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  1. Wilson Disease

    Science.gov (United States)

    ... Liver Foundation March of Dimes National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Wilson Disease Association See all related organizations Publications Order NINDS Publications Definition Wilson disease (WD) is a rare inherited disorder ...

  2. Wilson Disease

    Science.gov (United States)

    Wilson disease is a rare inherited disorder that prevents your body from getting rid of extra copper. You need ... copper into bile, a digestive fluid. With Wilson disease, the copper builds up in your liver, and ...

  3. [Wilson's disease

    OpenAIRE

    Duclos-Vallée, Jean-Charles; Ichaï, Philippe; Chapuis, Philippe; Misrahi, Micheline; Woimant, France

    2006-01-01

    http://www.huveaux.fr/fr_santesite.asp; Wilson's disease is an autosomal recessive disorder of copper excess. This illness results from mutations of the ATP7B gene chromosome 13. The discovery of the gene allowed a better understanding of cytosolic copper trafficking its relationship with ceruloplasmin synthesis. Symptomatic patients may present with hepatic, neurologic or psychiatric forms. Clinical and phenotypic evidences provide only presumptive arguments for this disease which can be rou...

  4. Wilson disease

    Science.gov (United States)

    ... nervous system and peripheral nervous system Copper urine test References Cox DW, Roberts EA. Wilson disease. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal ...

  5. Wilson's disease: current status.

    Science.gov (United States)

    Yarze, J C; Martin, P; Muñoz, S J; Friedman, L S

    1992-06-01

    To review current concepts about the pathogenesis, clinical manifestations, and treatment of Wilson's disease, with an emphasis on recent developments. Published information was identified using MEDLINE and through extensive manual searching of bibliographies in identified sources. The basic biochemical alteration responsible for deranged hepatobiliary copper homeostasis in Wilson's disease has yet to be identified. The gene for Wilson's disease has been mapped to chromosome 13, but the function of its gene product has not yet been determined. The clinical manifestations of Wilson's disease are varied and often nonspecific and include a range of hepatic, neurologic, and psychiatric findings. Penicillamine remains the drug of choice for the treatment of Wilson's disease, but recent experience suggests that trientine and zinc may be safe, effective alternatives. All three drugs are probably safe for use in pregnant patients with Wilson's disease. Liver transplantation is the only effective treatment for Wilsonian fulminant hepatic failure and corrects the underlying metabolic defect. Wilson's disease is a disorder of hepatobiliary copper excretion manifested predominantly by hepatic and neurologic copper toxicosis and inherited in an autosomal recessive pattern. Although the specific underlying biochemical defect remains to be defined, specific therapy is available and usually successful. Maintaining a high index of suspicion is critical in diagnosing this readily treatable inherited disease.

  6. Wilson Disease

    Science.gov (United States)

    ... things psychosis—when a person loses contact with reality Other Signs and Symptoms Other signs and symptoms ... analysis. A 24-hour urine collection will show increased copper in the urine in most patients who ...

  7. Wilson Disease

    Science.gov (United States)

    ... people taking zinc usually do not experience side effects, some people may experience stomach upset. A health care provider ... 738–4929 Email: nddic@info.niddk.nih.gov Internet: ... diseases to people with digestive disorders and to their families, health ...

  8. Long-Term Exclusive Zinc Monotherapy in Symptomatic Wilson Disease : Experience in 17 Patients

    NARCIS (Netherlands)

    Linn, Francisca H. H.; Houwen, Roderick H. J.; van Hattum, Jan; van der Kleij, Stefan; van Erpecum, Karel J.

    2009-01-01

    Exclusive monotherapy with zinc in symptomatic Wilson disease is controversial. Seventeen symptomatic patients with Wilson disease were treated with zinc only. The mean age at diagnosis and start of treatment was 18 years (range 13-26) with approximately half presenting as adolescents. Presentation

  9. Prevalence of ATP7B Gene Mutations in Iranian Patients With Wilson Disease

    OpenAIRE

    Zali, Narges; Mohebbi, Seyed Reza; Esteghamat, Sahar; Chiani, Mohsen; Haghighi, Mahdi Montazer; Hosseini-Asl, Seyed Mohammad-Kazem; Derakhshan, Faramarz; Mohammad-Alizadeh, Amir-Houshang; Malek-Hosseini, Seyed-Ali; Zali, Mohammad Reza

    2011-01-01

    Background Wilson disease (WD) is an autosomal recessive disorder. The WD gene, ATP7B, encodes a copper-transporting ATPase involved in the transport of copper into the plasma protein ceruloplasmin and in excretion of copper from the liver. ATP7B mutations cause copper to accumulate in the liver and brain. Objectives We examined the ATP7B mutation spectrum in Wilson disease patients in Iran. Patients and Methods Genomic DNA was extracted from patients with Wilson disease. The entire coding re...

  10. Clinical presentation and mutations in Danish patients with Wilson disease

    DEFF Research Database (Denmark)

    Møller, Lisbeth Birk; Horn, Nina; Jeppesen, Tina Dysgaard

    2011-01-01

    consistently indicative of WND, with the exception of the 24-h urine-Cu test, which is always outside the normal range. Mutations were identified in 100% of the screened ATP7B alleles (70 unrelated), including five novel mutations: p.1021K; p.G1158V; p.L1304F; IVS20-2A>G; Ex5_6del. In all, 70% of mutations...... were found in exons 8, 14, 17, 18, and 20. The most frequent mutation, p.H1069Q, comprised 18%. We propose a new and simple model that correlates genotype and age of onset. By assuming that the milder of two mutations is 'functionally dominant' and determines the age of onset, we classified 25....../27 mutations as either severe (age of onset 20 years), and correctly predicted the age of onset in 37/39 patients. This method should be tested in other Wilson populations....

  11. Wilson Disease: Case Report

    Directory of Open Access Journals (Sweden)

    Esra Tuğ

    2007-01-01

    Full Text Available Wilson Disease (WD is an autosomal recessive hereditary disease of human copper metabolism, which causes hepatic and neuropsychiatric diseases. Estimated prevalence is 1: 30.000. In WD, ATP7B gene located on chromosome 13 (13q14.3-q21.1, coding the protein for hepatic copper transport and, having an important role in copper metabolism has been affected. Clinical findings in WD are complex and, neurological symptoms such as tremor, disartria and psychiatric disorders, acute liver deficiency, chronic hepatit or cirrhosis may develop. For the last year, 27 years old female patient observed in other medical centre owing to benign positional vertigo applied to our department. Her sister and brother have been diagnosed as WD. No peripheral syptoms of hepatic disease or hepatosplenomegaly existed in our patient. Neurological examination was normal to except for positional tremor. Because our patient had rare clinical features for WD and bad prognosis, presented by us to emphasize necessity of the researched of the most frequent mutations seen in Turkiye.

  12. Treatment of Wilson's disease.

    Science.gov (United States)

    Jabłońska-Kaszewska, Irena; Dabrowska, Ewa; Drobińska Jurowiecka, Anna; Falkiewicz, Bogdan

    2003-08-01

    On the basis of literature review and own experience we presented the method of treatment of Wilson's disease. Causative treatment has been impossible so far, although gene therapy could be real in the future. Nowadays the principle of treatment is the elimination of the excess of easily mobilized copper by chelating agents or blocking the intestinal absorption of copper. Chelation therapy, aimed at mobilizing copper from the affected organs and promoting its excretion in the urine or stool is the most important. The major chelating agent is d-penicillamine, which is quite effective but not without some side effects. Alternative chelating agents such as trientine and tetrathiomolybdate have also been successfully employed. Zinc salts are also of therapeutic value. They promote copper excretion by inducing the synthesis of metallothionein in the intestine, thereby blocking copper absorption from the gut. Zinc salts have almost no side effects. They cannot be used as an initial treatment, but are very effective for maintenance therapy. The chelation therapy is ineffective in patients with acute liver failure with encephalopathy and hemolysis. In these cases, liver transplantation is the only hope for survival. Liver transplantations in patients with dominating psychoneurological symptoms are open to discussion.

  13. Small fiber dysfunction in patients with Wilson's disease

    Directory of Open Access Journals (Sweden)

    Francisco de Assis A. Gondim

    2014-08-01

    Full Text Available Objective: Patients with Wilson’s disease (WD may develop a wide variety of neuropsychiatric symptoms, but there are few reports of autonomic dysfunction. Here, we described evidence of small fiber and/or autonomic dysfunction in 4 patients with WD and levodopa-responsive parkinsonism. Method: We reviewed the charts of 4 patients with WD who underwent evaluation for the presence of neuromuscular dysfunction and water-induced skin wrinkling test (SWT. Results: Two men and 2 women (33±3.5 years with WD were evaluated. They all had parkinsonism at some point during their disease course. Parkinsonism on patient 4 almost completely subsided with treatment of WD. Two patients had significant sensory and 2 significant autonomic complaints, including syncopal spells. NCS/EMG was normal in all but SWT was abnormal in half of them (mean 4-digit wrinkling of 0.25 and 1. Discussion: A subset of patients with WD exhibit evidence of abnormal skin wrinkling test (small fiber neuropathy.

  14. The link between copper and Wilson's disease.

    Science.gov (United States)

    Purchase, Rupert

    2013-01-01

    Wilson's disease (hepatolenticular degeneration) is a rare inherited autosomal recessive disorder of copper metabolism leading to copper accumulation in the liver and extrahepatic organs such as the brain and cornea. Patients may present with combinations of hepatic, neurological and psychiatric symptoms. Copper is the therapeutic target for the treatment of Wilson's disease. But how did copper come to be linked with Wilson's disease? The answer encompasses a study of enzootic neonatal ataxia in lambs in the 1930s, the copper-chelating properties of British Anti-Lewisite, and the chemical analysis for copper of the organs of deceased Wilson's disease patients in the mid-to-late 1940s. Wilson's disease is one of a number of copper-related disorders where loss of copper homeostasis as a result of genetic, nutritional or environmental factors affects human health.

  15. [Wilson disease--evaluation of disease-related topics through the eyes of patients by patient-generated paintings--a cooperative study with the German patient organisation Verein morbus Wilson e. V].

    Science.gov (United States)

    Schäfer, M; Weiss, K H; Merle, U; Stremmel, W; Rasp, B

    2010-10-01

    The importance of disease-related topics can vary widely between patients and doctors. Patient organisations such as the German Verein Morbus Wilson e. V. can overcome this discrepancy. The goal of the present cooperative study was the collection of topics important to Wilson patients by asking patients to generate paintings about their disease. Patients with Wilson disease were asked by mail to draw paintings about their disease and to donate them to the Verein Morbus Wilson e. V. 32 paintings from 27 patients were donated. The majority of the patients added written comments to their art work. Disease-related topics included in the paintings were as follows: psychological work-up of the disease 33 % (n = 11), presentation of affected organs (liver/brain) 22 % (n = 6), therapy 19 % (n = 5), diagnostic path 15 % (n = 4), inheritance 15 % (n = 4), copper-related diet 11 % (n = 3). 33 % (n = 11) of the paintings were composed of two parts reflecting before and after the disease or presenting the individual time course of the disease. Psychological aspects of disease acceptance are the prominent topic in the paintings. The timepoint of diagnosis is experienced as major change in life. The paintings enable both the patient organisation and the caretakers to put more focus on the psychological aspects of the disease. Asking for paintings opens a new channel for patient-physician contacts and produces a feeling of interest and competence in patients. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Wilson's disease and hemochromatosis.

    Science.gov (United States)

    Neimark, Ezequiel; Schilsky, Michael L; Shneider, Benjamin L

    2004-02-01

    Wilson's disease (WD) and hereditary hemochromatosis (HH) are two inherited disorders with potentially devastating and life-threatening complications. Their eminent treatability makes diagnosis in adolescence or young adulthood critical. WD is the result of abnormal copper homeostasis, causing copper overload and end-organ damage. Chelation therapy can be highly efficacious in preventing manifestations of WD. HH is caused by inappropriate absorption of dietary iron, typically as the result of a specific mutation, C282Y, in the HFE gene. End-organ disease from iron accumulation is protean and includes progressive damage of the liver, pancreas, skin, heart, and pituitary. It is important to permit therapeutic phlebotomy to commence before the onset of complications.

  17. Metal element excretion in 24-h urine in patients with Wilson disease under treatment of D-penicillamine.

    Science.gov (United States)

    Huang, Lisu; Yu, Xiaodan; Zhang, Jun; Liu, Xiaoqing; Zhang, Yongjun; Jiao, Xianting; Yu, Xiaogang

    2012-05-01

    Wilson disease is an inherited autosomal recessive disorder causing copper accumulation and consequent toxicity. D-Penicillamine, a potent metal chelator, is an important therapy for Wilson disease. To investigate the changes of metal elements under the treatment of D-penicillamine, we determined the levels of Cu, Zn, Mg, Ca, Fe, Se, Mn, Pb, Hg, Cd, As, Tl, and Al by ICP-MS in 24-h urine of 115 Wilson disease patients who had received treatment with D: -penicillamine for 1 month to 22 years at maintenance doses, as well as 115 age-matched, healthy controls. The levels of Cu, Mg, Ca, Zn, Hg, Pb, Tl, Cd, and Mn in the 24-h urine of the cases were significantly higher than those of the controls (P elements may be altered in patients with Wilson disease under the treatment of D-penicillamine.

  18. D-penicillamine-induced ANA (+) ANCA (+) vasculitis in pediatric patients with Wilson's disease.

    Science.gov (United States)

    Lee, Yeonhee; Lee, Sang Taek; Cho, Heeyeon

    2016-05-01

    Anti-neutrophil cytoplasmic antibodies (ANCA) are associated with systemic vasculitis. The pathophysiology of ANCA-associated vasculitis (AAV) has not been clearly proven, and drug-induced ANCA-associated vasculitis has been reported. Wilson's disease is an inborn error of copper metabolism caused by a mutation in the copper transporting gene ATP7B, and traditional treatment is based on copper chelation with agents such as D-penicillamine. There have been rare reports that prolonged D-penicillamine therapy might cause adverse renal events such as membranous nephropathy and minimal change disease, but it is questionable if D-penicillamine induces ANCA-associated vasculitis. We describe 2 patients with Wilson's disease treated with D-penicillamine who presented with ANCA (+) vasculitis and renal involvement. The 2 patients also showed positive results for antinuclear antibody (ANA). Their kidney biopsy findings were compatible with crescentic/necrotizing glomerulonephritis, pauci-immune type. After diagnosis of AAV, D-penicillamine was stopped. Patients were then treated with plasmapheresis and immunosuppressants, including methylprednisolone pulse therapy and intravenous cyclophosphamide. One patient progressed to end-stage renal disease and the other showed persistent proteinuria. These cases suggest that D-penicillamine may induce ANA (+) ANCA (+) vasculitis with severe renal involvement in pediatric patients, and plasmapheresis combined with immunosuppressant should be considered.

  19. Wilson's disease and other neurological copper disorders.

    Science.gov (United States)

    Bandmann, Oliver; Weiss, Karl Heinz; Kaler, Stephen G

    2015-01-01

    The copper metabolism disorder Wilson's disease was first defined in 1912. Wilson's disease can present with hepatic and neurological deficits, including dystonia and parkinsonism. Early-onset presentations in infancy and late-onset manifestations in adults older than 70 years of age are now well recognised. Direct genetic testing for ATP7B mutations are increasingly available to confirm the clinical diagnosis of Wilson's disease, and results from biochemical and genetic prevalence studies suggest that Wilson's disease might be much more common than previously estimated. Early diagnosis of Wilson's disease is crucial to ensure that patients can be started on adequate treatment, but uncertainty remains about the best possible choice of medication. Furthermore, Wilson's disease needs to be differentiated from other conditions that also present clinically with hepatolenticular degeneration or share biochemical abnormalities with Wilson's disease, such as reduced serum ceruloplasmin concentrations. Disordered copper metabolism is also associated with other neurological conditions, including a subtype of axonal neuropathy due to ATP7A mutations and the late-onset neurodegenerative disorders Alzheimer's disease and Parkinson's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Wilson's Disease Association International

    Science.gov (United States)

    ... Back WDA Membership Latest News & Announcements Wilson's Warriors Events Back The Big WOW 2017 Annual Conference WDA Publications Back Downloads Corporate Sponsorship Forms Membership Forms Resources The Big WOW Newsletters ...

  1. [Therapy of Wilson disease].

    Science.gov (United States)

    Smolarek, C; Stremmel, W

    1999-04-01

    Wilson disease is a copper storage disease with autosomal-recessive trait that is predominantly a disorder of the adolescent and young adult. Clinical manifestations are dominated by hepatic and/or neurological symptoms. Diagnostic procedures include determination of total serum copper, free serum copper and serum ceruloplamin concentrations as well as urinary copper excretion. Confirmation of diagnosis may be achieved by liver biopsy and histological determination of copper content. The aim of treatment is reduction of tissue copper concentration and detoxification of copper. Drugs applied are the chelating agents. D-penicillamine and trientine, or zinc. The chelating agents induce renal and biliary copper excretion and increased synthesis of metallothionein, which attaches and detoxifies intracellular copper, leading to impaired absorption and binding of excess intracellular copper. Treatment with zinc results in induction of hepatic and intestinal metallothionein synthesis. Regular examinations of the parameters of copper metabolism are necessary in order to control the therapeutic effect. Free copper serum concentrations and urinary copper excretion should reach values below 10 micrograms/dl and 80 micrograms/day, respectively. A significant improvement of clinical symptoms and normalization of parameters of copper metabolism can be expected earliest six months after onset of therapy. Anti-copper treatment may be accompanied by copper-reduced diet. Lifelong therapy is required and provides life-expectancy near to normal. Interruption of treatment leads to reaccumulation of copper, often resulting in fulminant hepatic failure. This can also be observed as initial presentation in 5% of cases (predominant age 12 to 25 years). End stage liver disease and fulminant hepatic failure are indications for liver transplantation by which the genetic defect is phenotypically cured. Here decoppering treatment is no longer required. Whether severe neurological disorders may

  2. Genetics Home Reference: Wilson disease

    Science.gov (United States)

    ... 482-93. Review. Citation on PubMed Ferenci P. Pathophysiology and clinical features of Wilson disease. Metab Brain ... newborn screening? New Pages MDA5 deficiency type 2 diabetes mitochondrial complex I deficiency All New & Updated Pages ...

  3. Phenotypic and Genetic Characterization of a Cohort of Pediatric Wilson Disease Patients

    Directory of Open Access Journals (Sweden)

    Elnaghy Suzan

    2011-06-01

    Full Text Available Abstract Background In Egypt, Wilson disease seems to be under diagnosed and clinical data on large cohorts are limited. The aim of this study is to highlight the clinical, laboratory and genetic characteristics of this disease in our pediatric population as well as to report our experience with both treatment options and outcome. Methods The study included 77 patients from 50 unrelated families (62 were followed up for a mean period of 58.9 ± 6.4 months and 27 were asymptomatic siblings. Data were collected retrospectively by record analysis and patient interviews. Diagnosis was confirmed by sequencing of the ATP7B gene in 64 patients Results Our patients had unique characteristics compared to other populations. They had a younger age of onset (median: 10 years, higher prevalence of Kayser-Fleischer rings (97.6% in the symptomatic patients, low ceruloplasmin (93.5%, high rate of parental consanguinity (78.9% as well as a more severe course. 71.42% of those on long term D-penicillamine improved or were stable during the follow up with severe side effects occurring in only 11.5%. Preemptive treatment with zinc monotherapy was an effective non-toxic alternative to D-penicillamine. Homozygous mutations were found in 85.7%, yet limited by the large number of mutations detected, it was difficult to find genotype-phenotype correlations. Missense mutations were the most common while protein-truncating mutations resulted in a more severe course with higher incidence of acute liver failure and neurological symptoms. Conclusions Egyptian children with Wilson disease present with early Kayser-Fleischer rings and early onset of liver and neurological disease. The mutational spectrum identified differs from that observed in other countries. The high rate of homozygous mutations (reflecting the high rate of consanguinity may potentially offer further insights on genotype-phenotype correlation

  4. Cognitive impairment in Wilson's disease

    Directory of Open Access Journals (Sweden)

    Norberto Anizio Ferreira Frota

    Full Text Available Abstract Wilson's disease (WD or hepatolenticular degeneration is a rare, genetic and systemic disease, caused by a deficit in the metabolism of copper, leading to its accumulation in different organs, mainly the liver, followed by the central nervous system, especially the basal ganglia. When symptoms begin between the second and third decades of life, approximately 50% of the patients show neurological symptoms. Although dystonia and dysarthria are the most common neurological signs, cognitive changes have been reported since the first cases were described in 1912. Memory change is one of the most common impairments, but other cognitive changes have been reported, including dementia in untreated cases. In this article we review the cognitive changes in WD patients and the occurrence of dementia.

  5. Symptomatic copper deficiency in three Wilson's disease patients treated with zinc sulphate.

    Science.gov (United States)

    Dzieżyc, Karolina; Litwin, Tomasz; Sobańska, Anna; Członkowska, Anna

    2014-01-01

    Wilson's disease (WD) is caused by excess of copper that leads to accumulation of copper mainly in the liver, brain and needs life-long decoppering therapy. However, overtreatment with anti-copper agents may lead to copper deficiency which may cause neurological and hematological symptoms. Copper is an important cofactor for many enzymes. This report describes three WD patients with diagnosed copper deficiency during zinc sulphate (ZS) treatment. After 5-16 years of therapy all patients developed leucopenia. Spinal cord injury was manifested in two of the patients. One of them also presented myopathy. In conclusion, copper deficiency may occur in different time after treatment onset, therefore regular copper metabolism and hematological monitoring is necessary. Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  6. Liver transplantation for Wilson disease

    Science.gov (United States)

    Catana, Andreea M; Medici, Valentina

    2012-01-01

    The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID:22312450

  7. Genotype correlation with fine motor symptoms in patients with Wilson's disease.

    Science.gov (United States)

    Hermann, Wieland; Caca, Karel; Eggers, Birk; Villmann, Thomas; Clark, Daniel; Berr, Frieder; Wagner, Armin

    2002-01-01

    Wilson's disease, an autosomal recessive disorder of copper metabolism, is caused by about 200 different mutations of the ATP7B gene. Using a genotype-phenotype correlation, 36 patients were examined to see whether the disorder of the automatic handwriting movement depends on the genotype. The findings of this study indicated that no such link exists. Neither the profile of the impairment of the fine motor parameters nor the severity and frequency of pathological findings were different among the three genotype groups (homozygous for H1069Q, compound homozygous for H1069Q and other mutations). By contrast, fine motor disorders were found to correlate with the clinical symptoms recorded when therapy began. The pathophysiology of the basal ganglia and the cerebellar loop therefore cannot be directly attributed to the genotype of the mutation in the ATP7B gene. Copyright 2002 S. Karger AG, Basel

  8. Revised King's College score for liver transplantation in adult patients with Wilson's disease.

    Science.gov (United States)

    Petrasek, Jan; Jirsa, Milan; Sperl, Jan; Kozak, Libor; Taimr, Pavel; Spicak, Julius; Filip, Karel; Trunecka, Pavel

    2007-01-01

    Fulminant Wilson's disease (WD) is almost invariably fatal, and liver transplantation is the only life-saving treatment. Decompensated chronic WD usually responds to chelation therapy. Our aim was to validate 3 published scoring systems for deciding between chelation treatment and liver transplantation in patients with chronic decompensated and fulminant WD. Model for end-stage liver disease (MELD) score, as well as WD prognostic index (WPI) and its recently revised version (RWPI) were evaluated as predictors of the safety for chelation therapy. A group of 14 adult patients with decompensated chronic WD who improved on penicillamine treatment were compared with 21 patients with fulminant WD. The diagnosis of WD was based on increased urinary copper excretion and confirmed by elevated liver copper content and/or mutation analysis of the WD gene. The MELD score, WPI, and RWPI were calculated for all patients with WD. The accuracy of the MELD score, WPI, and RWPI for prediction of response to chelation therapy in patients with decompensated chronic WD was 0.968, 0.980, and 0.993, respectively. None of the decompensated chronic WD patients had a MELD score >30, RWPI >11, or WPI >7. RWPI showed the highest accuracy and the lowest false negativity compared with WPI and MELD. In conclusion, our data indicate that RWPI, originally proposed for pediatric patients, is also useful for adults. (c) 2006 AASLD.

  9. Mutation analysis of ATP7B gene in Turkish Wilson disease patients: identification of five novel mutations.

    Science.gov (United States)

    Simsek Papur, Ozlenen; Akman, Sezin Asik; Cakmur, Raif; Terzioglu, Orhan

    2013-04-01

    Wilson disease is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene that encodes a P-type copper transporting ATPase. The aim of this study was to screen and detect mutations of the ATP7B gene in unrelated Turkish Wilson disease patients (n = 46) and control group (n = 52). Mutations were screened and detected by DNA sequencing. 30 out of 46 patients had mutations. 24 different Wilson disease related mutations were identified in those patients. The distribution of mutations in ATP7B gene was as follow: 17 missense, 3 nonsense, 1 silent, 3 frameshift (1 insertion, 2 deletion). None of them were not found in the control group. Five out of 24 mutations were found to be novel. Four of them were missense (c.2363C > T, c.3106G > A, c.3451C > T, c.3733C > A). The last one was deletion (c.3111delC). 10 single nucleotide polymorphisms (SNPs) given in the literature were found in both control and patients groups. Moreover one new polymorphism in exon 18 (c.3727G > A) not reported previously was discovered in both groups. It was striking that most of the mutations were found in exons 8, 12-14. This is the first study covering Turkish Wilson disease patients and control groups for mutation screening in all the coding regions of ATP7B gene by DNA sequencing method and adding five new mutations and one polymorphism into the HUGO Wilson disease mutation database. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. Geographic variations in Wilson's disease.

    Science.gov (United States)

    Chu, N S; Hung, T P

    1993-07-01

    Certain features of Wilson's disease (WD) in Asia have been found to be different from those in other continents. The higher prevalence rate in Japan is presumably due to a higher consanguinity rate. In Chinese there is a tight linkage between WD and two gene loci for esterase D and retinoblastoma in the long arm of chromosome 13. The high proportion of patients with hepatic presentation accounts for early onset of WD in the Japanese and Chinese series. Skeletal involvement, leg hyperpigmentation, dark complexion, amenorrhea, epileptic seizures, and cerebral white matter degeneration are relatively more common among WD patients in Asia. Excessive copper in the liver appears to have a protective effect against hepatocellular carcinoma and type B hepatitis. Electrophysiological studies suggest widespread functional disturbances of the CNS in WD. Side-effects from penicillamine are rather frequent and often lead to interruption of the therapy. Trien is found to be effective without adverse reactions. Oral zinc therapy may be a suitable alternative for long-term management of WD patients in developing Asian countries.

  11. Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease.

    Science.gov (United States)

    Oe, Shinji; Miyagawa, Koichiro; Honma, Yuichi; Harada, Masaru

    2016-09-10

    Copper is an essential trace element, however, excess copper is harmful to human health. Excess copper-derived oxidants contribute to the progression of Wilson disease, and oxidative stress induces accumulation of abnormal proteins. It is known that the endoplasmic reticulum (ER) plays an important role in proper protein folding, and that accumulation of misfolded proteins disturbs ER homeostasis resulting in ER stress. However, copper-induced ER homeostasis disturbance has not been fully clarified. We treated human hepatoma cell line (Huh7) and immortalized-human hepatocyte cell line (OUMS29) with copper and chemical chaperones, including 4-phenylbutyrate and ursodeoxycholic acid. We examined copper-induced oxidative stress, ER stress and apoptosis by immunofluorescence microscopy and immunoblot analyses. Furthermore, we examined the effects of copper on carcinogenesis. Excess copper induced not only oxidative stress but also ER stress. Furthermore, excess copper induced DNA damage and reduced cell proliferation. Chemical chaperones reduced this copper-induced hepatotoxicity. Excess copper induced hepatotoxicity via ER stress. We also confirmed the abnormality of ultra-structure of the ER of hepatocytes in patients with Wilson disease. These findings show that ER stress plays a pivotal role in Wilson disease, and suggests that chemical chaperones may have beneficial effects in the treatment of Wilson disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease

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    Oe, Shinji, E-mail: ooes@med.uoeh-u.ac.jp; Miyagawa, Koichiro, E-mail: koichiro@med.uoeh-u.ac.jp; Honma, Yuichi, E-mail: y-homma@med.uoeh-u.ac.jp; Harada, Masaru, E-mail: msrharada@med.uoeh-u.ac.jp

    2016-09-10

    Copper is an essential trace element, however, excess copper is harmful to human health. Excess copper-derived oxidants contribute to the progression of Wilson disease, and oxidative stress induces accumulation of abnormal proteins. It is known that the endoplasmic reticulum (ER) plays an important role in proper protein folding, and that accumulation of misfolded proteins disturbs ER homeostasis resulting in ER stress. However, copper-induced ER homeostasis disturbance has not been fully clarified. We treated human hepatoma cell line (Huh7) and immortalized-human hepatocyte cell line (OUMS29) with copper and chemical chaperones, including 4-phenylbutyrate and ursodeoxycholic acid. We examined copper-induced oxidative stress, ER stress and apoptosis by immunofluorescence microscopy and immunoblot analyses. Furthermore, we examined the effects of copper on carcinogenesis. Excess copper induced not only oxidative stress but also ER stress. Furthermore, excess copper induced DNA damage and reduced cell proliferation. Chemical chaperones reduced this copper-induced hepatotoxicity. Excess copper induced hepatotoxicity via ER stress. We also confirmed the abnormality of ultra-structure of the ER of hepatocytes in patients with Wilson disease. These findings show that ER stress plays a pivotal role in Wilson disease, and suggests that chemical chaperones may have beneficial effects in the treatment of Wilson disease.

  13. [Complexity of the diagnosis of Wilson disease in clinical practice: our experience in 15 patients].

    Science.gov (United States)

    Huarte-Muniesa, María Pilar; Lacalle-Fabo, Esther; Uriz-Otano, Juan; Berisa-Prado, Silvia; Moreno-Laguna, Sira; Burusco-Paternáin, María Jesús

    2014-01-01

    Wilson disease (WD) is an inherited disorder that causes copper (Cu) accumulation, leading to mainly liver, neurological and/or psychiatric manifestations. In the absence of some of the typical features, diagnosis of WD is difficult and is based on the combination of clinical, biochemical and genetic testing. The aim of this study was to illustrate the complexity of the approach to WD in daily clinical practice. We retrospectively analyzed the medical records of patients with WD, including the clinical presentation, histological and biochemical findings, and follow up after treatment. We also carried out genetic testing, and the Leipzig diagnostic score was applied. We included 15 patients. Four were symptomatic, with liver (n=1), neurological (n=1), psychiatric (n=1) and mixed clinical manifestations (n=1), and 11 were presymptomatic, with elevated transaminases (n=8) and family study (n=3). We observed Kayser-Fleischer ring in 2 patients, both without neurologic symptoms. Ceruloplasmin ≤ 5 mg/dL was present in 73%, and 24-hour urinary Cu> 100 μg in 40%. Liver Cu was >250 μg/g.d.t. in 85% of the patients. The final diagnosis of WD was given by genetic testing (ATP7B gene mutations) in 5 patients with minimal disease features, including one symptomatic patient (psychiatric symptoms). We identified 5 previously reported mutations (p.M645R, p.R827W, p.H1069Q, p.P768L and p.G869R) and 3 unpublished mutations (p.L1313R, p.I1311T and p.A1179D); the most frequent mutation was p.M645R. After treatment, biochemical parameters (transaminases, urinary cooper) and symptoms improved, except in patients with neurological and psychiatric manifestations. Our series illustrates the important role of genetic testing in the diagnosis of WD. The identification of the p.M645R mutation in most of our patients should be kept in mind in the molecular analysis of the ATP7B gene in our region. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

  14. Insights into the management of Wilson's disease.

    Science.gov (United States)

    Kathawala, Mohmadshakil; Hirschfield, Gideon M

    2017-11-01

    Wilson's disease is a rare, inherited autosomal recessive disease of copper metabolism, in which the causative gene, ATP7B, results in absent or reduced function of the ATP7B transporter important for biliary excretion of copper and incorporation of copper into caeruloplasmin. Affected patients accumulate excessive copper within the liver, brain and other tissues. A disease mainly of children, adolescents and young adults; clinical features vary from the asymptomatic state to chronic liver disease, acute liver failure, and neuropsychiatric manifestations. Diagnosis requires a high index of suspicion and is based on a combination of clinical signs, biochemical tests, hepatic copper content assay and mutation analysis of the ATP7B gene; to date, there are more than 500 mutations of ATP7B in patients with Wilson's disease. Early recognition and treatment can result in an excellent prognosis whereas untreated disease is almost always fatal. Drug therapies include chelating agents, such as penicillamine or trientine, and zinc salts. Liver transplantation is curative correcting the underlying pathophysiology and is traditionally indicated in acute liver failure or end-stage liver disease refractory to medical therapy. This review provides an overview of various aspects of Wilson's disease including molecular basis of the disease, clinical features, diagnostic and management strategies with their current limitations.

  15. HFE gene mutations and iron metabolism in Wilson's disease.

    Science.gov (United States)

    Erhardt, Andreas; Hoffmann, Arne; Hefter, Harald; Häussinger, Dieter

    2002-12-01

    There is increasing evidence for an interaction between iron and copper metabolism. Iron indices (ferritin, transferrin saturation [TS], serum iron), liver parameters, the prevalence and significance of C282Y and H63D HFE mutations were studied in 40 unrelated, Caucasian patients with Wilson's disease and 295 healthy controls. Due to specific treatment Wilson's disease was well controlled in all but one patient. The allele frequencies for the C282Y (11.3% vs. 6.2%) and the H63D (18.8% vs. 16.4%) mutation did not differ between patients with Wilson's disease and healthy controls. One patient with C282Y homozygous HH and Wilson's disease was identified showing progressive liver disease despite reasonable venesection and copper chelation therapy. No differences in iron indices and liver values were seen between HFE heterozygous and HFE wildtype patients with Wilson's disease. Higher serum ferritin levels were noticed in patients with Wilson's disease compared to healthy controls (149 +/- 26 microg/l vs. 87 +/- 8 microg/l; P Wilson's disease in order to detect iron overload. HFE mutations other than C282Y homozygosity seem to have no impact on iron indices and liver parameters as long as Wilson's disease is controlled.

  16. Animal models of Wilson disease.

    Science.gov (United States)

    Medici, Valentina; Huster, Dominik

    2017-01-01

    Wilson disease (WD) is caused by ATPase copper-transporting beta (ATP7B) mutations and results in copper toxicity in liver and brain. Although the defective gene was identified in 1993, the specific mechanisms underlying copper toxicity and the remarkable phenotypic diversity of the disease are still poorly understood. Animal models harboring defects in the ATP7B homolog have helped to reveal new insights into pathomechanisms of WD. Four rodent models with ATP7B gene defects have been described - the Long-Evans Cinnamon (LEC) rat, inbred mouse models (toxic milk (tx), the Jackson Laboratory toxic milk (tx-j)), and the genetically engineered ATP7B(-/-) (knockout) mouse - all of which develop liver disease to different extents. Copper accumulation in parts of the brain accompanied by some neurologic involvement was revealed in LEC rats and tx/tx-j mice, but the pathology is less severe than human neurologic WD. Several dogs show hepatic copper toxicity resembling WD; however, brain involvement has not been observed and the underlying genetic defect is different. These models are of great value for examination of copper distribution and metabolism, gene expression, and investigation of liver and brain pathology. The availability of disease models is essential for therapeutic interventions such as drug, gene, and cell therapy. Findings made by animal studies may facilitate the development of specific therapies to ameliorate WD progression. © 2017 Elsevier B.V. All rights reserved.

  17. Pathological mitochondrial copper overload in livers of Wilson's disease patients and related animal models.

    Science.gov (United States)

    Zischka, Hans; Lichtmannegger, Josef

    2014-05-01

    In Wilson's disease (WD) and related animal models, liver mitochondria are confronted with an increasing copper burden. Physiologically, the mitochondrial matrix may act as a dynamic copper buffer that efficiently distributes the metal to its copper-dependent enzymes. Mitochondria are the first responders in the event of an imbalanced copper homeostasis, as typical changes of their structure are among the earliest observable pathological features in WD. These changes are due to accumulating copper in the mitochondrial membranes and can be reversed by copper-chelating therapies. At the early stage, copper-dependent oxidative stress does not seem to occur. On the contrary, however, when copper is massively deposited in mitochondria, severe structural and respiratory impairments are observed upon disease progression. This provokes reactive oxygen species and consequently causes the mitochondrial membranes to disintegrate, which triggers hepatocyte death. Thus, in WD mitochondria are prime targets for copper, and the excessive copper burden causes their destruction, subsequently provoking tissue failure and death. © 2014 New York Academy of Sciences.

  18. Is blinking of the eyes affected in extrapyramidal disorders? An interesting observation in a patient with Wilson disease.

    Science.gov (United States)

    Verma, Rajesh; Lalla, Rakesh; Patil, Tushar B

    2012-11-27

    Blinking of eye is a routine human activity which seldom attracts any attention of clinicians in health and disease. There is experimental evidence that blink rate is affected in extrapyramidal disorders affecting the balance of these neurotransmitters. However, no observations regarding blink rate in Wilson disease (WD) have been reported previously. We report a patient of WD with an increased spontaneous blink rate. A 24-year-old lady presented complaining of tremulousness of both upper limbs and head for 2 years, dysphagia and difficulty in speaking for 1.5 years and abnormal behaviour for last 1 year. We observed that her blink rate at rest was 32/min. Serum ceruloplasmin level was low (0.08 g/l). The patient was started on therapy with D-penicillamine, zinc sulphate, levodopa-carbidopa and trihexiphenidyl. At 1-month follow-up, patient's tremors were markedly decreased and blink rate at rest was decreased to 12/min.

  19. How Is Wilson Disease Inherited?

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  20. How Is Wilson Disease Diagnosed?

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  1. Copper removal strategies for Wilson's disease crisis in the ICU.

    Science.gov (United States)

    Reynolds, H V; Talekar, C R; Bellapart, J; Leggett, B A; Boots, R J

    2014-03-01

    Wilson's disease is a rare, inherited, autosomal recessive disorder of copper metabolism which leads to an accumulation of copper in body tissues. If a patient develops a Wilson's crisis, mortality can approach 100%. The treatment of such patients is mostly organ support but a possible treatment goal is to try to rapidly remove copper from their system. We performed a literature search on methods for de-coppering strategies for patients in intensive care with known Wilson's disease. We found 11 case reports where therapeutic plasma exchange was used and six case reports where various forms of albumin dialysis were used as techniques for rapidly reducing serum copper levels. To date, the case reports are encouraging that therapeutic plasma exchange and albumin dialysis can either delay or prevent the need for liver transplantation in patients with fulminant hepatic failure due to Wilson's disease. However, these case reports are mainly in the paediatric or young adult population, thus further studies in adults are warranted.

  2. Diagnosis and treatment of Wilson's disease.

    Science.gov (United States)

    Schilsky, Michael L

    2002-02-01

    Wilson's disease (WD) has moved on from being a recognized syndrome that was uniformly fatal to a curative disease for which the genetic basis has been discovered. Most pediatric patients present with hepatic manifestations, but some may have neurologic or psychiatric features. Clinical and biochemical screening, including liver biopsy for hepatic copper analysis, remain the standard for diagnosis, but haplotype analysis for siblings is now available and should be considered for family screening when possible. Lifelong medical therapy remains the mainstay of treatment, but treatment preferences are changing from penicillamine to alternative agents such as trientine and zinc. OLT remains lifesaving for those with fulminant WD and those in whom initial medical therapy fails. The future will probably see the application of rapid and accurate molecular diagnostic testing for this disorder and new therapeutic modalities such as hepatocyte transplantation, gene replacement therapy, and gene modification.

  3. Wilson disease : from clinical to molecular

    NARCIS (Netherlands)

    Houwen, Roderick Henk Johan

    1991-01-01

    Wilson disease is an autosomal recessive copper storage disease. It is characterized by an inability of the liver to; excrete copper into bile and to incorporate copper into ceruloplasmin. This results in a gradual accumulation of copper in the liver and subsequently in the brain and other organs,

  4. Pregnancy in Wilson disease - management and outcome.

    Science.gov (United States)

    Pfeiffenberger, Jan; Beinhardt, Sandra; Gotthardt, Daniel N; Haag, Nicola; Freissmuth, Clarissa; Reuner, Ulrike; Gauss, Annika; Stremmel, Wolfgang; Schilsky, Michael L; Ferenci, Peter; Weiss, Karl Heinz

    2017-08-31

    Introduction Wilson disease (WD) is a rare inherited disorder of copper metabolism causing toxic hepatic and neural copper accumulation. Clinical symptoms vary widely, from asymptomatic disease to acute liver failure or chronic liver disease without or with neuropsychiatric symptoms. Continuation of specific medical treatment for WD is recommended during pregnancy, but reports of pregnancy outcomes in WD patients are sparse. Patients and methods In a retrospective, multicenter study, 282 pregnancies in 136 WD patients were reviewed. Age at disease onset, age at conception and WD-specific treatments were recorded. Maternal complications during pregnancy, rate of spontaneous abortions and birth defects were analyzed with respect to medical treatment during pregnancy. Results Worsening of liver function tests was evident during 16/282 (6%) pregnancies and occurred in undiagnosed patients as well as in those under medical treatment. Liver test abnormalities resolved in all cases after delivery. Aggravation of neurological symptoms during pregnancy was rare (1%) but tended to persist after delivery. The overall spontaneous abortion rate in the study cohort was 73/282 (26%). Patients with an established diagnosis of WD receiving medical treatment experienced significantly fewer spontaneous abortions than patients with undiagnosed WD (Odds ratio: 2.853 [95% CI: 1.634-4.982]). Birth defects occurred in 7/209 (3%) live births. Conclusion Pregnancy in WD patients on anti-copper therapy is safe. The spontaneous abortion rate in treated patients was lower than that in therapy-naive patients. Although the teratogenic potential of copper chelators is a concern, the rate of birth defects in our cohort was low. Treatment for WD should be maintained during pregnancy, and patients should be monitored closely for hepatic and neurologic symptoms. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  5. [Wilson's disease and its pharmacological treatment].

    Science.gov (United States)

    Hayashi, Hisao; Suzuki, Rie; Wakusawa, Shinya

    2004-11-01

    Wilson's disease is an inherited copper toxicosis caused by defective putative copper transporting ATPase in the liver. Because of impaired biliary secretion, copper remains in the liver, resulting in chronic hepatic lesions including fatty metamorphosis, chronic hepatitis and cirrhosis. In the latter stage, extrapyramidal syndromes may develop with and without symptomatic hepatic lesions. Acute liver damage associated with hemolysis and deep jaundice may be the first manifestation. The majority of patients show hypoceruloplasminemia, which has been used as a screening test for the disease. A large number of mutations in the ATP7B gene have been reported. Thus, genetic diagnosis might be limitedly used to presymptomatic diagnosis of siblings when mutations are identified in an index patient. Introduction of penicillamine caused a revolution in the treatment of patients. Another chelater, trientine, is now available for those intolerant of penicillamine. Tetrathiomolibdate and zinc acetate are additional alternatives currently being tested. Hypoceruloplasminemia and further reduction after chelation therapy may be associated with iron overload. This complication is closely related with impaired transport of ferrous ion due to ferroxidase deficiency. Noncompliance and teratogenicity are other major concerns because any treatment with the agents listed above is a life long regimen. Despite various side effects of penicillamine, its teratogenicity is negligible. These data indicate that penicillamine is the first choice of drug for this disease.

  6. WILSON'S DISEASE (A report of two cases).

    Science.gov (United States)

    Kanitkar, M; JOSHi, S N; Roy, N Dutta

    1994-01-01

    Two cases of Wilson's disease are reported. First case presented with fulminant hepatic failure and had a fatal outcome. The second had an insiduous onset, neurological manifestations, and is progressing satisfactorily on zinc therapy. Problems in diagnosis and treatment are highlighted.

  7. Wilson's disease and other neurological copper disorders.

    Science.gov (United States)

    Bandmann, Oliver; Weiss, Karl Heinz; Kaler, Stephen G.

    2015-01-01

    Summary The classic copper metabolism disorder, Wilson disease (WD), was first defined in 1912. Both early onset presentations in infancy and late onset manifestations in adults > 70 years are now well recognized. Modern biochemical and genetic prevalence studies suggest that WD may be considerably more common than previously appreciated. Early diagnosis of WD is crucial to ensure that patients can be started on adequate treatment but uncertainty remains about the best possible choice of medication. Direct genetic testing for ATP7B mutations is increasingly available to confirm the clinical diagnosis of WD. WD needs to be differentiated from other conditions that present clinically with hepatolenticular degeneration or share biochemical abnormalities with WD, such as reduced serum cerulo plasmin levels. Disordered copper metabolism is also implied in an increasing number of other neurological conditions, including a subtype of axonal neuropathy due to ATP7A mutations, and the common late-onset neurodegenerative disorders Alzheimer’s disease and Parkinson’s disease. PMID:25496901

  8. HFE gene mutations and Wilson's disease in Sardinia.

    Science.gov (United States)

    Sorbello, Orazio; Sini, Margherita; Civolani, Alberto; Demelia, Luigi

    2010-03-01

    Hypocaeruloplasminaemia can lead to tissue iron storage in Wilson's disease and the possibility of iron overload in long-term overtreated patients should be considered. The HFE gene encodes a protein that is intimately involved in intestinal iron absorption. The aim of this study was to determine the prevalence of the HFE gene mutation, its role in iron metabolism of Wilson's disease patients and the interplay of therapy in copper and iron homeostasis. The records of 32 patients with Wilson's disease were reviewed for iron and copper indices, HFE gene mutations and liver biopsy. Twenty-six patients were negative for HFE gene mutations and did not present significant alterations of iron metabolism. The HFE mutation was significantly associated with increased hepatic iron content (Pgene wild-type. The HFE gene mutations may be an addictional factor in iron overload in Wilson's disease. Our results showed that an adjustment of dosage of drugs could prevent further iron overload induced by overtreatment only in patients HFE wild-type. 2009. Published by Elsevier Ltd.

  9. Diagnosis of Wilson's disease: a comprehensive review.

    Science.gov (United States)

    Mak, Chloe M; Lam, Ching-Wan

    2008-01-01

    Wilson's disease is an autosomal recessive disorder of copper metabolism. The culprit gene is ATP7B. The worldwide prevalence is about 1 in 30,000, which may vary by population. Higher prevalence rates were reported using more sensitive screening techniques and pilot population screening. Typical presentations include neuropsychiatric and hepatic dysfunction, whereas atypical presentations are protean. Diagnosis relies on a high clinical suspicion, typical neurological symptoms, presence of Kayser-Fleischer rings, and reduced serum ceruloplasmin concentration. The conventional value of gene mutations. Direct molecular diagnosis remains the most decisive tool. Other tests such as non-ceruloplasmin-bound copper are unreliable. Potential pitfalls and limitations of these diagnostic markers are critically reviewed in this paper. The mainstays of therapy are trientine, penicillamine, and/or zinc. Liver transplantation is lifesaving for those with advanced disease. Ceruloplasmin oxidase activity and serum free-copper concentration should be monitored in patients on long-term de-coppering therapy to prevent iatrogenic copper deficiency.

  10. Evaluation of oxidative events and copper accumulatıon in oral tissues of patients wıth Wilson's disease: three case report.

    Science.gov (United States)

    Ozturk, Mustafa; Karacelebi, Ezgi; Gungor, Kahraman; Coskun, Sule; Boysan, Esma

    2015-01-01

    Wilson's disease (WD), also known as hepatolenticular degeneration, was first described in 1912 by Kinnear Wilson. It is an autosomal recessive disorder caused by mutations in the ATP7B gene, a membrane-bound copper transporting ATPase. The disorder is caused by impairment of the copper transporting ATPase, ATP7B, in the liver, which disturbs copper transport, excretion into the bile, and incorporation into apoceruloplasmin. WD is an inherited copper metabolism disorder with pathological copper accumulation in many tissues, but especially in brain and liver. We conducted this study because copper accumulation in oral tissues in patients with WD have not been studied before. We think that copper accumulation and differences of oxidative events in oral tissues can cause tendency to periodontal diseases.

  11. Genetic and environmental modifiers of Wilson disease.

    Science.gov (United States)

    Medici, Valentina; Weiss, Karl-Heinz

    2017-01-01

    Wilson disease (WD) is characterized by remarkable variety in its phenotypic presentation. Patients with WD can present with hepatic, neurologic, and psychiatric symptoms combined in different and unpredictable ways. Importantly, no convincing phenotype-genotype correlation has ever been identified, opening the possibility that other genes, aside from ATPase copper-transporting beta (ATP7B), are involved in the pathogenesis of this condition. In addition, modifier genes, or genes that can affect the expression of other genes, may be involved. Clinical and basic science data indicate that environmental and dietary factors can potentially modify gene expression in WD and, consequently, its clinical presentation and course. In particular, previously studied genes include copper metabolism domain-containing 1 (COMMD1), antioxidant 1 copper chaperone (ATOX1), X-linked inhibitor of apoptosis (XIAP), apolipoprotein E (APOE), hemochromatosis (HFE), and 5,10-methylenetetrahydrofolate reductase (MTHFR). Dietary factors include iron and methyl group donors which could affect methionine metabolism and epigenetic mechanisms of gene expression regulation. Most of the work conducted in this field is in its initial stages but it has the potential to change the diagnosis and treatment of WD. © 2017 Elsevier B.V. All rights reserved.

  12. Wilson's disease: an analysis of 28 Brazilian children

    Directory of Open Access Journals (Sweden)

    Rodolpho Truffa Kleine

    2012-01-01

    Full Text Available 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.

  13. Wilson's disease--a rare psychiatric presentation.

    Science.gov (United States)

    Aravind, V K; Krishnaram, V D; Neethiarau, V; Srinivasan, K G

    2009-07-01

    The development of extrapyramidal syndrome characterised by rigidity, bradykinesia, dysphagia and dysarthria in a male individual with four distinct episodes of (mania like) behavioural disturbances with fairly good remission in a time frame of five years, in a male individual, was suspected to develop the neurological manifestations of Wilson's disease and was investigated. In the absence of Kayser-Fleischer ring by slit-lamp examination and with normal copper and ceruloplasmin serum levels, the diagnosis was possible because of the positive findings of the magnetic resonance imaging (MRI) studies and increased 24 hours urinary copper levels with the penicillamine challenge test. The findings and its implications are highlighted and discussed.

  14. Unusual imaging findings in Wilson's disease

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    Akhan, Okan; Akpinar, Erhan; Oto, Aytekin; Koeroglu, Mert; Oezmen, Mustafa N.; Akata, Deniz [Department of Radiology, Hacettepe University, Sihhiye/Ankara (Turkey); Bijan, Bijan [Abdominal Imaging/MR and Nonvascular Interventional Division, University of California, Davis, California (United States)

    2002-07-01

    We present unusual imaging findings in the liver of a patient with Wilson's disease. On US, the liver contours were irregular and its echogenicity was increased with multiple, small hypo- and hyperechoic nodules. Prominent perihepatic fat layer was noted to be increased in thickness. On CT and MR, multiple, small, enhancing nodules were detected in the liver in the early arterial phase after administration of intravenous contrast material. Biopsy was consistent with chronic parenchymal liver pathology with dysplastic changes but without evidence of hepatocellular carcinoma. To our knowledge, dysplastic nodules enhancing at the arterial phase and thickened perihepatic fat layer have not been previously reported in patients with Wilson's disease. (orig.)

  15. [Wilson disease. A case report and review of the literature].

    Science.gov (United States)

    Alva-Moncayo, Edith; Castro-Tarín, María; González-Serrano, Adolfo

    2011-01-01

    Wilson disease is a problem of cuprum metabolism, with recesive autosomic hereditary transmission and a prevalence of one in 30,000 habitants. The cuprum is deposit in a progressive and irreversible way in the liver and encephalus and it is not liberated with quelant treatment. Neurological manifestations are tremor, disartria, extrapiramidal manifestations or distonia. Ophthalmic exploration shows corneal limb with sign of Kayser-Fleischer. a 15-year-old masculine patient with previous hepatitis outbreak in two times. During the last year he presented distonia, bradicinecious, stiffness and indifference with ictericia. Ophthalmological examination reported Kayser-Fleisher rings. Magnetic resonance of brain showed high dense images in lenticular, pallidus globe and caudate nucleus suggestive of Wilson disease. Ceruloplasmin concentration, cuprum in the liver biopsy confirmed the diagnosis. the importance of the case was the hepatic initial manifestations and two years after presented with inexpressive face, and it was considered a psychiatric disease, but the neurological evaluation and the liver biopsy confirmed the diagnosis of Wilson disease.

  16. A novel COMMD1 mutation Thr174Met associated with elevated urinary copper and signs of enhanced apoptotic cell death in a Wilson Disease patient

    Directory of Open Access Journals (Sweden)

    Sengupta Mainak

    2010-06-01

    Full Text Available Abstract Wilson disease (WD results from accumulation of copper and caused due to mutations in ATP7B, a copper transporting ATPase. Besides regular hepatic and neurological symptoms, WD patients occasionally manifest atypical symptoms due to unknown cause. To understand the molecular etiology of atypical WD manifestations, we screened COMMD1, a gene implicated in canine copper toxicosis, in 109 WD patients including those with atypical symptoms. In a patient showing apoptotic symptoms and high urinary copper surpassing normal WD levels, we identified a novel, putative mutation in COMMD1. Two other changes were also identified in the gene. We have examined genotype-phenotype correlation between the detected changes and the atypical presentation of the WD patient.

  17. [The onset of psychiatric disorders and Wilson's disease].

    Science.gov (United States)

    Benhamla, T; Tirouche, Y D; Abaoub-Germain, A; Theodore, F

    2007-12-01

    Wilson's disease is an infrequent, autosomic recessive pathology, resulting from a loss of function of an adenosine triphosphatase (ATP7B or WDNP), secondarily to a change (more than 60 are described currently), insertion or deletion of the ATP7B gene located on the chromosome 13q14.3-q21.1, which involves a reduction or an absence of the transport of copper in the bile and its accumulation in the body, notably the brain. Wilson's disease is transmitted by an autosomic recessive gene located on the long arm of chromosome 13. The prevalence of the heterozygote is evaluated at 1/90 and the homozygote at 1/30,000. Consanguinity, frequent in the socially geographically isolated populations, increases the prevalence of the disease. The toxic quantities of copper, which accumulate in the liver since early childhood and perhaps before, remain concentrated in the body for years. Hence, cytological and histological modifications can be detected in the biopsies, before the appearance of clinical or biological symptoms of hepatic damage. The accumulation of copper in the liver is due to a defect in the biliary excretion of metal and is accompanied invariably by a deficit in ceruloplasmin; protein synthesized from a transferred ATP7B gene, which causes retention of the copper ions in the liver. The detectable cellular anomalies are of two types: hepatic lesions resulting in acute hepatic insufficiency, acute hepatitis and finally advanced cirrhosis and lesions of the central nervous system responsible for the neurological and psychiatric disorders. In approximately 40-50% of the patients, the first manifestation of Wilson's disease affects the central nervous system. Although copper diffuses in the liver towards the blood and then towards other tissues, it has disastrous consequences only in the brain. It can therefore cause either a progressive neurological disease, or psychiatric disorders. Wilson's disease begins in the form of a hepatic, neurological, or psychiatric

  18. Systems biology approach to Wilson's disease.

    Science.gov (United States)

    Burkhead, Jason L; Gray, Lawrence W; Lutsenko, Svetlana

    2011-06-01

    Wilson's disease (WD) is a severe disorder of copper misbalance, which manifests with a wide spectrum of liver pathology and/or neurologic and psychiatric symptoms. WD is caused by mutations in a gene encoding a copper-transporting ATPase ATP7B and is accompanied by accumulation of copper in tissues, especially in the liver. Copper-chelation therapy is available for treatment of WD symptoms and is often successful, however, significant challenges remain with respect to timely diagnostics and treatment of the disease. The lack of genotype-phenotype correlation remains unexplained, the causes of fulminant liver failure are not known, and the treatment of neurologic symptoms is only partially successful, underscoring the need for better understanding of WD mechanisms and factors that influence disease manifestations. Recent gene and protein profiling studies in animal models of WD began to uncover cellular processes that are primarily affected by copper accumulation in the liver. The results of such studies, summarized in this review, revealed new molecular players and pathways (cell cycle and cholesterol metabolism, mRNA splicing and nuclear receptor signaling) linked to copper misbalance. A systems biology approach promises to generate a comprehensive view of WD onset and progression, thus helping with a more fine-tune treatment and monitoring of the disorder.

  19. Wilson's disease presenting as rapid eye movement sleep behavior disorder: a possible window to early treatment.

    Science.gov (United States)

    Tribl, Gotthard G; Bor-Seng-Shu, Edson; Trindade, Mateus C; Lucato, Leandro T; Teixeira, Manoel J; Barbosa, Egberto R

    2014-09-01

    To describe characteristics of REM sleep behavior disorder in Wilson's disease. Questionnaire-based interviews (patients and relatives), neurological examinations, two-week prospective dream-diary, video-polysomnography, transcranial sonography, MRI. Four Wilson's disease cases with REM sleep behavior disorder were described; three had REM sleep behavior disorder as initial symptom. All showed mesencephalic tegmental/tectal sonographic hyperechogenicities and two presented ponto-mesencephalic tegmental MRI hyperintensities. This first description of REM sleep behavior disorder in Wilson's disease in literature documents REM sleep behavior disorder as a possible presenting symptom of Wilson's disease and adds further evidence to the parallelism of Parkinson's disease and Wilson's disease in phenotype and brainstem topography, which ought to be further studied. REM sleep behavior disorder has prognostic relevance for neurodegeneration in α-synucleinopathies. In Wilson's disease, usefulness of early diagnosis and treatment are already well established. REM sleep behavior disorder in Wilson's disease offers a possible theoretical model for potential early treatment in this extrapyramidal and brainstem paradigm syndrome, previewing the possibility of neuroprotective treatment for REM sleep behavior disorder in "pre-clinical" Parkinson's disease.

  20. Wilson — Konovalov Disease: Diagnostic Algorithms and Approaches to Treatment

    Directory of Open Access Journals (Sweden)

    S.L. Melanich

    2015-11-01

    Full Text Available Wilson — Konovalov disease is a hereditary disease characterized by progressive accumulation of copper, mainly affecting liver and brain. It is a rare disease and is often diagnosed on later stages, but it is now becoming more common. The article discusses the features of clinical symptoms, diagnostic algorithm for the diagnosis of Wilson — Konovalov disease. The points of treatment, prevention and prognosis are dwelt.

  1. [Advances in the molecular diagnosis of Wilson's disease].

    Science.gov (United States)

    Badenas Orquin, Celia

    2011-01-01

    Wilsońs disease is an autosomal recessive disorder characterized by toxic copper accumulation in the liver and subsequently in the brain and other organs. Clinical diagnosis is based on the detection of low serum ceruloplasmin concentrations, increased urinary copper excretion, Kayser-Fleisher rings in the cornea, and/or high copper levels in hepatic tissue. Diagnosis can be difficult when the typical symptoms of the disease are absent, a situation that can lead to a lack of prophylactic therapy in these patients. Molecular study has improved the diagnosis of this disease, even in doubtful cases. The present article outlines the various techniques applied in the molecular diagnosis of Wilson's disease and the most commonly described mutations. Currently, direct sequencing of the ATP7B gene is the most widely used method to detect mutations. Molecular study and identification of ATP7B gene mutations allow diagnosis of individuals with Wilson's disease and their relatives, as well as the possibility of genetic counselling and prenatal and preimplantation genetic diagnosis. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  2. Relative exchangeable copper: a promising tool for family screening in Wilson disease.

    Science.gov (United States)

    Trocello, Jean-Marc; El Balkhi, Souleiman; Woimant, France; Girardot-Tinant, Nadège; Chappuis, Philippe; Lloyd, Carla; Poupon, Joël

    2014-04-01

    Family screening is a main step for the diagnosis in Wilson disease. This study was undertaken to evaluate the value of relative exchangeable copper for family screening. Data from family screening were collected from the French National Center of Reference for Wilson disease. Subjects who were first- or second-degree relatives of the index case underwent clinical examination and biological parameters. Of 127 subjects examined, copper abnormalities or low ceruloplasminemia were detected in 21 subjects, corresponding to 5 patients with Wilson disease, 14 heterozygous ATP7B carriers and 2 subjects with no ATP7B mutations. Relative exchangeable copper determination significantly discriminates heterozygous ATP7B carriers and subjects with no ATP7B mutations from WD patients with a cutoff of 15%. Exchangeable copper appears to be a promising tool for family screening in Wilson disease. © 2013 International Parkinson and Movement Disorder Society.

  3. Cell therapy to remove excess copper in Wilson's disease.

    Science.gov (United States)

    Gupta, Sanjeev

    2014-05-01

    To achieve permanent correction of Wilson's disease by a cell therapy approach, replacement of diseased hepatocytes with healthy hepatocytes is desirable. There is a physiological requirement for hepatic ATP7B-dependent copper (Cu) transport in bile, which is deficient in Wilson's disease, producing progressive Cu accumulation in the liver or brain with organ damage. The ability to repopulate the liver with healthy hepatocytes raises the possibility of cell therapy in Wilson's disease. Therapeutic principles included reconstitution of bile canalicular network as well as proliferation in transplanted hepatocytes, despite toxic amounts of Cu in the liver. Nonetheless, cell therapy studies in animal models elicited major differences in the mechanisms driving liver repopulation with transplanted hepatocytes in Wilson's disease versus nondiseased settings. Recently, noninvasive imaging was developed to demonstrate Cu removal from the liver, including after cell therapy in Wilson's disease. Such developments will help advance cell/gene therapy approaches, particularly by offering roadmaps for clinical trials in people with Wilson's disease. © 2014 New York Academy of Sciences.

  4. Data mining approach to the evaluation of diagnostic tests in Wilson disease

    Science.gov (United States)

    Plutecki, Michal M.; Dądalski, Maciej; Socha, Piotr; Mulawka, Jan J.

    2009-06-01

    The purpose of this paper is to figure out a new, better than so-far-known, evaluation method of diagnostic tests in Wilson disease. In order to find the most interesting classification models various data mining techniques were applied to real, suffering from Wilson disease, set of patients. It occurred that a combination of two classification algorithms with its implementations in Weka environment may significantly increase classification ability.

  5. Intestinal expression of metal transporters in Wilson's disease.

    Science.gov (United States)

    Przybyłkowski, Adam; Gromadzka, Grażyna; Wawer, Adriana; Grygorowicz, Tomasz; Cybulska, Anna; Członkowska, Anna

    2013-12-01

    In Wilson's disease (WND), biallelic ATP7B gene mutation is responsible for pathological copper accumulation in the liver, brain and other organs. It has been proposed that copper transporter 1 (CTR1) and the divalent metal transporter 1 (DMT1) translocate copper across the human intestinal epithelium, while Cu-ATPases: ATP7A and ATP7B serve as copper efflux pumps. In this study, we investigated the expression of CTR1, DMT1 and ATP7A in the intestines of both WND patients and healthy controls to examine whether any adaptive mechanisms to systemic copper overload function in the enterocytes. Duodenal biopsy samples were taken from 108 patients with Wilson's disease and from 90 controls. CTR1, DMT1, ATP7A and ATP7B expression was assessed by polymerase chain reaction and Western blot. Duodenal CTR1 mRNA and protein expression was decreased in WND patients in comparison to control subjects, while ATP7A mRNA and protein production was increased. The variable expression of copper transporters may serve as a defense mechanism against systemic copper overload resulting from functional impairment of ATP7B.

  6. The Clinical Manifestations, Treatment Efficacy and Adverse Drug Reactions in 62 Iranian Child with Wilson Disease

    Directory of Open Access Journals (Sweden)

    Mehri Najafi

    2014-09-01

    Full Text Available Introduction: The Wilson disease is an autosomal recessive disease in which the liver, central nervous system, eyes, blood and other parts of the body involved. Timely diagnosis and appropriate treatment of the disease requires awareness of the clinical presentations of this disease in children.Methods: This case series study included 62 patients with Wilson disease who admitted to children's Medical Center in the years 2012-2003.Results: 56% of patients were male. The average age of diagnosis was 9.73 years old (5-17 years and this was higher in patients with early neurologic symptoms (P = 0.85.( 64.5% of the patients had the hepatic symptoms at the time of diagnosis and the most common type of hepatic involvement was cirrhosis (39.3% and hepatitis (17.5% respectively. 17.7% of the patients also had early neurological symptoms. A positive family history for the Wilson Disease were found in 27.4% of patients. 74.2% of patients had KF ring and the frequency of these symptom was higher in patients with early neurological involvement. 83.9% of patients were treated successfully with D-penicillamine and In 30% of patients, adverse drug reactions were seen.Conclusion: Children with unknown liver disease should be evaluated for Wilson disease and the first-degree relatives of patients should be screened. . D-penicillamine have important side effects, but due to the low cost and the availability is an appropriate drug to treat the Wilson disease..Key words: Wilson Disease, Hepatic Involvement, Neurologic Involvement , KF ring ,D-Penicillamine.

