Biomedical subjects

E Zorio

Publications and source records attributed to E Zorio.

11 recordsLinked to original sources

PubMed2006

Does amiodarone influence early mortality in heart transplantation?

The use of amiodarone before transplantation has been linked to an increased number of complications, acute graft failures, and early mortality after a heart graft. We undertook a retrospective, descriptive, case-controlled study involving early mortality and acute graft failure. The 396 consecutive patients included 25 subjects who had been prescribed amiodarone for at least 30 days before transplantation. We excluded retransplantations, pediatric transplantations, and combined transplantations. The endpoints were early mortality and acute graft failure. No significant differences were observed in early mortality and acute graft failures. The multivariate analysis did not reveal any variable that correlated with early mortality. Our study did not support the idea that amiodarone constituted a negative predictor of early survival or acute graft failure.

Amiodarone↗

PubMed2006

Evolutional changes in maintenance immunosuppression following heart transplantation.

UNLABELLED: Patients with a heart transplant (HT) may require changes in their immunosuppressive maintenance medication. The basic treatment regimen in our patients consisted of an anticalcineurin agent, an antimetabolite, and a steroid. OBJECTIVE: We undertook a descriptive study to quantify the incidence and causes of these changes and determine how they occur. MATERIALS AND METHODS: We included the 432 HT performed at our center from November 1987 to October 2005. The baseline treatment was considered to be the treatment given following HT, and the maintenance treatment was that taken at the time of data collection. Kaplan-Meier survival curves were constructed for the analysis. RESULTS: The most significant change was the switch from azathioprine to mycophenolate mofetil. The survival rate after 17 years was 66%. CONCLUSIONS: As in the international registries, there has been an evident reduction in the use of cyclosporine and more particularly of azathioprine, in favor of tacrolimus and mycophenolate mofetil, respectively. No changes in the use of steroids have been observed. These data reflect an increasingly greater use of immunosuppressive agents with reduced side effect profiles.

Azathioprine↗

PubMed2006

Induction therapy with daclizumab in heart transplantation--how many doses?

UNLABELLED: Since their introduction onto the market, interleukin-2 antagonists have been increasingly used by a growing number of transplant units. Their benefits versus OKT3 appear evident, although the optimal dose remains to be established. Our objective was to establish possible differences related to the use of two versus five doses of daclizumab. MATERIALS AND METHODS: This study evaluated 81 consecutive patients treated with two bolus doses of daclizumab (1 mg/kg) on days 1 and 14 posttransplantation. We excluded retransplantations, pediatric transplantations, and combined transplantations. We compared our series to a previous trial involving the administration of a single bolus dose every 14 days (five boluses in total). Study variables included the number of graft rejections, the number of infections, and the mortality. Statistical analysis was performed using the chi square and Student's t tests. Significance was set at P < .05. RESULTS: There were no differences between groups in the baseline characteristics of the patients. The number of rejection episodes during the first year was significantly lower among the patients in our series treated with two bolus doses of daclizumab than in the series of patients treated with five bolus doses: 24 (30%) vs 17 (61%) episodes (P = .003). No significant differences were observed for mortality: the group receiving two boluses registered 10 deaths (12%) versus two (7%) in the group receiving five boluses (P = .4), or infection rate: 11 patients (40%) in the group receiving five bolus versus 31 patients (38%) in the group given two bolus doses (P = .9). CONCLUSIONS: Our results suggested that induction therapy with two doses of daclizumab was at least as effective in preventing rejection as five doses, with no negative effects on patient survival.

Antibodies, Monoclonal↗

PubMed2006

Influence of immunosuppression regimen on heart transplantation survival.

