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Biomedical subjects

R Marcus

Publications and source records attributed to R Marcus.

At least 37 records · Page 2Linked to original sources
PubMed1998

Relationship of chronic endurance exercise to the somatotropic and sex hormone status of older men.

To investigate putative abrogating effects of habitual endurance exercise on age-related changes in endocrine function and body composition, we compared insulin-like growth factor-I (IGF-I), sex hormonal status and body composition in 15 Masters runners and 15 minimally exercising men (MEM) aged 60-70 years. A higher maximal oxygen uptake (VO2 max.) in the runners (41.4+/-1.6 compared with 27.3+/-1.4 ml/kg/min, P=0.0001; mean+/-S.E.M.) reflected our group allocations. Analysis of body composition and bone mineral density (BMD) by dual energy X-ray absorptiometry showed no group differences in lean tissue mass or in regional or whole body BMD, but MEM were heavier, reflecting greater adiposity. Of nine muscle groups tested, only quadriceps strength differed significantly, being greater in runners (60.3+/-2.8 compared with 51.1+/-2.3 kg, P=0.02). Total IGF-I (129+/-10 compared with 124+/-11 ng/ml, P=0.72) and IGF-binding protein-3 (2854+/-94 compared with 2623+/-128ng/ml, P=0.16), were similarly depressed compared with young adult norms in both groups. There was no relationship between total or bioavailable IGF-I and any body composition, BMD or muscle strength variable. In the runners, concentrations of total testosterone (19.1+/-0.8 compared with 15.0+/-0.9 nmol/l, P=0.002) and sex hormone binding globulin (SHBG) (124.4+/-21.6 compared with 67.7+/-11.6 nmol/l, P=0.03) were significantly greater, but the free androgen index was significantly lower (20.7+/-2.7 compared with 31.4+/-4.1, P=0.04). Directly measured free testosterone, however, was similar between the runners and MEM (47.9+/-1.8 compared with 47.1+/-2.0 nmol/l P=0.80). Therefore the group differences in total testosterone and free androgen index were due to their different SHBG concentrations. Although estrone concentration was higher in MEM (85.1+/-5.2 compared with 108+/-6.7 pmol/l, P=0.03), estradiol concentration was similar between groups (73.0+/-6.3 compared with 81.8+/-8.0 pmol/l, P=0.18), indicating that estrogens were not responsible for the increased SHBG in runners. These results indicate that even high levels of regular endurance exercise do not prevent the decline in the somatotropic axis that occurs with aging. Furthermore, the somatic effects of exercise in older men (reduced adiposity and increased regional muscle strength) occurred independently of somatotropic or androgen status. Although habitual exercise does not influence free testosterone concentrations in older men, it appears to enhance the age-associated increase in SHBG synthesis.

Aged↗
PubMed1997

A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group.

BACKGROUND: The average risk of human immunodeficiency virus (HIV) infection after percutaneous exposure to HIV-infected blood is 0.3 percent, but the factors that influence this risk are not well understood. METHODS: We conducted a case-control study of health care workers with occupational, percutaneous exposure to HIV-infected blood. The case patients were those who became seropositive after exposure to HIV, as reported by national surveillance systems in France, Italy, the United Kingdom, and the United States. The controls were health care workers in a prospective surveillance project who were exposed to HIV but did not seroconvert. RESULTS: Logistic-regression analysis based on 33 case patients and 665 controls showed that significant risk factors for seroconversion were deep injury (odds ratio= 15; 95 percent confidence interval, 6.0 to 41), injury with a device that was visibly contaminated with the source patient's blood (odds ratio= 6.2; 95 percent confidence interval, 2.2 to 21), a procedure involving a needle placed in the source patient's artery or vein (odds ratio=4.3; 95 percent confidence interval, 1.7 to 12), and exposure to a source patient who died of the acquired immunodeficiency syndrome within two months afterward (odds ratio=5.6; 95 percent confidence interval, 2.0 to 16). The case patients were significantly less likely than the controls to have taken zidovudine after the exposure (odds ratio=0.19; 95 percent confidence interval, 0.06 to 0.52). CONCLUSIONS: The risk of HIV infection after percutaneous exposure increases with a larger volume of blood and, probably, a higher titer of HIV in the source patient's blood. Postexposure prophylaxis with zidovudine appears to be protective.

