Targeted disruption of the FGF-2 gene affects the response to peripheral nerve injury

Basic fibroblast growth factor (FGF-2) is involved in the development, maintenance, and survival of the nervous system. To study the physiological role of endogenous FGF-2 during peripheral nerve regeneration, we analyzed sciatic nerves of FGF-2-deleted mice by using morphometric, morphological, and immunocytochemical methods. Quantification of number and size of myelinated axons in intact sciatic nerves revealed no difference between wild-type and FGF-2 knock-out (ko) animals. One week after nerve crush, FGF-2 ko mice showed about five times more regenerated myelinated axons with increased myelin and axon diameter in comparison to wild-types close to the injury site. In addition, quantitative distribution of macrophages and collapsed myelin profiles suggested faster Wallerian degeneration in FGF-2-deleted mice close to the lesion site. Our results suggest that endogenous FGF-2 is crucially involved in the early phase of peripheral nerve regeneration possibly by regulation of Schwann cell differentiation.     

The Influence of Laparoscopic Adjustable Gastric Banding on Gastroesophageal Reflux

Background: Laparoscopic adjustable gastric banding (LAGB) influences gastroesophageal reflux. Methods: 26 patients undergoing gastric banding were assessed by a questionnaire for symptom analysis, 24-hour pH monitoring, endoscopy and barium swallows, preoperatively, at 6 weeks and at 6 months after operation. Results: Gastric banding had minimal effect on heartburn scores, but regurgitation and belching scores increased significantly during follow-up. Use of acid-reducing drugs decreased significantly at 6 weeks and increased significantly at 6 months. Pathological reflux was present in 13 of the 26 patients preoperatively. At 6 months pathological reflux was found in only 6 of these 13 patients, but 4 of the 13 patients with preoperative normal reflux patterns had developed pathological reflux. 6 months after the operation esophagitis had disappeared in 6 patients and was increased in 9 patients. In 9 patients, a pouch was found at 6 months. Pouch formation was significantly correlated with the presence of pathological reflux, esophagitis and the use of acid-reducing medication. Preoperative presence of a hiatal hernia did not influence pouch formation or pathological reflux. Conclusion: LAGB decreases gastroesophageal reflux if there is no pouch formation during follow-up.     

Concomitant administration of the α-glucosidase inhibitor voglibose (AO-128) does not alter the pharmacokinetics of glibenclamide

Objective: Voglibose is a new and potent inhibitor of α-glucosidases used for treatment of diabetes mellitus. It increases gastro-intestinal motility and could thus affect absorption of other concurrently administered antidiabetic drugs. The aim of this study was to investigate whether or not voglibose modifies the pharmacokinetics of glibenclamide, a widely used oral antidiabetic, and the glibenclamide-induced decrease in fasting serum glucose. Methods: Twelve healthy male subjects were included in this double-blind cross-over study and received a single 1.75-mg dose of glibenclamide on the 8th day of continuous administration of either placebo (reference) or voglibose 5 mg t.i.d. (test). Blood samples were taken to determine the pharmacokinetic characteristics of gliben-clamide and the test/reference ratios were evaluated according to bioequivalence criteria. Additional blood samples were taken to measure serum glucose on the same day. Results: The concentration–time course of glibenclamide under concomitant voglibose administration was similar to that under placebo. The equivalence ratio (test/reference) for the pharmacokinetic characteristics AUC_normwas 1.03 (geometric mean; 0.95–1.11, 90% confidence interval) and C_max,norm1.01 (0.94–1.08). The parameters were within the accepted range of 0.8–1.25 (AUC) or 0.7–1.43 (C_max), thus fulfilling equivalence criteria and indicating no effect of voglibose on glibenclamide kinetics. The glibenclamide-induced decrease in fasting serum glucose concentration was similarly independent of placebo or voglibose co-administration. Conclusions: Voglibose did not interact with glibenclamide on a pharmacokinetic level. Concomitant treatment was well tolerated and has been proven to be safe for further clinical use. Received: 28 February 1997 / Accepted in revised form: 8 May 1997     

One year outcomes after glucose-insulin-potassium in ST elevation myocardial infarction. The Glucose-insulin-potassium study II

BackgroundThere are conflicting data concerning the effect of treatment with glucose–insulin–potassium (GIK) in ST segment elevation myocardial infarction (STEMI). Early studies showed beneficial effects of GIK, however, recent large sample size trials did not confirm this, or suggested only benefits in patients without heart failure. We aimed to evaluate long-term effects of GIK in patients with STEMI without signs of heart failure, all treated with reperfusion therapy.MethodsFrom August 2003 to December 2004, 889 STEMI patients without signs of heart failure were randomized to standard care (N = 445) or additional GIK infusion (N = 444). Glucose–potassium (20% glucose with 80 mmol potassium/l) was infused at 2 ml/kg body weight per hour for 12 h through a peripheral line. Short-acting insulin was started according to admission glucose and adjusted based on hourly measured glucose. Clinical end points were of number of death, reinfarction and revascularization at 1 year.ResultsOne year follow-up was available in 864 patients (97.2%), 432 in the GIK group and 432 in the control group. Mortality rate was 5.3% in GIK and 3.9% in control patients, p = 0.33. Rates of reinfarction and revascularization 4.6% vs. 4.6% and 15.5% and 15.0%, in GIK vs. control patients.ConclusionIn patients with STEMI without signs of heart failure treated with reperfusion therapy, GIK therapy offers no clinical benefit at 1 year.     