OBJECTIVE: To perform an analysis comparing long-term survival in heart transplant (HT) patients depending on the immunosuppressive regimen. MATERIALS AND METHODS: The study included 317 consecutive HT patients. We excluded pediatric cases, retransplants, combined transplants (lung and kidney), and immunosuppressive regimens with fewer than 10 cases. The six groups analyzed were: (1) OKT3 7 days + cyclosporine (CsA) + mycophenolate mofetil (MMF) + steroids (S); (2) OKT3 7 days + CsA + azathioprine (AZA) + S; (3) OKT3 10 days + CsA + MMF + S; (4) OKT3 10 days + CsA + AZA + S; (5) interleukin-2 (IL-2) antagonists + CsA + MMF + S; and (6) IL-2 antagonists + tacrolimus + MMF + S. Probability of survival was analyzed by Kaplan-Meier and log-rank methods. RESULTS: The groups were heterogeneous regarding the number of patients and follow-up. The baseline characteristics were similar, although there were differences in surgery times. The survivals by groups at the end of the follow-up period were: group 1: 75.8%; group 2: 51.2%; group 3: 63.6%; group 4: 25.3%; group 5: 91.2%; and group 6: 84.6%. A major reduction in survival was observed in the groups that were given induction with OKT3 monoclonal antibodies (groups 1, 2, 3, and 4), particularly when AZA was combined in the maintenance phase (groups 2 and 4) and when the induction dose was high (10-day therapy in groups 3 and 4). CONCLUSIONS: Our study suggested an association between the immunosuppressive regimen and the long-term survival of HT patients. The best results were obtained with an induction regimen based on IL-2 antagonists. On the basis of the survivals observed in this study, the maintenance combination we regard as "optimal" at this time is based on a combination of CsA, MMF, and steroids.

Adult↗

PubMed2006

Is there a correlation between brain naturietic peptide levels and echocardiographic and hemodynamic parameters in heart transplant patients?

BACKGROUND: Brain naturietic peptide (BNP) elevations have been reported in heart transplant patients both at baseline and during rejection. An association between BNP levels and certain echocardiographic and hemodynamic abnormalities has also been found in nontransplanted heart disease patients. We sought to determine whether BNP values were correlated with echocardiographic and hemodynamic parameters among a large cohort of heart transplant patients. MATERIALS AND METHODS: We studied 71 consecutive heart transplant patients, excluding combined grafts, retransplants, and pediatric cases. We performed 488 BNP determinations during catheterization and within 48 hours of echocardiography. Hemodynamic parameters included mean pulmonary artery pressure, right ventricular systolic and diastolic pressures. Doppler echocardiography parameters were wall thickness, ventricular mass, left and right ventricular end-diastolic and end-systolic diameters, isovolumic relaxation time, and mitral flow deceleration time. RESULTS: We observed significant correlations between BNP values and left ventricular size, ventricular mass, and a restrictive filling pattern. BNP levels were also significantly correlated with right ventricular size, mean pulmonary artery pressure, and right ventricular diastolic and end-diastolic pressures. CONCLUSIONS: In heart transplant patients, BNP levels positively correlated with ventricular diameters and a restrictive filling pattern. An increase in right ventricle and pulmonary artery pressures was associated with elevated BNP values.

Biomarkers↗

PubMed2006

Variations in the frequency and type of infections in heart transplantation according to the immunosuppression regimen.

OBJECTIVE: To evaluate the frequency of infection according to the immunosuppressive regimens used in our center. MATERIALS AND METHODS: From 259 consecutive heart transplants we excluded pediatric cases, retransplants, combined transplants (lung and kidney) and immunosuppressive regimens with fewer than 10 cases. The six groups analyzed were: (1) OKT3 (7 days) + cyclosporine (CsA) + mycophenolate mofetil (MMF) + steroids (S); (2) OKT3 (7 days) + CsA + azathioprine (AZA) + S; (3) OKT3 (10 days) + CsA + MMF + S; (4) OKT3 (10 days) + CsA + AZA + S; (5) interleukin-2 (IL-2) antagonists + CsA + MMF + S; (6) IL-2 antagonists + tacrolimus + MMF + S. Infection was considered significant when it causal hospital admission or prolonged hospitalization. RESULTS: With a total mean follow-up of 54 +/- 43 months, the total percentage of infection-free patients at the end of follow-up was 45.5%. Infection-free survival was lower among patients administered induction with OKT3 antibodies for 10 days, combined with cyclosporine, either with MMF (10%, group 3) or with azathioprine (27%, group 4), compared to those given IL-2 antagonists (particularly in combination with tacrolimus and MMF-69.2%, group 6). CONCLUSIONS: The results of this study showed that infection was frequent in heart transplantation. Furthermore, induction therapy with OKT3 monoclonal antibodies was associated with an important number of infections (particularly viral infections). Comparison of the treatment groups showed that the regimen associated with fever infections included an IL-2 receptor antagonist with tacrolimus, MMF, and S.

