Clinical Application of Liver MR Imaging in Wilson's Disease

Objective: To determine whether there is a correlation between liver MR findings and the clinical manifestations and severity of liver dysfunction in patients with Wilson`s disease. Materials and Methods: Two radiologists retrospectively evaluated MR images of the liver in 50 patients with Wilson`s disease. The Institutional Review Board approved this retrospective study and informed consent was waived. MR images were evaluated with a focus on hepatic contour abnormalities and the presence of intrahepatic nodules. By using Fisher`s exact test, MR findings were compared with clinical presentations (neurological and non-neurological) and hepatic dysfunction, which was categorized by the Child-Pugh classification system (A, B and C). Follow-up MR images were available for 17 patients. Results: Contour abnormalities of the liver and intrahepatic nodules were observed in 31 patients (62%) and 25 patients (50%), respectively. Each MR finding showed a statistically significant difference (p < 0.05) among the three groups of Child-Pugh classifications (A, n = 36; B, n = 5; C, n = 9), except for splenomegaly (p = 0.243). The mean age of the patients with positive MR findings was higher than that of patients with negative MR findings. For patients with Child-Pugh class A (n = 36) with neurological presentation, intrahepatic nodules, surface nodularity, and gallbladder fossa widening were more common. Intrahepatic nodules were improved (n = 8, 47%), stationary (n = 5, 29%), or aggravated (n = 4, 24%) on follow-up MR images. Conclusion: MR imaging demonstrates the contour abnormalities and parenchymal nodules of the liver in more than half of the patients with Wilson`s disease, which correlates with the severity of hepatic dysfunction and clinical manifestations.Cope-Yokoyama S, 2010, WORLD J GASTROENTERO, V16, P1487, DOI 10.3748/wjg.v16.i12.1487Akhan O, 2009, EUR J RADIOL, V69, P147, DOI 10.1016/j.ejrad.2007.09.029Taly AB, 2007, MEDICINE, V86, P112, DOI 10.1097/MD.0b013e318045a00eMerle U, 2007, GUT, V56, P115, DOI 10.1136/gut.2005.087262Akpinar E, 2007, EUR J RADIOL, V61, P25, DOI 10.1016/j.ejrad.2006.11.006Kozic D, 2006, ACTA RADIOL, V47, P624, DOI 10.1080/02841850600702176Kim TJ, 2006, AM J NEURORADIOL, V27, P1373SEO JK, 2006, KOREAN J HEPATOL, V12, P333Panagiotakaki E, 2004, AM J MED GENET A, V131A, P168, DOI 10.1002/ajmg.a.30345Chu WCW, 2004, AM J ROENTGENOL, V183, P1339ALA A, 2004, CLIN LIVER DIS, V8, P787Gitlin JD, 2003, GASTROENTEROLOGY, V125, P1868, DOI 10.1053/S0016-5085(03)01512-9Ferenci P, 2003, LIVER INT, V23, P139Akhan O, 2002, EUR RADIOL, V12, pS66, DOI 10.1007/s00330-002-1589-6Awaya H, 2002, RADIOLOGY, V224, P769, DOI 10.1148/radiol.2243011495Ito K, 1999, RADIOLOGY, V211, P723Ko SF, 1998, ABDOM IMAGING, V23, P56MERGO PJ, 1994, RADIOGRAPHICS, V14, P1291BULL PC, 1993, NAT GENET, V5, P327TANZI RE, 1993, NAT GENET, V5, P344DAVIES SE, 1989, HISTOPATHOLOGY, V15, P385CANCADO EL, 1987, ARQ NEURO-PSIQUIAT, V45, P131CHILD CG, 1964, LIVER PORTAL HYPERTE, P50

Factors associated with underutilization of antenatal care services in Indonesia: results of Indonesia Demographic and Health Survey 2002/2003 and 2007

