PubMed Health⌕ Search

Biomedical subjects

N Yonan

Publications and source records attributed to N Yonan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cardiac transplantation for cardiomyopathy and ischemic heart disease: differences in outcome up to 10 years.

BACKGROUND: Ischemic heart disease (IHD) and cardiomyopathy (CM) are the most common indications for heart transplantation. The aim of this study was to investigate the difference in clinical outcome between these two groups. METHODS: At our institution between 1987 and 1998 transplantation was performed in 133 patients with IHD and 87 with CM. Follow-up was complete for all patients (mean 87 months). RESULTS: Mean age at time of surgery was 51 +/- 5 years for IHD versus 39 +/- 9 years for CM recipients (p = 0.02). There was no difference in donor age, donor gender, or pre-operative hemodynamics between the two groups. The operative mortality was 11.2% in IHD recipients and 10.6% in CM recipients (p = 0.9). No differences were observed in intra-cardiac pressures or incidence of renal dysfunction, infection, or malignancy between the two groups. The incidence of peripheral vascular incidents was significantly higher for IHD recipients (13% vs 3%, p = 0.02). At 10 years, the incidence of coronary artery disease was 35% and 9%, respectively (p = 0.02). Mean NYHA status was 2.0 +/- 0.3 and 1.1 +/- 0.2 for IHD and CM recipients, respectively (p = 0.013). The actuarial survival at 1, 5, and 10 years was 77%, 62%, and 39% for IHD recipients compared with 85%, 82%, and 80% for CM recipients (p = 0.7, p < 0.0001 and p < 0.0001, respectively). CONCLUSION: After heart transplantation, medium- and long-term outcome is significantly better for CM than IHD recipients. In view of limited donor availability, it is appropriate to explore more vigorously alternative treatments for patients with severe ischemic left ventricular dysfunction.

Adult↗
PubMed2001

Influence of tumor necrosis factor-alpha gene-308 polymorphism on the development of coronary vasculopathy after cardiac transplantation.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) has been implicated in cardiovascular disease. Polymorphism of the TNF-alpha gene promoter region (position -308) influences an individual's production of TNF-alpha. This affects susceptibility to acute rejection after cardiac transplantation. Because the highest serum levels of TNF-alpha have been found in recipients with cardiac transplant vasculopathy and because TNF-alpha blockade can prevent the disease in rabbits, we investigated the effect of TNF-alpha promoter polymorphism on the development of vasculopathy in human cardiac allograft recipients. METHODS: Using sequence-specific primers to the TNF-alpha gene and polymerase chain reaction, the genotypes of 147 cardiac transplant recipients and 134 heart donors were identified. An association was sought between the presence of high-producing (A homozygotes, GA heterozygotes) or low-producing (G homozygotes) TNF-alpha genotype and the development of coronary vasculopathy, diagnosed by routine surveillance coronary angiography. RESULTS: We found that 31.9% of recipients and 27.0% of donors were high TNF-alpha producers. The presence of the high-producing TNF-alpha allele led to an earlier diagnosis of vasculopathy; 3.42 years (+/- 91.3 days) vs 3.84 years (+/- 76.3 days) for high- and low-producing cardiac graft recipients, respectively; 3.52 years (+/- 87.3 days) vs 3.78 years (+/- 77.4 days) for high- and low-producing donor grafts, respectively. However, neither of these differences were significant. By Kaplan Meier actuarial analysis and log-rank test, TNF-alpha polymorphism had no effect on the freedom from vasculopathy when considering either recipient (p = 0.99) or donor (p = 0.86) TNF-alpha genotype. Multivariate analysis identified increasing donor age and the number of acute rejection episodes of International Society for Heart and Lung Transplantation grade 3 or greater as independent risk factors for vasculopathy in both the recipient and donor cohorts. CONCLUSIONS: Polymorphism at position -308 in the promoter region of the TNF-alpha gene fails to predict the development of cardiac transplant-related vasculopathy and cannot be used as a genetic risk marker. This may be because of the effects of immunosuppressive treatment.

