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Biomedical subjects

L H Noel

Publications and source records attributed to L H Noel.

At least 19 recordsLinked to original sources
PubMed2005

[Membranous glomerulonephritis during primary Gougerot-Sjögren syndrome].

INTRODUCTION: Glomerulonephritis, mainly membranoproliferative or membranous (MG), is observed much less often than interstitial involvement in Sjögren's syndrome (SS). CASE: We report a case of MG revealed by thrombosis of the inferior vena cava and of a renal vein in a 40-year-old woman with primary SS, which began with polyarthritis, immune-type lymphadenopathy, and Hashimoto thyroiditis and did not include obvious sicca syndrome. After failure of moderate-dose steroids and then azathioprine, each over separate 9-month periods, the MG responded well within a few weeks to monthly alternation of methylprednisolone and oral cyclophosphamide for 6 months. DISCUSSION: SS may be an underestimated cause of glomerulonephritis, especially membranoproliferative and membranous glomerulonephritis. They should be considered even in the absence of obvious sicca syndrome. Although the prognosis is usually good, renal insufficiency can occur. In cases of MG, if moderate-dose steroids fail, monthly alternation of methylprednisolone and cyclophosphamide for 6 months appears effective and well tolerated, with a low risk of carcinogenicity.

Administration, Oral↗
PubMed1995

Protease resistance and binding of Ig light chains in myeloma-associated tubulopathies.

Kidney tubule dysfunction and lesions are frequent complications of myeloma, related to unknown properties of the monoclonal light chain. We have analyzed protease sensitivity and binding properties of urinary light chains from four patients with Fanconi's syndrome, 12 with cast nephropathy, and four control patients without myeloma-associated tubulopathy. All light chains were normal-sized, monomeric and/or dimeric, and none was N-glycosylated. Kinetic studies of light chain digestion by pepsin and the lysosomal enzyme cathepsin B showed the generation of a protease-resistant 12 kDa fragment, corresponding to the V domain of the kappa chain in the four Fanconi's syndrome patients; in two out of four the V domain was also completely resistant to trypsin. Western and dot blots revealed similar patterns of reactivity of light chains from patients with the Fanconi's syndrome towards other light chains. Properties of cast-nephropathy light chains were more heterogeneous but clearly differed from those of Fanconi's syndrome: (i) 9 out of 12 were of the lambda-type; (ii) only four yielded a transient 12 kDa fragment after cathepsin B digestion, but all showed some resistance to proteolysis of the entire molecule or a fragment thereof to at least one protease, at variance with control light chains; (iii) they displayed various patterns of reactivity with other light chains; (iv) 7 out of 12 reacted specifically with Tamm-Horsfall protein (THP) by ELISA, in contrast with those of Fanconi's syndrome. In one patient who presented with cast nephropathy and the Fanconi's syndrome, the light chain exhibited both partial resistance of the V kappa domain to cathepsin B and the highest reactivity with THP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1994

Distribution of integrin subunits in normal human kidney.

We evaluated on serial sections the distribution of a large number of integrin alpha and beta chains in normal adult human kidney: 1) the beta 1 chain and its corresponding alpha subunits (alpha 1, alpha 2, alpha 3, alpha 4, alpha 5, alpha 6), 2) alpha v and beta 3 chains, 3) the beta 2 chain and its corresponding alpha chains (alpha X, alpha M, alpha L), and 4) the beta 4 chain. We also evaluated ICAM-1, VCAM and ELAM and the major extracellular matrix components (ECM). A three step immunoperoxidase technique was used on frozen sections. Each cell of the kidney shows a specific distribution of these molecules. The relation with ECM and some of their ligands was evaluated. This immunohistochemical study shows that there is no strict colocalisation of a given ECM component with its specific receptor.

Adult↗
PubMed1994

Cyclosporin A nephropathy: standardization of the evaluation of kidney biopsies.

