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Biomedical subjects

F J Fricker

Publications and source records attributed to F J Fricker.

At least 19 recordsLinked to original sources
PubMed2005

Genetic linkage of a novel autosomal dominant restrictive cardiomyopathy locus.

BACKGROUND: In recent years, non-syndromic idiopathic cardiomyopathies have increasingly been characterised as autosomal dominant conditions caused by single gene mutations. Loci have been identified for hypertrophic and dilated cardiomyopathy, and in some cases the same loci are associated with restrictive cardiomyopathy (RCM). In a kindred with RCM that we previously reported, we ruled out the known cardiomyopathy loci and other candidate genes by linkage analysis and mutation screening. METHODS AND RESULTS: Here we report a genome-wide analysis in this family that has resulted in linkage to a region on chromosome 10. CONCLUSIONS: There are no genes in the interval that are known to cause idiopathic cardiomyopathy, and thus this linkage represents localisation of a new RCM locus.

Cardiomyopathy, Restrictive↗
PubMed2001

Safety and efficacy of pravastatin therapy for the prevention of hyperlipidemia in pediatric and adolescent cardiac transplant recipients.

BACKGROUND: Hyperlipidemia is common after cardiac transplantation and it is a risk factor for post-transplantation coronary artery disease. Immunosuppression with corticosteroids and cyclosporine has been associated with hyperlipidemia. Pravastatin, a HMG-CoA reductase inhibitor, has been shown to be effective and safe for cholesterol reduction in adult heart transplant recipients. To our knowledge the safety and efficacy of pravastatin therapy in pediatric and adolescent heart transplant populations have not been previously analyzed. Therefore, we evaluated lipid profiles, liver transaminases, rejection data, and possible side effects in pediatric and adolescent cardiac transplant recipients treated with pravastatin. METHODS: The study group consisted of 40 cardiac transplant recipients 10 to 21 years old (mean age 16.9 years). Twenty-two patients received pravastatin in addition to an immunosuppressive regimen of either cyclosporine or tacrolimus, azathioprine or mycophenolate mofetil, and prednisone. Serial determinations of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein, and triglycerides were available for all pravastatin-treated patients. Pre-treatment lipid values and hepatic transaminases were compared with those measured after therapy with pravastatin. Comparison of pravastatin-induced lipid reduction between groups treated with cyclosporine vs tacrolimus was also made. RESULTS: Patients receiving pravastatin experienced a mean 32 mg/dl decrease in TC (p < 0.005) and a mean 31 mg/dl decrease in LDL (p < 0.005), regardless of their immunosuppressive regimen. No statistical differences occurred in the magnitude of mean lipid reduction induced by pravastatin between the groups treated with cyclosporine vs tacrolimus. No significant changes in hepatic transaminase levels were noted, and no clinical evidence of pravastatin-induced myositis occurred in any subjects. CONCLUSION: Pravastatin therapy is effective and safe when used in pediatric and adolescent cardiac transplant recipients. Although the pravastatin-induced reduction in TC and LDL was more pronounced in patients receiving cyclosporine, the reduction was not statistically different from that in the tacrolimus group. No evidence of hepatic dysfunction or rhabdomyolysis in patients treated with pravastatin was noted. Long-term studies are required to evaluate the effect of pravastatin therapy on the incidence of accelerated coronary atherosclerosis in this population.

Adolescent↗
PubMed2001

Clinical and molecular studies of a large family with desmin-associated restrictive cardiomyopathy.