  7. Wilson's disease: a new gene and an animal model for an old disease.

    Science.gov (United States)

    Cuthbert, J A

    1995-08-01

    Wilson's disease is an autosomal recessive, inherited disorder of copper metabolism. In normal individuals, copper homeostasis is controlled by the balance between intestinal absorption of dietary copper and hepatic excretion of excess copper in bile. In Wilson's disease, hepatic copper is neither excreted in bile nor incorporated into ceruloplasmin and copper accumulates to toxic levels. The Wilson's disease gene (WND) encodes a putative copper-transporting protein that is expressed almost exclusively in the liver. The predicted structure of the protein product is that of a P-type ATPase with striking homology to bacterial copper transporters and the gene product of another inherited disorder of copper metabolism, Menkes' disease. A rat model of Wilson's disease has recently been identified. The Long-Evans Cinnamon (LEC) rat manifests elevated hepatic copper, defective incorporation of copper into ceruloplasmin, and reduced biliary excretion of copper. The rat homologue of the WND is abnormal in LEC rats. Clinical manifestations of Wilson's disease arise directly from copper-induced damage to hepatocytes (hepatic presentation) or indirectly after the release of copper from the liver with subsequent damage to the brain (neuropsychiatric presentation) and other organs. Genetic heterogeneity (different mutations in a single gene) may account for some of the variability in Wilsonian presentations. The diagnosis of Wilson's disease depends on the demonstration of disordered copper metabolism, manifested as elevated urinary and hepatic copper and low ceruloplasmin levels. However, none of the abnormal findings in Wilson's disease is pathognomonic. Genetic diagnosis, in the absence of family studies, is likely to be difficult since many different mutations result in the disease. Management of Wilson's disease involves decreasing excess levels of copper accumulated in the liver, brain, and other organs. Copper chelation therapy, to increase urinary excretion of copper, is

  8. Results of treatment of Wilson's disease--own observations.

    Science.gov (United States)

    Jabłońska-Kaszewska, Irena; Drobińska-Jurowiecka, Anna; Dabrowska, Ewa; Trocha, Hanna

    2003-08-01

    Causative treatment of genetically determined Wilson's disease (WD) has been impossible so far, although gene therapy could be real in the future. Nowadays the principle of treatment is the elimination of the excess of easily mobilized copper, bound by chelating agents, the most important of which is d-penicillamine, through the kidneys. Blocking of the intestinal absorption of copper by administration of zinc preparations, which additionally induce hepatic metallothionein synthesis, is also possible. The aim of our study was to present own observations and results of treatment of Wilson's disease. During the last 16 years, we have observed 33 patients aged 13-60 (mean age 27 years) with various forms of WD. The studied group consisted of 11 females and 21 males, admitted to hospital or seen at the Specialistic Outpatient Department of Hepatology with various diagnoses. In addition to standard laboratory tests, the levels of ceruloplasmin, serum and urine copper, as well as the activity of some hepatic enzymes, proteins and HBV/HCV infection markers were determined. The patients were also examined by a neurologist and an ophthalmologist, with psychiatric consultation if necessary. Taking into account the overall clinical presentation, the patients were divided into the following groups according to the form of the disease: fulminant, acute, hepatic, hepatic with neurological and psychiatric symptoms, neuropsychiatric, asymptomatic. All the patients were initially treated with d-penicillamine. In most of them, no side effects were observed. The treatment was continued according to the levels of copper excreted with urine (for 10 years at the longest). After obtaining clinical improvement with reduced amount of copper excreted with 24-h urine, we tapered d-penicillamine doses or even discontinued the drug, introducing zinc preparations. In asymptomatic carriers, zinc preparations were used throughout the period of treatment. Early institution of chelation treatment

  9. Currently Clinical Views on Genetics of Wilson's Disease.

    Science.gov (United States)

    Chen, Chen; Shen, Bo; Xiao, Jia-Jia; Wu, Rong; Duff Canning, Sarah Jane; Wang, Xiao-Ping

    2015-07-05

    The objective of this study was to review the research on clinical genetics of Wilson's disease (WD). We searched documents from PubMed and Wanfang databases both in English and Chinese up to 2014 using the keywords WD in combination with genetic, ATP7B gene, gene mutation, genotype, phenotype. Publications about the ATP7B gene and protein function associated with clinical features were selected. Wilson's disease, also named hepatolenticular degeneration, is an autosomal recessive genetic disorder characterized by abnormal copper metabolism caused by mutations to the copper-transporting gene ATP7B. Decreased biliary copper excretion and reduced incorporation of copper into apoceruloplasmin caused by defunctionalization of ATP7B protein lead to accumulation of copper in many tissues and organs, including liver, brain, and cornea, finally resulting in liver disease and extrapyramidal symptoms. It is the most common genetic neurological disorder in the onset of adolescents, second to muscular dystrophy in China. Early diagnosis and medical therapy are of great significance for improving the prognosis of WD patients. However, diagnosis of this disease is usually difficult because of its complicated phenotypes. In the last 10 years, an increasing number of clinical studies have used molecular genetics techniques. Improved diagnosis and prediction of the progression of this disease at the molecular level will aid in the development of more individualized and effective interventions, which is a key to transition from molecular genetic research to the clinical study. Clinical genetics studies are necessary to understand the mechanism underlying WD at the molecular level from the genotype to the phenotype. Clinical genetics research benefits newly emerging medical treatments including stem cell transplantation and gene therapy for WD patients.

  10. Outcomes of Hirschsprung's disease associated with Mowat-Wilson syndrome.

    Science.gov (United States)

    Bonnard, Arnaud; Zeidan, Smart; Degas, Vanessa; Viala, Jérome; Baumann, Clarisse; Berrebi, Dominique; Perrusson, Odile; El Ghoneimi, Alaa

    2009-03-01

    Mowat-Wilson syndrome (MWS) is a developmental disorder presenting with mental retardation, delayed motor development, and a wide spectrum of clinical features. Hirschsprung's disease (HD) is associated in almost 50% of cases. This report aims to analyze the course of HD and to evaluate the clinical outcomes of these patients. Between 1997 and 2007, 110 patients presenting with HD were diagnosed and managed in our institution. Five of them presented the association of HD and MWS. Their records were reviewed retrospectively. All of the 5 patients have a genetic disorder specific of MWS (nonsense mutation or deletion on SIP1 gene, locus 2q22). Two patients underwent transanal endorectal pull-through procedure for classic rectosigmoid HD. Three patients were operated on for total colonic aganglionosis using Duhamel procedure. The median follow-up was 4 (range, 0.3-7) years. Only one patient is doing well (rectosigmoid HD). Two patients have a stoma diversion for severe motility disorders. Of the 3 total colonic aganglionosis, one still has repeated episodes of obstruction requiring total parenteral nutrition (TPN). The 2 others still have repeated episodes of enterocolitis. All patients required a prolonged TPN (32.5 months in average). Hirschsprung's disease associated with MWS is a severe condition. Even in case of short segment HD, patients can present motility disorder requiring a prolonged TPN. Physician and surgeon should be aware about the evolution of this rare condition.

  11. Identification of two novel mutations in the ATP7B gene that cause Wilson's disease

    Institute of Scientific and Technical Information of China (English)

    Hong-Wen Zhu; Yu-Min Li; Zhong-Bin Tao; Gang Su; Qiao-Ying Jin; Liang-Tao Zhao; Jia-Rui Zhu; Jun Yan; Tian-Yu Yu; Jie-Xian Ding

    2017-01-01

    Background:Wilson's disease is an autosomal recessive disorder characterized by liver disease and/or neurologic deficits due to copper accumulation and is caused by pathogenic mutations in the ATP7B gene.Methods:Two unrelated Chinese patients born to nonconsanguineous parents who were diagnosed with earlyonset Wiison's disease.DNA sequencing and bioinformation analysis were conducted.Results:We have identified four mutations in two family trios,of which two were novel,namely,c.3028A>G(p.K1010E) and c3992T>G (p.Y1331X),in each patient.Conclusions:Gene testing is playing an important role in diagnosis of Wilson's disease.The early-onset of Wilson's disease is apparently not associated with P-ATPase domain in the ATP7B protein.Our findings further widen the spectrum of mutations involving the ATP7B gene.

  12. Middle-aged heterozygous carriers of Wilson's disease do not ...

    Indian Academy of Sciences (India)

    or infectious disease were excluded), were chosen as control subjects (CS). All WDHzc were subjected to neurological examination. They were questioned about history of any liver. Keywords. autosomal recessive; ATP7B; copper; heterozygous carrier; phenotype; Wilson's disease. Journal of Genetics, Vol. 89, No.

  13. Use of zinc-copper metabolic interactions in the treatment of Wilson's disease.

    Science.gov (United States)

    Brewer, G J; Yuzbasiyan-Gurkan, V; Lee, D Y

    1990-10-01

    Zinc acetate is becoming a well-established therapy for the treatment of Wilson's disease. It is excellent for maintenance therapy and for the treatment of the presymptomatic patient. Current evidence suggests that it will also be excellent for the treatment of the pregnant patient. Zinc acts by inducing intestinal cell metallothionein, which binds copper with high affinity, blocking its absorption, and causing its excretion in the stool. We have shown that zinc, even in doses as low as 25 mg daily, negatively affects copper balance. Zinc in doses of 50 mg three times daily, with all doses separated from food, controls the abnormal positive copper balance, blocks uptake of orally administered 64Cu, controls urine and plasma copper, prevents the reaccumulation of hepatic copper, and prevents the development or progression of symptoms of copper toxicosis in Wilson's disease patients. Zinc acetate will probably be licensed in the near future for the treatment of Wilson's disease. We recommend that physicians use urine and plasma copper, and urine zinc, as primary monitoring tools. In contrast to the comfortable situation with maintenance therapy, the initial treatment of acutely ill Wilson's disease patients is not well worked out. Patients with neurological disease often get worse initially on penicillamine, and zinc acts more slowly than is ideal. We have initiated studies of tetrathiomolybdate for this purpose. Studies of biliary secretions of normal subjects suggest that they excrete regulatory (excess) copper packaged in a protease-resistant ceruloplasmin fragment. This fragment is missing in Wilson's disease bile. The gene for Wilson's disease is on chromosome 13, close to the retinoblastoma locus.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Face of the giant panda sign in Wilson disease | Chakraborty | SA ...

    African Journals Online (AJOL)

    Wilson disease usually presents with neurological or hepatic manifestations. Magnetic resonance imaging (MRI) of the brain is most informative in diagnosing this disease, especially in patients with neurological features. High T2 signal intensity in the corpus striatum is the most commonly encountered MRI finding. The 'face ...

  15. Alagille Syndrome and Wilson Disease in Siblings: A Diagnostic Conundrum

    Directory of Open Access Journals (Sweden)

    Meghan Amson

    2012-01-01

    Full Text Available The authors describe two siblings, each with a different, rare genetic condition that affects liver function. The index case, the 18-year-old asymptomatic brother of a young man recently diagnosed with Wilson disease, presented for Wilson disease screening and was also found to have abnormal liver function suggestive of cholestasis. However, ceruloplasmin level, 24 h urine copper concentration and liver synthetic function were normal. Further hepatic investigations and genetic mutation analysis were performed, ultimately leading to a diagnosis of Alagille syndrome. He was treated with ursodiol, which resulted in normalization of his liver function tests. Subsequently, he was found to be a carrier for a mutation in the Wilson disease gene, ATP7B. In the present report, the potential implications of being a heterozygote for Wilson disease in the context of Alagille syndrome are discussed. Also stressed is that care must be exercised by the clinician when diagnosing family members who may present with two different disorders closely mimicking one another.

  16. Elevated copper impairs hepatic nuclear receptor function in Wilson's disease.

    Science.gov (United States)

    Wooton-Kee, Clavia Ruth; Jain, Ajay K; Wagner, Martin; Grusak, Michael A; Finegold, Milton J; Lutsenko, Svetlana; Moore, David D

    2015-09-01

    Wilson's disease (WD) is an autosomal recessive disorder that results in accumulation of copper in the liver as a consequence of mutations in the gene encoding the copper-transporting P-type ATPase (ATP7B). WD is a chronic liver disorder, and individuals with the disease present with a variety of complications, including steatosis, cholestasis, cirrhosis, and liver failure. Similar to patients with WD, Atp7b⁻/⁻ mice have markedly elevated levels of hepatic copper and liver pathology. Previous studies have demonstrated that replacement of zinc in the DNA-binding domain of the estrogen receptor (ER) with copper disrupts specific binding to DNA response elements. Here, we found decreased binding of the nuclear receptors FXR, RXR, HNF4α, and LRH-1 to promoter response elements and decreased mRNA expression of nuclear receptor target genes in Atp7b⁻/⁻ mice, as well as in adult and pediatric WD patients. Excessive hepatic copper has been described in progressive familial cholestasis (PFIC), and we found that similar to individuals with WD, patients with PFIC2 or PFIC3 who have clinically elevated hepatic copper levels exhibit impaired nuclear receptor activity. Together, these data demonstrate that copper-mediated nuclear receptor dysfunction disrupts liver function in WD and potentially in other disorders associated with increased hepatic copper levels.

  17. Update on the clinical management of Wilson's disease.

    Science.gov (United States)

    Hedera, Peter

    2017-01-01

    Wilson's disease (WD), albeit relatively rare, is an important genetic metabolic disease because of highly effective therapies that can be lifesaving. It is a great imitator and requires a high index of suspicion for correct and timely diagnosis. Neurologic, psychiatric and hepatologic problems in WD are very nonspecific, and we discuss the most common clinical phenotypes. The diagnosis remains laboratory based, and here we review the most important challenges and pitfalls in laboratory evaluation of WD, including the emerging role of genetic testing in WD diagnosis. WD is a monogenic disorder but has very high allelic heterogeneity with >500 disease-causing mutations identified, and new insights into phenotype-genotype correlations are also reviewed. The gold standard of therapy is chelation of excessive copper, but many unmet needs exist because of possible clinical deterioration in treated patients and potential adverse effects associated with currently available chelating medications. We also review the most promising novel therapeutic approaches, including chelators targeting specific cell types, cell transplantation and gene therapy.

  18. The treatment of Wilson's disease, a rare genetic disorder of copper metabolism.

    Science.gov (United States)

    Purchase, Rupert

    2013-01-01

    Wilson's disease is a rare autosomal recessive disease characterised by the deposition of copper in the brain, liver; cornea, and other organs. The overload of copper inevitably leads to progressive liver and neurological dysfunction. Copper overload in patients with Wilson's disease is caused by impairment to the biliary route for excretion of dietary copper A combination of neurological, psychiatric and hepatic symptoms can make the diagnosis of Wilson's disease challenging. Most symptoms appear in the second and third decades of life. The disease affects between one in 30,000 and one in 100,000 individuals, and is fatal if left untreated. Five drugs are currently available to treat Wilson's disease: British Anti-Lewisite; D-penicillamine; trientine; zinc sulfate or acetate; and ammonium tetrathiomolybdate. Each drug can reduce copper levels and/or transform copper into a metabolically inert and unavailable form in the patient. The discovery and introduction of these five drugs owes more to the inspiration of a few dedicated physicians and agricultural scientists than to the resources of the pharmaceutical industry.

  19. Liver imaging findings of Wilson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Akpinar, Erhan [Hacettepe University, Faculty of Medicine, Department of Radiology, 06100 Ankara (Turkey); Akhan, Okan [Hacettepe University, Faculty of Medicine, Department of Radiology, 06100 Ankara (Turkey)]. E-mail: akhano@tr.net

    2007-01-15

    Wilson's disease is a rare, autosomal-recessive inherited disorder of copper metabolism resulting in accumulation of copper in liver. The form of liver disease varies, depending on the severity of the disease at the time of diagnosis and pathological findings include fatty changes, acute hepatitis, chronic active hepatitis, cirrhosis and occasionally fulminant hepatic necrosis. Liver imaging findings reflect a wide range of physiopathological processes of the disease and also demonstrate the associated findings of cirrhosis in cases with advanced disease.

  20. Imaging findings of liver involvement of Wilson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Akhan, Okan [Hacettepe University, Faculty of Medicine, Department of Radiology, Sihhiye/Ankara (Turkey); Akpinar, Erhan [Hacettepe University, Faculty of Medicine, Department of Radiology, Sihhiye/Ankara (Turkey)], E-mail: erhan.akpinar@gmail.com; Karcaaltincaba, Musturay; Haliloglu, Mithat; Akata, Deniz; Karaosmanoglu, Ali Devrim; Ozmen, Mustafa [Hacettepe University, Faculty of Medicine, Department of Radiology, Sihhiye/Ankara (Turkey)

    2009-01-15

    Purpose: The major purpose of this paper is to outline and correlate US, CT and MR imaging findings of liver in patients with Wilson's disease. Materials and methods: Twenty-eight patients (10 male, 18 female, median age 16) with Wilson's disease were examined with US, CT and MRI. Liver echogenicity, echo pattern, contour irregularity, periportal thickness, perihepatic fat layer thickness, the presence of focal parenchymal lesion, and other associated findings were recorded by US in every patient. CT and MRI were done in 20 and 12 patients, respectively. Results: Contour irregularity was observed in 24 patients and heterogeneous parenchymal echo pattern was seen in 26 patients with US. The presence of increased perihepatic fat layer was observed in eight patients. Severe parenchymal atrophy was seen in all lobes of the liver including caudate in contrast to post-viral chronic liver disease. Nineteen patients had periportal thickening. US showed multiple hyper and/or hypoechoic nodules smaller than 1 cm in 13 patients. MRI demonstrated small nodular hypointense areas on T2-weighted images in five patients. In only one patient these nodules showed contrast enhancement in CT and MR and pathologically proved to be dysplastic nodule. Conclusion: Wilson's disease involving the liver has several unique radiological findings in comparison to other types of cirrhosis. These specific features include multiple nodular lesions in the liver, presence of perihepatic fat layer and normal caudate lobe which is contrary to other types cirrhosis. Liver injury in the Wilson's disease can be defined by imaging modalities, especially by US which we think is the most precise imaging modality to detect early parenchymal changes in the progress of the disease.

  1. Hereditary Multiple Cerebral Cavernous Malformations Associated with Wilson Disease and Multiple Lipomatosis.

    Science.gov (United States)

    Belousova, Olga B; Okishev, Dmitry N; Ignatova, Tatyana M; Balashova, Maria S; Boulygina, Eugenia S

    2017-09-01

    We report on a patient with 2 Mendelian diseases-symptomatic multiple familial cerebral cavernous malformations (FCCMs) and Wilson disease. Genetic analysis revealed single nucleotide polymorphisms in genes CCM2 and CCM3, associated with cavernous malformations, and homozygote mutation in the ATP7B gene, responsible for Wilson disease. FCCMs were symptomatic in 3 generations. The patient also had multiple lipomatosis, which is suggested to be a familial syndrome. In recent years there has been an increasing amount of publications linking FCCMs with other pathology, predominantly with extracranial and intracranial mesenchymal anomalies. The present study is the description of an unusual association between 2 independent hereditary diseases of confirmed genetic origin-a combination that has not been described previously. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Presentación clínica, diagnóstico y evolución a largo plazo en 29 pacientes con enfermedad de Wilson Clinical presentation, diagnosis, and long-term outcome of 29 patients with Wilson's disease

    Directory of Open Access Journals (Sweden)

    J. L. Rodrigo Agudo

    2008-08-01

    Full Text Available Objetivo: analizar las características clínicas, el tratamiento y evolución de los pacientes diagnosticados de enfermedad de Wilson (EW en la región de Murcia. Pacientes y método: se realizó un análisis retrospectivo de las historias clínicas de los 29 pacientes (edad media ± DE, 20,3 ± 13,4 años con EW diagnosticados en los últimos 16 años. Resultados: el motivo de consulta más frecuente fue el descubrimiento de transaminasas elevadas, en casi la mitad de los pacientes, seguido de temblor o distonía en el 17% respectivamente. El anillo de Kayser-Fleischer se objetivó en 17 de los 29 (58,6% pacientes (100% de los pacientes con afectación neurológica pura y en el 35,3% de los pacientes con clínica hepática pura; p Objective: to analyze the clinical characteristics, treatment, and follow-up of a cohort of 29 patients with Wilson's disease (WD within the region of Murcia. Patients and method: we reviewed the medical records of 29 cases of WD (mean age, 20.3 ± 13.4 years diagnosed during the last 16 years. Results: the most frequent reason for consultation was upon discovering a high transaminase level in almost half the patients, followed by tremors or dystonia in 17% of patients, respectively. A Kayser-Fleischer ring was observed in 17/29 (58.6% of patients (100% of patients with pure neurological involvement and 35% of patients with pure clinical hepatic disease; p < 0.001. Blood copper levels not associated with ceruloplasmin as well as cupruria were notably superior in patients with neurological symptoms and in those with liver cirrhosis at the time of diagnosis. Patient clinical symptoms remained stable with D-penicillamine or trientine, or improved during the observation period, for 18 out of 29 patients (62%, while 11 out of 29 patients (38% got worse. Conclusions: in our region patients with WD are diagnosed at a younger age, and in most cases for hepatic disease. Patients with neurological disease o liver cirrhosis had

  3. Dystonic Dysarthria in Wilson Disease: Efficacy of Zolpidem

    Directory of Open Access Journals (Sweden)

    Aurélia Poujois

    2017-10-01

    Full Text Available Wilson disease (WD is a rare genetic disorder characterized by copper overload in the liver and the brain. Neurological presentations are mainly related to the accumulation of copper in the basal ganglia, the brainstem, and the cerebellum. Dysarthria is a frequent symptom, with dystonic, spastic, or parkinsonian components and is usually resistant to medical or voice rehabilitation therapies. Here, we report the case of a patient with WD diagnosed at the age of 12, who presented a severe and constant dysarthria from dystonic origin which was unresponsive to benzodiazepines and anticholinergic drugs. When she was 25-year-old, she tried zolpidem at bedtime for sleeping difficulties and reported a paradoxical effect of this drug on her voice. To confirm the effect of zolpidem on her dystonic dysarthria, we realized a full evaluation of her dysarthria at baseline without zolpidem and after 4 days of treatment by 10 mg twice a day. Lexical access was evaluated by the semantic fluency; dysarthria by the Intelligibility Score, the spontaneous speech and reading rates, the maximum phonation time on the sustained vowel [a] and by a perceptive evaluation. Two hours after the intake of zolpidem, improvement of all the parameters tested, with the exception of the maximum phonation time, was observed. Semantic fluency increased by 59%, the spontaneous speech rate by 88% and the reading rate by 76%. General dystonia remained unchanged and the tolerance of zolpidem was satisfactory. Since then, the patient takes zolpidem 5 mg five times a day, and 4 years later shows persistent improvement in oral communication and a good drug tolerance. In this single-case study, we showed that regular daytime intake of zolpidem could have a persisting effect on a complex dystonic dysarthria that was resistant to usual medical treatments.

  4. Persistently and asymptomatic raised liver enzymes as a form of presentation of Wilson's disease at pediatric age

    Directory of Open Access Journals (Sweden)

    Catarina Matos

    2015-06-01

    Full Text Available Background: Wilson`s disease is a rare autosomal recessive disorder characterized by a change in the transport of copper in the liver, with progressive accumulation in this and other organs such as brain, kidney and cornea. Phenotypic expression of the disease varies widely and can range from elevated liver enzymes, fatty liver or gallstones in asymptomatic patients, to cirrhosis and fulminant hepatic failure, or disabling neuropsychiatric disease. Aim: To characterize a sample of patients with Wilson´s disease. Patients and Methods: Retrospective survey including children diagnosed with Wilson´s disease between 2002 and 2011 according to the criteria of the European Association for the Study of the Liver (2012. We analyzed family history; age, clinical data, imaging and histology at the time of diagnosis; genetic analysis; treatment and side effects; follow-up and current status. Results: We identified five patients. Three had a family history of disease. All were asymptomatic and had maintained raised liver enzymes. No patient had clinical stigmata of chronic liver disease. One female patient had overweight. All were treated with D-penicillamine, withdrawn in two patients because of side effects. Currently all patients remain asymptomatic, without evidence of progression of liver disease, with a median follow-up of 5 years and 3 months. Discussion: Our series show that Wilson´s disease may be present with raised liver enzymes in asymptomatic children. The overweight patient alerts us to screen the disease in overweight/obese patients with raised liver enzymes and/or steatosis persisting for more than six months after weight loss.

  5. Is Parkinson's disease the heterozygote form of Wilson's disease: PD = 1/2 WD?

    Science.gov (United States)

    Johnson, S

    2001-02-01

    Wilson's disease (WD) patients often present with Parkinson's disease (PD). Furthermore, most patients with PD have reduced ceruloplasmin, a characteristic of Wilson's disease. WD is an autosomal recessive disease (requires two faulty copies of a gene to produce a homozygote individual) that afflicts 1 in 1000 people. However, the number of people with one faulty copy (heterozygotes) is much larger, probably about 2% of the population. I hypothesize that the large number of heterozygotes for WD are at greatly increased risk for idiopathic PD, because these people accumulate free copper in the basal ganglia at a slower rate than homozygotes, which accounts for the fact that PD usually develops after 40 years of age. In WD, a ceruloplasmin deficiency results in accumulation of free Cu in the liver, brain, kidneys, etc. The excess Cu results in impaired Zn absorption, which would account for the low levels of Zn in the brains of PD patients. Moreover, the high levels of Fe found in the substantia nigra of PD patients may perhaps be explained by free Cu binding to iron binding protein-1 (IBP-1), causing it to malfunction and preventing it from detaching itself from the transferrin receptor (TfR) inhibition gene, resulting in expression of TfR even when the cell has plenty of Fe. The gradual accumulation of Fe and Cu would explain the damage inflicted on the substantia nigra by free radicals catalyzed by these two metals and which is exacerbated by the low levels of CuZnSOD, due to the Zn deficiency mentioned above. Moreover, if this hypothesis is correct, then PD could be used to help discover the gene (or genes) responsible for WD and vice versa. Furthermore, idiopathic PD could be prevented by identifying the heterozygote individuals and providing them with Zn supplementation, Cu chelation therapy and phlebotomy to eliminate Fe.

  6. Screening for Wilson disease in acute liver failure: a comparison of currently available diagnostic tests

    DEFF Research Database (Denmark)

    Korman, J.D.; Volenberg, I.; Balko, J.

    2008-01-01

    Acute liver failure (ALF) due to Wilson disease (WD) is invariably fatal without emergency liver transplantation. Therefore, rapid diagnosis of WD should aid prompt transplant listing. To identify the best method for diagnosis of ALF due to WD (ALF-WD), data and serum were collected from 140 ALF...... patients (16 with WD), 29 with other chronic liver diseases and 17 with treated chronic WD. Ceruloplasmin (Cp) was measured by both oxidase activity and nephelometry and serum copper levels by atomic absorption spectroscopy. In patients with ALF, a serum Cp

  7. A case of spatial neglect dysgraphia in Wilson's Disease.

    Science.gov (United States)

    Auclair, Laurent; Siéroff, Eric; Kocer, Serdar

    2008-01-01

    We report here on a single neuropsychological case study of a young girl, KH, who presented with Wilson's Disease (WD) associated with a peripheral spatial neglect dysgraphia without major problems in the standard clinical tests of spatial neglect. Few studies have demonstrated a visuospatial deficit in WD and to date there has been no report of neglect syndrome arising from WD. However, recent studies have demonstrated that neglect is frequently associated with brain damage including the primary site of WD, the basal ganglia. KHs writing abilities were evaluated just after her admission to the rehabilitation department and 6 months later. The baseline evaluation demonstrated that KH had neglect dysgraphia with verbal stimuli (e.g., words or sentences) although her deficit was less evident in drawing multiple geometric shapes. Six months after the initial evaluation, KH showed evidence of neglect dysgraphia only when writing was associated with a secondary memory task. KHs writing performance is discussed with reference to previous cases of spatial neglect dysgraphia and in the context of spatial neglect. We suggest that the asymmetry between verbal writing and nonverbal drawing disturbances was caused by different attentional loads.

  8. Atomic Absorption Spectrometry in Wilson's Disease and Its Comparison with Other Laboratory Tests and Paraclinical Findings

    OpenAIRE

    Mahjoub, Fatemeh; Fereiduni, Rana; Jahanzad, Isa; Farahmand, Fatemeh; Monajemzadeh, Maryam; Najafi, Mehri

    2012-01-01

    Objective Wilson's disease (WD) is an autosomal recessive disease with genetic abnormality on chromosome 13 causing defect in copper metabolism and increased copper concentration in liver, central nervous system and other organs, which causes different clinical manifestations. The aim of this study was to determine the sensitivity of different clinical and paraclinical tests for diagnosis of Wilson's disease. Methods Paraffin blocks of liver biopsy from 41 children suspicious of WD were colle...

  9. Wilson's disease: the 60th anniversary of Walshe's article on treatment with penicillamine.

    Science.gov (United States)

    Teive, Hélio A G; Barbosa, Egberto Reis; Lees, Andrew J

    2017-01-01

    This historical review describes Professor Walshe's seminal contribution to the treatment of Wilson's disease on the 60th anniversary of his pioneering article on penicillamine, the first effective treatment for the condition.

  10. Successful Splenectomy for Hypersplenism in Wilson's Disease: A Single Center Experience from China.

    Science.gov (United States)

    Li, Liang-Yong; Yang, Wen-Ming; Chen, Huai-Zhen; Wu, Yun-Hu; Fang, Xiang; Zhang, Jing; Wang, Zhen; Han, Yong-Sheng; Wang, Yu

    2015-01-01

    Splenomegaly and pancytopenia are common in Wilson's disease (WD) and splenectomy is one of the conventional treatments for splenomegaly and the associated pancytopenia. However, splenectomy remained controversial for hypersplenism in WD as it was reported that splenectomy leaded to serious emotional and neurological deterioration in WD patients with hypersplenism. In the current study, we present our experiences in 70 WD patients with hypersplenism who had undergone splenectomy, outlining the safety and efficacy of splenectomy in WD. The clinical database of 70 WD patients with hypersplenism who had undergone splenectomy in our hospital between 2009 and 2013 were reviewed and followed-up regularly. Before splenectomy, all the patients accepted a short period of anti-copper treatment with intravenous sodium 2, 3-dimercapto-1-propane sulfonate (DMPS). All the patients demonstrated a marked improvement in platelet and leucocyte counts after splenectomy. No severe postoperative complication was observed. In particular, none of the 37 patients with mixed neurologic and hepatic presentations experienced neurological deterioration after splenectomy, and none of the patients with only hepatic presentations newly developed neurological symptoms. During the one year follow-up period, no patient presented hepatic failure or hepatic encephalopathy, no hepatic patient newly developed neurological presentations, and only 3 patients with mixed neurologic and hepatic presentations suffered neurological deterioration and these 3 patients had poor compliance of anti-copper treatment. Quantative analysis of the neurological symptoms in the 37 patients using the Unified Wilson's Disease Rating Scale (UWDRS) showed that the neurological symptoms were not changed in a short-term of one week after splenectomy but significantly improved in a long-term of one year after splenectomy. Additionally, compared to that before splenectomy, the esophageal gastric varices in most patients

  11. Atp7b-/- mice as a model for studies of Wilson's disease.

    Science.gov (United States)

    Lutsenko, Svetlana

    2008-12-01

    Wilson's disease is a severe human disorder of copper homoeostasis. The disease is associated with various mutations in the ATP7B gene that encodes a copper-transporting ATPase, and a massive accumulation of copper in the liver and several other tissues. The most frequent disease manifestations include a wide spectrum of liver pathologies as well as neurological and psychiatric abnormalities. A combination of copper chelators and zinc therapy has been used to prevent disease progression; however, accurate and timely diagnosis of the disease remains challenging. Similarly, side effects of treatments are common. To understand better the biochemical and cellular basis of Wilson's disease, several animal models have been developed. This review focuses on genetically engineered Atp7b(-/-) mice and describes the properties of these knockout animals, insights into the disease progression generated using Atp7b(-/-) mice, as well as advantages and limitations of Atp7b(-/-) mice as an experimental model for Wilson's disease.

  12. Genotype-phenotype correlations in a mountain population community with high prevalence of Wilson's disease: genetic and clinical homogeneity.

    Directory of Open Access Journals (Sweden)

    Relu Cocoş

    Full Text Available Wilson's disease is an autosomal recessive disorder caused by more than 500 mutations in ATP7B gene presenting considerably clinical manifestations heterogeneity even in patients with a particular mutation. Previous findings suggested a potential role of additional genetic modifiers and environment factors on phenotypic expression among the affected patients. We conducted clinical and genetic investigations to perform genotype-phenotype correlation in two large families living in a socio-culturally isolated community with the highest prevalence of Wilson's disease ever reported of 1 ∶ 1130. Sequencing of ATP7B gene in seven affected individuals and 43 family members identified a common compound heterozygous genotype, H1069Q/M769H-fs, in five symptomatic and two asymptomatic patients and detected the presence of two out of seven identified single nucleotide polymorphisms in all affected patients. Symptomatic patients had similar clinical phenotype and age at onset (18 ± 1 years showing dysarthria and dysphagia as common clinical features at the time of diagnosis. Moreover, all symptomatic patients presented Kayser-Fleischer rings and lack of dystonia accompanied by unfavourable clinical outcomes. Our findings add value for understanding of genotype-phenotype correlations in Wilson's disease based on a multifamily study in an isolated population with high extent of genetic and environmental homogeneity as opposed to majority of reports. We observed an equal influence of presumed other genetic modifiers and environmental factors on clinical presentation and age at onset of Wilson's disease in patients with a particular genotype. These data provide valuable inferences that could be applied for predicting clinical management in asymptomatic patients in such communities.

  13. Truncating mutations in the Wilson disease gene ATP7B are associated with very low serum ceruloplasmin oxidase activity and an early onset of Wilson disease

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    Tuma Sabine

    2010-01-01

    Full Text Available Abstract Background Mutations in the gene ATP7B cause Wilson disease, a copper storage disorder with a high phenotypic and genetic heterogeneity. We aimed to evaluate whether 'severe' protein-truncating ATP7B mutations (SMs are associated with low serum ceruloplasmin oxidase activities and an early age of onset when compared to missense mutations (MMs. Methods The clinical phenotype of 59 genetically confirmed WD patients was analyzed retrospectively. Serum ceruloplasmin was measured by its oxidase activity with o-dianisidine dihydrochloride as substrate and immunologically. Results Thirty-nine patients had two MMs, 15 had the genotype SM/MM, and 5 patients had two SMs on their ATP7B alleles. Enzymatic and immunologic serum ceruloplasmin levels differed significantly between the three groups (P Conclusions In our German study cohort truncating ATP7B mutations were associated with lower ceruloplasmin serum oxidase levels and an earlier age of onset when compared to MMs. Measurement of serum ceruloplasmin oxidase might help to predict presence of truncating ATP7B mutations and might facilitate the mutation analysis.

  14. Atomic Absorption Spectrometry in Wilson's Disease and Its Comparison with Other Laboratory Tests and Paraclinical Findings.

    Science.gov (United States)

    Mahjoub, Fatemeh; Fereiduni, Rana; Jahanzad, Isa; Farahmand, Fatemeh; Monajemzadeh, Maryam; Najafi, Mehri

    2012-03-01

    Wilson's disease (WD) is an autosomal recessive disease with genetic abnormality on chromosome 13 causing defect in copper metabolism and increased copper concentration in liver, central nervous system and other organs, which causes different clinical manifestations. The aim of this study was to determine the sensitivity of different clinical and paraclinical tests for diagnosis of Wilson's disease. Paraffin blocks of liver biopsy from 41 children suspicious of WD were collected. Hepatic copper concentrations were examined with atomic absorption spectrophotometry (Australian GBC, model: PAL 3000). Fifteen specimens had hepatic copper concentration (dry weight) more than 250μg/g. Clinical and laboratory data and histologic slides of liver biopsies of these 15 children were reviewed retrospectively. Liver tissue was examined for staging and grading of hepatic involvement and also stained with rubeonic acid method for copper. Patients were 5-15 years old (mean age=9.3 years, standard deviation=2.6) with slight male predominance (9/15=60%). Five (33%) patients were 10 years old. Three (20%) of them were referred for icterus, 8 (54%) because of positive family history, 2 (13%) due to abdominal pain and 2 (13%) because of hepatosplenomegaly and ascites. Serum AST and ALT levels were elevated at the time of presentation in all patients. In liver biopsy, histological grade and stage was 0-8 and 0-6 respectively, 2 (13%) had cirrhosis, 1 (7%) had normal biopsy and 12 (80%) showed chronic hepatitis. Hepatic copper concentrations were between 250 and 1595 μg/g dry weight. The sensitivity of various tests were 85% for serum copper, 83% for serum ceruloplasmin, 53% for urinary copper excretion, 44% for presence of KF ring and 40% for rubeonic acid staining on liver biopsies. None of the tests stated in the article were highly sensitive for diagnosis of WD, so we suggest that diagnosis should be based on combination of family history, physical examination and different tests.

  15. Wilson's disease: the importance of measuring serum caeruloplasmin non-immunologically.

    Science.gov (United States)

    Walshe, J M

    2003-03-01

    Wilson's disease should be considered as a possible diagnosis in any child, adolescent or young adult with liver damage without other explanation, especially when haemolysis is present. However, it may also present in adolescents or young adults with neurological signs confined to the motor system. The first diagnostic screening test is the estimation of the serum caeruloplasmin and total serum copper concentrations, with calculation of the serum non-caeruloplasmin-bound ('free') copper. Serum caeruloplasmin, which contains copper, is best determined by measurement of its oxidase activity, as the immunonephelometric method measures both caeruloplasmin and the biologically inactive apo-form. Diagnosis may be confirmed by an elevated urinary copper excretion. All close relatives of an identified patient must be screened and, where doubt persists, investigation of the Wilson's gene at chromosome 13q14.3 can be employed. Lifelong follow-up studies are best conducted in a specialist centre. Compliance with chelating therapy (penicillamine or trientine) or administration of the metal antagonist tetrathiomolybdate or zinc is monitored by determination of the serum 'free' copper, which should be maintained at or near 1.6 micromol/L (10 microg/100 mL). Side-effects of therapy are detected by the estimation of urinary total protein, full blood count and erythrocyte sedimentation rate, clotting factors and liver function tests.

  16. Clinical Features and Therapeutic Response in Taiwanese Children With Wilson's Disease: 12 Years of Experience in a Single Center

    OpenAIRE

    Wang, Li-Ching; Wang, Jiaan-Der; Tsai, Chi-Ren; Cheng, Shao-Bin; Lin, Chieh-Chung

    2010-01-01

    Wilson's disease (WD) is an autosomal recessive defect of cellular copper export. Early diagnosis in children is difficult due to its obscure clinical presentations. The efficacy of zinc salts is well documented, although there are limited data concerning zinc use in pediatric patients with WD. Methods: We performed a retrospective analysis of clinical features, laboratory results and treatment responses in children with WD diagnosed at Taichung Veterans General Hospital between 1996 and 2...

  17. Truncating mutations in the Wilson disease gene ATP7B are associated with very low serum ceruloplasmin oxidase activity and an early onset of Wilson disease.

    Science.gov (United States)

    Merle, Uta; Weiss, Karl Heinz; Eisenbach, Christoph; Tuma, Sabine; Ferenci, Peter; Stremmel, Wolfgang

    2010-01-18

    Mutations in the gene ATP7B cause Wilson disease, a copper storage disorder with a high phenotypic and genetic heterogeneity. We aimed to evaluate whether 'severe' protein-truncating ATP7B mutations (SMs) are associated with low serum ceruloplasmin oxidase activities and an early age of onset when compared to missense mutations (MMs). The clinical phenotype of 59 genetically confirmed WD patients was analyzed retrospectively. Serum ceruloplasmin was measured by its oxidase activity with o-dianisidine dihydrochloride as substrate and immunologically. Thirty-nine patients had two MMs, 15 had the genotype SM/MM, and 5 patients had two SMs on their ATP7B alleles. Enzymatic and immunologic serum ceruloplasmin levels differed significantly between the three groups (P SMs (0.0 U/L; IQR, 0.0-0.0 U/L and 0.02 g/L; IQR, 0.01-0.02 g/L, respectively) and the highest in patients with two MMs (17.8 U/L; IQR, 5.8-35.1 U/L and 0.11 g/L; IQR,0.10-0.17 g/L, respectively). The age of onset was also significantly different between the three patient groups (P < 0.05), with SM/SM patients showing the earliest onset (13 years; IQR, 9-13 years) and patients with two MMs showing the latest onset (22 years; IQR, 14-27 years). By ROC curve analysis a ceruloplasmin oxidase level

  18. Endemic Tyrolean infantile cirrhosis is not an allelic variant of Wilson's disease.

    Science.gov (United States)

    Wijmenga, C; Müller, T; Murli, I S; Brunt, T; Feichtinger, H; Schönitzer, D; Houwen, R H; Müller, W; Sandkuijl, L A; Pearson, P L

    1998-01-01

    Recently, 138 cases of infantile cirrhosis originating in several families in the Austrian province of the Tyrol were reported. This endemic Tyrolean infantile cirrhosis (ETIC) is indistinguishable from Indian childhood cirrhosis (ICC), idiopathic copper toxicosis (ICT), and resembles the early forms of Wilson's disease (WND). It has been argued that ETIC might represent an allelic variant of the WND gene, which is a copper transporting P-type ATPase (ATP7B). Assuming that ETIC results from a founder effect, a possible role for ATP7B in ETIC was investigated by association studies and haplotype sharing. Because of its lethality, the mapping of ETIC was focused on obligate gene carriers, i.e. the patients' parents. Our data indicate that ETIC is a separate genetic entity, distinct from WND.

  19. Measurement of urinary copper excretion after 48-h d-penicillamine cessation as a compliance assessment in Wilson's disease.

    Science.gov (United States)

    Dzieżyc, Karolina; Litwin, Tomasz; Chabik, Grzegorz; Członkowska, Anna

    2015-01-01

    Treatment of Wilson's disease (WD) with anti-copper agents is effective in most compliant patients. During long-term treatment with chelating agents, a two-day interruption of the treatment should result in normal urinary copper concentrations (copper excretion analysis 48 h after interruption of chelating therapy. Thirty-two patients were enrolled. After DPA cessation, normalization of copper excretion was observed in 91% of reportedly compliant patients. The specificity and sensitivity values of this test were 87% and 77%, respectively. Measurement of 24-h urinary copper excretion after a 48-h interruption of DPA therapy in patients with WD is a reliable method for confirming patients' compliance.

  20. [Diagnosis and therapy of inheritable liver diseases: hemochromatisis, Wilson's disease and alpha-1-antitrypsin deficiency].

    Science.gov (United States)

    Strassburg, Ch P

    2005-01-19

    The recent years have seen significant progress in the area of genetically determined liver diseases. For hereditary hemochromatosis, Wilson's disease and alpha-1 antitrypsin deficiency the underlying genetic defects have been described and well characterized. Although a direct relationship between genetic defect and disease manifestation exists genetic test only have a limited diagnostic usefulness which requires exact knowledge of the underlying molecular pathology. The classical C282Y and H63D mutations of the HFE gene only show a penetrance of 10-20% in hemochromatosis and are not useful for population screening. Genetic screening for ATP7B (Wilson's disease) and alpha-1 antitrypsin deficiency variants is limited by the existence of a plethora of individual mutations. Genetic tests are mainly restricted to the counseling of families in whom these diseases are present. Foremost the diagnosis of the three diseases is reached by clinical, biochemical and in some instances also histological means which are supplemented and confirmed by the use of appropriate genetic tests.

  1. Hypercalciuria and nephrocalcinosis as early feature of Wilson disease onset: description of a pediatric case and literature review.

    Science.gov (United States)

    Di Stefano, Valeria; Lionetti, Elena; Rotolo, Novella; La Rosa, Mario; Leonardi, Salvatore

    2012-08-01

    Wilson's disease (WD) is a rare autosomal-recessive disorder characterized by a mutation in the ATP7B gene, located on chromosome 13, which encodes a protein involved in the metabolism of copper. We described the case of an Indian male with a history of polydipsia and polyuria, related to hypercalciuria and consequent nephrocalcinosis. The symptoms began at the age of five years old, but he was not diagnosed with WD until he reached an adolescent age. We started therapy with D-Penicillamine, B-vitamin complex and recommended a low copper diet. Renal involvement in Wilson's disease, characterizing by hypercalciuria, was firstly reported by Litin in 1959. Our case was different and peculiar from the previously described cases because the patient presented a very long history (10 years) of permanent hypercalciuria without any acute episode of nephrolithiasis.

  2. Which factors are associated with global cognitive impairment in Wilson's disease?

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    Norberto Anízio Ferreira Frota

    Full Text Available ABSTRACT Background: Patients with Wilson's disease (WD present cognitive impairment, especially in executive functions. Which other factors might be associated with global cognitive decline in these patients remains unclear. Objective: To assess which factors are associated with worse performance on a global cognitive test in patients with WD. Methods: Twenty patients with WD underwent cognitive assessment with the following tests: the Mini-Mental State Examination (MMSE, Dementia Rating Scale (DRS, verbal fluency test, brief cognitive battery, clock drawing test, Frontal Assessment Battery, Stroop test, Wisconsin card sorting test, Hopper test, cubes (WAIS and the Pfeffer questionnaire. MRI changes were quantified. Patients with poor performance on the DRS were compared to patients with normal performance. Results: Nine patients had a poor performance on the DRS. This group had lower educational level (9.11±3.58 × 12.82±3.06 and a greater number of changes on MRI (9.44±2.74 × 6.27±2.45. The presence of hyperintensity in the globus pallidus on MRI was more frequent in this group (66.6% vs 9.0%, with OR=5.38 (95% CI 0.85-33.86. Conclusion: Global cognitive impairment was prevalent in this sample of patients with WD and was associated with low educational level, number of changes on MRI and MRI hyperintensity in the globus pallidus.

  3. Atypical case of Wilson's disease with psychotic onset, low 24 hour urine copper and the absence of Kayser-Fleischer rings

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    Krstić Dragan

    2014-01-01

    Full Text Available Introduction. Wilson's disease is typically manifested in two clinical forms, neurological and hepatic and in rare cases it starts with psychiatric symptoms exclusively. We presented a rare atypical case of Wilson's disease with psychotic onset. Case report. A 22-year-old male patient was initially presented with predominant signs and symptoms of psychiatric disorder and then later with the development of neurological signs and symptoms. Neuroimaging, detected metal deposits in central nervous system (CNS but not in peripheral organs, while serum analysis excluded pantothenate-kinase associated neurodegeneration (PKAN and aceruloplasminemia. In favor of the diagnosis of Wilson's disease there were reduced concentrations of copper and ceruloplasmin concentrations and metal deposits in CNS, but other pathognomonic signs and symptoms were absent: in-creased copper in urine, Kayser-Fleischer rings in Descemet’s corneal membrane and deposits of copper in liver. Introduction of penicillamine treatment resulted in improvement in mental and general health of the patient. Molecular genetic analysis definitely confirmed the diagnosis of Wilson's disease. Conclusion. Wilson's disease can remain undetected for a long period of time if masked with dominant or exclusive psychiatric symptoms. If clear clinical symptoms and signs, and unambiguous laboratory findings are not present, it is necessary to perform molecular genetic analysis to confirm the definitive diagnosis.

  4. Doença de Wilson em crianças e adolescentes: diagnóstico e tratamento Wilson's disease in children and adolescents: diagnosis and treatment

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    Stephania de Andrade Sócio

    2010-06-01

    Pediatric Hepatology Ambulatory of the Hospital das Clínicas of Universidade Federal de Minas Gerais, Brazil, from 1985 to 2008. Data were collected by revision of medical charts and during clinical follow-up. RESULTS: Patients were 2.8 to 15.1 years old, with a mean age of 8.8±0.9 years. The disease main presentation was hepatic (53%, followed by the asymptomatic form, diagnosed by family screening. The Kayser-Fleischer ring was observed in 41% of the patients. The ceruloplasmin was altered in 15 out of 17 patients, and the urinary copper varied from 24 to 1000mcg/24h (median: 184mcg/24h. The treatment was stablished with D-penicillamine in all cases. Slight side effects were observed in five children, with no need to interrupt or change medication. Clinical and laboratory responses to treatment, with normalization of aminotransferases levels, were shown in 14 patients after a median of 10.7 months. Although treated, three patients died (one due to fulminant hepatitis and two due to severe hepatic failure. CONCLUSIONS: Wilson's disease is rare in the pediatric group. In children, the main presentation is the liver disease. The diagnosis can be established by reduced ceruloplasmin levels and elevated copper excretion in the 24-hour urine, but it demands high suspicion level. There are good tolerance and response to medical treatment.

  5. Wilson Disease Protein ATP7B Utilizes Lysosomal Exocytosis to Maintain Copper Homeostasis

    NARCIS (Netherlands)

    Polishchuk, Elena V.; Concilli, Mafalda; Iacobacci, Simona; Chesi, Giancarlo; Pastore, Nunzia; Piccolo, Pasquale; Paladino, Simona; Baldantoni, Daniela; van IJzendoorn, Sven C. D.; Chan, Jefferson; Chang, Christopher J.; Amoresano, Angela; Pane, Francesca; Pucci, Piero; Tarallo, Antonietta; Parenti, Giancarlo; Brunetti-Pierri, Nicola; Settembre, Carmine; Ballabio, Andrea; Polishchuk, Roman S.

    2014-01-01

    Copper is an essential yet toxic metal and its overload causes Wilson disease, a disorder due to mutations in copper transporter ATP7B. To remove excess copper into the bile, ATP7B traffics toward canalicular area of hepatocytes. However, the trafficking mechanisms of ATP7B remain elusive. Here, we

  6. Wilson disease: Histopathological correlations with treatment on follow-up liver biopsies

    Science.gov (United States)

    Cope-Yokoyama, Sandy; Finegold, Milton J; Sturniolo, Giacomo Carlo; Kim, Kyoungmi; Mescoli, Claudia; Rugge, Massimo; Medici, Valentina

    2010-01-01

    AIM: To investigate the progression of hepatic histopathology in serial liver biopsies from Wilson disease (WD) patients. METHODS: We report a group of 12 WD patients treated with zinc and/or penicillamine who underwent multiple follow-up liver biopsies. Demographic, clinical and laboratory data were gathered and all patients underwent an initial biopsy and at least one repeat biopsy. RESULTS: Time to repeat biopsy ranged from 2 to 12 years. Six patients (non-progressors) showed stable hepatic histology or improvement. In one case, we observed improvement of fibrosis from stage 2 to 0. Six patients (progressors) had worsening of fibrosis. There was no significant correlation between the histological findings and serum aminotransferases or copper metabolism parameters. The hepatic copper concentration reached normal levels in only two patients: one from the non-progressors and one from the progressors group. The estimated rate of progression of hepatic fibrosis in the entire group was 0 units per year in the time frame between the first and the second liver biopsy (4 years), and 0.25 between the second and the third (3 years). In the progressors group, the rate of progression of liver fibrosis was estimated at 0.11 fibrosis units per year between the first and second biopsy and, 0.6 fibrosis units between the second and third biopsy. CONCLUSION: The inability of clinical tools to detect fibrosis progression in WD suggests that a liver biopsy with hepatic copper quantification every 3 years should be considered. PMID:20333789

  7. Quality of Life and Psychiatric Symptoms in Wilson's Disease: the Relevance of Bipolar Disorders.

    Science.gov (United States)

    Carta, Mg; Mura, G; Sorbello, O; Farina, G; Demelia, L

    2012-01-01

    Wilson's disease is an inherited disorder caused by a gene located on chromosome 13, which involved copper transportation across cell membranes. The disease can cause a reduced incorporation of copper into ceruloplasmin resulting in accumulation of this metal in the liver, central nervous system, kidneys and other organs. The objective is to define the frequencies of psychiatric disorders in WD, the amount of impairment of Quality of Life [QoL] in patients with WD and the relevance of the psychiatric disorders in the QoL of people suffering by WD. This is a systematic review. The search of the significant articles was carried out in PubMed using specific key words. Such other neurological diseases, WD is characterized by chronic course and need of treatments, impairment of functional outcomes and high frequency of psychiatric symptoms, although a specific association between Bipolar Disorders and WD was recently found. Despite this, since today few studies are carried on WD patients' quality of life related to psychiatric symptoms. Some new reports showed a link between presence of Bipolar Disorders diagnosis, cerebral damage and low Qol. Prospective studies on large cohorts are required to establish the effective impact of psychiatric disorders comorbidity, particularly Bipolar Disorders, on quality of life in WD and to clarify the causal link between brain damage, psychiatric disorders and worsening of QoL.

  8. The sunflower cataract in Wilson's disease: pathognomonic sign or rare finding?

    Science.gov (United States)

    Langwińska-Wośko, Ewa; Litwin, Tomasz; Dzieżyc, Karolina; Członkowska, Anna

    2016-09-01

    The presence of Kayser-Fleischer ring in patients with Wilson's disease (WD) is well documented and included in diagnostic algorithms; however, data about the occurrence of the second postulated ophthalmological sign of WD, sunflower cataract (SC), are limited and even conflicting. The aim of our study was to verify the occurrence of SC in WD. From January 2010 to May 2015, 81 consecutive, newly diagnosed WD patients underwent detailed ophthalmological examinations, including slit lamp examination with special attention to lens transparency, to verify the presence of SC in WD-naive patients. SC was detected in only one (1.2 %) of the examined WD patients, did not impact visual acuity; moreover, completely disappeared following a year of treatment for WD. SC may be a very rare and reversible ophthalmological manifestation of WD that is observed seldom and only at the time of WD diagnosis. We postulate that a finding of SC in WD patients is an interesting finding that may occur in the course of WD, but it is not a pathognomonic sign of WD.

  9. [Wilson's disease in decision-making functions of Iowa gambling task].

    Science.gov (United States)

    Wang, Juan; Zhang, Fang-fang; Yu, Xu-en; Han, Yong-sheng; Han, Yong-zhu; Wang, Kai

    2012-05-22

    To explore the presence of impaired decision-making functions of Wilson's disease patients in Iowa gambling task (IGT) and its association with basal ganglia damage. Thirty-two IGT patients with WD (WD group) and 29 healthy people (control group) were recruited from the same period. And two options of high and low rewards were selected. Before the start of experiment, a basal figure of 2000 yuan was shown on computer display and they were prompted to win more money as much as possible. The general trend was observed with or without social learning effects. With the increased number of cards selected, the number of favorable and unfavorable selections shifted from negative to positive and gradually rose in the control group. However, such a pattern was absent in the WD group. The WD patients in the IGT group in Trial4 and Trial5 were significantly lower than the controls (P = 0.009 and P = 0.020). The WD IGT patients have significant impairments of policy-making functions due to the damage of basal ganglia. And the effects of copper metabolism on cerebral cortex should be further studied in WD patients.

  10. Effects of copper toxicity on response inhibition processes: a study in Wilson's disease.

    Science.gov (United States)

    Stock, Ann-Kathrin; Reuner, Ulrike; Gohil, Krutika; Beste, Christian

    2016-07-01

    Wilson's disease (WD) is a rare genetic disease causing copper deposits in various tissues. Given the specificity of the underlying pathology, it is a good model to investigate the effects of copper toxicity on cognitive functions in humans. If left untreated, WD results in neurodegeneration and organ failure, but irrespective of potential brain damage, the medication might reduce cortical norepinephrine (NE) levels. In line with this, dysexecutive symptoms including increased impulsivity have been reported for WD patients, but the underlying mechanisms have remained elusive. We investigated inhibition and the associated neurophysiological correlates in n = 26 WD patients with mild-to-moderate clinical symptoms and matched healthy controls who completed a Go/Nogo task, while an EEG was recorded. Although the behavioral data do not show increased impulsivity in WD, the neurophysiological data show that evaluative processing of successful inhibition (as reflected by the P3 component) was strongly compromised. This was reflected by a decrease in ACC activity which was positively correlated with the severity of WD symptoms, stressing the importance of copper (toxicity) for neurocognitive functioning and impulsivity. These changes are most likely due to a combination of NE deficiency induced by WD medication as well as WD-induced brain damage. The fact that changes were still evident on a neurophysiological level suggests that neurophysiological correlates of cognitive processes and functions provide a more sensitive index of toxicity and/or treatment efficiency than purely behavioral measures.

  11. Liver transplantation for hemochromatosis, Wilson's disease, and other metabolic disorders.

    Science.gov (United States)

    Tung, B Y; Kowdley, K V

    1997-08-01

    Liver transplantation provides an effective means for replacing a failing liver, in addition to correcting the underlying abnormality in many metabolic disorders. Results of liver transplantation for metabolic diseases have been generally encouraging, with the exception of hereditary hemochromatosis, in which infectious and cardiac complications appear to increase post-transplant mortality. Better pretransplant diagnosis of hemochromatosis, utilizing the recently identified putative gene, may help reduce post-transplant complications. In metabolic diseases, improved understanding of the underlying genetic and molecular defects will lead to advances in medical therapy and perhaps a decreased need for liver transplantation. NTBC therapy for hereditary tyrosinemia and purified glucocerebroside therapy for Gaucher disease are two such examples. The prospects of gene therapy are being actively pursued for many metabolic diseases, such as CF, hemophilia, and familial hypercholesterolemia. Until such investigation leads directly to clinical practice, however, liver transplantation remains an effective option for therapy for a wide range of metabolic diseases.

  12. Encephalopathy in Wilson disease: copper toxicity or liver failure?

    National Research Council Canada - National Science Library

    Ferenci, Peter; Litwin, Tomasz; Seniow, Joanna; Czlonkowska, Anna

    2015-01-01

    Hepatic encephalopathy (HE) is a complex syndrome of neurological and psychiatric signs and symptoms that is caused by portosystemic venous shunting with or without liver disease irrespective of its etiology...

  13. Update on the clinical management of Wilson's disease

    OpenAIRE

    Hedera P

    2017-01-01

    Peter Hedera Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA Abstract: Wilson’s disease (WD), albeit relatively rare, is an important genetic metabolic disease because of highly effective therapies that can be lifesaving. It is a great imitator and requires a high index of suspicion for correct and timely diagnosis. Neurologic, psychiatric and hepatologic problems in WD are very nonspecific, and we discuss the most common clinical phenotypes. The di...

  14. Currently Clinical Views on Genetics of Wilson's Disease

    OpenAIRE

    Chen Chen; Bo Shen; Jia-Jia Xiao; Rong Wu; Sarah Jane Duff Canning; Xiao-Ping Wang

    2015-01-01

    Objective: The objective of this study was to review the research on clinical genetics of Wilson′s disease (WD). Data Sources: We searched documents from PubMed and Wanfang databases both in English and Chinese up to 2014 using the keywords WD in combination with genetic, ATP7B gene, gene mutation, genotype, phenotype. Study Selection: Publications about the ATP7B gene and protein function associated with clinical features were selected. Results: Wilson′s disease, also named hepat...

  15. [Research on the correlation between Chinese medical syndrome types and objective indices of Wilson's disease].

    Science.gov (United States)

    Wang, Gong-qiang; Ma, Xin-feng; Wang, Wei; Sun, Quan; Zhou, Zhi-hua; Han, Yong-zhu

    2013-11-01

    To explore the correlation between Chinese medical syndrome types of Wilson's disease (WD) and clinical materials as well as physical and chemical indices. Totally 116 WD patients were typed by Chinese medical syndrome. The correlation between Chinese medical syndrome types and clinical materials as well as physical and chemical indices were analyzed using binary stepwise Logistic regression by SPSS 19.0 Software, taking the common Chinese medical syndrome types as the dependent variable and clinical materials as well as physical and chemical indices as the independent variables. Gan-Galibladder dampness-heat syndrome (GGDHS, 35.3%). Gan-stagnation and Pi-deficiency syndrome (GSPDS, 13.8%), Gan-Shen yin deficiency syndrome (GSYDS, 13.8%), and phlegm-dampness retention syndrome (PDRS, 12.1%) were most often seen. GGDHS was positively correlated with grade of K-F ring, total bilirubin (TBIL), alanine transaminase (ALT), laminin (LN) (P types, ceruloplasmin (CP), aspartate aminotransferase (AST), and total protein (TP) (P types were correlated with clinical materials, physical and chemical indices in WD patients, which could provide experimental reference for Chinese medical syndrome typing. GGDHS, GSPDS, GSYDS, and PDRS were most often seen.

  16. Brain copper, iron, magnesium, zinc, calcium, sulfur and phosphorus storage in Wilson's disease.

    Science.gov (United States)

    Faa, G; Lisci, M; Caria, M P; Ambu, R; Sciot, R; Nurchi, V M; Silvagni, R; Diaz, A; Crisponi, G

    2001-01-01

    Wilson's disease (WD) is an inherited disorder of copper metabolism characterised by juvenile liver cirrhosis and by neurological symptoms. Copper levels in brain in WD have been reported to be 10 to 15 fold normal values, depending on the different brain regions. Being very few data on copper distribution in central nervous system in WD available, it seemed of interest to study the concentration of copper and of other trace elements (Zn, P, Mg, Ca, Fe and S) in the brain of a patient died for WD. a 56 year old woman affected by WD was admitted to our hospital with signs of hepatic failure and died few days later. At autopsy, a brain slice extending from the left to the right hemisphere was divided in 28 samples. On each sample Copper, Iron, Magnesium, Phosphorus, Sulphur, Zinc and Calcium were determined by Induced Coupled Plasma Atomic Emission Spectroscopy. the mean concentration of copper, ranging from 88 to 158 microg/g of dry tissue in all the brain specimens was higher than literature reference values, while that of the other tested elements was considerably lower. 1) In the brain of WD patient examined the status of trace elements was extensively altered. Further studies are necessary to correlate the concentration of trace elements with pathological lesions and with clinical pictures. 2) The elements considered in our study showed an uneven distribution in different brain areas.