Adult↗
PubMed2000

Transforming growth factor beta in relation to cardiac allograft vasculopathy after heart transplantation.

BACKGROUND: Cardiac allograft vasculopathy is a frequent sequel to cardiac transplantation, but the role of cytokines on the subsequent development of vasculopathy is still largely unknown. METHODS: We retrospectively studied 172 heart transplant recipients to investigate the relationship between the development of vasculopathy and various factors including the presence of transforming growth factor (TGF-beta) in the graft. Endomyocardial biopsy specimens were stained with antibodies for TGF-beta and CD+68, and a TGF-beta staining score was derived. Vasculopathy was diagnosed by angiography and rejection was graded according to the International Society of Heart and Lung Transplantation classification. TGF-beta(1) genotype was determined by polymerase chain reaction analysis of DNA. RESULTS: After a mean follow-up period of 68 +/- 32 months, the prevalence of significant vasculopathy was 52%. The TGF-beta staining score was higher in patients with more severe vasculopathy (95% confidence interval = 8.9-12.1) than in those who showed minimal or mild vasculopathy score changes of more than 7 (95% confidence interval = 3.4-5.1), P =.0001. TGF-beta expression correlated with the degree of vasculopathy (r = 0.73, P <.0007) during the study period. Risks for vasculopathy were recipient homozygous TGF-beta genotype, recurrent rejection, recipient history of ischemic heart disease, donor male sex, old donor age (years), and donor history of subarachnoid hemorrhage. CONCLUSION: A strong association exists between the expression of TGF-beta in cardiac biopsy specimens and the development of vasculopathy. TGF-beta in the cardiac allograft is related to its genotype and to the number of rejection episodes. Strategies to down-regulate TGF-beta production might improve the outcome of cardiac allografts.

Adult↗
PubMed2000

Early and long-term results of heart transplantation after previous cardiac surgery.

OBJECTIVES: The aim of this study was to evaluate the preoperative management and long-term survival of patients undergoing heart transplantation as a redo-operation and compare the results with those obtained in patients undergoing transplantation as their first cardiac surgical procedure. METHODS: Between 1990 and 1997, 49 heart transplantation procedures were performed in patients who had undergone previous cardiac surgery (group A). This subgroup of patients was compared to 109 control patients who underwent cardiac transplantation as the primary cardiac procedure (group B). Patient groups were analysed regarding their preoperative, intra-operative, and postoperative variables in addition to survival. RESULTS: Pre-operative events were comparable in both groups but the duration of the operation was longer for group A (311+/-68 min) compared to group B (202+/-34 min); P=0.02. Post-operative exploration for bleeding was 6/49 patients in group A compared to 2/107 patients in group B (P=0.02). Post-operative blood loss and intensive care stay were greater for group A (1302+/-360 ml and 6.1+/-3.1 days, respectively) compared to group B (763+/-126 ml and 4.1+/-1.9 days, respectively); P=0.02. There was no difference in hospital mortality (group A 12.5%, group B 13 % P=0.9) and the 5-year survival rates were 68 and 71% for group A and B, respectively (P=0.9). CONCLUSIONS: Heart transplantation after previous open cardiac surgery is entirely justified in terms of outcome and graft function even in time of profound organ scarcity. Long-term events in these recipients are similar to patients in whom transplantation is the primary procedure.

Adult↗
PubMed2000

Polymorphism of the transforming growth factor-beta 1 gene correlates with the development of coronary vasculopathy following cardiac transplantation.

