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Antibodies directed against myeloperoxidase (anti-MPO) were detected, using a solid-phase ELISA and purified sputum myeloperoxidase as the substrate, in 54 sera from 22 patients. Anti-MPO were present in 17 patients with crescentic glomerulonephritis (CGN), Wegener's granulomatosis (WG) and microscopic polyarteritis (MPA), and thus are associated with different forms of vasculitis. Anti-MPO were also present in five out of 20 patients with systemic lupus erythematosus (SLE). Anti-MPO activity in SLE sera was low, in contrast to the high titers observed in patients with vasculitis. All positive sera had IgG anti-MPO (except two SLE sera) and most of them also contained low-titered IgM anti-MPO. Only three patients had high IgM anti-MPO activities, the significance of which remains to be determined. In patients with CGN, WG or MPA, the anti-MPO titer decreased following therapy and paralleled the disease activity. Thus, anti-MPO constitute a useful diagnostic tool and a sensitive marker of disease activity in this group of patients with vasculitis.

Six cases of chronic renal failure related to granulomatous renal sarcoidosis are reported and compared with data in the literature. The particular features of sarcoidosis granulomatous interstitial nephritis should be emphasised because presentation may be misleading. Renal failure usually presents with a rapidly progressive course, either isolated or associated with mild proteinuria and sterile leukocyturia, while extrarenal localisations may be absent. Diagnosis should be suspected on the basis of elevated or paradoxically normal serum calcium concentrations, due to increased plasma concentrations of calcitriol, while immunoreactive circulating parathormone concentrations are depressed. Calcitriol as well as angiotensin-converting enzyme could represent unregulated secretion products from granulomatous tissue and their plasma concentrations may roughly reflect activity of the disease. Early corticosteroid treatment dramatically improves renal function but long-term renal prognosis may be oblitered due to progressive chronic renal failure related to fibrosis scarring.

We present a mass-based readout for agglutination assays. The suspended microchannel resonator (SMR) is used to classify monomers and dimers that are formed during early stage aggregation, and to relate the total count to the analyte concentration. Using a model system of streptavidin functionalized microspheres and biotinylated antibody as the analyte, we obtain a dose-response curve over a concentration range of 0.63–630nM and show that the results are comparable to what has been previously achieved by image analysis and conventional flow cytometry.

We present an integrated microelectronic device for amplification and label-free detection of nucleic acids. Amplification by polymerase chain reaction (PCR) is achieved with on-chip metal resistive heaters, temperature sensors, and microfluidic valves. We demonstrate a rapid thermocycling with rates of up to 50 degrees C s(-1) and a PCR product yield equivalent to that of a bench-top system. Amplicons within the PCR product are detected by their intrinsic charge with a silicon field-effect sensor. Similar to existing optical approaches with intercalators such as SYBR Green, our sensing approach can directly detect standard double-stranded PCR product, while in contrast, our sensor does not require labeling reagents. By combining amplification and detection on the same device, we show that the presence or absence of a particular DNA sequence can be determined by converting the analog surface potential output of the field-effect sensor to a simple digital true/false readout.

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Most atomic force microscopes and cantilever-based sensors use an optical laser beam detection system to monitor cantilever deflections. We have developed a working model that accurately describes the way in which a position sensitive photodetector interprets the deflection of a cantilever in these instruments. This model exactly predicts the numerical relationship between the measured photodetector signal and the actual cantilever deflection. In addition, the model is used to optimize the geometry of such laser deflection systems, which greatly simplifies the use of any cantilever-based instrument that uses a laser beam detection system.

We present 8 cases of membranoproliferative glomerulonephritis (MPGN) associated with cryoglobulinemia and hepatitis C virus infection. We think that HVC infection may be searched during diagnostic of MPGN.

We report 28 cases of acute arterial thrombotic events and 13 other arterial manifestations during 155 cases of antiphospholipid syndrome.