  17. Cerebral neurotransmission in huntington's disease and wilson's disease; Zerebrale Neurotransmission bei Chorea Huntington und Morbus Wilson

    Energy Technology Data Exchange (ETDEWEB)

    Barthel, H.; Sabri, O. [Klinik und Poliklinik fuer Nuklearmedizin, Univ. Leipzig (Germany)

    2002-09-01

    Huntington's disease and Wilson's disease are hereditary disorders with different neuropsychiatric symptoms. In both cases, these symptoms are mainly attributed to functional alterations of neurons, which are located in the basal ganglia. According deficits have been found by investigating the dopaminergic neurotransmission with different PET and SPECT tracers. For both diseases, these deficits revealed to concordantly involve the pre- and postsynaptic compartment. Apart from the dopaminergic system, more recent studies showed alterations of other neurotransmitter systems, like the serotonergic, GABA-ergic and opioide system. Except for scientific studies, nuclear medicine imaging is not regularly required for primary diagnosis of both disorders. In the case of Huntington's disease, however, imaging can be helpful for differential diagnosis to other diseases with similar initial symptoms and to determine the organic manifestation of the gene defect. In addition, neurotransmitter imaging with radiortracers could gain more relevance in the future in supporting decisions on specific treatments or for therapy monitoring in both diseases. (orig.) [German] Bei der Chorea Huntington und dem Morbus Wilson handelt es sich um erbliche Erkrankungen mit unterschiedlicher neuropsychiatrischer Symptomatik, welche im Wesentlichen auf Funktionsstoerungen von im Basalganglienbereich lokalisierten Neuronen zurueckgefuehrt werden. Untersuchungen der dopaminergen Neurotransmission mit verschiedenen PET- und SPECT-Radiopharmaka ergaben dementsprechende Defizite, welche fuer beide Erkrankungen konkordant das prae- und postsynaptische Kompartment betrafen. Juengere Studien deuten darueber hinaus auf Stoerungen anderer Neurotransmitter-Systeme, wie z.B. des serotonergen, GABAergen und Opioid-Systems, hin. Ausserhalb von wissenschaftlichen Fragestellungen ist die nuklearmedizinische Bildgebung bei beiden Erkrankungen in der Primaerdiagnostik eher selten erforderlich. Im

  18. Biopolymer strategy for the treatment of Wilson´s disease

    Czech Academy of Sciences Publication Activity Database

    Vetrík, Miroslav; Mattová, J.; Macková, Hana; Kučka, Jan; Poučková, P.; Kukačková, Olivia; Brus, Jiří; Eigner-Henke, S.; Sedláček, Ondřej; Šefc, L.; Štěpánek, Petr; Hrubý, Martin

    2018-01-01

    Roč. 273, 10 March (2018), s. 131-138 ISSN 0168-3659 R&D Projects: GA ČR(CZ) GA16-02870S; GA MZd(CZ) NV15-25781A; GA MŠk(CZ) LM2015064; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : Wilson's disease * copper chelators * biopolymers Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 7.786, year: 2016

  19. Hepatic steatosis in Wilson disease--Role of copper and PNPLA3 mutations.

    Science.gov (United States)

    Stättermayer, Albert Friedrich; Traussnigg, Stefan; Dienes, Hans-Peter; Aigner, Elmar; Stauber, Rudolf; Lackner, Karoline; Hofer, Harald; Stift, Judith; Wrba, Friedrich; Stadlmayr, Andreas; Datz, Christian; Strasser, Michael; Maieron, Andreas; Trauner, Michael; Ferenci, Peter

    2015-07-01

    The earliest characteristic alterations of the liver pathology in Wilson disease (WD) include steatosis, which is sometimes indistinguishable from non-alcoholic fatty liver disease (NAFLD). Steatosis in WD may reflect copper-induced mitochondrial dysfunction. A genetic polymorphism in rs738409, in the patatin-like phospholipase domain-containing 3 gene (PNPLA3), is strongly associated with appearance of in NAFLD. This study evaluated the role of PNPLA3 and hepatic copper content for development of steatosis in patients with WD. Liver biopsies obtained at diagnosis and the PNPLA3 genotype were analyzed in 98 Caucasian patients with WD (male: 52 [53.1%]; mean age: 27.6 years [CI 95%: 24.8-30.4, range: 5.8-61.5]). Steatosis was graded as percentage of lipid containing hepatocytes by an expert hepatopathologist unaware of the results of genetic testing. Moderate/severe steatosis (>33% of hepatocytes) was observed in 28 patients (pediatric: n=13/26 [50.0%], adult: n=15/72 [20.8%]; p=0.01). Forty-six patients (46.9%; pediatric: n=7, adult: n=39; p=0.022) had cirrhosis. Multivariate logistic regression identified PNPLA3 G allele (OR: 2.469, CI 95%: 1.203-5.068; p=0.014) and pediatric age (OR: 4.348; 1.577-11.905; p=0.004) as independent variables associated with moderate/severe steatosis. In contrast, hepatic copper content did not impact on moderate/severe steatosis (OR: 1.000, CI 95%: 1.000-1.001; p=0.297). Steatosis is common in WD and the PNPLA3 G allele contributes to its pathogenesis. The role of hepatic copper concentration and ATP7B mutations in steatosis development deserve further investigations. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  20. Wilson's disease: two treatment modalities. Correlations to pretreatment and posttreatment brain MRI

    Energy Technology Data Exchange (ETDEWEB)

    Leiros da Costa, Maria do Desterro [Federal University of Paraiba, Movement Disorders Unit, Paraiba (Brazil); Spitz, Mariana; Bacheschi, Luiz Alberto; Barbosa, Egberto Reis [University of Sao Paulo, Movement Disorders Unit, Sao Paulo (Brazil); Leite, Claudia Costa; Lucato, Leandro Tavares [University of Sao Paulo, Department of Radiology, Sao Paulo (Brazil)

    2009-10-15

    Brain magnetic resonance imaging (MRI) studies on Wilson's disease (WD) show lack of correlations between neurological and neuroimaging features. Long-term follow-up reports with sequential brain MRI in patients with neurological WD comparing different modalities of treatment are scarce. Eighteen patients with neurological WD underwent pretreatment and posttreatment brain MRI scans to evaluate the range of abnormalities and the evolution along these different periods. All patients underwent at least two MRI scans at different intervals, up to 11 years after the beginning of treatment. MRI findings were correlated with clinical picture, clinical severity, duration of neurological symptoms, and treatment with two different drugs. Patients were divided into two groups according to treatment: d-penicillamine (D-P), zinc (Zn), and Zn after the onset of severe intolerance to D-P. MRI scans before treatment showed, in all patients, hypersignal intensity lesions on T2- and proton-density-weighted images bilaterally and symmetrically at basal nuclei, thalamus, brain stem, cerebellum, brain cortex, and brain white matter. The most common neurological symptoms were: dysarthria, parkinsonism, dystonia, tremor, psychiatric disturbances, dysphagia, risus sardonicus, ataxia, chorea, and athetosis. From the neurological point of view, there was no difference on the evolution between the group treated exclusively with D-P and the one treated with Zn. Analysis of MRI scans with longer intervals after the beginning of treatment depicted a trend for neuroimaging worsening, without neurological correspondence, among patients treated with Zn. Neuroimaging pattern of evolution was more favorable for the group that received exclusively D-P. (orig.)

  1. Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis.

    Science.gov (United States)

    Polishchuk, Elena V; Concilli, Mafalda; Iacobacci, Simona; Chesi, Giancarlo; Pastore, Nunzia; Piccolo, Pasquale; Paladino, Simona; Baldantoni, Daniela; van IJzendoorn, Sven C D; Chan, Jefferson; Chang, Christopher J; Amoresano, Angela; Pane, Francesca; Pucci, Piero; Tarallo, Antonietta; Parenti, Giancarlo; Brunetti-Pierri, Nicola; Settembre, Carmine; Ballabio, Andrea; Polishchuk, Roman S

    2014-06-23

    Copper is an essential yet toxic metal and its overload causes Wilson disease, a disorder due to mutations in copper transporter ATP7B. To remove excess copper into the bile, ATP7B traffics toward canalicular area of hepatocytes. However, the trafficking mechanisms of ATP7B remain elusive. Here, we show that, in response to elevated copper, ATP7B moves from the Golgi to lysosomes and imports metal into their lumen. ATP7B enables lysosomes to undergo exocytosis through the interaction with p62 subunit of dynactin that allows lysosome translocation toward the canalicular pole of hepatocytes. Activation of lysosomal exocytosis stimulates copper clearance from the hepatocytes and rescues the most frequent Wilson-disease-causing ATP7B mutant to the appropriate functional site. Our findings indicate that lysosomes serve as an important intermediate in ATP7B trafficking, whereas lysosomal exocytosis operates as an integral process in copper excretion and hence can be targeted for therapeutic approaches to combat Wilson disease. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Similarities and differences of MR findings between Japanese encephalitis and Wilson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Saha, Manash; Kumar, Sunil; Gupta, Rakesh K. [Department of Radiodiagnosis, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow (India); Das, Ashish [Department of Neurology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow (India)

    2002-04-01

    Although Japanese Encephalitis (JE) and Wilson's disease (WD) are different entities, MR findings in both these conditions are quite similar. The purpose of this retrospective study was to find out the similarities and differences between JE and WD on MR imaging. The study group comprised 25 proven cases of JE and 10 cases of WD. Spin echo (SE) TI- and T2-weighted imaging was performed on a 1.5-T MR system. Fourteen of these 35 cases (10 JE, 4 WD) were also examined using T1-weighted magnetization transfer (MT) SE sequence before and after contrast administration. Although both JE and WD showed similar topographical distribution of lesions, predominant involvement of the basal ganglia and thalami, there were some differences. Brain stem lesion was more frequent for WD than for JE, and posteromedial part of the thalami was spared in WD. The lesion characteristics were also different between both; in WD mixed intensity in the basal ganglia and hyperintense linear rim at the peripheral putamen was observed frequently, whereas hyperintense basal ganglia on T2-weighted images, subacute hemorrhage in the thalami and meningeal enhancement were seen only in the patients with JE. These characteristic lesion criteria may help in differentiation of JE from WD on MR imaging. (orig.)

  3. Lenticular nucleus hyperechogenicity in Wilson's disease reflects local copper, but not iron accumulation.

    Science.gov (United States)

    Walter, Uwe; Skowrońska, Marta; Litwin, Tomasz; Szpak, Grażyna Maria; Jabłonka-Salach, Katarzyna; Skoloudík, David; Bulska, Ewa; Członkowska, Anna

    2014-10-01

    In patients with Wilson's disease (WD) transcranial brain sonography typically reveals areas of increased echogenicity (hyperechogenicity) of the lenticular nucleus (LN). Correlation with T2-hypointensity on magnetic resonance images suggested that LN hyperechogenicity in WD is caused by trace metal accumulation. Accumulation of both, copper and iron, in the brain of WD patients has been reported. The present study was designed to elucidate whether LN hyperechogenicity in WD reflects accumulation of copper or iron. Post-mortem brains of 15 WD patients and one non-WD subject were studied with ultrasonography in an investigator-blinded fashion. LN hyperechogenicity was measured planimetrically by manual tracing as well as using digitized image analysis. The putaminal copper content was determined in samples of 11 WD brains and the non-WD brains using inductively coupled plasma mass spectrometry, and iron content was assessed using flame atomic absorption spectroscopy. LN was normal on ultrasonography only in the non-WD brain, but abnormal (hyperechogenic) in all WD brains. Digitized image analysis measures of LN hyperechogenicity and, by trend, manual measures correlated with putaminal copper content (Pearson test; digitized: r = 0.77, p = 0.04; manual: r = 0.57, p = 0.051) but not with iron content (each, p > 0.18). LN hyperechogenicity measures were unrelated to age at death of patients, age at onset of WD, WD duration, age of brain specimen, serum copper or serum ceruloplasmin (each, p > 0.1). We conclude that LN hyperechogenicity in WD reflects copper, but not iron accumulation. Further studies are warranted to elucidate the use of transcranial brain sonography for monitoring therapeutic effects of chelating agents in WD patients.

  4. Wilson?s disease presenting as rapid eye movement sleep behavior disorder: a possible window to early treatment

    Directory of Open Access Journals (Sweden)

    Gotthard G. Tribl

    2014-09-01

    Full Text Available Objective To describe characteristics of REM sleep behavior disorder in Wilson’s disease. Method Questionnaire-based interviews (patients and relatives, neurological examinations, two-week prospective dream-diary, video-polysomnography, transcranial sonography, MRI. Results Four Wilson’s disease cases with REM sleep behavior disorder were described; three had REM sleep behavior disorder as initial symptom. All showed mesencephalic tegmental/tectal sonographic hyperechogenicities and two presented ponto-mesencephalic tegmental MRI hyperintensities. Conclusion This first description of REM sleep behavior disorder in Wilson’s disease in literature documents REM sleep behavior disorder as a possible presenting symptom of Wilson’s disease and adds further evidence to the parallelism of Parkinson’s disease and Wilson’s disease in phenotype and brainstem topography, which ought to be further studied. REM sleep behavior disorder has prognostic relevance for neurodegeneration in α-synucleinopathies. In Wilson’s disease, usefulness of early diagnosis and treatment are already well established. REM sleep behavior disorder in Wilson’s disease offers a possible theoretical model for potential early treatment in this extrapyramidal and brainstem paradigm syndrome, previewing the possibility of neuroprotective treatment for REM sleep behavior disorder in “pre-clinical” Parkinson’s disease.

  5. Genetic variability in the methylenetetrahydrofolate reductase gene (MTHFR) affects clinical expression of Wilson's disease.

    Science.gov (United States)

    Gromadzka, Grażyna; Rudnicka, Magdalena; Chabik, Grzegorz; Przybyłkowski, Adam; Członkowska, Anna

    2011-10-01

    Wilson's disease (WND) is an autosomal recessive disorder of copper (Cu) transport, resulting from pathogenic mutations in the ATP7B gene. The reason for the high variability in phenotypic expressions of WND is unknown. Hepatotoxic and neurotoxic effects of homocysteine (Hcy), as well as interrelationships between Hcy and Cu toxicity, were documented. We genotyped the two 5,10-methylenetetrahydrofolate reductase (one of the key folate/Hcy pathway enzymes) gene (MTHFR) polymorphisms: C677T and A1298C in 245 WND patients. Next, we tested the modulation of WND phenotypes by genotypes of MTHFR. MTHFR C677T genotype distribution deviated from that expected from a population in Hardy-Weinberg equilibrium (C677T, χ(2) = 12.14, p = 0.0005). Patients with the MTHFR 1298C allele were younger at symptoms' onset than those without this allele (median (IQR) age, 24.9 (14.0) years vs. 28.5 (12.0) years, p = 0.006). Carriers of MTHFR "high activity" diplotype (double wild-type homozygotes 677CC/1298AA) manifested WND at older age, than non-carriers (median (IQR) age, 33.5 (9.0) years vs. 25.0 (13.0) years, p = 0.0009). Patients with the MTHFR 677T allele less frequently exhibited the neurological WND phenotype (31 (29.5%) vs. 36 (48.0%)), and more frequently presented with hepatic WND (44 (41.9%) vs. 22 (29.3%)), compared with subjects MTHFR 677T(-). We postulate that MTHFR polymorphism contributes to the phenotypic variability of WND. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  6. Wilson's Disease

    Science.gov (United States)

    ... healthy nerves, bones, collagen and the skin pigment melanin. Normally, copper is absorbed from your food, and ... you must inherit one copy of the defective gene from each parent. If you receive only one ...

  7. Brain iron accumulation in Wilson disease: a post mortem 7 Tesla MRI - histopathological study.

    Science.gov (United States)

    Dusek, P; Bahn, E; Litwin, T; Jabłonka-Salach, K; Łuciuk, A; Huelnhagen, T; Madai, V I; Dieringer, M A; Bulska, E; Knauth, M; Niendorf, T; Sobesky, J; Paul, F; Schneider, S A; Czlonkowska, A; Brück, W; Wegner, C; Wuerfel, J

    2017-10-01

    In Wilson disease (WD), T2/T2*-weighted (T2*w) MRI frequently shows hypointensity in the basal ganglia that is suggestive of paramagnetic deposits. It is currently unknown whether this hypointensity is related to copper or iron deposition. We examined the neuropathological correlates of this MRI pattern, particularly in relation to iron and copper concentrations. Brain slices from nine WD and six control cases were investigated using a 7T-MRI system. High-resolution T2*w images were acquired and R2* parametric maps were reconstructed using a multigradient recalled echo sequence. R2* was measured in the globus pallidus (GP) and the putamen. Corresponding histopathological sections containing the lentiform nucleus were examined using Turnbull iron staining, and double staining combining Turnbull with immunohistochemistry for macrophages or astrocytes. Quantitative densitometry of the iron staining as well as copper and iron concentrations were measured in the GP and putamen and correlated with R2* values. T2*w hypointensity in the GP and/or putamen was apparent in WD cases and R2* values correlated with quantitative densitometry of iron staining. In WD, iron and copper concentrations were increased in the putamen compared to controls. R2* was correlated with the iron concentration in the GP and putamen, whereas no correlation was observed for the copper concentration. Patients with more pronounced pathological severity in the putamen displayed increased iron concentration, which correlated with an elevated number of iron-containing macrophages. T2/T2*w hypointensity observed in vivo in the basal ganglia of WD patients is related to iron rather than copper deposits. © 2016 British Neuropathological Society.

  8. The neurotoxicity of iron, copper and manganese in Parkinson's and Wilson's diseases.

    Science.gov (United States)

    Dusek, Petr; Roos, Per M; Litwin, Tomasz; Schneider, Susanne A; Flaten, Trond Peder; Aaseth, Jan

    2015-01-01

    Impaired cellular homeostasis of metals, particularly of Cu, Fe and Mn may trigger neurodegeneration through various mechanisms, notably induction of oxidative stress, promotion of α-synuclein aggregation and fibril formation, activation of microglial cells leading to inflammation and impaired production of metalloproteins. In this article we review available studies concerning Fe, Cu and Mn in Parkinson's disease and Wilson's disease. In Parkinson's disease local dysregulation of iron metabolism in the substantia nigra (SN) seems to be related to neurodegeneration with an increase in SN iron concentration, accompanied by decreased SN Cu and ceruloplasmin concentrations and increased free Cu concentrations and decreased ferroxidase activity in the cerebrospinal fluid. Available data in Wilson's disease suggest that substantial increases in CNS Cu concentrations persist for a long time during chelating treatment and that local accumulation of Fe in certain brain nuclei may occur during the course of the disease. Consequences for chelating treatment strategies are discussed. Copyright © 2014 Elsevier GmbH. All rights reserved.

  9. Demonstrating Potential of Cell Therapy for Wilson's Disease with the Long-Evans Cinnamon Rat Model

    OpenAIRE

    Jaber, Fadi Luc; Sharma, Yogeshwar; Gupta, Sanjeev

    2017-01-01

    Wilson's disease (WD) is characterized by the inability to excrete copper (Cu) from the body with progressive tissue injury, especially in liver and brain. The molecular defect in WD concerns mutations in ATP7B gene leading to loss of Cu transport from the hepatocyte to the bile canaliculus. While drugs, e.g., Cu chelators, have been available for several decades, these must be taken lifelong, which can be difficult due to issues of compliance or side effects. Many individuals may require liv...

  10. Genetic analysis of 55 northern Vietnamese patients with Wilson ...

    Indian Academy of Sciences (India)

    Le Anh Tuan Pham

    2017-12-19

    Dec 19, 2017 ... It is a rare autosomal recessive genetic disorder of copper metabolism in which exces- sive amounts accumulate in the body, particularly in the liver, brain and eyes (Kayser–Fleischer ring in the cornea). Biochemical indicators for the disease include low serum concentrations of ceruloplasmin (<20 g/L) and ...

  11. Correction of liver disease following transplantation of normal rat hepatocytes into Long-Evans Cinnamon rats modeling Wilson's disease.

    Science.gov (United States)

    Irani, A N; Malhi, H; Slehria, S; Gorla, G R; Volenberg, I; Schilsky, M L; Gupta, S

    2001-03-01

    To establish the efficacy of cell therapy in Wilson's disease, we used the Long-Evans Cinnamon (LEC) rat model with atp7b gene mutation and copper toxicosis. Several groups of LEC rats were established, including animals pretreated with retrorsine to exacerbate copper toxicosis and inhibit proliferation in native hepatocytes followed by partial hepatectomy to promote liver repopulation. Hepatocytes from normal, syngeneic LEA rats were transplanted intrasplenically. Animal survival, biliary copper excretion, and hepatic copper were determined. The magnitude of liver repopulation was demonstrated by measuring serum ceruloplasmin and hepatic atp7b mRNA. Long-term survival in LEC rats treated with retrorsine, partial hepatectomy, and cell transplantation was up to 90%, whereas fewer than 10% of animals pretreated with retrorsine, without cell therapy, survived, P Wilson's disease.

  12. Disartria na doença de Wilson: análise de dois casos em fases distintas Dysarthria in Wilson's disease: analysis of two cases in different stages

    Directory of Open Access Journals (Sweden)

    Natália Casagrande Brabo

    2010-06-01

    Full Text Available TEMA: disartria na Doença de Wilson. PROCEDIMENTOS: estudo de caso de dois pacientes com o diagnóstico da doença, ambos adultos jovens, do sexo feminino e com seis anos de escolaridade. Quatro fonoaudiólogas realizaram a avaliação perceptivo-auditiva de modo independente, na qual foram investigados os seguintes parâmetros: tipo de voz, loudness, pitch, ataque vocal, instabilidade fonatória e ressonância. O grau de alteração de cada parâmetro foi mensurado através de uma escala analógico-visual. Além disso, foram obtidas medidas de inteligibilidade por transcrição ortográfica. A análise acústica foi realizada por meio do programa Praat, com a obtenção de medidas de frequência fundamental, de perturbação e ruído e medidas temporais. RESULTADOS: a fala de ambos os pacientes foi caracterizada por: redução do tempo máximo de fonação, voz soprosa e tensa, ataques vocais aspirados, instabilidade vocal, aumento de shimmer e proporção ruído-harmônico, hipernasalidade, redução da diadococinesia oral, da inteligibilidade e da velocidade da fala. Os resultados obtidos sugeriram que o paciente que cursa com a Doença de Wilson há mais tempo, apresentou prejuízo mais acentuado na maioria dos parâmetros perceptuais e acústicos analisados. CONCLUSÃO: foram identificadas manifestações comuns entre os casos, as quais podem constituir-se em traços característicos da fala de pacientes disártricos com Doença de Wilson. Todavia, diferenças também foram evidenciadas, as quais podem estar relacionadas ao tempo de evolução da doença.BACKGROUND: dysarthria in Wilson's disease. PROCEDURES: case study of two patients with disease's diagnosis, both young female adults, with six years of schooling. Perceptual analysis was done by four speech therapists. The following parameters were assessed: voice quality, loudness, pitch, vocal attack, vocal stability and resonance, as well as the degree of deviated parameters, measured

  13. Effect of molecular adsorbents recirculating system treatment in children with acute liver failure caused by Wilson disease.

    Science.gov (United States)

    Rustom, Najla; Bost, Muriel; Cour-Andlauer, Fleur; Lachaux, Alain; Brunet, Anne-Sophie; Boillot, Olivier; Bordet, Fabienne; Valla, Frederic; Richard, Nathalie; Javouhey, Etienne

    2014-02-01

    Because fulminant Wilson disease (WD) has an extremely poor prognosis, the use of liver support that can bridge patients to liver transplantation is lifesaving. We report the experience of albumin dialysis in acute liver failure (ALF) caused by WD in children. Chart review of children admitted for ALF secondary to acute WD and treated by the molecular adsorbents and recirculating system. Measures of copper level in blood and within the circuit during molecular adsorbents recirculating system (MARS) sessions were performed. Clinical and biological assessments after MARS session were reported. Four children, with a median age of 12.3 years, were treated from 2004 to 2009 for a severe ALF associated with acute renal failure, haemolysis, and severe cholestasis. All of the children had a new Wilson index >12. A total of 14 MARS sessions were performed, for a median duration of 7.5 hours. Tolerance was good, except for 1 child who experienced haemorrhage because of vascular injury following insertion of the dialysis catheter. A neurological improvement or stabilisation was noted in all of the children along with an improvement in the Fisher index and ammonia level after MARS treatment. MARS was able to remove copper, to decrease the serum copper level of 28% in mean, and to decrease the bilirubin and creatinin levels >25%. All of the children were subsequently underwent liver transplants with a good outcome without disability. MARS is able to remove copper and to stabilise children with ALF secondary to WD, allowing bridging to LT.

  14. The role of calculated non-caeruloplasmin-bound copper in Wilson's disease.

    Science.gov (United States)

    Duncan, Andrew; Yacoubian, Calum; Beetham, Robert; Catchpole, Anthony; Bullock, David

    2017-11-01

    Background US and European guidelines suggest the use of calculated non-caeruloplasmin-bound copper (free copper index) for the diagnosis and management of Wilson's Disease. However, there is concern that the required analytical measurements of caeruloplasmin and copper may not be sufficiently robust at the concentrations usually found. Methods Aliquots of six plasma specimens were sent to laboratories participating in the UK National External Quality Assessment Scheme for copper and caeruloplasmin. The variability of these two reported measurements and the calculated non-caeruloplasmin-bound copper concentrations were compared. The variability of caeruloplasmin reference ranges quoted by laboratories was also investigated. Results No laboratories use the required enzymatic methods in the calculation of non-caeruloplasmin-bound copper. The interlaboratory variations in caeruloplasmin concentrations and calculated non-caeruloplasmin-bound copper concentrations were very considerable so making clinical interpretation unreliable. Wide differences in the caeruloplasmin reference ranges used were also found. Conclusions Such variations of the calculated non-caeruloplasmin-bound copper concentrations and the predominant use of immunological methods for measuring caeruloplasmin preclude a clinical role for this calculated value in the investigation of Wilson's disease.

  15. Design of intrahepatocyte copper(I) chelators as drug candidates for Wilson's disease.

    Science.gov (United States)

    Gateau, Christelle; Delangle, Pascale

    2014-05-01

    Wilson's disease is an autosomal recessive disease caused by mutations on the ATP7B gene found on chromosome 13. Since the corresponding ATPase is in charge of copper (Cu) distribution and excretion in the liver, its malfunctioning leads to Cu overload. This short review deals with treatments of this rare disease, which aim at decreasing Cu toxicity and are, therefore, based on chelation therapy. The drugs used since the 1950s are described first, then a novel approach developed in our laboratory is presented. Since the liver is the main organ of Cu distribution in the body, we targeted the pool of intracellular Cu in hepatocytes. This Cu pool is in the +1 oxidation state, and therefore soft sulfur ligands inspired from binding sites found in metallothioneins were developed. Their targeting to the hepatocytes by functionalization with ligands of the asialoglycoprotein receptor led to their cellular incorporation and intracellular Cu chelation. © 2014 New York Academy of Sciences.

  16. Copper Inhibits the AlkB Family DNA Repair Enzymes under Wilson's Disease Condition.

    Science.gov (United States)

    Bian, Ke; Chen, Fangyi; Humulock, Zachary T; Tang, Qi; Li, Deyu

    2017-10-16

    Disturbed metabolism of copper ions can cause diseases such as Wilson's disease (WD). In this work, we investigated the inhibitory effect of Cu(II) ion in vitro on the AlkB family DNA repair enzymes, which are members of the Fe(II)/alpha-ketoglutarate-dependent dioxygenase and include human ALKBH2, ALKBH3, and E. coli AlkB proteins. None of the three proteins was significantly inhibited under normal cellular copper concentrations. However, under WD related condition, we observed that the activities of all three enzymes were strongly suppressed (from 95.2 to 100.0%). We also noted the repair efficiency under ds-DNA condition was less susceptible than ss-DNA to the inhibition.

  17. Structural and metabolic changes in Atp7b-/- mouse liver and potential for new interventions in Wilson's disease.

    Science.gov (United States)

    Huster, Dominik

    2014-05-01

    Wilson's disease (WD) is caused by ATP7B mutations and results in copper accumulation and toxicity in liver and brain tissues. The specific mechanisms underlying copper toxicity are still poorly understood. Mouse models have revealed new insights into pathomechanisms of hepatic WD. Mitochondrial damage is observed in livers of WD patients and in mouse models; copper induces fragmentation of mitochondrial membrane lipids, particularly cardiolipin, with deleterious effects on both mitochondrial integrity and function. Copper accumulation also induces chronic inflammation in WD livers, which is followed by regeneration in parts of the liver and occasionally neoplastic proliferation. Gene expression studies using microarrays have aided our understanding of the molecular basis of these changes. Copper overload alters cholesterol biosynthesis in hepatocytes resulting in reduced liver and serum cholesterol. Experiments are currently underway to elucidate the link between copper and cholesterol metabolism. These findings may facilitate the development of specific therapies to ameliorate WD progression. © 2014 New York Academy of Sciences.

  18. Rescue of ATP7B function in hepatocyte-like cells from Wilson's disease induced pluripotent stem cells using gene therapy or the chaperone drug curcumin.

    Science.gov (United States)

    Zhang, Shiqiang; Chen, Shen; Li, Wen; Guo, Xiangpeng; Zhao, Ping; Xu, Jianyong; Chen, Yan; Pan, Qiong; Liu, Xiaorong; Zychlinski, Daniela; Lu, Hai; Tortorella, Micky D; Schambach, Axel; Wang, Yan; Pei, Duanqing; Esteban, Miguel A

    2011-08-15

    Directed hepatocyte differentiation from human induced pluripotent stem cells (iPSCs) potentially provides a unique platform for modeling liver genetic diseases and performing drug-toxicity screening in vitro. Wilson's disease is a genetic disease caused by mutations in the ATP7B gene, whose product is a liver transporter protein responsible for coordinated copper export into bile and blood. Interestingly, the spectrum of ATP7B mutations is vast and can influence clinical presentation (a variable spectrum of hepatic and neural manifestations), though the reason is not well understood. We describe the generation of iPSCs from a Chinese patient with Wilson's disease that bears the R778L Chinese hotspot mutation in the ATP7B gene. These iPSCs were pluripotent and could be readily differentiated into hepatocyte-like cells that displayed abnormal cytoplasmic localization of mutated ATP7B and defective copper transport. Moreover, gene correction using a self-inactivating lentiviral vector that expresses codon optimized-ATP7B or treatment with the chaperone drug curcumin could reverse the functional defect in vitro. Hence, our work describes an attractive model for studying the pathogenesis of Wilson's disease that is valuable for screening compounds or gene therapy approaches aimed to correct the abnormality. In the future, once relevant safety concerns (including the stability of the mature liver-like phenotype) and technical issues for the transplantation procedure are solved, hepatocyte-like cells from similarly genetically corrected iPSCs could be an option for autologous transplantation in Wilson's disease.

  19. Mowat-Wilson syndrome: neurological and molecular study in seven patients

    Directory of Open Access Journals (Sweden)

    José Albino da Paz

    2015-01-01

    Full Text Available Objective To present a seven-cases serie of Mowat-Wilson syndrome (MWS. Method All patients with positive mutation for the ZEB2 were evaluated by a geneticist and a neurologist, with clinical and laboratorial characterization. Results A peculiar facies and mental retardation were present in all patients. The Denver II scale showed intense delay in all aspects, especially fine motor and adaptive. Acquired microcephaly was observed in five patients. Only one patient did not present epilepsy. Epilepsy was focal and predominating in sleep, with status epilepticus in three patients. The initial seizure was associated with fever in most patients (4/6. The EEG showed epileptic focal activity (5/7. The imaging studies revealed total agenesis (4/7 and partial agenesis of the corpus callosum (1/7. Conclusion Physicians who care for patients with mental retardation and epilepsy should be aware of SMW.

  20. Using Xas And Sxrf to Study Copper in Wilson Disease at the Molecular And Tissue Level

    Energy Technology Data Exchange (ETDEWEB)

    Ralle, M.; Blackburn, N.J.; Lutsenko, S.

    2009-06-05

    Wilson disease (WD) is a genetic disorder of copper metabolism associated with severe hepatic, neurological, and psychiatric abnormalities. In WD, the billiary copper excretion is impaired and copper accumulates in tissues, particularly in the liver and the brain. The affected gene, ATP7B, encodes the copper transporting ATPase, Wilson disease protein (WNDP). WNDP has six copper binding sites in the N-terminal portion of the molecule. Each site includes the conserved amino acid sequence MXCXXC, and binds 1 Cu(I) through its 2 cysteine residues. We performed X-ray absorption studies at the Cu K{sub {alpha}}-edge on the recombinant N-terminal domain of WNDP (N-WNDP). Copper was bound to N-WNDP either in vivo or in vitro in the presence of different reducing agents. We found that in N-WNDP copper is predominantly coordinated in a linear fashion by two cysteines, with the appearance of a Cu-Cu interaction when all metal binding sites are filled. Increasing amounts of reducing agents containing sulfide or phosphine groups led to binding of the exogenous ligands to copper thereby increasing the coordination number of copper from two to three. To better understand the role of copper in WD, we utilized livers of the 6-weeks-old Atp7b-/- mice (an animal model for WD) in which the copper concentration was 10--20-fold higher compared to that of the control mice. The distribution of copper in hepatocytes was evaluated by synchrotron based X-ray fluorescence microprobe (SXRF). We demonstrate that we can prepare liver slices that retain copper and can detect copper with subcellular resolution. On the same sections {mu}-XANES (spot size: 5 micron) was used to determine the oxidation state of copper.

  1. Using XAS and SXRF to Study Copper in Wilson Disease at the Molecular and Tissue Level

    Science.gov (United States)

    Ralle, Martina; Blackburn, Ninian J.; Lutsenko, Svetlana

    2007-02-01

    Wilson disease (WD) is a genetic disorder of copper metabolism associated with severe hepatic, neurological, and psychiatric abnormalities. In WD, the billiary copper excretion is impaired and copper accumulates in tissues, particularly in the liver and the brain. The affected gene, ATP7B, encodes the copper transporting ATPase, Wilson disease protein (WNDP). WNDP has six copper binding sites in the N-terminal portion of the molecule. Each site includes the conserved amino acid sequence MXCXXC, and binds 1 Cu(I) through its 2 cysteine residues. We performed X-ray absorption studies at the Cu Kα-edge on the recombinant N-terminal domain of WNDP (N-WNDP). Copper was bound to N-WNDP either in vivo or in vitro in the presence of different reducing agents. We found that in N-WNDP copper is predominantly coordinated in a linear fashion by two cysteines, with the appearance of a Cu-Cu interaction when all metal binding sites are filled. Increasing amounts of reducing agents containing sulfide or phosphine groups led to binding of the exogenous ligands to copper thereby increasing the coordination number of copper from two to three. To better understand the role of copper in WD, we utilized livers of the 6-weeks-old Atp7b-/- mice (an animal model for WD) in which the copper concentration was 10-20-fold higher compared to that of the control mice. The distribution of copper in hepatocytes was evaluated by synchrotron based X-ray fluorescence microprobe (SXRF). We demonstrate that we can prepare liver slices that retain copper and can detect copper with subcellular resolution. On the same sections μ-XANES (spot size: 5 micron) was used to determine the oxidation state of copper.

  2. Enfermedad de Wilson: revisión del tema Wilson’s disease: a review

    Directory of Open Access Journals (Sweden)

    Yeinis Paola Espinoza Herrera

    2010-02-01

    Full Text Available

    La Enfermedad de Wilson es un trastorno autosómico recesivo causado por mutaciones en el gen ATP7B que producen anormalidad en el metabolismo del cobre, con acumulación de este elemento en distintos órganos y tejidos. El diagnóstico se basa en la combinación del cuadro clínico con diversas pruebas bioquímicas, pues ninguna de ellas, aisladamente, es diagnóstica. En la actualidad se cuenta con un tratamiento efectivo para esta enfermedad, basado en la utilización de quelantes del cobre, para movilizarlo de los sitios donde se acumula y promover su excreción, así como de zinc para bloquear su absorción intestinal. El trasplante hepático es el tratamiento de elección en los pacientes con hepatopatía fulminante, así como en los que llegan a la cirrosis descompensada. En esta revisión se incluyen aspectos bioquímicos, genéticos, clínicos, diagnósticos y terapéuticos de esta enfermedad.

    Wilson’s disease is an autosomal recessive disorder caused by mutations in the ATP7B gene that lead to an abnormal metabolism of copper, resulting in the accumulation of this element in several organs and tissues. Its diagnosis is based on the combination of the clinical picture with various biochemical tests, neither one of which is, by itself, diagnostic of the disease

  3. Recent advance in the molecular genetics of Wilson disease and hereditary hemochromatosis.

    Science.gov (United States)

    Lv, Tingxia; Li, Xiaojin; Zhang, Wei; Zhao, Xinyan; Ou, Xiaojuan; Huang, Jian

    2016-10-01

    Metabolic liver diseases such as Wilson disease (WD) and hereditary hemochromatosis (HH) possess complicated pathogenesis and typical hereditary characteristics with the hallmarks of a deficiency in metal metabolism. Mutations in genes encoding ATPase, Cu + transporting, beta polypeptide (ATP7B) and hemochromatosis (HFE) or several non-HFE genes are considered to be causative for WD and HH, respectively. Although the identification of novel mutations in ATP7B for WD and HFE or the non-HFE genes for HH has increased, especially with the application of whole genome sequencing technology in recent years, the biological function of the identified mutations, as well as genotype-phenotype correlations remain to be explored. Further analysis of the causative gene mutation would be critical to clarify the mechanisms underlying specific disease phenotypes. In this review, we therefore summarize the recent advances in the molecular genetics of WD and HH including the updated mutation spectrums and the correlation between genotype and phenotype, with an emphasis on biological functional studies of the individual mutations identified in WD and HH. The weakness of the current functional studies and analysis for the clinical association of the individual mutation was also discussed. These works are essential for the understanding of the association between genotypes and phenotypes of these inherited metabolic liver diseases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Dream Recall Frequencies and Dream Content in Wilson's Disease with and without REM Sleep Behaviour Disorder: A Neurooneirologic Study.

    Science.gov (United States)

    Tribl, Gotthard G; Trindade, Mateus C; Schredl, Michael; Pires, Joana; Reinhard, Iris; Bittencourt, Thais; Lorenzi-Filho, Geraldo; Alves, Rosana Cardoso; de Andrade, Daniel Ciampi; Fonoff, Erich T; Bor-Seng-Shu, Edson; Machado, Alexandre A; Teixeira, Manoel J; Barbosa, Egberto R

    2016-01-01

    Objective. Violent dream content and its acting out during rapid eye movement sleep are considered distinctive for rapid eye movement sleep behaviour disorder (RBD). This study reports first quantitative data on dreaming in a cohort of patients with treated Wilson's disease (WD) and in patients with WD with RBD. Methods. Retrospective questionnaires on different dimensions of dreaming and a prospective two-week home dream diary with self-rating of emotions and blinded, categorical rating of content by an external judge. Results. WD patients showed a significantly lower dream word count and very few other differences in dream characteristics compared to age- and sex-matched healthy controls. Compared to WD patients without RBD, patients with WD and RBD reported significantly higher nightmare frequencies and more dreams with violent or aggressive content retrospectively; their prospectively collected dream reports contained significantly more negative emotions and aggression. Conclusions. The reduction in dream length might reflect specific cognitive deficits in WD. The lack of differences regarding dream content might be explained by the established successful WD treatment. RBD in WD had a strong impact on dreaming. In accordance with the current definition of RBD, violent, aggressive dream content seems to be a characteristic of RBD also in WD.

  5. Repeated transplantation of hepatocytes prevents fulminant hepatitis in a rat model of Wilson's disease.

    Science.gov (United States)

    Sauer, Vanessa; Siaj, Ramsi; Stöppeler, Sandra; Bahde, Ralf; Spiegel, Hans-Ullrich; Köhler, Gabriele; Zibert, Andree; Schmidt, Hartmut H J

    2012-02-01

    The outcome of consecutive hepatocyte transplants was explored in a rat model of Wilson's disease before the onset of fulminant hepatitis without preconditioning regimens. Rats received a high-copper diet in order to induce a rapid induction of liver failure. Sham-operated rats (15/15) developed jaundice and fulminant hepatitis, and they died within 4 weeks of first transplantation. Despite the continuation of a high dietary copper challenge, long-term survival was observed for a notable proportion of the transplanted animals (7/18). All survivors displayed normalized levels of hepatitis-associated serum markers and ceruloplasmin oxidase activity by posttransplant days 50 and 98, respectively. The liver copper concentrations, the liver histology, and the expression of marker genes were significantly restored within 4 months of transplantation in comparison with the control group. The high expression of a copper transporter gene (ATPase Cu++ transporting beta polypeptide) in the livers of the survivors indicated a high rate of repopulation by donor hepatocytes. Our data suggest that repeated cell transplantation can overcome the limitations of a single therapy session in rats with severe hepatic disease by functionally restoring the host liver without preconditioning. Copyright © 2011 American Association for the Study of Liver Diseases.

  6. Clinico-radiological correlation of Wilson's disease by magnetic resonance imaging, computed tomography and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Ken; Sakata, Chigusa; Nemoto, Hiroshi; Yokoi, Fuji; Sunohara, Nobuhiko (National Center of Neurology and Psychiatry, Kodaira, Tokyo (Japan)); Iio, Masaaki

    1991-02-01

    Five patients with Wilson's disease received repeated magnetic resonance imaging (MRI) and computed tomography (CT) examinations at intervals from 6 to 29 months. Four patients, except for asymptomatic one, also underwent positron emission tomography (PET). The significance and limitations of these imaging modalities were examined in the light of their correlation with clinical manifestations and their therapeutic evaluation. The following focal regions, detected on MRI, had a strong positive correlation with clinical manifestations: the lenticular nuclei for dystonia, the brain stem for abnormality of smooth persuit eye movements, and the caudate and lenticular nuclei for severe dysarthria/dysphagia. Follow-up MRI for 3 patients showed an improvement of findings in the lenticular nuclei, lateral part of the putamen, and brain stem, that was in accordance with improved clinical or neurologic manifestations, such as dystonia and cerebellar symptoms. Severe abnormality in the caudate nucleus was associated with poor prognosis. Repeated CT failed to show serial changes in any of the patients. Regional blood flow and oxygen metabolic rate, obtained by PET examinations, were slightly decreased in the thalamus that had normal findings on both MRI and CT, as well as in the cerebral cortex and basal ganglia. PET was, however, inferior to MRI in detecting fine foci within the basal ganglia. In conclusion, there was a good correlation between MRI findings, particularly foci of the caudate and lenticular nuclei, and clinical manifestations. Repeated MRI examinations were the most useful approach to the evaluation of therapeutic effects and prognosis. (N.K.).

  7. Woodrow Wilson's hidden stroke of 1919: the impact of patient-physician confidentiality on United States foreign policy.

    Science.gov (United States)

    Menger, Richard P; Storey, Christopher M; Guthikonda, Bharat; Missios, Symeon; Nanda, Anil; Cooper, John M

    2015-07-01

    World War I catapulted the United States from traditional isolationism to international involvement in a major European conflict. Woodrow Wilson envisaged a permanent American imprint on democracy in world affairs through participation in the League of Nations. Amid these defining events, Wilson suffered a major ischemic stroke on October 2, 1919, which left him incapacitated. What was probably his fourth and most devastating stroke was diagnosed and treated by his friend and personal physician, Admiral Cary Grayson. Grayson, who had tremendous personal and professional loyalty to Wilson, kept the severity of the stroke hidden from Congress, the American people, and even the president himself. During a cabinet briefing, Grayson formally refused to sign a document of disability and was reluctant to address the subject of presidential succession. Wilson was essentially incapacitated and hemiplegic, yet he remained an active president and all messages were relayed directly through his wife, Edith. Patient-physician confidentiality superseded national security amid the backdrop of friendship and political power on the eve of a pivotal juncture in the history of American foreign policy. It was in part because of the absence of Woodrow Wilson's vocal and unwavering support that the United States did not join the League of Nations and distanced itself from the international stage. The League of Nations would later prove powerless without American support and was unable to thwart the rise and advance of Adolf Hitler. Only after World War II did the United States assume its global leadership role and realize Wilson's visionary, yet contentious, groundwork for a Pax Americana. The authors describe Woodrow Wilson's stroke, the historical implications of his health decline, and its impact on United States foreign policy.

  8. Hepatocyte transplantation in the Long Evans Cinnamon rat model of Wilson's disease.

    Science.gov (United States)

    Park, Seon Mee; Vo, Kim; Lallier, Michel; Cloutier, Alexis-Simon; Brochu, Pierre; Alvarez, Fernando; Martin, Steven R

    2006-01-01

    Wilson's disease (WD), caused by a mutation in the P-type copper transporting ATPase (Atp7b) gene, results in excessive accumulation of copper in the liver. Long Evans Cinnamon rats (LEC) bear a mutation in the atp7b gene and share clinical characteristics of human WD. To explore hepatocyte transplantation (HT) as therapy for metabolic liver diseases, 8-week-old LEC rats (n = 12) were transplanted by intrasplenic injection of hepatocytes from donor Long Evans (LE) rats. Immunosuppression was maintained with intraperitoneal tacrolimus. The success of HT was monitored at 24 weeks of life. Serum aminotransferases and bilirubin peaked at 14-21 weeks in both HT rats and nontransplanted controls, but at 24 weeks, survival was 97% in LEC-HT versus 63% in controls. All transplanted rats showed restored biliary copper excretion and reduced liver iron concentration associated with increased ceruloplasmin oxidase activity. Liver tissue expressed atp7b mRNA (11.9 +/- 13.6%) indicative of engraftment of normal cells in 7 of 12 HT rats, associated with a reduced liver copper concentration compared to untreated LEC rats. Periportal islets of normal appearing hepatocytes, recognized by atp7b antibody, were observed in transplanted livers while lobular host cells showed persistent pleomorphic changes and inflammatory infiltrates. In conclusion, transplantation of normal hepatocytes prevented fulminant hepatitis, reduces chronic inflammation, and improved 6-month survival in LEC rats. Engraftment of transplanted cells, which express atp7b mRNA, repopulated the recipient liver with normal functional capacity.

  9. The plant decapeptide OSIP108 prevents copper-induced toxicity in various models for Wilson disease

    Energy Technology Data Exchange (ETDEWEB)

    Spincemaille, Pieter [Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, 3001 Heverlee (Belgium); Pham, Duc-Hung [Laboratory for Molecular Biodiscovery, KU Leuven, Campus Gasthuisberg, Herestraat 49, O and N2, 3000 Leuven (Belgium); Chandhok, Gursimran [Clinic for Transplantation Medicine, Münster University Hospital, Albert-Schweitzer-Campus 1, Building A14, D-48149 Münster (Germany); Verbeek, Jef [Department of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven (Belgium); Zibert, Andree [Clinic for Transplantation Medicine, Münster University Hospital, Albert-Schweitzer-Campus 1, Building A14, D-48149 Münster (Germany); Libbrecht, Louis [Department of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven (Belgium); Department of Pathology, University Hospital Ghent, De Pintelaan 185, 9000 Ghent (Belgium); Schmidt, Hartmut [Clinic for Transplantation Medicine, Münster University Hospital, Albert-Schweitzer-Campus 1, Building A14, D-48149 Münster (Germany); Esguerra, Camila V.; Witte, Peter A.M. de [Laboratory for Molecular Biodiscovery, KU Leuven, Campus Gasthuisberg, Herestraat 49, O and N2, 3000 Leuven (Belgium); Cammue, Bruno P.A., E-mail: bruno.cammue@biw.kuleuven.be [Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, 3001 Heverlee (Belgium); Department of Plant Systems Biology, VIB, Technologiepark 927, 9052 Ghent (Belgium); Cassiman, David [Department of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven (Belgium); Thevissen, Karin [Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, 3001 Heverlee (Belgium)

    2014-10-15

    Background: Wilson disease (WD) is caused by accumulation of excess copper (Cu) due to a mutation in the gene encoding the liver Cu transporter ATP7B, and is characterized by acute liver failure or cirrhosis and neuronal cell death. We investigated the effect of OSIP108, a plant derived decapeptide that prevents Cu-induced apoptosis in yeast and human cells, on Cu-induced toxicity in various mammalian in vitro models relevant for WD and in a Cu-toxicity zebrafish larvae model applicable to WD. Methods: The effect of OSIP108 was evaluated on viability of various cell lines in the presence of excess Cu, on liver morphology of a Cu-treated zebrafish larvae strain that expresses a fluorescent reporter in hepatocytes, and on oxidative stress levels in wild type AB zebrafish larvae. Results: OSIP108 increased not only viability of Cu-treated CHO cells transgenically expressing ATP7B and the common WD-causing mutant ATP7B{sup H1069Q}, but also viability of Cu-treated human glioblastoma U87 cells. Aberrancies in liver morphology of Cu-treated zebrafish larvae were observed, which were further confirmed as Cu-induced hepatotoxicity by liver histology. Injections of OSIP108 into Cu-treated zebrafish larvae significantly increased the amount of larvae with normal liver morphology and decreased Cu-induced production of reactive oxygen species. Conclusions: OSIP108 prevents Cu-induced toxicity in in vitro models and in a Cu-toxicity zebrafish larvae model applicable to WD. General significance: All the above data indicate the potential of OSIP108 as a drug lead for further development as a novel WD treatment. - Highlights: • Wilson disease (WD) is characterized by accumulation of toxic copper (Cu). • OSIP108 increases viability of Cu-treated cellular models applicable to WD. • OSIP108 injections preserve liver morphology of Cu-treated zebrafish larvae. • OSIP108 injections into zebrafish larvae abrogates Cu-induced oxidative stress.

  10. Brain MRI and SPECT in the diagnosis of early neurological involvement in Wilson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Piga, Mario; Satta, Loredana; Serra, Alessandra; Loi, Gianluigi [Policlinico Universitario, University of Cagliari, Nuclear Medicine, Department of Medical Science, Monserrato, Cagliari (Italy); Murru, Alessandra; Demelia, Luigi [Policlinico Universitario, University of Cagliari, Gastroenterology, Department of Medical Science, Monserrato, Cagliari (Italy); Sias, Alessandro [Policlinico Universitario, University of Cagliari, Radiology, Department of Medical Science, Monserrato, Cagliari (Italy); Marrosu, Francesco [Policlinico Universitario, University of Cagliari, Neurology, Department of Medical Science, Monserrato, Cagliari (Italy)

    2008-04-15

    To evaluate the impact of brain MRI and single-photon emission computed tomography (SPECT) in early detection of central nervous system abnormalities in patients affected by Wilson's disease (WD) with or without neurological involvement. Out of 25 consecutive WD patients, 13 showed hepatic involvement, ten hepatic and neurological manifestations, and twp hepatic, neurological, and psychiatric symptoms, including mainly movement disorders, major depression, and psychosis. Twenty-four healthy, age-gender matched subjects served as controls. All patients underwent brain MRI and {sup 99m}Tc-ethyl-cysteinate dimer (ECD) SPECT before starting specific therapy. Voxel-by-voxel analyses were performed using statistical parametric mapping to compare differences in {sup 99m}Tc-ECD brain uptake between the two groups. Brain MRI showed T2-weighted hyperintensities in seven patients (28%), six of whom were affected by hepatic and neurological forms. Brain perfusion SPECT showed pathological data in 19 patients (76%), revealing diffuse or focal hypoperfusion in superior frontal (Brodmann area (BA) 6), prefrontal (BA 9), parietal (BA 40), and occipital (BA 18, BA 39) cortices in temporal gyri (BA 37, BA 21) and in caudatus and putamen. Moreover, hepatic involvement was detected in nine subjects; eight presented both hepatic and neurological signs, while two exhibited WD-correlated hepatic, neurological, and psychiatric alterations. All but one patient with abnormal MRI matched with abnormal ECD SPECT. Pathologic MRI findings were obtained in six out of ten patients with hepatic and neurological involvement while abnormal ECD SPECT was revealed in eight patients. Both patients with hepatic, neurological, and psychiatric involvement displayed abnormal ECD SPECT and one displayed an altered MRI. These findings suggest that ECD SPECT might be useful in detecting early brain damage in WD, not only in the perspective of assessing and treating motor impairment but also in evaluating

  11. Advantages of Anterior Segment Optical Coherence Tomography Evaluation of the Kayser-Fleischer Ring in Wilson Disease.

    Science.gov (United States)

    Sridhar, Mittanamalli S

    2017-03-01

    To present anterior segment optical coherence tomography (AS-OCT) findings of the Kayser-Fleischer (KF) ring in Wilson disease (WD) and to discuss the potential advantages of evaluating the KF ring by AS-OCT. This is a retrospective case series of 7 patients with WD with KF rings seen in our institute during the study period (August 2015 to June 2016). All patients underwent slit-lamp examination of the cornea and AS-OCT (Optovue RTVue Premier). In 2 patients, the length of the KF ring was measured using the gray scale of AS-OCT. The KF ring on the gray scale of AS-OCT was visualized as a hyperreflective deep corneal layer at the level of Descemet membrane in all eyes. The OCT color scale revealed the KF ring as a greenish, greenish-yellow, yellow, or yellow-orange band. The gray scale of AS-OCT could easily measure the length of the KF ring in patients 6 and 7. AS-OCT is an alternative method of evaluating the KF ring in WD, which can be used in combination with slit-lamp examination. The KF ring can be easily measured using the gray scale of AS-OCT. Further studies are required to study the potential advantages of AS-OCT including assessing the density of the KF ring, as a tool to assess response to treatment in WD, in differentiating the KF ring of WD disease from copper deposits in other situations and pigmented corneal rings in non-Wilsonian liver disease.

  12. Demonstrating Potential of Cell Therapy for Wilson's Disease with the Long-Evans Cinnamon Rat Model.

    Science.gov (United States)

    Jaber, Fadi Luc; Sharma, Yogeshwar; Gupta, Sanjeev

    2017-01-01

    Wilson's disease (WD) is characterized by the inability to excrete copper (Cu) from the body with progressive tissue injury, especially in liver and brain. The molecular defect in WD concerns mutations in ATP7B gene leading to loss of Cu transport from the hepatocyte to the bile canaliculus. While drugs, e.g., Cu chelators, have been available for several decades, these must be taken lifelong, which can be difficult due to issues of compliance or side effects. Many individuals may require liver transplantation, which can also be difficult due to donor organ shortages. Therefore, achieving permanent cures via cell or gene therapy are of great interest for WD. Cell therapy is feasible because transplanted hepatocytes can integrate in liver parenchyma and restore deficient functions, including transport of Cu into bile. The availability of authentic animal models that recapitulate hepatic WD, especially the Long-Evans Cinnamon (LEC) rat, has advanced cell transplantation research in WD. We describe requirements for cell therapy in animal models with several standardized methods for studies to test or refine cell therapy strategies in WD.

  13. Wilson Disease: Epigenetic effects of choline supplementation on phenotype and clinical course in a mouse model.

    Science.gov (United States)

    Medici, Valentina; Kieffer, Dorothy A; Shibata, Noreene M; Chima, Harpreet; Kim, Kyoungmi; Canovas, Angela; Medrano, Juan F; Islas-Trejo, Alma D; Kharbanda, Kusum K; Olson, Kristin; Su, Ruijun J; Islam, Mohammad S; Syed, Raisa; Keen, Carl L; Miller, Amy Y; Rutledge, John C; Halsted, Charles H; LaSalle, Janine M

    2016-11-01

    Wilson disease (WD), a genetic disorder affecting copper transport, is characterized by hepatic and neurological manifestations with variable and often unpredictable presentation. Global DNA methylation in liver was previously modified by dietary choline in tx-j mice, a spontaneous mutant model of WD. We therefore hypothesized that the WD phenotype and hepatic gene expression of tx-j offspring could be modified by maternal methyl supplementation during pregnancy. In an initial experiment, female tx-j mice or wild type mice were fed control or choline-supplemented diets 2 weeks prior to mating through embryonic day 17. Transcriptomic analysis (RNA-seq) on embryonic livers revealed tx-j-specific differences in genes related to oxidative phosphorylation, mitochondrial dysfunction, and the neurological disorders Huntington's disease and Alzheimer disease. Maternal choline supplementation restored the transcript levels of a subset of genes to wild type levels. In a separate experiment, a group of tx-j offspring continued to receive choline-supplemented or control diets, with or without the copper chelator penicillamine (PCA) for 12 weeks until 24 weeks of age. Combined choline supplementation and PCA treatment of 24-week-old tx-j mice was associated with increased liver transcript levels of methionine metabolism and oxidative phosphorylation-related genes. Sex differences in gene expression within each treatment group were also observed. These results demonstrate that the transcriptional changes in oxidative phosphorylation and methionine metabolism genes in WD that originate during fetal life are, in part, prevented by prenatal maternal choline supplementation, a finding with potential relevance to preventive treatments of WD.

  14. A calix[2]triazole[2]arene-based fluorescent chemosensor for probing the copper trafficking pathway in Wilson's disease.

    Science.gov (United States)

    Cho, Jihee; Pradhan, Tuhin; Lee, Yun Mi; Kim, Jong Seung; Kim, Sanghee

    2014-11-21

    A pyrenyl-appended calix[2]triazole[2]arene displaying excellent selectivity for Cu(2+) over other metal ions in pyrenyl excimer emission changes was synthesized. The binding mode with Cu(2+) was supported through nuclear magnetic resonance (NMR) studies and density functional theory (DFT) calculations. Fluorescence imaging demonstrates that this new copper sensor is capable of detecting intracellular copper in living cells. Furthermore, through colocalization of the probe with organelle trackers as a function of time, it was observed that copper initially accumulates in lysosomes and then decreases. These results provide evidence for a close relationship between copper and lysosomes in Wilson's disease. This system is the first Cu(2+) ion-induced fluorescent turn-on system used for imaging copper trafficking over time in a Wilson's disease model.

  15. Clinical features and therapeutic response in Taiwanese children with Wilson's disease: 12 years of experience in a single center.

    Science.gov (United States)

    Wang, Li-Ching; Wang, Jiaan-Der; Tsai, Chi-Ren; Cheng, Shao-Bin; Lin, Chieh-Chung

    2010-04-01

    Wilson's disease (WD) is an autosomal recessive defect of cellular copper export. Early diagnosis in children is difficult due to its obscure clinical presentations. The efficacy of zinc salts is well documented, although there are limited data concerning zinc use in pediatric patients with WD. We performed a retrospective analysis of clinical features, laboratory results and treatment responses in children with WD diagnosed at Taichung Veterans General Hospital between 1996 and 2008. Diagnosis was established by low serum ceruloplasmin, high 24-hour urinary copper excretion, presence of Kayser-Fleischer rings, and mutation analysis. Eleven children were included in this study. The main initial presentations were impaired liver function tests (6/11) and hemolytic anemia (2/11). Gene studies in seven children showed six different mutations (G934D, R778Q, C490X, 304insC, IVS4-1 G > C, P992I) and one possible novel mutation (L1181P). All patients had improved liver function tests and hemoglobin levels after treatment with D-penicillamine, trientine and zinc supplement therapy. During a mean period of 3.4 +/- 2.1 years with zinc therapy, six patients had serum zinc levels above the normal limit, and seven patients had serum copper levels below the normal range. Serum ceruloplasmin and 24-hour urinary copper examinations could be used to rule out WD in children with chronic hepatitis and hemolytic anemia. Gene analysis is helpful for prompt diagnosis of asymptomatic siblings and patients with atypical features. Zinc treatment is generally safe in pediatric patients with WD. However, its adverse effects should be monitored. Copyright 2010 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.

  16. Long-term metabolic correction of Wilson's disease in a murine model by gene therapy.

    Science.gov (United States)

    Murillo, Oihana; Luqui, Daniel Moreno; Gazquez, Cristina; Martinez-Espartosa, Debora; Navarro-Blasco, Iñigo; Monreal, Jose Ignacio; Guembe, Laura; Moreno-Cermeño, Armando; Corrales, Fernando J; Prieto, Jesus; Hernandez-Alcoceba, Ruben; Gonzalez-Aseguinolaza, Gloria

    2016-02-01

    Wilson's disease (WD) is an autosomal recessively inherited copper storage disorder due to mutations in the ATP7B gene that causes hepatic and neurologic symptoms. Current treatments are based on lifelong copper chelating drugs and zinc salts, which may cause side effects and do not restore normal copper metabolism. In this work we assessed the efficacy of gene therapy to treat this condition. We transduced the liver of the Atp7b(-/-) WD mouse model with an adeno-associated vector serotype 8 (AAV8) encoding the human ATP7B cDNA placed under the control of the liver-specific α1-antitrypsin promoter (AAV8-AAT-ATP7B). After vector administration we carried out periodic evaluation of parameters associated with copper metabolism and disease progression. The animals were sacrificed 6months after treatment to analyze copper storage and hepatic histology. We observed a dose-dependent therapeutic effect of AAV8-AAT-ATP7B manifested by the reduction of serum transaminases and urinary copper excretion, normalization of serum holoceruloplasmin, and restoration of physiological biliary copper excretion in response to copper overload. The liver of treated animals showed normalization of copper content and absence of histological alterations. Our data demonstrate that AAV8-AAT-ATP7B-mediated gene therapy provides long-term correction of copper metabolism in a clinically relevant animal model of WD providing support for future translational studies. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  17. Uneven distribution of hepatic copper concentration and diagnostic value of double-sample biopsy in Wilson's disease.

    Science.gov (United States)

    Liggi, Mauro; Mais, Claudia; Demurtas, Mauro; Sorbello, Orazio; Demelia, Enrico; Civolani, Alberto; Demelia, Luigi

    2013-12-01

    BACKGROUND AND AIMS. Determination of hepatic copper (Cu) concentration is important in Wilson's disease (WD) diagnosis. The aim of this study was to evaluate uneven distribution of liver Cu concentration and the utility of double-sample biopsy in WD diagnosis. METHODS. Thirty-five WD patients (20 male; mean age 41 ± 9 years) were enrolled in the study and double-liver samples for biopsy were obtained. A further 30 WD patients, in whom Cu determination was performed using single-liver samples, were also enrolled as controls. RESULTS. A marked difference in hepatic Cu concentration was observed between the two sample groups (p < 0.0001). This difference is statistically significant for all levels of liver fibrosis (p < 0.001) and for the comparison of hepatic and neurological phenotypes (p < 0.01). The sensitivity of the Cu concentrations obtained from the double-sample biopsies for the conventional cut-off value of 250 mg/g dry weight of tissue was 85.7% compared to 80% in the single-sample biopsies. By lowering the cut-off value from 250 to 50 µg/g of dry weight of tissue, the sensitivity of Cu content to diagnose WD increased to 97% for double-sample liver biopsy compared to 93% for single-sample liver biopsy. CONCLUSIONS. Liver Cu content was unevenly distributed in the WD subjects, irrespective of fibrosis levels and disease phenotypes; hence WD can be misdiagnosed using single-sample liver Cu measurement. Double-sample biopsy sensitivity is greater than that obtained with single-sample biopsy and should therefore be considered to evaluate liver Cu concentration at initial diagnosis in all patients.

  18. Wilson's disease in Southern Brazil: genotype-phenotype correlation and description of two novel mutations in ATP7B gene

    Directory of Open Access Journals (Sweden)

    Ricardo Schmitt de Bem

    2013-08-01

    Full Text Available OBJECTIVE: Wilson's disease (WD is an inborn error of metabolism caused by abnormalities of the copper-transporting protein encoding gene ATP7B. In this study, we examined ATP7B for mutations in a group of patients living in southern Brazil. METHODS: 36 WD subjects were studied and classified according to their clinical and epidemiological data. In 23 subjects the ATP7B gene was analyzed. RESULTS: Fourteen distinct mutations were detected in at least one of the alleles. The c.3207C>A substitution at exon 14 was the most common mutation (allelic frequency=37.1% followed by the c.3402delC at exon 15 (allelic frequency=11.4%. The mutations c.2018-2030del13 at exon 7 and c.4093InsT at exon 20 are being reported for the first time. CONCLUSION: The c.3207C>A substitution at exon 14, was the most common mutation, with an allelic frequency of 37.1%. This mutation is the most common mutation described in Europe.

  19. The plant decapeptide OSIP108 prevents copper-induced toxicity in various models for Wilson disease.

    Science.gov (United States)

    Spincemaille, Pieter; Pham, Duc-Hung; Chandhok, Gursimran; Verbeek, Jef; Zibert, Andree; Libbrecht, Louis; Schmidt, Hartmut; Esguerra, Camila V; de Witte, Peter A M; Cammue, Bruno P A; Cassiman, David; Thevissen, Karin

    2014-10-15

    Wilson disease (WD) is caused by accumulation of excess copper (Cu) due to a mutation in the gene encoding the liver Cu transporter ATP7B, and is characterized by acute liver failure or cirrhosis and neuronal cell death. We investigated the effect of OSIP108, a plant derived decapeptide that prevents Cu-induced apoptosis in yeast and human cells, on Cu-induced toxicity in various mammalian in vitro models relevant for WD and in a Cu-toxicity zebrafish larvae model applicable to WD. The effect of OSIP108 was evaluated on viability of various cell lines in the presence of excess Cu, on liver morphology of a Cu-treated zebrafish larvae strain that expresses a fluorescent reporter in hepatocytes, and on oxidative stress levels in wild type AB zebrafish larvae. OSIP108 increased not only viability of Cu-treated CHO cells transgenically expressing ATP7B and the common WD-causing mutant ATP7B(H1069Q), but also viability of Cu-treated human glioblastoma U87 cells. Aberrancies in liver morphology of Cu-treated zebrafish larvae were observed, which were further confirmed as Cu-induced hepatotoxicity by liver histology. Injections of OSIP108 into Cu-treated zebrafish larvae significantly increased the amount of larvae with normal liver morphology and decreased Cu-induced production of reactive oxygen species. OSIP108 prevents Cu-induced toxicity in in vitro models and in a Cu-toxicity zebrafish larvae model applicable to WD. All the above data indicate the potential of OSIP108 as a drug lead for further development as a novel WD treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Copper balance and ceruloplasmin in chronic hepatitis in a Wilson disease animal model, LEC rats

    Energy Technology Data Exchange (ETDEWEB)

    Komatsu, Yutaka; Ogra, Yasumitsu; Suzuki, Kazuo T. [Graduate School of Pharmaceutical Sciences, Chiba University, Inage, Chiba 263-8522 (Japan)

    2002-09-01

    In an animal model of Wilson disease, Long-Evans rats with cinnamon-colored coat (LEC rats), copper (Cu) accumulates in the liver with age up to the onset of acute hepatitis owing to a hereditary defective transporter for the efflux of Cu, ATP7B. The plasma Cu concentration is low in LEC rats because of the excretion of apo-ceruloplasmin (apo-Cp). However, toward and after the onset of chronic hepatitis, plasma Cu concentration increases in the form of holo-Cp, while the liver Cu concentration is maintained at a constant level without the occurrence of fulminant hepatitis. In the present study, the material balance of Cu was studied in LEC rats with chronic hepatitis in order to elucidate the mechanisms underlying the increase of holo-Cp in plasma and the maintenance of Cu at a constant level in the liver. The relationship between the Cu concentration and ferroxidase activity of Cp was analyzed in the plasma of LEC rats of different ages and of Wistar rats fed a Cu-deficient diet for different durations. Cu was suggested to be delivered to Cp in an all-or-nothing manner, resulting in the excretion of fully Cu-occupied holo-Cp (Cu{sub 6}-Cp) or totally Cu-unoccupied Cu{sub 0}-Cp (apo-Cp), but not partially Cu-occupied Cu{sub n}-Cp (where n=1-5). The increase of holo-Cp in acute and chronic hepatitis in LEC rats was explained by the delivery of Cu, accumulating in the non-metallothionein-bound form, to Cp outside the Golgi apparatus of the liver. The plasma Cu concentration and ferroxidase activity were proposed to be specific indicators of the appearance of non-metallothionein-bound Cu in the liver of LEC rats. (orig.)

