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Biomedical subjects

R D Cohen

Publications and source records attributed to R D Cohen.

At least 55 records · Page 3Linked to original sources
PubMed1997

Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation.

Maternal protein restriction is a model of fetal programming of adult glucose intolerance. Perfused livers of 48-h- starved adult offspring of rat dams fed 8% protein diets during pregnancy and lactation produced more glucose from 6 mM lactate than did control livers from rats whose dams were fed 20% protein. In control livers, a mean of 24% of the glucose formed from lactate in the periportal region of the lobule was taken up by the most distal perivenous cells; this distal perivenous uptake was greatly diminished in maternal low protein (MLP) livers, accounting for a major fraction of the increased glucose output of MLP livers. In control livers, the distal perivenous cells contained 40% of the total glucokinase of the liver; this perivenous concentration of glucokinase was greatly reduced in MLP livers. Intralobular distribution of phosphenolpyruvate carboxykinase was unaltered, though overall increased activity could have contributed to the elevated glucose output. Hepatic lobular volume in MLP livers was twice that in control livers, indicating that MLP livers had half the normal number of lobules. Fetal programming of adult glucose metabolism may operate partly through structural alterations and changes in glucokinase expression in the immediate perivenous region.

Animals↗
PubMed1997

Reduced aortic lesions and elevated high density lipoprotein levels in transgenic mice overexpressing mouse apolipoprotein A-IV.

Transgenic mouse lines carrying several copies of the mouse apo A-IV gene were produced. Lipoprotein composition and function, and aortic lesion development were examined. Apo A-IV levels in the plasma of transgenic mice were elevated threefold compared with nontransgenic littermates on a chow diet, and sixfold in mice fed an atherogenic diet. Plasma concentrations of total cholesterol, HDL cholesterol, triglycerides, and free fatty acids were similar in transgenic and control mice fed a chow diet. However, with the atherogenic diet, male transgenic mice exhibited significantly higher levels of plasma triglycerides (P < 0.05), total cholesterol (P < 0.01), HDL cholesterol (P < 0.0001), and free fatty acids (P < 0.05), and lower levels of unesterified cholesterol (P < 0.05), than nontransgenic littermates. Expression of the apo A-IV transgene had a protective effect against the formation of diet-induced aortic lesions, with transgenics exhibiting lesion scores of approximately 30% those seen in control mice. HDL-sized lipoproteins isolated from transgenic mice fed the atherogenic diet promoted cholesterol efflux from cholesterol-loaded human monocytes more efficiently than comparable lipoproteins from nontransgenic counterparts. Plasma from transgenics also exhibited higher endogenous cholesterol esterification rates. Taken together, these results suggest that apo A-IV levels influence the metabolism and antiatherogenic properties of HDL.

Animals↗
PubMed1997

Interaction of workplace demands and cardiovascular reactivity in progression of carotid atherosclerosis: population based study.

OBJECTIVE: To examine the combined influence of workplace demands and changes in blood pressure induced by stress on the progression of carotid atherosclerosis. DESIGN: Population based follow up study of unestablished as well as traditional risk factors for carotid atherosclerosis, ischaemic heart disease, and other outcomes. SETTING: Eastern Finland. SUBJECTS: 591 men aged 42-60 who were fully employed at baseline and had complete data on the measures of carotid atherosclerosis, job demands, blood pressure reactivity, and covariates. MAIN OUTCOME MEASURES: Change in ultrasonographically assessed intima-media thickness of the right and left common carotid arteries from baseline to 4 year follow up. RESULTS: Significant interactions between workplace demands and stress induced reactivity were observed for all measures of progression (P < 0.04). Men with large changes in systolic blood pressure (20 mm Hg or greater) in anticipation of a maximal exercise test and with high job demands had 10-40% greater progression of mean (0.138 v 0.123 mm) and maximum (0.320 v 0.261 mm) intima-media thickness and plaque height (0.347 v 0.264) than men who were less reactive and had fewer job demands. Similar results were obtained after excluding men with prevalent ischaemic heart disease at baseline. Findings were strongest among men with at least 20% stenosis or non-stenotic plaque at baseline. In this subgroup reactive men with high job demands had more than 46% greater atherosclerotic progression than the others. Adjustment for atherosclerotic risk factors did not alter the results. CONCLUSIONS: Men who showed stress induced blood pressure reactivity and who reported high job demands experienced the greatest atherosclerotic progression, showing the association between dispositional risk characteristics and contextual determinants of disease and suggesting that behaviourally evoked cardiovascular reactivity may have a role in atherogenesis.

