Effects of exenatide vs. metformin on endothelial function in obese patients with pre-diabetes: a randomized trial.

BACKGROUND: Glucagon like peptide-1 (GLP-1) receptor agonist treatment may improve endothelial function via direct and indirect mechanisms. We compared the acute and chronic effects of the GLP-1 receptor agonist exenatide vs. metformin on endothelial function in patients with obesity and pre-diabetes. METHODS: We performed a randomized, open-label, clinical trial in 50 non-diabetic individuals (mean age 58.5 ± 10.0; 38 females) with abdominal obesity and either impaired fasting glucose, elevated HbA1c, or impaired glucose tolerance (IGT) who were randomized to receive 3-months of exenatide or metformin. Microvascular endothelial function, assessed by digital reactive hyperemia (reactive hyperemic index: RHI), C-reactive protein (CRP), circulating oxidized LDL (oxLDL), and vascular cell adhesion molecule-1 (VCAM-1) were measured at baseline and 3-months. Seven subjects with IGT participated in a sub-study comparing the effects of pre-administration of exenatide and metformin on postprandial endothelial function. RESULTS: There were no differences for the change in RHI (Δ exenatide: 0.01 ± 0.68 vs. Δ metformin: -0.17 ± 0.72, P = 0.348), CRP, oxLDL, or VCAM-1 between exenatide and metformin treatment. Triglycerides were reduced more with exenatide compared to metformin (Δ exenatide: -25.5 ± 45.7 mg/dL vs. Δ metformin: -2.9 ± 22.8 mg/dL, P = 0.032). In the sub-study, there was no difference in postprandial RHI between exenatide and metformin. CONCLUSIONS: Three months of exenatide therapy had similar effects on microvascular endothelial function, markers of inflammation, oxidative stress, and vascular activation, as metformin, in patients with obesity and pre-diabetes. CLINICAL TRIALS REGISTRATION: This study is registered on http://www.clinicaltrials.gov/: NCT00546728.

Ectopic ACTH-producing large cell neuroendocrine Pancoast tumour presenting as Horner syndrome.

We present an interesting case where a patient is presented with a droopy left eyelid (as part of Horner syndrome) and Cushingoid features which were a result of a Pancoast tumour (apical lung tumour in superior pulmonary sulcus) involving the left lung. This tumour was secreting ectopic adrenocorticotropic hormone (ACTH), a paraneoplastic endocrine phenomenon, which resulted in Cushing syndrome symptomatology. Though most ectopic ACTH-producing lung cancers are either small cell or carcinoid tumours, this was in fact a large cell neuroendocrine cancer (LCNEC). Patient underwent surgical resection and adjuvant/neoadjuvant chemotherapy with radiation; however, he succumbed to LCNEC given aggressive nature of the disease.

Comparative efficacy of topical moxifloxacin versus ciprofloxacin and vancomycin in the treatment of P. aeruginosa and ciprofloxacin-resistant MRSA keratitis in rabbits.

PURPOSE: To evaluate the in vivo efficacy of topical moxifloxacin 0.5% versus ciprofloxacin 0.3% in the treatment of Pseudomonas aeruginosa keratitis and topical moxifloxacin 0.5% versus vancomycin 50 mg/mL in the treatment of ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus (MRSA) keratitis in rabbits. METHODS: Experimental bacterial keratitis was induced in rabbits by corneal intrastromal injection. Infection proceeded for 12 hours, after which topical antibiotics were applied hourly for 12 hours. Corneal homogenates were plated with serial dilutions for quantitative bacteriology. RESULTS: Both moxifloxacin and ciprofloxacin performed significantly better than control in the treatment of Pseudomonas aeruginosa keratitis (P=0.0046 and 0.0069, respectively); there were no significant differences between these 2 drugs in bactericidal activity (P=0.1120). Moxifloxacin performed significantly better than control in the treatment of ciprofloxacin-resistant MRSA (P=0.0321) keratitis, and vancomycin showed a trend toward statistical significance in performing better than control (P=0.0576); there were no significant differences between these 2 drugs in bactericidal activity (P=0.5205). CONCLUSIONS: Topical moxifloxacin 0.5% and ciprofloxacin 0.3% have similar efficacy in the treatment of Pseudomonas aeruginosa keratitis in rabbits. Topical moxifloxacin 0.5% and vancomycin 50 mg/mL have similar efficacy in the treatment of ciprofloxacin-resistant MRSA keratitis in rabbits. These results suggest a potential value for topical moxifloxacin as a broad-spectrum agent in the treatment of bacterial keratitis.

Absorption of topical moxifloxacin ophthalmic solution into human aqueous humor.

PURPOSE: To investigate the absorption of moxifloxacin into human aqueous humor after administration of moxifloxacin hydrochloride ophthalmic solution, 0.5% as base. METHODS: Cataract patients were randomly allocated to receive 1 drop every 15 minutes for 4 doses before surgery (group 1) or 1 drop 4 times per day on the day before surgery plus the same preoperative regimen as group 1 (group 2). The last dose was administered 0.25, 0.50, 1, 2, or 3 hours before aqueous humor sampling. Samples from 30 patients per group were analyzed by a validated HPLC/MS/MS method. RESULTS: For group 1, the mean +/- SD C(max) was 1.50 +/- 0.75 microg/mL and occurred at 0.5 hour after dosing. The mean C(max) for group 2 was 1.74 +/- 0.66 microg/mL and was reached at 1 to 2 hours. Mean AUC(0-3h) for groups 1 and 2 were 3.16 +/- 0.29 and 4.41 +/- 0.48 microg.h/mL, respectively. The difference in AUC(0-3h) was statistically significant (P = 0.04), but the difference in Cmax was not. CONCLUSIONS: Topical moxifloxacin was well absorbed. Maximum moxifloxacin concentrations were approximately 30 times higher than the median MICs for common pathogens in bacterial endophthalmitis, indicating that either regimen may provide sufficient concentrations to prevent postoperative endophthalmitis.

Carvedilol-lisinopril combination therapy and endothelial function in obese individuals with hypertension.

The authors hypothesized that carvedilol controlled-release plus lisinopril combination therapy (C+L) would increase endothelial function and decrease oxidative stress to a greater extent than hydrochlorothiazide plus lisinopril combination therapy (H+L) in obese patients with hypertension. Twenty-five abdominally obese patients (aged 54.4±7.3 years; 14 women) with hypertension/prehypertension were enrolled in a 7-month (two 3-month treatment periods separated by a 1-month washout), randomized, double-blind, controlled, crossover clinical trial comparing C+L vs H+L. Endothelial function, measured by digital reactive hyperemic index (RHI), circulating oxidized low-density lipoprotein (oxLDL), 8-isoprostane, and asymmetric dimethylarginine (ADMA) were obtained at baseline, post-period 1, post-washout, and post-period 2. Analyses were adjusted for baseline measurements by analysis of covariance, with robust variance estimation for confidence intervals and P values. C+L treatment compared to H+L treatment significantly improved RHI (0.74, 95% confidence interval, 0.31-1.19, P =.001). This difference persisted after adjustment for the change in systolic blood pressure. No significant treatment differences were observed for oxLDL, 8-isoprostane, or ADMA. These data provide evidence that independent of blood pressure-lowering, C+L therapy improves endothelial function to a greater extent than H+L therapy. Levels of oxidative stress were not significantly different between treatments, suggesting that other mechanisms may be responsible for the improvement in endothelial function.