Patients with restrictive cardiomyopathy (RC) have impaired diastolic function, but intact systolic function until later stages of the disease, ultimately leading to heart failure. Primary RC is often sporadic, but also may be inherited in an autosomal dominant fashion, particularly the idiopathic forms. Recently there has been great interest in inherited cardiomyopathy associated with myocyte desmin deposition ('desminopathies'). In some such families, desmin or alpha-B crystallin gene mutation is the underlying cause, and the desmin accumulation affects skeletal muscle as well, usually causing skeletal myopathy. We describe a large family with apparent autosomal dominant inheritance of desmin-associated RC spanning four generations, with the age of onset and severity/rate of progression being highly variable. This family is relatively unique in that there is no symptom-based evidence of skeletal muscle involvement, and the known desminopathy and cardiomyopathy genes/loci have been ruled out. These data support literature suggesting that desmin deposition may be associated with different underlying gene defects, and that a novel desminopathy gene is responsible for the condition in this family.

Adolescent↗
PubMed2000

Increased expression of the lymphocyte early activation marker CD69 in peripheral blood correlates with histologic evidence of cardiac allograft rejection.

BACKGROUND: The human leukocyte membrane protein CD69 is an early activation marker induced in T lymphocytes, B cells, and natural killer cells in response to inflammatory stimuli. Cardiac catheterization and endomyocardial biopsy remain the "gold standard" for diagnosis of rejection after transplantation, and noninvasive methods of rejection surveillance have long been sought. We studied CD69 membrane protein expression in peripheral blood T lymphocytes obtained from pediatric cardiac transplant recipients at the time of biopsy and correlated the results with histologic rejection scores. METHODS: Heparinized whole blood samples were obtained from pediatric cardiac transplant recipients at the time of cardiac biopsy, as well as from control subjects. Lymphocytes were labeled with antibodies for CD3, CD4, CD8, and CD69 and analysis performed using flow cytometric methods. RESULTS: Resting CD69 expression (measured as a percentage of gated events) was significantly increased in patients with concurrent histologic evidence of rejection (International Society for Heart and Lung Transplantation grade > or =3A) when compared to those with minimal or no rejection and controls. Although statistically significant for both lymphocyte subsets, this relationship was more pronounced for CD8+ T cells (P<0.001) than for CD4+ T cells (P=0.001). When data were analyzed by rejection score, a percentage activation of the CD8+ subset (CD69+/CD8+ cells as a percentage of total gated events) exceeding 15% correlated with significant rejection. CONCLUSIONS: Measurement of the expression of the early activation marker CD69 in peripheral blood lymphocytes by flow cytometry may provide a noninvasive means of assessing immune activation and possible rejection in cardiac transplant recipients.

Adolescent↗
PubMed2000

Glucocorticoid-induced osteopenia in adolescent heart transplant recipients.

BACKGROUND: Glucocorticoid-induced cushingoid symptoms, including osteopenia and osteoporosis are well-documented in adult heart transplant recipients (HTR). Bone mineral density (BMD) of the axial skeleton is diminished by 10% to 20% within 60 days after transplantation (Tx) and most adult HTR fulfill World Health Organization criteria for osteoporosis (BMD > 2.5 SD below norm). At present, we do not know whether glucocorticoids have similar deleterious effects in adolescent HTR. METHODS: To determine the consequences of glucocorticoid immunosuppression on regional bone mineral density (BMD) and biochemical markers of bone metabolism in adolescent HTR, we studied 19 patients (aged 16 +/- 3) at 19 months (group mean) after Tx. We measured BMD (hydroxyapatite g/cm(2)) of the total body, lumbar spine, and pelvis using dual-energy X-ray absorptiometry (Lunar). Serum levels of bone-specific alkaline phosphatase and pyridinoline cross-links were determined by enzyme immunoassay in serum kits. RESULTS: The BMD of the lumbar spine (-12%), femur neck (-13%), femur trochanter (-12%), and ward's triangle (-16%) were significantly (p < 0.05) lower in adolescent HTR than age- and gender-matched norms. Serum levels of alkaline phosphatase (29 +/- 6 vs 22 +/- 3 U/liter) and pyridinoline cross-links (5.3 +/- 1.1 vs 3.8 +/- 0.7 mmol/liter) were significantly (p < 0.05) elevated in adolescent HTR, compared with age- and gender-matched controls studied in our laboratory. CONCLUSIONS: Our cross-sectional results demonstrate that BMD of the axial skeleton in adolescent HTR is significantly lower (-10% to 20%) than age-matched norms and that serum biochemical markers of bone metabolism are significantly elevated, suggesting accelerated bone turnover.

