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Biomedical subjects

R Sherwin

Publications and source records attributed to R Sherwin.

At least 55 records · Page 3Linked to original sources
PubMed1981

Epidemiology as a guide to clinical decisions--II. Diet and coronary heart disease.

Should clinicians prescribe fat-controlled diets to prevent coronary heart disease (CHD), and, if so, which patients should be given this advice? In this report, we use a three-step model to explain the hypothesis that dietary fats are a cause of CHD: dietary saturated fat and cholesterol raise serum cholesterol levels (step 1), which are a cause of subclinical coronary atherosclerosis (step 2), and, in turn, clinically manifest CHD (step 3). An evaluation of the scientific evidence for each step leads us to conclude that dietary fats definitely influence the level of serum cholesterol, and that serum cholesterol is probably a cause of atherosclerosis and CHD. To determine the clinical implications, we examined the potential of various foods to keep cholesterol levels lower, as well as the projected magnitude of reduction in CHD risk. The likelihood of benefit varies among patients, ranging from uncertain or trivial (for those with lower serum cholesterol levels, those who are free of other risk factors and the elderly) to substantial (for patients with higher serum cholesterol levels, those who have other risk factors and those who are young). This analysis supports an individualized approach to clinical management; each decision to prescribe a fat-controlled diet should be a judgment that depends on art-the therapeutic philosophy of each clinician and the particular needs of each patient-as well as on science. The implication for public health policies is that they should promote rather than a uniform eating pattern for all Americans, a uniform environment that enhances individual choices. This should include efforts to educate the medical profession and the public, and more comprehensive and informative foodlabeling practices.

Adult↗
PubMed1981

Screening and diagnosis when within-individual observations are Markov-dependent.

The statistical model currently used for determining the amount of regression to the mean that will occur in a screening study includes an assumption that repeat observations within the same subject are mutually independent. This assumption has been used in the determination of the number of repeat observations within an individual that is required to reduce the amount of regression to the mean or the probability of misclassification to a given value. In this paper the model is extended to the case in which repeat observations within an individual are Markov-dependent. New expressions are given for the regression to the mean, based on the time delay between screening and re-examination, and on the use of an average of several measurements for both screening and re-examination. The extended model is used to describe the conditional distribution of the long-term mean of an individual, given several measurements, and this distribution is suggested as a diagnostic tool. A method is presented for estimation of the autocorrelation coefficient in very short time series observed in several individuals. The autocorrelation in diastolic blood pressure is estimated from a set of repeat observations, one day apart, on a group of subjects.

Blood Pressure↗
PubMed1980

Nitrogen and sodium balance and sympathetic-nervous-system activity in obese subjects treated with a low-calorie protein or mixed diet.

Seven obese subjects were placed on a 400-kcal protein diet and on an isocaloric mixed diet (50 per cent protein and 50 per cent carbohydrate), three to 5 1/2 weeks for each diet. Despite twofold to fivefold increases in ketone levels in the blood and urine with the protein diet, net nitrogen balance was no different from that with the mixed diet (-2.1 +/- 0.9 vs. -2.6 +/- 0.4 g per day; mean +/- S.E.M.). However, net sodium loss with the protein diet (-382 +/- 117 mmol) was significantly greater than with the mixed diet (-25 +/- 105 mmol; P less than 0.02). Furthermore, maximal orthostatic decreases in systolic blood pressure with the protein diet (-28 +/- 3 mm Hg) were greater than with the mixed diet (-18 +/- 3 mm Hg; P less than 0.02) and were accompanied by symptoms of orthostatic hypotension in all patients. The protein diet (but not the mixed diet) also resulted in a 40 per cent decline in basal plasma levels of norepinephrine (P less than 0.01) and a failure of plasma norepinephrine to rise after two minutes of standing. We conclude that as compared with mixed diets, hypocaloric protein diets offer no advantage with respect to nitrogen metabolism but result in greater sodium depletion, a decrease in sympathetic-nervous-system activity, and the development of orthostatic hypotension.

Adult↗
PubMed1979

HDL-cholesterol levels in the Multiple Risk Factor Intervention Trial (MRFIT) by the MRFIT Research Group 1,2.

