Biomedical subjects

R W Emery

Publications and source records attributed to R W Emery.

118 records · Page 7Linked to original sources

PubMedDate not supplied

Steroid-free maintenance immunotherapy: Minneapolis Heart Institute experience.

Recent advances in immunotherapy have resulted in improved survival after heart transplantation. The use of OKT3 as an induction agent has allowed the identification of a subset of patients who can be successfully withdrawn from prednisone and maintained on only cyclosporine and azathioprine. The latter regimen offers several theoretic advantages in terms of freedom from complications of long-term steroid therapy. To compare both the long-term efficacy and toxicity of steroid-free maintenance immunosuppression with triple-drug therapy, the medical records of 68 patients undergoing transplantation at the Minneapolis Heart Institute during a 3-year period (1988 through 1990) were reviewed. Thirty-six patients were treated with OKT3 induction immunotherapy, 29 were successfully tapered off prednisone by 114 +/- 44 days after transplantation, whereas 32 patients were maintained on triple-drug therapy. The incidence of treated rejection was equivalent in both groups; however, the time to first rejection was longer in patients treated with OKT3/steroid-free maintenance (205 +/- 214 vs 27 +/- 17 days) (p = 0.02). Bacterial infections during the early posttransplant period were more common in the OKT3/steroid-free maintenance group (p = 0.008); however, fungal and viral infections were equally distributed between both groups. The incidence of hypertension was slightly higher in patients maintained on prednisone (67% vs 51%; p = 0.242).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

PubMedDate not supplied

OKT3 induction and steroid-free maintenance immunosuppression for treatment of high-risk heart transplant recipients.

A group of high-risk heart transplant patients (n = 35) were treated from May 1987 through June 1990, with murine-derived monoclonal CD3 antibody (OKT3) induction therapy and steroid-free maintenance immunosuppression. This group was compared with a group of transplant patients (n = 47) who were not considered high risk and who were treated simultaneously with triple-drug immunosuppression (cyclosporine, azathioprine, and prednisone). The 1- and 3-year actuarial survival rates were similar: 97% and 91% for the OKT3 and 92% and 85% for the triple-drug immunosuppression groups, respectively. The overall incidence of rejection was equal for both groups (56%). No rejection occurred during the OKT3 course and rejection episodes occurred significantly later in patients treated with OKT3, with a mean first rejection episode of 111 +/- 104 days versus 27 +/- 21 days for the triple-drug immunosuppression group (p less than or equal to 0.05). Bacterial infections were seen more frequently (29% vs 6% of the patients treated) in the early period (less than 3 months) in the OKT3 group (p = 0.01) and were associated with the use of mechanical assistance in this group. The incidence of late infections or cytomegalovirus disease was similar for both groups. Patients treated with OKT3 and subsequent steroid-free maintenance immunosuppression had no significant posttransplantation increases of serum cholesterol levels, and hypertension was less common. Initial hospitalization was longer (p less than or equal to 0.05) in the OKT3 group (23 +/- 19 vs 13 +/- 5 days) but after the initial discharge the number of hospital days for the first year was similar for both groups (8 +/- 14 vs 9 +/- 13 days). Ventricular function at 1 year after transplantation was similar for both groups with average ejection fraction of 57% and 59% for the OKT3 and triple-drug immunosuppression groups, respectively. In conclusion, high-risk patients treated with OKT3 and steroid-free maintenance immunosuppression were managed on smaller doses of immunosuppressive drugs in the early postoperative period, and had excellent long-term survival rates. In this group of patients, rejection was delayed and the incidence of hypercholesterolemia, hypertension, and steroid-induced complications was decreased. Such a regimen offers a relatively drug-free period in the early posttransplant stages and freedom from the long-term complications of steroids.

Actuarial Analysis↗

PubMedDate not supplied

Induction immunosuppression for patients bridged to transplantation.

From January 1987 through July 1989, nine patients (eight male, one female) underwent bridge to transplantation and were managed with a modified immunosuppression regimen based around the monoclonal antibody OKT3. Six patients were bridged with the Jarvik-7 70 cc total artificial heart, four patients with centrifugal ventricular assist devices, and one patient with a Novacor left ventricular assist system. In two patients two devices were used. There was one patient death at 29 days after transplantation because of acute rejection. One other patient had a rejection episode 368 days after transplantation, for an overall rejection incidence of 0.22 episodes/patient. Four infections occurred, and all were viral--three cytomegalovirus and one mumps. Posttransplant complications involving other organ systems were minimal. In follow-up, from 2 to 29 months, six patients are in New York Heart Association functional status class I and one is in class II. Six patients are not taking steroids. The serum cholesterol level in the patients not receiving steroids at 6 and 12 months is 151 +/- 11 and 171 +/- 23 mg/dl (+/- SEM), respectively. Because of these results we have expanded our indications for the modified regimen using OKT3 in patients with preoperative organ system dysfunction, in diabetic patients, in pediatric patients, in female patients, and in posttransplant patients who require mechanical assistance.