Analysis of Variance↗
PubMed1997

Lymphocyte predominant Hodgkin disease: clinico-pathologic features and results of treatment--the Pediatric Oncology Group experience.

PURPOSE: In this report, the Pediatric Oncology Group (POG) experience with lymphocyte predominant Hodgkin Disease (LPHD) in children is reviewed. MATERIALS AND METHODS: From 1984-1993, the POG conducted 3 clinical trials for advanced stage HD and 2 for early stage HD. There were 26 cases of LPHD in 613 patients in these trials. Patients' ages ranged from 3.1-17.8 years (mean of 12.9 years). There was a marked male predominance. RESULTS: Histologic subtypes were 17 nodular, 8 diffuse pattern; 1 was indeterminant. The sites involved at diagnosis were primarily the peripheral lymph nodes. Fourteen patients had stage (S) I disease; 9 had SII; 3 had SIII; there was no SIV disease. Only 4 of 26 patients had B symptoms. All 26 patients achieved complete remission, 10 with radiotherapy, 6 with chemotherapy and 10 with combined modality therapy. Treatment was not uniform since patients were registered on different protocols. Event-free survival after 5 years was 86.5 percent. Two patients developed and succumbed to large cell, T-cell type, non-Hodgkin lymphoma (NHL). CONCLUSIONS: Optimal treatment for LPHD should focus on efforts to limit the risk of second malignancy.

Adolescent↗
PubMed1997

Correspondence between theoretical models and dual energy x-ray absorptiometry measurements of femoral cross-sectional growth during adolescence.

We have developed an analytical model of long bone cross-sectional ontogeny in which appositional growth of the diaphysis is primarily driven by mechanical stimuli associated with increasing body mass during growth and development. In this study, our goal was to compare theoretical predictions of femoral diaphyseal structure from this model with measurements of femoral bone mineral and geometry by dual energy x-ray absorptiometry. Measurements of mid-diaphyseal femoral geometry and structure were made previously in 101 Caucasian adolescents and young adults 9-26 years of age. The data on measured bone mineral content and calculated section modulus were compared with the results of our analytical model of cross-sectional development of the human femur over the same age range. Both bone mineral content and section modulus showed good correspondence with experimental measurements when the relationships with age and body mass were examined. Strong linear relationships were evident for both parameters when examined as a function of body mass.

Absorptiometry, Photon↗
PubMed1997

Associations of vitamin C, calcium and protein with bone mass in postmenopausal Mexican American women.

We investigated the associations of vitamin C, calcium and protein intakes with bone mass at the femoral neck and lumbar spine in postmenopausal Mexican American women. Bone mass was measured by dual-energy X-ray absorptiometry (DXA) and expressed as areal (BMD, g/cm2) and volumetric (bone mineral apparent density or BMAD, g/cm3) bone mineral density. Diet was assessed using a modified version of the National Cancer Institute Food Questionnaire, which was administered by trained bilingual interviewers familiar with Mexican dietary practices. Data gathered from 125 subjects were analyzed using multiple linear regression analysis with age, body mass index (BMI), acculturation, years of estrogen use, physical activity, total energy intake, and the nutrient of interest as independent variables. Neither calcium nor calcium/protein ratio was associated with bone mineral density. There was evidence of a positive association between dietary vitamin C intake and femoral neck BMD (beta = 0.0002 g/cm2 per mg/day, SE = 0.00006, p < 0.05), but vitamin C was not associated with lumbar spine bone mass. Further investigation of the role of vitamin C in skeletal health is warranted.

Aged↗
PubMed1997

Functional consequences of the somatopause and its treatment.

