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Biomedical subjects

R Marcus

Publications and source records attributed to R Marcus.

At least 145 records · Page 8Linked to original sources
PubMed1994

Interactions of growth hormone and parathyroid hormone in renal phosphate, calcium, and calcitriol metabolism and bone remodeling in postmenopausal women.

The mechanisms underlying the effects of recombinant human growth hormone (rhGH) on vitamin D, mineral, and bone metabolism are not known. We examined whether these effects are mediated by parathyroid hormone (PTH) by measuring renal phosphorus (P) and calcium (Ca) handling, serum calcitriol, and markers of bone turnover for 24 h before and 72 h after an infusion of hPTH(1-34) in eight healthy postmenopausal women at baseline and following short-term (1 week) and sustained (5 weeks) rhGH treatment. On short-term rhGH, serum phosphorus and basal TmP/GFR were unaffected, but the fall in TmP/GFR after hPTH infusion was exaggerated (integrated response: -99.2 +/- 22.3 versus -144.1 +/- 15.0 minute-mg/dl, P = 0.0021). Basal calcitriol levels rose from 115 +/- 17 to 163 +/- 16 pM (P = 0.0002), but the increase in calcitriol following hPTH infusion was unaffected by short-term rhGH. The basal Ca excretion index (CEI) rose from 0.054 +/- 0.005 to 0.073 +/- 0.007 mM (P = 0.0095), but markers of bone turnover were unaffected. With sustained rhGH treatment, serum P (1.47 +/- 0.05 mM), basal TmP/GFR (4.29 +/- 0.24 mg/dl), and basal CEI (0.067 +/- 0.005 mM) were elevated compared with control values, and the PTH-induced lowering of TmP/GFR was again enhanced (-158.7 +/- 22.8 minute-mg/dl, P = 0.0021). Basal calcitriol concentrations returned to control levels (108 +/- 10 pM), but the calcitriol response to hPTH remained unchanged. Markers of bone remodeling were elevated with sustained rhGH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1994

Age-related differences in cross-sectional geometry of the forearm bones in healthy women.

Men exhibit age-related adaptive changes in long bone geometry, namely, endosteal resorption and periosteal apposition of bone, that help to preserve bone strength. It is not clear whether women undergo similar adaptive responses. To address this question, we assessed the bone mineral density and cross-sectional geometry of the radius and ulna at the one-third distal site by single photon absorptiometry and computed tomography (CT) in healthy young (n = 21, age 20-30 years) and older (n = 22, age 63-84 years) women. We used the CT data to compute the total subperiosteal, medullary, and cortical areas, as well as the maximum, minimum, and polar moments of inertia. We normalized the geometric parameters for bone length and performed comparisons using both the original and size-corrected data. Radial and ulnar bone mineral content and density were 20-30% lower in the older women (P < 0.0001). Ulnar width, total area, medullary area, and maximum and polar moment of inertia were greater in the older than in the younger women. Although we observed similar trends when we examined the radius data that were corrected for bone size, age-related differences in radial geometry were less pronounced and were not significant. We conclude that women undergo endosteal resorption and periosteal apposition of the ulna with age, thereby exhibiting an adaptive pattern that helps to preserve bone strength. The different behavior of these two bones suggests that local, rather than systemic, factors underlie this adaptation.

Adult↗
PubMed1994

Risk of secondary cutaneous malignancies in patients with long-standing mycosis fungoides.

BACKGROUND: Patients with mycosis fungoides (MF) are frequently treated with UV light and psoralen (PUVA), nitrogen mustard, and electron beam irradiation, modalities known to predispose persons to development of cutaneous malignancies. OBJECTIVE: We assessed the relation between these therapeutic modalities and the development of secondary cutaneous malignancies. METHODS: We reviewed the charts of all patients observed during the past year. RESULTS: We found that 7 of 71 patients had cutaneous neoplasms in an average follow-up time of 8.3 years. Orthovoltage radiation was used in five of seven cases and PUVA in four of seven. Five of seven patients had multiple neoplasms. CONCLUSION: The risk of the development of second malignancies from the treatment of MF is relatively small and appears to be related to the type of therapy.