Adult↗
PubMed1997

Frequent hangovers and cardiovascular mortality in middle-aged men.

We studied the relation between frequent hangovers and cardiovascular mortality in a representative population sample of middle-aged Finnish men who participated in the Kuopio Ischemic Heart Disease Risk Factor Study. Complete data on alcohol consumption, hangover frequency, prior cardiovascular diseases, and risk factors were obtained for 2,160 non-abstinent men. Frequent hangovers were rare in the three lowest alcohol consumption quartiles, but in the highest quartile, a total of 239 men (43.6%) reported having a hangover at least monthly. During an average follow-up time of 6.7 years, these men had a 2.36-fold (95% confidence interval = 1.02-5.48) risk of cardiovascular death compared with men with fewer hangovers, with adjustment for age and total alcohol consumption. The association was somewhat attenuated after adjustments for smoking, income, and prior cardiovascular diseases. Systolic blood pressure, body mass index, resting heart rate, or serum lipids had no appreciable role in the relation, but plasma fibrinogen concentration appeared as one possible pathway to increased risk of cardiovascular death in men who frequently experience hangovers. The findings underline the importance of preventive actions regarding not only the amount but also the way people consume alcohol.

Adult↗
PubMed1997

Ten years of experience with isolated urachal anomalies in children.

PURPOSE: The embryological and anatomical features of urachal anomalies have been well defined. Because of the variable clinical presentation, uniform guidelines for evaluation and treatment are lacking. In an attempt to establish a cost-effective approach leading to a favorable outcome, we reviewed the experience with urachal anomalies at a single institution in a 10-year period. MATERIALS AND METHODS: We reviewed the medical records and radiological studies of 12 boys and 9 girls newborn to 17 years old at presentation who were treated for a urachal anomaly. Diagnostic evaluation included voiding cystourethrography in 14 cases, ultrasound in 8, sinography in 7 and computerized tomography in 4. RESULTS: The 4 variants of urachal anomalies included a urachal sinus in 9 patients (43%), urachal cyst in 9 (43%), patent urachus in 2 (10%) and urachal diverticulum in 1 (4%). Treatment involved initial excision in 13 cases (61%) and secondary excision in 8 (39%). Staphylococcus aureus was the predominant organism recovered. CONCLUSIONS: Because of the variable presentation, the diagnosis of a urachal anomaly can be difficult. Our experience suggests that a cost-effective diagnostic approach can be developed based on the initial clinical evaluation. Whereas ultrasound is indicated when a urachal cyst or abscess is suspected on the initial study, sinography is the study of choice in the remainder of cases. A voiding cystourethrogram may not be required in view of the fact that none of the patients studied had an additional associated urinary tract anomaly.

Adolescent↗
PubMed1997

Evidence for hormone-sensitive lipase mRNA expression in human monocyte/macrophages.