Absorptiometry, Photon↗
PubMed2000

Balloon aortic valvotomy through a carotid cutdown in infants with severe aortic stenosis: results of the multi-centric registry.

OBJECTIVES: The purpose of this study was to evaluate the short and intermediate term results of infants who have undergone balloon aortic valvotomy from the carotid arterial approach, and to identify risk factors in those infants who had a poor outcome. METHODS: Between 1988 and 1999, balloon aortic valvotomy was attempted at four centres in 95 infants with severe aortic stenosis. Echocardiographic and hemodynamic data, and outcome, were analysed retrospectively. RESULTS: Valvotomy was accomplished in 92 of the 95 infants, with a median age of 5 days, a range from 0 to 191 days, and weighing 3.4 kg, with a range from 1.0 to 6.5 kg. Major procedural complications occurred in 10 infants. Post-procedural aortic regurgitation was severe in 5 patients. There were 13 early deaths, and 4 late deaths. The period of mean follow-up has been 2.1 years, with a range from 0 to 9.3 years. The actuarial survival at 3 years was 76 +/- 6%. Further interventions were needed in 19 patients, giving a 3-year freedom from reintervention of 67 +/- 6%. The 51 infants who were duct-dependent were further analyzed, and found to have a higher mortality (38%) compared to those infants not dependent on the arterial duct (5%). Risk factors for a poor outcome in the duct-dependent infants were mitral stenosis (p<0.005), a left ventricle which did not form the cardiac apex (p<0.005), and an aortic valve with a diameter of less than 6 mm (p<0.05). CONCLUSIONS: This multi-centric registry shows good results in the intermediate term for treating infants with severe aortic valvar stenosis with balloon valvotomy through a carotid arterial cutdown. Infants dependent on prostaglandin had a worse outcome, especially if they had any of the identified risk factors.

Analysis of Variance↗
PubMed2000

Metabolic aspects of myocardial disease and a role for L-carnitine in the treatment of childhood cardiomyopathy.

OBJECTIVES: A multicenter retrospective study was conducted to investigate the possible metabolic causes of pediatric cardiomyopathy and evaluate the outcome of patients treated with L-carnitine. METHODS: Seventy-six patients diagnosed with cardiomyopathy were treated with L-carnitine in addition to conventional cardiac treatment, and 145 patients were treated with conventional treatment only. There were 101 males and 120 females between 1 day and 18 years old. Cardiomyopathy diagnoses included dilated (148 patients), hypertrophic (42 patients), restrictive (16 patients), mixed diagnosis (11 patients), and 4 with an unknown type. Of 76 L-carnitine-treated patients, 29 (38%) had evidence to suggest a disorder of metabolism, and of 145 control patients, 15 (10%) were suspected to have a disorder of metabolism. These metabolic disorders were thought to be the cause for the cardiomyopathy of the patients. The duration of L-carnitine treatment ranged from 2 weeks to >1 year. Information was collected on length of survival (time-to-event), clinical outcome, echocardiogram parameters, and clinical assessments. Data were collected at intervals from baseline to study endpoint, death, transplant, or last known follow-up visit. RESULTS: L-Carnitine-treated patients were younger than control patients and had poorer clinical functioning at baseline, yet they demonstrated lower mortality and a level of clinical functioning and clinical severity comparable to control patients on conventional therapy by the end of the study. An analysis of the interaction between clinical outcome and concomitant medications unexpectedly revealed that the population of patients treated with angiotensin-converting enzyme (ACE) inhibitors (40% of patients) had significantly poorer survival (although their greater likelihood for poor survival may possibly have made them more likely to receive ACE inhibitors). CONCLUSION: Results suggest that L-carnitine provides clinical benefit in treating pediatric cardiomyopathy. There is a need for further exploration of potential explanatory factors for the higher mortality observed in the population of patients treated with ACE inhibitors.

