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Biomedical subjects

M Broyer

Publications and source records attributed to M Broyer.

At least 109 records · Page 6Linked to original sources
PubMed1994

A study of recombinant human erythropoietin in the treatment of anaemia of chronic renal failure in children on haemodialysis.

This was an open-label multicentre study of recombinant human erythropoietin (r-HuEPO) in 116 children aged 6 months to 20 years with anaemia of chronic renal failure undergoing haemodialysis. Haemoglobin concentration at entry ranged from 3.4 to 9.5 g/dl. r-HuEPO was given intravenously two or three times per week, the starting dose being 75 U/kg per week. This was subsequently titrated in steps of 75 U/kg per week with the goal of increasing haemoglobin concentration at the rate of 1 g/dl per 4 weeks into the range 9.6-11.2 g/dl (6-7 mmol/l), with treatment then continued for up to 1 year with the aim of maintaining the haemoglobin concentration within the target range. Of the 115 children in whom efficacy could be evaluated, 93 (81%) achieved the target haemoglobin and a further 6 had a rise in haemoglobin concentration of at least 2 g/dl. At 52 weeks, the median maintenance dose for children < 30 kg was 225 U/kg per week, compared with 107 U/kg per week for children > or = 30 kg. Analysis suggested that 150 U/kg per week would have been a more appropriate starting dose. The mean transfusion requirement fell from 8.9 to 0.7 units/patient per year. Of the 22 patients who failed to reach the target, 15 went on to transplantation and left the study prematurely. Sub-group analysis showed that similar doses lead to similar rates of rise in haemoglobin regardless of the severity of the original anaemia. Assessment of quality of life suggested that this may have improved with r-HuEPO.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Growth response to recombinant human growth hormone in short prepubertal children with chronic renal failure with or without dialysis. The European/Australian Study Group.

The growth-promoting effect of recombinant human growth hormone (GH) in children with chronic renal failure was assessed in eight clinical trials. A total of 103 prepubertal children participated in the trials, 34 of whom were undergoing dialysis. The children were treated with GH, 30 IU/m2/week (approximately 1 IU/kg/week), for up to 2 years, and various growth parameters, bone age and renal function were assessed before and during treatment. In all trials, the children showed clear catch-up growth and an improved height SDS after treatment with GH, although the increase in height was less in dialysis patients than in those not receiving dialysis. GH maintained its growth-promoting effect during the second year of treatment; the effect, however, was less marked than during the first year of treatment. Bone age appeared to advance in parallel with chronological age. Median serum creatinine increased from 204 mumol/l to 230 and 262 mumol/l after 12 and 24 months of treatment, respectively, due to increased muscle mass and/or progression of the underlying renal disease. The loss of estimated glomerular filtration rate/year was not different before and during GH treatment.

Adolescent↗
PubMed1994

Deletions in the COL4A5 collagen gene in X-linked Alport syndrome. Characterization of the pathological transcripts in nonrenal cells and correlation with disease expression.

The type IV collagen alpha 5 chain (COL4A5) gene of 88 unrelated male patients with X-linked Alport syndrome was tested for major gene rearrangements by Southern blot analysis, using COL4A5 cDNA probes. 14 different deletions were detected, providing a 16% deletion rate in the COL4A5 gene in the patient population. The deletions are dispersed all over the gene with different sizes, ranging from 1 kb to the complete absence of the gene (> 250 kb) in one patient. In four patients with intragenic deletions, absence of the alpha 3 (IV) chain in the glomerular basement membrane was demonstrated by immunohistochemical studies. This finding supports the hypothesis that abnormalities in the alpha 5 (IV) chain may prevent normal incorporation of the alpha 3 (IV) chain into the glomerular basement membrane. Direct sequencing of cDNA amplified from lymphoblast mRNA of four patients with internal gene deletions, using appropriate combinations of primers amplifying across the predicted boundaries of the deletions, allowed us to determine the effect of the genomic rearrangements on the transcripts and, by inference, on the alpha 5 (IV) chain. Regardless of the extent of deletion and of the putative protein product, the 14 deletions occur in patients with juvenile-type Alport syndrome.

Base Sequence↗
PubMed1994

Evaluation in patients with Alport syndrome of knowledge of the disease and attitudes toward prenatal diagnosis.