  1. A film of patients with movement disorders made in Queen Square, London in the Mid-1920s by Samuel Alexander Kinnier Wilson.

    Science.gov (United States)

    Reynolds, E H; Healy, D G; Lees, A J

    2011-12-01

    Through Edward Reynolds' collaboration with Samuel Alexander Kinnier Wilson's (SAKW) son, James, on Babylonian neurology and psychiatry, and his contact with James' nephew, Jim, grandson of SAKW, a remarkable film of patients with movement disorders, made by SAKW in the mid-1920s, has come to light. The 20-min silent film with captions by SAKW includes patients with senile tremor, Parkinson's disease and postencephalitic parkinsonism, hemiballismus, Huntington's chorea, Sydenham's chorea, hysterical palsy and tremor, multiple sclerosis, and progressive lenticular degeneration. Most of the patients are filmed in the square outside the National Hospital. The British Film Institute dates the film to 1924 and the captions to 1925. The case records of 6 of the 14 patients, who were admitted to the National Hospital, Queen Square, under the care of Dr. SAKW have been identified and summarized. SAKW may have been stimulated and facilitated to make this film through his personal contact with Charlie Chaplin with whom he stayed at his Californian estate, probably in the summer of 1924. The first films of neurological patients were made in Europe and USA at the beginning of the 20th century, although most have perished. This may be one of the oldest examples from UK. It is also notable for the inclusion of Wilson's disease and a brief shot of SAKW himself. Copyright © 2011 Movement Disorder Society.

  2. Wilson's disease: {sup 31}P and {sup 1}H MR spectroscopy and clinical correlation

    Energy Technology Data Exchange (ETDEWEB)

    Sinha, Sanjib; Taly, A.B.; Prashanth, L.K. [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neurology, Bangalore (India); Ravishankar, S.; Vasudev, M.K. [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neuroimaging and Interventional Radiology, Bangalore (India)

    2010-11-15

    Proton ({sup 1}H) magnetic resonance spectroscopy (MRS) changes are noted in Wilson's disease (WD). However, there are no studies regarding membrane phospholipid abnormality using {sup 31}P MRS in these patients. We aimed to analyze the striatal spectroscopic abnormalities using {sup 31}P and {sup 1}H MRS in WD. Forty patients of WD (treated, 29; untreated,11) and 30 controls underwent routine MR image sequences and in vivo 2-D {sup 31}P and {sup 1}H MRS of basal ganglia using an image-selected technique on a 1.5-T MRI scanner. Statistical analysis was done using Student's t test. The mean durations of illness and treatment were 6.2 {+-} 7.4 and 4.8 {+-} 5.9 years, respectively. MRI images were abnormal in all the patients. {sup 1}H MRS revealed statistically significant reduction of N-acetyl aspartate (NAA)/choline (Cho) and NAA/creatine ratios in striatum ({sup 1}H MRS) of treated patients compared to controls. The mean values of phosphomonoesters (PME) (p < 0.0001), phosphodiesters (PDE) (p < 0.0001), and total phosphorus (TPh) (p < 0.0001) were elevated in patients compared to controls. Statistically significant elevated levels of ratio of PME/PDE (p = 0.05) observed in the striatum were noted in treated patients as compared to controls in the {sup 31}P MRS study. The duration of illness correlated well with increased PME/PDE [p < 0.001], PME/TPh [p < 0.05], and PDE/TPh [p < 0.05] and decreased NAA/Cho [p < 0.05] ratios. There was correlation of MRI score and reduced NAA/Cho ratio with disease severity. The PME/PDE ratio (right) was elevated in the treated group [p < 0.001] compared to untreated group. There is reduced breakdown and/or increased synthesis of membrane phospholipids and increased neuronal damage in basal ganglia in patients with WD. (orig.)

  3. Cellular copper levels determine the phenotype of the Arg875 variant of ATP7B/Wilson disease protein

    Science.gov (United States)

    Gupta, Arnab; Bhattacharjee, Ashima; Dmitriev, Oleg Y.; Nokhrin, Sergiy; Braiterman, Lelita; Hubbard, Ann L.; Lutsenko, Svetlana

    2011-01-01

    In human disorders, the genotype-phenotype relationships are often complex and influenced by genetic and/or environmental factors. Wilson disease (WD) is a monogenic disorder caused by mutations in the copper-transporting P-type ATPase ATP7B. WD shows significant phenotypic diversity even in patients carrying identical mutations; the basis for such diverse manifestations is unknown. We demonstrate that the 2623A/G polymorphism (producing the Gly875→Arg substitution in the A-domain of ATP7B) drastically alters the intracellular properties of ATP7B, whereas copper reverses the effects. Under basal conditions, the common Gly875 variant of ATP7B is targeted to the trans-Golgi network (TGN) and transports copper into the TGN lumen. In contrast, the Arg875 variant is located in the endoplasmic reticulum (ER) and does not deliver copper to the TGN. Elevated copper corrects the ATP7B-Arg875 phenotype. Addition of only 0.5–5 μM copper triggers the exit of ATP7B-Arg875 from the ER and restores copper delivery to the TGN. Analysis of the recombinant A-domains by NMR suggests that the ER retention of ATP7B-Arg875 is attributable to increased unfolding of the Arg875-containing A-domain. Copper is not required for the folding of ATP7B-Arg875 during biosynthesis, but it stabilizes protein and stimulates its activity. A chemotherapeutical drug, cisplatin, that mimics a copper-bound state of ATP7B also corrects the “disease-like” phenotype of ATP7B-Arg875 and promotes its TGN targeting and transport function. We conclude that in populations harboring the Arg875 polymorphism, the levels of bioavailable copper may play a vital role in the manifestations of WD. PMID:21406592

  4. The potential of bone marrow stem cells to correct liver dysfunction in a mouse model of Wilson's disease.

    Science.gov (United States)

    Allen, Katrina J; Cheah, Daphne M Y; Lee, Xiao Ling; Pettigrew-Buck, Nicole E; Vadolas, Jim; Mercer, Julian F B; Ioannou, Panayiotis A; Williamson, Robert

    2004-01-01

    Metabolic liver diseases are excellent targets for correction using novel stem cell, hepatocyte, and gene therapies. In this study, the use of bone marrow stem cell transplantation to correct liver disease in the toxic milk (tx) mouse, a murine model for Wilson's disease, was evaluated. Preconditioning with sublethal irradiation, dietary copper loading, and the influence of cell transplantation sites were assessed. Recipient tx mice were sublethally irradiated (4 Gy) prior to transplantation with bone marrow stem cells harvested from normal congenic (DL) littermates. Of 46 transplanted tx mice, 11 demonstrated genotypic repopulation in the liver. Sublethal irradiation was found to be essential for donor cell engraftment and liver repopulation. Dietary copper loading did not improve cell engraftment and repopulation results. Both intravenously and intrasplenically transplanted cells produced similar repopulation successes. Direct evidence of functionality and disease correction following liver repopulation was observed in the 11 mice where liver copper levels were significantly reduced when compared with mice with no liver repopulation. The reversal of copper loading with bone marrow cells is similar to the level of correction seen when normal congenic liver cells are used. Transplantation of bone marrow cells partially corrects the metabolic phenotype in a mouse model for Wilson's disease.

  5. Novel ATPase Cu(2+ transporting beta polypeptide mutations in Chinese families with Wilson's disease.

    Directory of Open Access Journals (Sweden)

    Shaojuan Gu

    Full Text Available Wilson's disease (WD is an autosomal recessive inherited disorder caused by mutations in the ATPase Cu(2+ transporting beta polypeptide gene (ATP7B. The detailed metabolism of copper-induced pathology in WD is still unknown. Gene mutations as well as the possible pathways involved in the ATP7B deficiency were documented. The ATP7B gene was analyzed for mutations in 18 Chinese Han families with WD by direct sequencing. Cell viability and apoptosis analysis of ATP7B small interfering RNA (siRNA-treated human liver carcinoma (HepG2 cells were measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT assay and Hoechst 33342 staining. Finally, the expression of B-cell CLL/lymphoma 2 (BCL2, BCL2-associated X protein (BAX, sterol regulatory element binding protein 1 (SREBP1, and minichromosome maintenance protein 7 (MCM7 of ATP7B siRNA-treated cells were tested by real-time polymerase chain reaction (real-time PCR and Western blot analysis. Twenty different mutations including four novel mutations (p.Val145Phe, p.Glu388X, p.Thr498Ser and p.Gly837X in the ATP7B gene were identified in our families. Haplotype analysis revealed that founder effects for four mutations (p.Arg778Leu, p.Pro992Leu, p.Ile1148Thr and p.Ala1295Val existed in these families. Transfection of HepG2 cells with ATP7B siRNA resulted in decreased mRNA expression by 86.3%, 93.1% and 90.8%, and decreased protein levels by 58.5%, 85.5% and 82.1% at 24, 48 and 72 hours, respectively (All P<0.01. In vitro study revealed that the apoptotic, cell cycle and lipid metabolism pathway may be involved in the mechanism of WD. Our results revealed that the genetic cause of 18 Chinese families with WD and ATP7B deficiency-induce apoptosis may result from imbalance in cell cycle and lipid metabolism pathway.

  6. Chelation therapy in Wilson's disease: from D-penicillamine to the design of selective bioinspired intracellular Cu(I) chelators.

    Science.gov (United States)

    Delangle, Pascale; Mintz, Elisabeth

    2012-06-07

    Wilson's disease is an orphan disease due to copper homeostasis dysfunction. Mutations of the ATP7B gene induces an impaired functioning of a Cu-ATPase, impaired Cu detoxification in the liver and copper overload in the body. Indeed, even though copper is an essential element, which is used as cofactor by many enzymes playing vital roles, it becomes toxic when in excess as it promotes cytotoxic reactions leading to oxidative stress. In this perspective, human copper homeostasis is first described in order to explain the mechanisms promoting copper overload in Wilson's disease. We will see that the liver is the main organ for copper distribution and detoxification in the body. Nowadays this disease is treated life-long by systemic chelation therapy, which is not satisfactory in many cases. Therefore the design of more selective and efficient drugs is of great interest. A strategy to design more specific chelators to treat localized copper accumulation in the liver will then be presented. In particular we will show how bioinorganic chemistry may help in the design of such novel chelators by taking inspiration from the biological copper cell transporters.

  7. Zinc mono-therapy in pre-symptomatic Chinese children with Wilson disease: a single center, retrospective study.

    Directory of Open Access Journals (Sweden)

    Kuerbanjiang Abuduxikuer

    Full Text Available BACKGROUND: There is no official consensus regarding zinc therapy in pre-symptomatic children with Wilson Disease (WD; more data is needed. OBJECTIVE: To investigate the safety and efficacy of zinc gluconate therapy for Chinese children with pre-symptomatic WD. METHODS: We retrospectively analyzed pre-symptomatic children receiving zinc gluconate in a single Chinese center specialized in pediatric hepatology. Short-term follow-up data on safety and efficacy were presented, and effects of different zinc dosages were compared. RESULTS: 30 children (21 males aged 2.7 to 16.8 years were followed for up to 4.4 years; 26 (87% children had abnormal ALT at baseline. Most patients (73% received higher than the currently recommended dose of elemental zinc. Zinc gluconate significantly reduced mean ALT (p<0.0001, AST (p<0.0001, GGT (p<0.0001 levels after 1 month, and urinary copper excretion after 6 months (p<0.0054. Mean direct bilirubin levels dropped significantly at 1 month (p = 0.0175, 3 months (p = 0.0010, and 6 months (p = 0.0036. Serum zinc levels gradually increased and reached a significantly higher level after 6 months (p<0.0026, reflecting good compliance with the therapy. Complete blood count parameters did not change throughout the analysis period. 8 children experienced mild and transient gastrointestinal side effects. The higher zinc dose did not affect treatment response and was not associated with different or increased side effects when compared to conventional zinc dose. CONCLUSION: In our cohort, zinc gluconate therapy for Chinese children with pre-symptomatic WD was effective, and higher initial dose of elemental zinc had the same level of efficacy as the conventional dose.

  8. Proteomic analyzes of copper metabolism in an in vitro model of Wilson disease using surface enhanced laser desorption/ionization-time of flight-mass spectrometry

    NARCIS (Netherlands)

    Roelofsen, H; Balgobind, R; Vonk, RJ

    2004-01-01

    In Wilson disease, mutations in the ATP7B-gene lead to hepatic accumulation of copper that becomes toxic when the hepatic binding capacity is exceeded, leading to oxidative stress and acute liver failure. Several proteins are probably involved in dealing with the excess copper and oxidative stress.

  9. Phenotype-Genotype Correlation in Wilson Disease in a Large Lebanese Family: Association of c.2299insC with Hepatic and of p. Ala1003Thr with Neurologic Phenotype

    OpenAIRE

    Usta, Julnar; Wehbeh, Antonios; Rida, Khaled; El-Rifai, Omar; Estiphan, Theresa Alicia; Majarian, Tamar; Barada, Kassem

    2014-01-01

    Genotype phenotype correlations in Wilson disease (WD) are best established in homozygous patients or in compound heterozygous patients carrying the same set of mutations. We determined the clinical phenotype of patients with WD carrying the c.2298_2299insC in Exon 8 (c.2299insC) or the p. Ala1003Thr missense substitution in Exon 13 mutations in the homozygous or compound heterozygous state. We investigated 76 members of a single large Lebanese family. Their genotypes were determined, and cli...

  10. Comparison of transcranial sonography-magnetic resonance fusion imaging in Wilson's and early-onset Parkinson's diseases.

    Science.gov (United States)

    Mašková, Jana; Školoudík, David; Burgetová, Andrea; Fiala, Ondřej; Brůha, Radan; Záhoráková, Daniela; Serranová, Tereza; Slovák, Matěj; Ulmanová, Olga; Růžička, Evžen; Dušek, Petr

    2016-07-01

    Wilson's disease (WD) is a hereditary disorder caused by ATP7B mutations resulting in systemic copper accumulation. WD may manifest as early-adulthood parkinsonism; and atypical cases may be difficult to distinguish from early-onset Parkinson's disease (EO-PD), a neurodegenerative disorder with onset ≤40 years of age. The aim of our study was to compare transcranial sonography (TCS)-magnetic resonance fusion imaging in WD and EO-PD and examine whether TCS can provide clinically useful information. We examined 22 WD, 16 EO-PD, and 24 healthy control subjects. We measured echogenicity and determined presence of MRI signal changes in T2-weighted images in the substantia nigra (SN) and lentiform nucleus (NL). TCS with the capability of magnetic resonance fusion and Virtual Navigator was used. The echogenicity indices of SN and NL were processed using digital image analysis to eliminate subjective evaluation errors. Mean SN echogenicity index in EO-PD (39.8 ± 5.9 [SD]) was higher compared to WD (28.0 ± 4.6, p MRI T2 hyperintensity (p MRI abnormality. There are distinct TCS findings in WD and EO-PD complementary to MRI that can be utilized as highly sensitive and specific biomarkers of these disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Mowat-Wilson syndrome

    DEFF Research Database (Denmark)

    Engenheiro, E; Møller, R S; Pinto, M

    2008-01-01

    Mowat-Wilson syndrome (MWS) is an autosomal dominant developmental disorder with mental retardation and variable multiple congenital abnormalities due to mutations of the ZEB2 (ZFHX1B) gene at 2q22. MWS was first described in 1998 and the causative gene was delineated in 2001. Since then, 115...... different mutations of ZEB2 have been published in association with this syndrome in 161 individuals. However, recent reports suggest that due to the variability of the congenital abnormalities, this syndrome may still be underdiagnosed. We report two unrelated patients with MWS where the clinical diagnosis...

  12. Direct sequencing of mutations in the copper-transporting P-type adenosine triphosphate (ATP7B) gene for diagnosis and pathogenesis of Wilson's disease.

    Science.gov (United States)

    Zhang, D F; Teng, J F

    2016-09-23

    Copper-transporting P-type adenosine triphosphatase (ATP7B) has been identified as the pathogenic gene in hepatolenticular degeneration, or Wilson's disease (WD). The aim of this study was to explore the correlation between genetic mutations and the clinical profile of WD, and to discuss the value of mutation examination in its diagnosis for providing a scientific basis for the development of a method to examine genetic mutations. Sixty-eight Chinese Han patients with WD and 20 controls were included in this study. The ATP7B gene in DNA extracted from patient blood samples was amplified by PCR and sequenced. These sequences were compared against corresponding gene sequences obtained from healthy controls to statistically analyze the genetic mutations. Five of the nineteen mutations in ATP7B were newly detected mutations; moreover, 8 of these mutations were polymorphic (2 were newly identified). The Arg778Leu and Pro992Leu mutations in exons 8 and 13 were detected at the highest mutation frequencies of 25.74 and 16.91%, respectively. The frequencies of all other mutations were below 5%. However, the clinical manifestations of WD did not differ significantly in patients with the Arg778Leu and Pro992Leu mutations. Therefore, these mutations were considered as hotspot mutations in Chinese WD patients. However, we observed no significant correlation between these genetic types and the clinical symptoms of WD. The correlation between the mutation genotype and disease phenotype remains to be elucidated. In conclusion, the highly sensitive and specific direct DNA sequencing method can be used to screen for the causative genes of WD.

  13. Treatment with D-penicillamine or zinc sulphate affects copper metabolism and improves but not normalizes antioxidant capacity parameters in Wilson disease.

    Science.gov (United States)

    Gromadzka, Grażyna; Grażyna, Gromadzka; Karpińska, Agata; Agata, Karpińska; Przybyłkowski, Adam; Adam, Przybyłkowski; Litwin, Tomasz; Tomasz, Litwin; Wierzchowska-Ciok, Agata; Agata, Wierzchowska-Ciok; Dzieżyc, Karolina; Karolina, Dzieżyc; Chabik, Grzegorz; Grzegorz, Chabik; Członkowska, Anna; Anna, Członkowska

    2014-02-01

    Copper accumulation in tissues due to a biallelic pathogenic mutation of the gene: ATP7B results in a clinical phenotype known as Wilson disease (WD). Aberrations in copper homeostasis can create favourable conditions for superoxide-yielding redox cycling and oxidative tissue damage. Drugs used in WD treatment aim to remove accumulated copper and normalise the free copper concentration in the blood. In the current study the effect of decoppering treatment on copper metabolism and systemic antioxidant capacity parameters was analyzed. Treatment naïve WD patients (TNWD) (n = 33), those treated with anti-copper drugs (TWD) (n = 99), and healthy controls (n = 99) were studied. Both TNWD and TWD patients characterised with decreased copper metabolism parameters, as well as decreased total antioxidant potential (AOP), glutathione (GSH) level, activity of catalase, glutathione peroxidase (GPx), and S-transferase glutathione, compared to controls. TWD patients had significantly lower copper metabolism parameters, higher total AOP and higher levels of GSH than TWD individuals; however, no difference was observed between these two patient groups with respect to the rest of the antioxidant capacity parameters. Patients who had undergone treatment with D-penicillamine or zinc sulphate did not differ with respect to copper metabolism or antioxidant capacity parameters, with the exception of GPx that was lower in D-penicillamine treated individuals. These data suggest that anti-copper treatment affects copper metabolism as well as improves, but does not normalize, natural antioxidant capacity in patients with WD. We propose to undertake studies aimed to evaluate the usefulness of antioxidants as well as selenium as a supplemental therapy in WD.

  14. Evolution of exchangeable copper and relative exchangeable copper through the course of Wilson's disease in the Long Evans Cinnamon rat.

    Science.gov (United States)

    Schmitt, Françoise; Podevin, Guillaume; Poupon, Joël; Roux, Jérôme; Legras, Pierre; Trocello, Jean-Marc; Woimant, France; Laprévote, Olivier; Nguyen, Tuan Huy; El Balkhi, Souleiman

    2013-01-01

    Wilson's disease (WD) is an inherited disorder of copper metabolism leading to liver failure and/or neurological impairment. Its diagnosis often remains difficult even with genetic testing. Relative exchangeable copper (REC) has recently been described as a reliable serum diagnostic marker for WD. The aim of this study was to validate the use of REC in the Long Evans Cinnamon (LEC) rat, an animal model for WD, and to study its relevance under different conditions in comparison with conventional markers. Two groups of LEC rats and one group of Long-Evans (LE) rats were clinically and biologically monitored from 6 to 28 weeks of age. One group of LEC rats was given copper-free food. The other groups had normal food. Blood samples were collected each month and different serum markers for WD (namely ceruloplasmin oxidase activity, exchangeable copper (CuEXC), total serum copper and REC) and acute liver failure (serum transaminases and bilirubinemia) were tested. Every LEC rat under normal food developed acute liver failure (ALF), with 40% global mortality. Serum transaminases and bilirubinemia along with total serum copper and exchangeable copper levels increased with the onset of acute liver failure. A correlation was observed between CuEXC values and the severity of ALF. Cut-off values were different between young and adult rats and evolved because of age and/or liver failure. Only REC, with values >19%, was able to discriminate LEC groups from the LE control group at every time point in the study. REC sensitivity and specificity reached 100% in adults rats. REC appears to be independent of demographic or clinical data in LEC rats. It is a very simple and reliable blood test for the diagnosis of copper toxicosis owing to a lack of ATP7B function. CuEXC can be used as an accurate biomarker of copper overload.

  15. 1H NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease.

    Science.gov (United States)

    Xu, Jingjing; Jiang, Huaizhou; Li, Jinquan; Cheng, Kian-Kai; Dong, Jiyang; Chen, Zhong

    2015-01-01

    Wilson's disease (WD), also known as hepatoleticular degeneration (HLD), is a rare autosomal recessive genetic disorder of copper metabolism, which causes copper to accumulate in body tissues. In this study, rats fed with copper-laden diet are used to render the clinical manifestations of WD, and their copper toxicity-induced organ lesions are studied. To investigate metabolic behaviors of 'decoppering' process, penicillamine (PA) was used for treating copper-laden rats as this chelating agent could eliminate excess copper through the urine. To date, there has been limited metabolomics study on WD, while metabolic impacts of copper accumulation and PA administration have yet to be established. A combination of 1HNMR spectroscopy and multivariate statistical analysis was applied to examine the metabolic profiles of the urine and blood serum samples collected from the copper-laden rat model of WD with PA treatment. Copper accumulation in the copper-laden rats is associated with increased lactate, creatinine, valine and leucine, as well as decreased levels of glucose and taurine in the blood serum. There were also significant changes in p-hydroxyphenylacetate (p-HPA), creatinine, alpha-ketoglutarate (α-KG), dimethylamine, N-acetylglutamate (NAG), N-acetylglycoprotein (NAC) in the urine of these rats. Notably, the changes in p-HPA, glucose, lactate, taurine, valine, leucine, and NAG were found reversed following PA treatment. Nevertheless, there were no changes for dimethylamine, α-KG, and NAC as a result of the treatment. Compared with the controls, the concentrations of hippurate, formate, alanine, and lactate were changed when PA was applied and this is probably due to its side effect. A tool named SMPDB (Small Molecule Pathway Database) is introduced to identify the metabolic pathway influenced by the copper-laden diet. The study has shown the potential application of NMR-based metabolomic analysis in providing further insights into the molecular mechanism

  16. 1H NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease.

    Directory of Open Access Journals (Sweden)

    Jingjing Xu

    Full Text Available Wilson's disease (WD, also known as hepatoleticular degeneration (HLD, is a rare autosomal recessive genetic disorder of copper metabolism, which causes copper to accumulate in body tissues. In this study, rats fed with copper-laden diet are used to render the clinical manifestations of WD, and their copper toxicity-induced organ lesions are studied. To investigate metabolic behaviors of 'decoppering' process, penicillamine (PA was used for treating copper-laden rats as this chelating agent could eliminate excess copper through the urine. To date, there has been limited metabolomics study on WD, while metabolic impacts of copper accumulation and PA administration have yet to be established.A combination of 1HNMR spectroscopy and multivariate statistical analysis was applied to examine the metabolic profiles of the urine and blood serum samples collected from the copper-laden rat model of WD with PA treatment.Copper accumulation in the copper-laden rats is associated with increased lactate, creatinine, valine and leucine, as well as decreased levels of glucose and taurine in the blood serum. There were also significant changes in p-hydroxyphenylacetate (p-HPA, creatinine, alpha-ketoglutarate (α-KG, dimethylamine, N-acetylglutamate (NAG, N-acetylglycoprotein (NAC in the urine of these rats. Notably, the changes in p-HPA, glucose, lactate, taurine, valine, leucine, and NAG were found reversed following PA treatment. Nevertheless, there were no changes for dimethylamine, α-KG, and NAC as a result of the treatment. Compared with the controls, the concentrations of hippurate, formate, alanine, and lactate were changed when PA was applied and this is probably due to its side effect. A tool named SMPDB (Small Molecule Pathway Database is introduced to identify the metabolic pathway influenced by the copper-laden diet.The study has shown the potential application of NMR-based metabolomic analysis in providing further insights into the molecular

  17. Novel mutations of the ATP7B gene in Han Chinese families with pre-symptomatic Wilson's disease.

    Science.gov (United States)

    Yuan, Zhe-Feng; Wu, Wei; Yu, Yong-Lin; Shen, Jue; Mao, Shan-Shan; Gao, Feng; Xia, Zhe-Zhi

    2015-08-01

    Wilson's disease (WD) is an autosomal recessive genetic disorder of copper metabolism, caused by mutations in the ATP7B gene, resulting in copper accumulation in the liver, brain, kidney, and cornea and leading to significant disability or death if untreated. Early diagnosis and proper therapy usually predict a good prognosis, especially in pre-symptomatic WD. Genetic testing is the most accurate and effective diagnostic method for early diagnosis. The clinical and biochemical features of three unrelated Han Chinese families with pre-symptomatic WD were reported. The molecular defects in these families were investigated by polymerase chain reaction and DNA sequencing. Hundred healthy children with the same ethnic background served as controls. Bioinformatic tools (polymorphism phenotyping-2, sorting intolerant from tolerant, protein analysis through evolutionary relationships, and predictor of human deleterious single nucleotide polymorphisms) were combined and used to predict the functional effects of mutations. We identified 2 novel ATP7B mutations (p.Leu692Pro and p.Asn728Ser) and 3 known mutations (p.Met769fs, p.Arg778Leu and p.Val1216Met) in these Chinese WD families. These mutations were not observed in the 100 normal controls. The bioinformatic method showed that p.Leu692Pro and p.Asn728Ser mutations are pathogenic. Our research enriches the mutation spectrum of the ATP7B gene worldwide and provides valuable information for studying the mutation types and mode of inheritance of ATP7B in the Chinese population. Liver function analysis and genetic testing in young children with WD are necessary to shorten the time to the initiation of therapy, reduce damage to the liver and brain, and improve prognosis.

  18. Diagnosis of abnormal biliary copper excretion by positron emission tomography with targeting of (64)Copper-asialofetuin complex in LEC rat model of Wilson's disease.

    Science.gov (United States)

    Bahde, Ralf; Kapoor, Sorabh; Bhargava, Kuldeep K; Palestro, Christopher J; Gupta, Sanjeev

    2014-01-01

    Identification by molecular imaging of key processes in handling of transition state metals, such as copper (Cu), will be of considerable clinical value. For instance, the ability to diagnose Wilson's disease with molecular imaging by identifying copper excretion in an ATP7B-dependent manner will be very significant. To develop highly effective diagnostic approaches, we hypothesized that targeting of radiocopper via the asialoglycoprotein receptor will be appropriate for positron emission tomography, and examined this approach in a rat model of Wilson's disease. After complexing (64)Cu to asialofetuin we studied handling of this complex compared with (64)Cu in healthy LEA rats and diseased homozygous LEC rats lacking ATP7B and exhibiting hepatic copper toxicosis. We analyzed radiotracer clearance from blood, organ uptake, and biliary excretion, including sixty minute dynamic positron emission tomography recordings. In LEA rats, (64)Cu-asialofetuin was better cleared from blood followed by liver uptake and greater biliary excretion than (64)Cu. In LEC rats, (64)Cu-asialofetuin activity cleared even more rapidly from blood followed by greater uptake in liver, but neither (64)Cu-asialofetuin nor (64)Cu appeared in bile. Image analysis demonstrated rapid visualization of liver after (64)Cu-asialofetuin administration followed by decreased liver activity in LEA rats while liver activity progressively increased in LEC rats. Image analysis resolved this difference in hepatic activity within one hour. We concluded that (64)Cu-asialofetuin complex was successfully targeted to the liver and radiocopper was then excreted into bile in an ATP7B-dependent manner. Therefore, hepatic targeting of radiocopper will be appropriate for improving molecular diagnosis and for developing drug/cell/gene therapies in Wilson's disease.

  19. Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care

    DEFF Research Database (Denmark)

    Ivanovski, Ivan; Djuric, Olivera; Caraffi, Stefano Giuseppe

    2018-01-01

    to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS.MethodsIn a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental...... clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted...... to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.ConclusionKnowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.GENETICS in MEDICINE advance...

  20. Characterization of the Wilson disease gene: Genomic organization; alternative splicing; structure/function predictions; and population frequencies of disease-specific mutations

    Energy Technology Data Exchange (ETDEWEB)

    Petrukhin, K.; Chernov, I.; Ross, B.M. [Columbia Univ., New York, NY (United States)] [and others

    1994-09-01

    The Wilson disease (WD) gene has recently been identified as a putative copper-transporting ATPase with high amino acid similarity with the Menkes disease (MNK) gene. We have further characterized the WD gene by extending the 5{prime}-coding and non-coding DNA sequence and elucidating the intron/exon structure and genomic organization. Analysis of RNA transcripts from liver, brain, kidney and placenta reveals extensive alternative splicing which may provide a mechanism to regulate the quantity of functional protein product. Comparative sequence analysis shows that WD and MNK belong to the sub-family of heavy metal-transporting ATPases with several characterizing features which include unique amino acid motifs and distinct N-terminal and C-terminal transmembrane structure. Our data indicate that the 600 amino acid metal binding portion of the WD and MNK proteins was formed by gene duplication events and splicing of the 6 metal binding domain segment to a common ancestral protein. We have raised a WD-specific anti-peptide antibody to the N-terminal region and are beginning to explore the cellular and intracellular location of the WD protein. The metal-binding segment of the WD protein has been expressed in E. coli and metal binding assays are underway to characterize this aspect of the protein`s function. We have identified numerous disease-specific mutations and developed a rapid {open_quotes}reverse dot blot{close_quotes} screening protocol to determine mutation frequencies in different populations. The most common mutation disrupts the characteristic SEHP motif and accounts for more than 40% of WD cases in North American, Russian, and Swedish populations. This mutation has not been observed in our limited Sicilian sample.

  1. Askey-Wilson polynomial

    NARCIS (Netherlands)

    Koornwinder, T.H.

    2012-01-01

    Askey-Wilson polynomial refers to a four-parameter family of q-hypergeometric orthogonal polynomials which contains all families of classical orthogonal polynomials (in the wide sense) as special or limit cases.

  2. Bile salt-induced pro-oxidant liver damage promotes transplanted cell proliferation for correcting Wilson disease in the Long-Evans Cinnamon rat model.

    Science.gov (United States)

    Joseph, Brigid; Kapoor, Sorabh; Schilsky, Michael L; Gupta, Sanjeev

    2009-05-01

    Insights into disease-specific mechanisms for liver repopulation are needed for cell therapy. To understand the efficacy of pro-oxidant hepatic perturbations in Wilson disease, we studied Long-Evans Cinnamon (LEC) rats with copper toxicosis under several conditions. Hepatocytes from healthy Long-Evans Agouti (LEA) rats were transplanted intrasplenically into the liver. A cure was defined as lowering of copper to below 250 microg/g liver, presence of ATPase, Cu++ transporting, beta polypeptide (atp7b) messenger RNA (mRNA) in the liver and improvement in liver histology. Treatment of animals with the hydrophobic bile salt, cholic acid, or liver radiation before cell transplantation produced cure rates of 14% and 33%, respectively; whereas liver radiation plus partial hepatectomy followed by cell transplantation proved more effective, with cure in 55%, P < 0.01; and liver radiation plus cholic acid followed by cell transplantation was most effective, with cure in 75%, P < 0.001. As a group, cell therapy cures in rats preconditioned with liver radiation plus cholic acid resulted in less hepatic copper, indicating greater extent of liver repopulation. We observed increased hepatic catalase and superoxide dismutase activities in LEC rats, suggesting chronic oxidative stress. After liver radiation or cholic acid, hepatic lipid peroxidation levels increased, indicating further oxidative injury, although we did not observe overt additional cytotoxicity. This contrasted with healthy animals in which liver radiation and cholic acid produced hepatic steatosis and loss of injured hepatocytes. We concluded that pro-oxidant perturbations were uniquely effective for cell therapy in Wilson disease because of the nature of preexisting hepatic damage.

  3. PHYSICAL LOCALIZATION OF THE CHROMOSOMAL MARKER D13S31 PLACES THE WILSON DISEASE LOCUS AT THE JUNCTION OF BAND-Q14.3 AND BAND-Q21.1 OF CHROMOSOME-13

    NARCIS (Netherlands)

    KOOY, RF; VANDERVEEN, AY; VERLIND, E; HOUWEN, RHJ; SCHEFFER, H; BUYS, CHCM

    D13S31 is the marker closest to the Wilson disease locus according to genetic analysis. Its physical localisation was refined by fluorescent in situ hybridisation to the junction to chromosomal bands 13q14.3 and 13q21.1. Using polymerase chain reaction analysis, D13S31 and D13S59 (the closest

  4. Woodrow Wilson on Education

    Science.gov (United States)

    Berlin, Isaiah

    2012-01-01

    In this 1960 article Isaiah Berlin compares Woodrow Wilson's emphasis on the need to educate university students for life in the real world with the difference between Oxford "realism" and Cambridge "idealism" in the nineteenth century. Oxford favoured a Wilsonian preference for general education over (but not to the exclusion of) pure…

  5. Wilson disease mutation pattern with genotype-phenotype correlations from Western India: confirmation of p.C271* as a common Indian mutation and identification of 14 novel mutations.

    Science.gov (United States)

    Aggarwal, Annu; Chandhok, Gursimran; Todorov, Theodor; Parekh, Saloni; Tilve, Sharada; Zibert, Andree; Bhatt, Mohit; Schmidt, Hartmut H-J

    2013-07-01

    Wilson disease (WD) is an autosomal recessive disorder resulting from mutations in the ATP7B gene, with over 600 mutations described. Identification of mutations has made genetic diagnosis of WD feasible in many countries. The heterogeneity of ATP7B mutants is, however, yet to be identified in the Indian population. We analyzed the mutational pattern of WD in a large region of Western India. We studied patients (n = 52) for ATP7B gene mutations in a cohort of families with WD and also in first-degree relatives (n = 126). All 21 exon-intron boundaries of the WD gene were amplified and directly sequenced. We identified 36 different disease-causing mutations (31 exonic and five intronic splice site variants). Fourteen novel mutations were identified. Exons 2, 8, 13, 14, and 18 accounted for the majority of mutations (86.4%). A previously recognized mutation, p.C271*, and the novel mutation p.E122fs, were the most common mutations with allelic frequencies of 20.2% and 10.6%, respectively. Frequent homozygous mutations (58.9%) and disease severity assessments allowed analysis of genotype-phenotype correlations. Our study significantly adds to the emerging data from other parts of India suggesting that p.C271* may be the most frequent mutation across India, and may harbor a moderate to severely disabling phenotype with limited variability. © 2013 John Wiley & Sons Ltd/University College London.

  6. Characterization of timed changes in hepatic copper concentrations, methionine metabolism, gene expression, and global DNA methylation in the Jackson toxic milk mouse model of Wilson disease.

    Science.gov (United States)

    Le, Anh; Shibata, Noreene M; French, Samuel W; Kim, Kyoungmi; Kharbanda, Kusum K; Islam, Mohammad S; LaSalle, Janine M; Halsted, Charles H; Keen, Carl L; Medici, Valentina

    2014-05-07

    Wilson disease (WD) is characterized by hepatic copper accumulation with progressive liver damage to cirrhosis. This study aimed to characterize the toxic milk mouse from The Jackson Laboratory (Bar Harbor, ME, USA) (tx-j) mouse model of WD according to changes over time in hepatic copper concentrations, methionine metabolism, global DNA methylation, and gene expression from gestational day 17 (fetal) to adulthood (28 weeks). Included liver histology and relevant biochemical analyses including hepatic copper quantification, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) liver levels, qPCR for transcript levels of genes relevant to methionine metabolism and liver damage, and DNA dot blot for global DNA methylation. Hepatic copper was lower in tx-j fetuses but higher in weanling (three weeks) and adult tx-j mice compared to controls. S-adenosylhomocysteinase transcript levels were significantly lower at all time points, except at three weeks, correlating negatively with copper levels and with consequent changes in the SAM:SAH methylation ratio and global DNA methylation. Compared to controls, methionine metabolism including S-adenosylhomocysteinase gene expression is persistently different in the tx-j mice with consequent alterations in global DNA methylation in more advanced stages of liver disease. The inhibitory effect of copper accumulation on S-adenosylhomocysteinase expression is associated with progressively abnormal methionine metabolism and decreased methylation capacity and DNA global methylation.

  7. Early gestational gene transfer with targeted ATP7B expression in the liver improves phenotype in a murine model of Wilson's disease.

    Science.gov (United States)

    Roybal, J L; Endo, M; Radu, A; Gray, L; Todorow, C A; Zoltick, P W; Lutsenko, S; Flake, A W

    2012-11-01

    The ideal gene therapy for metabolical liver disorders would target hepatocytes before the onset of disease and be durable, non-toxic and non-immunogenic. Early gestational gene transfer can achieve such goals. Here, we demonstrate that prenatal gene transfer of human Atp7b reduces liver pathology and improves biochemical markers in Atp7b(-/-) mice, a murine model of Wilson's disease (WD). Following prenatal injection of lentivirus vector containing the human Atp7b gene under the transcriptional control of a liver-specific promoter, the full-length ATP7B was detectable in mouse livers for the entire duration of experiments (20 weeks after birth). In contrast to a marked pathology in non-injected animals, livers from age-matched treated mice consistently demonstrated normal gross and histological morphology. Hepatic copper content was decreased in the majority of treated mice, although remaining copper levels varied. Improvement of hepatic copper metabolism was further apparent from the presence of copper-bound ceruloplasmin in the sera and normalization of the mRNA levels for HMG CoA-reductase. With this approach, the complete loss of copper transport function can be ameliorated, as evident from phenotypical improvement in treated Atp7b(-/-) mice. This study provides proof of principle for in utero gene therapy in WD and other liver-based enzyme deficiencies.

  8. Characterization of Timed Changes in Hepatic Copper Concentrations, Methionine Metabolism, Gene Expression, and Global DNA Methylation in the Jackson Toxic Milk Mouse Model of Wilson Disease

    Directory of Open Access Journals (Sweden)

    Anh Le

    2014-05-01

    Full Text Available Background: Wilson disease (WD is characterized by hepatic copper accumulation with progressive liver damage to cirrhosis. This study aimed to characterize the toxic milk mouse from The Jackson Laboratory (Bar Harbor, ME, USA (tx-j mouse model of WD according to changes over time in hepatic copper concentrations, methionine metabolism, global DNA methylation, and gene expression from gestational day 17 (fetal to adulthood (28 weeks. Methods: Included liver histology and relevant biochemical analyses including hepatic copper quantification, S-adenosylmethionine (SAM and S-adenosylhomocysteine (SAH liver levels, qPCR for transcript levels of genes relevant to methionine metabolism and liver damage, and DNA dot blot for global DNA methylation. Results: Hepatic copper was lower in tx-j fetuses but higher in weanling (three weeks and adult tx-j mice compared to controls. S-adenosylhomocysteinase transcript levels were significantly lower at all time points, except at three weeks, correlating negatively with copper levels and with consequent changes in the SAM:SAH methylation ratio and global DNA methylation. Conclusion: Compared to controls, methionine metabolism including S-adenosylhomocysteinase gene expression is persistently different in the tx-j mice with consequent alterations in global DNA methylation in more advanced stages of liver disease. The inhibitory effect of copper accumulation on S-adenosylhomocysteinase expression is associated with progressively abnormal methionine metabolism and decreased methylation capacity and DNA global methylation.

  9. Phenotype-genotype correlation in Wilson disease in a large Lebanese family: association of c.2299insC with hepatic and of p. Ala1003Thr with neurologic phenotype.

    Directory of Open Access Journals (Sweden)

    Julnar Usta

    Full Text Available Genotype phenotype correlations in Wilson disease (WD are best established in homozygous patients or in compound heterozygous patients carrying the same set of mutations. We determined the clinical phenotype of patients with WD carrying the c.2298_2299insC in Exon 8 (c.2299insC or the p. Ala1003Thr missense substitution in Exon 13 mutations in the homozygous or compound heterozygous state. We investigated 76 members of a single large Lebanese family. Their genotypes were determined, and clinical assessments were carried out for affected subjects. We also performed a literature search retrieving the phenotypes of patients carrying the same mutations of our patients in the homozygous or compound heterozygous state. There were 7 consanguineous marriages in this family and the prevalence of WD was 8.9% and of carriers of ATP7B mutation 44.7%. WD was confirmed in 9 out of 76 subjects. All 9 had the c.2299insC mutation, 5 homozygous and 4-compound heterozygous with p. Ala1003Thr. Six of our patients had hepatic, 2 had neurologic and 1 had asymptomatic phenotype. Based on our data and a literature review, clear phenotypes were reported for 38 patients worldwide carrying the c.2299insC mutation. About 53% of those have hepatic and 29% have neurologic phenotype. Furthermore, there were 10 compound heterozygous patients carrying the p. Ala1003Thr mutation. Among those, 80% having c.2299insC as the second mutation had hepatic phenotype, and all others had neurologic phenotype. We hereby report an association between the c.2299insC mutation and hepatic phenotype and between the p. Ala1003Thr mutation and neurologic phenotype.

  10. Phenotype-genotype correlation in Wilson disease in a large Lebanese family: association of c.2299insC with hepatic and of p. Ala1003Thr with neurologic phenotype.

    Science.gov (United States)

    Usta, Julnar; Wehbeh, Antonios; Rida, Khaled; El-Rifai, Omar; Estiphan, Theresa Alicia; Majarian, Tamar; Barada, Kassem

    2014-01-01

    Genotype phenotype correlations in Wilson disease (WD) are best established in homozygous patients or in compound heterozygous patients carrying the same set of mutations. We determined the clinical phenotype of patients with WD carrying the c.2298_2299insC in Exon 8 (c.2299insC) or the p. Ala1003Thr missense substitution in Exon 13 mutations in the homozygous or compound heterozygous state. We investigated 76 members of a single large Lebanese family. Their genotypes were determined, and clinical assessments were carried out for affected subjects. We also performed a literature search retrieving the phenotypes of patients carrying the same mutations of our patients in the homozygous or compound heterozygous state. There were 7 consanguineous marriages in this family and the prevalence of WD was 8.9% and of carriers of ATP7B mutation 44.7%. WD was confirmed in 9 out of 76 subjects. All 9 had the c.2299insC mutation, 5 homozygous and 4-compound heterozygous with p. Ala1003Thr. Six of our patients had hepatic, 2 had neurologic and 1 had asymptomatic phenotype. Based on our data and a literature review, clear phenotypes were reported for 38 patients worldwide carrying the c.2299insC mutation. About 53% of those have hepatic and 29% have neurologic phenotype. Furthermore, there were 10 compound heterozygous patients carrying the p. Ala1003Thr mutation. Among those, 80% having c.2299insC as the second mutation had hepatic phenotype, and all others had neurologic phenotype. We hereby report an association between the c.2299insC mutation and hepatic phenotype and between the p. Ala1003Thr mutation and neurologic phenotype.

  11. Comparison of the disposition behavior of organic anions in an animal model for Wilson's disease (Long-Evans Cinnamon rats) with that in normal Long-Evans Agouti rats.

    Science.gov (United States)

    Itagaki, Shirou; Sugawara, Mitsuru; Kobayashi, Michiya; Miyazaki, Katsumi; Hirano, Takeshi; Iseki, Ken

    2004-04-01

    Long-Evans Cinnamon (LEC) rats have an abnormality similar to that observed in Wilson's disease in humans and are therefore a good animal model for the study of Wilson's disease. LEC rats develop hereditary hepatitis and severe jaundice. Mutant animals with hyperbilirubinemia have been widely used as animal models for human diseases. Among these mutant animals, Eisai hyperbilirubinemic rats (EHBR) have defective biliary excretion of organic anions. Thus, biliary excretion of sulfobromophthalein (BSP) and urinary excretion of phenolsulfonphthalein (PSP) in LEC rats were compared with those in Long-Evans Agouti (LEA) rats. In LEC rats, the excretion of BSP, a multidrug resistance-associated protein 2 (Mrp2/Abcc2) substrate, was significantly decreased compared to that in LEA rats. It has been reported that the transport function for organic anions on the kidney is maintained in EHBR. However, the urinary excretion of PSP is impaired in LEC rats. It is possible that organic anion transporters responsible for the urinary excretion of PSP in LEA rats and EHBR are impaired in LEC rats. It is important to elucidate the relationship between organic anion secretion and Wilson's disease.

  12. Clinical Features and Therapeutic Response in Taiwanese Children With Wilson's Disease: 12 Years of Experience in a Single Center

    Directory of Open Access Journals (Sweden)

    Li-Ching Wang

    2010-04-01

    Conclusion: Serum ceruloplasmin and 24-hour urinary copper examinations could be used to rule out WD in children with chronic hepatitis and hemolytic anemia. Gene analysis is helpful for prompt diagnosis of asymptomatic siblings and patients with atypical features. Zinc treatment is generally safe in pediatric patients with WD. However, its adverse effects should be monitored.

  13. Urinary Copper Elevation in a Mouse Model of Wilson's Disease Is a Regulated Process to Specifically Decrease the Hepatic Copper Load

    Science.gov (United States)

    Gray, Lawrence W.; Peng, Fangyu; Molloy, Shannon A.; Pendyala, Venkata S.; Muchenditsi, Abigael; Muzik, Otto; Lee, Jaekwon; Kaplan, Jack H.; Lutsenko, Svetlana

    2012-01-01

    Body copper homeostasis is regulated by the liver, which removes excess copper via bile. In Wilson's disease (WD), this function is disrupted due to inactivation of the copper transporter ATP7B resulting in hepatic copper overload. High urinary copper is a diagnostic feature of WD linked to liver malfunction; the mechanism behind urinary copper elevation is not fully understood. Using Positron Emission Tomography-Computed Tomography (PET-CT) imaging of live Atp7b−/− mice at different stages of disease, a longitudinal metal analysis, and characterization of copper-binding molecules, we show that urinary copper elevation is a specific regulatory process mediated by distinct molecules. PET-CT and atomic absorption spectroscopy directly demonstrate an age-dependent decrease in the capacity of Atp7b−/− livers to accumulate copper, concomitant with an increase in urinary copper. This reciprocal relationship is specific for copper, indicating that cell necrosis is not the primary cause for the initial phase of metal elevation in the urine. Instead, the urinary copper increase is associated with the down-regulation of the copper-transporter Ctr1 in the liver and appearance of a 2 kDa Small Copper Carrier, SCC, in the urine. SCC is also elevated in the urine of the liver-specific Ctr1−/− knockouts, which have normal ATP7B function, suggesting that SCC is a normal metabolite carrying copper in the serum. In agreement with this hypothesis, partially purified SCC-Cu competes with free copper for uptake by Ctr1. Thus, hepatic down-regulation of Ctr1 allows switching to an SCC-mediated removal of copper via kidney when liver function is impaired. These results demonstrate that the body regulates copper export through more than one mechanism; better understanding of urinary copper excretion may contribute to an improved diagnosis and monitoring of WD. PMID:22802922

  14. Urinary copper elevation in a mouse model of Wilson's disease is a regulated process to specifically decrease the hepatic copper load.

    Directory of Open Access Journals (Sweden)

    Lawrence W Gray

    Full Text Available Body copper homeostasis is regulated by the liver, which removes excess copper via bile. In Wilson's disease (WD, this function is disrupted due to inactivation of the copper transporter ATP7B resulting in hepatic copper overload. High urinary copper is a diagnostic feature of WD linked to liver malfunction; the mechanism behind urinary copper elevation is not fully understood. Using Positron Emission Tomography-Computed Tomography (PET-CT imaging of live Atp7b(-/- mice at different stages of disease, a longitudinal metal analysis, and characterization of copper-binding molecules, we show that urinary copper elevation is a specific regulatory process mediated by distinct molecules. PET-CT and atomic absorption spectroscopy directly demonstrate an age-dependent decrease in the capacity of Atp7b(-/- livers to accumulate copper, concomitant with an increase in urinary copper. This reciprocal relationship is specific for copper, indicating that cell necrosis is not the primary cause for the initial phase of metal elevation in the urine. Instead, the urinary copper increase is associated with the down-regulation of the copper-transporter Ctr1 in the liver and appearance of a 2 kDa Small Copper Carrier, SCC, in the urine. SCC is also elevated in the urine of the liver-specific Ctr1(-/- knockouts, which have normal ATP7B function, suggesting that SCC is a normal metabolite carrying copper in the serum. In agreement with this hypothesis, partially purified SCC-Cu competes with free copper for uptake by Ctr1. Thus, hepatic down-regulation of Ctr1 allows switching to an SCC-mediated removal of copper via kidney when liver function is impaired. These results demonstrate that the body regulates copper export through more than one mechanism; better understanding of urinary copper excretion may contribute to an improved diagnosis and monitoring of WD.

  15. Hypercalciuria and Nephrocalcinosis as Early Feature of Wilson Disease Onset: Description of a Pediatric Case and Literature Review

    OpenAIRE

    Di Stefano, Valeria; Lionetti, Elena; Rotolo, Novella; DE LA ROSA, MARIO; Leonardi, Salvatore

    2012-01-01

    Background: Wilson’s disease (WD) is a rare autosomal-recessive disorder characterized by a mutation in the ATP7B gene, located on chromosome 13, which encodes a protein involved in the metabolism of copper. Case Presentation: We described the case of an Indian male with a history of polydipsia and polyuria, related to hypercalciuria and consequent nephrocalcinosis. The symptoms began at the age of five years old, but he was not diagnosed with WD until he reached an adolescent age. We started...

  16. Mowat-Wilson syndrome: A case report

    Directory of Open Access Journals (Sweden)

    Čuturilo Goran

    2009-01-01

    Full Text Available Introduction. Mowat-Wilson syndrome (MWS is characterised by severe mental retardation and multiple congenital anomalies. Key features for diagnosis are specific facial dysmorphism with uplifted ear lobes and Hirschsprung's disease. Ganglionic disorders of the colon, both the number of ganglion cells and the length of the aganglionic segment vary significantly in these patients. The disease is caused by ZFHX1B gene mutation. The management of MWS is symptomatic. Case outline. We report a four-year old boy with mental retardation, specific facial dysmorphy and multiple anomalies. During prenatal follow-up intrauterine growth retardation was revealed. Karyotype was normal. Clinical findings showed that growth and mental retardation, gastrointestinal disturbance and heart defect were predominant. A gastrostoma was inserted. Hypoganglionosis of the colon caused severe obstipation. He had a severe stenosis of the pulmonary artery and was a candidate for cardiac surgery. There were several attempts to establish diagnosis, but so far, without results. Conclusion. Hirschsprung's disease/hypoganglionosis of the colon associated with other congenital anomalies or mental retardation require evaluation for dysmorphic syndromes. One of them is MWS, presented in this report.

  17. Wilson loops as precursors

    Energy Technology Data Exchange (ETDEWEB)

    Susskind, Leonard [Department of Physics, Stanford University, Stanford, California 94305-4060 (United States); Toumbas, Nicolaos [Department of Physics, Stanford University, Stanford, California 94305-4060 (United States)

    2000-02-15

    There is substantial evidence that string theory on AdS{sub 5}xS{sub 5} is a holographic theory in which the number of degrees of freedom scales as the area of the boundary in Planck units. Precisely how the theory can describe bulk physics using only surface degrees of freedom is not well understood. A particularly paradoxical situation involves an event deep in the interior of the bulk space. The event must be recorded in the (Schroedinger picture) state vector of the boundary theory long before a signal, such as a gravitational wave, can propagate from the event to the boundary. In a previous paper with Polchinski, we argued that the ''precursor'' operators which carry information stored in the wave during the time when it vanishes in a neighborhood of the boundary are necessarily non-local. In this paper we argue that the precursors cannot be products of local gauge invariant operators such as the energy momentum tensor. In fact gauge theories have a class of intrinsically non-local operators which cannot be built from local gauge invariant objects. These are the Wilson loops. We show that the precursors can be identified with Wilson loops whose spatial size is dictated by the UV-IR connection. (c) 2000 The American Physical Society.

  18. The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders

    Directory of Open Access Journals (Sweden)

    Hille Fieten

    2016-01-01

    Full Text Available The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to Wilson disease, which is characterized by a predominantly hepatic copper accumulation. The low incidence and the phenotypic variability of human copper toxicosis hamper identification of causal genes or modifier genes involved in the disease pathogenesis. The Labrador retriever was recently characterized as a new canine model for copper toxicosis. Purebred dogs have reduced genetic variability, which facilitates identification of genes involved in complex heritable traits that might influence phenotype in both humans and dogs. We performed a genome-wide association study in 235 Labrador retrievers and identified two chromosome regions containing ATP7A and ATP7B that were associated with variation in hepatic copper levels. DNA sequence analysis identified missense mutations in each gene. The amino acid substitution ATP7B:p.Arg1453Gln was associated with copper accumulation, whereas the amino acid substitution ATP7A:p.Thr327Ile partly protected against copper accumulation. Confocal microscopy indicated that aberrant copper metabolism upon expression of the ATP7B variant occurred because of mis-localization of the protein in the endoplasmic reticulum. Dermal fibroblasts derived from ATP7A:p.Thr327Ile dogs showed copper accumulation and delayed excretion. We identified the Labrador retriever as the first natural, non-rodent model for ATP7B-associated copper toxicosis. Attenuation of copper accumulation by the ATP7A mutation sheds an interesting light on the interplay of copper transporters in body copper homeostasis and warrants a thorough investigation of ATP7A as a modifier gene in copper-metabolism disorders. The identification of two new functional

  19. The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders

    Science.gov (United States)

    Fieten, Hille; Gill, Yadvinder; Martin, Alan J.; Concilli, Mafalda; Dirksen, Karen; van Steenbeek, Frank G.; Spee, Bart; van den Ingh, Ted S. G. A. M.; Martens, Ellen C. C. P.; Festa, Paola; Chesi, Giancarlo; van de Sluis, Bart; Houwen, Roderick H. J. H.; Watson, Adrian L.; Aulchenko, Yurii S.; Hodgkinson, Victoria L.; Zhu, Sha; Petris, Michael J.; Polishchuk, Roman S.; Leegwater, Peter A. J.; Rothuizen, Jan

    2016-01-01

    ABSTRACT The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to Wilson disease, which is characterized by a predominantly hepatic copper accumulation. The low incidence and the phenotypic variability of human copper toxicosis hamper identification of causal genes or modifier genes involved in the disease pathogenesis. The Labrador retriever was recently characterized as a new canine model for copper toxicosis. Purebred dogs have reduced genetic variability, which facilitates identification of genes involved in complex heritable traits that might influence phenotype in both humans and dogs. We performed a genome-wide association study in 235 Labrador retrievers and identified two chromosome regions containing ATP7A and ATP7B that were associated with variation in hepatic copper levels. DNA sequence analysis identified missense mutations in each gene. The amino acid substitution ATP7B:p.Arg1453Gln was associated with copper accumulation, whereas the amino acid substitution ATP7A:p.Thr327Ile partly protected against copper accumulation. Confocal microscopy indicated that aberrant copper metabolism upon expression of the ATP7B variant occurred because of mis-localization of the protein in the endoplasmic reticulum. Dermal fibroblasts derived from ATP7A:p.Thr327Ile dogs showed copper accumulation and delayed excretion. We identified the Labrador retriever as the first natural, non-rodent model for ATP7B-associated copper toxicosis. Attenuation of copper accumulation by the ATP7A mutation sheds an interesting light on the interplay of copper transporters in body copper homeostasis and warrants a thorough investigation of ATP7A as a modifier gene in copper-metabolism disorders. The identification of two new functional variants in

  20. The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders.

    Science.gov (United States)

    Fieten, Hille; Gill, Yadvinder; Martin, Alan J; Concilli, Mafalda; Dirksen, Karen; van Steenbeek, Frank G; Spee, Bart; van den Ingh, Ted S G A M; Martens, Ellen C C P; Festa, Paola; Chesi, Giancarlo; van de Sluis, Bart; Houwen, Roderick H J H; Watson, Adrian L; Aulchenko, Yurii S; Hodgkinson, Victoria L; Zhu, Sha; Petris, Michael J; Polishchuk, Roman S; Leegwater, Peter A J; Rothuizen, Jan

    2016-01-01

    The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to Wilson disease, which is characterized by a predominantly hepatic copper accumulation. The low incidence and the phenotypic variability of human copper toxicosis hamper identification of causal genes or modifier genes involved in the disease pathogenesis. The Labrador retriever was recently characterized as a new canine model for copper toxicosis. Purebred dogs have reduced genetic variability, which facilitates identification of genes involved in complex heritable traits that might influence phenotype in both humans and dogs. We performed a genome-wide association study in 235 Labrador retrievers and identified two chromosome regions containing ATP7A and ATP7B that were associated with variation in hepatic copper levels. DNA sequence analysis identified missense mutations in each gene. The amino acid substitution ATP7B:p.Arg1453Gln was associated with copper accumulation, whereas the amino acid substitution ATP7A:p.Thr327Ile partly protected against copper accumulation. Confocal microscopy indicated that aberrant copper metabolism upon expression of the ATP7B variant occurred because of mis-localization of the protein in the endoplasmic reticulum. Dermal fibroblasts derived from ATP7A:p.Thr327Ile dogs showed copper accumulation and delayed excretion. We identified the Labrador retriever as the first natural, non-rodent model for ATP7B-associated copper toxicosis. Attenuation of copper accumulation by the ATP7A mutation sheds an interesting light on the interplay of copper transporters in body copper homeostasis and warrants a thorough investigation of ATP7A as a modifier gene in copper-metabolism disorders. The identification of two new functional variants in ATP7A and

  1. [Jacqueline Wilson. Tracy Beakeri sari] / Krista Kivisalu

    Index Scriptorium Estoniae

    Kivisalu, Krista, 1968-

    2016-01-01

    Tutvustus: Wilson, Jacqueline. Tracy Beakeri lugu. [Tallinn] : Pegasus, 2015 ; Wilson, Jacqueline. Pühadeüllatus. [Tallinn] : Pegasus, c2015 ; Wilson, Jacqueline. Julgusmäng. [Tallinn] : Pegasus, c2015

  2. Wilson Disease: Frequently Asked Questions

    Science.gov (United States)

    ... copper supplements. If you are trying to gain weight and have been on appropriate therapy, drinking one can of Vanilla Boost Plus per day should not give you too much copper. You also can make your own high calorie drinks by mixing protein supplements with a milk shake. - Fred Askari, M.D., ...

  3. Sextet Model with Wilson Fermions

    DEFF Research Database (Denmark)

    Hansen, Martin; Pica, Claudio

    2017-01-01

    We present new results from our ongoing study of the SU(3) sextet model with two flavors in the two-index symmetric representation of the gauge group. In the simulations use unimproved Wilson fermions to investigate the infrared properties of the model. We have previously presented results for th...

  4. Mycobacterial disease in patients with rheumatic disease.

    NARCIS (Netherlands)

    Ingen, J. van; Boeree, M.J.; Dekhuijzen, P.N.R.; Soolingen, D van

    2008-01-01

    This Review focuses on the emergence of mycobacterial disease in patients undergoing treatment for rheumatic disease with four new drug classes--tumor necrosis factor (TNF) inhibitors, human interleukin (IL)-1 receptor antagonists, anti-CD20 antibodies and CD4(+) T-cell costimulation

  5. Mowat-Wilson-syndrom hos tre danske børn

    DEFF Research Database (Denmark)

    Nissen, Karin Bækgaard; Søndergaard, Charlotte; Thelle, Thomas

    2011-01-01

    Mowat-Wilson syndrome (MWS) is an autosomal dominant intellectual disability syndrome characterised by unique facial features and congenital anomalies such as Hirschsprung disease, congenital heart defects, corpus callosum agenesis and urinary tract anomalies. Some cases also present epilepsy...

  6. Application of the SCORE and Wilson-Grundy methods for the assessment of cardiovascular risk in community pharmacies.

    Science.gov (United States)

    Amariles, P; Machuca, M; Faus, M J; Baena, M I; Martinez-Martinez, F; Jimenez-Martin, J

    2008-10-01

    The assessment and follow-up of patients with risk factors, or with cardiovascular disease (CVD), involves estimating and monitoring their CVD risk (CVDR). There are different opinions about the most appropriate method for this. To compare the SCORE system and the Wilson-Grundy system (based on Framingham's study). A descriptive, observational study over 15 days in six pharmacies, with patients aged between 25 and 74 years, and with a prescription for medications related to hypertension, dyslipidaemia, CVD prevention or type-2 diabetes. Results of patients' absolute CVDR were assessed and compared using the SCORE system and the Wilson-Grundy method, adapted for Spain. The Chi-square test was used to compare proportions, and the Student t-test was used to compare mean values, including odds ratios (OR) and 95% confidence intervals (95%CI). A total of 257 patients [165 women, 92 men; mean (SD) age, 60.9 (10.8) years; percentage of previous medical history of hypertension (70.0%), dyslipidaemia (42.4%), type-2 diabetes (19.5%) and CVD (22.6%)] participated. With the CVDR assessed with SCORE, the distribution was as follows: low 35.8%, intermediate 21.0% and high 43.2%. The corresponding values using the Wilson-Grundy system was low 60.7%, intermediate 8.2% and high 31.1%. The cardiovascular risk of patients that attend community pharmacies with prescriptions for cardiovascular medications is significantly higher when assessed using the SCORE system than with the Wilson-Grundy method.

  7. The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers : a new canine model for copper-metabolism disorders

    NARCIS (Netherlands)

    Fieten, Hille; Gill, Yadvinder; Martin, Alan J.; Concilli, Mafalda; Dirksen, Karen; van Steenbeek, Frank G.; Spee, Bart; van den Ingh, Ted S. G. A. M.; Martens, Ellen C. C. P.; Festa, Paola; Chesi, Giancarlo; Sluis, van de Bart; Houwen, Roderick H. J. H.; Watson, Adrian L.; Aulchenko, Yurii S.; Hodgkinson, Victoria L.; Zhu, Sha; Petris, Michael J.; Polishchuk, Roman S.; Leegwater, Peter A. J.; Rothuizen, Jan

    2016-01-01

    The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to

  8. The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders

    NARCIS (Netherlands)

    Fieten, Hille; Gill, Yadvinder; Martin, Alan J.; Concilli, Mafalda; Dirksen, Karen; van Steenbeek, Frank G.; Spee, Bart; van den Ingh, Ted S. G. A. M.; Martens, Ellen C. C. P.; Festa, Paola; Chesi, Giancarlo; van de Sluis, Bart; Houwen, Roderick H. J. H.|info:eu-repo/dai/nl/087887991; Watson, Adrian L.; Aulchenko, Yurii S.; Hodgkinson, Victoria L.; Zhu, Sha; Petris, Michael J.; Polishchuk, Roman S.; Leegwater, Peter A. J.; Rothuizen, Jan

    2016-01-01

    The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to

  9. Wilson lines in quantum field theory

    CERN Document Server

    Cherednikov, Igor O; Veken, Frederik F van der

    2014-01-01

    The objective of this book is to get the reader acquainted with theoretical and mathematical foundations of the concept of Wilson loops in the context of modern quantum field theory. It teaches how to perform independently with some elementary calculations on Wilson lines, and shows the recent development of the subject in different important areas of research.

  10. Adequate protection of the public against food-transmitted diseases of microbial aetiology. Achievements and challenges, half a century after the introduction of the Prescott-Meyer-Wilson strategy of active intervention.

