Influence of exercise on nutritional requirements.

There is no consensus on the best diet for exercise, as many variables influence it. We propose an approach that is based on the total energy expenditure of exercise and the specific macro- and micronutrients used. di Prampero quantified the impact of intensity and duration on the energy cost of exercise. This can be used to determine the total energy needs and the balance of fats and carbohydrates (CHO). There are metabolic differences between sedentary and trained persons, thus the total energy intake to prevent overfeeding of sedentary persons and underfeeding athletes is important. During submaximal sustained exercise, fat oxidation (FO) plays an important role. This role is diminished and CHO's role increases as exercise intensity increases. At super-maximal exercise intensities, anaerobic glycolysis dominates. In the case of protein and micronutrients, specific recommendations are required. We propose that for submaximal exercise, the balance of CHO and fat favors fat for longer exercise and CHO for shorter exercise, while always maintaining the minimal requirements of each (CHO: 40% and fat: 30%). A case for higher protein (above 15%) as well as creatine supplementation for resistance exercise has been proposed. One may also consider increasing bicarbonate intake for exercise that relies on anaerobic glycolysis, whereas there appears to be little support for antioxidant supplementation. Insuring minimal levels of substrate will prevent exercise intolerance, while increasing some components may increase exercise tolerance.

Bortezomib administered pre-auto-SCT and as maintenance therapy post transplant for multiple myeloma: a single institution phase II study.

The appropriate induction therapy before and the role of maintenance therapy after auto-SCT for patients with multiple myeloma remain areas of active investigation. We conducted a study in 40 patients with bortezomib given sequentially pre-auto-SCT and as maintenance therapy post auto-SCT. Pre-transplant bortezomib was administered for two cycles followed by high-dose melphalan 200 mg/m(2) with auto-SCT of G-CSF-mobilized PBMCs. Post transplant bortezomib was administered weekly for 5 out of 6 weeks for six cycles. No adverse effects were observed on stem cell mobilization or engraftment. An overall response rate of 83% with a CR+very good partial remission (VGPR) of 50% was observed with this approach. Three-year Kaplan-Meier estimates of disease-free survival and overall survival (OS) were 38.2 and 63.1%, respectively. Bortezomib reduced CD8(+) cytotoxic T cell and CD56(+) natural killer cell PBL subsets and was clinically associated with high rates of viral reactivation to varicella zoster.

Statin therapy depresses total body fat oxidation in the absence of genetic limitations to fat oxidation.

Cholesterol lowering drugs are associated with myopathic side effects in 7% of those on therapy, which is reversible in most, but not all patients. This study tested the hypothesis that total body fat oxidation (TBFO) is reduced by statins in patients with genetic deficiencies in FO, determined by white blood cells (FOwbc) and by molecular analysis of common deficiencies, and would cause intolerance in some patients. Six patients on statin therapy without myopathic side effects (tolerant) and 7 patients who had previously developed statin-induced myopathic symptoms (intolerant) (age = 58 +/- 8.25 yrs, ht. = 169 +/- 11 cm, and wt. = 75.4 +/- 14.2 kg) were tested for TBFO (Respiratory Exchange Ratio, RER) pre- and during exercise. FOwbc was not significantly different between tolerant and intolerant (0.261 +/- 0.078 vs. 0.296 +/- 0.042 nmol/h per 10(9) wbc), or normals (0.27 +/- 0.09 nmol/h per 10(9) wbc) and no common molecular abnormalities were found. Pre-exercise RER (0.73 +/- 0.05 vs. 0.84 +/- 0.05) was significantly lower in the intolerant group and the VO2 at RER = 1.0 (1.27 +/- 0.32 vs. 1.87 +/- 0.60 L/min) greater than the tolerant. Post-exercise lactates were not different between groups. Although dietary fat intake was not different, blood lipoprotein levels, particularly triglycerides were 35% lower in tolerant than previously intolerant. TBFO and blood lipoproteins were reduced in tolerant patients in spite of the absence of genetic limitations, but not in the intolerant group as hypothesized. Although not conclusive, these data suggest the need for a prospective study of the effects of statins on fat oxidation.

The distribution of white blood cell fat oxidation in health and disease.

