股骨远端轴位X射线片对全膝关节假体置换术中股骨假体旋转力线的评估价值

目的:探讨股骨远端轴位X射线片对于确定股骨后髁扭转角的价值及在全膝关节假体置换术中的意义。方法:选择2004-01/2005-05在南方医院接受全膝关节置换术的患者22例,共30例膝(均可以弯曲到90°)行术前的股骨远端轴位X射线检查和膝关节CT扫描。轴位X射线片在膝关节屈曲90°,小腿重力牵引下拍摄,CT采用1mm薄层扫描。在X射线片和CT片上,分别标记出临床上髁轴和后髁轴,并计算出股骨后髁扭转角。应用SPSS13.0软件两组数据进行方差分析和相关性分析。结果:受检股骨远端在轴位X射线片上都得到了良好的显示,患者在检查过程中没有感到明显的不适。由轴位X射线片和CT片上测得的股骨后髁扭转角分别为(6.9±1.6)°,(6.8±1.5)°,两种方法测得的股骨后髁扭转角平均差值为(0.6±0.5)°,无显著性差异,且存在强相关(r=0.903,P<0.001)。结论:股骨远端轴位X射线片可用于全膝关节置换术前确定股骨假体旋转力线,具有同CT相当的准确性。     

个体经营药店参与结核病控制的阻碍因素:定性抽样调查分析

目的:分析阻碍个体经营药店参与结核病控制的潜在因素。方法:实验于2005-07在重庆市区完成。调查主要采用了定性的方法,共调查了29名对象,采用方便抽样和滚雪球抽样的方法对15家经营时间1年以上的个体经营药店的管理人员或者工作人员进行了个人深入访谈;采用目的性抽样的方法对4名卫生监督所,药监局以及结核病防治所的相关官员及领导进行了关键人物访谈;采用专题小组访谈的形式,对2家结防专业机构的10名医护人员进行访谈。采用定性方法对采访对象进行了个人深入访谈、小组访谈、关键人物访谈。借助MAXqda软件,采用主体框架法进行分析。主要调查内容:①药店参与结核控制的现状,包括宣传结核病知识,发现、转诊结核病例。②药店参与结核病例发现的能力,包括员工的专业背景知识,对结核病知识的了解,接受新知识的机会。③药店参与结核病控制的客观阻碍因素,包括利益冲突、消费者的态度等。结果:29名受访对象均进入结果分析。①药店是患者接受健康教育的一个潜在的、重要的部门,绝大部分顾客在购药时都会咨询药店工作人员的意见,药店在发现以及转诊结核病患者中也起到一定促进作用,药店工作人员曾有发现结核病疑似患者并建议其接受医生治疗的经历。②药店从业人员仅了解部分结核病基础知识,缺少对结核病相关知识的知晓。但部分员工有医学或护理方面的专业背景,并且接受新知识的渠道也较多,如定期职能部门培训、电视以及报纸宣传等,但结核病知识的专题培训却相当少。③虽然绝大多数药店从业人员都认为推荐患者去结防所治疗不会对药店生意造成太大的影响,但也有部分人认为利益冲突会间接影响到药店参与结核病控制的行为。结论:药店在结核病控制工作中起到一定促进作用,但药店从业人员对结核病相关知识的了解有必要加强,采取一系列可行性措施解除这些阻碍因素,利益冲突会间接影响到药店参与结核病控制的行为。     

Preparation and characterization of monoclonal antibodies recognizing two distinct differentiation antigens (Pro-Im1, Pro-Im2) on early hematopoietic cells

