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S Mitchell Harman

Publications and source records attributed to S Mitchell Harman.

13 recordsLinked to original sources
PubMed2003

Relation of aggressiveness of lipid-lowering treatment to changes in calcified plaque burden by electron beam tomography.

The comparative effects of more versus less aggressive low-density lipoprotein (LDL) cholesterol lowering (to </=80 vs >80 mg/dl) on calcified coronary plaque progression by electron beam tomography were evaluated in 182 consecutive asymptomatic patients after 1.2 years of treatment with statins alone or in combination with niacin. Despite the greater improvement in lipids in the </=80 versus >80 mg/dl groups, there were no differences in calcified plaque progression (9.3%/year vs 9.1%/year). We conclude that, with respect to LDL cholesterol lowering, "lower is better" is not supported by changes in calcified plaque progression.

Calcinosis↗
PubMed2003

Quantification of 8-iso-prostaglandin-F(2alpha) and 2,3-dinor-8-iso-prostaglandin-F(2alpha) in human urine using liquid chromatography-tandem mass spectrometry.

Quantification of 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) has been suggested to be a reliable indicator of lipid peroxidation that may be related to in vivo free radical generation, oxidative damage, and antioxidant deficiency. We have developed a LC-MS/MS method to quantify 8-iso- PGF(2alpha) and its dinor metabolite, 2,3-dinor-8-iso-prostaglandin F(2alpha) (2,3-dinor-8-iso-PGF(2alpha)), in human urine samples. After an initial purification step using an automated C18 solid phase extraction procedure, the urine sample was injected directly into a liquid chromatography (LC) system and detected with tandem mass spectrometry. The detection limit of the assay was 9 pg for 8-iso-PGF(2alpha) and 3 pg for 2,3-dinor-8-iso-PGF(2alpha) with both inter- and intraday variations of less than 12%. The inaccuracies were less than 3% for both analytes at three different levels. The urinary excretion rate of 2,3-dinor-8-iso-PGF(2alpha) was higher than that of 8-iso-PGF(2alpha), and changed in proportion to the parent compound (R = 0.70, n = 60). Values obtained with this method showed good linear correlation to duplicate 8-iso-PGF(2alpha) measurements performed with GCMS (R = 0.97, n = 15). The mean excretion rates of 8-iso-PGF(2alpha) and 2,3-dinor-8-iso-PGF(2alpha) were significantly higher in smokers than in nonsmokers (0.53 +/- 0.37 vs. 0.25 +/- 0.15 microg/g creatinine, p = 0.002 for 8-iso-PGF(2alpha) and 8.9 +/- 3.8 vs. 4.6 +/- 2.6 microg/g creatinine, p = 0.003 for 2,3-dinor-8-iso-PGF(2alpha), respectively). The excellent accuracy, reproducibility, and high throughput of this method should permit it to be used in large clinical studies and standard clinical laboratories.

Chromatography, High Pressure Liquid↗
PubMed2003

Comparison of the effects of atorvastatin versus simvastatin on subclinical atherosclerosis in primary preventionas determined by electronbeam tomography.

This study was designed to evaluate the effects of lipid-lowering therapy by atorvastatin versus simvastatin on calcified plaque progression, as determined by serial electron beam tomography (EBT), in primary prevention patients. In this observational study, serial EBT was performed before and after 1.2 years of atorvastatin (n = 103) and simavastatin therapy (n = 46); approximately 50% of each group was on niacin as well, in similar doses. There were no differences in demographic parameters between the groups. Total, low-density lipoprotein (LDL), and non-high-density lipoprotein (HDL) cholesterol were significantly higher in the atorvastatin group before treatment. Before treatment, EBT calcium score and volume scores were 469 and 378, respectively, in the atorvastatin patients, and 388 and 307, respectively, in the simvastatin patients (p = NS, atorvastatin vs simvastatin). After treatment, there were no differences in any lipid or EBT values between the groups. Post-treatment total cholesterol and LDL cholesterol were 156 and 79 mg/dl, respectively, in the atorvastatin cohort and 154 and 76 mg/dl, respectively, in the simvastatin group (p = NS). Calcium score and volume progressed 10.8%/year and 8.5%/year, respectively, in the atorvastatin group, and 7.5%/year and 7.8%/year in the simvastatin group (p = NS, atorvastatin vs simvastatin). We conclude that aggressive treatment with atorvastatin and simvastatin in the primary prevention population, to similar lipid levels, is associated with equal progression of EBT-determined calcified plaque. This suggests that these hydroxymethylglutaryl coenzyme A reductase inhibitors exhibit a "class effect" with respect to progression of subclinical atherosclerosis.

