Significance of the time course of ST segment elevation just after reperfusion therapy for acute myocardial infarction

The significance of the time course of ST segment elevation just after reperfusion therapy for acute myocardial infarction was investigated in 25 consecutive patients with acute myocardial infarction and ST elevation. The most elevated ST lead from the standard electrocardiogram on admission was continuously monitored as the ST trend for 72 hr including during the reperfusion procedure. The culprit artery was totally occluded and reperfused without flow delay. Left ventriculograms were obtained after reperfusion and 3-4 weeks later. The most elevated ST level before reperfusion was measured as the maximal level and the ST level 30 min after reperfusion as the reperfused level. The patients were divided into 2 groups, group ST > or = 50% (n = 12) with a decrease of less than 50% of the maximal ST level and group ST < 50% (n = 13) with a decrease of 50% or over 50%. Regional left ventricular wall motion of infarct site, end-diastolic left ventricular volume and ejection fraction were compared between the acute and chronic phase left ventriculograms in each group. In group ST > or = 50%, no significant change was detected in both regional and global ejection fraction, whereas end-diastolic left ventricular volume enlarged significantly in the chronic phase (acute 80 +/- 25 ml/m2 to chronic 95 +/- 17 ml/m2, p < 0.01). In group ST < 50%, regional and global ejection fraction both improved significantly (SD/chord: acute -2.2 +/- 1.5 to chronic -1.4 +/- 0.4, p < 0.001; ejection fraction: acute 50 +/- 14% to chronic 57 +/- 13%, p < 0.01) but end-diastolic left ventricular volume remained the same in the chronic phase. The peak creatine kinase level and the frequency of ST re-elevation at reperfusion were significantly higher in group ST > or = 50% than in group ST < 50% (creatine kinase: group ST > or = 50% 5,496 +/- 2,219 IU/l, group ST < 50% 1,913 +/- 1,180 IU/l, p < 0.0001; ST re-elevation: group ST > or = 50% 83%, group ST < 50% 38%, p < 0.05), although the time from onset of myocardial infarction to reperfusion, the maximal ST level, the degree of collateral development, and the frequency of pre-infarction angina were not different between the 2 groups. Rapid resolution of ST elevation after reperfusion is a useful marker of the improvement of left ventricular function in acute myocardial infarction.     

Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression

Fifty-two of 175 (30%) survivors of allogeneic marrow transplantation developed chronic graft-versus-hose diseases (GVHD). Five with limited chronic GVHD had an indolent clinical course with involvement of only the skin and liver. Forty-seven with extensive chronic GVHD had an unfavorable multiorgan disorder that resembled several autoimmune diseases. Thirteen patients with extensive disease (group I) were not treated and only 2 survive with Karnofsky scores >- 70%. Mortality resulted from infections and morbidity from sica syndrome, pulmonary and hepatic insufficiency, scleroderma-like skin disease, and contractures. Another 13 (group II) received a median of 8 mo prednisone and/or a brief course of antithymocyte globulin, and 3 survive without disability. The other 21 (group III) were treated with a combination of prednisone (1.0 mg/kg/q.o.d.) and either cyclophosphamide, procarbazine, or azathioprine (all 1.5 mg/kg/day) for a median of 13 mo. Combination therapy was well tolerated with only modest myelotoxicity. Fifteen in group III had a good and 4 a fair response to treatment while 2 with no response died. Azathioprine and prednisone was the most effective regimen. All therapy has been discontinued in 12 group III patients: GVHD returned in 5 (including 2 who died in spite of retreatment) while 7 remain free of GVHD for a median of 11 (range 6-30) mo observation. Only I group III survivor is disabled and 16 of the original 21 are alive 2-4 yr after transplant with Karnofsky scores of 70%-100%. Thus, combination immmunosuppression appears to favorably affect and, in some cases, premanently arrest the adverse natural course of extensive chronic GVHD.     

