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ABSTRACT: Tibial stress fractures increasingly affect athletes and military recruits, with few known effective management options. Electrical stimulation enhances regular fracture healing, but the effect on stress fractures has not been definitively tested.
Capacitively coupled electric field stimulation will accelerate tibial stress fracture healing.
Randomized controlled trial; Level of evidence, 1.
Twenty men and 24 women with acute posteromedial tibial stress fractures were referred from local clinicians. Subjects were randomly assigned active or placebo capacitively coupled electric field stimulation to be applied for 15 hours per day until healed, given supplemental calcium, and instructed to rest from provocative training. Healing was confirmed when hopping to 10 cm for 30 seconds could be achieved without pain.
No difference in time to healing was detected between treatment and placebo groups. Women in the treatment group healed more slowly than did the men (P = .05). Superior treatment compliance was associated with reduced time to healing (P = .003). Rest noncompliance was associated with increased time to healing (P = .05).
Whole-group analysis did not detect an effect of capacitively coupled electric field stimulation on tibial stress fracture healing; however, greater device use and less weightbearing loading enhanced the effectiveness of the active device. More severe stress fractures healed more quickly with capacitively coupled electric field stimulation.
Although the use of capacitively coupled electric field stimulation for tibial stress fracture healing may not be efficacious for all, it may be indicated for the more severely injured or elite athlete/recruit whose incentive to return to activity may motivate superior compliance.
The American journal of sports medicine 04/2008; 36(3):545-53. · 3.61 Impact Factor
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ABSTRACT: Recombinant human growth hormone (GH) and pioglitazone (PIO) in abdominally obese adults with impaired glucose tolerance were evaluated under the hypothesis that the combination attenuates GH-induced increases in glucose concentrations, reduces visceral adipose tissue (VAT), and improves insulin sensitivity over time.
Randomized, double-blind, placebo-controlled, 2 x 2 factorial design.
Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States.
62 abdominally obese adults aged 40-75 with impaired glucose tolerance.
GH (8 microg/kg/d, or placebo) and pioglitazone (30 mg/d, or placebo) for 40 wk.
Baseline and after 40 wk of treatment, VAT content was quantified by CT scan, glucose tolerance was assessed using a 75-g oral glucose tolerance test, and insulin sensitivity was measured using steady-state plasma glucose levels obtained during insulin suppression test.
BASELINE: body mass index (BMI), plasma glucose, and visceral fat content were similar. 40 wk: visceral fat area declined 23.9 +/- 7.4 cm(2) in GH group, mean difference from placebo: -28.1 cm(2) (95% CI -49.9 to -6.3 cm(2); p = 0.02). Insulin resistance declined 52 +/- 11.8 mg/dl with PIO, mean difference from placebo of -58.8 mg/dl (95% CI -99.7 to -18.0 mg/dl; p = 0.01). VAT and SSPG declined with GH and PIO combined, mean differences from placebo of -31.4 cm(2) (95% CI -56.5 cm(2) to -6.3 cm(2); p = 0.02) and -55.3 mg/dl (95% CI -103.9 to -6.7 mg/dl; p = 0.02), respectively. Fasting plasma glucose increased transiently in GH group. No significant changes in BMI were observed.
Addition of PIO to GH attenuated the short-term diabetogenic effect of GH; the drug combination reduced VAT and insulin resistance over time. GH plus PIO may have added benefit on body composition and insulin sensitivity in the metabolic syndrome.
PLoS Clinical Trials 02/2007; 2(5):e21. · 4.77 Impact Factor
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ABSTRACT: To determine the effect of capacitively coupled electric field stimulation on tibial stress fracture healing in men and women. Methods: A convenience sample of 20 men and 24 women with posteromedial tibial stress fractures was recruited. Subjects were randomly assigned an active or placebo OrthoPak(Registered) Bone Growth Stimulator (sinusoidal wave, 3-6 V, 60 kHz,5-10 mA), to be used for 15 hours per day until healed. Subjects were given supplemental calcium and instructed to rest from training. Healing was confirmed when hopping 10 cm off the ground for 30 seconds was pain free. Data was analyzed using 2-way ANOVA for effects of treatment and sex on healing time. Compliance and other between-group differences and relationships were examined via ANOVA, t-tests and correlation analyses. The influence of anthropometric and behavioral characteristics on time to healing was evaluated by multiple regression analysis. No difference in time to healing was detected between treatment and placebo groups. Treatment compliance was positively associated with reduced time to healing (p = 0.003). Rest non-compliance was associated with increased time to healing (p = 0.05). Female subjects healed more slowly than men (p = 0.05). Capacitively coupled electric fields did not accelerate tibial stress fracture healing in comparison with placebo treatment (modified rest), but women took longer to recover than men. Daily device use and weight bearing loading during treatment appeared to positively and negatively (respectively) influence the efficacy of the active device.
