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Biomedical subjects

S M Roth

Publications and source records attributed to S M Roth.

At least 19 recordsLinked to original sources

IGF2 genotype and obesity in men and women across the adult age span.

We studied a previously reported association between the IGF2 gene's ApaI polymorphism and obesity in 500 healthy men and women (19-90 y). We hypothesized that individuals homozygous for the IGF2 A allele (A/A) would exhibit lower body mass, BMI and DEXA-measured fat mass compared to G/G homozygotes. Subjects were categorized as exhibiting the G/G (n = 241), G/A (n = 197) or A/A (n = 62) genotype. Contrary to our hypothesis, no difference was observed in body mass, body mass index (BMI) or fat mass between the G/G and A/A genotype groups in the entire cohort. Surprisingly, Caucasian A/A individuals (n = 427) exhibited significantly higher fat mass compared to Caucasian G/G individuals (P < 0.05). In summary, individuals homozygous for the IGF2 G allele do not exhibit higher body mass, BMI or fat mass compared to A/A individuals; however, Caucasians with the A/A genotype exhibit higher fat mass than G/G individuals.

Adipose Tissue↗

Does age, sex, or ACE genotype affect glucose and insulin responses to strength training?

The purpose of the present study was to determine whether age, sex, or angiotensin I-converting enzyme (ACE) genotype influences the effects of strength training (ST) on glucose homeostasis. Nineteen sedentary young (age = 20-30 yr) men (n = 10) and women (n = 9) were studied and compared with 21 sedentary older (age = 65-75 yr) men (n = 12) and women (n = 9) before and after a 6-mo total body ST program. Fasting insulin concentrations were reduced in young men and in older men with ST (P < 0.05 in both). In addition, total insulin area under the curve decreased by 21% in young men (P < 0.05), and there was a trend for a decrease (11%) in older men (P = 0.06). No improvements in insulin responses were observed in young or older women. The ACE deletion/deletion genotype group had the lowest fasting insulin and insulin areas under the oral glucose tolerance test (OGTT) curve before training (all P < 0.05), but those with at least one insertion allele had a trend for a greater reduction in total insulin area than deletion homozygotes (P = 0.07). These results indicate that ST has a more favorable effect on insulin response to an OGTT in men than in women and offer some support for the hypothesis that ACE genotype may influence insulin responses to ST.

Adult↗

Muscle size responses to strength training in young and older men and women.

OBJECTIVES: To examine the possible influences of age and gender on muscle volume responses to strength training (ST). DESIGN: Prospective intervention study. SETTING: University of Maryland Exercise Science and Wellness Research Laboratories. PARTICIPANTS: Eight young men (age 20-30 years), six young women (age 20-30 years), nine older men (age 65-75 years), and ten older women (age 65-75 years). INTERVENTION: A 6-month whole-body ST program that exercised all major muscle groups of the upper and lower body 3 days/week. MEASUREMENTS: Thigh and quadriceps muscle volumes and mid-thigh muscle cross-sectional area (CSA) were assessed by magnetic resonance imaging before and after the ST program. RESULTS: Thigh and quadriceps muscle volume increased significantly in all age and gender groups as a result of ST (P < .001), with no significant differences between the groups. Modest correlations were observed between both the change in quadriceps versus the change in total thigh muscle volume (r = 0.65; P < .001) and the change in thigh muscle volume versus the change in mid-thigh CSA (r = 0.76, P < .001). CONCLUSIONS: The results indicate that neither age nor gender affects muscle volume response to whole-body ST. Muscle volume, rather than muscle CSA, is recommended for studying muscle mass responses to ST.

Adult↗

Skeletal muscle satellite cell characteristics in young and older men and women after heavy resistance strength training.

Skeletal muscle satellite cell proportions and morphology were assessed in healthy, sedentary young and older men and women in response to heavy resistance strength training (HRST). Fourteen young (20-30 years) men (n = 7) and women (n = 7) and 15 older (65-75 years) men (n = 8) and women (n = 7) completed 9 weeks of unilateral knee extension exercise training 3 days per week. Muscle biopsies were obtained from each vastus lateralis before and after training, with the nondominant leg serving as an untrained control. All four groups demonstrated a significant increase in satellite cell proportion in response to HRST (2.3 +/- 0.4% vs 3.1 +/- 0.4% for all subjects combined, before and after training, respectively; p < .05), with older women demonstrating the greatest increase (p < .05). Morphology data indicated a significant increase in the proportion of active satellite cells in after-training muscle samples compared with before-training samples and with control leg samples (31% vs 6% and 7%, respectively; p < .05). The present results indicate that the proportion of satellite cells is increased after HRST in young and older men and women, with an exaggerated response in older women. Furthermore, the proportion of satellite cells that appear morphologically active is increased as a result of HRST.