A series of monoclonal antibodies recognizing myeloid differentiation antigens were prepared by immunizing Balb/c mice with HL-60 cells. Hybrids secreting antibodies reactive with HL-60 cells but unreactive with peripheral blood mononuclear cells were isolated and further cloned. One clone was found to produce an IgG2a antibody recognizing an 85,000-dalton molecular weight surface glycoprotein, and a second clone was found to produce an IgM antibody recognizing a heat-stable determinant present on a glycolipid. We have termed these antigens Pro- Im1 and Pro-Im2, respectively (Pro for using HL-60 promyelocytes as an immunogen and Im for the presence of these antigens on immature cells). alpha Pro-Im1 and alpha Pro-Im2 were used to investigate the surface expression and tissue distribution of these two antigens. Pro-Im1 and Pro-Im2 were found to be brightly expressed on a fraction of fetal liver hematopoietic and bone marrow cells. Both antibodies mediated complement-dependent inhibition of CFU-GM, BFU-E, and CFU-GEMM formation assayed by soft agar colony and burst formation, indicating the expression of these antigens by early hematopoietic precursor cells. This was further confirmed by the induction of HL-60 cells by TPA to differentiate into more mature monocytes and macrophages, accompanied by the loss of both antigens. Pro-Im1 and Pro-Im2 were absent from peripheral blood monocytes, erythrocytes, and platelets, but Pro-Im2 was expressed on granulocytes. Both antigens were absent from thymocytes and peripheral T cells. Cytofluorographic analysis suggested their absence from peripheral blood B cells but that both were expressed on a minority of tissue B cells. Analysis of 150 cases of various myeloid and lymphoid malignancies demonstrated Pro-Im1 and Pro-Im2 expression on myeloblasts and promyelocytes from some acute myelogenous leukemias as well as some B cell malignancies, suggesting that these antigens are shared by early hematopoietic cells and a subset of B cells.     

Busulfan pharmacokinetics using a single daily high-dose regimen in children with acute leukemia

The pharmacokinetics of busulfan, given as a single daily dose (either 4 mg/kg or 150 mg/m2), was determined in 22 children undergoing bone marrow transplantation for acute leukemia. The single daily dose regimen showed similar pharmacokinetics to previously reported regimens of 4 x 1 mg/kg, except for fourfold higher mean peak plasma levels and negligible trough levels. Daily systemic exposure for single dose regimens based on weight (4 mg/kg) or surface area (150 mg/m2), respectively were very similar to regimens of (4 x 1 mg/kg) or (4 x 37.5 mg/m2). Dose (milligrams per kilogram), peak plasma level, and area under the curve (AUC) were all higher in 12 children treated with 150 mg/m2 busulfan than in 9 children treated with 4 mg/kg. AUC was age dependent for the 4 mg/kg dose but not for the 150 mg/m2 dose. The use of a 150 mg/m2 dose allows escalation of the dose above 4 mg/kg, eliminating the tendency for younger children to receive lower systemic exposure. Little toxicity was observed in this study. Clearance and distribution volume correlated negatively with age, and AUC correlated positively with dose (milligram per kilogram). Administration of busulfan as crushed rather than whole tablets reduced the delay time for appearance of busulfan in plasma but had no effect on absorption or other pharmacokinetic parameters.     

New variant of von Willebrand disease type II with markedly increased levels of von Willebrand factor antigen and dominant mode of inheritance: von Willebrand disease type IIC Miami

A variant of von Willebrand disease (vWD) was identified in six members of a kindred spanning four generations. The proband was a 46-year-old woman with a lifelong history of bleeding, a prolonged bleeding time (> 15 minutes), markedly elevated von Willebrand factor (vWF) antigen (vWF:Ag = 2.09 U/mL), slightly reduced ristocetin cofactor activity, and a plasma vWF multimer pattern similar to that of vWD type IIC. Similar findings were observed in her three children, mother, and brother. In affected family members, platelet and plasma vWF multimer patterns were discrepant with higher molecular weight multimers observed in platelet vWF. Following a 1-Des-amino-8-D-arginine vasopressin (DDAVP) challenge, the proband failed to normalize her bleeding time even though vWF: Ag rose by 70% and higher molecular weight multimers were increased slightly. Genetic studies were consistent with autosomal dominant inheritance of a mutation within the vWF gene. By sequencing of cloned genomic DNA, mutations were excluded in exons 4, 5, 14, and 15, which encode regions of the vWF propeptide proposed to be important in multimer biosynthesis. Mutations also were excluded in exons 28 to 31, which encompass the known mutations that cause vWD types IIA, IIB, and B. This new variant of vWD, characterized by autosomal dominant inheritance, a qualitative defect that resembles vWD type IIC, and increased plasma vWF:Ag, was tentatively designated vWD type IIC Miami.     