Cloning of the COL4A5 gene has now made possible prenatal testing for Alport syndrome with X-linked dominant inheritance. We interviewed 27 females and 24 males with Alport syndrome to evaluate their knowledge of the disease and its transmission, and their attitudes to prenatal testing. Twenty-two males and 8 females were on renal replacement therapy. In all cases transmission was compatible with X-linked disease. Only 59% of the interviewees (74% of women, 42% of men) knew that gender was the major determinant in progression of the disease. Knowledge of the mode of inheritance was adequate in only 25%, in both sexes. Seventy percent of the participants (78% of women, 63% of men) would use prenatal testing. Of the women in favor of prenatal diagnosis, 67% and 39% would terminate pregnancy in the case of an affected male or female fetus, respectively. Of the men in favor of prenatal diagnosis, 53% would consider termination of an affected fetus. In summary, a majority would use prenatal testing, but only one or two thirds of them wished to use selective abortion. As in other inherited disorders, there is a discrepancy between the demand for prenatal diagnosis and the decision to terminate pregnancy. Most of the participants who would terminate a pregnancy had, however, little knowledge of the clinical and genetic aspects of Alport syndrome on which to base such a decision. An important aspect of genetic counselling is to assist consultants in reaching a decision regarding future reproductive behaviour which is appropriate to their situation. This study underlines the need to improve education and counselling to assure appropriate use of prenatal testing.

Abortion, Eugenic↗
PubMed1994

[Treatment with recombinant human growth hormone (rhGH) in children with chronic kidney failure or renal transplantation].

BACKGROUND: Administration of recombinant human growth hormone (rhGH) to children with chronic renal failure (CRF), on conservative treatment or kidney transplanted, may induce acceleration of growth. We report our experience of the first 3 years of treatment in such children. PATIENTS AND METHODS: Eight children with CRF on conservative treatment and six kidney transplanted children were included in a European multicentric trial. All children were given rhGH, 30 Ul/m2 body surface area/week, as daily subcutaneous injections, for 12-36 months. RESULTS: The mean growth velocity in children with CRF increased from 3.8 +/- 0.4 cm/yr before treatment to 9.0 +/- 0.4 (P < 0.001), 6.5 +/- 0.3 (P < 0.002) and 5.4 +/- 0.5 cm/yr, after 12, 24 and 36 months of treatment, respectively. The height gain after 2 years of treatment was 1.2 SD (P < 0.001) with bone age advancement not greater than the increase in chronological age. There was a significant decrease in the inulin clearance after 1 year of treatment. In transplanted children, the mean height gain was less important, increasing from 3.2 +/- 0.4 cm/yr before treatment to 6.2 +/- 0.6 cm/yr after 12 months of treatment (P < 0.001). There was no significant decrease in the mean inulin clearance, but two patients experienced rejection crisis. CONCLUSIONS: A short-term rhGH treatment may improve growth velocity of CRF or transplanted children. The possible role of GH on decrease in glomerular filtration in CRF and on incidence of acute kidney rejection after transplantation remains to be evaluated in a large cohort of patients.

Adolescent↗
PubMed1994

[A review of 72 renal artery stenoses in a series of 715 kidney transplantations in children].

In a series of 715 renal transplantations performed between 1973 and 1989, 72 cases of renal artery stenosis (RAS) in 69 children (9.7%) were managed at Hôpital Necker Enfants Malades. Forty cases of RAS were treated exclusively by antihypertensive drugs. A good result was obtained in 82.5% of cases. Thirty three transluminal angioplasties (TLA) were performed in 23 children with 26 RAS. A good clinical result was obtained in 15 children with a total of 17 stenoses, corresponding to a success rate of 65%. Transluminal dilatation of anastomotic stenoses always failed. There were no cases of transplant thrombosis. Eleven RAS were operated, including 5 after failure of TLA. Eight patients (73%) obtained a clinical improvement. There were 2 postoperative thromboses. Antihypertensive treatment must be administered in every case. If medical treatment fails, and with the exception of anastomotic stenoses, TLA should be the first-line procedure, while surgery is reserved for failures of TLA and for anastomotic stenoses.

Adolescent↗
PubMed1994

[Treatment of anemia in hemodialyzed children using recombinant human erythropoietin (Eprex). Results of a French multicenter clinical trial].