Analysis of Variance↗
PubMed2003

The Kronos longevity research institute.

The Kronos Longevity Research Institute (KLRI), founded in Jan., 2000, is a Phoenix-based not-for-profit institution conducting clinical translational research aimed at early detection and prevention of age-related diseases and slowing or reversing the aging process. KLRI also provides education in biomedical gerontology for regional and national professional and lay communities. KLRI is privately funded, mainly by the Aurora Foundation. S. Mitchell Harman, M.D., Ph.D., founding Director and President is board-certified in internal medicine and endocrinology and a former section chief and acting clinical director of the National Institute on Aging, NIH, with an international reputation as a leader in the field of hormones and aging. Other professional staff are: a Clinical Director, Director of Exercise Sciences, Senior Scientist, and Clinical Study Coordinator. KLRI's facility includes a clinical study center (CSC), an exercise study center (ESC), and a molecular laboratory. Current research focuses on relationships among aging, endocrine function, oxidative stress, and sarcopenia. All research projects are pre-reviewed by KLRI's Scientific Advisory Board, a distinguished group of biomedical investigators. KLRI sponsors a series of bimonthly seminars in Phoenix and an annual two-day national symposium, with talks on biomedical gerontology presented by world-renowned experts. The institute has plans to double faculty, staff, and research activities by 2006, which will require new sources of funding. The aging demography of the first half of the century will make KLRI's research increasingly relevant to the population of the U.S. and the world.

Academies and Institutes↗
PubMed2003

The effects of growth hormone and sex steroid on lean body mass, fat mass, muscle strength, cardiovascular endurance and adverse events in healthy elderly women and men.

Decreases in growth hormone (GH) and insulin-like growth factor I occur with age, in addition to oestrogen deficiency in women and a reduction in the levels of testosterone in men. These age-related hormonal changes may contribute to reductions in lean body mass, muscle strength and cardiac endurance, which can be partially reversed in elderly people with GH treatment, and testosterone supplements and oestrogen/progestin hormone replacement therapy in men and women, respectively. These treatments are, however, thought to have potentially serious adverse effects. We conducted a study to evaluate the separate and interactive effects of GH and sex steroids on body composition, muscle strength and cardiac endurance as well as the rate of adverse events in healthy elderly people. The results of the study showed that although there were beneficial effects with GH and sex steroid treatment, a high percentage of adverse effects occurred after 26 weeks of treatment, demonstrating a need for more research on the safety of hormonal therapy in the elderly population.

Adipose Tissue↗
PubMed2002

Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial.

