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Biomedical subjects

J W Rowe

Publications and source records attributed to J W Rowe.

At least 91 records · Page 5Linked to original sources
PubMed1985

Acanthosis nigricans in obese women with hyperandrogenism. Characterization of an insulin-resistant state distinct from the type A and B syndromes.

Acanthosis nigricans and hyperandrogenism are commonly found in patients with extreme target cell resistance to insulin, as in the type A and B syndromes of insulin resistance. However, the significance of concurrent acanthosis nigricans and hyperandrogenism in other clinical settings is not clear. We observed acanthosis nigricans to be present in 5% (15 of 300) of patients being evaluated for hyperandrogenism, and carried out studies of insulin binding and action in a group (7) of these women. Although none were diabetic, all were insulin resistant as assessed by hyperinsulinemia when fasting and after oral glucose administration. All patients were obese (mean IBW, 169%). However, when matched to hyperandrogenized women of similar body weight, patients with acanthosis nigricans were clearly more hyperinsulinemic. Insulin binding to monocytes and red cells was decreased in patients with acanthosis, and the extent of decrease was predicted by the fasting insulin level. There was also marked resistance to exogenous insulin during euglycemic insulin clamp studies in the two patients so tested. Anti-insulin receptor antibodies were not detectable, ruling out the type B syndrome. Unlike the type A syndrome, insulin binding to monocytes of these patients increased after acute (2/2) and chronic (1/1) caloric restriction. In the latter patient, acanthosis nigricans remitted as insulin resistance and the insulin binding defect improved. We conclude that acanthosis nigricans is present in as many as 5% of women with clinically significant hyperandrogenism. These women, although not diabetic, have fairly marked insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acanthosis Nigricans↗
PubMed1985

Syncope in an elderly, institutionalised population: prevalence, incidence, and associated risk.

Although syncope is common in the elderly, little is known of its epidemiology and prognosis. A retrospective analysis of syncope in 711 very old (mean age 87 years) institutionalised patients revealed a 10 year prevalence of 23 per cent and one year incidence of 7 per cent. A two-year prospective follow-up of this population revealed a yearly incidence of 6 per cent and recurrence rate of 30 per cent. Of 67 patients who developed syncope during follow-up, a cause was established in 46; 14 (21 per cent) had cardiac and 32 (48 per cent) had non-cardiac aetiologies. Twenty-one cases (31 per cent) remained unexplained. Patients who developed syncope were initially more functionally disabled (p = 0.003) and subsequently changed function more frequently (p = 0.03) than those without the development of syncope, but two year rates of hospitalisation and death were not different between the two groups. Life-table survival analysis showed no difference in the mortality of subgroups with cardiac, non-cardiac, and unknown aetiologies of syncope. Syncope is common in multiply impaired elders and is likely a manifestation of co-morbid disease rather than an independent contributor to mortality.

Aged↗
PubMed1984

Whole body insulin resistance in myotonic dystrophy.

To quantitate the degree of whole body insulin resistance in patients with myotonic dystrophy, three separate euglycemic insulin infusions were given to ambulatory patients and the results compared with findings in normal control subjects. Basal glucose and insulin values were similar for the two groups. There was no significant difference in insulin clearance rates between normal subjects and patients at the three insulin infusion rates used. A highly significant decrease in the whole body glucose disposal rate was seen during the 120-minute insulin infusion in the patients with myotonic dystrophy compared with normal subjects at all three insulin dosages (20 mU/m2/min: 2.18 +/- 0.29 [standard error] versus 5.49 +/- 1.72 mg/kg/min, p less than 0.0001; 80 mU/m2/min: 4.16 +/- 0.34 versus 8.49 +/- 0.45 mg/kg/min, p less than 0.0001; 200 mU/m2/min: 5.22 +/- 0.53 versus 10.06 +/- 0.50 mg/kg/min, p less than 0.0001). These marked decreases in glucose disposal rates for the patients were adjusted in accordance with their 24-hour urinary creatinine excretion rate to correct for the difference in muscle mass between patients and controls. This adjusted glucose disposal rate was 15 to 25% lower (p less than 0.02) in the patients with myotonic dystrophy at insulin infusion rates of 20 and 80 mU. During the 200 mU insulin infusions, the adjusted glucose disposal rate remained lower than that in normal subjects but was of borderline statistical significance. These studies suggest that moderately severe whole body insulin resistance is responsible for the postprandial hyperinsulinemia typically seen in patients with myotonic dystrophy.

