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Biomedical subjects

S M Harman

Publications and source records attributed to S M Harman.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effects of strength training on total and regional body composition in older men.

The effects of a 16-wk strength-training program on total and regional body composition were assessed by dual-energy X-ray absorptiometry (DEXA), magnetic resonance imaging (MRI), and hydrodensitometry in 13 untrained healthy men [60 +/- 4 (SD) yr]. Nine additional men (62 +/- 6 yr) served as inactive controls. The strength-training program resulted in substantial increases in both upper (39 +/- 8%; P < 0.001) and lower (42 +/- 14%; P < 0.001) body strength. Total fat-free mass (FFM) increased by 2 kg (62.0 +/- 7.1 to 64.0 +/- 7.2 kg; P < 0.001), and total fat mass decreased by the same amount (23.8 +/- 6.7 to 21.8 +/- 6.0 kg; P < 0.001) when measured by DEXA. When measured by hydrodensitometry, similar increases in FFM (61.3 +/- 7.8 to 63.0 +/- 7.6 kg; P < 0.01) and decreases in fat mass (23.8 +/- 7.9 to 22.1 +/- 7.7 kg; P < 0.001) were observed. When measured by DEXA, FFM was increased in the arms (6.045 +/- 0.860 to 6.418 +/- 0.803 kg; P < 0.01), legs (19.416 +/- 2.228 to 20.131 +/- 2.303 kg; P < 0.001), and trunk (29.229 +/- 4.108 to 30.134 +/- 4.184 kg; P < 0.01), whereas fat mass was reduced in the arms (2.383 +/- 0.830 to 2.128 +/- 0.714 kg; P < 0.01), legs (7.583 +/- 1.675 to 6.945 +/- 1.551 kg; P < 0.001), and trunk (12.216 +/- 4.143 to 11.281 +/- 3.653 kg; P < 0.01) as a result of training.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1993

Tissue response to bioerodible, subcutaneous drug implants: a possible determinant of drug absorption kinetics.

The fibrous tissue compartments that develop in response to the subcutaneous implantation of bioerodible heat-fused rods of norethindrone and cholesterol (85 and 15%, respectively) were studied by light and electron microscopy at various intervals after implantation to determine whether the biological inflammatory response may play a role in drug absorption. Thirty-five regularly menstruating, sterilized (tubal ligation), healthy females each received four Annuelle rods. The microanatomy of seven of the largest implants (135 mg norethindrone) was studied. A dense fibrous biological compartment was found to surround each rod. By light microscopy no abnormal tissue response was revealed. Scanning and transmission electron microscopy showed that the surfaces of the rods were covered by a cellular matrix of mononuclear cells. The fibrous compartment was composed of a loose cellular bed immediately surrounding the norethindrone rod, a dense fibrous connective tissue envelope containing blood and lymphatic vessels, and an outer fatty connective tissue layer. Transmission electron microscopy confirmed that the cellular tissue immediately surrounding the rods was composed mainly of lipid laden macrophages. Norethindrone levels in tissue capsules at 3 and 10.5 months were 0.05 and 8.4% by weight, respectively. These observations suggest that the local inflammatory response plays a role in the active processing of this delivery system. This picture is qualitatively different from the general view of the fibrous capsule as a simple rate limiting membrane. The effects observed in this study suggest that a more complex, functional biological system develops in response to the subcutaneous introduction of a drug delivery device.

Absorption↗
PubMed1993

Oral arginine-lysine does not increase growth hormone or insulin-like growth factor-I in old men.

BACKGROUND: Older adults tend to have reduced growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) levels as well as changes in body composition which are partially reversed by GH injections. Arginine stimulates GH release, and lysine may amplify this response. We investigated whether oral arginine/lysine could be used to increase basal IGF-I and GH levels in non-obese old men (age 69 +/- 5 years; mean +/- SD) to values similar to those of untreated young men (age 26 +/- 4 years). METHODS: Two groups of 8 healthy old men were treated with 3 g of arginine plus 3 g of lysine or with placebo capsules twice daily for 14 days. Before and on day 14 of each treatment GH levels were determined in blood samples taken at 20-minute intervals from 2000-0800 h, IGF-I was measured at 0800 h, and a 1 microgram/kg GHRH stimulation test was done. RESULTS: At baseline, mean GH peak amplitude (p < .02) and serum IGF-I (p < .0001) were lower, whereas GHRH responses were similar, in old vs young men. Arginine/lysine did not significantly alter spontaneous or GHRH-stimulated GH levels, or serum IGF-I. Arginine absorption was age-independent. The correlation (p < .005) between measured increments in serum arginine and increases in serum GH after a single dose of arginine/lysine was similar in old and young groups. CONCLUSIONS: Our data suggest that oral arginine/lysine is not a practical means of chronically enhancing GH secretion in old men.

