Ascending Thoracic Aortic Aneurysms Protect Against Myocardial Infarctions

There has been increasing evidence that ascending thoracic aortic aneurysms (TAAs) protect against atherosclerosis. However, there have been no studies examining the relationship between ascending TAAs and clinical endpoints of atherosclerosis, such as stroke or peripheral arterial disease. In this study, we aim to characterize the relationship between TAAs and a specific clinical endpoint of atherosclerosis, myocardial infarction (MI). We compared prevalence of coronary artery disease (CAD) and MIs in 487 patients who underwent surgical repair for ascending TAAs to 500 control patients who did not have an ascending TAA. Multivariate binary logistic regression was used to calculate the odds of having MI if a patient had an ascending TAA versus any of several MI risk factors. There was a significantly lower prevalence of CAD and MI in the ascending TAA group than in the control TAA group. The odds of having a MI if a patient had a MI risk factor were all > 1 (more likely to have a MI), with the lowest statistically significant odds ratio being 1.54 (age; p = 0.001) and the highest being 14.9 (family history of MI; p < 0.001). The odds ratio of having a MI if a patient had an ascending TAA, however, was near 0 at 0.05 (p < 0.001). This study provides evidence that ascending TAAs protect against MIs, adding further support to the hypothesis that ascending TAAs protect against atherosclerotic disease.     

Pharmacodynamic properties of antiplatelet agents: current knowledge and future perspectives

Platelets play an important role in atherothrombotic disease. The currently available antiplatelet drugs target key steps of platelet activation including thromboxane A₂ synthesis, ADP-mediated signaling, and glycoprotein IIb/IIIa-mediated platelet aggregation. The improvement of our understanding on the pharmacokinetic and pharmacodynamic characteristics of these drugs enables the tailoring of the most appropriate anti-thrombotic therapy to the individual patient and risk situation in the daily clinical practice. However, current antiplatelet therapies are associated with increased bleeding risk. Thus, further research on platelet functions may give rise to numerous new antiplatelet agents with high anti-thrombotic efficiency and low adverse hemorrhagic side effects.     

New drugs for the treatment of coronary artery syndromes: otamixaban and ticagrelor

Acute coronary syndromes are a major cause of mortality and morbidity. The objective of this evaluation is to review the clinical trials of two new drugs being developed for the treatment of acute coronary syndromes. The first drug is the anticoagulant otamixaban, and the trial compared otamixaban with unfractionated heparin and eptifibatide in acute coronary syndromes. The second drug is the antiplatelet ticagrelor, and the trial compared ticagrelor with clopidogrel in acute coronary syndromes. In the SEPIA-ACS1 TIMI 42 trial, the primary efficacy endpoint occurred in 6.2% of subjects treated with unfractionated heparin and eptifibatide, and to a significantly lesser extent with otamixaban. In the PLATO trial, the primary efficacy endpoint had occurred less in the ticagrelor group (9.8%) than in the clopidogrel group (11.7%) at 12 months. Two new drugs for acute coronary syndromes, otamixaban and ticagrelor, have recently been shown to have benefits in subjects undergoing percutaneous interventions compared to the present standard regimens for this condition.     

ACAM2000: a newly licensed cell culture-based live vaccinia smallpox vaccine

Importance of the field: Migraine is an episodic, substantially inherited brain disorder affecting 15% of adults in Western Europe and North America, and is one of the commonest reasons for patients to see their physicians. While the World Health Organization considers that severe migraine can be as disabling as quadriplegia, unfortunately the condition remains undertreated. Until the 1990s, specific migraine therapies were limited to ergot derivatives.

Areas covered in this review: The triptans, serotonin 5-HT_1B/1D receptor agonists, revolutionized the acute management of migraine patients. However, although the triptans are generally effective and safe, not all patients can take them and many do not respond especially to oral therapies. Recently, progress has been made on the therapeutic front, particularly with new acute treatments. This review will focus on the therapeutic potential of ADX10059, a metabotropic glutamate receptor 5, negative allosteric modulator (mGluR5 NAM), in migraine. Data from a proof-of-concept study in episodic migraineurs demonstrated a significant improvement following acute treatment. A large European multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study is currently investigating the efficacy, safety and tolerability of the compound for migraine prevention.

