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Biomedical subjects

R Sherwin

Publications and source records attributed to R Sherwin.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effect of acute and chronic caffeine use on the cerebrovascular, cardiovascular and hormonal responses to orthostasis in healthy volunteers.

1. The effects of acute and chronic caffeine ingestion on supine- and tilt- (60 min at 70 degrees) induced changes in middle cerebral artery velocity (Vmca), heart rate, blood pressure and counter-regulatory hormone levels (catecholamines, growth hormone and cortisol) were studied in nine healthy volunteers. A double-blind, placebo-controlled design was used to study acute effects followed by an open study after 6 days of chronic caffeine use. 2. In the supine position, acute ingestion of caffeine (250 mg) was associated with a fall in Vmca [-11 cm/s, point estimate of difference versus placebo (95% confidence interval: -17, -6) cm/s, P < 0.001] and a rise in mean arterial pressure [+4 (1, 6) mmHg, P < 0.01] and plasma adrenaline levels [+138 (53, 223) pmol/l, P < 0.01]. After chronic caffeine use, the pressor and adrenaline responses, but not the drop in Vmca, were significantly attenuated. 3. On tilting to 70 degrees the fall in Vmca was greater with placebo than after acute caffeine ingestion [-10 (-14, -15) cm/s, P < 0.01], whereas increments (above supine values) in heart rate, mean arterial pressure and hormone levels were unchanged by caffeine. In contrast, the adrenaline [+126 (29, 282) pmol/l, P < 0.01] and noradrenaline [+0.6, 0.9) nmol/l, P < 0.05] responses to tilting were augmented after acute caffeine ingestion. Chronic caffeine supplementation did not alter the fall in Vmca associated with tilting, but significantly attenuated the adrenaline response (P < 0.01 compared with the acute study). 4. Acute caffeine ingestion and orthostasis are both associated with a reduction in Vmca and a rise in mean arterial pressure and adrenaline levels. The acute effects of caffeine on mean arterial pressure and adrenaline but not on Vmca are lost with sustained caffeine intake. These results suggest dissociation between the development of central and peripheral tolerance after chronic caffeine use.

Adult↗
PubMed1994

Correlates of bone mineral density in the postmenopausal estrogen/progestin interventions trial.

We assessed the cross-sectional relationship of age, menopausal years, body mass, previous estrogen use, and ethnic background to bone mineral status in a sample of 875 healthy postmenopausal women at the time they were recruited from the community to participate in a multicenter clinical trial. The women were 1-10 years postmenopause, 45-64 years of age, and had not received estrogen replacement therapy within 3 months of enrollment. Of the participants, 89% were white, 69% had a spontaneous menopause, and 53% had a history of previous estrogen replacement therapy. Bone mineral density (BMD) of the lumbar spine (L2-4) and proximal femur was measured by dual-energy x-ray absorptiometry. Results were consistent with a significant negative linear regression of BMD on age or years from menopause. Body mass index (BMI) correlated significantly with BMD at all sites (L 2-4 r = 0.28; femoral neck r = 0.34, p < 0.0001). BMD adjusted for age and BMI were higher at both sites in women who had taken estrogen versus those who had not (L2-4 0.976 +/- 0.009 versus 0.932 +/- 0.01; femoral neck 0.740 +/- 0.006 versus 0.708 +/- 0.008, p < 0.05). Adjusted BMD also increased with duration of ERT. Parity was negatively associated with L2-4 BMD (p = 0.03) but did not correlate significantly with BMD at the femoral neck. Black women had the highest L2-4 BMD, and Hispanic women had the highest femoral neck BMD, even when results were adjusted for age and BMI. When data were corrected for differences in bone size, these interethnic differences were no longer significant. We conclude that increased body mass is positively correlated with BMD, and this may confer a degree of skeletal protection to heavier postmenopausal women. Exposure for 5 years to exogenous estrogen is associated with significantly increased age- and BMI-adjusted BMD.

Absorptiometry, Photon↗
PubMed1993

Reproductive correlates of bone mass in elderly women. Study of Osteoporotic Fractures Research Group.

Results from previous studies of reproductive factors and bone density have been conflicting; some demonstrate a beneficial effect, but others show a detrimental effect on bone density. The present study investigates the association of parity, lactation, and menstruation with radial bone density in 2230 white women, 65 years of age and older. Bone density was assessed by single-photon absorptiometry. Linear multiple regression was utilized to determine if reproductive factors were associated with radial bone density. The number of births, duration of menstrual bleeding, age at menarche, and years menstruating were significant independent predictors of postmenopausal bone density of the radius. A 1.4% increase in distal radius bone density was observed with each additional birth. Women who began menstruation at age 9 had 6.3% higher bone density than women who began at age 16. Women who menstruated for 3 days during each menstrual cycle had 2.8% less distal radius bone density than women who bled for 7 days. Each decade of menstruation was associated with a 2% greater distal radius bone density. No difference in bone density was demonstrated for women who breast-fed and women who did not. Length of the menstrual cycle, amount of menstrual flow, and irregularity of the menstrual cycle were not significantly associated with radial bone mineral density. In conclusion, pregnancy and menstruation are associated with postmenopausal bone density of the radius.

