Design, synthesis and evaluation of new classes of nonquaternary reactivators for acetylcholinesterase inhibited by organophosphates.

A new series of nonquaternary conjugates for reactivation of both nerve agents and pesticides inhibited hAChE were described in this paper. It was found that substituted salicylaldehydes conjugated to aminobenzamide through piperidine would produce efficient reactivators for sarin, VX and tabun inhibited hAChE, such as L6M1R3, L6M1R5 to L6M1R7, L4M1R3 and L4M1R5 to L4M1R7. The in vitro reactivation experiment for pesticides inhibited hAChE of these new synthesized oximes were conducted for the first time. Despite they were less efficient than obidoxime, some of them were highlighted as equal or more efficient reactivators in comparison to 2-PAM. It was found that introduction of peripheral site ligands could increase oximes' binding affinity for inhibited hAChE in most cases, which resulted in greater reactivation ability.

Conjugates of salicylaldoximes and peripheral site ligands: Novel efficient nonquaternary reactivators for nerve agent-inhibited acetylcholinesterase.

A new family of nonquaternary reactivators for nerve agent-inhibited human acetylcholinesterase (hAChE) were designed, synthesized and tested in this paper. It was found that salicylaldoximes were able to quickly cleave the P-S bond of organophosphate and avoid the reinhibition phenomenon in the reactivation process, but they lacked reactivating ability due to poor affinity for AChE. Based on a dual site binding strategy, different peripheral site ligands of AChE were introduced to achieve extra affinity. The in vitro reactivation experiments demonstrated that some of the yielding conjugates exhibited similar or even superior ability to reactivate sarin-, VX- or tabun-inhibited hAChE in comparison with the mono- and bis-pyridinium aldoximes currently used. Moreover, due to greatly improved lipophilicity, these nonquaternary conjugates hold promise for the development of efficient centrally activating reactivators.

Laparoscopic Extravascular Stent Placement for Nutcracker Syndrome: A Report of 13 Cases.

OBJECTIVE: To report our techniques and experience of laparoscopic extravascular stent placement for nutcracker syndrome. PATIENTS AND METHODS: This study included 13 nutcracker syndrome patients who were treated by laparoscopic extravascular stent placement from June 2009 to August 2013. Clinical and surgical data and short-term outcomes were analyzed retrospectively. RESULTS: The average duration of the operation was 72 minutes and the average blood loss was 30 mL. The average postoperative length of stay was 6 days. Retroperitoneal hematoma was relieved by conservative therapy in one patient. The postoperative computed tomography showed that the blood outflow of the left renal vein was smooth and the inner diameter was also decreased. The gonadal vein varices diminished in diameter in four patients. The follow-up was 8-52 months (mean 32.6); symptoms resolved in 10 patients and improved in 2 patients. One patient developed recurrent gross hematuria because of migration of the extravascular stent. CONCLUSION: Laparoscopic extravascular stent placement appears feasible and safe and it is a minimally invasive alternative to open surgery.

[Factors associated with increased blood loss in patients undergoing radical cystectomy in a contemporary series].

OBJECTIVE: To evaluate factors predictive of blood loss in radical cystectomy in a contemporary series. METHODS: From December 1996 to December 2008, clinical data of 233 patients who underwent radical cystectomy were reviewed retrospectively. Various preoperative and operative factors were assessed for their association with blood loss using univariate, multivariate regression and correlation analysis. RESULTS: One hundred eighty-one patients underwent open radical cystectomy and 52 cases were treated by laparoscopic radical cystectomy. Overall mean operative time was (339 ± 84) minutes, and mean blood loss was (818 ± 756) ml. On univariate analysis, body mass index (F = 9.039), history of pelvic operation (t = -4.365), anesthetic techniques (t = 3.125), surgical type (t = 6.643), use of Ligasure (t = 6.923), and urethra resection (t = -1.984) correlated with blood loss. However, multiple linear regression showed that body mass index (R(2) = 0.256, P < 0.001), history of pelvic operation (R(2) = 0.222, P < 0.001), use of Ligasure (R(2) = 0.172, P < 0.001), and surgical type (R(2) = 0.271, P = 0.027) were significant predictors of blood loss. The transfusion was required in 176 of 233 patients (75.5%) with a median requirement of (649 ± 569) ml. Likewise logistical regression analysis revealed that older age (OR = 3.2, P = 0.010), female gender (OR = 33.7, P = 0.013), anemia (OR = 6.6, P = 0.039), increased blood loss (OR = 14.3, P < 0.001), open radical cystectomy (OR = 6.4, P = 0.036) and nonuse of Ligasure (OR = 10.1, P < 0.001) were predictors of transfusion need. CONCLUSIONS: Increased body mass index, history of pelvic operation, open radical cystectomy, and non-use of Ligasure were independent predictors of increased blood loss during radical cystectomy. Such a prediction formula has an important role in identifying high risk patient for increased blood loss and transfusion need before radical cystectomy.

