Synergistic effect of low dose Cyclosporine A and human interleukin 10 overexpression on acute rejection in rat lung allotransplantation

Objective: Electroporation mediated transfer of plasmid DNA into peripheral muscle results in high transfection efficiency. The aim of this study was to investigate the effect of gene transfer of human IL-10 (hIL-10) into the tibialis anterior muscle (MTA) in combination with low dose Cyclosporine A (CsA) on acute rejection of lung allografts in the rat. Methods: Lung allotransplantation was performed from male BN donor to male Fisher F344 rats. Gene transfer was achieved by intramuscular injection into the MTA of the recipient followed by electroporation (4×20 ms impulses at 200 V/cm) 24 h prior to the transplantation. Group A (n=5) received CsA (2.5 mg/kg bw ip) for 5 days post-transplant and group B (n=5) 2.5 μg of PCIK hIL-10 (plasmid expression vector containing human CMV immediate early gene promoter and enhancer) and a low dose CsA (2.5 mg/kg bw i.p.). Graft function was assessed by blood gas at day 5 after exclusion of the native lung. Animals were sacrificed and blood was drawn to measure serum hIL-10 levels (ELISA) and tissue was sampled for histological grading of rejection. Results: Local expression of hIL-10 was confirmed at the mRNA level by in situ hybridization. All group A control animals showed severe signs of rejection. At day 5 all grafts in group B showed good gas exchange mean PaO2 233±123 mmHg, vs 44±8 mmHg in group A. Histological examination revealed moderate to severe rejection in all animals in group A (IIIB, ISHLT) in contrast to low moderate rejection in group B (II–IIIA). hIL-10 serum levels on day 5 were 14±7 pg/ml in group B vs. 0 in group A. Conclusions: Electroporation mediated hIL-10 overexpression in a peripheral muscle of the recipient in combination with low dose CsA reduces acute rejection in this model of rat lung allotransplantation.     

A PC-based free text retrieval system for health care providers

The purpose of this paper is to describe the design and development of the Clinical Practice Library of Medicine (CPLM). CPLM is an investigational project aimed at providing health care practitioners with critical in-depth information similar to that obtained from a medical reference library or consultant. When used in conjunction with the physician's knowledge, CPLM can provide valuable diagnostic prompting information to assist in rapidly reaching a suitable diagnosis for timely administration of appropriate treatment. This system may also be used to assist paramedical professionals working in remote areas where other expert medical assistance may not be available.     

Enterobacter meningitis--treatment complicated by emergence of mutants resistant to cefotaxime

A case of Enterobacter cloacae meningitis in a postoperative patient is reported. A slow response to cefotaxime necessitated the use of gentamicin and trimethoprim-sulfamethoxazole for cure. Two types of resistance in the strain of E. cloacae isolated to cefotaxime were demonstrated: an inducible beta-lactamase that likely was the cause of the poor response to cefotaxime and a constitutive beta-lactamase in a mutant strain detected by a disc susceptibility test.     

The Effect of Flurbiprofen on Steady-State Plasma Lithium Levels

Study Objective . To evaluate the effects of flurbiprofen therapy on the pharmacokinetics of lithium. Design . Placebo-controlled, single-blind, crossover study. Setting . University-affiliated hospital. Patients . Eleven healthy women with bipolar disorder. Interventions . The subjects received therapeutic doses of lithium administered as an immediate-release capsule every 12 hours. In addition, they received one placebo tablet every 12 hours during phase I and flurbiprofen 100 mg every 12 hours during phase II of the study. Measurements and Main Results . Steady-state pharmacokinetic parameters were measured for each phase. Lithium trough plasma concentration (C_min) and area under the curve were statistically significantly increased (p<0.05) when patients received flurbiprofen. Flurbiprofen also caused decreases in lithium clearance and 24-hour lithium urine excretion, although the changes did not reach statistical significance. Clinically significant increases in C_min appeared to be associated with a greater than 1000-μg/24 hour decrease in urinary excretion of prostaglandin E₂. Conclusion . Patients with clinically normal renal function may experience an increase in lithium levels with the initiation of flurbiprofen therapy.     

Chemistry,Pharmacology, Pharmacokinetics,and Clinical Applications of Mesalamine for the Treatment of Inflammatory Bowel Disease

Mesalamine is the therapeutically active moiety of sulfasalazine used to treat inflammatory bowel disease. A controlled-release mesalamine capsule (Pentasa) is designed to release the agent continuously, and largely unaffected by intestinal pH, throughout the small and large bowel due to a diffusion-dependent, semipermeable ethylcellulose coating. It is a safe and efficacious single agent for inducing remission and producing therapeutic benefit in patients with mild to moderately active ulcerative colitis (UC) (2 or 4 g/day) or Crohn's disease (4 g/day), as well as for significantly enhancing quality of life for patients with mild to moderately active UC (2 or 4 g/day). It is also effective for maintaining remission in patients with quiescent UC and Crohn's disease (4 g/day). Disease location (left-sided UC or pancolitis) did not affect the agent's effect in active disease or maintaining remission. Fewer treatment-related adverse events were reported with mesalamine than with placebo in treating UC. In the treatment of active Crohn's disease, data showed no statistically significant differences in response for patients with ileitis, ileocolitis, or Crohn's colitis. This formulation of mesalamine may also be a possible steroid-sparing agent for patients with either active or quiescent Crohn's disease.