Long-term clinical outcome of mitral valve repair in asymptomatic severe mitral regurgitation

Objective: To assess the long-term survival, the incidence of cardiac complications and the factors that predict outcome in asymptomatic patients with severe degenerative mitral regurgitation (MR) undergoing mitral valve repair. Methods: Up to 143 asymptomatic patients (mean age 63 ± 12 years) with severe degenerative MR who underwent mitral valve repair between 1990 and 2001 were subsequently followed up for a median of 8 years. The study population was subdivided into three subgroups: patients with left ventricular (LV) dysfunction and/or dilatation (n = 18), patients with atrial fibrillation and/or pulmonary hypertension (n = 44) and patients without MR-related complications (n = 81). Results: For the patients, 10-year overall and cardiovascular survival was 82 ± 4% and 90 ± 3%. At 10 years, patients without preoperative MR-related complications had significantly better overall survival than patients with preoperative LV dysfunction and/or dilatation (89 ± 4% vs 57 ± 13%, log rank p = 0.001). Patients without preoperative MR-related complications also tended to have a better 10-year overall and cardiovascular survival than patients with atrial fibrillation and/or pulmonary hypertension (overall survival of 79 ± 8%), although this did not reach statistical significance (log rank p = 0.17). Cox regression analysis identified the baseline left ventricular ejection fraction and age as the sole independent predictors of outcome. Conclusion: Our data indicate that in asymptomatic patients with severe degenerative MR, mitral valve repair is associated with an excellent long-term prognosis. Nonetheless, the presence of preoperative MR-related complications, in particular LV dysfunction and/or dilatation, greatly attenuates the benefits of surgery. This suggests that mitral valve repair should be performed early, before any MR-related complications ensue.     

Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States

CONTEXT: Population-based estimates of the prevalence of disease-associated mutations, such as hemochromatosis (HFE) gene mutations, are needed to determine the usefulness of genetic screening. OBJECTIVE: To estimate the prevalence of the HFE mutations C282Y and H63D in the US population. DESIGN: Cross-sectional population-based study of samples in the DNA bank from phase 2 of the Third National Health and Nutrition Examination Survey conducted from 1992 to 1994. SETTING AND PARTICIPANTS: Genotyped samples of cells from a total of 5171 participants, cross-classified by sex, age, and race/ethnicity in the analysis. MAIN OUTCOME MEASURES: Estimates of the prevalence of C282Y and H63D mutations. RESULTS: The prevalence of C282Y homozygosity is estimated to be 0.26% (95% confidence interval [CI], 0.12%-0.49%); 1.89% (95% CI, 1.48%-2.43%) for H63D homozygosity; and 1.97% (95% CI, 1.54%-2.49%) for compound heterozygosity. The prevalence estimates for C282Y heterozygosity (C282Y/wild type) are 9.54% among non-Hispanic whites, 2.33% among non-Hispanic blacks, and 2.75% among Mexican-Americans. The prevalence estimates of the C282Y mutation in the US population are 5.4% (95% CI, 4.7%-6.2%) and 13.5% (95% CI, 12.5%-14.8%) for the H63D mutation. CONCLUSIONS: Estimates of prevalence of HFE mutations are within the expected range for non-Hispanic whites and blacks but the estimated prevalence of the C282Y mutation among Mexican-Americans is less than expected. Mutation data now need to be linked to clinically relevant indices, such as transferrin saturation level.     

MR imaging of facial nerve enhancement in Bell palsy or after temporal bone surgery

The authors evaluated magnetic resonance (MR) images obtained with intravenously administered gadolinium in ten patients who had facial paralysis and no facial nerve tumor. In patients with either Bell palsy (four patients) or facial paralysis after temporal bone surgery (six patients), intratemporal facial nerve enhancement was seen. Facial nerve enhancement on MR images proved to be a nonspecific finding.     

Inhibition of endotoxin-induced activation of the coagulation and fibrinolytic pathways using a recombinant endotoxin-binding protein (rBPI23)

A recombinant endotoxin-neutralizing protein, rBPI23, was shown to partially prevent endotoxin-induced activation of the fibrinolytic and coagulation systems in experimental endotoxemia in humans. In a placebo- controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg of body weight) and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). rBPI23 treatment significantly lowered the endotoxin-induced fibrinolytic response, ie, reduced the release of tissue-type plasminogen activator, urokinase- type plasminogen activator, plasminogen activator inhibitor antigen, and complex formation of plasmin alpha 2-antiplasmin (P = .0078 for each). Plasminogen activator inhibitor activity was also reduced, but not significantly according to the Hochberg method (P = .0304). The endotoxin-induced activation of the procoagulant state as reflected by increase in F1 + 2 fragments and TAT complexes was blunted by rBPI23 infusion (P = .0391 [not significant according to the Hochberg method] and .0078, respectively). These results indicate that rBPI23 is capable of reducing both the activation of the fibrinolytic and the coagulation systems after low-dose endotoxin infusion in humans.     

