Search PubMed⌕ Search

Biomedical subjects

E J O'Sullivan

Publications and source records attributed to E J O'Sullivan.

15 recordsLinked to original sources
PubMed1994

Risk/benefit ratio of perioperative OKT3 in cardiac transplantation.

To evaluate the risk/benefit ratio of perioperative OKT3 in cardiac transplant patients receiving triple-drug immunosuppression, patients who underwent cardiac transplantation between July 1, 1988 and December 31, 1989 (n = 33) and who received perioperative OKT3 were retrospectively compared with patients who underwent transplantation between January 1, 1990 and June 30, 1991 (n = 46), and who received no perioperative anti-T cell therapy. To allow similar follow-up, data were analyzed through June 30, 1990 for the OKT3 group and through December 31, 1991 for the no anti-T cell therapy group. Patients in the no anti-T cell therapy group waited longer for a donor organ; other pretransplant characteristics did not differ. The azathioprine dose 1 month after transplant was higher in the no anti-T cell therapy group (144 +/- 63 mg vs 109 +/- 55 mg, p = 0.016); other post-transplant immunosuppression was similar. The incidence of total and treated rejection and the time to the first rejection did not differ between the groups. The OKT3 group had a higher number of infections (0.8 +/- 0.9 vs 0.3 +/- 0.3, p = 0.006) and intravenously treated infections (0.5 +/- 0.6 vs 0.1 +/- 0.2, p = 0.004) per patient per month. Cytomegalovirus infection developed in 46% of the OKT3 group versus 22% of the no anti-T cell therapy group (p = 0.025). Patient survival did not differ between the groups. Thus, an immunosuppressive regimen that includes perioperative OKT3 increases infections, especially cytomegalovirus infections, without decreasing or delaying rejection or increasing survival.

Adult↗
PubMed1994

Intracoronary ultrasound assessment of morphological and functional abnormalities associated with cardiac allograft vasculopathy.

BACKGROUND: The diffuse nature of cardiac allograft vasculopathy makes early detection of the disease by traditional noninvasive methods or coronary angiography difficult. The aim of this study was to determine if there is a relation between abnormalities in vessel wall morphology, as assessed by intracoronary ultrasound, and a decreased vasodilatory response to the endothelium-dependent vasodilator papaverine hydrochloride and if cardiac allograft vasculopathy detected by coronary angiography is associated with specific intracoronary ultrasound findings. METHODS AND RESULTS: Twenty-three heart transplant recipients underwent 25 intracoronary ultrasound studies and 24 studies of coronary vasomotor tone 10 days to 8.3 years after surgery using a 20-mHz intracoronary ultrasound catheter. The studies were divided in two groups according to the presence (n = 7, group 1) or absence (n = 18, group 2) of angiographically evident cardiac allograft vasculopathy. Qualitative assessment of vessel wall morphology and quantitative analysis of the vasodilator response to the injection of papaverine hydrochloride into the coronary artery distal to the imaging site were performed off-line, and results for the two study groups were compared. A significantly higher percentage of patients with than without angiographic evidence of cardiac allograft vasculopathy had a three-interface vessel wall morphology by intracoronary ultrasound (100% versus 11%, P < .001). In two recipients who underwent two serial studies, the appearance of three interfaces in the vessel wall or a progressive thickening of the inner interface of the vessel wall occurred in conjunction with the appearance of angiographic cardiac allograft vasculopathy. The vasodilator response to papaverine was less in patients with than in those without angiographically evident cardiac allograft vasculopathy both in terms of absolute and relative increases in lumen diameter (+0.1 +/- 0.12 mm versus +0.3 +/- 0.17 mm, P < .05, and +5.1 +/- 5.3% versus +8.2 +/- 5.3%, P = NS) and lumen cross-sectional area (+0.5 +/- 0.6 mm2 versus +1.7 +/- 1.1 mm2, P < .02, and +7.1 +/- 8.8% versus 16.6 +/- 11.0%, P = .055), respectively. CONCLUSIONS: Intracoronary ultrasound assessment of vessel wall morphology and evaluation of vascular response to endothelium-dependent vasodilators are useful techniques for detecting cardiac allograft vasculopathy.

