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Biomedical subjects

V A Hughes

Publications and source records attributed to V A Hughes.

At least 19 recordsLinked to original sources

Do patients with nonmetastatic non-small cell lung cancer demonstrate altered resting energy expenditure?

BACKGROUND: The cancer cachexia syndrome occurs in patients with non-small cell lung cancer (NSCLC) and includes elevated resting energy expenditure (REE). This increase in REE leads to weight loss, which in turn confers a poor prognosis. This study was undertaken to determine whether the cancer cachexia syndrome occurs in patients with nonmetastatic NSCLC. METHODS: In this case-control study, 18 patients with nonmetastatic NSCLC (stages IA to IIIB) were matched to healthy controls on age (+/- 5 years), gender, and body mass index (+/- 3 kg/m2). Only 4 cancer patients had experienced > 5% weight loss. Cancer patients and controls were compared on the basis of: (1) unadjusted REE, as measured by indirect calorimetry; (2) REE adjusted for lean body mass, as measured by dual x-ray absorptiometry; (3) REE adjusted for body cell mass, as measured by potassium-40 measurement; and (4) REE adjusted for total body water, as measured by tritiated water dilution. RESULTS: We observed no significant difference in unadjusted REE or in REE adjusted for total body water. However, with separate adjustments for lean body mass and body cell mass, cancer patients manifested an increase in REE: mean difference +/- standard error of the mean: 140+/-35 kcal/day (p = 0.001) and 173+/-65 kcal/day (p = 0.032), respectively. Further adjustment for weight loss yielded similarly significant results. CONCLUSIONS: These results suggest that the cancer cachexia syndrome occurs in patients with nonmetastatic NSCLC and raise the question of whether clinical trials that target cancer cachexia should be initiated before weight loss.

Aged↗

Longitudinal muscle strength changes in older adults: influence of muscle mass, physical activity, and health.

The longitudinal changes in isokinetic strength of knee and elbow extensors and flexors, muscle mass, physical activity, and health were examined in 120 subjects initially 46 to 78 years old. Sixty-eight women and 52 men were reexamined after 9.7 +/- 1.1 years. The rates of decline in isokinetic strength averaged 14% per decade for knee extensors and 16% per decade for knee flexors in men and women. Women demonstrated slower rates of decline in elbow extensors and flexors (2% per decade) than men (12% per decade). Older subjects demonstrated a greater rate of decline in strength. In men, longitudinal rates of decline of leg muscle strength were approximately 60% greater than estimates from a cross-sectional analysis in the same population. The change in leg strength was directly related to the change in muscle mass in both men and women, and it was inversely related to the change in medication use in men. Physical activity declined yet was not directly associated with strength changes. Although muscle mass changes influenced the magnitude of the strength changes over time, strength declines in spite of muscle mass maintenance or even gain emphasize the need to explore the contribution of other cellular, neural, or metabolic mediators of strength changes.

Aged↗

Age- and gender-related differences in maximum shortening velocity of skeletal muscle fibers.

OBJECTIVE: To determine age- and gender-related differences in maximum unloaded shortening velocity (Vo) of Type I and IIA single muscle fibers. Muscle fibers must have a broad range of contractile velocities to generate the full range of power required for varied activities. DESIGN: Percutaneous needle biopsies of the vastus lateralis were obtained from 31 healthy subjects (n = 7 young men [YM], n = 7 young women [YW], n = 12 older men [OM], n = 12 older women [OW]). The slack test was used to determine Vo of individual fibers; 916 muscle fibers were chemically skinned. Fiber type was determined by myosin heavy chain isoform identification. RESULTS: Among men, Vo (fiber lengths/sec) was reduced with age in Type IIA fibers (OM vs. YM: 1.78 vs. 2.14; P < 0.05) but unchanged in Type I fibers. Among women, Vo was reduced with age in Type I fibers (OW vs. YW: 0.70 vs. 0.75; P < 0.05) but not IIA. OW had a lower Vo than did OM in both fiber types (Type I: OW = 0.70, OM = 0.77; Type IIA: OW = 1.51, OM = 1.78; P < 0.05). YW did not differ from YM. CONCLUSIONS: Both age and gender affect Vo. Age- and gender-related differences in Vo may partially explain the impairments in muscle function that occur with aging and the greater impairment in muscle function observed in OW compared with that observed in OM.

Adult↗

Sarcopenia: current concepts.