Carcinoma in Situ↗
PubMed1994

Regional fat distribution by dual-energy X-ray absorptiometry: comparison with anthropometry and application in a clinical trial of growth hormone and exercise.

1. The purpose of this study was to determine the suitability of ratios derived from dual-energy X-ray absorptiometry (DXA) whole body scans to assess regional fat distribution in older men and women by comparing them with the waist-to-hip ratio (WHR) and to evaluate their clinical utility by applying them in a clinical trial involving resistance exercise and recombinant human growth hormone. 2. Sixty-four healthy older adults (39 women and 25 men), aged 65-82 years, served as subjects. The ratios of trunk fat-to-total fat, trunk fat-to-body weight, trunk fat-to-limb fat and trunk fat % were determined by DXA. WHR was assessed on the same day, as was the ratio of subscapular/triceps skinfolds in men. Cardiovascular disease risk factors, functional capacity and serum lipids were also assessed. 3. A moderate relationship (r = 0.36-0.54) between the WHR- and DXA-derived ratios were observed for both men and women. Both DXA and WHR showed similar associations with cardiovascular disease risk factors. However, in men, all DXA ratios were able to detect subtle changes in regional fat distribution resulting from daily administration of recombinant human growth hormone in conjunction with resistance exercise for 10 weeks, whereas the WHR or subscapular/triceps ratios did not. 4. This suggests that DXA-derived ratios may be more sensitive than conventional anthropometric methods in the assessment and categorization of body fat distribution.

Absorptiometry, Photon↗
PubMed1994

The insulin-like growth factor I generation test: resistance to growth hormone with aging and estrogen replacement therapy.

Circulating IGF-I is primarily regulated by growth hormone, but other factors such as nutritional status may also influence IGF-I secretion. The effects of age, gender, and estrogen replacement on responsiveness of serum IGF-I to GH administration have not been directly studied. The high-affinity circulating GH-binding protein (GHBP) has the same structure as the extracellular domain of the GH receptor and may reflect the sensitivity to GH in humans. To examine these issues, we employed an IGF-I generation test in which a single dose of GH (0.1 mg/kg SQ) was administered to 31 healthy adults comprising five groups: young (20-29 years) males (YM), young females in the follicular phase of the menstrual cycle (YF), older (60-69 years) males (OM), older females not on estrogen replacement (OFN), and older females on oral estrogen replacement (OFE). Blood was sampled for IGF-I and GHBP over 72 hours following GH administration. OM had lower peak IGF-I levels (323 +/- 38 vs. 497 +/- 85 micrograms/l, p = 0.0015) and a lower IGF-I response to GH (delta IGF-I: 187 +/- 33 vs. 293 +/- 57 micrograms/l, p = 0.0085) than YM. OFE had lower basal IGF-I (63 +/- 11 vs. 133 +/- 19 micrograms/l, p = 0.0046), peak IGF-I (174 +/- 28 vs. 400 +/- 40 micrograms/l, p = 0.0015), and delta IGF-I (111 +/- 21 vs. 268 +/- 27 micrograms/l, p = 0.0085) than OFN. IGFBP-3 levels were unchanged 24 hours after GH administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Effect of a sustained program of resistance training on the acute growth hormone response to resistance exercise in older adults.

We have previously shown that an episode of resistance exercise provokes an acute rise in circulating growth hormone (GH), and that this rise is severely blunted in older men and women. To determine whether this impairment simply reflects the decreased physical fitness of older people, we studied the effects of long-term resistance training on circulating levels of GH and insulin-like growth factor I (IGF-I) and on the acute GH response to exercise in 5 men and 9 women, aged 69.6 +/- 1.1 yrs (SEM). Subjects were randomly assigned to either an exercise program, consisting of 12 weight-lifting exercises (3 sets of 8 repetitions, 3 times each week) or to a control group. After testing maximum baseline strength by the 1 RM method, subjects returned to the laboratory for assessment of basal GH and IGF-I levels and the GH response to exercise. Venous blood was drawn at baseline, after each of 12 exercises (3 sets of 8 repetitions at 85% 1 RM), and every 2 minutes into the first 10 minutes of recovery. The exercise circuit with blood sampling was repeated at 15, 30 and 52 weeks for both groups. Basal GH and IGF-I values did not change in either group throughout the training period nor did the GH secretory response to exercise. Three exercisers had a peak GH concentration greater than 8 micrograms/l after 30 weeks of training, although only one of these showed a significant increase (29 micrograms/l) after 52 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Muscle strength and fiber adaptations to a year-long resistance training program in elderly men and women.

