Similar lipid profile but improved long-term outcomes with sirolimus after cyclosporine withdrawal compared to sirolimus with continuous cyclosporine.

Renal transplant recipients show an increased risk of cardiovascular disease compared with a nontransplant population. Herein we have shown an analysis of a randomized controlled trial wherein 525 patients receiving a first or second (9.7%) renal allograft from a deceased (89.1%), a living-related (7.8%), or a living-unrelated donor (3.1%) received sirolimus (SRL), cyclosporine (CsA), and steroids (ST) at the time of transplantation with randomization at 3 months after transplantation of 430 eligible patients to continue on SRL-CsA-ST or to have CsA withdrawn with increased SRL trough targets (SRL-ST group). Graft survival, patient survival, and renal function at 5 years were analyzed by average fasting total cholesterol (200 mg/dL) and triglyceride (240 mg/dL) subgroups. At 5 years, total, high-density lipoprotein (HDL), and low-density lipoprotein [LDL] cholesterol and triglyceride values were similar between the groups. Statins ( approximately 80% of patients of both groups) were most effective to lower cholesterol ( approximately 50 mg/dL; P < .001; both groups), and fibrates ( approximately 25% of patients of both groups) were most effective to decrease triglycerides ( approximately 100 mg/dL; P < .001; both groups). Renal function and blood pressure were significantly better with SRL-ST. Hypercholesterolemia and hypertriglyceridemia were associated with reduced graft survival, patient survival, and calculated GFR, but the only significant difference was lower graft survival among SRL-CsA-ST patients with hypertriglyceridemia. Cardiovascular-related deaths were reported in 3.7% and 2.8% of patients in the SRL-CsA-ST and SRL-ST groups, respectively. In conclusion, when compared with continuous SRL-CsA-ST, CsA withdrawal at 3 months followed by SRL-ST significantly improved glomerular filtration rate (GFR) and blood pressure without a further increase in lipid parameters or an incidence of untoward effects from hyperlipidemia, despite a 2-fold higher SRL exposure.

Rapamycin (sirolimus, rapamune).

Rapamycin is a novel immunosuppressive agent that is undergoing clinical trials for use in allograft rejection therapy. This paper reviews its in-vitro biological properties, the current state of knowledge concerning its mechanism of action, and its therapeutic applications.

A comparison of cyclobenzaprine and placebo in the management of fibrositis. A double-blind controlled study.

The efficacy of cyclobenzaprine (Flexeril), as compared with placebo, was tested in a 12-week, double-blind, controlled trial of 120 patients with fibrositis. Of the patients who received placebo, 52% dropped out due to lack of efficacy of the drug, compared with 16% of patients taking cyclobenzaprine. The dropout rate due to adverse reactions was similar in the 2 groups. Patients taking cyclobenzaprine experienced a significant decrease in the severity of pain and a significant increase in the quality of sleep. There was a trend toward improvement in the symptoms of fatigue, but morning stiffness was not alleviated. These improvements in symptoms were associated with a significant reduction in the total number of tender points and in muscle tightness. Our findings indicate that cyclobenzaprine is a useful adjunct in treating patients with the fibrositis syndrome.

Patient outcome following inpatient vs outpatient treatment of rheumatoid arthritis.

To assess the short and longterm efficacy of intensive inpatient treatment of active rheumatoid arthritis (RA), 16 patients, the test group, admitted to a hospital based rheumatic disease unit (mean length of stay 12.4 days) were studied, using clinical and laboratory variables. The comparison group was similarly evaluated, using 10 outpatients with active RA to whom hospitalization was recommended, but refused by the patients. Both groups were studied intensively over a 12-week period. In addition, a 2-year followup was performed on 12 test group inpatients and 8 comparison group outpatients, using the same variables plus a functional status questionnaire. Health care costs were determined for both groups and corrected for a 1985 dollar value. The test group showed significant improvement in morning stiffness, pain, and joint score, whereas the comparison group improved only in pain score during the initial 12-week period. At 2 years, the test group and the comparison group showed significant improvement in morning stiffness, pain, grip strength, and joint score. The comparison group initially had a somewhat lower index of disease activity. The test group maintained their initial improvement and none required rehospitalization. Functional status scores were similar for both groups. Health care costs were initially higher for the test group ($5,065); followup care cost for the test group was $99 less/year than the comparison group over 2 years. Hospitalization on a rheumatic disease unit brought about prompt, sustained improvement in 2 weeks which required nearly 2 years to achieve in the comparison group. Such hospitalization of uncomplicated RA seems warranted to decrease disability and increase the quality of life.