CA Corresponding Author à These authors contributed equally to this study EVIDENCE suggests that cannabinoid receptors, the pharmacologcial target of cannabis-derived drugs, and their accompanying system of endogenous activators may be dysfunctional in schizophrenia. To test this hypothesis, we examined whether endogenous cannabinoid concentrations in cerebrospinal¯uid of schizophrenic patients are altered compared to nonschizophrenic controls. Endogenous cannabinoids were puri®ed from cerebrospinal¯uid of 10 patients with schizophrenia and 11 non-schizophrenic controls by high-performance liquid chromatography, and quanti®ed by isotope dilution gas-chromatography/massspectrometry. Cerebrospinal concentrations of two endogenous cannabinoids (anandamide and palmitylethanolamide) were signi®cantly higher in schizophrenic patients than non-schizophrenic controls ( p , 0.05). By contrast, levels of 2-arachidonylglycerol, another endogenous cannabinoid lipid, were below detection in both groups. The ®ndings did not seem attributable to gender, age or medication. Elevated anandamide and palmitylethanolamide levels in cerebrospinal¯uid of schizophrenic patients may re¯ect an imbalance in endogenous cannabinoid signaling, which may contribute to the pathogenesis of schizophrenia. NeuroReport 10:1665±1669 # 1999 Lippincott Williams & Wilkins.

Our data indicate a distinct role of free and bound leptin in the feedback regulating energy intake and expenditure and could have important implications for our understanding of the physiology and pathophysiology of leptin-dependent signalling.

Proteinuria and enzymuria were measured in 27 patients with Cystic Fibrosis before and after tobramycin therapy. Prior to treatment, kidney function was normal in 23 patients. Four patients showed a pathological proteinuria and two haematuria. Renal biopsy in one patient showed segmental basement membrane alterations on electron microscopy; there were no immunoglobulin deposits. During intravenous therapy with tobramycin (10 mg/kg per day) and azlocillin (100 mg/kg per day) mean urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion rose six-fold and mean urinary alaninaminopeptidase excretion increased ten-fold. After cessation of therapy, enzymuria rapidly returned to pretreatment values in all 14 patients. Aerosol tobramycin therapy in four patients did not affect urinary excretion of NAG. It can be concluded that tobramycin did not cause persistent renal damage in our patients, whether given intravenously or as an aerosol.

Patients with congenital cyanotic heart disease may develop a glomerulopathy with proteinuria and impaired renal function. In order to investigate this problem we conducted a study on 27 patients with uncorrected cyanotic heart disease who were between 1 day and 25 years old. As a consequence of hypoxaemia haematocrit was elevated to 57%. Proteinuria was above 150 mg/day/1.73 m2 body surface in 12 patients. Only one of 9 children under 10 years of age had pathological proteinuria presenting as isolated albuminuria. Seven out of 10 patients between 11 and 20 years had an elevated proteinuria with a glomerular pattern. Creatinine clearance was normal in these patients. All four patients above 20 years of age had a considerable glomerular proteinuria with a mean excretion of 5.7 g/24 h/1.73 m2 body surface. These patients suffered additionally from chronic cardiac failure and creatinine clearance was below the normal range. There was a clear relationship between pathological proteinuria and age of the patients and thus duration of hypoxaemia. Patients with pathological proteinuria had a significant higher erythrocyte count (7.3 +/- 1.3 vs 5.6 +/- 1.4 10(12)/l p less than 0.01) and a lower mean corpuscular haemoglobin. In summary, children with persistent congenital cyanotic heart disease have substantial risk of developing a glomerulopathy if the cyanosis remains unchanged for more than ten years.

Ifosfamide (IFO) chemotherapy has been reported to result in deToni-Debré-Fanconi syndrome in a minority of patients only, but evaluation of tubular transport capacities has identified a substantial number of patients as having subclinical tubular dysfunction. After completion of combination chemotherapy employing IFO (n = 37) or IFO plus cisplatinum (CPL) (n = 27), glomerular and tubular function was assessed in 64 patients by the urinary excretion of transferrin, IgG, albumin, alpha 1-microglobulin (A1M) and N-acetyl-beta-D-glucosaminidase. Sodium dodecyl sulphate polyacrylamide gel electrophoresis was performed in 21 patients. The determination of urinary marker proteins was compared with the glomerular filtration rate, the fractional phosphate and percent amino acid reabsorption. A reduced glomerular filtration rate was observed in 9.8% of patients. Tubular dysfunction was frequent, with a predominance of renal amino acid (57%) and A1M (48%) loss. IFO-mediated renal toxicity was dose dependent. CPL treatment resulted in significant enhancement of tubular toxicity induced by IFO, whereas concomitant gentamicin therapy did not affect tubular function. Measurement of urinary protein cannot replace other tests for tubular dysfunction in IFO-treated patients, because the spectrum of IFO-induced nephrotoxicity includes dysfunction of different and independent transport mechanisms of the proximal tubular system. Increased urinary A1M excretion is an important indicator of impaired tubular protein reabsorption.