Fat oxidation is important for maintaining health and for supplying energy for exercise. We have proposed that the predisposition for individual rates of fat oxidation is determined genetically but may be modulated by acute exercise or exercise training. The purpose of this study was to examine cellular fat oxidation in white blood cells (WBC) using [9,10-3H]palmitic acid. Sedentary controls free of symptoms (SED-C, n=32), were compared with known carnitine palmitoyltransferase (CPT) II-deficient patients (n =2), patients with fatiguing diseases (chronic fatigue syndrome, CFS, n=6; multiple sclerosis, MS, n=31), obesity (OB, n=5), eating disorders (ED, n=16), sedentary individuals prior to and after exercise (SED-Ex, n=12), exercise-trained sedentary individuals (SED-Tr, n=12), and elite runners (ER, n=5). Fat oxidation in WBC for all subjects was normally distributed (mean=0.270 +/- 0.090 nmol/h per 10(9) WBC) and ranged from 0.09 nmol/h per 10(9) WBC in CPT II-deficient patients to 0.59 nmol/h per 10(9) WBC in ER. There were no significant sex or acute exercise effects on WBC fat oxidation. Patients with MS, OB or ED were not different from SED-C; however, in CPT II-deficient patients, fat oxidation was low, while that of CFS patients was high. Exercise training in SED-C resulted in a 16% increase in fat oxidation but in ER it was still 97% higher than in SED-C. We propose that while WBC fat oxidation is not significantly affected by sex or acute exercise, and only by 15-20% with training, genetic factors play a role in determining both high and low fat oxidation in certain groups of individuals. The genetic predisposition for individual rates of fat oxidation may be easily measured using WBC fat oxidation, as has been shown for CPT II-deficient patients and for elite runners. Ranges of WBC fat oxidation that are abnormally low (<20 nmol/h per 10(9) WBC, normal 20-35) or high (>35 nmol/h per 10(9) WBC) are proposed based on genetic factors evaluated in this study.

Heart rate variability during dynamic exercise in elderly males and females.

It has been proposed that cardiac control is altered in the elderly. Power spectral analysis of heart rate variability (HRV) was performed on 12 male and 11 female elderly subjects (mean age 74 years) while at rest in supine and sitting positions, and at steady states during 5 min of exercise (35-95% peak oxygen consumption, VO2peak). There were no differences in power, measured as a percentage of the total of the high frequency peak (HF, centred at about 0.25 Hz; 13% in males vs 12% in females), low frequency peak (LF, centred at 0.09 Hz; 25% in males and 22% in females), and very low frequency component (VLF, at 0.03 Hz; 66% in males and 69% in females) between body positions at rest. There was no difference in spectral power between male and female subjects. Total power decreased as a function of oxygen consumption during exercise, LF% did not change up to about 14 ml x kg(-1) x min(-1) (40% and 80% VO2peak in males and females, respectively), then decreased towards minimal values in both genders. HF% power and central frequency increased linearly with metabolic demand, reaching higher values in male subjects than in female subjects at VO2peak, while VLF% remained unchanged. Thus, the power spectra components of HRV did not reflect the changes in autonomic activity that occur at increasing exercise intensities, confirming previous findings in young subjects, and indicated similar responses in both genders.

The effects of varying dietary fat on performance and metabolism in trained male and female runners.

OBJECTIVES: Low dietary fat intake has become the diet of choice for many athletes. Recent studies in animals and humans suggest that a high fat diet may increase VO2max and endurance. We studied the effects of a low, medium and high fat diet on performance and metabolism in runners. METHODS: Twelve male and 13 female runners (42 miles/week) ate diets of 16% and 31% fat for four weeks. Six males and six females increased their fat intakes to 44%. All diets were designed to be isocaloric. Endurance and VO2max were tested at the end of each diet. Plasma levels of lactate, pyruvate, glucose, glycerol, and triglycerides were measured before and after the VO2max and endurance runs. Free fatty acids were measured during the VO2max and endurance runs. RESULTS: Runners on the low fat diet ate 19% fewer calories than on the medium or high fat diets. Body weight, percent body fat (males=71 kg and 16%; females=57 kg and 19%), VO2max and anaerobic power were not affected by the level of dietary fat. Endurance time increased from the low fat to medium fat diet by 14%. No differences were seen in plasma lactate, glucose, glycerol, triglycerides and fatty acids when comparing the low versus the medium fat diet. Subjects who increased dietary fat to 44% had higher plasma pyruvate (46%) and lower lactate levels (39%) after the endurance run. CONCLUSION: These results suggest that runners on a low fat diet consume fewer calories and have reduced endurance performance than on a medium or high fat diet. A high fat diet, providing sufficient total calories, does not compromise anaerobic power.

Muscle function and gait in patients with knee osteoarthritis before and after muscle rehabilitation.

