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Biomedical subjects

V Baudouin

Publications and source records attributed to V Baudouin.

At least 19 recordsLinked to original sources
PubMed2001

Scintigraphic screening for renal damage in siblings of children with symptomatic primary vesico-ureteric reflux.

OBJECTIVE: To define prospectively the incidence of renal parenchymal lesions in the siblings of patients treated at one institution for primary vesico-ureteric reflux (VUR). PATIENTS AND METHODS: From January 1997 to October 1998, a prospective study including renal scintigraphy (using dimercaptosuccinic acid, DMSA) and a radionuclide cystogram was proposed systematically to the asymptomatic siblings of children treated for primary VUR. The radionuclide cystograms were interpreted as showing the presence or absence of VUR and the DMSA scan as symmetrical or asymmetrical differential function, with or with no renal defect. RESULTS: Fifty-five families gave informed consent, of whom 46 completed the study (eight refused secondarily and one was omitted by exclusion criteria), representing 46 symptomatic patients and 65 siblings. There were 17 siblings with VUR (26%) including two of 13 infants and 15 of 52 children aged > 18 months. One radionuclide cystogram failed. Of the 17 refluxing siblings, four had a history of symptomatic urinary tract infection; 62 of the 65 siblings had a DMSA scan, of which 56 were normal and six (10%) showed abnormalities (five asymmetrical differential function and one parenchymal defect). Only one of these six patients had VUR at the time of the evaluation and only one had a small kidney detected by ultrasonography on one side (and no VUR). There were no adverse effects associated with screening. CONCLUSION: This study confirms a significant overall incidence of VUR (26%) in the asymptomatic siblings of patients treated for primary VUR. From the results of the DMSA scan (only one sibling had a parenchymal defect), the systematic screening of asymptomatic siblings does not appear to be beneficial.

Adolescent↗
PubMed2000

Pharmacokinetics and tolerance of mycophenolate mofetil in renal transplant children.

Mycophenolate mofetil (MMF) is a prodrug that is hydrolyzed to the active immunosuppressant mycophenolic acid (MPA). The drug is now widely prescribed for adult renal transplant recipients and its use has been extended to pediatric patients, although pharmacological data in this age group are limited. Nine pediatric renal transplant recipients received MMF with corticosteroids and either cyclosporine or tacrolimus a median of 55 months (range 7.5-124 months) months after transplantation. The pharmacokinetic parameters of MPA and MPA glucuronide (MPAG) were determined at steady state by high-performance liquid chromatography after administration of MMF at the oral dose of 494+/-142 mg/m(2) twice daily. MPA was rapidly absorbed, with a peak concentration at 1.4 h. The mean plasma concentration of MPA at steady state was 4.7+/-1.3 microg/ml. The areas under the plasma concentration-time curves (AUCs) over 12 h (between two administrations) were 57.0+/-15.3 microg.h/ml for MPA and 1,515+/-722 microg.h/ml for MPAG, and the apparent oral clearance was 11.7+/-7.0 and 0.5+/-0.4 l/h for MPA and MPAG, respectively. Assuming that the pharmacokinetics of MPA was dose dependent, the mean concentration at steady state and the AUC for MPA were calculated for the recommended dosage schedule of 600 mg/m(2) every 12 h and were 6.3+/-2.7 microg/ml and 75.2+/-32.9 microg.h/ml, respectively. The tolerance of MMF was studied prospectively with a follow-up of 1.1+/-0.2 years. Gastrointestinal disorders requiring dosage reduction or discontinuation of therapy, observed in five of nine patients, occurred at an incidence higher than expected from adult data. Our results suggest that the dose of 600 mg/m(2) every 12 h extrapolated from adult data for use in pediatric patients would be associated with plasma levels and AUCs higher than expected and may be associated with a higher incidence of side-effects, primarily gastrointestinal.

Abdominal Pain↗
PubMed2000

WT1 splice-site mutations are rarely associated with primary steroid-resistant focal and segmental glomerulosclerosis.