Cardiac Catheterization↗
PubMed1993

Risk/benefit ratio of perioperative OKT3 in cardiac transplantation.

This study shows that perioperative OKT3 provides no benefit in terms of the time of onset or frequency of rejection or patient survival. However, it does result in an increased incidence of infection, particularly CMV infection. Thus, the risk/benefit ratio of perioperative OKT3 does not appear favorable. However, a multicenter, randomized trial including a larger number of patients and longer patient follow-up will be required to definitively answer the question.

Azathioprine↗
PubMed1992

Successful treatment of heart transplant rejection with photopheresis.

Photopheresis is a potential therapy for rejection in which reinfusion of mononuclear cells exposed to ultraviolet-A light ex vivo, after treatment with 8-methoxypsoralen in vivo, initiates host immune responses that specifically inhibit the cytotoxicity of the photomodulated mononuclear cells. Between May 1990 and January 1991, 7 heart transplant (HT) patients (age 42.2 +/- 16.7 [mean +/- SD] years) on triple immunosuppression (cyclosporine, corticosteroids, and azathioprine) had 9 episodes of non-hemodynamically compromising moderate rejection that were treated with photopheresis. These episodes of rejection occurred at an average of 114.4 +/- 180.5 (range 8-575) days after HT. After oral administration the mean serum level of 8-methoxypsoralen achieved was 129.0 +/- 72.4 ng/ml. An average of 10.4 +/- 9.6 x 10(9) mononuclear cells were treated with each photopheresis procedure. Photopheresis was performed twice when less than 5 x 10(9) mononuclear cells had been treated with the first procedure. Of 9 rejection episodes treated with photopheresis, 5 required 1 procedure and 4 required 2 procedures. Photopheresis was used to treat a single episode of rejection in 5 pts. and 2 separate rejection episodes in 2 additional pts. Eight of 9 episodes of rejection were successfully reversed by photopheresis as assessed by endomyocardial biopsy (EMB) performed 7 days after treatment. Immunohistochemical analysis of EMB samples revealed that postphotopheresis cell counts for T cells, B cells, and macrophages were reduced compared to pretreatment values and correlated with the histopathologic resolution of rejection. Hemodynamics were normal prephotopheresis and remained unchanged at the time when the postphotopheresis EMB showed no evidence rejection No adverse effects have been observed with photopheresis. Over a follow-up period of 5.3 +/- 4.0 months, rejection and infection rates/pt./follow-up months were 0.3 +/- 0.4 and 0.04 +/- 0.07, respectively. The preliminary, short term results of this pilot study indicate that photopheresis may be efficacious in the treatment of moderate rejection in hemodynamically stable HT patients and thus may be an alternative to corticosteroid pulses.

Adult↗
PubMed1992

Photopheresis versus corticosteroids in the therapy of heart transplant rejection. Preliminary clinical report.

BACKGROUND: Photopheresis is a technique in which reinfusion of mononuclear cells exposed to UV-A light ex vivo after in vivo treatment with 8-methoxypsoralen initiates host-immunosuppressive responses. METHODS AND RESULTS: To determine if photopheresis safely reverses International Society for Heart and Lung Transplantation (ISHLT) rejection grades 2, 3A, and 3B without hemodynamic compromise, 16 heart transplant patients with ISHLT rejection grades 2, 3A, and 3B were randomized to photopheresis or corticosteroid therapy. The average number of mononuclear cells treated with each photopheresis procedure was 9.8 +/- 9.1 x 10(9) (mean +/- SD). Photopheresis and corticosteroids reversed eight of nine and seven of seven episodes of rejection, respectively. The median time from initiation of treatment to rejection reversal was 25 days (range, 6-67 days) in the photopheresis group and 17 days (range, 8-33 days) in the corticosteroid group. Hemodynamics were normal before either treatment and did not change after reversal of rejection. No adverse reactions occurred with photopheresis, and all patients in either treatment group are alive. CONCLUSIONS: These preliminary, short-term results in prospectively randomized patients indicate that photopheresis may be as effective as corticosteroids for treating ISHLT rejection grades 2, 3A, and 3B. The apparently low toxicity and potential efficacy of photopheresis warrant further analysis of its role in the prevention and treatment of heart transplant rejection.

