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.     

A Rose by Any Other Name? The Potential Consequences of Microglial Heterogeneity During CNS Health and Disease

Microglial activation and macrophage infiltration into the CNS are common features of CNS autoimmune disease and of chronic neurodegenerative diseases. Because these cells largely express an overlapping set of common macrophage markers, it has been difficult to separate their respective contributions to disease onset and progression. This problem is further confounded by the many types of macrophages that have been termed microglia. Several approaches, ranging from molecular profiling of isolated cells to the generation of irradiation chimeric rodent models, are now beginning to generate rudimentary definitions distinguishing the various types of microglia and macrophages found within the CNS and the potential roles that these cells may play in health and disease.     

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.     

Caspofungin activity against clinical isolates of fluconazole-resistant Candida

A total of 7,837 clinical isolates of Candida were tested against fluconazole, and 351 resistant (fluconazole MIC >/=64 micro g/ml) isolates were identified (4% of the total tested). All fluconazole-resistant isolates were inhibited by caspofungin at concentrations that can be exceeded by standard doses (MIC at which 90% of the isolates were inhibited, 1 micro g/ml; 99% of the MICs were 相似文献   

Differential PsaA-, PspA-, PspC-, and PdB-specific immune responses in a mouse model of pneumococcal carriage

Larger numbers of pneumococci were detected in the nasal tract compared to the lung, cervical lymph nodes, and spleen 1, 2, 4, 7, 14, and 21 days after nasal challenge with Streptococcus pneumoniae strain EF3030. In this mouse model of pneumococcal carriage, peripheral S. pneumoniae pneumococcal surface adhesin A (PsaA)-specific humoral responses (immunoglobulin G2a [IgG2a] > IgG1 = IgG2b > IgG3) were significantly higher than pneumococcal surface protein A (PspA)-specific, genetic toxoid derivative of pneumolysin (PdB)-specific, or pneumococcal surface protein C (PspC)-specific serum antibody levels. However, PspA-specific mucosal IgA antibody levels were significantly higher than those against PsaA, PdB, and PspC. In general, both PsaA- and PspA-specific lung-, cervical lymph node-, nasal tract-, and spleen-derived CD4(+) T-cell cytokine (interleukin-4, interleukin-6, granulocyte-macrophage colony-stimulating factor, gamma interferon, and tumor necrosis factor alpha) and proliferative responses were higher than those for either PspC or PdB. Taken together, these findings suggest that PsaA- and PspA-specific mucosal responses as well as systemic humoral and T helper cell cytokine responses are predominantly yet differentially induced during pneumococcal carriage.     

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.     

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.