Only high levels of dabigatran attenuate catheter thrombosis in vitro and in rabbits.

In patients with mechanical heart valves, thromboembolic events were more frequent with dabigatran, an oral thrombin inhibitor, than with warfarin. This observation raises the possibility that dabigatran may be less effective than conventional anticoagulants in patients with other blood-contacting devices, such as catheters. To address this, we compared the capacity of dabigatran and/or heparin to inhibit catheter-induced thrombin generation in vitro and to attenuate catheter occlusion in rabbits. Using a catheter-induced thrombin generation assay, concentrations of dabigatran over 100 ng/ml prolonged the lag time and time to peak thrombin, and reduced the peak thrombin concentration and endogenous thrombin potential in a concentration-dependent fashion. Compared with saline in a rabbit model of catheter thrombosis, dabigatran prolonged the mean time to catheter occlusion by 2.9- and 1.9-fold when plasma levels were 173 and 140 ng/ml, respectively; values comparable to median peak levels in humans given dabigatran 150 mg twice daily. In contrast, low-dose dabigatran, which produced a level of 60 ng/ml; a value comparable to the trough level of dabigatran in humans, did not prolong the time to occlusion. Whereas a 70 U/kg bolus of heparin prolonged the mean time to occlusion by 3.4-fold, a 15 U/kg bolus had no effect. When low-dose dabigatran was given in combination with 15 U/kg heparin, the mean time to occlusion was prolonged by 2.7-fold. These findings suggest that only peak levels of dabigatran are sufficient to prevent catheter-induced clotting unless supplemented heparin is given.

Randomized clinical trial on the effect of coffee on postoperative ileus following elective colectomy.

BACKGROUND: Postoperative ileus is a common problem after abdominal surgery. It was postulated that coffee intake would decrease postoperative ileus after colectomy. METHODS: This was a multicentre parallel open-label randomized trial. Patients with malignant or benign disease undergoing elective open or laparoscopic colectomy were assigned randomly before surgery to receive either coffee or water after the procedure (100 ml three times daily). The primary endpoint was time to first bowel movement; secondary endpoints were time to first flatus, time to tolerance of solid food, length of hospital stay and perioperative morbidity. RESULTS: A total of 80 patients were randomized, 40 to each group. One patient in the water arm was excluded owing to a change in surgical procedure. Patient characteristics were similar in both groups. In intention-to-treat analysis, the time to the first bowel movement was significantly shorter in the coffee arm than in the water arm (mean(s.d.) 60·4(21·3) versus 74·0(21·6) h; P = 0·006). The time to tolerance of solid food (49·2(21·3) versus 55·8(30·0) h; P = 0·276) and time to first flatus (40·6(16·1) versus 46·4(20·1) h; P = 0·214) showed a similar trend, but the differences were not significant. Length of hospital stay (10·8(4·4) versus 11·3(4·5) days; P = 0·497) and morbidity (8 of 40 versus 10 of 39 patients; P = 0·550) were comparable in the two groups. CONCLUSION: Coffee consumption after colectomy was safe and was associated with a reduced time to first bowel action.

[Surgery and management: natural partners]. / Chirurgie und Management: natürliche Partner.

The term management is a description of the functions: planning, organization, leadership and control in institutions and the corresponding persons holding these powers. In order to efficiently lead a department of surgery, surgeons need to possess management qualities and have to be able to act as team leaders. Good management of a surgical department leads to avoidance of complications and increased profits as well as more efficient use of operating room capacities and a better organization within the department.

Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells.

Alterations in the cellular redox potential by homocysteine promote endothelial cell (EC) dysfunction, an early event in the progression of atherothrombotic disease. In this study, we demonstrate that homocysteine causes endoplasmic reticulum (ER) stress and growth arrest in human umbilical vein endothelial cells (HUVEC). To determine if these effects reflect specific changes in gene expression, cDNA microarrays were screened using radiolabeled cDNA probes generated from mRNA derived from HUVEC, cultured in the absence or presence of homocysteine. Good correlation was observed between expression profiles determined by this method and by Northern blotting. Consistent with its adverse effects on the ER, homocysteine alters the expression of genes sensitive to ER stress (ie, GADD45, GADD153, ATF-4, YY1). Several other genes observed to be differentially expressed by homocysteine are known to mediate cell growth and differentiation (ie, GADD45, GADD153, Id-1, cyclin D1, FRA-2), a finding that supports the observation that homocysteine causes a dose-dependent decrease in DNA synthesis in HUVEC. Additional gene profiles also show that homocysteine decreases cellular antioxidant potential (glutathione peroxidase, NKEF-B PAG, superoxide dismutase, clusterin), which could potentially enhance the cytotoxic effects of agents or conditions known to cause oxidative damage. These results successfully demonstrate the use of cDNA microarrays in identifying homocysteine-respondent genes and indicate that homocysteine-induced ER stress and growth arrest reflect specific changes in gene expression in human vascular EC.

Anesthetic and hemodynamic effects of dexmedetomidine during isoflurane anesthesia in a canine model.

Dexmedetomidine, an alpha 2-adrenergic agonist, was administered during isoflurane anesthesia to investigate its anesthetic sparing and hemodynamic effects in the canine model. Eleven healthy dogs were anesthetized with isoflurane, intubated, and allowed to breathe spontaneously. The animals were instrumented in order to measure or calculate mean arterial blood pressure (MABP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), cardiac output (CO), and systemic vascular resistance (SVR). Isoflurane minimum alveolar concentration (MAC), baseline hemodynamic measurements, and plasma catecholamine levels were determined. A 20 micrograms/kg bolus of dexmedetomidine was injected intravenously (IV) and MAC and hemodynamic values were redetermined. When isoflurane requirements were 33% of baseline, isoflurane was returned to 90% MAC and the alpha 2-antagonist, atipamezole, was administered. All dogs were treated with 40 micrograms/kg glycopyrrolate throughout the experiment to prevent any bradycardic response. Dexmedetomidine reduced isoflurane MAC by 86%. SVR, MABP, and LVEDP were significantly increased while CO and catechloamine levels were reduced. Atipamezole fully reversed the reduction in anesthetic requirements. MABP and catecholamine levels returned to baseline. SVR and LVEDP increased while CO decreased. The dogs exhibited a profound reduction in anesthetic requirement, reduced catecholamine levels, and changes in hemodynamic parameters with dexmedetomidine administration. The anesthetic sparing effect appears to be mediated by the alpha 2-receptor, since atipamezole reversed the reduction in MAC. Hemodynamic changes may be species or dose related, or due to differences in existing sympathetic tone. The role of dexmedetomidine warrants further study as an adjunct anesthetic agent.