We report in four patients with primary hyperaldosteronism a decrease in plasma aldosterone and an increase urinary Na/K during treatment with nadroparin (4100 or 615 a anti Xa IU).

Pharmacokinetics of cefadroxil, a new orally semisynthetic cephalosporin, was studied in 5 subjects with normal renal function and in 20 patients with varying degrees of renal insufficiency. All subjects received 1,000 mg per os in a single dose and the elimination phase was studied. In healthy subjects, elimination half-life (T1/2) was 1.39 +/- 0.06 h. Apparent volume of distribution was 0.305 liters/kg and area under the serum concentration versus time curve AUC was 82.94 +/- 19.98 microgram . h/ml. Peak level averaged 25.72 +/- 4.68 microgram . ml-1 and occurred at 1.20 +/- 0.45 h postingestion. 93.0 +/- 3.6% of the dose was recovered in urine during the first 24 h. Renal and serum clearance averaged 166.7 and 172.4 ml . min-1/1.73 m2, respectively. In patients with renal insufficiency, T1/2 increased to 25.49 h in severe chronic renal failure. Renal impairment did not significantly modify volume of distribution. During a 6- to 8-hour hemodialysis session, antibiotic serum concentrations decreased by 75.4 +/- 5.6%. Dosage schedules could be suggested on the basis of these pharmacokinetic results.

A 35 year-old woman developed severe systemic lupus erythematosus 9 years after thymectomy for myasthenia gravis. "Seric Thymic Factor" (STF) was low; T helpers subset, T helpers/T suppressors ratio and to a lesser extent T suppressors subset were decreased. Suppressor cell function investigated by Concanavaline A lymphocyte reactivity was low. Under cyclophosphamide, plasmapheresis and steroids all clinical and biological symptoms improved but STF remained low; T helpers, T suppressors subsets and T helpers/T suppressors ratio increased but did not reach the normal range. Statistical and immunological arguments suggest that the association between systemic lupus erythematosus and myasthenia gravis did not occur only by chance. Moreover, thymectomy might have played a role by decreasing the number and function of some subpopulations of lymphocytes.

The elimination kinetics of aztreonam (SQ 26,776), a new, completely synthetic, monocyclic beta-lactam antibiotic, were studied after the administration of a single 1g intravenous dose. Five healthy volunteers and 20 patients with various degrees of renal insufficiency were enrolled in this study. Concentrations of aztreonam in serum and urine were determined by both microbiological and high pressure liquid chromatography (HPLC) assays. The pharmacokinetic parameters for aztreonam were calculated on the basis of a 2-compartment open model. Serum concentrations of aztreonam at 10 minutes after administration were approximately 100 micrograms/ml in all subjects, regardless of renal function (HPLC assay). The mean serum half-life during the alpha-phase showed no important variation with renal function. The mean serum half-life during the beta-phase was 1.8 hours in normal subjects and 8.4 hours in haemodialysis patients (HPLC assay). There was a linear correlation between the serum clearance of aztreonam and creatinine clearance. The mean cumulative urinary recovery of aztreonam in 48 hours was 60 to 70% of the administered dose in normal subjects but this was reduced in the presence of renal insufficiency. SQ 26,992, the microbiologically inactive metabolite of aztreonam resulting from hydrolytic opening of the beta-lactam ring, was undetectable in the serum of normal subjects but was found in low levels in uraemic patients. Half of a 1g intravenous dose of aztreonam was eliminated during 4 hours of haemodialysis. Guidelines for administration of aztreonam in the presence of renal failure are given.