Sarcopenia, the loss of muscle mass and strength with age, is becoming recognized as a major cause of disability and morbidity in the elderly population. Sarcopenia is part of normal aging and does not require a disease to occur, although muscle wasting is accelerated by chronic diseases. Sarcopenia is thought to have multiple causes, although the relative importance of each is not clear. Neurological, metabolic, hormonal, nutritional, and physical-activity-related changes with age are likely to contribute to the loss of muscle mass. In this review, we discuss current concepts of the pathogenesis, treatment, and prevention of sarcopenia.

Humans↗

The effect of gender and body composition method on the apparent decline in lean mass-adjusted resting metabolic rate with age.

BACKGROUND: Declining resting energy expenditure (REE) is a hallmark of normal aging, but the cause of this decline remains controversial. Some, but not all, studies have shown that the decline in REE with age is eliminated after adjustment for fat-free mass (FFM). METHODS: We examined the effect of four body composition methods used to assess FFM (underwater weighing [UWW], bioimpedance analysis [BIA], tritium dilution, and total body potassium [TBK]) on the relationship between REE and age in 30 healthy men and 101 healthy women aged 18 to 87 years. RESULTS: The decline in REE with age was significant in women (-80.3 kJ/d/y, p < .004) but not in men (-46.9 kJ/d/y, p = .328). After adjustment for FFM, the decline in REE with age persisted when FFM was measured by BIA, UWW, or tritium dilution, but no decline was seen when TBK was used to adjust for FFM. In both women and men, fat mass was significantly associated with REE after adjusting for age and FFM. CONCLUSION: It is the decline in cell mass with age, detectable by TBK but not by other methods, rather than any metabolic alteration, that explains the decline in FFM-adjusted REE with age.

Adult↗

Skeletal muscle fiber quality in older men and women.

Whole muscle strength and cross-sectional area (WMCSA), and contractile properties of chemically skinned segments from single fibers of the quadriceps were studied in 7 young men (YM, 36.5 +/- 3. 0 yr), 12 older men (OM, 74.4 +/- 5.9 yr), and 12 older women (OW, 72.1 +/- 4.3 yr). WMCSA was smaller in OM compared with YM (56.1 +/- 10.1 vs. 79.7 +/- 13.1 cm(2); P = 0.031) and in OW (44.9 +/- 7.5; P < 0.003) compared with OM. Age-related, but not sex-related, differences in strength were eliminated after adjusting for WMCSA. Maximal force was measured in 552 type I and 230 type IIA fibers. Fibers from YM (type I = 725 +/- 221; type IIA = 792 +/- 271 microN) were stronger (P < 0.001) than fibers from OM (I = 505 +/- 179; IIA = 577 +/- 262 microN) even after correcting for size. Type IIA fibers were stronger (P < 0.005) than type I fibers in YM and OM but not in OW (I = 472 +/- 154; IIA = 422 +/- 97 microN). Sex-related differences in type I and IIA fibers were dependent on fiber size. In conclusion, differences in WMCSA explain age-related differences in strength. An intrinsic defect in contractile proteins could explain weakness in single fibers from OM. Sex-related differences exist at the whole muscle and single fiber levels.

Adult↗

Aging of skeletal muscle: a 12-yr longitudinal study.

The present study examines age-related changes in skeletal muscle size and function after 12 yr. Twelve healthy sedentary men were studied in 1985-86 (T1) and nine (initial mean age 65.4 +/- 4.2 yr) were reevaluated in 1997-98 (T2). Isokinetic muscle strength of the knee and elbow extensors and flexors showed losses (P < 0.05) ranging from 20 to 30% at slow and fast angular velocities. Computerized tomography (n = 7) showed reductions (P < 0.05) in the cross-sectional area (CSA) of the thigh (12.5%), all thigh muscles (14.7%), quadriceps femoris muscle (16.1%), and flexor muscles (14. 9%). Analysis of covariance showed that strength at T1 and changes in CSA were independent predictors of strength at T2. Muscle biopsies taken from vastus lateralis muscles (n = 6) showed a reduction in percentage of type I fibers (T1 = 60% vs. T2 = 42%) with no change in mean area in either fiber type. The capillary-to-fiber ratio was significantly lower at T2 (1.39 vs. 1. 08; P = 0.043). Our observations suggest that a quantitative loss in muscle CSA is a major contributor to the decrease in muscle strength seen with advancing age and, together with muscle strength at T1, accounts for 90% of the variability in strength at T2.

Aged↗

The reproducibility of the Bruce protocol exercise test for the determination of aerobic capacity in older women.