    Science.gov (United States)

    Mossel, D A

    1989-12-01

    No dramatic change in the approach to supplying microbiologically safe foods and meals to the consumer occurred immediately upon the introduction, in the 1930's, by S.C. Prescott and K.F. Meyer in the U.S. and Sir Graham Wilson in the U.K. of the principle of taking preventive remedial measures rather than merely examining final product samples. Thus morbidity and the economic impact of food-borne disease of microbial aetiology continued to rise and new food-transmitted pathogens continued to be identified. The 1930 strategy was not implemented until 1970 when food processing specialists in the U.S. launched a similar approach under the new acronym 'HACCP' (hazard analysis: critical control points). This relies on (i) identification, by meticulous ecological studies, of hazardous practices and locations, termed 'critical points' by the new generation; (ii) elimination of such hazards by developing processing techniques designed to control contamination and colonization of foods--also given an innovative term, viz. GMP; (iii) validation of the elaborated procedures by a new stem to the Science of Public Health: risk assessment, perhaps better termed Safety Science; (iv) upon introduction of the validated GMP's monitoring limited numbers of samples--which have become fully representative because of process management--for ecologically valid marker organisms, indicating incidental going-out-of-control of manufacture or distribution. This implementation of the Prescott-Meyer-Wilson maxim has been given the name longitudinally integrated safety assurance, charmingly acronymized to LISA. Introduction of LISA eliminates all previously existing or perceived difficulties about microbiological target values ('standards') for foods. These can henceforth be empirically assessed from surveys on samples obtained from factories or catering establishments previously inspected for adherence to LISA, deficiencies having, where necessary, been rectified prior to the examination of

  11. Estimation of Wilson's disease incidence and carrier frequency in the Korean population by screening ATP7B major mutations in newborn filter papers using the SYBR green intercalator method based on the amplification refractory mutation system.

    Science.gov (United States)

    Kim, Gu-Hwan; Yang, Jeong Yoon; Park, Jung-Young; Lee, Jin Joo; Kim, Ju Hyun; Yoo, Han-Wook

    2008-09-01

    Wilson's disease (WD), an autosomal recessive disorder of copper transport, is one of the most common inherited metabolic disorders in Korea. Despite its frequency, the incidence and carrier frequency of WD has not yet been estimated in the Korean population. We therefore screened for four major missense mutations (p.Arg778Leu, p.Ala874Val, p.Leu1083Phe, and p.Asn1270Ser) of the ATP7B gene in 476 newborn filter papers by real-time multiplex PCR and melting curve analysis using the SYBR Green intercalator method based on the amplification refractory mutation system test. Newborn filter papers with abnormal melting curves were subjected to subsequent sequence analysis. Three mutated alleles, one p.Arg778Leu and two p.Ala874Val, were detected among the 476 newborn filter papers (952 alleles). The carrier frequency and incidence of WD in the Korean population were determined as 1 in 88.2 and 30,778, respectively, by reversely calculating based on the Hardy-Weinberg law.

  12. Kenneth Wilson and lattice QCD

    CERN Document Server

    Ukawa, Akira

    2015-01-01

    We discuss the physics and computation of lattice QCD, a space-time lattice formulation of quantum chromodynamics, and Kenneth Wilson's seminal role in its development. We start with the fundamental issue of confinement of quarks in the theory of the strong interactions, and discuss how lattice QCD provides a framework for understanding this phenomenon. A conceptual issue with lattice QCD is a conflict of space-time lattice with chiral symmetry of quarks. We discuss how this problem is resolved. Since lattice QCD is a non-linear quantum dynamical system with infinite degrees of freedom, quantities which are analytically calculable are limited. On the other hand, it provides an ideal case of massively parallel numerical computations. We review the long and distinguished history of parallel-architecture supercomputers designed and built for lattice QCD. We discuss algorithmic developments, in particular the difficulties posed by the fermionic nature of quarks, and their resolution. The triad of efforts toward b...

  13. Symptom Status Predicts Patient Outcomes in Persons with HIV and Comorbid Liver Disease

    Directory of Open Access Journals (Sweden)

    Wendy A. Henderson

    2012-01-01

    Full Text Available Persons living with human immunodeficiency virus (HIV are living longer; therefore, they are more likely to suffer significant morbidity due to potentially treatable liver diseases. Clinical evidence suggests that the growing number of individuals living with HIV and liver disease may have a poorer health-related quality of life (HRQOL than persons living with HIV who do not have comorbid liver disease. Thus, this study examined the multiple components of HRQOL by testing Wilson and Cleary’s model in a sample of 532 individuals (305 persons with HIV and 227 persons living with HIV and liver disease using structural equation modeling. The model components include biological/physiological factors (HIV viral load, CD4 counts, symptom status (Beck Depression Inventory II and the Medical Outcomes Study HIV Health Survey (MOS-HIV mental function, functional status (missed appointments and MOS-HIV physical function, general health perceptions (perceived burden visual analogue scale and MOS-HIV health transition, and overall quality of life (QOL (Satisfaction with Life Scale and MOS-HIV overall QOL. The Wilson and Cleary model was found to be useful in linking clinical indicators to patient-related outcomes. The findings provide the foundation for development and future testing of targeted biobehavioral nursing interventions to improve HRQOL in persons living with HIV and liver disease.

  14. Genetics Home Reference: Mowat-Wilson syndrome

    Science.gov (United States)

    ... expression, and they typically have friendly and happy personalities. Mowat-Wilson syndrome is often associated with an unusually small head ( microcephaly ), structural brain abnormalities, and intellectual disability ranging from moderate to severe. Speech is absent ...

  15. Eigenvalue distributions of Wilson loops

    Energy Technology Data Exchange (ETDEWEB)

    Lohmayer, Robert

    2010-07-01

    In the first part of this thesis, we focus on the distribution of the eigenvalues of the unitary Wilson loop matrix in the two-dimensional case at arbitrary finite N. To characterize the distribution of the eigenvalues, we introduce three density functions (the ''symmetric'', the ''antisymmetric'', and the ''true'' eigenvalue density) which differ at finite N but possess the same infinite-N limit, exhibiting the Durhuus-Olesen phase transition. Using expansions of determinants and inverse determinants in characters of totally symmetric or totally antisymmetric representations of SU(N), the densities at finite N can be expressed in terms of simple sums involving only dimensions and quadratic Casimir invariants of certain irreducible representations of SU(N), allowing for a numerical computation of the densities at arbitrary N to any desired accuracy. We find that the true eigenvalue density, adding N oscillations to the monotonic symmetric density, is in some sense intermediate between the symmetric and the antisymmetric density, which in turn is given by a sum of N delta peaks located at the zeros of the average of the characteristic polynomial. Furthermore, we show that the dependence on N can be made explicit by deriving integral representations for the resolvents associated to the three eigenvalue densities. Using saddle-point approximations, we confirm that all three densities reduce to the Durhuus-Olesen result in the infinite-N limit. In the second part, we study an exponential form of the multiplicative random complex matrix model introduced by Gudowska-Nowak et al. Varying a parameter which can be identified with the area of the Wilson loop in the unitary case, the region of non-vanishing eigenvalue density of the N-dimensional complex product matrix undergoes a topological change at a transition point in the infinite-N limit. We study the transition by a detailed analysis of the average of the

  16. Disease: H00908 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00908 Mowat-Wilson syndrome Mowat-Wilson syndrome (MWS) is a multiple congenital a...[KO:K09299] ICD-10: Q43.1 OMIM: 235730 PMID:17958891 Garavelli L, Mainardi PC Mowat-Wilson syndrome. Orphane...thews RP Intrahepatic biliary anomalies in a patient with Mowat-Wilson syndrome uncover a role for the zinc

  17. The CUREA Program at Mount Wilson

    Science.gov (United States)

    Turner, Paula C.; LoPresto, J. C.; Simmons, M.

    2006-12-01

    For fifteen years, Mount Wilson Observatory has been host to a unique educational program designed to introduce undergraduate students of physics and astronomy to elements of observational solar and stellar astrophysics. Founded by faculty members from four-year colleges who dubbed themselves the Consortium for Undergraduate Research and Education in Astronomy (CUREA), the CUREA program is an intensive two-week course in observational astronomy. It includes lectures by astronomers and physicists, observational exercises in both solar and stellar astrophysics, tours of various research facilities on the mountain and in the Los Angeles area, and an observational mini-project designed and executed by each student during the second week of the program. This paper will present the program’s curriculum and goals, a brief history, and examples of observational projects undertaken by recent participants. CUREA is administered by the Mount Wilson Observatory Association, using facilities provided by the Mount Wilson Institute.

  18. Thyroid Disease in the Older Patient

    Science.gov (United States)

    ... Older Patients and Thyroid Disease Older Patients and Thyroid Disease DEFINITION: WHAT DO THE FOLLOWING PATIENTS OVER ... and, as always, require lifelong follow-up. Adult Thyroid Information Anaplastic Thyroid Cancer Complementary and Alternative Medicine ...

  19. The Wilson Governments Policy Towards ELDO

    Science.gov (United States)

    Baker, R.

    This paper discusses the formation and motivation behind the Wilson government's policy towards ELDO. In particular the December 1965 report for the Minister of Aviation, Roy Jenkins, and the assumptions that it makes about the validity of launchers in general and British involvement in ELDO are examined. This examination sustains the argument that the Wilson government wanted to pull out of ELDO from the beginning, and that the only reason that it did not was because of political damage and financial liability. The examination also helps to illustrate why the UK government actively worked towards the demise of ELDO.

  20. College-age twins: university admission policies / twin research: birth weight and neuromotor performance; transfusion syndrome markers; vanishing twins and fetal sex determination; mz twin discordance for wilson's disease / media: big at birth; planned separation of conjoined twins; x factor twins; Cinema: the identical.

    Science.gov (United States)

    Segal, Nancy L

    2014-12-01

    There is a lack of research findings addressing the unique college admissions issues faced by twins and other multiples. The advantages and disadvantage twins face, as reported by college administrators, twins and families are reviewed. Next, recent research addressing twins' birth weight and neuromotor performance, transfusion syndrome markers, the vanishing twin syndrome and monozygotic (MZ) twin discordance for Wilson's disease is described. News items concerning the birth of unusually large twins, the planned separation of conjoined twins, twin participants in the X Factor games and a film, The Identical, are also summarized.

  1. Spectrum of the Wilson Dirac operator at finite lattice spacings

    DEFF Research Database (Denmark)

    Akemann, G.; Damgaard, Poul Henrik; Splittorff, Kim

    2011-01-01

    We consider the effect of discretization errors on the microscopic spectrum of the Wilson Dirac operator using both chiral Perturbation Theory and chiral Random Matrix Theory. A graded chiral Lagrangian is used to evaluate the microscopic spectral density of the Hermitian Wilson Dirac operator...... as well as the distribution of the chirality over the real eigenvalues of the Wilson Dirac operator. It is shown that a chiral Random Matrix Theory for the Wilson Dirac operator reproduces the leading zero-momentum terms of Wilson chiral Perturbation Theory. All results are obtained for fixed index...... of the Wilson Dirac operator. The low-energy constants of Wilson chiral Perturbation theory are shown to be constrained by the Hermiticity properties of the Wilson Dirac operator....

  2. Wilson Fermions with Four Fermion Interactions

    DEFF Research Database (Denmark)

    Rantaharju, Jarno; Drach, Vincent; Hietanen, Ari

    2015-01-01

    We present a lattice study of a four fermion theory, known as Nambu Jona-Lasinio (NJL) theory, via Wilson fermions. Four fermion interactions naturally occur in several extensions of the Standard Model as a low energy parameterisation of a more fundamental theory. In models of dynamical electrowe...

  3. Kenneth G Wilson (1936–2013)

    Indian Academy of Sciences (India)

    winner of the 1982 Nobel Prize in Physics. The piece brings out the bare facts of Wilson's life in his own words – very few of them, in fact. No one reading it would realize that he was one of the most celebrated among twentieth-century theoretical physicists for changing the perceptions of strongly interacting systems – either ...

  4. Cora Wilson Stewart: Crusader against Illiteracy.

    Science.gov (United States)

    Nelms, Willie

    This book is a biography of Cora Wilson Stewart, a Rowan County, Kentucky, school superintendent who rose to prominence with the establishment of the Moonlight Schools for adults with low literacy levels in 1911. It presents the details of her Kentucky crusade against illiteracy, then examines the personal part of her life as well as her later…

  5. Chronic diseases among older cancer patients.

    OpenAIRE

    Deckx, L.D.; Akker, M.A. van der; Metsemakers, J.M.; Knottnerus, A.K.; Schellevis, F.G.; Buntinx, F.B.

    2011-01-01

    Introduction: With the growing number of older cancer patients, the burden of chronic diseases among older cancer patients will become increasingly important. Chronic diseases often interfere with treatment decisions and prognosis for cancer patients. However, little is known about the occurrence of chronic diseases among older cancer patients. Aim: We aim to examine the frequency of pre-existing and subsequent chronic diseases among cancer patients above age 60 in comparison with non-cancer ...

  6. Cerebrovascular disease in pediatric patients

    Directory of Open Access Journals (Sweden)

    Rotta Newra Tellechea

    2002-01-01

    Full Text Available Although rare in childhood, stroke may have a serious impact when it happens in this stage of life. Also, it may be the first sign of a systemic disease. We report 12 cases of patients with stroke treated in the Neuropediatrics Unit of Hospital de Clínicas de Porto Alegre (HCPA from March 1997 to March 2000. All patients, from term infants to 12-year-old children hospitalized in the Pediatrics Unit of HCPA, had clinical suspicion of stroke, which was later confirmed by radiological studies. Patient follow up ranged from 1 to 6 years (mean = 3.4 years. Presenting symptoms were hemiparesis in 9 patients, seizures in 7, deviation of labial commissure in 3, and loss of consciousness in 1. The increase in the number of cases of childhood stroke identified and later confirmed by noninvasive methods had helped in the determination of different ethiologies of stroke: the most frequent being hematologic, cardiac and genetic diseases. However, our study included 6 newborns with stroke whose ethiology was not identified. Seven children with seizures received phenobarbital. Six term infants had neonatal seizures secondary to stroke and restricted to the first 72 hours of life.

  7. Chronic Disease Management - The Patient's Perspective.

    Science.gov (United States)

    Browne, K; Divilly, D; McGarry, M; Sweeney, C; Kelly, M E

    2017-02-10

    A paucity of data exists on Irish patients' perspective of chronic disease management. This study explores patients' views on what is the most appropriate setting for their chronic disease management, the advantages and disadvantages of these settings, and where they get information on their condition. Semi-structured qualitative interviews were carried out with 24 patients. Three main themes emerged: Current Care Model, Health Literacy and Treatment Burden. Patients believe that the GP-patient relationship plays a pivotal role in the provision of chronic disease management. Health literacy and psychosocial burden were found to impact significantly on the lives of patients with chronic disease(s).

  8. Symmetries of Ginsparg-Wilson Chiral Fermions

    OpenAIRE

    Mandula, Jeffrey E.

    2009-01-01

    The group structure of the variant chiral symmetry discovered by Luscher in the Ginsparg-Wilson description of lattice chiral fermions is analyzed. It is shown that the group contains an infinite number of linearly independent symmetry generators, and the Lie algebra is given explicitly. CP is an automorphism of this extended chiral group, and the CP transformation properties of the symmetry generators are found. The group has an infinite-parameter invariant subgroup, and the factor group, wh...

  9. CLASSICS Kenneth G. Wilson – Biographical

    Indian Academy of Sciences (India)

    science from the United States whom we have covered in Resonance came from small town, non-academic backgrounds. Kenneth Wilson is a notable exception. His father ... I went often to M.I.T. to use their com puter and eat lunch with the M.I.T. theory group, led by Francis Low. In 1962 I went to CERN for a calendar year, ...

  10. Wilson lines in the MHV action

    Science.gov (United States)

    Kotko, P.; Stasto, A. M.

    2017-09-01

    The MHV action is the Yang-Mills action quantized on the light-front, where the two explicit physical gluonic degrees of freedom have been canonically transformed to a new set of fields. This transformation leads to the action with vertices being off-shell continuations of the MHV amplitudes. We show that the solution to the field transformation expressing one of the new fields in terms of the Yang-Mills field is a certain type of the Wilson line. More precisely, it is a straight infinite gauge link with a slope extending to the light-cone minus and the transverse direction. One of the consequences of that fact is that certain MHV vertices reduced partially on-shell are gauge invariant — a fact discovered before using conventional light-front perturbation theory. We also analyze the diagrammatic content of the field transformations leading to the MHV action. We found that the diagrams for the solution to the transformation (given by the Wilson line) and its inverse differ only by light-front energy denominators. Further, we investigate the coordinate space version of the inverse solution to the one given by the Wilson line. We find an explicit expression given by a power series in fields. We also give a geometric interpretation to it by means of a specially defined vector field. Finally, we discuss the fact that the Wilson line solution to the transformation is directly related to the all-like helicity gluon wave function, while the inverse functional is a generating functional for solutions of self-dual Yang-Mills equations.

  11. The Legacy of G. Wilson Knight

    Directory of Open Access Journals (Sweden)

    Raw Laurence

    2017-06-01

    Full Text Available G. Wilson Knight (1897-1985 was one of the most influential Shakespearean critics of the mid-twentieth century. This piece surveys his work from 1930 until the early 1980s. Much affected by the First World War, he developed a style of criticism based on Christian principles of respect for other people and belief in an all-powerful God. Many of his most famous pieces (in THE WHEEL OF FIRE, for instance argue for human insignificance in an indifferent universe. It is up to all of us as individuals to develop methods of coping with this world. Wilson Knight’s ideas gained particular currency during the Second World War, when Britain’s very future seemed at risk due to the threat of Nazi invasion. Although much derided for his use of transcendent language—especially by his contemporary F. R. Leavis—Wilson Knight’s ideas seem to have acquired new significance in a globalized world, where individuals fight to main their identity in a technology-driven environment.

  12. Ted Wilson passes on the torch

    CERN Multimedia

    2003-01-01

    As part of the Laboratory's outreach programme, the CERN Accelerator School (CAS) brings together students and experienced physicists from all over the world with the aim of promoting the understanding of accelerator physics. As head of the School for 11 years, Ted Wilson became a CERN ambassador to the outside community. He retired in March, handing over the reigns of the CAS to Daniel Brandt. Ted Wilson and his assistant, Suzanne von Wartburg, during an EPAC meeting in 1994.The accelerator schools allowed some time for relaxation in the local surrounding for students as well as for the director of CAS.As a boy, Ted Wilson could have embarked on a career in pop music rather than physics, rubbing shoulders at secondary school in Liverpool with two of the future Beatles. But prefering classical music and answering the call of science, he took the more serious of the two paths, studying physics first at Oxford University then at the Rutherford Laboratory. After a year at CERN and four years at the Rutherford La...

  13. Hyperuricaemia in congenital heart disease patients.

    Science.gov (United States)

    Martínez-Quintana, Efrén; Rodríguez-González, Fayna

    2015-01-01

    Hyperuricaemia is associated with traditional cardiovascular risk factors such as type 2 diabetes or dyslipidaemia and a higher mortality. Out of 528 congenital heart disease patients, 329 patients, including 190 male and 139 female patients, in whom uric acid determination was performed, were studied and followed up to determine survival. Male congenital heart disease patients with high serum uric acid concentrations (>7 mg/dl) showed significantly (p congenital heart disease patients with lower serum uric acid levels (≤7 mg/dl). Meanwhile, female congenital heart disease patients with higher serum uric acid concentrations (>5.7 mg/dl) were significantly (p congenital heart disease patients with lower serum uric acid concentrations (≤5.7 mg/dl). During a median follow-up of 90 months, 16 out of 528 congenital heart disease patients died - 14 patients of cardiac origin and two patients of non-cardiac origin - of whom 10 were hypoxaemic. Kaplan-Meier analysis showed no significant differences in mortality between male and female congenital heart disease patients with high and low serum uric acid level concentrations. Hypoxaemia, body mass index, and C-reactive protein concentrations are higher in hyperuricaemic congenital heart disease patients, although no significant differences were seen in mortality between congenital heart disease patients with high and low serum uric acid concentrations.

  14. A STUDY OF PREDICTION OF DIFFICULT INTUBATION USING MALLAMPATI AND WILSON SCORE CORRELATING WITH CORMACK LEHANE GRADING

    Directory of Open Access Journals (Sweden)

    Vaishali Chandrashekhar

    2015-06-01

    Full Text Available BACKGROUND : This study was carried out to evaluate usefulness of preoperative Mallampati & Wilson’s score grading as a predictor for difficult laryngoscopy & intubation . AIMS : To determine the accuracy of the modified Mallampati test and Wilson score for predicting difficult tracheal intubation and correlation with Cormack Lehane grading . METHODS : This prospective randomized cross sectional Study carried out in 200 patients , posted for surgical procedure under GA with ETT intubation. Preoperative airway assessment using Mallampati grading (MPG & Wilson score done. Conventional anesthesia t echnique followed. Cormack Lehane grading done at laryngoscopy & correlated with previous scores for each patient. RESULTS : A MPG of I/II was found in 140 patients (70% , while 60 patients (30% were class III/IV. 138 patients (69% had a Wilson score of 0 /1 , while 60(30% had a score of 2/3 and 2 patients (1% scored ≥4. One hundred & eighty patients (90% were classified as Cormack - Lehane grade I/II , while 20 patients (10% were considered grade III/IV. Of the 60 patients with a Wilson score of 2/3 , 6 cas es (10% two attempts were required and in 2 cases (3.3% in spite of more than two attempts intubation proved impossible with the conventional laryngoscope , articulated McCoy blade was used. Two patients with a Wilson score ≥4 were intubated with gum elas tic bougie , using articulated McCoy blade. Overall , out of 200 , in 6 patients (3% two attempts of intubation was required and 4 patients (2% intubation required the use of some kind of gadget other than conventional laryngoscope and more than 2 attempts. The correlation between the Cormack - Lehane classification and the number of endotracheal intubation attempts showed that of the 180 patients with I / II grade , 4 patients (1.3% two attempts were required. Of the 20 patients classified as Cormack - Lehane III/IV , 4 cases (20% intubation proved impossible with conventional technique. This

  15. Associations between disease severity, coping and dimensions of health-related quality of life in patients admitted for elective coronary angiography – a cross sectional study

    Directory of Open Access Journals (Sweden)

    Hanestad Berit R

    2008-05-01

    Full Text Available Abstract Background In patients with suspected coronary artery disease (CAD, the overall aim was to analyse the relationships between disease severity and both mental and physical dimensions of health related quality of life (HRQOL using a modified version of the Wilson and Cleary model. Methods Using a cross-sectional design, 753 patients (74% men, mean age 62 years, referred for elective cardiac catheterisation were included. The measures included 1 physiological factors 2 symptoms (disease severity, self-reported symptoms, anxiety and depression 3 self-reported functional status, 4 coping, 5 perceived disease burden, 6 general health perception and 7 overall quality of life. To analyse relationships, we performed linear and ordinal logistic regressions. Results CAD and left ventricular ejection fraction (LVEF were significantly associated with symptoms of angina pectoris and dyspnea. CAD was not related to symptoms of anxiety and depression, but less depression was found in patients with low LVEF. Angina pectoris and dyspnea were both associated with impaired physical function, and dyspnea was also negatively related to social function. Overall, less perceived burden and better overall QOL were observed in patients using more confronting coping strategy. Conclusion The present study demonstrated that data from cardiac patients to a large extent support the suggested model by Wilson and Cleary.

  16. Chronic diseases among older cancer patients.

    NARCIS (Netherlands)

    Deckx, L.D.; Akker, M.A. van der; Metsemakers, J.M.; Knottnerus, A.K.; Schellevis, F.G.; Buntinx, F.B.

    2011-01-01

    Introduction: With the growing number of older cancer patients, the burden of chronic diseases among older cancer patients will become increasingly important. Chronic diseases often interfere with treatment decisions and prognosis for cancer patients. However, little is known about the occurrence of

  17. ORAL HEALTH IN PATIENTS WITH LIVER DISEASES

    Directory of Open Access Journals (Sweden)

    Vladimir E. Panov

    2011-12-01

    Full Text Available In most of the patients with chronic hepatitis B and C, the disease progression to liver cirrhosis and a liver transplantation is necessary. Untreated oral diseases (including dental problems can lead to infections and sepsis and may cause many complications in transplanted patients and a prerequisite dental evaluation is usually recommended for potential organ transplant candidates.Our aim was to determine the dental status in patients with chronic liver disease, knowing that liver transplant will be a life choices.

  18. [Inpatients days in patients with respiratory diseases and periodontal disease].

    Science.gov (United States)

    Fernández-Plata, Rosario; Olmedo-Torres, Daniel; Martínez-Briseño, David; González-Cruz, Herminia; Casa-Medina, Guillermo; García-Sancho, Cecilia

    2017-01-01

    Periodontal disease is a chronic inflammatory gingival process that has been associated with the severity of respiratory diseases. In Mexico a prevalence of 78% was found in population with social security and > 60 years old. The aim of this study is to establish the association between periodontal disease and respiratory diseases according to the inpatient days. A cross-sectional study was conducted from January to December 2011. We included hospitalized patients, ≥ 18 years of age, without sedation or intubated. A dentist classified patients into two groups according to the severity of the periodontal disease: mild-to-moderate and severe. We estimated medians of inpatient days by disease and severity. Negative binomial models were adjusted to estimate incidence rate ratios and predicted inpatient days. 3,059 patients were enrolled. The median of observed and predicted inpatient days was higher in the group of severe periodontal disease (p disease, tuberculosis, and influenza had the highest incidence rates ratios of periodontal disease (p periodontal disease is positively -associated with inpatient days of patients with respiratory diseases.

  19. Radiotherapy in patients with connective tissue diseases.

    Science.gov (United States)

    Giaj-Levra, Niccolò; Sciascia, Savino; Fiorentino, Alba; Fersino, Sergio; Mazzola, Rosario; Ricchetti, Francesco; Roccatello, Dario; Alongi, Filippo

    2016-03-01

    The decision to offer radiotherapy in patients with connective tissue diseases continues to be challenging. Radiotherapy might trigger the onset of connective tissue diseases by increasing the expression of self-antigens, diminishing regulatory T-cell activity, and activating effectors of innate immunity (dendritic cells) through Toll-like receptor-dependent mechanisms, all of which could potentially lead to breaks of immune tolerance. This potential risk has raised some debate among radiation oncologists about whether patients with connective tissue diseases can tolerate radiation as well as people without connective tissue diseases. Because the number of patients with cancer and connective tissue diseases needing radiotherapy will probably increase due to improvements in medical treatment and longer life expectancy, the issue of interactions between radiotherapy and connective tissue diseases needs to be clearer. In this Review, we discuss available data and evidence for patients with connective tissue diseases treated with radiotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Therapeutic plasma exchange in patients with neurological diseases: multicenter retrospective analysis.

    Science.gov (United States)

    Kaya, Emin; Keklik, Muzaffer; Sencan, Mehmet; Yilmaz, Mehmet; Keskin, Ali; Kiki, Ilhami; Erkurt, Mehmet Ali; Sivgin, Serdar; Korkmaz, Serdal; Okan, Vahap; Doğu, Mehmet Hilmi; Unal, Ali; Cetin, Mustafa; Altuntaş, Fevzi; Ilhan, Osman

    2013-06-01

    Therapeutic plasma exchange (TPE), is a procedure, changing pathologic substances in the plasma of patients with replacement fluid. TPE has an increasing list of indications in recent years such as neurological, connective tissue, hematological, nephrological, endocrinological and metabolic disorders. We report our multicenter data about therapeutic plasma exchange in patients with neurological diseases. Six University Hospitals' aphaeresis units medical records about neurologic diseases were reviewed retrospectively. Hundred and fifteen patients and 771 TPE sessions from six aphaeresis units' were included to this study. Of the 115 patients, 53 (46%) were men and 62 (54%) were women. The median age was 50 (range: 5-85) years. Of these patients 58.3% were Guillain-Barre syndrome (GBS), 17.4% were acute disseminated encephalomyelitis (ADEM), 10.4% were chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), 7% were multiple sclerosis, 6.1% were myasthenia gravis (MG) and 0.9% were Wilson disease (WD). The median number of TPE sessions per patient was 5 (range 1-72). Human albumin was used as a replacement fluid in 66% and fresh frozen plasma was used in 34% of cases. TPE was done through central venous catheters in 66%, and peripheral venous access in 34% of patients. Some complications were seen in patients (18.3%) during TPE sessions. These complications were, complications related to catheter placement procedure (8.7%), hypotension (3.5%), hypocalcaemia (3.5%) and allergic reactions (1.7%). The complication ratios were 2.7% in total 771 TPE procedures. TPE procedure was terminated in 6% of sessions depending on these complications. Overall responses to TPE were noted in 89.5% of patients. In conclusion; Therapeutic plasma exchange is an effective treatment option in several neurologic diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Contraception in Patients with Rheumatic Disease.

    Science.gov (United States)

    Sammaritano, Lisa R

    2017-05-01

    Contraception represents an important area of reproductive health for patients with rheumatic diseases given the potential pregnancy risks associated with active disease, teratogenic medications, and severe disease-related damage. A high proportion of patients with rheumatic disease do not use effective contraception. Long-acting contraceptives are most effective. Antiphospholipid-negative patients with stable systemic lupus erythematosus may use oral combined contraceptives. Antiphospholipid-positive patients, or patients with rheumatic disease with other risk factors for thrombosis, should avoid estrogen-containing contraceptives. Contraceptive methods should be addressed by both the rheumatologist and gynecologist to determine the safest, most effective, and most convenient form for each patient. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Suicide in patients with motor neuron disease

    DEFF Research Database (Denmark)

    Bak, Søren; Stenager, E N; Stenager, Egon

    1994-01-01

    The aim of the present study was to assess, through an epidemiological study, whether suicide risk is increased in patients with motor neuron disease (MND). The study involved 116 patients with MND. In the study period 92 patients died, 47 males and 45 females. No patients committed suicide...

  3. Symmetries of Ginsparg-Wilson chiral fermions

    Science.gov (United States)

    Mandula, Jeffrey E.

    2009-10-01

    The group structure of the variant chiral symmetry discovered by Lüscher in the Ginsparg-Wilson description of lattice chiral fermions is analyzed. It is shown that the group contains an infinite number of linearly independent symmetry generators, and the Lie algebra is given explicitly. CP is an automorphism of this extended chiral group, and the CP transformation properties of the symmetry generators are found. The group has an infinite-parameter invariant subgroup, and the factor group, whose elements are its cosets, is isomorphic to the continuum chiral symmetry group. Features of the currents associated with these symmetries are discussed, including the fact that some different, noncommuting symmetry generators lead to the same Noether current. These are universal features of lattice chiral fermions based on the Ginsparg-Wilson relation; they occur in the overlap, domain-wall, and perfect-action formulations. In a solvable example, free overlap fermions, these noncanonical elements of lattice chiral symmetry are related to complex energy singularities that violate reflection positivity and impede continuation to Minkowski space.

  4. Hexagon Wilson Loop OPE and Harmonic Polylogarithms

    CERN Document Server

    Papathanasiou, Georgios

    2013-01-01

    A recent, integrability-based conjecture in the framework of the Wilson loop OPE for N=4 SYM theory, predicts the leading OPE contribution for the hexagon MHV remainder function and NMHV ratio function to all loops, in integral form. We prove that these integrals evaluate to a particular basis of harmonic polylogarithms, at any order in the weak coupling expansion. The proof constitutes an algorithm for the direct computation of the integrals, which we employ in order to obtain the full (N)MHV OPE contribution in question up to 6 loops, and certain parts of it up to 12 loops. We attach computer-readable files with our results, as well as an algorithm implementation which may be readily used to generate higher-loop corrections. The feasibility of obtaining the explicit kinematical dependence of the first term in the OPE in principle at arbitrary loop order, offers promise for the suitability of this approach as a non-perturbative description of Wilson loops/scattering amplitudes.

  5. Progressive hip joint subluxation in Saul-Wilson syndrome.

    Science.gov (United States)

    Chinen, Yasutsugu; Kaneshi, Takuya; Kamiya, Takeshi; Hata, Kenichiro; Nishimura, Gen; Kaname, Tadashi

    2015-11-01

    Saul-Wilson syndrome (SWS) is a rare congenital skeletal syndrome characterized by postnatal onset of short stature, relative microcephaly, frontal bossing, prominent eyes with shallow orbits, midface hypoplasia, cataract, and generalized skeletal changes, including spondylar dysplasia, overtubulation of the long bones with metaphyseal flaring and megaepiphyses, coxa valga, elbow deformity, and brachydactyly. We describe a boy with the overall clinical and radiological features fitting the characteristics of SWS, although cataract, elbow deformity, and overt brachydactyly were not seen. He presented with painful hip joint due to hip subluxation in late childhood, which exacerbated with age and ultimately, required surgical intervention. Awareness of this orthopedic complication in SWS is essential in the management of patients with SWS. © 2015 Wiley Periodicals, Inc.

  6. Peripheral arterial disease in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Pecci, R; De La Fuente Aguado, J; Sanjurjo Rivo, A B; Sanchez Conde, P; Corbacho Abelaira, M

    2012-10-01

    Cardiovascular disease (CV) is the second leading cause of morbidity and mortality in chronic obstructive pulmonary disease (COPD). Peripheral arterial disease (PAD) is associated with cardiovascular disease, and its risk factors are common to other atherosclerotic diseases. The objective is to determine the prevalence of PAD in a population of patients with COPD using the ankle / brachial index (ABI) and to investigate the relationship between PAD and lung disease severity. In a prospective cross-sectional study, 246 patients with COPD were recruited. Patients were enrolled consecutively according to their admission to Povisa hospital from September 1, 2008, until March 1, 2010, and were assessed by clinical history, spirometry and ABI. The COPD severity was graded by GOLD criteria in spirometry. Overall, 84 patients (36.8%) had abnormal ABI results and 59 (70.2%) were asymptomatic for PAD. COPD patients with PAD had a higher prevalence of moderate to severe COPD (61.9% vs. 41.7%, P=0.004), lower mean forced expiratory volume in 1 second (FEV1) values (46.7% ± 15 vs. 52.3±14%, P=0.001) and a higher prevalence of hypertension (69% vs. 54.3%, P=0.03) and previous cardiovascular disease (34.5% vs. 21.3%, P=0.03). There was a high prevalence of asymptomatic PAD in the COPD patients we examined. Abnormal ABI results were associated with a higher prevalence of cardiovascular risk factors and more severe lung disease. The diagnosis of peripheral arterial disease in COPD is important because this is an entity that limits the patient's physical activity and impairs their quality of life in addition to turn it into a high cardiovascular risk patient that requiring additional therapeutic measures.

  7. Heart Valve Disease among Patients with Hyperprolactinaemia

    DEFF Research Database (Denmark)

    Steffensen, Charlotte; Maegbaek, Merete Lund; Laurberg, Peter

    2012-01-01

    Increased risk of heart valve disease during treatment with certain dopamine agonists, such as cabergoline, has been observed in patients with Parkinson's disease. The same compound is used to treat hyperprolactinemia, but it is unknown whether this also associates with heart valve disease....

  8. Integrating Patient Concerns into Parkinson's Disease Management.

    Science.gov (United States)

    Lim, Shen-Yang; Tan, Ai Huey; Fox, Susan H; Evans, Andrew H; Low, Soon Chai

    2017-01-01

    Parkinson's disease (PD) is a complex motor and non-motor disorder and management is often challenging. In this review, we explore emerging approaches to improve the care of patients, drawing from the literature regarding patient-centred care, patient and caregiver perspectives and priorities, gaps in knowledge among patients and caregivers and the need for accurate information, individual variability in disease manifestations, prognostication of disease course, new developments in health technologies and personalized medicine, specialty care, pharmacological and non-pharmacological management, financial burden, lifestyle and work-related issues, support groups and palliative care.

  9. Fisher, Wall and Wilson on "Punishment": A Critique

    Science.gov (United States)

    Wilson, P. S.

    1973-01-01

    Discussion based on Wilson on the justification of punishment,'' by M. Fisher and G. Wall, Journal of Moral Education, v1 n3; and The justification of punishment,'' by J. Wilson, British Journal of Educational Studies, v19 pt2. (CB)

  10. Wilson Dslash Kernel From Lattice QCD Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Balint [Jefferson Lab, Newport News, VA; Smelyanskiy, Mikhail [Parallel Computing Lab, Intel Corporation, California, USA; Kalamkar, Dhiraj D. [Parallel Computing Lab, Intel Corporation, India; Vaidyanathan, Karthikeyan [Parallel Computing Lab, Intel Corporation, India

    2015-07-01

    Lattice Quantum Chromodynamics (LQCD) is a numerical technique used for calculations in Theoretical Nuclear and High Energy Physics. LQCD is traditionally one of the first applications ported to many new high performance computing architectures and indeed LQCD practitioners have been known to design and build custom LQCD computers. Lattice QCD kernels are frequently used as benchmarks (e.g. 168.wupwise in the SPEC suite) and are generally well understood, and as such are ideal to illustrate several optimization techniques. In this chapter we will detail our work in optimizing the Wilson-Dslash kernels for Intel Xeon Phi, however, as we will show the technique gives excellent performance on regular Xeon Architecture as well.

  11. ABJM Wilson loops in arbitrary representations

    Energy Technology Data Exchange (ETDEWEB)

    Hatsuda, Yasuyuki [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group; Tokyo Institute of Technology (Japan). Dept. of Physics; Honda, Masazumi [High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki (Japan); Moriyama, Sanefumi [Nagoya Univ. (Japan). Kobayashi Maskawa Inst. and Graduate School of Mathematics; Okuyama, Kazumi [Shinshu Univ., Matsumoto, Nagano (Japan). Dept. of Physics

    2013-06-15

    We study vacuum expectation values (VEVs) of circular half BPS Wilson loops in arbitrary representations in ABJM theory. We find that those in hook representations are reduced to elementary integrations thanks to the Fermi gas formalism, which are accessible from the numerical studies similar to the partition function in the previous studies. For non-hook representations, we show that the VEVs in the grand canonical formalism can be exactly expressed as determinants of those in the hook representations. Using these facts, we can study the instanton effects of the VEVs in various representations. Our results are consistent with the worldsheet instanton effects studied from the topological string and a prescription to include the membrane instanton effects by shifting the chemical potential, which has been successful for the partition function.

  12. Nucleon form factors with light Wilson quarks

    CERN Document Server

    Green, Jeremy; Krieg, Stefan; Meinel, Stefan; Negele, John; Pochinsky, Andrew; Syritsyn, Sergey

    2013-01-01

    We present nucleon observables - primarily isovector vector form factors - from calculations using 2+1 flavors of Wilson quarks. One ensemble is used for a dedicated high-precision study of excited-state effects using five source-sink separations between 0.7 and 1.6 fm. We also present results from a larger set of calculations that include an ensemble with pion mass 149 MeV and box size 5.6 fm, which nearly eliminates the uncertainty associated with extrapolation to the physical pion mass. The results show agreement with experiment for the vector form factors, which occurs only when excited-state contributions are reduced. Finally, we show results from a subset of ensembles that have pion mass 254 MeV with varying temporal and spatial box sizes, which we use for a controlled study of finite-volume effects and a test of the "$m_\\pi L=4$" rule of thumb.

  13. Obituary: Peter Robert Wilson, 1929-2007

    Science.gov (United States)

    Snodgrass, Herschel B.

    2009-01-01

    It is with great sadness that I report the passing of Peter Robert Wilson, a well-known and well-loved figure in the solar physics community. Peter was on the faculty of the Department of Applied Mathematics at the University of Sydney for 39 years, and Chair of the department for 24 of these years. He was the author or co-author of more than 80 scientific research papers and a book, Solar and Stellar Activity Cycles (1994), published by Cambridge University Press. He died suddenly of a heart attack, at his home in Glebe, Australia, in the early morning of 11 November 2007. Peter was an organizer of, and participant in, many international conferences and workshops. He traveled extensively, holding visiting appointments at the University of Colorado (JILA), at Cambridge University, at the College de France (Paris), and at the California Institute of Technology [CalTech]. Most of his work was in the field of solar physics, but he also did some work on the philosophy of science and on tides. Peter came from a line of mathematicians. His father, Robert Wilson, immigrated to Australia from Glasgow in 1911, and became a mathematics teacher at Scotch College, a private school in Melbourne. There his name was changed to 'Bill' because 'Bob' was already taken." Peter's enjoyment of this story as characteristic of Australian academia (as any fan of Monty Python would understand) is indicative of his infectious sense of humor. In a similar vein, he claimed ancestry traced back to the eighteenth-century Scottish mathematician Alexander Wilson, Professor of Astronomy at the University of Glasgow. That Wilson is famous in the solar physics community for his discovery, known as the "Wilson Effect," of the photospheric depressions associated with sunspots. Peter himself could not resist writing a paper on this subject, and was delighted when the bait was taken by some less-informed colleagues who chided him for "naming an effect after himself." "Bill" Wilson married Naomi

  14. Geographical knowledge in patients with Alzheimer's disease.

    Science.gov (United States)

    Beatty, W W; Bernstein, N

    1989-01-01

    Geographical knowledge, a measure of remote memory for visuospatial information, was studied in mildly and moderately demented patients who met NINCDS-Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease. Alzheimer's disease patients were moderately impaired on a test that emphasizes locating gross features of US geography and profoundly impaired in locating cities on a map of the region of the United States in which they resided. The possibility that performance on tests of geographical knowledge can be used to predict impending difficulties of demented patients in wayfinding is discussed.

  15. Liver Disease

    Science.gov (United States)

    ... from one or both of your parents can cause various substances to build up in your liver, resulting in liver damage. Genetic liver diseases include: Hemochromatosis Hyperoxaluria and oxalosis Wilson's disease Cancer and other growths Examples include: Liver cancer Bile ...

  16. Dental considerations in patients with heart disease

    OpenAIRE

    Cruz Pamplona, Marta; Jiménez Soriano, Yolanda; Sarrión Pérez, María Gracia

    2011-01-01

    Summary: Cardiovascular diseases are one of the main causes of death in the developed world, and represent the first cause of mortality in Spain. In addition to their associated morbidity, such disorders are important due to the number of affected individuals and the many patients subjected to treatment because of them. Objective: An update is provided on the oral manifestations seen in patients with arterial hypertension, ischemic heart disease, arrhythmias and heart failure, and...

  17. Cardiovascular diseases in Patients with Bipolar disease: Pragmatic Management.

    Science.gov (United States)

    Jesus, Cátia; Jesus, Inês; Agius, Mark

    2016-09-01

    Bipolar disorder (BD), also known as manic-depressive illness, is a condition characterized by unusual shifts in mood, energy, activity levels, and the ability to carry out day-to-day tasks. Bipolar disorder is known to be a chronic and disabling disease associated with higher incidence of obesity, diabetes, metabolic syndrome, dyslipidemias, hypertension and tobacco use which all together are known risk factors for the development of Cardiovascular diseases. With this research we wish to collect evidence to show how Cardiovascular diseases (CVD) affect Patients with Bipolar disease, the burden it can have in patients lives, to understand how this problem has been assessed so far and present suggestions that may improve the health care of these patients. Our study is a literature based research. With our study we concluded that patients with BD are at higher risk of CVD and at an earlier age compared with the general population. Also, there is a lack of proper monitoring and consideration of the cardiovascular risk factors in patients with Bipolar disorder whether by primary care physicians or psychiatrists even though it plays a critical role in the general outcome of this patients and also leads to increase in mortality and morbidity rates.

  18. Pentazocine dependence among sickle cell disease patients ...

    African Journals Online (AJOL)

    Introduction: Sickle cell disease is a chronic disease. Severe bone pain is commonly the hallmark of clinical features. This commonly necessitates the use of analgesics especially Opioids which unfortunately have a high potential to produce dependence. The complications of dependence in patients on any psychoactive ...

  19. Mowat-Wilson syndrome presenting with fever-associated seizures.

    Science.gov (United States)

    Seo, Se Eun; Kim, Se Hee; Lee, Seung Tae; Choi, Jong Rak; Lee, Joon Soo; Kim, Heung Dong; Kang, Hoon-Chul

    2017-12-20

    Mowat-Wilson syndrome (MWS) is a disorder caused by mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene. Diagnosis of MWS can be challenging to neurologists, because its manifestations are diverse and the spectrum of genetic mutations are broad. Here, we describe two patients with MWS who initially showed atypical forms of fever-triggered seizures during childhood. Both had characteristic facial features, cognitive impairment, and genito-urinary anomalies consistent with MWS. By performing targeted next-generation sequencing (NGS) using a gene panel for epilepsy, we were able to identify a nonsense mutation (c.1965C>A) in the ZEB2 gene of one patient and a frameshift mutation (c.2348dupC) in the other patient. Fever-induced seizures can be presenting signs of MWS. MWS should be considered in the differential diagnosis of fever-induced seizures, especially when the patient has distinctive facial features and multiple anomalies, including cardiac, genito-urinary, and eye defects.

  20. Cerebrovascular disease in pediatric patients

    National Research Council Canada - National Science Library

    Newra Tellechea Rotta; Alexandre Rodrigues da Silva; Flora Luciana Figueira da Silva; Lygia Ohlweiler; Eraldo Belarmino Jr; Valéria Raimundo Fonteles; Josiane Ranzan; Orlando Javier Ramos Rodriguez; Régis Osório Martins

    2002-01-01

    ... de Clínicas de Porto Alegre (HCPA) from March 1997 to March 2000. All patients, from term infants to 12-year-old children hospitalized in the Pediatrics Unit of HCPA, had clinical suspicion of stroke, which was later confirmed by radiological studies...

  1. Osteoporosis in adult patients with celiac disease.

    Science.gov (United States)

    Kemppainen, T; Kröger, H; Janatuinen, E; Arnala, I; Kosma, V M; Pikkarainen, P; Julkunen, R; Jurvelin, J; Alhava, E; Uusitupa, M

    1999-03-01

    We investigated the bone mineral density (BMD) and prevalence of osteopenia and osteoporosis in adult celiac patients with varying disease states. In this cross-sectional study the data on the severity of celiac disease and BMD were collected from 77 celiac patients (28 newly diagnosed and 49 previously diagnosed celiac patients), and BMD results were compared with those of 157 control subjects matched for age, gender, and menopausal status. The celiac patients had significantly lower BMD than the control subjects at the lumbar spine (-6%) and femoral neck (-5%). The mean BMD did not differ significantly among celiac patients classified by severity of disease. Based on Z scores, 35% of the celiac patients and 17% of the control subjects had low BMDs for age at the lumbar spine (p = 0.005), whereas 31% of celiac patients and 16% of control subjects had Z scores of celiac patients, but only 5% of control subjects, were classified as having osteoporosis (T score osteoporosis was rare at the femoral neck in both groups (3% vs. 1%, p = 1.00). Prevalence of osteopenia and osteoporosis was highest in newly diagnosed celiac patients and in patients with disease not in remission. A low 25-(OH)D vitamin concentration was a typical biochemical abnormality in our patients (64% of men and 71% of women). The main associated variables of low BMD were age (men), low serum vitamin D level, low body weight, and postmenopausal status (women). The present study suggests that celiac disease constitutes a risk factor for osteoporosis. This finding applies particularly to untreated and poorly treated patients.

  2. [Parasitic diseases in pediatric cancer patients].

    Science.gov (United States)

    Bialek, R

    2005-11-01

    Parasitic infections are rare events in pediatric oncology. Transmission routes and diseases of most parasites do not differ significantly from those seen in otherwise healthy children. However, latent asymptomatic infections with Cryptosporidium spp., Leishmania spp., Strongyloides stercoralis and Toxoplasma gondii might exacerbate during immunosuppression. Screening in asymptomatic patients is often unsuccessful due to the low sensitivity of available assays except in toxoplasmosis. This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH) for the appropriate diagnostic procedures and antiparasitic treatment immunocompromised patients.

  3. Mortality in patients with Parkinson's disease

    DEFF Research Database (Denmark)

    Wermuth, L; Stenager, E; Stenager, E

    1995-01-01

    INTRODUCTION: After the introduction of L-dopa the mortality rate in Parkinson's disease (PD) patients has changed, but is still higher than in the background population. MATERIAL & METHODS: Mortality, age at death and cause of death in a group of PD patients compared with the background population...

  4. Psychological assessment of patients with Meniere's disease

    NARCIS (Netherlands)

    van Cruijsen, N.; Jaspers, J. P. C.; van de Wiel, H. B. M.; Wit, H. P.; Albers, F. W. J.

    The objective of this study was to evaluate daily stressors, coping, personality, physical and mental health, and quality of life in Meniere patients. 110 consecutive patients with definite Meniere's disease were assessed using the Dutch Daily Hassles List, Coping Inventory for Stressful Situations

  5. [Hypothyroidism in patients with heart disease].

    Science.gov (United States)

    Jiskra, Jan

    Hypothyroidism is frequently found in patients with heart disease. It is a risk factor for atherosclerosis and ischemic heart disease and has a direct negative effect on both the left and right ventricular functions (hypothyroidism-induced cardiomyopathy). The confirmed manifest hypothyroidism is always a reason for replacement therapy with levothyroxine; regarding patients with heart disease, we always begin treatment with a small dose and increase it gradually. The treatment of subclinical hypothyroidism in patients with heart disease is disputable and its benefits probably depend on age. At a higher age, the therapy-related risks often outweigh its benefits, so we make do with the target levels of the thyroid stimulating hormone being within the upper band of the normal range, or even slightly above it, rather than overdosing the patient. To summarize in a simplified way, the treatment of subclinical hypothyroidism in patients with heart disease is the most effective in younger individuals, mainly those aged below 65, while at a higher age > 80 years the risk usually outweighs the benefit.Key words: cardiovascular risk - hypothyroidism - ischemic heart disease - left ventricular dysfunction - right ventricular dysfunction - subclinical hypothyroidism - thyroid peroxidase antibodies.

  6. Nutritional care for patients with Crohn's disease.

    Science.gov (United States)

    Afonso, J J; Rombeau, J L

    1990-02-01

    Protein calorie malnutrition, in addition to deficits of other nutrients, occurs frequently among patients with Crohn's disease. In most instances the mechanisms by which these deficits occur are multifactorial. The most appropriate method to assess nutritional status includes a nutritionally oriented medical history and physical examination combined with a measurement of serum albumin. If the gut can be used safely, enteral nutrition is the preferred feeding method for Crohn's disease patients needing nutritional support. The advantages of enteral nutrition are stimulatory effects on gastrointestinal structure and function and reduced cost when compared to parenteral feeding. If the gastrointestinal tract cannot be used safely, parenteral nutrition is recommended. The presence of Crohn's disease among prepubertal children produces serious growth failure which can be reduced or arrested by appropriate nutritional interventions. Significant numbers of Crohn's disease patients ar now receiving both enteral and parenteral nutrition in the home setting.

  7. MANAGEMENT OF ORAL AND DENTAL DISEASES IN MEDICALLY COMPROMISED PATIENTS (Patient with Diseases of Cardiovascular System)

    OpenAIRE

    Afi Savitri Sarsito

    2015-01-01

    The treatment of oral and dental diseases in healthy patients can be performed with general standard and usually do not cause problems. On the other hand treatment of oral and dental diseases in medically compromised patients, especially one with disease of cardiovascular system must be performed with specific standard or otherwis emay evoke serious problems. Therefore the treatment needs to be compromised with the condition of the patients as well as the medication they are taking. This pape...

  8. Current treatments for patients with Alzheimer disease.

    Science.gov (United States)

    Osborn, Gerald G; Saunders, Amanda Vaughn

    2010-09-01

    There is neither proven effective prevention for Alzheimer disease nor a cure for patients with this disorder. Nevertheless, a spectrum of biopsychosocial therapeutic measures is available for slowing progression of the illness and enhancing quality of life for patients. These measures include a range of educational, psychological, social, and behavioral interventions that remain fundamental to effective care. Also available are a number of pharmacologic treatments, including prescription medications approved by the US Food and Drug Administration for Alzheimer disease, "off-label" uses of medications to manage target symptoms, and controversial complementary therapies. Physicians must make the earliest possible diagnosis to use these treatments most effectively. Physicians' goals should be to educate patients and their caregivers, to plan long-term care options, to maximally manage concurrent illnesses, to slow and ameliorate the most disabling symptoms, and to preserve effective functioning for as long as possible. The authors review the various current treatments for patients with Alzheimer disease.

  9. Clinical features and disease progression in moyamoya disease patients with Graves disease.

    Science.gov (United States)

    Chen, Jian-Bin; Lei, Ding; He, Min; Sun, Hong; Liu, Yi; Zhang, Heng; You, Chao; Zhou, Liang-Xue; Zhou, Ling-Xue

    2015-10-01

    The present study aimed to clarify the incidence and clinical features of disease progression in adult moyamoya disease (MMD) patients with Graves disease (GD) for better management of these patients. During the past 18 years, 320 adult Chinese patients at West China Hospital were diagnosed with MMD, and 29 were also diagnosed with GD. A total of 170 patients (25 with GD; 145 without GD) were included in this study and were followed up. The mean follow-up was 106.4 ± 48.6 months (range 6-216 months). The progression of the occlusive lesions in the major intracranial arteries was measured using cerebral angiography and was evaluated according to Suzuki's angiographic staging. Information about cerebrovascular strokes was obtained from the records of patients' recent clinical visits. Both angiographic progression and strokes were analyzed to estimate the incidences of angiographic progression and strokes using Kaplan-Meier analysis. A multivariate logistic regression model was used to test the effects of sex, age at MMD onset, disease type, strokes, and GD on the onset of MMD progression during follow-up. During follow-up, the incidence of disease progression in MMD patients with GD was significantly higher than in patients without GD (40.0% vs 20.7%, respectively; p = 0.036). The interval between initial diagnosis and disease progression was significantly shorter in MMD patients with GD than in patients without GD (p = 0.041). Disease progression occurred in both unilateral MMD and bilateral MMD, but the interval before disease progression in patients with unilateral disease was significantly longer than in patients with bilateral disease (p = 0.021). The incidence of strokes in MMD patients with GD was significantly higher than in patients without GD (48% vs 26.2%, respectively; p = 0.027). The Kaplan-Meier survival curve showed significant differences in the incidence of disease progression (p = 0.038, log-rank test) and strokes (p = 0.031, log-rank test) between

  10. Ladder exponentiation for generic large symmetric representation Wilson loops

    OpenAIRE

    Correa, Diego; Massolo, Fidel(Instituto de Física La Plata, CONICET, Universidad Nacional de La Plata, C.C. 67, La Plata, 1900, Argentina)

    2015-01-01

    A recent proposal was made for a large representation rank limit for which the expectation values of N = 4 $$ \\mathcal{N}=4 $$ super Yang-Mills Wilson loops are given by the exponential of the 1-loop result. We verify the validity of this exponentiation in the strong coupling limit using the holographic D3-brane description for straight Wilson loops following an arbitrary internal space trajectory.

  11. Taking Charge: Walter Sydney Adams and the Mount Wilson Observatory

    Science.gov (United States)

    Brashear, R.

    2004-12-01

    The growing preeminence of American observational astronomy in the first half of the 20th century is a well-known story and much credit is given to George Ellery Hale and his skill as an observatory-building entrepreneur. But a key figure who has yet to be discussed in great detail is Walter Sydney Adams (1876-1956), Hale's Assistant Director at Mount Wilson Observatory. Due to Hale's illnesses, Adams was Acting Director for much of Hale's tenure, and he became the second Director of Mount Wilson from 1923 to 1946. Behind his New England reserve Adams was instrumental in the growth of Mount Wilson and thus American astronomy in general. Adams was hand-picked by Hale to take charge of stellar spectroscopy work at Yerkes and Mount Wilson and the younger astronomer showed tremendous loyalty to Hale and Hale's vision throughout his career. As Adams assumed the leadership role at Mount Wilson he concentrated on making the observatory a place where researchers worked with great freedom but maintain a high level of cooperation. This paper will concentrate on Adams's early years and look at his growing relationship with Hale and how he came to be the central figure in the early history of Mount Wilson as both a solar and stellar observatory. His education, his years at Dartmouth and Yerkes (including his unfortunate encounter with epsilon Leonis), and his formative years on Mount Wilson are all important in learning how he shaped the direction of Mount Wilson and the development of American astronomy in the first half of the 20th century. This latter history cannot be complete until we bring Adams into better focus.

  12. Mortality in patients with pituitary disease.

    LENUS (Irish Health Repository)

    Sherlock, Mark

    2010-06-01

    Pituitary disease is associated with increased mortality predominantly due to vascular disease. Control of cortisol secretion and GH hypersecretion (and cardiovascular risk factor reduction) is key in the reduction of mortality in patients with Cushing\\'s disease and acromegaly, retrospectively. For patients with acromegaly, the role of IGF-I is less clear-cut. Confounding pituitary hormone deficiencies such as gonadotropins and particularly ACTH deficiency (with higher doses of hydrocortisone replacement) may have a detrimental effect on outcome in patients with pituitary disease. Pituitary radiotherapy is a further factor that has been associated with increased mortality (particularly cerebrovascular). Although standardized mortality ratios in pituitary disease are falling due to improved treatment, mortality for many conditions are still elevated above that of the general population, and therefore further measures are needed. Craniopharyngioma patients have a particularly increased risk of mortality as a result of the tumor itself and treatment to control tumor growth; this is a key area for future research in order to optimize the outcome for these patients.

  13. Dental profile of patients with Gaucher disease

    Directory of Open Access Journals (Sweden)

    Mann Jonathan

    2003-07-01

    Full Text Available Abstract Background This study was conducted to determine whether patients with Gaucher disease had significant dental pathology because of abnormal bone structure, pancytopenia, and coagulation abnormalities. Methods Each patient received a complete oral and periodontal examination in addition to a routine hematological evaluation. Results Gaucher patients had significantly fewer carious lesions than otherwise healthy carriers. Despite prevalence of anemia, there was no increase in gingival disease; despite the high incidence of thrombocytopenia, gingival bleeding was not noted; and despite radiological evidence of bone involvement, there was no greater incidence loss of teeth or clinical tooth mobility. Conclusions These data represent the first survey of the oral health of a large cohort of patients with Gaucher disease. It is a pilot study of a unique population and the results of the investigation are indications for further research. Based on our findings, we recommend regular oral examinations with appropriate dental treatment for patients with Gaucher disease as for other individuals. Consultation between the dentist and physician, preferably one with experience with Gaucher disease, should be considered when surgical procedures are planned.

  14. Psychosocial interventions for patients with chronic disease

    Directory of Open Access Journals (Sweden)

    Deter Hans-Christian

    2012-01-01

    Full Text Available Abstract Treatment of patients with chronic diseases will be one of the main challenges of medicine in the future. This paper presents an overview of different origins, mechanism, and symptoms necessary for understanding new and different interventions that include a psychosomatic view. In a psychosomatic therapeutic intervention there are very different targets, such as psychological symptoms, personality traits, attitudes toward disease and life, risk behaviour, and social isolation and as biological targets the change of autonomic imbalance and of the effects of the psycho-endocrinological or psycho-immunological stress responses. And there are also different psychosomatic measures that influence the individual biological, psychological and sociological targets. There is a need to give different answer to different questions in the field of psychosomatic and behavioral medicine. Comparative effectiveness research is an important strategy for solving some methodological issues. What is the target of treatment for different diseases: Symptom reduction, healing, or limiting progression to the worst case - the death of patients. We know that, the patient-physician relationship is important for every medical/therapeutic action for patients with chronic diseases. This volume of BioPsychoSocial Medicine will present four different psychosomatic treatment studies from the clinical field in the sense of phase 2 studies: Reports of patients with obesity, anorexia nervosa, chronic somatoform pain and coronary artery disease were presented

  15. Sleep disturbances in patients with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Smiljković Tatjana

    2010-01-01

    Full Text Available Introduction Sleep problems, common in Parkinson's disease (PD, are the consequence of the neurodegenerative process, as well as of neurochemical changes on one side, and of drug intake on the other side. Objective To estimate the frequency of sleep problems and its correlation with the disease, therapy and demographic factors in patients with idiopathic Parkinson's disease. Methods The study enrolled 65 consecutive patients who fulfilled criteria for idiopathic PD. The original questionnaire was performed to obtain demographic, disease and treatment data. The patients were tested with standardized scales: unified PD rating scale (UPDRS and Hoehn and Yahr staging scale (HY scale. Mini mental stage examination (MMSE was performed for the evaluation of cognitive status. Parkinson's disease sleep scale (PDSS was applied for the assessment of sleep problems. Results There were 37 male and 28 female patients. Negative correlations (p<0.01 were found between mean total PDSS and mean total UPDRS, as well as the mean scores of each part of UPDRS and HY stage. There was no difference in PDSS scores regarding gender. Analyzing each item in the PDSS scale, the lowest score was obtained for item 8 (nocturia. We did not find any difference in total PDSS scores between the patients on d-agonist and those who did not take d-agonist. Regarding amantadin, intake there were differences between groups for items concerning nocturnal motor symptoms. Conclusion Patients in advanced stages of the disease and worse motility have more prominent sleep problems. Drug therapy has important impact on sleep quality in patients with PD. .

  16. Neoplastic pericardial disease. Analysis of 26 patients

    Directory of Open Access Journals (Sweden)

    Helena Nogueira Soufen

    1999-01-01

    Full Text Available PURPOSE: To characterize patients with neoplastic pericardial disease diagnosed by clinical presentation, complementary test findings, and the histological type of tumor. METHODS: Twenty-six patients with neoplastic pericardial disease were retrospectively analyzed. RESULTS: Clinical manifestations and abnormalities in chest roentgenograms and electrocardiograms were frequent, but were not specific. Most patients underwent surgery. There was a high positivity of the pericardial biopsy when associated with the cytological analysis of the pericardial liquid used to determine the histological type of the tumor, particularly when the procedure was performed with the aid of pericardioscopy. CONCLUSION: The correct diagnosis of neoplastic pericardial disease involves suspicious but nonspecific findings during clinical examination and in screen tests. The suspicious findings must be confirmed through more invasive diagnostic approaches, in particular pericardioscopy with biopsy and cytological study.

  17. LOCAL ANESTHETICS IN PATIENTS WITH CARDIOVASCULAR DISEASES.

    Directory of Open Access Journals (Sweden)

    risto Daskalov

    2015-03-01

    Full Text Available A significant problem in the dental medicine is pain alleviation. Many studies in the dental anesthesiology result in the production of new agents for locoregional anesthesia. Objective: This article aim to present the results of the last studies on the effect of the local anesthetics used in the oral surgery on patients with cardiovascular diseases. Material: A general review of the existing literature on the effect of the adrenaline, included as vasoconstrictor in the local anesthetics, used in patients with cardiovascular diseases is made. The benefits of vasoconstrictors for the quality of the anesthetic effect are proven. Conclusion: A small amount of adrenaline in the anesthetic solution does not result in complications development in patients with controlled cardiovascular diseases. Articaine is recommended agent of first choice for local anesthesia in the oral surgery.

  18. Dental considerations in patients with liver disease

    OpenAIRE

    Cruz Pamplona, Marta; Margaix Muñoz, María; Sarrión Pérez, María Gracia

    2011-01-01

    Introduction: Liver diseases are very common, and the main underlying causes are viral infections, alcohol abuse and lipid and carbohydrate metabolic disorders. The liver has a broad range of functions in maintaining homeostasis and health, and moreover metabolizes many drug substances. Objective: An update is provided on the oral manifestations seen in patients with viral hepatitis, alcoholic and non-alcoholic liver disease, cirrhosis and hepatocellular carcinoma, and on the dent...

  19. MANAGEMENT OF ORAL AND DENTAL DISEASES IN MEDICALLY COMPROMISED PATIENTS (Patient with Diseases of Cardiovascular System

    Directory of Open Access Journals (Sweden)

    Afi Savitri Sarsito

    2015-08-01

    Full Text Available The treatment of oral and dental diseases in healthy patients can be performed with general standard and usually do not cause problems. On the other hand treatment of oral and dental diseases in medically compromised patients, especially one with disease of cardiovascular system must be performed with specific standard or otherwis emay evoke serious problems. Therefore the treatment needs to be compromised with the condition of the patients as well as the medication they are taking. This paper explains the management of oral and dental diseases in patients with disease of cardiovascular system usually found such as hypertension, infective endocarditis, rheumatic fever and rheumatic heart diseases where the cooperation between dentist and internist is extremely recommended.

  20. Cardiovascular disease in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Naranjo, Antonio; Sokka, Tuulikki; Descalzo, Miguel

    2008-01-01

    ABSTRACT: INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross......-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. METHODS: The study involved a clinical assessment by a rheumatologist and a self-report questionnaire...

  1. [Metronome therapy in patients with Parkinson disease].