Adult↗
PubMed1984

Effect of exogenous vasopressin on vasopressin release.

To characterize the influence of extracellular volume status on vasopressin pharmacokinetics, eleven young (aged 19-31 yr) and four old (aged 62-80 yr) subjects received bolus injections of 1 mU/kg Pitressin or synthetic arginine vasopressin following 6 days of sodium depletion (10 meq Na/day) or sodium loading (250 meq Na/day). In six young subjects the rapid decline in plasma vasopressin (pAVP) following the initial peak was interrupted by a second peak 5-30 pg/ml in magnitude 7.5-20 min after injection. In four of these subjects the second peak was larger following sodium depletion as compared with sodium loading. In the elderly a small (4 pg/ml) second peak was present in one sodium-depleted subject. Of five sodium-depleted subjects with central diabetes insipidus, none showed a secondary rise in pAVP. These results indicate that exogenous vasopressin may stimulate the release of endogenous AVP, an effect that appears to be enhanced by sodium depletion and is virtually absent in the elderly. There was no effect of age, volume status, or diabetes insipidus on AVP pharmacokinetics.

Adult↗
PubMed1983

Postprandial reduction in blood pressure in the elderly.

We evaluated the effects of a meal on systolic blood pressure and heart rate in elderly institutionalized subjects (mean age +/- S.E.M., 87 +/- 1) with and without histories of syncope and in young normal subjects. Pulse and blood pressure were measured before the test meal and at intervals for up to 60 minutes afterward. By 35 minutes mean systolic blood pressure had declined a maximum of 25 +/- 5 mm Hg in 10 elderly subjects with syncope and 24 +/- 9 mm Hg in 10 elderly subjects without syncope (P less than 0.03); the level then stabilized without further change until 60 minutes. There were no changes in blood pressure in 11 young subjects or in elderly subjects not given a meal. The postprandial change in systolic pressure was not related to medications or diagnoses. Compensatory cardioacceleration was minimal in the elderly, suggesting impaired baroreflexes. Our observations show that postprandial reductions in blood pressure may predispose the elderly to symptomatic hypotension.

Adolescent↗
PubMed1983

Post-cough heart rate response: influence of age, sex, and basal blood pressure.

Although the chronotropic response to cough may provide an index of the capacity for cardioacceleration, how the heart rate change may be influenced by age is not established. In 213 healthy men and women aged 20-90 yr we measured the heart rate response following three forceful coughs performed over a 3-s period. Resting heart rate was not age related. Increasing age was associated with a linear reduction in cough-induced maximum rise in heart rate (r = -0.58, P less than 0.0001) and a prolongation of the time to peak heart rate (P less than 0.001). The responses were not different between women and men. Multiple regression analysis performed on age and systolic, diastolic, and mean basal arterial pressure measurements revealed that age was the sole variable that correlated significantly with peak heart rate response. Thus advancing age is associated with a decline in the amplitude and rapidity of the chronotropic response to cough. These age-related changes are independent of the basal arterial pressure and may contribute to the decreased cardiovascular homeostatic response to stress, such as upright posture or volume depletion, which is commonly observed in the elderly.

Adult↗
PubMed1983

Characterization of the insulin resistance of aging.

