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Biomedical subjects

F H Epstein

Publications and source records attributed to F H Epstein.

At least 181 records · Page 10Linked to original sources
PubMed1983

International mortality trends and secular changes.

The decline in mortality from coronary heart disease (CHD) in several countries, notably the United States, in the 1970s has drawn attention to the need for monitoring secular trends in mortality and morbidity from this disease internationally and to discover the reasons for any upward or downward changes. Mortality trends for CHD in 27 countries are seen to vary widely, being very similar for men and women. It is, however, important to view CHD not in isolation but in terms of total mortality (TM) and other specific causes of death. For a more comprehensive picture, it is also necessary to go back two more decades into the 1950s, requiring the use of a broader diagnostic category "nonrheumatic and hypertensive heart disease" (HD). Using examples from selected countries, it is shown that CHD and HD run generally in parallel, that HD trends often though not always determine TM, and that cancer trends may or may not follow those for HD. Since preventive measures for CHD are likely to be beneficial for the prevention of other diseases as well, the concomitant study of trends for several chronic disorders ought to be rewarding.

Adult↗
PubMed1983

Selective glutathione depletion on function and structure of the isolated perfused rat kidney.

The role of glutathione (GSH) in the preservation of renal function and the pathogenesis of renal injury has been investigated using the isolated perfused rat kidney as a model. In kidneys perfused for 80 min with 5 mM glucose as the only exogenous substrate, tissue GSH becomes depleted, renal function deteriorates, and a degenerative change appears, restricted to the medullary thick ascending limb. These abnormalities can be ameliorated by providing amino acid supplements or by adding GSH itself to the perfusion. To distinguish between the effects of amino acid supplementation and GSH depletion per se, selective depletion of GSH was accomplished in several different ways. Synthesis of GSH was inhibited by the addition of dl-buthionine-SR-sulfoximine, a specific inhibitor of gamma-glutamyl cysteine synthetase. GSH depletion was also produced by 2-cyclohexene-1-one and diethylmaleate, both known to diminish the concentration of GSH selectively without affecting protein thiols. Perfused kidneys selectively depleted of GSH showed significant impairment of concentrating ability, and less marked decreases in tubular reabsorption of sodium. The degenerative changes in the medullary thick ascending limb, on the other hand, were unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1983

Mechanism and control of hyperosmotic NaCl-rich secretion by the rectal gland of Squalus acanthias.

Secretion of chloride from blood to lumen is accomplished in the rectal gland of elasmobranchs by a process of secondary active transport involving the co-transport of Cl- with Na+ across the basolateral membranes of rectal gland cells. Energy is provided by ATP via membrane Na-K-ATPase, which establishes an electrochemical gradient favouring Na+ influx into the cell. The involvement of K+ in the co-transport mechanism, so as to provide a ratio of 1 Na+:1 K+:2 Cl- entering the cell, would increase the energetic efficiency of the process, and is consistent with the Cl/O2 ration of 27-30 observed in secreting rectal glands. Secretion is stimulated by cyclic AMP (cAMP) and by vasoactive intestinal peptide (VIP) and adenosine, which activate adenylate cyclase. Activation of the gland in vivo probably occurs via VIP-secreting nerves as well as circulating agents; it is inhibited by somatostatin. Cyclic AMP probably stimulates chloride secretion by at least three mechanisms: (1) increasing chloride conductance across the luminal cell membrane, (2) enhancing the co-transport pathway for transmembrane movements of Na+, K+ and Cl- and (3) activating Na-K-ATPase.

Animals↗
PubMed1983

Effect of chronic salt loading on renal Na-K-ATPase activity in the rat.