Patients with knee osteoarthritis (OA) have reduced functional capacity and muscle function that improves significantly after quantitative progressive exercise rehabilitation (QPER). The effects of these changes on the biomechanics of walking have not been quantified. Our goal was to quantify the effects of knee OA on gait before and after QPER. Bilateral kinematic and kinetic analyses were performed using a standard link-segment analysis on seven women (60.9 +/- 9.4 years) with knee OA. All functional capacity, muscle function and gait variables were initially reduced compared to age-matched controls. Muscle strength, endurance and contraction speed were significantly improved (55%, 42% and 34%, respectively) after 2 months of QPER (p < 0.05), as were function (13%), walking time (21%), difficulty (33%) and pain (13%). There were no significant changes in the gait variables after QPER. To use the QPER improvements to the best advantage, gait retraining may be necessary to "re-programme' the locomotor pattern.

Reduced muscle function in patients with osteoarthritis.

The purpose of this study was to determine whether subjects with knee osteoarthritis (OA) had reduced muscle strength at various muscle lengths, endurance, contraction velocity and functional capacity, compared with control subjects and whether the decrease was related to functional capacity. Forty-five men and 45 women with knee OA were compared with a control group (41 males, 63 females) of similar age for functional capacity, maximal isometric strength (in vivo length-tension relationship) and endurance (in vivo force-time relationship) of knee flexion and extension and maximal angular velocity (in vivo force-velocity relationship) of knee extension. The OA subjects had increased difficulty (2.03 +/- 0.53) and pain (1.65 +/- 0.29) for activities of daily living (ADLs) and significantly lower strength for extension (72%) and flexion (56%), endurance for the quadriceps (203%) and hamstrings (214%) and velocity (128%). The reductions were greater at longer muscle lengths. These data demonstrate that patients with knee OA have reduced muscle function and functional capacity compared to controls.

Energetics of underwater swimming with SCUBA.

Underwater swimming has unique features of breathing apparatus (SCUBA), thermal protective gear, and fins. The energy cost of underwater swimming is determined by the drag while swimming and the net mechanical efficiency. These are influenced by the cross-sectional area of the diver and gear and the frequency of the leg kick. The speeds that divers can achieve are relatively low, thus the VO(2) increases linearly with values of VO(2)*d(-1) of 30-50 l*km(-1)for women and men, respectively. Diving experience had little effect on VO(2) for women; however, male divers with experience had lower VO(2) than beginners. The location and density of the gear can alter the diver's attitude in the water and increase the energy cost of swimming by 30 percent at slow speeds. The type of fin used has an effect on the depth and frequency of the kick, thus on drag and efficiency, with a range of VO(2) from 25 to 50 l*km(-1). A large flexible fin had the lowest energy cost and a large rigid fin the highest. Adding extra air tanks or a dry suit increased the cost of swimming by 25 percent. The energy cost of underwater swimming is influenced by gender, gear and its placement, fin type, and experience of the diver.

Application of quantitative and progressive exercise rehabilitation to patients with osteoarthritis of the knee.

Osteoarthritis (OA) is one of the most prevalent and disabling diseases in the elderly, a rapidly growing segment of the population. OA is typically treated with a combination of drugs and inactivity, with total joint arthroplasty as the final treatment alternative. This paper reviews the potential of a non-surgical intervention for patients with OA, namely exercise rehabilitation. Several types of exercise rehabilitation are considered: home exercise (HE), physical therapy (PT), cycle exercise (CE) and a new program, quantitative progressive exercise rehabilitation (QPER). The HE program demonstrated improvements in some physiological and functional variables; however, these improvements were minimal. PT had a greater effect than HE on quadriceps and hamstring muscle strength and endurance and functional performance; however, PT had no effect on muscle contraction speed. The QPER program improved motor unit activation, quadriceps and hamstring muscle strength and endurance, contraction speed and all aspects of functional performance. In addition, QPER, although not aerobic, improved cardiorespiratory fitness and maximal workrate of VO2. This program significantly reduced difficulty, dependency and pain (during rest, exercise and at night). It would appear that the therapy of choice would be QPER since it reduces symptoms, improves joint integrity and may lead to delays in arthroplasty. These changes could improve the quality of life of patients with OA, as well as other diseases, and reduce medical costs.

Quantitative evaluation of a home exercise program on muscle and functional capacity of patients with osteoarthritis.

