Ventricular rate stabilization for the prevention of pause dependent ventricular tachyarrhythmias: results from a prospective study in 309 ICD recipients

Reviews of stored electrograms from ICDs revealed a 5-30% incidence of short-long-short intervals preceding the onset of recurrent ventricular tachyarrhythmias. Rate stabilization by dedicated antibradycardia pacing algorithms has, therefore, been suggested to prevent onset of pause dependent tachyarrhythmias. However, the clinical efficacy of this approach has not been studied systematically. In a prospective multicenter crossover study, patients were randomized to activation or deactivation of an implemented ventricular rate stabilization algorithm (VRS) after first implant of a dual chamber ICD. After 3 months, all patients were crossed over to the alternate programming. The rate of appropriate spontaneous VA episodes was compared between VRS On and VRS Off. Stored electrograms were reviewed for evaluation of the mode of onset of tachyarrhythmias. Overall efficacy analysis was based on 309 patients enrolled in the study. Forty percent (124/309) of the patients experienced 4,973 VA episodes. Based on an intention-to-treat analysis, VRS Off and On arrhythmia incidence was 10.2 and 6.6 normalized to 3 months, respectively (risk reduction 35%; P = 0.18) On an on-treatment basis, a reduction from 9.0 episodes to 8.1 episodes (10% risk reduction, P = 0.24) was seen. In an extended Cox model adjusting for confounding variables, the relative risk for recurrent episodes was 0.92 during VRS On compared to Off (95% CI: 0.58-1.48; P = 0.74). During VRS Off, pause dependent onset was documented in only 36 (8%) of 427 visually analyzed episodes. There was no significant reduction in the incidence of recurrent ventricular tachyarrhythmias with VRS On compared to the Off programming in this prospective study.     

Histamine as a therapeutic alternative in migraine prophylaxis: a randomized, placebo-controlled, double-blind study

This study was undertaken to test the efficacy of the subcutaneous administration (twice a week) of consecutively increasing doses of histamine (0.1 to 1 ng) in the prophylaxis of migraine, compared to placebo, under a controlled, double-blind, clinical trial for 12 weeks. Sixty patients were selected, under criteria established by the International Headache Society (both sexes, 18 to 65 years of age, a migraine history of more than 1 year, one to six headache attacks per month), having no additional neurological or cardiovascular pathologies, and after a complete clinical and laboratory examination including computer-assisted tomography. Comparison between the groups treated with placebo (n = 30) and histamine (n = 30), on data collected for the 4th, 8th, and 12th weeks of treatment, revealed that histamine exerted a significantly (P < .0001) greater reduction (compared to placebo) in the frequency, intensity, and duration of migraine attacks, as well as on the use of rescue medication. No significant (P > .05) adverse experiences or side effects in either group developed to impede the blinding of the study or the planned order of events. We conclude that the subcutaneous administration of histamine (at very low doses) constitutes a novel and effective therapeutic approach in migraine prophylaxis, aimed at limiting excessive inflammatory responses involved in the pathophysiology of migraine through the activation of H3 receptors.     

脊髓损伤的病理生理及非手术疗法的研究进展

脊髓损伤是交通、劳动和运动意外事故中常见的创伤类型,是一种严重的致残性损伤,往往导致损伤节段以下肢体功能严重障碍。导致脊髓损伤难以治疗的关键是继发性损伤,所以如何治疗继发性损伤成为治疗脊髓损伤的重点。脊髓损伤的治疗主要是通过手术或者药物缓解脊髓损伤引起的继发性损伤。随着对生物机理的认识越来越深刻,一些药物或者干细胞疗法在治疗脊髓损伤表现出巨大的潜力,这将为治疗脊髓损伤提供新的视野和希望。本文就脊髓损伤病理生理,以及一些近年来出现的治疗脊髓损伤新的药物及手段做综述。     

Pathophysiology of mild endometriosis: review of literature

Endometriosis is a puzzling condition and the literature ischaracterized by a large number of uncontrolled reports on itsaetiology and pathophysiology. In particular the relationshipbetween mild endometriosis and subfecundity is uncertain. Thispaper critically reviews the published literature on the pathogenesis,prevalence, menstrual symptomatology and natural history ofendometriosis. Furthermore, factors implicated in causing subfecundityin relation to endometriosis and the impact of various treatmentsin enhancing fertility among women with mild endometriosis havebeen assessed.     

Insight into the complex pathophysiology of sickle cell anaemia and possible treatment

Sickle cell anaemia (SCA) is the consequence of abnormal haemoglobin production due to an inherited point mutation in the β‐globin gene. The resulting haemoglobin tetramer is poorly soluble when deoxygenated, and when this is prolonged, intracellular gelation of sickle haemoglobin occurs, followed by haemoglobin polymerisation. If many cycles of sickling and unsickling occur, the red cell membrane will be disrupted leading to haemolysis and vaso‐occlusive events. Recent studies have also shown that leucocyte adhesion molecules and nitric oxide (NO) depletion are involved in endothelial damage. New insights in SCA pathophysiology and vascular biology have shown that cell‐derived microparticle (MP) generation is also involved in the vaso‐occlusion. Endothelial damage is perpetuated by impaired production or increased consumption of protective modulators such as protein C, protein S and NO. New therapeutic interventions should address these aspects of SCA pathogenesis. To date, the only US‐FDA‐approved therapy to prevent painful vaso‐occulsive episodes is hydroxyurea that reduces haemoglobin polymerisation in sickle cells by increasing the production of foetal haemoglobin and L‐glutamine. However, several new drugs have been tested in the last years in randomised clinical trials. We here report an update on the current status of knowledge on SCA.