Adult↗
PubMed1990

Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients.

BACKGROUND: A sudden increase in the incidence of post-transplantation lymphoproliferative disorder among the patients in our cardiac-transplantation program was temporally related to introduction of the immunosuppressive drug OKT3. This monoclonal antibody has come to be widely used in recent years both to prevent and to treat rejection after cardiac transplantation. METHODS: In order to identify variables that predict the development of post-transplantation lymphoproliferative disorder, we analyzed retrospectively a series of 154 consecutive cardiac-transplant recipients at a single institution. Univariate analyses and multivariate analysis by logistic regression were performed. RESULTS: Among 75 patients who did not receive OKT3, post-transplantation lymphoproliferative disorder developed in 1 (1.3 percent), as compared with 9 of 79 patients who received the drug (11.4 percent); the incidence among the OKT3-treated patients was ninefold higher (odds ratio, 9.5; 95 percent confidence interval, 1.6 to 54.7). According to multivariate analysis, the only factor significantly associated with the development of post-transplantation lymphoproliferative disorder was the use of OKT3 (P = 0.001). A significant increase in risk with increasing doses was also apparent: 4 of 65 patients who received a cumulative dose of 75 mg of OKT3 or less (6.2 percent) had post-transplantation lymphoproliferative disorder, whereas 5 of 14 patients who received more than 75 mg had the disorder (35.7 percent; P less than 0.001). CONCLUSION: The addition of OKT3 to the immunosuppressive regimen increases the incidence of post-transplantation lymphoproliferative disorder after cardiac transplantation, and the risk increases sharply after cumulative doses greater than 75 mg. We suggest that the risks and benefits of prophylactic OKT3 administration be reassessed in the light of these findings, particularly since the value of prophylactic immunotherapy in cardiac-transplant recipients remains to be clearly established.

Antibodies, Monoclonal↗
PubMed1989

Predictors of late acute orthotopic heart transplant rejection.

To identify predictors of late acute rejection after orthotopic heart transplantation (OHT), 53 patients who received transplants between March 1984 and March 1987 and who survived at least 1 year postoperatively were followed up for 402-1,151 days (mean, 841 days). Fourteen patients experienced 22 moderate or severe rejection episodes more than 1 year after OHT (LR); 39 were nonrejectors (NR). Twelve of 14 (86%) LR and only 14 of 39 (36%) NR had two or more moderate or severe rejection episodes within the first year after OHT (p less than 0.001). The LR had significantly higher numbers of infections more than 1 year after OHT (2.0 vs. 0.9; p less than 0.05). Nine of 22 (40%) late acute rejection episodes followed within 1 month of infection. Human leukocyte antigen reactivity before OHT, follow-up hemodynamics, length of survival, incidence of diabetes mellitus, coronary artery disease 1 year after OHT, mean cyclosporine levels, and mean daily prednisone doses were similar in LR and NR patients. We conclude that 1) OHT recipients with two or more moderate or severe rejection episodes in the first year after OHT are at higher risk of developing late acute rejection and may require closer long-term rejection surveillance and more aggressive maintenance immunosuppression and 2) the possible relation between infection and subsequent acute rejection episodes in OHT recipients requires further investigation.

Adult↗
PubMedDate not supplied

Cytomegalovirus infections in heart transplant recipients: relationship to immunosuppression.

