613例新涂阳肺结核病例的队列分析

目的探讨新登记涂阳肺结核病例的转归,评价肺结核传染源控制效果。方法对613例新发涂阳肺结核病例的资料进行队列分析。结果新登记涂阳肺结核,以青壮年多发,以待业、家务和务农为主,集中于农猎区和林区,营养状况偏低。治愈率呈逐年上升趋势,严格执行全程督导化疗。结论严格执行DOTS的技术规范是控制肺结核传染源的主要措施。     

Metabolism of a G protein-coupled receptor modulator, including two major 1,2,4-oxadiazole ring-opened metabolites and a rearranged cysteine-piperazine adduct

Metabolites of a G protein-coupled receptor modulator containing 1,2,4-oxadiazole and piperazine substructures were identified in vitro in human, rat, and dog hepatocyte incubates and in vivo in rat plasma, bile, urine, and feces by using 14C-radiolabeled parent compound. Exposure coverage for the major circulating metabolites in humans at steady state and in preclinical species used in drug safety assessments was determined by using pooled plasma samples collected from a human multiple ascending dose study and a 3-month rat toxicokinetic study. Metabolites M1 and M2, which were formed by opening of the 1,2,4-oxadiazole ring, were observed as major metabolites both in vitro and in vivo across species. The carboxylic acid metabolite M2 was presumably formed through reductive N-O bond cleavage of the oxadiazole ring and subsequent hydrolysis. However, the mechanism for the formation of the unusual N-cyanoamide metabolite M1 remains uncertain. Neither M1 nor M2 had any target activity, as did parent drug P. In rat bile, rearranged Cys-piperazine and Gly-Cys-piperazine adducts, involving the formation of a five-membered heteroaromatic imidazole derivative from a six-membered piperazine ring, were observed as minor metabolites. These findings support a previously reported mechanism regarding glutathione detoxification for piperazine bioactivation products.     

Identities and frequencies of mutations of the otoferlin gene (OTOF) causing DFNB9 deafness in Pakistan

Mutations in OTOF , encoding otoferlin, cause non-syndromic recessive hearing loss. The goal of our study was to define the identities and frequencies of OTOF mutations in a model population. We screened a cohort of 557 large consanguineous Pakistani families segregating recessive, severe-to-profound, prelingual-onset deafness for linkage to DFNB9 . There were 13 families segregating deafness consistent with linkage to markers for DFNB9 . We analyzed the genomic nucleotide sequence of OTOF and detected probable pathogenic sequence variants among all 13 families. These include the previously reported nonsense mutation p.R708X and 10 novel variants: 3 nonsense mutations (p.R425X, p.W536X, and p.Y1603X), 1 frameshift (c.1103_1104delinsC), 1 single amino acid deletion (p.E766del) and 5 missense substitutions of conserved residues (p.L573R, p.A1090E, p.E1733K, p.R1856Q and p.R1939W). OTOF mutations thus account for deafness in 13 (2.3%) of 557 Pakistani families. This overall prevalence is similar, but the mutation spectrum is different from those for Western populations. In addition, we demonstrate the existence of an alternative splice isoform of OTOF expressed in the human cochlea. This isoform must be required for human hearing because it encodes a unique alternative C-terminus affected by some DFNB9 mutations.     

Transmission permeability of tuberculosis involving immigrants, revealed by a multicentre analysis of clusters

In recent years, the number of cases of tuberculosis (TB) among immigrants in Spain has increased markedly, and led to this analysis of the recent transmission patterns of TB in the immigrant population in Madrid. The countries from which the highest number of immigrant cases have been reported were Ecuador (21%), Romania (16%), Morocco (12%), Peru (11%) and Bolivia (9%). Fifty-one per cent of the cases were from South America. In a multicentre study (2004–2006), IS 6110 restriction fragment length polymorphism and spoligotyping were used to genotype the Mycobacterium tuberculosis isolates from 632 immigrant cases from 47 countries. A total of 183 cases (29%) were grouped into 59 clusters, which are markers of potential transmission events. Most of the clusters (81%) included patients living in different healthcare districts, and 54% of the clusters were multinational. When a sample of 478 autochthonous cases was included, 53% of the clusters involving immigrants also included autochthonous cases. This study revealed marked transmission permeability among nationalities and between the immigrant and the autochthonous populations.     

2006年陕西公众结核病防治知识核心信息知晓情况调查

目的了解陕西公众结核病知识核心信息知晓情况,为更有效地开展结核病防治健康教育提供依据。方法采用分层系统随机抽样方法,在全省抽取7个县区共8119名城乡居民。使用统一设计的调查问卷对调查对象进行入户面对面询问式调查。结果调查对象的核心信息总知晓率为49.5%,其中男性总知晓率为52.0%,女性为47.0%,城区居民总知晓率为62.7%,农村居民为47.5%。自述周围有人患有肺结核病的人群,其核心信息总知晓率为60.9%。12~19岁组、小学及以下文化程度者、学生和农民知晓率较低。调查对象对肺结核病的传染性、传播途径的知晓率较高,而一半或超过一半的调查对象不知道当地有检查和治疗结核病的专门机构、结核病人应到专门机构检查治疗、国家有免费检查治疗政策、不应该歧视结核病人,尤其是对＂咳嗽咳痰3周以上或有咯血、血痰症状者应怀疑得了肺结核病＂这条核心信息的知晓率只有20.2%。结论被调查人员结核病核心信息知晓率较低,不同特征居民间知晓率有差别,应根据当地居民结核防治知识的知晓情况制定相关政策。     

Intracranial non-Hodgkin lymphoma occurring after treatment of Hodgkin disease

Patients with successfully treated Hodgkin disease are at increased risk for the development of second malignancies. We present two cases of intracranial non-Hodgkin lymphoma that appeared following successful treatment of Hodgkin disease. The appearance of the lymphomas on computed tomographic images is shown, and possible predisposing factors, differential diagnosis, and clinical implications are discussed.     

Preliminary investigations on androgen receptor gene mutations in infertile men

A total of 50 men were selected from all patients attending an infertility clinic on the basis of oligozoospermia or azoospermia with concentrations of luteinizing hormone >6 IU/l and testosterone >30 nmol/l. Six of these men responded to written invitation and DNA was extracted from blood leukocytes. Individual exons of the androgen receptor gene were amplified by polymerase chain reaction and screened for the presence of mutations by denaturing gradient gel electrophoresis. The glutamine rich portion of exon 1 was sequenced directly. All of the coding sequence of the gene was examined except the glycine rich portion of exon 1 in all patients. No mutations or deletions were identified. Androgen receptor gene mutations do not appear to be present in infertile men with biochemical disturbances compatible with androgen resistance. It is therefore unlikely that such mutations are a major factor in the pathogenesis of oligozoospermia/azoospermia and infertility.