Adult↗

CNTF genotype is associated with muscular strength and quality in humans across the adult age span.

The relationship between ciliary neurotrophic factor (CNTF) genotype and muscle strength was examined in 494 healthy men and women across the entire adult age span (20-90 yr). Concentric (Con) and eccentric (Ecc) peak torque were assessed using a Kin-Com isokinetic dynamometer for the knee extensors (KE) and knee flexors (KF) at slow (0.52 rad/s) and faster (3.14 rad/s) velocities. The results were covaried for age, gender, and body mass or fat-free mass (FFM). Individuals heterozygous for the CNTF null (A allele) mutation (G/A) exhibited significantly higher Con peak torque of the KE and KF at 3.14 rad/s than G/G homozygotes when age, gender, and body mass were covaried (P < 0.05). When the dominant leg FFM (estimated muscle mass) was used in place of body mass as a covariate, Con peak torque of the KE at 3.14 rad/s was also significantly greater in the G/A individuals (P < 0.05). In addition, muscle quality of the KE (peak torque at 3.14 rad x s(-1) x leg muscle mass(-1)) was significantly greater in the G/A heterozygotes (P < 0.05). Similar results were seen in a subanalysis of subjects 60 yr and older, as well as in Caucasian subjects. In contrast, A/A homozygotes demonstrated significantly lower Ecc peak torque at 0.52 rad/s for both KE and KF compared with G/G and G/A groups (P < 0.05). No significant relationships were observed at 0.52 rad/s between genotype and Con peak torque. These data indicate that individuals exhibiting the G/A genotype possess significantly greater muscular strength and muscle quality at relatively fast contraction speeds than do G/G individuals. Because of high positive correlations between fast-velocity peak torque and muscular power, these findings suggest that further investigations should address the relationship between CNTF genotype and muscular power.

Adult↗

Utility of duplex surveillance following iliac artery angioplasty and primary stenting.

PURPOSE: To evaluate the clinical outcome and patency rates after iliac artery angioplasty and primary stenting using a noninvasive surveillance protocol that includes duplex ultrasonography. METHODS: Sixty-seven patients (64 men; mean age 61 +/- 9 years, range 45-83) underwent stenting of 84 iliac systems for claudication (63%), rest pain (9%), tissue loss (20%), or failing lower limb bypass graft (8%). The surveillance algorithm included aortoiliac duplex scanning within 1 month and serial limb pressure measurements and femoral artery waveform analyses during follow-up. Iliac systems with a peak systolic velocity >300 cm/s and velocity ratio >2.0 by duplex and/or symptomatic or hemodynamic deterioration were considered failing and an indication for angiography. RESULTS: During intermediate-term follow-up ranging to 36 months (mean 12), life table primary, assisted primary, and secondary patency rates for the treated iliac systems were 78%, 90%, and 98%, respectively, at 18 months. Assisted primary iliac system patency at 18 months was significantly worse in the 20 (24%) limbs having an outflow bypass done with or prior to iliac stenting (83% versus 100% without bypass, p = 0.01). Indirect clinical indicators found 17 (20%) suspected failing iliac systems, in which duplex imaging correctly identified 5 of 6 recurrent iliac stenoses and facilitated secondary endovascular intervention. Three (4%) stent occlusions occurred in the treated iliac systems despite surveillance. CONCLUSIONS: Duplex surveillance after iliac stenting localizes failing inflow segments, optimizes assisted patency of the treated iliac system, and possesses greatest utility in patients with multilevel occlusive disease and outflow reconstructions.

Aged↗

Skeletal muscle satellite cell populations in healthy young and older men and women.

