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Biomedical subjects

G W Strain

Publications and source records attributed to G W Strain.

At least 19 recordsLinked to original sources

Twenty-four-hour mean plasma testosterone concentration declines with age in normal premenopausal women.

The 24-h mean plasma concentration of total testosterone (T) was measured in 33 healthy, regularly cycling, nonobese women between 21 and 51 yr of age. Percent free T was measured in 17 of them. Plasma dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) were measured in 24 of them, and the DHEA-to-T and DHEAS-to-T ratios were calculated. It was found that the concentration of total T showed a steep decline with age; the regression equation was: T (nanomoles per L) = 37.8 x age-1.12 (r = -0.54; P < 0.003). According to this equation, the expected T concentration of a woman of 40 would be 0.61 nmol/L, about half that of a woman of 21 (1.3 nmol/L). The percent free T did not vary significantly with age, so free T concentration likewise showed a steep decline with age. The DHEA-to-T and DHEAS-to-T ratios were both age invariant, clearly because the levels of DHEA and DHEAS also decline steeply with age, as previously reported.

Adult

Improvement of plasma lipoprotein profiles during high-flux dialysis.

Patients undergoing maintenance hemodialysis therapy have increased mortality due to cardiovascular disease. One possible etiologic factor for this increased mortality is the lipid abnormalities associated with chronic renal failure. These include elevated triglyceride (TG) and decreased high-density lipoprotein (HDL) concentrations. Lipoprotein profiles of patients undergoing chronic hemodialysis with either saponified cellulose ester (CE) (N = 9) or polysulfone (PS) high-flux dialysis membranes (N = 10) were compared. Patients in each group received similar amounts of heparin during the dialysis. CE-dialyzed patients showed no alteration in serum TG, HDL, low-density lipoprotein, or total cholesterol when predialysis and postdialysis values were compared. PS patients, on the other hand, had a significant decrease in TG concentrations (P < 0.01) as well as a significant rise in HDL (P < 0.01). These changes might signify activation of lipoprotein lipase (LPL) during dialysis. LPL activity in PS sera was significantly greater than LPL in CE sera. Moreover, sera from PS patients inhibited LPL much less than did sera from CE patients. These findings suggest that a circulating substance not dialyzable with cellulosic membranes inhibits LPL in uremic subjects and is removed during dialysis with a PS membrane. Alternatively, the greater biocompatibility of PS may produce less LPL inhibitory cytokines during dialysis. The improvement of lipoprotein profiles in patients receiving dialysis with PS membranes may, in the long term, lead to less morbidity and mortality from atherosclerotic disease.

Adult

The relationship of weight-height indices of obesity to body fat content.

The measurement called desirable body weight (DBW) was derived by actuaries to indicate that weight which is associated with the lowest mortality. Percent deviation from DBW has become a standard measure of fatness. A different obesity index, body mass index (BMI), is weight in kilograms divided by the square of height in meters. Many workers consider both measures inferior to the measurement of body fat content (BFC). We compared the three measures of fatness in 40 men aged 18-50 and 48 women aged 21-47, ranging from nonobese to extremely obese. Total BFC was determined by isotope dilution of 3H-labeled water. DBWs used were those listed in the US Air Force Examination Manual of 1971; these approximate the midpoint of the range of medium-frame values in the 1959 Metropolitan Life Insurance Tables, but have the advantage of providing a single value for each height. We found nearly perfect correlation (r = 0.99, p < 0.001) between BMI and percent deviation from DBW in both men and women ranging from 14% below to 305% above DBW. Correlations between percent deviation from DBW and total BFC were extremely high: 0.95 (p < 0.001) for the men and 0.94 (p < 0.001) for the women, essentially the same as correlations between BMI and BFC, which were 0.96 (p < 0.001) for the men and 0.95 (p < 0.001) for the women. It appears that the two technically simple weight-height indices, BMI and percent deviation from DBW, give just as accurate a measurement of fatness as the technically complex measurement of total BFC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue

Food intake of very obese persons: quantitative and qualitative aspects.

