155 vascular injuries: a retrospective study in Kuwait, 1992-2000.

OBJECTIVES: To audit the management of vascular trauma in Kuwait, 1992-2000. DESIGN: Retrospective open study. SETTING: Vascular surgery unit, teaching hospital, Kuwait. SUBJECTS: 155 patients with vascular injuries, most of which (n = 118) involved the extremities. 21 had neck injuries, 10 abdominal, and 6 chest. INTERVENTION: Revascularisation usually using the long saphenous vein in addition to direct repair or end-to-end anastomosis. MAIN OUTCOME: Morbidity (amputation) and mortality. RESULTS: Four lower limb grafts failed, two of which (2/69, 3%) required amputation. Overall, four patients died (3%), one of pulmonary embolism and 3 of severe injuries to major abdominal vessels. 3/10 patients with abdominal vascular trauma died. Mean (SD) follow up period was 4.4 (2) years. CONCLUSIONS: Civilian violence has increased in Kuwait. Vascular trauma to abdominal vessels is associated with high mortality. Autogenous saphenous vein forms an excellent conduit for revascularisation.     

Preoperative Neutrophil-to-Lymphocyte Ratio as a Prognostic Predictor after Curative Resection for Hepatocellular Carcinoma

BACKGROUND: This study was designed to evaluate the impact of an elevated preoperative neutrophil-to-lymphocyte ratio (NLR) on outcome after curative resection for hepatocellular carcinoma (HCC). METHODS: Patients undergoing resection for HCC from January 1994 to May 2007 were identified from the hepatobiliary database. Demographics, laboratory analyses, and histopathology data were analyzed. RESULTS: A total of 96 patients were identified with a median age at diagnosis of 65 (range, 15-85) years. The 1-, 3-, and 5-year overall survival rates were 80%, 58%, and 52%, respectively. Although the presence of microvascular invasion, NLR >or=5, and R1 resection margin were adverse predictors of overall survival, there were no independent predictors identified on multivariate analysis. The 1-, 3-, and 5-year disease-free survival rates were 74%, 63%, and 57%, respectively. Preoperative tumor biopsy, NLR >or= 5, multiple liver tumors, microvascular invasion, and R1 resection margin were all predictors of poorer disease-free survival. Multivariate analysis showed that a NLR >or= 5 and R1 resection margin were independent predictors of poorer disease-free survival. The median disease-free survival of those with a NLR >or= 5 was 8 months compared with 18 months for those with a NLR < 5. CONCLUSION: Preoperative NLR >or= 5 was an adverse predictor of disease-free and overall survival.     

Vascular Risk Factors as Predictors of Sexual Function Following Coronary Artery Bypass Graft

IntroductionA strong association between cardiovascular risk factors and erectile dysfunction (ED) was suggested. Coronary artery bypass grafting (CABG) is the gold standard for surgical myocardial revascularization.AimWe herein evaluate the impact of vascular risk factors on postoperative sexual functions in patients undergo CABG.Main Outcome MeasuresED severity by the International Index of Erectile Function (IIEF-5) and penile duplex study.MethodsThe present study included 100 patients who underwent CABG. The patients were evaluated by an abridged form of the IIEF-5 questionnaire, followed by CABG. Six months after surgery the erectile function of all patients was revaluated utilizing the IIEF-5.ResultsNumber of risk factors was significantly associated with postoperative change in IIEF-5 score (P = 0.02). A post hoc analysis of the association revealed that patients with one risk factor were significantly more likely to have increased IIEF-5 scores (N = 18), whereas those with two or more risk factors were significantly more likely to have decreased IIEF-5 scores (N = 21, P < 0.05). Furthermore, those with no risk factors were significantly more likely to be stable (N = 8) compared with those with more than two risk factors, who were more likely to have decreased scores (P < 0.05). The hierarchical logistic regression results showed that when examining all risk factors simultaneously, because of multicollinearity, only hyperlipidemia was significantly associated with postoperative ED (odds ratio [OR] = 11.33, confirdence interval [CI] = 1.25, 102.82). Frequency of intercourse was also significantly associated with postoperative ED after controlling for risk factors (OR = 0.71, CI = 0.52, 0.97).ConclusionsThis data clearly shows that the number of cardiovascular risk factors is an essential predictive factor for sexual function following surgery. Only hyperlipidemia may play a predictive role for the future sexual function of patients undergo CABG. Mohamed OA, Hamed HA, Roaiah MF, Helmy T, Mahran A, and Bennett CJ. Vascular risk factors as predictors of sexual function following coronary artery bypass graft. J Sex Med 2009;6:2017–2023.     

A possible mechanism for exonuclease 1-independent eukaryotic mismatch repair

Mismatch repair contributes to genetic stability, and inactivation of the mammalian pathway leads to tumor development. Mismatch correction occurs by an excision-repair mechanism and has been shown to depend on the 5′ to 3′ hydrolytic activity exonuclease 1 (Exo1) in eukaryotic cells. However, genetic and biochemical studies have indicated that one or more Exo1-independent modes of mismatch repair also exist. We have analyzed repair of nicked circular heteroduplex DNA in extracts of Exo1-deficient mouse embryo fibroblast cells. Exo1-independent repair under these conditions is MutLα-dependent and requires functional integrity of the MutLα endonuclease metal-binding motif. In contrast to the Exo1-dependent reaction, we have been unable to detect a gapped excision intermediate in Exo1-deficient extracts when repair DNA synthesis is blocked. A possible explanation for this finding has been provided by analysis of a purified system comprised of MutSα, MutLα, replication factor C, proliferating cell nuclear antigen, replication protein A, and DNA polymerase δ that supports Exo1-independent repair in vitro. Repair in this system depends on MutLα incision of the nicked heteroduplex strand and dNTP-dependent synthesis-driven displacement of a DNA segment spanning the mismatch. Such a mechanism may account, at least in part, for the Exo1-independent repair that occurs in eukaryotic cells, and hence the modest cancer predisposition of Exo1-deficient mammalian cells.     

