Treatment of refractory cardiac allograft rejection with OKT3 monoclonal antibody.

OKT3 monoclonal antibody is a murine monoclonal antibody specific for the T lymphocyte T3 cell surface receptor that mediates antigen recognition. The use of OKT3 monoclonal antibody for the treatment of cardiac allograft rejection refractory to conventional therapy with high-dose steroids and antithymocyte globulin is described. Seven patients received 5 mg of OKT3 monoclonal antibody intravenously per day for 10 to 14 days. Diagnosis of moderate or severe rejection was made in all seven from right ventricular endomyocardial biopsy. Biopsy was repeated 48 to 72 hours and seven to 10 days after OKT3 monoclonal antibody was begun. With treatment, four patients had a complete response, with improvement on both early and late biopsy. Two patients had partial responses, with improvement on early biopsy followed by worsening rejection on late biopsy. One patient died of graft failure six hours after receiving OKT3 monoclonal antibody. Adverse events were common in the first two days of therapy but were well tolerated. It is concluded that OKT3 monoclonal antibody is useful in the treatment of refractory cardiac allograft rejection.

Age-associated decline in cardiac allograft rejection.

The influence of age on cardiac allograft rejection was studied in 57 consecutive recipients. Twenty-one subjects were 54 years of age or older (mean, 57.7 +/- 0.6 years [+/- SEM]; range, 54 to 63 years) and 36 subjects were 52 years of age or younger (mean, 39.9 +/- 1.8 years; range, 16 to 52 years; p less than 0.001). The older recipients had fewer rejection episodes during the first four months following cardiac transplantation (0.24 +/- 0.05 episodes per month versus 0.72 +/- 0.09 episodes per month; p less than 0.001) and during the total duration of follow-up (0.20 +/- 0.03 episodes per month versus 0.40 +/- 0.07 episodes per month; p = 0.045), and experienced their first rejection episode later (50.4 +/- 4.0 days versus 27.7 +/- 8.5 days; p = 0.008). Younger age was found to add significantly as a predictor of rejection in a multivariate analysis that controlled for sex, immunosuppressive agents, cause of heart failure, and pretransplantation lymphocyte cross-match status (r = 0.64, p less than 0.05). Decreased rejection frequency occurred without a concomitant increase in the serious infection rate (67 percent in both groups). The 12-month actuarial survival was 100 percent in the older group and 94 percent in the younger group (p = NS). Decreased rejection in the older recipients is likely a manifestation of an age-associated decline in immune function and might represent an advantage in transplantation for carefully selected older patients.

A randomized trial of the immunosuppressive efficacy of vincristine in cardiac transplantation.

We evaluated the efficacy of the addition of the lymphoblasticidal agent vincristine to standard immunosuppression in heart transplantation in a prospective randomized study of 92 patients (46 to receive and 46 to not receive vincristine) with a follow-up period of 12 months. Patients received either equine antithymocyte globulin for the first week or OKT3 monoclonal antibody (OKT3) for the first 10 or 14 days after transplantation. Six to eight doses of vincristine were given over 9-12 weeks, beginning 2 days after completion of ATG or OKT3. The number of rejection episodes in the first six months posttransplantation, the percentage of patients corticosteroid maintenance-free at one year, cumulative immunosuppressive drug doses, deaths, infections, and neuropathy were followed. The addition of vincristine resulted in more patients achieving corticosteroid maintenance-free status at one year (vincristine 68%, no vincristine 38%, P = 0.01). In comparing patients at relatively high risk for rejection (those younger than 55 years and all females) with those at relatively low risk (males older than 55 years), only the high-risk vincristine-treated patients showed significantly fewer rejection episodes and a higher corticosteroid maintenance status at one year (66% vs. 32%, P = 0.01). There were no significant differences in survival (vincristine 96%, no vincristine 98%), infection, or amounts of other immunosuppressive agents used. The major side effect was neuropathy, which occurred more frequently in the vincristine-treated group (43% vs. 18%, P less than .001). We conclude that vincristine acts as an immunosuppressive agent in cardiac transplantation, particularly in patients at higher risk for rejection.