Preliminary data from the Multiple Risk Factor Intervention Trial (MRFIT) have been examined for evidence that the program has an influence on plasma HDL-cholesterol. The overall mean level of this lipoprotein in the initial cohort of 1,084 men was not altered by two years of participation in this risk factor reduction project. However, changes did occur, both upwards and downwards, in some individuals. There were significant negative associations between change in HDL-cholesterol and changes in body mass, VLDL-cholesterol, LDL-cholesterol, and serum thiocyanate (a measure of cigarette smoking exposure); and there was a small positive association with change in reported alcohol intake. Multiple regression analysis revealed each of these associations to be independent of the others. The fat-controlled diet designed to lower total serum cholesterol did not decrease HDL-cholesterol levels. We conclude that conventional risk reduction programs are not likely to lower circulating HDL-cholesterol, and that program components such as weight reduction and smoking cessation may increase the levels.

Alcohol Drinking↗
PubMed1979

Influence of somatostatin on glucagon- and epinephrine-stimulated hepatic glucose output in the dog.

Glucose kinetics were measured using [3-3H]glucose in conscious dogs during the infusion of: 1) glucagon alone; 2) glucagon plus somatostatin with insulin replacement; 3) epinephrine alone; and 4) epinephrine plus somatostatin with insulin and glucagon replacement. Infusion of glucagon alone resulted in a 10-15 mg/dl rise in plasma glucose and a transient 45% rise in glucose production. When somatostatin and insulin were added, a four- to fivefold greater rise in plasma glucose and glucose production was observed. Glucagon levels were comparable to those achieved with infusion of glucagon alone, whereas peripheral insulin levels increased three- to fourfold above baseline, suggesting adequate replacement of preinfusion portal insulin levels. Infusion of epinephrine alone produced a 40% rise in plasma glucose and a 100% rise in glucose production. When somatostatin, insulin, and glucagon were added to epinephrine, the rise in glucose production was reduced in 65% despite replacement of glucagon levels and presumably mild portal insulin deficiency. These findings suggest that somatostatin: 1) potentiates the stimulatory effect of physiologic hyperglucagonemia on glucose production independent of insulin availability and 2) blunts the stimulatory effect of physiologic increments of epinephrine independent of glucagon availability.

Animals↗
PubMed1979

Influence of continuous physiologic hyperinsulinemia on glucose kinetics and counterregulatory hormones in normal and diabetic humans.

The effects of continuous infusions of insulin in physiologic doses on glucose kinetics and circulating counterregulatory hormones (epinephrine, norepinephrine, glucagon, cortisol, and growth hormone) were determined in normal subjects and diabetics. The normals received insulin at two dose levels (0.4 and 0.25 mU/kg per min) and the diabetics received the higher dose (0.4 mU/kg per min) only. In all three groups of studies, continuous infusion of insulin resulted in an initial decline in plasma glucose followed by stabilization after 60-180 min. In the normal subjects, with the higher insulin dose there was a fivefold rise in plasma insulin. Plasma glucose fell at a rate of 0.73+/-0.12 mg/min for 45 min and then stabilized at 55+/-3 mg/dl after 60 min. The initial decline in plasma glucose was a result of a rapid, 27% fall in glucose output and a 33% rise in glucose uptake. Subsequent stabilization was a result of a return of glucose output and uptake to basal levels. The rebound increment in glucose output was significant (P < 0.05) by 30 min after initiation of the insulin infusion and preceded, by 30-45 min, a significant rise in circulating counterregulatory hormones. With the lower insulin infusion dose, plasma insulin rose two- to threefold, plasma glucose initially fell at a rate of 0.37+/-0.04 mg/min for 75 min and stabilized at 67+/-3 mg/dl after 75 min. The changes in plasma glucose were entirely a result of a fall in glucose output and subsequent return to base line, whereas glucose uptake remained unchanged. Plasma levels of counterregulatory hormones showed no change from basal throughout the insulin infusion. In the diabetic group (plasma glucose levels 227+/-7 mg/dl in the basal state), the initial rate of decline in plasma glucose (1.01+/-0.15 mg/dl) and the plateau concentration of plasma glucose (59+/-5 mg/dl) were comparable to controls receiving the same insulin dose. However, the initial fall in plasma glucose was almost entirely a result of suppression of glucose output, which showed a twofold greater decline (60+/-6%) than in controls (27+/-5%, P <0.01) and remained suppressed throughout the insulin infusion. In contrast, the late stabilization in plasma glucose was a result of a fall in glucose uptake to values 50% below basal (P < 0.001) and 39% below that observed in controls at termination of the insulin infusion (P < 0.01). Plasma norepinephrine and glucagon failed to rise during the insulin infusion, whereas plasma epinephrine, cortisol, and growth hormone rose to values comparable to controls receiving the same insulin dose. It is concluded that (a) in normal and diabetic subjects, physiologic hyperinsulinemia results in an initial decline followed by stabilization of plasma glucose despite ongoing infusion of insulin; (b) in the normal subjects, a rebound increase in glucose output is the initial or principal mechanism counteracting the fall in plasma glucose and occurs (with an insulin dose of 0.25 mU/kg per min) in the absence of a rise in circulating counterregulatory hormones; (c) in diabetics, although the changes in plasma glucose are comparable to controls, the initial decline is a result of an exaggerated suppression of glucose output, whereas the stabilization of plasma glucose occurs primarily as a consequence of an exaggerated fall in glucose uptake; and (d) failure of plasma norepinephrine as well as glucagon to rise in the diabetics may contribute to the exaggerated suppression of glucose output.

