Gepirone extended-release: new evidence for efficacy in the treatment of major depressive disorder

OBJECTIVE: To assess the efficacy and tolerability of the 5-HT(1A) agonist gepirone in extended-release formulation (gepirone-ER) versus placebo in patients with major depressive disorder. METHOD: Patients aged 18 to 70 years were eligible if they satisfied DSM-IV criteria for moderate-to-severe major depressive disorder and had a baseline 17-item Hamilton Rating Scale for Depression (HAM-D-17) score > or = 20. After a 4- to 7-day placebo washout period, patients were randomly assigned to receive either placebo (N = 106) or gepirone-ER (20-80 mg/day) (N = 103) for 56 days. Assessments were done at weeks 1-4, 6, and 8. RESULTS: Mean change from baseline in HAM-D-17 score within the intent-to-treat group (gepirone, N = 101; placebo, N = 103) was significantly greater with gepirone-ER than placebo at weeks 3 (p =.013) and 8 (p =.018). Significantly (p <.05) more patients receiving gepirone-ER than placebo were HAM-D-17 responders at weeks 3 (33.7% vs. 18.8%, respectively) and 4 (38.6% vs. 24.8%, respectively) and HAM-D-17 remitters at weeks 6 (24.8% vs. 13.9%, respectively) and 8 (28.7% vs. 14.9%, respectively). Mean change from baseline for HAM-D-25 total score was significantly (p < pr =.05) greater with gepirone-ER at all assessments except week 6. The proportion of HAM-D-25 responders was significantly greater (p < or =.05) with gepirone-ER at weeks 3 and 8. Gepirone-ER was well tolerated: 9.8% of the gepirone-ER group and 2.8% of the placebo group discontinued due to adverse events. Common adverse events were considered mild and included dizziness, nausea, and insomnia. Gepirone-ER did not differ statistically compared with placebo in weight gain or sedation. Furthermore, preliminary evidence suggested that gepirone-ER may not be associated with sexual dysfunction. No serious adverse events occurred in gepirone-treated patients. CONCLUSION: Gepirone-ER is effective for the short-term treatment of major depressive disorder and is well tolerated.     

Development and characterization of mucoadhesive microspheres bearing salbutamol for nasal delivery

Mucoadhesive drug delivery systems are those that provide intimate contact of the drug with the mucosa for an extended period of time. In our present work, mucoadhesive chitosan microspheres were prepared by emulsion solvent method. Formulations were characterized for various physicochemical attributes, shape, surface morphology, size, and size distribution, drug payload, swelling ability, and mucoadhesion. The effect of drug, citric acid, and permeation enhancer concentration on the physicochemical properties was studied. Crosslinked chitosan microspheres showed very good mucoadhesion, which was decreased on increasing the drug concentration and citric acid concentration, and slightly improved upon incorporation of permeation enhancer. The in vitro drug release and in vitro drug permeability through mucous membrane were performed, and slow release/permeation was noted with chitosan citrate complexed microspheres compared with noncomplexed chitosan microspheres. The in vivo performance of mucoadhesive microspheres formulations showed prolonged and controlled release of salbutamol as compared with oral administration of conventional dosage form.     

Robotic radical cystectomy and urinary diversion in the management of bladder cancer

The authors have explored the versatility of the da Vinci robot for pelvic surgery to develop the technique of robotic radical cystectomy in conjunction with the Urology and Nephrology Center in Mansoura, Egypt, a world leader in conventional (open) cystectomy. This approach, which is designed to minimize the time required for surgery, is a sandwich technique in which the cystectomy and the neobladder-urethral anastomosis are performed with robotic assistance and the urinary diversion is performed extracorporeally. This article reviews the published literature and details the authors' current technique of robotic radical cystectomy and urinary diversion.     

P.C. Sen Memorial best paper award on rural health practice: A study on visual acuity and vitamin A deficiency among primary school students in Naxalbari Village, Darjeeling district of West Bengal

331 primary school students studying from Nursery classes to Class IV in 2 randomly selected schools in Naxalbari Village in Darjeeling district of West Bengal were tested for visual acuity (VA), Vitamin A deficiency (VAD) and Bitot's spot. 329 students could be tested for visual acuity whereas all 331 students were tested for VAD and Bitot's spot. The prevalence of abnormal Visual Acuity (VA) (VA < 6/9 in any eye) in this study group was 3.65% and it was highest in 7-8 years age group in both the sexes contributing to 75% of the total students having abnormal VA. All these children fell within 50th percentile of weight and height for their respective age and sex. Hindu & ST children accounted for 91.67% & 50% abnormal VA respectively; however, when presence of abnormal VA was compared with its absence between 2 sexes, Hindu and Muslim students and in different castes, no statistically significant differences were found (p > .05). Students of Class-I and Class-II contributed 25% and 50% respectively and together accounted for 75% of abnormal VA. Prevalence of VAD was 8.16%. Among sufferers of VAD Hindus (81.48%) and ST (51.85%) were the main contributors; the differences between presence and absence of VAD in 2 sexes, among 3 religious groups were not statistically significant (p > .05); however, differences among ST and NonSCST groups, and again SC, ST and Non-SCST groups were statistically significant (p < .05). Prevalence of Bitot's spot was 3.63%. Among the students having Bitot's spot, females (58.33%) outnumber the males (41.67%); but the difference between presence and absence of Bitot's spot in 2 sexes was not statistically significant (p > .05). 83.33% each of Hindus and STs had Bitot's spot. No SC and no Muslim student had this spot; the differences between presence and absence of Bitot's spot between Hindu and Christian students were statistically significant (p < .01); similarly when the findings were considered between ST and NonSCST students the difference was found to be statistically highly significant (p < .001).     