The purpose of the present investigation was to assess satellite cell populations and morphology in m. vastus lateralis biopsies obtained from young (20-30 years) and older (65-75 years) healthy, sedentary men and women. Multiple muscle biopsies were obtained from 14 young individuals (men, n = 7; women, n = 7) and 15 older individuals (men, n = 8; women, n = 7). Muscle fibers were viewed longitudinally using a Zeiss EM 10 CA electron microscope. All myonuclei and satellite cells were counted and satellite cells were photographed for morphological analysis. The proportion of satellite cells [satellite cells/(myonuclei + satellite cells)] did not differ among the four subject groups (1.7-2.8%), nor did proportions differ when subject groups were combined for age and gender comparisons. Few morphological differences were noted between groups; however, lipofuscin granules were more prominent in satellite cells from older subjects and women demonstrated significantly larger satellite cell and satellite cell nucleus areas than men. Mitochondria from satellite cells (regardless of group) were more pallid and exhibited fewer cristae than mitochondria located in the adjacent muscle fiber. The results of the current investigation suggest that, despite findings in animal models, satellite cell populations are not significantly lower in healthy, sedentary older compared to young adult men and women.

Adult↗

Muscle biopsy and muscle fiber hypercontraction: a brief review.

The percutaneous muscle biopsy technique is an important tool used in exercise and applied physiology to study human skeletal muscle structure, adaptation, and regeneration. One important use of this technique has been the assessment of ultrastructural muscle damage, especially in tissue samples obtained following strenuous exercise protocols, often involving eccentric muscle actions. In this brief review, we define and describe hypercontracted fibers, and outline how such fibers may adversely affect the interpretation of muscle damage from fixed tissue. Evidence suggests that hypercontracted fibers present in healthy skeletal muscle samples are likely to be artifacts related to the muscle biopsy procedure, as opposed to intrinsic degeneration present prior to the biopsy. When hypercontracted fibers are noted as being intrinsic to a muscle sample (e.g., in myopathy or following an extreme eccentric stimulus), such fibers are generally associated with the infiltration of inflammatory cells, indicative of a regenerative response. In contrast, hypercontracted fibers resulting from the biopsy procedure are not typically associated with an inflammatory response. The major sources of hypercontracted fibers are outlined and recommendations for their interpretation are discussed.

Anesthetics↗

Intraoperative duplex monitoring of infrainguinal vein bypass procedures.

PURPOSE: The purpose of this study was to evaluate intraoperative duplex scanning of infrainguinal vein bypass grafts to detect technical and hemodynamic problems, monitor their repair, and correlate findings with the incidence of thrombosis and stenosis repair rates within 90 days of operation. METHODS: Color duplex scanning was used at operation to assess vein/anastomotic patency and velocity spectra waveforms of 626 infrainguinal vein bypass grafts (in situ saphenous, 228 grafts; nonreversed translocated saphenous, 170 grafts; reversed saphenous, 147 grafts; alternative [arm, lesser saphenous], 81 grafts) to the popliteal (n = 267 grafts), infrageniculate (n = 323 grafts), or pedal artery (n = 36 grafts). The entire bypass graft was scanned after intragraft injection of papaverine hydrochloride (30-60 mg) to augment graft flow. Vein/anastomotic/artery segments with velocity spectra that indicate highly disturbed flow (peak systolic velocity, >180 cm/sec; spectral broadening; velocity ratio at site, >3) were revised. Grafts with a low peak systolic velocity less than 30 to 40 cm/s and high outflow resistance (absent diastolic flow) underwent procedures (distal arteriovenous fistula, sequential bypass grafting) to augment flow; if this was not possible, the grafts were treated with an antithrombotic regimen, including heparin, dextran, and antiplatelet therapy. RESULTS: Duplex scanning prompted revision of 104 lesions in 96 (15%) bypass grafts, including 82 vein/anastomotic stenoses, 17 vein segments with platelet thrombus, and 5 low-flow grafts. Revision rate was highest (P <.01) for alternative vein bypass grafts (27%) compared with the other grafting methods (reversed vein bypass grafts, 10%; nonreversed translocated, 13%; in situ, 16%). A normal intraoperative scan on initial imaging (n = 464 scans) or after revision (n = 67 scans) was associated with a 30-day thrombosis rate of 0.2% and a revision rate of 0.8% for duplex-detected stenosis (peak systolic velocity, >300 cm/s; velocity ratio, >3.5). By comparison, 20 of 95 bypass grafts (21%) with a residual (n = 29 grafts) or unrepaired duplex stenosis (n = 53 grafts) or low flow (n = 13 grafts) had a corrective procedure for graft thrombosis (n = eight grafts) or stenosis (n = 12 grafts; P <.001). Overall, 8% of patients with bypass grafts underwent a corrective procedure within 90 days of operation. Secondary graft patency was 99.4% at 30 days and 98.8% at 90 days (eight graft failures). CONCLUSION: The observed 15% intraoperative revision rate coupled with a low 90-day failure/revision rate (2.5%) for bypasses with normal papaverine-augmented duplex scans supports the routine use of this diagnostic modality to enhance the precision and early results of infrainguinal vein bypass procedures.

