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Biomedical subjects

J M Suc

Publications and source records attributed to J M Suc.

At least 19 recordsLinked to original sources

[Study of CD45 isoforms on T CD8 lymphocytes, in the peripheral blood and the graft in patients after kidney transplantation].

We report characterization of CD45 isoforms expressed by CD8+ lymphocytes in peripheral blood and in the graft of 40 kidney transplanted patients who underwent kidney biopsy on the basis of clinical signs suggesting rejection. Standard histological examination of the biopsy fragments and three-color cytofluorimetric analysis of lymphocytes extracted from the same fragments by mechanical and enzymatic treatment were performed simultaneously and compared to the peripheral blood lymphocytes. In 14/40 biopsies where lymphocyte extraction succeeded, the predominant subset was CD8 (CD4/CD8 mean ratio was 0.53). Almost all CD8+ cells were activated: among these CD8+ cells, 55 percent were HLA-DR+, and 68 percent CD45RO+, i.e. of a memory cell type with cytotoxic activity. This situation resembles the in vitro observation made during mitogenic stimulation of lymphocytes by phytohemagglutinin, OKT3 or CML ("culture mixte lymphocytaire"). Beside their evident interest for the diagnosis, these data could be useful for our understanding of the physiopathology of the rejection crisis.

Biopsy, Needle

[Optimization of renal transplantation].

In 1990, 1,949 renal transplantations were performed in France, with a graft survival rate of 89% at one year and 70% at five years. To improve on these results it would be necessary to pursue a dynamic policy in all fields of transplantation: in view of the ever growing number of patients on the transplantation list, more kidneys should be collected; hyperimmunized recipients should undergo reinforced exchanges to have compatible kidneys; immunosuppression must be optimized: just a using cyclosporin and monoclonal antibodies has resulted in a significant advance, so should the discovery of new drugs, such as FK 506, or of more specific monoclonal antibodies, be a source of progress; the complications of immunosuppression must be controlled: prevention protocols and antiviral treatments have considerably reduced the incidence of viral infections. The emergence of malignant tumours directly related to the degree of immunosuppression can be prevented by a rational use of immunosuppressants and by systematic detection. All these advances make it possible to extend the indications of renal transplantation to subjects at risk, notably patients more than 60 years old, and diabetic patients who can successfully benefit from a dual kidney-pancreas transplantation.

France

Evidence for intrarenal kallikrein storage during chromate-induced acute renal failure in rat.

During the course of chromate-induced acute renal failure (ARF), urinary kallikrein excretion (UKE), a serine protease of distal tubule origin in the normal animal was decreased but tissue kallikrein concentration (TK) was increased, suggesting intracellular accumulation. Severe morphological lesions were observed in proximal tubular cells which showed brush border damage, numerous vesicles, necrosis and liquefaction of cytoplasmic material. Less marked changes were also present in distal tubules: large apical vacuoles and swollen mitochondria. Compared to normal rats, using the peroxidase-anti-peroxidase (PAP) method for light microscopy, greater kallikrein immunoreactivity was detected along the apical pole in distal tubules, on the membrane and in the cytoplasm as well as in the glomerulus. By immunoelectron microscopy, kallikrein was found in the connecting apical area, along the luminal, basolateral and basement membranes, in some vesicles, in Golgi apparatus and on ribosomes bound to endoplasmic reticulum. In the glomerulus, kallikrein was observed along the luminal surface of endothelial cell. After 14 days a progressive recovery of renal function, tissue morphology and UKE towards control values was observed. The presence of immunoreactive kallikrein in the glomerulus observed only during ARF confirmed the previous demonstration of kallikrein mRNA in the glomerulus. The cellular accumulation results more likely from a dysfunction of a general secretory mechanism due to cell membrane alteration than from a specific inhibition of kallikrein production and secretion.

Acute Kidney Injury

[Crescent: structure, evolution, pathogenesis].

