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Biomedical subjects

G Dureau

Publications and source records attributed to G Dureau.

At least 37 records · Page 2Linked to original sources
PubMed1995

Post-transplant lymphoproliferative disorders with genetic abnormalities commonly found in malignant tumours.

Post-transplant lymphoproliferative disorders (PTLD) are potentially fatal complications of organ transplants. Impairment of the immune system by immunosuppressive drugs is the assumed cause of PTLD. The Epstein-Barr virus (EBV) is detected in most of the PTLD studied and is considered as the main aetiological agent. The clinical course of PTLD patients remains unpredictable, some lymphoproliferations regress after discontinuation of the immunosuppressive treatment, others behave as true malignant tumours. The mechanism by which a viro-induced lymphoproliferation evolves to an autonomous tumour remains unclear, and little is known about the genetic changes that occur during this process. We report two cases of fatal EBV-associated PTLD in heart transplant recipients. Both tumours were monoclonal and carried numerous chromosomal abnormalities, including a classic t(8;14)(q24;q32) with rearrangement of the MYC proto-oncogene. One tumour demonstrated an amplification of the proto-oncogene N-MYC. The EBNA2 gene was not expressed in tumoral cells, suggesting that the chromosomal abnormalities contributed the function of EBNA2 in these cells. The morphology of the tumours indicated that the cases presented here were not Burkitt's lymphomas. These findings provide some clues with regard to the genetic changes which lead to a B-cell malignancy in some transplant patients.

Adult↗
PubMed1995

Spectral analysis of blood pressure variability in heart transplant patients.

The cardiac transplant patient provides a unique model for the study of blood pressure variability in the absence of heart rate variability. We examined the harmonic and fractal components of blood pressure variability in 14 heart transplant patients (12 men, 2 women; 21 to 62 years of age) and in age-and sex-matched control subjects during seated rest, supine rest, and supine rest with fixed-pace breathing (12 respirations per minute). Heart rate was faster in transplant patients than in control subjects, with much less heart rate variability (P < .0001). Spectral analysis of blood pressure variability revealed no difference in total power for either systolic or diastolic pressure, but transplant patients had less low-frequency (0 to 0.15 Hz) harmonic spectral power in both systolic (P < .01) and diastolic (P < .03) pressure and more high-frequency power (0.15 to 0.5 Hz) in diastolic pressure than control subjects. The ratio of high-frequency power in diastolic relative to systolic pressure was consistently higher (P < .0001) in the transplant patients (0.29 to 0.51) than in control subjects (0.11 to 0.13). The slope of the fractal component of systolic pressure was approximately 1.8 in both transplant patients and control subjects. This was greater than the slope for heart rate variability (approximately 1.1 in control subjects). These data provide clear evidence of independence of the fractal component of heart rate and blood pressure variabilities in both transplant patients and control subjects. The heart rate component of the arterial baroreflex minimized high-frequency diastolic pressure changes while contributing to low-frequency variations in both systolic and diastolic pressures.

Adult↗
PubMed1995

[Value of coronary angiography in the diagnosis of coronary artery disease of the transplanted heart. Coronary angiography and arteriosclerosis of the graft].

The diagnostic value of coronary angiography, a widespread method of detection of transplant coronary artery disease, was studied in 17 cardiac transplant patients with reference to histological examination. In the 6 coronary segments studied, the only significant but weak correlation that was found was for the distal left anterior descending artery: the correlations were not statistically significant in the other 5 segments. Coronary angiography underestimated lesions and false negative results were frequently reported (66 and 27% respectively). The limitations of coronary angiography may be explained by the technical artefacts related to both methods of evaluation and the anatomically diffuse and distal nature of transplant coronary artery atherosclerosis. A more reliable diagnostic method would seem to be required in view of the clinical importance of this pathology.

Coronary Angiography↗
PubMed1994

The beneficial effect of dietary antioxidant supplementation on platelet aggregation and cyclosporine treatment in heart transplant recipients.

