Hepatic osteodystrophy in chronic cholestasis: evidence for a multifactorial etiology

Children with cholestatic liver disease have been thought to develop hepatic osteodystrophy resulting from vitamin D and calcium malabsorption, resulting in secondary hyperparathyroidism and osteomalacia or rickets. However, treatment with vitamin D has not always proven successful in improving the bone disturbance. The aim of our study was to determine the role of vitamin D deficiency in the pathogenesis of hepatic osteodystrophy. We studied five patients, three female and two male, ages 0.9-19 yr, with biopsy-proven chronic cholestatic liver disease and previously low serum levels of vitamin D despite oral intake of vitamin D preparations. Patients were admitted to the Clinical Research Center for 8 days for sunlight deprivation and ultraviolet light substitution and for determinations of serum 25-hyroxyvitamin D(25(OH)) D2 and -D3, osteocalcin, and type I collagen telopeptide (ICTP), the last two being markers of bone formation and resorption, respectively. Samples were taken on admission, at discharge, and 1 month later. Results demonstrated low serum levels of osteocalcin and normal circulating levels of ICTP. Admission serum 25(OH)D2 levels were uniformly low or undetectable and remained so. Admission levels of circulating 25(OH)D3 were normal or low and did not rise during ultraviolet light therapy or subsequent resumption of oral vitamin D therapy and remained low 1 month later. These results indicate that in the face of low-normal to low total 25(OH)D levels, the low osteocalcin and normal ICTP levels suggest that decreased bone formation and not increased bone resorption is the main determinant of bone loss in a subset of children with chronic cholestatic liver disease.     

Antileishmanial activity of a linalool-rich essential oil from Croton cajucara

The in vitro leishmanicidal effects of a linalool-rich essential oil from the leaves of Croton cajucara against Leishmania amazonensis were investigated. Morphological changes in L. amazonensis promastigotes treated with 15 ng of essential oil per ml were observed by transmission electron microscopy; leishmanial nuclear and kinetoplast chromatin destruction, followed by cell lysis, was observed within 1 h. Pretreatment of mouse peritoneal macrophages with 15 ng of essential oil per ml reduced by 50% the interaction between these macrophages and L. amazonensis, with a concomitant increase by 220% in the level of nitric oxide production by the infected macrophages. Treatment of preinfected macrophages with 15 ng of essential oil per ml reduced by 50% the interaction between these cells and the parasites, which led to a 60% increase in the amount of nitric oxide produced by the preinfected macrophages. These results provide new perspectives on the development of drugs with activities against Leishmania, as linalool-rich essential oil is a strikingly potent leishmanicidal plant extract (50% lethal doses, 8.3 ng/ml for promastigotes and 8.7 ng/ml for amastigotes) which inhibited the growth of L. amazonensis promastigotes at very low concentrations (MIC, 85.0 pg/ml) and which presented no cytotoxic effects against mammalian cells.     

Peroxynitrite enhances the ability of Salmonella dublin to invade T84 monolayers

In the intestine, epithelial cells continually produce and secrete low levels of nitric oxide (NO). Salmonella sp. invade epithelium by responding to environmental stimuli. The aims of this study were to determine the effect of reactive nitrogen intermediates (RNIs) on S. dublin and S. typhimurium growth and invasion of T84 epithelial monolayers. Intracellular NO formation was inhibited by 7-nitroindazole (7-NI) or N(G)-monomethyl-L-arginine, monoacetate (L-NMMA); extracellular NO and peroxynitrite were scavenged with ferro-hemoglobin or urate. The effect of authentic peroxynitrite (ONOO-); 3-morpholino-sydnonimine (SIN-1), which releases ONOO- via NO and superoxide; spermine NONOate, which releases only NO; or superoxide generated by xanthine oxidase and pterin on S. dublin and S. typhimurium growth and invasion were examined. Inhibition of NO synthesis and scavenging of extracellular NO or peroxynitrite reduced S. dublin invasion into T84 monolayers and enhanced bacterial growth. Pre-exposure of S. dublin to ONOO- and SIN-1 increased subsequent bacterial invasion into T84 monolayers. Conversely, exposure of bacteria to spermine NONOate or superoxide did not affect S. dublin invasion. In contrast, S. typhimurium invasion was not affected by pre-treatment with NO donors. In conclusion, exposure of S. dublin to ONOO- enhances the ability of the bacteria to invade epithelial cells. These results suggest that luminal ONOO- may have a novel role as an extracellular signal between invasive bacteria and epithelial cells.     