The Impact of On-pump Coronary Artery Bypass Surgery vs. Off-pump Coronary Artery Bypass Surgery on Sexual Function

IntroductionErectile dysfunction and ischemic heart disease are common health problems that affect elderly individuals. Despite advances in treatment strategies, cardiopulmonary bypass (CPB) has been used for coronary artery bypass grafting (CABG) for over three decades for surgical myocardial revascularization.AimTo discuss the difference between the on pump and the newer alternative—the off-pump CABG (OPCABG) surgery—on the sexual function.MethodsThis prospective study included 100 patients who underwent CABG.Main Outcome MeasuresThe patients were evaluated by an abridged form of International Index of Erectile Function questionnaire (IIEF-5), Pharmaco-Penile Duplex Ultrasound and finally by the European System for Cardiac Operative Risk Evaluation. The patients were underwent either on-pump CABG or OPCABG. Six months after surgery, the erectile function was revaluated according to the same preoperative measures.ResultsPatients included in the study were classified into two matched groups: group I—patients who underwent on-pump CABG (N = 50); and group II—patients who underwent OPCABG (N = 50). The frequency of intercourse was significantly higher in OPCABG (P < 0.05) after surgery. The mean ± standard deviation of the IIEF-5 scores of the on-pump group postoperatively became 12.48 ± 7.19 whereas it became 15.88 ± 6.67 in the off-pump group (P < 0.05). Moreover, the number of patients who reported postoperative improvement of their IIEF-5 score was significantly higher in OPCABG group (N = 23) compared with the conventional on-pump CABG group (N = 13) (P < 0.05). There was no significant change in the duplex ultrasound after surgery between both groups.ConclusionsThe OPCABG has a diminished impact on the sexual function of patients compared with the conventional on-pump CABG. Therefore, the type of operation can be considered a predictive factor of sexual function following CAB surgery. Mohamed OA, Bennett CJ, Farid RM, Helmy T, Mahran A, and Hamed HA. The impact of on-pump coronary artery bypass surgery vs. off-pump coronary artery bypass surgery on sexual function. J Sex Med **;**:**–**.     

Relative bioavailability of griseofulvin lyophilized dry emulsion tablet vs. immediate release tablet: A single-dose, randomized, open-label, six-period, crossover study in healthy adult volunteers in the fasted and fed states

The oral bioavailability of griseofulvin (GF) formulated as a fast disintegrating lyophilized dry emulsion (LDE) tablet was studied and compared to the commercially available immediate release (IR) tablet, as a reference, in both the fasted and fed states in nine healthy volunteers after a single oral dose (125mg) in a crossover design. Furthermore the LDE tablets were ingested with and without water under both the fasted and fed states. In the fasted state, the rate of absorption was found to be significantly faster from LDE tablets, in the presence and absence of water, as shown by a higher C(max) (more than two times higher, p=0.0001) and a shorter t(max) (by more than 3h, p=0.0001) compared to IR tablets. The extent of absorption, expressed as AUC, from LDE tablets in the presence and absence of water was 65% and 77% larger and statistically significantly different relative to the mean AUC from IR tablets (p=0.006). In the fed state, C(max) from LDE tablets ingested with and without water was found to be about 30% and 50% higher, respectively, than the immediate release tablets. A shorter t(max) was also shown whether LDE tablets were ingested with or without water in the fed state as compared to immediate release tablets. The mean AUC from LDE tablets under fed conditions in the presence of water was about 21% larger and was not statistically significantly different from AUC from immediate release tablets (p=0.517). When ingested without water, AUC from LDE tablets was about 43% larger and statistically significantly different relative to AUC from IR tablets (p=0.033). The mean AUC from the LDE tablet ingested with water under fed conditions relative to AUC from LDE tablet ingested without water was not statistically significantly different (p=0.454). Results show that the food effect of the high fat meal is very pronounced in case of the immediate release tablets, Fulvin, than in case of LDE tablets whether given with or without water.     

A novel poly(ADP-ribose) polymerase inhibitor, ABT-888, radiosensitizes malignant human cell lines under hypoxia

The chemo- and radioresponse of tumor cells can be determined by genetic factors (e.g., those that modify cell cycle arrest, DNA damage repair or cell death) and microenvironmental factors, such as hypoxia. Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme that rapidly recognizes and binds to DNA breaks to facilitate DNA strand break repair. Pre-clinical data suggest that PARP inhibitors (PARPi) may potentiate the effects of radiotherapy and chemotherapy. However, it is unclear as to whether PARPi are effective against hypoxic cells. We therefore tested the role for a novel PARPi, ABT-888, as a radiosensitizing agent under hypoxic conditions. Using human prostate (DU-145, 22RV1) and non-small cell lung (H1299) cancer cell lines, we observed that ABT-888 inhibited both recombinant PARP activity and intracellular PARP activity (86% to 92% decrease in all 3 cells lines following 2.5muM treatment). ABT-888 was toxic to both oxic and hypoxic cells. When ABT-888 was combined with ionizing radiation (IR), clonogenic radiation survival was decreased by 40-50% under oxic conditions. Under acute hypoxia, ABT-888 radiosensitized malignant cells to a level similar to oxic radiosensitivity. To our knowledge, this is the first study to demonstrate that inhibition of PARP activity can sensitize hypoxic cancer cells and the combination of IR-PARPi has the potential to improve the therapeutic ratio of radiotherapy.