Fludarabine: a new agent with major activity against chronic lymphocytic leukemia

Fludarabine was used to treat 68 patients with previously treated chronic lymphocytic leukemia (CLL). Nine (13%) patients achieved a complete remission and 30 (44%) a partial remission. The response rates for Rai stages 0 to 2, 3, and 4 were 64%, 58%, and 50% respectively. Seventeen (43%) of the 40 Rai stage 1 to 3 patients and four (19%) of the Rai stage 4 patients returned to Rai stage 0. Survival was strongly correlated with the final Rai stage achieved. The survival of the 11 partial responders with residual disease consisting only of residual bone-marrow nodules was similar to the complete responders (36+ months) and superior to the other partial response patients (16 months). The response to fludarabine was rapid, with 36 (92%) of the 39 responders having achieved at least a partial response following the first three courses. Complete responses occurred in the blood, liver, spleen, and lymph nodes in 48% to 69% of the patients. Eradication of all disease in the bone marrow occurred in only 13% of the cases. Neutropenia and thrombocytopenia occurred in 56% and 25% of evaluable courses. Major infections occurred in 9% of evaluable courses and fevers of unknown origin or minor infections in 12% of courses respectively. Myelosuppression and infection were more common in patients with initial Rai stages 3 and 4 and in nonresponding patients. Other toxicity was mild. No CNS toxicity was noted.     

WHO生存质量评估简表的等价性评价

目的评价WHO生存质量评估简表(WHOQOL-BREF)在13个国家的等价性。方法采用多组验证性因子分析方法,对世界卫生组织生存质量研究小组提供的13个国家的数据进行分析,评价WHOQOL-BREF不同国家的等价性。结果各个国家的各个领域的Cronbachα系数均大于0·7,分布在0·7至0·88之间。除了英国和挪威之外,其它国家的社会关系领域的Cronbachα系数均大于0·65。采用根据世界卫生组织生存质量研究小组研制量表时构建的四因子模型对数据分别进行拟合,拟合优度指数(CFI)均大于0·8,其中德国、西班牙和美国的拟合优度指数大于0·9。多组验证性因子分析发现模型拟合尚可,CFI等于0·88,各个国家的因子负荷不全相等,因子负荷的轮廓相似。结论WHOQOL-BREF在13个国家具有相同的因子结构,且有等价性。     

Manubriosternal subluxation/dislocation can lead to manubriosternal septic arthritis in patients with kyphoscoliosis

Locally deranged joint anatomy can predispose to septic arthritis which can be managed by surgical debridement. We present a case of manubriosternal subluxation/dislocation caused by kyphoscoliosis leading to manubriosternal septic arthritis.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.