Extracapillary crescent is an elementary lesion which can be superimposed to any type of glomerulonephritis, or constitute the main lesion as in vasculitis, or appear to be idiopathic. One must oppose cellular crescent which is partially reversible, to irreversible fibrous crescent. Cellular composition of crescents has been much controversial: initially considered as having an epithelial-cell origin, then an exclusive macrophagic origin, crescents are in fact composed of epithelial cells, monocytes-macrophages and lymphocytes all together. The former are prevailing when Bowman's capsule (BC) is intact, whereas macrophages predominate when there is extensive damage of GBM and of BC. The initial event in crescent formation appear to be breaches in glomerular capillary wall, leading the deposition of fibrin within Bowman's space. The consequence is the proliferation of parietal epithelial cells and of activated macrophages followed by a production, in series, of cytokines and growth factors.

Animals

[Micropolyarteritis].

Micropolyarteritis are defined as necrotizing inflammatory lesion of the wall of small vessels affecting different organs. A necrotizing crescentic glomerulonephritis without immuno-deposits is observed in the kidney, frequently involved in this microscopic form of systemic vasculitis. Micropolyarteritis are regrouped with Wegener's syndrome and isolated pauci-immune necrotizing crescentic glomerulonephritis as "ANCA-related vasculitis", whose diagnosis is assessed throw renal biopsy and prognosis dependent on immuno-suppressive treatment. Sixty-one patients treated in our nephrology department for a RPGN during these ten recent years have been retrospectively studied. Among them, twenty-five patients presented clinical and morphologic aspects compatible with the diagnosis of micropolyarteritis. We present their clinical aspects and evolution under treatment.

Antibodies, Antineutrophil Cytoplasmic

[Anti-polynuclear neutrophil cytoplasmic antibodies of the perinuclear type or p-ANCA].

Some neutrophil cytoplasmic auto-antibodies produce perinuclear immuno staining of alcohol-fixed neutrophils called P-Anca pattern. These autoantibodies show chiefly reactivity with myeloperoxidase in Elisa but other specificities have been detected (elastase, cathepsin, lactoferrin). These P-Anca anti-MPO are more frequent with renal angiitis but P-Anca (anti-MPO negative) are associated with other diseases without renal failure (rheumatoid arthritis, Gougerot-Sjogren and ulceritis colitis).

Antibodies, Antineutrophil Cytoplasmic

Combined liver kidney transplantation in primary hyperoxaluria type I. Prevention of the recidive of calcium oxalate deposits in the renal graft.

We report the case of a 31-year-old patient who underwent combined liver and kidney transplantation for primary hyperoxaluria type I. Intensive hemodialysis was performed before the intervention and post-operatively in order to maintain plasma oxalate levels near the normal range. In spite of the correction of the liver enzyme deficiency, oxalate removal from the tissular stores led to prolonged hyperoxaluria, more longer than one year after the transplantation, as already reported. This increased urinary oxalate excretion exposes the renal graft to the risk of recurrence of calcium oxalate deposits and stone formation during a prolonged period. Hemodialysis in the postoperative period and fluid intake allowing a large urine volume might be able to decrease the concentration of urinary oxalate under the critical value of 300 mumol/l, at which supersaturation of urine in respect of calcium oxalate occurs.

Adult

[Sustained-released verapamil and ambulatory recording of blood pressure in mild to moderate essential hypertension].

