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Selected AbstractsThe impact of CD34+ cell dose on platelet engraftment in pediatric patients following unmanipulated haploidentical blood and marrow transplantation,PEDIATRIC BLOOD & CANCER, Issue 6 2009Ying-Jun Chang PhD Abstract Objective Unmanipulated haploidentical blood and marrow transplantation has been developed as an alternative transplant strategy for pediatric patients with hematological diseases. The aim of this study was to investigate the effects of donor and recipient characteristics on hematopoietic recovery in pediatric patients following unmanipulated haploidentical transplantation. Methods Factors correlating with hematopoietic recovery in 133 pediatric patients after unmanipulated haploidentical transplantation were analyzed retrospectively. Results All patients reached an absolute neutrophil count of 500/µl in a median of 12 days (range, 9,49 days). One hundred thirty-three patients reached an untransfused platelet count of more than 20,000/µl in a median of 15 days (range, 7,180 days). Univariate analysis showed five factors associated with platelet engraftment. These were time to transplantation after diagnosis (P,=,0.072), infused nuclear cells/kg of recipient weight (P,=,0.028), CD3+ cells/kg of recipient weight (P,=,0.082), CD4+ cells/kg of recipient weight (P,=,0.083), and CD34+ cells/kg of recipient weight (P,=,0.012). Multivariate analysis showed that infused CD34+ cells/kg of recipient weight (CD34+ cells more than 2.42,×,106/kg vs. less than or equal to 2.42,×,106/kg, HR,=,1.733; 95% CI 1.222,2.549; P,=,0.002) were significantly associated with an increased risk of platelet engraftment. Patients receiving a CD34+ cell dose more than 2.42,×,106/kg had a short time [12 days (range, 7,176 days)] to achieve an untransfused platelet engraftment, compared to 18 days (range, 7,180 days) in patients receiving a lower dose (P,<,0.001). Conclusions Our results suggest that low number of CD34+ cells in allografts is a critical factor associated with delayed platelet engraftment after unmanipulated haploidentical transplantation in pediatric patients. Pediatr Blood Cancer 2009;53:1100,1106. © 2009 Wiley-Liss, Inc. [source] An increase in insulin sensitivity and basal beta-cell function in diabetic subjects treated with pioglitazone in a placebo-controlled randomized studyDIABETIC MEDICINE, Issue 6 2004T. M. Wallace Abstract Aims To investigate the effect of treatment with pioglitazone on beta-cell function and insulin sensitivity in Type 2 diabetes. Methods Thirty subjects with diet-controlled Type 2 diabetes were randomized to 3 months treatment with pioglitazone (n = 19) or placebo (n = 11). All subjects underwent basal sampling for homeostatic model assessment (HOMA), followed by an intravenous glucose tolerance test and hyperglycaemic clamp, followed by an euglycaemic hyperinsulinaemic clamp; at baseline and after treatment. Results All results are expressed as mean (sem). Pioglitazone increased basal insulin sensitivity by 24.7% (7.8) HOMA-%S vs. 2.1% (5.9) in the placebo group (P = 0.02). Stimulated insulin sensitivity, M/I, increased in the pioglitazone group compared with placebo: +15.1 (2.8) l kg,1 min,1 vs. +3.2 (2.9) l kg,1 min,1, respectively (P = 0.009). Pioglitazone increased adiponectin by 39.3 (6.3), ng/ml compared with a decrease of 0.8 (1.3) ng/ml with placebo (P = 0.00004). HOMA-%B increased with pioglitazone, +11.5% (4.8) vs. ,2.0% (4.8) with placebo (P = 0.049), but there was no change in stimulated beta-cell function as determined by hyperglycaemic clamps. There was a significant reduction in the proinsulin/insulin ratio in the pioglitazone group, ,0.057 (0.02) compared with placebo, +0.004 (0.02) (P = 0.03). There was a significant reduction in HbA1c of 0.6% (0.1) in the pioglitazone group compared with placebo (P = 0.003). There was no significant weight gain associated with pioglitazone therapy: +0.7 (sem 0.6) kg vs. +1.1 (sem 0.5) kg in placebo group (P = NS). Conclusions Basal beta-cell function and insulin sensitivity improved following pioglitazone therapy. The improvement in proinsulin to insulin ratio suggests that beta-cells are under less stress. [source] Clinical Trial: High-dose furosemide plus small-volume hypertonic saline solutions vs. repeated paracentesis as treatment of refractory ascitesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009G. LICATA Summary Background, In patients with cirrhosis, ascites is defined as refractory when it cannot be mobilized or recurs early in standard diuretic therapy. Aim, To compare the safety and efficacy of intravenous high-dose furosemide + hypertonic saline solutions (HSS) with repeated paracentesis in patients with cirrhosis and refractory ascites. Patients and methods, Eighty-four subjects (59/25 M/F) with cirrhosis, mostly of viral aetiology, admitted for refractory ascites, were randomly assigned to receive furosemide (250,1000 mg/bid i.v.) plus HSS (150 mL H2O with NaCl 1.4,4.6% or 239,187 mEq/L) (60 patients, Group A) or to repeated paracentesis and a standard diuretic schedule (24 patients, Group B). Results, During hospitalization, Group A patients had more diuresis (1605 ± 131 mL vs. 532 ± 124 mL than Group B patients; P < 0.001) and a greater loss of weight at discharge (,8.8 ± 4.8 kg vs. ,4.5 ± 3.8 kg, P < 0.00). Control of ascites, pleural effusions and/or leg oedema was deemed significantly better in Group A. Conclusions, This randomized pilot study suggests that HHS plus high-dose furosemide is a safe and effective alternative to repeated paracentesis when treating hospitalized patients with cirrhosis and refractory ascites. Larger studies will be needed to evaluate long-term outcomes such as readmission and mortality. [source] Managing childhood obesity: when lifestyle change is not enoughDIABETES OBESITY & METABOLISM, Issue 11 2010C. Hearnshaw The management of childhood obesity is a clinical dilemma. Paediatricians will see those children whose weight is at the severe end of the spectrum with obesity-related co-morbidities and for whom more intensive weight loss therapies may be appropriate. A literature review was performed (January 1995,January 2010) of the roles of pharmacotherapy or bariatric surgery in the management of childhood obesity. Three hundred and eighty-three abstracts were reviewed and 76 full-text articles were requested. Of these, 34 were excluded and a total of 21 pharmacotherapy papers and 22 papers on surgery were reviewed in detail. All studies involved adolescents. Pharmacotherapy: Most studies were small and of short duration, the notable exceptions being two large RCTs of sibutramine and orlistat. Sibutramine led to a mean estimated change in BMI from baseline of ,3.1 kg/m2 vs. ,0.3 kg/m2 for placebo over 12 months. Orlistat was also beneficial with a mean reduction in BMI of 0.55 vs. an increase of 0.31 kg/m2 in the placebo group at 12 months. Bariatric surgery: Most papers presented clinical observations and there were no randomised controlled trials (RCTs). Robust selection criteria were not used and ideal candidate selection remains unclear. Most papers showed a significant benefit of surgery in severely obese adolescents in the short term but long-term data were sparse. There were a surprisingly large number of papers examining the benefits of intensive weight management in obese adolescents. The study design of many was inadequate and the role of pharmacotherapy or surgery in childhood obesity remains unclear. [source] | ||||||||||