Anastomosis, Surgical↗

Effects of age, gender, and myostatin genotype on the hypertrophic response to heavy resistance strength training.

BACKGROUND: Because of the scarcity of data available from direct comparisons of age and gender groups using the same relative training stimulus, it is unknown whether older individuals can increase their muscle mass as much as young individuals and whether women can increase as much as men in response to strength training (ST). In addition, little is known about whether the hypertrophic response to ST is affected by myostatin genotype, a candidate gene for muscle hypertrophy. METHODS: Eleven young men (25 +/- 3 years, range 21-29 years), 11 young women (26 +/- 2 years, range 23-28 years), 12 older men (69 +/- 3 years, range 65-75 years), and 11 older women (68 +/- 2 years, range 65-73 years) had bilateral quadriceps muscle volume measurements performed using magnetic resonance imaging (MRI) before and after ST and detraining. Training consisted of knee extension exercises of the dominant leg three times per week for 9 weeks. The contralateral limb was left untrained throughout the ST program. Following the unilateral training period, the subjects underwent 31 weeks of detraining during which no regular exercise was performed. Myostatin genotype was determined in a subgroup of 32 subjects, of which five female subjects were carriers of a myostatin gene variant. RESULTS: A significantly greater absolute increase in muscle volume was observed in men than in women (204 +/- 20 vs 101 +/- 13 cm3, p < .01), but there was no significant difference in muscle volume response to ST between young and older individuals. The gender effect remained after adjusting for baseline muscle volume. In addition, there was a significantly greater loss of absolute muscle volume after 31 weeks of detraining in men than in women (151 +/- 13 vs 88 +/- 7 cm3, p < .05), but no significant difference between young and older individuals. Myostatin genotype did not explain the hypertrophic response to ST when all 32 subjects were assessed. However, when only women were analyzed, those with the less common myostatin allele exhibited a 68% larger increase in muscle volume in response to ST (p = .056). CONCLUSIONS: Aging does not affect the muscle mass response to either ST or detraining, whereas gender does, as men increased their muscle volume about twice as much in response to ST as did women and experienced larger losses in response to detraining than women. Young men were the only group that maintained muscle volume adaptation after 31 weeks of detraining. Although myostatin genotype may not explain the observed gender difference in the hypertrophic response to ST, a role for myostatin genotype may be indicated in this regard for women, but future studies are needed with larger subject numbers in each genotype group to confirm this observation.

Adult↗

High-volume, heavy-resistance strength training and muscle damage in young and older women.

To determine possible age differences in muscle damage response to strength training, ultrastructural muscle damage was assessed in seven 20- to 30-yr-old and six 65- to 75-yr-old previously sedentary women after heavy-resistance strength training (HRST). Subjects performed unilateral knee-extension exercise 3 days/wk for 9 wk. Bilateral muscle biopsies from the vastus lateralis were assessed for muscle damage via electron microscopy. HRST resulted in a 38 and 25% increase in strength in the young and older women, respectively (P < 0.05), but there were no between-group differences. In the young women, 2-4% of muscle fibers exhibited damage before and after training in both the trained and untrained legs (P = not significant). In contrast, muscle damage increased significantly after HRST, from 5 to 17% of fibers damaged (P < 0.01), in the older women in the trained leg compared with only 2 and 5% of fibers damaged in the untrained leg before and after training, respectively. The present results indicate that older women exhibit higher levels of muscle damage after chronic HRST than do young women.

Adult↗

Strength training in the elderly: effects on risk factors for age-related diseases.

