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Biomedical subjects

F R Pruvot

Publications and source records attributed to F R Pruvot.

At least 37 records · Page 2Linked to original sources

Consecutive successful pregnancies in a combined liver and kidney transplant recipient with type 1 primary hyperoxaluria.

Pregnancy is now a common, but high-risk event, in young women who have received transplants. Consequences to the fetus are known, but pregnancy may also interfere with graft function. We report the outcome of two successive and successful pregnancies in a 29-year-old woman with type 1 hyperoxaluria, who received a combined liver and kidney transplant. Two healthy children were born at 35 and 37 weeks of gestation, with low birth weight. Liver function remained normal before, during, and after pregnancies up to 52 months after transplantation. Renal function was impaired before the first conception, worsened during both pregnancies, and returned to the previous level in both immediate postpartum periods. However, renal function has declined 17 months after the last delivery. This report shows the feasibility of successive pregnancies in multiple organ transplant recipients, but raises the question of long-term maternal kidney graft survival.

Adult↗

A randomized controlled trial of pentoxifylline for the prevention of delayed graft function in cadaveric kidney graft.

Ischemia/reperfusion has been implicated in the mechanism of delayed graft function (DGF). Pentoxifylline (PTX) has been shown to suppress TNF alpha (released by activated macrophages, inhibiting subsequent superoxide anion release from neutrophil activation. In addition, PTX decreases cyclosporine (CsA) induced renal endothelial release and vasoconstriction. Thus, administration of PTX to renal transplant patient could be an excellent approach to prevent DGF and vascular toxicity of CsA in the early graft period. One hundred-and-forty consecutive patients receiving cadaveric kidney transplantation were registered in a randomized double-blind study comparing PTX vs. a placebo. PTX had no demonstrable effect on the incidence of DGF, on the rapidity of the renal function recovery, and on the ability to use higher doses of CsA in the first month post-graft.

Adult↗

[Liver transplantation in an adolescent with cystic fibrosis].

BACKGROUND: Orthotopic liver transplantation (OLT) is an effective treatment for patients with cystic fibrosis end stage liver disease, especially those with only mild pulmonary involvement. Long-term follow-up in such transplanted patients is still lacking. CASE REPORT: A 15-year-old girl with cystic fibrosis received an OLT because of severe decompensated cirrhosis. She had been colonized by Pseudomonas aeruginosa for 3 years and had pancreatic insufficiency; she also had mild glucose intolerance. Postoperatively she developed diabetes mellitus requiring insulin therapy for 9 months. Oral cyclosporin was poorly absorbed so that she was given a new emulsion of cyclosporin (Neoral) that was better absorbed. A rapid pubertal catch-up was obtained but the patient remained colonized by Pseudomonas aeruginosa. CONCLUSION: This 3-year postoperative follow-up confirms that OLT can represent a good alternative in those patients with severe liver disease and mild pulmonary involvement.

Adolescent↗

Liver transplantation without the use of fresh frozen plasma.

In orthotopic liver transplantations (OLT), fresh frozen plasma (FFP) is classically used to normalize coagulation factor concentrations. In this study, 28 OLT were performed without the use of FFP. According to their preoperative factor V (FV) levels, two groups of patients were defined: Group 1 (13 patients, FV > 10% and < 60%) and Group 2 (15 patients, FV > 60%). Spontaneous evolution of coagulation factors, concentration, and bleeding were observed during OLT and up to 48 h after surgery. Total intraoperative bleeding was similar in both groups (3460 +/- 2700 mL and 3470 +/- 2110 mL in Groups 1 and 2, respectively). Levels of clotting factors were not different between groups after the anhepatic stage. The lowest values were noted after reperfusion. Thirty-six hours after surgery, all levels of clotting factors in both groups were more than 50%, with FV level increasing the most rapidly. Hematocrit from the subhepatic drainage liquid was 1.8% and less than 1% at 24 and 48 h, respectively, after surgery. No reintervention for bleeding was necessary. These results suggest that, in OLT, correct hemostasis can be assumed without FFP use when hyperfibrinolysis, platelet count, fibrinogen rate, and hemodynamic status are controlled.