Administration, Oral↗
PubMed1993

Human growth hormone and human aging.

In humans, both aging and GH deficiency are associated with reduced protein synthesis, decreased lean body and bone mass, and increased percent body fat. In healthy individuals, spontaneous and stimulated GH secretion, as well as circulating IGF-I and IGFBP-3 levels, are significantly decreased with advancing age. The extent to which these age-related changes in GH and IGF-I contribute to alterations in body composition and function remains to be elucidated. GH treatment of GH-deficient adults or old men with reduced IGF-I levels with exogenous GH increases plasma IGF-I, nitrogen retention, and lean body mass, decreases percent body fat, and exerts little effect on bone mineral density. Short-term adverse effects of GH therapy have been minimized by using low-dose regimens, but it is still uncertain whether long-term GH supplementation in adult life increases the risk of metabolic abnormalities or malignancy. Administration of GHRH, which has been shown to maintain the pattern of pulsatile GH secretion in old men, may represent another possible physiological approach to therapy. It may be justifiable initially to limit use of GH to certain elderly patients such as those suffering from catabolic illnesses, malnourishment, burns, cachexia, etc. A great deal more research will be necessary to determine whether normalization of GH and IGF-I levels in healthy older persons will lead to improvements in their physical and psychological functional capacity and quality of life.

Adult↗
PubMed1993

Continuous subcutaneous infusions of growth hormone (GH) releasing hormone 1-44 for 14 days increase GH and insulin-like growth factor-I levels in old men.

Twice daily sc injections of GHRH increase serum GH and IGF-I levels in healthy old men to values like those of untreated young men by producing high amplitude GH peaks after the injections. In the present study, we measured baseline insulin-like growth factor-I (IGF-I) 24-h profiles of GH release, and responses to GHRH stimulation tests in healthy young and old men. Old men were then given, in random order, 1 and 2 mg continuous sc GHRH 1-44 infusions daily for 14 days with an intervening 14-day treatment-free period. The study protocol was repeated on day 14 of each treatment. At baseline, mean duration of GH peaks (P < 0.005) and IGF-I levels (P < 0.0001) were lower in old men. Both doses increased (vs. old basal) mean 24-h GH, integrated area under the GH curve, and GH peak number (P < 0.05), as well as serum IGF-I (P < 0.001). Interpeak GH levels also increased during low (P < 0.01) and high (P < 0.05) dose treatment. Significant increases in mean GH and integrated area under the GH curve occurred only during the day (0800-2000 h) during both low (P < 0.01) and high (P < 0.05) dose treatment. Treatment also decreased nocturnal peak GH amplitude and duration. GH responses to GHRH stimulation tests did not differ with age at baseline, or in old men after treatment. Thus, continuous, short-term sc administration of GHRH to healthy old men restores subnormal GH secretion and IGF-I levels by increasing GH peak frequency and interpeak secretion, particularly during the day.

Adult↗
PubMed1992

Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men.

