WorldWideScience

Sample records for multiple disease types

  1. Effect of disease duration on personality type in multiple sclerosis patients and healthy individual

    Sahar Vesal

    2016-01-01

    Full Text Available Background: Multiple sclerosis may have profound emotional consequences. The relation between psychological and physical factors could lead patients toward unforeseen disease. This study focuses on multiple sclerosis (MS disease duration on personality type A and B in relation to individuals' behaviors. Materials and Methods: This descriptive-analytical study was conducted in Isfahan Alzahra hospital in 2013. Three hundred MS patients and 100 healthy individuals were determined. The distributed questionnaires related to MS patients and considering the descriptive statistics such as demographic variables. Data were analyzed by SPSS software (version 18 based on Chi-square test and independent T-test. Results: Disease duration varied between 1 to 38 years: 30% (1-4 years, 38% (5-10 years, 20% (10-20 years, and 12% (more than 20 years. Significant relationship was observed between disease duration and tendency to type A (higher stress. This relation was positive and significant in Relapsing Remitting MS patients; but negative correlation was seen in Secondary Progressive MS patients. These patients tended to type B (lower stress when disease duration increased. Conclusions: Individuals with disease duration of one year and less than one year tend to type A personality, while patients with increment of disease duration have tendency to type B.

  2. Cushing Disease in a patient with Multiple Endocrine Neoplasia type 2B.

    Kasturi, Kannan; Fernandes, Lucas; Quezado, Martha; Eid, Mary; Marcus, Leigh; Chittiboina, Prashant; Rappaport, Mark; Stratakis, Constantine A; Widemann, Brigitte; Lodish, Maya

    2017-06-01

    Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal-dominant cancer syndrome characterized in part by metastatic medullary thyroid cancer (MTC) and pheochromocytoma. Cushing disease is a rare cause of endogenous hypercortisolism in children. We describe a 21-year-old African-American male who was diagnosed at age 10 with an ACTH-secreting pituitary microadenoma. At age 16 he developed medullary thyroid cancer and was found to have multiple endocrine neoplasia type 2B with the characteristic M918T mutation of the RET proto-oncogene. Following thyroidectomy, he was initiated on Vandetanib, a tyrosine kinase inhibitor, and has since had stable disease over the last 5 years. Our patient is the first individual with MEN2B to be described with Cushing disease. The RET oncogene may play a role in pituitary tumorigenesis; alternatively, the coexistence of these two entities may represent an extremely rare coincidence.

  3. Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals

    Tsuji, Shoji; Martin, B.M.; Stubblefield, B.K.; LaMarca, M.E.; Ginns, E.I.; Barranger, J.A.

    1988-01-01

    Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is ∼80% informative in all Gaucher patients studied

  4. Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals

    Tsuji, Shoji; Martin, B.M.; Stubblefield, B.K.; LaMarca, M.E.; Ginns, E.I. (National Institute of Mental Health, Bethesda, MD (USA)); Barranger, J.A. (Childrens Hospital of Los Angeles, CA (USA))

    1988-04-01

    Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is {approx}80% informative in all Gaucher patients studied.

  5. Multiple intracranial aneurysms and moyamoya disease associated with microcephalic osteodysplastic primordial dwarfism type II: surgical considerations.

    Waldron, James S; Hetts, Steven W; Armstrong-Wells, Jennifer; Dowd, Christopher F; Fullerton, Heather J; Gupta, Nalin; Lawton, Michael T

    2009-11-01

    Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare genetic syndrome characterized by extremely small stature and microcephaly, and is associated in 25% of patients with intracranial aneurysms and moyamoya disease. Although aneurysmal subarachnoid hemorrhage and stroke are leading causes of morbidity and death in these patients, MOPD II is rarely examined in the neurosurgical literature. The authors report their experience with 3 patients who presented with MOPD II, which includes a patient with 8 aneurysms (the most aneurysms reported in the literature), and the first report of a patient with both moyamoya disease and multiple aneurysms. The poor natural history of these lesions indicates aggressive microsurgical and/or endovascular therapy. Microsurgery, whether for aneurysm clip placement or extracranial-intracranial bypass, is challenging due to tight surgical corridors and diminutive arteries in these patients, but is technically feasible and strongly indicated when multiple aneurysms must be treated or cerebral revascularization is needed.

  6. Endogenous and recombinant type I interferons and disease activity in multiple sclerosis

    Sellebjerg, Finn; Krakauer, Martin; Limborg, Signe

    2012-01-01

    the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells), and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion......Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-ß lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship...... with endogenous type I IFN-like activity, the effect of IFN-ß therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells...

  7. Target intervention against multiple-risk markers to reduce cardiovascular disease in patients with type 2 diabetes

    Gaede, Peter; Pedersen, Oluf

    2004-01-01

    The risk of cardiovascular disease is markedly increased in patients with type 2 diabetes with a prevalence twice as high compared to the background population. With the recognition of multiple concomitant risk factors for both microvascular as well as cardiovascular disease in type 2 diabetic pa...