Adult↗

[Inhaled nitric oxide test for patients with stable chronic obstructive pulmonary disease: value and feasibility].

Patients suffering from chronic lung disease (CLDP) often develop secondary pulmonary hypertension (HP), which contributes to right ventricular dysfunction and worsens their prognosis. In order to evaluate the severity of this HP, pharmacodynamics tests are periodically proposed to these patients. Therefore, the administration of vasodilators is limited by systemic and pulmonary side-effects. Inhaling nitric oxide gas (NO) has been reported to induce a selective pulmonary vasodilation. The purpose of this study was to evaluate the safety and efficacy of an inhaled NO test perfected in our service. Sixteen CLDP were investigated in the absence of acute pulmonary failure. All had severe pre-capillary HP, confirmed after placement of a thermodilution pulmonary-artery catheter (mean pulmonary artery pressure >20 mmHg, pulmonary capillary wedge pressure >12 mmHg). Each subject breathed spontaneously NO in a concentration of 10 ppm for 15 minutes. They were connected through a facial mask and a one-way valve put on the inspiratory connection of a ventilator (Drager-Evita), to a tank of nitrogen with a NO concentration of 900 ppm. Hemodynamic variables and gas exchange were measured before, during and after gas inhalation. The inspired fractions of NO and NO2 were determined using a Polytron analyser (Drager). The methemoglobin levels were measured with spectrophotometry (OSM3). Inhaled NO acts as a selective pulmonary arterial vasodilator, without systemic effect. The action on the shunt is variable. Methemoglobin levels are remained <0.01%. All the patients were satisfied with the way of NO administration. In view of the lack of systemic effects, its seems that the NO inhaled test proposed in this study may be used accurately to evaluate the HP of chronic lung disease patients.

Adult↗

[Pregnancy after hepatic transplantation: what is the maternal risk?].

OBJECTIVES AND METHODS: We report 7 pregnancies which occurred from 1988 to 1995 in 5 women who underwent liver transplantation. The immunosuppression regimen associated cyclosporine, azathioprine and prednisone. RESULTS: Mean age at conception was 25. During pregnancy, cholestasis occurred in 2 women. None of the patients experienced rejection. An increase in serum creatinine was observed in 3 cases. Serum uric acid increased in the third trimester of pregnancy in 6 cases, associated with arterial hypertension in 3 cases. In 4 cases, toxemia led to premature delivery. Seven childbirths occurred between the 34th and 38th week of gestation, by vaginal delivery (n = 3) or caesarean section (n = 4). Newborn weights ranged from 1,350 g to 3,100 g. A favorable outcome was observed in all mothers, with a follow-up ranging from 2 months to 7 years after delivery. CONCLUSION: These results suggest that a successful pregnancy is possible after liver transplantation in young women with normal hepatic function and treated with cyclosporine. The risk of toxemia is mainly related to renal function before pregnancy.

Adult↗

Implication of cyclosporine in up-regulation of Bcl-2 expression and maintenance of CD8 lymphocytosis in cytomegalovirus-infected allograft recipients.

T cell homeostasis and CD4/CD8 ratios are normally reestablished by apoptotic clearance of activated T cells after immune stimulation. In allograft recipients with cytomegalovirus infection, CD8 lymphocytosis persists after negativation of viral cultures, contrary to immunocompetent hosts. We investigated the expression of Bcl-2 protein, an intracellular suppressor of apoptosis, and of CD95 (APO-1/Fas), a membrane inducer of apoptosis, in peripheral blood lymphocytes from 45 solid organ recipients. During the viremic phase of CMV infection, we found absence or diminished expression of Bcl-2 protein and increased expression of CD95 antigen in activated CD8+ T cells. Opposite evolution of these molecular regulators of apoptosis was reflected by the presence of 10-25% of apoptotic lymphocytes with fragmented DNA, as shown by both in situ nick translation and electrophoresis. Normalization of Bcl-2 expression was progressive over several months but still lower than in uninfected allograft recipients. These results suggest that the initial evolution of CMV infection in allograft recipients resembles acute viral infection in immunocompetent hosts. Conversely, we showed that overexpression of Bcl-2 protein in lymphocytes from uninfected allograft recipients, and culture of unstimulated normal lymphocytes with 0.5 micrograms/ml cyclosporine led to an increase in the expression of intracellular Bcl-2. This up-regulation of Bcl-2 protein by cyclosporine suggests the acquisition of resistance to apoptosis. Thus, the reversion of balance between T cell death and survival after acute CMV infection might be impeded by cyclosporine. Combination of CMV latent infection and cyclosporine therapy appears therefore critical to shift the homeostatic maintenance of the peripheral lymphocyte compartment toward persistingly high numbers of CD8+ T cells.