The effect of chronic salt loading in rats fed regular chow diet on renal Na-K-ATPase was studied. The high salt intake was associated with increased filtered load of sodium (control: 126 +/- 3.9 mueq/min, salt loaded: 146 +/- 2.5, mueq/min, P less than 0.001), increased net reabsorption of sodium (control: 125.3 +/- 3.9 mueq/min, salt load: 134.8 +/- 2.4 mueq/min, P less than 0.05), increased urinary excretion of potassium (control: 2.4 +/- 0.09 mueq/min/min; salt loaded: 3.0 +/- 0.1 mueq/min, P less than 0.001) and increase in single kidney weight (control: 0.798 +/- 0.010 g, salt loaded: 0.937 +/- 0.015 g, P less than 0.001). The above mentioned changes were associated with significant increase in renal microsomal and whole homogenate medullary Na-K-ATPase activity in the salt loaded group (microsomes: control 74.1 +/- 4.9 mumole Pi/mg prot/hr, salt loaded 112.7 +/- 6.0 mumole Pi/mg prot/hr, P less than 0.001; whole homogenate: control 22.7 +/- 1.0 mumole Pi/mg prot/hr, salt load 29.4 +/- 1.6 mumole Pi/mg prot/hr, P less than 0.005), while cortical and papillary Na-K-ATPase activity remained unchanged. Taken together, these results show that increased filtered and reabsorbed load of sodium, which follows high salt intake, is associated with an increased renal Na-K-ATPase activity. The preferential rise in medullary enzymatic activity may be interpreted as suggesting that these changes may stem from increased delivery and reabsorption of sodium in the ascending limb of Henle's loop.

Adenosine Triphosphatases↗
PubMed1982

[Blood pressure, renin angiotensin aldosterone system and other cardiovascular risk factors in children of essential hypertensives (author's transl)].

In the present study, blood pressure, the renin angiotensin aldosterone system, and other cardiovascular risk factors, such as glucose, cholesterine, and triglycerides, were investigated in 294 offspring of essential hypertensives (5-34 years) and in 122 children of normotensive parents (5-34 years). Offspring of essential hypertensives showed statistically significant higher systolic and diastolic blood pressure values than those of normotensive parents (p less than 0.003, less than 0.005, respectively). Furthermore, in children of hypertensive parents a statistically significant higher body weight and body mass index than in controls could be observed (p less than 0.006, less than 0.001, respectively). With the exception of statistically significant, lower mean supine plasma aldosterone values (p less than 0.02) in children of hypertensive parents, no major differences between the two groups were seen in stimulated aldosterone, supine and stimulated plasma renin activity, and plasma cortisol. Furthermore, in the present study, 41 hypertensive parents, 65 (normotensive) spouses of hypertensives, and 47 (normotensive) parents of control children were investigated. As expected, hypertensive parents showed statistically significant higher blood pressure values than parents of control children and their spouses (p less than 0.001). Interestingly, hypertensive parents had not only a higher body mass index than control parents but also than their spouses (p less than 0.01 and less than 0.02, respectively). These findings support a genetic disposition as being the underlying cause of higher body weight in hypertensives and make it less probable that a higher food intake in hypertensive families is responsible for this phenomenon. The results of the present study indicate that early body weight control in children of hypertensive parents may be an important contribution to the prevention of hypertension.

Adolescent↗
PubMed1982

[Prevention of coronary heart disease. A study of 2 rural communities of Zurich].

This study aimed at reducing risk factors for coronary heart disease through improving living habits in the population. It was conducted in a rural community in the canton of Zürich; a similar community without an intervention programme served for comparison. Data from questionnaires and examinations in random population samples examined at the start and a year later (1974-75) indicated that a favourable effect on smoking habits was achieved while blood-pressure levels were reduced in both communities, presumably because hypertensives were referred to their physician in the intervention as well as in the control area. Serum-cholesterol level and eating habits could not be demonstrably influenced. However, there was a trend toward weight reduction and an increase in physical activity in the intervention community. On comparing the initial findings, based on random samples, with an independent new sample examined at the end of the study, no overall changes in risk-factor levels could be found in the general population but the statistical power to show an effect is impaired by small numbers. The intensity of the intervention programme was limited by the available means; it was well accepted by the population.

