Complex urethral disruptions: In pursuit of a successful reconstruction

OBJECTIVES: We analyzed the methods and outcomes of urethroplasty in men with complex urethral disruptions. METHODS: The medical records of 40 men with complex urethral disruptions were analyzed. Surgical methods were individualized according to stricture location, severity and length of the stricture, bladder neck characteristics and presence of complicating factors. Patients were divided into four groups based on the above characteristics. RESULTS: End-to-end urethroplasty performed in six patients with short bulbar strictures (<3 cm) was successful in all. Elaborated perineal repair was performed in 10 patients with intermediate (3-6 cm) strictures with or without complicating factors. Elaborated perineal repair with urethral substitution was performed in nine patients with long segment stricture (>6 cm). Abdominal transpubic repair was successfully applied to patients with rectourethral fistula or lacerated bladder neck. Success rate of anastomotic urethroplasty was 95% while over all success rate was 85%. CONCLUSION: Guidelines for urethral reconstruction of complex urethral disruptions are predicated on stricture length, location, bladder neck characteristics and associated complicating factors. End-to-end urethroplasty with stricture excision is highly reliable for short strictures for which previous operative repair have failed. Elaborated perineal repair is extremely versatile for intermediate and longer strictures with associated complicating factors. Abdominal transpubic urethroplasty is effective for patients with rectourethral fistula or lacerated bladder neck.     

Graded Pneumatic Dilation using Rigiflex Achalasia Dilators in Patients with Primary Esophageal Achalasia

Pneumatic dilation is the initial therapy for primary esophageal achalasia. Recently, polyethylene balloon (Rigiflex) dilators have been used with varying success and complication rate. We performed a total of 47 dilations in 29 consecutive patients with achalasia using the Rigiflex dilators. The 3.0-cm balloon was always used first. If there was no symptomatic response, a 3.5-cm balloon was used after 4–8 wk. If there was still no symptomatic response after 4-8 wk, a 4.0-cm dilator was used. Eighteen (62%) patients were successfully dilated with a 3.0-cm balloon only. Of 11 patients not responding to a 3.0-cm balloon, five were dilated successfully with a 3.5-cm balloon. Of six patients not responding to a 3.5-cm balloon, four were successfully dilated with a 4.0-cm balloon dilator. Two patients eventually required surgery. The overall success with Rigiflex balloon dilator was achieved in 27 of 29 (93%) patients. There were no complications. We conclude that pneumatic dilation for esophageal achalasia performed in a graded fashion starting with Rigiflex 3.0-cm balloon dilator has a high success rate without complications in patients with achalasia.     

Regional alterations of brain biogenic amines and GABA/glutamate levels in rats following chronic lead exposure during neonatal development

Wistar rat pups were administered either a high dose of lead acetate (400 g lead/g body weight/day) or a low dose (100 g lead/g body weight/day) by gastric intubation, from 2 days through 60 days of age. The rats on both these doses exhibited statistically significant decreases in body and brain weights throughout the lead treatment period. A group of rats on high dose was also rehabilitated by discontinuing the lead from 60 days of age. In these rats, at 160 days of age, the body weight but not the brain weight recovered to normal levels. During the lead intake, the rats on high dose revealed significant elevations in the levels of noradrenaline (NA) in the hippocampus (HI), cerebellum (CE), hypothalamus (HY), brainstem (BS), and accumbens-striatum (SA). The elevated levels in all the above regions except in the HY persisted even after rehabilitation. The dopamine (DA) levels changed significantly in opposite directions in HY (elevation) and BS (reduction) during the lead treatment, and the HY recovered after rehabilitation. Under lead, the serotonin (5HT) levels were elevated significantly in the HI, BS and MC (motor cortex), while after rehabilitation the abnormality persisted only in the MC. Low dose lead treatment was also effective on the same areas of brain. In the low dose group, estimation of the levels of GABA and glutamate were also done, and a significant decrease of GABA in CE and glutamate in MC was observed. The differences observed in the neurotoxic effects (none or significant) of lead in the different regions for each of the transmitters (NA, DA, 5HT) supports the interesting conclusion that the vulnerability of the axon terminals of any given type is dependent on some regional factors, although the projections of the different regions originate from an apparently similar category of neurons in the brain stem.     