11/2006;
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ABSTRACT: Overweight adults with impaired glucose tolerance have a 5-10% risk of developing diabetes per year, and insulin resistance is an important cause of progression to diabetes in these individuals. Weight loss has been shown to improve insulin sensitivity and prevent or delay progression to diabetes. According to recent studies, the improvement in insulin sensitivity that occurs with weight loss is closely linked to the reduction of visceral adipose tissue (VAT), the collection of intra-abdominal adipose depots that includes omental and intrahepatic fat. After controlling for BMI, whole body fat, and subcutaneous fat, only VAT is an independent predictor of endogenous insulin sensitivity and glucose tolerance before or after weight loss. This, in turn, suggests that reducing VAT is crucial to improving insulin sensitivity and preventing diabetes in high-risk individuals. Recombinant human growth hormone (GH) is a lipolytic drug that reduces total body, abdominal, and visceral fat in growth hormone-deficient (GHD) adults. Several studies have reported substantial reductions in VAT following GH treatment in this population. Like GHD adults, abdominally obese individuals have increased VAT, insulin resistance, and growth hormone levels that are below normal during continuous 24-h monitoring. These similarities have prompted a number of recent investigations in abdominally obese adults that reported significant reductions in truncal and visceral fat and an improvement in insulin sensitivity following prolonged GH administration. However, other studies have shown that insulin resistance and glucose concentrations transiently worsen during the first few weeks of GH treatment and that these deleterious effects can persist even after VAT reduction has occurred. Prior studies involving GH treatment were generally limited to adults who were normoglycemic at baseline. Less is known about the effects of GH in adults with impaired glucose tolerance or diabetes. The effects of GH used in conjunction with insulin sensitizers on glycemic control and VAT in patients with impaired glucose tolerance will be reviewed.
Growth Hormone & IGF Research 08/2006; 16 Suppl A:S62-7. · 2.16 Impact Factor
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ABSTRACT: High-altitude anorexia leads to a hormonal response pattern modulated by both hypoxia and caloric restriction (CR). The purpose of this study was to compare altitude-induced neuroendocrine changes with or without energy imbalance and to explore how energy sufficiency alters the endocrine acclimatization process. Twenty-six normal-weight, young men were studied for 3 wk. One group [hypocaloric group (HYPO), n = 9] stayed at sea level and consumed 40% fewer calories than required to maintain body weight. Two other groups were deployed to 4,300 meters (Pikes Peak, CO), where one group (ADQ, n = 7) was adequately fed to maintain body weight and the other [deficient group (DEF), n = 10] had calories restricted as above. HYPO experienced a typical CR-induced reduction in many hormones such as insulin, testosterone, and leptin. At altitude, fasting glucose, insulin, and epinephrine exhibited a muted rise in DEF compared with ADQ. Free thyroxine, thyroid-stimulating hormone, and norepinephrine showed similar patterns between the two altitude groups. Morning cortisol initially rose higher in DEF than ADQ at 4,300 meters, but the difference disappeared by day 5. Testosterone increased in both altitude groups acutely but declined over time in DEF only. Adiponectin and leptin did not change significantly from sea level baseline values in either altitude group regardless of energy intake. These data suggest that hypoxia tends to increase blood hormone concentrations, but anorexia suppresses elements of the endocrine response. Such suppression results in the preservation of energy stores but may sacrifice the facilitation of oxygen delivery and the use of oxygen-efficient fuels.
