Biomedical subjects
D Chevet
Publications and source records attributed to D Chevet.
Fibrinogen A alpha chain mutation (Arg554 Leu) associated with hereditary renal amyloidosis in a French family.
A French family with hereditary renal amyloidosis (HRA) was studied. The disease presented in 7 of the 8 affected individuals with proteinuria or the nephrotic syndrome. The age of onset was in the fifth decade of life. There is currently no sign of extrarenal involvement in any affected individual. However, the nephropathy in this family is progressive and led to terminal renal failure in 4 patients. Immunohistochemistry studies of glomerular amyloid deposits suggested that the amyloid protein was the fibrinogen A alpha chain. Direct DNA sequencing revealed a G 4993 T transversion and subsequently Arg 554 Leu mutation in the fibrinogen A alpha chain. This is the first description of this fibrinogen A alpha chain mutation in Europe. This family is of French descent and cannot be related to the previously reported Peruvian/Mexican and African-American kindreds.
[Factitious hyperchloremia disclosing bromide poisoning. 4 cases].
BACKGROUND: When routine blood chemistry shows elevated chloride alone, another anion (bromide, iodine, fluoride) may be involved. CASE REPORTS: Hyperchloremia and decreased anion gap was observed in four patients. Chloremia ranged from 134 to 174 mmol/l at initial blood tests. Careful history taking led to the discovery of long-term use of calcium bromogalacto-glucomate. Specific assay with inductively coupled plasma mass spectrometry (ICPMS) confirmed the presence of bromide in the blood. Chloridemia returned to normal levels after discontinuing use of bromine. DISCUSSION: Bromism is not a common diagnosis. Risks include neurological and psychiatric disorders due to bromide diffusion through the blood-brain barrier. Clinical manifestations have been described including skin lesions, digestive intolerance, and fever. Bromide is contained in certain prescription drugs. Patients should be warned against the adverse effects of overuse.
Familial lecithin:cholesterol acyltransferase deficiency: molecular analysis of a compound heterozygote: LCAT (Arg147 --> Trp) and LCAT (Tyr171 --> Stop).
Lecithin:cholesterol acyltransferase (LCAT) is responsible for the formation of the majority of plasma cholesteryl esters. Familial LCAT deficiency is associated with corneal opacity, anemia and proteinurea and typically results in renal failure in the 4-5th decade; this syndrome is equally characterized by the quasi-absence of plasma LCAT activity with variable enzyme mass and very low levels of plasma cholesteryl esters. In this study, we report detailed analyses of plasma lipids and lipoprotein profile in two sisters (CM and ML) presenting classical homozygous LCAT-deficiency; the younger sibling (CM) had proteinurea from an early age whereas the older sister (ML) has never exhibited renal dysfunction. We investigated the molecular defect in the 45 year-old woman (proband CM) exhibiting all clinical and biochemical features of familial LCAT deficiency: a plasma cholesterol level of 105 mg/dl, of which 95% was unesterified, an HDL-cholesterol of 6.5 mg/dl and an apo A-I level of 52 mg/dl. The proband (CM) displayed a plasma cholesterol esterification rate which corresponded to 2% of normal LCAT activity; plasma LCAT protein concentration was 0.56 microg/ml and equivalent to approximately 10% of normal LCAT mass. Analysis by single strand conformation polymorphism (SSCP) of the PCR products corresponding to exons 4 and 5 of the LCAT gene revealed a visible band shift. Sequence analyses of exons 4 + 5 revealed two separate single point mutations: a C --> T transition replacing Arg147 by Trp and a T --> G transition converting Tyr171 to a stop codon. The presence of these two point mutations was confirmed by restriction enzyme analyses: the C --> T transition abolished a MwoI site whereas the T --> G transition created an AvrII site. The Arg147 mutation was associated with a non-secreted protein. The Tyr171 mutation resulted in formation of a truncated protein lacking the catalytic site. In summary, we have identified an LCAT deficient patient corresponding to a compound heterozygote for the Arg147 --> Trp mutation and a new molecular defect involving a Tyr171 --> Stop mutation in the LCAT gene.
