Outcomes in patients with rheumatoid arthritis and myocardial infarction

Background

Patients with rheumatoid arthritis have an increased risk for accelerated atherosclerosis. It is unknown, however, whether rheumatoid arthritis also increases in-hospital mortality after a myocardial infarction or influences the therapy patients receive.

Methods

A cross-sectional analysis of 1,112,676 patients with myocardial infarction in the 2003-2005 Nationwide Inpatient Sample was performed.

Results

Patients with rheumatoid arthritis were 39% more likely to receive medical therapy (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.30-1.49) than interventional therapy. By using logistic regression, we adjusted for confounding variables to determine the effect of rheumatoid arthritis on the selection of therapy and found that rheumatoid arthritis itself was associated with a 38% increased likelihood of undergoing thrombolysis (OR, 1.38; 95% CI, 1.10-1.71) and a 27% increased likelihood of undergoing percutaneous coronary intervention (OR, 1.27; 95% CI, 1.17-1.39). For the primary outcome measure, we determined that patients with rheumatoid arthritis overall had a 24% better in-hospital mortality compared with other patients with a myocardial infarction (OR, 0.76; 95% CI, 0.68-0.86), which was 34% better after adjusting for confounding variables (OR, 0.66; 95% CI, 0.59-0.74). This better in-hospital mortality was seen in patients with rheumatoid arthritis undergoing medical therapy (adjusted OR, 0.67; 95% CI, 0.59-0.75) and percutaneous coronary intervention (adjusted OR, 0.47; 95% CI, 0.32-0.70), but not in patients undergoing thrombolysis or coronary artery bypass grafting.

Conclusions

Among patients with myocardial infarction, rheumatoid arthritis was associated with an increased use of thrombolysis and percutaneous coronary intervention. Moreover, patients with rheumatoid arthritis had an in-hospital survival advantage, particularly those undergoing medical therapy and percutaneous coronary intervention.     

Regression of prostate cancer xenografts by RLIP76 depletion

RLIP76 plays a central role in radiation and chemotherapy resistance through its activity as a multi-specific ATP-dependent transporter which is over-expressed in a number of types of cancers. RLIP76 appears to be necessary for cancer cell survival because both in vitro cell culture and in vivo animal tumor studies show that depletion or inhibition of RLIP76 causes selective toxicity in malignant cells. RLIP76 induces apoptosis in cancer cells through the accumulation of endogenously formed GS-E. The results of our in vivo studies demonstrate that administration of RLIP76 antibodies, siRNA or anti-sense to mice bearing xenografts of PC-3 prostate cancer cells leads to near complete regression of established subcutaneous xenografts with no apparent toxic effects. Since anti-RLIP76 IgG (which inhibit RLIP76-mediated transport), siRNA and antisense (which deplete RLIP76) showed similar tumor regressing activities, our results indicate that the inhibition of RLIP76 transport activity at the cell surface is sufficient for observed anti-tumor activity. These studies indicate that RLIP76 serves a key effector function for the survival of prostate cancer cells and that it is a valid target for cancer therapy.     

Poly(ethylene glycol)-modified thiolated gelatin nanoparticles for glutathione-responsive intracellular DNA delivery

Poly(ethylene glycol) (PEG)-modified thiolated gelatin (PEG-SHGel) anoparticles were developed as a long-circulating passively targeted delivery system that responds to intracellular glutathione concentrations to enhance DNA delivery and transfection. Reporter plasmid expressing enhanced green fluorescent protein (EGFP-N1) was encapsulated in the nanoparticles. DNA-containing gelatin (Gel) and thiolated gelatin (SHGel) nanoparticles were found to have a size range of 220 to 250 nm, whereas surface modification with PEG resulted in particles with a slightly larger size range of 310 to 350 nm. PEG modification was confirmed by electron spectroscopy for chemical analysis (ESCA), where an increase in the ether peak intensities of the C1s spectra corresponds to the surface presence of ethylene oxide residues. In addition, the PEG-SHGel nanoparticles released encapsulate plasmid DNA in response to varying concentrations of glutathione (up to 5.0 mM GSH in phosphate-buffered saline, or PBS). The stability of the encapsulated DNA was confirmed by agarose gel electrophoresis. Finally, from the qualitative and quantitative results of in vitro transfection studies in murine fibroblast cells (NIH3T3), PEG-Gel and PEG-SHGel nanoparticles afforded the highest transfection efficiency of the reporter plasmid. The results of these studies show that PEG-modified thiolated gelatin nanoparticles could serve as a very efficient nanoparticulate vector for systemic DNA delivery to solid tumors where the cells are known to have significantly higher intracellular GSH concentrations.     

Management of overactive bladder syndrome

Overactive bladder (OAB) syndrome is the term used to describe the symptom complex of urinary urgency with or without urge incontinence, usually with frequency and nocturia. Drug treatment continues to have an important role in the management of women with OAB. Other treatment options include conservative management with lifestyle interventions, modification of fluid intake, and physiotherapy including bladder retraining. Surgery remains the last resort in the treatment and is usually reserved for intractable detrusor overactivity, as it is associated with significant morbidity. This article reviews the management of the overactive bladder with specific focus on newer developments in the medical treatment of OAB in women.