Adult↗
PubMed1982

Predicting coronary heart disease in siblings--a multivariate assessment: the Framingham Heart Study.

The incidence of clinically recognized coronary heart disease and its relation to risk factors have been studied for 596 sibships in the Framingham Heart Study cohort. Only the 186 pairs of brothers were considered in the multivariate analysis, since the rate of coronary heart disease in women is low. Multiple logistic regression was performed by using endpoints of coronary heart disease as the dependent variable for the younger brother of the pair. Age, Metropolitan relative weight, systolic blood pressure, total cholesterol, cigarette smoking and endpoints of coronary heart disease for the older brother represent the independent variables. The incidence of myocardial infarction in the older brother is significantly related to myocardial infarction experience of the younger brother, even after the strong effects of total cholesterol, systolic blood pressure and cigarette smoking were controlled. These findings suggest that family history of myocardial infarction may be an important independent predictor of myocardial infarction, and suggest that familial aggregation for coronary heart disease may result from predisposition to disease, possibly genetic, that is not reflected in the measured levels of total cholesterol, systolic blood pressure or cigarette smoking.

Analysis of Variance↗
PubMed1982

Relationship among gluconeogenesis, QO2, and Na+ transport in the perfused rat kidney.

The relationship among sodium transport (TNa), oxygen consumption (QO2), and gluconeogenesis was studied in isolated perfused rat kidneys in which glucose formation was enhanced by providing pyruvate as a substrate and by prior treatment with methylprednisolone. TNa was increased abruptly by increasing perfusion pressure as to increase GFR or by lowering the albumin concentration of a hyperoncotic perfusate as to allow glomerular filtration to occur. Increases in TNa of 40% were accompanied by little or no increase in QO2, whereas gluconeogenesis decreased 55-80%. Conversely, a decrease in perfusion pressure that lowered TNa produced an increase in glucose formation without a change in QO2. When gluconeogenesis was blocked with 0.15 mM 3-mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase, QO2 increased together with TNa as perfusion pressure was raised. The results suggest that the energy needed for ion transport by the kidney may under some circumstances be borrowed from nontransport functions and, therefore, that basal oxygen consumption may vary with the rate of reabsorptive transport.

Animals↗
PubMed1982

Improved function with amino acids in the isolated perfused kidney.

When isolated rat kidneys are perfused with glucose as the only substrate, there is a progressive diminution in glomerular filtration rate and fractional reabsorption of sodium. This is most marked after 1 h. Renal glutathione content rapidly falls and is less than 30% of control levels after 1 h. Renal concentrating ability is markedly impaired and structural lesions are consistently observed in cells lining the thick ascending limb of Henle's loop. Addition of 20 physiologic amino acids including cysteine to the perfusate prevents the fall in renal glutathione, prevents the anatomical damage to ascending limb cells, permits GFR and fractional sodium reabsorption to remain high and close to their initial levels for as long as 4 h, and improves renal concentrating capacity. If amino acid supplementation is limited to three precursors of glutathione--cysteine, glycine, and glutamic acid--renal glutathione content is preserved and concentrating ability is improved, but GFR and fractional sodium reabsorption are not maintained as well as with comprehensive amino acid supplements. The results suggest that amino acid deficiency and glutathione depletion may contribute to disturbances in renal structure and function.

Absorption↗
PubMed1982

Redox state of cytochrome aa3 in isolated perfused rat kidney.

Optical spectroscopy was used to evaluate mitochondrial anoxia in the isolated perfused rat kidney by determining the percentage of cytochrome aa3 in the reduced state. Despite high levels of plasma flow (greater than 20 ml . g-1 . min-1) and venous PO2 (greater than 300 mmHg), 25--40% of cytochrome aa3 appeared to be in its reduced form. Agents that alter metabolism or transport primarily in renal cortex had little or no effect on the redox state of cytochrome aa3. These included 3-mercaptopicolinate, an inhibitor of gluconeogenesis; 2-tetradecylglycidic acid, an inhibitor of fat metabolism via carnitine-fatty acyltransferase, and acetazolamide. In contrast, a decrease in medullary transport induced by the loop diuretics bumetanide or furosemide produced an increase in cytochrome aa3 oxidation consistent with a decrease in transport-related oxygen consumption in the hypoxic area. The results suggest that substantial portions of the kidney, particularly in the renal medulla, may normally operate on the brink of anoxia despite high PO2 in artery and vein.