To determine whether dietary antioxidant supplementation can reduce platelet reactivity in heart transplant recipients, 20 patients were prospectively randomized to receive either 500 IU vitamin E orally per day in the form of acetate for 2 months or no vitamin E. Blood creatinine (P = 0.01) and lymphocyte count (P = 0.009) significantly decreased only in supplemented patients, whereas the cyclosporine blood level was not modified. Platelet aggregation was stable in control patients but significantly decreased in supplemented patients in response to either thrombin (from 8.3 +/- 0.9% of maximum aggregation to 3.7 +/- 0.7, P = 0.001) or ADP (secondary wave: from 44.7 +/- 5.9% to 33.2 +/- 7.0, P = 0.02). Thus antioxidant supplementation tended to improve immunosuppression (by reducing lymphocyte count), to reduce cyclosporine nephrotoxicity, and to decrease the high thrombotic risk associated with heart transplantation.

Administration, Oral↗
PubMed1994

Comparison of different techniques of hypothermic pig heart preservation.

The aim of this study was to compare several methods of hypothermic heart preservation. Isolated pig hearts were preserved for 24 hours in cold cardioplegic solution (St. Thomas' Hospital modified solution) by continuous perfusion (group I), microperfusion (group II), or simple storage (group III). The findings were then compared with those from hearts harvested and immediately reperfused (the control group). Group III hearts showed lower adenosine triphosphate preservation (0.47 +/- 0.18 mumol/g) than did group I and II hearts and the control hearts (1.86 +/- 0.40, 1.98 +/- 0.27, and 1.84 +/- 0.55 mumol/kg, respectively). Electronic microscopy studies also revealed that the myocardial cells in the group III hearts appeared to be damaged. After the hearts had undergone preservation, myocardial function was studied for 60 minutes under nonworking conditions using an ex vivo functional testing system. For group III, the mean left ventricular developed pressure and ventricular compliance (16 +/- 22 and 63 +/- 48 mm Hg, respectively) differed significantly from those for group I (83 +/- 26 and 0 +/- 0 mm Hg, respectively), group II (83 +/- 33 and 14 +/- 18 mm Hg, respectively), and the control group (115 +/- 13 and 0 +/- 0 mm Hg, respectively). We concluded from our findings that perfusion methods are superior to cold storage but inadequate to maintain heart viability for the long term during hypothermia. These techniques must be improved before they can be adopted for clinical use.

Adenine Nucleotides↗
PubMed1994

Fluid-regulating and sympathoadrenal hormonal responses to peak exercise following cardiac transplantation.

Orthotopic heart transplantation results in cardiac denervation that can disrupt the normal regulation of hydromineral balance. This study compared the exercise-induced variations in plasma osmolality; atrial natriuretic peptide (ANP), arginine vasopressin (AVP), norepinephrine (NE), epinephrine (E), and dopamine (DA) concentrations; and plasma renin activity (PRA) of six cardiac transplant recipients (HTX) and six healthy age-matched controls (C) submitted to graded upright maximal cycling. Venous blood samples were obtained at rest, at submaximal (70% O2 uptake) and peak exercise, and after 10 and 30 min of sitting recovery. Peak O2 uptake was not different between groups despite lower maximal heart rate in HTX (136 +/- 6 vs. 183 +/- 9 beats/min). Baseline plasma ANP and PRA were higher in HTX (203 +/- 55 pg/ml and 29.9 +/- 7.4 ng.ml-1 x h-1) than in C (71 +/- 17 pg/ml and 5.4 +/- 0.96 ng.ml-1 x h-1); AVP was lower in HTX than in C (1.1 +/- 0.3 vs. 3.2 +/- 0.8 pg/ml; P < 0.05); and circulating E, NE, and DA were not different between groups. Exercise resulted in more marked increases in HTX than in C for ANP (300 vs. 100%), AVP (2,000 vs. 300%), NE (860 vs. 500%), and DA (611 vs. 187%) but not for PRA and a higher E response in C than in HTX (455 vs. 1,258%). These observations confirm that the potential for ANP release to central volume loading is independent of intact cardiac innervation. The exaggerated AVP response in HTX could, however, reflect the absence of inhibitory influences consecutive to denervation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1994

Platelet aggregation and HDL cholesterol are predictive of acute coronary events in heart transplant recipients.