A prospective comparison of murine monoclonal CD-3 (OKT3) antibody-based and equine antithymocyte globulin-based rejection prophylaxis in cardiac transplantation. Decreased rejection and less corticosteroid use with OKT3.

To test the efficacy of murine monoclonal CD-3 antibody (OKT3) in early prophylaxis for cardiac allograft rejection, we conducted a 6-month trial, prospectively assigning 51 patients to receive either equine antithymocyte globulin-based (n = 25) or OKT3-based (n = 26) early prophylaxis. ATG patients received 8 days of ATG (10 mg/kg), with the first dose given preoperatively. OKT3 patients received 14 days of OKT3 (5 mg) beginning on the second postoperative day. Corticosteroid and azathioprine administration were similar during early prophylaxis. Cyclosporine was begun preoperatively in ATG patients and on the fourth postoperative day in OKT3 patients. In addition, patients in both groups were randomized to receive or not receive eight weekly administrations of vincristine (0.025 mg/kg). While infection rate (0.8 +/- 0.2 infections/patient in both groups [mean +/- SEM]) and mortality (1 patient in each group) did not differ, OKT3-based early prophylaxis delayed the first rejection episode (76 +/- 11 days vs. 36 +/- 8 days, P = 0.005) and decreased the risk of rejection during the 6-month follow-up (P less than 0.001, product-limit analysis). Overall, the OKT3 group manifested 1.5 +/- 0.2 episodes of rejection/patient compared with 2.2 +/- 0.2 episodes/patient in the ATG group (P = 0.036). Despite similar 6-month cumulative cyclosporine and azathioprine dosages, six month average corticosteroid administration was less in the OKT3 group (12.2 +/- 1.5 mg prednisone equivalent/m2/day versus 19.3 +/- 2.1 mg prednisone equivalent/m2/day, P = 0.008), fewer OKT3 patients subsequently required additional cytolytic therapy for rejection (2 [8%] versus 12 [48%], P = 0.001), and more patients in the OKT3 group were successfully weaned off maintenance corticosteroids (22 [88%] versus 11 [46%], P = 0.002). We conclude that, relative to an equine ATG-based protocol, OKT3-based early prophylaxis results in less rejection, permitting less chronic corticosteroid administration.

Invest in yourself. Yoga as a self-care strategy.

A widening recognition of the mind-body-spirit connection in western medicine has resulted in a growing interest in ancient health practices such as yoga. As complementary therapies enter mainstream medical settings, nurses and other healthcare providers need a fundamental understanding of these modalities to be able to advise patients effectively. This article provides an overview of yoga and details the benefits of yoga practice.

Combined heart failure transplant program: advantages in assessing medical compliance.

Compliance, motivation, and strong family support have been identified as important factors to the success of heart transplantation. Approaches to psychosocial evaluations determining suitability of candidates vary among transplant centers. Although testing, interviewing, and retrospective analyses of patient profiles are valuable, they do not allow for longitudinal evaluation of patients who have been denied transplantation under these standard methods of assessment. The Utah Cardiac Transplant Program (UCTP) combines heart failure and transplant services to provide maximum conventional and experimental therapy to patients with end-stage cardiac dysfunction. A single medical team provides care to all patients. From March 8, 1985 to November 1, 1986, UCTP evaluated 170 patients, assigning 57 to conventional medication therapy, 72 to experimental medication therapy, and 41 directly to heart transplantation. Of the 72 patients assigned to experimental therapy, 21 were subsequently assigned to heart transplantation. In the initial evaluation of four patients, it was determined that they did not have adequate family support or emotional stability to undergo transplantation. After monitoring these four patients through a drug study, it was found that the initial evaluation was incorrect, as the patients demonstrated the ability to adhere to a complex regimen involving multiple diagnostic tests, clinic visits, and medication therapy. Three of these patients subsequently underwent successful transplantations and are alive with a mean follow-up time of 212 days. In conclusion, combining all modalities of treatment for end-stage heart disease into one unified program has definite advantages that include longitudinal evaluation of patients previously denied transplantation.