To document the caloric intake of very obese persons and investigate the food choices and dietary composition that maintain severe obesity, we studied the self-selected food intake required to maintain stable weight in two groups of very obese subjects: 11 inpatients with a mean weight 181% above desirable body weight and 35 outpatients with a mean weight 125% above desirable body weight. Qualitative and quantitative food intake were evaluated using records obtained on the hospital metabolic ward for the inpatients and using self-recorded food records for the outpatients. Absolute caloric intake in both groups was greater in proportion to the degree of obesity (deviation from desirable body weight); caloric intake per unit of lean body mass (kilocalories per gram urinary creatinine) was constant regardless of the degree of obesity and was essentially the same as that of normal nonobese persons. Food records indicated that the obese subjects maintained their high caloric intake by consuming mostly foods of high caloric density, with occasional binge eating. They largely avoided foods of low intrinsic energy density and modified-calorie foods, ie, foods with decreased fat, nonnutritive sweeteners, or fillers. By substituting foods of lower caloric density for usual food choices from the same food group, obese persons could decrease caloric intake by 20% and increase potential for notable weight loss.

Adult

Androgen binding to ammonium sulfate precipitates of human adipose tissue cytosols.

Although androgens are believed to influence the distribution of human adipose tissue and have been detected in human fat, receptors for these sex hormones have yet to be identified. These studies demonstrate that a high-affinity, limited-capacity binding component for the synthetic androgen methyltrienolone (R1881) exists in ammonium sulfate precipitates of human adipose tissue cytosols. The equilibrium dissociation constant (Kd = 0.1 to 0.4 nmol/L, n = 6) and the number of binding sites (2 to 26 fmol/mg protein, n = 22) are consistent with those reported for androgen receptors in rat prostate, human prostatic carcinoma, MCF-7 cells, and baboon myocardium. The relative steroid-binding specificities of the human adipose tissue androphile (R1881 approximately 5 alpha-dihydrotestosterone greater than testosterone greater than estradiol approximately progesterone much greater than dexamethasone) are similar, but not identical, to those reported for androgen receptors in rat prostate (R1881 greater than 5 alpha-dihydrotestosterone approximately testosterone greater than estradiol greater than progesterone much greater than cortisol) and baboon myocardium (R1881 greater than 5 alpha-dihydrotestosterone greater than testosterone greater than progesterone greater than estradiol much greater than cortisol). The function of the androgen-binding component in human adipose tissue is not known.

Adipose Tissue

Plasma free and non-sex-hormone-binding-globulin-bound testosterone are decreased in obese men in proportion to their degree of obesity.

It is known that plasma total testosterone (T) is decreased in obese men in proportion to the degree of obesity, but similar information is not available for plasma free T and non-sex-hormone-binding globulin (SHBG)-bound T. We measured the 24-h mean plasma total T in 48 healthy (non-weight-stable men, aged 18-55 yr, with body mass indexes (BMI) ranging from 21-95 kg/m2. Free T and non-SHBG-bound T were calculated using the measured total T, the concentrations of albumin and SHBG, and the association constants of T to albumin and SHBG. Total body fat content was measured by deuterium-water isotope dilution. Findings were as follows. 1) BMI was very highly correlated with total body fat content (r = 0.96; P less than 0.001); thus, the degree of obesity can be calculated just as appropriately from simple height and weight measurements as from measurements of total body fat content. 2) Total, non-SHBG-bound, and free T were all highly correlated inversely with BMI; for total T, r = -0.727, P less than 0.01; for non-SHBG-bound T, r = 0.677, P less than 0.01; and for free T, r = -0.653, P less than 0.01. Thus, free T and non-SHBG-bound T are decreased in obese men in proportion to the degree of obesity, just as is the case for total T; percentage-wise, the decrease was the same for all 3 parameters.

Adult

Effect of massive weight loss on hypothalamic-pituitary-gonadal function in obese men.