BACKGROUND: To study the effects of resistance training on muscle strength and size in older people, we enrolled 8 men and 17 women (mean age 68.2 +/- 1 SEM) into a one-year exercise trial. METHODS: Subjects were randomly assigned to exercise or control groups. Muscle biopsies were obtained from 11 subjects (8 exercisers/3 controls) at baseline and after 15 weeks; exercisers underwent another biopsy at 30 weeks. After testing maximum strength using the 1-RM method, the exercisers began a 12-exercise circuit (3 sets of 8 repetitions at 75% of 1-RM), 3 times a week. The controls repeated the strength testing every 15 weeks. They were asked to continue usual activities and not to start any exercise program. RESULTS: With exercise, muscle strength increased, average increases ranging from 30% (hip extensors) to 97% (hip flexors). Strength increased rapidly over 3 months, then plateaued for the duration of the experiment. No strength changes were observed in sedentary controls. Cross-sectional area of type 1 muscle fibers increased in exercisers by 15 weeks (29.4 +/- 1%, p < .02) and after 30 weeks (58.5 +/- 13.7%, p < .002) compared to baseline. Type 2 fiber area did not change at 15 weeks, but increased by 30 weeks of training (66.6 +/- 9.5%, p < .0002). CONCLUSIONS: These results suggest that prolonged moderate to high intensity resistance training may be carried out by healthy older adults with reasonable compliance, and that such training leads to sustained increases in muscle strength. These improvements are rapidly achieved and are accompanied by hypertrophy of both type 1 and type 2 muscle fibers.

Aged↗
PubMed1994

Quantifying the effect of hand preference on upper limb bone mineral and soft tissue composition in young and elderly women by dual-energy X-ray absorptiometry.

The purpose of this study was to quantify the effect that hand preference has on upper limb bone mineral and soft tissue composition in healthy young and elderly women. Bone mineral content (BMC) in grams, bone mineral density (BMD) in g cm-2, fat-free soft tissue (FFST) in grams, fat tissue (g), and percent fat were determined by dual-energy X-ray absorptiometry (DXA) for dominant and non-dominant upper limbs as well as total body fat (%) in 25 young (26.6 +/- 4.3 years, mean +/- SD) and 35 elderly women (68.4 +/- 2.9 years). For both groups, the dominant upper limb had a greater BMC (P < 0.001), BMD (young, P < 0.001; elderly, P < 0.05), and FFST mass (P < 0.001), and a lower percent fat (young, P < 0.01; elderly, P < 0.05) than the non-dominant limb; however, there was no difference between limbs for total fat mass. BMC, BMD, and FFST in the dominant limb of young women were 7.1%, 1.8%, and 5.1% greater than the non-dominant limb, while for older women the differences were 5.3%, 1.0%, and 4.2%. Relative fat of the dominant limb was 3.0% and 1.3% less than the non-dominant limb for young and older women, respectively. Age did not affect the percent bone mineral or soft tissue difference. A higher bone mineral and FFST mass in the dominant limb is expected due to the greater activity demands placed upon these tissues. However, a larger bone and FFST mass increases the total mass of the dominant limb, resulting in a dilution of the fat tissue mass and hence a reduced fat percent for the limb. This study indicates that hand preference affects the tissue composition of the upper limb in both young and elderly women, resulting in an increased bone mineral and FFST mass with no change in absolute fat mass. Hand preference should be taken into account when upper limb bone mineral and/or soft tissue composition is assessed.

Absorptiometry, Photon↗
PubMed1994

Estrogen replacement therapy and memory in older women.