Laparoscopic total radical hysterectomy by the Pune technique: our experience of 248 cases

STUDY OBJECTIVE: To describe our experience and technique of total laparoscopic radical hysterectomy with pelvic lymphadenectomy, which is the largest single- institution study. DESIGN: Retrospective, nonrandomized study (Canadian Task Force classification II-2). SETTING: Private hospital. PATIENTS: Two hundred forty-eight patients with International Federation of Gynecology and Obstetrics stage IA2 (n = 32) and IB1 (n = 216) of cancer of the cervix. INTERVENTION: Total laparoscopic type III radical hysterectomy with bilateral pelvic lymphadenectomy was done. Simple repetitive steps were used to perform this surgery and develop an easily replicable technique. Harmonic Shears, bipolar coagulation, and vascular clips were used. Resection of the cardinal and uterosacral ligaments was performed with LigaSure (LigaSure Vessel Sealing System; Valleylab, Tyco Healthcare, Boulder, CO) or the Harmonic Shears (Ethicon Endo-Surgery, Inc., Cincinnati, OH). Pelvic lymph node dissection was done. MEASUREMENTS AND MAIN RESULTS: Histopathologically, there were 183 (73%) cases of squamous carcinoma, 52 (20%) adenocarcinomas, and 13 (5%) adenosquamous carcinomas. Four patients needing anterior exenteration because of bladder involvement were excluded from data analyses. The operation was performed entirely by laparoscopy in all patients and by the same surgical team. The patients' median age was 61 years. The median operative time was 92 minutes (range 65-120 minutes). The median number of resected pelvic nodes was 18. The median blood loss was 165 mL. The median length of stay was 3 days. All 15 intraoperative complications were tackled laparoscopically. No patients were converted to the open technique. There were no deaths in our series. Seventeen patients had complications within 2 months of surgery. Seven patients had recurrences after a median follow-up of 36 months. CONCLUSION: Our technique of total laparoscopic radical hysterectomy, developed over 248 cases, can be performed safely. It is an easily replicable technique. This procedure reduces the morbidity associated with abdominal radical hysterectomy. All of the complications can also be tackled laparoscopically, which does not further add to the morbidity.     

Three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis and molecular docking-based combined in silico rational approach to design potent and novel TRPV1 antagonists

The discovery of clinically relevant antagonists of TRPV1 for neuropathy pain therapy has proven to be a challenging task. For better understanding of the molecular interactions of antagonists with TRPV1 receptor, a series of chroman and tetrahydroquinoline ureas were analyzed by k-nearest neighbor molecular field analysis (kNN-MFA) and molecular docking. To elucidate the structural properties required for activity as TRPV1 antagonists, we report here kNN-MFA-based 3D-QSAR model for chroman and tetrahydroquinoline ureas as potent TRPV1 antagonists. Sphere exclusion method was used for dividing the compounds into training (26 compounds) and test (5 compounds) set. Overall model classification accuracy was 81.35 % (q ² = 0.8135, representing internal validation) in training set and 81.44 % (pred_r ² = 0.8144, representing external validation) in test set using stepwise forward as a method of variable selection. The stereo view of molecular rectangular grid field of 3D-QSAR using this approach showed that steric and hydrophobic effects dominantly determine binding affinities. Furthermore, the crystal structure of TRPV1 was obtained from protein data bank (PDB code 2NYJ, resolution 3.20 Å), and docking of 31 TRPV1 antagonists into putative binding sites of the TRPV1 were studies. Molecular docking was employed to explore the binding mode between these compounds and the receptor, as well as help understanding the structure–activity relationship revealed by kNN-MFA. Our QSAR model and molecular docking results corroborate with each other and propose directions for the design of new antagonists with better activity toward TRPV1.