BACKGROUND: Expression of transforming growth factor-beta1 (TGF-beta1) is central to vascular repair due to its effects on smooth muscle cell, monocyte/macrophage, leucocyte, and extracellular matrix accumulation and proliferation. Genetic polymorphism at position +915 of the TGF-beta1 gene determines the degree of cytokine production in response to injury. We investigated this allelic variation on the development of cardiac transplant-related coronary vasculopathy (CV). METHODS: Using sequence-specific primers to the TGF-beta1 gene region of interest, a polymerase chain reaction (PCR) and gel electrophoresis identified the genotype in 129 cardiac transplant recipients. An association was sought between the presence of a high- (GG) or low/intermediate-producing (CC/GC) genotype and the development of coronary vasculopathy diagnosed by coronary angiography. RESULTS: C allele carriers made up 10.9% of the recipient population but were significantly less likely to develop coronary vasculopathy (p = 0. 0361). Mean time to diagnosis was 1240.5 days in G homozygotes relative to 2266.5 days in C allele carriers (p = 0.002). Pre- and 1-year posttransplant clinical variables were equivalent between the 2 groups. Multivariate analysis identified the GG genotype (p = 0. 042, hazard ratio 3.01, [95% CI, 1.056-10.99]), donor age (p = 0.002, hazard ratio 1.063, [95% CI, 1.029-1.097]), and number of acute-rejection episodes of grade 3 or greater in the first year (p = 0.029, hazard ratio 1.11, [95% CI, 1.05-1.26]) as significant predictors of vasculopathy. CONCLUSION: This study demonstrates a correlation between a high-producing TGF-beta1 genotype and an earlier onset of cardiac-transplant coronary vasculopathy. This gives an important insight into the pathophysiology of cardiac transplant vasculopathy and suggests new treatment options.

Adult↗
PubMed2000

A prospective study of a quantitative PCR ELISA assay for the diagnosis of CMV pneumonia in lung and heart-transplant recipients.

BACKGROUND: Qualitative polymerase chain reaction (PCR) for the identification of cytomegalovirus (CMV) infection has a low predictive value for the identification of CMV pneumonia. This study prospectively evaluated the application of a quantitative PCR Enzyme-Linked Immuno-Sorbent Assay (ELISA) assay in 9 lung- and 18 heart-transplant recipients who did not receive ganciclovir prophylaxis. METHODS: DNA was collected from peripheral blood polymorphonuclear leucocytes (PMNL) posttransplantation. Oligonucleotide primers for the glycoprotein B gene (149 bp) were used in a PCR ELISA assay using an internal standard for quantitation. CMV disease was defined as histological evidence of end organ damage. RESULTS: The median level CMV genome equivalents in patients with CMV disease was 2665/2 x 10(5) PMNL (range 1,200 to 61,606) compared to 100 x 10(5) PMNL (range 20 to 855) with infection but no CMV disease (p = 0.036). All patients with CMV disease had genome equivalents levels of >1200/2 x 10(5) PMNL. A cut-off level of 1,200 PMNL had a positive predictive value for CMV disease of 100% and a negative predictive value of 100%. The first detection of levels of CMV genome equivalents above a level of 1200/2 x 10(5) PMNL was at a median of 58 days (range 47 to 147) posttransplant. CONCLUSIONS: Quantitative PCR assays for the diagnosis of CMV infection may predict patients at risk of CMV disease and thereby direct preemptive treatment to high-risk patients.

Antigens, Viral↗
PubMed1999

Zonal allocation for thoracic organs in the united kingdom: Has it been successful? A single-center view.

