RENAL DISEASE ASSOCIATED WITH ANTINEUTROPHIL CYTOPLASMIC ANTIBODY: 39 PATIENTS OVER A 5-YEAR PERIOD

SUMMARY We have reviewed 39 adult patients who presented over a 5-year period with biopsy confirmed renal disease in association with positive antineutrophil cytoplasmic antibody (18 with C-ANCA, 21 with P-ANCA). Twenty-three (59%) had primary systemic vasculitis, typically with aggressive renal histology including focal necrotising and crescentic glomerulonephritis. In the remaining patients a wide range of clinical syndromes and renal histological appearances were apparent: 30 had abnormal renal function (serum creatinine >140 μmol/l), including 17 who were initially dialysis-dependent. Intensive immunosuppression was administered in 33 cases. When response was assessed at 3 months, renal function was stable or improved in 17 (52%), 5 of whom were able to discontinue dialysis. There was, however, an appreciable early mortality and, at latest follow-up (1–57 months), 12 patients had died and 8 were on the dialysis programme. On immunosuppression, ANCA became negative in the majority (median time 1.5 months) but recurred during clinical relapse in 11 cases. In asymptomatic patients (12 cases), the reappearance of ANCA positivity did not herald clinical relapse. The ANCA assay has increased awareness of systemic vasculitis but not removed the need for histological confirmation before instituting immunosuppression.     

四种心肌克隆钾通道的表达和电生理记录

为建立一种研究离子通道的有效模型 ,笔者应用分子生物学技术 ,将包含有Kv1.4、Kv1.5、Herg和KvLQT1等几种心肌克隆钾离子 (K+ )通道cDNA的质粒经扩增 ,提取 ,以及纯化后转录为mRNA。经微注射技术分别将它们注射入克隆离子通道表达系统———非洲爪蟾卵母细胞内 ,然后应用膜片钳技术记录上述克隆离子通道电流。结果 :获得了四种克隆通道的电流 时间关系曲线 (I/t)和电流 电压关系曲线 (I/V)。结论 :本实验结果证明所采用的技术稳定可靠 ,并为今后开展克隆离子通道结构和功能的关系以及抗心律失常药物与离子通道相互作用的研究提供了坚实的基础。     

血管成形术和支架辅助血管成形术治疗颅内动脉粥样硬化的报告标准（上）

背景和目的颅内动脉粥样硬化可造成众多患者发生缺血性卒中。过去10年间血管内治疗技术已经取得突破性进展,能够开展颅内动脉粥样硬化性狭窄的血管内治疗。采用血管成形术和支架辅助阻管成形术治疗颅内动脉粥样硬化性狭窄的患者例数不断增加。但是鉴于目前血管成形术和支架辅助血管成形术治疗狭窄性和闭塞性颅内动脉粥样硬化仍缺乏普遍认可的临床和放射学评估以及皿管内治疗技术及预后的规范,此文就是提供该方面报告标准、术语和书面定义的共识性建议。报告摘要报告标准是在技术评价委员会、神经介入外科学会、介入放射学会、美国神经外科医师协会和神经外科医师代表大会的脑血管外科分会、美国神经科学会的卒中和介入神经病学分会的联合写作组共同起草完成。对1997年1月-2007年12月间,美国国立图书馆医学文献数据库（PubMed）进行计算机检索,旨在确定已发表的狭窄性颅内动脉粥样硬化的神经介入治疗中,能用作质量评价基准的资料。我们尽可能地确定影响神经介入治疗成功及并发症可能性的危险调节变量。对狭窄性和闭塞性颅内动脉粥样硬化进行麻管内治疗的临床试验设计中,不同临床和技术问题可能影响血管内治疗的疗效,此文章为这些问题提供相关的理论基础。该指南中包括对血管内治疗试验报告标准的建议。虽然制定规范和标准主要是出于研究用途,但是这也将有助于临床实践,还适用于所有相关的出版物。结论总之,报告标准提出的建议将有助于构建有效的研究数据库,同时促进产生科学可靠的研究结果,使相似研究之间或内部能够进行可靠的比较。存某些情况下,为报告和出版的一致性,本文中的定义可能是写作组专家的共识性建议。这些建议将促使不同研究组的结果具有直接可比性。     

Thromboembolic and bleeding complications in acute leukemia

The risk of both thromboembolic and bleeding complications is high in acute leukemia. This double hazard has a significant negative impact on the morbidity and mortality of patients with this disease. The clinical manifestations of both complications show special features specific to the form of acute leukemia. Recognition of these characteristics is important in the diagnosis and management of acute leukemia. In this article, several additional issues are addressed, including the features of bleeding and thrombosis in acute promyelocytic leukemia, the current understanding of the leukostasis syndrome and the iatrogenic complications including catheter-associated thrombosis, and the adverse effects of therapeutic agents used in acute leukemia. As regards the bleeding complications, thrombocytopenia is a major cause. Corrective measures, including recent guidelines on platelet transfusions, are provided.     