Strength training (ST) is considered a promising intervention for reversing the loss of muscle function and the deterioration of muscle structure that is associated with advanced age. This reversal is thought to result in improvements in functional abilities and health status in the elderly by increasing muscle mass, strength and power and by increasing bone mineral density (BMD). In the past couple of decades, many studies have examined the effects of ST on risk factors for age-related diseases or disabilities. Collectively, these studies indicate that ST in the elderly: (i) is an effective intervention against sarcopenia because it produces substantial increases in the strength, mass, power and quality of skeletal muscle; (ii) can increase endurance performance; (iii) normalises blood pressure in those with high normal values; (iv) reduces insulin resistance; (v) decreases both total and intra-abdominal fat; (vi) increases resting metabolic rate in older men; (vii) prevents the loss of BMD with age; (viii) reduces risk factors for falls; and (ix) may reduce pain and improve function in those with osteoarthritis in the knee region. However, contrary to popular belief, ST does not increase maximal oxygen uptake beyond normal variations, improve lipoprotein or lipid profiles, or improve flexibility in the elderly.

Accidental Falls↗

Strength training for the prevention and treatment of sarcopenia.

There is a progressive loss of muscle strength, muscle mass and muscle quality with advanced age, which results in a condition known as sarcopenia. In this review, the authors outline the magnitude of these losses, their functional consequences, and the efficacy of strength training (ST) as an intervention strategy for delaying, preventing or reversing the effects of sarcopenia. The question of whether sex differences and genetics influence the effects of sarcopenia and responses to ST are also discussed. Although many potential mechanisms for sarcopenia exist, their specific contributions are still unknown. Nevertheless, proposed mechanisms of sarcopenia are outlined and, where information is available, we examine the effects of ST on these potential mechanisms, which include neurogenic factors, anabolic hormones, protein synthesis, gene expression, muscle morphology, and muscle regeneration. Finally, the potential impact of genetics in the muscle response to both sarcopenia and ST is discussed. The evidence presented suggests that ST is an effective intervention for improving strength, muscle mass and muscle quality and delaying the onset of physical disability in the elderly. However, sex differences and genetic factors may play an important role in determining the muscular response to aging and ST.

Aged↗

Frequent sequence variation in the human myostatin (GDF8) gene as a marker for analysis of muscle-related phenotypes.

Myostatin is a recently identified member of the transforming growth factor-beta family of regulatory factors, also known as growth and differentiation factor 8 (GDF8). The nucleotide sequence of human myostatin was determined in 40 individuals. The invariant promoter contains a consensus MyoD binding site, and the coding sequence contains five missense substitutions in conserved amino acid residues (A55T, K153R, E164K, P198A, and I225T). Two of these, A55T in exon 1 and K153R in exon 2, are polymorphic in the general population with significantly different allele frequencies in Caucasians and African Americans (P < 0.001). Neither of the common polymorphisms had a significant impact on muscle mass response to strength training in either Caucasians or African Americans, although skewed allele frequencies preclude detection of small effects. These allelic variants provide markers for examining association between the myostatin gene and interindividual variation in muscle mass and differences in loss of muscle mass with aging.

Amino Acid Substitution↗

A rational algorithm for duplex scan surveillance after carotid endarterectomy.

