Urinary diversion with use of ileal and sigmoid conduits

Two hundred eighteen patients underwent urinary diversion: 156 with ileal and 62 with sigmoid conduits. There were no significant differences between the two groups regarding frequency of conduit morbidity or patient survival. The ileal conduit is preferred for urinary diversion with anterior exenteration, whereas the sigmoid conduit is preferable for urinary diversion with total exenteration.     

Analysis of sequential treatment protocols for endometriosis-associated infertility

The evaluation of comparative pregnancy data in clinical studies is subject to a variety of biases. One such bias, when treated patients are retrospectively compared with untreated control subjects, results from the fact that treated patients must remain infertile from time of diagnosis to time of treatment while no such requirements is maintained for untreated control subjects. This bias is also apparent when patients undergo sequential treatments and transfer from one comparison group to another. We have eliminated this problem by applying the Mantel-Byar approach for constructing and comparing modified life tables that reflect sequential changes of treatment status. To illustrate this we applied commonly used methods of analysis as well as the Mantel-Byar method to infertile endometriosis patients attempting pregnancy. One hundred thirty consecutive patients were evaluated retrospectively, with 42 undergoing expectant management only, seven experiencing a conservative surgical procedure only, and 81 having a conservative surgical procedure after a variable period of expectant management. Use of Mantel-Byar analysis revealed no significant overall increase in pregnancy rate with conservative surgical procedures versus expectant management (chi 2 = 0.225, df = 1). To further assess the potential value of conservative surgical procedures in fertility enhancement, the data were stratified by degree of endometriosis. The adjusted chi 2 was 1.621. No significant difference was noted between the two therapeutic approaches with mild disease (n = 35, chi 2 = 0.0175) or moderate endometriosis (n = 59, chi 2 = 0.424). Conservative surgical procedures appear to be therapeutic, however, in women with severe disease (n = 36, chi 2 = 5.12, p less than 0.05). These results differed substantially from those obtained with the more biased analytic methods routinely used in clinical fertility trials. This study illustrates the utility of the Mantel-Byar approach as a valuable tool in the evaluation of response time data involving transient therapeutic states and one particularly adaptable to retrospective infertility studies involving sequential treatment approaches.     

Expression of cyclooxygenase-2 in association with clinicopathological prognostic factors and molecular markers in epithelial ovarian cancer

OBJECTIVES: This study examines whether expression of COX-2 is associated with clinicopathological features and other molecular markers of ovarian cancer. METHODS: Sixty-four paraffin-embedded tissue specimens were obtained from patients with ovarian cancer who received cytoreductive surgery and combination chemotherapy. Tissue specimens were subjected to immunohistochemical analysis using antibodies to COX-2, p53, and VEGF. RESULTS: Increased COX-2 expression significantly correlated with histologic type (mucinous 5.6% vs. non-mucinous 65.2%, P<0.001). COX-2 expression was also significantly associated with stage, tumor grade, residual disease status, and presence of ascites. COX-2 expression correlated positively with expression of p53 (P=0.006) and VEGF (P=0.025). Although survival was lower in patients with high COX-2 expression than in those without high COX-2 expression (P<0.001), only tumor grade and stage were independent prognostic indicators. In patients with non-mucinous cancer, COX-2 expression correlated with stage (P<0.001) and presence of ascites (P=0.033). CONCLUSIONS: Our results suggest that expression of COX-2 in ovarian cancers is specific to histologic type of tumor and is associated with poor clinicopathologic prognostic factors. Expression of COX-2 also correlates well with expression of p53 and VEGF.     

3-氯丙二醇和2、3-氧丙醇合并长期、间歇给药对恒河猴及大鼠毒性作用的观察

本文介绍了3-氯丙二醇和2,3-氧丙醇合并长期间歇用药对猴及大鼠的毒性观察,结果表明,以日剂量5mg/kg 3-氯丙二醇和75mg/kg 2,3-氧丙醇合并应用,可导至大鼠可逆性不育;对猴及大鼠的内脏器官、骨髓细胞增生度及微核数量、末梢血液细胞计数、分类,以及猴的染色体常规检查未见明显影响。表明合并用药有用药量小,给药时间短、起效快、毒性低等优点。     

SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA–target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC–MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.     

Development of cyclosporin A-loaded hyaluronic microsphere with enhanced oral bioavailability

To develop a hyaluronic microsphere with the improved oral bioavailability of poorly water-soluble cyclosporin A (CsA), the microspheres were prepared with varying ratios of sodium hyaluronate (HA)/sodium lauryl sulfate (SLS)/CsA using a spray-drying technique. The effects of HA and SLS on the dissolution and solubility of CsA in microspheres were investigated. The CsA-microsphere prepared with HA/SLS/CsA at the ratio of 4/2/1 gave the highest solubility and dissolution rate of CsA among those formulae tested. As solubility and dissolution rate of CsA were increased about 17- and 2-fold compared to CsA powder, respectively, this CsA-microsphere was selected as an optimal formula for oral delivery in rats. The CsA-microsphere and Sandimmun neoral sol gave significantly higher blood levels compared with CsA powder alone. Moreover, the AUC, T(max) and C(max) values of CsA in CsA-microsphere were not significantly different from those in Sandimmun neoral sol in rats, indicating that CsA-microsphere was bioequivalent to the commercial product in rats. Our results demonstrated that the CsA-microsphere prepared with HA and SLS, with improved bioavailability of CsA, might have been useful to deliver a poorly water-soluble CsA.