An open study in 25 patients evaluated the efficacy and safety of Isoptine S.R., in some cases associated with Aldactazine in mild to moderate essential hypertension. After a placebo period of 2 weeks, the patients received sustained release verapamil (240 mg/24 hours) in a single morning dose for 6 months. An increase in the dosage (360 mg/24 hours in two subdoses) could be made during the first month of treatment if the diastolic blood pressure remained greater than or equal to 95 mmHg. If the diastolic blood pressure persisted at these levels at the second monthly assessment, a tablet of Aldactazine was associated. The blood pressure was evaluated by means of conventional clinical determinations and 24-hour ambulatory recordings carried out at the time of inclusion and then after 3 and 6 months of treatment. From the first month of treatment, the casual blood pressure determinations in the supine and standing position fell highly significantly (p less than 0.0001), resulting in a mean reduction of 22.3 mmHg in the systolic blood pressure (-12.6%) and of 17.4 mmHg in the diastolic blood pressure (-17%). The ambulatory recordings of blood pressure also showed a significant reduction in the mean systolic blood pressure over 24 hours (p less than 0.05 at the 3rd month of treatment), in the mean diastolic blood pressure over 24 hours (p less than 0.01) and the mean pressure (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[The European experience of liver-kidney transplantation for primary hyperoxaluria type I. Prevention of recurrent intrarenal oxalate deposits].

Following simultaneous liver-kidney transplantation for primary hyperoxaluria type I, although the missing enzyme is provided by the liver transplant, there is a risk of recurrent calcium oxalate crystal formation in the implanted kidney. The necessary kidney protection methods are extrarenal blood purification, principally haemodialysis and haemofiltration, and an abundant diuresis ensured by copious fluid intakes together with prescription of diuretics. These therapeutic measures reduce the oxalate concentrations in both blood and urine. Oxalates are excreted in large amounts over a long period, owing to the formation of important tissue deposits during systemic oxalosis.

Follow-Up Studies

Immunotactoid glomerulopathy and cutaneous vasculitis.

A 22-year-old woman presented glomerulonephritis with Schönlein-Henoch-like syndrome and monoclonal abnormality. One month later, she developed a rapidly progressive glomerulonephritis with hypertension and persistent purpura. In the two renal biopsies performed during the first and the second attack, mesangial expansion and thickening of the glomerular capillary walls (associated with 50% of crescents in the second biopsy) were observed on light microscopy. By immunofluorescence faint deposits of immunoglobulins (light and heavy chains) and complement components were found present in the mesangium. Electron microscopy showed tubular microfibrils measuring 19-24 nm in the mesangium, subendothelial and subepithelial areas. A skin biopsy performed during the first attack demonstrated leukocytoclastic skin vasculitis. By immunofluorescence, no deposits were observed. Congo red staining for amyloid and cryoglobulinemia were negative. This case is similar to an entity recently described and named immunotactoid glomerulopathy.

Adult

Fanconi's syndrome, kappa light-chain myeloma, non-amyloid fibrils and cytoplasmic crystals in renal tubular epithelium.

A 59-year-old woman with kappa light-chain myeloma had Fanconi's syndrome characterized by renal glycosuria, generalized aminoaciduria, bicarbonaturia and decrease of phosphorus and uric acid reabsorption. A bone marrow biopsy showed the presence of 27% of dystrophic plasma cells; the cytoplasm of these cells was intensely stained with anti-kappa light-chain monoclonal antibodies. By light microscopy, the renal biopsy revealed a tubulointerstitial nephritis without glomerular lesions and with intratubular casts. By immunofluorescence, no deposits were observed along the glomerular and tubular basement membranes, but a positivity with anti-kappa light chain was noticed in some tubular epithelia and casts. By electron microscopy, fibrils (35-nm diameter) were observed in the cytoplasm of proximal tubular cells. These fibrils were situated in vesicles (100- to 600-nm diameter) in the luminal side of tubular cells. In the basal pole of the cell, fibrils seemed to group in crystals (120- to 200-nm diameter). Only kappa light-chain protein was demonstrated in these fibrils and crystals by an immunoelectron microscopic technique. These data suggested the pathogenic role of the fibrils and crystals present in tubular epithelium in the tubular proximal syndrome.

Bone Marrow

Renal complications of intravesical bacillus Calmette-Guérin therapy.

We report 3 patients who developed signs of systemic infection and renal insufficiency after intravesical bacillus Calmette-Guérin (BCG) instillations for a bladder cancer. Renal biopsy showed tubulo-interstitial nephritis with or without epithelioid granulomas in 2 cases, and mesangial glomerulonephritis in the last case. All patients had granulomatous hepatitis in association. It seems that hematogenous dissemination via a traumatic instillation of BCG and/or an immune-complex mechanism may have contributed to the renal damage, which was only partially reversible in 2 patients.

