Lymphocyte predominance Hodgkin's disease (nodular paragranuloma)–a bcl-2 negative germinal centre lymphoma

Hodin's disease, lymphocyte predominance type (nodular paragranuloma), is of germinal centre origin and the tumours cells have a B-cell phenotype. As the t(14;18) translocation, and the subsequent expression of bcl-2 protein by germinal centre cells, is the most characteristic finding of centroblastic-centrocytic lymphoma, we have tested a series of 11 cases of lymphocyte predominance Hodgkin's disease, using Southern blot analysis for the major breakpoint region and the minor breakpoint cluster region, polymerase chain reaction with primers for the major and minor breakpoint cluster region, and immunohistological studies with a monoclonal antibody specific for the bcl-2 protein. All three techniques gave negative results in the cases of Hodgkin's disease, establishing a clear differentiation from centroblastic-centrocytic lymphoma. These findings are useful in the differential diagnosis between the two entities and raise the question of the non-clonal nature of lymphocyte predominance Hodgkin's disease.     

An experimental model for canine visceral leishmaniasis

Seven mixed-breed dogs were challenged with either promastigotes or amastigotes of Leishmania donovani infantum strains recently isolated from naturally infected dogs. Different routes and numbers of parasites were utilized and each dog was monitored for at least 1 year post-infection. Anti-parasite specific antibody levels were measured by enzyme-linked immunosorbence, immunofluorescence, crossed-immune electrophoresis and Western blotting on crude antigen. Western blotting on two pure parasite proteins, dp72 and gp70-2, was also done. Mitogenic and antigen-specific stimulation of peripheral blood lymphocytes was monitored; and the haematological, clinical and parasitological parameters measured. Dogs challenged with amastigotes exhibited a more pronounced humoral response to leishmanial antigens. Only in one case was strong antigen-specific proliferation detected. Clinical signs of disease, including hypergammaglobulinaemia, enlarged lymph nodes and the presence of parasites, were also more apparent in the dogs challenged with amastigotes. None of the seven dogs died. Serum antibodies to leishmanial antigens were apparent between 1.5 to 3 months following challenge and correlated with the appearance of enlarged lymph nodes, hypergammaglobulinaemia and the presence of parasites in tissue biopsies. Serum antibodies remained chronically high in these dogs throughout the period of the study. Only one dog (1/3) challenged intravenously with promastigotes and the dog challenged intradermally with amastigotes produced transient antibody responses to leishmanial antigen.     

Inhibition of Lipid Peroxidation by Sesquiterpenoid in Heterotheca inuloides

A sesquiterpenoid, 7-hydroxy-3,4-dihydrocadalin, isolated from a Mexican medicinal plant Heterotheca inuloides was evaluated as an antioxidant. This sesquiterpenoid inhibited mitochondrial and microsomal lipid peroxidation induced by Fe(III)-ADP/NADH or Fe(III)-ADP/NADPH. Furthermore, 7-hydroxy-3,4-dihydrocadalin protected red cells against oxidative haemolysis. This sesquiterpene was thus shown to be effective in protecting biological systems against oxidative stresses.     

Radiofrequency Ablation of Symptomatic but Benign Ventricular Arrhythmias

Two cases are presented where ablation of severely symptomatic ventricular arrhythmias not responding to medical therapy was accomplished with radiofrequency current application. After a routine programmed stimulation protocol, a quadripolar ablation catheter with a 4-mm tip was advanced percutaneously into the left ventricle in one case and into the right ventricle in the second case; and after precise pace mapping, the arrhythmogenic focus was successfully ablated using radiofrequency current. The postablation ambulatory recording revealed virtual eradication of ventricular ectopy in both cases. In conclusion, in severely symptomatic cases of "benign" ventricular arrhythmias, radiofrequency ablation offers an effective therapeutic alternative.     

新型分子靶向药物联合放疗在肺癌中的应用

非小细胞肺癌(non-small cell lung cancer, NSCLC)约占肺癌总病例数的80%-85%,对于III期患者 来说,NSCLC约占肺癌总病例数的40%.不可切除III期NSCLC的治疗为以铂类为基础的化疗联合胸部放疗. 本文将综述正在研发中且有可能用于联合治疗的新型靶向制剂.其中最具前景的策略之一为表皮生长因子受 体(epidermal growth factor receptor, EGFR)通路的抑制.放疗可激活EGFR信号,通过诱导细胞增殖并增强DNA 修复而导致放疗抵抗.几项临床前模型研究表明西妥昔单抗与放疗联合具有协同效应.几项II期试验评估了西 妥昔单抗与放疗同步使用的安全性与疗效,结果喜人.吉非替尼对多种细胞系具有放疗增敏作用,其与放疗 的联合已被试验用于不可切除III期NSCLC的治疗.然而,放化疗后使用吉非替尼作为维持治疗的结果不容乐 观.一项I期试验评估了厄洛替尼与放化疗联合的疗效.放疗可通过损伤细胞膜、DNA以及微血管内皮细胞而 诱导肿瘤死亡,而这反过来可增加促血管生成生长因子的产生.抗血管生长制剂可降低血管密度,但可改善 肿瘤的含氧量.应用血管内皮生长因子受体(vascular endothelial growth factor receptor, VEGFR)抑制剂可通过阻 断亚致死量辐射损伤的修复而增强放疗对人NSCLC的疗效.厄洛替尼、贝伐珠单抗与胸部放疗联合试验正在 进行中.该三种药物联合治疗的新策略尚需制订.由于放疗可增强HSP90分子伴侣的功能从而引起肺癌细胞的 放疗抵抗,此通路的阻断剂可通过抑制HIF-1α和VEGF的表达进而抑制肺癌细胞的生存和血管生成,因而可能 用于减少放疗抵抗.在NSCLC和间皮瘤的临床前模型中,Aurora激酶抑制剂似乎对放疗具有增效作用.     

Is atrial fibrillation associated with pulmonary embolism?

Summary. Background: A pulmonary embolism (PE) is thought to be associated with atrial fibrillation (AF). Nevertheless, this association is based on weak data. Objectives: To assess whether the presence of AF influences the clinical probability of PE in a cohort of patients with suspected PE and to confirm the association between PE and AF. Patients/methods: We retrospectively analyzed the data from two trials that included 2449 consecutive patients admitted for a clinically suspected PE. An electrocardiography (ECG) was systematically performed and a PE was diagnosed by computer tomography (CT). The prevalence of AF among patients with or without a PE was compared in a multivariate logistic regression model. Results: The prevalence of PE was 22.8% (519/2272) in patients without AF and 18.8% (25/133) in patients with AF (P = 0.28). After adjustment for confounding factors, AF did not significantly modify the probability of PE (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.42–1.11). However, when PE suspicion was based on new‐onset dyspnea, AF significantly decreased the probability of PE (OR 0.47, 95% CI 0.26–0.84). If isolated chest pain without dyspnea was the presenting complaint, AF tended to increase the probability of PE (OR 2.42, 95% CI 0.97–6.07). Conclusions: Overall, the presence of AF does not increase the probability of PE when this diagnosis is suspected. Nevertheless, when PE suspicion is based on new‐onset dyspnea, AF significantly decreases the probability of PE, as AF may mimic its clinical presentation. However, in patients with chest pain alone, AF tends to increase PE probability.