BACKGROUND: Donor splice-site de novo heterozygous mutations in intron 9 of the Wilms' tumor gene (WT1) have been reported in Frasier syndrome, which is defined by the association of focal and segmental glomerulosclerosis (FSGS), male pseudohermaphroditism, and gonadoblastoma. These splice-site mutations alter the WT1 alternative splicing leading to two WT1 isoforms, with (+) or without (-) three amino acids, lysine-threonine-serine (KTS), between zinc fingers 3 and 4. The aim of this work was to investigate the possibility that some cases of primary steroid-resistant nephrotic syndrome associated with FSGS may be caused by WT1 splice-site mutations. METHODS: We analyzed WT1 exons 8 and 9 and the surrounding exon/intron boundary DNA sequences in 37 children with nonfamilial primary steroid-resistant nephrotic syndrome. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the relative ratio of +KTS/-KTS transcripts from immortalized lymphocyte RNA. RESULTS: One boy with FSGS and associated pathologies (diaphragmatic hernia, proximal hypospadias, and unilateral testicular ectopia) was found to carry the heterozygous 1228 +4 C-->T splice-site mutation. RT-PCR quantitation of the +KTS/-KTS transcripts from immortalized lymphocyte RNA of this patient showed a diminution of the +KTS/-KTS isoform ratio (0.43), which is identical to that reported in patients with Frasier syndrome. Using the same approach, healthy control subjects have +KTS/-KTS ratios ranging from 1.50 to 2.00. CONCLUSIONS: This study expands the range of the phenotypic presentation of the intron 9 splice-site WT1 mutations and adds to the already reported heterogeneity of primary steroid-resistant nephrotic syndromes. We suggest that these mutations are not likely to be a common cause of isolated steroid-resistant nephrotic syndrome, and recommend a WT1 exon 9/intron 9 splice-site study in children with primary steroid-resistant nephrotic syndrome if genital or diaphragmatic anomalies are associated. The identification of such WT1 mutations has practical implications for the management of these patients.

Adolescent↗
PubMed2000

Effect of individual plasma lipoprotein(a) variations in vivo on its competition with plasminogen for fibrin and cell binding: An in vitro study using plasma from children with idiopathic nephrotic syndrome.

Simultaneous natural changes in lipoprotein(a) [Lp(a)] and plasminogen occur in the nephrotic syndrome and offer a unique opportunity to investigate their effects on plasminogen activation under conditions fashioned in vivo. Plasminogen, Lp(a), and apolipoprotein(a) in plasma were characterized, and their competitive binding to carboxy-terminal lysine residues of fibrin and cell membrane proteins was determined in nephrotic children during a flare-up of the disease (61 cases) and after 6 weeks (33 cases) and 6 months (42 cases) of remission. Low plasminogen concentrations (median 1.34 micromol/L, range 0.39 to 1.96 micromol/L) and high Lp(a) levels (median 0.27 g/L, range 0.07 to 2. 57 g/L) were detected at flare-up. These changes were associated with an increased Lp(a) binding ratio onto fibrin (3.13+/-0.48) and cells (1.53+/-0.24) compared with binding ratios of control children (1.31+/-0.19 and 1.05+/-0.07, respectively) with normal plasminogen and low Lp(a) (median 0.071 g/L). After 6 weeks and 6 months of remission, the values for net decrease in Lp(a) binding to fibrin were 1.7+/-0.22 (after 6 weeks) and 1.88+/-0.38 (after 6 months) and were correlated with low Lp(a) concentrations (median 0.2 g/L, range 0.07 to 0.8 g/L; and median 0.12 g/L, range 0.07 to 1.34 g/L) and inversely associated with increased plasminogen levels (median 1.82 micromol/L, range 1.4 to 2.1 micromol/L; and median 1.58 micromol/L, range 1.1 to 2.1 micromol/L). These studies provide the first quantitative evidence that binding of Lp(a) to lysine residues of fibrin and cell surfaces is directly related to circulating levels of both plasminogen and Lp(a) and that these glycoproteins may interact as competitive ligands for these biological surfaces in vivo. This mechanism may be of relevance to the atherothrombotic role of Lp(a), particularly in nephrotic patients.

Adolescent↗
PubMed1999

Post graft development of short children treated with growth hormone before kidney graft.

Sixteen prepubertal patients with chronic renal failure (CRF) were given daily recombinant human growth hormone (rhGH) treatment (1.2 IU/kg per week) for 2.6+/-1.6 years until kidney transplant. Therapy was then discontinued and the patients followed for a further 3. 5+/-1.4 years. During treatment, mean height increased from -3.0+/-0. 9 standard deviation score (SDS) to -1.9+/-1.4 SDS (P<0.001) at the time of transplantation, corresponding to a mean height gain of +1. 2+/-0.9 SDS. After discontinuation of rhGH therapy, prepubertal children continued a partial catch-up growth with a height gain of +0.5+/-0.8 SDS for the follow-up period. Conversely, negative changes of height were observed in pubertal transplanted children: -0.5+/-0.4 SDS in patients grafted at early stages of puberty (P2-P3) and -0.15+/-0.9 SDS in patients grafted at late stages of puberty (P4-P5). These data confirmed the benefit of rhGH therapy in CRF patients. Nevertheless, only early initiation of rhGH treatment led some of these patients to their target height at transplantation, thus preserving their potential growth. Reinitiation of rhGH therapy after transplantation should be considered in order to complete catch-up growth to target height in prepubertal children.