What the reader will gain: The reader will have the basic principles of migraine management and the potential for glutamate-targeted approaches.

Take home message: Targeting glutamatergic transmission in migraine may provide a novel preventive therapy that is effective and well-tolerated.     

规范转院转诊 减少医疗纠纷 提高医疗质量

首诊医疗机构及其医务人员在接诊后，在最大限度保护患者生命健康的同时，对需要转院转诊的患者，除承担法定的转诊义务外，还要严格遵守转诊程序。按照相应的法律法规，正确合理地转院转诊，对于减少医疗纠纷，提高医疗质量有着重要的意义。本文着重分析转诊转院的法定义务和规范程序，并对特殊情况的转院转诊进行探讨。     

Halofantrine in the treatment of acute malaria: A multi-centre study in 268 patients

Summary

The clinical efficacy and tolerability of halofantrine, a new antimalarial schizontocide, was studied in a multi-centre trial involving 268 patients ranging in age from 6 months to 58 years. The patients were suffering from acute uncomplicated malaria due to either P.vivax or P. falciparum. Patients were treated orally with 3 doses of halofantrine hydrochloride, 500?mg/6-hourly in adults or 8?mg/kg body weight 6-hourly in children. The overall cure rate was 96.9%. The mean fever clearance time for different species was as follows: P. vivax — 39.1 hours, P. falciparum — 43.2 hours, mixed infection — 60.0 hours, and the mean parasitaemia clearance times were 47.7, 55.1 and 72.0 hours, respectively. Recrudescence was reported in 11 (4.1%) patients, although all of them were parasite-free on Day 7 post-treatment. No haematological or biochemical abnormalities were noted. The drug was very well tolerated and no significant side-effects were reported. Halofantrine was found to be highly effective in acute malaria and offers an important alternative to existing medications.     

Principles in the management of chronic kidney disease

Chronic kidney disease (CKD) is the term used to describe renal disease or impairment which has persisted for three months. This paper presents a brief overview of CKD, including classification, epidemiology, aetiology, clinical presentation, investigations and a discussion regarding the principles of management. The aims of management include: preservation of remaining renal function, avoiding further injury, correction of electrolyte disturbances, anaemia and fluid imbalance and also maintenance of good nutrition, bone health and growth. Some children will progress to end-stage disease and there is a brief discussion of renal replacement therapy. Prognosis depends largely on the cause of CKD. Where children should be followed-up is dictated primarily by their renal function and the likely clinical course.     

4-Hydroxynonenal regulates mitochondrial function in human small airway epithelial cells

Prolonged exposure to oxidative stress causes Acute Lung Injury (ALI) and significantly impairs pulmonary function. Previously we have demonstrated that mitochondrial dysfunction is a key pathological factor in hyperoxic ALI. While it is known that hyperoxia induces the production of stable, but toxic 4-hydroxynonenal (4-HNE) molecule, it is unknown how the reactive aldehyde disrupts mitochondrial function. Our previous in vivo study indicated that exposure to hyperoxia significantly increases 4-HNE-Protein adducts, as well as levels of MDA in total lung homogenates. Based on the in vivo studies, we explored the effects of 4-HNE in human small airway epithelial cells (SAECs). Human SAECs treated with 25 μM of 4-HNE showed a significant decrease in cellular viability and increased caspase-3 activity. Moreover, 4-HNE treated SAECs showed impaired mitochondrial function and energy production indicated by reduced ATP levels, mitochondrial membrane potential, and aconitase activity. This was followed by a significant decrease in mitochondrial oxygen consumption and depletion of the reserve capacity. The direct effect of 4-HNE on the mitochondrial respiratory chain was confirmed using Rotenone. Furthermore, SAECs treated with 25 μM 4-HNE showed a time-dependent depletion of total Thioredoxin (Trx) proteins and Trx activity. Taken together, our results indicate that 4-HNE induces cellular and mitochondrial dysfunction in human SAECs, leading to an impaired endogenous antioxidant response.