacidosis in rats.

Studies were made of the mechanism whereby hepatic gluconeogenesis is increased in diabetic ketoacidosis (DKA) despite evidence in vitro of inhibition of gluconeogenesis by systemic acidosis. In perfused livers taken from normal rats, marked inhibition of lactate uptake and glucose output was achieved by simulation of metabolic acidosis in the perfusate. In perfused livers obtained from animals with DKA, lactate uptake and glucose output were greater than in normal perfused liver at all values of perfusate pH, and it was not possible to demonstrate significant inhibition of gluconeogenesis from lactate by perfusate acidosis. Varying severity of acidosis was induced in rats by (a) HCl infusion, (b) NH4Cl ingestion or (c) experimental DKA. Hepatic intracellular pH (pHi) was measured in vivo by 31P-n.m.r. spectroscopy. Whereas at the severer degrees of systemic acidosis marked falls in hepatic pHi were seen in the HCl- and NH4Cl-treated animals, little fall was seen in rats with DKA. The protection of hepatic pHi in rats with DKA was not due to differences in respiratory compensation compared with the other groups. It is suggested that this protection of hepatic pHi in DKA may be responsible for the failure of acidotic inhibition of gluconeogenesis from lactate. Possible reasons for pHi protection in DKA are considered. There is no difference in hepatic energy status as assessed in vivo by ATP/Pi ratios between control, DKA and NH4Cl-treated rats. DKA rats show a striking decrease in hepatic glycerophosphoethanolamine content.

3-Hydroxybutyric Acid↗
PubMed1989

Sex differentials in morbidity and mortality risks examined by age and cause in the same cohort.

Many studies indicate that women live longer than men but report more physical illness. This report is the first prospective study of sex ratios for morbidity and mortality due to a variety of causes in a single cohort: a random sample of 5,239 adults, aged 30 years or older in 1965, who have been followed through 1983 (19 years) by cause and age. For both cancer incidence and mortality there was a female excess before age 50 years, followed by a male excess peaking between ages 60 and 69 years. Sex ratios for ischemic heart disease mortality, on the other hand, indicated a male excess at virtually all ages, and that these sex ratios declined with age. However, three measures of heart disease morbidity (self-reported chest pain, heart trouble, and high blood pressure) demonstrated a female excess that did not vary by age. All four measures of functional disability (impaired self-care, impaired mobility, cessation of work, and reduction of work) demonstrated a female excess that did not vary by age (with the exception of a male excess in impaired self-care in adults aged 30 to 39 years). Further analyses of sex differences in health need to acknowledge the heterogeneity of the relation of sex to disease, and the complex age-sex interaction that varies remarkably with both cause and manifestation of outcome (morbidity vs. mortality).

Adult↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