四肢关节专用低场强MRI评估对膝关节损伤的诊断价值

目的：分析四肢关节专用低场强MRI诊断膝关节损伤的临床应用价值。 方法：于2004-12/2005-10解放军总医院全军骨科研究所收治经手术、关节镜检查或临床证实的膝关节损伤患者40例（43个膝关节）。应用Atorscan0.2T永磁型四肢关节专用低场强磁共振机,对膝关节损伤的MRI表现进行分析。 结果：四肢关节专用低场强MRI对半月板、前交叉韧带、骨挫伤等均可作出正确诊断。 结论：四肢关节专用低场强MRI对膝关节损伤的综合诊断具有重要意义,是膝关节损伤较理想的一种非创伤性检查方法。     

Blood transfusion exposure does not influence survival in patients with carcinoma of the breast

There is abundant evidence of immune modulation induced by exposure to blood transfusions. Some studies have demonstrated a detrimental effect of transfusion on the recurrence of malignant disease and survival. We retrospectively studied the impact of blood transfusion exposure on 229 patients with breast cancer who were seen from July 1973 to September 1980, had at least 5 years' follow-up and had been randomized by therapy at the time of diagnosis. The patients were divided into four groups according to transfusion history: Group 1 (111 patients), no transfusion; Group 2 (34 patients), first transfusion after mastectomy; Group 3 (41 patients), first transfusion at mastectomy; and Group 4 (43 patients), first transfusion before mastectomy. All transfused patients received red cells or whole blood or both. At the time of analysis, 124 (54%) of the patients had died. Only Group 2 was statistically associated with decreased survival; recurrence of disease was 85 percent in this group, compared with 53 percent to 61 percent in the other three groups (p = 0.006, log-rank test). In general, Group 2 patients received transfusions because of recurrent disease. We conclude that transfusions before or at mastectomy are not associated with increased recurrence or reduced survival in patients with breast cancer.     

MS-qFRET: A quantum dot-based method for analysis of DNA methylation

DNA methylation contributes to carcinogenesis by silencing key tumor suppressor genes. Here we report an ultrasensitive and reliable nanotechnology assay, MS-qFRET, for detection and quantification of DNA methylation. Bisulfite-modified DNA is subjected to PCR amplification with primers that would differentiate between methylated and unmethylated DNA. Quantum dots are then used to capture PCR amplicons and determine the methylation status via fluorescence resonance energy transfer (FRET). Key features of MS-qFRET include its low intrinsic background noise, high resolution, and high sensitivity. This approach detects as little as 15 pg of methylated DNA in the presence of a 10,000-fold excess of unmethylated alleles, enables reduced use of PCR (as low as eight cycles), and allows for multiplexed analyses. The high sensitivity of MS-qFRET enables one-step detection of methylation at PYCARD, CDKN2B, and CDKN2A genes in patient sputum samples that contain low concentrations of methylated DNA, which normally would require a nested PCR approach. The direct application of MS-qFRET on clinical samples offers great promise for its translational use in early cancer diagnosis, prognostic assessment of tumor behavior, as well as monitoring response to therapeutic agents.Aberrant DNA hypermethylation is observed at classic tumor-suppressor genes, which are known to be genetically mutated and cause inherited forms of cancer (Jones and Baylin 2002). Tumor cells display a larger number of genes inactivated by promoter hypermethylation than by genetic mutations (Schuebel et al. 2007). Furthermore, these abnormal epigenetic changes appear to be an early event that precedes detection of genetic mutations (Esteller et al. 1999; Feinberg and Tycko 2004; Yamada et al. 2005). Thus, detection of promoter hypermethylation is a valuable tool for early diagnosis of cancer, monitoring tumor behavior, as well as measuring response of tumors to targeted therapy (Esteller et al. 2000; Gore et al. 2006b; Brock et al. 2008).The number of tools available to assess DNA methylation demonstrates the extensive interest that has been invested in understanding the role of epigenetics in carcinogenesis (Laird 2003). One of the more common techniques used for the detection of methylation is methylation-specific PCR (MSP) (Herman et al. 1996). The technique relies on sodium bisulfite treatment of DNA, which converts unmethylated cytosines to uracils while leaving methylated cytosines unaffected. The modified sequences are then amplified with specific primers, and the amplified products are identified using gel electrophoresis. However, this standard MSP approach offers only qualitative analysis and cannot discern relative amounts of methylation. Although real-time PCR-based MSP methods (Lo et al. 1999; Eads et al. 2000) enable quantitative analysis, they may lack the sensitivity for direct screening of challenging samples, such as sputum, where the DNA from tumor cells is minimal, thereby requiring a nested PCR approach (Brandes et al. 2005; Belinsky et al. 2006; Machida et al. 2006; Kim et al. 2007).Methylation-specific quantum dot fluorescence resonance energy transfer (MS-qFRET) combines the high specificity of MSP and the high sensitivity and simplicity of the quantum dot FRET (QD-FRET) technology (Zhang et al. 2005). MS-qFRET facilitates a straightforward approach for both a qualitative and quantitative detection of methylated DNA, as well as allowing detection of low-abundance methylated DNA. The sensitivity of the MS-qFRET is first examined here, followed by a demonstration of its ability to quantify methylation, both in cell lines, as well as in myelodysplastic syndrome (MDS) patient samples. The advantages of MS-qFRET are also highlighted by its capability of multiplexing reactions and its potential application for high-throughput screening. Finally, the sensitivity of this technique is validated in patient sputum samples that contain very low concentrations of DNA.     

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.     

Some Diagnostic Aids in Acute Anterior Poliomyelitis

A presentation of the National Foundation for Infantile Paralysis in the Scientific Exhibits Section of the Centennial Convention of the American Medical Association, Atlantic City, June 1947.