Reduced Toxicity Conditioning with Busulfan, Fludarabine, Alemtuzumab and Allogeneic Stem Cell Transplantation From HLA-Matched Sibling Donors in Children with High Risk Sickle Cell Disease Results in Long Term Donor Chimerism and Low Incidence of aGVHD

Purpose It is still equivocal whether oxygen uptake recovery kinetics are limited by oxygen delivery and can be improved by supplementary oxygen. The present study aimed to investigate whether measurements of muscle and pulmonary oxygen uptake kinetics can be used to assess oxygen delivery limitations in healthy subjects. Methods Sixteen healthy young adults performed three sub-maximal exercise tests (6 min at 40% Wmax) under hypoxic (14%O2), normoxic (21%O2) and hyperoxic (35%O2) conditions on separate days in randomized order. Both Pulmonary VO2 and near infra red spectroscopy (NIRS) based Tissue Saturation Index (TSI) offset kinetics were calculated using mono-exponential curve fitting models. Results Time constant τ of VO2 offset kinetics under hypoxic (44.9 ± 7.3s) conditions were significantly larger than τ of the offset kinetics under normoxia (37.9 ± 8.2s, p = 0.02) and hyperoxia (37±6s, p = 0.04). TSI mean response time (MRT) of the offset kinetics under hypoxic conditions (25.5 ± 13s) was significantly slower than under normoxic (15 ± 7.7, p = 0.007) and hyperoxic (13 ± 7.3, p = 0.008) conditions. Conclusion The present study shows that there was no improvement in the oxygen uptake and muscle oxygenation recovery kinetics in healthy subjects under hyperoxic conditions. Slower TSI and VO2 recovery kinetics under hypoxic conditions indicate that both NIRS and spiro-ergometry are appropriate non-invasive measurement tools to assess the physiological response of a healthy individual to hypoxic exercise

Functional Outcome After Successful Internal Fixation Versus Salvage Arthroplasty of Patients With a Femoral Neck Fracture

Objectives: To determine patient independency, health-related and disease-specific quality of life (QOL), gait pattern, and muscle strength in patients after salvage arthroplasty for failed internal fixation of a femoral neck fracture. Design: Secondary cohort study to a randomized controlled trial. Setting: Multicenter trial in the Netherlands, including 14 academic and nonacademic hospitals. Patients: Patients after salvage arthroplasty for failed internal fixation of a femoral neck fracture were studied. A comparison was made with patients who healed uneventfully after internal fixation. Intervention: None (observatory study). Main Outcome Measurements: Patient characteristics, SF-12, and Western Ontario McMaster osteoarthritis index scores were collected. Gait parameters were measured using plantar pressure measurement. Maximum isometric forces of the hip muscles were measured using a handheld dynamome

Safety and efficacy of exercise training in adults with Pompe disease: Evalution of endurance, muscle strength and core stability before and after a 12 week training program

Background: Pompe disease is a proximal myopathy. We investigated whether exercise training is a safe and useful adjuvant therapy for adult Pompe patients, receiving enzyme replacement therapy. Methods: Training comprised 36 sessions of standardized aerobic, resistance and core stability exercises over 12 weeks. Before and after, the primary outcome measures safety, endurance (aerobic exercise capacity and distance walked on the 6 min walk test) and muscle strength, and secondary outcome measures core stability, muscle function and body composition, were evaluated. Results: Of 25 patients enrolled, 23 successfully completed the training. Improvements in endurance were shown by increases in maximum workload capacity (110 W before to 122 W after training, [95 % CI of the difference 6 · 0 to 19 · 7]), maximal oxygen uptake capacity (69 · 4 % and 75 · 9 % of normal, [2 · 5 to 10 · 4]), and maximum walking distance (6 min walk test: 492 meters and 508, [-4 · 4 to 27 · 7]). There were increases in muscle strength of the hip flexors (156 · 4 N to 180 · 7 N [1 · 6 to 13 · 6) and shoulder abductors (143 · 1 N to 150 · 7 N [13 · 2 to 35 · 2]). As an important finding in secondary outcome measures the number of patients who were able to perform the core stability exercises rose, as did the core stability balancing time (p < 0.05, for all four exercises). Functional tests showed small reductions in the time needed to climb four steps (2 · 4 sec to 2 · 1, [- 0 · 54 to -0 · 04 ]) and rise to standing position (5 · 8 sec to 4 · 8, [-2 · 0 to 0 · 0]), while time to run, the quick motor function test results and body composition remained unchanged. Conclusions: Our study shows that a combination of aerobic, strength and core stability exercises is feasible, safe and beneficial to adults with Pompe disease

