Wilson's disease: an analysis of 28 Brazilian children

OBJECTIVES: Clinical-laboratory and evolutionary analysis of twenty-eight patients with Wilson's disease. METHODS: Twenty-eight children (twelve females and sixteen males) with Wilson's disease were evaluated retrospectively between 1987 and 2009, with a follow-up of 72 months (1 -240 months). The clinical, laboratory, and histologic features at diagnosis were recorded at the end of the study. RESULTS: The median age at diagnosis was 11 years (2 -18 years). Twelve patients were asymptomatic, seven had hepatitis symptoms, five had raised aminotransferase levels, three had hepatomegaly associated with neurological disorders, one had fulminant hepatitis with hemolytic anemia, and six patients presented with a Kayser-Fleischer ring. A histological analysis revealed that six children had chronic hepatitis, seven had cirrhosis, two had steatosis, one had portal fibrosis, and one had massive necrosis. The treatment consisted of D-penicillamine associated with pyridoxine for 26 patients. Adverse effects were observed in the other two patients: one presented with uncontrollable vomiting and the other demonstrated elastosis perforans serpiginosa. At the end of the study, all 26 treated patients were asymptomatic. Twenty-four of the patients were treated with D-penicillamine and pyridoxine, and two were treated with trientine and zinc sulfate. A liver transplant was performed in one patient with fulminant hepatitis, but the final patient died 48 hours after admission to the intensive care unit. CONCLUSIONS: Family screenings associated with early treatment are important in preventing Wilson's disease symptoms and potentially fatal disease progression. The study suggests that Wilson's disease must be ruled out in children older than two years presenting with abnormal levels of hepatic enzymes because of the heterogeneity of symptoms and the encouraging treatment results obtained so far.

Urinary copper excretion before and after oral intake of D-penicillamine in parents of patients with Wilson's disease

Background: Urinary copper excretion higher than 100 mu g/24 h is useful for diagnosing Wilson's disease. D-Penicillamine challenge test may produce higher levels than 1400 mu g/24 h, allowing for better diagnostic accuracy. This study investigated whether heterozygotes reach this value and compared copper serum levels, ceruloplasmin, and urinary copper excretion before and after administering D-penicillamine to the parents of Wilson's disease patients. Methods: Fifty parents of adult patients were enrolled to obtain copper serum levels and ceruloplasmin along with 24-h urinary copper excretion before and after administering 1 g D-penicillamine. Results: Serum ceruloplasmin and copper levels were significantly lower in fathers than in mothers (mean 21.8 x 27.8 mg%; 71.4 x 88.0 mu g%; p <= 0.001). The mean of basal 24-h urinary copper excretion was higher in fathers (26.2 x 18.7 mu g/24 h, p = 0.01), but did not differ between the genders after D-penicillamine (521.7 x 525.3, range 31.6-1085.1 mu g/24 h, p = 0.8). Conclusions: The mean values of serum copper, ceruloplasmin, and basal urinary copper excretion were different between males and females. The current diagnostic threshold of 24-h urinary copper excretion after D-penicillamine was not reached by heterozygotes. The increased urinary copper excretion after D-penicillamine challenge was much higher than fivefold the upper limit of normal urinary copper excretion in the majority of heterozygotes and should not be taken into account when diagnosing Wilson's disease. (C) 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The 1420 Ma Indiavai Mafic Intrusion (SW Amazonian Craton): Paleomagnetic results and implications for the Columbia supercontinent

The configuration and the timing of assembly and break-up of Columbia are still matter of debate. In order to improve our knowledge about the Mesoproterozoic evolution of Columbia, a paleomagnetic study was carried out on the 1420 Ma Indiavai mafic intrusive rocks that crosscut the polycyclic Proterozoic basement of the SW Amazonian Craton, in southwestern Mato Grosso State (Brazil). Alternating field and thermal demagnetization revealed south/southwest ChRM directions with downward inclinations for sixteen analyzed sites. These directions are probably carried by SD/PSD magnetite with high coercivities and high unblocking temperatures as indicated by additional rock magnetic tests, including thermomagnetic data, hysteresis data and the progressive acquisition of isothermal remanent magnetization. Different stable magnetization components isolated in host rocks from the basement 10 km NW away to the Indiavai intrusion, further support the primary origin of the ChRM. A mean of the site mean directions was calculated at Dm = 209.8 degrees, Im = 50.7 degrees (alpha(95) = 8.0 degrees, K = 22.1), which yielded a paleomagnetic pole located at 249.7 degrees E, 57.0 degrees S (A(95) = 8.6 degrees). The similarity of this pole with the recently published 1420 Ma pole from the Nova Guarita dykes in northern Mato Grosso State suggests a similar tectonic framework for these two sites located 600 km apart, implying the bulk rigidity of the Rondonian-San Ignacio crust at that time. Furthermore these data provide new insights on the tectonic significance of the 1100-1000 Ma Nova Brasilandia belt-a major EW feature that cuts across the basement rocks of this province, which can now be interpreted as intracratonic, in contrast to previous interpretation. From a global perspective, a new Mesoproterozoic paleogeography of Columbia has been proposed based on comparison of these 1420 Ma poles and a 1780 Ma pole from Amazonia with other paleomagnetic poles of similar age from Baltica and Laurentia, a reconstruction in agreement with geological correlations. (C) 2012 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.