Cardiomyopathies↗
PubMed1999

Dobutamine stress echocardiography: experience in pediatric heart transplant recipients.

BACKGROUND: Transplant coronary arteriopathy causes late death and is difficult to detect noninvasively. Dobutamine stress echocardiography is being used for risk stratification in adult recipients at some transplant centers, thus we investigated its role in a pediatric population. METHODS: We performed 46 stress echo studies (mean age = 11.8 years; mean years post transplantation = 4.3). An atropine/dobutamine protocol (5-40 mcg/kg/min) was used to attain a predicted target heart rate. Serial echocardiographic images were acquired at baseline and at each increment of dobutamine and recovery, and were digitized online. Data were correlated with endomyocardial biopsy (n = 23), coronary angiography (n = 26) or autopsy (n = 6). All studies were well tolerated. RESULTS: Target heart rate was achieved in 41/46 (89%) studies. The mean heart rate significantly increased from 95 to 169 beats/min and mean systolic blood pressure from 123 to 153 mm Hg (p<.05). The mean peak pressure-rate product was 23,041 beats-mm Hg/min. Coronary arteriopathy was confirmed in 5 patients by angiography (n = 3) explanted heart (n = 1) or autopsy (n = 4). In this group, abnormalities included a new reversible wall motion abnormality (n = 2), left ventricular cavity dilation with stress (n = 3), ischemia (n = 2), increased mitral insufficiency (n = 1) and marked diastolic dysfunction (n = 1). A positive study predicted death or graft failure (p< .0005). CONCLUSIONS: Echocardiographic abnormalities during stress correlated with coronary arteriopathy in this small cohort of patients; however, larger multi-center studies are warranted to assess the utility of dobutamine stress echocardiography for risk stratification for coronary disease in pediatric transplant recipients.

Adolescent↗
PubMed1999

Tacrolimus-based triple-drug immunosuppression minimizes serum lipid elevations in pediatric cardiac transplant recipients.

BACKGROUND: Immunosuppression with corticosteroids and cyclosporine has been associated with hyperlipidemia, a risk factor for post-transplant coronary artery disease. The recent development of tacrolimus has created an alternative to cyclosporine-based triple drug immunotherapy. One potential benefit that has been reported in patients receiving tacrolimus is a minimization of elevation of both total and LDL cholesterol, compared to those increases observed in patients receiving cyclosporine-based immunosuppression. It is unclear in previous studies whether this beneficial effect is related to tacrolimus directly or to its corticosteroid sparing potential. To study this relationship, we compared lipid profiles from pediatric cardiac transplant recipients treated with corticosteroids, and either cyclosporine or tacrolimus. METHODS: The study group consisted of 23 patients (mean age = 12.3 years) with pre-transplant and serial post-transplant determinations of total cholesterol, LDL, HDL, and triglycerides. Patients were separated into 4 study groups, defined by immunosuppressive regimen (cyclosporine vs. tacrolimus) and prednisone dose (>0.10 mg/kg/day vs. < or =0.10 mg/kg/day). RESULTS: Patients who received cyclosporine and higher doses of prednisone experienced a mean 74 mg/dl increase from baseline in total cholesterol (p = .0001). None of the other 3 treatment groups demonstrated a statistically significant elevation. Similar trends were observed in LDL and triglyceride alterations between the 4 study groups. Interestingly, patients treated with tacrolimus and higher doses of prednisone demonstrated a significant rise in HDL from baseline (p = .0001), although those who received cyclosporine and higher dose prednisone failed to exhibit this rise. CONCLUSION: The minimal degree of lipid alteration seen in patients receiving tacrolimus and higher doses of prednisone indicates that this effect was not solely based upon the steroid-sparing properties of tacrolimus therapy. The data also suggests a possible synergistic effect between cyclosporine and higher doses of prednisone on hyperlipidemia. Therefore, in pediatric patients requiring higher corticosteroid doses late after transplantation, use of tacrolimus rather than cyclosporine may lead to more favorable lipid profiles and help minimize the risk of post-transplant coronary arteriopathy.