Eradication of minimal disease in severe combined immunodeficient mice with disseminated Daudi lymphoma using chemotherapy and an immunotoxin cocktail

Severe combined immunodeficient (SCID) mice injected intravenously with a human Burkitt's lymphoma cell line (Daudi) develop disseminated lymphoma (SCID/Daudi), which is fatal in 100% of the mice. Early treatment of these mice with either an immunotoxin (IT) cocktail (consisting of anti-CD19-ricin A chain plus anti-CD22-ricin A chain) or chemotherapy significantly prolonged survival but was not curative. Combination therapy with the IT cocktail and any one of three chemotherapeutic drugs (doxorubicin, cytoxan, or camptothecin) cured the mice. Cure was demonstrated by both histopathologic examination of treated mice and, more importantly, by adoptive transfer of cells from organs of the cured mice to naive SCID mice where 100 tumor cells would have caused disease in the recipients. These results provide a strong rationale for combining IT therapy with conventional chemotherapy in the treatment of B-cell neoplasia.     

Acute myelomonocytic leukemia with abnormal eosinophils and inv(16) or t(16;16) has a favorable prognosis

Inv(16)(p13q22) and t(16;16)(p13;q22) are recurring chromosomal rearrangements which juxtapose the metallothionein gene cluster at 16q22 with other DNA sequences from 16p13. We have studied 20 men and 13 women who had acute nonlymphocytic leukemia; 27 patients had an inv(16) and six patients had a t(16;16). Eight patients also had trisomy 22, and four had trisomy 8. All but two patients had the unique morphologic features of acute myelomonocytic leukemia with abnormal eosinophils (M4Eo). In one patient with M4 leukemia, abnormal eosinophils were not observed in the marrow. A second patient had acute monocytic leukemia, plus abnormal eosinophils. Eosinophils constituted 1% to 46% (median, 6%) of the bone marrow cells, and in all but a single patient, the eosinophils exhibited distinctly abnormal morphology. Twenty-five patients have had a complete remission (78% of treated patients). Nine patients have remained in remission longer than 24 months. No patient had symptoms of central nervous system (CNS) disease at diagnosis, and none had CNS leukemic mass lesions at any time. Treatment with high-dose cytarabine may have provided prophylactic CNS therapy. Four additional patients with chromosomal rearrangements involving a breakpoint at 16q22 but not at 16p13 have had different morphological features and different clinical courses. Thus, the juxtaposition of genes at 16p13 and 16q22, which occurs both in the inv(16) and the t(16;16), results in a specific subset of acute nonlymphocytic leukemia that has a favorable prognosis.     

Cognitive outcomes at ages seven and nine years in South African children from the children with HIV early antiretroviral (CHER) trial: a longitudinal investigation