Adult↗
PubMed1979

Necrolytic migratory erythema without glucagonoma.

Two patients with clinical and histologic findings consistent with necrolytic migratory erythema are presented. Unlike previously described patients with this disorder, neither patient had substantially elevated glucagon levels nor an associated pancreatic islet cell tumor. The cause of the skin disease in these patients remains unknown but may be related to the underlying small-bowel disorder present in both.

Adult↗
PubMed1978

Pathophysiology of diabetes mellitus.

Techniques have been developed for examining the binding of insulin to its target cells and for evaluating the in vivo action of insulin, rekindling interest in the possible role of insulin resistance in adult-onset diabetes. A host of new data have accumulated regarding the contribution of glucagon to the syndrome.

Amino Acids↗
PubMed1978

Effect of sequential infusions of glucagon and epinephrine on glucose turnover in the dog.

Conscious dogs were infused with 1) glucagon (3 ng/kg.min) alone for 120 min followed by glucagon plus epinephrine (0.1 microgram/kg.min) for 60 min and 2) epinephrine alone (150 min) followed by epinephrine plus glucagon for 90 min. Glucagon alone caused a 10--15 mg/dl rise in plasma glucose and a 45% increase in glucose production that returned to baseline by 75--120 min. After addition of epinephrine, glucose production rose again by 80%. Infusion of epinephrine alone resulted in unchanged plasma glucagon levels, a 60--70 mg/dl rise in plasma glucose, and an 80--100% rise in glucose production that returned to baseline by 60--120 min. When glucagon was added, glucose output promptly rose again by 85%. When glucagon was infused alone, there was a rise in glucose uptake, whereas, with epinephrine, glucose uptake failed to rise and glucose clearance fell by 35--50%. We conclude that 1) hepatic refractoriness to persistent elevations of glucagon or epinephrine is specific for the hormone infused; 2) epinephrine stimulates glucose production in the conscious dog in the absence of a rise in plasma glucagon; 3) the hyperglycemic response to glucagon or epinephrine is determined in part by accompanying changes in glucose utilization.

Animals↗
PubMed1977

Renal extraction of glucagon in rats with normal and reduced renal function.

To examine the role of the kidney in the mechanism of impaired metabolic clearance of glucagon in renal failure, the renal handling of endogenous pancreatic glucagon was studied in rats with normal renal function and rats with renal insufficiency produced by 70% surgical ablation. Mean +/- SE renal extraction of glucagon in animals with normal renal function was 39 +/- 5%. Urinary losses of glucagon accounted for less than 2% of renal extraction. In contrast, in the animals with renal insufficiency (glomerular filtration rate reduced to one-third of normal), arterial glucagon increased 40% and renal extraction and extraction rate per gram kidney weight of glucagon were negligible, despite filtered loads of 204 +/- 42 pg/min per g kidney wt. These findings indicate a major role of the kidney in the metabolic clearance of glucagon under normal conditions and suggest that during renal insufficiency elevated plasma levels of glucagon occur, at least in part, as a result of a decreased renal turnover of the hormone.