Analysis of Variance↗
PubMed1998

Clinical relevance of in vitro propagation of activated lymphocytes from endomyocardial biopsy samples of pediatric heart transplant recipients.

In vivo activated T-lymphocytes can be cultured from endomyocardial biopsy samples of human cardiac allografts, sometimes even in the absence of histological rejection. We investigated the clinical relevance of this "lymphocyte growth assay" in pediatric heart transplant recipients. Specifically, we wished to determine if: (i) positive lymphocyte growth from EMB samples in the absence of significant rejection identifies a patient as being at increased risk for the development of acute rejection; (ii) withdrawal or major dose reduction of corticosteroids in the presence of lymphocyte growth results in high risk of rebound rejection; and (iii) presence of lymphocyte growth during acute rejection helps predict the response to treatment. Cultures were performed on 789 consecutive EMB samples from 65 pediatric heart transplant recipients in media containing 30 U/ml of recombinant IL-2. T-lymphocytes were cultured from 16% of EMB samples with low grade rejection (grade 0-1b) and from 34% of EMB samples with grade 2-4 rejection. EMB samples obtained early post-transplant (<180 days) were significantly more likely to yield positive lymphocyte growth compared to biopsies obtained late for any given rejection grade. Lymphocyte growth was comparable between patients managed with cyclosporine or tacrolimus based immunosuppression. For 227 EMB samples without rejection, a subsequent EMB sample was obtained within 12 weeks. Lymphocyte cultures were positive in 47 of these 227 EMB samples (21%), and in 19 out of 47 (40%) cases acute rejection (grade 2-4) was present on the follow-up EMB sample. By contrast, of 180 biopsies without growth, only 29 (16%) showed rejection at the next EMB (p<0.0001). When a follow-up biopsy was performed within 12 weeks of corticosteroid withdrawal, "rebound rejection" was observed in 3 out of 10 (30%) cases where the previous EMB sample yielded positive lymphocyte growth and in 4 out of 38 (11%) cases when it did not (p=0.29). The presence of lymphocyte growth in association with rejection was also predictive of whether rejection would resolve following high dose intravenous corticosteroid therapy (persistent rejection in 33 out of 50 (66%) cases with positive growth, versus 25 out of 80 (31%) cases without growth (p<0.0001)). Thus, positive lymphocyte growth is strongly associated with higher grade of rejection and earlier time from transplantation. Lymphocyte growth in the absence of rejection indicates high risk for rejection within the next 12 weeks. Growth in association with acute rejection indicates high probability of persistence of rejection following treatment with high dose corticosteroids.

Adolescent↗
PubMed1997

Posttransplantation lymphoproliferative disorders in pediatric thoracic organ recipients.

OBJECTIVE: To determine the frequency, predisposing factors, clinical presentation, and outcome of posttransplantation lymphoproliferative disorders (PTLDs) in pediatric thoracic organ transplant recipients. METHODS: Retrospective review of the medical records of all 120 children who survived longer than 1 month after thoracic organ transplantation at our center. RESULTS: PTLD was diagnosed in 14 patients (11.7%), including 7.7% of heart and 19.5% of heart-lung/lung recipients. Presentation of PTLD was variable, ranging from asymptomatic lung nodules on chest radiograph to diffuse multiorgan failure. Treatment with a reduction of immunosuppression and antiviral therapy resulted in resolution of PTLD in eight patients. Eight patients died. PTLD contributed to death in five. No patient seropositive for Epstein-Barr virus (EBV) before transplantation had PTLD. There was a significant association between primary EBV infection after transplantation and the presence of PTLD. CONCLUSIONS: PTLD occurs with greater frequency in pediatric thoracic organ transplant recipients than in the adult transplant population. Primary EBV infection after transplantation is the major risk factor for the development of PTLD. Patients in whom primary EBV infection develops after transplantation should be managed with a reduction in immunosuppression and with heightened surveillance for the development of PTLD.