Cotton gene expression profiles in resistant Gossypium hirsutum cv. Zhongzhimian KV1 responding to Verticillium dahliae strain V991 infection.

Verticillium wilt of cotton (Gossypium hirsutum) is a widespread and destructive disease that is caused by the soil-borne fungus pathogen Verticillium dahliae (V. dahliae). To study the molecular mechanism in wilt tolerance, suppression subtractive hybridization (SSH) and dot blot techniques were used to identify the specifically expressed genes in a superior wilt-resistant cotton cultivar (G. hirsutum cv. Zhongzhimian KV1) after inoculation with pathogen. cDNAs from the root tissues of Zhongzhimian KV1 inoculated with V. dahliae strain V991 or water mock were used to construct the libraries that contain 4800 clones. Based on the results from dot blot analysis, 147 clones were clearly induced by V. dahliae and selected from the SSH libraries for sequencing. A total of 92 up-regulated and 7 down-regulated non-redundant expressed sequences tags (ESTs) were identified as disease responsive genes and classified into 9 functional groups. Two important clues regarding wilt-resistant G. hirsutum were obtained from this study. One was Bet v 1 family; the other was UbI gene family that may play an important role in the defense reaction against Verticillium wilt. The result from real-time quantitative reverse transcription polymerase chain reaction showed that these genes were activated quickly and transiently after inoculation with V. dahliae.

[The analysis of perioperative complications during radical cystectomy using a standardized reporting system].

OBJECTIVES: To analyze the perioperative complications of radical cystectomy using a standardized reporting methodology. METHODS: The clinical data of 233 cases of radical cystectomy from January 1996 to December 2008 were reviewed. Two hundred male patients and 33 female patients were included. The mean age was 58.9 years old. All complications within 30 days of surgery were recorded and classified using a 5-grade modification of the Clavien system. RESULTS: Overall mean operative time was 339 (170 - 610) minutes, and mean blood loss was 818 (range 100 to 3500) ml. Of the 233 subjects at least 1 postoperative complication developed in 84 (36.1%), including five cases of intraoperative complications. According to the modified Clavien system, 27 patients (11.6%) had grade 1, 38(16.3%) had grade 2, 16(6.9%) had grade 3, and 3(1.7%) had grade 4 complications. The most frequent complication was gastrointestinal complications (15.9%), then the incision-related complications (15.0%) and lung infections (4.7%). An association between hypoproteinemia and any complication was found after adjusting for confounding variables (OR = 2.963, 95%CI: 1.451 - 6.050, P = 0.003), and American society of anesthesia score (ASA score) was significantly associated with any major complication (OR = 2.520, 95%CI: 1.003 - 6.332, P = 0.049). CONCLUSIONS: Radical cystectomy is associated with a high perioperative complications, using the modification of the Clavien system has allowed us to stratify complications during radical cystectomy. Hypoproteinemia is independently associated with any complication in these patients and ASA score was significantly associated with any major complication.

The prognostic value of hydronephrosis in bladder cancer treated by radical cystectomy.