To determine the relationship of cytomegalovirus infections (CMVI) to immunosuppression in heart transplants, we retrospectively compared demographic and clinical variables in 154 consecutive heart transplant patients. Forty-one CMVI were compared; of these, 30 (73%) were identified in tissue, and nine (22%) were identified by blood or urine culture. Twenty (49%) of the CMVI were self-limited, and 21 (51%) were progressive, requiring treatment. When comparing patients with and without CMVI, demographic variables, mean preexisting heart disease, cyclosporine level, cumulative corticosteroid dose, and the use of anti-T-cell antibodies were examined. Only the use of OKT3 was significantly associated with the subsequent development of CMVI. Although CMVI subsequently developed in 30 of 79 (38%) patients who had received OKT3, CMVI developed in only 11 of 75 (15%) patients who had not received OKT3 (p = 0.01). Furthermore, the incidence of CMVI increased with increasing total OKT3 dose (none, 11 of 64 [17%]; < or = 75 mg, 23 of 66 [35%]; > 75 mg, 6 of 14 [43%]; p = 0.01). Logistic regression showed that the only two variables predictive of CMVI were the use of OKT3 (p = 0.0023) and ischemic rather than idiopathic heart disease before transplantation (p = 0.0098). Rejection rates, incidence of allograft vasculopathy, and 1-year actuarial survival were not influenced by previous CMVI. Pneumocystis carinii pneumonia occurred more frequently in patients with CMVI than in those without (13 of 41 [32%] patients versus 3/113 [3%] patients; p < 0.001). No correlation existed between CMVI and lymphoproliferative disorder (p = 0.84).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Oversizing of donor hearts: beneficial or detrimental?

To determine the effects of donor/recipient weight mismatch on allograft function and survival after orthotopic heart transplantation, we retrospectively compared the clinical and the hemodynamic characteristics of recipients weighing more than their donor ("undersized") with those of recipients weighing less than their donor ("oversized"). The median follow-up period was 24 months (range, 0 to 67 months). In 88 patients (59%) donor weight was 1% to 46% less than recipient weight (13.5 +/- 8.9 means +/- SD). In 61 patients (41%) donor weight exceeded recipient weight by 0% to 139% (20% +/- 23%). When recipient ideal body weight was used in the analysis, 75 patients (51%) were undersized by 1% to 59% (13% +/- 10%), and 72 patients (49%) were oversized by 0% to 67% (19% +/- 18%). Preoperative transpulmonary gradient, ventricular function, and exercise tolerance were similar in the two groups. The number and severity of episodes of rejection and infection after transplantation were also similar in the two groups 1, 6, and 12 months after transplantation. When recipient ideal weight was used in the analysis, right ventricular (RV) and left ventricular (LV) ejection fractions (EFs) were within normal limits (RVEF greater than 40%; LVEF greater than or equal to 45%) and similar in the two groups. When recipient actual weight was used in the analysis, the LVEF measured at 12 months after heart transplantation was higher in the oversized than in the undersized group (52 +/- 11 vs 46 +/- 10; p less than 0.05). Postoperative hemodynamic values and exercise tolerance were similar in the two groups regardless of whether recipient weight or ideal body weight were used in the analysis. Forty-six recipients died 0 to 46 months (median, 7 months) after orthotopic heart transplantation. In a Cox regression model, recipients with donor weight greater than recipient ideal weight had a significantly greater risk of death within the follow-up period than did recipients with donor weight less than recipient ideal weight (relative risk = 2.19; p less than 0.05). When percent donor weight/recipient ideal weight mismatch was used as a continuous variable, donor heart oversizing was negatively related to survival, independent of preoperative transpulmonary gradient values (p less than 0.05). In contrast to common belief, oversizing of donor hearts does not improve the outcome of orthotopic heart transplant recipients who have reversible preoperative pulmonary hypertension. Acceptance of undersized donor hearts is not detrimental to allograft function and recipient survival. Use of undersized donor hearts may maximize the use of critically scarce donor organs.