Suboptimal chlorine treatment of drinking water leads to selection of multidrug-resistant Pseudomonas aeruginosa

The present study was undertaken to investigate the spectrum of bacteria present in the River Gomti water before and after chlorination for drinking purposes. We observed that the strains of Pseudomonas aeruginosa that survived chlorination on three out of seven occasions were resistant to almost all the antibiotics tested. The chlorine-resistant bacteria had mucoid colonies and grew better at 24 degrees C. All attempts to isolate the plasmid responsible for chlorine resistance were unsuccessful. Laboratory experiments using different strains of the P. aeruginosa in distilled water showed that only the resistant strain survived chlorine treatment at a dose of < or =500 microg/L. Similar results were obtained when water collected from seven different sites on the River Gomti was treated with graded doses of chlorine. At the higher dose of chlorine, all the bacteria died in 30 min, whereas with lower doses all the bacteria survived. The present study underscores the importance of measuring water chlorine concentrations to assure they are sufficiently high to remove pathogenic bacteria from drinking water. To our knowledge, this is the first report in the literature of the selection of multidrug-resistant bacteria by suboptimal chlorine treatment of water.     

The technique of apical dissection of the prostate and urethrovesical anastomosis in robotic radical prostatectomy

OBJECTIVE: To describe the technique of dissecting the apex of the prostate and a modified single running-suture urethrovesical anastomosis in patients undergoing robot-assisted radical prostatectomy for organ-confined prostate cancer. PATIENTS AND METHODS: Over 550 robot-assisted radical prostatectomies have been undertaken using Vattikuti Institute Prostatectomy (VIP) technique in patients with localized carcinoma of the prostate. We present a critical analysis of the first 120 procedures by one surgeon (M.M.) at our institution using this newly developed technique of urethrovesical anastomosis preceded by dissecting the apex of the prostate. RESULTS: The mean time for the urethrovesical anastomosis was 13 min. All but 24 patients had their catheter removed 4 days after surgery, as indicated by a cystogram. The catheter was removed successfully at 7 days in the remaining 24 patients who had a mild leak on cystography. Two patients had urinary retention within a week of removing the catheter and had to be re-catheterized. Continence was evaluated using standardized criteria before and after the procedure. The patients also replied to a mailed validated questionnaire survey; 96% were continent at 3 months and the remaining 4% used a thin pad for security. CONCLUSIONS: We report a technique of dissecting the apex of the prostate and prostatovesical junction for dividing the bladder neck, and a modified single running-suture urethrovesical anastomosis, in patients undergoing robot-assisted radical prostatectomy for organ-confined cancer of the prostate. The same principles can also be applied for the anastomosis during pure laparoscopic procedures and for urethro-neovesical anastomosis in patients undergoing robotic radical cystoprostatectomy for carcinoma of the bladder.     

Thrombolytic therapy for prosthetic valve thrombosis: a study based on serial Doppler echocardiographic evaluation.

Sixteen patients with echocardiographic and cinefluoroscopic evidence of Bj?rk-Shiley prosthetic valve obstruction (13 mitral valves and 3 aortic valves) were treated with intravenous streptokinase. Streptokinase was administered as an initial bolus of 250,000 units for 30 minutes, followed by an infusion of 100,000 units/hr. Serial cinefluoroscopy and echocardiography (M-mode, two-dimensional, and Doppler) were performed at 0, 24, 48, and 72 hours of treatment. The end point of treatment was defined as near normalization of clinical, echocardiographic, and fluoroscopic parameters. Successful thrombolysis was achieved in all patients. The average duration of streptokinase therapy was 43 hours (range 2 to 72 hours). Two of 16 patients had minor systemic embolism during therapy. Short-term follow-up has shown sustained benefit in 14 of 16 patients. Two patients have had rethrombosis of the mitral prosthetic valves and have undergone thrombectomy. Our study demonstrates the feasibility, safety, and efficacy of thrombolytic therapy in the treatment of prosthetic valve thrombosis. It also emphasizes the role of serial Doppler echocardiography in guiding the duration of therapy and assessing its efficacy.     

Calcium antagonists can be classified using in vitro toxicity and potency indices.

The toxicity of eleven calcium antagonists from different chemical families was determined in rat hepatocyte primary cultures. The calcium antagonist potency of the same compounds was also determined in isolated rabbit aortic rings contracted with high K+. The hepatocytotoxicity of the calcium antagonists was not directly linked to blockade of voltage-operated calcium channels, since there was no correlation between the rank order of hepatotoxicity and that for calcium antagonist potency. The toxicity and calcium antagonist potency of each calcium antagonist examined were used to calculate an in vitro therapeutic index value for each compound. It was observed that therapeutic indices fell into three distinct groups and we therefore propose that the in vitro therapeutic index can be used to subclassify the calcium antagonist group of drugs. The proposed classification corresponds very closely with one already suggested by Spedding on pharmacological grounds. In conclusion, the in vitro therapeutic index may provide a useful tool in the characterization and subclassification of novel calcium antagonist compounds.