To study the ability of weight loss to reverse the hyperestrogenemia-induced hypogonadotropic hypogonadism that occurs in obese men, we measured the 24-h mean plasma free and total estradiol (E2), total estrone, FSH, LH, and free and total testosterone concentrations in 11 healthy obese men (100-305% above desirable body weight) and again 5-39 months later after weight loss of 26-129 kg and restabilization at the new weight. Weight loss produced significant increases in mean plasma total testosterone [240 +/- 116 (+/- SD, 8.5 +/- 4.0) to 377 +/- 113 ng/dL (13.0 +/- 4.0 nmol/L); P less than 0.01], free testosterone [9.5 +/- 5.0 (329 +/- 173) to 13.4 +/- 4.3 ng/dL (464 +/- 149 pmol/L); P less than 0.025], and FSH (6.5 +/- 4.7 to 10.9 +/- 8.5 IU/L; P less than 0.025). Plasma LH was lower than levels in normal men before and after weight loss and did not change significantly (10.3 +/- 4.8 and 10.8 +/- 6.8 IU/L, respectively). There was no change in plasma total E2 [54 +/- 26 (196 +/- 94) to 50 +/- 13 pg/mL (180 +/- 50 pmol/L)], free E2 [1.48 +/- 0.7 (5.37 +/- 2.54) to 1.33 +/- 0.42 pg/mL (4.83 +/- 1.45 pmol/L)], or total estrone [75 +/- 38 (280 +/- 140) to 82 +/- 24 (300 +/- 90) pmol/L], and sex hormone-binding globulin rose from 9.2 +/- 3.2 to 12.9 +/- 5.4 nmol/L (P less than 0.005). The increases in plasma free and total testosterone and sex hormone-binding globulin were proportional to the degree of weight loss. Thus, the hypogonadotropic hypogonadism was largely reversed by the weight loss without any decrease in hyperestrogenemia, its presumed cause. We postulate a change in hypothalamic-pituitary function with weight loss, such that GnRH-gonadotropin secretion becomes less sensitive to suppression by a given amount of estrogen.

Adult

Partial reversal of the hypogonadotropic hypogonadism of obese men by administration of corticosuppressive doses of dexamethasone.

Obese men have hyperestrogenemia-induced hypogonadotropic hypogonadism (HHG), due, we believe, to increased rarmatization of adrenal androgens by the increased bulk of aromatase-containing adipose tissue. We studied the effects of corticosuppressive doses of dexamethasone (D) on 24-h mean plasma total and free estradiol (E2), estrone (E1), LH, FSH, total and free testosterone, delta 4-androstenedione (delta 4), and sex-hormone-binding globulin (SHBG) in nine obese men and five normal-weight controls. In the obese men, the following hormones fell: E2 [59 +/- 19 to 39 +/- 11 pg/ml (P less than 0.01)], E1 [93 +/- 41 to 50 +/- 25 pg/ml; (P less than 0.01)], delta 4-androstenedione [120 +/- 80 to 55 +/- 27 ng/dl; (P less than 0.02)]; free E2 [1.6 +/- 0.4 to 1.1 +/- 0.2 pg/ml; (P less than 0.01)], SHBG [12.8 +/- 5.3 to 8.2 +/- 3 nM/l; (P less than 0.04)]. FSH rose from 4.8 +/- 3.2 to 7.6 +/- 4.2 miu/ml (P less than 0.01). LH, total and free testosterone showed no significant change. In the nonobese men, there were decreases in total E2 [(34 +/- 6.8 to 25 +/- 10 pg/ml; P less than 0.04)], SHBG [16.8 +/- 7.5 to 10.4 +/- 2.0 nM/l: P less than .05.], free E2 [0.9 +/- 0.2 to 0.7 +/- 0.3 pg/ml: P less than 0.05], delta 4 [91.4 +/- 3.6 to 33.4 +/- 16.7 ng/dl; P less than .01] and total T [492 +/- 44 to 393 +/- 121 ng/dl; P less than 0.04]. There was no significant change in E1, FSH, LH or free T.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Differential binding of dexamethasone to ammonium sulfate precipitates of human adipose tissue cytosols.

Saturation analysis of the binding of [3H]dexamethasone [( 3H]DEX) to ammonium sulfate precipitates (ASPs) confirmed the presence of a limited-capacity, high-affinity binder in human adipose tissue cytosols. Various non-radioactive steroids competed with [3H]DEX for binding to the ASPs in the following sequence: dexamethasone (DEX) approximately equal to triamcinolone acetonide (TA) greater than progesterone (P) much greater than estradiol (E2). The steroid specificity of the binder precipitated by AS was consistent with the specificities reported for glucocorticoid receptors in a number of systems. In order to investigate possible regional differences, glucocorticoid binding to ASPs derived from adipose tissues removed from two different sites in the same subject was quantitated. ASPs of human omental adipose tissue bound significantly more [3H]DEX than did similar preparations of subcutaneous adipose tissue from the abdominal wall (116 +/- 32 vs. 50 +/- 22 fmol/mg protein; mean +/- SD; p less than 0.02). The findings are consistent with reports from other laboratories suggesting that intra-abdominal fat is more responsive to glucocorticoids than is subcutaneous adipose tissue.