OBJECTIVES: To evaluate the prognostic impact of hydronephrosis in bladder cancer treated by radical cystectomy. METHODS: We performed a retrospective review of 126 patients with transitional cell carcinoma of bladder, who underwent radical cystectomy at our hospital from January 2003 through May 2010. The relationship between hydronephrosis, tumor stage, and lymph node status was analyzed. We evaluated the effect of hydronephrosis on the recurrence-free survival of bladder cancer by using log-rank test and multivariate Cox regression analysis. RESULTS: Thirty-four patients had unilateral hydronephrosis and five patients had bilateral hydronephrosis. There were 59.0% of tumors with stage ≥pT3a, and 30.8% with pT2, 10.2% with pT1 in the Hydronephrosis group respectively compared to 14.9%, 59.8%, and 25.3% in the Non-hydronephrosis group (χ2 = 25.680, P<0.001). The 5-year recurrence-free survival rates in the Hydronephrosis group were significantly lower than the Non-hydronephrosis group (42.5±10.3% vs. 68.8±8.1%, P=0.001). When adjusted to the different stages stratum, the recurrence-free survival rates among patients with stage pT1-2pN- or lymph node metastasis did not differ significantly whether they had evidence of preoperative hydronephrosis or not, while they differed significantly in the subgroup of stage ≥pT3a,pN-. Multivariate analysis showed that hydronephrosis was not an independent prognostic factor for recurrence-free survival except pathological stage and lymph node status. CONCLUSIONS: Preoperative hydronephrosis predicts advanced stages in transitional cell carcinoma of bladder and exactly effects the survival mainly in higher stage tumor without metastasis.

Comparison of surgical stress response to laparoscopic and open radical cystectomy.

OBJECTIVES: To prospectively compare stress response to laparoscopic and open radical cystectomy by the measurement of humoral mediators and the incidence of systemic inflammatory response syndrome (SIRS). METHODS: Thirty-eight patients undergoing radical cystectomy were prospectively assessed. Blood samples were obtained from all patients before surgery, during surgery, 72 h after surgery. Serum levels of interleukin (IL)-6 and interferon (IFN)-gamma were measured using an enzyme-linked immunosorbent assay. We also investigated the incidence and duration of SIRS in the two groups. RESULTS: The two groups had comparable perioperative variables except for less estimated blood loss in the laparoscopic group. The IL-6 levels increased during and after surgery in the two groups (P < 0.001). However, the IL-6 levels in the laparoscopic group were significantly lower than those in the open group during and after surgery (P = 0.006, P < 0.001). The incidence of SIRS was 57.1% in the laparoscopic group and 79.2% in the open group (P = 0.149). The mean duration of SIRS was 1.4 days in the laparoscopic group and 2.8 days in the open group (P = 0.032). The IFN-gamma levels decreased, but there was no difference in the two groups over the entire period assessed. Multivariate analysis demonstrated that the group (laparoscopic versus open) was the only influencing factor on the levels of IL-6 and the duration of SIRS. CONCLUSIONS: Our study suggests that the laparoscopic group is markedly less stressful and it has a shorter duration of SIRS than the open group.

Comparison of hand-assisted laparoscopic and open radical cystectomy for bladder cancer.

PURPOSE: To present our experience of hand-assisted laparoscopic radical cystectomy (HALRC) and compare it with open radical cystectomy (ORC). PATIENTS AND METHODS: During the period between May 2004 and November 2007, 31 patients underwent HALRC and 39 patients underwent ORC for bladder cancer. The patient demographics, intraoperative variables and postoperative outcomes were compared retrospectively. RESULTS: There was no statistically significant difference with regard to age, sex, body mass index, and urinary diversion in the 2 groups. In the HALRC group, 20 patients had stage pT2 or less, 7 had pT3 disease, and 4 had stage pT4 disease. In the ORC group, 29 patients had stage pT2 or less, 5 had pT3 disease, and 5 had stage pT4 disease. All margins in both groups were negative. The HALRC group had decreased blood loss (250.9 vs. 812.8 ml, p < 0.001) and a lower rate of transfusion (9.7 vs. 76.9%, p < 0.001), but similar mean operative time (365.7 vs. 362.6 min, p = 0.862). Time to liquid diet was significantly less in the HALRC group versus the ORC group (4.3 vs. 6.3 days, p < 0.001). The median number of lymph nodes were similar between the HALRC and ORC groups (14 vs. 15, p = 0.377). Six patients developed perioperative complications in the HALRC group and 12 patients had complications in the ORC group (19.4 vs. 30.8%, p = 0.278). Late complications occurred in 3 patients (2 parastomal hernias and 1 ureteroenteral stricture) in the HALRC group. CONCLUSIONS: Compared with ORC, HALRC patients had decreased blood loss, less transfusion requirements, and quicker intestinal recovery. Long-term follow-up in a larger cohort of patients is needed to assess the long-term oncological and functional outcomes.