Aging is associated with decreased GH and insulin-like growth factor-I (IGF-I) levels and lean body mass, and increased body fat. Recombinant human GH treatment of old men partially reverses body composition changes. Administration of GH-releasing hormone (GHRH) to GH-deficient children and young adults increases GH and IGF-I levels while preserving physiological GH release. We investigated whether GHRH injections restore GH and IGF-I levels in old men to the levels in young men. Healthy young (n = 9; 26.2 +/- 4.1 yr; mean +/- SD) and old (n = 10; 68.0 +/- 6.2 yr) nonobese men underwent baseline blood sampling for measurements of IGF-I and 24-h profiles of GH release, followed by iv bolus GHRH stimulation tests. Old men then took, randomly, both low (0.5 mg) and high (1 mg) dose GHRH-(1-29) sc injections twice daily for 14 days, with an intervening 14-day nontreatment period. The study protocol was repeated on day 14 of each treatment. At baseline, the mean peak duration of spontaneous GH release (P less than 0.005) and IGF-I levels (P less than 0.0001) were lower in the old men. GHRH treatment evoked dose-related increases in all parameters, with significant differences (vs. old basal values) in mean 24-h GH (P less than 0.001), area under peaks (P less than 0.001), peak amplitude (P less than 0.05), and IGF-I (P less than 0.005) only at the high dose. After high dose treatment, there were no significant differences in these parameters between age groups. Peak and integrated responses to iv GHRH stimulation tests did not differ between young and old men either before or during GHRH treatment. Baseline serum levels of both testosterone (P less than 0.01) and phosphate (P less than 0.05) were lower in the older men. Phosphate levels increased (P less than 0.05) during GHRH treatment. GHRH treatment did not affect fasting glucose, urinary C-peptide, blood pressure, or chemistry and hematology profiles. Thus, short term sc administration of GHRH to healthy old men reverses age-related decreases in GH and IGF-I, suggesting that prolonged treatment could improve age-related alterations in body composition.

Adipose Tissue↗
PubMed1991

Transdermal estradiol with oral progestin: biological and clinical effects in younger and older postmenopausal women.

The purpose of this study was to compare the biochemical and clinical effects of transdermal estrogen replacement therapy (tERT) in younger and older postmenopausal women. We treated 15 younger (less than 60 y) and 13 older (greater than or equal to 60 y) healthy postmenopausal women (45-72 y) with four successive 8-week regimens of tERT at doses of 0 to 150 micrograms/day, combined with cyclic oral medroxyprogesterone acetate (MPA). In both age groups, there were similar (p = .0001) dose-responsive increases in plasma estrogen levels and decreases in LH and FSH levels, although LH values were lower in older women both before and after tERT (p less than .02). The addition of MPA further suppressed LH and, to a lesser extent, FSH in both younger and older women. The ratio of estrogenized to nonestrogenized vaginal cells increased with tERT (p less than .007) in both age groups, but significant symptomatic improvement of vaginal irritation was noted only at the highest tERT dose. Adverse effects unrelated to age included short-term nausea in 4/28 women, and skin irritation at the patch sites in 20/28 women. Vaginal bleeding was of shorter duration, but breast tenderness was more common in older women. Further studies of long-term tERT effects in elderly women are indicated.

Administration, Cutaneous↗
PubMed1991

Effects of progestin-opposed transdermal estrogen administration on growth hormone and insulin-like growth factor-I in postmenopausal women of different ages.

Prior studies in women have shown a positive correlation of endogenous estrogen levels with spontaneous and stimulated GH secretion and basal insulin-like growth factor-I (IGF-I) levels. In postmenopausal women, estrogen replacement therapy (ERT) by the oral route increases basal and GHRH-stimulated GH secretion but decreases basal IGF-I levels. To assess the corresponding effects of transdermal ERT (tERT) on this axis, we administered four 8-week regimens of transdermal 17 beta-estradiol (Estraderm; 0, 50, 100, or 150 micrograms/day) combined with oral medroxyprogesterone acetate (10 mg each day) during weeks 3-4 and 7-8 of each 8-week regimen (except placebo) to 28 healthy nonobese postmenopausal women, aged 45.3-71.8 yr. Basal levels of estradiol (E2), GH, and IGF-I as well as GH responsivity to bolus iv administration of GH-releasing hormone-(1-44) (1 micrograms/kg), were measured before tERT and at weeks 6 and 8 of each regimen; estrone (E1) levels were measured before tERT and at week 6 of each regimen. Before tERT, age was inversely correlated with both the peak GH response to GHRH (r = -0.43; P less than 0.02) and basal IGF-I levels (r = -0.37; P less than 0.05), but not with basal E2, E1, or GH levels. There were progressive increases in plasma E2 and E1 levels with increasing doses of tERT (P = 0.0001), independent of age (P greater than 0.2) and body mass index (P greater than 0.2). Mean basal GH and IGF-I levels were not altered significantly by tERT or medroxyprogesterone acetate. Peak and integrated GH secretory responses to exogenous GHRH decreased with increasing tERT dose (P less than 0.01) in both younger and older postmenopausal women. Our findings suggest that the known effects of tERT on bone and other tissues are not mediated via increases in circulating levels of immunoreactive GH or IGF-I, but do not preclude the possibility of tERT-induced increases in the biological activity or paracrine action of IGF-I.

