Philippe Remy

Presynaptic dopaminergic function in the striatum of schizophrenic patients

The dopaminergic hypothesis of schizophrenia postulates increased brain dopaminergic activity. Two previous studies reported increased 18F-DOPA uptake with positron emission tomography in schizophrenic patients (n = 5, n = 7). In the present study, striatal dopaminergic function was assessed in vivo in six untreated schizophrenics and seven control subjects, comparable for age and sex. The 18F-fluoro-L-DOPA (18F-DOPA) uptake rate constant Ki was determined in the caudate and putamen using coregistered positron emission tomography and magnetic resonance imaging. No difference between groups for mean Ki was found. The variability of the 18F-DOPA uptake values was higher in the caudate (p < 0.01) and in the putamen (p < 0.001) in schizophrenic patients than in control subjects, suggesting that schizophrenia is a disorder involving heterogeneous states of the striatal presynaptic dopaminergic function.

Immunomodulation with Low-Dose Immunoglobulins for Moderate IgA Nephropathy and Henoch-Schönlein Purpura

Recently, our group has shown that a 3-month course of intravenous immunoglobulin (2 g/kg/monthly) followed by 6 months of intramuscular immunoglobulins (IMIG, 16.5%, 0.35 ml/kg every 15 days) was able to slow or to stop the decline in the glomerular filtration rate, to reduce proteinuria, hematuria, leukocyturia and the histological index of activity on renal biopsy in patients with severe forms of IgA nephropathy (IGAN) and Henoch-Schönlein purpura (HSP). The aim of this open prospective trial was to evaluate the efficacy and safety of low-dose immunoglobulin therapy in moderate IGAN and HSP with permanent proteinuria. Fourteen patients with moderate IGAN [idiopathic IGAN: n = 11; chronic idiopathic HSP: n = 3] and permanent albuminuria were treated with polyvalent IMIG (16.5%) for 9 months (0.35 ml/kg once a week for 1 month, followed by 0.35 ml/kg every 15 days for a further 8 months). Eligibility criteria in the study were Lee histological stage I, II or III, albuminuria between 300 and 2,000 mg/day and a glomerular filtration rate > 70 ml/min/1.73 m2. IMIG were well tolerated and only 1 patient withdrew from the trial. No viral, renal or immunological side effects were observed. IMIG induced a significant decrease in albuminuria as well as in the histological activity index in the 11 cases in which a follow-up biopsy was performed. There was also a decrease in serum IgA, serum beta 2-microglobulin and IgA immune complex levels, and an increase in serum IgG1 levels. Twelve of the 13 evaluable patients improved during treatment.

A Multitracer Dopaminergic PET Study of Young-Onset Parkinsonian Patients With and Without Parkin Gene Mutations

The impact of parkin gene mutations on nigrostriatal dopaminergic degeneration is not well established. The purpose of this study was to characterize by PET using 18F-fluoro-l-3,4-dihydroxyphenylalanine (18F-fluoro-l-DOPA), 11C-PE2I, and 11C-raclopride the pattern of dopaminergic lesions in young-onset Parkinson disease (YOPD) patients with or without mutations of the parkin gene and to correlate the clinical and neuropsychologic characteristics of these patients with PET results. Methods: A total of 35 YOPD patients were enrolled (16 with parkin mutation, 19 without). The uptake constant (Ki) of 18F-fluoro-l-DOPA and the binding potential (BP) of 11C-PE2I (BPDAT) and of 11C-raclopride (BPD2) were calculated in the striatum. Comparisons were made between the 2 groups of YOPD and between controls and patients. For each radiotracer, parametric images were obtained, and statistical parametric mapping (SPM) analysis using a voxel-by-voxel statistical t test was performed. Correlations between the cognitive and motor status and PET results were analyzed. Results: In YOPD patients, 18F-fluoro-l-DOPA Ki values were reduced to 68% (caudate) and 40% (putamen) of normal values (P < 0.0001). This decrease was symmetric and comparable for nonparkin and parkin patients. No correlation was found between the Ki values and cognitive or motor status. 11C-PE2I BPDAT values in YOPD patients were decreased to 56% (caudate) and 41% (putamen) of normal values (P < 0.0001) and did not differ between the 2 YOPD populations. The mean 11C-raclopride BPD2 values were reduced to 72% (caudate) and 84% (putamen) of the normal values (P < 0.02) and did not differ between nonparkin and parkin patients. SPM analyses showed in patients an additional decrease of 11C-raclopride in the frontal cortex and a decrease of 18F-fluoro-l-DOPA and 11C-PE2I uptake in the substantia nigra bilaterally (P < 0.05, false-discovery rate–corrected). Conclusion: Carriers of parkin mutations are indistinguishable on PET markers of dopaminergic dysfunction from other YOPD patients with long disease duration.

