Late atrioventricular block after heart transplantation.

Bradyarrhythmia requiring permanent pacing after heart transplantation remains a common problem. Sinus node dysfunction is the most common indication, and late onset of atrioventricular (AV) block has rarely been reported. We report the case of a patient who developed advanced AV block at 41 months after transplantation. Right bundle branch block with progressive increase of QRS complex duration was noted in serial electrocardiograms. At the time of late AV block development, the patient did not have acute rejection and coronary angiogram was normal. The mechanism of late onset of AV block is unclear, but it may be caused by progressive conduction.     

Classification tree analysis of second neoplasms in survivors of childhood cancer

Background  

Reports on childhood cancer survivors estimated cumulative probability of developing secondary neoplasms vary from 3,3% to 25% at 25 years from diagnosis, and the risk of developing another cancer to several times greater than in the general population.     

Enantioselective metabolism and cytotoxicity of R-ifosfamide and S-ifosfamide by tumor cell-expressed cytochromes P450.

The anticancer prodrug ifosfamide (IFA) contains a chiral phosphorous atom and is administered in the clinic as a racemic mixture of R-IFA and S-IFA. Hepatic cytochrome P450 (P450) enzymes exhibit enantioselective preferences in the metabolism of R-IFA and S-IFA; however, the impact of this selectivity on P450-dependent anticancer activity is not known. Presently, the metabolism and cytotoxicity of R-IFA and S-IFA were determined in 9L gliosarcoma and Chinese hamster ovary tumor cells expressing an IFA-activating P450 enzyme and by in vitro steady-state kinetic analysis using cDNA-expressed P450 enzymes. Tumor cells expressing P450 enzyme CYP3A4 were the most sensitive to R-IFA cytotoxicity, whereas tumor cells expressing CYP2B1 or CYP2B6 were most sensitive to cyclophosphamide (CPA), an isomer of IFA. Correspondingly, CYP3A4-expressing cells and cDNA-expressed CYP3A4 metabolized R-IFA to yield the active, 4-hydroxylated metabolite at a 2- to 3-fold higher rate than they metabolized S-IFA or CPA. CYP2B cells and cDNA-expressed CYP2B enzymes metabolized CPA almost exclusively by 4-hydroxylation, whereas R-IFA and S-IFA were substantially converted to inactive, N-dechloroethylated metabolites. Further investigation revealed that CYP3A1, a rat enzyme, exhibited superior kinetic properties compared with the human enzyme CYP3A4, with R-IFA and S-IFA both metabolized with high catalytic efficiency by 4-hydroxylation and with a K(m) value of 200 microM, approximately 5-fold lower than CYP3A4. Based on these kinetic parameters and metabolic profiles, R-IFA is expected to exert greater anticancer activity than S-IFA or CPA against tumors that express CYP3A enzymes, whereas tumors expressing CYP2B enzymes may be more sensitive to CPA treatment.     

Personality styles in patients with fibromyalgia,major depression and healthy controls

Background  

The fibromyalgia syndrome (FMS) is suggested to be a manifestation of depression or affective spectrum disorder. We measured the cognitive style of patients with FMS to assess personality styles in 44 patients with fibromyalgia syndrome (FMS) by comparing them with 43 patients with major depressive disorder (MDD) and 41 healthy controls (HC).     

尼麦角林在脑血管病中的应用

尼麦角林是一种麦角生物碱衍生物，广泛应用于脑血管病患者认知障碍的治疗。多项临
床前研究显示，尼麦角林对于认知障碍的改善可能与以下因素有关：尼麦角林除能够改善脑循环，
促进神经递质释放外，还具有营养神经及抗氧化等作用。目前的研究认为，尼麦角林能够改善患者
卒中后抑郁相关的情绪障碍以及有效改善血管性痴呆，提高患者的日常生活能力。同时，尼麦角林具
有良好的安全性，目前暂无尼麦角林治疗导致纤维化或麦角中毒的研究报道。本文就尼麦角林在神
经系统的作用机制、临床疗效及安全性进行综述，以期为临床应用提供参考。