OBJECTIVES: The purpose of this study was to analyze the impact of the zonal allocation system for thoracic organs on the outcome of our transplant activity. METHODS: We analyzed the results of thoracic transplants performed between 1987 and 1998. The transplants were divided into 3 groups: local donors retrieved by our team (171 hearts and 61 lungs; DL group); distant donors retrieved by our team (58 hearts and 35 lungs; DD group); and distant donors retrieved by other teams (51 hearts and 41 lungs; DX group). RESULTS: No significant differences were observed among the groups in early postoperative events for either heart or lung transplantation. Heart transplants: Cardiac index was 2.6 +/- 0.4 L/m(2) for the DL group, 2.7 +/- 0.6 L/m(2) for the DD group, and 2.5 +/- 0.7 L/m(2) for the DX group (P =.4). The 30-day mortalities were 9.1%, 9.1%, and 8.3% ( P =.5) and the 1-year survivals 83%, 80%, and 82% ( P =.4) for the DL, DD, and DX groups, respectively. Lung transplants: Alveolar-arterial oxygen gradient was 358 +/- 19 mm Hg for the DL group, 345 +/- 17 mm Hg for the DD group, and 329 +/- 21 mm Hg for the DX group (P =.07). The 30-day mortalities were 9.9%, 10.5%, and 12.8% (P =.2) and the 1-year survivals 79%, 75%, and 77% (P =.3) for the DL, DD, and DX groups, respectively. CONCLUSION: Zonal allocation for thoracic organs has been successfully applied to our program. Using donor organs retrieved by other teams, we have achieved equivalent outcomes for both heart and lung transplantation.

Actuarial Analysis↗
PubMed1999

Bicaval and standard techniques in orthotopic heart transplantation: medium-term experience in cardiac performance and survival.

OBJECTIVE: The aim of this study was to compare the medium-term results of right heart pressures, tricuspid valve dysfunction, overall cardiac performance, and survival between the bicaval and standard techniques. METHOD: Between 1991 and 1997, 201 heart transplantations were performed in our center. Right heart catheterization was performed up to 12 months after transplantation. Echocardiography was used to assess left ventricular and tricuspid valve function. RESULT: The standard technique was used in 105 cases, and the bicaval technique was used in 96 cases. There was no difference in the age, preoperative parameters, pulmonary hemodynamics, or ischemic time between the 2 groups. Right atrial pressure (4.3 +/- 4.0 mm Hg for the bicaval vs 10.9 +/- 4.8 mm Hg for standard technique) and mean pulmonary artery pressure (17.5 +/- 5.3 mm Hg and 22.5 +/- 5.2 mm Hg, respectively) were lower for the bicaval recipients up to 12 months after the operation (P =.001 and. 01, respectively). Left ventricular ejection fraction was higher for the recipients of the bicaval technique up to the most recent measurement (P =.005). The prevalence of moderate or severe tricuspid regurgitation was higher in the recipients of the standard technique up to the most recent measurement (28% vs 7%; P =.02). The actuarial survival at 1, 3, and 5 years was 74%, 70%, and 62% for the recipients of the standard technique versus 87%, 82%, and 81% for the recipients of the bicaval technique (P <.03, <.04, and <.02, respectively). CONCLUSION: The bicaval technique maintains good left ventricular function, lower incidence and severity of tricuspid valve dysfunction, and improved survival compared with the standard technique.

Actuarial Analysis↗
PubMed1999

The development of a quantitative PCR ELISA to determine HCMV DNAaemia levels in heart, heart/lung and lung transplant recipients.

The adaptation of the polymerase chain reaction (PCR) enzyme-linked immunosorbent assay (ELISA) using a co-amplified DNA standard to quantitate the human cytomegalovirus (HCMV) glycoprotein B (gB) gene in clinical samples is described. The PCR ELISA is a solution hybridisation system with colorimetric end stage detection of amplicons. A DNA internal standard (IS) was designed by replacing a probe sequence used currently within the gB region with a heterogeneous sequence, allowing co-amplification with the same oligonucleotide primer sets and differentiation by probe hybridisation. Two DNA fragments homologous to the gB and IS sequences were generated and used for co-amplification studies to construct a standard curve. From this the copy number of the gB gene present in clinical samples could be interpolated. Co-amplification with 1000 IS copies allowed quantitation of 10-1000000 gB DNA copies in a single PCR. This assay was validated subsequently using blood samples tested by the HCMV antigenaemia assay and showed a trend of increasing HCMV DNAaemia with increasing antigenaemia levels. This rapid assay avoids using gel electrophoresis and cumbersome quantitative systems. It has the potential for early identification of patients at high risk of developing HCMV disease, and for therapeutic monitoring.