Adipose Tissue

L-tryptophan does not increase weight loss in carbohydrate-craving obese subjects.

Eight subjects, aged 26 to 50 years, who had long histories of carbohydrate (CHO) craving and were more than 45 kg above desirable body weight participated in a randomized, double-blind, crossover pilot study on the effects of L-tryptophan on weight loss and mood state. One g of tryptophan with 10 g of CHO was administered three times a day, 30 min before meals, as an adjunct to a weight-loss protocol that included nutritional consultation teaching low fat, high fiber diets ranging from 1200-1600 kcals/day, behavior modification, and supportive therapy. During the pretreatment period, body weight and plasma tryptophan levels were measured and the Beck Depression Inventory, SCL 90 rating, and Profile-of-Mood State (POMS) were used to assess mood. During the treatment periods, subjects kept daily records of food intake and the timing of medication. All patients were seen at least biweekly. After six weeks on medication, baseline measurements were repeated and the crossover between tryptophan and placebo was implemented. After an additional six weeks on placebo or tryptophan, the same measurements were repeated. For the eight patients who completed the three-month protocol, the mean weight loss for six weeks on placebo was 1.14 kg and for six weeks on tryptophan was 2.3 kg. Mean Beck scores were 8.8 during the control period, 8.3 on placebo, and 10.9 on tryptophan. Mean SCL 90 ratings were 69.2 during the control, 54.6 on placebo, and 64.2 on tryptophan. Mean scores for total mood disturbance on the POMS were 48 during the control period, 43 on placebo, and 52 on tryptophan.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Elevated 24-hour mean plasma concentration of FSH in men with cirrhosis of the liver.

Twenty-four-hour mean plasma concentrations of estradiol, estrone, testosterone, LH and FSH were measured in 6 men with typical alcoholic liver cirrhosis and in 17 age-matched controls. Plasma estradiol levels were markedly elevated in the cirrhotic patients, as has been reported before. Plasma levels of estrone, testosterone and LH did not differ significantly from normal. The most striking finding was marked elevation of the plasma FSH level: the mean value in the cirrhotic group was 19.5 mIU/ml (95% confidence limits, 13-29), more than twice the mean control value, 9.7 mIU/ml (95% confidence limits, 7.0-13) (p less than 0.0005). This consistent elevation of FSH in cirrhotic men may be due to a deficient testicular secretion of inhibin as a result of alcohol toxicity to the testes.

Adult

Do fat cell morphometrics predict weight loss maintenance?

A comprehensive psychosocial approach was used to treat 44 otherwise healthy obese patients, 49-332 percent above desirable weight, whose fat cell morphometrics arbitrarily placed them into three groups: seven with predominant fat-cell hypertrophy, 18 with predominant hyperplasia, and 19 with mixed hypertrophy and hyperplasia. Continuous psychological support was provided to all patients, and life-style was altered by nutrition education and behavior modification. Psychiatric referral was made when indicated. Four of the 45 patients, who were refractory to treatment, were referred for surgery. Successful treatment was defined as maintenance of a weight loss of 18 kg or more for one year. Two of the seven hypertrophic, seven of the 18 hyperplastic, and 11 of the 19 mixed hypertrophic-hyperplastic patients had successful results without surgery. Overall success rate was 45 percent, and did not differ significantly according to fat cell morphometrics. Although greater weight losses were maintained in correlation with the extent of hyperplasia P less than 0.005, the percentage weight change from intake weights was similar. In summary, a program of continuous psychological support, nutrition education, and behavior modification resulted in a substantially higher rate of successful one-year maintenance of weight loss than is generally reported for the treatment of markedly obese patients. Further long-term follow-up is in progress. In contradiction to predictions based on adipose cell morphometrics, those patients with simple hypertrophy of their fat cells were not more successful in maintaining a weight change. Although maintenance varied from 18.2 kg to 52 kg for those successfully treated, a weight loss of approximately 20 percent of the intake was sustained.

Adipose Tissue

Subnormal 24-hour mean plasma LH concentration and elevated plasma FSH/LH ratio in obese premenopausal women. A possible human counterpart of the slow-GnRH-pulsing model in primates.