Animals↗
PubMed1977

Amino acid and protein metabolism in diabetes mellitus.

In normal man, the fasting state is characterized by release of alanine and glutamine from muscle and in situ muscle catabolism of branched chain amino acids (lecucine, isoleucine, and valine). The alanine released by muscle is utilized by the liver for gluconeogenesis. Muscle nitrogen repletion occurs during protein feeding primarily by means of selective hepatic escape and muscle uptake of branched chain amino acids in ingested protein. In the diabetic, amino acid catabolism is exaggerated in the fasting state as reflected by increased uptake of alanine by the liver for gluconeogenesis and accelerated branched chain amino acid catabolism in muscle. After protein feeding, uptake of branched chain amino acids by muscle is reduced and these amino acids accumulate in increased amounts in arterial blood. Protein feeding also exaggerates the hyperglycemia of diabetes by causing an increase in hepatic glucose production. Diabetes is thus characterized by accelerated protein catabolism during fasting as well as diminished nitrogen repletion and hyperglycemia after protein feeding. The hyperketonemia of diabetes may however, have a restraining influence on protein catabolism thereby reducing alanine availability for gluconeogenesis.

Alanine↗
PubMed1976

Evanescent effects of hypo- and hyperglucagonemia on blood glucose homeostasis.

Hypoglucagonemia (induced by somatostatin) and hyperglucagonemia (induced by infusion of physiologic amounts of glucagon) have only evanescent effects on blood glucose regulation. Despite on-going glucagon suppression by somatostatin, fasting hyperglycemia develops within 4-6 hr of insulin suppression, indicating that (1) basal glucagon secretion is not essential for the development of the diabetic state; and (2) insulin-deficiency (rather than altered glucagon secretion) is the dominant long-term factor determining glucose homeostasis in the diabetic. With respect to hyperglucagonemia, only a transient increase in splanchnic glucose output is observed in normal and diabetic subjects in response to physiologic increments in this hormone. The exaggerated hyperglycemic effect of glucagon observed in diabetics1 is thus a consequence of the failure to metabolize the glucose traniently released into the systemic circulation in response to the glucagon rather than a result of persistent stimulation of hepatic glucose production. These observations thus further underscore the essentiality of insulin deficiency in the diabetogenic action of glucagon.

Animals↗
PubMed1976

Insulin, glucagon, and somatostatin in normal physiology and diabetes mellitus.

Studies are reviewed in which the roles of insulin and glucagon in normal physiology and in diabetes are examined. In normal man, glucose ingestion is accompanied by a rise in insulin and fall in glucagon and is primarily disposed of in the liver, an organ sensitive to both hormones. However, infusions of glucagon in physiologic amounts indicate that insulin secretion rather than glucagon inhibition is the primary factor determining glucose disposal. Furthermore, minor elevations in blood glucose elicit increments in insulin concentration and inhibition of hepatic glucose output in the absence of changes in plasma glucagon. The primary physiologic role of glucagon is to prevent the hypoglycemia that would otherwise accompany noncarbohydrate (protein)-mediated insulin secretion. In diabetic as well as normal patients the stimulatory effect of glucagon on hepatic glucose production is evanescent. Increases in glucagon or changes in the I/G ratio can bring about deterioration in glucose tolerance or in diabetic control only so long as absolute insulin deficiency is present or pharmacologic elevations in glucagon are produced. After somatostatin administration, prolonged hypoinsulinemia in normal subjects is observed to result in fasting hyperglycemia in the absence of basal glucagon secretion. In diabetic patients the improvement in postprandial hyperglycemia produced by somatostatin can be accounted for by its inhibitory action on carbohydrate absorption in the gastrointestinal tract. It is concluded that insulin deficiency is the primary pathophysiologic disturbance in diabetes. While glocagon may worsen the consequences of insulin lack, it is neither sufficient nor necessary for the development of diabetes.

Carbohydrate Metabolism↗