The decline in the function of the growth hormone-releasing hormone, growth hormone, insulin-like growth factor (GHRH-GH-IGF) axis has been termed the somatopause. Many of the catabolic sequelae seen in normal aging has been attributed to this decrease in circulating GH and IGF-I. In order to provide hormone replacement therapy for the somatopause, elderly subjects have been treated with GH, IGF-I, or both hormones together. Whereas numerous beneficial effects on body composition, strength, and quality of life have been reported in some studies, other studies have reported only marginal functional improvements. Moreover, it is clear that both hormones can cause significant morbidity.

Aged↗
PubMed1997

Skeletal status of men with early and late ankylosing spondylitis.

PURPOSE: To assess the influence of extent of disease on the skeletal status of men with ankylosing spondylitis (AS). PATIENTS AND METHODS: Fourteen men with AS were studied at entry and again after 15 months. Bone mineral density (BMD) was assessed by single photon absorptiometry (SPA), dual energy x-ray absorptiometry (DXA), and quantitative computed tomography (QCT). Calciotropic hormones and bone turnover were also assessed, and biopsies of iliac crest and skin were taken after tetracycline double-labeling from 10 subjects. Clinical evaluation and Health Assessment Questionnaires were used to assess functional status. RESULTS: Of the 14 participants, 7 had sacroiliitis alone without radiologic evidence of spinal involvement (early disease) and 7 had sacroiliitis with extensive vertebral calcifications and immobilization (late disease). QCT baseline lumbar spine BMD was very low in both groups compared with normative standards (Z score = -3.08 +/- 1.83, P < 0.0001) and did not change significantly over 15 months. This low BMD was more marked in late disease than in early disease subjects (P < 0.01). DXA BMD at the lumbar spine was lower than predicted in early disease subjects (Z score = -1.08 +/- 0.67, P = 0.005) but not in the late disease group. DXA BMD was also low at the all three hip sites (Z score = -0.96 +/- 0.86, P < 0.01). Significant differences between late disease group and normative values were apparent at all hip sites. Values in early disease subjects, however, did not differ from age-predicted norms. Bone mineral status did not change significantly over the 15-month period of observation. Circulating parathyroid hormone (PTH) and vitamin D metabolites were normal in both groups as were creatinine clearance and urinary excretion of calcium and hydroxyproline. Osteocalcin levels were normal in all but the two youngest subjects in the early disease group. Histomorphometry of the iliac crest showed no consistent change in bone turnover. Bone volume and trabecular width were low in many cases. Cancellous bone volume correlated with lumbar spine BMD by QCT (r = 0.69, P = 0.026) but not with DXA. Although beneficial changes occurred in exercise tolerance and pain over time, anthropometric measurements did not improve. CONCLUSION: BMD is low in both the axial and peripheral skeleton in men with AS and is independent of spinal immobilization. Anterioposterior lumbar spine DXA in late AS is less useful than QCT in determining the degree of osteopenia in late AS. Bone mineral deficits in AS do not reflect measurable metabolic derangement or hypogonadism. Although bone histomorphometry suggests both trabecular thinning and loss of structural elements as mechanisms involved in low bone volume, the exact cause of osteopenia in AS remains to be determined.

Absorptiometry, Photon↗
PubMed1997

Dynamic muscle strength alterations to detraining and retraining in elderly men.

To investigate the effects of cessation and subsequent resumption of training on muscle strength in elderly men, 11 men (aged 65-77 years), just completing a 24-week randomized controlled trial of recombinant human growth hormone (rhGH) and resistance exercise (rhGH, n = 6; placebo, n = 5), detrained for 12 weeks and subsequently retrained for 8 weeks. During the detraining and retraining phase, subjects did not receive rhGH. The resistance programme included three sets of eight repetitions at 75% of one-repetition maximum (1-RM), three times per week, for 10 upper and lower body exercises. Dynamic muscle strength was assessed by the 1-RM method every 2 weeks for 44 weeks. Needle biopsies of vastus lateralis muscle were obtained from seven men. Muscle strength increased during initial training by 40.4 +/- 5.5% (mean +/- SEM), ranging from 26.0 +/- 5.0 to 83.9 +/- 15.6%, depending on muscle group. Increased strength was accompanied by hypertrophy (P < 0.05) of type I (17.4 +/- 4.1%) and II (25.8 +/- 12.4%) muscle fibres. Of initial strength gains, only 29.9 +/- 5.2% was lost with detraining. However, type I and II fibre cross-sectional area reverted to pretraining values. After 8 weeks of retraining, muscle strength returned to trained values, but without a significant change in fibre morphology. The results indicate that elderly men lose some muscle strength following short-term detraining, but that only a brief period of retraining suffices to regain maximal strength. Reversal of fibre cross-sectional area with detraining, and only modest improvement with retraining, suggests that much of the retention in strength with detraining and reacquisition of lost strength with retraining reflects neural adaptation.