<p>Abstract</p> <p>Background</p> <p>Antenatal care aims to prevent maternal and perinatal mortality and morbidity. In Indonesia, at least four antenatal visits are recommended during pregnancy. However, this service has been underutilized. This study aimed to examine factors associated with underutilization of antenatal care services in Indonesia.</p> <p>Methods</p> <p>We used data from Indonesia Demographic and Health Survey (IDHS) 2002/2003 and 2007. Information of 26,591 singleton live-born infants of the mothers' most recent birth within five years preceding each survey was examined. Twenty-three potential risk factors were identified and categorized into four main groups, external environment, predisposing, enabling, and need factors. Logistic regression models were used to examine the association between all potential risk factors and underutilization of antenatal services. The Population Attributable Risk (PAR) was calculated for selected significant factors associated with the outcome.</p> <p>Results</p> <p>Factors strongly associated with underutilization of antenatal care services were infants from rural areas and from outer Java-Bali region, infants from low household wealth index and with low maternal education level, and high birth rank infants with short birth interval of less than two years. Other associated factors identified included mothers reporting distance to health facilities as a major problem, mothers less exposed to mass media, and mothers reporting no obstetric complications during pregnancy. The PAR showed that 55% of the total risks for underutilization of antenatal care services were attributable to the combined low household wealth index and low maternal education level.</p> <p>Conclusions</p> <p>Strategies to increase the accessibility and availability of health care services are important particularly for communities in rural areas. Financial support that enables mothers from poor households to use health services will be beneficial. Health promotion programs targeting mothers with low education are vital to increase their awareness about the importance of antenatal services.</p

Disease-Associated Mutations That Alter the RNA Structural Ensemble

Genome-wide association studies (GWAS) often identify disease-associated mutations in intergenic and non-coding regions of the genome. Given the high percentage of the human genome that is transcribed, we postulate that for some observed associations the disease phenotype is caused by a structural rearrangement in a regulatory region of the RNA transcript. To identify such mutations, we have performed a genome-wide analysis of all known disease-associated Single Nucleotide Polymorphisms (SNPs) from the Human Gene Mutation Database (HGMD) that map to the untranslated regions (UTRs) of a gene. Rather than using minimum free energy approaches (e.g. mFold), we use a partition function calculation that takes into consideration the ensemble of possible RNA conformations for a given sequence. We identified in the human genome disease-associated SNPs that significantly alter the global conformation of the UTR to which they map. For six disease-states (Hyperferritinemia Cataract Syndrome, β-Thalassemia, Cartilage-Hair Hypoplasia, Retinoblastoma, Chronic Obstructive Pulmonary Disease (COPD), and Hypertension), we identified multiple SNPs in UTRs that alter the mRNA structural ensemble of the associated genes. Using a Boltzmann sampling procedure for sub-optimal RNA structures, we are able to characterize and visualize the nature of the conformational changes induced by the disease-associated mutations in the structural ensemble. We observe in several cases (specifically the 5′ UTRs of FTL and RB1) SNP–induced conformational changes analogous to those observed in bacterial regulatory Riboswitches when specific ligands bind. We propose that the UTR and SNP combinations we identify constitute a “RiboSNitch,” that is a regulatory RNA in which a specific SNP has a structural consequence that results in a disease phenotype. Our SNPfold algorithm can help identify RiboSNitches by leveraging GWAS data and an analysis of the mRNA structural ensemble

ST2 and IL-33 in pregnancy and pre-eclampsia.

Normal pregnancy is associated with a mild systemic inflammatory response and an immune bias towards type 2 cytokine production, whereas pre-eclampsia is characterized by a more intense inflammatory response, associated with endothelial dysfunction and a type 1 cytokine dominance. Interleukin (IL)-33 is a newly described member of the IL-1 family, which binds its receptor ST2L to induce type 2 cytokines. A soluble variant of ST2 (sST2) acts as a decoy receptor to regulate the activity of IL-33. In this study circulating IL-33 and sST2 were measured in each trimester of normal pregnancy and in women with pre-eclampsia. While IL-33 did not change throughout normal pregnancy, or between non-pregnant, normal pregnant or pre-eclamptic women, sST2 was significantly altered. sST2 was increased in the third trimester of normal pregnancy (p&lt;0.001) and was further increased in pre-eclampsia (p&lt;0.001). This increase was seen prior to the onset of disease (p&lt;0.01). Pre-eclampsia is a disease caused by placental derived factors, and we show that IL-33 and ST2 can be detected in lysates from both normal and pre-eclampsia placentas. ST2, but not IL-33, was identified on the syncytiotrophoblast layer, whereas IL-33 was expressed on perivascular tissue. In an in vitro placental perfusion model, sST2 was secreted by the placenta into the 'maternal' eluate, and placental explants treated with pro-inflammatory cytokines or subjected to hypoxia/reperfusion injury release more sST2, suggesting the origin of at least some of the increased amounts of circulating sST2 in pre-eclamptic women is the placenta. These results suggest that sST2 may play a significant role in pregnancies complicated by pre-eclampsia and increased sST2 could contribute to the type 1 bias seen in this disorder