• In one patient with pulmonary sarcoidosis, hypertension occurred during the course of the disease. Aortography showed extensive narrowing of the right renal artery. Surgical exploration disclosed extensive periaortic and perirenal fibrosis. This fibrosis encircled the right renal artery and caused extrinsic compression. Pathological examination disclosed a large amount of histiocyte epithelioid infiltration in various samples of the fibrosis and particularly in the adventitia of the renal artery, highly suggestive of sarcoidal angiitis. Surgical biopsy was performed on both kidneys. The right kidney, protected by arterial stenosis, was little altered, while the left kidney showed extensive interstitial, tubular, and glomerular lesions. The glomerular lesions were focal and segmental hyalinosis. (Arch Intern Med 140:1240-1242, 1980)

Apalcillin is a new semisynthetic penicillin used as a sodium salt. More than 4,000 patients have been treated with this antibiotic, but increased serum creatinine levels were noted in 18 cases. In 5 of these cases, apalcillin was possibly responsible, and in 13 it was doubtful. We decided to study renal function of normal volunteers treated with 4 g of apalcillin. Three periods were studied: a pretreatment control period of 80 min followed by a treatment period of 60 min and a posttreatment period of 40 min. Inulin and p-aminohippurate (PAH) infusion were continued during all three periods. At the beginning of the treatment period, 2 g of apalcillin was injected as a bolus, followed by infusion of 2 g of apalcillin over 1 h. Urinary volume was measured every 20 min. Creatinine, insulin, and PAH clearances and urinary excretion of sodium, potassium, calcium, and magnesium were calculated for each period. Urinary beta-2-microglobulin excretion was also assessed. Analysis of variance was done. We observed no variation in clearances of creatinine or inulin or in urinary electrolyte output. PAH clearance was significantly decreased during apalcillin infusion. Apalcillin appeared to compete with PAH for proximal tubular secretion but induced no further renal dysfunction.

The pharmacokinetics of single doses (15 mg/kg) of cefotaxime and each of its metabolites were examined in six normal subjects and 24 patients who showed various degrees of renal insufficiency. An additional nine patients with renal failure were entered into a multiple-dose study in which cefotaxime (1 g) was given twice daily for five to seven days. After intravenous administration, the levels of cefotaxime in serum declined in two phases. The half-life for the terminal phase was 1.10 +/- 0.78 hr. Cefotaxime administered intramuscularly was well absorbed from the injection site (91% +/- 19%) and produced maximal levels of 25.5 +/- 3.5 microgram/ml in serum at approximately 0.5 hr after injection. The levels of the desacetyl metabolite in serum were comparatively low, and the half-life of this metabolite was 1.3 hr. Microbiologic measurements of cefotaxime showed that the half-life of the drug was lower in normal subjects (1.71 +/- 0.90 hr) than in patients with severe renal impairment (half-life, 10.20 +/- 3.43 hr). However, this difference was due primarily to desacetylcefotaxime. Specific measurement by high-performance liquid chromatography indicated only a slight increase in the half-life of cefotaxime, whereas the increase in half-life of desacetylcefotaxime was greater. The most pronounced increases in half-life of metabolites occurred when values for creatinine clearance in patients were below about 5 ml/min per 1.73 m2. When cefotaxime was administered repetitively, the ratio of maximal serum levels after the last dose to those after the first dose demonstrated minimal accumulation of intact drug. The average accumulation of desacetylcefotaxime in this group of patients was about twofold, and that for metabolites M2 and M3 was approximately fourfold. This accumulation of metabolites was observed only in those patients with severe renal impairment and was not excessive. Hemodialysis caused a significant reduction in the half-life of both cefotaxime and desacetylcefotaxime. Recommendations are made for the adjustment of dosing schedules in patients with renal failure.