Rehabilitation of patients with osteoarthritis of the knees is typically based on home exercise. These programs are believed to benefit patients and have been shown to qualitatively improve strength. The purpose of the present study was to quantify the effects of a 3-mo home exercise program on muscle function and functional capacity. The progressive program included flexibility, strength, endurance, active range of motion and functional activities. Nineteen subjects (67.4 +/- 7.5 yr) with osteoarthritis of the knees began the program, with only nine completing it. The subjects initially had significantly reduced muscle function and functional capacity. Maximal isometric strength of knee extension increased significantly at a knee flexion position of 45 degrees for hip flexion positions of 120 degrees and 60 degrees (35%); however, it failed to increase at longer muscle lengths. There were no significant improvements in hamstring strength. Maximal angular velocity improved after 3 mo of exercise (40%). Muscle endurance did not improve significantly. Although there was a slight increase in functional capacity, these data failed to demonstrate significant clinical or statistical improvement in overall function in patients after home exercise.

Effects of a muscle exercise program on exercise capacity in subjects with osteoarthritis.

Maximal aerobic power and muscle function have been shown to decrease with age and to be even lower in patients with osteoarthritis (OA). This study was designed to determine if subjects with OA who underwent only a muscle exercise program had improved exercise capacity and cardiovascular fitness. A maximal graded exercise test was given before and after 3 months of exercise (isometric, isotonic, and isometric force generated as a function of time contractions, three times a week). Maximal strength and the tension-time index improved significantly. Peak aerobic power increased from 15.99 +/- 3.96 mL.kg-1.min-1 to 20.34 +/- 3.29 mL.kg-1.min-1. On average, maximal walking speed increased from 2.0 +/- 0.6 mph to 2.4 +/- 0.7mph. Exercise time increased 22%, from 9.2 +/- 2.3 minutes to 11.2 +/- 2.7 minutes. There were significant reductions in submaximal heart rate (15b.min-1) and systolic blood pressure (15mmHg) after training. It would appear that the reduction in aerobic fitness of subjects with OA is secondary to their reduced muscle function. By improving muscle function, increases in exercise capacity and aerobic fitness occurred.

Effects of a quantitative progressive rehabilitation program applied unilaterally to the osteoarthritic knee.

Decreases in muscular strength, endurance, and angular velocity have previously been demonstrated in the elderly. Osteoarthritis (OA), especially of the knee, may cause further reductions in these parameters and lead to functional limitations. This study measured the effects of a quantitative progressive exercise muscle rehabilitation program (QPE) that was added to a physical therapy (PT) program. Forty subjects (20 men and 20 women) with OA of the knees were randomly selected from a group of volunteers (N = 437) for the 3-month program. Measurements of strength, endurance, angular velocity, and the Jette Functional Status Index were determined before and after 1, 2, and 3 months of the program. The QPE program was composed of isometric, isotonic, isotonic with resistance, endurance, and speed contractions prescribed in a progressive sequence. Muscle strength (14% and 29%) and endurance (38% and 43%) increased significantly (p < 0.05, ANOVA for repeated measures) for both the quadriceps and hamstrings, respectively, after rehabilitation. There were marked decreases in walking time and the difficulty and pain experienced during functional activities.

Cardiovascular, neuromuscular, and metabolic alterations with age leading to frailty.

As members of our society live longer, a greater percentage of the population will be older. These demographic changes will stress our social and medical delivery system, unless interventions can alter the course leading to frailty. Maximal aerobic power decreases with age, due to a decrease in cardiac output, and is exacerbated by cardiovascular disease. Asymptomatic aging does not reduce cardiovascular function to an extent that would lead to loss of function. Metabolism, endurance, and contraction velocity and muscle strength remain relatively high until 40, 50, and 60 years of age, respectively. After age 60, there are dramatic decreases (approximately 10% per year) which lead to loss of function and independence. The loss of muscle function leads to an increase in the likelihood of falls (approximately 4-fold). Exercise programs utilizing "aerobic" exercise activities do not lead to an increase in muscle function, whereas programs designed specifically for muscle can increase function and, presumably, reduce the risk of falls and injuries.

Quantitative effects of physical therapy on muscular and functional performance in subjects with osteoarthritis of the knees.

