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Biomedical subjects

G W Strain

Publications and source records attributed to G W Strain.

At least 37 records · Page 2Linked to original sources

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↗

Mild Hypogonadotropic hypogonadism in obese men.

To evaluate the pituitary-gonadal axis of obese men, we compared the 24-hour mean plasma concentrations of total and free testosterone and of dihydrotestosterone, FSH, and LH in 21 healthy obese men, aged 18-50, and 24 age-matched healthy nonobese men. In the obese men, we also measured the volume of ejaculate and the number and motility of sperm, and investigated libido by psychiatric interview, and potency by history and by measurement of nocturnal penile tumescence. As a group, the obese men had less than two-thirds the normal mean plasma levels of total testosterone, free testosterone, and FSH; the difference from normal was highly significant for all three. 24 hr LH levels were normal, which is inappropriately low in view of the subnormal testosterone levels. 24 hr mean levels of dihydrotestosterone and spermatogenesis, libido, and potency were essentially normal. Taken together, the findings represent a state of mild hypogonadotropic hypogonadism, which thus appears to be characteristic of obese men. This abnormality probably results from partial suppression of the pituitary by the elevated plasma estrogen levels we and others find in these men.

Adolescent↗

Age variation of the 24-hour mean plasma concentrations of androgens, estrogens, and gonadotropins in normal adult men.

The 24-h mean plasma concentrations of androgens (dihydrotestosterone and total and free testosterone), estrogens (estrone and estradiol), and gonadotropins (LH and FSH) were measured in 35 healthy men, aged 21-85 yr, who were rigorously screened to exclude factors known or suspected to alter endocrine function. The plasma total testosterone concentration showed a slow continuous decline with age, decreasing about 35% between 21 and 85 yr of age; the free testosterone level was closely correlated with that of total testosterone over the entire observed concentration range. The concentrations of dihydrotestosterone, estrone, estradiol, and LH were age invariant. The concentration of FSH showed a continuous linear increase with age; the level at age 85 was about 2.5 times the level at age 21. The following conclusions were drawn. 1) Testosterone secretion appears to decline slowly and continuously throughout adult life in men. 2) Measurement of the plasma free testosterone level adds no independent information in healthy men, since its level is closely correlated with that of total testosterone at all concentrations. 3) The continuous rise with age in FSH concentration while LH is age invariant cannot be explained by changes in testosterone or estrogen production, but might be due to a decline of inhibin production with age.

Adult↗

Obese young men have elevated plasma estrogen levels but obese premenopausal women do not.

The 24 hr mean plasma concentrations of estrone (E2) and estradiol (E2) were measured in 18 healthy, regularly cycling obese women; 16 healthy, regularly cycling nonobese women; 18 healthy obese men; and 33 healthy nonobese men. The obese men showed significant elevations of both E1 (67 pg/ml versus 49 pg/ml control; P less than 0.005) and E2 (37 pg/ml versus 28 pg/ml; P less than 0.005), but the obese women showed no significant elevation of either E1 or E2. The most likely explanation for the absence of significant hyperestrogenemia in the obese women despite evidence that such women have increased androstenedione-to-estrone conversion is that the latter source of estrogen is too small in comparison with estradiol secretion to cause a statistically detectable increment in plasma estrogen levels.

Adult↗

Sex difference in the influence of obesity on the retention of a tracer of 3H-estradiol.

The influence of obesity on the retention of a tracer of 3H-estradiol was studied in 15 nonobese premenopausal women, 15 obese premenopausal women (49%-274% above desirable weight), and 27 young men ranging in weight from 5% below to 330% above a desirable weight. The women showed a clear-cut inverse linear correlation between the 72 hr excretion of radioactivity and the percent deviation from desirable weight over the entire weight range examined (y equals 66 minus 0.10x, r equals -0.59, P less than 0.005); the average excretion in the 6 most obese women (145%-272% above desirable weight) was 45 plus or minus 11 (SD)%, significantly lower than the values of 65 plus or minus 12% in 15 nonobese women (P less than 0.025). The obese men showed no correlation whatever between excretion of radioactivity and relative body weight; the average excretion of the 6 most obese men was 55 plus or minus 7, not significantly different from the value of 56 plus or minus 12 in nonobese men. This sex difference makes untenable the hypothesis previously proposed by others that retention of estradiol tracers is obese women (men were not studied ) is due to simple solubility of estrogens in fat. Various alternative possibilities to explain the present data are discussed and it is concluded that a possibility worth examining is that the adipose tissue of women contains specific estrogen binding protein (? receptor) while the adipose tissue of men does not.