Clotting factor activity levels and bleeding risk in people with haemophilia playing sports

Background

Improved treatment options for people with haemophilia (PWH) have increased the possibilities for sports participation, but the risk of sports-induced bleeding (SIB) is still considered considerable by many.

Aim

To assess sports associated injury- and bleeding risk in PWH and to assess clotting levels associated with safe sports participation.

Methods

Sports injuries and SIBs were prospectively collected for 12 months in PWH aged 6–49 without inhibitors playing sports at least once weekly. Injuries were compared according to factor levels, severity, joint health, sports risk category and sports intensity. Factor activity at the time of injury was estimated using a pharmacokinetic model.

Results

125 participants aged 6–49 (41 children, 90% haemophilia A; 48% severe, 95% severe on prophylaxis) were included. Sports injuries were reported by 51 participants (41%). Most participants (62%) reported no bleeds at all and only 16% reported SIBs. SIBs were associated with factor levels at time of injury (OR: 0.93/%factor level (CI 0.88–0.99); p = .02), but not with haemophilia severity (OR: 0.62 (CI 0.20–1.89); p = .40), joint health, sports risk category or sports intensity. PWH with factor levels <10% during sports injury had a bleeding risk of 41% versus 20% in those with higher (>10%) factor levels.

Conclusion

The results of this study emphasize the importance of clotting factor levels in prevention of bleeds. This information is vital for patient counselling and tailoring prophylactic treatment with clotting factors and non-replacement therapy.     

Long-term follow-up after invasive approach of coronary artery disease in daily practice

BACKGROUND: To assess long-term survival in unselected patients with coronary artery disease in who an invasive approach is considered. METHODS: All patients with significant coronary artery disease who were presented for coronary revascularisation to two tertiary centres in 1992 were included. Follow-up data were collected in September 2002. Multivariate Cox' proportional-hazards regression analysis was applied to assess the independent relation between variables and 10-year survival. RESULTS: A total of 877 patients were included in this analysis. Mean age was 62 and the most common clinical diagnosis was chronic stable angina (60%). Diabetes was present in 12% of the patients. During the follow-up period, 233 patients (27%) died. Predictors of long-term survival were increasing age, diabetes, peripheral vascular disease and a decreased left ventricular function. Compared to medical treated patients, those treated with revascularisation (either by PCI or CABG) had a decreased long-term mortality (p<0.05). Of the patients with PCI 27% had died, compared to 24% in those who had CABG and 36% of those who were treated medically. However, after adjusting for differences in baseline variables, conservative treatment was no significant predictor of long-term mortality. After multivariable analyses, increasing age, decreased left ventricular function and diabetes were independent predictors of long-term mortality. CONCLUSIONS: In patients with coronary artery disease in whom an invasive approach is considered, increasing age, impaired left ventricular function and diabetes are the strongest predictors of long-term mortality. After adjustments for differences in baseline variables, invasive treatment is not associated with a lower long-term mortality.     

Prognostic value of admission glucose and glycosylated haemoglobin levels in acute coronary syndromes

BACKGROUND: Admission hyperglycaemia is associated with poorer prognosis in patients with an acute coronary syndrome (ACS). Whether hyperglycaemia is more important than prior long-term glucose metabolism, is unknown. AIM: To investigate the prognostic value of admission glucose and HbA(1c) levels in patients with ACS. METHODS: We measured glucose and HbA(1c) at admission in 521 consecutive patients with suspected ACS. Glucose was categorized as <7.8 (n = 305), 7.8-11.0 (n = 138) or > or =11.1 mmol/l (n = 78); HbA(1c) as <6.2% (n = 420) or > or =6.2% (n = 101). Mean follow-up was 1.6 +/- 0.5 years. RESULTS: The diagnosis of ACS was confirmed in 332 patients (64%), leaving 189 (36%) with atypical chest pain. In ACS patients, mortality by glucose category (<7.8, 7.8-11.0 or > or =11.1 mmol) was 9%, 8% and 25%, respectively (p = 0.001); mortality by HbA(1c) category (<6.2% vs. > or =6.2%) was 10% vs. 17%, respectively (p = 0.14). On multivariate analysis, glucose category was significantly associated with mortality (HR 3.0, 95% CI 1.1-8.3), but HbA(1c) category was not (HR 1.5, 95%CI 0.6-4.2). DISCUSSION: Elevated admission glucose appears more important than prior long-term abnormal glucose metabolism in predicting mortality in patients with suspected ACS.