冷冻温度对聚乙烯醇水凝胶性能的影响

目的:冷冻温度对制备性能优良的聚乙烯醇水凝胶有较大的影响,拟通过采用反复冷冻-融化方法制备聚乙烯醇水凝胶,探讨在不同冷冻温度下制备的聚乙烯醇水凝胶的物理性能和力学性能,寻求制备聚乙烯醇水凝胶的最佳冷冻温度。方法:实验于2007-04/06在中国矿业大学材料学院摩擦学与可靠性工程实验室完成。实验选用白色絮状的聚乙烯醇20-99作为原料,按一定比例将聚乙烯醇溶于去离子水中,在恒温水浴箱中于90℃下加热4h,配制成一定浓度的聚乙烯醇水溶液;然后将聚乙烯醇水溶液在超低温冷冻储存箱中冷冻成型,冷冻温度分别设为-10℃,-15℃,-20℃,-25℃,-30℃,冷冻时间为6～10h,取出试样后室温下融化2～4h,上述冷冻-融化过程重复3次制得聚乙烯醇水凝胶。实验选用聚乙烯醇的质量分数为15%,制备不同厚度的聚乙烯醇水凝胶试样若干备用。测试各种冷冻温度下制备的聚乙烯醇水凝胶的密度、含水率、再溶胀性和结晶度等物理性能以及弹性模量和应力松弛等力学性能。结果:聚乙烯醇水凝胶的物理性能和力学性能随冷冻温度的不同而明显变化;-20℃反复冷冻融化制备的聚乙烯醇水凝胶具有较好的物理性能和力学性能,其密度为1.06543g/cm3,含水率为82.61%,再溶胀率达238.8%,结晶度为74.03%,弹性模量为0.0974MPa。结论:-20℃是反复冷冻-融化法制备聚乙烯醇水凝胶的常选冷冻温度。     

Risk factors for anaemia in human immunodeficiency virus/hepatitis C virus-coinfected patients treated with interferon plus ribavirin

The most frequent and the most troublesome adverse effect of interferon plus ribavirin-based therapy is anaemia. The aim of this analysis was to determine the incidence and risk factors of anaemia (Hb < 10 g/dL) in human immunodeficiency virus/hepatitis C virus (HCV)-coinfected patients receiving anti-HCV therapy. We reviewed all cases of anaemia occurring among 416 patients participating in a randomized, controlled 48-week trial comparing peginterferon (peg-IFN) alpha 2b plus ribavirin with interferon alpha-2b plus ribavirin. Univariate and multivariate analyses were used to identify links with antiretroviral treatments, HCV therapy and clinical and laboratory findings. Sixty-one (15.9%) of the 383 patients who received at least one dose of anti-HCV treatment developed anaemia. In multivariate analysis the risk of anaemia was significantly associated with zidovudine (OR, 3.27 95% CI, 1.64-6.54, P = 0.0008) and peg-IFN (OR, 2.35; 95% CI, 1.16-4.57, P = 0.0179). The risk of anaemia was lower in patients with higher baseline haemoglobin levels (OR, 0.35 95% CI, 0.26-0.49, P < 0.0001) and in patients receiving protease inhibitor-based antiretroviral therapy (OR, 0.51 95% CI, 0.30-0.86, P = 0.0114). Zidovudine discontinuation could help to avoid anaemia associated with anti-HCV therapy.     

The effect of sulphasalazine on neutrophil superoxide generation in rheumatoid arthritis

The production of superoxide by the peripheral blood neutrophils of 19 patients with active rheumatoid arthritis was measured during treatment with sulphasalazine (SASP). The response to drug treatment was determined by change in plasma viscosity, CRP, early morning stiffness and articular index over a 10-point scale. Of the 19 patients studied, eight were considered to have responded well to SASP and seven to have responded poorly or not at all. Over the treatment period, plateau levels of superoxide production fell in seven of the eight responders (P = 0.028) compared with a non-significant fall in 3/7 of the non- responder groups. The initial rate of superoxide production also fell in the responder group, but this was not statistically significant. Initial values in both the responder and non-responder groups were comparable with those seen for normal controls. Analysis of drug levels showed all patients to be compliant with drug treatment; however, drug levels and neutrophil activity were not correlated. Studies of the effect of SASP and sulphapyridine on superoxide production in vitro showed no difference between good and poor responders. These results suggest that there is no inherent difference between good and poor responders regarding the susceptibility of their neutrophils to SASP. SASP's action on neutrophils, therefore, appears not to be its main mechanism of disease-modifying activity in RA.      

Hereditary defects in fibrinolysis associated with thrombosis.