Intravenous recombinant human erythropoietin (Eprex Cilag) was used in 28 hemodialyzed children, treated in 3 French paediatric centers, from November 1989 to November 1990. Transfusion dependency disappeared in all cases: the number of transfusions decreased from 7.3 unit/patient/year to 0.6 unit/pt/year. The mean haemoglobin concentration for the whole group increased from 6.6 +/- 0.8 g/dl, to 9.2 +/- 1.2 at 6 months and 9.7 +/- 0.7 g/dl at 1 year. Twenty-two out of 28 children reached the target haemoglobin value of 9.6 g/dl (6 mmol/dL) within a mean time of 16.5 weeks. Poor responses were due to either a premature withdrawal of treatment because of renal transplantation, or too low a dosage for the age. The study showed indeed that the dose requirement was significantly dependent on physical development: the mean dosage required to maintain haemoglobin concentration at the target value was 300 U/kg/week in children weighing less than 20 kg, 222 U/kg/week in 20-30 kg children, and 135 U/kg/week in those weighing more than 30 kg (p = 0.02). The only complication was an increase in blood pressure, observed in 43% of cases. The increase of anti-hypertensive medication was always successful in controlling blood pressure, and hospitalization was required in only one case. The improvement in general condition was obvious, and in several cases, the cognitive abilities seemed to improve. The growth deficit remained unchanged.

Adolescent↗
PubMed1994

Recurrence of de novo membranous glomerulonephritis on renal grafts.

An updated study of the glomerular lesions found in renal grafts in children showed 3 features of interest. 1) In our experience, the incidence of the occurrence of de novo membranous glomerulonephritis (MGN) remains around 9% (48 of 530 grafts). 2) Of the 29 patients we reported in a previous study [Antignac et al. 1988], 18 lost their grafts and 7 received a second graft. Four of these 7 patients recurred de novo MGN on their second graft. Their clinical course is reported in detail. 3) In our population of transplanted children, of the 55 patients who received a second graft, the only recipients who developed a de novo MGN were the 4 patients who had already developed de novo MGN on their first graft. The various factors possibly involved in the pathogenesis of de novo MGN are reviewed. The high incidence of recurrence of de novo MGN indicates that host factors play a major role in the development of this nephropathy.

Child↗
PubMed1994

[Characteristic aspects of vascular complications in renal transplantation in children].

In a series of 859 transplantations performed in children and adolescents from January 1973 to December 1992, vascular thrombosis accounted for 18% of all graft losses (2nd cause of graft failure), and 57% of early failures (within 2 months). Renal veins and arteries were equally affected. The young age of the donors and recipients constituted the main risk factor, thrombosis accounting for 40 and 37% respectively of all graft losses in donors and recipients < 5 years old. This explained the lower survival rate of these age groups after grafting, as reported in most published pediatric series. The prophylactic use of a low molecular weight heparin in high-risk grafts may help to decrease its incidence. A renal artery stenosis, located a few cm beyond the anastomosis in 2/3 of cases, was observed in 10% of grafts. Often severe hypertension (HBP) with cerebral complications, responsible for permanent sequelae in some cases, was the prominent symptom. Anti-hypertensive drug therapy was sufficient to control HBP in 40 cases out of 72, and in 10 of these, a spontaneous regression of the stenosis was remarked within a few months after repeated angiography. Transluminal angioplasty was used on 26 stenosis and was effective in 2/3 of cases; the recurrence rate, however, was 27%.

Adolescent↗
PubMed1993

Anti-OKT3 response following prophylactic treatment in paediatric kidney transplant recipients.

The anti-OKT3 response was studied in 40 paediatric kidney transplant recipients receiving OTK3 as a prophylactic treatment in association with azathioprine and prednisone. Only 1 patient experienced a reversible acute rejection episode while receiving OKT3. OKT3 induced a rapid disappearance of CD3+ cells, but significant proportions of CD3+ cells reappeared before the end of the treatment in 14 patients. Wide variations in circulating OKT3 levels were observed and in only 50% of patients could stable circulating OKT3 levels be detected until discontinuation of treatment. Anti-OKT3 antibodies detected by the enzyme-linked immunosorbent assay (ELISA) (anti-idiotypic and anti-isotypic antibodies) developed in 91% of patients. Anti-idiotypic antibodies detected by the immunofluorescence inhibition test were found in the sera of 71% of patients, always when high titres of anti-OKT3 antibodies were detected by ELISA. As it has recently been shown that anti-idiotypic antibodies are associated with failure of subsequent OKT3 treatment, we conclude that OKT3 should be restricted to steroid-resistant rejection crises in paediatric patients.

Adolescent↗