Age Factors↗
PubMed1999

Cystography after the Cohen ureterovesical reimplantation: is it necessary at a training center?

PURPOSE: Reimplantation by the Cohen procedure has a low rate of recurrent reflux, although postoperative cystography is done routinely at most centers. According to the French training program for pediatric surgery and urology residents, reimplantation is the main pediatric urology procedure performed during residency. We determine whether it is necessary to perform postoperative cystography routinely and whether the fact that the procedure is done by a junior surgeon modifies management. MATERIALS AND METHODS: A total of 268 children with primary vesicoureteral reflux underwent ureteral reimplantation by the Cohen transtrigonal technique. Bilateral reimplantation was done in 97% of the cases. Reimplantation was performed by a surgery resident assisted by a clinical fellow or senior consultant surgeon in 37% of the cases. Routine cystography and renal ultrasound were done in all patients postoperatively. Followup ranged from 6 months to 5 years (mean 10 months). RESULTS: In 2 children (0.7%) with recurrent reflux surgery was not performed by a resident. One of the 2 children had asymptomatic persistent reflux and no further surgery was done. In the other child postoperative cystography was normal at 6 months. One year later she had acute pyelonephritis with recurrent unilateral reflux and underwent repeat reimplantation. CONCLUSIONS: Routine cystography is not necessary after bilateral Cohen reimplantation. Reflux recurrence is low even at a training center where surgery may be performed by junior surgeons.

Child↗
PubMed1999

[Passage from sandimmun to neoral in kidney transplantation in children].

BACKGROUND: The cyclosporine microemulsion formulation Neoral, which allows a better absorption and a more regular pharmacokinetic profile, is proposed for replacing the original formulation, Sandimmun. The present study reports the results of conversion from Sandimmun to Neoral in children with a kidney graft, a population for which information remains limited. METHODS AND PATIENTS: Twenty children, 2.5 to 10.5 years of age, who had a kidney graft with a stable renal function for between six months to five years (m = 2.6) were the subjects of this study. The patients were switched from Sandimmun to Neoral at the same dose, adjusted afterwards on a cyclosporine trough level. RESULTS: After six months, the mean dose decreased from 9.1 mg/kg/d to 8.4 mg/kg/d, i.e., 12.5%. After one year, the mean dose was 7 mg mg/kg/d, i.e., 28%. Of the 65% of patients who had a decreased dose, most of them had the highest dose of Sandimmun at the start. Mean serum creatininemia levels slightly increased from 85.6 to 89.5 mumol/L after six months (P = 0.03). None of the patients had a rejection crisis during the first six months under Neoral. Blood pressure did not change significantly, hirsutism improved in two cases but increased or appeared in two cases as well. Gingival hypertrophy increased or appeared in four cases. DISCUSSION: A decrease in the dose was decided on either to maintain the trough CsA blood level in the desired range or because of the appearance of a symptom suggesting a side effect of cyclosporine, especially the increase of creatinemia. The trough level did not appear to be the best index for adapting the dose. CONCLUSION: In stable pediatric kidney transplant recipients, the switch from Sandimmun to Neoral provided a reduction in drug dosage in 65% of cases without an increase in adverse events.

Age Factors↗
PubMed1999

Thiopurine methyltransferase activity and its relationship to the occurrence of rejection episodes in paediatric renal transplant recipients treated with azathioprine.