    Science.gov (United States)

    Enzensberger, W; Oberländer, U; Stecker, K

    1997-12-01

    We studied 10 patients with Parkinson's disease and 12 patients with Parkinson-plus-syndrome, trying to improve patients' gait by application of various external rhythmic stimuli, including metronome stimulation (96 beats per minute = middle andante). The test course of the patients was 4 x 10 meters and 3 U-turns. The patients' gait quality under stimulation was compared with their free walk (velocity, number of steps, number of freezing episodes). Metronome stimulation significantly reduced the time and number of steps needed for the test course and also diminished the number of freezing episodes. March music stimulation was less effective and tactile stimulation (rhythmically tapping on the patient's shoulder) even produced negative results. The positive effect of metronome stimulation was also found, when the tests were not performed inside the hospital building, but outside in the hospital parc. Metronome stimulation was comparably effective in both patient sub-groups examined in this study (M. Parkinson, Parkinson-plus-syndrome) and seems to be an important additional help in the treatment of these patients. Electronical metronomes are not expensive, easy in handling, and portable. A theoretical explanation of metronome stimulation effectivity in patients with Parkinson's disease still needs to be elucidated.

  2. Crohn disease and the gynecologic patient.

    Science.gov (United States)

    Sides, Cleve; Trinidad, Mari Charisse; Heitlinger, Leo; Anasti, James

    2013-01-01

    Although Crohn disease (CD) is considered an inflammatory bowel disease, extraintestinal gynecologic manifestations are varied, frequent, and oftentimes difficult to manage. Its predilection for young and reproductive-age women makes it an important disease process for the gynecologist to understand, as its complications can have long-term repercussions on the developmental, sexual, reproductive, and psychological health of affected women. Patients may present with a variety of vulvovaginal, perineal, perianal, and urologic complaints. Perianal involvement from an intestinal fistula is the most common skin manifestation seen in CD. Other gynecologic manifestations include metastatic CD and rectovaginal and urovaginal fistulas. Recognition and accurate diagnosis of extraintestinal gynecologic manifestations, as well as a good understanding of the gynecologic effects of chronic disease, are necessary for optimal management. The article provides an overview of CD and highlights the gynecologic considerations in caring for women affected by this disease.

  3. A STUDY OF PREDICTION OF DIFFICULT INTUBATION USING MALLAMPATI AND WILSON SCORE CORRELATING WITH CORMACK LEHANE GRADING

    OpenAIRE

    Vaishali Chandrashekhar; Jaideep; Medha K; Sandhya P; Manish

    2015-01-01

    BACKGROUND : This study was carried out to evaluate usefulness of preoperative Mallampati & Wilson’s score grading as a predictor for difficult laryngoscopy & intubation . AIMS : To determine the accuracy of the modified Mallampati test and Wilson score for predicting difficult tracheal intubation and correlation with Cormack Lehane grading . METHODS : This prospective randomized cross sectional Study carried out in 200 patients , poste...

  4. Subsequent leukaemia in autoimmune disease patients.

    Science.gov (United States)

    Hemminki, Kari; Liu, Xiangdong; Försti, Asta; Ji, Jianguang; Sundquist, Jan; Sundquist, Kristina

    2013-06-01

    Previous studies have shown that patients diagnosed with some autoimmune (AI) diseases are at an increased risk of leukaemia but limited data are available on survival. We systematically analysed the risks (standardized incidence ratio, SIR) and survival (hazard ratio, HR) in nine types of leukaemia among 402 462 patients hospitalized for any of 33 AI diseases and compared to persons not hospitalized for AI diseases. Risk for all leukaemia was increased after 13 AI diseases and survival was decreased after six AI diseases. SIRs were increased after all AI diseases for seven types of leukaemia, including SIR 1·69 (95% confidence interval (CI): 1·29-2·19) for acute lymphoblastic leukaemia (ALL), 1·85 (95% CI: 1·65-2·07) for acute myeloid leukaemia, 1·68 (95% CI: 1·37-2·04) for chronic myeloid leukaemia, 2·20 (95% CI: 1·69-2·81) for 'other myeloid leukaemia', 2·45 (95% 1·99-2·98) for 'other and unspecified leukaemia', 1·81 (95% CI: 1·11-2·81) for monocytic leukaemia, and 1·36 (95% CI: 1·08-1·69) for myelofibrosis. The HRs were increased for four types of leukaemia, most for myelofibrosis (1·74, 95% CI: 1·33-2·29) and ALL (1·42, 95% CI: 1·03-1·95). Some AI diseases, including rheumatoid arthritis, were associated with increased SIRs and HRs in many types of leukaemia. The present data showed increases in risk and decreases in survival for many types of leukaemia after various AI diseases. Leukaemia is a rare complication in AI disease but findings about this comorbidity at the time of leukaemia diagnosis may help to optimize the treatment and improve survival. © 2013 John Wiley & Sons Ltd.

  5. Detection of arousals in Parkinson's disease patients

    DEFF Research Database (Denmark)

    Sørensen, Gertrud Laura; Kempfner, Jacob; Jennum, Poul

    2011-01-01

    suffering from Parkinson's disease (PD). The proposed algorithm uses features from EEG, EMG and the manual sleep stage scoring as input to a feed-forward artificial neural network (ANN). The performance of the algorithm has been assessed using polysomnographic (PSG) recordings from a total of 8 patients...

  6. Helping Patients Cope with Inflammatory Bowel Disease.

    Science.gov (United States)

    1984-01-01

    Recovery (mastectomy patients) and the Ostomy Association. They consist of people with Inflammatory Bowel Disease. Members support one another by sharing...problems 10 unique to single people. Subjects such as dating, social relationships, sexuality , and career planning are discussed. The couples group

  7. Infection in Sickle Cell Disease Patients

    African Journals Online (AJOL)

    Rev Olaleye

    ABSTRACT: This study aimed to determine retrospectively, the prevalence of hepatitis C virus infection in relation to a background history of blood transfusion; through anti HCV antibody screening test, amongst adult sickle cell disease patients. Anti HCV antibody was tested for in the serum of 92 consecutively selected ...

  8. [Chronic kidney disease in the elderly patient].

    Science.gov (United States)

    Mora-Gutiérrez, José María; Slon Roblero, María Fernanda; Castaño Bilbao, Itziar; Izquierdo Bautista, Diana; Arteaga Coloma, Jesús; Martínez Velilla, Nicolás

    Chronic kidney disease (CKD) is widely prevalent worldwide, with a special impact on elderly population. Around half of people aged over 75 meet diagnostic criteria for CKD according to the recent 'Kidney disease improving global outcomes' (KDIGO) 2012 clinical practice guideline on the evaluation and management of CKD. However, geriatric patients have characteristics that may not be addressed by general guidelines. Therefore, it is important to know the natural history of the disease, symptoms, and 'red-flags' that could help in the management of these patients. In this review, a complete approach is presented on the pathophysiology, diagnosis, and treatment of CKD in the geriatric population. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Quinoa Well Tolerated in Patients with Celiac Disease

    Science.gov (United States)

    ... Celiac Disease Quinoa Well Tolerated in Patients with Celiac Disease FOR IMMEDIATE RELEASE Tuesday, January 21, 2014 8: ... to the gluten-free diet of patients with celiac disease is well-tolerated, and does not exacerbate the ...

  10. Electrocardiographic characteristics of patients with chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Warnier, Miriam J.; Rutten, Frans H.; Numans, Mattijs E.; Kors, Jan A.; Tan, Hanno L.; de Boer, Anthonius; Hoes, Arno W.; de Bruin, Marie L.

    2013-01-01

    Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease. Electrocardiography (ECG) carries information about cardiac disease and prognosis, but studies comparing ECG characteristics between patients with and without COPD are lacking. We related ECG

  11. Electrocardiographic Characteristics of Patients with Chronic Obstructive Pulmonary Disease

    NARCIS (Netherlands)

    Warnier, M.J.; Rutten, F.H.; Numans, M.E.; Kors, J.A.; Tan, H.L.; de Boer, A.; Hoes, A.W.; de Bruin, M.L.

    2013-01-01

    Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease. Electrocardiography (ECG) carries information about cardiac disease and prognosis, but studies comparing ECG characteristics between patients with and without COPD are lacking. We related ECG

  12. Heart failure in patients with kidney disease.

    Science.gov (United States)

    Tuegel, Courtney; Bansal, Nisha

    2017-12-01

    Heart failure (HF) is a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD), and the population of CKD patients with concurrent HF continues to grow. The accurate diagnosis of HF is challenging in patients with CKD in part due to a lack of validated imaging and biomarkers specifically in this population. The pathophysiology between the heart and the kidneys is complex and bidirectional. Patients with CKD have greater prevalence of traditional HF risk factors as well as unique kidney-specific risk factors including malnutrition, acid-base alterations, uraemic toxins, bone mineral changes, anemia and myocardial stunning. These risk factors also contribute to the decline of kidney function seen in patients with subclinical and clinical HF. More targeted HF therapies may improve outcomes in patients with kidney disease as current HF therapies are underutilised in this population. Further work is also needed to develop novel HF therapies for the CKD population. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. Articular manifestations in patients with Lyme disease.

    Science.gov (United States)

    Vázquez-López, María Esther; Díez-Morrondo, Carolina; Sánchez-Andrade, Amalia; Pego-Reigosa, Robustiano; Díaz, Pablo; Castro-Gago, Manuel

    To determine the percentage of Lyme patients with articular manifestations in NW Spain and to know their evolution and response to treatment. A retrospective study (2006-2013) was performed using medical histories of confirmed cases of Lyme disease showing articular manifestations. Clinical and laboratory characteristics, together with the treatment and evolution of the patients, were analysed. Seventeen out of 108 LD confirmed patients (15.7%) showed articular manifestations. Regarding those 17 patients, 64.7%, 29.4% and 5.9% presented arthritis, arthralgia and bursitis, respectively. The knee was the most affected joint. Articular manifestations were often associated to neurological, dermatological and cardiac pathologies. Otherwise, most patients were in Stage III. The 11.8% of the cases progressed to a recurrent chronic arthritis despite the administration of an appropriate treatment. Lyme disease patients showing articular manifestations should be included in the diagnosis of articular affections in areas of high risk of hard tick bite, in order to establish a suitable and early treatment and to avoid sequels. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  14. Nonsurgical treatment of patients with periodontal disease.

    Science.gov (United States)

    Loesche, W J; Giordano, J; Soehren, S; Hutchinson, R; Rau, C F; Walsh, L; Schork, M A

    1996-05-01

    To determine whether the short-term use of systemic antimicrobials (metronidazole or doxycycline) and locally delivered antimicrobials (metronidazole, chlorhexidine) in patients with advanced forms of periodontal disease could prevent the normally necessary access surgery. Ninety-four patients were randomly assigned with the use of a double-blind protocol. There was a 93% reduction in the need for periodontal surgery about individual teeth and an 81% reduction in the need for tooth extractions. Only 93 teeth of an initial total of 783 teeth actually needed surgery or extractions. Eighty-one percent of the patients entered into the maintenance phase of treatment without needing surgical treatments. These findings indicate that a treatment paradigm based on the diagnosis and treatment of anaerobic infections is likely to be successful in those patients for whom access surgery is recommended.

  15. Strings in bubbling geometries and dual Wilson loop correlators

    Science.gov (United States)

    Aguilera-Damia, Jeremías; Correa, Diego H.; Fucito, Francesco; Giraldo-Rivera, Victor I.; Morales, Jose F.; Pando Zayas, Leopoldo A.

    2017-12-01

    We consider a fundamental string in a bubbling geometry of arbitrary genus dual to a half-supersymmetric Wilson loop in a general large representation R of the SU( N) gauge group in N=4 Supersymmetric Yang-Mills. We demonstrate, under some mild conditions, that the minimum value of the string classical action for a bubbling geometry of arbitrary genus precisely matches the correlator of a Wilson loop in the fundamental representation and one in a general large representation. We work out the case in which the large representation is given by a rectangular Young tableau, corresponding to a genus one bubbling geometry, explicitly. We also present explicit results in the field theory for a correlator of two Wilson loops: a large one in an arbitrary representation and a "small" one in the fundamental, totally symmetric or totally antisymmetric representation.

  16. Anticardiolipin antibodies in patients with Behcet's disease

    Directory of Open Access Journals (Sweden)

    Maja Zivkovic

    2011-02-01

    Full Text Available The aims of this study are to determine anticardiolipin antibodies in patients with Sy Behcet and to determine correlation between the levels of anticardiolipin antibodies in serum in patients with clinic systemic and ocular manifestations. The study was conducted on 11 patients with Behcet disease (group I, and on 11 healthy subjects (group II. Anticardiolipin antibodies –aCL were determined by the standard ELISA method, where 1GPL= 1 microgram/ml IgG aCL and 1 MPL= 1 microgram/ml IgM, and were considered negative < 10 GPL or MPL, low positive (10-40 GPL and MPL, or high positive (>40 GPL and MPL. In the group of 11 patients with the diagnosis Sy Behcet, 6 of them were (54.5% with values of anticardiolipin antibodies over 10 positive. In the control group of the healthy examinees aCl were positive in 2 cases (18.2%. There are no statistically significant differences in the presence of systemic clinic characteristics between aCl positive and negative patients. All the patients with SY Behcet in whom anticardiolipn antibodies were found have extremely severe visual damage which is not present in the group of those patients where the values of aCl were low. The difference is statistically significant. The level of anticardiolipin antibodies is increased in the patients with Behcet. There are no statistically significant differences in the presence of systemic clinical characteristics between aCL positive and negative patients. Visual acuity in patients with SY Behcet is statistically significantly much lower in patients who had increased values of aCL.

  17. CHARGE-like presentation, craniosynostosis and mild Mowat-Wilson Syndrome diagnosed by recognition of the distinctive facial gestalt in a cohort of 28 new cases.

    Science.gov (United States)

    Wenger, Tara L; Harr, Margaret; Ricciardi, Stefania; Bhoj, Elizabeth; Santani, Avni; Adam, Margaret P; Barnett, Sarah S; Ganetzky, Rebecca; McDonald-McGinn, Donna M; Battaglia, Domenica; Bigoni, Stefania; Selicorni, Angelo; Sorge, Giovanni; Monica, Matteo Della; Mari, Francesca; Andreucci, Elena; Romano, Silvia; Cocchi, Guido; Savasta, Salvatore; Malbora, Baris; Marangi, Giuseppe; Garavelli, Livia; Zollino, Marcella; Zackai, Elaine H

    2014-10-01

    Mowat-Wilson syndrome (MWS) is characterized by moderate to severe intellectual disability and distinctive facial features in association with variable structural congenital anomalies/clinical features including congenital heart disease, Hirschsprung disease, hypospadias, agenesis of the corpus callosum, short stature, epilepsy, and microcephaly. Less common clinical features include ocular anomalies, craniosynostosis, mild intellectual disability, and choanal atresia. These cases may be more difficult to diagnose. In this report, we add 28 MWS patients with molecular confirmation of ZEB2 mutation, including seven with an uncommon presenting feature. Among the "unusual" patients, two patients had clinical features of charge syndrome including choanal atresia, coloboma, cardiac defects, genitourinary anomaly (1/2), and severe intellectual disability; two patients had craniosynostosis; and three patients had mild intellectual disability. Sixteen patients have previously-unreported mutations in ZEB2. Genotype-phenotype correlations were suggested in those with mild intellectual disability (two had a novel missense mutation in ZEB2, one with novel splice site mutation). This report increases the number of reported patients with MWS with unusual features, and is the first report of MWS in children previously thought to have CHARGE syndrome. These patients highlight the importance of facial gestalt in the accurate identification of MWS when less common features are present. © 2014 Wiley Periodicals, Inc.

  18. BPS Wilson loops in Minkowski spacetime and Euclidean space

    OpenAIRE

    Ouyang, Hao; Wu, Jun-Bao; Zhang, Jia-ju

    2015-01-01

    We give evidence that spacelike BPS Wilson loops do not exist in Minkowski spacetime. We show that spacelike Wilson loops in Minkowski spacetime cannot preserve any supersymmetries, in $d = 4$ $\\mathcal N = 4$ super Yang-Mills theory, $d = 3$ $\\mathcal N = 2$ super Chern-Simons-matter theory, and $d = 3$ $\\mathcal N = 6$ Aharony-Bergman-Jafferis-Maldacena theory. We not only show this using infinite straight lines and circles as examples, but also we give proofs for general curves. We attribu...

  19. G. Terence Wilson: Award for Distinguished Scientific Applications of Psychology.

    Science.gov (United States)

    2014-11-01

    The APA Award for Distinguished Scientific Applications of Psychology is presented to a person who, in the opinion of the Committee on Scientific Awards, has made distinguished theoretical or empirical advances leading to the understanding or amelioration of important practical problems. The 2014 recipient is G. Terence Wilson, who received the award for "his outstanding contributions to the nature and theory of behavior therapy." Wilson's award citation, biography, and a selected bibliography are presented here. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  20. Mortality in Swedish patients with Hirschsprung disease.

    Science.gov (United States)

    Löf Granström, Anna; Wester, Tomas

    2017-11-01

    Hirschsprung disease (HSCR) has previously been associated with increased mortality. The aim of this study was to assess mortality in patients with Hirschsprung disease in a population-based cohort. This was a nationwide, population-based cohort study. The study exposure was HSCR and the study outcome was death. The cohort included all individuals with HSCR registered in the Swedish National Patient Register between 1964 and 2013 and ten age- and sex-matched controls per patient, randomly selected from the Population Register. Mortality and cause of death were assessed using the Swedish National Causes of Death Register. The cohort comprised 739 individuals with HSCR (565 male) and 7390 controls (5650 male). Median age of the cohort was 19 years (range 2-49). Twenty-two (3.0%) individuals with HSCR had died at median age 2.5 years (range 0-35) compared to 49 (0.7%) controls at median age 20 years (0-44), p < 0.001. Hazard ratio for death in HSCR patients compared to healthy controls was 4.77 (confidence interval (CI) 95% 2.87-7.91), and when adjusted for Down syndrome, the hazard ratio was 3.6 (CI 95% 2.04-6.37). The mortality rate in the HSCR cohort was 3%, which was higher than in controls also when data were adjusted for Down syndrome.

  1. Spiritual Needs of Patients with Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Harold G. Koenig

    2010-11-01

    Full Text Available For many patients confronted with chronic diseases, spirituality/religiosity is an important resource for coping. Patients often report unmet spiritual and existential needs, and spiritual support is also associated with better quality of life. Caring for spiritual, existential and psychosocial needs is not only relevant to patients at the end of their life but also to those suffering from long-term chronic illnesses. Spiritual needs may not always be associated with life satisfaction, but sometimes with anxiety, and can be interpreted as the patients’ longing for spiritual well-being. The needs for peace, health and social support are universal human needs and are of special importance to patients with long lasting courses of disease. The factor, Actively Giving, may be of particular importance because it can be interpreted as patients’ intention to leave the role of a `passive sufferer´ to become an active, self-actualizing, giving individual. One can identify four core dimensions of spiritual needs, i.e., Connection, Peace, Meaning/Purpose, and Transcendence, which can be attributed to underlying psychosocial, emotional, existential, and religious needs. The proposed model can provide a conceptual framework for further research and clinical practice. In fact, health care that addresses patients’ physical, emotional, social, existential and spiritual needs (referring to a bio-psychosocial-spiritual model of health care will contribute to patients’ improvement and recovery. Nevertheless, there are several barriers in the health care system that makes it difficult to adequately address these needs.

  2. Depression in patients with coronary heart disease.

    Science.gov (United States)

    Carney, Robert M; Freedland, Kenneth E

    2008-11-01

    Approximately 20% of patients with coronary heart disease (CHD) have major depression and 20% have minor depression at any given point in the course of their illness. Depression causes significant psychological and social morbidity, and is a risk factor for further cardiac morbidity and mortality. Although there are many possible biological and behavioral mechanisms, the causal pathways through which depression increases the risk for cardiac events and death are not well understood. Despite the morbidity associated with depression, and the devastating impact it has on the quality of life of patients with CHD, it is underdiagnosed and often left untreated. This article describes screening techniques for use in primary care and cardiology settings, and discusses the safety and efficacy of available treatments for depression in patients with CHD.

  3. Sleepwalking in patients with Parkinson disease.

    Science.gov (United States)

    Poryazova, Rositsa; Waldvogel, Daniel; Bassetti, Claudio L

    2007-10-01

    To report the occurrence of adult-onset (de novo) sleepwalking in a series of 6 patients with idiopathic Parkinson disease (PD). Case series. Outpatient clinic for movement disorders. Of 165 consecutive patients with PD seen for 2 years, 6 patients with adult-onset sleepwalking were identified. These patients underwent a systematic clinical assessment of their extrapyramidal and sleep problems, which included standard questionnaires, clinical examination, and estimation of PD severity (motor score of the Unified PD Rating Scale and Hoehn and Yahr stage). Five of 6 patients had a video-polysomnography recording that was scored according to international criteria. Patients included 3 women and 3 men with a mean (+/-SD) age of 66 +/- 12 years (range, 46-78 years). The mean (+/-SD) Unified PD Rating Scale score was 25 +/- 9 (range, 10-35) and the mean (+/-SD) Hoehn and Yahr stage was 2.5 +/- 1.0 (range, 1.0-4.0). Medications in these patients included levodopa (n = 6), dopamine agonists (n = 4), selective serotonin reuptake inhibitor antidepressants (n = 3), and hypnotics (n = 3). All patients had at least 1 concomitant sleep-wake disorder, including rapid eye movement sleep behavior disorder (n = 4) and insomnia (n = 4). In 2 of 6 patients, the latency between onset of PD and appearance of sleepwalking was more than 4 years. Neurodegenerative changes associated with PD at the brainstem level can affect the "ascending" control of state transition (leading to dissociated arousals from non-rapid eye movement and/or rapid eye movement sleep) and the "descending" control of locomotion and muscle tone, together giving rise to various sleep-associated behavioral disturbances including sleepwalking, rapid eye movement sleep behavior disorder, and overlap parasomnia.

  4. Auditory Dysfunction in Patients with Cerebrovascular Disease

    Directory of Open Access Journals (Sweden)

    Sadaharu Tabuchi

    2014-01-01

    Full Text Available Auditory dysfunction is a common clinical symptom that can induce profound effects on the quality of life of those affected. Cerebrovascular disease (CVD is the most prevalent neurological disorder today, but it has generally been considered a rare cause of auditory dysfunction. However, a substantial proportion of patients with stroke might have auditory dysfunction that has been underestimated due to difficulties with evaluation. The present study reviews relationships between auditory dysfunction and types of CVD including cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, cerebrovascular malformation, moyamoya disease, and superficial siderosis. Recent advances in the etiology, anatomy, and strategies to diagnose and treat these conditions are described. The numbers of patients with CVD accompanied by auditory dysfunction will increase as the population ages. Cerebrovascular diseases often include the auditory system, resulting in various types of auditory dysfunctions, such as unilateral or bilateral deafness, cortical deafness, pure word deafness, auditory agnosia, and auditory hallucinations, some of which are subtle and can only be detected by precise psychoacoustic and electrophysiological testing. The contribution of CVD to auditory dysfunction needs to be understood because CVD can be fatal if overlooked.

  5. Treatment of patients with von Willebrand disease

    Directory of Open Access Journals (Sweden)

    Tuohy E

    2011-04-01

    Full Text Available Emma Tuohy1, Emma Litt1, Raza Alikhan1,21Department of Haematology, University Hospital of Wales, Cardiff, UK; 2Haemophilia and Thrombosis Centre, University Hospital of Wales, Cardiff, UKAbstract: Von Willebrand disease (vWD is the most common hereditary bleeding disorder. The aim of therapy is to correct the dual hemostatic defect, due to defective platelet adhesion-aggregation and abnormal coagulation due to Factor VIII (FVIII deficiency. The choice of treatment depends on a number of factors, including the severity of the bleed, the procedure planned, the subtype and severity of the disease and the age and morbidity of the patient. Desmopressin (DDAVP is the treatment of choice for type 1 vWD as it increases endogenous release of FVIII and von Willebrand factor (vWF and is also used in some subtypes of type 2 vWD. In those patients in whom DDAVP is ineffective or contraindicated, levels can be restored by infusing vWF:FVIII concentrates. The role of antifibrinolytic treatment is an important adjunct to replacement therapy during minor or major surgery involving mucosal surfaces. The dosing and timing of vWF:FVIII concentrates is important depending on the nature of the surgical procedure. The role of secondary prophylaxis needs to be further defined.Keywords: von Willebrand disease, treatment, DDAVP 

  6. Obituary: Andrew Stephen Wilson, 1947-2008

    Science.gov (United States)

    Veilleux, Sylvain

    2009-01-01

    On 24 May 2008, Andrew Stephen Wilson passed away at the age of 61, in his home in Silver Spring, Maryland, from complications resulting from a painful spinal illness. Andrew was arguably one of the first truly multi-wavelength astronomers of his generation. His scientific work on active galactic nuclei [AGN] spanned the entire electromagnetic spectrum from the radio to the X-rays. Andrew was born in Doncaster, Yorkshire, England, on 26 March 1947. He was the younger of two brothers whose births were separated by the Second World War. His father, Norman, came from a relatively affluent family who were coal merchants. His mother, Mary, came from a less comfortable background, one of seven children, daughter of a skilled cabinet maker/French polisher, who went through a very hard time during the depression. As a teacher, she placed enormous value on hard work and education as a way of gaining advancement in life. When Andrew was four, the family moved to Skipton, a nice market town in the Yorkshire dales. Andrew went to a small village school until age eleven when he entered Ermysted's Grammar School. He was an enthusiastic soccer and cricket player. He never lost his enthusiasm for soccer and supported the local soccer team, Leeds United, for all his life. Andrew also followed the Yorkshire county cricket team. Andrew's interest in astronomy stemmed from the fact that at Ermysted's Grammar School someone donated a four-inch refracting telescope, so he and his friends used to go back in the evenings to investigate the rings of Saturn, the moons of Jupiter, and various nebulae. While an undergraduate at Cambridge, Andrew joined the astronomy club and ground an 8-inch mirror by hand as a part of a telescope that he set up in the backyard of his parents' house. Andrew spent hours observing with this telescope, and it was the wonder of the family. At Cambridge, Andrew obtained his bachelor's degree with first-class honors in 1969. During a short visit in London with his

  7. Nambu-Jona-Lasinio model with Wilson fermions

    DEFF Research Database (Denmark)

    Rantaharju, Jarno; Drach, Vincent; Pica, Claudio

    2017-01-01

    We present a lattice study of a Nambu-Jona-Lasinio (NJL) model using Wilson fermions. Four-fermion interactions are a natural part of several extensions of the Standard Model, appearing as a low-energy description of a more fundamental theory. In models of dynamical electroweak symmetry breaking ...

  8. Are scattering amplitudes dual to super Wilson loops?

    CERN Document Server

    Belitsky, A V; Sokatchev, E

    2012-01-01

    The MHV scattering amplitudes in planar N=4 SYM are dual to bosonic light-like Wilson loops. We explore various proposals for extending this duality to generic non-MHV amplitudes. The corresponding dual object should have the same symmetries as the scattering amplitudes and be invariant to all loops under the chiral half of the N=4 superconformal symmetry. We analyze the recently introduced supersymmetric extensions of the light-like Wilson loop (formulated in Minkowski space-time) and demonstrate that they have the required symmetry properties at the classical level only, up to terms proportional to field equations of motion. At the quantum level, due to the specific light-cone singularities of the Wilson loop, the equations of motion produce a nontrivial finite contribution which breaks some of the classical symmetries. As a result, the quantum corrections violate the chiral supersymmetry already at one loop, thus invalidating the conjectured duality between Wilson loops and non-MHV scattering amplitudes. W...

  9. BOOK REVIEW: Democracy and Political Life in Nigeria | Wilson ...

    African Journals Online (AJOL)

    In this review of Victor Dike's book - \\"Democracy and Political Life in Nigeria\\", Inam Wilson underscores the author's attempts to draw a connection between Nigeria's chequered political history and her present economic trajectory to explain why Nigeria is today facing numerous sociopolitical and economic challenges, ...

  10. Municipal Broadband in Wilson, North Carolina: A Study

    Science.gov (United States)

    O'Boyle, Timothy

    2012-01-01

    Relatively little empirical attention has been paid to the political economy of publicly-retailed fiber-optic broadband internet service. To address this gap in the literature, this dissertation examines the history, dynamics and trends in the municipal broadband movement. In specific, Wilson, North Carolina's Greenlight service is examined in…

  11. String theory duals of Wilson loops from Higgsing

    Science.gov (United States)

    Lietti, Marco; Mauri, Andrea; Penati, Silvia; Zhang, Jia-ju

    2017-08-01

    For three-dimensional ABJ(M) theories and N=4 Chern-Simons-matter quiver theories, we construct two sets of 1/2 BPS Wilson loop operators by applying the Higgsing procedure along independent directions of the moduli space, and choosing different massive modes. For theories whose dual M-theory description is known, we also determine the corresponding spectrum of 1/2 BPS M2-brane solutions. We identify the supercharges in M-theory and field theory, as well as the supercharges preserved by M2-/anti-M2-branes and 1/2 BPS Wilson loops. In particular, in N=4 orbifold ABJM theory we find pairs of different 1/2 BPS Wilson loops that preserve exactly the same set of supercharges. In field theory they arise by Higgsing with the choice of either particles or antiparticles, whereas in the dual description they correspond to a pair of M2-/anti-M2-branes localized at different positions in the compact space. This result enlightens the origin of classical Wilson loop degeneracy in these theories, already discussed in arXiv:1506.07614. A discussion on possible scenarios that emerge by comparison with localization results is included.

  12. Anaemia and blood transfusion in the ICU | Wilson | Southern ...

    African Journals Online (AJOL)

    Southern African Journal of Critical Care. Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 20, No 1 (2004) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Anaemia and blood transfusion in the ICU. GS Wilson. Abstract.

  13. Rodin, Patton, Edison, Wilson, Einstein: Were They Really Learning Disabled?

    Science.gov (United States)

    Adelman, Kimberly A.; Adelman, Howard S.

    1987-01-01

    The practice of posthumously diagnosing historical figures is discussed. Emphasis is on the unsatisfactory nature of evidence found for those diagnosed as learning-disabled or dyslexic and the possibility of other explanations for identified problems. Posthumous diagnoses of Auguste Rodin, George Patton, Thomas Edison, Woodrow Wilson, and Albert…

  14. Caring for Patients With Intractable Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Masako Nagase

    2014-08-01

    Full Text Available This is a qualitative descriptive study examining nurses’ attitudes about caring for patients with intractable neurological diseases, with a focus on dedication and conflicts. Semistructured interviews were conducted on 11 nurses with more than 5 years of clinical experience in addition to more than 3 years of experience in neurology wards. Senior nursing officers from each hospital selected the participants. In general, these nurses expressed distress over the inevitable progression of disease. Nurses talked about the “basis of dedication,” “conflicts with dedication,” “reorganization for maintaining dedication,” and “the reason for the change from conflict to commitment.” “Reorganization for maintaining dedication” meant that nurses were able to handle the prospect of rededicating themselves to their patients. Furthermore, “the reason for the change from conflict to commitment” referred to events that changed nurses’ outlooks on nursing care, their pride as nurses, or their learning experiences. They felt dedicated and conflicted both simultaneously and separately. While committing to their patients’ physical care, nurses were empowered to think positively and treat patients with dignity in spite of the care taking much time and effort, as well as entailing considerable risk.

  15. Olfactory training in patients with Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Antje Haehner

    Full Text Available OBJECTIVE: Decrease of olfactory function in Parkinson's disease (PD is a well-investigated fact. Studies indicate that pharmacological treatment of PD fails to restore olfactory function in PD patients. The aim of this investigation was whether patients with PD would benefit from "training" with odors in terms of an improvement of their general olfactory function. It has been hypothesized that olfactory training should produce both an improved sensitivity towards the odors used in the training process and an overall increase of olfactory function. METHODS: We recruited 70 subjects with PD and olfactory loss into this single-center, prospective, controlled non-blinded study. Thirty-five patients were assigned to the olfactory training group and 35 subjects to the control group (no training. Olfactory training was performed over a period of 12 weeks while patients exposed themselves twice daily to four odors (phenyl ethyl alcohol: rose, eucalyptol: eucalyptus, citronellal: lemon, and eugenol: cloves. Olfactory testing was performed before and after training using the "Sniffin' Sticks" (thresholds for phenyl ethyl alcohol, tests for odor discrimination, and odor identification in addition to threshold tests for the odors used in the training process. RESULTS: Compared to baseline, trained PD patients experienced a significant increase in their olfactory function, which was observed for the Sniffin' Sticks test score and for thresholds for the odors used in the training process. Olfactory function was unchanged in PD patients who did not perform olfactory training. CONCLUSION: The present results indicate that olfactory training may increase olfactory sensitivity in PD patients.

  16. A Ramanujan-type measure for the Askey-Wilson polynomials

    Science.gov (United States)

    Atakishiyev, Natig M.

    1995-01-01

    A Ramanujan-type representation for the Askey-Wilson q-beta integral, admitting the transformation q to q(exp -1), is obtained. Orthogonality of the Askey-Wilson polynomials with respect to a measure, entering into this representation, is proved. A simple way of evaluating the Askey-Wilson q-beta integral is also given.

  17. Chronic Obstructive Pulmonary Disease in Elderly Patients.

    Science.gov (United States)

    Cortopassi, Felipe; Gurung, Puncho; Pinto-Plata, Victor

    2017-11-01

    Chronic obstructive pulmonary disease (COPD) is prevalent in the elderly population, with high impact on quality of life, morbidity, and mortality. The diagnosis is usually made based on symptoms and spirometry values that support the presence of airflow obstruction. However, the condition is frequently underdiagnosed. COPD is associated with premature aging and several other medical conditions that can partially explain its underdiagnosis and management. There are several pharmacologic and nonpharmacologic interventions proven to be effective in ameliorating the symptoms of COPD. Appropriate drug delivery and reduction of side effects is also pivotal in the management of patients with COPD. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Moyamoya Disease with Coexistent Hypertriglyceridemia in Pediatric Patient

    OpenAIRE

    Jacqueline Chan; Fabiola D’Ambrosio Rodriguez; Deepank Sahni; Claudia Boucher-Berry

    2016-01-01

    Moyamoya disease is a rare chronic and progressive cerebrovascular disease of the arteries of the circle of Willis that can affect children and adults. It has been associated with multiple diseases, including immunologic, like Graves’ disease, diabetes mellitus, and SLE. Hyperlipidemia has been recognized in patients with Moyamoya disease with an incidence of 27–37%. However, no case in pediatric patients has been reported of the coexistence of Moyamoya disease and hyperlipidemia. Here we pre...

  19. Lower Muscle Endurance in Patients with Alcoholic Liver Disease

    Science.gov (United States)

    Andersen, Henning; Aagaard, Niels K.; Jakobsen, Johannes; Dorup, Inge; Vilstrup, Hendrik

    2012-01-01

    Patients with alcoholic liver disease often complain of restricted physical capacity, which could be due to decreased muscle endurance. The aim of this study was to assess the muscular endurance in patients with alcoholic liver disease. In a cross sectional study, 24 patients with alcoholic liver disease and 22 controls were evaluated using…

  20. New knowledge of genetic pathogenesis of hemochromatosis and Wilson's disease.

    Science.gov (United States)

    Bacon, B R; Schilsky, M L

    1999-01-01

    Discovery of the gene for WD has greatly enhanced our understanding of this disorder at the cellular level and has set the stage for future testing of new modes of therapy. Improvements in analytic methods for detecting mutations in genomic DNA will someday enable a rapid and cost-effective method of screening for this disorder. Until then, the time-tested clinical and biochemical evaluation, including measurement of ceruloplasmin oxidase activity, slit-lamp examination for Kayser-Fleischer rings, and measurement of hepatic copper content, will continue to remain the standard for establishing the diagnosis of WD.

  1. Middle-aged heterozygous carriers of Wilson's disease do not ...

    Indian Academy of Sciences (India)

    . Rudnicka2 A. Czlonkowska1 2. Institute of Psychiatry and Neurology, Second Department of Neurology, 02–957 Warsaw, Poland; Medical University of Warsaw, Department of Experimental and Clinical Pharmacology, 00–325 Warsaw, ...

  2. Wilson-Mikity syndrome in a newborn: findings of initial and follow-up high-resolution CT

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Young Chil; Shin, Hyun Joon; Hong, Seong Jin [Konkuk University Chungju Hospital, Chungju (Korea, Republic of)

    2005-11-15

    Wilson-Mikity Syndrome, a form of chronic lung disease, is rarely developed with the widespread use of mechanical ventilaton. There has always been difficulty distinguishing it from bronchopulmonary dysplasia. The etiology and pathogenesis of this disease are still unknown. There are no reports in Korean literature about high-resolution (HR) CT follow-up of this disease. Diffuse interstitial thickening, which was noted on the initial examination, decreased, but some focal hyperinflations remained on follow-up HRCT. Further studies with HRCT will help to understand the progression of the disease, and will help to develop treatment and management programs.

  3. Exercise training for patients with cardiovascular disease.

    Science.gov (United States)

    Casillas, J M; Gremeaux, V; Damak, S; Feki, A; Pérennou, D

    2007-07-01

    This review surveys effort training, a validated and recommended therapy, in patients with atheromatous cardiovascular disease. This true therapy reduces mortality by 25-35%, reduces clinical manifestations and complications (rhythm problems, thrombosis) and improves physical capacity, reintegration and quality of life. The effects are essentially linked to improved metabolic performance of muscles and reduced endothelial dysfunction, insulin resistance and neurohormonal abnormalities. Training also has an impact on the evolution of major risk factors, especially diabetes and arterial hypertension. The risks are limited as long as the contraindications are respected and the programmes supervised. The indications (stable angina, chronic heart failure, peripheral arterial disease) should be described more precisely by taking into account functional criteria: physical deconditioning, exclusion, compliance, mood swings, and seriousness of risk factors. The training programme should be tailor made and based on evaluation of the patient's adaptation to effort, in terms of frequency, intensity and duration of the exercises. Various types of exercise include overall or segmental physical training; concentric, eccentric, even isokinetic muscle contraction exercises; and proprioceptive rehabilitation. However, knowledge is lacking about the molecular mechanisms of the effects of training, the most effective intensity of effort, and strategies to develop physical activity in this ever-growing population for both primary and secondary prevention.

  4. [Hyperhomocysteinemia in patients with cardiovascular disease].

    Science.gov (United States)

    Baszczuk, Aleksandra; Kopczyński, Zygmunt

    2014-01-02

    Homocysteine (Hcy) is an endogenous, non-structural protein, a sulfur-containing amino acid emerging on the pathway of methionine and cysteine, actively involved in numerous biochemical reactions. Total concentration of homocysteine in plasma of healthy humans is low and its level is between 5.0 and 15.0 mmol/l, assessed with the use of HPLC, or 5.0-12.0 mmol/l, using immunoassay methods. Higher concentration of this amino acid in blood is called hyperhomocysteinemia. Hyperhomocysteinemia is significantly correlated with cardiovascular disease and its complications: heart attacks and strokes. It is believed that hyperhomocysteinemia damages endothelial cells, reduces the flexibility of vessels, and adversely affects the process of hemostasis. In addition, hyperhomocysteinemia enhances the adverse effects of risk factors such as hypertension, smoking, and impaired glucose, lipid and lipoprotein metabolism, as well as promoting the development of inflammation. The concentration of homocysteine can be effectively lowered by supplementation with folic acid and vitamins B12 and B6. However, intervention studies conducted in the past decade did not confirm the clinical benefit of vitamin therapy lowering the level of homocysteine in blood of patients with cardiovascular disease. Moreover, there is not clear evidence from genetic studies that the presence of the gene for MTFHR polymorphism 677C>T, which is one of the most common causes of hyperhomocysteinemia, is also associated with the development of cardiovascular disease. These results led the researchers to discuss the role of homocysteine in the development and treatment of cardiovascular disease as well as the need for further research on this issue.

  5. Hyperhomocysteinemia in patients with cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Aleksandra Baszczuk

    2014-01-01

    Full Text Available Homocysteine (Hcy is an endogenous, non-structural protein, a sulfur-containing amino acid emerging on the pathway of methionine and cysteine, actively involved in numerous biochemical reactions. Total concentration of homocysteine in plasma of healthy humans is low and its level is between 5.0 and 15.0 mmol/l, assessed with the use of HPLC, or 5.0–12.0 mmol/l, using immunoassay methods. Higher concentration of this amino acid in blood is called hyperhomocysteinemia. Hyperhomocysteinemia is significantly correlated with cardiovascular disease and its complications: heart attacks and strokes. It is believed that hyperhomocysteinemia damages endothelial cells, reduces the flexibility of vessels, and adversely affects the process of hemostasis. In addition, hyperhomocysteinemia enhances the adverse effects of risk factors such as hypertension, smoking, and impaired glucose, lipid and lipoprotein metabolism, as well as promoting the development of inflammation. The concentration of homocysteine can be effectively lowered by supplementation with folic acid and vitamins B12 and B6. However, intervention studies conducted in the past decade did not confirm the clinical benefit of vitamin therapy lowering the level of homocysteine in blood of patients with cardiovascular disease. Moreover, there is not clear evidence from genetic studies that the presence of the gene for MTFHR polymorphism 677C>T, which is one of the most common causes of hyperhomocysteinemia, is also associated with the development of cardiovascular disease. These results led the researchers to discuss the role of homocysteine in the development and treatment of cardiovascular disease as well as the need for further research on this issue.

  6. Neuroimaging findings in Mowat-Wilson syndrome

    DEFF Research Database (Denmark)

    Garavelli, Livia; Ivanovski, Ivan; Caraffi, Stefano Giuseppe

    2017-01-01

    of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined. METHODS: Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough...... review of published cases, and evaluated genotype-phenotype correlations. RESULTS: Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white...

  7. The Expert Patient and Chronic Respiratory Diseases

    Directory of Open Access Journals (Sweden)

    Louis-Philippe Boulet

    2016-01-01

    Full Text Available The concept of “expert patient” has been developed in the last two decades to define a patient who has a significant knowledge of his/her disease and treatment in addition to self-management skills. However, this concept has evolved over the last years, and these patients are now considered, not only to be more efficient in the management of their own condition and communicating effectively with health professionals, but to also act as educators for other patients and as resources for the last, provide feedback on care delivery, and be involved in the production and implementation of practice guidelines, as well as in the development and conduct of research initiatives. There are some barriers, however, to the integration of this new contributor to the health care team, and specific requirements need to be considered for an individual to be considered as an expert. This new player has, however, a potentially important role to improve current care, particularly in respiratory health.

  8. INTESTINAL PERMEABILITY IN PATIENTS WITH CELIAC-DISEASE AND RELATIVES OF PATIENTS WITH CELIAC-DISEASE

    NARCIS (Netherlands)

    van Elburg, R. M.; Uil, J. J.; Mulder, C. J.; Heymans, H. S.

    1993-01-01

    The functional integrity of the small bowel is impaired in coeliac disease. Intestinal permeability, as measured by the sugar absorption test probably reflects this phenomenon. In the sugar absorption test a solution of lactulose and mannitol was given to the fasting patient and the

  9. INTESTINAL PERMEABILITY IN PATIENTS WITH CELIAC-DISEASE AND RELATIVES OF PATIENTS WITH CELIAC-DISEASE

    NARCIS (Netherlands)

    VANELBURG, RM; UIL, JJ; MULDER, CJJ; HEYMANS, HSA

    The functional integrity of the small bowel is impaired in coeliac disease. Intestinal permeability, as measured by the sugar absorption test probably reflects this phenomenon. In the sugar absorption test a solution of lactulose and mannitol was given to the fasting patient and the

  10. Exploring employment in consultation reports of patients with neuromuscular diseases

    NARCIS (Netherlands)

    Minis, M.A.H; Cup, E.H.C.; Heerkens, Y.H.; Engels, J.A.; Engelen, B.G.M. van; Oostendorp, R.A.B.

    2012-01-01

    Minis MA, Cup EH, Heerkens YF, Engels JA, van Engelen BG, Oostendorp RA. Exploring employment in consultation reports of patients with neuromuscular diseases. OBJECTIVES: To explore consultation reports for patient and employment characteristics and recommendations on employment regarding patients

  11. Gender disparities in disease-specific health status in postoperative patients with peripheral arterial disease

    DEFF Research Database (Denmark)

    Mastenbroek, M H; Hoeks, S E; Pedersen, Susanne S.

    2012-01-01

    To investigate gender disparities in disease-specific health status (HS), 3- and 5-year post-intervention in peripheral arterial disease (PAD) patients.......To investigate gender disparities in disease-specific health status (HS), 3- and 5-year post-intervention in peripheral arterial disease (PAD) patients....

  12. Time estimation in mild Alzheimer's disease patients

    Directory of Open Access Journals (Sweden)

    Nichelli Paolo

    2009-07-01

    Full Text Available Abstract Background Time information processing relies on memory, which greatly supports the operations of hypothetical internal timekeepers. Scalar Expectancy Theory (SET postulates the existence of a memory component that is functionally separated from an internal clock and other processing stages. SET has devised several experimental procedures to map these cognitive stages onto cerebral regions and neurotransmitter systems. One of these, the time bisection procedure, has provided support for a dissociation between the clock stage, controlled by dopaminergic systems, and the memory stage, mainly supported by cholinergic neuronal networks. This study aimed at linking the specific memory processes predicted by SET to brain mechanisms, by submitting time bisection tasks to patients with probable Alzheimer's disease (AD, that are known to present substantial degeneration of the fronto-temporal regions underpinning memory. Methods Twelve mild AD patients were required to make temporal judgments about intervals either ranging from 100 to 600 ms (short time bisection task or from 1000 to 3000 ms (long time bisection task. Their performance was compared with that of a group of aged-matched control participants and a group of young control subjects. Results Long time bisection scores of AD patients were not significantly different from those of the two control groups. In contrast, AD patients showed increased variability (as indexed by increased WR values in timing millisecond durations and a generalized inconsistency of responses over the same interval in both the short and long bisection tasks. A similar, though milder, decreased millisecond interval sensitivity was found for elderly subjects. Conclusion The present results, that are consistent with those of previous timing studies in AD, are interpreted within the SET framework as not selectively dependent on working or reference memory disruptions but as possibly due to distortions in different

  13. Exercise manual for liver disease patients.

    Science.gov (United States)

    Limongi, Vivian; Dos Santos, Daniele Costa; de Oliveira da Silva, Aurea Maria; Boin, Ilka de Fátima Santana Ferreira; Stucchi, Raquel Silveira Bello

    2016-06-24

    To increase inspiratory muscle strength and improve the quality of life of candidates for liver transplantation. Twenty-three candidates for liver transplantation participated in the control group and 14 made up the intervention group. The control group consisted of 18 men and 5 women, body mass index (BMI) 27.3 ± 4.5 kg/m(2) and Model for End-Stage Liver Disease (MELD) 18.2 ± 6.1. The intervention group consisted of 11 men and 3 women, BMI 28.6 ± 5.4 kg/m(2) and MELD 18 ± 4.5. The presence or absence of ascites was identified in the first patient evaluation and after three months. We evaluated maximal inspiratory pressure (MIP) and maximal expiratory pressure, spirometry, root mean square (RMS) of diaphragm and rectus abdominis, and the quality of life. The exercises were performed daily by patients at home for three months and were supervised at distance monthly. The manual consisted of diaphragmatic breathing exercises, diaphragmatic isometric exercise, Threshold IMT(®), lifting upper limbs with a bat and strengthening the abdomen. There was significant difference (P = 0.01) between the first (initial) and the third month (final) MIP in the control group and in the intervention group, but there was no difference (P = 0.45) between the groups. The RMS of the diaphragm was lower (P = 0.001) and the functional capacity was higher (P = 0.006) in the intervention group compared to the control. The general health and mental health domains received higher scores after three months in the control group (P = 0.01) and the intervention group (P = 0.004), but there was no significant difference between them. The comparison between the presence of initial ascites with the presence of ascites was performed after three months in the control group (P = 0.083) and intervention group (P = 0.31). There was no significant difference, in relation to the presence of ascites after three months between groups (P = 0.21). In the intervention group, patients with ascites at the end

  14. Nonalcoholic Fatty Liver Disease (NAFLD): Approach in the Adolescent Patient.

    Science.gov (United States)

    Roberts, Eve A; Yap, Jason

    2006-09-01

    Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver disease whose hallmark is the accumulation of large-droplet fat in hepatocytes. This metabolic disorder occurs mainly in overweight or obese individuals. The disease mechanism involves hyperinsulinemia and hepatic insulin resistance, not ethanol abuse. NAFLD may be the hepatic manifestation of the "metabolic syndrome" classically associated with type 2 diabetes mellitus and cardiovascular disease. NAFLD ranges from simple steatosis, which is the least rapidly progressing disorder, to nonalcoholic steatohepatitis to cirrhosis, which can evolve to chronic liver failure. The high prevalence of NAFLD in children has been recognized only in the past 5 to 10 years, as rates of childhood obesity have soared. Accordingly, the best strategies for diagnosis and treatment of childhood NAFLD are a work in progress and remain controversial. Weight reduction through a healthy diet and regular medium-intensity exercise is the mainstay of current treatment. Few research data are available to guide pharmacologic therapy. Certain points regarding management of childhood NAFLD require emphasis: It is a serious liver disease that requires detailed clinical investigation. Other liver diseases causing fatty liver and/or abnormal liver tests, notably Wilson disease and chronic viral hepatitis, need to be excluded. Liver biopsy can provide critical diagnostic and staging information. Associated genetic or endocrine disorders need to be identified. Treatment should begin with a low-glycemic index diet that provides adequate nutrients but is low in harmful fats and eliminates foods causing postprandial hyperglycemia. Initially, this can target two to three problem foods so that it is easy for the adolescent to follow. Regular exercise suited to the capabilities and interests of the teenager should be added to the daily routine. Where possible, a team approach, including a dietician and psychologist, should be utilized, as

  15. Exact results for Wilson loops in arbitrary representations

    Energy Technology Data Exchange (ETDEWEB)

    Fiol, Bartomeu; Torrents, Genís [Departament de Física Fonamental i Institut de Ciències del Cosmos, Universitat de Barcelona,Martí i Franquès 1, 08028 Barcelona, Catalonia (Spain)

    2014-01-08

    We compute the exact vacuum expectation value of 1/2 BPS circular Wilson loops of N=4 U(N) super Yang-Mills in arbitrary irreducible representations. By localization arguments, the computation reduces to evaluating certain integrals in a Gaussian matrix model, which we do using the method of orthogonal polynomials. Our results are particularly simple for Wilson loops in antisymmetric representations; in this case, we observe that the final answers admit an expansion where the coefficients are positive integers, and can be written in terms of sums over skew Young diagrams. As an application of our results, we use them to discuss the exact Bremsstrahlung functions associated to the corresponding heavy probes.

  16. Improved quasi parton distribution through Wilson line renormalization

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jiunn-Wei [Department of Physics, Center for Theoretical Sciences, and Leung Center for Cosmology and Particle Astrophysics, National Taiwan University, Taipei, 106, Taiwan (China); Center for Theoretical Physics, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Ji, Xiangdong [INPAC, Department of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai, 200240 (China); Maryland Center for Fundamental Physics, Department of Physics, University of Maryland, College Park, MD 20742 (United States); Zhang, Jian-Hui, E-mail: jianhui.zhang@physik.uni-regensburg.de [Institut für Theoretische Physik, Universität Regensburg, D-93040 Regensburg (Germany)

    2017-02-15

    Recent developments showed that hadron light-cone parton distributions could be directly extracted from spacelike correlators, known as quasi parton distributions, in the large hadron momentum limit. Unlike the normal light-cone parton distribution, a quasi parton distribution contains ultraviolet (UV) power divergence associated with the Wilson line self energy. We show that to all orders in the coupling expansion, the power divergence can be removed by a “mass” counterterm in the auxiliary z-field formalism, in the same way as the renormalization of power divergence for an open Wilson line. After adding this counterterm, the quasi quark distribution is improved such that it contains at most logarithmic divergences. Based on a simple version of discretized gauge action, we present the one-loop matching kernel between the improved non-singlet quasi quark distribution with a lattice regulator and the corresponding quark distribution in dimensional regularization.

  17. New supersymmetric Wilson loops in ABJ(M) theories

    Energy Technology Data Exchange (ETDEWEB)

    Cardinali, V., E-mail: cardinali@fi.infn.it [Dipartimento di Fisica, Universita di Firenze and INFN Sezione di Firenze, Via G. Sansone 1, 50019 Sesto Fiorentino (Italy); Griguolo, L., E-mail: griguolo@fis.unipr.it [Dipartimento di Fisica, Universita di Parma and INFN Gruppo Collegato di Parma, Viale G.P. Usberti 7/A, 43100 Parma (Italy); Martelloni, G., E-mail: martelloni@fi.infn.it [Dipartimento di Fisica, Universita di Firenze and INFN Sezione di Firenze, Via G. Sansone 1, 50019 Sesto Fiorentino (Italy); Seminara, D., E-mail: seminara@fi.infn.it [Dipartimento di Fisica, Universita di Firenze and INFN Sezione di Firenze, Via G. Sansone 1, 50019 Sesto Fiorentino (Italy)

    2012-12-05

    We present two new families of Wilson loop operators in N=6 supersymmetric Chern-Simons theory. The first one is defined for an arbitrary contour on the three dimensional space and it resembles the Zarembo construction in N=4 SYM. The second one involves arbitrary curves on the two dimensional sphere. In both cases one can add certain scalar and fermionic couplings to the Wilson loop so it preserves at least two supercharges. Some previously known loops, notably the 1/2 BPS circle, belong to this class, but we point out more special cases which were not known before. They could provide further tests of the gauge/gravity correspondence in the ABJ(M) case and interesting observables, exactly computable by localization techniques.

  18. [Frequency of celiac disease among patients with psoriasis].

    Science.gov (United States)

    Calderón H, Perla; Valdés A, Pilar; Zemelman D, Viviana; Poniachik T, Jaime; Hurtado H, Carmen; Garmendia M, María Luisa; Abumohor G, Patricia; Echavarri P, María Cristina

    2007-10-01

    A possible relationship has been reported between psoriasis and celiac disease, with common pathogenic mechanisms that may need further investigation. To investigate the presence of clinical and serological markers for celiac disease in a group of Chilean psoriatic patients. We included 80 psoriatic patients (42 males) aged 16 to 79 years, whose serum was tested for antitransglutaminase antibodies (ATGA) and antiendomysial antibodies (AEMA). Patients with weakly positive AEMA tests were also tested for antigliadin antibodies (AGA). In six patients (7.5%), AEMA and AGA were positive and one patient was positive for ATGA. An upper gastrointestinal endoscopy and duodenal biopsy was offered to these six patients and five accepted the procedure. Only one had a pathological diagnosis of celiac disease. Only one of 80 patients with psoriasis had celiac disease (1.2%). Other four patients with positive serologic markers had a normal duodenal biopsy. This group of patients may have latent celiac disease and they should be followed up.

  19. Chiral symmetry on the lattice with Wilson fermions

    Energy Technology Data Exchange (ETDEWEB)

    Bochicchio, M.; Maiani, L.; Martinelli, G.; Rossi, G.; Testa, M.

    1985-12-16

    The chiral properties of the continuum limit of lattice QCD with Wilson fermions are studied. We show that a partially conserved axial current can be defined, satisfying the usual current algebra requirements. A proper definition of the chiral symmetry order parameter, <0 vertical stroke anti psi psi vertical stroke 0>, is given, and the chiral properties of composite operators are investigated. The implications of our analysis to the lattice determination of non-leptonic weak amplitudes are also discussed. (orig.).

  20. Disease and patient characteristics in NP-C patients: findings from an international disease registry

    Directory of Open Access Journals (Sweden)

    Patterson Marc C

    2013-01-01

    Full Text Available Abstract Background Niemann-Pick disease type C (NP-C is a rare neurovisceral disease characterized by progressive neurodegeneration and premature death. We report data recorded at enrolment in an ongoing international NP-C registry initiated in September 2009 to describe disease natural history, clinical course and treatment experience of NP-C patients in clinical practice settings. Methods The NPC Registry is a prospective observational cohort study. Participating sites are encouraged to evaluate all consecutive patients with a confirmed diagnosis of NP-C, regardless of their treatment status. All patients undergo clinical assessments and medical care as determined by their physicians. Data are collected through a secure internet-based data collection system. Results As of 19th March, 2012, 163 patients have been enrolled in centres across 14 European countries, Australia, Brazil and Canada. The mean (SD age at enrolment was 19.6 (13.0 years. In general there was a long lag time between the mean (SD age at neurological onset (10.9 (9.8 years and age at diagnosis (15.0 (12.2 years. Among all enrolled patients, 107 were diagnosed based on combined genetic testing and filipin staining. Sixteen (11% out of 145 patients with available age-at-neurological-onset data had early-infantile neurological onset, 45 (31% had late-infantile onset; 45 (31% had juvenile onset and 39 (27% had adolescent/adult onset. The frequencies of neonatal jaundice, hepatomegaly and/or splenomegaly during infancy were greatest among early-infantile patients, and decreased with increasing age at neurological onset. The most frequent neurological manifestations were: ataxia (70%, vertical supranuclear gaze palsy (VSGP; 70%, dysarthria (66%, cognitive impairment (62%, dysphagia (52%. There were no notable differences in composite NP-C disability scores between age-at-neurological-onset groups. Miglustat therapy at enrolment was recorded in 117/163 (72% patients. Conclusions

  1. Wilson Martins: between the intelligentsia and the university (1951

    Directory of Open Access Journals (Sweden)

    Névio de Campos

    2012-05-01

    Full Text Available Abstract The purpose of this article is to analyze the presence of Ortega y Gasset in the Parana’s State group during the 1950s, especially his influence in the thinking of Wilson Martins, and to emphasize the debate on the ideas of the intellectual and the university. The article discusses about the contributions of this Parana’s thinker on the Parana’s university teaching constituting and organizing process, and emphasizes that the Wilson Martins’ role consisted in promoting the debate on the presence of the intellectual person in modern society, attributing the mission as guardian of the moral and herald of cultural renovation, without forgetting the Brazilian and European political-cultural context as the founding background to higher education. It bases itself on the speech entitled “The rebellion against intelligence and the mission of the university”, that occurred at the University of Parana in 1951, and on the work The History of Brazilian Intelligence, written by Wilson Martins.

  2. The epsilon regime with twisted mass Wilson fermions

    CERN Document Server

    Bar, Oliver; Shindler, Andrea

    2010-01-01

    We investigate the leading lattice spacing effects in mesonic two-point correlators computed with twisted mass Wilson fermions in the epsilon-regime. By generalizing the procedure already introduced for the untwisted Wilson chiral effective theory, we extend the continuum chiral epsilon expansion to twisted mass WChPT. We define different regimes, depending on the relative power counting for the quark masses and the lattice spacing. We explicitly compute, for arbitrary twist angle, the leading O(a^2) corrections appearing at NLO in the so-called GSM^* regime. As in untwisted WChPT, we find that in this situation the impact of explicit chiral symmetry breaking due to lattice artefacts is strongly suppressed. Of particular interest is the case of maximal twist, which corresponds to the setup usually adopted in lattice simulations with twisted mass Wilson fermions. The formulae we obtain can be matched to lattice data to extract physical low energy couplings, and to estimate systematic uncertainties coming from ...

  3. Nutrition management in the adult patient with Crohn's disease ...

    African Journals Online (AJOL)

    Malnutrition, nutrient deficiencies and osteoporosis are common in patients with Crohn's disease, regardless of disease activity. While the role of diet in the pathogenesis of the disease remains inconclusive, upon diagnosis, nutrition therapy plays an integral role in patient care. Successful nutrition intervention involves ...

  4. Screening for celiac disease in patients with osteoporosis.

    Science.gov (United States)

    Legroux-Gérot, Isabelle; Leloire, Olivier; Blanckaert, Franck; Tonnel, François; Grardel, Bruno; Ducrocq, Jean-Louis; Cortet, Bernard

    2009-03-01

    Whether patients with osteoporosis should be screened for celiac disease is controversial. The objective of this study was to measure the prevalence of asymptomatic celiac disease in a cohort of patients with osteoporosis. We studied 140 patients (133 postmenopausal women and 7 men) aged 40-75 years (mean age, 62.9+/-9.4 years) with primary osteoporosis diagnosed by absorptiometry (spine or hip T-score celiac disease in our cohort of patients with osteoporosis. Despite the small sample size, our results cast doubt on the need for celiac-disease screening in osteoporotic patients who have no gastrointestinal symptoms.

  5. POLYCYSTIC KIDNEY DISEASE IN A PATIENT WITH ...

    African Journals Online (AJOL)

    hi-tech

    2003-01-01

    Jan 1, 2003 ... Autosomal dominant polycystic kidney disease is a multisystem disease involving many organs. An association with other diseases such as tuberous sclerosis, von Hippel-Lindau disease and Marfan syndrome have been previously described. We describe a 35 year old female with achondroplasia who ...

  6. The Mount Wilson-University of California Connection from Hussey and Seares to Mayall and Olin Wilson

    Science.gov (United States)

    Osterbrock, D. E.

    2004-12-01

    George Ellery Hale, who founded Mount Wilson Solar Observatory, first visited Lick Observatory in 1890, soon after his graduation from MIT. After his parents' deaths, when he began openly planning a Yerkes Observatory ``expedition" to California, Hale's friend James E. Keeler, then Lick Observatory Director, invited him (in 1899) to locate it on Mt.Hamilton. Hale thanked him, but replied that sites further south would have more clear weather. He had probably already decided on Mount Wilson. There were many close connections between the University of California and Mount Wilson Observatory from that time right up to the present. W.J. Hussey was the Lick astronomer who carried out the official site survey that confirmed Mount Wilson as the best site. Harold Palmer (UC Astronomy PhD 1903) was the first new staff member Hale hired, but he only lasted a few months. The two main reasons for the continuing connection were the geographical proximity of Pasadena and the Bay Area, and the fact that for many years UC was the outstanding graduate astronomy department in the country, producing numerous well trained observational research astronomers. However in the early years the reasons were more complicated. After Palmer, the next three hired at MWO were Arthur King, the first UC Physics PhD (1903); Harold Babcock, (UC Engineering BS 1907); and F.H. Seares (UC Astronomy BS 1895). Harold Babcock trained his son in astronomy almost from birth, and Horace (UC Astronomy PhD 1938) joined the MWO staff after World War II and became its Director in 1964. Palmer and Edward Fath (UC PhD 1909) were less successful at MWO and soon departed. These and numerous other MWO astronomers with UC backgrounds will be mentioned, and their careers discussed.

  7. Prevalence of mucocutaneous findings in Celiac disease patients

    Directory of Open Access Journals (Sweden)

    Derya Yayla

    2015-12-01

    Full Text Available Background and Design: Celiac disease is an immune-mediated enteropathy which develops as a result of exposure to gluten in food products in individuals with a genetic predisposition. Gastrointestinal and extra-gastrointestinal clinical findings can be seen in these patients. An increased frequence of autoimmune diseases has been reported in patients with celiac disease. Some dermatological diseases, such as dermatitis herpetiformis, vitiligo, psoriasis, alopecia areata and recurrent aphthous stomatitis have been reported to be more common among patients with celiac disease. However, there are no controlled studies on this subject. The aim of this study was to identify the mucocutaneous symptoms seen in celiac patients and to compare these findings with a control group. Materials and Methods: Forty-nine celiac patients and 54 age-and sex-matched healthy volunteers were included in the study. In the patient group, celiac disease history, height and weight parameters, the medications of the patients, compliance to a gluten-free diet, concomitant skin disorders and additional illnesses were questioned; height and weight parameters, diagnosed illnesses, and medications were questioned in the control group. Dermatological analyses were performed in all participants. Results: Mucocutaneous findings were found to be present in 38 patients (77.6% in the celiac patient group and in 31 (57.4% individuals in the control group. The presence of mucocutaneous findings in celiac patients was significantly more common than in the control group. While immune-mediated mucocutaneous diseases were detected in 8 celiac patients (16.3%, none of the individuals in the control group had immune-mediated mucocutaneous diseases and a statistically significant difference was found between the two groups. Conclusion: In celiac patients, the frequency of immune-mediated mucocutaneous diseases and all mucocutaneous diseases were found to be increased. Therefore, we suggest

  8. The Prevalence of Fabry Disease in Patients with Chronic Kidney Disease in Turkey: The TURKFAB Study

    OpenAIRE

    Kultigin Turkmen; Aydın Guclu; Garip Sahin; Ismail Kocyigit; Levent Demirtas; Fatih Mehmet Erdur; Erkan Sengül; Oktay Ozkan; Habib Emre; Faruk Turgut; Hilmi Unal; Murat Karaman; Cengiz Acıkel; Hasan Esen; Ebru Balli

    2016-01-01

    Background/Aims: Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of α-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. Methods: This prospective stud...