To clarify the nature of the insulin resistance of aging we studied the dose response for insulin-induced glucose disposal and the binding of insulin to circulating monocytes in healthy young and old men. A total of 49 two-hour euglycemic insulin clamp studies were performed in 17 young and 10 old healthy nonobese subjects. While the old group had lower estimates of lean body mass and greater estimates of total body fat than the young group, these differences did not exceed 5% and did not reach statistical significance. Insulin was infused at 20 mU/m2 per min (young = 8, old = 5); 80 mU/m2 per min (young = 13, old = 9); 200 mU/m2 per min (young = 9, old = 5). Increasing levels of hyperinsulinemia were associated with dose-dependent increases in steady-state glucose infusion rates in young and old. The maximal glucose infusion rates (milligrams per kilogram body weight per minute) were the same for young and old. However, the dose-response curve was shifted to the right in the old subjects. In the four individuals in each age group in whom studies were performed at each dose level, the Km was 54 +/- 14 microU/ml in the young and 113 +/- 11 microU/ml in the old (P less than 0.02). Correction of glucose infusion rate for lean body mass had no effect on comparisons between age groups. These data indicate an age-associated decline in sensitivity of peripheral tissues to insulin without a change in maximal tissue responsiveness. Studies of insulin binding with 14 young and 9 old subjects indicated no effect of age on the insulin binding to receptors on circulating monocytes (young = 5.25 +/- 0.35; old = 6.22 +/- 0.53% of 125I-insulin bound/10(7) cells). These studies suggest that aging may be associated with a postreceptor defect in insulin action manifested by decreased whole-body tissue sensitivity to insulin without a change in tissue responsiveness.

Adult↗
PubMed1982

Effect of age on insulin stimulation of sympathetic nervous system activity in man.

Previous studies have shown that oral glucose increases plasma norepinephrine (NE) in man, an effect which is more pronounced in the elderly. Recently we have shown that hyperinsulinemia results in a dose-dependent increase in sympathetic nervous system (SNS) activity in young men independent of changes in blood glucose. We now report studies of the influence of hyperinsulinemia on SNS activity in healthy elderly. Euglycemic glucose clamp studies were performed at 2 insulin infusion rates, 2 mU/kg/min (young 22-37 yr, n = 7; old 63-77 yr, n = 9) and 5 mU/kg/min (young 22-36 yr, n = 7; old 64-75 yr, n = 5) nonobese men. Control studies were performed in 5 young and 3 old subjects. In control studies there were no significant changes in NE or cardiovascular measures in either group. Insulin infusion at 2 mU/kg/min in young subjects were associated with significant increases in NE, (p less than 0.001) pulse (p less than 0.05), pulse pressure (p less than 0.005) and double product (pulse x systolic pressure) (p less than 0.01). In contrast 2 mU/kg/min insulin infusion in the elderly did not result in an increase in NE, and cardiovascular changes were limited to an increase in pulse pressure (p less than 0.01). The changes in NE at this insulin infusion dose were greater in the young than in the old (p less than 0.005). Insulin infusion at 5 mU/kg/min in young subjects were associated with significant increases in NE, (p less than 0.001) mean arterial blood pressure (MABP) (p less than 0.001), pulse pressure (p less than 0.001) and double product (p less than 0.001). In contrast 5 mU/kg/min insulin infusion in the elderly did not result in an increase in NE, and cardiovascular changes were limited to a decrease in MABP (p less than 0.001) only. The change in NE and MABP at this insulin infusion dose were greater in the young than in the old (p less than 0.001) for each). In the young group the increases in NE were greater during the 2 mU/kg/min studies than in the control studies (p less than 0.001) and the increases in NE during the 5 mU/kg/min studies were greater than during the 2 mU/kg/min studies (p less than 0.001). In the old group there were no differences in NE or cardiovascular measures between the control, 2 mU or 5 mU insulin infusions. These studies indicate diminished insulin-induced SNS activation in the elderly. The disparity in the elderly between the enhanced SNS response to oral glucose and the blunted response to intravenous insulin and glucose suggests that splanchnic factors may mediate the SNS activation after oral glucose.

Adult↗
PubMed1982

Vascular smooth muscle cell growth kinetics in vivo in aged rats.

Age is a risk factor in the development of atherosclerosis. In this study we investigated the hypothesis that proliferation of vascular smooth muscle cells (SMCs), an integral part of atherosclerotic plaque formation, changes with age. SMC growth kinetics of old rats (21-24 months) were compared to those of young adult rats (3-4 months). Rat aortas were denuded of their endothelium and the animals were killed after [3H]thymidine and Evans blue injections at 0-28 days after denudation. Incorporation of [3H]thymidine into SMC peaked in the young animals by day 2, whereas the older animals responded to endothelial removal with greater incorporation at day 2 and a more sustained rate of incorporation peaking at day 4. The [3H]thymidine incorporation curves decreased sharply from their peaks at 2 and 4 days, respectively, and paralleled each other after day 7. [3H]Thymidine uptake reflected the subsequent SMC intimal growth as measured morphometrically, with old animals showing greater numbers of intimal SMC than did the younger animals. The difference in response of SMC to injury with age suggests that aging produces a change in the vascular SMC that enhances proliferation. This change in response implies that the more pronounced atherosclerotic plaque growth seen with aging may be a result of an age-related increase in response to injury rather than merely the accumulation of time-related intimal change.