Aged↗
PubMed1997

Effect of rhGH and rhIGF-I treatment on protein utilization in elderly women.

To assess the effect of recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor I (rhIGF-I) on protein utilization, 14 women, age 66-82 yr, were invited to participate in studies of nitrogen balance (n = 14), whole body protein turnover (n = 14), and muscle protein synthesis (n = 8). They were studied both 1 wk before and during the last week of a 1-mo regimen, to which they had been randomly assigned, of either 0.025 mg rhGH/kg once daily or rhIGF-I at 0.015 (low), 0.03 (mid), or 0.06 (high) mg/kg twice daily. Nitrogen balance increased significantly after 1 wk of treatment in all groups (P < 0.05). After 1 mo, the magnitude of this effect had diminished by 50% in the rhGH group but remained elevated throughout the treatment period with all doses of rhIGF-I. Both protein synthesis and breakdown, measured by a primed constant infusion of [15N]glycine, were significantly increased with rhGH (9% and 8%, respectively), low-dose rhIGF-I (4.5% and 4%), and high-dose rhIGF-I (18% and 17%). Net synthesis was significantly increased with rhGH (48%) and high- and mid-dose rhIGF-I (27% and 196%, respectively). Muscle protein synthesis as measured by incorporation of [1-13C]leucine increased significantly with rhGH (50%) and the mid (67%) and high (57%) doses of rhIGF-I. These data show that whole body and muscle protein synthesis are responsive to growth factor stimulation in elderly women.

Aged↗
PubMed1997

Skeletal effects of growth hormone and IGF-I in adults.

Three processes occur in the skeleton; modelling during growth, fracture repair and remodelling. Remodelling is bone resorption coupled to bone formation, and alterations in the remodelling balance are the final pathway to bone loss. Therapeutic agents are now available to minimize the normal phenomenon of age-related bone loss and protect against osteoporotic fracture. These agents reduce the rate of bone resorption, have positive effects on bone mass and some reduce fracture rates. None, however, restore bone mineral to normal levels. GH has been considered for this role due to its positive effects in vitro and in vivo. GH-deficient adults have low BMD compared to healthy controls, and the reasons for this finding are discussed. A neglected factor is a measurement artefact from the use of DXA. Long-term GH therapy can lead to clinically important increases in BMD in GH-deficient adults. The results from studies of GH administration to healthy elderly populations are also presented. The small rise of lumbar BMD or maintenance of BMD at the hip seen in these studies are no better than results achieved with cheaper, easier to administer therapies. Investigation of other agents in the somatotrophic axis, are, however, potentially promising and warrant further investigation.

Adult↗
PubMed1997

Skeletal effects of cyclic recombinant human growth hormone and salmon calcitonin in osteopenic postmenopausal women.