  9. Lumbar Spine Surgery in Patients with Parkinson Disease.

    Science.gov (United States)

    Schroeder, Joshua E; Hughes, Alexander; Sama, Andrew; Weinstein, Joseph; Kaplan, Leon; Cammisa, Frank P; Girardi, Federico P

    2015-10-21

    Parkinson disease is the second most common neurodegenerative condition. The literature on patients with Parkinson disease and spine surgery is limited, but increased complications have been reported. All patients with Parkinson disease undergoing lumbar spine surgery between 2002 and 2012 were identified. Patients' charts, radiographs, and outcome questionnaires were reviewed. Parkinson disease severity was assessed with use of the modified Hoehn and Yahr staging scale. Complications and subsequent surgeries were analyzed. Risk for reoperation was assessed. Ninety-six patients underwent lumbar spine surgery. The mean patient age was 63.0 years. The mean follow-up duration was 30.1 months. The Parkinson disease severity stage was Parkinson disease severity stage of ≥3 (p Parkinson disease is good, with improvement of spine-related pain. A larger prospective study is warranted. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

  10. Cardiovascular disease and cognitive function in maintenance hemodialysis patients

    Science.gov (United States)

    Cardiovascular disease (CVD) and cognitive impairment are common in dialysis patients. Given the proposed role of microvascular disease on cognitive function, particularly cognitive domains that incorporate executive functions, we hypothesized that prevalent systemic CVD would be associated with wor...

  11. Dobutamine Stress Echocardiography Safety in Chagas Disease Patients

    Directory of Open Access Journals (Sweden)

    Daniela do Carmo Rassi

    Full Text Available Abstract Background: A few decades ago, patients with Chagas disease were predominantly rural workers, with a low risk profile for obstructive coronary artery disease (CAD. As urbanization has increased, they became exposed to the same risk factors for CAD of uninfected individuals. Dobutamine stress echocardiography (DSE has proven to be an important tool in CAD diagnosis. Despite being a potentially arrhythmogenic method, it is safe for coronary patients without Chagas disease. For Chagas disease patients, however, the indication of DSE in clinical practice is uncertain, because of the arrhythmogenic potential of that heart disease. Objectives: To assess DSE safety in Chagas disease patients with clinical suspicion of CAD, as well as the incidence of arrhythmias and adverse events during the exam. Methods: Retrospective analysis of a database of patients referred for DSE from May/2012 to February/2015. This study assessed 205 consecutive patients with Chagas disease suspected of having CAD. All of them had their serology for Chagas disease confirmed. Results: Their mean age was 64±10 years and most patients were females (65.4%. No patient had significant adverse events, such as acute myocardial infarction, ventricular fibrillation, asystole, stroke, cardiac rupture and death. Regarding arrhythmias, ventricular extrasystoles occurred in 48% of patients, and non-sustained ventricular tachycardia in 7.3%. Conclusion: DSE proved to be safe in this population of Chagas disease patients, in which no potentially life-threatening outcome was found.

  12. Outcomes of Bowel Resection in Patients with Crohn's Disease.

    Science.gov (United States)

    Moghadamyeghaneh, Zhobin; Carmichael, Joseph C; Mills, Steven D; Pigazzi, Alessio; Stamos, Michael J

    2015-10-01

    There is limited data regarding outcomes of bowel resection in patients with Crohn's disease. We sought to investigate complications of such patients after bowel resection. The Nationwide Inpatient Sample databases were used to examine the clinical data of Crohn's patients who underwent bowel resection during 2002 to 2012. Multivariate regression analysis was performed to investigate outcomes of such patients. We sampled a total of 443,950 patients admitted with the diagnosis of Crohn's disease. Of these, 20.5 per cent had bowel resection. Among patients who had bowel resection, 51 per cent had small bowel Crohn's disease, 19.4 per cent had large bowel Crohn's disease, and 29.6 per cent had both large and small bowel Crohn's disease. Patients with large bowel disease had higher mortality risk compared with small bowel disease [1.8% vs 1%, adjusted odds ratio (AOR): 2.42, P Crohn's disease (AOR: 1.90, P Crohn's disease, 20.5 per cent underwent bowel resection during 2002 to 2012. Although colonic disease has a higher mortality risk, small bowel disease has a higher risk of postoperative fistula.

  13. [Nursing care in elderly patients with cardiovascular disease].

    Science.gov (United States)

    Enç, Nuray; Öz Alkan, Havva

    2017-09-01

    Aging is a process that has biological, physiological, psychological, sociological and chronological dimensions and can be defined from different directions. The incidence of cardiovascular diseases such as hypertension, coronary heart disease, heart failure, dysrhythmia and heart valve diseases is increasing with age. Cardiovascular diseases are the most common cause of death in people over 65 years of age. It also causes serious health problems and poses a significant burden on the health care system. Nurses have important responsibilities in the care of the elderly patients with cardiovascular system disease. Appropriate nursing care for elderly patient provides positive contributions to patient care outcomes.

  14. Prevalence and overlap of Disease Management Program diseases in older hospitalized patients

    DEFF Research Database (Denmark)

    Juul-Larsen, Helle Gybel; Petersen, Janne; Sivertsen, Ditte Maria

    2017-01-01

    of 4649 acutely hospitalized medical patients ≥65 years admitted to Copenhagen University Hospital, Hvidovre, Denmark, in 2012, and divided patients into six PD groups (type 2 diabetes, chronic obstructive pulmonary disease, cardiovascular disease, musculoskeletal disease, dementia and cancer), each......Many countries, like Denmark, have tailored Disease Management Programs (DMPs) based on patients having single chronic diseases [defined institutionally as "program diseases" (PDs)], which can complicate treatment for those with multiple chronic diseases. The aims of this study were (a) to assess...... defined by several ICD-10 codes predefined in the DMPs. Of these patients, 904 (19.4%) had 2 + PDs, and there were 47 different combinations of the six different PDs. The most prevalent pair of PDs was type 2 diabetes with cardiovascular disease in 203 (22.5%) patients, of whom 40.4% had an additional PD...

  15. Biomarkers in Serbian patients with Gaucher disease.

    Science.gov (United States)

    Sumarac, Zorica; Suvajdžić, Nada; Ignjatović, Svetlana; Majkić-Singh, Nada; Janić, Dragana; Petakov, Milan; Dorđević, Maja; Mitrović, Mirjana; Dajak, Marijana; Golubović, Milka; Rodić, Predrag

    2011-08-01

    The aim of the study was to evaluate the efficiency of the biomarkers chitotriosidase (Chito), total acid phosphatase (TACP), angiotensin converting enzyme (ACE) and ferritin in the diagnosis of Gaucher disease (GD) and to assess the utility of biomarkers for monitoring the effects of enzyme replacement therapy (ERT). Forty treatment-naive Gaucher patients were studied. 27/40 GP were put on ERT and monitored every 6 months. The baseline median values of Chito, TACP, ACE and ferritin were highly elevated in GP: 10216 nmol/mL/h, 26.1 U/L, 253 U/L, 515 μg/L, and 555 μg/L, respectively. The only significant difference between mild and moderate GP subgroups is observed for Chito activity (p=0.0116). During ERT, Chito showed the steepest decrease in regard to TACP and ACE, mainly within the first year (71.4%). Among these biomarkers, Chito proved to be the most useful biomarker for diagnosing GD and monitoring the ERT. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  16. Clinical Characteristics of Nocardia Infection in Patients with Rheumatic Diseases

    Science.gov (United States)

    Yamagata, Mieko; Hirose, Koichi; Ikeda, Kei; Nakajima, Hiroshi

    2013-01-01

    Although Nocardiosis has considerable recurrence and mortality rates, characteristics and risk factors of Nocardia infection have not been assessed in patients with rheumatic diseases. Here, we examined the characteristics and risk factors of Nocardia infection in rheumatic disease patients in our hospital. Ten rheumatic disease patients who developed Nocardia infection were identified by retrospectively reviewing the medical records. Possible predisposing factors for Nocardia infection were high-dose glucocorticoid treatment, concomitant use of immunosuppressants, preexisting pulmonary diseases, and diabetes mellitus. All patients had pulmonary Nocardiosis, and six of them had disseminated Nocardiosis when their pulmonary lesions were identified. PMID:24171035

  17. Genetic analysis of 55 northern Vietnamese patients with Wilson ...

    Indian Academy of Sciences (India)

    2017-12-19

    Dec 19, 2017 ... Center for Gene-Protein Research, Hanoi Medical University, Hanoi 100000, Vietnam; Department of Biochemistry, Hanoi Medical University, Hanoi 100000, Vietnam; Clinical Genetics Unit, Department of Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden ...

  18. Cardiovascular Disease Risk in Patients with Rheumatic Diseases.

    Science.gov (United States)

    Mackey, Rachel H; Kuller, Lewis H; Moreland, Larry W

    2017-02-01

    Evidence suggests the greater than 1.5 increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA) is related to an accelerated burden of subclinical atherosclerosis that develops before the diagnosis of RA. Dyslipidemia in RA is better quantified by lipoproteins and apolipoproteins than cholesterol levels. Current risk factors likely underestimate CVD risk partly by underestimating prior risk factor levels. To reduce CVD risk in RA, control disease activity and aggressively treat CVD risk factors. Some of the two-fold higher risk of heart failure and total mortality in RA may be due to myocardial disease caused by inflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Respiratory disease terminology: Discordance between pulmonologists and patients.

    Science.gov (United States)

    Singh, Nishtha; Singh, Sheetu; Jain, Nirmal Kumar; Singh, Virendra

    2017-01-01

    A number of local dialects and languages exist in India, which leads to a single disease being addressed by a number of names which may overlap with other disease names also. This creates misunderstanding and is a hindrance to effective patient-doctor communication. The paper aims to find out how effectively the name of the respiratory disease is communicated to the patient. The terminology used by patients to describe their disease was also noted at limited level. The study was conducted in the form of parallel cross-sectional surveys, among pulmonologists and patients. Among the members of the Indian Chest Society and those attending the National Conference on Pulmonary Diseases (NAPCON-2015), 1028 pulmonologists participated in the online survey which was the first part of the study. The term used to address the common respiratory disease was inquired in the survey. To find the response of patients, a questionnaire was given to the patients attending four respiratory disease clinics of a city. They were inquired about the name of respiratory disease they were suffering from. Pneumonia was the disease which was communicated with exact terminology by 898 (87.4%) doctors to their patients. In contrast, idiopathic pulmonary fibrosis was communicated with precise terminology by only 171 (16.6%) doctors. Pulmonary tuberculosis was exactly told by 708 (69%), asthma by 731 (71.1%), and chronic obstructive pulmonary disease by 593 (57.7%) doctors. However, only 17.6% of the 1122 patients participating in the survey had a knowledge of the name of disease they were suffering from. The exact terminology of the common respiratory diseases is not effectively used by many doctors and most of the patients. The study identifies an important gap in patient-doctor communication, and therefore, highlights the need of effective patient education.

  20. How might physical activity benefit patients with Parkinson disease?

    NARCIS (Netherlands)

    Speelman, A.D.; Warrenburg, B.P.C. van de; Nimwegen, M.L. van; Petzinger, G.M.; Munneke, M.; Bloem, B.R.

    2011-01-01

    Parkinson disease (PD) is a neurodegenerative disorder characterized by progressive motor and nonmotor impairments. These impairments incline many patients towards a sedentary lifestyle, which has many deleterious consequences. Accumulating evidence suggests that patients with PD might benefit from

  1. Rehabilitation of discharged patients with Chronic Obstructive Pulmonary Disease

    DEFF Research Database (Denmark)

    Morsø, Lars; Sall Jensen, Morten; von Plessen, Christian

    2017-01-01

    BACKGROUND: Rehabilitation after hospital stay implies several benefits for patients with chronic obstructive pulmonary disease (COPD); still few patients are referred and participate in rehabilitation programs. We conducted a case study to investigate the effects of interventions targeting...

  2. Physical Activity Recommendations in Patients with Chronic Obstructive Pulmonary Disease

    NARCIS (Netherlands)

    Hartman, Jorine E.; Boezen, H. Marike; Zuidema, Menno J.; de Greef, Mathieu H. G.; ten Hacken, Nick H. T.; Boezen, Hendrika

    2014-01-01

    Background: Physical activity recommendations are hardly studied in patients with chronic obstructive pulmonary disease (COPD), and specifically recommendations that are individualized to a patient's aerobic fitness level are not studied. Objectives: To compare individualized (relative) and

  3. Understanding valvular heart disease in patients with systemic autoimmune diseases.

    Science.gov (United States)

    Maksimowicz-McKinnon, Kathleen; Mandell, Brian F

    2004-11-01

    Specific systemic autoimmune diseases are associated with distict valvular heart disorders. We discuss the valvular disorders associated with rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid antibody syndrome, the seronegative spondyloarthropathies, the systemic vasculitides, and scleroderma.

  4. The quality of life at patients with coeliac disease

    OpenAIRE

    Fousková, Petra

    2008-01-01

    The bachelor's thesis deals with the coeliac disease and the quality of life with this disease. It's divided into two parts - a theoretical part and a practical part. The first, theoretical part, contains description of coeliac disease with symptoms, diagnostic procedures, therapy and the history of disease, too. The second part is experimental. The quality of life at the patients with coeliac disease was uncovered through the question blank. The data were evaluated and the results are descri...

  5. Ultrasonographic imaging of inflammatory bowel disease in pediatric patients

    Science.gov (United States)

    Chiorean, Liliana; Schreiber-Dietrich, Dagmar; Braden, Barbara; Cui, Xin-Wu; Buchhorn, Reiner; Chang, Jian-Min; Dietrich, Christoph F

    2015-01-01

    Inflammatory bowel disease (IBD) is one of the most common chronic gastrointestinal diseases in pediatric patients. Choosing the optimal imaging modality for the assessment of gastrointestinal disease in pediatric patients can be challenging. The invasiveness and patient acceptance, the radiation exposure and the quality performance of the diagnostic test need to be considered. By reviewing the literature regarding imaging in inflammatory bowel disease the value of ultrasound in the clinical management of pediatric patients is highlighted. Transabdominal ultrasound is a useful, noninvasive method for the initial diagnosis of IBD in children; it also provides guidance for therapeutic decisions and helps to characterize and predict the course of the disease in individual patients. Ultrasound techniques including color Doppler imaging and contrast-enhanced ultrasound are promising imaging tools to determine disease activity and complications. Comparative studies between different imaging methods are needed. PMID:25954096

  6. Psychosocial factors in patients with ischemic heart disease

    OpenAIRE

    Billing, Ewa

    1996-01-01

    PSYCHOSOClAL FACTORS IN PATIENTS WITH ISCHEMIC HEART DISEASE.Ewa Billing, Karolinska Institute, Danderyd Hospital, Department of Medicine, Danderyd, Sweden.. The aim of the study was to evaluate psychosocial variables in patients with ischemic heartdisease and the relationships between psychosocial variables and severity and prognosis of disease.Patients with stable angina pectoris and patients with a first myocardial infarction were included, and theevaluations were performed by two differen...

  7. Moyamoya Disease with Coexistent Hypertriglyceridemia in Pediatric Patient

    Directory of Open Access Journals (Sweden)

    Jacqueline Chan

    2016-01-01

    Full Text Available Moyamoya disease is a rare chronic and progressive cerebrovascular disease of the arteries of the circle of Willis that can affect children and adults. It has been associated with multiple diseases, including immunologic, like Graves’ disease, diabetes mellitus, and SLE. Hyperlipidemia has been recognized in patients with Moyamoya disease with an incidence of 27–37%. However, no case in pediatric patients has been reported of the coexistence of Moyamoya disease and hyperlipidemia. Here we present a case of a 9-year-old female diagnosed with Moyamoya disease after a stroke with incidental finding of familial hypercholesterolemia. This finding will make our patient a very unique case, since there has not been any reporting of Moyamoya disease and hypercholesterolemia association.

  8. Healthcare maintenance in elderly patients with inflammatory bowel disease.

    Science.gov (United States)

    Shrestha, Manish P; Ruel, Joannie; Taleban, Sasha

    2017-01-01

    The increasing number of older patients (age ≥60 years) with inflammatory bowel disease (IBD) highlights the importance of healthcare maintenance in this vulnerable population. Older IBD patients are more susceptible and have higher rates of many disease- and treatment-related adverse effects. Compared to younger IBD patients, older patients are at increased risk for infection, malignancy, bone disease, eye disease, malnutrition and thrombotic complications. Preventive strategies in the elderly differ from those in younger adults and are imperative. Changes to the immune system with aging can decrease the efficacy of vaccinations. Cancer screening guidelines in older IBD patients have to account for unique considerations, such as life expectancy, functional performance status, multimorbidity, financial status, and patient desires. Additionally, providers need to be vigilant in screening for osteoporosis, ocular disease, depression, and adverse events arising from polypharmacy.

  9. Cardiovascular Dysfunction in Patients with End-stage Liver Disease

    Directory of Open Access Journals (Sweden)

    Merceds Susan Mandell

    2008-07-01

    Full Text Available Most patients with advanced liver disease have a normal or even supernormal ejection fraction judged by echocardiogra-phy. Thus, physicians previously assumed that cardiac function was normal in most patients with liver disease. However, further investigation has uncovered multiple problems in cardiac performance that place patients at risk of heart failure. Patients with liver disease have defects in both systolic and diastolic function that only become obvious with physiologic stress such as liver transplantation. In addition there are additional defects in the electromechanical coupling of the heart that can have significant clinical consequences. These collective pathologic changes are termed “cirrhotic cardiomyopathy” and occur to some degree in all patients with liver disease. This review will explore the pathophysiology of cardiovascular changes in patients with end-stage liver disease.

  10. Patient-centered care in Parkinson's disease

    NARCIS (Netherlands)

    Eijk, M. van der

    2015-01-01

    Patient centeredness means providing care that is respectful of and responsive to individual patient preferences, needs and values, and ensuring that patient values guide all clinical decisions’.The concept assumes that both physicians and patients are experts; physicians in diagnostic and

  11. Celiac disease and other autoimmune diseases in patients with collagenous colitis.

    Science.gov (United States)

    Vigren, Lina; Tysk, Curt; Ström, Magnus; Kilander, Anders F; Hjortswang, Henrik; Bohr, Johan; Benoni, Cecilia; Larson, Lasse; Sjöberg, Klas

    2013-08-01

    Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Patients with CC answered questionnaires about demographic data and disease activity. The patient's files were scrutinized for information about autoimmune diseases. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjögren's syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.

  12. Higher rank ABJM Wilson loops from matrix models

    Energy Technology Data Exchange (ETDEWEB)

    Cookmeyer, Jonathan [Haverford College,370 Lancaster Avenue, Haverford, PA, 19041 (United States); Liu, James T. [Michigan Center for Theoretical Physics, Department of Physics, University of Michigan,450 Church Street, Ann Arbor, MI, 48109 (United States); Zayas, Leopoldo A. Pando [The Abdus Salam International Centre for Theoretical Physics,Strada Costiera 11, Trieste, 34014 (Italy)

    2016-11-21

    We compute the vacuum expectation values of 1/6 supersymmetric Wilson loops in higher dimensional representations of the gauge group in ABJM theory. We present results for the m-symmetric and m-antisymmetric representations by exploiting standard matrix model techniques. At leading order, in the saddle point approximation, our expressions reproduce holographic results from both D6 and D2 branes corresponding to the antisymmetric and symmetric representations, respectively. We also compute 1/N corrections to the leading saddle point results.

  13. The Nambu Jona-Lasinio model with Wilson fermions

    CERN Document Server

    Rantaharju, Jarno

    2017-01-01

    We present a lattice study of a Nambu Jona-Lasinio (NJL) model using Wilson fermions. Four fermion interactions are a natural part of several extensions of the Standard Model, appearing as a low energy description of a more fundamental theory. In models of dynamical electroweak symmetry breaking they are used to endow the Standard Model fermions with masses. In infrared conformal models these interaction, when sufficiently strong, can alter the dynamics of the fixed point, turning the theory into a (near) conformal model with desirable features for model building. As a first step toward the nonperturbative study of these models, we study the phase space of the ungauged NJL model.

  14. Syndrome parkinsonien secondaire à une maladie de Wilson chez ...

    African Journals Online (AJOL)

    Nous apportons une observation d'un cas de la maladie de Wilson, révélé par un syndrome parkinsonien. Le diagnostic a reposé sur les troubles neuropsychiques, la présence de l'anneau cornéen de Kayser-Fleischer, et les troubles du métabolisme du cuivre. Le scanner cérébral était normal, et l'IRM cérébrale a montré ...

  15. The Wilson flow and the finite temperature phase transition

    Energy Technology Data Exchange (ETDEWEB)

    Wandelt, M. [Department of Mathematics, School of Mathematics and Natural Sciences,Bergische Universität Wuppertal, Gaußstr. 20, 42119 Wuppertal (Germany); Knechtli, F. [Department of Physics, School of Mathematics and Natural Sciences,Bergische Universität Wuppertal, Gaußstr. 20, 42119 Wuppertal (Germany); Günther, M. [Department of Mathematics, School of Mathematics and Natural Sciences,Bergische Universität Wuppertal, Gaußstr. 20, 42119 Wuppertal (Germany)

    2016-10-12

    We consider the determination of the finite temperature phase transition in the Yang-Mills SU(3) gauge theory. We compute the difference of the spatial and temporal energy density at a physical Wilson flow time. This difference is zero in the confined phase and becomes non zero in the deconfined phase. We locate the phase transition by using a new technique based on an exponential smoothing spline. This method is an alternative to the determination of the phase transition based on the Polyakov loop susceptibility and can also be used with dynamical fermions.

  16. B-physics with $N_f=2$ Wilson fermions

    CERN Document Server

    Bernardoni, F; Bulava, J; Della Morte, M; Fritzsch, P; Garron, N; Gerardin, A; Heitger, J; von Hippel, G; Simma, H; Sommer, R

    2014-01-01

    We report the final results of the ALPHA collaboration for some B-physics observables: $f_B$, $f_{B_s}$ and $m_b$. We employ CLS configurations with 2 flavors of $O(a)$ improved Wilson fermions in the sea and pion masses ranging down to 190 MeV. The b-quark is treated in HQET to order $1/m_b$. The renormalization, the matching and the improvement were performed non-perturbatively, and three lattice spacings reaching $a=0.048$ fm are used in the continuum extrapolation.

  17. Dual conformal transformations of smooth holographic Wilson loops

    Energy Technology Data Exchange (ETDEWEB)

    Dekel, Amit [Nordita, KTH Royal Institute of Technology and Stockholm University, Roslagstullsbacken 23, SE-106 91 Stockholm (Sweden)

    2017-01-19

    We study dual conformal transformations of minimal area surfaces in AdS{sub 5}×S{sup 5} corresponding to holographic smooth Wilson loops and some other related observables. To act with dual conformal transformations we map the string solutions to the dual space by means of T-duality, then we apply a conformal transformation and finally T-dualize back to the original space. The transformation maps between string solutions with different boundary contours. The boundary contours of the minimal surfaces are not mapped back to the AdS boundary, and the regularized area of the surface changes.

  18. Respiratory disease terminology: Discordance between pulmonologists and patients

    Directory of Open Access Journals (Sweden)

    Nishtha Singh

    2017-01-01

    Full Text Available Context: A number of local dialects and languages exist in India, which leads to a single disease being addressed by a number of names which may overlap with other disease names also. This creates misunderstanding and is a hindrance to effective patient–doctor communication. Aims: The paper aims to find out how effectively the name of the respiratory disease is communicated to the patient. The terminology used by patients to describe their disease was also noted at limited level. Settings and Design: The study was conducted in the form of parallel cross-sectional surveys, among pulmonologists and patients. Methods: Among the members of the Indian Chest Society and those attending the National Conference on Pulmonary Diseases (NAPCON-2015, 1028 pulmonologists participated in the online survey which was the first part of the study. The term used to address the common respiratory disease was inquired in the survey. To find the response of patients, a questionnaire was given to the patients attending four respiratory disease clinics of a city. They were inquired about the name of respiratory disease they were suffering from. Results: Pneumonia was the disease which was communicated with exact terminology by 898 (87.4% doctors to their patients. In contrast, idiopathic pulmonary fibrosis was communicated with precise terminology by only 171 (16.6% doctors. Pulmonary tuberculosis was exactly told by 708 (69%, asthma by 731 (71.1%, and chronic obstructive pulmonary disease by 593 (57.7% doctors. However, only 17.6% of the 1122 patients participating in the survey had a knowledge of the name of disease they were suffering from. Conclusions: The exact terminology of the common respiratory diseases is not effectively used by many doctors and most of the patients. The study identifies an important gap in patient–doctor communication, and therefore, highlights the need of effective patient education.

  19. Chagas disease and systemic autoimmune diseases among Bolivian patients in Switzerland

    Directory of Open Access Journals (Sweden)

    Yves Jackson

    2018-02-01

    Full Text Available BACKGROUND Chronic cardiomyopathy occurs in 20-40% of the patients with Chagas disease. Autoimmune mechanisms may contribute to its pathogenesis. We diagnosed several cases of systemic autoimmune diseases among Bolivian migrants in Geneva with a high prevalence of Chagas disease. OBJECTIVES We tested the hypothesis of a clinical association between systemic autoimmune diseases and Chagas disease, particularly with the development of cardiomyopathy. METHODS We retrospectively searched the medical records of all Bolivian patients visiting Geneva University Hospitals between 2012 and 2015 for diagnosis of Chagas disease or systemic autoimmune diseases. FINDINGS Of the 2,189 eligible patients, 28 [1.3%; 95% confidence interval (CI = 0.9-1.9%] presented with systemic autoimmune disease. The Chagas status was known in 903 (41.3% patient, of whom 244 (27.0%; 95% CI = 24.2-30.0% were positive. Eight (28.6%; 95% CI = 15.3-47.1% of the 28 cases of systemic autoimmune disease had Chagas disease. We found no association between both entities (p = 1.000 or with Chagasic cardiomyopathy (p = 0.729. Moreover, there was no evidence of a temporal relationship between antiparasitic chemotherapy and the development of systemic autoimmune diseases. CONCLUSIONS Our results do not support a clinical association between chronic Chagas disease and systemic autoimmune diseases. However, prospective studies in areas endemic for Chagas disease should better assess the prevalence of systemic autoimmune diseases and thus a possible relationship with this infection.

  20. Chagas disease and systemic autoimmune diseases among Bolivian patients in Switzerland.

    Science.gov (United States)

    Jackson, Yves; Pula, Drenusha Vieira de Mello; Finckh, Axel; Chizzolini, Carlo; Chappuis, François

    2018-02-05

    Chronic cardiomyopathy occurs in 20-40% of the patients with Chagas disease. Autoimmune mechanisms may contribute to its pathogenesis. We diagnosed several cases of systemic autoimmune diseases among Bolivian migrants in Geneva with a high prevalence of Chagas disease. We tested the hypothesis of a clinical association between systemic autoimmune diseases and Chagas disease, particularly with the development of cardiomyopathy. We retrospectively searched the medical records of all Bolivian patients visiting Geneva University Hospitals between 2012 and 2015 for diagnosis of Chagas disease or systemic autoimmune diseases. Of the 2,189 eligible patients, 28 [1.3%; 95% confidence interval (CI) = 0.9-1.9%] presented with systemic autoimmune disease. The Chagas status was known in 903 (41.3%) patient, of whom 244 (27.0%; 95% CI = 24.2-30.0%) were positive. Eight (28.6%; 95% CI = 15.3-47.1%) of the 28 cases of systemic autoimmune disease had Chagas disease. We found no association between both entities (p = 1.000) or with Chagasic cardiomyopathy (p = 0.729). Moreover, there was no evidence of a temporal relationship between antiparasitic chemotherapy and the development of systemic autoimmune diseases. Our results do not support a clinical association between chronic Chagas disease and systemic autoimmune diseases. However, prospective studies in areas endemic for Chagas disease should better assess the prevalence of systemic autoimmune diseases and thus a possible relationship with this infection.

  1. On some 1/4 BPS Wilson-'t Hooft loops

    Science.gov (United States)

    Liu, Chang-Yong; Qin, Li

    2015-10-01

    In this paper, we investigate the 1/4 BPS Wilson-'t Hooft loops in N=4 supersymmetric Yang-Mills theory. We use the bulk D3-brane solutions with both electric and magnetic charges on its world-volume to describe some of 1/4 BPS Wilson-'t Hooft loops. The D3-brane supersymmetric solutions are derived form requiring κ-symmetry. We find the two consistent constraints for Killing spinors and calculate the conserved charges of straight 1/4 BPS Wilson-'t Hooft loops and expectation values of circular 1/4 BPS Wilson-'t Hooft loops separately.

  2. Role of hepatic resection for patients with carcinoid heart disease

    DEFF Research Database (Denmark)

    Bernheim, A.M.; Connolly, H.M.; Rubin, J.

    2008-01-01

    OBJECTIVE: To evaluate the effects of resection of hepatic carcinoid metastases on progression and prognosis of carcinoid heart disease. PATIENTS AND METHODS: From our database of 265 consecutive patients diagnosed as having carcinoid heart disease from January 1, 1980, through December 31, 2005,...

  3. Lipid profile in sickle cell disease patients with chronic kidney ...

    African Journals Online (AJOL)

    Background: Dyslipidaemia is reported to occur in patients with sickle cell disease as well as patients with chronic kidney disease irrespective of the haemoglobin genotype. This study aimed at evaluating lipid profile in subjects with sickle cell anaemia (HbSS), sickle cell trait (HbAS) and normal haemoglobin genotype ...

  4. the metabolic syndrome among patients with cardiovascular disease ...

    African Journals Online (AJOL)

    Objectives: To determine the frequency of occurrence of the Metabolic Syndrome among patients presenting with cardiovascular disease at the Korle Bu Teaching Hospital, Ghana. Methods: This was a case-control study of 100 con-secutive cardiovascular disease patients and 100 age- and sex- matched controls who ...

  5. Profile of Ear Diseases among Elderly Patients in Sagamu, South ...

    African Journals Online (AJOL)

    The importance of screening for hearing impairment in the elderly patients was also stressed. KEYWORDS: Cerumen, Ear disease, Elderly, Otitis, Presbycusis. Erratum Note: Olusola AS on the article “Profile of Ear Diseases among Elderly Patients in Sagamu, South-Western Nigeria” on Page Nig. J. Med 2013. 143-147.

  6. Depression among Patients with Parkinson's Disease in a Nigerian ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    86.10. Table 2: Frequency of non-motor features among. Parkinson's disease patients. Non motor feature. Persistent low mood. Pain. Frequency %. N=36. 30. 27 ... tertiary care setting. Some investigators have argued that patients with Parkinson's disease in hospital settings are more likely to experience depression than ...

  7. Urinary Exertion Of Calcium By Urinary Stone Disease Patients And ...

    African Journals Online (AJOL)

    To compare the urinary excretion of calcium by subjects in a known area of high incidence of urinary stone disease, and a known area of low incidence, 12 adult male patients with idiopathic calcigerous urinary stone disease in south-East Nigeria and 55 similar patients from Scotland, United Kingdom were analyzed ...

  8. [Chronic fatigue syndrome in patients with vibration disease].

    Science.gov (United States)

    Kir'iakov, V A; Saarkoppel', L M; Krylova, I V; Sukhova, A V

    2013-01-01

    The article presents study results that demonstrate chronic fatigue syndrome in patients with vibration disease. Clinical manifestations of chronic fatigue syndrome are characterized by changes in the emotional-volitional and cognitive areas. Application of nootropic drug cortexin increases the efficiency of rehabilitation in patients with vibration disease with chronic fatigue syndrome.

  9. Serum YKL-40, a potential new marker of disease activity in patients with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Vind, Ida; Johansen, J S; Price, P A

    2003-01-01

    BACKGROUND: YKL-40 is secreted by macrophages and neutrophils and is a growth factor for vascular endothelial cells and fibroblasts. Elevated serum concentrations of YKL-40 are found in patients with diseases characterized by inflammation or ongoing fibrosis. The aim of this study was to seek...... were used to assess disease activity. Serum YKL-40 (determined by ELISA) was related to C-reactive protein (CRP) and disease activity. RESULTS: In patients with UC, the median serum YKL-40 rose with increasing disease activity, and patients with severe active disease had higher serum YKL-40 (median 59...

  10. Obstructive Sleep Apnea in Patients with Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Pantaree Aswanetmane

    2014-07-01

    Full Text Available Obstructive sleep apnea (OSA and chronic obstructive pulmonary disease (COPD are common disorders in clinical practice and are associated with significant cardiovascular morbidity. The simultaneous occurrence of OSA and COPD happens frequently and is referred to as an overlap syndrome. These patients often have very poor quality sleep and more nocturnal hypoxemia. This combination may increase the severity of metabolic complications and cardiovascular disease, and these patients have increased mortality when compared to patients with either COPD or OSA alone. The treatment of overlap syndrome should focus on both coexisting diseases and includes continuous positive airway pressure, oxygen supplementation, and medications for chronic lung disease.

  11. Hypertensive organ damage in patients with vascular disease

    NARCIS (Netherlands)

    Vlek, A.L.M.

    2009-01-01

    Hypertension is one of the most common vascular risk factors, and is an important cause of development of different vascular diseases. The main aim of this thesis was to determine the burden of hypertension-associated vascular diseases and end-organ damage in patients with manifest vascular disease.

  12. Incidence of RET mutations in patients with Hirschsprung's disease

    NARCIS (Netherlands)

    Sancandi, M; Ceccherini, [No Value; Costa, M; Fava, M; Chen, B; Wu, Y; Hofstra, R; Laurie, T; Griffths, M; Burge, D; Tam, PKH

    Background: RET mutations have been reported variously to affect 7% to 41% of Hirschsprung's disease (HSCR) patients depending on familial or sporadic occurrence of the disease, length of aganglionosis and possible association with other disease phenotypes. The authors report a study of the

  13. Factors associated with gastro-duodenal disease in patients ...

    African Journals Online (AJOL)

    Background: There is a high prevalence of gastro-duodenal disease in sub Saharan Africa. Peptic ulcer disease in dyspeptic patients, 24.5%, was comparable to prevalence of gastro-duodenal disease among symptomatic individuals in developed countries (12 – 25%). Limited data exists regarding its associated risk ...

  14. Periodontal disease in diabetic patients - clinical and histopathological aspects.

    Science.gov (United States)

    Corlan Puşcu, Dorina; Ciuluvică, Radu Constantin; Anghel, Andreea; Mălăescu, Gheorghe Dan; Ciursaş, Adina Nicoleta; Popa, Gabriel Valeriu; Agop Forna, Doriana; Busuioc, Cristina Jana; Siloşi, Izabela

    2016-01-01

    Periodontal disease is one of the most frequent diseases affecting people all over the world. The relation between periodontal disease and diabetes mellitus raised the interest both of dentists and doctors treating metabolic diseases, as the two conditions influence one another. In our study, we analyzed a number of 75 patients with diabetes mellitus and periodontal disease that presented to the medical consultory for conditions of the dental maxillary system. The clinical study showed that periodontal disease and diabetes may affect young adults as well, still this pathological association more frequently appears after the age of 50. The disease was identified especially in the women living in urban area. The clinical examination of the dental maxillary system identified the presence of gingival ulcerations, dental calculus, gingival bleeding, radicular leftovers with anfractuous margins, fixed prostheses with an inappropriate cervical adjustment. Of the systemic diseases associated to periodontal disease and diabetes mellitus, there was observed that 66.66% of the patients also suffered from cardiovascular diseases (high blood pressure, ischemic cardiopathy, heart failure), and 37.33% suffered from obesity. The histopathological and immunohistochemical tests highlighted the presence of an inflammatory chronic, intense reaction, mainly formed of lymphocytes, plasmocytes, macrophages and granulocytes, heterogeneously disseminated and alteration of the structure of marginal and superficial periodontium. The inflammatory reaction in the patients with periodontal disease and diabetes was more intense than in the patients with periodontal disease without diabetes.

  15. Short review of dental care for patients with cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Puškar Slobodan

    2016-01-01

    Full Text Available Introduction: The basic knowledge about cardiovascular diseases (CVD s, the symptoms and complications that can occur during dental interventions in patients suffering from cardiovascular diseases, and how to handle such patients during the dental intervention are essential to every dentist. Dental patients suffering from cardiovascular diseases that are not adequately treated have a significantly higher risk of cardiovascular event during the dental intervention. Results: The most common cardiovascular diseases that need special dental care are: arterial hypertension, coronary heart disease, cerebrovascular disease, heart rhythm disorders and heart failure. Conclusion: Particular attention is needed when patients are treated with anticoagulant and /or antiplatelet therapy or when prevention of bacterial endocarditis is required.

  16. Prevalence and overlap of Disease Management Program diseases in older hospitalized patients

    DEFF Research Database (Denmark)

    Juul-Larsen, Helle Gybel; Petersen, Janne; Sivertsen, Ditte Maria

    2017-01-01

    Many countries, like Denmark, have tailored Disease Management Programs (DMPs) based on patients having single chronic diseases [defined institutionally as "program diseases" (PDs)], which can complicate treatment for those with multiple chronic diseases. The aims of this study were (a) to assess....... The range of the cumulative incidence of being readmitted within 90 days was between 28.8% for patients without a PD and 46.6% for patients with more than one PD. PDs overlapped in many combinations, and all patients had a high probability of being readmitted. Hence, developing strategies to create a new...

  17. Hormones and arterial stiffness in patients with chronic kidney disease.

    Science.gov (United States)

    Gungor, Ozkan; Kircelli, Fatih; Voroneanu, Luminita; Covic, Adrian; Ok, Ercan

    2013-01-01

    Cardiovascular disease constitutes the major cause of mortality in patients with chronic kidney disease. Arterial stiffness is an important contributor to the occurrence and progression of cardiovascular disease. Various risk factors, including altered hormone levels, have been suggested to be associated with arterial stiffness. Based on the background that chronic kidney disease predisposes individuals to a wide range of hormonal changes, we herein review the available data on the association between arterial stiffness and hormones in patients with chronic kidney disease and summarize the data for the general population.

  18. Osteoporosis in chronic obstructive pulmonary disease patients

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Schwarz, Peter

    2008-01-01

    The purpose of this review is to examine the state of knowledge and clinical practice in the association of chronic obstructive pulmonary disease to osteoporosis and fracture incidence.......The purpose of this review is to examine the state of knowledge and clinical practice in the association of chronic obstructive pulmonary disease to osteoporosis and fracture incidence....

  19. Suicidal behavior among Turkish patients with Parkinson’s disease

    OpenAIRE

    Ozdilek B; Gultekin BK

    2014-01-01

    Betul Ozdilek,1 Bulent Kadri Gultekin21Department of Neurology, 2Department of Psychiatry, Erenkoy Mental Health and Neurology Training and Research Hospital, Istanbul, TurkeyObjective: To investigate the predictors of suicidal ideation and attempts among Turkish Parkinson’s disease (PD) patients.Materials and methods: The study comprised 120 patients with PD. Clinical findings were obtained by using the Unified Parkinson’s Disease Rating Scale. Disease severity was measur...

  20. Epiretinal membrane removal in patients with Stargardt disease

    Directory of Open Access Journals (Sweden)

    Muna Bhende

    2015-01-01

    Full Text Available Epiretinal membranes (ERMs in Stargardt disease have been known to undergo spontaneous separation in children. Results of surgical intervention in adult patients with Stargardt disease have rarely been reported. A retrospective review of results of surgical intervention for ERM causing visual impairment in two adult patients of Stargardt disease was carried out. Both patients developed ERM in one eye during their follow-up period with the resultant drop in their preexisting visual acuity. Postsurgery, restoration of foveal contour with some improvement in visual acuity was observed in both patients. No adverse effect of surgery was noted.

  1. Transvascular lipoprotein transport in patients with chronic renal disease

    DEFF Research Database (Denmark)

    Jensen, Trine Krogsgaard; Nordestgaard, Børge Grønne; Feldt-Rasmussen, Bo

    2004-01-01

    BACKGROUND: While increased plasma cholesterol is a well-established cardiovascular risk factor in the general population, this is not so among patients with chronic renal disease. We hypothesized that the transvascular lipoprotein transport, in addition to the lipoprotein concentration in plasma......, determines the degree of atherosclerosis among patients with chronic renal disease. METHODS: We used an in vivo method for measurement of transvascular transport of low-density lipoprotein (LDL) in 21 patients with chronic renal disease and in 42 healthy control patients. Autologous 131-iodinated LDL...... was reinjected intravenously, and the 1-hour fractional escape rate was taken as index of transvascular transport. RESULTS: Transvascular LDL transport tended to be lower in patients with chronic renal disease than in healthy control patients [3.3 (95% CI 2.4-4.2) vs. 4.2 (3.7-4.2)%/hour; NS]. However...

  2. Holographic Wilson loops, dielectric interfaces, and topological insulators

    Science.gov (United States)

    Estes, John; O'Bannon, Andy; Tsatis, Efstratios; Wrase, Timm

    2013-05-01

    We use holography to study (3+1)-dimensional N=4 supersymmetric SU(Nc) Yang-Mills theory (SYM) in the large-Nc and large-coupling limits, with a (2+1)-dimensional interface where the Yang-Mills coupling or θ angle changes value, or “jumps.” We consider interfaces that either break all supersymmetry or that preserve half of the N=4 supersymmetry thanks to certain operators localized to the interface. Specifically, we compute the expectation values of a straight timelike Wilson line and of a rectangular Wilson loop in the fundamental representation of SU(Nc). The former gives us the self-energy of a heavy test charge while the latter gives us the potential between heavy test charges. A jumping coupling or θ angle acts much like a dielectric interface in electromagnetism: the self-energy or potential includes the effects of image charges. N=4 SYM with a jumping θ angle may also be interpreted as the low-energy effective description of a fractional topological insulator, as we explain in detail. For nonsupersymmetric interfaces, we find that the self-energy and potential are qualitatively similar to those in electromagnetism, despite the differences between N=4 SYM and electromagnetism. For supersymmetric interfaces, we find dramatic differences from electromagnetism which depend sensitively on the coupling of the test charge to the adjoint scalars of N=4 SYM. In particular, we find one special case where a test charge has a vanishing image charge.

  3. Comments on higher rank Wilson loops in N = 2∗

    Science.gov (United States)

    Liu, James T.; Zayas, Leopoldo A. Pando; Zhou, Shan

    2018-01-01

    For N = 2∗ theory with U( N ) gauge group we evaluate expectation values of Wilson loops in representations described by a rectangular Young tableau with n rows and k columns. The evaluation reduces to a two-matrix model and we explain, using a combination of numerical and analytical techniques, the general properties of the eigen-value distributions in various regimes of parameters ( N, λ , n, k) where λ is the 't Hooft coupling. In the large N limit we present analytic results for the leading and sub-leading contributions. In the particular cases of only one row or one column we reproduce previously known results for the totally symmetry and totally antisymmetric representations. We also extensively discusss the N = 4 limit of the N = 2∗ theory. While establishing these connections we clarify aspects of various orders of limits and how to relax them; we also find it useful to explicitly address details of the genus expansion. As a result, for the totally symmetric Wilson loop we find new contributions that improve the comparison with the dual holographic computation at one loop order in the appropriate regime.

  4. Interest rates in quantum finance: the Wilson expansion and Hamiltonian.

    Science.gov (United States)

    Baaquie, Belal E

    2009-10-01

    Interest rate instruments form a major component of the capital markets. The Libor market model (LMM) is the finance industry standard interest rate model for both Libor and Euribor, which are the most important interest rates. The quantum finance formulation of the Libor market model is given in this paper and leads to a key generalization: all the Libors, for different future times, are imperfectly correlated. A key difference between a forward interest rate model and the LMM lies in the fact that the LMM is calibrated directly from the observed market interest rates. The short distance Wilson expansion [Phys. Rev. 179, 1499 (1969)] of a Gaussian quantum field is shown to provide the generalization of Ito calculus; in particular, the Wilson expansion of the Gaussian quantum field A(t,x) driving the Libors yields a derivation of the Libor drift term that incorporates imperfect correlations of the different Libors. The logarithm of Libor phi(t,x) is defined and provides an efficient and compact representation of the quantum field theory of the Libor market model. The Lagrangian and Feynman path integrals of the Libor market model of interest rates are obtained, as well as a derivation given by its Hamiltonian. The Hamiltonian formulation of the martingale condition provides an exact solution for the nonlinear drift of the Libor market model. The quantum finance formulation of the LMM is shown to reduce to the industry standard Bruce-Gatarek-Musiela-Jamshidian model when the forward interest rates are taken to be exactly correlated.

  5. Approach to the patient with Parkinson disease.

    Science.gov (United States)

    Johnson, Kevin E

    2015-06-01

    Parkinson disease (PD) is a progressive neurodegenerative disease with motor, nonmotor, and behavioral findings. Imaging technology advances have allowed the characterization of the underlying pathologic changes to the brain and identification of specific lesions in dopaminergic neurons. Although certain imaging techniques allow for detection up to 20 years before the onset of motor symptoms, these advances have yet to produce meaningful treatments to halt the disease or reverse its course. Current treatments are directed at optimizing symptomatic management. Referral to a movement disorder specialist familiar with PD should be considered for providers with limited familiarity in diagnosis or treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Dementia and functional decline in patients with Parkinson's disease

    OpenAIRE

    Stella, Florindo; Banzato, Claudio Eduardo Muller; Quagliato, Elizabeth Maria Aparecida Barasnevicius; Viana, Maura Aparecida; Christofoletti, Gustavo

    2008-01-01

    Abstract Functional decline in Parkinson's disease (PD), characterized by reduced ability to carry out activities of daily living, usually results from typical motor impairment and may be aggravated by concomitant cognitive impairment. Objective: To compare the functional decline in Parkinson's disease between patients with dementia and cognitively preserved patients. Methods: From an original sample composed of 50 patients with a clinical diagnosis of idiopathic PD seen in a consecutive se...

  7. Vascular disease patient information page: Abdominal aortic aneurysm (AAA).

    Science.gov (United States)

    Moennich, Laurie Ann; Mastracci, Tara M

    2014-10-01

    Abdominal aortic aneurysm is a silent but often fatal disease. AAA is most common in older people, with both modifiable (such as smoking) and hereditary (family history of AAA) risk factors influencing disease development. Screening for AAA can aid in the early diagnosis and treatment of the disease, reducing complications and death amongst those affected. Advancements in screening techniques, surgical innovations, and graft development strive to further improve patient outcomes and disease management.

  8. Care of the Pregnant Patient With Inflammatory Bowel Disease.

    Science.gov (United States)

    Mahadevan, Uma; Matro, Rebecca

    2015-08-01

    Inflammatory bowel disease affects women in their peak reproductive years. Patients and physicians often have questions regarding the effect of inflammatory bowel disease on a woman's ability to conceive and to carry a pregnancy safely to term as well as the effect of inflammatory bowel disease and the medications used to treat it on pregnancy outcomes. Women with inflammatory bowel disease have the same rates of fertility as women without inflammatory bowel disease unless they have had prior surgery in the pelvis or active disease. However, women with inflammatory bowel disease do have higher rates of adverse pregnancy outcomes. A multidisciplinary approach involving gastroenterologists, obstetricians, and maternal-fetal medicine physicians should focus on preconception planning and disease optimization before pregnancy. Women with inflammatory bowel disease should be followed as high-risk obstetric patients. Most medications used to treat inflammatory bowel disease can be continued safely during pregnancy and lactation. The greatest risk to the pregnancy is active disease, which can be precipitated by discontinuation of effective maintenance medications. Preconception counseling should include education regarding the low risk of most inflammatory bowel disease medications during pregnancy and lactation and the high risk of a significant disease flare during pregnancy. This review outlines important considerations for obstetricians caring for women with inflammatory bowel disease before and during pregnancy and in the postpartum period.

  9. Eye Disease in Patients with Diabetes Screened with Telemedicine.

    Science.gov (United States)

    Park, Dong-Wouk; Mansberger, Steven L

    2017-02-01

    Telemedicine with nonmydriatic cameras can detect not only diabetic retinopathy but also other eye disease. To determine the prevalence of eye diseases detected by telemedicine in a population with a high prevalence of minority and American Indian/Alaskan Native (AI/AN) ethnicities. We recruited diabetic patients 18 years and older and used telemedicine with nonmydriatic cameras to detect eye disease. Two trained readers graded the images for diabetic retinopathy, age-related macular degeneration (ARMD), glaucomatous features, macular edema, and other eye disease using a standard protocol. We included both eyes for analysis and excluded images that were too poor to grade. We included 820 eyes from 424 patients with 72.3% nonwhite ethnicity and 50.3% AI/AN heritage. While 283/424 (66.7%) patients had normal eye images, 120/424 (28.3%) had one disease identified; 15/424 (3.5%) had two diseases; and 6/424 (1.4%) had three diseases in one or both eyes. After diabetic retinopathy (104/424, 24.5%), the most common eye diseases were glaucomatous features (44/424, 10.4%) and dry ARMD (24/424, 5.7%). Seventeen percent (72/424, 17.0%) showed eye disease other than diabetic retinopathy. Telemedicine with nonmydriatic cameras detected diabetic retinopathy, as well as other visually significant eye disease. This suggests that a diabetic retinopathy screening program needs to detect and report other eye disease, including glaucoma and macular disease.

  10. Predictive factors of small bowel patency in Crohn's disease patients

    Directory of Open Access Journals (Sweden)

    Andreia Albuquerque

    2016-02-01

    Full Text Available Background: Patency capsule was developed to avoid small bowel video capsule endoscopy retention, namely in patients with Crohn's disease. Aims: To evaluate the predictive factors of small bowel patency in Crohn's disease patients. Patients and methods: Retrospective analysis including 151 Crohn's disease patients submitted to patency capsule (Agile® Patency Capsule from 2011 to 2012. Patients that excreted the intact patency capsule were classified as having a patent small bowel (without patency capsule retention, other patients were considered to have negative patency of the small bowel (patency capsule retention. Results: Patients had a mean age of 41±14 years, 54% were female and 25% had been previously submitted to surgery. Stricturing disease was seen in 20% of cases and penetrating disease in 16% of cases. Left-sided colonic lesions and ileal strictures were observed at colonoscopy in 13% and 9% of patients, respectively. In our sample, 28% of patients had negative patency of the small bowel (patency capsule retention. In multivariate analysis, independent factors that were associated with negative patency of the small bowel in Crohn's disease patients were stricturing (OR 10.16, p < 0.001 and penetrating phenotypes (OR 11.73, p = 0.001, left-sided colonic lesions (OR 3.77, p = 0.038, ileal stricture (OR 9.76, p = 0.003; previous intestinal surgery was found to be protective (OR 0.16, p = 0.006. Conclusions: Stricturing or penetrating disease, ileal strictures, no previous surgery and left-sided colonic lesions were the factors associated with negative small bowel patency in Crohn's disease patients.

  11. BODY COMPOSITION IN PATIENTS WITH CROHN'S DISEASE AND ULCERATIVE COLITIS.

    Science.gov (United States)

    Back, Ivi Ribeiro; Marcon, Sonia Silva; Gaino, Natalia Moreno; Vulcano, Daniela Salate Biagioni; Dorna, Mariana de Souza; Sassaki, Ligia Yukie

    2017-01-01

    The nutritional status of individuals with inflammatory bowel diseases is directly related to the severity of the disease and is associated with poor prognosis and the deterioration of immune competence. To assess the nutritional status and the body composition of outpatients with inflammatory bowel diseases. A cross-sectional study was conducted with clinical and nutritional assessment of patients with Crohn's disease and ulcerative colitis. Patients were classified according to the clinical activity through Crohn's Disease Activity Index and Mayo Score. Nutritional assessment consisted of anthropometric measurements of current weight, height, mid-arm circumference, triceps skinfold thickness and thickness of adductor policis muscle, with subsequent calculation of BMI, arm muscle circumference and the mid-arm muscle area (MAMA). The phase angle (PhA) and lean and fat mass were obtained with the use of electrical bioimpedance. Descriptive statistics, chi-square test or Fisher exact test, ANOVA and t-test. We evaluated 141 patients of which 54 (38.29%) had Crohn's disease and 87 (61.70%) ulcerative colitis. The mean age was 43.98 (±15.68) years in Crohn's disease and 44.28 (±16.29) years for ulcerative colitis. Most of the patients were in clinical remission of the disease (Crohn's disease: 88.89%; ulcerative colitis: 87.36%). Regarding the nutritional classification using BMI, it was found that 48.15% of Crohn's disease patients were eutrophic and 40.74% were overweight or obese; among patients with ulcerative colitis, 52.87% were classified as overweight or obese. When considering the triceps skinfold, it was observed in both groups a high percentage of overweight and obesity (Crohn's disease: 75.93%; ulcerative colitis: 72.42%). Crohn's disease patients showed the most affected nutritional status according to the nutritional variables when compared to patients with ulcerative colitis (BMI: 24.88 kg/m² x BMI: 26.56 kg/m², P=0.054; MAMA: 35.11 mm x MAMA: 40

  12. Risk of primary biliary cirrhosis in patients with coeliac disease

    DEFF Research Database (Denmark)

    Sørensen, Henrik Toft; Thulstrup, Ane Marie; Blomqvist, P

    1999-01-01

    BACKGROUND: Several case reports, but only a few studies, have examined the coexistence of coeliac disease and primary biliary cirrhosis. AIM: To estimate the risk of primary biliary cirrhosis in two national cohorts of patients with coeliac disease in Denmark and Sweden. METHODS: Through record...... linkage all Danish patients hospitalised with coeliac disease were followed for possible occurrence of primary biliary cirrhosis from 1 January 1977 until 31 December 1992. All patients hospitalised with coeliac disease in Sweden from 1987 to 1996 were also followed in a separate analysis. RESULTS......: A total of 896 patients with coeliac disease were identified in Denmark with a median follow up period of 9.1 years for a total of 8040 person-years at risk. Two cases of primary biliary cirrhosis were observed where 0.07 were expected, giving a standardised incidence ratio of 27.6 (95% confidence...

  13. Survival Analysis of Patients with End Stage Renal Disease

    Science.gov (United States)

    Urrutia, J. D.; Gayo, W. S.; Bautista, L. A.; Baccay, E. B.

    2015-06-01

    This paper provides a survival analysis of End Stage Renal Disease (ESRD) under Kaplan-Meier Estimates and Weibull Distribution. The data were obtained from the records of V. L. MakabaliMemorial Hospital with respect to time t (patient's age), covariates such as developed secondary disease (Pulmonary Congestion and Cardiovascular Disease), gender, and the event of interest: the death of ESRD patients. Survival and hazard rates were estimated using NCSS for Weibull Distribution and SPSS for Kaplan-Meier Estimates. These lead to the same conclusion that hazard rate increases and survival rate decreases of ESRD patient diagnosed with Pulmonary Congestion, Cardiovascular Disease and both diseases with respect to time. It also shows that female patients have a greater risk of death compared to males. The probability risk was given the equation R = 1 — e-H(t) where e-H(t) is the survival function, H(t) the cumulative hazard function which was created using Cox-Regression.

  14. Analysis of electrocardiogram in chronic obstructive pulmonary disease patients.

    Science.gov (United States)

    Lazović, Biljana; Svenda, Mirjana Zlatković; Mazić, Sanja; Stajić, Zoran; Delić, Marina

    2013-01-01

    Chronic obstructive pulmonary disease is the fourth leading cause of mortality worldwide. It is defined as a persistent airflow limitation usually progressive and not fully reversible to treatment. The diagnosis of chronic obstructive pulmonary disease and severity of disease is confirmed by spirometry. Chronic obstructive pulmonary disease produces electrical changes in the heart which shows characteristic electrocardiogram pattern. The aim of this study was to observe and evaluate diagnostic values of electrocardiogram changes in chronic obstructive pulmonary disease patients with no other comorbidity. We analyzed 110 electrocardiogram findings in clinically stable chronic obstructive pulmonary disease patients and evaluated the forced expiratory volume in the first second, ratio of forces expiratory volume in the first second to the fixed vital capacity, chest radiographs and electrocardiogram changes such as p wave height, QRS axis and voltage, right bundle branch block, left bundle branch block, right ventricular hypertrophy, T wave inversion in leads V1-V3, S1S2S3 syndrome, transition zone in praecordial lead and QT interval. We found electrocardiogram changes in 64% patients, while 36% had normal electrocardiogram. The most frequent electrocardiogram changes observed were transition zone (76.36%) low QRS (50%) and p pulmonale (14.54%). Left axis deviation was observed in 27.27% patients. Diagnostic values of electrocardiogram in patients with chronic obstructive pulmonary disease suggest that chronic obstructive pulmonary disease patients should be screened electrocardiographically in addition to other clinical investigations.

  15. Screening for anxiety disorders in patients with coronary artery disease

    NARCIS (Netherlands)

    Bunevicius, A.; Staniute, M.; Brozaitiene, J.; Pop, V.J.M.; Neverauskas, J.; Bunevicius, R.

    2013-01-01

    Background Anxiety disorders are prevalent and associated with poor prognosis in patients with coronary artery disease (CAD). However, studies examining screening of anxiety disorders in CAD patients are lacking. In the present study we evaluated the prevalence of anxiety disorders in patients with

  16. High probability of disease in angina pectoris patients

    DEFF Research Database (Denmark)

    Høilund-Carlsen, Poul F.; Johansen, Allan; Vach, Werner

    2007-01-01

    ) in patients with a high probability of coronary artery disease. PATIENTS AND METHODS: A prospective series of 357 patients referred for coronary angiography (CA) for suspected stable angina pectoris were examined by a trained physician who judged their type of pain and Canadian Cardiovascular Society grade...

  17. Chronic osteoyelitis in patients with sickle cell disease | Nwadiaro ...

    African Journals Online (AJOL)

    Objective: To determine the baseline pattern and audit management modalities of chronic osteomyelitis in patients with sickle cell disease. Design: A retrospective study. Setting: Jos University Teaching Hospital, Jos, Nigeria from August 1993 to July 1997. Patients: Twenty four patients with concomitant chronic sickle cell ...

  18. QT interval prolongation in patients with hypertensive heart disease ...

    African Journals Online (AJOL)

    Conclusion: This study demonstrated high prevalence of prolonged QTc in patients with hypertensive heart disease. Affected patients had significantly higher prevalence of several factors associated with increased morbidity and mortality. Assessment of QTc is recommended for risk stratification in patients with HHD.

  19. Proportion of patients in the Uganda rheumatic heart disease ...

    African Journals Online (AJOL)

    Abstract: Introduction: Since the establishment of the Uganda Rheumatic Heart Registry, over 900 patients have been enrolled. We sought to stratify the patients in the registry according to disease severity and optimal management strategy. Methods: We reviewed data of 618 patients who had enrolled in the Registry ...

  20. Proportion of patients in the Uganda rheumatic heart disease ...

    African Journals Online (AJOL)

    Introduction: Since the establishment of the Uganda Rheumatic Heart Registry, over 900 patients have been enrolled. We sought to stratify the patients in the registry according to disease severity and optimal management strategy. Methods: We reviewed data of 618 patients who had enrolled in the Registry between March ...

  1. Sentence Comprehension in Slovak-Speaking Patients with Alzheimer's Disease

    Science.gov (United States)

    Marková, Jana; Horváthová, Lubica; Králová, Mária; Cséfalvay, Zsolt

    2017-01-01

    Background: According to some studies, sentence comprehension is diminished in Alzheimer's disease (AD) patients, but they differ on what underlies the sentence comprehension impairment. Sentence comprehension in AD patients has been studied mainly in the English language. It is less clear how patients with AD speaking a morphologically rich…

  2. Addiction or pseudoaddiction in sickle cell disease patients: Time to ...

    African Journals Online (AJOL)

    Objective: The objective of this report is to highlight the background factors associated with opioid abuse among Sickle Cell Disease (SCD) patients. Patients: Eleven patients aged 13-53 years (mean, 26.1yrs) which included six female and five male were seen in the last six year at a tertiary health facility. The modes of ...

  3. [5 patients with Takayasu's disease in The Netherlands].

    Science.gov (United States)

    van den Berkmortel, F W; Wollersheim, H; Heijstraten, F M; Thien, T

    1995-06-03

    To describe the patients with Takayasu's disease in the University Hospital Nijmegen, and to compare these patients with literature. Retrospective, descriptive. University Hospital Nijmegen. All patients with Takayasu's disease in the period of 1980-1993 were traced via medical registration codes. These patients are described and compared with the literature. Five patients with Takayasu's disease were found, 3 women and 2 men, 4 Dutch and I Turkish female. The diagnosis in all patients was made before the age of 21 and confirmed by angiography. Four of the 5 patients presented initially with general complaints, and, except for patient A, all had a pulse or blood pressure difference (left-right) to the disadvantage of the left arm. Occlusion of the left subclavian artery occurred finally in all cases. Four patients had associated diseases as described in the literature. Four of the 5 showed no progression on prednisone therapy. Until now no patient has died, with a mean follow-up of 10 years. Takayasu's disease is rare in the Netherlands. First symptoms are general fatigue and a pulse/blood pressure difference. Early detection by medical history, physical examination and angiography appears beneficial, because early treatment may have a favourable effect on prognosis.

  4. Suicidal behavior among Turkish patients with Parkinson's disease.

    Science.gov (United States)

    Ozdilek, Betul; Gultekin, Bulent Kadri

    2014-01-01

    To investigate the predictors of suicidal ideation and attempts among Turkish Parkinson's disease (PD) patients. The study comprised 120 patients with PD. Clinical findings were obtained by using the Unified Parkinson's Disease Rating Scale. Disease severity was measured by the Hoehn and Yahr staging scale, and the Schwab and England Activities of Daily Living scale was used for patient disability. Psychiatric evaluation was performed by the same psychiatrist using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Axis I Disorders. Severity of depression was measured with the Hamilton Depression Rating Scale. Suicidal ideation and attempts were considered positive if experienced during the patient's lifetime. The Suicide Probability Scale was used to assess the risk of suicide. Data were analyzed by logistic regression models to identify variables associated with suicidal ideation and attempts. Based on logistic regression analysis, education level, age of disease onset, disease duration, depression, and history of impulse-control disorder (ICD) behaviors were significant predictors of suicidal ideation. The risk rate in the presence of depression and history of ICD behaviors was increased by 5.92 and 4.97, respectively. Additionally, lifetime prevalence of suicidal ideation was found in 11.6% (14 of 120) of PD patients, although no patient had ever attempted suicide. Turkish patients with PD who exhibit a high risk for suicidal ideation also experience disease starting at an earlier age, longer disease duration, presence of depression, and ICD behaviors, and should be monitored carefully.

  5. Abdominal fat and risk of coronary heart disease in patients with peripheral arterial disease

    NARCIS (Netherlands)

    Brouwer, Beate G.; Visseren, Frank L. J.; Stolk, Ronald P.; van der Graaf, Yolanda

    Objective: We investigated whether the presence of concomitant coronary heart disease (CHD) in patients with peripheral arterial disease (PAD) can be explained by intra-abdominal fat accumulation and compared different measures of adiposity as predictors of CHD in patients with PAD. Research Methods

  6. Advance care planning for patients with advanced neurology diseases.

    Science.gov (United States)

    Cheung, Ka-Chi; Lau, Vikki Wai-Kee; Un, Ka-Chun; Wong, Man-Sheung; Chan, Kwok-Ying

    2017-10-13

    Advanced neurology diseases including motor neuron disease (MND) are usually progressive life-limiting illness and could be devastating for patients, families and caregivers. Although medical technologies, such as enteral feeding and non-invasive ventilation, may prolong life expectancy of the patients, their utilization prompts important ethical questions in regard to their quality of life (QoL). Little attention had been paid on how ACP practice would practically help with patients suffering from different neurology diseases. We are unaware of any published studies on ACP practice among patients with different neurology diseases. In our study, we assessed end-of-life (EOL) care preferences, documentation, and communication in patients with various types of advanced neurology diseases. This was a retrospective chart review of all patients referred to the neuro-palliative care team (NPCT) in a local acute hospital in Hong Kong. The study was approved by the institutional review board of the University of Hong Kong. NPCT consultation was hand abstracted from the electronic health record if there was a subspecialty palliative care (PC) consultation note during the study period. Hand abstraction of data also included any content related to advance care planning (ACP) [advance directive (AD), resuscitation order, ventilator support, artificial feeding, patient wishes, legacy]. For patient who signed AD, items including cardiopulmonary resuscitation (100%), mechanical ventilation (100%), artificial nutrition and hydration (80%) were mentioned more frequently than other EOL interventions. For patients who had ACP but without AD, the most common diagnosis is bad stroke (60%). Place of death, artificial nutrition and hydration were most mentioned EOL interventions. EOL decision making in patients with advanced neurology disease is often delayed. This study showed that MND patients are readier to discuss their EOL issues and signed their AD. The NPCT can play a valuable

  7. [Arterial stiffness in patients with chronic obstructive pulmonary disease].