Drug Therapy, Combination↗

PubMed2006

Circulating activated protein C is reduced in young survivors of myocardial infarction and inversely correlates with the severity of coronary lesions.

BACKGROUND: Cardiovascular risk factors for myocardial infarction (MI) are less frequent in younger than in older MI survivors. Therefore, the thrombotic component of MI may play a more important role at a young age. As activated protein C (APC) provides systemic anticoagulant and anti-inflammatory protection, a low plasma APC level may be an arterial thrombotic risk factor. AIM: To determine whether there is an association between reduced APC levels and early MI and severe coronary lesions. METHODS: APC was measured in 231 young MI survivors and 231 controls. RESULTS: Low APC levels were significantly associated with MI. Compared with the fourth quartile, the odds ratio (OR) for APC values in the first quartile was 3.7 [95% confidence interval (CI) = 2.1-6.4], and 3.2 (1.5-7.0) after adjustment for cardiovascular risk factors. Moreover, each decrease of 0.43 ng mL(-1) (1 SD) in APC increased the OR 1.7 times (1.4-2.2), and 1.5 times (1.2-1.9) after adjustment for cardiovascular risk factors. Low APC levels were also associated with the number of coronary arteries affected and with the severity of coronary lesions (P < 0.001). CONCLUSIONS: There is a significant association between low circulating APC levels and both early MI and the extent and severity of coronary atherosclerosis, which might be related to the anticoagulant and anti-inflammatory properties of APC.

Adult↗

PubMed2005

Influence of induction therapy on rejection and survival in heart transplantation.

BACKGROUND AND AIMS: Immunosuppressive therapy has undergone great changes in recent years as a result of the introduction of new drugs, presumed a prior to be more effective and better tolerated. The greatest advance seems to have been the introduction of interleukin-2 (IL-2) receptor antagonists. The objective of this study was to determine whether the use of IL-2 receptor antagonists in induction therapy has implications for the development of rejection and survival. MATERIALS AND METHODS: Three hundred sixty-five consecutive cardiac transplant patients who received induction therapy were included. Heart-lung and transplants in children under 10 years were excluded. Three groups were compared according to the induction therapy (OKT3, 10 days; OKT3, 7 days; and IL-2R antagonists). Each treatment corresponded to a time period: OKT3 10 days from June 1989 to April 1994; OKT3 7 days from May 1994 to October 2002; and IL-2R antagonists from November 2002 to May 2004. Baseline characteristics of recipient and donor, surgical times, postsurgical complications, maintenance immunosuppression, number of rejections, time (days) to first rejection, and probability of survival at 1 year were recorded. We used analysis of variance, chi(2) test, Kaplan-Meier curves, and log-rank test as appropriate. A P-value < .05 was considered significant. RESULTS: There were significant differences in the characteristics of the transplanted patients in the various time periods. Thus, recipients in the OKT3 10 day group had worse status but better donors, whereas recipients in the IL-2R antagonists group had better status but older donors with longer duration of ischemia. The incidence of acute graft failure was similar in the three groups. The number of rejection episodes in the first year was higher among the OKT3 groups (OKT3 10 days, 1.7 +/- 1.3; OKT3 7 days, 1.2 +/- 1.2; IL-2R antagonists, 1.0 +/- 1.2; P = .02) and the probability of survival at 1 year was also lower (OKT3 10 days, 74%; OKT3 7 days, 77%; IL-2R antagonists, 94%; P = .0007). CONCLUSIONS: Induction therapy with IL-2 antagonists offers important advantages over treatment with OKT3 in terms of survival, with absolute and relative risk reductions of 20% and 27%. Furthermore, it did not increase the number of rejections, although this may have been due to the greater use of MMF versus azathioprine.

Adolescent↗

PubMed2005

Risk factors affecting survival in heart transplant patients.

