Introduction: Visual orientation and attention are impaired in schizophrenia. Engagement and disengagement of attention and the ability to prompt responses to a stimulus in patients before and after six weeks of risperidone were compared to controls.Methods: Ten unmedicated (nine naive) schizophrenic patients, and eleven controls performed 1) A visual orienting task, the Cued Target Detection task (CTD), with the detection of a visual stimulus in valid, invalid, no cue and double cue trials, two conditions for fixation offset for a modulation of visual fixation: Gap: 200 ms before target; No Gap: simultaneous with target, 2) Choice Reaction Time (CRT 0.5 and 2 s delays). Results: At baseline, patients showed longer RT than controls in CRT, but not in CTD, with in CTD, no facilitation of RT with the gap procedure. The alertness index was almost null in CTD-Gap and comparable to controls in CTD-No Gap. Efficiency to detect attended stimuli (CTD-No Gap) and warning effect (CRT 0.5 s) were negatively correlated to disorganization. After treatment, readiness to act in CRT had decreased. In CTD-No Gap, change in PANSS disorganization was correlated to an increased validity index, change in negative sub-score was correlated to decreased attention cost.Conclusion: Untreated patients displayed a deficit of Gap effect and a slowing in sustained attention. Disorganization interfered with warning and visual detection. After treatment, its improvement and negative symptoms improvement were associated with better visual detection. These alterations in visual orienting provide new evidence for an oculomotor dysregulation of attentional engagement in schizophrenia. (C) 2009 Elsevier Inc. All rights reserved.

OBJECTIVE:To investigate the efficacy and tolerability of direct initiation of long-acting injectable risperidone (LAIR) in adults with schizophrenia or other psychotic disorders requiring a change of treatment.METHODS:Patients clinically stable for one month or more on their previous medication received 25 mg of LAIR (increased to 37.5 or 50 mg, if necessary) every 14 days for six months.RESULTS:Of 202 patients (70% male, mean age 38 years), the majority (86%) had DSM-IV schizophrenia (mainly paranoid). Previous treatments were atypical antipsychotics (65%), depot (34%) and oral (9%) conventional neuroleptics. Mean total positive and negative syndrome scale (PANSS) score was significantly reduced from baseline to treatment endpoint (79.4 versus 68.3, P<0.001), as were all subscale and symptom factor scores. The clinical global impression-disease severity (CGI-S), general assessment of functioning (GAF), health-related quality of life (SF-36) and patient satisfaction with treatment were also improved significantly. At endpoint, 31% rated the treatment as 'very good' compared with 8% at baseline. The total extrapyramidal symptoms rating scale (ESRS) and Parkinsonism subscale scores were reduced significantly (P<0.001) from baseline at one month and further improved until treatment endpoint.CONCLUSION:LAIR significantly improved disease symptoms, patient functioning, movement disorders, health-related quality of life and treatment satisfaction. It therefore provides a useful option for the management of patients with psychotic disorders.

This study assessed the safety and effectiveness of the atypical antipsychotic olanzapine for the treatment of inpatients with acute schizophrenia. Furthermore, we evaluated patterns of use of olanzapine and their relationship to safety and effectiveness.This was a prospective, comparative, nonrandomized, open-label, observational study of 848 patients with schizophrenia (International Classification of Diseases, 10th edition) hospitalized due to an acute psychotic episode. Data were collected during patients’ entire hospital stay. Safety of antipsychotic therapy was assessed with an extrapyramidal symptoms questionnaire (based on the Udvalg for Kliniske Undersøgelser scale) and the report of spontaneous adverse events. Clinical status was assessed with the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions-Severity of Illness (CGI-S). A multivariate statistical approach was employed.Patients treated with olanzapine in monotherapy had the lowest risk of developing extrapyramidal symptoms (11.2%), whereas patients treated with conventional antipsychotics had a higher risk (39.0%; p < 0.001). Patients treated with olanzapine in monotherapy (even patients with prominent positive symptoms) displayed a higher rate of response compared with conventional antipsychotics-treated patients (p =.007).Olanzapine is a safe and effective treatment for patients with acute schizophrenia in the hospital setting, even for patients with prominent positive or agitation symptoms.Este estudio evaluó la seguridad y la efectividad del antipsicótico atípico olanzapina en el tratamiento hospitalario de la esquizofrenia, así como los patrones de uso de olanzapina y su relación con la seguridad y la efectividad.Se trató de un estudio prospectivo, comparativo, no aleatorizado, abierto, observacional, de 848 pacientes con esquizofrenia (Clasificación Internacional de Enfermedades, décima edición) hospitalizados a causa de un episodio psicótico agudo. Los datos se recogieron durante la totalidad de su estancia hospitalaria. La seguridad del tratamiento antipsicótico se evaluó mediante un cuestionario de síntomas extrapiramidales basado en la escala Udvalg for Kliniske Undersøgelser, así como mediante la recogida de efectos adversos autorreferidos por el paciente. La situación clínica se evaluó mediante la Escala Breve de Evaluación Psiquiátrica (BPRS) y la escala de Impresión Clínica Global-Severidad de la Enfermedad (CGIS). Se utilizó un método estadístico multivariante.Los pacientes tratados con olanzapina en monoterapia mostraron el menor riesgo de desarrollar síntomas extrapiramidales, mientras que los tratados con antipsicóticos convencionales mostraron el mayor riesgo (p < 0,001). Los pacientes tratados con olanzapina en monoterapia (incluso aquellos con síntomas positivos prominentes) demostraron una mayor tasa de respuesta que los tratados con antipsicóticos convencionales (p = 0,007).La olanzapina constituye un tratamiento seguro y efectivo para pacientes con un episodio agudo de esquizofrenia tratados en el ámbito hospitalario, incluso para aquellos con síntomas positivos o de agitación prominentes.