OBJECTIVE: To study the relationship between estrogen hormone replacement therapy and recall of proper names and words in cognitively intact older women. DESIGN: A case-control study using subjects matched on age and education. PARTICIPANTS: From a group of 278 older (age range 55 to 93 years) community-dwelling women volunteers for memory research, 72 older women taking estrogen replacement therapy were matched on age and education with a group of 72 women not taking estrogen. MEASUREMENTS: Dependent measures were performances on: a proper name recall test and a word recall test. RESULTS: Proper name recall was significantly better in those receiving estrogen (mean = 4.3; SD = 3.3) than in those not receiving estrogen (mean = 3.1; SD = 2.5), P = 0.01. There was also significantly greater variance in the name recall scores of the group taking estrogen than in the group not taking estrogen. For word recall, there was no significant difference between those subjects taking estrogen (mean = 6.4; SD 3.8) and those not taking estrogen (mean = 5.8; SD 3.7), P > 0.10. CONCLUSIONS: Estrogen use was associated with enhanced recall of proper names. Previous failures to find differences associated with estrogen use may reflect the memory measures used or an increased inter-individual variability of the estrogen-taking group, as was observed in the present study. Interpretation of these results should be tempered by their retrospective nature.

Aged↗
PubMed1994

Sex-specific determinants of increased left ventricular mass in the Tecumseh Blood Pressure Study.

BACKGROUND: Left ventricular hypertrophy (LVH) defined by either ECG or echocardiographic criteria is a risk factor for cardiovascular morbidity and mortality. A number of determinants of LVH have been described in previous studies, principally male sex, hypertension, obesity, and aortic valvular stenosis. We examined the distribution of LV mass (LVM) in a population of 18- to 42-year-old normotensive men and women who were free of valvular heart disease to establish sex-specific normal values for LVM index (LVMI) and to determine the correlates of LVMI. METHODS AND RESULTS: LVM was derived from measurements obtained by M-mode echocardiography. Average LVMI is significantly greater in men (102.9 +/- 0.7 g/m2) than women (88.2 +/- 0.7 g/m2). By defining LVH as an LVMI greater than the 90th percentile, we developed sex-specific criteria for LVH: men, > 125.4 g/m2; women, > 110 g/m2. We found that LVH in men is associated with indices of enhanced sympathetic nervous system reactivity and with elevated fasting insulin and triglyceride levels, which may be caused by insulin resistance. In women, LVH was associated with higher body weight and obesity. CONCLUSIONS: Before the onset of hypertension, increased LVMI appears to have different determinants in men and women. We suggest that early LVH in young men is a manifestation of hyperkinetic borderline hypertension, a state previously shown to be associated with increased sympathetic nervous system activity and insulin resistance. The hyperkinetic state is less prevalent in young women, in whom increased adiposity seems to be the predominant factor associated with LVH.

Adult↗
PubMed1994

Effects of recombinant human growth hormone on metabolic indices, body composition, and bone turnover in healthy elderly women.