The role of hormone-sensitive lipase (HSL) in the hydrolysis of adipose tissue triacylglycerol to provide free fatty acids for energy requirements has been well established. However, the role of HSL in other tissues, including macrophages, is not well understood. The demonstration that HSL is capable of hydrolyzing cholesteryl esters at approximately the same rate as triacylglycerol raised the possibility that HSL activity in macrophages may influence the accumulation of cholesteryl esters in foam cells of atherosclerotic lesions. We and others have previously demonstrated that HSL mRNA is expressed in murine peritoneal macrophages and macrophage cell lines; however, it was previously reported that HSL mRNA is absent in human monocyte-derived macrophages, suggesting that a species difference may exist. To clarify this point, we have further examined the issue of HSL mRNA expression in human macrophages. In the current study, we demonstrate that HSL mRNA is detectable in human monocyte-derived macrophages and in the THP-1 human monocyte cell line using reverse transcription coupled to polymerase chain reaction (RT-PCR). Specific amplification of cDNA derived from mRNA was ensured by using primers that span an intron within the human HSL gene, and the identity of PCR products as HSL was confirmed by hybridization to HSL cDNA and by DNA sequencing. Using a semiquantitative PCR assay, we establish that HSL mRNA levels in monocyte/macrophages are approximately 1/40 the levels in human adipose tissue. These results indicate that further studies addressing the role of HSL in macrophage metabolism and its potential role in development of foam cells in human atherosclerotic lesions are warranted.

Adipose Tissue↗
PubMed1997

An increasing prevalence of hearing impairment and associated risk factors over three decades of the Alameda County Study.

OBJECTIVES: This study assessed changes in the prevalence of hearing impairment in persons aged 50 years and older over the past 30 years and identified risk factors. METHODS: Age-adjusted hearing impairment prevalence rates at four time intervals were calculated from the Alameda County Study (n = 5108). Logistic regression models analyzed risk factors from 1974 for 1994 incident hearing impairment. RESULTS: The prevalence of hearing impairment nearly doubled between 1965 and 1994. The increase was significantly greater for men. The higher incidence was associated with potentially high-noise-exposure occupations for men and with symptoms and conditions associated with ototoxic drug use for both men and women. Exercise was protective. CONCLUSIONS: Given the serious health and social consequences of hearing impairment, its increasing prevalence is cause for concern.

Age Distribution↗
PubMed1997

Frequent attendance at religious services and mortality over 28 years.

OBJECTIVES: This study analyzed the long-term association between religious attendance and mortality to determine whether the association is explained by improvements in health practices and social connections for frequent attenders. METHODS: The association between frequent attendance and mortality over 28 years for 5286 Alameda Country Study respondents was examined. Logistic regression models analyzed associations between attendance and subsequent improvements in health practices and social connections. RESULTS: Frequent attenders had lower mortality rates than infrequent attenders (relative hazard [RH] = 0.64;95% confidence interval [CI] = 0.53,0.77). Results were stronger for females. Health adjustments had little impact, but adjustments for social connections and health practices reduced the relationship (RH = 0.77; 95% CI = 0.64, 0.93). During follow-up, frequent attenders were more likely to stop smoking, increase exercising, increase social contacts, and stay married. CONCLUSIONS: Lower mortality rates for frequent religious attenders are partly explained by improved health practices, increased social contacts, and more stable marriages occurring in conjunction with attendance. The mechanisms by which these changes occur have broad intervention implications.

Alcohol Drinking↗
PubMed1997

Effects of diet and chemical form of selenium on selenium metabolism in sheep.

The effects of diet composition and chemical form of Se on intestinal flow, absorption, and retention of Se were determined in sheep by the balance technique and by disappearance of Se from sites along the gastrointestinal tract with reference to dual-phase digesta markers. Six sheep with ruminal and duodenal cannulas were used in a crossover design with a split-plot arrangement of the Se isotope treatments. Sheep were fed a forage (alfalfa hay)-based (.37 mg Se/kg) or concentrate (barley)-based (.27 mg Se/kg) diet at 90% of ad libitum intake. Selenium stable isotopes (enriched [77Se]yeast, enriched [82Se]selenite) and fluid (Co-EDTA) and particulate (Cr-mordanted fiber) markers were administered simultaneously into the rumen four times daily for 7 d, and total collections of feces and urine were made every 24 h for these and the following 7 d. A larger proportion (51 to 61%) of the Se tracers flowing to the duodenum was associated with the particulate fraction, mainly as bacteria-associated Se, than with the fluid fraction. The [82Se]selenite was more available (P < .05) for absorption and retention than [77Se]yeast, indicating that inorganic chemical forms of Se are as available to the ruminant as organic forms of Se commonly found in feedstuffs. Selenium absorption and retention were greater (P < .05) in sheep receiving the concentrate-based diet than in sheep receiving the forage-based diet. Thus, the availability of Se from inorganic and organic sources in sheep seems to be influenced by diet composition.

