Comparison of vildagliptin and acarbose monotherapy in patients with Type 2 diabetes: a 24-week,double-blind,randomized trial

Aims To compare the efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor, vildagliptin, with the alpha glucosidase inhibitor, acarbose, in drug-naive patients with Type 2 diabetes. Methods This multi-centre, randomized, double-blind, parallel-arm study compared the efficacy and tolerability of vildagliptin (100 mg daily, given as 50 mg twice daily, n = 441) and acarbose (up to 300 mg daily, given as three equally divided doses, n = 220) during 24-week treatment in drug-naive patients with Type 2 diabetes. Results Monotherapy with vildagliptin or acarbose decreased glycated haemoglobin (HbA_1c) (baseline ≈ 8.6%) to a similar extent during 24-week treatment. The adjusted mean change from baseline to end-point (AMΔ) in HbA_1c was −1.4 ± 0.1% and −1.3 ± 0.1% in patients receiving vildagliptin and acarbose, respectively, meeting the statistical criterion for non-inferiority (upper limit of 95% confidence interval for between-treatment difference ≤ 0.4%). The decrease in fasting plasma glucose was similar with acarbose (−1.5 ± 0.2 mmol/l) and vildagliptin (−1.2 ± 0.1 mmol/l). Body weight did not change in vildagliptin-treated patients (−0.4 ± 0.1 kg) but decreased in acarbose-treated patients (−1.7 ± 0.2 kg, P < 0.001 vs. vildagliptin). The proportion of patients experiencing any adverse event (AE) was 35% vs. 51% in patients receiving vildagliptin or acarbose, respectively; gastrointestinal AEs were significantly more frequent with acarbose (25.5%) than vildagliptin (12.3%, P < 0.001). No hypoglycaemia was reported for either group. Conclusions Vildagliptin is effective and well tolerated in patients with Type 2 diabetes, demonstrating similar glycaemic reductions to acarbose, but with better tolerability.     

几种伪随机序列应用于诱发电位检测的性能比较

伪随机序列技术作为一种快速检测诱发电位的技术已得到重视。本文主要对几种常用序列Ｍ序列、巴克序列和格雷互补序列等应用于诱发电位检测时的性能进行研究，分别给出了它们的解卷积算法及用于诱发电位检测时相对于平均法的信噪比改善倍数。理论及实验表明，Ｍ序列在检测信噪比改善方面较另两种序列好。     

Alterations of excitation-contraction coupling and excitation coupled Ca(2+) entry in human myotubes carrying CAV3 mutations linked to rippling muscle

Rippling muscle disease is caused by mutations in the gene encoding caveolin-3 (CAV3), the muscle-specific isoform of the scaffolding protein caveolin, a protein involved in the formation of caveolae. In healthy muscle, caveolin-3 is responsible for the formation of caveolae, which are highly organized sarcolemmal clusters influencing early muscle differentiation, signalling and Ca(2+) homeostasis. In the present study we examined Ca(2+) homeostasis and excitation-contraction (E-C) coupling in cultured myotubes derived from two patients with Rippling muscle disease with severe reduction in caveolin-3 expression; one patient harboured the heterozygous c.84C>A mutation while the other patient harbored a homozygous splice-site mutation (c.102+ 2T>C) affecting the splice donor site of intron 1 of the CAV3 gene. Our results show that cells from control and rippling muscle disease patients had similar resting [Ca(2+) ](i) and 4-chloro-m-cresol-induced Ca(2+) release but reduced KCl-induced Ca(2+) influx. Detailed analysis of the voltage-dependence of Ca(2+) transients revealed a significant shift of Ca(2+) release activation to higher depolarization levels in CAV3 mutated cells. High resolution immunofluorescence analysis by Total Internal Fluorescence microscopy supports the hypothesis that loss of caveolin-3 leads to microscopic disarrays in the colocalization of the voltage-sensing dihydropyridine receptor and the ryanodine receptor, thereby reducing the efficiency of excitation-contraction coupling.     

Protonentherapie mit „Spot-Scanning“ bei Rhabdomyosarkomen im frühen Kindesalter

PURPOSE: To evaluate the feasibility and acute toxicity of spot-scanning proton therapy under deep sedation in young children with rhabdomyosarcomas (RMS). PATIENTS AND METHODS: Since 2004, children requiring sedation can be admitted for proton therapy at Paul Scherrer Institute (PSI), Villigen, Switzerland. Children under 5 years of age with RMS of the head and the trunk were analyzed. All children were enrolled in a multidisciplinary treatment protocol and prospective, standardized evaluation of side effects was performed. RESULTS: Nine children were included aged 0.9-3.8 years (embryonal RMS in six, and alveolar, undifferentiated or nonclassified in one each). The tumor site was parameningeal (n = 4), orbital (n = 3), head and neck (n = 1), and prostate (n = 1). All children were in IRS group III. Total proton dose was 46-54 CGE (cobalt-gray equivalent). Only the myelotoxicity exceeded grade 3 or 4 (RTOG/EORTC). CONCLUSION: Proton therapy for RMS in early children is feasible and well tolerated. The prospective standardized evaluation of toxicity and quality of life needs to be continued.     

VH and VL gene analysis in sporadic Burkitt's lymphoma shows somatic hypermutation, intraclonal heterogeneity, and a role for antigen selection

Tumor cell lines and one tumor biopsy from seven cases of Epstein-Barr virus (EBV) genome-negative sporadic Burkitt's lymphoma (BL) have been investigated for usage and mutational pattern of Ig variable region genes. The VH genes were derived from the VH 3 (one) and VH4 (six) families and both the IgM-positive (six) and the IgA-positive (one) were all mutated from their germline counterparts. The VL genes were derived from V kappa 1 (one), V kappa 3 (one), V lambda 1 (four), and V lambda 2 (one) families and were also somatically hypermutated. Biopsy material from one of the IgM-positive cases showed VH and VL sequences that matched the derived cell line, with additional intraclonal sequence heterogeneity, indicating that the tumor cells had undergone posttranformation somatic mutation. Mutational patterns in V(H) genes did not show a conventional role for antigen in selecting tumor cell sequences. In contrast, patterns in VL sequences were consistent with a role for antigen in five of seven cases. The pattern of extensive scattered somatic hypermutation and intraclonal variation is similar to that in VH sequences of EBV genome-positive endemic BL, although the degree of mutational activity is less. These common features indicate that B cells involved in the two variants of BL may share a common clonal history.