Biomedical subjects

J E Fildes

Publications and source records attributed to J E Fildes.

4 recordsLinked to original sources

PubMed2005

Angiotensin converting enzyme insertion/deletion polymorphism does not influence postcardiac transplantation hypertension onset or progression.

BACKGROUND: The angiotensin converting enzyme insertion deletion polymorphism (ACE I/D) has been associated with much cardiovascular pathology, including posttransplantation hypertension. Hypertension is a significant cause of morbidity and mortality after cardiac transplantation. We investigated the influence of the ACE I/D polymorphism on posttransplantation hypertension. METHODS: A total of 211 heart transplant recipients and 154 corresponding donors were genotyped for the ACE I/D polymorphism by polymerase chain reaction. ACE enzymatic activity was measured by spectrophotometric kinetic analysis. Sitting systolic and diastolic blood pressures were recorded at 3 consecutive visits, and the mean was calculated. Clinical data, including demographics and medication, were collected for all recipients. Results were analyzed by the chi-square test and analysis of variance, taking a p value of <0.05 to be significant. RESULTS: A total of 41.7% of the subjects were hypertensive (diastolic blood pressure >90 mm Hg) at the time of the study, with 79.6% taking at least one antihypertensive agent. We found no difference between the number of antihypertensive agents, cyclosporin dose and level, renal function, or systolic blood pressure for the different recipient or donor genotypes. We also found no significant correlation between ACE enzymatic activity and systolic or diastolic blood pressure. CONCLUSIONS: Our study of 211 recipients and 154 corresponding donors is the largest investigation of this polymorphism in a cardiac transplantation population. We found no apparent relationship between the ACE genotype (of either donor or recipient) and systemic hypertension (absolute measurements and the number or dose of antihypertensive agents used).

Alleles↗

PubMed2005

Donor CCR5 Delta32 polymorphism and outcome following cardiac transplantation.

BACKGROUND: Chemokines regulate the recruitment and trafficking of leukocytes during an immune response. Animal models have shown correlations between chemokine production and leukocyte infiltration during allograft rejection. Also, antagonism of chemokine receptors in transplant models has produced prolonged graft survival. Individuals homozygous for a 32 base pair deletion in the CC chemokine receptor 5 (CCR5) gene have an inactive receptor. Renal transplant recipients homozygous for the deletion have been shown to survive significantly longer than those heterozygous or homozygous for the wild type allele. CCR5 ligands are upregulated during allograft rejection aiding infiltration of leukocytes. We investigated the influence of CCR5Delta32 polymorphism on outcome following human cardiac transplantation. METHODS: Recipients and corresponding donors were genotyped for CCR5Delta32 polymorphism using polymerase chain reactions. RESULTS: We found no correlation between recipient genotype and outcome following transplantation. However, there was a significant correlation between donor genotype and mortality in patients transplanted for a nonischemic condition (DD = n/a, ID = 4%, II = 25%, P = .0014). CONCLUSIONS: The induction of CCR5 expression in endomyocardial biopsy tissue is known to correlate with leukocyte graft infiltration. We suggest that donor CCR5 may be more important for leukocyte trafficking during rejection than recipient CCR5 expression. The CCR5 gene is highly conserved, and due to the small population available for this study, more work is required from other centers.

Base Sequence↗

PubMed2005

The effects of ACE inhibition on serum angiotensin II concentration following cardiac transplantation.

AIMS: ANGII mediates vascular neointimal formation through smooth muscle cell stimulation and enhanced production of growth factors leading to increased arterial medial layer thickness, which is a characteristic of transplant arteriosclerosis. ACE inhibition is known to be of benefit to patients with cardiovascular risk factors. We aimed to determine the effect of ACE inhibitor therapy on ACE enzymatic activity and serum ANGII levels following cardiac transplantation. METHODS: A total of 43 serum samples from eight transplant recipients were used for analysis. Samples were taken monthly from the date of transplant for the initial 6 months. ANGII was measured using sandwich ELISA. ACE enzymatic activity was measured using spectrophotometric kinetic analysis. RESULTS: There was a significant reduction in ACE enzymatic activity among individuals treated with ACE inhibitor therapy (18.0 +/- 16.6 vs 31.8 +/- 23.4, P = .008). We found significantly higher ANGII serum levels in patients receiving ACE inhibitor therapy compared to those not (2.4 +/- 2.1 vs 8.0 +/- 7.4, P = .002). There was also a significant positive correlation between ACE enzymatic activity and ANGII serum level (coefficient 0.332, P = .03). CONCLUSIONS: Our results suggest an effective ACE independent pathway for ANGII conversion. Chymase can convert ANGI with higher affinity than ACE. Also, chymase is stored in mast cells, which infiltrate the myocardium following transplantation. This data indicate that pharmacological chymase inhibition may be a possible therapeutic strategy following transplantation.

Adult↗

PubMed2004

The influence of donor age on transplant coronary artery disease and survival post heart transplantation: is it safe to extend donor age?

BACKGROUND: Due to the increasing demand for suitable cardiac donor organs, acceptance criteria need to be re-evaluated. We retrospectively analyzed the effect of donor age on survival following cardiac transplantation. METHOD: Three hundred thirty-five cardiac transplant recipients and corresponding donor data were reviewed using SPSS. RESULTS: Seventy-two recipients had early posttransplant angiography or postmortem data available. The mean donor age of recipients with evidence of graft coronary artery disease (32.5 +/- 11.7 years) was significantly higher than that of recipients free of transplant coronary artery disease (TCAD) (24.8 +/- 9.4 years; P=.003). Recipient of organs from donors aged less than 50 years were less likely to develop TCAD than those of donors aged over 50 years (odds ratio 0.333; 95% CI 0.239-0.465; P=.044). TCAD also occurred much earlier posttransplantation in recipients of organ from donors over 50 years (mean time 6.5 years; median 5.0 years) than those of donors under 50 years (mean time 12.7 years; median 14.0 years). CONCLUSION: We observed no increase in mortality associated with cardiac donors over 50 years. However, increased donor age was associated with an increased incidence of TCAD.

Adult↗