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.

Alteration in plasma antioxidant capacities in chronic renal failure and hemodialysis patients: a possible explanation for the increased cardiovascular risk in these patients.

OBJECTIVE: The high incidence of cardiovascular diseases in chronic renal failure (CRF) and hemodialyzed (HD) patients is now well established and the involvement of oxidative stress has been hypothesized in these phenomena. The aim of our study was to evaluate the level of oxidative stress in healthy controls (CTL) compared with CRF and HD patients before (pre-HD) and after (post-HD) the dialysis session, carried out on a high biocompatible polyacrylonitrile membrane AN69. METHODS: Several indicators of the extracellular redox status were evaluated in plasma. The ascorbyl free radical (AFR) was directly measured using electron spin resonance spectroscopy (ESR) and expressed with respect to the vitamin C level to obtain a direct index of oxidative stress. Indirect plasma parameters such as vitamin E, thiol and uric acid levels were also quantified. The plasma antioxidant status (PAS) was evaluated by the allophycocyanin test. Nitric oxide (NO) stable-end metabolites: nitrites and nitrates (NO(x)), were measured in plasma. RESULTS: In CRF patients, vitamin C and thiol levels were low, and the AFR/vitamin C ratio high compared with the CTL. On the other hand, PAS and uric acid levels were shown to be higher in CRF patients. After the dialysis session, vitamin C level decreased and AFR/vitamin C ratio increased. The thiol levels were shown to be increased, in return PAS and uric acid levels were significantly lower after the dialysis session. NO(x) levels rose during CRF, but were significantly decreased after the dialysis procedure. No differences in vitamin E status were observed between CTL, CRF and HD patients. CONCLUSION: Our study demonstrates that profound disturbances in the extracellular redox system occur during the course of chronic renal failure and hemodialysis, and may provide an explanation for the cardiovascular complications in these patients.

Vitamin E-coated dialyzer reduces oxidative stress in hemodialysis patients.

The high incidence of cardiovascular disease in hemodialyzed (HD) patients is well established and oxidative stress has been involved in this phenomenon. The aim of our study was to evaluate if a vitamin E-coated dialyzer could offer protection to HD patients against oxidative stress. Sixteen HD patients were successively assessed for one month (i) on a high biocompatible synthetic dialyzer (AN) and (ii) on a vitamin E-coated dialyzer (VE). Blood samples were taken before and after the dialysis session at the end of each treatment period. HD session conducted with the AN dialyzer was responsible for acute oxidative stress, significantly assessed after HD by a decreased plasma vitamin C level and an increased ascorbyl free radical (AFR)/vitamin C ratio used as an index of oxidative stress. Plasma elastase activity, reflecting neutrophil activation, was also increased; soluble P-selectin, reflecting platelet activation, did not show any variation. The use of the VE dialyzer was associated with a less extended oxidative stress compared with the AN membrane: basal vitamin C level was higher, and after the HD session AFR/vitamin C ratio and elastase activity were not significantly increased. Plasma vitamin E levels were not affected. Our study demonstrates that HD is associated with oxidative stress, which can be partially prevented by the use of a vitamin E-coated dialyzer. Our data suggest that this dialyzer may exert a site-specific scavenging effect on free radical species in synergy with a reduced activation of neutrophils.

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.

Pulmonary uptake of Tc-99m-Labeled methylene diphosphonate in a patient with a parathyroid adenoma.

Intense diffuse uptake of Tc-99m-labeled methylene diphosphonate was seen in both lungs of a patient submitted to surgery for a primary parathyroid adenoma. Five scans performed over the 3 yr following the operation showed persistence of lung uptake despite restoration of normal blood calcium concentration. Mild chronic renal failure caused by the hypercalcemia also persisted postoperatively. The present case confirms that pulmonary uptake of bone tracer can occur asymptomatically when both hypercalcemia and renal failure are present. Lung uptake of a bone tracer probably reflects tissue deposition of hydroxyapatite rather than of amorphous structures. Correction of the hypercalcemia failed to resolve the abnormal scan pictures.

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.

Acute renal failure following collective intoxication by Cortinarius orellanus.

Twenty-six young men with no previous medical history all ingested mushroom soup, exclusively made with Cortinarius orellanus. They were hospitalized 10-12 days after the incident. On admission, 12 patients presented with acute tubulointerstitial nephritis with acute renal failure; 8 required haemodialysis. In addition to symptomatic treatment, 9 patients were given corticosteroids. In this group of 12 patients, 8 recovered rapidly, and the other 4 suffered from chronic renal failure for several months. In the other group of 14 patients, initial leukocyturia was observed in 12 cases, although renal function remained normal during a one-year follow-up. Hepatic acetylation and hydroxylation tests performed after 6 months in 22 patients did not provide any explanation for the strong individual sensitivity to the renal toxicity of this fungus.

[An immunoelectrophoretic study of plasma lipoproteins in a case of familial deficiency of lecithin-cholesterol acyltransferase (author's transl)]. / Etude immunoélectrophorétique des lipoprotéines plasmatiques dans un cas de deficience familiale en lécithine-cholésterol acyltransferase

The lipid composition and apopeptide patterns of plasma LDL and VLDL have been studied in a patient with LCAT deficiency, using two-dimensional immunoelectrophoresis. After absorption of a fat meal an elevation of VLDL apopeptides C was observed. Apo-LDL also showed an abnormal relative increase of apo-C. After heparin-induced lipolysis, a shift of apo-C from chylomicra and VLDL to LDL was noticed by the striking increase of apo-C in this last lipoprotein class. In view of the present and previously published results the possible mechanisms involved in lipoprotein catabolism in LCAT deficiency are discussed.

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.

[Factitious hyperchloremia disclosing bromide poisoning. 4 cases]. / Hyperchlorémie factice révélatrice d'intoxication par le brome. 4 observations.

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.

[Aseptic meningitis after isotope cisternography. 2 Cases]. / Méningite aseptique après cisternographie isotopique. Deux observations

In these two patients, as in 13 others described in the literature, a typical meningitic syndrome with excitement, confusion and a fever of 104degrees F (40degrees C) appeared 4-6 hours following the intra-thecal injection. Subsequent lumbar puncture usually reveals a cloudy C.S.F. under increased pressure. The polymorphs and proteins are increased but the glucose remains normal. There are no bacteria either on direct examination or after culture. All the patients receive antibiotics. After a course of three days, the symptoms and the fever have disappeared and the C.S.F. became normal. Bacterial contamination can be ruled out. The relative roles of iodine, radio-acitivity itself, albumine and of the radio-active element which are only used for this radiotracer are discussed. The tracer contains neither stabilizer nor pH buffer. One must presume that the syndrome is due to a direct toxic action rather than to an immunological or allergic reaction. Furthermore, it is of interest that similar reactions, without infection, are seen after spinal anaesthesia and intra-thecal injection of such differing substances such as iodine contrast media, gamma globulins, other isotopes or toxic substances (Lysol) (111In-DTPA).

[Regression of retroperitoneal fibrosis treated by tamoxifen]. / Régression d'une fibrose rétro-péritonéale traitée par le tamoxifène.

By analogy with desmoid tumours, tamoxifen has been used in the treatment of idiopathic retroperitoneal fibrosis. The authors report the 6th case of retroperitoneal fibrosis treated by tamoxifen alone, which had not recurred 11 months after stopping treatment.

[Extracapillary glomerulonephritis]. / Les glomérulonéphrites extracapillaires.

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.