Faculty Bibliography

We investigated the incidence of silent myocardial ischemia and infarction as assessed by dipyridamole thallium scintigraphy in 30 diabetic patients with peripheral vascular disease and without clinical suspicion of coronary artery disease. Seventeen patients (57%) had thallium abnormalities, with reversible thallium defects compatible with ischemia in 14 patients (47%) and evidence of prior, clinically silent myocardial infarction in 11 patients (37%). Thallium abnormalities were most frequent in patients with concomitant hypertension and cigarette smoking (p = 0.001). These results suggest that unsuspected coronary artery disease is common in this particular group of patients with diabetes mellitus.

The murine monoclonal CD3 antibody (OKT3) is effective in the treatment of refractory renal and cardiac allograft rejection and holds promise for improving rejection prophylaxis in heart transplantation. Although the administration of OKT3 is associated with many side effects, arteritis has not been previously reported. We report the development of acute necrotizing temporal arteritis associated with the deposition of mouse immunoglobulin G in a heart transplant recipient receiving OKT3 treatment of refractory rejection.

OKT3 monoclonal antibody (OKT3) has already proved to be a valuable edition to the immunosuppression armamentarium available in cardiac transplantation. It is highly effective in treating refractory rejection, where approximately 90% of subjects may be salvaged. It may be even more valuable in prophylaxis, where in combination with an antibody suppression strategy and low-dose, "delayed" cyclosporine it appears to afford near complete protection against rejection. Moreover, OKT3-based prophylaxis seems to impact favorably on the rejection rate after the prophylaxis course has been completed. Adverse reactions are common and generally manageable, although occasional serious clinical events do occur.

Cytomegalovirus (CMV) infection is a frequent cause of serious illness in heart transplant patients and may cause life-threatening pneumonia, with a reported mortality of greater than 50%. We investigated the clinical efficacy of a new antiviral agent, 9(1,3-dihydroxy-2-proproxymethyl)-guanine (DHPG) in the treatment of CMV pneumonia in heart transplant patients. Four of these patients with biopsy-proved CMV pneumonia were treated with DHPG, with resolution of pneumonia and no relapse at a mean follow-up period of 21 weeks. DHPG may be useful in the treatment of CMV pneumonia in heart transplant patients.

Corticosteroid maintenance immunosuppression therapy was successfully discontinued in 24 of 46 patients (52%) who underwent orthotopic heart transplantation between March 8, 1985 and September 1, 1986. In the remaining 22 patients three or more rejection episodes occurred within a 4-month period, and these patients were subsequently maintained on low to moderate dosages of corticosteroids. Patients successfully withdrawn from corticosteroid maintenance (group 1) have remained rejection free for 208 +/- 33 days (mean +/- SEM) after discontinuation of the maintenance therapy with corticosteroids, and their immunosuppression therapy has consisted only of cyclosporine (mean overall cumulative dose 198 +/- 11 mg/m2/day [5.17 +/- 0.35 mg/kg/day]) and azathioprine (mean overall cumulative dose 67.7 +/- 5.4 mg/m2/day [1.74 +/- 0.13 mg/kg/day]), with the most recent serum cyclosporine level and white blood cell count being 146 +/- 10 ng/ml and 5400 +/- 200/microliters, respectively. In contrast to the patients who continue to require maintenance therapy with corticosteroids (group 2), group 1 patients developed their first episode of rejection later (46.8 +/- 8.3 days versus 25.4 +/- 6.1 days, p = 0.040) and reject less frequently during the first 4 months after transplantation (1.7 +/- 0.2 episodes versus 2.6 +/- 0.2 episodes, p = 0.005) as well as during the entire follow-up period (0.21 +/- 0.02 episodes/month versus 0.30 +/- 0.02 episodes/month, p = 0.005). The decreased propensity to reject and subsequent corticosteroid discontinuation resulted in a decreased cumulative dose of corticosteroids in group 1 patients (10.9 +/- 1.9 mg prednisone equivalent/m2/day [0.28 +/- 0.04 mg/kg/day] versus 17.0 +/- 1.2 mg prednisone equivalent/m2/day [0.42 +/- 0.04 mg/kg/day], p = 0.011 [p = 0.026]).(ABSTRACT TRUNCATED AT 250 WORDS)