Adolescent↗

Characterization, quantification, and localization of passenger T lymphocytes and NK cells in human liver before transplantation.

Quantification and localization of the main lymphocyte populations were studied in the livers of normal (n = 8) and brain dead (n = 8) subjects. Cytometric analysis performed on mononuclear cell suspensions obtained from liver biopsies was compared to an automatic image analysis of immunostained sections. The overall number of liver associated lymphocytes was in the usual range of peripheral blood content (2 to 9x10(9) cells). Phenotypic analysis showed predominant NK and CD8+ cells that highly expressed class II antigen and CD25 and CD69 activation markers. Quantitative mapping of these activated lymphocytes revealed their preferential localization in the portal tract and the perisinusoidal area as compared to the pericentrolobular zone, especially in donor livers. This strategic localization could suggest a possible early cooperation between donor lymphocytes and initial infiltrating cells from the recipient and could explain the special immunological status of allografted livers.

Biopsy↗

Diagnostic and predictive value of an immunohistochemical profile in asymptomatic acute rejection of renal allografts.

We have retrospectively studied the diagnostic and predictive value of immunohistochemical characterization of adhesion molecules (ICAM-1, CD54, VCAM-1) and HLA-DR antigen in a homogeneous clinical group of 36 patients. Between 1 January 1991 and 31 January 1993, 130 patients received a kidney transplant in our unit. Biopsies of renal allografts were only performed in asymptomatic patients who had graft dysfunction, revealed by an isolated serum creatinine increase. Available frozen samples were included in this study (n = 44). The 35 cases of acute rejection diagnosed by biopsy corresponded to mild acute rejection according to the Banff classification criteria. First, we compared the expression of HLA-DR, ICAM-1 and VCAM-1 to morphological data to determine if the immunohistochemical data improved the histopathological diagnosis when the interstitial infiltrate was mild with slight tubulitis. We also studied the phenotype of infiltrating cells with monoclonal antibodies directed against T helper cells, T cytotoxic-suppressor cells, activated T cells and macrophages. Expression on tubular epithelium and density of each type of cell was graded semiquantitatively. Expression of HLA-DR, ICAM-1 and VCAM-1 was observed on tubular epithelium and endothelium in both acute rejection and other causes of graft dysfunction, limiting its diagnostic value. Activated T cells expressing CD69-AIM (activation inducer molecule) and/or HLA-DR were frequently observed in acute rejection (24/35 (69%) and 25/35 (71%) respectively) but not in other causes of renal dysfunction. We then studied the prognostic usefulness of the immunohistochemical profile in acute rejection. Of 27 patients, 12 had a progressively decreased renal function or returned to dialysis within one year after transplantation while the other 15 had a stable graft function after at least 18 months of follow-up. In the group of bad prognosis (n = 12), corticosteroid-resistant rejection episodes were significantly more frequent (p < 0.01). In this group, nine patients had an overexpression of HLA-DR on tubular epithelium versus one patient in the group of stable graft function (chi 2c = 10.57, p < 0.002). Seven patients included in the group of bad prognosis showed tubular overexpression of both ICAM-1 and VCAM-1 versus one patient in the other group chi 2c = 6.23, p < 0.02). Moreover, patients of the first group had a significantly higher number of interstitial macrophages as compared with those who had stable graft function (chi 2c = 4.87, p < 0.01). Thus, our data show that the immunohistochemical profile studied is of little value in the diagnosis of renal allograft rejection. However, an intense tubular expression of HLA-DR and/or both ICAM-1 and VCAM-1, and a high number of interstitial macrophages are significantly related to unfavorable graft outcome.

Acute Disease↗