心肌梗死大鼠心肌细胞凋亡及磷酸肌酸的干预

目的:缺血引起的心肌能量供应不足是心肌细胞凋亡主要的因素之一,观察补充外源性能量磷酸肌酸对缺血心肌细胞凋亡和心功能的影响。方法:实验于2003-04/06在解放军总医院老年心血管病研究所实验室完成。选用SD大鼠50只,按随机数字表法分为3组:①磷酸肌酸组19只,结扎左冠状动脉制作心肌梗死模型,结扎前30min按200mg/kg的剂量腹腔注射磷酸肌酸1次。②缺血对照组21只,心肌缺血方法同磷酸肌酸组,结扎前30min腹腔注射相同体积的50g/L葡萄糖注射液1次。③正常对照组10只,仅在冠状动脉下穿线,不结扎冠状动脉,其余同缺血对照组。结扎冠状动脉6h后,取各组大鼠心脏标本做石蜡切片,缺口末端标记法染色,高倍镜下计数心肌细胞凋亡指数,凋亡指数=凋亡心肌细胞数/心肌细胞总数;取心脏标本前,测左心室收缩压、舒张末压和压力变化速度,并进行组间比较。结果:磷酸肌酸组大鼠造模时死亡9只;缺血对照组造模时死亡10只,造模成功后6h内死亡1只,进入结果分析共30只大鼠,每组10只。①缺血对照组大鼠的左心室舒张末压显著高于正常对照组[(13.9±5.3vs.2.8±3.2)mmHg(P<0.01)],左心室压力变化速度显著低于正常对照组[(705.8±111.7vs.1141.7±94.5)mmHg/s(P<0.01)];磷酸肌酸组大鼠的左心室舒张末压显著低于缺血对照组[(8.9±3.5)mmHg(P<0.05)];左心室压力变化速度显著高于缺血对照组[(841.5±76.1)mmHg/s(P<0.01)];左心室收缩压与缺血对照组差异无显著性意义(P>0.05)。②磷酸肌酸组大鼠的心肌细胞凋亡指数显著低于缺血对照组(0.203±0.054vs.0.278±0.052,P=0.006)。结论:补充外源性能量磷酸肌酸可以减少缺血后心肌细胞凋亡,并改善心功能,磷酸肌酸抑制缺血心肌细胞凋亡可能是改善心肌梗死后心功能的主要作用途径之一。     

Automated Objective Scoring of Histologically Apparent Cartilage Degeneration Using a Custom Image Analysis Program

Histologic assessment of cartilage degradation has traditionally involved semiquantitative techniques, the most commonly utilized being the Mankin scale. Such assessments depend on human observer subjectivity, and thus have drawn criticism on the basis of associated inter‐ and intraobserver variability. We report a newly developed computational image analysis procedure for fully automated and fully objective assessment of the Mankin scale. Image processing routines were developed in a widely used programming environment (Matlab®) to analyze cartilage degradation. One hundred and twenty‐five histology images incorporating a wide range of degradation features were analyzed by the algorithm and by seven observers experienced in cartilage histologic assessment. Based on random effects linear statistical models, the computer program performed well, showing a correlation of 0.88 between its Mankin scores and latent (average of human observers') image scores. Regarding the four subcomponents of the Mankin scale, computer program correlations with observer scores were best for surface defect and proteoglycan depletion, but less favorable for cellularity and tidemark invasion. While limitations exist with image processing techniques, the new algorithm provides an objective and automated method for analyzing cartilage histology sections, consistent with human observer grading. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 522–528, 2009     

Effects of aldosterone receptor blockade in patients with mild-moderate heart failure taking a beta-blocker

AIMS: Spironolactone improves prognosis in severe heart failure (HF). We investigated its effects in patients with mild-moderate HF treated with an ACE inhibitor and beta-blocker. METHODS AND RESULTS: Randomised, double-blind, parallel-group, 3-month comparison of placebo and spironolactone (25 mg daily) in 40 patients in New York Heart Association (NYHA) class I (20%), II (70%) or III (10%), with a left ventricular ejection fraction of <40%. The mean (standard error) changes from baseline in the spironolactone and placebo groups were, respectively: i) B-type natriuretic peptide (BNP) -53.4(22.2) pg/mL and +3.3(12.1) pg/mL, P=0.04, ii) pro-collagen type III N-terminal amino peptide (PIIINP) -0.6(0.2) micromol/L and +0.02(0.2) micromol/L, P=0.02 and iii) creatinine +10.7(3.2) micromol/L and -0.3(2.6) micromol/L, P=0.01. Compared with placebo, spironolactone therapy was associated with a reduction in self-reported health-related quality of life: change in visual analog score: -6 (3) vs. +6 (4); P=0.01. No differences were observed on other biochemical, neurohumoral, exercise and autonomic function assessments. CONCLUSION: In patients with mild-moderate HF, spironolactone reduced neurohumoral activation (BNP) and a marker of collagen turnover (PIIINP) but impaired renal function and quality of life. The benefit-risk ratio of aldosterone blockade in mild HF is uncertain and requires clarification in a large randomised trial.     

