SCA6 is caused by moderate CAG expansion in the alpha1A-voltage- dependent calcium channel gene

Recently, moderate (CAG)>20 repeat expansions in the alpha1A-voltage- dependent calcium channel gene (CACNL1A4) have been identified in a previously unmapped type of SCA which has been named SCA6. We investigated the (CAG)n repeat length of the CACNL1A4 gene in 733 patients with sporadic ataxia and in 46 German families with dominantly inherited SCA which do not harbor the SCA1, SCA2, or MJD1/SCA3 mutation, respectively. The SCA6 (CAG)n expansion was identified in 32 patients most frequently with late manifestation of the disease. The (CAG)n stretch of the affected allele varied between 22 and 28 trinucleotide units and is therefore the shortest trinucleotide repeat expansion causing spinocerebellar ataxia. The (CAG)n repeat length is inversely correlated with the age at onset. In 11 parental transmissions of the expanded allele no repeat instability has been observed. Repeat instability was also not found for the normal allele investigating 431 meioses in the CEPH families. Analyzing 248 apparently healthy octogenerians revealed one allele of 18 repeats which is the longest normal CAG repeat in the CACNL1A4 gene reported. The SCA6 mutation causes the disease in approximately 10% of autosomal dominant SCA in Germany. Most importantly, the trinucleotide expansion was observed in four ataxia patients without obvious family history of the disease which necessitates a search for the SCA6 (CAG)n expansion even in sporadic patients.      

Cumulative risk of developing polyps or malignancy at the ileal pouch-anal anastomosis in patients with familial adenomatous polyposis

Restorative proctocolectomy with an ileal pouch-anal anastomosis is performed in an increasing number of patients with familial adenomatous polyposis (FAP). Two techniques are currently used to construct an ileal pouch-anal anastomosis: (1) a double-stapled anastomosis between the pouch and the anal canal and (2) mucosectomy with a hand-sewn iteoanal anastomosis at the dentate line. Although this procedure is thought to abolish the risk of colorectal adenoma, an increasing number of case reports have been published concerning the development of adenoma at the anastomotic site. The purpose of this study was to evaluate the overall cumulative risk of developing adenomatous polyps after ileal pouch-anal anastomosis and to compare the cumulative risk after either anastomotic technique. A total of 126 consecutive FAP patients undergoing a restorative proctocolectomy were identified from polyposis registries in The Netherlands, Denmark, Italy, Germany, and New York. Life-table analysis was used to calculate the cumulative risk of developing polyps in 97 patients with at least 1 year of endoscopic follow-up (median 66 months, range 12 to 188 months). A double-stapled anastomosis was used in 35 patients, whereas in 62 patients a handsewn anastomosis with a mucosectomy was performed. In 13 patients polyps developed at the anastomotic site, four with severe and four with moderate dysplasia. None of the patients developed a carcinoma at the anastomotic site. The cumulative risk of developing a polyp at the anastomotic site was 8% (95% confidence interval 2% to 14%) at 3.5 years and 18% (95% confidence interval 8% to 28%) at 7 years, respectively. The risk of developing a polyp at the anastomotic site within 7 years was 31 % for patients with a double-stapled vs. 10% for patients with a hand-sewn anastomosis with mucosectomy (P = 0.03 [log-rank test]). Because FAP patients undergoing a restorative proctocolectomy with either a double-stapled or hand-sewn anastomosis have a substantial risk of developing adenomatous polyps at the anastomotic site, lifelong endoscopic surveillance is mandatory in both groups. Presented at the Thirty-Ninth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, La., May 17–20, 1998.     

Effect of nutritional route on colonic anastomotic healing in the rat

Although early enteral feeding has been shown to benefit cutaneous healing when compared to parenteral feeding, the effect of the route of nutritional support in gastrointestinal anastomotic healing has not been defined. The aim of the present study was to determine whether the route of nutritional support influences colonic anastomotic healing. Twenty male Sprague-Dawley rats weighing 270 to 290 grams underwent identical surgical manipulation consisting of central venous catheterization, gastrostomy insertion, and distal colonic anastomosis (single-layer, inverted). Identical nutrient infusates composed of 4.25% amino acids, 25% dextrose, and vitamins were administered, with half the animals receiving the infusions via the gastrostomy and the other half via the venous catheter. Animals were killed 5 days after surgery. There were no differences in nutritional parameters between the parenterally and enterally fed groups. Colonic anastomotic bursting pressure was significantly higher in the enterally fed group (180 ±6 vs. 150±11 mm Hg; P<0.01). The measured insoluble collagen and total protein content in anastootic tissue were enhanced in the enterally supported group. The fraction of soluble (newly synthesized) collagen did not differ between the two groups. The data demonstrate that the route of nutrient administration influences colonic anastomotic healing. The preservation of colonic structural collagen in the enteral group may improve the ability of the gut to hold sutures and thus enhance anastomotic healing. Presented at the Thirty-Ninth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, La., May 17–20, 1998.     

