Randomised clinical trial: the effects of a multispecies probiotic vs. placebo on innate immune function, bacterial translocation and gut permeability in patients with cirrhosis.

BACKGROUND: Probiotics may correct intestinal dysbiosis and proinflammatory conditions in patients with liver cirrhosis. AIM: To test the effects of a multispecies probiotic on innate immune function, bacterial translocation and gut permeability. METHODS: In a randomised, double blind, placebo-controlled study, stable cirrhotic out-patients either received a daily dose of a probiotic powder containing eight different bacterial strains (Ecologic Barrier, Winclove, Amsterdam, The Netherlands) (n = 44) or a placebo (n = 36) for 6 months and were followed up for another 6 months. RESULTS: We found a significant but subclinical increase in neutrophil resting burst (2.6-3.2%, P = 0.0134) and neopterin levels (7.7-8.4 nmol/L, P = 0.001) with probiotics but not with placebo. Probiotic supplementation did not have a significant influence on neutrophil phagocytosis, endotoxin load, gut permeability or inflammatory markers. Ten severe infections occurred in total; one during intervention in the placebo group, and five and four after the intervention has ended in the probiotic and placebo group, respectively. Liver function showed some improvement with probiotics but not with placebo. CONCLUSIONS: Probiotic supplementation significantly increased serum neopterin levels and the production of reactive oxygen species by neutrophils. These findings might explain the beneficial effects of probiotics on immune function. Furthermore, probiotic supplementation may be a well-tolerated method to maintain or even improve liver function in stable cirrhosis. However, its influence on gut barrier function and bacterial translocation in cirrhotic patients is minimal.

Knotting of percutaneous endoscopic jejunostomy feeding tubes in two patients with Parkinson's disease and continuous Duodopa® treatment.

Continuous intraduodenal infusion of levodopa/carbidopa (Duodopa®) via PEJ tubes is increasingly used in patients with advanced stages of Parkinson's disease. Tube-related complications such as kinking or coiling have been frequently reported. We herein describe two cases of tube dysfunction in patients with Parkinson's disease and continuous Duodopa® treatment due to knotting of the distal end of the tube. The mechanisms of knotting are unclear although a causative role of impaired gastrointestinal motility either by Parkinson's disease itself or Duodopa® treatment might be suspected.

Comparison of three carbon dioxide sources on phlebotomine sand fly capture in Egypt.

Lighted Centers for Disease Control and Prevention (CDC) light traps were baited with carbon dioxide (CO2) produced from three different sources to compare the efficacy of each in collecting phlebotomine sand flies in Bahrif village, Aswan Governorate, Egypt. Treatments consisted of compressed CO2 gas released at a rate of 250 ml/min, 1.5 kg of dry ice (replaced daily) sublimating from an insulated plastic container, CO2 gas produced from a prototype FASTGAS (FG) CO2 generator system (APTIV Inc., Portland, OR), and a CDC light trap without a CO2 source. Carbon dioxide was released above each treatment trap's catch opening. Traps were placed in a 4 x 4 Latin square designed study with three replications completed after four consecutive nights in August 2007. During the study, 1,842 phlebotomine sand flies were collected from two genera and five species. Traps collected 1,739 (94.4%) Phlebotomus papatasi (Scopoli), 19 (1.0%) Phlebotomus sergenti, 64 (3.5%) Sergentomyia schwetzi, 16 (0.9%) Sergentomyia palestinensis, and four (0.2%) Sergentomyia tiberiadis. Overall treatment results were dry ice (541) > FG (504) > compressed gas (454) > no CO2 (343). Total catches of P. papatasi were not significantly different between treatments, although CO2-baited traps collected 23-34% more sand flies than the unbaited (control) trap. Results indicate that the traps baited with a prototype CO2 generator were as attractive as traps supplied with CO2 sources traditionally used in sand fly surveillance efforts. Field-deployable CO2 generators are particularly advantageous in remote areas where dry ice or compressed gas is difficult to obtain.

Converting hemodialysis patients from intravenous paricalcitol to intravenous doxercalciferol - a dose equivalency and titration study.

AIMS: Doxercalciferol and paricalcitol are used to treat hyperparathyroidism in chronic kidney disease. This study was conducted to define equivalent dose requirements to convert patients from intravenous paricalcitol to intravenous doxercalciferol. METHODS: Following a 4-week baseline period using a fixed dose of paricalcitol, 42 adult hemodialysis subjects were assigned to receive a fixed dose of doxercalciferol for 4 weeks using a conversion factor of either 50 or 65% of the prior paricalcitol dose. During a 12-week titration period the doxercalciferol dose was adjusted to optimize iPTH levels into the range of 150 - 300 pg/ml. Annual costs to achieve equivalent iPTH control were calculated for both vitamin D analogs. RESULTS: During the doxercalciferol fixed-dose period, the average dose of doxercalciferol was 2.1 +/- 1.3 microg and 3.1 +/- 1.8 microg in the 50 and 65% dose conversion groups, respectively. During this period mean iPTH in the 50% dose conversion group increased by 24 pg/ml (p = 0.017). During the dose titration period, doxercalciferol was increased to bring iPTH within the target range. Calcium control was maintained with both conversion factors, while slightly better phosphorus control was seen in the 65% dose conversion group. Annualized treatment cost for doxercalciferol was 28% less expensive per patient than paricalcitol. CONCLUSION: Patients can be managed safely and effectively with conversion and dose titration from paricalcitol to doxercalciferol. Both conversion strategies maintained iPTH at clinically satisfactory levels. Furthermore, doxercalciferol therapy resulted in drug acquisition cost-savings.

