Etiology and epidemiological analysis of glaucoma-filtering bleb infections in a tertiary eye care hospital in South India.

PURPOSE: To evaluate the microbial etiology and associated risk factors among patients with blebitis following trabeculectomy. MATERIALS AND METHODS: A retrospective analysis of all culture-proven blebitis was performed in patients who underwent trabeculectomy between January 2004 and December 2008. A standardized form was filled out for each patient, documenting sociodemographic features and information pertaining to risk factors. Swabbing of the infected bleb surface was performed for all suspected cases and further subjected to microbiological analysis. RESULTS: A total of 23 patients with culture-proven blebitis were treated during the study period, with a mean age of 59.2 years (59.2 ± SD: 12.8; range, 30-81 years). Duration of onset was early (≤ 36 months) in six (26%) cases and late (> 36 months) in 17 (74%) cases with a range between 15 and 144 months (mean, 82.91 months; SD: 41.89). All 23 blebs were located superiorly and of which, 21 (91%) were microcystic avascular, 1 (4%) diffuse avascular, and 1 (4%) vascular flattened. The predominant risk factor identified was bleb leak (35%; 8 of 23) followed by thin bleb (22%; 5 of 23) and blepharitis (17%; 4 of 23). Bleb leaks (100%) were recorded only in patients with late onset (≥ 9 years) of infection (P< 0.001), while the incidence of ocular surface disease (100%) occurred early (≤ 3 years) (P< 0.001). Use of topical steroids was associated frequently with cases of thin blebs (80%; 4 of 5) (P< 0.001), while topical antibiotics showed bleb leaks (88%; 7 of 8) (P< 0.001). Coagulase-positive staphylococci were frequently recovered from blebitis with thin blebs (71%; 5 of 7) (P = 0.001), Coagulase-negative staphylococci (CoNS) with bleb leak (100%; 8 of 8) (P< 0.001), Corynebacterium with blepharitis (100%; 3 of 3) (P = 0.001), and Streptococci with releasable sutures (75%; 3 of 4) (P = 0.001). CONCLUSION: Bleb leak is the principal risk factor responsible for late-onset blebitis, while early-onset blebitis could be ascribed to ocular surface diseases. Streptococci were mainly responsible for early onset of infection, while the late onset was due to CoNS.

Pasireotide (SOM230) demonstrates efficacy and safety in patients with acromegaly: a randomized, multicenter, phase II trial.

CONTEXT: Pasireotide (SOM230) is a novel multireceptor ligand somatostatin analog with affinity for somatostatin receptor subtypes sst(1-3) and sst(5). Because most GH-secreting pituitary adenomas express sst(2) and sst(5), pasireotide has the potential to be more effective than the sst(2)-preferential somatostatin analogs octreotide and lanreotide. OBJECTIVE: Our objective was to evaluate the efficacy and safety of three different doses of pasireotide in patients with acromegaly. DESIGN: We conducted a phase II, randomized, multicenter, open-label, three-way, crossover study. PATIENTS: Sixty patients with acromegaly, defined by a 2-h five-point mean GH level higher than 5 microg/liter, lack of suppression of GH to less than 1 microg/liter after oral glucose tolerance test, and elevated IGF-I for age- and sex-matched controls. Patients could have had previous surgery, radiotherapy, and/or medical therapy or no previous treatment. INTERVENTION: After treatment with octreotide 100 microg s.c. three times daily for 28 d, each patient received pasireotide 200, 400, and 600 microg s.c. twice daily in random order for 28 d. MAIN OUTCOME MEASURE: A biochemical response was defined as a reduction in GH to no more than 2.5 microg/liter and normalization of IGF-I to age- and sex-matched controls. RESULTS: After 4 wk of octreotide, 9% of patients achieved a biochemical response. After 4 wk of pasireotide 200-600 microg s.c. bid, 19% of patients achieved a biochemical response, which increased to 27% after 3 months of pasireotide; 39% of patients had a more than 20% reduction in pituitary tumor volume. Pasireotide was generally well tolerated. CONCLUSIONS: Pasireotide is a promising treatment for acromegaly. Larger studies of longer duration evaluating the efficacy and safety of pasireotide in patients with acromegaly are ongoing.

Comparison of vildagliptin and acarbose monotherapy in patients with Type 2 diabetes: a 24-week, double-blind, randomized trial.