Abortion, Induced↗
PubMed1992

Influence of basal androgen levels in euandrogenic women on glucose homeostasis.

OBJECTIVE: To evaluate possible relationships between insulin action and the normal variations of serum androgens in euandrogenic women. DESIGN: Prospective evaluation of insulin action in normal nonobese women using hyperglycemic and euglycemic hyperinsulinemic clamp techniques, correlating insulin action to serum testosterone (T), free T, androstenedione (A), and dehydroepiandrosterone sulfate (DHEAS). Statistical analysis used Spearman's rank correlation. SETTING: Yale University Clinical Research Center. PARTICIPANTS: Nonobese females with normal oral glucose tolerance tests, on no medications known to affect glucose metabolism, having the following range of serum androgen levels: T, 0.69 to 3.12 nmol/L; free T, 0.17 to 1.25 nmol/L; A, 2.48 to 11.31 nmol/L; DHEAS, 0.68 to 10.61 mumol/L. Total number of patients studied: hyperglycemic clamps, n = 58; euglycemic hyperinsulinemic clamps, n = 43. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Pancreatic insulin secretion in response to hyperglycemia and insulin action as assessed by insulin-mediated glucose utilization using the euglycemic, hyperinsulinemic clamp technique. RESULTS: We identified no significant correlation between serum androgens and either glucose uptake or insulin-mediated glucose utilization. Glucose-stimulated insulin release was negatively correlated with serum T and free T throughout the normal range of these hormones. CONCLUSION: We conclude that, within the normal range, variations of serum androgens are not correlated with changes in the response to insulin. It seems unlikely, therefore, that modest increases of serum androgens within the normal range are responsible for inducing insulin resistance.

Androgens↗
PubMed1992

Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group.

BACKGROUND: With increased efforts to lower serum cholesterol levels, it is important to quantify associations between serum cholesterol level and causes of death other than coronary heart disease, for which an etiologic relationship has been established. METHODS: For an average of 12 years, 350,977 men aged 35 to 57 years who had been screened for the Multiple Risk Factor Intervention Trial were followed up following a single standardized measurement of serum cholesterol level and other coronary heart disease risk factors; 21,499 deaths were identified. RESULTS: A strong, positive, graded relationship was evident between serum cholesterol level measured at initial screening and death from coronary heart disease. This relationship persisted over the 12-year follow-up period. No association was noted between serum cholesterol level and stroke. The absence of an association overall was due to different relationships of serum cholesterol level with intracranial hemorrhage and nonhemorrhagic stroke. For the latter, a positive, graded association with serum cholesterol level was evident. For intracranial hemorrhage, cholesterol levels less than 4.14 mmol/L (less than 160 mg/dL) were associated with a twofold increase in risk. A serum cholesterol level less than 4.14 mmol/L (less than 160 mg/dL) was also associated with a significantly increased risk of death from cancer of the liver and pancreas; digestive diseases, particularly hepatic cirrhosis; suicide; and alcohol dependence syndrome. In addition, significant inverse graded associations were found between serum cholesterol level and cancers of the lung, lymphatic, and hematopoietic systems, and chronic obstructive pulmonary disease. No significant associations were found of serum cholesterol level with death from colon cancer, with accidental deaths, or with homicides. Overall, the inverse association between serum cholesterol level and most cancers weakened with increasing follow-up but did not disappear. The association between cholesterol level and death due to cancer of the lung and liver, chronic obstructive pulmonary disease, cirrhosis, and suicide weakened little over follow-up. CONCLUSIONS: The association of serum cholesterol with specific causes of death varies in direction, strength, gradation, and persistence. Further research on the determinants of low serum cholesterol level in populations and long-term follow-up of participants in clinical trials are necessary to assess whether inverse associations with noncardiovascular disease causes of death are consequences of noncardiovascular disease, whether serum cholesterol level and noncardiovascular disease are both consequences of other factors, or whether these associations are causal.

Adult↗
PubMed1987

Bias and precision of cholesterol analysis by physician's office analyzers.