The objectives of this study were to determine whether cyclic administration of recombinant human GH, with or without the antiresorptive agent, salmon calcitonin (CT), provides clinically meaningful increases in bone mineral density (BMD) at the lumbar spine and proximal femur in postmenopausal osteopenic women. The design of the study was a randomized clinical trial consisting of 12 56-day treatment cycles. Each cycle was initiated by a 12-day period of hormone administration, followed by 44 days of supplemental calcium only. Cycles of hormone administration consisted of 7 daily injections of recombinant GH (20 micrograms/kg.day) or its placebo, followed by 5 daily injections of salmon CT (100 U/day) or its placebo. The study was performed at the Palo Alto Veterans Affairs medical center. The patients were 84 healthy women with lumbar spine BMD more than 1 SD below the average value for a healthy 25-yr-old Caucasian woman. BMD was measured at the lumbar spine and proximal femur by dual energy x-ray absorptiometry. Biochemical markers of bone turnover and circulating insulin-like growth factor I were also measured. GH treatment increased insulin-like growth factor I concentrations from low values at baseline (112 +/- 56 ng/mL) to the young normal range (approximately 430 +/- 125 ng/mL). Groups receiving GH plus CT or GH plus placebo increased lumbar spine BMD at 2 yr by 2.70 +/- 0.81% (P < 0.01) and 1.72 +/- 0.74% (P < 0.05; intention to treat analysis). No significant change occurred in women receiving placebo plus CT or combined placebo. Significant increases in total hip BMD of 1-2% were observed for the GH plus placebo and placebo plus CT groups, with a nonsignificant trend in the GH plus CT group. For the femoral trochanter, significant increases were observed in the GH plus CT and placebo plus CT groups only. No significant change in femoral neck BMD was observed in any group. Women taking replacement estrogen had the same BMD response as those who were estrogen deficient. No significant increase in BMD was observed between 24 and 36 months in the 62 women who returned for a 3 yr measurement. In response to GH, short term increases in resorption and formation markers were observed, but these had decreased before the next treatment cycle. No long term changes in resorption markers were observed, but women in the GH groups showed a sustained rise in circulating osteocalcin over the entire 2-yr protocol. GH given cyclically with or without CT for 2 yr achieved statistically significant increases in BMD of the lumbar spine and selected areas of the hip in postmenopausal women. These gains were less marked than those achieved with estrogen or bisphosphonates and were associated with a relatively high incidence of adverse experiences. Therefore, it is unlikely that cyclic GH with or without CT will prove clinically useful in the treatment of postmenopausal women with osteoporosis.

Aged↗
PubMed1997

Bone mass and hip axis length in healthy Asian, black, Hispanic, and white American youths.

The primary objective of this study was to examine the associations of ethnicity, diet (calcium, protein, energy), and weight-bearing activity with dual-energy X-ray absorptiometry (DXA)-measured bone mass and hip axis length (HAL) in 423 Asians, blacks, Hispanics, and non-Hispanic Caucasians, aged 9-25 years. Bone mass was expressed as bone mineral content (BMC), bone mineral density (BMD), and bone mineral apparent density (BMAD). The data were analyzed using multiple linear regression, after stratifying for gender and pubertal stage and adjusting for height and weight. With few exceptions, Asians and Hispanics had comparable bone mass to whites at all pubertal stages. Greater femoral neck BMAD in black than white females was observed at all pubertal stages. Black males displayed greater BMD and BMAD than white males at all sites in early puberty and at the femoral neck in maturity. Calcium was positively and protein negatively related to BMAD at the femoral neck in early pubertal females. Among males, calcium was negatively associated with whole body BMC and BMD and spine BMD and BMAD in midpuberty. Weight-bearing activity was not associated with bone mass in females; in males, it was positively related only to femoral neck BMC in early puberty. There was an absence of evidence for ethnic differences in HAL among females. In males, we observed shorter HAL in mature Asians and blacks than whites. Neither diet nor activity was associated with HAL.

Absorptiometry, Photon↗
PubMed1997

Vitamin D receptor polymorphisms, bone mineral density, and bone metabolism in postmenopausal Mexican-American women.

