分娩期连续电子胎心监护用于胎儿评估

1背景 在美国，每4例孕妇中有3例在产群中及分娩时使用电子胎儿监护（EFM）（NCHS1993）。1989年，美国妇产科学院（ACOG1989）发表了一项声明，对于低危妊娠既可使用EFM，也可使用间断性胎心听诊；但是，美国预防保健委员会（USPSTF1989）和加拿大的定期健康检查委员会（CTFPHE1994）对高危妊娠仍保留使用EFM。尽管有人对EFM的效果和安全性表示担忧（Thacker 1987：Thacker 1995），     

Unusual presentation of perirenal lung metastases

Lung cancer is not commonly known to metastasise to the perirenal space, with only five such cases previously published. We present an unusual case of perirenal lung metastases manifesting as diffuse perinephric stranding which to our knowledge has not been described before.     

Beyond Prostate-specific Antigen - Future Biomarkers for the Early Detection and Management of Prostate Cancer

Prostate-specific antigen is currently commonly used as a screening biomarker for prostate cancer, but it has limitations in both sensitivity and specificity. The development of novel biomarkers for early cancer detection has the potential to improve survival, reduce unnecessary investigations and benefit the health economy. Here we review the use and limitations of prostate-specific antigen and its subtypes, urinary biomarkers including PCA3, alpha-methylacyl-CoA racemase, the TMPRSS2-ERG fusion gene and microseminoprotein-beta, and other novel markers in both serum and urine. Many of these biomarkers are at early stages of development and require evaluation in prospective trials to determine their potential usefulness in clinical practice. Genetic profiling may allow for the targeting of high-risk populations for screening and may offer the opportunity to combine biomarker results with genotype to aid risk assessment.     

Low IPSS score and bone marrow hypocellularity in MDS patients predict hematological responses to antithymocyte globulin.

Immunosuppressive therapy has been shown to induce sustained hematological responses in a subset of patients with myelodysplastic syndromes (MDS). In particular, antithymocyte globulin (ATG), a polyclonal immunoglobulin induces hematological responses in up to 60% of MDS patients. We report herein on the results of a retrospective multicenter study on the use of ATG in the treatment of 96 patients with MDS. Patients were evaluated for duration of response to ATG, as well as survival after administration of ATG. The median age of the cohort was 54.7 years (range: 19-75 years), with a median follow-up of 33.8 months (range: 0.8-133 months). A total of 40 patients (42%) achieved a hematological response, of which 30 patients (75%) had a durable hematological response lasting a median duration of 31.5 months (range: 6-92 months). On multivariate analysis, both low International Prognostic Scoring System (IPSS) and bone marrow (BM) hypocellularity were independent predictive factors for improved response to ATG (IPSS Int-2/high: odds ratio (OR) 0.08, P=0.018 and BM normo/hypercellularity: OR 0.49, P=0.012). In addition, IPSS was the sole predictor of overall survival, with Int-2/high risk patients having a significantly poorer survival outcome (OR 0.08, P<0.01). In conclusion, this study identifies BM hypocellularity and a low IPSS as important factors predicting response to ATG.     

β-Amyloid precursor protein and tau protein levels are differently regulated in human cerebellum compared to brain regions vulnerable to Alzheimer's type neurodegeneration

It is well established that the human brain exhibits regional variability in its vulnerability to Alzheimer's disease (AD) pathology. We set out to determine if this regional vulnerability is reflected in the expression pattern, or processing, of two key proteins involved in AD pathology, the β-amyloid precursor protein (APP) and tau, by immunoblotting. Our data demonstrate that APP processing and APP protein levels are not different between AD patients and healthy, age-matched subjects, but that levels of mature APP are greatly reduced in cerebellum compared to regions of the brain most vulnerable to AD, entorhinal cortex and hippocampus. In addition, protein levels of tau are significantly reduced in cerebellum compared to all other human brain regions examined. Unexpectedly, protein levels of glycogen synthase kinase 3 (GSK3), a major tau kinase, are at their lowest in hippocampus. The observations demonstrate that both mature APP as well as total APP and tau protein levels are greatly reduced in human cerebellum, a region of the human brain most resistant to AD pathology.     