[Recent advances in the study of new antifungal lead compounds].

In recent years, the incidence and mortality rate of invasive fungal infection have increased dramatically, and it is of great significance to develop novel antifungal agents with new chemical structure and new mode of action. In this review, novel antifungal lead compounds reported from 2007 to 2009 are reviewed. Moreover, their chemical structures, antifungal activities and structure-activity relationships have been summarized, which can provide useful information for future study of antifungal agents.

Hand-assisted versus pure laparoscopic radical cystectomy: a clinical outcome comparison.

OBJECTIVES: To compare hand-assisted laparoscopic radical cystectomy (HALRC) with the standard laparoscopic radical cystectomy (LRC) in an attempt to delineate their role in bladder cancer treatment. METHODS: We retrospectively analyzed 51 patients who underwent HALRC (HALRC group, 31 cases) or LRC (LRC group, 20 cases). Urinary diversion was performed extracorporeally through the hand port or the incision for specimen retrieval, respectively, in the two groups. Baseline patient characteristics, intraoperative parameters, and postoperative outcomes were evaluated. RESULTS: There was no statistically significant difference in age, sex, body mass index, previous abdominal surgeries, or tumor stage between the two groups. Although the LRC group yielded a significantly smaller incision for urinary diversion than the HALRC group (7.3 cm vs 6.2 cm, P < 0.05), mean operative time, mean estimated blood loss, blood transfusion rate, time to oral intake and complications were similar in the two groups. Hernia formation was observed with increased frequency in the HALRC group. No patients in the HALRC group and only one patient (5%) in the LRC group presented a positive margin. CONCLUSIONS: The HALRC group yielded the same outcomes as the LRC group, except with a larger incision. The hand-assisted approach might be preferred for obese patients or those having multiple previous abdominal surgeries.

Hand-assisted laparoscopic radical cystectomy and extracorporeal urinary diversion: experience with 31 cases.

OBJECTIVES: To report our techniques and experience with hand-assisted laparoscopic radical cystectomy and extracorporeal urinary diversion for bladder cancer. METHODS: Between May 2004 and November 2007, 31 patients (mean age 61.3 years, range 40-79) underwent hand-assisted laparoscopic radical cystectomy with extracorporeal urinary diversion for bladder cancer. Five patients had previously undergone abdominal surgeries. Data were collected with respect to patient demographics, perioperative outcomes and short-term oncological follow up. RESULTS: Twenty-four patients underwent an ileal conduit and seven patients underwent an orthotopic neobladder. Mean operative time was 365.7 min (range 245 to 530). Estimated blood loss was 250.9 cc (range 100 to 500), with a transfusion rate of 9.7%. Oral liquids were resumed at 4.3 days and the mean hospital stay was 19.7 days. There were no intraoperative complications. Postoperative early complications (within 30 days of surgery) occurred in six patients (19.4%). Two wound infections, one urinary leak, one wound dehiscence, one bowel obstruction and one alimentary tract hemorrhage were all treated conservatively. Late complications occurred in three patients (two parastomal hernias and one ureteroenteric stricture). With a mean follow up of 18 months, 27 patients had no evidence of disease. One patient died because of cancer and one died for unrelated causes. One was alive with local recurrences and one with lung metastasis. CONCLUSIONS: Hand-assisted laparoscopic radical cystectomy is a safe, reproducible and minimally invasive option for bladder cancer patients.