Barriers to prenatal care and poor pregnancy outcomes among women with syphilis in the Russian Federation

We studied predictors of no prenatal care (PNC) and influence of no PNC on pregnancy outcome in a multisite study of 1071 women with syphilis in Russia. We assessed PNC utilization, HIV testing, syphilis treatment, and pregnancy outcome. We found that 37% of women with syphilis received no PNC, and 1% was HIV infected. Lacking official residency status was independently related to no PNC (adjusted odds ratio [AOR]: 8.1; 95% confidence intervals [CI]: 5.3-12.3). Among women with inadequately treated current syphilis, those without PNC were more likely to have a stillborn infant than those with PNC (25% vs. 3%, odds ratio [OR] 9.5, 95% CI 4.0-23.5). Women with adequately treated current syphilis and no PNC were more likely to deliver a low birth weight (OR 3.8; 95% CI 1.8-8.1) or preterm infant (OR 3.9; 95%CI 1.8-8.7). Women with previous or current syphilis and no PNC were significantly more likely to abandon their infants.     

Utility of B-type natriuretic peptide in predicting medium-term mortality in patients undergoing major non-cardiac surgery

This study was conducted to assess the ability of preoperative B-type natriuretic peptide levels to predict medium-term mortality in patients who undergo major noncardiac surgery. During a median of 654 days of follow-up, 33 patients from a total cohort of 204 patients (16%) died, 17 from cardiovascular causes. The optimal cutoff in this cohort, determined using a receiver-operating characteristic curve, was >35 pg . ml(-1). This was associated with a 3.5-fold increase in the hazard of death (p = 0.001) and a 6.9-fold increase in the hazard of cardiovascular mortality (p = 0.003). In conclusion, these findings extend recent work demonstrating that B-type natriuretic peptide levels obtained before major noncardiac surgery can be used to predict perioperative morbidity and indicate that they also forecast medium-term mortality, particularly cardiovascular death.     

Congenital syphilis in Russia: the value of counting epidemiologic cases and clinical cases

BACKGROUND: Congenital syphilis (CS) reports in Russia increased 26-fold from 1991 to 1999. Case reports included only infants who were clinical cases, had persistent serologic changes, or confirmed syphilitic stillbirth. Although not reported, policies stipulate that infants of inadequately treated or untreated mothers receive preventive penicillin treatment. GOAL: We examined whether risk factors and consequences for epidemiologic cases of CS (infants of inadequately treated mothers) resembled those of clinical cases and differed from those of noncases (infants of adequately treated mothers). STUDY DESIGN: A retrospective record review from Maternity Houses in 5 sites identified 715 syphilis-infected women who gave birth. RESULTS: Among women with maternal syphilis, 11% (n = 81) of infants were clinical cases, 56% (n = 402) were epidemiologic cases, and 33% (n = 232) were noncases of CS. Compared with noncases, maternal risk factors for epidemiologic cases included nonresidence (P <0.01), late syphilis (P <0.01), unemployment (P <0.01), no prenatal care (P <0.01), and syphilis testing at >/=28 weeks (P <0.01). Each of these was also significant for being a clinical case. Associated consequences of CS for the epidemiologic cases included increases in stillbirth (P <0.01), preterm birth (P <0.01), low birth weight (P <0.01), transfer to a pediatric hospital (P <0.01), and abandonment (P <0.05). Each of these except stillbirth was significantly elevated among clinical cases. Nearly half of the epidemiologic cases had no record of any penicillin treatment for the infant. Epidemiologic cases were significantly more likely than noncases to have no clinical or laboratory follow up. CONCLUSION: In Russia, maternal risk factors and perinatal consequences for epidemiologic cases of CS resembled those of clinical cases. Expanding national reporting to include epidemiologic cases would strengthen CS prevention and monitoring.     

Brivudin compared with famciclovir in the treatment of herpes zoster: effects in acute disease and chronic pain in immunocompetent patients. A randomized, double-blind, multinational study

OBJECTIVE: This was a double-blind, randomized multicentre trial comparing efficacy and safety of brivudin (125 mg, once a day) and famciclovir (250 mg, three times a day), both given orally for 7 days, in the treatment of herpes zoster. METHODS: A total of 2027 immunocompetent zoster patients>or=50 years with zoster-related pain at presentation were included. Outcome measures embraced prevalence of postherpetic neuralgia (PHN), defined as at least moderate pain 3 months after treatment initiation, duration of PHN, prevalence and duration of zoster-associated pain (ZAP), duration of vesicle formation and rash healing. RESULTS: The prevalence of PHN at month 3 was 11.3% with brivudin and 9.6% with famciclovir [per-protocol (PP) population]. Equivalence of the two drugs could be demonstrated (P=0.01, PP and intention-to-treat analysis). The median duration of PHN was 46.5 days with brivudin and 58 days with famciclovir (P=0.54, PP analysis). Prevalence and duration of ZAP did not differ significantly between treatment groups. The prevalence of PHN was higher in patients>or=65 years (brivudin: 16.4%, famciclovir: 16.4%), and in patients with severe rash (brivudin: 13.4%, famciclovir: 15.7%), without significant differences between treatment groups. In patients>or=65 years, median duration of PHN was shorter with brivudin than with famciclovir (39.5 vs. 57.5 days), although the difference was not statistically significant. The two drugs had equivalent efficacy in being able to accelerate the stop of vesicle formation, and lesion healing. Adverse events were similar in nature and prevalence among groups. CONCLUSIONS: The study demonstrated equivalent efficacy of brivudin and famciclovir in the treatment of herpes zoster regarding the prevention of chronic pain and the resolution of signs and symptoms of acute herpes zoster. Compared with famciclovir, brivudin provides equivalent efficacy and safety at a more convenient once-daily dose schedule.