    Science.gov (United States)

    2012-01-01

    To estimate arterial stiffness (AS) in patients with chronic obstructive pulmonary disease (COPD). A total of 112 COPD patients over 40 years of age entered a population-based trial. The patients with coronary heart diseases, peripheral vascular atherosclerosis, other severe chronic diseases in exacerbation were withdrawn. The control group consisted of 26 healthy volunteers matched by gender and age. AS was measured at arteriograph "Tensioclinic" ("Tensiomed", Hungary). COPD patients, first of all elderly ones, had abnormal properties of arterial wall. Increased arterial rigidity and pulse wave reflection (accelerated pulse wave velocity and high index of augmentation) are strongly associated with elevation of central arterial pressure. High arterial wall stiffness in COPD patients suggests an increased risk of cardiovascular diseases that necessitates examination in prospective studies.

  8. Clostridium difficile infection in a patient with Crohn disease.

    Science.gov (United States)

    Hsu, Chien-Hui; Jeng, Yung-Ming; Ni, Yen-Hsuan

    2012-06-01

    Crohn disease is a chronic inflammatory disorder, which is rare in pediatric patients. The definite etiology and mechanism to induce an acute exacerbation of Crohn disease remains mostly unknown. The authors report on a 14-year-old girl with Crohn disease who has acute gastrointestinal symptoms caused by toxin A-producing Clostridium difficile, which mimicked a flare-up of Crohn disease. There was no preceding antibiotic prescription before the episode. The disease activity did not improve after steroid treatment, which is unusual for Crohn disease. However, all symptoms were dramatically relieved after eradication of C difficile, and led to a symptom-free period for more than 3 years. This case report aims to address the unusual presentation of a usual pathogen, C difficile, in a pediatric patient with Crohn disease. Copyright © 2012. Published by Elsevier B.V.

  9. Cardiovascular disease in patients with end-stage renal disease on hemodialysis in a developing country

    Directory of Open Access Journals (Sweden)

    Leila S. V. Silva

    2012-01-01

    Full Text Available Cardiovascular disease is the main cause of death among patients with end-stage renal disease (ESRD. The present study was undertaken to identify the main cardiovascular diseases and their risk factors in 160 patients with ESRD on hemodialysis (HD in Brazil. Their mean age was 47 ± 39 years. The main risk factors for cardiovascular diseases were arterial hypertension (89.4%, dyslipidemia (78.3%, low high-density lipoprotein levels (84.2% and low physical activity (64.1%. Family history of coronary insufficiency and high low-density lipoprotein levels were significantly associated with coronary artery disease (P = 0.005 and P = 0.029, respectively. Sedentary life style, diabetes mellitus, secondary hyperparathyroidism and hyperglycemia also showed a significant association with the underlying vascular disease (P = 0.017, P = 0.039, P = 0.037 and P = 0.030, respectively. Hypercalcemia, hypertension and black race were factors significantly associated with left ventricular systolic dysfunction (P = 0.01, P = 0.0013 and P = 0.024, respectively. Our study shows that the most prevalent cardiovascular diseases in patients with ESRD were left ventricular hypertrophy, atherosclerotic disease, valvular disease and coronary artery disease. Hypertension and dyslipidemia were the common risk factors associated with cardiovascular diseases. The present study was undertaken to identify the main cardiovascular diseases and their risk factors in 160 patients with ESRD on HD in a single center in Brazil.

  10. [Autonomy of the patient with chronic diseases: from passive patient to active patient].

    Science.gov (United States)

    González Mestre, Assumpció

    2014-01-01

    Due to social, economic and cultural changes, there has been a transformation of Health Services around the world. A new figure has emerged from this: the Active Patient, more responsible, with more information and willing to change his life as a chronic patient. In order to respond to this new situation, several countries have established initiatives such as self-reliance programmes for chronic patients. The aim of this article is to underline the Expert Patient Programme Catalonia(®) and to explain its operation and the results obtained up until now. The purpose of this program is to improve the experience of chronic disease by patients, from meetings in which an expert patient provides his knowledge and experiences to a group of patients with the same disease, with the aim of promoting changes in habits and lifestyles that improve the quality of life and the coexistence of the person with his chronic process. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  11. The Prevalence of Fabry Disease in Patients with Chronic Kidney Disease in Turkey: The TURKFAB Study

    Directory of Open Access Journals (Sweden)

    Kultigin Turkmen

    2016-12-01

    Full Text Available Background/Aims: Fabry disease is a treatable cause of chronic kidney disease (CKD characterized by a genetic deficiency of α-galactosidase A. European Renal Best Practice (ERBP recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. Methods: This prospective study assessed α-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. Results: Three (all males of 313 CKD patients (0.95% were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%, tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%, heat intolerance (71%, and abdominal pain (57%. The most frequent manifestations in female patients were fatigue and cornea verticillata (50%, and tinnitus, vertigo and angiokeratoma (25%. Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever. Conclusions: The prevalence of Fabry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin.

  12. The Prevalence of Fabry Disease in Patients with Chronic Kidney Disease in Turkey: The TURKFAB Study.

    Science.gov (United States)

    Turkmen, Kultigin; Guclu, Aydın; Sahin, Garip; Kocyigit, Ismail; Demirtas, Levent; Erdur, Fatih Mehmet; Sengül, Erkan; Ozkan, Oktay; Emre, Habib; Turgut, Faruk; Unal, Hilmi; Karaman, Murat; Acıkel, Cengiz; Esen, Hasan; Balli, Ebru; Bıtırgen, Gulfidan; Tonbul, Halil Zeki; Yılmaz, Mahmut Ilker; Ortiz, Alberto

    2016-01-01

    Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of α-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. This prospective study assessed α-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. Three (all males) of 313 CKD patients (0.95%) were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%), tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%), heat intolerance (71%), and abdominal pain (57%). The most frequent manifestations in female patients were fatigue and cornea verticillata (50%), and tinnitus, vertigo and angiokeratoma (25%). Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever. The prevalence of Fabry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin. © 2016 The Author(s) Published by S. Karger AG, Basel.

  13. Recurrent Cholangitis in a Patient with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Caroli's Disease.

    Science.gov (United States)

    Hasegawa, Eiko; Sawa, Naoki; Hoshino, Junichi; Suwabe, Tatsuya; Hayami, Noriko; Yamanouchi, Masayuki; Sekine, Akinari; Hiramatsu, Rikako; Imafuku, Aya; Kawada, Masahiro; Ubara, Yoshifumi; Imamura, Tsunao; Takaichi, Kenmei

    We herein present a rare case of an autosomal dominant polycystic kidney disease (ADPKD) patient with Caroli's disease, a congenital embryonic biliary tree ductal plate abnormality often associated with autosomal recessive polycystic kidney disease. A 76-year-old woman with ADPKD on hemodialysis was admitted to our hospital with recurrent cholangitis and hepatobiliary stones. Caroli's disease was diagnosed according to typical imaging findings of cystic intrahepatic bile duct dilatation and the central dot sign. Hepatobiliary system abnormalities such as Caroli's disease should be considered in febrile ADPKD patients, even in the absence of typical clinical signs or symptoms.

  14. Patient education and disease activity: A study among rheumatoid arthritis patients

    NARCIS (Netherlands)

    Brus, H.L.M.; Brus, Herman L.M.; Taal, Erik; van de Laar, Mart A F J; Rasker, Johannes J.; Wiegman, O.

    1997-01-01

    Objective: To determine whether patients experiencing high disease activity derive more benefit from patient education than those experiencing low disease activity. - Methods: Data from a randomized study on the effects of a program of patient education were analyzed retrospectively. Four subgroups

  15. The Cultural Origins and Play Philosophy of Playworkers: An Interview with Penny Wilson

    Science.gov (United States)

    American Journal of Play, 2009

    2009-01-01

    Penny Wilson is a playworker--one of a group of professionals who facilitate children's play in adventure playgrounds, parks, and other settings, principally in the United Kingdom. Wilson grew up in the Southeast of England and spent much of her childhood playing on the coast near her family home. She studied illustration in art school, settled in…

  16. War, Medicine, and Cultural Diplomacy in the Americas: Frank Wilson and Brazilian cardiology.

    Science.gov (United States)

    Kropf, Simone P; Howell, Joel D

    2017-10-01

    American cultural diplomacy played a key role in the institutionalization of Brazilian cardiology. In 1942, Frank Wilson, an internationally recognized pioneer in electrocardiography, made an extended wartime visit to Rio de Janeiro and São Paulo. The visit was sponsored by the United States Department of State as part of Roosevelt's Good Neighbor Policy and brought Wilson together with a group of physicians who would establish the specialty of cardiology in Brazil. This US cultural and diplomatic initiative strengthened an academic network that was already evolving and would eventually prove to be of benefit to both sides. Latin American physicians began in the 1920s to visit Wilson's laboratory at the University of Michigan, where they established the relationships on which Wilson would build. While affiliation with the "Wilson school" advanced the cause of Brazilian cardiologists who sought to establish themselves as specialists, cooperation with Latin American physicians benefitted Wilson in his pursuit of wider recognition for his innovations in the use of electrocardiography (ECG). Wilson's identity as a scientific ambassador to Latin America helped in legitimating his approach to the clinical application of the ECG. A close examination of Wilson's relationship to Brazilian cardiology demonstrates the role played by science and medicine as a part of wartime cultural diplomacy, as well as the dynamics of the transnational circulation of scientific knowledge and practices. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. "Mens Sana in Corpore Sano": Human Values in Thomas Wilson's "The Arte of Rhetorique."

    Science.gov (United States)

    Luehring, Janet

    In 1553 the work that is touted as the first complete book written in English on rhetoric was published, Thomas Wilson's "Arte of Rhetorique." It became so popular it enjoyed eight printings within its century. Wilson was not a person to translate and read just for knowledge; he believed that knowledge should be imparted to the general…

  18. The Modern First Lady and Public Policy: From Edith Wilson through Hillary Rodham Clinton.

    Science.gov (United States)

    Black, Allida M.

    2001-01-01

    Discusses the role in and influence on public policy of twentieth century First Ladies including Edith Roosevelt, Helen Taft, Ellen Wilson, Edith Wilson, Florence Harding, Lou Henry Hoover, Eleanor Roosevelt, Jacqueline Kennedy, Lady Bird Johnson, Rosalynn Carter, Nancy Reagan, Barbara Bush, and Hillary Rodham Clinton. (CMK)

  19. Serological diagnosis of Chagas disease in HIV-infected patients

    Directory of Open Access Journals (Sweden)

    Dulce Stauffert

    2015-06-01

    Full Text Available INTRODUCTION: This study assessed the rate of request for the serological diagnosis of Chagas disease among human immunodeficiency virus (HIV-infected patients treated at the Specialized Care Service of Pelotas, Rio Grande do Sul, Brazil. METHODS: This cross-sectional study used secondary data obtained from the medical records of 252 patients aged between 18 and 75 years. RESULTS: The serological diagnosis of Chagas disease was requested only in 3.2% of cases. CONCLUSIONS: The results demonstrate poor adherence to protocols on the part of healthcare professionals, indicating the need to reevaluate the procedures applied to HIV-infected patients from endemic regions for both diseases.

  20. Providing dental treatment for patients with cardiovascular disease.

    Science.gov (United States)

    Waters, B G

    1995-01-01

    The appropriate management of dental patients with cardiovascular disease is contingent on appropriate assessment and evaluation. Baseline vital signs, a good medical history and medical evaluation are all essential for the safe delivery of care. All patients with cardiovascular disease can be managed using the following guidelines: 1. Properly assess the patient. This should include an assessment by the dentist and also a medical consultation if required. 2. Establish what medications the patient is taking along with the dose and timing and note any potential drug interactions and side effects. 3. Use short appointments (less than one hour), preferably in the morning. 4. Premedication should be considered to alleviate anxiety. The intraoperative use of nitrous oxide and oxygen is also a reasonable strategy for patients with cardiovascular disease, particularly those with ischemic heart disease. 5. Effective local anesthesia is important in order to avoid undue stress during the appointment as long as the guidelines for the administration of epinephrine are followed. The use of epinephrine impregnated gingival displacement cord should be strictly avoided in patients with cardiovascular disease. 6. For patients with angina pectoris, a fresh supply of nitroglycerin should be available at the time of the appointment. Prophylactic nitroglycerin has been shown to be effective in the prevention of both hypertension and angina pectoris during dental treatment. The appointment should be terminated early if the patient becomes overly anxious. In the event of cardiovascular symptoms during dental treatment, all work should be stopped. Emergency measures should be instituted if necessary. Preparations for emergencies should be undertaken by all dentists. The treatment of patients with cardiovascular disease is relatively simple if the proper steps are taken. The use of blood pressure measurements on all patients will help to screen for undiagnosed hypertension and all

  1. Moderately increased risk of urinary stone disease in patients with biopsy-verified coeliac disease.

    Science.gov (United States)

    Ludvigsson, J F; Zingone, F; Fored, M; Ciacci, C; Cirillo, M

    2012-02-01

    Urinary stone disease is a mal-absorptive disorder that is a significant health problem because of its high prevalence and incidence. However, there are few population-based studies on the risk of urinary stone disease in patients with coeliac disease (CD). To examine the risk of urinary stone disease in CD. Population-based cohort study. Using small intestinal biopsy report data from 1969 to 2008 obtained from all Swedish pathology departments (n = 28), we identified 28 735 patients with CD (equal to Marsh 3: villous atrophy). Patients were then matched for gender, age, county and calendar year to 142 177 reference individuals from the Swedish general population. We used Cox regression to estimate hazard ratios (HRs) for future urinary stone disease and conditional logistic regression to calculate odds ratios (ORs) for urinary stone disease before diagnosis of CD. Individuals with urinary stone disease were identified through the Swedish National Patient Register that contains data on inpatient care, outpatient care and day surgery. During follow-up, 314 individuals with CD and 1142 reference individuals developed urinary stone disease. This corresponded to a 27% increased risk of urinary stone disease in CD [95% confidence interval (CI) = 1.12-1.44]. CD patients had an absolute risk of urinary stone disease of 107/100 000 person-years (excess risk of 23/100 000). Risk estimates were similar in men and women, and did not differ according to age at CD diagnosis. Conditional logistic regression found that patients with CD were at a slightly increased risk also of prior urinary stone disease (OR = 1.19; 95% CI = 1.06-1.33). In this study, coeliac disease was associated with a moderately increased risk of urinary stone disease both before and after coeliac disease diagnosis. © 2012 Blackwell Publishing Ltd.

  2. A conceptual disease model for adult Pompe disease.

    Science.gov (United States)

    Kanters, Tim A; Redekop, W Ken; Rutten-Van Mölken, Maureen P M H; Kruijshaar, Michelle E; Güngör, Deniz; van der Ploeg, Ans T; Hakkaart, Leona

    2015-09-15

    Studies in orphan diseases are, by nature, confronted with small patient populations, meaning that randomized controlled trials will have limited statistical power. In order to estimate the effectiveness of treatments in orphan diseases and extrapolate effects into the future, alternative models might be needed. The purpose of this study is to develop a conceptual disease model for Pompe disease in adults (an orphan disease). This conceptual model describes the associations between the most important levels of health concepts for Pompe disease in adults, from biological parameters via physiological parameters, symptoms and functional indicators to health perceptions and final health outcomes as measured in terms of health-related quality of life. The structure of the Wilson-Cleary health outcomes model was used as a blueprint, and filled with clinically relevant aspects for Pompe disease based on literature and expert opinion. Multiple observations per patient from a Dutch cohort study in untreated patients were used to quantify the relationships between the different levels of health concepts in the model by means of regression analyses. Enzyme activity, muscle strength, respiratory function, fatigue, level of handicap, general health perceptions, mental and physical component scales and utility described the different levels of health concepts in the Wilson-Cleary model for Pompe disease. Regression analyses showed that functional status was affected by fatigue, muscle strength and respiratory function. Health perceptions were affected by handicap. In turn, self-reported quality of life was affected by health perceptions. We conceptualized a disease model that incorporated the mechanisms believed to be responsible for impaired quality of life in Pompe disease. The model provides a comprehensive overview of various aspects of Pompe disease in adults, which can be useful for both clinicians and policymakers to support their multi-faceted decision making.

  3. Nonmotor symptoms in patients suffering from motor neuron diseases

    Directory of Open Access Journals (Sweden)

    Rene Günther

    2016-07-01

    Full Text Available Background: The recently postulated disease spreading hypothesis has gained much attention, especially for Parkinson’s disease (PD. The various nonmotor symptoms (NMS in neurodegenerative diseases would be much better explained by this hypothesis than by the degeneration of disease-specific cell populations. Motor neuron disease (MND is primarily known as a group of diseases with a selective loss of motor function. Recent evidence, however, suggests disease spreading into nonmotor brain regions also in MND. The aim of this study was to comprehensively detect NMS in patients suffering from MND.Methods: We used a self-rating questionnaire including 30 different items of gastrointestinal, autonomic, neuropsychiatric and sleep complaints (NMSQuest which is an established tool in PD patients. 90 MND patients were included and compared to 96 controls.Results: In total, MND patients reported significantly higher NMS scores (median: 7 points in comparison to controls (median: 4 points. Dribbling, impaired taste/smelling, impaired swallowing, weight loss, loss of interest, sad/blues, falling and insomnia were significantly more prevalent in MND patients compared to controls. Interestingly excessive sweating was more reported in the MND group. Correlation analysis revealed an increase of total NMS score with disease progression.Conclusions: NMS in MND patients seemed to increase with disease progression which would fit with the recently postulated disease spreading hypothesis. The total NMS score in the MND group significantly exceeded the score for the control group, but only 8 of the 30 single complaints of the NMSQuest were significantly more often reported by MND patients. Dribbling, impaired swallowing, weight loss and falling could primarily be connected to motor neuron degeneration and declared as motor symptoms in MND.

  4. Clinical impact of exercise in patients with peripheral arterial disease.

    Science.gov (United States)

    Novakovic, Marko; Jug, Borut; Lenasi, Helena

    2017-08-01

    Increasing prevalence, high morbidity and mortality, and decreased health-related quality of life are hallmarks of peripheral arterial disease. About one-third of peripheral arterial disease patients have intermittent claudication with deleterious effects on everyday activities, such as walking. Exercise training improves peripheral arterial disease symptoms and is recommended as first line therapy for peripheral arterial disease. This review examines the effects of exercise training beyond improvements in walking distance, namely on vascular function, parameters of inflammation, activated hemostasis and oxidative stress, and quality of life. Exercise training not only increases walking distance and physiologic parameters in patients with peripheral arterial disease, but also improves the cardiovascular risk profile by helping patients achieve better control of hypertension, hyperglycemia, obesity and dyslipidemia, thus further reducing cardiovascular risk and the prevalence of coexistent atherosclerotic diseases. American guidelines suggest supervised exercise training, performed for a minimum of 30-45 min, at least three times per week, for at least 12 weeks. Walking is the most studied exercise modality and its efficacy in improving cardiovascular parameters in patients with peripheral arterial disease has been extensively proven. As studies have shown that supervised exercise training improves walking performance, cardiovascular parameters and quality of life in patients with peripheral arterial disease, it should be encouraged and more often prescribed.

  5. Elective Thoracolumbar Spine Fusion Surgery in Patients with Parkinson Disease.

    Science.gov (United States)

    Puvanesarajah, Varun; Jain, Amit; Qureshi, Rabia; Carstensen, S Evan; Tyger, Rosemarie; Hassanzadeh, Hamid

    2016-12-01

    Few data are available concerning clinical outcomes in patients with Parkinson disease who undergo elective thoracolumbar spine fusion surgery. The goal of this study is to elucidate complication and revision rates after posterior thoracolumbar fusion surgery in patients with Parkinson disease, with a focus on how Parkinson disease modifies these rates. The PearlDiver database (2005-2012) was queried for patients who underwent posterior approach thoracolumbar fusion from 2006 to 2011. Cohorts of patients with a previous diagnosis of Parkinson disease (n = 4816) and without (n = 280,702) were compared. Multivariate analysis that included various comorbidities and demographics was used to calculate effects of Parkinson disease on development of postoperative infection and major medical complications within 90 days and revision surgery within 1 year. For analyses, significance was set at P Parkinson disease was significantly associated with an increased risk for medical complications (adjusted odds ratio, 1.22; 95% confidence interval, 1.11-1.34; P Parkinson disease are more likely to require revision surgery and have higher rates of adverse medical events postoperatively. Patients with Parkinson disease should be appropriately selected to ensure favorable clinical outcomes. Copyright © 2016. Published by Elsevier Inc.

  6. Electrocardiographic characteristics of patients with chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Warnier, Miriam J; Rutten, Frans H; Numans, Mattijs E

    2013-01-01

    Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease. Electrocardiography (ECG) carries information about cardiac disease and prognosis, but studies comparing ECG characteristics between patients with and without COPD are lacking. We related ECG...... patients (9% versus 14%, p = 0.01). The prevalence of ECG abnormalities increased with severity of pulmonary obstruction. ECG abnormalities, especially conduction abnormalities are common in COPD patients, and the prevalence of ECG abnormalities increases with severity of COPD. This underlines......, including resting 12-lead ECG and pulmonary function tests. The reference group (n = 293) was a sample from the general population, also aged 65 or older, without COPD. Abnormal ECGs were more prevalent in COPD patients (50%) than in patients without COPD (36%, p = 0.054). Conduction abnormalities were...

  7. Caloric requirements in patients with inflammatory bowel disease.

    Science.gov (United States)

    Barot, L R; Rombeau, J L; Feurer, I D; Mullen, J L

    1982-01-01

    Measured resting energy expenditure (REE) was compared to predicted basal energy expenditure (BEE) in 35 consecutive patients with nonseptic inflammatory bowel disease (IBD) and 20 healthy volunteers. Patients with IBD were groups greater or less than 90% ideal body weight (IBW). The BEE in kcal/day was found to be equivalent to the measured REE in both patient groups. It is suggested that the BEE be used to determine caloric requirements in nonseptic patients with inflammatory bowel disease. Patients less than 90% IBW had significantly higher measured energy expenditure (26.4 +/- 1.0) per kg body weight than either controls (21.2 +/- 0.7) or patients greater than or equal to 90% IBW (21.2 +/- 0.8), p less than 0.001. It is suggested that this increased expenditure is due to a combined effect of weight loss and intrinsic disease. PMID:7055399

  8. Wolman disease in patients with familial hemophagocytic ...

    African Journals Online (AJOL)

    Solaf Elsayed

    2015-09-26

    Sep 26, 2015 ... The pregnancy was uncomplicated and he was deliv- ered by CS with a birth weight of 3.5 kg. His condition started at the age of 2.5 months when the ... Wolman disease, severe anemia and thrombocytopenia, increased ferritin and both foamy histiocytes and hemophago- cytic cells in bone marrow [8].

  9. Treatment options for patients with Gaucher disease

    African Journals Online (AJOL)

    Rabah M. Shawky

    2016-02-28

    Feb 28, 2016 ... Abstract Gaucher disease is the most common lysosomal storage disorder due to deficiency of. Я-glucocerebrosidase. Since the introduction of Ceredase in 1991, enzyme replacement therapy has been the mainstay of treatment with its major disadvantage of long life dependency on biweekly. IV therapy.

  10. Quality of life in chronic disease patients

    Directory of Open Access Journals (Sweden)

    Kalliopi Megari

    2013-09-01

    Full Text Available During the past decades there was an increasing predominance of chronic disorders, with a large number of people living with chronic diseases that can adversely affect their quality of life. The aim of the present paper is to study quality of life and especially Health-related quality of life (HRQoL in chronic diseases. HRQOL is a multidimensional construct that consists of at least three broad domains - physical, psychological, and social functioning - that are affected by one’s disease and/or treatment. HRQoL is usually measured in chronic conditions and is frequently impaired to a great extent. In addition, factors that are associated with good and poor HRQoL, as well as HRQoL assessment will be discussed. The estimation of the relative impact of chronic diseases on HRQoL is necessary in order to better plan and distribute health care resources aiming at a better HRQoL. [«All the people perceive the concept of living good or being well, that is the same as being happy». (Aristotle. 384-322 BC. Ethica Nichomachea

  11. Thyroid functional disease: an under-recognized cardiovascular risk factor in kidney disease patients

    OpenAIRE

    Rhee, Connie M.; Brent, Gregory A; Kovesdy, Csaba P; Soldin, Offie P.; Nguyen, Danh; Budoff, Matthew J; Brunelli, Steven M.; Kalantar-Zadeh, Kamyar

    2015-01-01

    Thyroid functional disease, and in particular hypothyroidism, is highly prevalent among chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In the general population, hypothyroidism is associated with impaired cardiac contractility, endothelial dysfunction, atherosclerosis and possibly higher cardiovascular mortality. It has been hypothesized that hypothyroidism is an under-recognized, modifiable risk factor for the enormous burden of cardiovascular disease and death in ...

  12. [Anti-hypertensive therapies in patients with heart disease].

    Science.gov (United States)

    Tanaka, Komei; Minamino, Tohru

    2015-11-01

    Abstract Hypertension is the major cause of cardiovascular disease. Persistent hypertension leads to cardiovascular remodeling and resulted in heart diseases such as coronary artery disease, heart failure, and arrhythmia. The presence of hypertension could also be a precipitating factor of heart diseases and form vicious cycle. Therefore, perfect blood pressure control is essential for the prevention of cardiovascular events. Additionally, it is ideal to choose anti-hypertensive agents, which have cardiovascular-protective effects as well as strong blood pressure-lowering effects. We herein describe anti-hypertensive therapies in patients with heart disease in accordance with JSH2014 and JCS guidelines.

  13. Infection Diseases in Geriatric Patients Who Admitted to Emergency Department

    OpenAIRE

    Orhan Akpinar

    2014-01-01

    Aim: In this study, it was aimed to investigate infectious disease frequency, most admission compliant, consultation type, the outpatient and hospitalization rates in geriatric patients who admitted to emergency department.Material and Method: Identification study was applied with computer based patient registration scan in 65 years or older patients who admitted to emergency department between 01.01.2011-31.12.2011. Results: Data of 115185 patients were evaluated for one year period. Geriatr...

  14. Local anesthesia selection algorithm in patients with concomitant somatic diseases.

    Science.gov (United States)

    Anisimova, E N; Sokhov, S T; Letunova, N Y; Orekhova, I V; Gromovik, M V; Erilin, E A; Ryazantsev, N A

    2016-01-01

    The paper presents basic principles of local anesthesia selection in patients with concomitant somatic diseases. These principles are history taking; analysis of drugs interaction with local anesthetic and sedation agents; determination of the functional status of the patient; patient anxiety correction; dental care with monitoring of hemodynamics parameters. It was found that adhering to this algorithm promotes prevention of urgent conditions in patients in outpatient dentistry.

  15. Knowledge, Beliefs and Attitudes of Psoriasis Patients About the Disease

    Directory of Open Access Journals (Sweden)

    Aslı Küçükünal

    2013-05-01

    Full Text Available Background and Design: This study evaluates the patients’ knowledge, opinions and attitudes about psoriasis.Materials and Methods: A total of 111 patients over the age of 18, clinically and histopathologically diagnosed with chronic plaque-type psoriasis were included in the study. Patients who have psychiatric illness and inadequate intelligence were excluded. A questionnaire including items on knowledge, opinions and attitudes on psoriasis were filled out by the patients and the results were analyzed statistically.Results: One hundred-eleven (45 female, 66 male patients were included in our study. 6.3% of patients did not know the diagnosis of their disease. 68.5% of patients thought that psoriasis was a contagious disease while18% thought that psoriasis was a hereditary condition. 88.3% of patients declined that they were informed about the disease by the doctor. 62.2% of patients believed that they had adequate information about psoriasis. 51.4% of patients believed that doctors gave them enough information about psoriasis. 44.1% of patients knew that psoriasis was aggravated by stress while 38.7% did not know any of the aggravating factors of psoriasis. 70.3% of patients believed that psoriasis would spread if not treated. Patients mostly (98.2% had idea about topical treatment options. 82% of patients were afraid of having psoriasis on their face. 5.4% of patients were uncomfortable with the idea of their partners’ having psoriasis. 72.1%, 88.3%, 72.1% of patients reported no negative effect of psoriasis on their relations with friends, family members, work or school life, respectivelyDiscussion: Our results showed that psoriasis patients do not have adequate knowledge about the disease. We think that dermatologists should pay more attention to inform and raise awareness of patie

  16. ABO Blood Group Distribution in Patients with Peptic Ulcer Disease

    OpenAIRE

    Gonzáles Flores, Pedro; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; Monge Salgado, Eduardo; Servicio de Gastroenterología, Hospital Nacional Daniel Alcides Carrión, Callao

    2014-01-01

    OBJETIVE: To determinate the ABO blood group distribution in patients with peptic ulcer disease ( PUD ). METHODS: Descriptive and retrospective study. Clinical records of patients with endoscopic diagnosis of peptic ulcer and ABO blood group typification between june 1994 and november 1996 were reviewed. Blood donnors and patients that attended the blood bank between july and august 1996 were taken as controls. RESULTS: 100 patients were studied. In controls 73% were blood group O, whereas in...

  17. Screening Fabry's disease in chronic kidney disease patients not on dialysis: a multicenter study.

    Science.gov (United States)

    Yeniçerioğlu, Yavuz; Akdam, Hakan; Dursun, Belda; Alp, Alper; Sağlam Eyiler, Funda; Akın, Davut; Gün, Yelda; Hüddam, Bülent; Batmazoğlu, Mehmet; Gibyeli Genek, Dilek; Pirinççi, Serhat; Ersoy, İsmail Rıfkı; Üzüm, Atilla; Soypaçacı, Zeki; Tanrısev, Mehmet; Çolak, Hülya; Demiral Sezer, Sibel; Bozkurt, Gökay; Akyıldız, Utku Oğan; Akyüz Ünsal, Ayşe İpek; Ünübol, Mustafa; Uslu, Meltem; Eryılmaz, Ufuk; Günel, Ceren; Meteoğlu, İbrahim; Yavaşoğlu, İrfan; Ünsal, Alparslan; Akar, Harun; Okyay, Pınar

    2017-11-01

    Fabry's disease is an X-linked inherited, rare, progressive, lysosomal storage disorder, affecting multiple organs due to the deficient activity of α-galactosidase A (α-Gal A) enzyme. The prevalence has been reported to be 0.15-1% in hemodialysis patients; however, the information on the prevalence in chronic kidney disease not on dialysis is lacking. This study aimed to determine the prevalence of Fabry's disease in chronic kidney disease. The patients older than 18 years, enclosing KDIGO 2012 chronic kidney disease definitions, not on dialysis, were enrolled. Dried blood spots on Guthrie papers were used to analyze α-Gal A enzyme and genetic analysis was performed in individuals with enzyme activity ≤1.2 μmol/L/h. A total of 1453 chronic kidney disease patients not on dialysis from seven clinics in Turkey were screened. The mean age of the study population was 59.3 ± 15.9 years. 45.6% of patients were female. The creatinine clearance of 77.3% of patients was below 60 mL/min/1.73 m 2 , 8.4% had proteinuria, and 2.5% had isolated microscopic hematuria. The mean value of patients' α-Gal A enzyme was detected as 2.93 ± 1.92 μmol/L/h. 152 patients had low levels of α-Gal A enzyme activity (≤1.2 μmol/L/h). In mutation analysis, A143T and D313Y variants were disclosed in three male patients. The prevalence of Fabry's disease in chronic kidney disease not on dialysis was found to be 0.2% (0.4% in male, 0.0% in female). Fabry's disease should be considered in the differential diagnosis of chronic kidney disease with unknown etiology even in the absence of symptoms and signs suggestive of Fabry's disease.

  18. Blood pressure fluctuation and hypertension in patients with Parkinson's disease

    Science.gov (United States)

    Tsukamoto, Tetsuro; Kitano, Yoshimi; Kuno, Sadako

    2013-01-01

    Objectives Blood pressure (BP) abnormalities have been known in Parkinson's disease (PD) patients. The present study aimed at determining how the BPs of PD patients fluctuate in a day. Methods A total of 37 PD patients and 44 OD (other disease) patients, all of who were inpatients, were monitored every 30 min by 24-h ambulatory blood pressure monitoring (ABPM). Results The average systolic BP and the number of patients who showed postprandial hypotension were not different between the two groups. However, occurrence of nocturnal hypertension, BP fluctuation of over 100 mmHg in a day and BP of over 200 mmHg were significantly more frequently observed in the PD patients than in the OD patients. In the PD patients, these parameters were not different between those who were suffering from the disease for less than 10 years and those with the disease for 10 years or longer, as well as between those who had a Hoehn–Yahr staging scale of 2–3 and those with a scale of 4–5. Conclusion Twenty-four-hour ABPM, not BP measurement once a day, enables us to determine the actual BP in PD patients. Although hypotension is a severe risk factor for falling and syncope, we emphasize the importance of monitoring rather hypertension and fluctuating BP in PD patients that may lead to a variety of other undesirable conditions. Management of hypotension, hypertension, and BP fluctuation is an important issue in the future. PMID:24363973

  19. Celiac disease and diabetes mellitus diagnosed in a pediatric patient with Hirschsprung disease.

    Science.gov (United States)

    Menchise, Alexandra Nicole; Condino, Adria A; Levitt, Marc A; Hebra, Andre; Wilsey, Michael J

    2013-02-01

    Hirschsprung disease is a disorder of neural crest migration characterized by intestinal aganglionosis along a variable segment of the gastrointestinal tract. It is a complex disorder associated with several syndromes. Celiac disease is an autoimmune enteropathy characterized by dietary intolerance to gluten proteins and can be associated with autoimmune conditions such as diabetes mellitus. Celiac disease can mimic Hirschsprung disease when presenting with constipation and abdominal distention. We present the case of celiac disease diagnosed in a patient with Hirschsprung disease who subsequently developed type one diabetes mellitus.

  20. Prevalence of coeliac disease in patients with thyroid autoimmunity.

    Science.gov (United States)

    Valentino, R; Savastano, S; Tommaselli, A P; Dorato, M; Scarpitta, M T; Gigante, M; Micillo, M; Paparo, F; Petrone, E; Lombardi, G; Troncone, R

    1999-01-01

    The occurrence of autoimmune thyroid disorders among patients with coeliac disease (CD) is well documented, but the exact prevalence of CD among patients with autoimmune thyroid diseases (ATD) is as yet unclear. We screened 150 newly diagnosed patients with ATD by serum endomysial antibody detection (EmA). In 5 subjects (3.3%) EmA positivity was found; all underwent jejunal biopsy. On gluten-free diet an excellent clinical and histological response was recorded with an improvement of hypothyroidism and reduction of the thyroxine dosage. Our data suggest a significant high prevalence (3.3%) of CD in patients with ATD, in particular with Hashimoto's thyroiditis.

  1. Nutritional support of surgical patients with inflammatory bowel disease.

    Science.gov (United States)

    Wagner, I Janelle; Rombeau, John L

    2011-08-01

    Patients with inflammatory bowel disease (IBD) in need of surgery are often malnourished, which in turn increases the risk for postoperative complications. Malnutrition in IBD patients who must undergo surgery is due to the disordered activity of the diseased intestine, decreased dietary intake, and adverse effects of potent medications. IBD operations predispose patients to both macronutrient and micronutrient deficiencies. If the gut can be used safely it is the preferential route for feeding, though preoperative and postoperative parenteral nutrition remains a viable alternative for severely malnourished patients. New nutrient therapies include immunonutrition, fish oils, and probiotics. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. How do patients conceptualize chronic obstructive pulmonary disease?

    National Research Council Canada - National Science Library

    Goldman, RE; Mennillo, L; Stebbins, P; Parker, DR

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is a leading cause of death in the United States, yet even at risk or diagnosed patients misunderstand COPD and its consequences for their quality of life and mortality...

  3. Generalized Vitiligo Associated Autoimmune Diseases in Japanese Patients Their Families

    Directory of Open Access Journals (Sweden)

    Tomohiko Narita

    2011-01-01

    Conclusions: Among Japanese vitiligo patients, there is a subgroup with strong evidence of genetically determined susceptibility to not only vitiligo, but also to autoimmune thyroid disease and other autoimmune disorders.

  4. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis

    DEFF Research Database (Denmark)

    Chertow, Glenn M; Block, Geoffrey A; Correa-Rotter, Ricardo

    2012-01-01

    Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk ...

  5. Priority Settings in patients with Chronic Diseases and Cancer

    DEFF Research Database (Denmark)

    Arreskov, Anne Beiter; Graungaard, Anette Hauskov; Søndergaard, Jens

    Priority setting in patients with cancer and comorbidities Background and aim As both the cancer incidence and the number of patients diagnosed with chronic diseases are increasing, a growing population of cancer survivors will also deal with comorbid chronic diseases. The period after completed...... cancer treatment, where patients are transitioning to survivorship, might be a vulnerable time. Uncertainty about health status, physical- and emotional symptoms from cancer disease and treatment, and perhaps uncertainty about which doctor to consult, might influence patients’ priorities and attention...... to comorbidities. Some studies show that participation in regular follow-up consultations concerning comorbid chronic diseases and lifestyle are lower among cancer survivors than non-cancer patients. This could be explained by changes in the patient’s priority setting or in the doctor’s priority and attempt...

  6. Steroid allergy in patients with inflammatory bowel disease.

    LENUS (Irish Health Repository)

    Malik, M

    2007-11-01

    Background: Contact allergy to a steroid enema leading to worsening of inflammatory bowel disease (IBD) has recently been reported. This study was designed to look for evidence of steroid allergy in patients with IBD.

  7. Interdisciplinary Management of Patient with Advanced Periodontal Disease.

    Science.gov (United States)

    Kochar, Gagan Deep; Jayan, B; Chopra, S S; Mechery, Reenesh; Goel, Manish; Verma, Munish

    2016-01-01

    This case report describes the interdisciplinary management of an adult patient with advanced periodontal disease. Treatment involved orthodontic and periodontal management. Good esthetic results and dental relationships were achieved by the treatment.

  8. Circular Wilson loops in defect conformal field theory

    Science.gov (United States)

    Aguilera-Damia, Jeremías; Correa, Diego H.; Giraldo-Rivera, Victor I.

    2017-03-01

    We study a D3-D5 system dual to a conformal field theory with a codimension-one defect that separates regions where the ranks of the gauge groups differ by k. With the help of this additional parameter, as observed by Nagasaki, Tanida and Yamaguchi, one can define a double scaling limit in which the quantum corrections are organized in powers of λ/k 2, which should allow to extrapolate results between weak and strong coupling regimes. In particular we consider a radius R circular Wilson loop placed at a distance L, whose internal space orientation is given by an angle χ. We compute its vacuum expectation value and show that, in the double scaling limit and for small χ and small L/R, weak coupling results can be extrapolated to the strong coupling limit.

  9. The Mount Wilson Optical Shop during the Second World War

    Science.gov (United States)

    Abrahams, P.

    2004-12-01

    During the Second World War, the Optical Shop of Mount Wilson Observatory, located in Pasadena, engaged in a variety of exacting and pioneering ventures in optical design and fabrication. Roof prisms for military optics were produced on a large scale, leading to the production of an instruction manual, for guidance in other workshops. Triple mirrors, or autocollimating corner cubes, were another precision part made in large numbers. Aerial photography was extensively developed. Test procedures for measuring resolution of lenses were researched. Various camera shutters and film sweep mechanisms were devised. The most significant work concerned Schmidt cameras, for possible use in night-time aerial photography. Variations included a solid Schmidt, and the Schmidt Cassegrain, which was fabricated for the first time at MWO. Key figures include Don Hendrix, Roger Hayward, Aden Meinel, and Walter Adams.

  10. Holomorphic variables in magnetized brane models with continuous Wilson lines

    CERN Document Server

    Camara, Pablo G; Dudas, Emilian

    2010-01-01

    We analyze the action of the target-space modular group in toroidal type IIB orientifold compactifications with magnetized D-branes and continuous Wilson lines. The transformation of matter fields agree with that of twisted fields in heterotic compactifications, constituting a check of type I/heterotic duality. We identify the holomorphic N = 1 variables for these compactifications. Matter fields and closed string moduli are both redefined by open string moduli. The redefinition of matter fields can be read directly from the perturbative Yukawa couplings, whereas closed string moduli redefinitions are obtained from D-brane instanton superpotential couplings. The resulting expressions reproduce and generalize, in the presence of internal magnetic fields, previous results in the literature.

  11. Therapy of obese patient with Cardiovascular Disease

    OpenAIRE

    Jindal, Ankur; Whaley-Connell, Adam; Brietzke, Stephen; Sowers, James R

    2013-01-01

    Obesity has reached epidemic proportions and is a significant public health concern. Obesity is associated with increased diabetes, cardiovascular and kidney disease, and associated morbidity and mortality. Despite the increasing public health problem of obesity, there is a dearth of effective treatment options. Following the FDA mandated withdrawal of sibutramine, the treatment options for obesity were limited to orlistat as the only pharmacological treatment option for long term management ...

  12. Mitochondrial Diseases: Clinical Features- Management of Patients

    Directory of Open Access Journals (Sweden)

    Filiz Koc

    2003-02-01

    Full Text Available Mitochondria are unique organells which their own DNA in cells. Human mitochondrial DNA is circular, double-stranded molecule and small. Because all mitochondria are contributed by the ovum during the formation of the zygote, the mitochondrial genom is transmitted by maternal inheritance. Multisystem disorders such as deafness, cardiomyopathy, miyopathy can be seen in mitochondrial diseases. [Archives Medical Review Journal 2003; 12(0.100: 14-31

  13. Celiac disease prevalence in patients with iron deficiency anemia.

    Science.gov (United States)

    Çekın, Ayhan Hilmi; Çekın, Yeşim; Sezer, Cem

    2012-01-01

    Iron deficiency anemia may be the first presenting finding of celiac disease, which is a common autoimmune disorder triggered by the intake of certain proteins. The aim of this study was to determine the prevalence of celiac disease in patients with iron deficiency anemia of obscure origin. Eighty-four patients with the diagnosis of iron deficiency anemia of obscure origin were included in the study. Histologic findings for celiac disease were investigated in biopsy specimens taken from the second part of the duodenum of all subjects. Patients were also screened using anti-endomysial and anti-gliadin antibodies. The diagnosis of celiac disease was confirmed by both serological positivity and histopathological findings. In 6 of 84 patients (7.14%), both serologic and histopathologic findings were correlated with celiac disease. After six months under a gluten-free diet, their mean hemoglobin levels increased from 10.3 ± 0.64 to 12.97 ± 1.48 g/dl (p=0.002). One patient with positive serology for celiac disease but normal duodenal mucosal biopsies also improved clinically after a gluten-free diet at the end of the follow-up and was considered as celiac disease. Six of these 7 celiac disease patients (85.7%) were premenopausal women, with a mean age of 37.5 ± 8.45 years. Clinicians should consider celiac disease as a possible cause of anemia in all patients with iron deficiency anemia of obscure origin, even in menstruating women. Serologic screening tests should be performed in premenopausal women with iron deficiency anemia, especially when anemia is refractory to oral iron treatment.

  14. Self-monitoring of health data by patients with a chronic disease: does disease controllability matter?

    Science.gov (United States)

    Huygens, Martine W J; Swinkels, Ilse C S; de Jong, Judith D; Heijmans, Monique J W M; Friele, Roland D; van Schayck, Onno C P; de Witte, Luc P

    2017-03-20

    There is a growing emphasis on self-monitoring applications that allow patients to measure their own physical health parameters. A prerequisite for achieving positive effects is patients' willingness to self-monitor. The controllability of disease types, patients' perceived self-efficacy and health problems could play an essential role in this. The purpose of this study is to investigate the relationship between patients' willingness to self-monitor and a range of disease and patient specific variables including controllability of disease type, patients' perceived self-efficacy and health problems. Data regarding 627 participants with 17 chronic somatic disease types from a Dutch panel of people with chronic diseases have been used for this cross-sectional study. Perceived self-efficacy was assessed using the general self-efficacy scale, perceived health problems using the Physical Health Composite Score (PCS). Participants indicated their willingness to self-monitor. An expert panel assessed for 17 chronic disease types the extent to which patients can independently keep their disease in control. Logistic regression analyses were conducted. Patients' willingness to self-monitor differs greatly among disease types: patients with diabetes (71.0%), asthma (59.6%) and hypertension (59.1%) were most willing to self-monitor. In contrast, patients with rheumatism (40.0%), migraine (41.2%) and other neurological disorders (42.9%) were less willing to self-monitor. It seems that there might be a relationship between disease controllability scores and patients' willingness to self-monitor. No evidence is found of a relationship between general self-efficacy and PCS scores, and patients' willingness to self-monitor. This study provides the first evidence that patients' willingness to self-monitor might be associated with disease controllability. Further research should investigate this association more deeply and should focus on how disease controllability influences

  15. Gravity duals of half-BPS Wilson loops

    Energy Technology Data Exchange (ETDEWEB)

    D' Hoker, Eric; Estes, John; Gutperle, Michael [Department of Physics and Astronomy, University of California, Los Angeles, CA 90095 (United States)

    2007-06-15

    We explicitly construct the fully back-reacted half-BPS solutions in Type IIB supergravity which are dual to Wilson loops with 16 supersymmetries in N = 4 super Yang-Mills. In a first part, we use the methods of a companion paper to derive the exact general solution of the half-BPS equations on the space AdS{sub 2} x S{sup 2} x S{sup 4} x {sigma}, with isometry group SO(2, 1) x SO(3) x SO(5) in terms of two locally harmonic functions on a Riemann surface {sigma} with boundary. These solutions, generally, have varying dilaton and axion, and non-vanishing 3-form fluxes. In a second part, we impose regularity and topology conditions. These non-singular solutions may be parametrized by a genus g {>=} 0 hyperelliptic surface {sigma}, all of whose branch points lie on the real line. Each genus g solution has only a single asymptotic AdS{sub 5} x S{sup 5} region, but exhibits g homology 3-spheres, and an extra g homology 5-spheres, carrying respectively RR 3-form and RR 5-form charges. For genus 0, we recover AdS{sub 5} x S{sup 5} with 3 free parameters, while for genus g {>=} 1, the solution has 2g+5 free parameters. The genus 1 case is studied in detail. Numerical analysis is used to show that the solutions are regular throughout the g = 1 parameter space. Collapse of a branch cut on {sigma} subtending either a homology 3-sphere or a homology 5-sphere is non-singular and yields the genus g-1 solution. This behavior is precisely expected of a proper dual to a Wilson loop in gauge theory.

  16. Duodopa pump treatment in patients with advanced Parkinson's disease

    DEFF Research Database (Denmark)

    Karlsborg, Merete; Korbo, Lise; Regeur, Lisbeth

    2010-01-01

    Patients with advanced Parkinson's disease (PD) often develop motor complications including fluctuations and involuntary movements (dyskinesias). In Denmark, treatment has comprised Deep Brain Stimulation (DBS) since the late 1990s, and as from 2002 use of a subcutaneous apomorphine pump. Monothe......Patients with advanced Parkinson's disease (PD) often develop motor complications including fluctuations and involuntary movements (dyskinesias). In Denmark, treatment has comprised Deep Brain Stimulation (DBS) since the late 1990s, and as from 2002 use of a subcutaneous apomorphine pump...

  17. Impaired vascular reactivity in patients with chronic kidney disease

    DEFF Research Database (Denmark)

    Tetzner, Fabian; Scholze, Alexandra; Wittstock, Antje

    2008-01-01

    Patients with chronic kidney disease (CKD) show increased cardiovascular morbidity. We hypothesized that vascular properties which can be routinely evaluated noninvasively are related to different stages of CKD and their clinical and biochemical characteristics.......Patients with chronic kidney disease (CKD) show increased cardiovascular morbidity. We hypothesized that vascular properties which can be routinely evaluated noninvasively are related to different stages of CKD and their clinical and biochemical characteristics....

  18. Obstructive sleep apnea in chronic obstructive pulmonary disease patients.

    LENUS (Irish Health Repository)

    Lee, Ruth

    2011-03-01

    Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) represent two of the most prevalent chronic respiratory disorders and cardiovascular diseases are major co-morbidities in both. Co-existence of both disorders (overlap syndrome) occurs in 1% of adults and overlap patients have worse nocturnal hypoxemia and hypercapnia than COPD and OSA patients alone. The present review discusses recent data concerning the pathophysiological and clinical significance of the overlap syndrome.

  19. Osteoprotegerin and mortality in hemodialysis patients with cardiovascular disease

    DEFF Research Database (Denmark)

    Winther, Simon; Christensen, Jeppe Hagstrup; Flyvbjerg, Allan

    2013-01-01

    Abstract BACKGROUND: Patients treated with hemodialysis (HD) have an increased mortality, mainly caused by cardiovascular disease (CVD). Osteoprotegerin (OPG) is a glycoprotein involved in the regulation of the vascular calcification process. Previous studies have demonstrated that OPG is a progn......Abstract BACKGROUND: Patients treated with hemodialysis (HD) have an increased mortality, mainly caused by cardiovascular disease (CVD). Osteoprotegerin (OPG) is a glycoprotein involved in the regulation of the vascular calcification process. Previous studies have demonstrated that OPG...

  20. [Palliative care of patients with terminal obstructive pulmonary disease].

    Science.gov (United States)

    von Plessen, Christian; Nielsen, Thyge L; Steffensen, Ida E; Larsen, Shuruk Al-Halwai; Taudorf, Ebbe

    2011-10-17

    Terminal chronic obstructive pulmonary disease (COPD) and advanced cancer have similar prognosis and symptom burden. However, palliative care of patients with terminal COPD has been neglected in Denmark. We describe the symptoms of terminal COPD and suggest criteria for defining the palliative phase of the disease. Furthermore we discuss the prognostic and ethical challenges for patients, their families and their caregivers. Finally, we summarize the current evidence for palliative treatment of dyspnoea and ways to evaluate response to treatment.

  1. Prevalence and overlap of Disease Management Program diseases in older hospitalized patients.

    Science.gov (United States)

    Juul-Larsen, Helle Gybel; Petersen, Janne; Sivertsen, Ditte Maria; Andersen, Ove

    2017-09-01

    Many countries, like Denmark, have tailored Disease Management Programs (DMPs) based on patients having single chronic diseases [defined institutionally as "program diseases" (PDs)], which can complicate treatment for those with multiple chronic diseases. The aims of this study were (a) to assess the prevalence and overlap among acutely hospitalized older medical patients of PDs defined by the DMPs, and (b) to examine transitions between different departments during hospitalization and mortality and readmission within two time intervals among patients with the different PDs. We conducted a registry study of 4649 acutely hospitalized medical patients ≥65 years admitted to Copenhagen University Hospital, Hvidovre, Denmark, in 2012, and divided patients into six PD groups (type 2 diabetes, chronic obstructive pulmonary disease, cardiovascular disease, musculoskeletal disease, dementia and cancer), each defined by several ICD-10 codes predefined in the DMPs. Of these patients, 904 (19.4%) had 2 + PDs, and there were 47 different combinations of the six different PDs. The most prevalent pair of PDs was type 2 diabetes with cardiovascular disease in 203 (22.5%) patients, of whom 40.4% had an additional PD. The range of the cumulative incidence of being readmitted within 90 days was between 28.8% for patients without a PD and 46.6% for patients with more than one PD. PDs overlapped in many combinations, and all patients had a high probability of being readmitted. Hence, developing strategies to create a new generation of DMPs applicable to older patients with comorbidities could help clinicians organize treatment across DMPs.

  2. Absence of high-affinity calreticulin autoantibodies in patients with systemic rheumatic diseases and coeliac disease

    DEFF Research Database (Denmark)

    Jørgensen, C S; Hansen, K B; Jacobsen, Søren

    2005-01-01

    Calreticulin has been reported to be an autoantigen in various autoimmune connective tissue diseases and in coeliac disease. Previous studies have used incubation buffers with low salt and low detergent concentrations (low stringency conditions) with serum albumin or other proteins as a blocking...... binding (high stringency conditions). Using the high stringency conditions, we screened sera from 107 patients with systemic lupus erythematosus, sera from patients with other systemic autoimmune diseases and from children with coeliac disease for the presence of high-affinity calreticulin autoantibodies...... by immunoblotting and ELISA. None of the sera contained high-affinity calreticulin antibodies. It is concluded that calreticulin is not a common autoantigen in patients with autoimmune connective tissue diseases or coeliac disease....

  3. Role of smoking in periodontal disease among diabetic patients.

    Science.gov (United States)

    Obradović, R; Kesić, L J; Gasić, J; Petrović, M; Zivković, N

    2012-01-01

    The objective of the study was to analyse the effect of smoking on periodontal disease in diabetic patients. One hundred and fifty patients participated in the study Fifty patients with Type 1 diabetes mellitus (DM) and periodontal disease were the first group; 50 patients with Type 2 DM and periodontal disease were the second group, and 50 non-diabetic patients with periodontal disease were the third group. After anamnesis was taken, the variable in the analysis was smoker/non-smoker The status of the oral hygiene and periodontal condition was recorded using Plaque index, Supragingival calculus index, Subgingival calculus index, Gingival index, Periodontal Disease Index and Community Periodontal Index of Treatment Needs, by the periodontologist. Except Gingival index, mean values of all investigated indices were higher in smokers in all investigated groups. Periodontal disease is more advanced in diabetic smokers compared to diabetic non-smokers. It can be concluded that smoking negatively affects the course of diabetic periodontal disease and increases the risk of attachment loss. Diabetic smokers are at high risk for poor periodontal prognosis, and they should be included in careful periodontal treatment.

  4. Cryptosporidiosis in patients with diarrhea and chronic liver diseases.

    Science.gov (United States)

    Mousa, Nasser; Abdel-Razik, Ahmed; El-Nahas, Hala; El-Shazly, Atef; Abdelaziz, Mohammad; Nabih, Marwa; Hamed, Magdy; Eissa, Mohammad; Effat, Narmin; Eldars, Walled

    2014-12-15

    The aim of this study was to evaluate the epidemiology and clinical significance of Cryptosporidium in patients with diarrhea and chronic liver diseases. The study included 150 patients with chronic liver diseases and diarrhea, and 50 subjects with diarrhea as a control group. Stool samples were screened for the presence of Cryptosporidium by microscopic examination after modified Ziehl-Neelsen staining and detection of Cryptosporidium coproantigen by enzyme-linked immunosorbent assay (ELISA). The prevalence of Cryptosporidium infection in patients with chronic liver diseases was 30% (45/150) versus 14% (7/50) in controls. Cryptosporidium infection increased with the progression of chronic liver diseases from Child-Pugh class A to Child-Pugh class C (p 9 (pdiarrhea associated with Cryptosporidium infection developed hepatic encephalopathy, and only diarrhea was identified as a precipitating factor for hepatic encephalopathy. Cryptosporidium is one of the important causes of diarrhea in patients with chronic liver diseases. The infection significantly increased with the progression of chronic liver diseases. In patients with advanced chronic liver diseases, Cryptosporidium infection may be a precipitating factor of hepatic encephalopathy.

  5. Arterial Disease in Patients With Human Immunodeficiency Virus Infection

    OpenAIRE

    Stein, James H.; Currier, Judith S.; HSUE, Priscilla Y

    2014-01-01

    With advances in antiretroviral therapy, individuals with human immunodeficiency virus (HIV) infection are living longer and increasingly die of non-HIV related diseases such as cardiovascular disease (CVD). Several observational studies suggest that HIV-infected patients on ART are at increased CVD risk; however, the precise mechanisms underlying the association between HIV infection and CVD risk are uncertain. Atherosclerosis and arterial disease in HIV-infected individuals is a multifactor...

  6. Patients with psoriasis have an increased risk of cardiovascular diseases

    DEFF Research Database (Denmark)

    Ahlehoff, Ole; Gislason, Gunnar; Lindhardsen, Jesper

    2012-01-01

    Psoriasis is a chronic immunoinflammatory disease that affects 2-3% of the population and shares pathophysiologic mechanisms and risk factors with cardiovascular diseases. Studies have suggested psoriasis as an independent risk factor for cardiovascular disease and Danish guidelines...... on cardiovascular risk factor modification in patients with psoriasis and psoriatic arthritis have recently been published. We provide a short review of the current evidence and the Danish guidelines....

  7. Pulmonary function tests in patients with Parkinson's disease: A ...

    African Journals Online (AJOL)

    Background: In Parkinson's disease (PD), morbidity and mortality are commonly caused by respiratory disorders from pulmonary function ... Key words: Nigeria, Parkinson's disease, pulmonary function. Date of Acceptance: 25-Jun-2015 .... patient becomes sedentary, and exercise training as a part. Table 1: Comparison of ...

  8. Small bowel ultrasound in patients with celiac disease

    Energy Technology Data Exchange (ETDEWEB)

    Bartusek, D. [Department of Radiology, Masaryk University hospital Brno (Czech Republic)], E-mail: dbartusek@fnbrno.cz; Valek, V. [Department of Radiology, Masaryk University hospital Brno (Czech Republic)], E-mail: v.valek@fnbrno.cz; Husty, J. [Department of Radiology, Masaryk University hospital Brno (Czech Republic)], E-mail: jhusty@fnbrno.cz; Uteseny, J. [Department of Pediatric Internal Medicine, Masaryk University hospital Brno (Czech Republic)], E-mail: juteseny@fnbrno.cz

    2007-08-15

    Objective: Celiac disease (CD) is a common, lifelong disease with small bowel malabsorption based on genetically conditioned gluten intolerance. The clinical manifestation could be very heterogeneous. The proof of celiac disease is now based mainly on clinical and laboratory (antibodies and enterobiopsy) signs, which are in some cases problematic and inconvenient. Materials and methods: In our study we have examined 250 patients with suspection or with proven celiac disease and we evaluated specific ultrasound small bowel changes in this group. In the next step, we chose 59 patients with laboratory proved celiac disease and we statistically compared ultrasound, other laboratory and clinical findings in different forms and stages of the disease. Results: Specific small bowel pathologies in patients with celiac disease (like changes of intestinal villi in different parts of small bowel, abnormal peristalsis and mesenterial lymphadenopathy) can be well visualized by ultrasound and in combination with clinical and laboratory signs ultrasound examination could have an important role in screening, determination of diagnosis and monitoring of patients with different forms of celiac disease.

  9. Renal disease in HIV infected patients at University of Benin ...

    African Journals Online (AJOL)

    Background: HIV related renal disease is a common occurrence in patients with HIV infection. It is the third leading cause of end stage renal disease among African-American males between the ages of 20 and 64 years in USA. Renal function impairment has been reported at all stages of HIV infection. The aim of this study ...

  10. Assessment of dyslipidemia in renal disease patients | Digban ...

    African Journals Online (AJOL)

    Dyslipidemia is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high density lipoprotein level that contributes to the development of atherosclerosis. Lipid pattern of renal disease patients were determined. One hundred volunteers were recruited for this study which comprised of sixty renal disease ...

  11. Management of sickle cell disease in patients undergoing cardiac surgery.

    Science.gov (United States)

    Crawford, Todd C; Carter, Michael V; Patel, Rina K; Suarez-Pierre, Alejandro; Lin, Sophie Z; Magruder, Jonathan Trent; Grimm, Joshua C; Cameron, Duke E; Baumgartner, William A; Mandal, Kaushik

    2017-02-01

    Sickle cell disease is a life-limiting inherited hemoglobinopathy that poses inherent risk for surgical complications following cardiac operations. In this review, we discuss preoperative considerations, intraoperative decision-making, and postoperative strategies to optimize the care of a patient with sickle cell disease undergoing cardiac surgery. © 2017 Wiley Periodicals, Inc.

  12. Adherence of adult Chronic Kidney Disease patients with regard to ...

    African Journals Online (AJOL)

    Objective: Chronic Kidney Disease (CKD) has become a major health problem as a result of complicated interrelationships with diabetes mellitus, hypertension and other associated diseases. Effective management of CKD depends on patient's adherence to their dialysis plan, medications, dietary and fluid restrictions.

  13. Huntington\\'s disease: Genetic heterogeneity in black African patients

    African Journals Online (AJOL)

    Objective. Huntington's disease (HD) has been reported to occur rarely in black patients. A new genetic variant– Huntington's disease-like 2 (HDL2) – occurring more frequently in blacks, has recently been described. The absence of an expanded trinucleotide repeat at the chromosome 4 HD locus was previously regarded ...

  14. Immune activation and nutritional status in adult Crohn's disease patients.

    Science.gov (United States)

    Reimund, J-M; Arondel, Y; Escalin, G; Finck, G; Baumann, R; Duclos, B

    2005-06-01

    Recent attention focused on the effect of inflammatory cytokines on intermediary metabolism contributing to the nutritional disturbances observed in acute or chronic inflammatory diseases. To examine the interactions between immune activation and nutritional parameters in adult Crohn's disease patients. We analysed anthropometric and biochemical nutritional parameters in 40 Crohn's disease patients and 26 healthy controls, and related them to inflammatory and immune markers. Weight, body mass index, mid-arm circumference, triceps skinfold thickness, as well as albumin, transthyretin, retinol binding protein, insulin growth factor-I and Vitamin A were significantly decreased in Crohn's disease patients and negatively correlated to disease activity. By contrast, erythrocyte sedimentation rate, fibrinogen, C-reactive protein, alpha1-acylglycoprotein, soluble receptor of interleukin-2, blood neopterin, tumour necrosis factor-alpha and interleukin-1beta concentrations were significantly higher in patients and positively correlated to disease activity. Nutritional parameters and acute phase reactants were linked to tumour necrosis factor-alpha and interleukin-1beta concentrations, and markers of nutritional status were negatively correlated to positive acute phase reactants. In Crohn's disease, inflammatory cytokines appear partly responsible for decreased nutritional status. Thus, nutritional intervention to correct nutritional (in particular protein) depletion, and/or therapeutic intervention reducing inflammation and therefore restoring adequate nutritional proteins synthesis, appears a major therapeutic goal in active Crohn's disease.

  15. Steven Johnson syndrome in a patient with Cushing's disease.

    Science.gov (United States)

    Mustafa, N; Periyasamy, P; Kamaruddin, N

    2009-09-01

    Cushing's syndrome is a pathological condition associated with excessive cortisol production, the commonest etiology being Cushing's disease. Corticosteroids in high doses have been used in the management of Steven Johnson Syndrome (SJS) with favourable outcome. We describe a patient with Cushing's disease who developed SJS, one week after taking sperulina a product from sea-weed while waiting for transphenoidal surgery.

  16. Collection of hematopoietic stem cells from patients with autoimmune diseases

    NARCIS (Netherlands)

    Burt, RK; Fassas, A; Snowden, JA; Kozak, T; Wulffraat, NM; Nash, RA; Dunbar, CE; Arnold, R; Prentice, G; Bingham, S; Marmont, AM; McSweeney, PA; van Laar, J.M.

    We reviewed data from 24 transplant centers in Asia, Australia, Europe, and North America to determine the outcomes of stem cell collection including methods used, cell yields, effects on disease activity, and complications in patients with autoimmune diseases. Twenty-one unprimed bone marrow

  17. Knowledge about coronary artery disease among patients admitted ...

    African Journals Online (AJOL)

    Conclusion: Our cardiac patients have poor knowledge about their disease and improvement on this level of education is needed. Keywords: Coronary artery disease, Knowledge, Acute coronary syndrome. Résumé Introduction: La maladie d'artère coronaire est une maladie meurtère grave partout dans le monde entire.

  18. Palliative Care for Patients and Families With Parkinson's Disease

    NARCIS (Netherlands)

    Bouca-Machado, R.; Titova, N.; Chaudhuri, K.R.; Bloem, B.R.; Ferreira, J.J.

    2017-01-01

    Parkinson's disease is the second most common neurodegenerative disease worldwide. There is widespread consensus that Parkinson patients, their carers, and clinicians involved in their care would benefit from a fully integrated, need-based provision of palliative care. However, the concept of

  19. Diabetic foot disease in Ethiopian patients: A hospital based study

    African Journals Online (AJOL)

    Bernt Lindtjørn

    stage of their life, and foot diseases are leading cause of hospitalization among such patients (2-4). The presentation of diabetic foot disease is variable, ranging from cellulitis, abscesses, and ulcers to gangrene. Surgical management depends on the presentation, and varies from minor debridement, incision and drainage, ...

  20. Pattern of pericardial diseases in HIV positive patients at University ...

    African Journals Online (AJOL)

    Rationale. Pericarditis has been reported as the most common cardiac complication of HIV disease, followed by pericardial effusion. Methods. A retrospective review was conducted of all 68 patients treated for pericardial diseases between August 2003 and July 2008 at University College Hospital, Ibadan, Nigeria.