[Imaging spinal cord cystic lesions in adults]. / Imagerie des lésions kystiques du canal rachidien chez l'adulte.

Intrarachidian cystic lesions are frequent, with highly varied causes. They can be classified according to their location into intramedullary cystic lesions and extramedullary cystic lesions. In these two categories, they can then be regrouped according to the tissue from which they develop. MRI is the first-choice examination for the study of the intracanal contents and the differential diagnosis between the various lesions.

[Normal and abnormal meningeal enhancement: MRI features]. / Les prises de contraste méningées normales et pathologiques en IRM.

The authors describe normal imaging of the meninges and meningeal spaces and MR (magnetic resonance) imaging findings in tumoral and nontumoral diseases. Dural or/and pial enhancement may be related to tumoral, infectious or granulomatous diseases.

[Imaging in acute toxic encephalopathy]. / Imagerie des encephalopathies toxiques aigues.

Neuroimaging, particularly MR imaging, plays a major role for the diagnosis of many acute toxic encephalopathies. Toxic disorders are related to drugs (immunosuppressive agents, chemotherapeutic agents, anti-epileptic drugs, heroin...), to metals (lead, manganese, mercury...), and to industrial and environmental chemicals (solvent, carbon monoxide...). MR imaging with diffusion and perfusion imaging provides information regarding brain lesions induced by the toxic agents (vasogenic edema, cytotoxic edema, infarction, hemorrhage, demyelination...).

[Spinal extradural meningiomas: MRI findings in two cases]. / LES MENINGIOMES RACHIDIENS EXTRADURAUX: DONNEES IRM A PROPOS DE DEUX OBSERVATIONS.

Spinal extradural meningiomas are rare and may be easily confused with malignant neoplasms. We report two unusual cases of epidural spinal meningioma one within the left C6-C7 foramen and the other within the left posterolateral epidural space at the T3-T4 level. Low signal intensity of the tumor on T2-wi, thickening and enhancement of the dura with only the possibility of bone erosion are the most characteristic MR findings.

[Brain MR imaging of chronic alcoholism]. / Imagerie par résonance magnétique (IRM) des complications encéphaliques de l'alcoolisme.

Brain complications from chronic alcoholism (Wernicke encephalopathy, central pontine myelinolysis, Marchiafava-Bignami disease, Korsakoff's syndrome, hepatic encephalopathy, cerebellar atrophy, hemorrhagic and ischemic brain lesions) may be diagnosed by MR imaging.

[Epidermoid cyst of the fourth ventricle: four case reports]. / Les kystes épidermoïdes du quatrième ventricule: à propos de quatre cas.

Patients with epidermoid cyst of the fourth ventricle usually present with headaches and/or disequilibrium. These cysts are characterized by a focal lesion that is nearly isodense to CSF at CT and nearly isointense to CSF on T1W and T2W MR images. MRI using FLAIR and diffusion weighted images as well as 3D CISS acquisitions is useful to better characterize the lesions and their relation with the vermis, foramen magnum and CP angle cisterns. DWI images are useful for postsurgical evaluation of residual tumor. Extension of the cyst into the CP angle cisterns usually precludes complete surgical resection.

[Value of MRI findings in Gayet-Wernicke encephalopathy]. / Apport de l'IRM dans l'exploration de l'encéphalopathie de Gayet-Wernicke.

Wernicke encephalopathy (Wernicke-Korsakoff encephalopathy) is related to thiamine deficiency. We report the MRI findings in four patients with visualization of bilateral and symmetrical hyperintense foci on T2W and FLAIR images involving the periaqueductal gray matter, the mamillary bodies and around the third ventricle. Diffusion weighted images obtained in two patients demonstrated mild hypersignal in the same areas. Contrast enhancement within the mamillary bodies was noted in one patient. Follow-up MRI obtained in three patients showed rapid regression of signal abnormalities without correlation with good clinical outcome.

[Intracerebral radiation-induced cavernous angiomas]. / Les angiomes caverneux cérébraux induits par la radiothérapie.

We present four cases of cerebral cavernous angioma that developed after radiatherapy for brain tumor in three cases and for cavernous angioma in one case. The time interval between irradiation and the detection of the cavernous angioma varied from three to nine years and the doses from 24 to 60 Grays. Brain hemorrhage appeared in two cases. Explanation for the formation of cavernous malformations is unclear but is probably related to proliferation and dilatation of the vascular endothelium with formation of capillary telangiectasis with evolution to cavernous angiomas. The pediatric brain appears particularly vulnerable to radiation injury. The risk of hemorrhage appears higher than with spontaneous cavernous malformations.

Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver.