Adolescent↗

PubMedDate not supplied

Analysis of risk factors for acute allograft rejection after heart transplantation.

The diagnosis of cardiac allograft rejection is currently based on endomyocardial biopsy and histologic evaluation. Since the introduction of cyclosporine, cardiac biopsy has been recognized as the only reliable method of diagnosis. From July 1985 to June 1986, 22 transplant patients were studied during the early posttransplant period to evaluate other characteristics of allograft rejection. The immunosuppressive protocol included cyclosporine, azathioprine, prednisone, and prophylactic rabbit antithymocyte globulin. Acute rejection was established by standard histologic criteria. Twenty-four positive and 123 negative biopsy findings were obtained. Clinical variables (age, sex, immunosuppressive regimen, cyclosporine dosage, ECG voltage), biologic variables (level of cyclosporine, white blood cells, blood urea nitrogen, creatinine, bilirubin, prolactin, urinary polyamines, blood type, HLA typing), and immunologic variables (T-cell subsets) were analyzed in regard to the histologic diagnosis of acute rejection. Four variables (WBC, prolactin, total urinary polyamines, N-acetyl putrescine) were found to have a significant univariate association with acute rejection. These variables were studied by multivariate discriminant analysis. The only factors found to have independent predictive value for acute rejection were prolactin and N-acetyl putrescine peaks occurring before acute rejection. When we used these factors, a discriminant function correctly predicted acute rejection episodes, as well as negative biopsy results, in 74% of the cases in this group of patients.

Biopsy↗

PubMedDate not supplied

Surgical approach to combined coronary revascularization and abdominal aortic aneurysmectomy.

Combined repair of peripheral vascular disease and myocardial revascularization has become accepted treatment in selected patients. Two of our patients underwent such a procedure. One patient suffered an intraoperative dissection of the ascending aorta following myocardial revascularization. Ascending aortic replacement and vein graft reimplantation was accomplished as well as repair of the abdominal aortic aneurysm. Because of this experience we recommend that following myocardial revascularization, aortic cannulation be maintained during repair of the abdominal aortic aneurysm. This allows immediate access to cardiopulmonary bypass should untoward cardiovascular events occur during aneurysm repair.

Aged↗

PubMedDate not supplied

Urinary polyamines are noninvasive markers of heart allograft rejection.

Histologic evaluation of the heart allograft biopsy is currently the generally accepted method to monitor for rejection after transplantation. A noninvasive marker of host prerejection immunologic activation might be a useful clinical tool and provide the basis for a more continuous evaluation than is available with the biopsy technique. Urinary polyamine levels, in the context of immune activation, may fluctuate as an indicator of lymphocyte proliferation and organ rejection. To test this hypothesis cervical heterotopic heart transplantation was performed in six dogs that did not receive immunosuppression therapy. Daily percutaneous transmural biopsy of the transplanted heart and urine samples were collected. Urinary polyamines were measured by high-pressure liquid chromatography. Between 2 and 4 days after transplantation all allografts showed a histologic picture of mild to moderate rejection. The urinary excretion of total polyamines and putrescine fraction increased during the rejection process after transplantation, attaining a maximum from the first to the third day after operation. This early elevation suggests that urinary polyamines are markers of immune activation and unmodified heart allograft rejection. Further studies need to be done to define a potential clinical application of urinary polyamines as markers of cellular metabolic activity of the immune system and allograft rejection.

Animals↗

PubMedDate not supplied

Prolactin as a marker of rejection in human heart transplantation.

Prolactin has been shown to play a role in the modulation of the immune system. In addition, recent laboratory evidence suggests that circulating prolactin might fluctuate as a function of immunologic events. To evaluate the role of prolactin as a predictor of rejection, 22 heart and heart-lung transplant patients were studied from July 1985 to May 1986. Daily plasma prolactin levels were measured by radioimmunoassay. Endomyocardial biopsy and histologic evaluation of the allografts were used to define rejection episodes. Thirteen of 14 documented rejection episodes were preceded by a specific elevation of circulating prolactin. A significant elevation of prolactin occurred 6 and 8 days before 14 rejection episodes that were diagnosed by biopsy but not before 109 biopsies were taken that had negative results. The normal values for circulating prolactin are defined by a preoperative mean in a range of 0 to 15 ng/ml (95% confidence limit). The sensitivity of prolactin to predict rejection is 79%, the specificity is 92%, and the positive predictive value is 61%. A large data variability gives a low accuracy to the test as a predictor of allograft rejection. To be useful clinically, the accuracy needs to be improved through a better understanding of prolactin physiology and its relation to the immune system.