Osteoarthritis (OA) of the knees is a functionally limiting disability. Physical therapy (PT) is considered a useful treatment for OA, although evidence is qualitative. The purpose of this study was to quantitatively measure the effects of a 3-month PT program (n = 40; 20 men and 20 women) with knee OA. Muscle function and functional assessment parameters were measured. All data were analyzed by repeated measures analysis of variance (p < 0.05). There were no significant changes in handgrip strength and endurance, limb volume, or angular velocity after PT. Maximal muscle length was significantly increased. Muscle strength significantly increased for the hamstrings (9% and 19%) and quadriceps (8% and 24%) for the men and women, respectively. Endurance improved for the quadriceps (26% and 39%) and hamstrings (18% and 28%) for men and women, respectively. Functionally, there were significant improvements in the ability to climb stairs, rise from a chair, and walk. Walking time (50 ft) and the difficulty and pain of performing various activities decreased. Most improvements had occurred after 1 month of PT. For the first time, the effects of a PT program have been quantitatively measured for patients with knee OA.

Essential and other fatty acids in plasma in schizophrenics and normal individuals from Japan.

Plasma phospholipid and cholesterol ester fatty acid levels were measured in samples from normal individuals, schizophrenics, and patients with affective and paranoid disorders in Japan. The schizophrenics were divided into groups with normal and reduced platelet sensitivity to the aggregation-inhibiting effects of prostaglandin (PG) E1. As in samples from schizophrenics in several other countries, linoleic acid levels were significantly below normal, as was the ratio of linoleic acid to its metabolites. Phospholipid fatty acid levels were normal in patients with paranoid or affective disorders. When the schizophrenics were divided into those with and without an abnormal response to PGE1, oleic acid was higher and eicosapentaenoic acid lower in those patients with an abnormal response. This study lends further support to the idea that schizophrenics may differ from controls in their essential fatty acid and eicosanoid metabolism.

Muscle rehabilitation: its effect on muscular and functional performance of patients with knee osteoarthritis.

Muscle function and functional performance are limited in patients with osteoarthritis (OA). Although aerobic exercise can increase aerobic power and reduce fatigue, it does not appear to improve muscle function. The purpose of this study was to demonstrate the effect of a muscle rehabilitation program on muscle strength, endurance, speed, and function for patients with OA of the knees. Fifteen men (67.6 +/- 6.1 years) with OA of the knees underwent a four-month exercise program, three times per week. Muscle strength, endurance, and speed were 50% less in OA patients than in controls. After rehabilitation, there was a significant increase in strength (35%), endurance (35%), and speed (50%). Deficiencies and improvements in the muscles were greater at longer muscle lengths. Increases in muscle function were associated with decreased dependency (10%), difficulty (30%), and pain (40%). The average increase in all measured parameters was 10% and 25% after two and four months of rehabilitation, respectively. Improvements were sustained for eight months after rehabilitation. The muscle rehabilitation program was designed specifically to improve function; the improved muscle function was translated into improved functional performance.

Muscle rehabilitation in impaired elderly nursing home residents.

Based on observations of changes in muscle function associated with aging, and the exacerbation of these changes with frailty, a program of muscle strengthening has been developed to correct specific defects in muscles. This pilot study was undertaken on 18 functionally impaired nursing home residents (age range 60 to 90 years) with markedly deteriorated muscle function (50%) secondary to age, disuse, and multiple chronic illnesses. Fourteen of the subjects completed the six-week program without adverse effects. In 75% of the patients, there was improved muscle function, with endurance, strength, and speed increasing 35%, 15%, and 10%, respectively. After the program, many subjects increased their spontaneous activity and decreased their dependency. The improvements were still evident four months after rehabilitation. These results suggest that it may be possible, through a carefully supervised, short-term program of muscle rehabilitation, for nursing home residents to achieve an enhanced level of physical functioning.

Maximal isometric torque of knee extension as a function of muscle length in subjects of advancing age.

Many neuromuscular diseases are associated with muscle weakness. Assessment of this weakness by manual muscle testing or with hand-held equipment has been criticized. Furthermore, muscle length influences peak force development. One hundred fifty-three female and 116 male asymptomatic subjects between the ages of 20 and 80 (approximately 20 per decade) were studied. Maximal strength of the quadriceps group was determined isometrically, on a specially designed bench, at 3 hip angles (45 degrees, 90 degrees, and 180 degrees of extension), which represent three rectus femoris muscle lengths. Maximal strength was observed at a hip angle of 180 degrees and did not decrease significantly from 20 to 50 years of age, although the values for the male and female subjects over 50 years were significantly decreased (approximately 15% per decade). The increase in strength as the muscle was lengthened from 45 degrees to 180 degrees hip angle was about 80% (of the force at 45 degrees) in 20-year-olds; strength decreased progressively with age to a value of approximately 50% in the 70-year-olds. This greater reduction in maximal strength at longer quadriceps muscle lengths has functional significance in rising from a chair, climbing stairs, and eventually, walking and standing.