Amelioration of weight gain after heart transplantation by corticosteroid-free maintenance immunosuppression. UTAH Cardiac Transplant Program.

After heart transplantation, recipients frequently become obese. Although the cause is undoubtedly multifactorial, administration of corticosteroids may contribute to posttransplant obesity. To test this hypothesis, we retrospectively reviewed the change in body weight with respect to corticosteroid use after transplantation in all 110 recipients surviving 1 year in the UTAH Cardiac Transplant Program. Fifty-two recipients (47%, group 1) were unable to be withdrawn from maintenance corticosteroids, and 58 recipients (53%, group 2) were successfully withdrawn, the latter group requiring only cyclosporine and azathioprine long-term maintenance immunosuppression. The change in weight from the time of transplantation to 1 year after transplantation in group 1 was 8.7 +/- 1.1 kg; group 2 patients gained only 4.9 +/- 0.9 kg (p = 0.009). In conclusion, successful withdrawal of maintenance corticosteroids after heart transplantation decreased posttransplant weight gain, suggesting that posttransplant obesity is in part related to use of corticosteroids.

Rejection prophylaxis with murine monoclonal CD-3 antibody (OKT3): considerations for early hospital discharge.

Murine monoclonal CD-3 antibody (OKT3) is a significant new addition to the immunosuppressant armamentarium for treatment of heart transplant rejection. In the Utah Transplantation Affiliated Hospitals (UTAH) Cardiac Transplant Program, Salt Lake City, a broad experience with OKT3 has been acquired. Fifteen patients were treated for refractory rejection, whereas 68 patients were treated for early rejection prophylaxis therapy utilizing either 10- or 14-day protocols. To facilitate early hospital discharge, 12 patients were able to complete OKT3 therapy as outpatients. A retrospective review of length of initial hospital stay and clinical results revealed that patients who received OKT3 had an average hospital stay (+ standard deviation) of 17.1 days, and their 12-month survival was 96%. Patients who received antithymocyte globulin and/or steroids had an average stay of 27.4 days (p less than 0.05) and a 12-month survival of 93%. In conclusion, the possibility for reduced hospital stay and consequent cost reduction exists with the use of OKT3, especially when completion of therapy can be managed in an outpatient setting.

Beta-adrenergic supersensitivity of the transplanted human heart is presynaptic in origin.

An increase in cardiac beta-adrenergic sensitivity or beta-receptor density or both has been described in several animal species after denervating the heart. The transplanted human heart is also denervated and, therefore, may exhibit supersensitivity to beta-adrenergic agonists and an increase in beta-adrenergic receptor density. In 16 patients examined 1-3 months after orthotopic cardiac transplantation, beta-adrenergic receptor density measured by [125I]iodocyanopindolol binding in endomyocardial biopsy specimens was not significantly different in transplant recipients compared with normal controls (transplant = 1,429 +/- 199, control = 1,728 +/- 263 fmol/g wet wt; p = NS). However, when normalized to Lowry protein, the [125I]iodocyanopindolol in beta-adrenergic receptor density in biopsy tissue from transplant recipients was significantly lower than in tissue from controls (transplant = 58.1 +/- 6.2, control = 93.5 +/- 13.4 fmol/g Lowry protein; p = 0.011). Atrial sinus node activity of the denervated donor heart and the innervated atrial cuff of the native recipient heart could be detected on the surface electrocardiogram in six patients. In these six patients, the heart rate response to graded infusions of epinephrine (taken up by the adrenergic nerve terminals) and isoproterenol (not taken up by the adrenergic nerve terminals) was measured. The epinephrine dose-response curve in transplanted donor atria was significantly to the left of the native recipient atrial dose-response curve (p less than 0.0001). The isoproterenol dose-response curves for native and transplanted atria were not different. We conclude that myocardial beta-adrenergic receptors are not increased in human orthotopic cardiac allografts and that there is no evidence for beta-receptor-mediated supersensitivity of postsynaptic origin.(ABSTRACT TRUNCATED AT 250 WORDS)