Treatment of idiopathic retroperitoneal fibrosis with tamoxifen.
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Acquired vein stenosis of renal allograft--percutaneous treatment with self-expanding metallic stent.
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Papillary necrosis: a late complication of nephropathia epidemica?
In the following we describe a case of nephropathia epidemica, which exhibited, a few years after acute infection, arterial hypertension and multiple papillary necrosis. Papillary necrosis was diagnosed by i.v. pyelography and CT Scan. A complete evaluation of the patient failed to show any other etiology for medullary necrosis. If arterial hypertension has already been reported as a complication of nephropathia epidemica, papillary necrosis is exceptional, but may be explained by the severe vascular troubles engendered by Hantavirus infection in kidney medulla.
Must erythropoietin be injected by the subcutaneous route for every hemodialyzed patient?
A multicenter, prospective, and controlled trial was performed to evaluate the efficacy and tolerance of intravenous (i.v.) and subcutaneous (s.c.) recombinant erythropoietin (rH-EPO) administration routes in 49 long-term hemodialyzed patients on maintenance phase of treatment, to determine the usefulness of replacing i.v. route by SC route in all of them. Each of these patients had already been treated with rH-EPO by the i.v. route for at least 6 months and included in the protocol on stabilized consumption phase. We arbitrarily chose three strata according to previous needs: Stratum A (> 150 U/kg/week) for eight patients, Stratum B (100 to 150 U/kg/week) for 12 patients, and Stratum C (< 100 U/kg/week) for 29 patients. In each stratum, the further treatment route (i.v. or s.c.) was randomized. Finally, 25 patients continued with i.v. route, and the other 24 changed to the s.c. route. The objective was to maintain a stable hemoglobin level, ranging from 9 to 10 g/dL. Tolerance and consumption in each group (i.v. and s.c.) were compared 4 months later. Globally, for an identical efficacy, rH-EPO needs were lesser using s.c. route (84 U/kg/week) than i.v. route (112 U/kg/week) (P = 0.02). However, when the strata were studied, it transpires that this benefit existed only for consumers having the highest needs (Stratum A) and not for the others. With regard to tolerance, only thrombotic events might be less frequent by using s.c. route, but the significance threshold is not reached (P = 0.09). Thus, replacing i.v. route by SC route, especially in high consumers, reduces the cost of treatment by rH-EPO. This benefit might be dependent on previous needs.
Idiopathic retroperitoneal fibrosis and HLA antigens.
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[B lymphocytes of patients with complete IgA deficiency secrete IgA in response to interleukin 10].
We have previously shown that human B lymphocytes cultured in the CD40 system, composed of an anti-CD40 mAb presented by a CD32-transfected fibroblastic cell line, proliferate but do not secrete immunoglobulins (Igs). However, the addition of particles of Staphylococcus aureus Cowan (SAC) induces B cell to secrete considerable amounts of Igs even in the absence of exogenous cytokines (CD40/SAC system). Additionally, B lymphocytes cultured in the CD40 system in the presence of human IL-10, produce high level of IgM, IgG and IgA, which are further increased by addition of SAC. Here, we have studied the capacity of peripheral blood lymphocytes from patients with IgA deficiency (IgA-D) to secrete Igs, particularly IgA after CD40 triggering. Peripheral blood mononuclear cells (PBMNC) from IgA-D patients cultured in the CD40/SAC system produced IgM and IgG, but no IgA. The addition of IL-10 to the cultures, enhanced the production of IgM and IgG and most strikingly induced the production of high amounts of IgA. The addition of IL-10 to PBMNC from IgA-D patients activated through CD40 alone resulted in the production of IgA. Thus, IL-10 can remove the block in B cell differentiation and allows B cells from IgA-D patients to differentiate into IgA secreting cells.
Azathioprine toxicity, 6-mercaptopurine accumulation and the "poor" 6-thiopurine methylator phenotype.
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CD4 and CD25 monoclonal antibody cocktail in kidney transplant rejection prophylaxis: clinical results of a pilot study.