Long-term administration of macrolideantibiotics reduces sputum production in patients with chronic airwaydiseases, probably by inhibiting airway inflammation. The objective ofthe present study was to determine the acute effects of a macrolide onairway chloride secretion and sputum production.We first investigated the effect of erythromycintreatment on chloride diffusion potential difference (CPD) acrosstracheal mucosa in vivo. Next, we conducted adouble-blind, parallel-group study examining the effect of 7 days oftreatment with clarithromycin (400 mg/d), amoxicillin (1,500 mg/d), orcefaclor (750 mg/d) in patients with chronic bronchitis orbronchiectasis without apparent respiratory infection.IV administration of erythromycin decreased the CPD of rabbit tracheal mucosa in a dose-dependent manner. Treatment ofpatients with clarithromycin decreased sputum production, whereasamoxicillin and cefaclor treatment had no effect. The percentage ofpatients whose sputum decreased > 30% from baseline (responders) was38% in the clarithromycin group, 7% in the amoxicillin group, and 0%in the cefaclor group. During treatment with clarithromycin, the sputumsolid composition increased and chloride concentration decreased inresponders, but these changes were not observed in nonresponders.Short-term administration of 14-memberedmacrolide reduces chronic airway hypersecretion, presumably byinhibiting chloride secretion and the resultant water secretion acrossthe airway mucosa.

Composition of Indian Russell's viper (Daboia russelii russelii) venom, a medically important snake and member of “Big Four” snakes of India was done by gel filtration chromatography followed by tandem mass spectrometry. The MS/MS analyses of tryptic digested gel filtration peaks divulged the presence of 63 different proteins belonging to 12 families. Phospholipase A2 (PLA2), serine proteases, metalloproteases, cysteine-rich secretory proteins, l-amino acid oxidase, C-type lectin-like proteins, kunitz-type serine protease inhibitor, disintegrin, nucleotidase, phosphodiesterase, vascular endothelial growth factor and vascular nerve growth factor families were identified. PLA2 enzymes with isoforms of N-, S- and H-type based on their first N-terminal amino acid residue were observed. The venom is also found to be rich in RVV-X, RVV-V and thrombin-like enzymes. Homologues of disintegrins with RGD and RTS motifs were also observed. The high percentage of PLA2 and proteases in the venom proteome could be responsible for the observed coagulopathy, haemorrhage and edema which can be correlated with the clinical manifestations of Russell's viper envenomation. This is the first proteomic analysis of Indian D. russelii venom which might assist in understanding the pathophysiological effects of viper envenomation. Such study will also be important for developing more effective antivenom for viper bite management.

This report presents data from the extension phase of a 6-month trial that evaluated the efficacy of risperidone long-acting injectable (RLAI) in stable psychotic patients requiring a treatment change. Patients continued to receive RLAI every 2 weeks for a maximum of 12 months from study entry. Symptoms were assessed using the PANSS after 1, 3, 6, 9 and 12 months of treatment (or treatment endpoint). Remission of severity criteria were defined as ≤3 points in all PANSS items suggested by the Remission in Schizophrenia Working Group. 715 patients (63% male) entered the extension phase and 508 completed the 12-month study. The mean PANSS total score at Day 0 was 74.9±22.7. This was significantly reduced after 1 month (67.7 ±22.3, p≤0.001), with continued improvements over the 12 months of the study until treatment endpoint (59.7±21.9). Significant improvements from Day 0 to endpoint were also seen in the scores for all PANSS subscales and symptom factors. The proportion of patients who met the PANSS severity criteria for remission increased from 29% at Day 0 to 60% at endpoint, and the proportion of patients who met these criteria for ≤ 6 months increased from 24% at Month 6 to 45% at endpoint. Treatment with RLAI for up to 12 months provided significant and sustained improvements in symptom control in patients with schizophrenia. These improvements may help patients to achieve and remain in remission.