Adult↗
PubMedDate not supplied

Prospective randomized trial of OKT3- versus horse antithymocyte globulin-based immunosuppressive prophylaxis in heart transplantation.

To compare monoclonal anti-T3-receptor antibody (OKT3) and horse antithymocyte globulin (HATG) immunoprophylaxis, 23 heart transplant recipients were randomized to OKT3 (N = 12) 5 mg IV x 14 days of HATG (N = 11) 5 mg/kg IV x 10 days and followed up for 216 +/- 137 days receiving triple immunosuppression. Recipient groups were demographically and clinically similar. First rejection occurred later in OKT3 recipients vs HATG recipients (31.7 +/- 18.3 vs 15.1 +/- 2.3 days; p less than 0.01), but the first rejection necessitating intensified immunosuppression occurred at similar times (30.9 +/- 14.6 vs 21.9 +/- 10.2 days; NS). Phenotypic characterization of peripheral blood lymphocytes by flow cytometry revealed that OKT3 and HATG recipients had similar decreases in total T lymphocytes and lymphocyte subpopulations. During the follow-up period rejection rates in the OKT3- and in the HATG-treated patients were 3.4 +/- 2.7 and 5.9 +/- 4.7, respectively (NS). The number of rejection episodes per recipient treated with intensified immunosuppression was 1.4 +/- 1.2 in the OKT3- and 2.0 +/- 3.1 in the HATG-treated patients (NS). Infection rates were 4.9 +/- 5.2 in the OKT3- and 2.7 +/- 1.7 in the HATG-treated patients (NS). The number of infection episodes that necessitated intravenous antimicrobial therapy was 2.7 +/- 2.3 in the OKT3- and 1.6 +/- 1.3 in the HATG-treated recipients (NS). The number and length of hospitalizations were similar in patients given OKT3-based or HATG-based immunoprophylaxis. We conclude that immunosuppressive prophylaxis with OKT3 vs HATG in heart transplant recipients is associated with a slightly lower incidence and severity of rejection and slightly higher infection rates.

Animals↗
PubMedDate not supplied

Influence of preoperative transpulmonary gradient on late mortality after orthotopic heart transplantation.

We reviewed the transpulmonary gradient, pulmonary arterial systolic pressure, pulmonary vascular resistance (Wood units), and pulmonary vascular resistance index (Wood units X Body surface area), recorded preoperatively in 109 recipients aged 44.6 +/- 13.5 (mean +/- SD) years who underwent orthotopic heart transplantation between March 1984 and March 1988, to identify which measure of pulmonary hypertension most accurately predicts poor outcome after orthotopic heart transplantation. These recipients were followed up as many as 57 (24.7 +/- 14.5) months after their transplant procedure. Preoperative hemodynamic values were as follows: transpulmonary gradient, 10.4 +/- 4.7 mm Hg; pulmonary artery systolic pressure, 53.6 +/- 14.8 mm Hg; pulmonary vascular resistance, 2.7 +/- 1.8 Wood units; pulmonary vascular resistance index, 4.9 +/- 2.7. Nineteen recipients died within 1 year after orthotopic heart transplantation. Causes of death were acute rejection (8), chronic rejection (1), infection (2), nonspecific orthotopic heart transplant failure (4), bowel ischemia (1), pancreatitis (1), lymphoma (1), and liver failure (1). Preoperative pulmonary arterial systolic pressure, pulmonary vascular resistance, and pulmonary vascular resistance index were not predictive of 1-month, 6-month, or 1-year mortality. One-month mortality rates of orthotopic heart transplant recipients with transpulmonary gradient greater than or equal to 12 mm Hg and of those with transpulmonary gradient less than 12 mm Hg were not significantly different (11% vs 3%; p = 0.12). The 6-month mortality rate of orthotopic heart transplant recipients with transpulmonary gradient greater than or equal to 12 mm Hg, however, was five times greater than that of orthotopic heart transplant recipients with transpulmonary gradient less than 12 mm Hg (24% vs 5%; p = 0.003), and 12-month mortality of orthotopic heart transplant recipients with transpulmonary gradient greater than or equal to 12 mm Hg was increased sevenfold when compared with that of orthotopic heart transplant recipients with transpulmonary gradient less than 12 mm Hg (36% vs 5%; p = 0.0005). These results suggest that presently used measures of pulmonary hypertension do not predict mortality in the first month after orthotopic heart transplantation, but that elevated preoperative transpulmonary gradient is associated with a significant increase in mortality at 6 and 12 months after orthotopic heart transplantation. Prospective randomized trials are needed to determined whether extended preload and afterload reduction before and/or after transplant will favorably influence long-term prognosis of orthotopic heart transplant recipients with elevated preoperative transpulmonary gradient.