BACKGROUND AND AIMS: Cholestasis is associated with retention of potentially toxic bile acids and alterations in hepatocellular transporter expression. Conversely, nontoxic ursodeoxycholic acid (UDCA) stimulates bile secretion and counteracts cholestasis. This study aimed to determine the effects of UDCA and cholic acid (CA) on the expression of hepatocellular transporters for bile acids (Ntcp, Bsep), organic anions (Oatp1, Mrp2), organic cations (Mdr1a/b), and phospholipids (Mdr2) in mouse liver. METHODS: Bile flow/composition was analyzed in UDCA- or CA-fed mice. Transporter expression was studied by reverse-transcription polymerase chain reaction, Western blotting, and immunofluorescence microscopy. RESULTS: UDCA had no effect on basolateral Ntcp and down-regulated Oatp1, whereas canalicular Bsep and Mrp2 were up-regulated. CA down-regulated basolateral Ntcp and Oatp1, whereas canalicular Bsep, Mrp2, and Mdr1a/b were up-regulated. Neither UDCA nor CA affected Mdr2 expression. Both UDCA and CA stimulated biliary bile acid and glutathione excretion, although only CA increased phospholipid and cholesterol excretion. CONCLUSIONS: Down-regulation of basolateral and up-regulation of canalicular transporters in response to CA may represent a defense mechanism, in an attempt to prevent hepatocellular accumulation of potentially toxic bile acids. The therapeutic effects of UDCA may be caused in part by stimulation of canalicular transporter expression in the absence of hepatocellular toxicity.

Genetic disorders and molecular mechanisms in cholestatic liver disease--a clinical approach.

Cholestasis may result from genetic or acquired defects in bile secretion. Cloning of hepatobiliary transporter genes has advanced our understanding of the molecular basis of bile formation and cholestasis. Hereditary mutations of transporter genes, exposure to cholestatic injury (eg, drugs, hormones, cytokines), or the combination of both can result in reduced expression and function of hepatobiliary transport systems. These molecular changes impair hepatic uptake and excretion of bile salts and other organic anions (eg, bilirubin). Other molecular changes contibuting to cholestasis include alterations of membrane fluidity, cytoskeleton, vesicle movement, and cell contacts. Transporter mutations can be diagnosed at the molecular genetic level. Gene therapy and hepatocyte transplantation could be used in the future to correct hereditary transport defects. Drugs used to treat cholestatic liver diseases (eg, ursodeoxycholic acid) stimulate and partially restore defective transporter expression and function. New information on the molecular mechanisms of cholestasis should lead to the development of novel drugs for cholestatic liver diseases.

Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases.

Reduced hepatobiliary transporter expression could explain impaired hepatic uptake and excretion of bile salts and other biliary constituents resulting in cholestasis and jaundice. Because little is known about alterations of hepatobiliary transport systems in human cholestatic liver diseases, it was the aim of this study to investigate such potential changes. Hepatic mRNA levels in hepatobiliary transport systems for bile salts (NTCP, BSEP), organic anions (OATP2, MRP2, MRP3), organic cations (MDR1), phospholipids (MDR3), and aminophospholipids (FIC1) were determined in 37 human liver biopsies and control livers by competitive reverse-transcription polymerase chain reaction (RT-PCR). Transporter tissue distribution was investigated by immunofluorescence microscopy. In patients with inflammation-induced icteric cholestasis (mainly cholestatic alcoholic hepatitis), mRNA levels of NTCP, OATP2, and BSEP were reduced by 41% (P <.001), 49% (P <.005), and 34% (P <.05) compared with controls, respectively. In addition, NTCP and BSEP immunostaining was reduced. MRP2 mRNA levels remained unchanged, but canalicular immunolabeling for MRP2 was also decreased. mRNA expression of MRP3, MDR1, MDR3, and FIC1 remained unchanged. In contrast to the alterations of transporter expression in inflammation-induced icteric cholestasis, transporter expression did not change in anicteric cholestasis caused by primary biliary cirrhosis (PBC) stages I and II. In conclusion, reduced expression of hepatobiliary transport systems for bile salts and other organic anions may contribute to inflammation-induced cholestasis in humans. Reduction of transporter gene expression can occur at the mRNA level as observed for NTCP, OATP2, and BSEP. However, reduced MRP2 immunostaining in the presence of conserved MRP2 mRNA levels suggests an additional role for posttranscriptional/posttranslational mechanisms.

Favorable outcome in a large left heart air embolism: lessons from an unusual complication of a noninvasive chest scan.

OBJECTIVE: To report an unusual life-threatening complication of the performance of a computed tomographic (CT) scan of the chest. DESIGN: Case report. SETTING: University hospital. PATIENT: An intubated patient with blunt thoracic trauma. INTERVENTION: Performance of a CT scan of the chest at full inspiration. MAIN RESULT: With air insufflation, a large left ventricular air embolism occurred as a consequence of an airway breach, revealed by the simultaneous existence of a mild bilateral anterior pneumothorax. CONCLUSION: CT scan of the chest in patients at risk of airway breach (patients with acute respiratory distress syndrome, trauma patients) should first be performed at full expiration, not full inspiration.