Administration, Intravesical

Immunofluorescent deposits on the tubular basement membrane in human renal transplant.

In this retrospective study, the presence of tubular basement membrane (TBM) deposits of IgG and/or C3 was demonstrated in 41 renal transplants (out of 95 studied). The follow-up of these transplants varied from 9 to 19 years. The deposits were of 'linear' type in 9 cases (circulating anti-TBM antibodies were detected in 7 cases by radioimmunoassay tests and/or indirect immunofluorescence), 'granular' type in 22 cases and 'atypical' with linear and granular segments in 10 cases. Light microscopic diagnosis was acute rejection in 26 cases (33 biopsies) associated with deposits along the TBM:linear (6 cases), granular (13 cases) and atypical (7 cases). Chronic rejection present in 15 transplants (21 biopsies) was associated with linear (2 cases), granular (9 cases) and atypical (4 cases) deposits along the TBM. Electron microscopic study of renal tubules showed altered TBM with thickening, lamellation and splitting. Electron-dense deposits were not demonstrated in cases of linear deposits. A long-term follow-up study did not show any difference in survival of transplants presenting acute or chronic rejection associated or not with TBM deposits. If we consider the outcome of the transplants with TBM deposits, those with granular type seemed to have the poorest prognosis at long term, whatever the type of rejection. In the linear TBM deposits group, all the transplant nephrectomies which occurred (7 out of 9 cases) have been performed within 5 years.

Adolescent

Increase in urinary kallikrein excretion following hemodialysis.

Urinary kallikrein excretion (UKE) was measured in 20 patients before and after hemodialysis (HD). When compared to the values of normal subjects (136 +/- 56 micrograms/24 h, n = 100), UKE was decreased in all patients before HD (6.6 +/- 5.8 micrograms/24 h, p less than 0.001, n = 20). After HD a significant increase in 24-hour UKE was observed in all patients (18.6 +/- 7.2 micrograms/24 h, p less than 0.05, n = 20). Expressed as the individual percent increase, the UKE enhancement ranged from 16 to 670%. It was due to an enhancement in the excretion of the active form which represented 52 +/- 6.8% before HD and reached 76.3 +/- 7.5% of the total form after HD (p less than 0.01). The excretion of the inactive form remained unchanged. The increase in UKE was found to be significantly correlated with reductions in urinary sodium, potassium, and osmolality (r = -0.826, r = -0.568, r = -0.847, respectively, p less than 0.01, n = 20). The increase in UKE following HD could not be explain by an increase in aldosterone as urinary aldosterone decreased. A transient improvement in intracellular homeostasis (removal of inhibitory toxins and normalization of osmotic pressure) could be evoked. The increase in UKE 24 h after HD points out a new situation confirming the relations of UKE with changes in osmolality and extracellular volume.

Adult

Pharmacokinetics of a low molecular weight heparin (Fraxiparine) in various stages of chronic renal failure.

This study investigates the pharmacokinetics of a low molecular weight heparin (Fraxiparine) after a single bolus intravenous injection of 100 antifactor Xa IC U.kg-1 in 3 groups of patients affected by chronic renal insufficiency of various severity: group A (n = 7) was composed of hemodialyzed patients; groups; B (n = 7) had a creatinine clearance ranging from 10 to 20 ml.min-1 and group C (n = 5) from 30 to 50 ml.min-1. There was no significant difference between the pharmacokinetic parameters determined in the 3 groups of patients and no correlation between these parameters and the creatinine clearance. However, when compared to the values established in a group of 12 healthy volunteers, the half-life of disappearance of the antifactor Xa activity was significantly prolonged. Therefore it is advised to monitor antifactor Xa activity in patients affected by chronic renal insufficiency of any severity to avoid a possible accumulation phenomenon.

Adult