Electrical stimulation restores the specificity of sensory axon regeneration

Electrical stimulation at the time of nerve repair promotes motoneurons to reinnervate appropriate pathways leading to muscle and stimulates sensory neurons to regenerate. The present experiments examine the effects of electrical stimulation on the specificity of sensory axon regeneration. The unoperated rat femoral cutaneous branch is served by 2-3 times more DRG neurons than is the muscle branch. After transection and repair of the femoral trunk, equal numbers of DRG neurons project to both branches. However, 1 h of electrical stimulation restores the normal proportion of DRG neurons reinnervating skin and muscle. To ask if the redistribution of stimulated neurons results from enhanced specificity of target reinnervation, we developed a new technique of sequential double labeling. DRG neurons projecting to the femoral muscle branch were prelabeled with Fluoro Gold 2 weeks before the nerve was transected proximally and repaired with or without 1 h of 20-Hz electrical stimulation. Three weeks after repair, the muscle nerve was labeled a second time with Fluororuby. The percentage of regenerating neurons that both originally served muscle and returned to muscle after nerve repair increased from 40% without stimulation to 75% with stimulation. Electrical stimulation thus dramatically alters the distribution of regenerating sensory axons, replacing normally random behavior with selective reinnervation of tissue-specific targets. If the enhanced regeneration specificity resulting from electrical stimulation is found to improve function in a large animal model, this convenient and safe technique may be a useful adjunct to clinical nerve repair.     

Administration of diazepam during status epilepticus reduces development and severity of epilepsy in rat

Prevention of epileptogenesis after brain insults, such as status epilepticus (SE), head trauma, or stroke, remains a challenge. Even if epilepsy cannot be prevented, it would be beneficial if the pathologic process could be modified to result in a less severe disease. We examined whether early discontinuation of SE reduces the risk of epilepsy or results in milder disease. Epileptogenesis was triggered with SE induced by electrical stimulation of the amygdala. Animals (n = 72) were treated with vehicle or diazepam (DZP, 20 mg/kg) 2 h or 3 h after the beginning of SE. Electrode-implanted non-stimulated rats served as controls for histology. All animals underwent continuous long-term video-electroencephalography monitoring 7-9 weeks and 11-15 weeks later to detect the occurrence and severity of spontaneous seizures. As another outcome measure, the severity of hippocampal damage was assessed in histologic sections. In the vehicle group, 94% of animals developed epilepsy. DZP treatment reduced the percentage of epileptic animals to 42% in the 2-h DZP group and to 71% in the 3-h DZP group (p < 0.001 and p < 0.05 compared to the vehicle group, respectively). If epilepsy developed, the seizures were less frequent in DZP-treated animals compared to the vehicle group (median 16.4 seizures/day), particularly in the 2-h DZP group (median 0.4 seizures/day). Finally, if DZP treatment was started 2 h, but not 3 h after SE, the severity of hippocampal cell loss was milder and the density of mossy-fiber sprouting was lower than in the vehicle group. These data indicate that treatment of SE with DZP within 2 h reduces the risk of epilepsy later in life, and if epilepsy develops, it is milder.     

Topiramate add-on in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial

OBJECTIVE: We tested the hypothesis that topiramate is more effective than placebo in reducing symptoms in patients with treatment-resistant schizophrenia when combined with ongoing antipsychotic medication. METHOD: Twenty-six hospitalized treatment-resistant patients with chronic DSM-IV-diagnosed schizophrenia participated in a randomized, double-blind, placebo-controlled trial in which 300 mg/day of topiramate was gradually added to their ongoing treatment (clozapine, olanzapine, risperidone, or quetiapine) over two 12-week crossover treatment periods. Data were collected from April 2003 to November 2003. RESULTS: In intention-to-treat analysis, topiramate was more effective than placebo in reducing Positive and Negative Syndrome Scale general psychopathologic symptoms (effect size = 0.7, p = .021), whereas no significant improvement was observed in positive or negative symptoms. CONCLUSION: Glutamate antagonist topiramate may be an effective adjuvant treatment in reducing general psychopathologic symptoms in patients with schizophrenia resistant to treatment with second-generation antipsychotics.     

Attention orienting by another's gaze direction in children with autism

BACKGROUND: The aim of this study was to investigate attention orienting triggered by another's gaze direction in autism. METHOD: Twelve high-functioning children with autism and gender- and age-matched normal control children were studied using two tasks. In the first task, children were asked to detect laterally presented target stimuli preceded by centrally presented facial cue stimuli in which gaze was either straight ahead or averted. The direction of the cue was either congruent, neutral, or incongruent with respect to the laterality of the target stimulus. In the second task, children were asked to discriminate the direction of eye gaze. RESULTS: The results showed that another person's static gaze direction triggered an automatic shift of visual attention, both in children with autism and in normally developing children. The children in both groups were also able to overtly discriminate the direction of the gaze. CONCLUSION: These results seem to suggest that, in children with autism, the visual system processes information about another person's gaze direction and sends this information to those areas that subserve reflexive attention orienting. However, future studies are needed to investigate whether the processing of eyes and gaze direction relies on similar neural mechanisms in children with autism and in normally developing children.     

