Complications of catheter ablation for atrial fibrillation: incidence and predictors

Introduction: Pulmonary vein (PV) isolation by catheter ablation is an increasingly used strategy to treat atrial fibrillation (AF). Complication rates from AF ablation reported in different case series vary widely. We conducted a retrospective analysis of 641 consecutive ablation procedures to assess complication rates, temporal trends, and clinical predictors of adverse outcomes.
Methods: All patients (n = 517) undergoing catheter ablation for AF at Johns Hopkins Hospital between February, 2001 and June, 2007 were prospectively enrolled in a database. Data from 641 consecutive procedures were analyzed and complications considered if they occurred within 30 days of ablation. Major complications were defined as those that required intervention, resulted in long-term disability, or prolonged hospitalization.
Results: Thirty-two major complications occurred in 641 procedures (5%). Among the patients with major complications, seven had cerebrovascular accident (CVA), eight had tamponade, one had PV occlusion with hemoptysis, and 11 had vascular injury requiring surgical repair and/or transfusion. No periprocedural deaths occurred, and no instances of esophageal injury were seen. Complication rates were higher during the first 100 cases (9.0%) than during the subsequent 541 (4.3%). Major adverse clinical events were associated with age > 70 years (P = 0.007; odds ratio 3.7, 95% confidence interval 1.4–9.6) and female gender (P = 0.014; odds ratio 3.0, 95% confidence interval 1.3–7.2). No other clinical or procedural predictors of complication were identified.
Conclusions: Complication rates from AF ablation remain significant, despite improved techniques and increased awareness of procedural risks. Both advanced age and female gender predict major adverse events, suggesting careful consideration of the risk/benefit profile in these patients prior to ablation.     

Development and in vitro-in vivo relationship of controlled-release microparticles loaded with tramadol hydrochloride

In conclusion, the controlled-release microparticles of TmH can be developed via phase separation method. The development and optimization of controlled-release microparticles of tramadol hydrochloride (TmH) for the oral delivery and their in vitro and in vivo correlation was prime objective of the present study. Four formulations of controlled-released microparticles were developed and optimized in terms of encapsulation efficiency, dissolution study and release kinetics. Among all formulated microparticles F-3 (ratio of TmH:EC 1:2) and F-4 (ratio of TmH:EC 1:3) presented the better characteristics in reference to entrapment efficiency, release kinetics and dissolution profile compared to other formulations (F-1, F-2). For in vivo analysis a new HPLC analytical method was developed and validated. The optimized formulations were subjected to in vivo studies to calculate various pharmacokinetic parameters, i.e., C(max), t(max), AUC(0-∞) and MRT. The in vitro dissolution and in vivo absorption data was correlated with the help of Wagner-Nelson method. F-3 showed a good in vitro-in vivo correlation with a correlation determination of 0.9957. Moreover, lower T(max), t(1/2) and MRT, and higher values of C(max) and K(e) were observed for F-3. The control formulation (immediate-release) presented lowest values of t(1/2), MRT and T(max) but the highest values of C(max) and K(e). The controlled-release microparticles (F-3 and F-4) could sustain the drug release within therapeutic level up to 24 h and good IVIVC is expected from them.     

Formulation, Antimicrobial and Toxicity Evaluation of Bioceramic based Ofloxacin Loaded Biodegradable Microspheres for Periodontal Infection

In the present study an attempt has been made to load Poly (Lactic-Co-glycolic acid) microspheres with hydroxyapatite (HA) and ofloxacin and propose the composite microspheres to be used as local drug delivery system with the drug releasing capability for periodontitis treatment. A modified single emulsion method has been used for the preparation of microspheres. Experiments were conducted to optimize the formulation by RSM-Box-Behnken Method, which is an independent quadratic design involving three or four independent variables against a pre determined set of dependant parameters. The particle size of composite microspheres was analyzed and the average size was found to be 22.05 μm. Photomicrographs and scanning electron micrographs showed that the composite microspheres are spherical in shape and porous in nature. The microbiological activity of optimized formulation was evaluated using strain: S. aureus-ATCC- 29213 and E. coli-ATCC-25922. In vivo/in situ toxicity evaluation of the formulation was assessed by MTT assay and the formulation was found to be biocompatible.     

Patterns of chemotherapy-induced hepatic injury and their implications for patients undergoing liver resection for colorectal liver metastases

Background and aims  Neoadjuvant chemotherapy is increasingly being used to enlarge the cohort of patients who can be offered hepatic resection for malignancy. However, the impact of these agents on the liver parenchyma itself, and their effects on clinical outcomes following hepatic resection remain unclear. This review identifies patterns of regimen-specific chemotherapy-induced hepatic injury and assesses their impact on outcomes following hepatic resection for colorectal liver metastases (CLM). Methods  An electronic search was performed using the MEDLINE (US Library of Congress) database from 1966 to May 2007 to identify relevant articles related to chemotherapy-induced hepatic injury and subsequent outcome following hepatic resection. Results  The use of the combination of 5-flourouracil and leucovorin is linked to the development of hepatic steatosis, and translates into increased postoperative infection rates. A form of non-alcoholic steatohepatitis (NASH) related to chemotherapy and otherwise known as chemotherapy-associated steatohepatitis (CASH) is closely linked to irinotecan-based therapy and is associated with inferior outcomes following hepatic surgery mainly due to hepatic insufficiency and poor regeneration. Data on sinusoidal obstruction syndrome (SOS) following treatment with oxaliplatin are less convincing, but there appears to be an increased risk for intra-operative bleeding and decreased hepatic reserve associated with the presence of SOS. Intra-arterial floxuridine therapy damages the extrahepatic biliary tree in addition to causing parenchymal liver damage, and has been shown to be associated with increased morbidity after hepatic resection. Conclusion  Agent-specific patterns of damage are now being recognized with increasing use of neoadjuvant chemotherapy prior to surgery. The potential benefits and risks of these should be considered on an individual patient basis prior to hepatic resection.     

Genetic and Epigenetic Analysis of Recurrent Hydatidiform Mole

Familial biparental hydatidiform mole (FBHM) is a maternal‐effect autosomal recessive disorder in which recurrent pregnancy failure with molar degeneration occurs. The phenotype mimics molar pregnancy due to androgenesis, despite the normal genetic makeup of the conceptus. FBHM appears to result from a failure to establish correct maternal epigenetic identity at imprinted loci during oogenesis. Several women affected with FBHM have previously been shown to have biallelic mutations in the NLRP7 gene (NALP7). Here, we present the results of epigenetic and mutational analysis on FBHM patients from 11 families, 10 of them novel. We demonstrate a methylation defect at imprinted loci in tissue from four new FBHM cases. Biallelic NLRP7 mutations, including eight previously undescribed mutations, were found in all but one family. These results indicate for the first time that maternal imprints at some loci may be correctly specified in FBHM conceptions, since differential methylation of SGCE/PEG10 was preserved in all four cases. © 2009 Wiley‐Liss, Inc.