AJP Endocrinology and Metabolism 07/2006; 290(6):E1078-88. · 4.75 Impact Factor
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Anne L Friedlander,
Barry Braun,
Margaret Pollack,
Jay R MacDonald,
Charles S Fulco,
Steve R Muza,
Paul B Rock,
Gregory C Henderson,
Michael A Horning,
George A Brooks, Andrew R Hoffman,
Allen Cymerman
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ABSTRACT: The effects of prolonged caloric restriction (CR) on protein kinetics in lean subjects has not been investigated previously. The purpose of this study was to test the hypotheses that 21 days of CR in lean subjects would 1) result in significant losses of lean mass despite a suppression in leucine turnover and oxidation and 2) negatively impact exercise performance. Nine young, normal-weight men [23 +/- 5 y, 78.6 +/- 5.7 kg, peak oxygen consumption (Vo2 peak) 45.2 +/- 7.3 ml.kg(-1).min(-1), mean +/- SD] were underfed by 40% of the calories required to maintain body weight for 21 days and lost 3.8 +/- 0.3 kg body wt and 2.0 +/- 0.4 kg lean mass. Protein intake was kept at 1.2 g.kg(-1).day(-1). Leucine kinetics were measured using alpha-ketoisocaproic acid reciprocal pool model in the postabsorptive state during rest and 50 min of exercise (EX) at 50% of Vo2 peak). Body composition, basal metabolic rate (BMR), and exercise performance were measured throughout the intervention. At rest, leucine flux (approximately 131 micromol.kg(-1).h(-1)) and oxidation (R(ox); approximately 19 micromol.kg(-1).h(-1)) did not differ pre- and post-CR. During EX, leucine flux (129 +/- 6 vs. 121 +/- 6) and R(ox) (54 +/- 6 vs. 46 +/- 8) were lower after CR than they were pre-CR. Nitrogen balance was negative throughout the intervention ( approximately 3.0 g N/day), and BMR declined from 1,898 +/- 262 to 1,670 +/- 203 kcal/day. Aerobic performance (Vo2 peak, endurance cycling) was not impacted by CR, but arm flexion endurance decreased by 20%. In conclusion, 3 wk of caloric restriction reduced leucine flux and R(ox) during exercise in normal-weight young men. However, despite negative nitrogen balance and loss of lean mass, whole body exercise performance was well maintained in response to CR.
AJP Endocrinology and Metabolism 10/2005; 289(3):E446-55. · 4.75 Impact Factor
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ABSTRACT: Hypobaric hypoxia and heightened metabolic rate increase free radical production.
We tested the hypothesis that antioxidant supplementation would reduce oxidative stress associated with increased energy expenditure (negative energy balance) at high altitude (HA 4300 m).
For 12 d at sea level (SL), 18 active men were fed a weight-stabilizing diet. Testing included fasting blood and 24-h urine samples to assess antioxidant status [plasma alpha-tocopherol, beta-carotene, lipid hydroperoxides (LPO), and urinary 8-hydroxydeoxyguanosine (8-OHdG)] and a prolonged submaximal (55% Vo2peak) oxidative stress index test (OSI) to evaluate exercise-induced oxidative stress (plasma LPO, whole blood reduced and oxidized glutathione, glutathione peroxidase, and urinary 8-OHdG). Subjects were then matched and randomly assigned to either a placebo or antioxidant supplement group for a double-blinded trial. Supplementation (20,000 IU of beta-carotene, 400 IU alpha-tocopherol acetate, 500 mg ascorbic acid, 100 microg selenium, and 30 mg zinc, or placebo) was begun 3 wk prior to and throughout a 14-d HA intervention. At HA, subjects' daily energy intake and expenditure were adjusted to achieve a caloric deficit of approximately 1400 kcal. Fasting blood and 24-h urine samples were collected throughout HA and the OSI test was repeated on HA day 1 and day 13.
Resting LPO concentrations increased and urinary 8-OHdG concentrations decreased over HA with no effect of supplementation. Prolonged submaximal exercise was not associated with increased concentrations of oxidative stress markers at SL or HA.
Antioxidant supplementation did not significantly affect markers of oxidative stress associated with increased energy expenditure at HA.