AIMS: To compare the efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor, vildagliptin, with the alpha glucosidase inhibitor, acarbose, in drug-naive patients with Type 2 diabetes. METHODS: This multi-centre, randomized, double-blind, parallel-arm study compared the efficacy and tolerability of vildagliptin (100 mg daily, given as 50 mg twice daily, n = 441) and acarbose (up to 300 mg daily, given as three equally divided doses, n = 220) during 24-week treatment in drug-naive patients with Type 2 diabetes. RESULTS: Monotherapy with vildagliptin or acarbose decreased glycated haemoglobin (HbA(1c)) (baseline approximately 8.6%) to a similar extent during 24-week treatment. The adjusted mean change from baseline to end-point (AMDelta) in HbA(1c) was -1.4 +/- 0.1% and -1.3 +/- 0.1% in patients receiving vildagliptin and acarbose, respectively, meeting the statistical criterion for non-inferiority (upper limit of 95% confidence interval for between-treatment difference < or = 0.4%). The decrease in fasting plasma glucose was similar with acarbose (-1.5 +/- 0.2 mmol/l) and vildagliptin (-1.2 +/- 0.1 mmol/l). Body weight did not change in vildagliptin-treated patients (-0.4 +/- 0.1 kg) but decreased in acarbose-treated patients (-1.7 +/- 0.2 kg, P < 0.001 vs. vildagliptin). The proportion of patients experiencing any adverse event (AE) was 35% vs. 51% in patients receiving vildagliptin or acarbose, respectively; gastrointestinal AEs were significantly more frequent with acarbose (25.5%) than vildagliptin (12.3%, P < 0.001). No hypoglycaemia was reported for either group. CONCLUSIONS: Vildagliptin is effective and well tolerated in patients with Type 2 diabetes, demonstrating similar glycaemic reductions to acarbose, but with better tolerability.

Metformin-glibenclamide versus metformin plus rosiglitazone in patients with type 2 diabetes inadequately controlled on metformin monotherapy.

AIM: This double-blind study evaluated the efficacy and safety of metformin-glibenclamide tablets vs. metformin plus rosiglitazone therapy in patients with type 2 diabetes inadequately controlled on metformin monotherapy. SUBJECTS AND METHODS: After an open-label, metformin lead-in phase, 318 patients were randomly assigned to treatment based on metformin-glibenclamide 500/2.5 mg tablets (initial daily dose 1000/5 mg) or metformin 500 mg plus rosiglitazone 4 mg (initial daily dose 1000-2000 mg + 4 mg, depending on previous treatment) for 24 weeks. Doses were titrated to achieve the therapeutic glycaemic target. The primary efficacy variable was the change in HbA1C. RESULTS: At week 24, metformin-glibenclamide tablets resulted in significantly greater reductions in HbA1C (-1.5%) and fasting plasma glucose [-2.6 mmol/l (-46 mg/dl)] than metformin plus rosiglitazone [-1.1%, p < 0.001; -2 mmol/l (-36 mg/dl), p = 0.03]. More patients receiving metformin-glibenclamide attained HbA1C <7.0% than did those in the metformin plus rosiglitazone group (60 vs. 47%) and had fasting plasma glucose levels <7 mmol/l (<126 mg/dl) by week 24 (34 vs. 25%). Both treatments were well tolerated. Frequency of adverse gastrointestinal events was comparable between groups. Four per cent of patients receiving metformin-glibenclamide withdrew because of symptomatic hypoglycaemia contrasted with 3% of patients receiving metformin plus rosiglitazone who withdrew because of persistent hyperglycaemia. Hypoglycaemic events were mild or moderate in intensity and were easily self-managed. CONCLUSIONS: Metformin-glibenclamide tablets resulted in significantly greater reductions in HbA1C and fasting plasma glucose compared with metformin plus rosiglitazone in patients with type 2 diabetes inadequately controlled on metformin monotherapy.

Pharmacodynamic and pharmacokinetic properties of a premixed 85/15 human insulin preparation.