Aged↗
PubMed1991

Spontaneous and glucocorticoid-inhibited adrenocorticotropic hormone and cortisol secretion are similar in healthy young and old men.

We investigated the effects of age on pituitary-adrenocortical function in healthy young (21-38 yr, n = 11) vs. old (66-78 yr, n = 11) men by drawing frequent serial basal blood samples from 2000-0800 h for measurement of ACTH and cortisol, followed by an iv ovine CRH (oCRH) stimulation test. Subjects were readmitted at intervals and given increasing doses of oral dexamethasone (0.15, 0.3, 0.6, 1 mg) at midnight, followed by repeat blood sampling from 0400-0800 h and oCRH testing. We compared mean hormone levels for the entire 12-h and three component 4-h periods of the basal visit, and for each 4-h dexamethasone visit using the Mann-Whitney U test and repeated measures analysis of variance. Pulsatile secretion was characterized using the Pulsar computer program. Basal mean 12-h and 4-h ACTH and cortisol values did not differ with age (P greater than 0.1). Pulse analysis revealed no age change in the corresponding values for peak frequency, amplitude, or duration for either hormone examined. Increasing doses of dexamethasone produced progressive inhibition of mean ACTH and cortisol levels (P less than 0.001) as well as decreased (P less than 0.01) pulse frequency, amplitude, and duration with no age differences (P greater than 0.1). ACTH and cortisol responses to oCRH were progressively suppressed by increasing doses of dexamethasone (P less than 0.02) and did not differ between age groups (P greater than 0.3) except for a slightly higher peak cortisol response (P = 0.05) in the older men at the 0.3 mg dexamethasone dose. We conclude that basal and oCRH-stimulated ACTH and cortisol secretion, as well as sensitivity of the ACTH-cortisol axis to glucocorticoid feedback suppression, are essentially unaltered with age in healthy men.

Adrenocorticotropic Hormone↗
PubMed1990

Thyroid hormone elevations during acute psychiatric illness: relationship to severity and distinction from hyperthyroidism.

Acute psychiatric illness may be accompanied by transient hyperthyroxinemia. The mechanism of this phenomenon was examined by determining the role of thyrotropin (TSH) in the genesis of this state. Serial measurements of TSH, thyroxine (T4), free T4 index (FT4I), triiodothyronine (T3), and free T3 index (FT3I) were performed in 45 acutely hospitalized patients with major psychiatric disorders. Twenty-two (49%) patients exhibited significant elevations (greater than or equal to 2 SD above mean value of controls) of one or more thyroid hormone (or index) levels. Among depressed patients with elevated FT4I, TSH was higher (p less than .05) on the day of the peak FT4I than on the day of the FT4I nadir. There were significant positive correlations between psychiatric symptom severity and levels of FT4I among both depressed (p less than .01) and schizophrenic (p less than .025) patients. These data show that elevations of T4, FT4I, T3, and FT3I are common among psychiatric inpatients, especially early in their hospitalization, and that levels of thyroid hormones are correlated with severity of psychiatric symptomatology. TSH is higher early in the acute phase of illness and is not suppressed in the face of elevated thyroid hormone levels, a finding that distinguishes this phenomenon from ordinary hyperthyroidism. Elevations of peripheral thyroid hormone levels, particularly among depressed patients, may result from a centrally-mediated hypersecretion of TSH.

Adult↗
PubMed1988

Comparison of the effects of lung cancer, benign lung disease, and normal aging on pituitary-gonadal function in men.