Interleukins,laminin and epstein - barr virus latent membrane protein 1 (EBV LMP1) Promote metastatic phenotype in nasopharyngeal carcinoma

Background  

Nasopharyngeal carcinoma (NPC) is a type of neoplasm that is highly prevalent in East Asia and Africa with Epstein-Barr virus (EBV), genetic, and dietary factors implicated as possible aetiologic factors. Previous studies suggested the association of certain cytokines with the invasion and metastatic properties of NPC. The present study examined the roles of EBV latent membrane protein-1 (LMP1), interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-β1) and laminin in the regulation of matrix-metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) in NPC. The effects of these factors on bmi-1, an oncogene, and ngx6, a tumour suppressor gene, were also investigated.     

Limited Margins Using Modern Radiotherapy Techniques Does Not Increase Marginal Failure Rate of Glioblastoma

PURPOSE: We investigate the patterns of failure in the treatment of glioblastoma(GBM) based on clinical target volume(CTV) margin size,dose delivered to the site of initial failure,and the use of temozolomide and intensity-modulated radiotherapy(IMRT).METHODS: Between August 2000 and May 2010,161 patients with GBM were treated with radiotherapy with or without concurrent temozolomide.Patients were treated with CTV expansions that ranged from 5 to 20 mm using a shrinking field technique.Patterns of failure and time to progression and overall survival were compared based on CTV margin,use of temozolomide,and use of IMRT.Kaplan Meier analysis was used to estimate survival times,and χ test was used for comparison of cohorts.RESULTS: For patients treated with 5-,10-,and 15-to 20-mm CTV,79%,77%,and 86% experienced failures in the 60 Gy volume,respectively.Forty-eight percent,55%,and 66% of patients with 5-,10-,and 15-to 20-mm CTV experienced failures in the 46 Gy volume,respectively.There was no statistical difference between patients treated with 5-,10-,15-to 20-mm margins with regard to 60 Gy failure(P=0.76),46 Gy failure(P=0.51),or marginal failure(P=0.73).Eighty percent of patients receiving temozolomide experienced failures in the 60 Gy volume.There was no increased likelihood of marginal failures in patients receiving IMRT(P =0.97).CONCLUSIONS: Modern treatment techniques including use of concurrent temozolmide,limited CTV margin size,and IMRT have not greatly changed the patterns of failure of GBM.     

临床医护

细菌的耐药笥民为一个全球性问题,并从医院扩展到了家庭及社区。同时,抗生素的滥用对微生物的生态环境造成了极大的破坏。我们可以通过改变抗生素的使用频度和改变耐药性基因来逆转药性问题,同时需要有一个全球性的监测系统来追踪耐药菌的、去向及新菌种的出现。     

Antihypertensive efficacy of metoprolol XL/Low dose chlorthalidone (6.25 mg) combination: a randomized,comparative study in Indian patients with mild-to-moderate essential hypertension

Objective

High blood pressure is one of the most important risk factors, directly responsible for increasing the cardiovascular morbidity and mortality. The primary objective was to evaluate the efficacy of metoprolol XL/chlorthalidone against metoprolol XL/hydrochlorothiazide with respect to mean fall in systolic and diastolic blood pressure. The secondary objective was to compare the response rates and to evaluate the tolerability of study medications in patients with mild-tomoderate essential hypertension.

Methods

Total 130 eligible patients (65: metoprolol XL 25 mg/chlorthalidone 6.25 mg; 65: metoprolol XL 25 mg/HCTZ 12.5 mg) were enrolled in this randomized, comparative, multicentric, 12-weeks study. Sixty-two patients from each group completed the study. After 4-weeks of treatment, non-responders from chlorthalidone 6.25 mg combination group were shifted to metoprolol XL 50 mg/chlorthalidone 12.5 mg and non-responders from HCTZ 12.5 mg combination group were escalated to metoprolol XL 50 mg/HCTZ 12.5 mg.

Results

The study treatment groups were comparable with respect to demography and baseline disease characteristics. Both the starting therapies were comparable with respect to mean fall in SBP (p = 0.788) and DBP (p = 0.939), and response rates (p = 1.0) after 4-weeks of therapy. Also both the step-up therapies showed similar mean fall in SBP (p = 0.277) and DBP (p = 0.507) at the end of 12-weeks. However, significantly more number of patients from chlorthalidone 12.5 mg/metoprolol XL 50 mg group responded to therapy as compared to that from HCTZ 12.5 mg/metoprolol XL 50 mg group (p = 0.045). All the reported adverse events were of mild-to-moderate intensity. There were no clinically significant trends in electrolytes (Na⁺, K⁺, Cl^-)and fasting blood sugar, evident across the treatment groups.

Conclusion

Chlorthalidone in combination with metoprolol XL is as effective and well tolerated as widely used combination of metoprolol XL/HCTZ, thus providing an alternative therapeutic option.