An advisory board of nephropathologists with personal experience in the evaluation of biopsies from patients treated with cyclosporin A (CyA) was set up to address the following problems: 1. Definition of CyA nephropathy as seen in patients with autoimmune diseases; 2. Evaluation of the reliability and reproducibility of the diagnostic criteria for the different morphological lesions seen in CyA nephropathy; 3. Classification of the morphological lesions according to their clinical relevance; 4. Estimation of the possible progression of CyA nephropathy with continuous CyA therapy. The most frequent lesions attributable to CyA therapy in patients with autoimmune diseases are tubular atrophy, interstitial fibrosis, and arteriolar hyalinosis. All other lesions are rare. The reproducibility and diagnostic reliability is high for tubular atrophy and interstitial fibrosis, but low for arteriolar lesions even among experienced nephropathologists. The biopsies may be classified according to the severity of tubular atrophy, interstitial fibrosis and arteriolar hyalinosis with regard to their clinical relevance: In group I (within normal limits), CyA therapy can be continued; in group III (moderate-to-severe CyA-related lesions), CyA should be stopped if possible. Among group II biopsies (slight CyA-related abnormalities), no recommendation can be made in the absence of a second biopsy after a further year of CyA therapy. No clear-cut answer can be given concerning the progression of CyA-induced lesions. However, no significant progression has been found in the cases studied to date.

Adolescent↗
PubMed1994

The kidney in cyclosporin A-treated diabetic patients: a long-term clinicopathological study.

This was an analysis of the renal investigations performed in 248 cyclosporin A (CyA)-treated patients who had recent-onset type I insulin-dependent diabetes mellitus (IDDM) to assess the clinicopathological relationships, risk factors and predictive indices of CyA nephrotoxicity, and renal function observed with different CyA treatment regimens. There were four different protocols, using initial CyA dosages ranging from 7.5 to 10 mg/kg/day, with dose modification according to serum creatinine concentration, which was measured regularly in some patients for up to 9 years after starting treatment. Kidney biopsies were obtained from 125 patients (74 adults and 51 children) who had received only CyA for an average duration of 13 months before biopsy and had no other sources of renal injury at this stage of IDDM. Of these patients, 58% showed normal or minimal changes on biopsy, 26% showed slight abnormalities, and 16% showed medium-grade (grade III nephropathy) abnormalities. Lesion severity was related to the degree of interstitial fibrosis and tubular atrophy which, in turn, was related to the use of high maximum CyA dosages. Patients' age, and excessive CyA dose and blood trough levels were the main risk factors, and serum creatinine increase was the best predictive factor of CyA-induced nephropathy. However, CyA-induced renal dysfunction was essentially reversible on dosage reduction, and morphological changes were not followed by progressive renal insufficiency when CyA doses were low and adjusted according to serum creatinine levels. We conclude that, at present, it is recommended that low-dose CyA in combination with other non-nephrotoxic immunosuppressive strategies be used in patients with IDDM.

Adult↗
PubMed1993

Antineutrophil cytoplasm antibodies in systemic polyarteritis nodosa with and without hepatitis B virus infection and Churg-Strauss syndrome--62 patients.

OBJECTIVE: Antibodies directed against components of neutrophil cytoplasm have been detected in various systemic vasculitides and especially in Wegener's granulomatosis. In polyarteritis nodosa (PAN) and Churg-Strauss syndrome, few data are available and correlation between clinical manifestations and antineutrophil cytoplasm antibodies (ANCA) has not been established. Therefore, we tested, before treatment of vasculitis, 62 consecutive patients suffering from PAN with hepatitis B virus (HBV) markers, PAN of unknown etiology or Churg-Strauss syndrome. METHODS: Only patients with PAN and Churg-Strauss syndrome were included in the study. The diseases were histologically and/or angiographically proven. Every patient's serum was tested by an indirect immunofluorescence assay (IFA) and, in 37 cases, by an enzyme linked immunosorbent assay (ELISA). RESULTS: ANCA detected by IFA were observed in 10.7% of the patients with PAN with HBV markers, in 27.3% of the patients with PAN without HBV markers and in 66.7% of the patients with Churg-Strauss syndrome. When ELISA was performed, 11.1% of the patients with PAN associated with HBV infection, 20% of the patients with PAN without HBV markers and 55.6% of the patients with Churg-Strauss syndrome were positive. ANCA were positively correlated with asthma and purpura and negatively correlated with HBV markers. CONCLUSION: Regardless of the technique used, Churg-Strauss syndrome was associated with ANCA in about 60% of the cases while, in PAN of unknown etiology, ANCA were found in about 25% of cases. In contrast, IFA and ELISA only detected ANCA in a limited number of cases of PAN related to HBV infection. ELISA positivity in patients with PAN and Churg-Strauss syndrome was usually associated with antimyeloperoxidase antibodies. In our cases of PAN, ANCA and purpura were significantly correlated, suggesting that, in these cases, small vessels are involved and therefore macroscopic and microscopic PAN coexist. Thus it seems that ANCA are essentially present in the cases of small vessel vasculitis, as has been described, and are not a marker of pure macroscopic PAN, at least at our present level of understanding of these antibodies.

