Strychnine-blocked glycine receptor is removed from synapses by a shift in insertion/degradation equilibrium

The long-term inhibition by strychnine of glycine receptor activity in neurons provokes the receptor's selective intracellular accumulation and disappearance from synapses. This could result either from a disruption of the postsynaptic anchoring of the receptor or from an arrest of its exocytic transport. In this study we combined biochemical and fluorescence microscopy analyses to determine on a short time scale the fate of the strychnine-inactivated glycine receptor. Quantification of the cellular content of receptor showed that the rapid accumulation depends on protein synthesis. Cell surface biotinylation of neurons demonstrated that strychnine did not accelerate the turnover rate of the receptor. Labeling of endosomes indicated that, in strychnine-treated cells, the accumulated receptor is not blocked in the endosomal transport pathway. Taken together, these results indicate that strychnine does not destabilize the postsynaptic receptor but triggers its disappearance from synapses by a nondegradative sequestration of newly synthesized molecules in a nonendocytic compartment.     

Deteriorating ischaemic stroke. cytokines,soluble cytokine receptors,ferritin, systemic blood pressure,body temperature,blood glucose,diabetes, stroke severity,and CT infarction-volume as predictors of deteriorating ischaemic stroke

The immune reactivity implicated in the pathogenesis of Guillain-Barré syndrome (GBS) and related diseases, which occur following infection with specific strains of Campylobacter jejuni bearing sialylated lipopolysaccharide structures that cross-react with specific gangliosides, is consistent with provocation of inflammation via molecular mimicry. In this review, we have focused upon microbial characteristics and structures, the fine structure of the essential carbohydrate determinants, and the application of our proposed criteria, modified from those of Koch for causation of infectious and of Witebsky for autoimmune diseases, to the circumstance of infectious induction of autoimmune disorder.     

Time trends in organ position and volume in patients receiving prostate three-dimensional conformal radiotherapy.

Using multiple computed tomography (CT) scans, 50 patients undergoing prostate radiotherapy were tested for clinically significant time trends in the target and surrounding critical structures. Significant trends were observed toward increasing bladder volume and increasing bowel-to-planning target volume separation; however, no trends were observed in the prostate, seminal vesicles, or rectum. The subset of patients undergoing hormone therapy was also tested and did not independently exhibit any significant time trends.     

Patient characteristics associated with differences in patients' evaluation of their general practitioner

Background  

Knowledge of the extent to which patient characteristics are systematically associated with variation in patient evaluations will enable us to adjust for differences between practice populations and thereby compare GPs. Whether this is appropriate depends on the purpose for which the patient evaluation was conducted. Associations between evaluations and patient characteristics may reflect gaps in the quality of care or may be due to inherent characteristics of the patients. This study aimed to determine such associations in a setting with a comprehensive list system and gate-keeping.     

Long Term Follow-up of HNPCC Gene Mutation Carriers: Compliance with Screening and Satisfaction with Counseling and Screening Procedures

Hereditary non polyposis colorectal cancer (HNPCC) is a hereditary predisposition to colorectal and endometrial cancer, caused by mutations of the mismatch repair (MMR) genes MSH2, MLH1 and MSH6. Regular colonoscopy reduces the incidence of colorectal cancer in mutation carriers dramatically. The aim of this study was to evaluate the use of colonoscopy by proven HNPCC mutation carriers. We also evaluated the satisfaction with the counseling and screening procedures at the long term. A questionnaire survey was performed among 94 proven MMR gene mutation carriers. Data were analyzed using univariate and multivariate analysis. The average time of follow-up was 3,5 years (range 0.5–8.5 years). The response rate was 74%. The proportion of unaffected mutation carriers under colonoscopic screening increased from 31 to 88% upon genetic testing, and for gynecological screening from 17 to 69%. However, more than half of the responders experienced colonoscopy as unpleasant or painful. About 97% felt well informed during counseling, and 88% felt sufficiently supported. Ten percent of the responders reported a high cancer worry that was significantly (P = 0.007) associated with a high perceived cancer risk. Six responders (9%) regretted being tested. Remarkably, of 4 of these 6 a close relative died recently of cancer. Problems with obtaining a disability or life insurance or mortgage were experienced by 4 out 10 healthy carriers opting for these services. In conclusion, genetic testing for HNPCC considerably improves compliance for screening, which will result in a reduction of HNPCC-related cancer morbidity and mortality in mutation carriers. Most HNPCC gene mutation carriers cope well with their cancer susceptibility on the long term.     

New antiarrhythmic agents for atrial fibrillation and atrial flutter

Atrial fibrillation is the most common sustained cardiac arrhythmia and is a frequent reason for antiarrhythmic therapy. Existing antiarrhythmic drugs have important side effects and presently the therapy to maintain sinus rhythm is not superior to a strategy of controlling excessive heart rate. This review summarises current strategies to improve antiarrhythmic therapy for atrial fibrillation. The most important strategies are: i) to develop drugs without proarrhythmic effects--development of drugs devoid of QT prolonging potential is the main strategy; ii) multiple channel-blocking drugs--inspired by the efficacy of amiodarone, several drugs are being developed that have similar electrophysiological properties as amiodarone, but without the extracardiac side effects; iii) drugs that act exclusively in the atria--the atria contain specific potassium channels, and several drugs that act only on these channels are in development; and iv) antiarrhythmic therapy without effects on ion channels--inhibition of the renin-angiotensin system and steroid therapy has been shown to have some effect in the treatment of atrial fibrillation. Many drugs are in development and the therapeutic scenario for treatment of atrial fibrillation may change quickly.     

Nitrogen accumulation during closed circuit anesthesia depends on the type of surgery

STUDY OBJECTIVE: The aim of this study is to test the hypothesis that the amount of nitrogen that accumulates within the closed breathing system would be greater during open abdominal surgery than during superficial surgery with small wounds. DESIGN: Prospective, comparative study. SETTING: Operating rooms of a university hospital. PATIENTS: Fourteen American Society of Anesthesiologists physical status I and II adult patients scheduled for abdominal surgery (n = 7) or tympanoplasty (n = 7). INTERVENTIONS: After induction of anesthesia and endotracheal intubation, the patients were denitrogenated for 30 minutes using 100% oxygen at a fresh gas flow of 10 L/min. The breathing system was then closed and patients were anesthetized using 60% xenon in oxygen, supplemented with epidural anesthesia in the abdominal surgery group and sevoflurane in the tympanoplasty group. MEASUREMENTS: Nitrogen concentration in the breathing system was determined by gas chromatography immediately before and 2 hours after the breathing system was closed. MAIN RESULTS: The median (range) increase in nitrogen concentration during the 2-hour period of closed circuit anesthesia was greater in the abdominal surgery patients than in the tympanoplasty patients (6.5% [4.0%-10.2%] vs 2.5% [1.4%-8.4%], P = 0.035, Mann-Whitney U test). CONCLUSIONS: The amount of nitrogen accumulation during closed circuit anesthesia is greater during open abdominal surgery than in superficial surgery such as tympanoplasty. We postulate that during open abdominal surgery, nitrogen in the ambient air enters the body across the peritoneum and then diffuses into the alveoli to be exhaled.