BACKGROUND: Many patients with diabetes use mixtures of fast-acting (regular human) insulin and intermediate-acting (neutral protamine Hagedorn [NPH]) insulin to control their blood glucose levels. Premixed insulin is available in a 70%/30% mixture and a 50%/50% mixture of NPH/regular human insulin. For some patients, however, a premixed formulation containing > or =30% regular human insulin can provide too much fast-acting insulin, potentially causing an increased risk for hypoglycemia in the early hours after injection. OBJECTIVE: The pharmacokinetic and pharmacodynamic properties of a premixed formulation of 85% NPH insulin and 15% regular human insulin (85/15) were compared with those of a premixed 70%/30% NPH/regular human insulin preparation and 100% NPH insulin. METHODS: A 12-hour euglycemic clamp approach was used to assess glucose-lowering effects and serum insulin levels in 36 healthy male volunteers in a single-dose (0.5 U/kg), randomized, double-blind, 3-period, crossover study. RESULTS: From 0 to 8 hours after injection, the glucose-lowering effects and serum insulin levels for the 85/15 premixed insulin preparation were significantly greater than those for NPH insulin (P < or = 0.05) but significantly less than those for the 70/30 premixed insulin preparation. The mean (+/- SEM) maximum glucose infusion rate (GIRmax) was 8+/-0.6 mg/(min x kg) for the 85/15 preparation, 7+/-0.6 mg/(min x kg) for NPH, and 9+/-0.6 mg/(min x kg) for the 70/30 preparation, with time to peak GIR (tmax(GIR)) occurring at 313, 360, and 272 minutes, respectively. Time to peak insulin levels did not differ significantly for the 3 preparations, but maximum serum insulin concentration (Cmax(ins)) was significantly different between the groups (70/30 premix: 54+/-2.2 microU/mL; 85/15 premix: 44+/-2.4 microU/mL; NPH: 35+/-1.7 microU/mL). Glucodynamic effect and serum insulin levels did not differ significantly among preparations during the interval from 8 to 12 hours after injection. Mean serum C-peptide levels ranged from -0.6 to 1.0 ng/mL for each preparation during the 12-hour period after injection. CONCLUSIONS: The 85/15 premixed insulin preparation demonstrated clinical pharmacokinetic and pharmacodynamic properties that were intermediate between, and significantly different from, those of NPH insulin and the 70/30 premixed insulin preparation.

Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes.

Glycogen synthase (GS) activity is reduced in skeletal muscle of type 2 diabetes, despite normal protein expression, consistent with altered GS regulation. Glycogen synthase kinase-3 (GSK-3) is involved in regulation (phosphorylation and deactivation) of GS. To access the potential role of GSK-3 in insulin resistance and reduced GS activity in type 2 diabetes, the expression and activity of GSK-3 were studied in biopsies of vastus lateralis from type 2 and nondiabetic subjects before and after 3-h hyperinsulinemic (300 mU x m(-2) x min(-1))-euglycemic clamps. The specific activity of GSK-3alpha did not differ between nondiabetic and diabetic muscle and was decreased similarly after 3-h insulin infusion. However, protein levels of both alpha and beta isoforms of GSK-3 were elevated (approximately 30%) in diabetic muscle compared with lean (P < 0.01) and weight-matched obese nondiabetic subjects (P < 0.05) and were unchanged by insulin infusion. Thus, both basal and insulin-stimulated total GSK-3 activities were elevated by approximately twofold in diabetic muscle. GSK-3 expression was related to in vivo insulin action, as GSK-3 protein was negatively correlated with maximal insulin-stimulated glucose disposal rates. In summary, GSK-3 protein levels and total activities are 1) elevated in type 2 diabetic muscle independent of obesity and 2) inversely correlated with both GS activity and maximally insulin-stimulated glucose disposal. We conclude that increased GSK-3 expression in diabetic muscle may contribute to the impaired GS activity and skeletal muscle insulin resistance present in type 2 diabetes.

One hour in 1 ATA oxygen enhances rat alveolar macrophage chemiluminescence and fungal cytotoxicity.

The purpose of this study was to determine if 100% O2 would enhance rat pulmonary alveolar macrophage (PAM) oxidative killing of conidia of the fungus Neurospora crassa. First, we found that incubation in 100% O2 had no effect on conidia viability in the absence of PAM. We obtained resident PAM from nonpretreated anesthetized male Sprague-Dawley rats by bronchoalveolar lavage. Compared with similar air exposures we found that 1 h in vitro exposure of PAM to 100% O2 (1.0 atmosphere absolute) increased their killing of opsonized phagocytized conidia by 52%, without altering phagocytosis. A reactive oxygen killing mechanism is suggested because 1) 100% O2 increased PAM chemiluminescence (CL) by 60% both at rest and during 1 h of phagocytosis, and 2) PAM in 100% O2 killed albino conidia (lacking free radical-quenching carotenoids) 2.9 times more readily than they killed wild-type conidia. Compared with air, 100% O2 delayed the PAM respiratory burst time to peak by 18% but did not alter the burst maximal acceleration. The latter and the similar 60% increase in PAM CL in 100% O2 both at rest and during 1 h of phagocytosis suggests a nonenzymatic O2 enhancement of the respiratory burst. Changed timing of burst events in 100% O2 suggests early O2 toxicity. We conclude that 1 h in 100% O2 increases PAM free radical production and fungicidal activity.