The pharmacokinetics of two oral forms of fosfomycin, tromethamine (trometamol) salt and calcium salt, were studied in five young (age, 29 +/- 3 [standard deviation] years) and eight elderly (age, 72 +/- 6 years) adults. The subjects received a single 40-mg/kg (body weight) (approximately equal to 3-g) calcium fosfomycin dose and a 25-mg/kg (approximately equal to 2-g) tromethamine fosfomycin dose in fosfomycin acid form. Blood and urine samples were collected for 24 h. Antibiotic concentrations in serum and urine were measured by microbiological assay. In all subjects, the peak levels of the calcium salt in serum were two- to fourfold lower than those of the tromethamine salt (6 to 7 and 18 to 22 micrograms/ml, respectively), indicating poor intestinal absorption of the calcium form. The elimination half-life of the two oral forms was about 5 h in young adults, and the half-life was only moderately longer in elderly subjects, with large individual variations: 8.28 +/- 5.51 h for tromethamine fosfomycin and 11.80 +/- 6.86 h for calcium fosfomycin. In elderly subjects, absorption of the tromethamine salt form was not modified, but the time to peak level was delayed for the calcium salt (2.58 +/- 0.54 h versus 1.41 +/- 0.67 h in young adults). Pharmacokinetic elimination of the two forms of fosfomycin was only moderately affected in elderly subjects; we observed lower urinary elimination, about 58 versus 28% of the dose in 24-h urines for the tromethamine salt and decreased renal clearance of both forms. However, the dosages of tromethamine and calcium fosfomycin need not be adjusted for elderly subjects who have endogenous creatinine clearances above 50 ml/min per 1.73 m2.

The pharmacokinetics of temocillin were investigated in five normal subjects and in 20 uraemic patients. Normal subjects were given single intravenous doses of 3.75, 7.5 and 15 mg/kg of temocillin and a single intramuscular dose of 7.5 mg/kg. Patients with renal impairment were given 7.5 mg/kg of the antibiotic intravenously. A three-compartment open model was used to calculate kinetic data after iv administration. Pharmacokinetic parameters of temocillin were similar both for the three iv doses and for the im dose. The terminal serum half-lives (T1/2 beta) averaged 4.75-5.88 h. The central distribution volume (Vc) and the apparent volume of distribution (Vd area) were 0.093-0.111 and 0.268-0.303 l/kg, respectively. Renal and total body clearances were within 27.4-34.1 and 40.2-47.8 ml/min/1.73 m2, respectively. 67.4-71.5% of the dose was recovered unchanged in urine over 24 h. Intramuscular dosing of 7.5 mg/kg gave a mean peak level of 26.71 mg/l at 1.67 h. In uraemic patients, similar maximum serum concentrations were found after a single 7.5 mg/kg iv dose. The terminal half-life increased according to the degree of renal failure, from 5 h in normal subjects to about 30 h in severe uraemic patients. Renal impairment did not significantly modify Vd area, fractional clearance (Cr/GFR) and non renal clearance. 65.2% of the antibiotic was removed during haemodialysis. Dosage adjustments of temocillin in uraemic patients are proposed.

The pharmacokinetics of azlocillin were investigated in five healthy subjects and in 16 subjects with chronic renal failure. After intravenous bolus injection of a single dose of 30 mg/kg in normal subjects, pharmacokinetic data were calculated, using a two-compartment open body model. The mean distribution serum half-life (T 1/2α ) was 0.11 h, and the mean elimination serum half-life (T 1/2β ) was 0.89 h. The volume of the central compartment ( V C ) was 7.36 liters/1.73 m 2 , and the apparent volume of distribution ( V dss ) was 14.15 liters/1.73 m 2 , i.e., 21.9% of body weight. The T 1/2β after a 30-min intravenous infusion of 80 mg/kg to the same healthy subjects was 1.11 h. Serum clearances ( C S ) for the 30- and 80-mg/kg doses were 215.0 and 152.9 ml/min per 1.73 m 2 . The mean renal clearances ( C R ) were 145.2 and 94.1 ml/min per 1.73 m 2 for the respective doses. Between 61.8 and 69.6% of the injected dose was recovered in urine during the first 24 h. The elimination half-life in subjects with chronic renal impairment increased with the degree of renal insufficiency. After a 30-min intravenous infusion of 80 mg/kg the T 1/2β values were 2.03, 4.01, and 5.66 h with creatinine clearances ( C cr ) within 30 to 50, 10 to 30, and 2 , respectively. Urinary elimination was inversely related to the degree of renal impairment. In four patients out of and on a 6-h hemodialysis session mean elimination half-life values were 6.53 and 2.81 h, respectively. The fraction of drug removed by dialysis was 45.8%. The linear relationships between the elimination of half-life (T 1/2β ) and serum creatinine and the elimination rate constant (β) and creatinine clearance ( C cr ) provided a basis for adjustment of dosage in renal failure.

