Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

胃、结直肠癌术前区域性动脉化疗几个相关问题

胃、结直肠癌根治性切除术复发转移是严重影响术后5 a生存率提高的重要原因.以手术为主综合治疗已成为新的趋势,其中术前区域性动脉化疗(preoperative regional-arterial chemotherapy,PRAC)尤为值得重视.本文介绍了术前PRAC的概念、作用机制和影响区域性动脉化疗疗效的相关因素,并就术前区域性动脉化疗在胃、结直肠癌综合治疗中的评价进行讨论.     

Generalized,severe epidermolysis bullosa simplex caused by a Keratin 5 p.E477K mutation

Epidermolysis bullosa simplex (EBS) is a skin fragility disorder resulting from mutations of structural proteins in the epidermis. We provide a brief report of long‐term survival and reproduction in a mother with EBS due to keratin 5 (KRT5) c.1429G > A (p.E477K) mutation, which causes a particularly severe form of the disease.     

Early Breastfeeding Cessation Among HIV-Infected and HIV-Uninfected Women in Western Cape Province,South Africa

As part of the Mother-Infant Health Study, we describe infant feeding practices among HIV-infected and HIV-uninfected mothers over a 12-month period when the Western Cape Province prevention of mother-to-child transmission (PMTCT) program was transitioning from a policy of exclusive formula feeding to one of exclusive breastfeeding. Two hundred pairs of mother and HIV-uninfected infant were included in the analysis, among whom 81 women were HIV uninfected and breastfeeding. Of the 119 HIV-infected mothers, 50 (42%) were breastfeeding and 69 (58%) were formula feeding. HIV-infected mothers predominantly breastfed for 8.14 (7.71–15.86) weeks; HIV-uninfected mothers predominantly breastfed for 8.29 (8.0–16.0) weeks; and HIV-infected mothers predominantly formula fed for 50.29 (36.43–51.43) weeks. A woman’s HIV status had no influence on the time to stopping predominant breastfeeding (P?=?0.20). Our findings suggest suboptimal duration of breastfeeding among both HIV-infected and HIV-uninfected mothers. Providing support for all mothers postdelivery, regardless of their HIV status, may improve breastfeeding practices.     

Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

Efficacy of the Za self-expandable metal stent for palliation of malignant biliary obstruction

BACKGROUND: The efficacy and safety of the uncoated self-expandable Za metal stent for palliation of malignant distal biliary obstruction was prospectively analyzed. METHODS: Twenty-one patients with unresectable malignant tumors involving mid to distal common bile duct who presented with obstructive jaundice underwent endoscopic implantation of an uncoated self-expandable metal stent. Technical success with stent placement, adverse events, patient survival, duration of stent patency, and device performance were analyzed. RESULTS: Endoscopic biliary stenting was successful in all patients. No adverse events were encountered. The mean follow-up period of the 21 patients was 128 days (range, 3-263): 14 died of progressive disease at mean of 81 days (range, 3-210), 3 remain alive (at days 239, 250, and 263), and 4 were lost to follow-up (at days 90, 91, 92, and 116). The mean duration of stent patency was 249 days. Tumor ingrowth was observed in one patient (5%). Minor technical problems were encountered in 3 patients: 1 proximal deployment, 1 distal deployment, and difficulty associated with the delivery system in 1. CONCLUSIONS: The Za-metal stent provided effective palliation for patients with inoperable malignant biliary tumors. Although minor technical problems were encountered with stent deployment, the overall stent patency, efficacy, and safety profile appear satisfactory.     

Clinically significant differences between point-of-care analysers and a standard analyser for monitoring the International Normalized Ratio in oral anticoagulant therapy: a multi-instrument evaluation in a hospital outpatient setting.

The increasing number of patients requiring oral anticoagulant therapy has lead to an expansion in the use of point-of-care test (POCT) analysers for measuring the International Normalized Ratio (INR) for monitoring purposes. Availability of new technology inevitably leads to comparisons with standard methodologies, and studies to date have reached varying conclusions about the comparability of POCT INRs with conventional testing. We compared the performance of five POCT instruments (Hemochron Junior Signature, ProTime, CoaguChek S, INRatio and TAS) against Innovin thromboplastin on a Sysmex CA1500 automated analyser. The Hemochron Junior Signature, ProTime and CoaguChek S demonstrated strong correlation with the laboratory method (R2 > 0.94). These three analysers demonstrated higher percentages of paired results within 0.5 INR units (81.5, 92.0 and 74.0%, respectively); the INRatio and TAS demonstrated 54.2 and 62.2%, respectively. Within INR ranges of up to 2.0, 2.1-3.0, 3.1-4.0 and above 4.0, none of the POCT analysers demonstrated significant agreement with the standard method in every range. All POCT instruments showed a degree of bias and greater variation from the standard method at INR values above 3.0. These data indicate the potential for POCT analysers to generate INR values sufficiently different from conventional methods that they may impact on clinical decision-making.     

GSTM1 null polymorphism at the glutathione S-transferase M1 locus: phenotype and genotype studies in patients with primary biliary cirrhosis.

Studies were carried out to test the hypothesis that the GSTM1 null phenotype at the mu (mu) class glutathione S-transferase 1 locus is associated with an increased predisposition to primary biliary cirrhosis. Starch gel electrophoresis was used to compare the prevalence of GSTM1 null phenotype 0 in patients with end stage primary biliary cirrhosis and a group of controls without evidence of liver disease. The prevalence of GSTM1 null phenotype in the primary biliary cirrhosis and control groups was similar; 39% and 45% respectively. In the primary biliary cirrhosis group all subjects were of the common GSTM1 0, GSTM1 A, GSTM1 B or GSTM1 A, B phenotypes while in the controls, one subject showed an isoform with an anodal mobility compatible with it being a product of the putative GSTM1*3 allele. As the GSTM1 phenotype might be changed by the disease process, the polymerase chain reaction was used to amplify the exon 4-exon 5 region of GSTM1 and show that in 13 control subjects and 11 patients with primary biliary cirrhosis, GSTM1 positive and negative genotypes were associated with corresponding GSTM1 expressing and non-expressing phenotypes respectively. The control subject with GSTM1 3 phenotype showed a positive genotype.