ERIC-PCR genotypic characterization of Haemophilus parasuis isolated from Brazilian swine

Haemophilus parasuis infection, known as Gl��sser���s disease, is characterized by fibrinous polyserositis, arthritis and meningitis in piglets. Although traditional diagnosis is based on herd history, clinical signs, bacterial isolation and serotyping, the molecular-based methods are alternatives for species-specific tests and epidemiologic study. The aim of this study was to characterize H. parasuis strains isolated from different states of Brazil by serotyping, PCR and ERIC-PCR. Serotyping revealed serovar 4 as the most prevalent (24 %), followed by serovars 14 (14 %), 5 (12 %), 13 (8 %) and 2 (2 %), whereas 40 % of the strains were considered as non-typeable. From 50 strains tested 43 (86%) were positive to Group 1 vtaA gene that have been related to virulent strains of H.parasuis. ERIC-PCR was able to type isolates tested among 23 different patterns, including non-typeable strains. ERIC-PCR patterns were very heterogeneous and presented high similarity between strains of the same animal or farm origin. The results indicated ERIC-PCR as a valuable tool for typing H. parasuis isolates collected in Brazil.

The transcription factor encyclopedia

Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field.

Framingham risk score and alternatives for prediction of coronary heart disease in older adults

Background Guidelines for the prevention of coronary heart disease (CHD) recommend use of Framingham-based risk scores that were developed in white middle-aged populations. It remains unclear whether and how CHD risk prediction might be improved among older adults. We aimed to compare the prognostic performance of the Framingham risk score (FRS), directly and after recalibration, with refit functions derived from the present cohort, as well as to assess the utility of adding other routinely available risk parameters to FRS. Methods Among 2193 black and white older adults (mean age, 73.5 years) without pre-existing cardiovascular disease from the Health ABC cohort, we examined adjudicated CHD events, defined as incident myocardial infarction, CHD death, and hospitalization for angina or coronary revascularization. Results During 8-year follow-up, 351 participants experienced CHD events. The FRS poorly discriminated between persons who experienced CHD events vs. not (C-index: 0.577 in women; 0.583 in men) and underestimated absolute risk prediction by 51% in women and 8% in men. Recalibration of the FRS improved absolute risk prediction, particulary for women. For both genders, refitting these functions substantially improved absolute risk prediction, with similar discrimination to the FRS. Results did not differ between whites and blacks. The addition of lifestyle variables, waist circumference and creatinine did not improve risk prediction beyond risk factors of the FRS. Conclusions The FRS underestimates CHD risk in older adults, particularly in women, although traditional risk factors remain the best predictors of CHD. Re-estimated risk functions using these factors improve accurate estimation of absolute risk.

Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

Executive Reorganization: Building a State Government That Worked for People -- Tom Harrison, Diana Dowling & Sheena Wilson ���In the Crucible of Change���

One of the primary accomplishments of Governor Forrest Anderson in 1969-71 was the reorganization of the Executive Branch of Montana government, something that had been attempted six different times between 1919 and 1962 as state government had grown from twenty agencies to almost 200 uncontrolled boards, bureaus and commissions. The chaotic structure of the executive branch disempowered governors of both parties and empowered the private corporations and organizations that were the power structure of Montana. With remarkable political acumen, Governor Anderson figured out how to get that near impossible job done. Central to his efforts was the creation of an Executive Reorganization Commission, including eight legislators and the Governor, the adoption of a Constitutional Amendment that limited the executive branch to no more than twenty departments under the Governor, and the timely completion of a massive research effort to delineate the actual structure of the twenty departments. That story is told in this episode by three major players in the effort, all involved directly with the Executive Reorganization Commission: Tom Harrison, Diana Dowling and Sheena Wilson. Their recollections reflect an insider���s perspective of this significant accomplishment that helped change Montana ���In the Crucible of Change.��� Tom Harrison is a former Republican State Representative and State Senator from Helena, who was a member of the Executive Reorganization Commission. As Majority Leader in the Montana House of Representatives in 1971, he was the primary sponsor of the House���s executive reorganization bill and helped shepherd the Senate���s version to passage. Harrison was the Republican candidate for Attorney General in 1976 after which he practiced private law for 3 more decades. He served in the Montana Army National Guard for almost 34 years, rising to the rank of Colonel in the position of Judge Advocate General. He was a founding Director of Federal Defenders of Montana (legal representation for indigents accused within the Federal Judicial System); appointed Chairman of the original Montana State Fund (workers' compensation insurance) by Gov. Stephens; served as President of the Montana Trial Lawyers Association, Helena Kiwanis Club and St. Peter's Community Hospital Foundation, as well as Chairman and Director of AAA MountainWest; and was a founder, first Chairman and Director of the Valley Bank of Helena for over 25 years. Diana Dowling was an attorney for the Executive Reorganization Commission and helped draft the legislation that was passed. She also worked for Governor Forrest Anderson and for the 1972 Constitutional Convention where she prepared and directed publication of official explanation of the new Constitution that was mailed to all Montana voters. Diana was Executive Director of the Montana Bar Association and for 20 years held various legal positions with the Montana Legislative Council. For 12 years she was a commissioner on the National Conference of Commissioners on Uniform State Laws and for 7 years was a member of Montana State Board of Bar Examiners. Diana was the first director of the Montana Lottery, an adjunct professor at both Carroll College and the UM Law School, and an administrative officer for Falcon Press Publishing Co. Diana is currently - and intends to continue being - a perpetual college student. Sheena Wilson came fresh out of the University of Montana to become a Research Assistant for the Executive Reorganization Commission. Later she worked for seven years as a field representative in Idaho and Montana for the Mountain Plains Family Education Program, for thirteen years with Congressman Pat Williams as Executive Assistant in Washington and Field Assistant here in Montana, owned and managed a Helena restaurant for seven years, worked as Executive Assistant for State Auditor John Morrison and was Deputy Chief of Staff for Governor Brian Schweitzer his full 8 years in the Governorship. Though currently ���retired���, Sheena serves on the Montana Board of Investments, the Public Employees Retirement Board and the Capitol Complex Advisory Council and is a partner in a dry-land wheat farm in Teton County that was homesteaded by her great uncle.