Adult↗
PubMed1993

Anti-GBM disease: predictive value of clinical, histological and serological data.

Twenty-nine patients with anti-glomerular basement membrane (GBM) disease, defined by circulating anti-GBM antibodies and/or linear deposits of immunoglobulin G along GBM, were studied retrospectively to identify prognostic indicators of renal outcome and pulmonary involvement. Patients consisted of 18 males and 11 females aged 6 to 76 years (mean 35.2 +/- 20.2). Goodpasture syndrome developed in 14, disease was confined to renal manifestations in 14 and isolated pulmonary involvement was present in a single case. Pulmonary disease was significantly associated with current smoking (p < 0.01). Among the 29 patients, end-stage renal failure requiring dialysis was initially observed in 16 (55%). Ten of them had anti-GBM glomerulonephritis (GN) and 4 presented with Goodpasture syndrome; the two other patients died very soon after the beginning of the disease. The 17 patients with an unfavourable renal evolution (group 1) and the 12 patients with favourable evolution or chronic renal failure (group 2) were compared. No significant difference was noted between the two groups concerning the age at onset of the disease, sex, cigarette smoking or pulmonary involvement. Conversely, creatininemia over 600 mumol/l, oligoanuria, absence of normal glomeruli, a high percentage of circumferential crescents, circulating anti-GBM antibodies detected by immunofluorescence, and a high level of circulating anti-GBM antibodies evaluated by ELISA were features which indicate an unfavourable renal course (p < 0.01).

Adult↗
PubMed1993

["Idiopathic" extracapillary glomerulonephritides without immune deposits are vascularitides: clinical and serologic analysis].

To determine the spectrum of systemic diseases potentially associated with pauci-immune rapidly progressive glomerulonephritis (GN), most of which being considered as idiopathic, we have analyzed extra-renal manifestations, occurrence of extra-glomerular vasculitis and incidence and specificity of ANCAs in 40 patients selected only on histological criteria. Extra-renal symptoms were unexpectedly observed in all patients but one, and were suggestive of vasculitis in 24 of them. Extra-glomerular vasculitis was evidenced in 18 kidney biopsies and four biopsies from other organs. Among the 33 patients with suspected or established vasculitis, 13 had presumed or biopsy-proven Wegener's granulomatosis (WG), three had a macroscopic form of polyarteritis nodosa and 17 had a clinical presentation compatible with the so-called microscopic polyarteritis previously described in the british literature. An additional patient had clinical signs of WG without clinical and histological evidence of vasculitis. ANCAs were detected in 28/33 and 25/34 sera tested by IF and ELISA, respectively: 19 contained anti-myeloperoxidase (MPO) antibodies and 6 had anti-proteinase 3 (Pr3) activity. Anti-MPO and anti-Pr3 antibodies were present in all clinical subgroups but with various incidences: anti-MPO antibodies were surprisingly more often detected (6/12) than anti-Pr3 (4/12) in patients with suspected or histologically proven WG but anti-Pr3 antibodies were nonetheless 3- to 4-fold more frequent in WG than in non-WG systemic vasculitis (1/12) and necrotizing CGN without evidence of extra-renal vasculitis (1/10). These results strongly suggest that pauci-immune necrotizing CGNs belong to the broad spectrum of necrotizing vasculitides affecting glomerular capillaries. This hypothesis is also supported by the good response of patients to immunosuppressive treatments known for their efficacy in vasculitides, whereas these treatments are usually less successful in severe forms of extra-capillary GN with immune deposits.

Glomerulonephritis↗
PubMed1993

Necrotizing crescentic glomerulonephritis without significant immune deposits: a clinical and serological study.

