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This study reports our preliminary experience with mycophenolate mofetil (MMF)-based immune suppression after lung transplantation. Thirteen patients (group 1) received MMF as primary therapy immediately after transplantation. Use of MMF was associated with a linearized rate of 0.85 episodes of acute rejection per 100 patient days during the first 3 months after transplantation, as compared with rates of 1.49 and 1.38, observed in two groups of historical control subjects (p = .094 and p = .053, respectively). Rejection rates after the first 3 months were not lower than in historical control subjects. Nine additional patients were switched from azathioprine to MMF because of recurrent episodes of high-grade acute rejection (group 2). In this group, the linearized rate of acute rejection episodes declined significantly (p = .004) after initiation of MMF therapy. These data suggest a potential role for MMF in reducing the rate of acute rejection episodes after lung transplantation.

ABO matched cynomolgus monkey to baboon heterotopic xenografts were performed using three different immunosuppressant regimens. Group 1 (n = 4) baboons, which did not receive immunosuppression, had a mean graft survival of 9 days. Group 2 (n = 6) received cyclosporine (CsA) and methylprednisolone acetate which prolonged graft survival to an average of 78 days. Group 3 (n = 5) received CsA, Pred, and azathioprine (Aza) as well as steroid pulses and antithymocyte globulin (ATG) for rejection episodes. Survival in this group averaged 94 days. In Group 4 (n = 3), the same regimen as group 3 was used; however, Mycophenolate Mofetil was substituted for Aza. This resulted in a mean survival of 296 days. Histologic examination of the coronary vasculature in baboons treated with Mofetil showed a reduction in vascular pathologic changes when compared to those treated with Aza. Long-term cardiac xenograft survival is possible using currently available immunosuppressive agents.

Hyperacute rejection is a serious complication of xenogeneic organ transplantation. It is believed that platelets play a pivotal role in this phenomenon. In this study, we provide the first known evidence of the efficacy of the PAF receptor antagonist, tulopafant, in improvement in graft function and histology of discordant cardiac xenografts. Transplantation of guinea pig hearts into recipient rats resulted in hyperacute rejection. Pretreatment of recipient animals with tulopafant (but not indomethacin) extended rejection time by 4-5-fold. Histological examination revealed marked diminution of both interstitial hemorrhage and deposition of platelet and granulocytes in capillaries of cardiac xenografts when recipient animals were pretreated with tulopafant.

In the United States, heart donor availability has increasingly failed to keep pace with rising demand. Transplant data were obtained from the United Network for Organ Sharing for 1988, 1989, and 1990 and by survey of 50 heart transplantation centers, which performed 1932 transplantations between 1983 and 1989. According to the United Network for Organ Sharing, 512 patients on the waiting list died in 1988; 527, in 1989; 650, in 1990, and if present trends continue more than 800 will have died in 1991. Similar numbers of patients were inactivated or removed from the list each year. Only 49% of patients (1647 of 3390) on the heart transplant waiting list at some time in 1988 underwent the procedure in that year. For 1989 the figure fell to 42% (1630 of 3915 patients). Survey data revealed a threefold increase in the ratio of the number of patients who died/number of patients who underwent transplantation from 0.07 in 1983 to 0.21 in 1989 and in the ratio (number of patients who died+number of patients who were removed from the list)/number of patients who underwent transplantation from 0.12 in 1983 to 0.38 in 1989. The major causes of death among waiting patients were congestive heart failure (46%) and arrhythmia (29%). From 1983 to 1989, 55% (134 of 243) of those patients with documented urgency status died in the intensive care unit; 45% (109 of 243) died elsewhere. Waiting time for patients dying in the intensive care unit rose from 10.7 days in 1985 to 50.3 days in 1989; patients dying out of the intensive care unit waited 103.7 days in 1985 and 85.6 days in 1989. In conclusion, the number and proportion of potential recipients who die awaiting heart transplantation is increasing every year. Congestive heart failure and arrhythmia are the major causes of death, and similar numbers of patients die in and out of the intensive care unit.

The prognosis of patients with a history of successfully treated malignancy, who subsequently undergo organ transplantation and long-term immunosuppression, is uncertain. We report the case of a 14-year-old girl in whom doxorubicin-induced cardiomyopathy developed after aggressive therapy for a fibroblastic osteosarcoma. The patient underwent orthotopic heart transplantation and remains in remission 14 months after surgery.

Cognitive and complex motor performance may be impaired by extended sleep deprivation, but objective data concerning the effects in residents of the sleep deprivation engendered by usual hospital on-call schedules are scant and conflicting. We studied three cohorts of surgical residents (N = 26) who were on call every other night. Each resident kept a sleep diary, gave a self-assessment of motivation and fatigue, and underwent a battery of psychometric tests each morning for 18 or 19 days. The psychometric tests measured cognition, discernment, visual and auditory vigilance, and rapid eye-hand coordination. Sleep deprivation was defined as the lack of four hours of continuous sleep during the preceding 24 hours, and it occurred during 89% of the on-call nights. Daily testing in a repeated-measures design allowed each participant to serve as his or her own control. Sleep deprivation did not affect overall cognitive or motor performance. Further analysis of the correlation between sleep parameters (total sleep and longest uninterrupted sleep interval) and performance on each component of the psychometric test battery identified changes in performance on some tests but only trivial effects due to sleep. The assumption that sleep deprivation associated with usual on-call schedules impairs cognitive and motor performance of residents such that clinical care of patients may be compromised is not supported by our observations.

This study evaluated the effects of increasing plasma endotoxin (Difco 055:B5) concentration by intravenous and intrarenal infusion on renal hemodynamics and renal function. Plasma endotoxin was increased to 130-150 ng/ml (infusion rate of 32 micrograms/min) in two groups of dogs and changes in plasma endotoxin concentration were correlated with arterial pressure (AP), glomerular filtration rate (GFR), renal blood flow (RBF), and urinary sodium excretion (UNaV) for 4 hr. In group 1, intrarenal endotoxin infusion decreased AP, GFR, RBF, and UNaV equally between infused and contralateral noninfused kidneys. In dogs with unilateral renal denervation (group 2), intravenous endotoxin maximally decreased AP, GFR, RBF, and UNaV in both kidneys by 90 min. Despite continued endotoxin infusion, RBF and GFR then spontaneously increased after 90 min, and by 240 min these values were significantly greater in the innervated kidneys compared with denervated kidneys (P less than 0.05). In both groups of dogs, the spontaneous increase in GFR and RBF was associated with a spontaneous increase in arterial pressure. These data suggest that renal dysfunction during moderate endotoxemia may be mediated by systemic hemodynamic changes rather than by direct intrarenal toxicity and that renal innervation may protect against endotoxin-induced reductions in RBF and GFR.