Body Weight↗

Nutrition, brain function and behavior.

Current food intake has been shown to directly affect neurotransmission, with resultant modification of behavior. The role of vitamin co-factors in brain function is discussed, with emphasis on changes in mood and neurological function with deficiency. The use of megadoses of vitamins for the treatment of psychiatric diseases has little scientific support at this time. Current research also does not substantiate the Feingold thesis of improvement in childhood hyperkinesis when an additive-free diet is consumed. The effects of medications used to moderate mood are related to changes in nutrient intake that in turn alters weight status. In addition, the effect of certain nutrients modifying the dose response to mood altering drugs has been discussed. Finally evidence for mood state directly affecting the capacity of the body to utilize nutrients is presented.

Adolescent↗

Abnormal 24-hr mean plasma concentrations of dehydroisoandrosterone and dehydroisoandrosterone sulfate in women with primary operable breast cancer.

The 24-hr mean plasma concentrations of dehydroisoandrosterone (DHA) and dehydroisoandrosterone sulfate were measured in 11 women with primary operable breast cancer, ages 31 to 78 years, and in 37 normal women, ages 21 to 75 years. In contrast to the marked and progressive decline of DHA and dehydroisoandrosterone sulfate concentration with age in the normal women, the concentrations of both steroids were age invariant in the cancer patients. The premenopausal patients had subnormal plasma DHA and dehydroisoandrosterone sulfate levels, while the post menopausal patients had supranormal levels. Since the plasma DHA/androsterone ratio was normal in the premenopausal patients and significantly elevated in the postmenopausal patients, it is postulated that the subnormal plasma adrenal androgen levels in the premenopausal patients were due principally to diminished production of these steroids, while the elevated plasma levels in the postmenopausal patients were due principally to slowed metabolic removal. Reports in the literature that DHA inhibits the development of breast cancer in mice suggest that the subnormal plasma DHA levels in premenopausal breast cancer may have clinical significance.

Adult↗

Plasma levels of thyroxine and triiodothyronine in women with breast cancer.

24-hour mean plasma levels of T3 and T4 were compared in 29 rigorously selected breast cancer patients (all stages) and 27 healthy women, and 8 A.M. "spot" plasma T4 levels were compared in 43 consecutive unselected breast cancer patients (all stages), 22 women with other-than-breast cancer, 21 women with miscellaneous non-cancerous illnesses, and the same 27 healthy women. The 24-hour T3 levels were the same in the breast cancer patients and healthy controls, but the 24-hour T4 levels were significantly higher in the cancer patients (7.7 vs 5.8 micrograms/dl, p less than 0.001); equal elevations were present in all stages of cancer. Spot T4 levels were likewise significantly higher in the breast cancer patients than in the healthy controls (8.8 vs 7.3 micrograms/dl, p less than 0.005). The women with other-than-breast cancer and the women with miscellaneous non-cancerous illnesses also showed significant elevations of spot T4 levels, indistinguishable from those of the breast cancer patients. It is concluded that breast cancer patients as a group show significant hyperthyroxinemia and that this finding may represent a second nonspecific abnormality of thyroid hormones in disease, hypotriiodothyroninemia (low-T3 syndrome) being the first.

Adult↗

Cortisol production in obesity.