The anti-inflammatory effect of diazoxide in coronary artery bypass grafting

Many therapeutic strategies have been designed to suppress the inflammatory response in patients undergoing coronary artery bypass grafting (CABG). Pharmacological preconditioning with diazoxide is an alternative in effective cardioprotective strategies, but more evidence is required to show its effect on the inflammatory response. Forty patients with stable angina who were scheduled for isolated elective CABG operations were randomized into control and diazoxide (DZX) groups. In the DZX group, 1.5 mg/kg diazoxide was infused intravenously in 5 min followed by a 5-min washout before commencing the cardiopulmonary bypass. In the control group, placebo infusion was given similarly. Blood samples for cytokine measurement were collected from the radial artery and coronary sinus perioperatively, and hemodynamic data were recorded. Thirty-six patients fulfilled the data collection. Cardiac index (CI) increased in both groups over time as compared with baseline. In the DZX group, the increase of CI was greater than that in the control group (P = 0.002). Systemic and coronary sinus plasma levels of IL-6, IL-8, and IL-10 increased significantly after reperfusion in both groups as compared with baseline (P < 0.05). IL-6 and IL-8 both reached the peak value at 6 h after cardiopulmonary bypass. IL-10 reached peak level at 20 min after reperfusion in both groups. There was significantly higher IL-10 in DZX groups (P = 0.015). The ratios of IL-6 to IL-10 and IL-8 to IL-10 were significantly lower in DZX groups than in controls (P = 0.025 and P = 0.041 for each, respectively). Pharmacological preconditioning with DZX in CABG patients shifts the circulating inflammatory cytokine balance toward the anti-inflammatory direction.     

Antiarrhythmic Effect of Ischemic Preconditioning in Recent Unstable Angina Patients Undergoing Coronary Artery Bypass Grafting

Coronary artery bypass grafting (CABG) for unstable angina pectoris patients results in a higher incidence of arrhythmia and higher arrhythmic cardiac mortality. Ischemic preconditioning (IP) has proved effective in suppressing ischemia reperfusion arrhythmias in animals and in humans. The purpose of the present study was to investigate whether IP protects against postoperative arrhythmias in recent unstable angina patients undergoing urgent CABG. Forty-one patients with recent unstable angina and three-vessel coronary artery disease admitted for CABG were randomized into an IP group and a control group. The IP protocol involved twice occluding the ascending aorta with a cross-clamp for 2 minutes, followed by 3 minutes of reperfusion. Twenty-four-hour continuous electrocardiography (24-h ECG) was recorded from the preoperative day to the 2nd postoperative day. The incidences of supraventricular extrasystole (SVES), ventricular extrasystole (VES), supraventricular tachycardia (SVT), and ventricular tachycardia (VT) were 95.2%, 85.7%, 26.2%, and 26.2%, respectively, before surgery and 100.0%, 100.0%, 88.1%, and 76.2%, respectively, after surgery. IP significantly reduced the incidence of VT and the severity of SVES, VES, SVT, and VT after surgery. The period of mechanical ventilation and the length of stay in the intensive care unit were significantly shorter in the IP group. In summary, rhythm disturbances are common in CABG patients with recent unstable angina. IP significantly reduces rhythm disturbances, including SVES, VES, SVT, and VT after CABG. The findings indicate that IP could constitute an additional myocardial protective strategy in recently unstable angina patients undergoing CABG.     

Pulmonary artery blood temperature at admission to the intensive care unit is predictive of outcome after on-pump coronary artery bypass surgery

OBJECTIVE: To evaluate whether pulmonary artery blood (PA) temperature on admission to the intensive care unit (ICU) is predictive of postoperative outcome after isolated on-pump coronary artery bypass grafting (CABG). DESIGN: A retrospective study on 1639 patients who underwent isolated on-pump CABG in whom PA temperature at admission to the ICU was available for review. RESULTS: Thirty-three patients (2.0%) died during the in-hospital stay and 87 patients (5.3%) developed low cardiac output syndrome. PA temperature at admission to the ICU was significantly associated with an increased risk of overall postoperative death (p = 0.002), cardiac death (p = 0.03), and low cardiac output syndrome (p < 0.0001), and was significantly correlated with prolonged length of ICU stay (p < 0.0001) and postoperative bleeding (p = 0.001). Patients with high PA temperature had significantly more severe comorbidities, and longer aortic cross-clamping and cardiopulmonary bypass time. The receiver operating characteristic curve showed that PA temperature at admission to the ICU in predicting postoperative death had an area under the curve of 0.660 (p = 0.002) and its best cut-off value was 36.4 degrees C (sensitivity: 63.6%, specificity: 65.2%). When the PA temperature at admission to the ICU was > or = 36.4 degrees C, the postoperative mortality and low cardiac output syndrome rates were 3.6 and 8.3%, whereas they were 1.1 and 3.7% when the PA temperature at admission to the ICU was < 36.4 degrees C (p = 0.001, p < 0.0001), respectively. CONCLUSION: Patients having a PA temperature > or =36.4 degrees C at admission to the ICU after CABG seem to be at higher risk of poor postoperative outcome.     

Cyclic time patterns of death from suicide in northern Finland

BACKGROUND: Time patterns of suicide have been attributed not only to social and psychological factors but also to direct geophysical effects. Seasonal variations in day length and temperature seem likely to contribute to the timing of the suicide process. METHODS: We analysed all suicides (n=1658) committed in a northern province of Finland during a period of 153 months. Daily data on the number of suicides, local weather conditions and geomagnetic storms were compiled and modelled with Poisson regression using the province population as the denominator, and with the means of harmonic series for seasonal variation. Time series analysis of monthly numbers of suicides was carried out using the seasonal-trend decomposition procedure based on loess. RESULTS: Marked fluctuations in the number of suicides occurred during the study period (P=0.01). There was significant seasonal variation in death from suicide (P=0.01), but analysis of the meteorological data showed no evidence of effect on the risk of suicide. LIMITATIONS: Assessment of mental disorder or alcohol consumption was missing, since only data derived from death certificate was available for each case. CONCLUSIONS: The seasonal effect was significant, but remained modest compared to sex and age as risk factors for suicide. Preventive measures need to be tailored according to time of the year.