We conducted a controlled trial of recombinant human GH (rhGH) in 27 healthy elderly women (66.7 +/- 3.0 yr), of whom 8 took a stable dose of replacement estrogen throughout the study (plus estrogen group). Hormone or placebo was given as a single daily injection. A total of 19 women were assigned to receive rhGH at an initial daily dose of 0.043 mg/kg BW. After several weeks, 50% dose reductions were necessitated by side-effects. The last 7 subjects to be enrolled began treatment at this reduced level. A total of 13 women assigned to rhGH and 14 women assigned to placebo completed 6 months of drug treatment. In the rhGH group, 6 women took estrogen; thus, the effects of rhGH were assessed separately by estrogen status. Circulating insulin-like growth factor-I (IGF-I) levels were similar at baseline (rhGH, 133 +/- 40.4 micrograms/L; placebo, 128 +/- 13). rhGH increased IGF-I and IGF-I-binding protein-3 (IGFBP-3) in all subjects [6 month IGF-I in plus estrogen women, 230 +/- 25.4 micrograms/L; in those not receiving estrogen (minus estrogen), 308 +/- 21.3]. No changes in IGF-I or IGFBP-3 occurred with placebo (IGF-I, 144 +/- 21.3 micrograms/L). Skinfold thickness measurements showed an 11% decrease in fat mass (P < 0.005) and a 9% decrease in percent fat after 6 months of rhGH treatment. No significant difference in nitrogen balance was seen in either group at 6 months, but rhGH increased creatinine clearance by 9.2% (P < 0.05). rhGH dramatically increased markers of bone turnover, with more pronounced effects in minus estrogen women. Hydroxyproline excretion increased by 20% and 80%, and pyridinoline excretion increased by 44% and 75% in plus and minus estrogen subgroups, respectively. Osteocalcin concentrations increased by more than 60% in minus estrogen women (P < 0.05), but did not change in the plus estrogen group. No changes were observed in circulating type I procollagen extension peptide in either group, and no change in any turnover marker was seen in the placebo group. rhGH did not alter blood pressure or circulating L-T4 levels, but a transient increase in serum T3 was observed in the minus estrogen group at 3 months. rhGH decreased low density lipoprotein cholesterol in the minus estrogen group, but otherwise no significant changes in circulating lipoproteins or fibrinogen were observed. Eight women assigned to rhGH and 14 placebo-treated women remained on blinded treatment through 12 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1994

Effect of recombinant human growth hormone on the muscle strength response to resistance exercise in elderly men.

Normal aging is characterized by detrimental changes in body composition, muscle strength, and somatotropic function. Reduction in muscle strength contributes to frailty and risk for fracture in the elderly. Although older adults increase muscle strength as a result of resistance exercise training, the strength gains quickly level off, with only modest increases thereafter despite continued training. To investigate whether age-related deficits in the somatotropic axis limit the degree to which muscle strength can improve with resistance training in older individuals, we conducted a double blind, placebo-controlled exercise trial. Eighteen healthy elderly men (65-82 yr) initially underwent progressive weight training for 14 weeks to invoke a trained state. Subjects were then randomized to receive either 0.02 mg/kg BW.day recombinant human GH (rhGH) or placebo, given sc, while undertaking a further 10 weeks of strength training. Sequential measurements were made of muscle strength (one repetition maximum), body composition (dual energy x-ray absorptiometry), and circulating levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3. For each exercise, strength increased for both groups (P = 0.0001) through 14 weeks of training, with little improvement thereafter. Increases in muscle strength ranged from 24-62% depending on the muscle group. Baseline plasma IGF-I concentrations were similar in both groups (mean +/- SEM, 106 +/- 9 micrograms/L), approximately half that observed in healthy young adults. In the rhGH group, IGF-I levels increased to 255 +/- 32 micrograms/L at week 15 and 218 +/- 21 micrograms/L at week 24 (P < 0.001). In the placebo group, IGF-I increased slightly to 119 +/- 6 micrograms/L at 24 weeks. IGF-binding protein-3 also increased in the rhGH group (P < 0.05). rhGH had no effect on muscle strength at any time, and no systematic difference in muscle strength was observed between groups throughout the study. Body weight did not change in either group, but lean body mass increased, and fat mass decreased (P < 0.05) in the rhGH group. Supplementation with rhGH does not augment the response to strength training in elderly men. These results suggest that deficits in GH secretion do not underlie the time-dependent leveling off of muscle strength seen with training in the elderly and provide no support for the popular view of GH as an ergogenic aid.

Aged↗
PubMed1994

XNEOr: development and evaluation of an expert system to improve the quality and cost of decision-making in neuro-oncology.

The treatment of brain tumors requires a large team of medical experts. However, the process of medical decision-making for these patients is hampered by the frequent inaccessibility of the experts because of conflicting scheduling, inconsistencies in the management of different patients, and the fact that multiple experts often yield multiple opinions. The goals of this work were (1) to develop and validate an expert system to assist the medical team deliver efficient, quality care to children with recurrent medulloblastoma, a common type of pediatric brain tumor, and (2) to determine if the expert system can be used as an educational tool. The results of our study indicate that residents enjoy learning by using XNEOr, the brain tumor expert system. XNEOr enabled residents to order appropriate ancillary tests for patients and to make fewer incorrect treatment decisions. The potential net effect of residents using XNEOr may be increased patient and family satisfaction and decreased probability of medical liability. At a time of important changes in our health care system, novel expert systems hold promise as tools to reduce medical costs, improve the quality of multi-expert medical care, and advance health care education.