Interim PET/CT-based prognostic model for the treatment of diffuse large B cell lymphoma in the post-rituximab era

The prognostic accuracy of interim ¹⁸F-fluoro-2-dexoy-d-glucose positron emission tomography/computerized tomography (PET/CT) using three different methods of response assessments during rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy was investigated in 186 patients with newly diagnosed diffuse large B cell lymphoma (DLBCL). The response of interim PET/CT was assessed based on a combined evaluation of the Deauville five-point scale (5-PS), the rates of reduction in the maximal standardized uptake value (ΔSUVmax), and the rates of reduction in the metabolic tumor volume (ΔMTV2.5). Positivity on the 5-PS, the optimal cutoff of ΔSUVmax, or the optimal cutoff of ΔMTV2.5 could each predict disease progression. Over a median follow-up of 22.8 months, the assessment of responses based on the 5-PS, ΔSUVmax, and ΔMTV2.5 had prognostic value for progression-free survival. When patients were allocated a score of 0 to 3 depending on the presence of an inadequate response by visual, ΔSUVmax, or ΔMTV2.5, the outcomes of patients with a score of 0 were significantly superior to those with a score of 1, 2, or 3. The interim PET/CT response based on visual, SUV-based, and MTV-based assessment had significant negative predictive value for disease progression and a high potential for predicting outcomes of patients with DLBCL.     

国内六大行政区域六城市中老年人群膝关节骨性关节炎患病危险因素比较

目的：了解中国不同地区间中老年人群膝关节骨性关节炎患病危险因素。方法：调查时间为2005—07／08。①从中国六大行政区（西北，华北，华东。中南，东北，西南）选出六城市（西安，石家庄，上海。广州，哈尔滨市，成都），用分层多阶段整群抽样方法，抽取6218名40岁及以上具有正式户口常住男女人群进行膝关节骨性关节炎的流行病学问卷调查（包括一般情况、现病史、既往史、体格检查、X射线片检查情况和疾病诊断6个方面，共计94个问题141个变量指标），并对其中4808名有症状者进行X射线平片膝正侧位投照。②膝关节骨性关节炎诊断标准为临床症状阳性加X射线Kellgren ＆ Lawrence分级二级及以上者。③计算患病率，并采用Epilnf06．0和SPSS 10．0软件对其中83个变量进行多因素非条件Logistfc回归分析，表示疾病与暴露因素之间联系强度的指标用比值比（OR），若OR〉1，说明疾病发生危险性增加，与暴露因素呈正关联；若OR〈1，说明疾病发生危险性减少，与暴露因素呈负关联。 结果：①六城市膝关节骨性关节炎总患病率为15．6％，其中西安7．7％，石家庄11．2％，上海9．8％。广州30．5％，哈尔滨16．9％，成都17．5％，各城市患病率比较差异显著（P〈0．01）。②Logistic回归分析膝关节骨性关节炎在大部分城市有共同的危险因素如年龄大（OR=1．032—1．181），使用蹲坑排便年限长（OR=1．021-1．077），体质量高（OR=1．048—1．073），和开始饮酒年龄大（OR=1．008～1．028）；而从事专职体育运动（OR=1．651，西安），骨质疏松病史（OR=3．311，石家庄），吸烟（OR=2．654，石家庄），类风湿关节炎病史（OR=4．964，上海），文化程度高（OR=2．593，上海），女性（OR=2．510，广州），姐妹骨关节炎史（OR=13．251，哈尔滨），母亲骨关节炎史（OR=5．683，成都）等危险因素分别在不同地区出现． 结论：年龄大、使用蹲坑排便年限长、体质量高和开始饮酒年龄大是中国六地区膝关节骨性关节炎患病的共同危险因素，同时，不同地区主要危险因素又有一定差异。     

Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint

The ATR-dependent DNA damage response pathway can respond to a diverse group of lesions as well as inhibitors of DNA replication. Using the Xenopus egg extract system, we show that lesions induced by UV irradiation and cis-platinum cause the functional uncoupling of MCM helicase and DNA polymerase activities, an event previously shown for aphidicolin. Inhibition of uncoupling during elongation with inhibitors of MCM7 or Cdc45, a putative helicase cofactor, results in abrogation of Chk1 phosphorylation, indicating that uncoupling is necessary for activation of the checkpoint. However, uncoupling is not sufficient for checkpoint activation, and DNA synthesis by Polalpha is also required. Finally, using plasmids of varying size, we demonstrate that all of the unwound DNA generated at a stalled replication fork can contribute to the level of Chk1 phosphorylation, suggesting that uncoupling amplifies checkpoint signaling at each individual replication fork. Taken together, these observations indicate that functional uncoupling of MCM helicase and DNA polymerase activities occurs in response to multiple forms of DNA damage and that there is a general mechanism for generation of the checkpoint-activating signal following DNA damage.