Conduction studies in peripheral cat nerve using implanted electrodes: III. The effects of prolonged constriction on the distal nerve segment

Electrophysiological properties were monitored in detail in chronically constricted peripheral nerves by implanted, multicontact nerve cuff electrodes and correlated with morphometric histology in selected cases. The physiological and histological responses in nerve to a range of constricting cuffs of standard sizes were readily graded. The initial response to any significant constriction was a transient, focal conduction slowing or block at the constriction, followed by more protracted distal effects; the latter ranged from loss of excitability consistent with "dying-back" degeneration to reductions in conduction velocity consistent with histologically observed atrophy. Smaller myelinated fibers tended to have similar but less pronounced changes than larger diameter fibers. Recordings from ventral and dorsal roots showed that distal degeneration was more pronounced in motor than in sensory fibers of similar caliber. Electronmicroscopical measurements showed that basal laminas were relatively preserved around even the most atrophic and demyelinated axons. Perimeter measurements of the basal lamina could be used to estimate the diameter of the original nerve fiber.     

Chronic portal venous hypertension. The effect on liver blood flow and liver function and the development of esophageal varices

Portal venous hypertension was induced in G?ttingen minipigs by banding the portal vein. The pigs were checked repeatedly during the following 24 weeks. Portal pressure increased immediately on banding, from 8.4 +/- 0.7 mm Hg to 19.4 +/- 0.7 mm Hg, and remained constant throughout the observation period. Within 5 weeks all pigs developed esophageal varices, as demonstrated by portal angiography and endoscopy. The experimentally induced portal hypertension was accompanied by a 65% decrease in hepatic blood flow, most probably caused by almost complete shunting of portal venous blood. The hepatic arterial flow appeared to be within normal limits and sufficient to cover the oxygen demand of the liver; to judge from the splanchnic elimination rate of galactose, the hemodynamic changes did not affect the functional capacity of the liver.     

Liraglutide,a once‐daily human GLP‐1 analogue,improves pancreatic B‐cell function and arginine‐stimulated insulin secretion during hyperglycaemia in patients with Type 2 diabetes mellitus

Aims To assess the effect of liraglutide, a once‐daily human glucagon‐like peptide‐1 analogue on pancreatic B‐cell function. Methods Patients with Type 2 diabetes (n = 39) were randomized to treatment with 0.65, 1.25 or 1.9 mg/day liraglutide or placebo for 14 weeks. First‐ and second‐phase insulin release were measured by means of the insulin‐modified frequently sampled intravenous glucose tolerance test. Arginine‐stimulated insulin secretion was measured during a hyperglycaemic clamp (20 mmol/l). Glucose effectiveness and insulin sensitivity were estimated by means of the insulin‐modified frequently sampled intravenous glucose tolerance test. Results The two highest doses of liraglutide (1.25 and 1.9 mg/day) significantly increased first‐phase insulin secretion by 118 and 103%, respectively (P < 0.05). Second‐phase insulin secretion was significantly increased only in the 1.25 mg/day group vs. placebo. Arginine‐stimulated insulin secretion increased significantly at the two highest dose levels vs. placebo by 114 and 94%, respectively (P < 0.05). There was no significant treatment effect on glucose effectiveness or insulin sensitivity. Conclusions Fourteen weeks of treatment with liraglutide showed improvements in first‐ and second‐phase insulin secretion, together with improvements in arginine‐stimulated insulin secretion during hyperglycaemia.     

Pharmacological interventions for improved colonic anastomotic healing: A meta-analysis

AIM: To identify pharmaceuticals for the prophylaxis of anastomotic leakage (AL), we systematically reviewed studies on anastomosis repair after colorectal surgery.METHODS: We searched PubMed and EMBASE for articles published between January 1975 and December 2012. We included studies in English with the primary purpose of promoting healing of anastomoses made in the colon or rectum under uncomplicated conditions. We excluded studies on adverse events from interventions, nutritional interventions or in situ physical supporting biomaterials. The primary outcome was biomechanical strength or AL. We performed meta-analyses on therapeutic agents investigated by three or more independent research groups using the same outcome. The DerSimonian-Laird method for random effects was applied with P < 0.05.RESULTS: Of the 56 different therapeutic agents assessed, 7 met our inclusion criteria for the meta-analysis. The prostacyclin analog iloprost increased the weighted mean of the early bursting pressure of colonic anastomoses in male rats by 60 mmHg (95%CI: 30-89) vs the controls, and the immunosuppressant tacrolimus increased this value by 29 mmHg (95%CI: 4-53) vs the controls. Erythropoietin showed an enhancement of bursting pressure by 45 mmHg (95%CI: 14-76). The anabolic compound growth hormone augmented the anastomotic strength by 21 mmHg (95%CI: 7-35), possibly via the up-regulation of insulin-like growth factor-1, as this growth factor increased the bursting pressure by 61 mmHg (95%CI: 43-79) via increased collagen deposition. Hyperbaric oxygen therapy increased the bursting pressure by 24 mmHg (95%CI: 13-34). Broad-spectrum matrix metalloproteinase inhibitors increased the bursting pressure by 48 mmHg (95%CI: 31-66) on postoperative days 3-4. In the only human study, the AL incidence was not significantly reduced in the 103 colorectal patients treated with aprotinin (11.7%) compared with the 113 placebo-treated patients (9.7%).CONCLUSION: This systematic review identified only one randomized clinical trial and seven therapeutic agents from pre-clinical models that could be explored further for the prophylaxis of AL after colorectal surgery.