Adolescent↗
PubMed1997

Long-term survivors of pediatric heart transplantation: a multicenter report of sixty-eight children who have survived longer than five years.

OBJECTIVE: Short-term survival after pediatric heart transplantation is now excellent, but ultimately the efficacy of this procedure will depend on duration and quality of survival. We sought to evaluate the clinical course of long-term survivors of heart transplantation in childhood. METHODS: Patients who had undergone heart transplantation at the university hospitals of Stanford, Columbia, and Pittsburgh between 1975 and 1989 and survived longer than 5 years from transplantation were identified and their clinical courses retrospectively reviewed. RESULTS: Sixty eight children have survived more than 5 years from transplantation, and 60 (88%) are currently alive with a median follow-up of 6.8 years (5 to 17.9 years). Thirteen have survived more than 10 years from transplantation. Renal dysfunction caused by immunosuppressive agents was common, and two patients required late renal transplantation. Lymphoproliferative disease or other neoplasm occurred in 12 patients, but none resulted in death. Coronary artery disease was diagnosed in 13 patients (19%), leading to retransplantation in eight. Death after 5 years was related to acute or chronic rejection in 5 of 8 cases. Two of the deaths were directly related to noncompliance with immunosuppressive medication. All survivors are in New York Heart Association class 1. CONCLUSIONS: Long-term survival with good quality of life can be achieved after heart transplantation in childhood, though complications of immunosuppression remain common. Posttransplantation coronary artery disease is emerging as the main factor limiting long term graft and patient survival.

Adolescent↗
PubMed1997

New-onset diabetes mellitus in pediatric thoracic organ recipients receiving tacrolimus-based immunosuppression.

BACKGROUND: Tacrolimus has a negative effect on the pancreatic beta islet cell, and both glucose intolerance and diabetes mellitus are well-recognized complications of tacrolimus-based immunosuppression among adult solid organ transplant recipients. METHODS: To determine the association between tacrolimus and new-onset diabetes mellitus in childhood, we reviewed data on 78 pediatric heart and heart-lung/lung recipients receiving tacrolimus-based immunosuppression. Trough tacrolimus levels, fasting and random blood glucose levels, and corticosteroid requirements were reviewed. Diabetes was defined as glucose intolerance requiring long-term insulin treatment more than 30 days after transplantation. RESULTS: No patient had diabetes before introduction of tacrolimus. In heart-lung/lung recipients, 12 of 28 (43%) had development of diabetes at a median follow-up of 7 months (range 1 to 39). In this group diabetes developed in three of eight (38%) patients with cystic fibrosis and nine of 20 (45%) without (p = NS). In contrast, only two of 50 (4%) heart transplant recipients had development of diabetes. Of the 14 patients with diabetes, 10 had development of diabetes during augmentation of immunosuppression with pulsed corticosteroids. Tacrolimus trough levels were significantly lower in heart compared with heart-lung/lung transplant recipients (9.4 +/- 3.3 versus 15.3 +/- 0.9 ng/ml) (p < 0.01), and at latest follow-up significantly fewer heart transplant recipients were treated with maintenance corticosteroids (28% versus 75%; p < 0.01). In the heart-lung/lung group, no significant difference in tacrolimus levels was found between patients with and without diabetes, nor was there a significant difference in the average corticosteroid dose or number of pulses of corticosteroids per patient. CONCLUSIONS: New-onset diabetes mellitus is rare in pediatric heart transplant recipients receiving tacrolimus-based immunosuppression, but it occurs with a high incidence after pediatric heart-lung/lung transplantation and usually develops during pulsed corticosteroid therapy. However, it is currently not possible to predict which heart-lung/ lung transplant recipients will have development of this serious complication.