我省长学制医学教育的回顾与思考

我省七年制医学教育开办了近20年,为社会培养了一批深受欢迎、质量较好和具有较高综合素质的高层次医学人才。建立与我省经济发展水平相适应的以五年制为主体、重点发展八年制的医学教育学制体系,是我省高等医学教育发展的必然趋势。     

Genomic patterns resembling BRCA1- and BRCA2-mutated breast cancers predict benefit of intensified carboplatin-based chemotherapy

Introduction

BRCA-mutated breast cancer cells lack the DNA-repair mechanism homologous recombination that is required for error-free DNA double-strand break (DSB) repair. Homologous recombination deficiency (HRD) may cause hypersensitivity to DNA DSB-inducing agents, such as bifunctional alkylating agents and platinum salts. HRD can be caused by BRCA mutations, and by other mechanisms. To identify HRD, studies have focused on triple-negative (TN) breast cancers as these resemble BRCA1-mutated breast cancer closely and might also share this hypersensitivity. However, ways to identify HRD in non-BRCA-mutated, estrogen receptor (ER)-positive breast cancers have remained elusive. The current study provides evidence that genomic patterns resembling BRCA1- or BRCA2-mutated breast cancers can identify breast cancer patients with TN as well as ER-positive, HER2-negative tumors that are sensitive to intensified, DSB-inducing chemotherapy.

Methods

Array comparative genomic hybridization (aCGH) was used to classify breast cancers. Patients with tumors with similar aCGH patterns as BRCA1- and/or BRCA2-mutated breast cancers were defined as having a BRCA-like^CGH status, others as non-BCRA-like^CGH. Stage-III patients (n = 249) had participated in a randomized controlled trial of adjuvant high-dose (HD) cyclophosphamide-thiotepa-carboplatin (CTC) versus 5-fluorouracil-epirubicin-cyclophosphamide (FE₉₀C) chemotherapy.

Results

Among patients with BRCA-like^CGH tumors (81/249, 32%), a significant benefit of HD-CTC compared to FE₉₀C was observed regarding overall survival (adjusted hazard ratio 0.19, 95% CI: 0.08 to 0.48) that was not seen for patients with non-BRCA-like^CGH tumors (adjusted hazard ratio 0.90, 95% CI: 0.53 to 1.54) (P = 0.004). Half of all BRCA-like^CGH tumors were ER-positive.

Conclusions

Distinct aCGH patterns differentiated between HER2-negative patients with a markedly improved outcome after adjuvant treatment with an intensified DNA-DSB-inducing regimen (BRCA-like^CGH patients) and those without benefit (non-BRCA-like^CGH patients).     

新疆紫草颗粒剂与汤剂对药物流产效果影响的比较性研究

目的:比较新疆紫草颗粒剂与紫草汤剂对米非司酮配伍米索前列醇药物流产效果的影响,及不良反应。方法:将648例妊娠38-45　d、要求终止妊娠的妇女,随机分成3组,各组在米非司酮配伍米索前列醇药物流产时分别加服紫草颗粒剂或安慰剂或紫草汤剂,对3组的流产效果、出血时间、月经恢复时间等及不良反应进行观察。结果:紫草颗粒剂组和汤剂组的完全流产率(97.74%、97.70%)、平均出血时间(12.0±4.1　d、12.7±3.8　d)均无显著性差异(P均>0.05),且均显著优于安慰剂组(91.90%、14.3±4.8　d)(P均<0.05)。3组药物流产后月经恢复时间均无显著性差异。但紫草汤剂服用时有明显异味。结论:　紫草颗粒剂祛除了紫草的异味,服用方便,对其提高药物流产疗效与紫草汤剂相同,有必要进一步探讨。     

