Improved glycaemic control with no weight gain: a 26-week, open label, non-randomised, non-interventional observational study on type 2 diabetes subjects using insulin detemir.

The aim of this study was to evaluate the weight change from baseline while using insulin detemir in subjects with type 2 diabetes mellitus under normal clinical practice conditions. It was a multicentre, open label, non-randomised, non-interventional, observational, safety and efficacy study in subjects using insulin detemir for the treatment of type 2 diabetes mellitus. In this study, the mean body weight decreased marginally by -0.8 kg at the end of week 26 from baseline. Change in mean body weight during the study was not statistically significant (p > 0.05). There was a statistically significant (p < -0.05) change in waist circumference (-0.7 cm) from baseline at week 26. Mean fasting plasma glucose reduced significantly (p < 0.0001) from 199.1 mg/dl at initiation of insulin detemir to 141.3 mg/dl at week 13 and 115.8 mg/dl at week 26. Mean HbA1c reduced significantly (p < 0.0001) from 9.2% at initiation of insulin detemir to 7.8% at week 13 and 7.2% at week 26. Insulin dose changed marginally from the baseline (15.1 units) to week 26 (15.3 units). Majority of the subjects (89%) were on once daily insulin detemir. Before initiating insulin detemir proportion of subjects experiencing at least one episode of hypoglycaemia during the past four weeks was 8.8% (n = 884). It was reduced 2.4% (n = 241) at week 13 and 1.6% (n = 164) at week 26 following initiation of insulin detemir. There were no major nocturnal hypoglycaemic episodes during 26 weeks of insulin detemir therapy. In conclusion, this study indicates that insulin detemir is safe, effective and weight neutral.

A limited sampling strategy for tacrolimus in renal transplant patients.

AIMS: To develop and validate limited sampling strategy (LSS) equations to estimate area under the curve (AUC(0-12)) in renal transplant patients. METHODS: Twenty-nine renal transplant patients (3-6 months post transplant) who were at steady state with respect to tacrolimus kinetics were included in this study. The blood samples starting with the predose (trough) and collected at fixed time points for 12 h were analysed by microparticle enzyme immunoassay. Linear regression analysis estimated the correlations of tacrolimus concentrations at different sampling time points with the total measured AUC(0-12). By applying multiple stepwise linear regression analysis, LSS equations with acceptable correlation coefficients (R(2)), bias and precision were identified. The predictive performance of these models was validated by the jackknife technique. RESULTS: Three models were identified, all with R(2) > or = 0.907. Two point models included one with trough (C(0)) and 1.5 h postdose (C(1.5)), another with trough and 4 h postdose. Increasing the number of sampling time points to more than two increased R(2) marginally (0.951 to 0.990). After jackknife validation, the two sampling time point (trough and 1.5 h postdose) model accurately predicted AUC(0-12). Regression coefficient R(2) = 0.951, intraclass correlation = 0.976, bias [95% confidence interval (CI)] 0.53% (-2.63, 3.69) and precision (95% CI) 6.35% (4.36, 8.35). CONCLUSION: The two-point LSS equation [AUC(0-12) = 19.16 + (6.75.C(0)) + (3.33.C1.5)] can be used as a predictable and accurate measure of AUC(0-12) in stable renal transplant patients prescribed prednisolone and mycophenolate.

4-aminopyridine-induced contracture in frog ventricle is due to calcium released from intracellular stores.

The aim of the study is to demonstrate the presence of intracellular calcium store in frog ventricle based on contractures induced by 4-aminopyridine in calcium-free media. Frog-ventricular strips were subjected to field stimulation at 0.2 Hz and the force of contraction was recorded after stabilization. The preparation was then kept quiescent for some time in solutions with different sodium concentrations, containing 0 or 1 mmol/L calcium. Caffeine, 4-aminopyridine (4-AP), or tetraethylammonium chloride was then added. Frog skeletal muscle preparations were used as positive controls for the caffeine experiments. Frog ventricular preparations did not develop contractures (sustained contractions) in the presence of caffeine (25 mmol/L), while frog skeletal muscle preparations developed caffeine-induced contractures. However, 4-AP (16 mmol/L) was able to induce contractures in quiescent frog ventricular preparations, even when they were superfused with calcium-free solution. 4-AP contractures in frog ventricle were seen in the presence of nifedipine also. Amplitude of 4-AP evoked contractures in frog ventricle were much larger in low sodium (30 mmol/L) and sodium-free (sodium substituted by lithium) solutions than in normal sodium solution, suggesting that the route of extrusion of the cytosolic calcium (released from intracellular stores by 4-AP) is the sodium calcium exchanger, which gets reversed in low sodium solutions. Tetraethylammonium chloride (TEA) was not able to induce contractures in frog ventricle suggesting that the contracture evoked by 4-AP is not due to its potassium channel blocking effect. In quiescent frog skeletal muscle preparations, caffeine as well as 4-AP induced contractures in calcium-free solutions. We therefore conclude that there is a caffeine-insensitive, 4-AP sensitive intracellular calcium store in the frog ventricle.

Topical phenytoin solution for treating pressure ulcers: a prospective, randomized, double-blind clinical trial.

STUDY DESIGN: Prospective, randomized, double-blind clinical trial. OBJECTIVES: To evaluate the efficacy of topical phenytoin solution in treating pressure ulcers among patients with spinal cord disorders and to evaluate the systemic absorption of topical phenytoin. SETTING: Physical Medicine and Rehabilitation Unit, Christian Medical College, Vellore, India. METHODS: Twenty-eight patients with stage 2 pressure ulcers were randomized to receive either phenytoin solution (5 mg/ml) or normal saline dressing on their ulcers once daily for 15 days. Efficacy of the treatment was determined by assessing the reduction in Pressure Ulcer Scores for Healing (PUSH 3.0), ulcer volume and ulcer size as on day 16. Serum phenytoin concentrations were estimated to determine the systemic absorption of topical phenytoin. RESULTS: Statistically insignificant but marginally higher reduction in PUSH 3.0 scores and ulcer size were seen with topical phenytoin treatment. Systemic absorption of topical phenytoin was negligible. No adverse drug events were detected during the study. CONCLUSIONS: Phenytoin solution is a safe topical agent that accelerates healing of pressure ulcers. However, its efficacy is only slightly more than normal saline treatment.