The 24-hour mean plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured during the follicular phase of the menstrual cycle in 15 healthy, regularly cycling obese women (59-218% above desirable weight) and 9 healthy, regularly cycling nonobese women (14% below to 14% above desirable weight). The obese women showed slightly but not significantly higher FSH values (12.5 vs. 9.6 mIU/ml), definitely and significantly lower LH values (11 vs. 17 mIU/ml; p less than 0.005) and markedly and very significantly higher FSH/LH ratios (1.2 vs. 0.62; p less than 0.0005). These abnormalities may represent a human counterpart of the slow-GnRH-pulsing model of primates: monkeys in which the GnRH secretory centers have been ablated and that receive GnRH infusions at subnormal pulsing rates show slightly elevated FSH levels, markedly decreased LH levels, greatly elevated FSH/LH ratios and anovulation.

Adult

Abnormal levels of plasma hormones in men with prostate cancer: evidence toward a "two-disease" theory.

The 24-hr mean plasma concentrations of 13 hormones or hormone metabolites (cortisol, testosterone, dihydrotestosterone, dehydroisoandrosterone, dehydroisoandrosterone sulfate, androsterone, androsterone sulfate, estrone, thyroxine, triiodothyronine, LH, FSH, and prolactin) were measured in 16 rigorously screened patients (aged 55-80) with stage C or D prostate cancer and 36 normal men. Nine of the hormones showed no abnormalities in the patients but four (testosterone, dihydrotestosterone, cortisol, and estrone) showed abnormalities. Testosterone and dihydrotestosterone, which, respectively, decreased with age and showed no change with age in the normal men, rose sharply with age in the patients. The patients' curves crossed the normal curves at about age 65; patients 65 or above showed normal values while patients under age 65 showed significantly subnormal levels of both hormones: testosterone averaged 282 ng/dl in patients vs 434 ng/dl in controls (P less than 0.0001) and dihydrotestosterone averaged 70 ng/dl in patients vs 99 ng/dl in controls (P less than 0.01). Cortisol, which was age invariant in the normal men, fell sharply with age in the patients; patients under 65 had significantly elevated levels (10.1 vs 6.9 micrograms/dl; P less than 0.0001), while patients 65 or older had normal levels. Estrone levels were age invariant in both patients and controls, but the mean level in patients was markedly elevated (81 vs 47 pg/ml in controls; P less than 0.001). The cortisol/testosterone ratio almost completely separated prostate cancer patients under 65 from normal men, but did not discriminate patients 65 or older from normal. The findings indicate that prostate cancer patients under 65 differ markedly in their endogenous hormonal pattern from patients 65 or older. This leads us to propose a "two-disease" theory of prostate cancer, with possible differences in genetic factors and prognosis.

Age Factors

Sex difference in the influence of obesity on the 24 hr mean plasma concentration of cortisol.

The 24 hr mean plasma cortisol concentration was measured in 65 healthy women ranging from 21% below to 218% above desirable weight and in 47 healthy men ranging from 5% below to 330% above desirable weight. In the women, there was a clear-cut inverse linear correlation between the plasma cortisol concentration and the percent deviation from desirable weight (y = 7.5 -- 0.3 x; r = -0.49; p less than 0.001); the relation of free to total cortisol concentration was weight-invariant; the MCR of cortisol in the most obese women was much higher than that of nonobese women (340 +/- 76 versus 211 +/- 31 liters/gm urinary creatinine; p less than 0.01). In the men, the plasma cortisol level and MCR were weight-invariant. To account for the finding in women of a linear correlation of the decrement in plasma cortisol level with the percent deviation from desirable weight (which in turn is nearly perfectly correlated with the total body fat content), we postulate that a given weight of adipose tissue in women takes up a constant amount of cortisol; this in turn suggests that their adipose tissue contains a saturable binding system such as corticosteroid receptor. By the same logic, the weight-invariance of plasma cortisol and MCR in men suggests the absence of significant amounts of corticosteroid receptor in their adipose tissue. The finding that the increased cortisol MCR of obese women results in decreased plasma cortisol levels rather than an increase in cortisol production (the latter, corrected for muscle mass, is normal in obesity: Strain et al, Metabolism 29:980, 1980) suggests a defect in their cortisol ACTH feedback system. Such a defect, presumably hypothalamic, is not unexpected in the light of reports of defective hypothalamic control of prolactin and growth hormone secretion in obesity.

Body Weight