The plasminogen-plasmin system involves proteolytic enzymes which are primarily responsible for the degradation of fibrin deposits in blood vessels. Through intricate interactions between the various components and inhibitors, a balance is maintained between profibrinolysis and impaired fibrinolytic activity. Several hereditary defects have been described affecting functional plasminogen concentrations, plasminogen activator levels, and plasminogen activator inhibitor activity. These defects have been implicated as risk factors for thrombosis based on a multitude of case reports associating impaired fibrinolysis with thrombosis. However, under close scrutiny, the role of decreased fibrinolysis as an etiologic factor in thrombosis has not been firmly established. Rather, dysfibrinolysis may manifest itself through an accentuation of an underlying thrombophilic state such as recurrent thrombotic episodes. Further evaluation of impaired fibrinolytic activity in conjunction with an underlying thrombophilic condition is warranted.     

The human cardiac mast cell: localization, isolation, phenotype, and functional characterization

We have isolated and characterized the human cardiac mast cell (CMC) and compared this novel mast cell (MC type with MC obtained from uterus, skin, and lung. Heart tissue was obtained from 14 patients with cardiomyopathy (CMP, heart transplantation). CMC were isolated by enzymatic digestion using collagenase, pronase-E, hyaluronidase, and DNAse. Substantial amounts of CMC (0.5% to 1.5% of isolated cells) were found in the atrial appendages but not in ventricular digests or other sites of the heart (< 0.1%). In situ staining of atrial tissue revealed the presence of CMC in the myocardium (2.16 +/- 0.7 MC/mm2), endocardium (2.24 +/- 0.9 MC/mm2), and epicardium. As assessed by combined toluidine blue/immunofluorescence staining with monoclonal antibodies (MoAbs), isolated CMC expressed surface IgE, the receptor for stem cell factor (c-kit receptor/CD117), the p24 antigen (CD9), the Pgp-1 homing receptor (CD44), the pan leukocyte antigen (CD45), and the ICAM-1 antigen (CD54). CMC were not recognized by MoAbs to lymphocyte function associated antigen 2 (LFA-2; CD2), T-cell receptor (TcR; CD3), T4 antigen (CD4), LFA-1 alpha-chain (CD11a), C3biR alpha-chain (CD11b), CR4 alpha-chain (CD11c), LPS-R related Ag (CD14), 3-FAL/x-hapten (CD15), Fc gamma RIII (CD16), lactosylceramid (CDw17), the B-cell antigen CD19, or CR1 (CD35). In situ expression of leukocyte antigens on CMC was demonstrable by indirect immunoperoxidase staining technique and double-labeling immunohistochemistry. Almost all CMC (90%) reacted with MoAbs against tryptase and chymase and thus were MCTC. Cardiac mast cells were also stained by the heparin-binding dye Berberine sulfate and expressed measurable amounts of histamine (4.6 +/- 1.4 pg per cell). Cross linking of either IgE receptor or SCF receptor (c-kit) on CMC resulted in histamine secretion (non-specific release: < 6% of total histamine, alpha IgE induced: 12% to 52%; SCF-induced release: 9% to 18%), whereas neither substance P (a skin MC agonist) nor the basophil agonist FMLP showed an effect on CMC. Together, the CMC is an MCTC primarily located in the appendage of the atrium. This novel type of MC exhibits surface membrane antigen and functional properties similar to those of lung and uterus MC.     

The effect of platelets in the activation of human blood coagulation factor IX by factor XIa

We report here the effect of activated human platelets on the activation of human factor IX by human factor XIa. Factor IXa formed during activation was determined via its ability to activate bovine factor X. To increase sensitivity, phospholipids and bovine factor VIIIa were present in the assay. The kinetic parameters of the factor IX activation were determined in the presence of 10 mmol/L CaCl2. The Km for factor IX was 0.30 mumol/L and kcat was 2.4 s-1. Activated human platelets inhibited factor IX activation by factor XIa in a dose- dependent manner, whereas unstimulated platelets had no effect. Factor IX activation was inhibited for more than 90% at a platelet concentration of 4 X 10(8)/mL, whereas concentrations of less than 10(6)/mL had no influence. The inhibitory effect could be induced by thrombin, collagen, calcium ionophore A 23187, and adrenalin. The appearance of inhibitory activity could be blocked by the addition of the prostacyclin analogue ZK 36374 at any time during platelet activation. Stirring during platelet activation was not necessary. These results suggest that the inhibition is caused by a release reaction. This was confirmed by centrifugation experiments that showed that the inhibitory activity could be recovered from the supernatant of the activated platelets. The inhibitory activity was destroyed upon boiling and was susceptible to trypsin digestion. Passage of platelet supernatant over ACA 22 showed that the inhibitory activity eluted with an apparent molecular weight of less than 1,200,000 but greater than 669,000. The inhibition of factor XIa was reversible. These data suggest that platelets release an antiprotease of factor XIa that reversibly inhibits factor XIa. Lineweaver-Burk analysis showed that the inhibitor caused both an increase in Km for factor IX and a decrease in kcat of factor IXa formation by factor XIa.