Aging↗
PubMed1982

Potassium homeostasis during hyperinsulinemia: effect of insulin level, beta-blockade, and age.

The euglycemic glucose clamp technique was used to evaluate the influence of level and duration of hyperinsulinemia, presence of beta-adrenergic blockade, and subject age on insulin-mediated changes in plasma potassium. In 16 young subjects, 2-h insulin infusions at 20 (n = 6), 80 (n = 13), and 200 (n = 8) mU.m-2.min-1 resulted in dose-dependent declines in plasma potassium (P less than 0.001 at all doses) during the 1st h. During the 2nd h plasma potassium declined during the 20 mU.m-2.m-1 infusions, was stable during the 80 mU.m-2.m-1 infusions, and rose slightly during the 200 mU.m-2.min-1 infusions. There was a significant reciprocal relationship between the changes in plasma potassium during the 1st and 2nd h of study (r = 0.99, P less than 0.01). During 4-h infusions (80 mU.m-2.min-1, n = 6) plasma potassium declined during the first 90 min (p less than 0.001) and rose thereafter until the end of the infusion (P less than 0.05). Studies with and without propranolol infusion at two insulin dose levels (20 and 80 mU.m-2.min-1) in six young subjects showed no effect of beta-blockade, and studies at three insulin dose levels [20 (n = 5), 80 (n = 6), and 200 (n = 6) mU.m-2.min-1 in 10 older males (63-77 yr] showed no effect of age on the changes in plasma potassium during hyperinsulinemia. These results suggest the presence of a regulatory mechanism influencing insulin-mediated alterations in plasma potassium. This mechanism appears uninfluenced by age or beta-adrenergic blockade.

Adrenergic beta-Antagonists↗
PubMed1982

Age-related failure of volume-pressure-mediated vasopressin release.

Osmoreceptor sensitivity, as estimated by the plasma vasopressin (AVP) response to hypertonic saline infusion, increases with age. We studied volume-pressure sensitivity, as estimated by the plasma AVP response to orthostasis, in healthy young (19-31 yr old; n = 12) and old (62-80 yr old; n = 15) subjects. After remaining recumbent overnight (minimum of 8 h), subjects stood quietly for 8 min. Cardiovascular changes on standing were not influenced by age. The peak plasma AVP response was greater in the young than in the old (P = 0.02, by rank sum test). When categorized as responders (peak AVP response, greater than or equal to 3 pg/ml) or nonresponders (peak response, less than 3 pg/ml), the young group included 11 responders and 1 nonresponder, while the old group included 8 responders and 7 nonresponders (P = 0.03, by Fisher exact test). There was no difference in the marked increase in plasma norepinephrine on standing between old responders (n = 6) and old nonresponders (n = 4). These studies indicate that failure to release AVP in response to orthostasis is more common in the elderly than in the young. The intact norepinephrine response to orthostatis in the elderly, regardless of the AVP response, suggests that the age-related defect is distal to the vasomotor center in the afferent limb of the baroreceptor reflex arc. Insensitivity to the volume and pressure changes accompanying hypertonic saline infusion may contribute to the previously noted augmented AVP response of the elderly to hyperosmolality.

Adult↗
PubMed1982

Influence of age on clearance of insulin in man.