We studied the bias and precision of serum cholesterol analysis by physician's office analyzers. Total imprecision (CV range, %) for analysis of serum pools was: Abbott Vision 1.5%-1.9%; Ames Seralyzer 3.9%-4.5%; BMD Reflotron 2.3%-3.8%; Chrometrics Cholesterol Test System 2.3%-2.8%; Kodak DT-60 1.6%-2.2%. The Ames Seralyzer exhibited an excessive between-run component of variation. We collected, from 109 volunteers, samples of venous serum, heparin-treated whole blood, heparin-treated plasma, and fingerstick whole blood, and analyzed each type (where possible) with each system; serum was also analyzed in duplicate (by a proposed Reference Method) at the Centers for Disease Control. For assays with serum, the BMD Reflotron and Kodak DT-60 exhibited negative bias. All systems gave lower results for plasma and whole blood than for serum. All systems except the Kodak DT-60 were less precise for analysis of patients' sera than for analysis of serum pools; between-specimen variables may influence the results of these systems.

Cholesterol↗
PubMed1984

Beta-adrenergic blockade is more effective in suppressing adrenaline-induced glucose production in Type 1 (insulin-dependent) diabetes.

To examine whether diabetes affects the ability of beta-blockade to suppress adrenaline-stimulated hepatic glucose production, we infused adrenaline with and without propranolol into normal subjects and diabetic patients receiving a constant insulin infusion in basal amounts. In normal subjects, propranolol did not block the transient 50%-60% rise in glucose production during adrenaline infusion. In contrast, propranolol virtually abolished adrenaline-induced hyperglycaemia and glucose production was virtually abolished by propranolol in the diabetic patients, even though they demonstrated an exaggerated response to adrenaline alone (persistent increase in glucose production of 50%-90% above baseline). When insulin was infused together with adrenaline and propranolol in normal subjects in doses exceeding those given to the diabetics (plasma insulin rose threefold), the rise in glucose production was still threefold greater than in the diabetic patients (p less than 0.02). We conclude that beta-blockade is more effective in suppressing the hepatic response to adrenaline in diabetics than in normal subjects. Our data may explain why diabetic subjects are more vulnerable to hypoglycaemia during treatment with propranolol.

Adolescent↗
PubMed1984

Sudden death in men with increased risk of myocardial infarction. The MRFIT Programme.

The Multiple Risk Factor Intervention Trial (MRFIT) was a randomised clinical trial of the preventability of fatal first heart attacks among middle-aged men at high risk of coronary heart disease (CHD). After screening 361,662 men aged 35 to 57 years, 12,866 men currently free of CHD at the upper end of the risk spectrum on the basis of their levels of serum cholesterol, diastolic blood pressure and cigarette smoking were randomised either to 'special intervention' (SI) or to 'usual care' (UC). Those SI men with a sustained diastolic blood pressure greater than or equal to 90mm Hg (following attempted weight loss, if indicated) received pharmacological treatment in the form of a protocol of 'stepped care'. UC men were referred to their usual source of medical care. At the termination of the study - after 6 to 8 years of intervention - no significant differences in overall deaths from CHD or from all causes were observed between the SI and UC groups. However, among the subgroup of individuals who had both a diastolic blood pressure greater than or equal to 90mm Hg and abnormalities of the resting electrocardiogram at baseline there was an excess of deaths from CHD in the SI group compared with the UC group (36 vs 21), and most of the excess deaths were sudden (20 vs 8).

Adult↗
PubMed1981

The Bacon Chow study: maternal nutrition supplementation and birth weight of offspring.

This study is a randomized controlled double-blind trial on the effects of nutrition supplement of pregnant and lactating women on their offspring. The study was conducted by the late Dr. Bacon Chow in 14 villages in Sui-Lin township, a farming area about 180 miles from Taipei, Taiwan. Two hundred ninety-four women were randomly assigned to one of two treatment groups. The daily supplement for one group provided 800 kcal and 40 g of protein/day; for the other group it only provided 80 kcal/day. Supplementation began after 3 wk of the delivery of a first study infant, continued throughout lactation, and through the pregnancy and lactation of a second study infant. Between group comparisons on the birth weight, number of low birth weight infants, or incidence of fetal deaths showed no statistically significant findings. However, the birth weight of the second study infant was statistically different and higher than that of the first study infant in the high supplement group. Moreover, in the low supplement group there was a correlation of 0.22 (p = 0.06) between the change scores for birth weight from the first to the second study infant and the quantity of supplements consumed during the last trimester of pregnancy. There was also in this same group a significant slope in a linear regression of birth weight on total daily caloric intake during the 3rd trimester of pregnancy for the male second study infants. These findings are partly in agreement with findings from three other large supplementation studies in Colombia, Guatemala, and New York. In this study the findings indicate that caloric supplementation does result in a small yet statistically meaningful increment in birth weight within a population which is not nutritionally at risk.

Birth Weight↗