  8. A multiple treatment comparison meta-analysis of monoamine oxidase type B inhibitors for Parkinson's disease.

    Binde, C D; Tvete, I F; Gåsemyr, J; Natvig, B; Klemp, M

    2018-05-30

    To the best of our knowledge, there are no systematic reviews or meta-analyses that compare rasagiline, selegiline and safinamide. Therefore, we aimed to perform a drug class review comparing all available monoamine oxidase type B (MAO-B) inhibitors in a multiple treatment comparison. We performed a systematic literature search to identify randomized controlled trials assessing the efficacy of MAO-B inhibitors in patients with Parkinson's disease. MAO-B inhibitors were evaluated either as monotherapy or in combination with levodopa or dopamine agonists. Endpoints of interest were change in the Unified Parkinson's Disease Rating Scale (UPDRS) score and serious adverse events. We estimated the relative effect of each MAO-B inhibitor versus the comparator drug by creating three networks of direct and indirect comparisons. For each of the networks, we considered a joint model. The systematic literature search and study selection process identified 27 publications eligible for our three network analyses. We found the relative effects of rasagiline, safinamide and selegiline treatment given alone and compared to placebo in a model without explanatory variables to be 1.560 (1.409, 1.734), 1.449 (0.873, 2.413) and 1.532 (1.337, 1.757) respectively. We also found all MAO-B inhibitors to be efficient when given together with levodopa. When ranking the MAO-B inhibitors given in combination with levodopa, selegiline was the most effective and rasagiline was the second best. All of the included MAO-B inhibitors were effective compared to placebo when given as monotherapy. Combination therapy with MAO-B inhibitors and levodopa showed that all three MAO-B inhibitors were effective compared to placebo, but selegiline was the most effective drug. © 2018 The British Pharmacological Society.

  9. High-accuracy detection of early Parkinson's Disease using multiple characteristics of finger movement while typing.

    Warwick R Adams

    Full Text Available Parkinson's Disease (PD is a progressive neurodegenerative movement disease affecting over 6 million people worldwide. Loss of dopamine-producing neurons results in a range of both motor and non-motor symptoms, however there is currently no definitive test for PD by non-specialist clinicians, especially in the early disease stages where the symptoms may be subtle and poorly characterised. This results in a high misdiagnosis rate (up to 25% by non-specialists and people can have the disease for many years before diagnosis. There is a need for a more accurate, objective means of early detection, ideally one which can be used by individuals in their home setting. In this investigation, keystroke timing information from 103 subjects (comprising 32 with mild PD severity and the remainder non-PD controls was captured as they typed on a computer keyboard over an extended period and showed that PD affects various characteristics of hand and finger movement and that these can be detected. A novel methodology was used to classify the subjects' disease status, by utilising a combination of many keystroke features which were analysed by an ensemble of machine learning classification models. When applied to two separate participant groups, this approach was able to successfully discriminate between early-PD subjects and controls with 96% sensitivity, 97% specificity and an AUC of 0.98. The technique does not require any specialised equipment or medical supervision, and does not rely on the experience and skill of the practitioner. Regarding more general application, it currently does not incorporate a second cardinal disease symptom, so may not differentiate PD from similar movement-related disorders.

  10. Effects of disease duration on the clinical features and brain glucose metabolism in patients with mixed type multiple system atrophy.

    Lyoo, C H; Jeong, Y; Ryu, Y H; Lee, S Y; Song, T J; Lee, J H; Rinne, J O; Lee, M S

    2008-02-01

    To study the effect of disease duration on the clinical, neuropsychological and [(18)F]-deoxyglucose (FDG) PET findings in patients with mixed type multiple system atrophy (MSA), this study included 16 controls and 37 mixed-type MSA patients with a shorter than a 3-year history of cerebellar or parkinsonian symptoms. We classified the patients into three groups according to the duration of parkinsonian or cerebellar symptoms (Group I = battery. We compared the FDG PET findings of each group of patients with controls. Group I patients frequently had memory and frontal executive dysfunction. They showed hypometabolism in the frontal cortex, anterior cerebellar hemisphere and vermis. They had parkinsonian motor deficits, but no basal ganglia hypometabolism. Group II and III patients frequently had multiple domain cognitive impairments, and showed hypometabolism in the frontal and parieto-temporal cortices. Hypometabolism of the bilateral caudate and the left posterolateral putamen was observed in Group II, and whole striatum in Group III. In summary, the cortical hypometabolism begins in the frontal cortex and spreads to the parieto-temporal cortex in MSA. This spreading pattern coincides with the progressive cognitive decline. Early caudate hypometabolism may also contribute to the cognitive impairment. Parkinsonian motor deficits precede putaminal hypometabolism that begins in its posterolateral part. Cerebellar hypometabolism occurs early in the clinical courses and seems to be a relevant metabolic descriptor of cerebellar deficits.