Base Sequence↗
PubMed1999

CA repeat allele polymorphism in the first intron of the human interferon-gamma gene is associated with lung allograft fibrosis.

Interferon-gamma (IFN-gamma) is an inflammatory cytokine that has been implicated in the development of fibrosis in inflamed tissues. In this study we have analysed the association between genetically-determined high IFN-gamma production and development of fibrosis in lung transplants. The human IFN-gamma gene has a variable length CA repeat in the first intron. Our previous study showed that polymorphism of this microsatellite is associated with individual variation in the levels of IFN-gamma production. In vitro production of IFN-gamma showed significant correlation with presence of allele #2 (p < 0.01). In this study allele #2 was found to be associated with allograft fibrosis defined by transbronchial biopsy. An analysis of two groups of lung transplant recipients showed a significant increase in the frequency of allele #2 in the group which developed fibrosis after transplantation compared to the group that did not (p < 0.005). We postulate that the production of IFN-gamma, which is under genetic control, can influence the development of fibrosis in lung allografts.

Adenine↗
PubMed1999

Heart transplantation for peripartum cardiomyopathy: a report of three cases and a literature review.

Peripartum cardiomyopathy is a devastating medical condition and carries a mortality of up to 60% with medical treatment. The authors describe their experience of successful outcome of three cases with heart transplantation and review the literature. The importance of performance of endomyocardial biopsy for all peripartum cardiomyopathy patients is emphasized. It is recommended that heart transplantation should only be offered to myocarditis negative patients.

Adult↗
PubMed1999

The effect of 'renal-dose' dopamine on renal tubular function following cardiac surgery: assessed by measuring retinol binding protein (RBP).

OBJECTIVE: Acute renal failure complicating open heart surgery is not uncommon. Dopamine infusion (2.5-4.0 microg/kg per min) has often been advocated for prophylactic 'renal protection' in this setting despite little objective evidence of real benefit. We aimed to investigate whether dopamine offers any 'renal protection' in patients with normal heart and kidney functions undergoing routine coronary artery bypass grafting (CABG). Urinary excretion of retinol-binding protein (RBP), previously validated as a sensitive and accurate marker of early renal tubular injury, was used to assess the renal effects of dopamine during the first postoperative week. METHODS: Forty consecutive patients from the elective waiting list were prospectively randomized into two equal groups: those in Group A received dopamine infusion at 'renal dose' (2.5-4.0 microg/kg per min) starting from induction of anaesthesia for 48 h, whereas those in Group B served as untreated controls. Daily measurements were made of weight-adjusted urine output (ml/kg), fluid balance (input/output), serum creatinine, blood urea and urinary RBP. Statistical comparisons were made using Mann-Whitney U-test. RESULTS: The two groups matched in terms of age, time and temperature on cardiopulmonary bypass, number of grafts performed and perioperative haemodynamic status. No differences were detected in the weight-adjusted urine output, fluid balance, serum creatinine and blood urea between the groups. Control subjects (Group B) showed an increase in urinary RBP during the first and second postoperative days (323+/-4 microg/ mmolCr and 50+/-3 microg/mmolCr; mean+/-SD). However, patients treated with dopamine (Group A) demonstrated much greater urinary excretion of RBP over the same period (1257+/-15 microg/mmolCr and 449+/-21 microg/mmolCr; P = 0.0006 and 0.03) than those in Group B. CONCLUSIONS: Dopamine given at 'renal-dose' appears to offer no renal protection in patients with normal heart and kidney functions undergoing elective coronary surgery. On the contrary, it exacerbates the severity of renal tubular injury during the early postoperative period. Based on these findings we do not recommend the use of dopamine for routine renal prophylaxis in this group of patients.

Acute Kidney Injury↗