We retrospectively determined serum total testosterone (T), fraction of T bound, free T index, LH, and FSH levels in 122 men with malignant lung disease, 32 men with benign lung disease, and 106 normal men. Men with malignant and, to a lesser extent, benign lung disease had decreased serum total T and free T index values at the 5th percentiles, with elevations of LH and FSH levels at the 95th percentiles. Linear regression analysis showed reductions in total T and free T index and increases in FSH, but not LH, levels with age in each group. Using multivariate analysis, we found stronger independent effects of disease than age on serum total T and fraction of T bound, but a greater influence of age on free T index. Serum LH values differed by diagnosis, whereas FSH differed by age. Relative to values in the normal men, mean serum total T levels were reduced in men with lung cancer; the fraction of T bound was decreased in the men with lung cancer and increased in the men with benign lung disease, the free T index was decreased in the men with both malignant and benign lung disease, and LH was increased in the men with lung cancer. The hormone and hormone binding results were similar in men with different types of lung cancer. Biochemical evidence of primary and secondary (or combined primary and secondary) hypogonadism was present in 50-59% and 28-32%, respectively, of the men with malignant and benign lung disease vs. 10% of the normal men. These data suggest that 1) there is an increased prevalence of both pituitary gonadotropic and testicular dysfunction in men with malignant and, to a lesser extent, benign chronic lung disease, and 2) the effects of illness are independent of, and quantitatively greater than, those due to age.

Adult↗
PubMed1987

Reproductive hormones in aging men. III: Basal and LHRH-stimulated serum concentrations of the common alpha-subunit of the glycoprotein hormones.

In a previous study, we described unaltered basal serum levels of sex steroids, increased basal luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and diminished and/or delayed gonadotropin responses to exogenous luteinizing hormone releasing hormone (LHRH) in 69 healthy men, aged 25 to 89 years, in the Baltimore Longitudinal Study of Aging. Here we report basal and LHRH-stimulated serum concentrations of the common alpha-subunit of the glycoprotein hormones in 53 of these same men, divided into groups: A, 25 to 49 years, (n = 22); B, 50 to 69 years, (n = 18); and C, 70 to 89 years, (n = 13). There were no significant (p greater than .2) age-related alterations in basal serum concentrations of the alpha-subunit. Using repeated measures analysis of variance (ANOVA), we found a significant difference between basal levels and peak responses to LHRH for alpha-subunit in each group (p less than .001); however, age per se did not influence the magnitude of this response (p greater than .1). Frequency distribution analysis of the time of the peak alpha-subunit response across age groups demonstrated a significant age-related delay in the timing of the peak alpha response (p less than .03). These data, in conjunction with our prior observations, suggest that in healthy men there may be age-related alterations in the secretion and/or metabolic clearance of pituitary gonadotropins and their component subunits.

Adult↗
PubMed1986

Hydrophilic cyclodextrin derivatives enable effective oral administration of steroidal hormones.

Condensation products of beta-cyclodextrin with propylene oxide or epichlorohydrin, which are amorphous and thus very soluble in water, were used to form complexes with testosterone, progesterone, and estradiol. Sublingual/buccal administration of tablets of these complexes led to effective absorption and entry of the hormones into the systemic circulation, followed by gradual elimination; rapid first-pass loss was avoided. beta-Cyclodextrin itself, its 2,6-dimethyl derivative, and a nonionic detergent did not enable effective buccal absorption. Absorption from the GI tract of hormones complexed with hydrophilic cyclodextrins was also less effective. Effective absorption of drugs from the oral cavity requires (a) that the drug and solubilizer form a complex of the inclusion type which dissolves completely and rapidly and (b) that the solubilizer neither enters nor damages oral tissue.

Administration, Oral↗
PubMed1986

Basal serum prolactin levels and prolactin responses to constant infusions of thyrotropin releasing hormone in healthy aging men.