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Azathioprine-induced pancytopenia in homozygous thiopurine methyltransferase-deficient renal transplant recipients: a family study.
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Interleukin 10 induces B lymphocytes from IgA-deficient patients to secrete IgA.
We have previously shown that human B lymphocytes cultured in the CD40 system, composed of an anti-CD40 mAb presented by a CD32-transfected fibroblastic cell line, proliferate but do not secrete antibodies. However, the addition of particles of Staphylococcus aureus Cowan (SAC) induces B cell differentiation even in the absence of exogenous cytokines (CD40/SAC system). Additionally, B lymphocytes cultured in the CD40 system in the presence of human IL-10, produce IgM, IgG, and IgA, and Ig levels are further increased by SAC. Here, we have studied the capacity of peripheral blood lymphocytes from patients with IgA deficiency (IgA-D) to secrete Igs, particularly IgA after CD40 triggering. Peripheral blood mononuclear cells (PBMNC) from IgA-D patients cultured in the CD40/SAC system produced IgM and IgG, but not IgA. The addition of IL-10 to the cultures, enhanced the production of IgM and IgG and most strikingly induced the production of high amounts of IgA. The addition of IL-10 to PBMNC from IgA-D patients activated through CD40 alone resulted in the production of IgA. Thus, SAC and anti-CD40 mAb stimulate B cells to differentiate into cells secreting IgG and IgM whereas IL-10 plays a central role in inducing B cells from IgA-D patients to differentiate into IgA secreting cells.
Normal range of [99mTc]MAG-3 renogram parameters in renal transplant recipients.
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[Peritoneal tuberculosis and continuous ambulatory peritoneal dialysis].
Depressed immunity in uremic patients increases by ten the risk of tuberculosis. In such patients, 40% of tuberculosis manifestations are extrapulmonary, and peritoneum is involved in about 6% of the cases. Seventeen cases of peritoneal tuberculosis have been so far reported in CAPD patients, and we add a new case. The prognosis of the disease is severe since 8 patients died. Three deaths out of 8 are directly linked to tuberculosis. Indeed, peritoneal tuberculosis diagnosis is hard and often late, at least for two main reasons: at first, it can be difficult to exclude the other causes of lymphocytic peritonitis (viral, fungal, bacterial, etc.), secondly, growth of mycobacteria in dialysate effluent cultures is late and inconstant. Omental biopsy in lymphocytic peritonitis of unknown origin could be of great value for an early diagnosis. Despite the adaptation of antituberculous drugs doses, side-effects are not so rare: optical neuritis and liver toxicity in our case. In spite of ultrafiltration loss, stopping CAPD is not always necessary, as in the reported case.
Acquired selective immunoglobulin A deficiency in renal transplant recipients.
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[Extracapillary glomerulonephritis].
Extracapillary glomerulonephritis is characterized by cell proliferation within the urinary space of 50% of the glomeruli, where it covers more than 50% of the filtration chamber, associated with acute or rapidly progressive renal failure. It is a model of curable human renal failure. Extracapillary cell proliferation is an elementary lesion which may complicate any glomerulopathy and many systemic diseases, or appear to be primary. Its clinical manifestations may be extremely marked in some systemic diseases, but they may be minimal and delay a diagnosis which rests entirely on renal biopsy. An early renal biopsy commands the prognosis which depends on the finding of young cellular crescents that respond to treatment before fibrous transformation sets in. Experiments in animals and man suggest that cell proliferation results from rupture of the capillary walls and from the production of polymerized fibrin in the urinary space. This is followed by a cascade of reactions, with increased synthesis of local mediators issued from resident and invasive glomerular cells. These data constitute the basis of modern therapies, such as emboli of methylprednisolone, plasma exchange and immunodepressive drugs, aimed not only at a possible aetiological treatment but also at the cell proliferation itself. The use of such treatments, whose risks must be carefully weighted, has transformed the prognosis of extracapillary glomerulonephritis, since almost 50% of the cases the kidneys survive at 5 years.