Animals↗
PubMed1997

Predictors of disability retirement.

OBJECTIVES: Disability retirement may increase as the work force ages, but there is little information on factors associated with retirement because of disability. This is the first prospective population-based study of predictors of disability retirement including information on workplace, socioeconomic, behavioral, and health-related factors. METHODS: The subjects were 1038 Finnish men who were enrolled in the Kuopio Ischemic Heart Disease Risk Factor Study, who were 42, 48, 54, or 60 years of age at the beginning of the study, and who participated in a 4-year follow-up medical examination. RESULTS: Various job characteristics predicted disability retirement. Heavy work, work in uncomfortable positions, long workhours, noise at work, physical job strain, musculoskeletal strain, repetitive or continuous muscle strain, mental job strain, and job dissatisfaction were all significantly associated with the incidence of disability retirement. The ability to communicate with fellow workers and social support from supervisors tended to reduce the risk of disability retirement. The relationships persisted after control for socioeconomic factors, prevalent disease, and health behavior, which were also associated with disability retirement. CONCLUSIONS: The strong associations found between workplace factors and the incidence of disability retirement link the problem of disability retirement to the problem of poor work conditions.

Adult↗
PubMed1997

Secular trends in ischemic heart disease mortality in California versus the United States, 1980 to 1991.

We compare the recent trends in ischemic heart disease mortality in California and the United States. Because California was among the first states to have declines in ischemic heart disease mortality, an examination of these recent trends may provide important clues for upcoming national trends. Age-adjusted and -specific ischemic heart disease mortality rates were calculated by sex for persons aged 35 and older during the years 1980 to 1991. Log-linear regression modeling was used to estimate the average annual percentage change in mortality. Between 1980 and 1991, the annual age-adjusted ischemic heart disease mortality declined less in California than in the United States for both women (1.9% versus 3.1%) and men (3.1% versus 3.5%). In California, it increased slightly between 1986 and 1990 for the oldest women and men. The slower rates of decline in mortality of this disease in California compared with the United States and the rising rates among the most elderly Californians suggest that careful attention should be paid to these trends in death rates of and risk factors for this disease in California.

Adult↗
PubMed1996

Do cardiovascular risk factors explain the relation between socioeconomic status, risk of all-cause mortality, cardiovascular mortality, and acute myocardial infarction?

Much remains to be understood about how low socioeconomic status (SES) increases cardiovascular disease and mortality risk. Data from the Kuopio Ischemic Heart Disease Risk Factor Study (1984-1993) were used to estimate the associations between acute myocardial infarction and income, all-cause mortality, and cardiovascular mortality in a population-based sample of 2,272 Finnish men, with adjustment for 23 biologic, behavioral, psychologic, and social risk factors. Compared with the highest income quintile, those in the bottom quintile had age-adjusted relative hazards of 3.14 (95% confidence interval (CI) 1.77-5.56), 2.66 (95% CI 1.25-5.66), and 4.34 (95% CI 1.95-9.66) for all-cause mortality, cardiovascular mortality, and AMI, respectively. After adjustment for risk factors, the relative hazards for the same comparisons were 1.32 (95% CI 0.70-2.49), 0.70 (95% CI 0.29-1.69), and 2.83 (95% CI 1.14-7.00). In the lowest income quintile, adjustment for risk factors reduced the excess relative risk of all-cause mortality by 85%, that of cardiovascular mortality by 118%, and that of acute myocardial infarction by 45%. These data show how the association between SES and cardiovascular mortality and all-cause mortality is mediated by known risk factor pathways, but full "explanations" for these associations will need to encompass why these biologic, behavioral, psychologic, and social risk factors are differentially distributed by SES.

