A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

We examined the relationship between a functional polymorphism (667C-- >T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-- >carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.      

Patterns of treatment of patients with prostate cancer initially managed with surveillance: results from The CaPSURE database. Cancer of the Prostate Strategic Urological Research Endeavor

PURPOSE: We determined the demographic and clinical profile of men who elect surveillance as the initial management of prostate cancer as well as the incidence and predictors of secondary treatment of these patients. MATERIALS AND METHODS: The Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) is a national disease registry of patients with various stages and treatments of prostate cancer. Using this database of 4,458 men we identified 329 (8.2%) who elected surveillance as the initial management of prostate cancer. Patients choosing watchful waiting were compared to other CaPSURE participants using the chi-square test. The likelihood of treatment initiation in the watchful waiting group was calculated using the Kaplan-Meier method. After adjusting for patient age, race, prostate specific antigen (PSA) at diagnosis, clinical T stage and total Gleason score the Cox proportional hazards regression model was used to determine significant predictors of treatment initiation. RESULTS: Compared with others in the database, patients on watchful waiting were more likely to be 75 years old or older (51% versus 16%, p <0.001), white (93% versus 85%, p <0.001), and have lower serum PSA (p <0.001), organ confined disease (97% versus 88%, p <0.001) and a total Gleason score of 7 or less (97% versus 88%, p <0.001). In the watchful waiting group there was a 52% likelihood of treatment initiation within 5 years of the diagnosis. Significant predictors of secondary treatment were age younger than 65 years and elevated serum PSA at diagnosis. Neither race, extraprostatic stage cT3 disease nor higher total Gleason score was a significant predictor of treatment. CONCLUSIONS: Men who elect initial watchful waiting for prostate cancer tend to be older, have lower serum PSA and more favorable disease characteristics than those who seek treatment. PSA at diagnosis is the dominant factor for predicting secondary treatment.     

罗格列酮单用或者与阿伐他汀联合使用对于2型糖尿病患者心血管疾病的非传统标志物的作用

背景和目的:罗格列酮与阿伐他汀联合疗法已经被证实对于2型糖尿病患者的血糖控制以及脂质水平都有益处。本试验将通过检测罗格列酮与阿伐他汀联合疗法对于2型糖尿病患者的生物标记水平的作用来研究该联合疗法对血管炎的作用。方法:30例患有2型糖尿病和高脂血症的患者被纳入治疗。对这些患者给予罗格列酮单一疗法4mg/d,持续3个月,然后在接下来的3个月中给予这些患者阿伐他汀10mg/d作为联合疗法。在研究开始时,罗格列酮单一疗法之后以及罗格列酮与阿伐他汀联合治疗之后测量炎性生物标记物,包括高敏C-反应蛋白(hs-CRP)、基质金属蛋白酶9(MMP…     

Pubertät und Adoleszenz – „Zeit des Erwachens der Männlichkeit“

Monatsschrift Kinderheilkunde - Mit dem Erwachen der Pubertät und der Beantwortung der Frage nach dem eigenen ?Ich“ stellt sich für Jungen auch die Frage nach der...     

Response to strict and liberalized specific carbohydrate diet in pediatric Crohn’s disease

AIM: To investigate the specific carbohydrate diet(SCD) as nutritional therapy for maintenance of remission in pediatric Crohn's disease(CD). METHODS: Retrospective chart review was conducted in 11 pediatric patients with CD who initiated the SCD as therapy at time of diagnosis or flare. Two groups defined as SCD simple(diet alone, antibiotics or 5-ASA) or SCD with immunomodulators(corticosteroids and/or stable thiopurine dosing) were followed for one year and compared on disease characteristics, laboratory values and anthropometrics.RESULTS: The mean age at start of the SCD was 11.8 ± 3.0 years(range 6.6-17.6 years) with five patients starting the SCD within 5 wk of diagnosis. Three patients maintained a strict SCD diet for the study period and the mean time for liberalization was 7.7 ± 4.0 mo(range 1-12) for the remaining patients. In both groups, hematocrit, albumin and ESR values improved while on strict SCD and appeared stable after liberalization(P-value 0.006, 0.002, 0.002 respectively). The majority of children gained in weight and height percentile while on strict SCD, with small loss in weight percentile documented with liberalization. CONCLUSION: Disease control may be attainable with the SCD in pediatric CD. Further studies are needed to assess adherence, impact on mucosal healing and growth.     

