What does a structured review of the effectiveness of exercise interventions for persons with multiple sclerosis tell us about the challenges of designing trials?

OBJECTIVE: The goal of this review is to ascertain the extent to which the current body of research on the role of exercise in multiple sclerosis (MS) provides sufficiently strong evidence to guide regular exercise prescription. METHODS: We searched CINAHL, COCHRANE, EMBASE, and MEDLINE between 1950 and December 2007 with combinations of MeSH terms and keywords. We assessed the methodological quality of selected randomized controlled trials (RCTs) of exercise interventions using the Physiotherapy Evidence Database scale and evaluated the effects of the exercise interventions by calculating effect sizes (ES) for the target outcomes. RESULTS: Eleven RCTs met the criteria, all with acceptable methodological quality. The ES ranged from -0.36 to 3.50 on the target outcomes. Only one study had 95% confidence intervals clearly excluding a value of 0. Measures of body functions and structures and activities were the most common target outcomes of interventions. CONCLUSION: Although there was some evidence to support positive effects of exercise on physical and psychosocial functioning and on quality of life, our review revealed insufficient research in this area, making it difficult to guide regular exercise prescription. Furthermore, it also emphasizes the methodological challenges in these RCTs leading us to believe that there is a great need for high quality RCTs in this area, contributing evidence for regular exercise and physical activity prescription for persons with MS.

Hepatic ketogenesis and peripheral ketone body utilization in the ruminant.

Hepatic and alimentary ketogenesis occur at similar rates in fed, nonpregnant, nonlactating goats, sheep and dairy cows. Alimentary ketogenesis begins to diminish within 24 h after fasting but compensatory increases in hepatic ketogenesis maintain total splanchnic release and, therefore, no change in circulating concentrations of ketone bodies is observed. By the third day of fast the gut is utilizing acetoacetate and beta-hydroxybutyrate and alimentary ketogenesis has ceased. Hepatic ketogenesis of both ketone bodies accelerates rapidly due to portal-drained visceral and hindquarter lipolysis and subsequent hepatic fatty acid uptake and total circulating concentrations are doubled. During pregnancy and lactation in sheep and cows alimentary ketogenesis is maintained as long as digestible organic matter intake is constant. Hepatic and total splanchnic release of beta-hydroxybutyrate increases in late gestation and early lactation. Again, this is due to increased portal-drained visceral and hindquarter free fatty acid release and hepatic free fatty acid uptake. Hindquarter uptake of both ketones during late gestation is similar to the ratio observed in nonpregnant fed sheep but the percentage of utilization decreases, perhaps reflecting partitioning to uteroplacental tissues. Hindquarter uptake of both ketone bodies in sheep increases in early lactation due to increased circulating concentrations because extraction ratios are similar to those of fed animals. Ketosis during pregnancy in sheep and lactation in cows may be prevented by beta-hydroxybutyrate stimulation of pancreatic insulin production. However, an insulin-independent intrahepatic mechanism apparently occurs in sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in energy metabolite and regulatory hormone concentrations and net fluxes across splanchnic and peripheral tissues in fed and progressively fasted ewes.

Effects of fasting on glucose, ketone bodies, free fatty acids (FFA), insulin and glucagon metabolism were studied in eight fed, five 1-d-fasted and five 3-d-fasted ewes. The 3-d fast decreased blood glucose from 55 to 49 mg/dl due to a 40% reduction in its splanchnic output. Plasma FFA increased from 280 to 872 and 912 microM in 1- and 3-d-fasted ewes concomitant with increased omental and peripheral release. Hepatic uptake of FFA increased three- and fourfold and was concentration-dependent. Consequently, hepatic release of acetoacetate and beta-hydroxybutyrate increased from -43 and 276 to 90 and 1304 mumol/min, respectively, in 3-d-fasted ewes. Alimentary ketogenesis ceased entirely due to lack of substrate and gut tissue was actually utilizing both ketone bodies by d 3 of fast. Lower hindquarter utilization of both ketone bodies increased with increasing circulating concentrations. Insulin seemed to be the major mechanism of regulation of glucose, FFA and ketone body metabolism since pancreatic production and arterial concentrations of insulin decreased with progressive fasting. No changes were observed in glucagon concentrations or net fluxes, and therefore the role of glucagon was passive and secondary to that of insulin.