CONTEXT: Hormone administration to elderly individuals can increase lean body mass (LBM) and decrease fat, but interactive effects of growth hormone (GH) and sex steroids and their influence on strength and endurance are unknown. OBJECTIVE: To evaluate the effects of recombinant human GH and/or sex steroids on body composition, strength, endurance, and adverse outcomes in aged persons. DESIGN, SETTING, AND PARTICIPANTS: A 26-week randomized, double-blind, placebo-controlled parallel-group trial in healthy, ambulatory, community-dwelling US women (n = 57) and men (n = 74) aged 65 to 88 years recruited between June 1992 and July 1998. INTERVENTIONS: Participants were randomized to receive GH (starting dose, 30 micro g/kg, reduced to 20 micro g/kg, subcutaneously 3 times/wk) + sex steroids (women: transdermal estradiol, 100 micro g/d, plus oral medroxyprogesterone acetate, 10 mg/d, during the last 10 days of each 28-day cycle [HRT]; men: testosterone enanthate, biweekly intramuscular injections of 100 mg) (n = 35); GH + placebo sex steroid (n = 30); sex steroid + placebo GH (n = 35); or placebo GH + placebo sex steroid (n = 31) in a 2 x 2 factorial design. MAIN OUTCOME MEASURES: Lean body mass, fat mass, muscle strength, maximum oxygen uptake (VO(2)max) during treadmill test, and adverse effects. RESULTS: In women, LBM increased by 0.4 kg with placebo, 1.2 kg with HRT (P =.09), 1.0 kg with GH (P =.001), and 2.1 kg with GH + HRT (P<.001). Fat mass decreased significantly in the GH and GH + HRT groups. In men, LBM increased by 0.1 kg with placebo, 1.4 kg with testosterone (P =.06), 3.1 kg with GH (P<.001), and 4.3 kg with GH + testosterone (P<.001). Fat mass decreased significantly with GH and GH + testosterone. Women's strength decreased in the placebo group and increased nonsignificantly with HRT (P =.09), GH (P =.29), and GH + HRT (P =.14). Men's strength also did not increase significantly except for a marginally significant increase of 13.5 kg with GH + testosterone (P =.05). Women's VO(2)max declined by 0.4 mL/min/kg in the placebo and HRT groups but increased with GH (P =.07) and GH + HRT (P =.06). Men's VO(2)max declined by 1.2 mL/min/kg with placebo and by 0.4 mL/min/kg with testosterone (P =.49) but increased with GH (P =.11) and with GH + testosterone (P<.001). Changes in strength (r = 0.355; P<.001) and in VO(2)max (r = 0.320; P =.002) were directly related to changes in LBM. Edema was significantly more common in women taking GH (39% vs 0%) and GH + HRT (38% vs 0%). Carpal tunnel symptoms were more common in men taking GH + testosterone (32% vs 0%) and arthralgias were more common in men taking GH (41% vs 0%). Diabetes or glucose intolerance occurred in 18 GH-treated men vs 7 not receiving GH (P =.006). CONCLUSIONS: In this study, GH with or without sex steroids in healthy, aged women and men increased LBM and decreased fat mass. Sex steroid + GH increased muscle strength marginally and VO( 2)max in men, but women had no significant change in strength or cardiovascular endurance. Because adverse effects were frequent (importantly, diabetes and glucose intolerance), GH interventions in the elderly should be confined to controlled studies.

Aged↗
PubMed2002

Growth hormone and sex steroid effects on bone metabolism and bone mineral density in healthy aged women and men.

BACKGROUND: Aging is associated with concomitant declines in activity of the growth hormone (GH) and gonadal steroid axes, and in bone mineral density (BMD), in both sexes. Long-term estrogen replacement slows bone loss and prevents fractures in postmenopausal women, whereas the effects of supplementation of GH or testosterone on bone metabolism and BMD in aged individuals remains uncertain. METHODS: Using a randomized, placebo-controlled, double-blind study design, we investigated the separate and interactive effects of 6 months of administration of recombinant human GH and/or gonadal steroids on bone biochemical markers and BMD in 125 healthy, older (>65 years) women (n = 53) and men (n = 72) with age-related reductions in GH and gonadal steroids. RESULTS: In women, administration of GH, but not GH + hormone replacement therapy (HRT), increased serum levels of osteocalcin and procollagen peptide (PICP) and increased urinary excretion of deoxypyridinoline (DPD) crosslinks. Urinary calcium excretion decreased after HRT. In men, GH, and to a greater extent GH + T, increased osteocalcin. GH increased serum PICP, and GH + T increased urinary DPD. Urinary calcium excretion was unaffected by hormone treatment in men. In women, administration of HRT and GH + HRT, but not GH, increased BMD at the lumbar spine, femoral neck, and distal radius. In men, GH + T led to a small decrease in BMD at the proximal radius; there were no other significant effects of hormone administration on BMD. CONCLUSIONS: These data suggest that short-term administration of HRT exerts beneficial effects on bone metabolism and BMD in postmenopausal women, which are not significantly altered by the coadministration of GH. In andropausal men, T administration to achieve physiologic levels did not result in significant effects on bone metabolism or BMD, whereas GH + T increased one marker of bone formation and decreased one marker of bone resorption. Given the known biphasic actions of GH on bone and the apparent favorable biochemical effects of GH + T in men, the longer-term effects of GH + T on BMD in aged men remain to be clarified.