We measured serum prolactin (PRL) levels by RIA before and during a 240-min constant infusion of TRH (0.4 microgram/min iv) in three similarly sized groups of healthy aging men 30 to 49, 50 to 69, and 70 to 96 years. Basal data were evaluated by analysis of variance with Duncan's multiple range test and regression analysis. Mean basal serum PRL level was elevated (p less than .05) in the oldest group, attributable to PRL elevations (between 20 and 40 ng/ml) in 4 men over 75 years. Serum PRL levels decreased (p less than .001) from -30 min to 0 min before TRH infusion in all groups, but there was no age-dependent difference (p greater than .3) in the magnitude of the reduction. Repeated measures analysis of variance showed increased serum PRL levels (p less than .001) during TRH infusion in all age groups, and an age-dependent increase (p less than .05) in magnitude of peak PRL response. This significant difference was between the two oldest age groups early in the infusion. Chi-square analysis revealed an increased (p less than .05) frequency of early (less than 120 min) peak responses in the oldest age group. The present data suggest that basal and TRH-stimulated PRL secretion may be augmented in some healthy older men.

Adult↗
PubMed1986

Responses of growth hormone (GH) and somatomedin-C to GH-releasing hormone in healthy aging men.

Although controversy exists regarding the effects of aging on GH secretory responses to indirect stimulation, in the only prior study of GH-releasing hormone (GHRH)-mediated GH secretion decreased GH responsivity occurred in healthy men after age 40 yr. We measured serum GH before and up to 180 min after and somatomedin-C (SM-C) levels before and 24 h after single morning bolus iv injections of GHRH-(1-44)-NH2 (1 microgram/kg) in 50 healthy fasted men, aged 21-86 yr, from the Baltimore Longitudinal Study of Aging. Only subjects with a body mass index (BMI; kilograms per m2) between 20.0 and 29.0 were studied. Basal serum GH levels were undetectable (less than 0.7 ng/ml) in all but 2 men. Neither the frequency of GH responses (P greater than 0.8), the magnitude of response (P greater than 0.2), nor the timing (P greater than 0.05) of the peak GH responses to GHRH were significantly altered with age. Although BMI values did not vary significantly with age in our study group, there was a significant negative correlation (r = -0.37; P less than 0.01) of peak GH with BMI. Regression analysis revealed a slight but significant increase in the level of fasting blood sugar with age, but no significant correlation between fasting blood sugar and peak GH levels. Serum levels of SM-C were significantly lower in older men both before (P less than 0.001) and 24 h after (P less than 0.02) GHRH injection. Repeated measures analysis of variance revealed significant (P less than 0.001) responses of SM-C to endogenous GH elevations produced by GHRH at all ages, but no age-dependent alterations in the magnitudes of these responses (P greater than 0.7). Our findings suggest that increasing age in adult men has little effect on the secretory responsiveness of pituitary somatotropes to GHRH. However, the finding of lower serum levels of SM-C with intact SM-C responsivity to endogenous GH is compatible with prior observations of an age-related decrease in the total daily spontaneous secretion of GH.

Adult↗
PubMed1986

Responses of plasma adrenocorticotropin, cortisol, and dehydroepiandrosterone to ovine corticotropin-releasing hormone in healthy aging men.

To assess the effects of age on both the pituitary ACTH response to corticotropin-releasing hormone (CRH) and the secretory responses of cortisol (F) and dehydroepiandrosterone (DHEA) to endogenous rises in ACTH, we measured evening basal and ovine CRH (oCRH; 1 mu/kg)-stimulated plasma concentrations of ACTH,F, and DHEA in 49 healthy men, aged 21-86 yr. By analysis of variance, we found no change with age in either the basal concentration of ACTH or the magnitude of the peak ACTH response to oCRH. Older men had higher basal F levels (P less than 0.05), while basal plasma levels of CBG and ratios of F to CBG did not vary significantly with age (P greater than 0.1). We also found no significant increase with age in the magnitude of the peak F response to oCRH (P greater than 0.2), although peak F responses occurred significantly earlier (P less than 0.03) in the older men. Basal plasma levels of DHEA decreased significantly with age (P less than 0.001), as did the magnitude of peak DHEA responses to endogenous ACTH rises (P less than 0.01). There was no alteration in the timing of the peak DHEA response with age (P greater than 0.7). We conclude that while ACTH and F responses to evening injections of oCRH are well maintained in healthy aging men, that of DHEA is discordantly decreased. The present findings are compatible with the hypotheses that there is a diminished sensitivity of ACTH secretion to negative feedback regulation by glucocorticoids in older men, and there is an ACTH-independent age-related diminution in adrenal androgen secretion.

Adrenocorticotropic Hormone↗