BACKGROUND: Certain cardiovascular risk factors have been linked to morbidity and mortality in heart transplant (HT) patients. The sum of various risk factors may have a large cumulative negative effect, leading to a substantially worse prognosis and the need to consider whether HT is contraindicated. The objective of this study was to determine whether the risk factors usually available prior to HT result in an excess mortality in our setting that contraindicates transplantation. MATERIALS AND METHODS: Consecutive patients who underwent heart transplantation from November 1987 to January 2004 were included. Heart-lung transplants, retransplants, and pediatric transplants were excluded. Of the 384 patients, 89% were men. Mean age was 52 years (range, 12 to 67). Underlying disease included ischemic heart disease (52%), idiopathic dilated cardiomyopathy (36%), valvular disease (8%), and other (4%). Variables considered risk factors were obesity (BMI >25), dyslipidemia, hypertension, prior thoracic surgery, diabetes, and history of ischemic heart disease. Survival curves by number of risk factors using Kaplan-Meier and log-rank for comparison of curves. RESULTS: Overall patient survival at 1, 5, 10, and 13 years was 76%, 68%, 54%, and 47%, respectively. Survival at 10 years, if fewer than two risk factors were present, was 69%; 59% if two or three factors were present; and 37% if more than three associated risk factors were present (P = .04). CONCLUSIONS: The presence of certain risk factors in patients undergoing HT resulted in lower survival rates. The combination of various risk factors clearly worsened outcomes. However, we do not believe this should be an absolute contraindication for transplantation.

Adolescent↗

PubMed2005

The multifunctional protein C system.

The protein C pathway is a major regulator of blood coagulation, since it controls the conversion of prothrombin to thrombin through a feedback inhibition mechanism. Protein C circulates in plasma as an inactive zymogen and is activated on the surface of endothelial cells by the thrombin-thrombomodulin complex, a process that can be further enhanced when protein C binds to its membrane receptor, the endothelial-cell protein C receptor. Activated protein C (APC) is then released from the complex, binds protein S and inhibits thrombin formation by inactivating coagulation factors Va and VIIIa. The importance of the protein C anticoagulant pathway is emphasized by the increased risk of venous thromboembolism (VTE) associated with protein C and protein S deficiencies, the factor V Leiden mutation, and reduced circulating APC levels. The protein C pathway also plays a significant role in inflammatory processes, since it prevents the lethal effects of E. coli-associated sepsis in animal models and improves the outcome of patients with severe sepsis. APC seems to display anti-apoptotic and neuroprotective activities. Thus, it reduces organ damage in animal models of sepsis, ischemic injury, endothelial cell injury, or stroke. Further research will hopefully widen the current therapeutic perspectives in all these illnesses, where these effects might play a crucial role in their treatment. This review will summarize the mechanisms that contribute to these biological activities of the protein C pathway.

Animals↗

PubMed2003

Expression of several components of the plasminogen activator and matrix metalloproteinase systems in endometriosis.

BACKGROUND: Endometriosis is considered a benign disease that has the ability to invade normal tissue. As in neoplastic growth, local extracellular proteolysis may take place. The aim of this study is to analyse several components of the plasminogen activator (PA) pathway and the matrix metalloproteinase (MMP) system in endometriotic tissue, endometrium and peritoneal fluid from women with and without endometriosis (controls). METHODS AND RESULTS: Thirty-nine women with endometriosis and 35 controls were studied. In eutopic endometrium of women with endometriosis, the antigenic levels of urokinase-type PA (uPA) and MMP-3 were elevated when compared with endometrium from controls. Ovarian endometriotic tissues had higher antigenic levels of PA inhibitor type 1 (PAI-1) and tissue inhibitor of metalloproteinases type 1 (TIMP-1) than endometrium. The peritoneal fluid from women with endometriosis showed a significant increase in uPA levels compared with controls. CONCLUSIONS: The increase in antigenic levels of uPA and MMP-3 in endometrium of women with endometriosis might contribute to the invasive potential of endometrial cells. Once the ovarian endometriotic cyst is developed, an increase in PAI-1 and TIMP-1 is detected and significant proteolytic activity is no longer observed. This increase in inhibitors and decrease in proteolytic activity could explain the frequent clinical finding of isolated endometriotic cyst without invasion of the surrounding ovarian tissue.

Adult↗