Aged↗
PubMed2002

Is there an antiaging medicine?

In spite of considerable hype to the contrary, there is no convincing evidence that currently existing so-called "antiaging" remedies promoted by a variety of companies and other organizations can slow aging or increase longevity in humans. Nevertheless, a variety of experiments with laboratory animals indicate that aging rates and life expectancy can be altered. Research going back to the 1930s has shown that caloric restriction (also called dietary restriction) extends life expectancy by 30-40% in experimental animals, presumably at least partially by delaying the occurrence of age-dependent diseases. Mutations that decrease production of insulin growth factor I in laboratory mammals, and those that decrease insulin-like signaling in nematodes and fruit flies, have increased life expectancy as well. Other general strategies that appear promising include interventions that reduce oxidative stress and/or increase resistance to stress; hormone and cell replacement therapies may also have value in dealing with specific age-related pathologies. This article reports the findings of a consensus workshop that discussed what is known about existing and future interventions to slow, stop, or reverse aging in animals, and how these might be applied to humans through future research.

Aging↗
PubMed2002

Interrelationships of serum testosterone and free testosterone index with FFM and strength in aging men.

Muscle mass and strength losses during aging may be associated with declining levels of serum testosterone (T) in men. Few studies have shown a direct relationship between T and muscle mass and strength. Subjects were 262 men, aged 24-90 yr, from the Baltimore Longitudinal Study of Aging, who had T and sex hormone-binding globulin sex hormone-binding globulin (SHBG) measurements, from which the free T index (FTI) was calculated (T/SHBG) from serum samples collected longitudinally since 1963, total body fat mass and arm and leg fat-free mass (FFM) by dual-energy X-ray absorptiometry and arm and leg strength by dynanomometry. Mixed-effects models estimated T and FTI at the time of mass and strength measurements. Age, total body fat, arm and leg FFM, T, and FTI were significantly associated with concentric and eccentric strength. FTI, not T, was modestly, but directly, related to arm and leg strength after fat, arm and leg FFM, height, and age were accounted for and indirectly through body mass. FTI is a better predictor of arm and leg strength than T in aging men.

Adult↗
PubMed2002

Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men.

Circulating testosterone (T) levels have behavioral and neurological effects in both human and nonhuman species. Both T concentrations and neuropsychological function decrease substantially with age in men. The purpose of this prospective, longitudinal study was to investigate the relationships between age-associated decreases in endogenous serum T and free T concentrations and declines in neuropsychological performance. Participants were volunteers from the Baltimore Longitudinal Study of Aging, aged 50-91 yr at baseline T assessment. Four hundred seven men were followed for an average of 10 yr, with assessments of multiple cognitive domains and contemporaneous determination of serum total T, SHBG, and a free T index (FTI). We administered neuropsychological tests of verbal and visual memory, mental status, visuomotor scanning and attention, verbal knowledge/language, visuospatial ability, and depressive symptomatology. Higher FTI was associated with better scores on visual and verbal memory, visuospatial functioning, and visuomotor scanning and a reduced rate of longitudinal decline in visual memory. Men classified as hypogonadal had significantly lower scores on measures of memory and visuospatial performance and a faster rate of decline in visual memory. No relations between total T or the FTI and measures of verbal knowledge, mental status, or depressive symptoms were observed. These results suggest a possible beneficial relationship between circulating free T concentrations and specific domains of cognitive performance in older men.

Aged↗