Mercaptopurine in childhood leukaemia: the effects of dose escalation on thioguanine nucleotide metabolites

The current U.K. trial protocol (UKALL XI) for childhood lymphoblastic leukaemia demands mercaptopurine (MP) dose escalation in children who tolerate daily 75  mg/m² MP (100% dose) without cytopenias. The previous trial (UKALL X) did not. MP metabolism was studied in a group of UKALL XI children ( n =21) who tolerated 100% dosages and who were matched in this respect with a similar group of UKALL X children. Red blood cell MP derived thioguanine nucleotide (TGN) concentrations were measured in both groups under comparable conditions; at 75  mg/m² MP there was no significant difference. MP dose escalation in the UKALL XI children produced higher TGN concentrations (TGNs at 100% vs 125% dosages, median difference 90  pmol/8×10⁸ RBCs, 95% CI 25 to 165  pmol, P <0.02). Assayed at the time of cytopenia induced dose reduction, the UKALL XI children had accumulated significantly higher TGN concentrations than the UKALL X children (median difference 78  pmol/8×10⁸ RBCs, 95% CI 20 to 144, P <0.02). These findings indicate that dose escalation in children tolerant of 100% MP dosages produces higher peak TGN concentrations.     

Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine

To investigate the in vivo role of NMDA receptor stimulation in HIV-1-related CNS neurotoxicity, we evaluated the neuroprotective potential of the NMDA receptor antagonist memantine in transgenic mice which have gp120-induced CNS damage. Brains of mice treated chronically with memantine and of untreated controls were analysed for structural damage by laser scanning confocal microscopy of sections immunolabeled for microtubule-associated protein-2 (MAP-2) and synaptophysin. Qualitative and quantitative analysis of confocal images revealed that memantine treatment substantially decreased neuropathology in gp120 transgenic mice; this included statistically significant improvements in both dendritic and presynaptic terminal density. These results provide in vivo evidence that gp120 can activate neurotoxic pathways that can ultimately result in aberrant NMDA receptor stimulation and neuronal damage in the CNS. They also suggest that clinically tolerated NMDA receptor antagonists may be useful in the prevention of neuronal damage in HIV-1-infected patients.     

肱骨外髁骨折165例病案分析

总结分析了165例肱骨外髁骨折。初诊时,漏诊12例,误诊91例,闭合复位失败55例。按骨折不同类型和软组织损伤情况分别从七个方面:1.无移位骨折,2.移位或翻转移位骨折,3.软组织嵌入闭合复位困难,4.局部严重肿胀,5.陈旧性骨折,6.骨折畸形愈合并发肘外(内)翻严重,7.并发肘关节僵硬,提示了不同的治疗方法。介绍了手术时如何辨认骨折面、清除疤痕组织和骨痂、松解粘连的力法,以及1枚克氏针加粗丝线内固定法的操作要点。     

微量元素锌在佝偻病治疗中的效果观察

目的 :探讨补充锌 +维生素D +钙剂治疗佝偻病的效果。方法 :随机分为 3组 ,每组各 5 3例。对照组给予常规治疗 (即维生素D +钙剂 ) ,治疗 1组先给予锌治疗 1个月后 +常规治疗 ,治疗 2组同时给予锌 +常规治疗。 3个月为 1疗程。治疗前后检测血清微量元素及骨碱性磷酸酶 (BALP)等项目。结果 :治疗 1、2组疗效好于对照组 ,差异非常显著 (P <0 0 1) ;治疗1组疗效好于治疗 2组 ,差异有显著性 (P <0 0 5 )。结论 :治疗大多数伴低锌的佝偻病先补锌 1个月 ,再加常规治疗 ,疗效更佳。     

Multiple sclerosis: myelin basic protein induced mRNA expression of proinflammatory cytokines in mononuclear cells is suppressed by interferon-β 1b in vitro

Beta-interferon (IFN-β) is a promising treatment in multiple sclerosis (MS), reducing the exacerbation rate and MRI lesion burden, as well as the disease progression in relapsing-remitting MS. IFN-β was originally defined by its antiviral effects, but the interest has recently been focused on its immunomodulatory properties. Myelin basic protein (MBP) is one of several autoantigens considered to be the target for autoaggressive immune responses, which eventually might lead to the development of MS. To study in-vitro effects of IFN-β1b on MBP induced cytokine expression, mRNA for the Th1 cytokines IFN-γ and TNF-α, the Th2 related IL-4 and IL-6, the cytolytic perforin and the immune response downregulating TGF-β was measured with in situ hybridization after culture of blood mononuclear cells (MNC) in the presence and absence of MBP. Numbers of cells expressing IFN-γ, TNF-α, perforin and IL-4 mRNA were significantly suppressed after culture with 10 U/ml IFN-β1b. No such effect was seen on MBP induced IL-6 or TGF-β mRNA expression. These observations suggest that one of the major effects of IFN-β1b is the induction of a shift in the cytokine mRNA profile towards a more immunosuppressive pattern. In parallel in vitro tests, the control substance dexametasone (40 μg/ml) reduced the numbers of cells expressing mRNA for all cytokines under study with the exception of TGF-β, to an extent equal to or even more pronounced than IFN-β1b.     

An Experimental Study on the Relationship Between Artificial Korotkoff Sounds and Self-Excited Oscillation Using a Circulatory Simulator

In the medical field, Korotkoff sounds have been explained as sounds generated by the disturbed blood flow in the artery. However, in the biomechanics field, Korotkoff sounds are considered to be produced and/or modified by the self-excited oscillation of a collapsed artery. The self-excited oscillation is an oscillation of the arterial wall. In addition, it is influenced by the nonlinear pressure–flow relationships in the artery and the arterial compliance. In this paper, we proposed an arterial-compliance-measuring method, using Korotkoff sounds. We constructed a circulatory simulator with a brachial model that mimics the physiological circulation, because in vivo resolution of nonlinear pressure–flow relationships is very difficult. The simulator was utilized to generate artificial Korotkoff sounds similar to those in auscultation in the brachial model. Additionally, we prepared latex tubes as artificial brachial arteries. In the experiment, we investigated the relationship between the self-excited oscillation and Korotkoff sounds by the distinguishing its frequency characteristics. The frequency of the sounds was changed by the variation of the tube compliance. As a result, we have found that the changes of the sounds largely depended on the difference of the tube compliance in this simulator. In conclusion, Korotkoff sounds contain useful information for predicting brachial arterial compliance. These experiments indicate the effectiveness of noninvasive measurement for brachial arterial compliance using Korotkoff sounds.     

HCVRNA阳性的丙型肝炎诊断和治疗探讨

HCVRNA阳性的丙型肝炎46例，均经临床和／或组织学确诊。治疗组24例用IFNa－nl或a－2b3×106IU，隔日一次；对照组22例用一般护肝药物。HCVRNA12周转阴率治疗组为83．3％，对照组为9．0％（P＜0．001）。ALT和AST复常率治疗组也优于对照组（P＜0．05）。随访观察满48周者治疗组15例中HCVRNA持续转阴11例（73．3％）．对照组5例均持续阳性。治疗组中5例做了Ⅰ～Ⅲ型HCV基因分型，结果均为Ⅱ型。同时对急、慢性丙型肝炎的发病过程和病理诊断作了讨论。     

5105例乙肝三系统分布形式调查分析

本文对5105例乙肝三系统检测结果的32种组合形式出现率进行了统计分析,并引 入年龄因素分层分析。分析讨论了19岁以下、20～39岁、40～59岁及60岁以上四组受检者乙肝三系 统检测结果表现与分布的异同,并据此结合文献报道资料提出了预防处理意见。