Adult↗
PubMed1996

A method for determination in situ of variations within the hepatic lobule of hepatocyte function and metabolite concentrations.

A method is described for the production of detailed maps of intralobular variations of hepatocyte function and metabolite concentrations, based on variable destruction by digitonin of the lobule from the centrilobular direction. Instead of the conventional approach, in which isolated hepatocytes are then prepared and studied in suspension, perfusion is continued after digitonin treatment and the function of the unaffected lobular remnants is determined, or mean metabolite concentrations are measured by 31P-NMR. These measurements are plotted against the degree of destruction, determined precisely after each study by automated quantitative histomorphometry. These plots are transformed into curves of the function or metabolite concentration of nominal single cells at any point along the radius of the lobule. Gluconeogenesis from lactate remained stable, although reduced, even after 85-90% lobular destruction, predominated periportally and disappeared by 50% along the radius of the lobule. In 31P-NMR studies, employing 1.5 mM lactate as substrate, narrowing of the intracellular P1 resonance was observed as digitonin destruction increased; this was attributed to a decrease in the intralobular heterogeneity of the intracellular pH, which fell from approx. 7.9 to < 7.4 along the first 16% of the lobular radius (from the periportal end) and to < 7.3 in the remainder of the lobule. The ATP concentration rose, and then fell, along the radius of the lobule in a centripetal direction. The method is potentially generally applicable to a wide range of hepatocellular functions and to the measurement of metabolite concentrations, most conveniently those susceptible to estimation by NMR.

Animals↗
PubMed1996

Natural history of leisure-time physical activity and its correlates: associations with mortality from all causes and cardiovascular disease over 28 years.

The association between leisure-time physical activity and 28-year (1965-1993) risk of death from all causes and cardiovascular disease was studied in 6,131 adults who participated in the Alameda County Study in Northern California. Because study participants were interviewed on a number of occasions, it was possible to include in the analyses information on changes over time in levels of leisure-time physical activity as well as changes in a wide variety of other risk factors. There were 47,616 person-years of observation for males (639 deaths from all causes and 321 from cardiovascular disease) and 57,666 person-years of observation for females (587 deaths from all causes and 388 from cardiovascular disease). In analyses in which only the baseline values of all covariates were included, a four-point increase on the leisure-time physical activity scale, the interquartile range, was associated with reduced risk of death from all causes (relative risk (RR) = 0.90, 95% confidence interval (CI) 0.83-0.99) and cardiovascular disease (RR = 0.85, 95% CI 0.75-0.97). When time-varying information on leisure-time physical activity and all other covariates was included, there was still a protective effect for all-cause and cardiovascular disease mortality (RR = 0.84, 95% CI 0.77-0.92 and RR = 0.81, 95% CI 0.71-0.93, respectively). The association between leisure-time physical activity and risk of death was not altered when information on variations over time in leisure-time physical activity and many determinants and consequences of physical activity were explicitly included in survival models.

Adolescent↗
PubMed1996

Successful aging: predictors and associated activities.

Six-year predictors of successful aging were analyzed for 356 Alameda County Study men and women aged 65-95 years measured prospectively in 1984 and followed to 1990. Successful aging was defined as needing no assistance nor having difficulty on any of 13 activity/mobility measures plus little or no difficulty on five physical performance measures. After adjusting for baseline successful aging, sex, and age, the authors found that 1984 predictors of 1990 successful aging included income above the lowest quintile (odds ratio (OR) = 2.01, 95% confidence interval (CI) 0.99-4.11), > or = 12 years of education (OR = 1.67, 95% CI 0.98-2.84), white ethnicity (OR = 2.12, 95% CI 0.93-4.86), diabetes (OR = 0.10, 95% CI 0.01-0.79), chronic obstructive pulmonary disease (OR = 0.41, 95% CI 0.17-0.97), arthritis (OR = 0.43, 95% CI 0.26-0.71), and hearing problems (OR = 0.48, 95% CI 0.25-0.89). Adjusting for all variables, the authors found that behavioral and psychosocial predictors included the absence of depression (OR = 1.94, 95% CI 1.10-3.42), having close personal contacts (OR = 1.82, 95% CI 1.05-3.18), and often walks for exercise (OR = 1.77, 95% CI 1.00-3.12). Cross-sectional comparisons at follow-up revealed significantly higher community involvement, physical activity, and mental health for those aging successfully.