AIMS: Azathioprine is a prodrug commonly used in combination therapy to prevent allograft rejection after renal transplantation. After conversion to 6-mercaptopurine, the drug is metabolized into 6-thioguanine nucleotides (6-TGN) and catabolized by thiopurine methyltransferase (TPMT), an enzyme under monogenic control. The aim of this study was to evaluate the inter- and intraindividual variability of red blood cell thiopurine methyltransferase and 6-TGN concentrations and their relationship to the clinical effects of azathioprine in paediatric patients. METHODS: In the present study, the inter- and intraindividual variations in red blood cell TPMT activity and 6-TGN concentrations and their relationship to the actions of azathioprine were evaluated during the first year after renal transplantation in 22 paediatric patients. RESULTS: 6-TGN concentration reached steady-state values after 6 months and correlated negatively with TPMT activity (P=0.004). Initial TPMT activity (median: 20.8 nmol h-1 ml-1, range 7.8-34.6) and 6-TGN concentration at steady-state (median: 80 pmol 8 x 10(8-1) cells, range not detected to 366) were not related to the occurrence of rejection episodes during the period of the study. In contrast, TPMT activity and the percentage difference in TPMT activity from the day of transplantation determined at month 1 were higher in the patients with rejection episodes by comparison with those that did not reject during the first 3 months or the first year following transplantation (P<0.005). CONCLUSIONS: We report a relationship between TPMT activity and occurrence of rejection in paediatric kidney transplant patients undergoing azathioprine therapy. These data suggest a link between high red blood cell TPMT activity and poor clinical outcome probably caused by rapid azathioprine catabolism.

Antimetabolites↗
PubMed1999

Evidence that modifications of Lp(a) in vivo inhibit plasmin formation on fibrin--a study with individual plasmas presenting natural variations of Lp(a).

In the present study we have investigated the effect of individual variations in the concentration of Lp(a) on plasmin formation at the surface of fibrin. The plasma Lp(a) concentrations from 20 nephrotic children were high at flare-up of the disease (0.43+/-0.45 g/l) and decreased progressively with remission at both 6 weeks (0.28+/-0.24 g/l) and 6 months (0.24+/-0.288 g/l). In contrast, the concentration of plasminogen showed an inverse variation, with low values at flare-up (1.27+/-0.34 microM) and normal values at remission (1.66+/-0.17 microM at 6 weeks and 1.99+/-0.21 microM at 6 months). An increase in plasmin formation (from 0.62+/-0.49 to 0.73+/-0.61, and 0.84+/-0.75 pmol/well) and a decrease in apo(a) binding (from 5.45+/-2.42 to 4.54+/-2.12, and 3.93+/-1.51 fmol/well) on the surface of fibrin, were concomitantly observed from flare-up to remission at 6 weeks and at 6 months, respectively. Values for plasmin formation parallel the amount of plasminogen bound. The low concentration of plasminogen found at flare-up may also have contributed to the increased binding of Lp(a) as indicated by a decrease in the maximal amount of Lp(a) bound (Bmax) to fibrin as a function of plasma plasminogen concentrations. Bmax was 1.51 fmol in the absence of plasminogen and decreased to 1.1 fmol and 0.93 fmol at respectively 1 and 2 microM of plasminogen. Altogether, these data constitute the first quantitative evidence indicating that plasmin formed at the surface of fibrin may vary with modifications of the concentration of Lp(a) in vivo.

Adolescent↗
PubMed1998

Cytokine mRNA and protein expression in a mixed leukocyte reaction before and after allogeneic transfusions. Groupe Coopératif de Transplantation d'Ile de France.

BACKGROUND: The precise mechanism by which pretransplant blood transfusions may favorably influence the graft outcome in human transplantation remains unknown. Here, we explored whether the mechanism might be related to an alteration of cytokine response to transplantation antigens. METHODS: Eight patients awaiting kidney transplantation were selected to receive a single planned pretransplant blood transfusion. Before transfusion and 7 days after transfusion, peripheral blood mononuclear cells from these patients were isolated and in vitro stimulated in a one-way mixed leukocyte reaction (MLR) by using allogeneic fixed Epstein Barr virus-transformed cells as stimulators. RESULTS: The use of a semiquantitative reverse-transcriptase polymerase chain reaction cycle technique to analyze cytokine mRNAs revealed that allostimulation by donor cells clearly induced accumulation of interleukin (IL)-2, IL-4, interferon (IFN)-gamma, and IL-10 mRNA in peripheral blood mononuclear cells collected both before and after transfusion (eight of eight patients). However, both T helper 1 (IFN-gamma) and T helper 2 (IL-4) cytokine responses were more elevated after transfusion in eight of eight patients, as were IL-2 responses in five of eight patients. Such up-regulation of cytokine responses by transfusion was mostly directed against blood donor cells. Indeed, after stimulation by third-party cells, this up-regulation was both inconstant (two of three patients) and of less intensity, and no change was detected after stimulation by autologous cells (three of three patients). CONCLUSIONS: That IL-2, IL-4, and IFN-gamma responses to donor cells were increased by transfusion was further supported by results on cytokine secretion showing increased levels of IL-2 (P < 0.05), IFN-gamma (P = 0.054), and IL-4 (P < 0.05) proteins in supernatants of posttransfusion MLR as compared with pretransfusion MLR. In contrast, transfusion-induced changes in the amount of IL-10 mRNAs were not obvious and were quite variable from one patient to another.

