Low dose zolmitriptan as a 5-HT neuroendocrine challenge agent in humans

The 5-HT1B/D agonist sumatriptan has been used in a number of studies as a neuroendocrine challenge agent. Whether its neuroendocrine effects are centrally mediated is unclear, however, since sumatriptan shows minimal penetration of the central nervous system. Zolmitriptan shows a greater penetration into the central nervous system than sumatriptan, and has recently been shown to be an effective challenge agent. In order to determine the neuroendocrine, temperature and side effects of a 2.5 mg oral dose of zolmitriptan, 17 healthy volunteers underwent a placebo controlled, repeated measures, double blind neuroendocrine challenge. Zolmitriptan or placebo were administered, and cortisol, growth hormone, prolactin, blood pressure and temperature, were measured over four hours after the dose of zolmitriptan. Zolmitriptan at this dose was well tolerated by all subjects, with minimal side effects and only minor effects on blood pressure. There was a significant increase in serum growth hormone after zolmitriptan compared to placebo, however there were no significant effects on cortisol, prolactin or oral temperature. The neuroendocrine effects of 2.5 mg of orally administered zolmitriptan are similar to previously reported effects of sumatriptan, with minimal side effects.     

Effect of the anxiolytic drug buspirone on prolactin and corticosterone secretion in stressed and unstressed rats

Buspirone is an atypical anxiolytic drug that exerts its action at a receptor site other than the GABA-benzodiazepine-chloride ionophore complex. The present study examined the effect of buspirone on plasma prolactin and corticosterone levels in both control and stressed rats. In unstressed rats, buspirone produced dose-dependent increases in plasma prolactin and corticosterone levels. The minimal doses of buspirone which led to significant elevations in plasma prolactin and corticosterone levels were 1.0 and 2.0 mg/kg (IP), respectively. The effect of buspirone on both hormones was maximal 30 minutes after injection. The plasma levels of prolactin and corticosterone were significantly elevated in rats that were stressed using a conditioned fear paradigm. Buspirone produced a dose-dependent attenuation of the stress-induced increase in prolactin secretion. The stress-induced increase in corticosterone secretion was inhibited by the 0.5 mg/kg (IP) dose but not by the 2.0 mg/kg (IP) dose of buspirone, which increased corticosterone secretion both in stressed and unstressed rats. These data suggest that the effect of buspirone on plasma prolactin and corticosterone levels may be mediated by two different mechanisms of action.     

An echo-cardiographic (M-mode & 2D) analysis of thalassaemia major

25 cases of thalassaemia major were studied by 2D and M-mode echocardiography. A significantly increased (p less than 0.001) mean value (100.8 +/- 27.37 msec, range 80 to 140 msec) of A2-E (early relaxation period) interval on M-mode was observed in thalassemia in comparison to mean level (82.6 +/- 5.7, range 60 to 100 msec) of control population. No significant differences were noted in FS % (fractional shortening) and EF% (ejection fraction) when compared to corresponding normal values respectively. Mean serum iron concentration (142.2 +/- 29.1 micrograms/dl, range 102 to 192 micrograms/dl) was significantly higher in thalassaemia as compared to normal population (mean 106.3 +/- 11.4 micrograms/dl, range 75 to 120 micrograms/dl). There was also a direct correlation between serum iron concentration and A2-E interval. 11 patients (44%) showed abnormal A2-E interval but only 3 patients (12%) showed abnormal percentage of FS and EF. It is therefore concluded that A2-E interval will help to detect early left ventricular dysfunction much before overt and irreversible heart failure becomes manifest and which will also help to optimise transfusion and chelation therapy.     

Association of HLA phenotype with primary non-response to recombinant hepatitis B vaccine: a study from north India.