Activities of Daily Living↗
PubMed1996

Moderately intense physical activities and high levels of cardiorespiratory fitness reduce the risk of non-insulin-dependent diabetes mellitus in middle-aged men.

BACKGROUND: Physical activity has been advocated as an important factor in the primary prevention of non-insulin-dependent diabetes mellitus (NIDDM), but information concerning the specific intensities and durations that are protective has been unavailable. OBJECTIVE: To examine prospectively the association between self-reported levels of the intensity and duration of physical activities, and cardiorespiratory fitness (assessed by respiratory gas exchange) and incident cases of NIDDM (assessed by the oral glucose tolerance test) in a population-based sample of 897 middle-aged Finnish men. RESULTS: After adjustment for age, baseline glucose values, body mass index, serum triglyceride levels, parental history of diabetes, and alcohol consumption, moderately intense physical activities (> or = 5.5 metabolic units) that were undertaken for at least a 40-minute duration per week were associated with a reduced risk of NIDDM (odds ration [OR], 0.44; 95% confidence interval [CI], 0.22-0.88). Activities with less than an intensity of 5.5 metabolic units, regardless of their duration, were not protective. Cardiorespiratory fitness levels greater than 31.0 mL of oxygen per kilogram per minute were protective against NIDDM (OR, 0.26; 95% CI, 0.08-0.82). A subgroup of men at high risk of NIDDM, because they were overweight and were hypertensive and had a positive parental history of NIDDM, who engaged in moderately intense physical activities above the 40-min/wk duration reduced their risk of NIDDM by 64% compared with men who did not participate in such activities. CONCLUSIONS: After adjustment for age, baseline glucose levels, and known risk factors, physical activities with an intensity of 5.5 metabolic units or greater and a duration of 40 minutes or greater per week protected against the development of NIDDM. These protective effects were even more pronounced in a subgroup of men who were at high risk for the development of the disease.

Adult↗
PubMed1996

Inequality in income and mortality in the United States: analysis of mortality and potential pathways.

OBJECTIVE: To examine the relation between health outcomes and the equality with which income is distributed in the United States. DESIGN: The degree of income inequality, defined as the percentage of total household income received by the less well off 50% of households, and changes in income inequality were calculated for the 50 states in 1980 and 1990. These measures were then examined in relation to all cause mortality adjusted for age for each state, age specific deaths, changes in mortalities, and other health outcomes and potential pathways for 1980, 1990, and 1989-91. MAIN OUTCOME MEASURE: Age adjusted mortality from all causes. RESULTS: There was a significant correlation (r = -0.62 [corrected], P < 0.001) between the percentage of total household income received by the less well off 50% in each state and all cause mortality, unaffected by adjustment for state median incomes. Income inequality was also significantly associated with age specific mortalities and rates of low birth weight, homicide, violent crime, work disability, expenditures on medical care and police protection, smoking, and sedentary activity. Rates of unemployment, imprisonment, recipients of income assistance and food stamps, lack of medical insurance, and educational outcomes were also worse as income inequality increased. Income inequality was also associated with mortality trends, and there was a suggestion of an impact of inequality trends on mortality trends. CONCLUSION: Variations between states in the inequality of the distribution of income are significantly associated with variations between states in a large number of health outcomes and social indicators and with mortality trends. These differences parallel relative investments in human and social capital. Economic policies that influence income and wealth inequality may have an important impact on the health of countries.

Adolescent↗