The reproducibility of the Bruce exercise test protocol for the determination of maximal aerobic activity was evaluated in sedentary older women. Seventeen women between the ages of 51 and 68 yr performed five maximal graded exercise tests to volitional fatigue on a treadmill. VO2max (mL.kg-1.min-1) values averaged 27.5 +/- 1.1; 28.3 +/- 1.3; 28.4 +/- 1.3; 29.6 +/- 1.5; and 28.2 +/- 1.4 for trials 1-5, respectively, and were not significantly different. Criteria for a plateau in VO2 at the point of exhaustion were met in 21 out of 85 tests (25%). The mean coefficient of variation VO2max for the subjects for the 5 tests was 6.5% (range, 2.0-14%). Pearson's correlation coefficients for the study variables were significant, indicating good agreement between repeated tests (r2: between 0.70 to 0.89). Although there were no significant differences among the mean VO2max values in the 5 trials, 11 subjects had a 1.0 ml.kg-1.min-1 or greater increase in the VO2max from test 1 to test 2, and only 6 subjects had no change or a decrease in VO2max. The mean difference between T2 and T3 was lower (T1 vs T2: 0.8 mL.kg-1.min-1, T2 vs T3: 0.1 mL.kg-1.min-1) indicating slightly better agreement between the second and third set. Estimates of the between and within subject variance revealed a low within subject variance (4.2 (mL.kg-1.min-1)2) compared to the between subject variance (22.1 (mL.kg-1.min-1)2). This study demonstrates that a commonly used exercise testing protocol generates highly reproducible measurements of VO2max in women between 51 and 68 yr. The mean differences between tests and the high level of agreement between repeated tests suggests that a single measurement of VO2max can be performed to assess functional aerobic capacity in this population.

Aged↗

Long-term effects of a high-carbohydrate diet and exercise on insulin action in older subjects with impaired glucose tolerance.

Carbohydrate metabolism was assessed in 20 glucose-intolerant subjects before and after 12 wk on a high-carbohydrate diet (HC) or the diet combined with exercise training (HC-EX). The diet provided 60% of energy as carbohydrate and 20% as fat. Neither treatment altered fasting glucose or insulin concentrations or their response to a meal. During a glucose clamp (216 pmol insulin/L) glucose disposal increased from 13.2 +/- 0.83 to 14.6 +/- 0.83 mumol.kg fat-free mass-1.min-1 (P < 0.05) in both groups. During more pronounced hyperinsulinemia (654 pmol/L) glucose disposal did not change significantly (49.9 +/- 3.8 to 50.7 +/- 3.8 mumol.kg fat-free mass-1.min-1). Muscle glycogen increased in the HC-EX group (78.5 +/- 8.1 to 161.1 +/- 15.7 mmol glucose/kg muscle), with no changes in the HC group. These results do not support the recommendation to increase the dietary carbohydrate content for improving postprandial glucose metabolism or insulin action in glucose-intolerant adults unless combined with exercise training, which promotes muscle glycogen storage.

Aged↗

Muscle strength and body composition: associations with bone density in older subjects.

This study investigated the relationship between isokinetic muscle strength and bone density (SPA and DPA) in men and women aged 45-77 yr. Regression models were adjusted for age, weight, smoking status, and calcium supplementation. Elbow extensors (but not flexors) peak torque was correlated with radial density in men (partial r = 0.26, P < 0.05) and women (partial r = 0.24, P < 0.05). Knee flexor (but not extensor) peak torque in women was significantly correlated with spine density (partial r = 0.28, P < 0.05), and muscle mass was significantly correlated with Ward's triangle density (partial r = 0.35, P < 0.05). No associations between knee flexor or extensor muscle strength and spine or femur bone density were observed in men. Fat-free mass (FFM, hydrodensitometry) was associated with all bone density sites in males and females (partial r = 0.30-0.55; P < 0.05). These results demonstrate that 1) significant associations observed between elbow extensor strength and radial bone density in men and women may reflect loading along the longitudinal axis of the radius associated with elbow extensor activity; and 2) significant associations exist between knee flexor muscle strength and lumbar density in women only. Additionally, the associations between FFM and bone density do not necessarily reflect associations between isokinetic muscle strength and bone density.

Aged↗

Military body fat standards and equations applied to middle-aged women.