West Nile virus: case report with MR imaging findings

We report a case of serologically proved West Nile virus encephalitis. Striking bilateral hyperintensities were noted in the basal ganglia and thalami on T2-weighted and fluid-attenuated inversion recovery MR images, similar to previous accounts of the imaging findings in cases of Japanese encephalitis. Recognition of the MR imaging appearance of this entity is important because of the expanding epidemic.     

Management of urethral recurrence in patients with Studer ileal neobladder

OBJECTIVE: The overall risk of urethral recurrence (UR) of transitional cell carcinoma (TCC) in patients with orthotopic neobladder ranges from 2% to 6%. We are presenting herein our experience in order to evaluate and define the management of these patients, since the cases with urethral recurrence in patients with orthotopic neobladder are very scarce. MATERIALS AND METHODS: Five hundred and sixteen radical cystectomies due to TCC were performed at our Centre between January 1990 and February 1998. One hundred and thirty-eight of them (26.7%) underwent an orthotopic neobladder procedure with the Studer's technique. We are reviewing five cases of UR in patients with orthotopic neobladder, the cystectomy indications and the differences between the clinical and the pathologic stages. We are also assessing its clinical presentation, diagnosis, treatment and evolution. RESULTS: Five patients (3.6%) from 50 to 71 years old with Studer's orthotopic neobladder presented with UR. All of those neobladders were initially superficial TCC, mostly multifocal, and all had failed the endovesical treatment. Endoscopic treatment was administered in two cases with superficial UR. One patient with urethral CIS received intraurethral BCG instillations. One case because of multiplicity, and another due to the presence of an infiltrating urethral tumour, underwent urethrectomy and neobladder exeresis. In both cases, the intact 15-20cm isoperistaltic proximal ileal limb of the Studer-type orthotopic neobladder was used as an ileal conduit. CONCLUSIONS: UR in patients with orthotopic bladder substitution is unusual. A conservative approach is possible when dealing with superficial recurrences. In cases of urethrectomy, the isoperistaltic proximal ileal limb of the Studer neobladder may be used as an ileal conduit.     

Minimum effective doses of haloperidol for the treatment of first psychotic episode: a comparative study with risperidone and olanzapine

Minimum doses of haloperidol might show similar efficacy and side-effects compared to atypical antipsychotics. The objectives of this study were to compare the efficacy of minimum doses of haloperidol with standard doses of risperidone and olanzapine on a 6-month open trial in first psychotic episode patients and to examine the effect of compliance on their outcome. Forty-two patients were recruited and started on flexible doses of these drugs. Olanzapine was given with no cost to the patients. Efficacy and side-effects were monitored every 3 months using standardized assessments. Thirty patients completed the study. All treatment groups showed improvement in positive, negative and depressive symptoms. There were no differences in side-effects among them. The haloperidol group required higher doses of anticholinergics. The rate of treatment discontinuation was higher in the risperidone group due to the direct cost. Minimum doses of haloperidol might prove to be a good choice of treatment for patients with a first episode of psychosis.     

Gelatin particle indirect agglutination and enzyme-linked immunosorbent assay for diagnosis of strongyloidiasis using Strongyloides venezuelensis antigen

Routine microscopical examination of stool specimens for diagnosis of strongyloidiasis is insensitive and serological methods using Strongyloides stercoralis antigen are at present not available for field studies. We evaluated 2 techniques, enzyme-linked immunosorbent assay (ELISA) and gelatin particle indirect agglutination (GPIA), using an antigen obtained from the rodent parasite, S. venezuelensis. Fifty-four Peruvian patients with different clinical forms of strongyloidiasis were studied: 12 asymptomatic, 31 symptomatic, and 11 hyperinfection cases. Our results demonstrate that both ELISA and GPIA using S. venezuelensis antigen are useful for diagnosis of strongyloidiasis, with sensitivities of 74.1% and 98.2%, respectively and a specificity of 100% for both techniques. We found that GPIA is a highly sensitive test for patients with suspected chronic infection and/or hyperinfection. In the hyperinfection cases, significantly lower concentrations of specific immunoglobulin antibodies and eosinophils (P < 0.001) were found compared with the asymptomatic and symptomatic cases.