Effect of acquired immune deficiency syndrome wasting on the protein metabolic response to acute exercise.

Wasting is a major complication of human immunodeficiency virus (HIV) infection, which remains prevalent even in the era of highly-active antiretroviral therapy. We have previously shown that progressive resistance exercise can increase lean body mass (LBM) significantly in patients with wasting, and that exercise does not increase circulating HIV RNA concentrations. We examined the effect of 1 bout of moderately difficult exercise on whole body protein kinetics in 10 patients with HIV wasting and 12 patients with HIV infection without wasting. At baseline, there were no differences between the groups in whole body leucine flux, oxidation, or nonoxidative leucine disposal (NOLD, a measure of whole body protein synthesis). Six days after exercise, NOLD was significantly higher in the wasted patients compared with the nonwasted ones (82.2 +/- 16.7 v 66.5 +/- 15.2 micromol/kg LBM/h, P <.03). The change in NOLD between baseline and day 6 was significantly different between the 2 groups (+9.0 +/- 9.2 v -3.3 +/- 5.7 micromol/kg LBM/h, P <.02). These data indicate that the ability to respond to exercise with protein synthesis is maintained in HIV wasting.

Hormonal influences on stress-induced neutrophil mobilization in health and chronic fatigue syndrome.

This investigation tested the hypotheses that women diagnosed with chronic fatigue syndrome (CFS) would exhibit significantly greater systemic indices of exercise-induced leukocyte mobilization and inflammation (neutrophilia, lactoferrin release, complement activation) than controls matched for age, weight, and habitual activity and that responses in the luteal phase of the menstrual cycle would be greater than in the follicular phase. Subjects stepped up and down on a platform adjusted to the height of the patella for 15 min, paced by metronome. Blood samples were collected under basal conditions (the day before exercise) and following exercise for determination of circulating neutrophils and plasma concentrations of lactoferrin, C3a des arg, and creatine kinase. Complete, 24-hr urine collections were made for determination of cortisol excretion. For all subjects, circulating neutrophil counts increased 33% (P < 0.0001) and lactoferrin increased 27% (P = 0.0006) after exercise, whereas plasma C3a des arg and creatine kinase did not increase. No indication of an exaggerated or excessive response was observed in the CFS patients compared to the controls. In healthy women, circulating neutrophil numbers exhibited previously described relationships with physiological variables: basal neutrophil counts correlated with plasma progesterone concentrations (R = 0.726, P = 0.003) and the exercise-induced neutrophilia correlated with both urinary cortisol (R = 0.660, P = 0.007) and plasma creatine kinase (R = 0.523, P = 0.038) concentrations. These relationships were not observed in the CFS patients (R = 0.240, P = 0.370; R = 0.042, P = 0.892; and R = 0.293, P = 0.270; respectively). These results suggest that normal endocrine influences on the circulating neutrophil pool may be disrupted in patients with CFS.

The relationship between growth hormone kinetics and sarcopenia in postmenopausal women: the role of fat mass and leptin.

Sarcopenia, the decline in body cell mass (BCM) and especially in muscle mass with age, is an important age-related cause of frailty and loss of independence in the elderly. Because the decline in BCM with age parallels a decline in GH secretion from young adulthood to old age, loss of GH secretion has been considered an important contributory cause of sarcopenia in the elderly. To test this hypothesis in a group of healthy postmenopausal women (n = 15; mean +/- SD age, 66.9 +/- 7.8 yr), 24-h GH concentrations and secretory kinetics were correlated with BCM (measured by whole body counting of 40K) and percent body fat (measured by dual energy x-ray absorptiometry or neutron inelastic scattering). Serum leptin levels were determined as a measure of adipocyte mass. Contrary to prediction, GH secretion was lower in women with higher BCM (r = 0.50; P < 0.05), whereas their mean fat mass was higher (r = 0.51, P < 0.05). These data indicate that sarcopenia in postmenopausal women is not associated with reduced GH secretion and is inversely correlated with fat mass. Serum leptin levels were inversely associated with GH secretion (r = -0.67; P < 0.006). Although a causal relationship has not been demonstrated, these data suggest that leptin could modulate GH secretion through its action on the aging hypothalamic-pituitary axis, or that GH regulates leptin secretion.

Protein metabolism in rheumatoid arthritis and aging. Effects of muscle strength training and tumor necrosis factor alpha.

OBJECTIVE: To determine the effects of rheumatoid arthritis (RA) on whole-body protein metabolism. METHODS: We examined protein metabolism and its hormonal and cytokine mediators before and 12 weeks after progressive resistance muscle strength training in 8 healthy young (mean +/- SD age 25 +/- 2 years) and 8 healthy elderly (70 +/- 5 years) men and women, and in 8 adults with RA (42 +/- 13 years). An additional 6 healthy elderly subjects (69 +/- 3 years) served as a swimming-only control group. RESULTS: Subjects with RA had higher rates of protein breakdown than did young or elderly healthy subjects (79.9 +/- 17.2 versus 60.3 +/- 5.8 and 63.7 +/- 12.4 mumoles/gm total body potassium/hour, respectively, P < 0.05), while there was no effect of age per se. Patients treated with methotrexate had normal rates of protein breakdown (P < 0.01 versus RA without methotrexate; P not significant versus healthy young subjects). Increased protein catabolism in RA was no longer evident after strength training. In multiple regression analysis, levels of tumor necrosis factor alpha (TNF alpha) (r = 0.47, P = 0.01) and growth hormone (r = -0.51, P = 0.006) were associated with protein breakdown, and plasma glucagon levels were inversely correlated with protein synthesis (r = -0.45, P = 0.02). Growth hormone (r = -0.56, P = 0.002) and glucagon (r = 0.45, P = 0.04, levels were associated with protein oxidation. CONCLUSION: Adults with RA have increased whole-body protein breakdown, which correlates with growth hormone, glucagon, and TNF alpha production.

Primary surgical treatment of carcinoma stage I of the uterine cervix.

476 cases of Stage I-IV invasive carcinoma of the uterine cervix were treated at the Gynecology Departments in Karlstad and Orebro in 1965-75. 232 (48.7%) were classified Stage I, 198 (85.3%) of them were treated with primary surgery (57 Stage IA and 141 Stage IB). Thirty-four were given primary radiotherapy because of advanced age or co-existing conditions contra-indicating surgery. Of the 141 patients with primary surgery for Stage IB, squamous epithelial carcinoma was established in 88.7% and adenocarcinoma in 11.3%. Surgery revealed lymph node metastases in 13 (9.2%). Postoperative radiotherapy was given to all patients with lymph node metastases, to 3 patients with tumor thrombi in the parametrial vessels, and to 6 in whom surgery had conceivably not been radical. Urinary tract complications requiring reconstructive surgery occurred in 8 (4.0%). The 5-year survival rate with Stage IB was 91.5%, corrected for intercurrent diseases, 5-year survival was 92.8%. Of the 13 with lymph node metastases, 7 were still alive after 5 years. The 5-year survival rate for those without demonstrable lymph node metastases was 94.5%, corrected 96.0%.