Adult↗
PubMedDate not supplied

Long-term follow-up of heart transplant recipients treated with murine antihuman mature T cell monoclonal antibody (OKT3): the Loyola experience.

We describe the long-term follow-up of 25 patients treated with murine antihuman mature T cell (OKT3) monoclonal antibody at Loyola University Medical Center. After OKT3 rescue therapy, 12 patients were monitored for 16.5 +/- 6.5 months. Twenty-two moderate and three severe rejection episodes occurred 11 to 469 days (166.8 +/- 126.0) after OKT3 therapy in nine of 12 patients. During the follow-up period three patients died, and one required retransplantation because of recurrent rejection. The coronary arteries of three failed allografts had severe intimal thickening and infiltration with lymphocytes. Thirteen patients received OKT3 for prophylactic immunosuppression, and their course was compared to that of 13 patients who underwent transplantation during the same period but were given prophylactic horse antihuman thymocyte globulins (HATG). There were no differences between the two drugs with respect to long-term incidence and severity of rejection and infection, cardiac allograft function, and survival. Our results indicate that, despite successful reversal with OKT3, heart transplant recipients with refractory rejection remain plagued by recurrent rejection. Cardiac allografts in recipients who die as a result of recurrent rejection show evidence of immune-mediated vasculitis, which results in severe and diffuse coronary luminal narrowing. OKT3 and HATG appear to be equally effective for rejection prophylaxis.

Adult↗
PubMedDate not supplied

HLA-DR incompatibility predicts heart transplant rejection independent of immunosuppressive prophylaxis.

To determine whether immunosuppressive prophylaxis reduces the effect of HLA-DR incompatibility on rejection, we compared clinical and immunologic variables of patients given horse antithymocyte globulin, OKT3, or no immunosuppressive prophylaxis. Median follow-up was 27 months. Groups were similar in race; preoperative HLA reactivity; ABO matching; number of HLA-A, -B, -C, and -DR mismatches; and rejection severity. Patients given immunosuppressive prophylaxis were younger (p = 0.04), had a greater frequency of preoperative ischemic disease (p = 0.03), and had a higher 6-month rejection rate (p = 0.02). A highly significant association was found between the number of mismatches at the HLA-DR locus and rejection severity (p = 0.005). Within the OKT3-based immunosuppressive prophylaxis group and the no immunosuppressive prophylaxis group a significant association was found between the number of HLA-DR mismatches and rejection severity (p = 0.01 and p = 0.009, respectively). A similar trend was identified in the group given horse antithymocyte globulin-based immunosuppressive prophylaxis. Logistic regression, used to identify independent predictors of rejection, showed that the number of HLA-DR mismatches and not the use or type of immunosuppressive prophylaxis is significantly associated with rejection (p = 0.0009). One-year patient survival was 83% in the group with two HLA-DR mismatches and 85% in the group with one or no HLA-DR mismatch. Thus the lower rejection rates in patients with one or no HLA-DR mismatch were not associated with a 1-year survival, which was better than that of patients with two HLA-DR mismatches. The potential benefit of HLA-DR matching on rejection and patient survival must be confirmed by larger prospective studies.

Adolescent↗