Liver cell necrosis during administration of clozapine

A 38-year-old woman was treated for mutism with clozapine. After a week liver function disturbances developed, which disappeared when the treatment was discontinued. Histopathological investigation of a liver biopsy specimen revealed extensive liver cell necrosis. So far two patients have been described with cholestatic jaundice induced by clozapine, and one patient with toxic hepatitis due to clozapine.     

Detection of obstructive uropathy in the fetus: predictive value of sonographic measurements of renal pelvic diameter at various gestational ages

OBJECTIVE: The goal of our study was to analyze the fetal renal pelvic diameters measured sonographically at several gestational intervals in live-born neonates subsequently found to have either obstructive uropathy or normal kidneys. This information will improve the efficacy of sonography in the diagnosis of obstructive uropathy. SUBJECTS AND METHODS: From an ongoing prospective study assessing the significance of fetal renal pelvic diameters of 4 mm or more at obstetric sonography, the findings in 29 obstructed kidneys in 24 babies were compared with the findings in 380 kidneys from 233 infants who had no obstruction. Twenty-three infants had unilateral obstruction of the ureteropelvic junction, two had unilateral renal obstruction at the ureterovesical junction, one had posterior urethral valves and in addition had both kidneys obstructed because of obstruction at the ureterovesical junction, one kidney was obstructed because of megaloureter, and one kidney was obstructed because of obstruction in a duplex collecting system. Obstruction was identified on nephrostograms, excretory urograms, or radionuclide renograms. The sonographic findings were compared at three gestational age ranges: 16-23 weeks' gestation, 24-30 weeks' gestation, and 31-40 weeks' gestation. The progression of pelvic dilatation in both groups (12 obstructed and 86 unobstructed) was analyzed for the subset of kidneys examined in all three time periods. RESULTS: At 16-23 weeks' gestation, the difference in mean pelvic diameter between obstructed and unobstructed kidneys was not statistically significant, but the difference between obstructed and unobstructed groups at 24-30 weeks' and 31-40 weeks' gestation was significant (p < .001). Renal pelvic diameter showed a much greater rise in diameter through pregnancy in the obstructed group than in the unobstructed group (p < .0003). The sensitivity of the cutoff point of 4-mm renal pelvic diameter for detecting obstruction was 76% before 23 weeks' gestation, including kidneys with a marked decrease in function postnatally; the sensitivity of a 10-mm cutoff point at 16-23 weeks' gestation was 12%. The likelihood that a fetus had renal obstruction increased with increasing diameter of the fetal renal pelvis in all three time periods. CONCLUSION: Kidneys with significant obstruction postnatally may have no dilatation of the renal pelvis before 23 weeks' gestation. Most obstructed kidneys had pelvic diameters of less than 10 mm before 23 weeks' gestation. During pregnancy, renal pelvic diameter increases at a greater rate in kidneys that later are shown to be obstructed than in those that are not obstructed.     

Endothelial cell injury caused by Candida albicans is dependent on iron

MRL-lpr/lpr mice spontaneously develop manifestations of autoimmunity including arthritis, vasculitis, and glomerulonephritis. The paramagnetic molecule nitric oxide has been implicated as an effector molecule in initiation and propagation of these inflammatory conditions. In this study, we utilized electron paramagnetic resonance spectroscopy to directly detect nitrosylated protein complexes as products of nitric oxide in whole blood and in kidneys of MRL-lpr/lpr mice. Electron paramagnetic resonance spectra of blood samples from MRL-lpr/lpr mice showed nitrosyl hemoglobin species. Amounts of blood nitrosyl hemoglobin in MRL-lpr/lpr mice were significantly increased as compared to age-matched control mice. Electron paramagnetic resonance spectra of MRL-lpr/lpr kidney tissue exhibited a signal characteristic of a dinitrosyl-iron-dithiolate complex at g approximately 2.04. Formation of nitrosylated nonheme protein in diseased kidneys is associated with development of glomerulonephritis in the autoimmune mice. The presence of nitrosylated nonheme protein indicates the formation of nitric oxide within the kidneys of the diseased mice signifying in situ renal nitric oxide formation.     

The effects of environmental conditions on the in vitro activity of selected antimicrobial agents against Escherichia coli

Serotonin (5-hydroxytryptamine, 5-HT) may play an important role in the pathogenesis of schizophrenia. Previous studies suggested that the efficacy of atypical neuroleptic drugs (e.g., risperidone and clozapine) on negative symptoms may be related to the 5-HT2a receptor. Although association studies between MspI polymorphism (T102C) and the 5-HT2a receptor gene and schizophrenia have been reported, their results are still controversial. The aim of this study was to examine the association between T102C polymorphism of the 5-HT2a receptor gene and schizophrenia as well as the association between the polymorphism and negative symptoms in a Japanese population (106 patients with schizophrenia and 109 healthy controls). No significant positive associations were observed. Our results suggest that the 5-HT2a receptor gene is not involved in the pathogenesis of schizophrenia or negative symptoms.