The hepatitis B vaccine is considered to be highly immunogenic and has a good safety profile. In adults, it has a primary non-response rate of 5%-10%. Causes of nonresponse to hepatitis B vaccine include age, sex, obesity smoking. Certain human leucocyte antigen (HLA) phenotypes have been known to be associated with responsiveness to the vaccine, and found to be different in different ethnic groups, such as Caucasians and Orientals. The study was designed to identify the HLA phenotypes that are associated with non-responsiveness to hepatitis B virus (HBV) vaccination amongst a cohort of Indian subjects who agreed to participate in the vaccination programme. The study was offered to 107 volunteers, of whom 102 were found to be negative for HBV markers (hepatitis B surface antigen [HBsAg], anti-HBc, anti-HBe, anti-HBs, hepatitis Be antigen [HBeAg]) . All 102 volunteers were offered recombinant hepatitis B vaccine (20 microg) at 0, 1, and 6 months. Anti-HBs antibody titres were tested on days 90 and 210 of the first vaccine dose. HLA typing was done using standard microlymphotoxicity tests. The seroconversion rate of the hepatitis B vaccine was 86.3% (88/102). Fifteen nonresponders (15/102) and 15 of the 88 responders were randomly selected after age and sex matching for the purpose of studying the HLA phenotypes. HLA subtypes A1, B15, B40, A10 and DQ2 were found to be increased among nonresponders while HLA- A11, C3, DR10, DR51 (p>0.05) were the most common phenotypes amongst the responders. Further studies are needed to characterize the HLA phenotypes amongst the responders in different ethnic groups in India with respect to HBV vaccination.     

A successful anticoagulation protocol for the first HeartMate II implantation in the United States

Bleeding and thrombus formation are common problems with life-threatening implications in patients receiving a left ventricular assist device. We describe the anticoagulation protocol for the 1st patient in the United States to undergo successful implantation of the HeartMate II left ventricular assist system.     

Probiotics ameliorates LPS induced neuroinflammation injury on Aβ 1–42, APP, γ-β secretase and BDNF levels in maternal gut microbiota and fetal neurodevelopment processes

Metabolic Brain Disease - The gut microbiota influences brain development and functioning through the gut-brain axis. This is first study regulate maternal gut microbiota and fetal neurodevelopment...     

Postoperative atrial fibrillation and mortality after coronary artery bypass surgery

OBJECTIVES: We sought to determine if the occurrence of postoperative atrial fibrillation (AF) affects early or late mortality following coronary artery bypass surgery (CABG). BACKGROUND: Atrial fibrillation is the most common arrhythmia seen following CABG. METHODS: The Texas Heart Institute Cardiovascular Research Database was used to identify all patients that developed AF after isolated initial CABG from January 1993 to December 1999 (n = 994). This population was compared with patients who underwent CABG during the same period but did not develop AF (n = 5,481). In-hospital end points were adjusted using logistic regression models to account for baseline differences. Long-term survival was evaluated using a retrospective cohort design, where Cox proportional hazards methods were used to adjust for baseline differences, and with case-matched populations (n = 390, 195 per arm). RESULTS: Atrial fibrillation was diagnosed in 16% of the population. Postoperative AF was associated with greater in-hospital mortality (odds ratio [OR] 1.7, p = 0.0001), more strokes (OR 2.02, p = 0.001), prolonged hospital stays (14 vs. 10 days, p < 0.0001), and a reduced incidence of myocardial infarction (OR 0.62, p = 0.01). At four to five years, survival was worse in patients who developed postoperative AF (74% vs. 87%, p < 0.0001 in the retrospective cohort; 80% vs. 93%, p = 0.003 in the case-matched population). On multivariate analysis, postoperative AF was an independent predictor of long-term mortality (adjusted OR 1.5, p < 0.001 in the retrospective cohort; OR 3.4, p = 0.0018 in the case-matched population). CONCLUSIONS: The occurrence of AF following CABG identifies a subset of patients who have a reduced survival probability following CABG. The impact of various strategies, such as antiarrhythmics and warfarin, aimed at reducing AF and its complications deserves further study.