Absolute cortisol production was estimated from the urinary excretion of tetrahydro metabolites of cortisol in 74 healthy women varying in weight from 12% below to 218% above desirable weight, and in 37 healthy men varying in weight from 3% below to 139% above desirable weight, and was measured by isotope dilution (after 14C tracers) in 26 of the women and 23 of the men. The relationship of both parameters to urinary creatinine excretion (as a measure of lean body mass) and to percent deviation from desirable weight (relative weight) was determined. Both absolute cortisol production and urinary creatinine excretion showed a significant positive linear correlation with relative weight in the men and women, but cortisol production/g urinary creatinine excretion (by isotope dilution or by tetrahydro metabolite excretion) was weight-invariant in both sexes. The geometric mean of cortisol production/g creatinine was 12.9 mg/g in men and 14.5 mg/g in women; the difference was not statistically significant. The geometric mean of tetrahydro metabolite excretion/g creatinine was 3.7 mg/g in men and 3.8 mg/g in women; the difference was not statistically significant. The average ratio of cortisol production to tetrahydro metabolite excretion was 3.5 in men and 3.8 in women, values not significantly different from one another and closely confirming our previously reported value of 3.6, based on the conversion of cortisol tracers to radioactive urinary tetrahydro metabolites. It is concluded that there is no functionally significant elevation of cortisol production in obese men or women: the increase in absolute production is solely a consequence of greater lean body mass, and the production/U lean body mass is weight-invariant. It appears desirable to make any comparisons of one group of patients with another in terms of cortisol production/g urinary creatinine in order to eliminate body size and obesity as confounding factors, so that disease-related differences may emerge clearly.

Carbon Radioisotopes↗

Sex differences in the twenty-four-hour mean plasma concentrations of dehydroisoandrosterone (DHA) and dehydroisoandrosterone sulfate (DHAS) and the DHA to DHAS ratio in normal adults.

The 24-h mean plasma concentrations of dehydroisoandrosterone (DHA) and dehydroisoandrosterone sulfate (DHAS) and the DHA to DHAS ratio were determined in 37 normal women, aged 21-75 yr, and 32 normal men, aged 21-72 yr. As predicted from our study of sex differences in the metabolism of DHAS, women showed a markely higher DHA to DHAS ratio than men at all ages; the geometric mean for women was 7.5 x 10(-3) and that for men was 3.9 x 10(-3) (P less than 0.0001); and the mean for premenopausal women (6.7 x 10(-3) did not differ significantly from that for postmenopausal women (8.6 x 10(-3)). The two steroids showed a clear-cut linear inverse correlation between concentration and age in both sexes, and menopause was "nonevent" in the age progression for both steroids in the women. The slopes of the concentration vs. age curves were considerably greater in the women, as a reuslt of which the sex differences in concentrations of these steroids changed with age. Under age 50 yr, the plasma DHA concentration of women was considerably higher than that of men [462 +/- 187 (mean +/- SD) vs. 336 +/- 103; P less than 0.025], while the concentrations of DHAS showed no significant sex difference ((77 +/- 38 vs. 101 +/- 67; P greater than 0.1). In persons 50 yr of age or over, plasma DHA concentrations were about the same in women and men (238 +/- 119 vs. 287 +/- 121; P greater than 0.1), but plasma DHAS concentrations were very much lower in women (31 +/- 21 vs. 83 +/- 49; P less than 0.0001).

Adult↗

Subnormal plasma adrenal androgen levels in men with uremia.

The 24-h mean plasma concentrations of 8 hormones were measured in 11 men with chronic uremia and 32 normal men. Our findings confirm previous reports of subnormal levels of testosterone, T3, and T4 and elevated levels of LH, PRL, and cortisol. In addition, we observed a new finding: markedly subnormal levels of the adrenal androgens dehydroisoandrosterone (DHA) and DHA sulfate. The mean DHA level in the patients was 164 +/- 46 (SD) ng/dl, compared with 320 +/- 124 in age-matched controls (P < 0.0001); the geometric mean DHA sulfate level was 40 micrograms/dl (95% confidence limits, 11-113) in the patients and 76 micrograms/dl (95% confidence limits, 26-214) in age-matched controls (P = 0.005). The depression of adrenal androgen levels in the face of elevated cortisol levels suggests a biosynthetic block in the adrenal cortex at the step where the C-19 and C-21 pathways diverge, namely the removal of the 2-carbon side chain by C-17, 20-lyase. If a similar defect were present in the testes, it could account for the diminished synthesis of testosterone, which is a further metabolite of DHA in the testes.

Adult↗

Psychological impediments to weight loss.

An understanding of the possible psychologic impediments to weight loss can promote improved therapeutic intervention for the obese patient. Certain psychological tasks are imposed by chronic medical illness including obesity. The universal stresses that accompany medical illness, the basic threat to self-esteem and sense of intactness, the fear--of loss of love and approval, of loss of control of function, of injury to body parts, of pain, and of guilt--all become psychological impediments thwarting weight loss and its maintenance. The physician's awareness of these psychological stresses helps him identify areas of necessary support.

Anxiety, Separation↗