Low Prevalence of Antibodies to Hepatitis C Virus among Adult Patients with Idiopathic Membranoproliferative Type I Glomerulonephritis in France

Dr. Guy Rostoker, Service de Néphrologie, Hôpital Henri-Mondor, 51 ‚ avenue du Maréchal-de-Lattre-de-Tassigny, F94010 Créteil (France) Dear Sir, The hepatitis C virus (HCV) has been reported in association with chronic hepatitis, cirrhosis, hepatoma, but also mixed cryoglo-bulinemia [1]. Moreover, case reports of patients with membranoproliferative type I glomerulonephritis and HCV infection most often associated with cryoglobulinemia have been recently published [2-4], suggesting that chronic HCV replication may induce this immune complex nephropathy. HCV has been shown not to be associated with three other types of primary glomerulonephritis in France: membranous nephropathy, IgA nephropathy, and idiopathic nephrotic syndrome (minimal-change disease plus segmental glomerulosclerosis plus IgM nephropathy) [5]. We, therefore, studied the sera of 35 adult patients with idiopathic membranoproliferative glomerulonephritis type I followed at the Department of Nephrology. None exhibited extrarenal symptoms or had cryoglobulinemia. There were 21 men and 14 women. Their median age was 37 (range 17-65), years. Eleven of them have terminal renal failure requiring hemodialysis. Three of these 11 patients are now living with a renal graft. HCV antibodies were detected by means of two second-generation enzyme-linked immuno-sorbent assays (Ortho Diagnostic System, USA; Sanofi Diagnostics Pasteur, France). Twenty of these 35 patients were tested again at least 6 months after the first test with one new third-generation enzyme-linked immu-nosorbent assay to avoid a silent preserologic period or antibodies directed only against the NS 5 protein of HCV (Ortho Diagnostic System, USA). All patients were negative for HCV antibodies. We conclude that HCV is rarely associated with idiopathic membranoproliferative glomerulonephritis type I in France. Therefore, a role for HCV in this nephropathy appears unlikely. References

Biocompatibility of Haemodialysis Membranes: Haemodialysis-Related Leukotriene B4 and C4 Generation

UNLABELLED The aim of our study was (1) to verify whether haemodialysis (HD) with cuprophane (CUP) and polyacrylonitrile (PAN) membranes is associated with the release of vasoactive leukotriene (LT) C4 and chemotactic LTB4 and (2) to analyse the respective roles of lipoxygenase and cyclo-oxygenase metabolites of arachidonic acid in membrane bio-incompatibility. The investigation was performed in 10 uremic patients using hollow-fibre dialysers and dialysed successively, in random order, with CUP and PAN membranes. The arterial and venous (from dialyser) blood was sampled for the measurement of biochemical parameters, plasma LTC4, LTB4 and prostaglandins (PG) 6-keto-F1 alpha, E2, F2 alpha and thromboxane B2 before and after 15, 30 and 240 min of HD. Eicosanoids were measured by RIA after prior extraction and HPLC separation. RESULTS CUP HD was associated with a marked early leukopenia and a delayed decrease in blood pO2. Simultaneously, plasma LTB4 and LTC4 increased significantly in arterial blood after 30 min of HD and in venous blood at the end of session of 240 min. Cyclo-oxygenase metabolites increased as well, but nonsignificantly, with a maximum at the end of HD. PAN HD did not significantly change white blood cell count, pO2, or plasma eicosanoid levels. CONCLUSION CUP membranes stimulate the release of proinflammatory and vasoactive LTB4 and LTC4. PAN membrane haemodialysis is without such side effects. The release of LTs may be an additional valuable marker of membrane bioincompatibility.