The single dose pharmacokinetic profiles of long-acting injectable (LAI) risperidone and oral risperidone were extrapolated to steady-state. Plasma concentrations of the active moiety (unchanged risperidone + 9-hydroxy-risperidone) were measured by radioimmunoassay up to 72 h after a single oral 1 mg dose of risperidone in healthy volunteers (n = 12), and up to 84 days after a single intramuscular injection of 50 mg LAI risperidone in schizophrenic patients (n = 26). These data were projected to multiple dose regimens (4 mg/day for the oral formulation and 50 mg every 2 weeks for LAI formulation) using the software package WinNonlin, and average steady-state pharmacokinetic profiles were predicted. The most interesting results, obtained at steady-state, were a lower predicted peak plasma level (46 vs. 62 ng/ml) and a lower predicted degree of fluctuation between Cssmax and Cssmin (53 vs 145%) with LAI compared to oral administration, which is in line with actual steady state data on LAI risperidone. In conclusion, the pharmacokinetic profile of LAI risperidone administered every 2 weeks ensures a steady-state profile with concentrations falling in the interval observed with an equivalent oral dose but with lower and less fluctuations (i.e. 1/2 weeks vs 1/day).

Objective:To assess the efficacy and safety of long-acting injectable risperidone(LAIR) in patients with schizophrenia.Methods:A total of 48 schizophrenia patients with symptoms lasting over 1 year were collected,and treated with LAIR and oral risperidone tablets for 4 weeks followed by LAIR alone for 8 weeks.The efficacy was evaluated using the Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression Scales for severity(CGI-S) and Personal and Social Performance Scale(PSP).The adverse reactions were evaluated using the TESS,AIMS,BARS Scale,laboratory indexes,vital signs,medical and electrocardiographic examinations.Results:After treatment with LAIR alone for 8 weeks,the total effective rate(PANSS reduced ≥30%)was 80.5% ;mean reduction in CGI-S was 2.1 ;the rate of patients with increased PSP ≥7 was 85.32%.LAIR mildly affected weight-gain profile and caused less extrapyramidal reactions.There were no significant changes in vital signs,medical and electrocardiographic examinations,but 7.0% patients had an increase in glutamate pyruvate transaminase(GPT) activity.Conclusions:LAIR significantly improves the social performance in patients with schizophrenia,and can be used as the first line antipsyehotie for monotherapy.

PURPOSE:To study the pharmacokinetics of topiramate (TPM) at steady state in children younger than 4 years comedicated with other antiepileptic drugs (AEDs). METHODS:Twenty-two children aged 6 months to 4 years with pharmacoresistant partial or generalized epilepsy were enrolled in an open-label prospective study. Children were assigned to different groups according to comedication with enzyme-inducing AEDs (n = 8), valproic acid (VPA) (n = 6), or other AEDs not known to affect drug metabolism (neutral AEDs, n = 7). One child was receiving treatment with both enzyme-inducing AEDs and VPA. After dose titration, blood samples were collected at steady state just before and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 h after the morning dose of TPM. Pharmacokinetic parameters were determined by a noncompartmental method. RESULTS:TPM apparent oral clearance (CL/F) was significantly higher in children taking enzyme-inducing AEDs (85.4 +/- 34.0 ml/h/kg) than in those receiving VPA (49.6 +/- 13.6 ml/h/kg) or neutral AEDs (46.5 +/- 12.8 ml/h/kg). Conversely, dose-normalized areas under the plasma TPM concentration curves (0-12 h) were significantly lower in enzyme-induced patients than in patients receiving VPA or other AEDs. CONCLUSIONS:Compared with children not receiving enzyme inducers, children younger than 4 years who receive concomitant enzyme-inducing AEDs need higher doses (milligrams per kilogram) to achieve comparable plasma TPM concentrations.

In order to evaluate the attractiveness of France for conducting international clinical trials, a survey was performed among pharmaceutical companies that are based in France or that have affiliates in France. The survey concerned international phase II and III clinical studies carried out in 2002 and 2003. Ten pharmaceutical companies representing 36% of the French market completed the survey. 134 trials were analysed in total. France recruited 8.3% of the overall number of patients recruited, and 15.0% of those recruited within Europe. France was within the overall mean with regard to the percentage of active centres (78.5% versus 79.5%) and the percentage of patients evaluable according to protocol (86.8% versus 87.3%). In contrast, France ranked within the last third of analysed countries with respect to the speed of recruitment (1.5 versus 1.9 patients/centre/month), and the number of queries per observation (16.8 versus 10.9). The analysis of the qualitative indicators of performance showed that, although the perception of pharmaceutical companies towards the quality of French medicine and administrative authorities is positive, France notably needs to improve the productivity of its clinical research in order to enhance its attractiveness for the pharmaceutical sponsors of clinical trials.