Brain Neoplasms↗
PubMed1994

A randomized phase II study of low-dose cytosine arabinoside (LD-AraC) plus granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in myelodysplastic syndromes (MDS) with a high risk of developing leukemia. EORTC Leukemia Cooperative Group.

In a randomized phase II study, patients with myelodysplastic syndromes (MDS) with 10-30% blasts in the bone marrow and hematopoietic failure were treated with low-dose Ara C (2 x 10 mg/m2 subcutaneously (s.c.) days 1-14) and rhGM-CSF (fully glycosylated, Sandoz/Schering-Plough, 2 x 150 micrograms protein/day s.c.) given either following Ara C (days 15-21) or simultaneously (days 8-14) for 1-5 cycles. 108 patients with a median age of 65 years, range 17-80 years and refractory anemia with an excess of blasts (RAEB, n = 54), RAEB with transformation (RAEBt, n = 50) or with chronic myelomonocytic leukemia (CMML, n = 4) were evaluable. Complete remission was achieved in 15 cases (14%), 11 had a partial response (10%), and 16 a minor response (15%). Stable disease was reached in 35 cases (32%). There were 16 cases of toxic death (15%), progression occurred in 15 patients (14%). No differences existed between the two treatment arms with respect to response and duration of response. Prognostic factors for poor response included the presence of cytogenetic abnormalities and a history of previous blood transfusions. Major adverse events during treatment were hemorrhage (55%), infections (54%), and fever associated with GM-CSF administration (40%). The overall response rate ws 39%, median duration was 12.5 months from start of treatment which allowed responding patients to lead good quality life without further therapy. The question whether the combination is indeed superior to LD-Ara C alone is not settled but will be evaluated in an ongoing clinical trial.

Acute Disease↗
PubMed1993

Surveillance of HIV infection and zidovudine use among health care workers after occupational exposure to HIV-infected blood. The CDC Cooperative Needlestick Surveillance Group.

OBJECTIVE: To study the risk for human immunodeficiency virus (HIV) infection and the patterns of use and associated toxicity of zidovudine among health care workers after an occupational exposure to HIV. DESIGN: An ongoing, prospective surveillance project conducted by the Centers for Disease Control and Prevention. PARTICIPANTS: Exposed workers voluntarily reported by 312 U.S. health care facilities from August 1983 to June 1992. RESULTS: Four of 1103 enrolled workers with percutaneous exposure to HIV-infected blood seroconverted (HIV seroconversion rate, 0.36%; upper limit of the 95% Cl, 0.83%); no enrolled workers with mucous membrane (n = 75) or skin (n = 67) contact seroconverted. During October 1988 to June 1992, 31% of 848 enrolled workers used zidovudine after exposure; this proportion increased from 5% during October through December 1988 to 43% during January through June 1992. Despite using zidovudine after exposure, one worker became infected with a strain of HIV that was apparently sensitive to zidovudine. Adverse symptoms, most commonly nausea, malaise or fatigue, and headache, were reported by 75% of workers using zidovudine; 31% of workers did not complete planned courses of zidovudine because of adverse events. CONCLUSIONS: The risk for HIV seroconversion after percutaneous exposure to HIV-infected blood is 0.36%, which is similar to previous estimates. Zidovudine is used after exposure by a sizable proportion of health care workers enrolled in the project despite frequent, minor, associated symptoms. Documented failures of postexposure zidovudine prophylaxis, including in one worker enrolled in this study, indicate that if zidovudine is protective, any protection afforded is not absolute. Postexposure zidovudine, if used, requires careful consideration of possible risks and benefits.

Centers for Disease Control and Prevention, U.S.↗