Patientennutzen und Anwendungsmerkmale der Behandlung irritierter Haut mit dexpanthenolhaltiger Salbe

Background

Products containing dexpanthenol are used to treat irritated and inflamed skin. So far there is a lack of data for the evidence of patient-relevant benefits.

Objective

Assessment of the patient-relevant benefit of ointments containing dexpanthenol in the self-medicated therapy of irritated skin.

Methods

Prospective, observational study in a network of 392 pharmacies. Consecutive recruitment of n=1,886 patients with symptoms of irritated skin, including non-inflammatory intervals of atopic eczema, other xerotic skin conditions and impairment of skin barrier. The patient-relevant benefit was ascertained prior to and 7–10 days after treatment through the patient-benefit index (PBI).

Results

The PBI showed that 91.5% of the patients experienced a relevant benefit from treatment. 94.7% directly indicated to have had achieved successful therapeutic results. All symptoms of irritated skin (e.g. xerosis, erythema, desquamation) significantly improved (p≤0,001). The subjective response was independent of age, gender and underlying skin disease.

Conclusion

High patient-relevant benefits were observed in the treatment of irritated skin with dexpanthenol ointment.     

Injury to the femoral vessels--the Lebanese War experience

Over a 10-year-period extending from January 1976 to September 1986, 800 peripheral vascular injuries were surgically treated at the American University of Beirut Medical Centre. Of these, 150 were operated on because of injury to the femoral vessels. Bullets were the commonest wounding agents (60% of cases). Thirty-seven patients had a femoral artery injury, 27 a femoral vein injury and 86 combined femoral artery and vein damage. Twenty-three per cent of the patients had an associated fracture of the femur. Patients with fractures had an 11% amputation rate compared with 1% for those without fractures. Our data reveals the importance of venous reconstruction in the presence of an arterial injury instead of its ligation (P less than 0.05), particularly when there is an associated fracture of the femur. Thirty-seven per cent of patients were in shock on admission (systolic BP 90 mmHg). The amputation rate in these patients was 6.8% in contrast to 1% in the haemodynamically stable group (P less than 0.05). The overall amputation rate was 3.3%. Complications occurred in 36.6% of patients and the mortality was 4.0%.     

多索茶碱及其片剂的高效液相色谱分析

多索茶碱及其片剂的高效液相色谱分析刘春胜，何秀峰，王云萍，谷士杰，周同惠（中国医学科学院、中国协和医科大学药物研究所，北京１０００５０）多索茶碱（ｄｏｘｏｆｙｌｌｉｎｅ）是用于治疗支气管哮喘合并支气管痉挛的慢性阻塞性肺部疾病的新一代黄嘌吟衍生物，其药...     

Distinct Neuropsychological Mechanisms May Explain Delayed- Versus Rapid-Onset Antidepressant Efficacy

The biochemical targets for antidepressants are relatively well established, but we lack a clear understanding of how actions at these proteins translate to clinical benefits. This study used a novel rodent assay to investigate how different antidepressant drugs act to modify affective biases that have been implicated in depression. In this bowl-digging task, rats encounter two equal value learning experiences on separate days (one during an affective manipulation and the other during control conditions). This induces an affective bias that is quantified using a preference test in which both digging substrates are presented together and the individual rats’ choices recorded. The assay can be used to measure affective biases associated with learning (when the treatment is given at the time of the experience) or examine the modification of previously acquired biases (when the treatment is administered before the preference test). The rapid-onset antidepressant ketamine, but not the delayed-onset antidepressant, venlafaxine, attenuated the previously acquired FG7142-induced negative bias following systemic administration. Venlafaxine but not ketamine induced a positive bias when administered before learning. We then used local drug infusions and excitotoxic lesions to localize the effects of ketamine to the medial prefrontal cortex and venlafaxine to the amygdala. Using a modified protocol we also showed that positive and negative biases amplified further when the numbers of substrate–reinforcer associations are increased. We propose that this pattern of results could explain the delayed onset of action of venlafaxine and the rapid onset of action but lack of long-term efficacy seen with ketamine.