Military circumference equations are used to assess compliance of military personnel with body fat (BF) standards. The purpose of the present study was to determine the ability of military equations to correctly classify 62 women aged 40-60 yr (50.9 +/- 6.2, mean +/- SD) as overfat or underfat using underwater weighing (UWW) as the reference method and military BF standards as diagnostic cutoffs. Values for the mean +/- SD percent BF from UWW, Army, Marine Corps, and Navy equations were 29.5 +/- 7.1, 27.3 +/- 4.7, 25.7 +/- 5.8, and 30.3 +/- 5.1, respectively. The Army and Marine Corps equations underpredicted percent BF compared to UWW, P < 0.05. Bland-Altman plots showed a lack of agreement in predicting percent BF in women 40-60 yr between equation and UWW-derived percent BF. This finding was supported by the low agreement in correctly classifying an individual as meeting or exceeding the BF standards, range 25%-57%, Cohen's kappa. The low sensitivities (range 20%-74%) and higher specificities (range 80%-98%) of the equations indicated they identified individuals who met the BF standards better than those who exceeded them. Caution must be exercised when using military prediction equations to assess compliance with military BF standards in healthy middle-aged women.

Adipose Tissue↗

Lipoprotein response to exercise training and a low-fat diet in older subjects with glucose intolerance.

The purpose of this study was to determine the effect of aerobic exercise training (Ex), a low-fat diet (LF, 19% fat), or combined interventions (LF-Ex) on lipoprotein cholesterol (LDL, HDL, and VLDL) and triglyceride (TG) concentrations in glucose-intolerant subjects while their weight was maintained. Baseline dietary fat and carbohydrate composition, body composition, body mass index, age, and lipoprotein cholesterol were not different among groups. Aerobic capacity increased in both exercise groups (P < 0.01) and remained unchanged in the LF group. Body composition was unaltered and change in body weight (kg) was small: Ex, -0.8 +/- 0.4, (P < 0.05); LF, +0.4 +/- 0.4; (NS); LF-Ex, -1.4 +/- 0.4 (P < 0.01). Exercise alone did not significantly affect lipoprotein cholesterol or TG concentrations. In LF and LF-Ex, respectively, decreases (P < 0.02) in total cholesterol (-0.66 +/- 0.24 and -0.42 +/- 0.21 mmol/L), HDL (-0.14 +/- 0.07 and -0.26 +/- 0.04), and LDL (-0.60 +/- 0.25 and -0.23 +/- 0.13) were seen after 12 wk, whereas VLDL and TG remained unchanged. Our data indicate that beneficial effects of exercise training on lipid indexes are not observed in subjects with impaired glucose tolerance on either an average US diet or a low-fat diet if substantial changes in weight or body composition do not occur.

Aged↗

Exercise increases muscle GLUT-4 levels and insulin action in subjects with impaired glucose tolerance.

A decline in insulin sensitivity is associated with aging, inactivity, and obesity. The effects of exercise training on glucose homeostasis independent of weight loss in older glucose-intolerant individuals are not well established. We examined the effects of exercise training on oral glucose tolerance, insulin action, and concentration of the GLUT-4 glucose transporters in skeletal muscle. Exercise training at 50 and 75% of heart rate reserve was performed for 12 wk in 18 individuals (age = 64 +/- 2, body fat = 37.0 +/- 1.5%). Peripheral insulin action was determined 96 h after the last exercise bout using a two-step hyperinsulinemic-euglycemic glucose clamp (insulin = 192 and 708 pmol/l). Percent body fat and fat-free mass (FFM) were unchanged with training. Diet composition, assessed by diet record, did not change over the 12 wk. Improved oral glucose tolerance was observed, as exhibited by lower plasma glucose concentrations after training (P < 0.05), whereas plasma insulin response remained unchanged. The rate of glucose disposal was unchanged during the low insulin concentration but increased 11.0% at the high insulin concentration (P < 0.05) after training (54.4 +/- 4.4 vs. 60.4 +/- 5.5 mumol.kg FFM-1.min-1). Skeletal muscle glycogen and GLUT-4 concentration increased 24 and 60%, respectively, with training. There was no direct relationship between the change in GLUT-4 protein and the change in glucose disposal rate. These findings demonstrate that chronic exercise training without changes in body composition improves peripheral insulin action in subjects with impaired glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Reliability of isokinetic muscle strength testing in 45- to 78-year-old men and women.

