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Biomedical subjects

R Andres

Publications and source records attributed to R Andres.

24 records · Page 2Linked to original sources

Antipyrine metabolism in man: influence of age, alcohol, caffeine, and smoking.

Age has been shown to influence drug metabolism but effects of aging could be due to other variables that influence metabolism and differ with age. Plasma half-life and metabolic clearance rate of antipyrine were studied in 307 healthy male subjects, aged 18 to 92. Half-life was 16.5% longer and metabolic clearance rate was 18.5% less in a group of the older than in the younger subjects. Both caffeine and cigarette use were positively correlated with the rate of antipyrine metabolism. Multiple regression analysis showed that the effect of smoking was partially responsible for the age differences in antipyrine metabolism. Smoking explained 12% of the variance in metabolic clearance rate and age explained 3%. Our results suggest that studies attempting to quantify the effects of aging on drug metabolism must also take into account other factors that differ with age.

Adolescent

The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man.

The effects of insulin on the renal handling of sodium, potassium, calcium, and phosphate were studied in man while maintaining the blood glucose concentration at the fasting level by negative feedback servocontrol of a variable glucose infusion. In studies on six water-loaded normal subjects in a steady state of water diuresis, insulin was administered i.v. to raise the plasma insulin concentration to between 98 and 193 muU/ml and infused at a constant rate of 2 mU/kg body weight per min over a total period of 120 min. The blood glucose concentration was not significantly altered, and there was no change in the filtered load of glucose; glomerular filtration rate (CIN) and renal plasma flow (CPAH) were unchanged. Urinary sodium excretion (UNaV) decreased from 401 plus or minus 46 (SEM) to 213 plus or minus 18 mueq/min during insulin administration, the change becoming significant (P smaller than 0.02) within the 30-60 min collection period. Free water clearance (CH2O) increased from 10.6 plus or minus 0.6 to 13 plus or minus 0.5 ml/min (P smaller than 0.025); osmolar clearance decreased and urine flow was unchanged. There was no change in plasma aldosterone concentration, which was low throughout the studies, and a slight reduction was observed in plasma glucagon concentration. Urinary potassium (UKV) and phosphate (UPV) excretion were also both decreased during insulin administration; UKV decreased from 66 plus or minus 9 to 21 plus or minus 1 mueq/min (P smaller than 0.005), and tupv decreased from 504 plus or minus 93 to 230 plus or minus 43 mug/min (P smaller than 0.01). The change in UKV was associated with a significant reduction in plasma potassium concentration. There was also a statistically significant but small reduction in plasma phosphate concentration which was not considered sufficient alone to account for the large reduction in UPV. Urinary calcium excretion (UCaV) increased from 126 plus or minus 24 to 200 plus or minus 17 mug/min (P smaller than 0.01). These studies demonstrate a reduction in UNaV associated with insulin administration that occurs in the absence of changes in the filtered load of glucose, glomerular filtration rate, renal blood flow, and plasma aldosterone concentration. The effect of insulin on CH2O suggests that insulin's effect on sodium excretion is due to enhancement of sodium reabsorption in the diluting segment of the distal nephron.

Aldosterone

The role of growth hormone in the glucose intolerance of uremia.

The fasting plasma growth hormone (GH) concentration and the plasma growth hormone response to sustained hyperglycemia was examined in 8 chronically uremic subjects before and after hemodialysis employing the hyperglycemia clamp technique. The plasma glucose concentration was acutely raised and maintained at +125 mg/100 ml above basal levels. Since the glucose concentration was held constant, the glucose infusion rate is an index of glucose metabolism (M) and M divided by the plasma insulin response (I) is a measure of tissue sensitivity to insulin. Predialysis, the fasting GH concentration, 4.0 +/- 1.0 ng/ml, was significantly greater than controls, 0.3 +/- 0.1 ng/ml (p less than 0.01), and failed to suppress normally following sustained hyperglycemia. Both M, 4.23 +/- 0.36 mg/kg x min, and M/I, 5.05 +/- 0.79 mg/kg x min per microU/ml, were significantly reduced compared to controls (p less than 0.001). There was no correlation between either the fasting GH concentration or the GH response to sustained hyperglycemia and either M or M/I. Following dialysis both M, 6.30 +/- 0.64 mg/kg x min, and M/I, 8.39 +/- 1.06 mg/kg x min per microU/ml, increased (p less than 0.01) without significant change in either the fasting GH level, 4.0 +/- 1.2 ng/ml, or the plasma GH response to hyperglycemia. It is concluded that while deranged GH physiology is a common accompaniment of the uremic state, it is not responsible for the glucose intolerance and tissue insensitivity to insulin observed in uremia.

Adult

Cholesterol as a risk factor for coronary heart disease in elderly men. The Baltimore Longitudinal Study of Aging.

In order to explore the relationship of cholesterol to coronary heart disease (CHD), defined as angina pectoris, myocardial infarction, and sudden coronary death, in older men, a group of 1052 men, participants in the Baltimore Longitudinal Study on Aging, were examined. Subjects were stratified into three age groups, 28 to 64, 65 to 74, and 75 to 97 years old. In all three age groups, cholesterol was a significant risk factor for CHD. In the oldest age group (n = 250), the relationship between cholesterol and risk was linear (P = .003) as opposed to younger age groups where the relationship was exponential. This study extends the age range in which hypercholesterolemia has been shown to be associated with CHD to include the 75- to 97-year range.

Adult

Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease.

OBJECTIVE: To evaluate longitudinal changes in prostate-specific antigen (PSA) levels in men with and without prostate disease. DESIGN: Case-control study of men with and without prostate disease who were participants in a prospective aging study. SETTING: Gerontology Research Center of the National Institute on Aging; the Baltimore (Md) Longitudinal Study of Aging. PATIENTS: Sixteen men with no prostate disease (control group), 20 men with a histologic diagnosis of benign prostatic hyperplasia (BPH), and 18 men with a histologic diagnosis of prostate cancer. OUTCOME MEASURES: Multiple PSA and androgen determinations on serum samples obtained from 7 to 25 years prior to histologic diagnosis or exclusion of prostate disease. RESULTS: Changes in androgen levels with age did not differ between groups. Control subjects did not show a significant change in PSA levels with age. There was a significant difference in the age-adjusted rate of change in PSA levels between groups (prostate cancer greater than BPH greater than control; P less than .01). At 5 years before diagnosis when PSA levels did not differ between subjects with BPH and prostate cancer, rate of change in PSA levels (0.75 micrograms/L per year) was significantly greater in subjects with prostate cancer compared with control subjects and subjects with BPH. Also, rate of change in PSA levels distinguished subjects with prostate cancer from subjects with BPH and control subjects with a specificity of 90% and 100%, respectively. CONCLUSIONS: The most significant factor affecting serum PSA levels with age is the development of prostate disease. Rate of change in PSA levels may be a sensitive and specific early clinical marker for the development of prostate cancer.

Aged