Adult↗
PubMed1998

Human complement factor H deficiency associated with hemolytic uremic syndrome.

This study reports on six cases of deficiency in the human complement regulatory protein Factor H (FH) in the context of an acute renal disease. Five of the cases were observed in children presenting with idiopathic hemolytic uremic syndrome (HUS). Two of the children exhibited a homozygous deficiency characterized by the absence of the 150-kD form of Factor H and the presence, upon immunoblotting, of the 42-kD Factor H-like protein 1 (FHL-1) and other FH-related protein (FHR) bands. Southern blot and PCR analysis of DNA of one patient with homozygous deficiency ruled out the presence of a large deletion of the FH gene as the underlying defect for the deficiency. The other four children presented with heterozygous deficiency and exhibited a normal immunoblotting pattern of proteins of the FH family. Factor H deficiency is the only complement deficiency associated with HUS. These observations suggest a role for FH and/or FH receptors in the pathogenesis of idiopathic HUS.

Acute Disease↗
PubMed1998

[Surgical aspects of renal transplantation in children].

Review of a series of 90 renal transplantations performed in 86 children revealed 3 cases of early or late mortality and 28 cases of major surgical complications, predominantly vascular (13 cases) and urological complications (12 cases). The time to onset, the diagnosis and the management of these complications are reviewed. This study again emphasizes the importance of graft selection (donor age) and the value of living related donor renal transplantation.

Adolescent↗
PubMed1997

Cytotoxic T lymphocyte changes after HLA-DR match and HLA-DR mismatch blood transfusions.

In the present study, we analyzed transfusion-induced cytolytic T lymphocyte (CTL) changes in patients who received either a one-HLA-DR-match or a zero-HLA-DR-match pretransplant blood transfusion. Twenty-four nonimmunized naive patients awaiting kidney transplantation received one planned, HLA-typed blood transfusion. The frequencies of CTL precursors (CTLp) directed against blood donor cells and controls were evaluated before and sequentially at days 7, 28, and 60 after transfusion. Results showed that sharing one HLA-DR between donor and recipient did not prevent CTL sensitization. Indeed, (1) An increase of donor-specific CTLp frequencies was observed in 8 of 11 patients who received a zero HLA-DR match (71%), as well as in 9 of 13 patients who received a one-HLA-DR-match (69%) transfusion. (2) This increase occurred with similar kinetics in the two groups, as it was highly significant 7 days after transfusion (P=0.002 and P=0.0035 in the first and second groups, respectively) but transient; CTLp frequencies returned to pretransfusion levels by day 60 after transfusion in both groups. (3) Finally, the magnitude of this increase was similar in the DR-match and DR-mismatch groups. Thus, if it is confirmed, in clinical practice, that one DR match between the blood donor and the patient would improve the tolerance effect of pretransplant blood transfusion, this phenomenon is unlikely to be related to the prevention of CTL sensitization.

Blood Donors↗
PubMed1997

Value of Doppler ultrasound for the diagnosis of renal artery stenosis in children.

To evaluate the reliability of Doppler ultrasonography (US) in identifying children with renal artery stenosis (RAS) among those with hypertension, we compared Doppler US results in 22 hypertensive children (mean age 8.9 +/- 4.3 years), with (13 cases) and without RAS at angiography, and in 33 normotensive children (mean age 8.8 +/- 4.7 years). We observed 2 false-negatives and 2 false-positives with Doppler US. Of the 2 false-negative diagnoses, I had RAS on an accessory renal artery located behind a normal upper polar artery and the other was observed in a patient with bilateral multiple stenosis of the very distal segments of renal arteries. The 2 false-positive diagnoses were due to sinuous left renal artery and to technical reasons, respectively. In another patient, Doppler US showed a tight RAS, while arteriography was normal. RAS was subsequently confirmed by a second arteriography. Peak systolic velocity values of Doppler US were significantly higher in patients with proven angiographic RAS (3.44 +/- 0.66 m/s) than in hypertensive patients with normal renal arteries at angiography (0.99 +/- 0.35 m/s, P < 0.0001) and normotensive healthy children (1.04 +/- 0.23 m/s, P < 0.0001). With the use of multiple views, and the experience acquired with practice, false-negatives or false-positives due to the geometry of the renal artery can be avoided. Nevertheless, very distal stenosis can be missed by Doppler US.

Angiography↗