PURPOSE: This study was undertaken to determine the appropriate timing and frequency of duplex ultrasound scanning after carotid endarterectomy (CEA) for the detection of high-grade stenosis caused by recurrent carotid stenosis or contralateral atherosclerotic disease progression. METHODS: In 221 patients who underwent 242 CEAs, duplex scanning was performed before, during, and after operation (in 3-month to 6-month intervals). High-grade internal carotid artery (ICA) stenosis (peak systolic velocity, >300 cm/s; diastolic velocity, >125 cm/s; ICA/common carotid artery ratio, >4) prompted the recommendation for repair. An average of four postoperative scanning procedures was performed during a mean follow-up period of 27.4 months. RESULTS: Intraoperative duplex scan results prompted the immediate revision of 12 repairs (4.9%), and one perioperative stroke (<1%) occurred. Six CEAs (2.7%) had asymptomatic recurrent stenosis (>50% diameter-reduction [DR]; systolic velocity, >125 cm/s) develop. Only one of six patients had >75% DR stenosis develop and underwent reoperation (<1% yield for CEA surveillance). The yield of surveillance of the unoperated ICA was higher (P =.003), and 12% of unoperated sides had progressive stenosis (n = 21) or occlusion (n = 3) develop, which led to seven CEAs for high-grade stenosis. Disease progression to >75% DR stenosis was five times as frequent (P =.002) in patients with >50% DR stenosis initially. All patients but one who required contralateral endarterectomy for disease progression had >50% ICA stenosis when first seen. During the follow-up period, no disabling strokes ipsilateral to an operated carotid artery occurred, but three strokes occurred in the hemisphere of the contralateral unoperated ICA. CONCLUSION: The yield of duplex scan surveillance after CEA was low. Only 13 patients (5.9%) had severe disease develop to warrant additional intervention. Progression of contralateral disease rather than restenosis was the most common abnormality that was identified. Duplex scanning at 1-year to 2-year intervals after CEA is adequate when a technically precise repair is achieved and minimal contralateral disease (<50% DR) is present. A policy of duplex scan surveillance and reoperation for high-grade stenosis was associated with a 1.6% incidence rate of disabling stroke during the follow-up period.

Adult↗

Strength training normalizes resting blood pressure in 65- to 73-year-old men and women with high normal blood pressure.

OBJECTIVE: To determine the effects of heavy resistance strength training (ST) on resting blood pressure (BP) in older men and women. DESIGN: Prospective intervention study. SETTING: University of Maryland Exercise Science Laboratory. PARTICIPANTS: Twenty-one sedentary, healthy older men (69 +/- 1 year, n = 11) and women (68 +/- 1 year, n = 10) served as subjects for the study. INTERVENTION: Six months of progressive whole body ST performed 3 days per week using Keiser K-300 air-powered resistance machines. MEASUREMENTS: One-repetition maximum (1 RM) strength was measured for seven different exercises before and after the ST program. Resting BP was measured on six separate occasions before and after ST for each subject. RESULTS: Substantial increases in 1 RM strength were observed for upper body (UB) and lower body (LB) muscle groups for men (UB: 215 vs 265 kg; LB: 694 vs 838 kg; P < .001) and women (UB: 128 vs 154 kg; LB: 441 vs 563 kg; P < .001). The ST program led to reductions in both systolic (131 +/- 2 vs 126 +/- 2 mm Hg, P < .010) and diastolic (79 +/- 2 vs 75 +/- 1 mm Hg, P < .010) BP. Systolic BP was reduced significantly in men (134 +/- 3 vs 127 +/- 2 mm Hg, P < .01) but not in women (128 +/- 3 vs 125 +/- 3 mm Hg, P < .01), whereas diastolic BP was reduced following training in both men (81 +/- 3 vs 77 +/- 1, mm Hg, P = .054) and women (78 +/- 2 vs 74 +/- 2 mm Hg, P = .055). CONCLUSIONS: Six months of heavy resistance ST may reduce resting BP in older persons. According to the latest guidelines from the Joint National Committee for the Detection, Evaluation, and Treatment of Hypertension, the changes in resting BP noted in the present study represent a shift from the high normal to the normal category.

Aged↗

Ultrastructural muscle damage in young vs. older men after high-volume, heavy-resistance strength training.

This study assessed ultrastructural muscle damage in young (20-30 yr old) vs. older (65-75 yr old) men after heavy-resistance strength training (HRST). Seven young and eight older subjects completed 9 wk of unilateral leg extension HRST. Five sets of 5-20 repetitions were performed 3 days/wk with variable resistance designed to subject the muscle to near-maximal loads during every repetition. Biopsies were taken from the vastus lateralis of both legs, and muscle damage was quantified via electron microscopy. Training resulted in a 27% strength increase in both groups (P < 0.05). In biopsies before training in the trained leg and in all biopsies from untrained leg, 0-3% of muscle fibers exhibited muscle damage in both groups (P = not significant). After HRST, 7 and 6% of fibers in the trained leg exhibited damage in the young and older men, respectively (P < 0.05, no significant group differences). Myofibrillar damage was primarily focal, confined to one to two sarcomeres. Young and older men appear to exhibit similar levels of muscle damage at baseline and after chronic HRST.

Actin Cytoskeleton↗