宫颈癌组织Raf激酶抑制蛋白和NF—κBp65表达及其临床意义

目的研究宫颈癌组织中Raf激酶抑制蛋白（RKIP）和核因子xBp65（NF-κBp65）的表达,探讨二者表达之间的相关性及其与宫颈癌各临床病理因素之间的关系。方法用免疫组织化学方法检测69例宫颈癌组织、37例宫颈上皮内瘤变组织和18例正常宫颈组织的RKIP和NF-κBp65表达,并分析其与宫颈癌临床病理学特征的关系。结果宫颈癌组织中RKIP的表达低于宫颈上皮内瘤变及正常宫颈组织,而NF-κBp65的表达高于宫颈上皮内瘤变及正常宫颈组织,差异有统计学意义（Hc=45．124、38．107,Z=4．309～5．159,P〈O．01）;RKIP和NF—κBp65在宫颈癌组织中的表达均与临床分期、有无淋巴结转移及肿瘤分化程度有关（χ^2=5．150～11．917,P〈0．05）。宫颈癌组织中RKIP与NF-κBp65的表达呈显著负相关（r=-0．464,P〈O．01）。结论RKIP表达的减少或缺失与宫颈癌的发生、发展密切相关,RKIP表达的减少或缺失可能通过上调NF—κBp65的表达促进宫颈癌的侵袭和转移。     

TRAIL-receptor expression is an independent prognostic factor for survival in patients with a primary glioblastoma multiforme

SummaryPurpose In order to improve the survival of patients with a glioblastoma multiforme tumor (GBM), new therapeutic strategies must be developed. The use of a death inducing ligand such as TRAIL (TNF Related Apoptosis Inducing Ligand) seems a promising innovative therapy. The aim of this study was to quantify the expression of the death regulating receptors TRAIL-R1, TRAIL-R2 and TRAIL on primary GBM specimens and to correlate this expression with survival.Experimental design Expression of TRAIL and TRAIL-receptors was assessed by immunohistochemistry, both quantitatively (% of positive tumor cells) and semi-quantitatively (staining intensity) within both the perinecrotic and intermediate tumor zones of primary GBM specimens. RT-PCR of GBM tissue was performed to show expression of TRAIL receptor mRNA.Results Immunohistochemistry showed a slight diffuse intracytoplasmic and a stronger membranous staining for TRAIL and TRAIL receptors in tumor cells. Semi-quantitative expression of TRAIL showed a significantly higher expression of TRAIL in the perinecrotic zone than in the intermediate zone of the tumor (P=0.0001). TRAIL-R2 expression was significantly higher expressed than TRAIL-R1 (P=0.005). The antigenic load of TRAIL-R2 was positively correlated with survival (P=0.02). Multivariate analysis of TRAIL-R1 within the study group (n=62) showed that age, gender, staining intensity, antigenic load, % of TRAIL-R1 expression, were not statistically correlated with survival however radiotherapy was significantly correlated (multivariate analysis: age: P=0.15; gender: P=0.64; staining intensity: P=0.17; antigenic load: P=0.056; % of TRAIL-R1 expression: P=0.058; radiotherapy: P=0.0001). Subgroup analysis of patients who had received radiotherapy (n=47) showed a significant association of % of TRAIL-R1 expression and the antigenic load of TRAIL-R1 with survival (multivariate analysis: P=0.036, respectively, P=0.023).Multivariate analysis of TRAIL-R2 staining intensity and antigenic load, within the study group (P=0.004, respectively, P=0.03) and the subgroup (P=0.002, respectively, P=0.004), showed a significant association with survival. RT-PCR analysis detected a negative relation between the amount of TRAIL-R1 mRNA and the WHO grade of astrocytic tumors (P=0.03).Conclusions TRAIL-R1 and TRAIL-R2 expression on tumor cells are independent prognostic factors for survival in patients with a glioblastoma multiforme. Both receptors could be targets for TRAIL therapy. As TRAIL-R2 is more expressed, in comparison with TRAIL-R1, on GBM tumor cells, TRAIL-R2 seems to be of more importance as a target for future TRAIL therapy than TRAIL-R1.     

Seizures in children with low-grade tumors： outcome after tumor resection and risk factors for uncontrolled seizures

OBJECT： The goals of this study were to define the incidence of seizures in children with low-grade tumors, study seizure outcome after lesionectomy in these children, and identify risk factors for poor seizure outcome, METHODS： The authors performed a retrospective chart review of children who harbored low-grade brain tumors, experienced seizures, and were treated in a single institution, Statistical analyses included step-wise as well as single-variable binary logistic regression analyses.