To determine the spectrum of systemic diseases associated with pauci-immune necrotizing crescentic glomerulonephritis, we have analysed extra-renal manifestations, occurrence of extra-glomerular vasculitis and incidence and specificity of antinuclear cytoplasmic antibodies (ANCA) in 40 patients selected only on renal histological criteria. Extra-renal symptoms were unexpectedly observed in all patients but one, and were suggestive of vasculitis in 24. Extra-glomerular vasculitis was seen in 18 kidney biopsies and four biopsies from other organs. Among the 33 patients with suspected or established vasculitis, 13 had presumed or biopsy-proven Wegener's granulomatosis, three had a macroscopic form of polyarteritis nodosa and 17 could not be adequately classified. An additional patient had clinical signs of Wegener's granulomatosis without clinical and histological evidence of vasculitis. ANCAs were detected in 28 of 33 and 25 of 34 sera tested by immunofluorescence and enzyme-linked immunoassay, respectively: 19 contained anti-myeloperoxidase antibodies and six had anti-proteinase 3 activity. Anti-myeloperoxidase and anti-proteinase 3 antibodies were present in all clinical subgroups but with various frequencies: anti-myeloperoxidase antibodies were more common (six of 12) than anti-proteinase 3 (four of 12) in patients with suspected or histologically proven Wegener's granulomatosis. Anti-proteinase 3 antibodies were 3- to 4-fold more common in patients with Wegener's granulomatosis than in those with systemic vasculitis of other causes (one of 12) or necrotizing crescentic glomerulonephritis without evidence of extra-renal vasculitis (one of 10). These results strongly suggest that pauci-immune necrotizing crescentic glomerulonephritis belongs to the broad spectrum of necrotizing vasculitides affecting glomerular capillaries. This study shows substantial improvement in renal prognosis and life expectancy with aggressive immunosuppressive therapy despite the older age of the patients, dissemination of the vasculitic process and often delayed diagnosis.

Adult↗
PubMed1992

Determination of anti-neutrophil cytoplasm antibodies (ANCA) specificity by immunofluorescence on chronic myelocytic leukemia cells.

ANCA positive sera, detected by the standard immunofluorescence method, derived from 37 patients with vasculitis were studied using formalin-acetone fixed chronic myelocytic leukemia cells (CML). All 37 sera were positive on CML cell smears. Furthermore formalin-actone fixation selectively impaired antinuclear antibody binding without reducing ANCA staining and thus facilitated differentiation of these autoantibodies which is often difficult with the standard immunofluorescence method. Two unequivocal and mutually exclusive ANCA binding patterns were identified using the CML smears: (1) type I with diffuse granular binding confined to the polymorphonuclear (PMN) cell lineage and preferentially staining immature cells; (2) type II with similar binding to the PMN cell lineage and, in addition, granular staining of the basophils. All type I antibodies were associated with a c-ANCA pattern suggesting that the major antigen recognized by these antibodies, recently identified as proteinase 3, is not detectable in basophils. The type II pattern was detected in both p-ANCA (84%) and c-ANCA (16%) positive sera. The type I sera remained positive on PMN cells from a myeloperoxidase (MPO) deficient subject and anti-MPO antibodies could not be detected in this group by ELISA. Conversely the type II pattern occurred in the presence of anti-MPO antibodies identified by immunofluorescence, ELISA and dot-blot with the exception of a single serum with antilactoferrin antibody. Type I binding only was observed in Wegener's granulomatosis (WG) but both patterns were found in microscopic polyarteritis (MPA) and rapidly progressive glomerulonephritis (RPGN).

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1992

Antineutrophil cytoplasmic antibodies in IgA nephropathy and Henoch-Schönlein purpura.

The frequency, isotype, and specificity of antineutrophil cytoplasmic antibodies were investigated in a cross-sectional study of 100 patients with IgA nephropathy and 30 children with Henoch-Schönlein purpura. Two of the patients with IgA nephropathy had high titres of antineutrophil cytoplasmic antibodies which were of IgG isotype and confirmed as antimyeloperoxidase antibodies in solid-phase ELISA and inhibition experiments. Antineutrophil cytoplasmic antibodies were not detected in the children with Henoch-Schönlein purpura and none of the patients in either group had IgA antineutrophil cytoplasmic antibodies. A further 20 IgA nephropathy and 10 Henoch-Schönlein purpura patients were studied longitudinally in different clinical phases at 4-monthly intervals over a 2-year period. None of these patients had or developed antineutrophil cytoplasmic antibodies. We conclude that IgA antineutrophil cytoplasmic antibodies are not involved in the vasculitis of Henoch-Schönlein purpura or in the pathogenesis of glomerular injury in IgA nephropathy. The detection of IgG antimyeloperoxidase antibodies in a small minority of IgA nephropathy patients extends the spectrum of diseases associated with autoimmunity to this antigen but is of uncertain significance.

Antibodies, Antineutrophil Cytoplasmic↗