Animals↗
PubMed1982

The treatment of sickle cell anemia with induced hyponatremia.

Since the rate of polymerization of sickle hemoglobin is exquisitely dependent on its concentration, a small reduction in intracellular hemoglobin concentration should cause a significant inhibition of sickling. In three patients with homozygous sickle cell anemia, sustained hyponatremia was induced by a program consisting of a high fluid intake, a low salt diet and a vasopressin analog, DDAVP. During periods of hyponatremia, mean corpuscular hemoglobin concentration (MCHC) fell 13% and in vitro sickling was reduced as assessed by morphology and oxygen affinity. The frequency and duration of sickle cell crises appeared to be decreased during periods when patients were hyponatremic. These preliminary results indicate that reduction in intracellular hemoglobin concentration is an effective approach to the treatment of sickle cell anemia.

Anemia, Sickle Cell↗
PubMed1982

Epidemiological research strategies for multiple factor studies.

Epidemiological approaches to the study of chronic diseases with multiple aetiology are reviewed. Sources of hypotheses, the place of epidemiology within the total framework of medical research, types of epidemiological studies, problems of methodology and the complexity of the simultaneous measurement of a multiplicity of factors and influences are discussed, with special reference to the psychosocial aspects of cardiovascular disease. Future strategies include prospective epidemiological investigation but also the parallel development of new predictive tests which link psychological stresses to disease mechanisms, providing a base for preventive action.

Chronic Disease↗
PubMed1981

[Blood pressure study in school-children of Zurich. I. Results in the age group 7 to 12 years].

A longitudinal blood pressure study of 1575 children aged 7-11 years was started in 1977. 308 12-year-old children were rescreened one year later. The blood pressure was recorded at school in the sitting position using random-zero-sphygmomanometers and the largest cuff to fit the upper arm easily (10 cm and 12 cm wide). Systolic and diastolic II (disappearance of sounds) pressures were measured, and the mean of two readings (1st/2nd, or 3rd/4th if indicated) was used. The blood pressure values were remarkably low, with mean systolic pressures of 98 mm Hg or less and diastolic pressures of 55 mm Hg or less. The highest readings observed were 140 mm Hg systolic and 95 mm Hg diastolic in two 11-year-old children. The systolic blood pressure correlated best with weight (r = 0.38 in boys and 0.45 in girls), and, in decreasing order, with height (r = 0.32/0.40), age (r = 0.28/0.32) and triceps skinfold thickness (r = 0.24/0.26). Correlation with pulse rate was poor (r = 0.09/0.06). However, a multiple regression analysis showed that weight and pulse rate are the only variables which contribute significantly to explaining the variance of systolic blood pressure (17% in boys and 24% in girls). At constant height levels there was no correlation between systolic blood pressure and age, but the correlation with weight remained good and with skinfold thickness fair. Thus, the blood pressure in children aged 7-12 years correlates better with indices of body size (weight and Quetelet index) than with fatness, except in clearly obese children. Repeated blood pressure recordings correlated significantly with values obtained one year earlier: in boys, r = 0.49 for systolic and 0.34 for diastolic pressures, in girls, r = 0.58 (systolic) and 0.41 (diastolic). Repeatedly elevated systolic blood pressures, i.e. values within the upper decile, were observed four times more frequently than could have been expected by chance alone (in 14 of 36 children = 39%). Positive tracking correlations of blood pressure are therefore demonstrable in childhood.

Blood Pressure↗