The vast majority of bone-marrow-derived cells integrated into mdx muscle fibers are silent despite long-term engraftment

Bone-marrow-derived cells can contribute nuclei to skeletal muscle fibers. However, serial sectioning of muscle in mdx mice implanted with GFP-labeled bone marrow reveals that only 20% of the donor nuclei chronically incorporated in muscle fibers show dystrophin (or GFP) expression, which is still higher than the expected frequency of "revertant" fibers, but there is no overall increase above controls over time. Obviously, the vast majority of incorporated nuclei either never or only temporarily turn on myogenic genes; also, incorporated nuclei eventually loose the activation of the beta-actin::GFP transgene. Consequently, we attempted to enhance the expression of dystrophin. In vivo application of the chromatin-modifying agents 5-azadeoxycytidine and phenylbutyrate as well as local damage by cardiotoxin injections caused a small increase in dystrophin-positive fibers without abolishing the appearance of "silent" nuclei. The results thus confirm that endogenous repair processes and epigenetic modifications on a small-scale lead to dystrophin expression from donor nuclei. Both effects, however, remain below functionally significant levels.     

Common Deficiencies of <Emphasis Type="Italic">in vitro</Emphasis> Binding Bioequivalence (BE) Studies Submitted in Abbreviated New Drug Applications (ANDAs)

There are several drug products that bind phosphate or bile acid in the gastrointestinal (GI) tract to exert their therapeutic efficacy. In vitro binding studies are used to assess bioequivalence (BE) of these products. The objective of this study is to identify the common deficiencies in Abbreviated New Drug Applications (ANDAs) for these products. Deficiencies were compiled from ANDAs containing in vitro binding BE studies. The deficiencies were classified into eight categories: Pre-Study Method Validation, During-Study Sample Analysis, Study Design, Study Procedure, Dissolution/Disintegration, Analytical Site Inspection, Data Submission, and Formulations. Within each category, additional subcategories were defined to characterize the deficiencies. A total of 712 deficiencies from 95 ANDAs for 11 drug products were identified and included in the analysis. The four categories with the most deficiencies were During-Study Sample Analysis (27.8%), Pre-Study Method Validation (17.3%), Data Submission (16.7%), and Study Design (15.7%). For the During-Study Sample Analysis category, failure to submit complete raw data or analytical runs ranked as the top deficiency (32.8%). For the Study Design category, using an unacceptable alternate study design (26.8%) was the most common deficiency. Within this category, other commonly occurring deficiencies included incorrect/insufficient number of absorbent concentrations, failure to pre-treat drug product with acid, insufficient number of replicates in study, incorrect calculation of k1 and k2 values, incorrect dosage form or pooled samples used in the study, and incorrect pH of study medium. The review and approval of these products may be accelerated if these common deficiencies are addressed in the original ANDA submissions.     

Surgical Management of Gastro-oesophageal Reflux Disease After One Anastomosis Gastric Bypass — a Systematic Review

Gastro-oesophageal reflux disease (GORD) after one anastomosis gastric bypass (OAGB) remains a concern. We reviewed the current literature on revisional surgery after OAGB for GORD. MEDLINE, EMBASE, and PubMed databases were searched. We identified 21 studies, appraising 13,658 OAGB patients. A total of 230 (1.6%) patients underwent revisional surgery for GORD. Revision to Roux-en-Y configuration was performed in 211 (91.7%) patients. Six (2.6%) patients had a Braun entero-enterostomy added to the OAGB. Thirteen (5.6%) patients underwent excluded stomach fundoplication (ESF). Reflux symptoms resolved in 112 (48.6%) patients, persisted in 13 (5.6%) patients, and were not reported in 105 (45.6%) patients. Revisional surgery after OAGB for GORD appears to be rare, and when required, conversion to Roux-en-Y configuration is the commonest choice.