Aviation Space and Environmental Medicine 11/2004; 75(10):881-8. · 0.88 Impact Factor
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Medicine & Science in Sports & Exercise 04/2004; 36(5):S108-S109. · 4.43 Impact Factor
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ABSTRACT: Insulin sensitivity and the activity of the hypothalamic-growth hormone (GH)- insulin-like growth factor-I (IGF-I) axis both decline with age. Treatment with IGF-I increases insulin sensitivity in healthy young subjects. We hypothesized that increasing plasma IGF-I in postmenopausal women to levels characteristic of young women would enhance insulin sensitivity. To test the hypothesis, fasting glucose kinetics and insulin sensitivity were measured in 24 healthy, normoglycemic, postmenopausal women before and after 5 weeks of treatment with either recombinant human (rh)IGF-I (15 microg/kg body weight/d twice daily) or placebo in a double-blind study. Diet energy content and composition were rigidly controlled to maintain energy balance. A hyperglycemic clamp (8 mmol/L) coupled with stable isotope infusion ([6,6(2)H]glucose) was performed before and after treatment to assess whole-body insulin sensitivity; defined as the glucose rate of disappearance (Rd) or rate of infusion (GRIF) scaled to the steady-state insulin concentration (I). There were no differences in fasting glucose or insulin concentrations, glucose kinetics, or glucose oxidation after either treatment. During the clamps, steady-state insulin concentrations with placebo (pre = 151 +/- 28 pmol/L, post = 173 +/- 31 pmol/L) were slightly different than with IGF-I (pre = 182 +/- 37 pmol/L, post = 163 +/- 33 pmol/L), but the variations were not significant. No significant changes in whole-body insulin sensitivity were observed after treatment with IGF-I, calculated as Rd/I (pre = 17.7 +/- 2.6 microg/kg/min/pmol/L, post = 19.3 +/- 2.0 microg/kg/min/pmol/L for IGF-I v pre = 24.2 +/- 2.5 microg/kg/min/pmol/L, post = 22.8 +/- 3.4 microg/kg/min/pmol/L for placebo) or as GRIF/I (pre = 18.0 +/- 3.9 microg/kg/min/pmol/L, post = 22.3 +/- 3.5 microg/kg/min/pmol/L for IGF-I v pre = 26.4 +/- 6.2 microg/kg/min/pmol/L, post = 26.9 +/- 4.8 microg/kg/min/pmol/L for placebo). Baseline insulin sensitivity in women using hormone replacement therapy (HRT, n = 15) was similar to nonusers (n = 9), but HRT users derived a greater portion of energy expenditure from carbohydrate oxidation compared with nonusers. HRT use had no impact on the response to IGF-I. Overall, we observed subtle, but physiologically insignificant, variations after IGF-I treatment in the direction of enhanced insulin sensitivity. The data suggest that 5 weeks of low-dose rhIGF-I treatment has no material influence on whole-body insulin sensitivity in normoglycemic postmenopausal women.
Metabolism 10/2003; 52(9):1182-90. · 2.66 Impact Factor
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ABSTRACT: Background: Tibial stress fractures increasingly affect athletes and military recruits, with few known effective management options. Electrical stimulation enhances regular fracture healing but the effect on stress fractures has not been definitively tested. Hypothesis: Capacitively coupled electric field stimulation (CCEFS) will accelerate tibial stress fracture healing. Study design: Double blind, randomized controlled clinical trial. Methods: 20 men and 24 women with acute posteromedial tibial stress fracture were referred from local clinicians. Subjects were randomly assigned active or placebo CCEFS to be applied for 15 hours per day until healed, given supplemental calcium and instructed to rest from provocative training. Healing was confirmed when hopping to 10 cm for 30 seconds could be achieved without pain. Results: No difference in time to healing was detected between treatment and placebo groups. Females in the treatment group healed more slowly than males (p = 0.05). Superior treatment compliance was associated with reduced time to healing (p = 0.003). Rest non-compliance was associated with increased time to healing (p = 0.05). Conclusions: Whole group analysis did not detect an effect of CCEFS on tibial stress fracture healing, however, greater device use and less weight bearing loading enhanced the effectiveness of the active device. More severe stress fractures healed more quickly with CCEFS. Clinical relevance: While the use of CCEFS for tibial stress fracture healing may not be efficacious for all, it may be indicated for the more severely injured or elite athlete/recruit whose incentive to return to activity may motivate superior compliance. Yes Yes