With advancing age, glucose-induced insulin release is decreased in vitro, yet circulating insulin levels after glucose challenge are not decreased in the elderly. Age-related changes in insulin clearance may contribute to this discrepancy. We employed the 2-h euglycemic clamp technique to examine insulin clearance (C1) during steady-state insulin infusions (N = 53) at rates of 20, 80, and 200 mU/m2/min in healthy young (N = 16, age range 22-37 yr, relative weight 1.07 +/- 0.03) and old (N = 10, age range 63-77 yr, relative weight 1.14 +/- 0.03) men. Steady-state insulin levels were statistically significantly higher (P less than 0.01) in the elderly at each infusion rate. C1 was 40% lower (p less than 0.01) in the infusion rate. There was no effect of increasing relative weight on C1 within age groups. Within each age group, C1 was similar in insulin infusion rates of 20 and 80 mU/m2/min (young P less than 0.05, old P less than 0.001), implying a saturable system for insulin clearance. Alterations in C1 contribute to changes in insulin levels with age and may reconcile the discrepancy between in vivo and in vitro studies of glucose-induced insulin release. These results indicate the value of evaluating C1 as one determinant of circulating insulin level in states of abnormal insulin physiology.

Adult↗
PubMed1982

Impaired in vivo insulin clearance in patients with severe target-cell resistance to insulin.

The concentration of insulin in plasma is determined by both its rate of secretion and its rate of clearance from the plasma compartment. The effect of marked insulin resistance on insulin clearance in vivo has not been determined in man. We have employed the euglycemic insulin clamp technique to measure insulin sensitivity and insulin clearance in 16 control subjects and in 4 subjects with marked target-cell resistance to insulin. Two insulin-resistant patients had reduced receptor concentration on peripheral mononuclear cells, and two patients had normal receptor number and affinity. During 80-mU/m2/min insulin clamp studies, the clearance rate in each insulin-resistant patient was lower than that in any controls; the mean insulin clearance rate was 511 +/- 74 ml/m2/mon in control subjects and 205 ml/m2/min (P less than 0.001) in insulin-resistant patients. These findings demonstrate an association between marked target-cell resistance to insulin and impaired in vivo insulin clearance, and suggest an important role for receptor-mediated pathways in insulin clearance in vivo.

Adult↗
PubMed1981

Cross-sectional and longitudinal changes in the erythrocyte sedimentation rate in men.

The erythrocyte sedimentation rate (ESR) was determined on 1480 initially "healthy" male participants of the Normative Aging study on three successive examinations over a ten year period. Cross-sectional analysis revealed a significant correlation between age and ESR (r = 0.20, p less than 0.001) with generally higher ESR values in older individuals. Longitudinal analysis showed significant increases in ESR among "healthy" subjects who continued to pass our criteria for good health over a ten year period (p less than 0.001) and among "excluded" subjects who did not pass these criteria (p less than 0.001). Longistic regression analysis indicated that the ESR was significantly related to risk of death among subjects less than 45 years of age (p = 0.04) but not among subjects 45 + years (p = 0.39).

Adult↗
PubMed1980

Clinical and histological skin changes in chronic renal failure: evidence for a dialysis-resistant, transplant-responsive microangiopathy.

The relation between chronic renal failure and the clinical and histological findings in normal-looking skin was studied in twenty-seven patients with minimum to marked rises of serum creatinine; eleven of these were on maintenance haemodialysis, and three were successful renal transplant recipients. Clinical findings, including pruritus and xerosis which affected 48% and 60%, respectively, of the patients overall, correlated strongly with severity of renal failure. Histological examination revealed endothelial cell activation and/or necrosis, basement membrane zone thickening, and reduplication of the basal lamina involving both venules and arterioles in all specimens. The microangiopathy was severe in 18 of 24 (75%) of the uraemic specimens, but severity correlated poorly with serum creatinine level, haemodialysis status, or known duration of renal failure, except that it was less severe in the first 2 years (p < 0.02). In contrast, the microangiopathy was very much less severe in the transplant recipients than in haemodialysed patients (p < 0.02) and, in the patient studied both before and after transplantation, changes regressed from severe to moderate within 2 months of transplantation. Other histological findings present in many specimens did not correlate with vessel changes. The findings establish the existence of a potentially reversible microangiopathy in normal-looking skin of patients with chronic renal failure. Further study is needed to determine if it reflects the same pathological process that underlies the development of accelerated atherosclerosis responsible for about half the deaths among patients on maintenance haemodialysis.

Adolescent↗