The test-retest reliability of isokinetic muscle strength testing was determined in 45- to 78-year-old men (N = 71; mean age = 60.2 years) and women (N = 107; mean age = 60.0 years). The dynamic muscle strength of the knee and elbow extensor (KE, EE) and flexor (KF, EF) muscle groups was measured at slow (60 degrees/sec) and fast (K = 240 degrees/sec; E = 180 degrees/sec) angular velocities using a Cybex II isokinetic dynamometer on two occasions seven to ten days apart. The mean peak torque in the second test was significantly higher (p < 0.001) in all muscle groups and both angular velocities tested in both sexes. The angle at which peak torque occurred did not change from the first to the second test except in the KF of females tested at 60 degrees/sec. Pearson's correlation coefficients (CCs; p < 0.01) in males ranged from .68 to .77 in the knee and from .71 to .84 in the elbow. In females, the CCs (p < 0.01) ranged from .58 to .74 in the knee and from .67 to .78 in the elbow. Thus in a large number of older men and women at least two tests may be necessary to determine isokinetic peak torque.

Adult↗

A cross-sectional study of muscle strength and mass in 45- to 78-yr-old men and women.

The isokinetic strength of the elbow and knee extensors and flexors was measured in 200 healthy 45- to 78-yr-old men and women to examine the relationship between muscle strength, age, and body composition. Peak torque was measured at 60 and 240 degrees/s in the knee and at 60 and 180 degrees/s in the elbow by use of a Cybex II isokinetic dynamometer. Fat-free mass (FFM) was estimated by hydrostatic weighing in all subjects, and muscle mass (MM) was determined in 141 subjects from urinary creatinine excretion. FFM and MM were significantly lower (P less than 0.001) in the oldest group. Strength of all muscle groups at both testing speeds was significantly (P less than 0.006) lower (range 15.5-26.7%) in the 65- to 78- than in the 45- to 54-yr-old men and women. When strength was adjusted for FFM or MM, the age-related differences were not significant in all muscle groups except the knee extensors tested at 240 degrees/s. Absolute strength of the women ranged from 42.2 to 62.8% that of men. When strength was expressed per kilogram of MM, these gender differences were smaller and/or not present. These data suggest that MM is a major determinant of the age- and gender-related differences in skeletal muscle strength. Furthermore, this finding is, to a large extent, independent of muscle location (upper vs. lower extremities) and function (extension vs. flexion).

Adipose Tissue↗

Peripheral effects of endurance training in young and old subjects.

The effects of 12 wk of endurance training at 70% peak O2 consumption (VO2) were studied in 10 elderly (65.1 +/- 2.9 yr) and 10 young (23.6 +/- 1.8 yr) healthy men and women. Training had no effect on weight or body composition in either group. The elderly had more adipose tissue and less muscle mass than the young. Initial peak VO2 was lower in the elderly, but the absolute increase of 5.5-6.0 ml.kg-1.min-1 after training was similar for both groups. Muscle biopsies taken at rest showed that, before training, muscle glycogen stores were 61% higher in the young. Before training, glycogen utilization per joule during submaximal exercise was higher in the elderly. Glycogen stores and muscle O2 consumption increased significantly in response to training in the elderly only. After training, the proportion of energy derived from whole body carbohydrate oxidation during submaximal exercise declined in the young only. The absolute changes that training produced in peak VO2 were similar in both age groups, but the 128% increase in muscle oxidative capacity was greater in the elderly, suggesting that peripheral factors play an important role in the response of the elderly to endurance exercise.

Adult↗

The effects of high intensity exercise on muscle and plasma levels of alpha-ketoisocaproic acid.

Alpha-ketoisocaproic acid (KIC) is the product of the transamination of the indispensable amino acid leucine, which is the first step in the complete degradation of leucine. To determine the effects of intense exercise on muscle and blood levels of KIC, 7 male volunteers performed cycle exercise to exhaustion. After pedaling at an intensity of 90 W for 3 min, the load was increased by 60 W every 3 min until volitional fatigue. Muscle biopsies were obtained prior to and immediately after exercise and rapidly frozen for later determination of KIC. During exercise, blood lactate levels increased as expected, while plasma KIC levels did not change. Following exercise, plasma KIC levels rose significantly with peak values occurring 15 min after exercise and did not return to pre-exercise values until 60 min after exercise. In contrast, muscle KIC levels increased during exercise from a pre-exercise mean of 49.4 +/- 4.1 mumol X kg-1 wet wt to 78.1 +/- 6.5 mumol X kg-1 after exercise, an average increase of 48% (P less than 0.05). These data indicate that during intense exercise, leucine transamination in muscle may continue at a faster rate than the decarboxylation of KIC. In addition, plasma levels of KIC did not reflect the intracellular accumulation of KIC during exercise, suggesting a delay in the diffusion of KIC from muscle.

Humans↗