Adult↗

PubMedDate not supplied

Changes in health-related quality of life and depression in heart transplant recipients.

BACKGROUND: The intent of this study was to measure health-related quality of life and depression in 94 heart transplant recipients. METHODS: Changes in health-related quality of life and depression were examined by administering the Sickness Impact Profile and the Beck Depression Inventory before heart transplantation, as well as 4, 8, 12, 24, 36, 48, and 60 months after surgery. RESULTS: Sickness Impact Profile scores obtained before heart transplantation highlighted the greatest health-related quality of life dysfunction in work, sleep and rest, home management, and recreation and pastimes. Posttransplantation measures suggested improvement (p < 0.05) in emotional behavior, home management, mobility, ambulation, depression, eating behavior, social interaction, body care and movement, sleep and rest, recreation and pastimes, depression, and physical, overall, and psychosocial functioning. Continued improvement was noted up to 5 years after transplantation although patients continued to have marked work-related dysfunction. Age, medication regimen, rejection episodes, and a variety of preoperative medical variables were not related to health-related quality of life. Actuarial survival rates at 1, 2, 3, 4, and 5 years were 89%, 87%, 80%, 79%, and 79%, respectively. CONCLUSIONS: Our results suggest that as early as 4 months after heart transplantation, patients show excellent functioning in most health-related quality of life areas. Survival rates are encouraging. Patients did not generally experience problems with depression within the first 4 months after heart transplantation. Notable problems remain after transplantation in rate of return to work where only 53% returned to work by 5 years after heart transplantation.

Actuarial Analysis↗

PubMedDate not supplied

Implantation of the implantable cardioverter defibrillator in the heart transplant candidate.

Because the major cause of death in patients awaiting heart transplantation results from out-of-hospital sudden cardiac arrest, the use of the implantable cardioverter defibrillator has been proposed as a bridge to transplantation. To provide a safe and simple implantation procedure that also easily allows access to cardiopulmonary bypass at the time of transplantation, a modified subxiphoid approach is reported.

Defibrillators, Implantable↗

PubMedDate not supplied

The impact of steroid withdrawal on the development of lipid abnormalities and obesity in heart transplant recipients.

Hyperlipidemia and obesity are common problems after heart transplantation, which may increase the risk of chronic graft atherosclerosis. The intent of this study was to (1) determine the impact of a history of hyperlipidemia on the occurrence of lipid abnormalities after transplantation, (2) compare lipid profiles of those patients being treated with triple-drug immunosuppression versus those patients weaned from prednisone therapy, and (3) identify any factors that would predict which patients are at highest risk for the development of hyperlipidemia after transplantation. Of 89 patients who lived for more than 12 months, 35 patients had a history of hyperlipidemia before heart transplantation (cholesterol level of more than 240 mg/dl; low-density lipoprotein cholesterol level of more than 160 mg/dl). The most dramatic rise in cholesterol level was observed in patients with no history of hyperlipidemia who were treated with triple-drug immunosuppression, in whom a 64% increase occurred versus a 24% increase in patients receiving steroid-free immunosuppression (p < 0.001). In patients with a history of hyperlipidemia, cholesterol level increased by 20% with triple-drug immunosuppression versus 14% with steroid-free immunosuppression (p = 0.613); however, 83% of the patients in the triple-drug group and 92% in the steroid-free group had elevated cholesterol levels. Multiple regression analysis revealed that significant independent and additive (p < 0.00001) contributions with respect to percent change in cholesterol level were evident for (1) a negative history of hyperlipidemia (p = 0.005), (2) triple-drug immunosuppression (p = 0.0021), and (3) female sex (p = 0.0113). A negative history of hyperlipidemia was predictive of the percent change in low-density lipoprotein cholesterol level (p = 0.0049), and triple-drug immunosuppression administration predicted the percent change in high-density lipoprotein cholesterol (p = 0.0119). Patients with a positive history of hyperlipidemia had higher lipid values at 12 and 24 months after transplantation; however, patients with no previous history of hyperlipidemia experienced the greatest percent change in both cholesterol and low-density lipoprotein levels. Patients receiving prednisone therapy gained more weight (9.0 +/- 7.0 kg) as compared with those patients tapered from prednisone therapy (5.9 +/- 8.6 kg); however, neither the increase in actual weight (p = 0.120) nor the increase in percent ideal body weight (14% +/- 11% versus 9% +/- 13%, respectively) were significant (p = 0.133). This study identified that postoperative weight gain is best predicted by premorbid habitus, rather than the type of immunosuppression used.(ABSTRACT TRUNCATED AT 400 WORDS)

Cholesterol↗