BACKGROUND: Sudden death (SD) and acute myocardial infarction (AMI) are the main complications limiting long-term survival after heart transplantation (HT). They are unpredictable and, at present, unpreventable. Platelet aggregation (PA) has recently emerged as a significant prognostic indicator in nontransplanted coronary disease patients. The main purpose of the present study was to evaluate to what extent PA could predict SD and AMI in long-term survivors of HT independently of serum lipid levels. METHODS AND RESULTS: We studied 207 patients. All received triple immunosuppressive therapy. During follow-up, the incidence of SD and AMI was determined, and the independent role of PA as predictor was evaluated with other usual risk factors by a Cox multivariate regression model. There were 11 SDs and 14 AMIs after an average follow-up of 642 days, giving an average incidence rate of 7.3 events per year per hundred patients. By univariate analysis, the most potent predictors were ADP-induced platelet aggregation (positive association) and total cholesterol (negative association). Age and length of time since transplant were not predictors. By multivariate analysis, only the secondary wave of ADP-induced platelet aggregation (P = .001) and high-density lipoprotein cholesterol (P = .03) were independent predictors. The relative risk of SD or AMI based on a comparison between patients with high (> 36%) or low (< 36%) ADP-induced platelet aggregation was 4.3 (95% confidence interval, 1.9 to 9.5, P = .0001). CONCLUSIONS: This study provides the first demonstration of an association between increased platelet aggregation and subsequent SD or AMI in HT recipients. It suggests that platelets and thrombosis also are implicated in the pathogenesis of AMI and SD in HT recipients. Identification of a safe and effective antiplatelet therapy should be actively pursued.

Adolescent↗
PubMed1994

[Pericardium and heart transplantation].

The authors emphasise the role of the pericardium in the post-operative complications of cardiac transplantation: its role is as important as it is underestimated in its frequency, severity and the pathogenic discussions that it induces. This study, based on a retrospective analysis of 191 anatomo-clinical cases (156 autopsies and 35 retransplantations) of patients undergoing cardiac transplantation before the 1/03/1993 including macroscopic and histopathologic analysis of the pericardial lesions, histochemical analysis of the lymphocytic populations, and analysis of associated coronary and myocardial lesions. The results were classified as early or late (after the 75th postoperative day) complications. Early complications included 27 suppurating mediastino-pericarditis (13 aspergillosis and 14 bacterial), 16 autonomous non-infective pericardial complications (6 haemopericardiums, 6 organised compressive haematomas, 4 early constrictive pericarditis) and 9 lymphocytic epicarditis associated with acute myocardial rejection. Late complications included one common constrictive symphysis and 14 reactivated epicarditis associated with transplantation coronary disease (chronic rejection) with associated lymphoplasmocytic nodules and a myocardial vasculitis. These observations suggest two important conclusions: 1) the need for active diagnostic measures to detect pericardial complications in cases of cardiac transplant dysfunction in the early postoperative period with no signs of acute rejection on myocardial biopsy: the presence of epicardial lesions on biopsy should be taken into account and not just assumed to be a postoperative epiphenomenon; 2) the presence of epicarditis due to reactivated epicarditis may cause inextensible hardening of the epicardium which adds to the effects of restrictive cardiomyopathy of chronic rejection.

Adult↗
PubMed1994

[Cutaneous Kaposi's sarcoma with pulmonary carcinomatous lymphangitis in patient with heart transplantation].

The great strides in organ transplantation have been accompanied by some specific pathologies, notably, neoplasia, including Kaposi's sarcoma which occupies the third place in frequency after cutaneous tumours and malignant lymphomas. We report a case of cutaneous Kaposi's sarcoma developing some six months after a cardiac transplant. The modulation of immuno-suppression and treatment with Alpha interferon allowed an initial stabilisation of the cutaneous lesions. However, there were secondary developments of the lesions and, 21 months after the initial presentation, the patient developed a diffuse infiltrating pneumonia leading to death. The autopsy revealed lymphangitis carcinomatosis of Kaposi's sarcoma type. This observation underlines the therapeutic difficulties seen in Kaposi's sarcoma after organ transplantation when there is no alternative to allow a significant reduction or cessation of immuno-suppression.

Carcinoma↗
PubMed1993

Quantitative reduction of MTT by hearts biopsies in vitro is an index of viability.