Adolescent↗
PubMed1996

A six-minute walk test for assessing exercise tolerance in severely ill children.

OBJECTIVES: The primary objective of this study was to compare exercise tolerance, heart rate, and oxyhemoglobin saturation (Sao2) between a traditional progressive maximal exercise test and a self-paced, 6-minute walk test in severely ill children. STUDY DESIGN: Seventeen patients (9 to 19 years of age) performed a progressive maximal exercise test on a cycle ergometer and a self-paced, 6-minute walk test as part of the evaluation for possible heart, lung, or combined heart and lung transplantation. Physical work capacity and peak oxygen uptake were measured during the progressive cycle test. The walk test was performed in a hospital corridor, with patients trying to cover as much distance as possible in 6 minutes at their own pace. Oxyhemoglobin saturation and heart rate were monitored continuously by pulse oximetry and compared between the two tests. RESULTS: The distance walked in 6 minutes correlated with peak oxygen uptake (r = 0.70, p < 0.01) and physical work capacity (r = 0.64, p < 0.005). The minimum (Min) Sao2 on the bike test correlated significantly with Min Sao2 on the walk test (r = 0.82, p < 0.001), with 11 of 17 patients having a lower Min Sao2 on the walk test than the bike test (mean Min Sao2, 84% and 86%, respectively). The peak heart rate did not correlate significantly between the bike and walk tests (r = 0.25), although significantly lower (p < 0.01) values were observed on the walk (148 beats/min) than bike (169 beats/min) test. CONCLUSIONS: The results suggest that the 6-minute self-paced walk test may provide an alternative method for assessing functional capacity in severely ill children, and that Sao2 measured during progressive exercise testing on a cycle ergometer may not reflect the degree of oxyhemoglobin desaturation during self-paced walking in some patients with severe cardiopulmonary disease.

Adolescent↗
PubMed1996

A prospective trial of tacrolimus (FK 506) in clinical heart transplantation: intermediate-term results.

Between January 1, 1989, and December 31, 1994, we have treated 122 primary heart recipients with FK 506 (group I) and 121 with cyclosporine (group II). Fifty patients in the cyclosporine (CyA) group received no lympholytic induction (CyA alone) and 71 others received lympholytic induction with either rabbit antithymocyte globulin or OKT3 (CyA+LI). The mean follow-up was longer in the FK 506 group than in the CyA groups (3.2 +/- 1.3 vs 2.3 +/- 1.8 years; p< 0.01). Patient survival did not differ on the basis of the type of immunosuppression used. At 3 months after transplantation, the freedom from rejection in the FK 506 group was higher than that of the CyA-alone group (47% vs 22%, p < 0.01) but similar to that of the CyA+LI group (47% vs 53%). The linearized rejection rate (episodes/100 patient-days) of the FK 506 group (0.09 episodes) was lower (p < 0.05) than that of the CyA-alone group (0.26) and the CyA+LI group (0.13). The requirement for pulsed steroids to treat rejection was less in common in the FK 506 group than in either CyA group. Eighteen patients in the CyA group had refractory rejections; all resolved with FK 506 rescue. Two patients in the FK 506 group had refractory rejection that resolved with total lymphoid irradiation (n=1) and methotrexate therapy (n=1). Patients receiving FK 506 had a lower risk of hypertension and required a lower dose of steroids. Although the mean serum creatinine concentration at 1 year was higher in the FK 506 group, this difference disappeared after 2 years. No patients required discontinuation of FK 506 because of its side effects. Our intermediate-term results indicate that FK 506 compares favorably with CyA as a primary immunosuppressant in heart transplantation.

Adult↗