1. The pharmacokinetics of a single 1 mg dose of cilazapril were determined in six subjects with normal renal function and in 19 uraemic patients with various degrees of renal impairment. 2. Significant decreases in systolic and diastolic blood pressure were noted in all groups of subjects between 2 and 8 h after administration of 1 mg cilazapril. 3. There was a significant correlation between ACE inhibition at 24 h and creatinine clearance (CrCL). 4. For cilazapril, Cmax and tmax were independent of creatinine clearance. AUC(24) was inversely related to CrCL and apparent plasma clearance (CL/F) was directly related to CrCL. 5. For cilazaprilat, Cmax and tmax were related to creatinine clearance. AUC(24) was inversely related to CrCl and apparent plasma clearance (CL/F) was directly related to CrCL. 6. Dialysis clearance was approximately 2 l h-1 for cilazapril and for cilazaprilat. 7. The effects of renal impairment on cilazapril and cilazaprilat kinetics were similar to those observed for other inhibitors of angiotensin-converting enzyme such as captopril, enalapril and lisinopril. 8. It may be necessary to modify doses of cilazapril for the treatment of essential hypertension in uraemic patients. When creatinine clearance was below 15 ml min-1 cilazaprilat concentrations were increased, half-lives were prolonged and ACE inhibition remained above 90% for at least 24 h. A reduced dosage is indicated for these patients. 9. In patients requiring haemodialysis, maintenance doses of 0.5 mg given after each haemodialysis session are sufficient.

La polykystose rénale autosomique dominante (PKRAD) est la maladie rénale héréditaire la plus fréquente. Deux gènes peuvent en être responsables : le gène PKD1 dans 85% des cas et le gène PKD2 dans 15% des cas. Ces gènes codent respectivement pour la polycystine 1 et la polycystine 2, des protéines situées sur le cil primaire des cellules tubulaires épithéliales rénales et sensibles aux variations du flux tubulaire. Leur altération induit une perturbation de la signalisation calcique intracellulaire qui déclenche une prolifération cellulaire et le développement de kystes. L'augmentation du nombre et de la taille des kystes aboutit à la destruction du parenchyme rénal et conduit à l'insuffisance rénale terminale. L'apparition précoce d'une hypertension artérielle, avant le développement de l'insuffisance rénale est caractéristique de la maladie. Cette hypertension artérielle survient plus précocement que dans la population générale et n'est pas rare chez l'enfant. Elle contribue à la dégradation de la fonction rénale. Pendant longtemps, l'hypertension artérielle a été attribuée à une activation du système rénine angiotensine consécutif à la compression des vaisseaux rénaux par les kystes. Récemment, la mise en évidence de l'expression des polycystines dans la paroi vasculaire, sur les cellules endothéliales et sur les cellules musculaires lisses, a permis d'envisager d'autres mécanismes impliqués dans la pathogénèse de l'hypertension artérielle. Les polycystines pourraient en effet être impliquées dans la mécanotransduction des contraintes de cisaillement qui s'exercent sur la paroi des cellules endothéliales. Elle pourraient être également impliquées dans la régulation du tonus myogénique. Leur altération pourrait expliquer les anomalies fonctionnelles et structurales vasculaires observées dans la polykystose rénale autosomique dominante. Nous présentons dans ce travail une revue de la littérature sur les caractéristiques épidémiologiques, physiopathologiques et thérapeutique de l'hypertension artérielle dans la polykystose rénale autosomique dominante. Nous discutons les données de la littérature à la lumière des avancées récentes et émettons des hypothèses physiopathologiques. Enfin, nous présentons le protocole de notre travail de recherche actuellement en cours au CHU de Rouen.