Results of a high-resolution genome screen of 437 Alzheimer's disease families

Alzheimer's disease (AD) is a devastating neurodegenerative disorder of late life with complex inheritance. Mutations in three known genes lead to the rare early-onset autosomal dominant form of AD, while a common polymorphism (epsilon 4) in the gene encoding apolipoprotein E (APOE ) is a risk factor for more typical late-onset (>60 years) AD. A recent study concluded that there are up to four additional genes with an equal or greater contribution to the disease. We performed a 9 cM genome screen of 437 families with AD, the full National Institute of Mental Health (NIMH) sample, which has been carefully ascertained, evaluated and followed by our group over the last decade. Performing standard parametric and non-parametric linkage analyses, we observed a 'highly significant' linkage peak by Lander and Kruglyak criteria on chromosome 19q13, which probably represents APOE. Twelve additional locations-on 1q23, 3p26, 4q32, 5p14, 6p21, 6q27, 9q22, 10q24, 11q25, 14q22, 15q26 and 21q22-met criteria for 'suggestive' linkage [i.e. two-point lod score (TLS) >/=1.9 and/or multipoint lod score (MLS) >/=2.2] in at least one of our analyses. Although some of these will surely prove to be false positives, these linkage signals should provide a valuable framework for future studies aimed at identifying additional susceptibility genes for late-onset AD.     

Evidence for linkage of nonsyndromic cleft lip with or without cleft palate to a region on chromosome 2

Results from a genome-wide screen of 10 multiplex families ascertained through probands with nonsyndromic cleft lip with or without cleft palate (CL/P) in Mexico, Argentina, and the United States yielded suggestive evidence of linkage to chromosomes 2, 6, 17 and 18. Fine mapping excluded all regions except chromosome 2. Subsequent analysis was performed on the original 10 families plus an additional 16 families using 31 markers on chromosome 2. This analysis showed intriguing evidence of linkage to 2q (Zlr=2.26, empirical P-value=0.028 in a chromosome-wide analysis). Transmission disequilibrium tests also revealed evidence of linkage and disequilibrium for two markers in this region (D2S168 and D2S1400 with P-values=0.022 and 0.006, respectively). A subset of these 26 families provided additional evidence for a susceptibility gene for CL/P on 2q, suggesting that further studies of genes in this region are warranted.     

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。     

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.     

The Consumer Quality Index Hip Knee Questionnaire measuring patients' experiences with quality of care after a total hip or knee arthroplasty

Background  

The Dutch Consumer Quality Index Hip Knee Questionnaire (CQI Hip Knee) was used to assess patients' experiences with and evaluations of quality of care after a total hip (THA) or total knee arthroplasty (TKA). The aim of this study is to evaluate the construct validity and internal consistency reliability of this new instrument and to assess its ability to measure differences in quality of care between hospitals.     

Intraoperative radiotherapy of skull base cancer.

As the head and neck surgeon expands the boundaries of resectability into the skull base, the margin of tumor clearance diminishes. Intraoperative radiotherapy (IORT) can be used as an adjunct to skull base surgery and external beam radiation to enhance local control in areas with close margins or remaining microscopic disease. During the period from May 1982 to May 1988, 25 patients underwent IORT of the skull base following resection and prior to closure to treat microscopic disease in 9 patients, sterilize close margins in 14 patients, and attempt to eliminate remaining gross disease in 2 patients. The types of tumors treated were 13 squamous cell carcinomas, 4 adenoid cystic carcinomas, 3 high-grade mucoepidermoid carcinomas, 3 sarcomas, 1 malignant mixed tumor, and an oncocytic adenocarcinoma. The majority of the tumors either originated in the sinuses or were skull base extensions of oral cavity or oropharyngeal cancers. In 22 patients with 1-year follow-up, IORT prevented local recurrence in 14 (64%) patients. This may represent improved control of local disease in patients who historically have a very dismal prognosis. The indications, techniques, and complications of this exciting therapeutic modality are also reviewed.     

Primary mediastinal large cell lymphoma is characterized by an inverted pattern of large tumoral mass and low {beta}2 microglobulin levels in serum and frequently elevated levels of serum lactate dehydrogenase

BACKGROUND: Primary mediastinal large cell lymphoma (PMLCL) is an emergingentity. New parameters can help define it. MATERIALS AND METHODS: Retrospective analysis of medical records from 35 patients treatedat The University of Texas M.D. Anderson Cancer Center from1985 to 1990. Immunohistochemical evaluation of tissue specimens.Determination of survival (S) and time to treatment failure(TTF). RESULTS: The median age was 34 years and 69% were females. Eighty-threepercent presented with symptoms of mediastinal involvement.While 100% of the patients presented with bulky mediastinaldisease and 72% had elevated pretreatment serum lactate dehydrogenase,only 6% presented with an elevated pretreatment serum ß₂microglobulin. The lymphoma cells lacked CD21 staining. Forthe 18 patients treated initially at M.D. Anderson Cancer Center,S and TTF curves rates after doxorubicin-based regimens (plusradiotherapy in 14 cases) were 72% and 61%, respectively, at5 years follow-up (median, 42 months). Four out of six patientswho received autologous bone marrow transplant as salvage therapyare currently alive without disease at follow-up times of 21,25, 32, and 54 months. CONCLUSIONS: Primary mediastinal large cell lymphoma has characteristic clinicopathologicalfeatures to which another can be added, that of an invertedpattern of bulky disease, high LDH and low ß₂M inserum. The response to therapy is comparable to that of intermediate-gradelymphomas, although the numbers in the study are small. Ourpreliminary data suggest a possible role for autologous bonemarrow transplantation (ABMT) as salvage therapy. primary mediastinal lymphoma, clinical, pathology, prognosis