The aim of this study is to evaluate the use of tetrazolium reductase (TR) activity as an indicator of myocardial viability in an isolated arrested pig heart biopsy model. Methyl Tetrazolium (MTT) is cleaved by an enzyme in the presence of coenzymes NAD, NADP. Cleavage yields a highly colored formazan product which is DMSO soluble. Efficient bioreduction of MTT has been investigated with heart biopsies. The relationship between MTT reduction and (1) oxygen consumption (r = 0.96, P < 0.001), (2) the sum of the adenine nucleotide levels (r = 0.87, P < 0.001) and (3) localization of coloration, has been established. The use of MTT in colorimetric assays offers high sensitivity. MTT reduction is a valid method. It is rapid and reproducible, and can be used as an indicator of myocardial viability. The MTT test has been used to rapidly compare the effect of different cardioplegic solutions (St Thomas and improved St Thomas) on hypothermic cardiac preservation. Significant differences have been established between the two solutions (P < 0.01).

Adenine Nucleotides↗
PubMed1993

Bone loss after cardiac transplantation: effects of calcium, calcidiol and monofluorophosphate.

Of 203 patients who underwent cardiac transplantation and were given long-term treatment with cyclosporine and 0.3 mg/kg per day prednisone, 123 were studied prospectively for at least 6 months and 46 for up to 2 years to evaluate the effects on lumbar bone mineral density (BMD) and calcium metabolism of a combined therapy with calcium, calcidiol and disodium monofluorophosphate (MFP). The population was arbitrarily assigned to one of two groups. Group I consisted of patients who had a lumbar spine BMD Z score above -1.5 SD as compared with an age- and sex-matched population and no vertebral fractures. They received daily 1 g elemental calcium and 25 micrograms (1000 IU) calcidiol. Group II consisted of patients who received daily the same doses of calcium and calcidiol combined with 200 mg MFP, and was divided into two subgroups: (a) osteopenic subjects who had a lumbar spine BMD Z score below -1.5 SD without vertebral fractures and (b) osteoporotic subjects with vertebral fractures. If serum creatinine was higher than 140 mumol/l the daily dose of MFP was tapered to 100 mg. Fifty-four and 27 patients from group I and 38 and 19 patients from group II were followed respectively for 12 and 24 months. In both groups serum parathyroid hormone levels were significantly reduced from the twelfth month in parallel with a significant increase in serum 25-OHD levels. No decline in lumbar BMD occurred in non-osteopenic and non-osteoporotic patients (group 1) who received the calcium and calcidiol supplement. In group II, where MFP was added, a significant and linear increase in lumbar BMD was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Lipid peroxides and antioxidant defenses in accelerated transplantation-associated coronary arteriosclerosis.

Accelerated coronary artery disease develops in most if not all heart transplant recipients within the first year after transplantation. Increased lipid peroxidation seems to be involved in atherogenesis. In these patients we have investigated whether there is an association between lipid peroxidation, reduced antioxidant defenses, and some conventional coronary risk factors. Lipid peroxides, lipids, uric acid, albumin, antioxidant enzymes and their cofactors (the trace elements selenium, iron, copper, and zinc) have been determined in heart transplant recipients compared with nonrecipients with coronary artery disease. Lipid peroxides (p = 0.002) and uric acid (p = 0.01) were higher and zinc (p = 0.001) was lower in heart transplant recipients. Thirteen of 30 transplant recipients compared with one of 30 nonrecipients (p < 0.001) had very low (less than 10 mumol/L) zinc levels. Antioxidant enzymes and other trace elements were not significantly different. In univariate regression analysis, zinc correlated positively with albumin (p = 0.02) and negatively with lipid peroxides (p < 0.05). Uricemia had a strongly positive correlation with hydroperoxides (r = 0.45; p = 0.0001). In stepwise multivariate regression analysis, lipids, uricemia, creatinine, and zinc were significant (p < or = 0.004) predictors of the lipid peroxide level. Cyclosporine and corticosteroid dosages were significant (p = 0.01) determinants of zinc concentration in the transplant recipients. Although a causal relationship between increased lipid peroxidation and accelerated arteriosclerosis is not definitely demonstrated, the results of this analysis suggest new insights into conventional coronary disease risk factors and possible therapeutic interventions; further controlled trials are needed.

Adult↗