Common polymorphisms in the vitamin D receptor (VDR) gene have been shown to correlate with bone mineral density (BMD). However, attempts to replicate the original findings in other populations have yielded variable results. These disparities may reflect ethnic or environmental differences in the expression of the VDR effect upon BMD. We examined a relatively ethnically homogeneous group of 103 healthy postmenopausal Caucasian women of Mexican descent living in Northern California. We determined the VDR genotype and measured the BMD at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry, as well as several biochemical indices of mineral metabolism. The prevalence of the BB genotype, associated in previous studies with the lowest BMD, was 8% and highly linked to the tt genotype. Absolute and age-adjusted BMD at both hip and spine showed a trend toward lower BMD in the BB, AA, and tt genotypes, but this trend did not achieve statistical significance. There were no consistent intergroup differences in change in BMD over 2 years of follow-up, nor in mean serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin, or total urinary pyridinolines. Intact parathyroid hormone concentrations were significantly higher in subjects with the AA genotype, with a trend toward higher values in those with the BB and tt genotypes as well. Our data suggest that there may be a decrease in BMD associated with the B, A, and t alleles, but the intergroup difference in BMD is 0.2-0.5 standard deviations (SD) at the lumbar spine and 0.3 SD at the femoral neck, decreases that are smaller than previously reported. Given the relatively low prevalence of the BB/tt genotype in Mexican-American Caucasians, a larger sample would be required to detect a significant association between VDR alleles and differences in BMD of the magnitude suggested by our data. We conclude that a genotype effect of this magnitude, if present, would be clinically relevant, but the impact on BMD is too small to detect with statistical significance in a study of this size.

Aged↗
PubMed1997

High-impact exercise promotes bone gain in well-trained female athletes.

Maximizing peak bone mass, as well as reducing its loss after menopause, is important for the prevention of osteoporosis. One mode of activity, gymnastics training, invokes high impact loading strains on the skeleton which may have powerful osteogenic effects. To examine the role of athletic activity, specifically gymnastics, on bone mineral density (BMD) accretion, we monitored longitudinal changes in regional and whole body BMD in collegiate women gymnasts and competitive athletes whose skeletons are exposed to differential loading patterns: runners and swimmers. Two cohorts were studied. Cohort I = 26 gymnasts (19.7 +/- 1.2 years), 36 runners (21.1 +/- 2.7 years) and 14 nonathletic women (19.3 +/- 1.7 years) followed over an 8-month period. Cohort II = 8 gymnasts (18.9 +/- 1.1 years), 11 swimmers (20.0 +/- 2.3 years) and 11 nonathletic women (19.0 +/- 1.2 years) followed over a 12-month period. Lumbar spine (L2-4), femoral neck, and whole body BMD (g/cm2) were assessed by dual-energy X-ray absorptiometry. For cohort I, the percent change in lumbar spine BMD after 8 months was significantly greater (p = 0.0001) in the gymnasts (2.8 +/- 2.4%) than in the runners (-0.2 +/- 2.0%) or controls (0.7 +/- 1.3%). An increase in femoral neck BMD of 1.6 +/- 3.6% in gymnasts was also greater (p < 0.05) than runners (-1.2 +/- 3.0%) and approached significance compared with controls (-0.9 +/- 2.2%, p = 0.06). For cohort II, gymnasts gained 2.3 +/- 1.6% at the lumbar spine which differed significantly (p < 0.01) from changes in swimmers (-0.3 +/- 1.5%) and controls (-0.4 +/- 1.7%). Similarly, the change at the femoral neck was greater (p < 0.001) in gymnasts (5.0 +/- 3.4%) than swimmers (-0.6 +/- 2.8%) or controls (2.0 +/- 2.3%). The percent change in BMD at any site did not differ between eumenorrheic and irregularly menstruating athletes. These results indicate that bone mineral at clinically relevant sites, the lumbar spine and femoral neck, can respond dramatically to mechanical loading characteristic of gymnastics training in college-aged women. This occurred despite high initial BMD values and was independent of reproductive hormone status. The results provide evidence to support the view that high impact loading, rather than selection bias, underlies high BMD values characteristic of women gymnasts. Because all athletes underwent resistance training throughout the year of study, muscle strengthening activity did not appear to be a significant factor in the skeletal response observed in gymnasts. We conclude that activities resulting in high skeletal impacts may be particularly osteotropic for young women.

Absorptiometry, Photon↗