Glycaemic instability is an underestimated problem in Type II diabetes

The aim of the present study was to assess the level of glycaemic control by the measurement of 24 h blood glucose profiles and standard blood analyses under identical nutritional and physical activity conditions in patients with Type II diabetes and healthy normoglycaemic controls. A total of 11 male patients with Type II diabetes and 11 healthy matched controls participated in a 24 h CGMS (continuous subcutaneous glucose-monitoring system) assessment trial under strictly standardized dietary and physical activity conditions. In addition, fasting plasma glucose, insulin and HbA(1c) (glycated haemoglobin) concentrations were measured, and an OGTT (oral glucose tolerance test) was performed to calculate indices of whole-body insulin sensitivity, oral glucose tolerance and/or glycaemic control. In the healthy control group, hyperglycaemia (blood glucose concentration >10 mmol/l) was hardly present (2+/-1% or 0.4+/-0.2/24 h). However, in the patients with Type II diabetes, hyperglycaemia was experienced for as much as 55+/-7% of the time (13+/-2 h over 24 h) while using the same standardized diet. Breakfast-related hyperglycaemia contributed most (46+/-7%; P<0.01 as determined by ANOVA) to the total amount of hyperglycaemia and postprandial glycaemic instability. In the diabetes patients, blood HbA(1c) content correlated well with the duration of hyperglycaemia and the postprandial glucose responses (P<0.05). In conclusion, CGMS determinations show that standard measurements of glycaemic control underestimate the amount of hyperglycaemia prevalent during real-life conditions in Type II diabetes. Given the macro- and micro-vascular damage caused by postprandial hyperglycaemia, CGMS provides an excellent tool to evaluate alternative therapeutic strategies to reduce hyperglycaemic blood glucose excursions

Early or advanced stage type 2 diabetes is not accompanied by in vivo skeletal muscle mitochondrial dysfunction

Objective: Several lines of evidence support a potential role of skeletal muscle mitochondrial dysfunction in the pathogenesis of insulin resistance and/or type 2 diabetes. However, it remains to be established whether mitochondrial dysfunction represents either cause or consequence of the disease. We examined in vivo skeletal muscle mitochondrial function in early and advanced stages of type 2 diabetes, with the aim to gain insight in the proposed role of mitochondrial dysfunction in the aetiology of insulin resistance and/or type 2 diabetes. Methods: Ten long-standing, insulin-treated type 2 diabetes patients, 11 subjects with impaired fasting glucose, impaired glucose tolerance and/ or recently diagnosed type 2 diabetes, and 12 healthy, normoglycaemic controls, matched for age and body composition and with low habitual physical activity levels were studied. In vivo mitochondrial function of the vastus lateralis muscle was evaluated from post-exercise phosphocreatine (PCr) recovery kinetics using 31P magnetic resonance spectroscopy (MRS). Intramyocellular lipid (IMCL) content was assessed in the same muscle using single-voxel 1H MRS. Results: IMCL content tended to be higher in the type 2 diabetes patients when compared with normoglycaemic controls (P=0.06). The 31P MRS parameters for mitochondrial function, i.e. PCr and ADP recovery time constants and maximum aerobic capacity, did not differ between groups. Conclusions: The finding that in vivo skeletal muscle oxidative capacity does not differ between long-standing, insulin-treated type 2 diabetes patients, subjects with early stage type 2 diabetes and sedentary, normoglycaemic controls suggests that mitochondrial dysfunction does not necessarily represent either cause or consequence of insulin resistance and/or type 2 diabetes. © 2008 Society of the European Journal of Endocrinology

Exercise training improves glycemic control in long-standing insulin-treated type 2 diabetic patients

Regular exercise represents an effective strategy to prevent and/or treat type 2 diabetes ( 1 , 2 ). However, the clinical benefits of exercise intervention in a vastly expanding group of long-standing insulin-treated type 2 diabetic patients with comorbidities are less evident. As these patients generally experience muscle weakness ( 3 – 6 ), cardiovascular comorbidities ( 7 – 10 ), and/or exercise intolerance ( 3 , 11 – 13 ), it has proven difficult or even impossible for them to adhere to an intense endurance exercise training regimen ( 14 , 15 ). In the present study, we investigated the feasibility and benefits of a low-impact exercise intervention program, combining both endurance and resistance-type exercise, in long-standing insulin-treated type 2 diabetic patients with a high cardiovascular risk profile. We assessed the impact of 5 months of exercise training on glycemic control, body composition, workload capacity, and whole-body as well as skeletal muscle oxidative capacity