IntroductionMany children living with HIV (CLWH) display impaired cognition. Although early combination antiretroviral therapy (ART) produces improved cognitive outcomes, more long‐term outcome data are needed. After concluding the Children with HIV Early antiRetroviral (CHER) trial in 2011, we investigated cognitive performance, at seven and nine years of age. Participants had been randomized to deferred ART (ART‐Def; n = 22); immediate time‐limited ART for 40 weeks (ART‐40W; n = 30) and immediate time‐limited ART for 96 weeks (ART‐96W; n = 18). We also recruited HIV‐exposed uninfected (CHEU; n = 28) and HIV‐unexposed (CHU; n = 35) children.MethodsData were collected between May 2012 and December 2017. Mixed‐model repeated‐measures ANOVAs assessed differences over time between CLWH (ART‐40W, ART‐96W and ART‐Def) and CHIV‐ CHEU and CHU between ART‐Early (ART‐40W and ART‐96W), ART‐Def, CHEU and CHU; and between ART‐40W, ART‐96W, ART‐Def, CHEU and CHU.ResultsAll comparisons found significant effects of Time for most outcome variables (better scores at nine than at seven years; ps < 0.05). The first ANOVAs found that for (a) motor dexterity, CLWH performed worse than CHIV‐ at seven years (p < 0.001) but improved to equivalence at nine years, (b) visual‐spatial processing and problem solving, only CLWH (p < 0.04) showed significant performance improvement over time and (c) working memory and executive function, CLWH performed worse than CHIV‐ at both seven and nine years (p = 0.03 and 0.04). The second ANOVAs found that for (a) working memory, CHU performed better than ART‐Early and CHEU (p < 0.01 and <0.04), and (b) motor dexterity, ART‐Def performed worse than ART‐Early, CHEU and CHU at seven years (p = 0.02, <0.001 and <0.001 respectively) but improved to equivalence at nine years (ps > 0.17). Similarly, for motor dexterity, ART‐Def performed worse than ART‐96W, CHEU and CHU at seven years (p < 0.04, <0.001 and <0.001) but improved to equivalence at nine years (ps > 0.20).ConclusionsAlthough neurocognitive developmental trajectories for treatment groups and controls were largely similar (i.e. performance improvements from 7 to 9), all ART‐treated children, regardless of treatment arm, remain at risk for cognitive deficits over early school ages. Although the nature of these deficits may change as cognitive development proceeds, there are potential negative consequences for these children’s future learning, reasoning and adaptive functioning.     

Human neutrophil elastase alters human alpha-thrombin function: limited proteolysis near the gamma-cleavage site results in decreased fibrinogen clotting and platelet-stimulatory activity

During blood coagulation, polymorphonuclear leukocytes release elastase in amounts that can exceed 100 nmol/L. We therefore studied the interaction between human leukocyte elastase and human alpha-thrombin. Elastase cleaved the thrombin B chain (Ala 150-Asn 151) near the gamma- cleavage site, resulting in two fragments held together by noncovalent interactions. The NH2-terminal fragment (FI), mol wt approximately 18,000, was disulfide-linked to the thrombin A chain. The COOH-terminal fragment (FII), mol wt approximately 13,000, contained the active-site serine and formed a covalent bond with antithrombin III. Heparin accelerated proteolysis of alpha-thrombin by elastase. Proteolyzed alpha-thrombin (T theta) retained full amidolytic activity; however, the concentration of T theta causing 50% maximal platelet aggregation and adenosine triphosphate (ATP) release was 7.9 nmol/L (1.1 nmol/L for alpha-thrombin and 220 nmol/L for gamma-thrombin). Fibrinogen clotting activity of T theta and gamma-thrombin was 32% and 1% that of alpha- thrombin, respectively. Elastase released during the coagulation process may modulate thrombin activity. In addition, elastase-modified thrombin may be a useful probe of the structure and function of the gamma-cleavage region.     

Durability of responses to interferon alfa-2b in advanced hairy cell leukemia

Previous studies have demonstrated that significant hematologic improvement occurs in the majority of patients with hairy cell leukemia (HCL) treated with partially purified or recombinant interferon (IFN). Fifty-three patients received IFN alfa-2b for at least 3 months in a dose of 2 X 10(6) U/m2 subcutaneously thrice weekly. Of the 49 patients evaluable for response (at least 6 months of IFN therapy), there were ten complete responses and 29 partial responses for a total response rate of 80%. The peripheral blood counts and bone marrow continued to improve over the course of a full year of therapy. IFN was well tolerated, with no patients discontinuing therapy because of toxicity. Transient myelosuppression occurred in most patients during the first 1 to 2 months of therapy, occasionally precipitating a transfusion requirement. After IFN treatment was discontinued, there was a marked decrease in normal marrow elements and a relative increase in marrow hairy cells. This was associated with a transient increase in normal elements in the peripheral blood. Only one of 24 patients followed after receiving IFN for a median of 8.5 months (range, 3 to 16 months) has required further therapy. We conclude that low-dose IFN alfa-2b is highly effective in advanced HCL; responding patients should be treated for at least 1 year. The decision to initiate a second course of IFN therapy should be based primarily on peripheral blood counts and the clinical status of the patient rather than on the bone marrow.