Nasal response to stress test in healthy subjects: an experimental pilot study

European Archives of Oto-Rhino-Laryngology - Stress has been suspected to play a role in rhinitis. The role of stress on nasal patency has been not yet elucidated. The aim was to evaluate the...     

TGF beta-1 and neurological function after hypoxia-ischemia in adult rats

The present study compared the short-term and long-term neuroprotective and neurobehavioral effects of transforming growth factor beta-1 (TGF beta-1) after hypoxic-ischemic injury in adult rats. TGF beta-1 (10 ng) or vehicle were administered intracerebroventricularly (i.c.v.) 2 h after hypoxia-ischemia. Adhesive removal test was assessed after 10 or 40 days, and the neuronal outcome then determined. TGF beta-1 significantly increased the area of intact cortex compared with vehicle 10 days after the injury, with a significant improvement in neurological function. In contrast, after 40 days recovery TGFbeta-1 neither improved neuronal outcome nor neurological function, suggesting TGFbeta-1 can transiently improve functional and histological recovery from hypoxia-ischemia.     

Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism

The Autism Genome Project has assembled two large datasets originally designed for linkage analysis and genome-wide association analysis, respectively: 1,069 multiplex families genotyped on the Affymetrix 10 K platform, and 1,129 autism trios genotyped on the Illumina 1 M platform. We set out to exploit this unique pair of resources by analyzing the combined data with a novel statistical method, based on the PPL statistical framework, simultaneously searching for linkage and association to loci involved in autism spectrum disorders (ASD). Our analysis also allowed for potential differences in genetic architecture for ASD in the presence or absence of lower IQ, an important clinical indicator of ASD subtypes. We found strong evidence of multiple linked loci; however, association evidence implicating specific genes was low even under the linkage peaks. Distinct loci were found in the lower IQ families, and these families showed stronger and more numerous linkage peaks, while the normal IQ group yielded the strongest association evidence. It appears that presence/absence of lower IQ (LIQ) demarcates more genetically homogeneous subgroups of ASD patients, with not just different sets of loci acting in the two groups, but possibly distinct genetic architecture between them, such that the LIQ group involves more major gene effects (amenable to linkage mapping), while the normal IQ group potentially involves more common alleles with lower penetrances. The possibility of distinct genetic architecture across subtypes of ASD has implications for further research and perhaps for research approaches to other complex disorders as well.     

Thrombolysis for Restoration of Patency to Haemodialysis Central Venous Catheters: A Systematic Review

Urokinase, previously used to restore patency to thrombosed haemodialysis catheters, is now unavailable in North America.We performed systematic reviews of four questions related to the safety and efficacy of alternative agents for catheter thrombolysis, searching Medline and the Cochrane Controlled Clinical Trials Register.In dialysis patients, large case series have documented that urokinase is safe and effective (>70%% efficacy for catheter instillation, and >80%% for systemic lysis). Experience with streptokinase is limited and allergic complications develop with repeated use. Studies of catheter instillation with 1–2[emsp4 ]mg of tPA per lumen reported short-term success in 83–98%% of uses. One non-peer-reviewed study described 44–59%% success using systemic tissue plasminogen activator (tPA), 2.5[emsp4 ]mg through each of 2 lumens, over 1[emsp4 ]h. Meta-analysis of randomized comparisons of urokinase and tPA as full-dose thrombolytic agents suggested that 1[emsp4 ]mg tPA was likely equivalent in thrombolytic potency to 36,000 units urokinase. In nondialysis populations, four case series suggested that catheter instillation with 0.5–2[emsp4 ]mg tPA was effective and safe in reestablishing patency, and a randomized controlled trial found 2–4[emsp4 ]mg tPA more effective than 5,000–10,000 units urokinase. No complications have been reported in any patient treated with systemic or local tPA for catheter thrombolysis. In studies of fistula thrombolysis with 5–50[emsp4 ]mg tPA major complications occurred in one episode in 130 patients treated.This review suggests that 1–2[emsp4 ]mg/lumen tPA is a suitable dose for catheter instillation and likely to be more effective than 5000 units/lumen urokinase. Systemic lysis with 5–10[emsp4 ]mg tPA is likely to be safe and effective in suitably selected patients. Further studies are needed.