  11. Type D, anxiety and depression in association with quality of life in patients with Parkinson's disease and patients with multiple sclerosis

    Dubayova, Tatiana; Krokavcova, Martina; Nagyova, Iveta; Rosenberger, Jaroslav; Gdovinova, Zuzana; Middel, Berrie; Groothoff, Johan W.; van Dijk, Jitse P.

    The present study examines the role of Type D personality, anxiety and depression in quality of life (QoL) in patients with two chronic neurological diseases-Parkinson's disease (PD) and multiple sclerosis (MS). This cross-sectional study included 142 PD patients (73 % males; mean age 67.6 +/- A 9.2

  12. Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease.

    James E Peters

    2016-03-01

    Full Text Available Genome-wide association studies (GWAS have transformed our understanding of the genetics of complex traits such as autoimmune diseases, but how risk variants contribute to pathogenesis remains largely unknown. Identifying genetic variants that affect gene expression (expression quantitative trait loci, or eQTLs is crucial to addressing this. eQTLs vary between tissues and following in vitro cellular activation, but have not been examined in the context of human inflammatory diseases. We performed eQTL mapping in five primary immune cell types from patients with active inflammatory bowel disease (n = 91, anti-neutrophil cytoplasmic antibody-associated vasculitis (n = 46 and healthy controls (n = 43, revealing eQTLs present only in the context of active inflammatory disease. Moreover, we show that following treatment a proportion of these eQTLs disappear. Through joint analysis of expression data from multiple cell types, we reveal that previous estimates of eQTL immune cell-type specificity are likely to have been exaggerated. Finally, by analysing gene expression data from multiple cell types, we find eQTLs not previously identified by database mining at 34 inflammatory bowel disease-associated loci. In summary, this parallel eQTL analysis in multiple leucocyte subsets from patients with active disease provides new insights into the genetic basis of immune-mediated diseases.

  13. Bladder Diseases - Multiple Languages

    ... PDF Health Information Translations Spanish (español) Expand Section Bladder Diseases: MedlinePlus Health Topic - English Enfermedades de la vejiga: Tema de salud de MedlinePlus - español (Spanish) National ...

  14. Type 1 diabetes and multiple sclerosis

    Nielsen, N.M.; Westergaard, T.; Frisch, M.

    2006-01-01

    BACKGROUND: Type 1 diabetes mellitus (T1D) and multiple sclerosis (MS) contribute considerably to the burden of autoimmune diseases in young adults. Although HLA patterns of T1D and MS are considered mutually exclusive, individual and familial co-occurrence of the 2 diseases has been reported...... Multiple Sclerosis Register were used to identify patients with T1D, defined as patients in whom diabetes was diagnosed before age 20 years (N = 6078), and patients with MS (N = 11 862). First-degree relatives (N = 14,771) of patients with MS were identified from family information in the Danish Civil....... OBJECTIVE: To assess the co-occurrence of T1D and MS by estimating the risk for MS in patients with T1D and the risk for T1D in first-degree relatives of patients with MS. DESIGN, SETTING, AND PARTICIPANTS: Two population-based disease registers, the Danish Hospital Discharge Register and the Danish...

  15. Enhanced levels of mitochondrial enzyme 17β-hydroxysteroid dehydrogenase type 10 in patients with Azheimer disease and multiple sclerosis

    Krištofíková, Z.; Bocková, Markéta; Hegnerová, Kateřina; Bartoš, A.; Klaschka, J.; Říčný, J.; Řípová, D.; Homola, Jiří

    2009-01-01

    Roč. 10, č. 5 (2009), s. 1174-1179 ISSN 1742-206X R&D Projects: GA MZd NR9322 Institutional research plan: CEZ:AV0Z20670512 Keywords : 17beta-HSD 10 * Alzheimer disease * SPR sensor Subject RIV: JB - Sensors, Measurment, Regulation Impact factor: 4.015, year: 2009

  16. Multiple myeloma with extramedullary disease.

    Oriol, Albert

    2011-11-01

    Plasmacytoma is a tumor mass consisting of atypical plasma cells. Incidence of plasmacytomas associated with multiple myeloma range from 7% to 17% at diagnosis and from 6% to 20% during the course of the disease. In both situations, occurrence of extramedullary disease has been consistently associated with a poorer prognosis of myeloma. Extramedullary relapse or progression occurs in a variety of clinical circumstances and settings, and therefore requires individualization of treatment. Alkylating agents, bortezomib, and immunomodulatory drugs, along with corticoids, have been used to treat extramedullary relapse but, because of the relatively low frequency or detection rate of extramedullary relapse, no efficacy data are available from controlled studies in this setting.

  17. Multiple endocrine neoplasia type I

    Fischer, H.J.; Lois, J.F.; Gomes, A.S.

    1985-01-01

    A case of multiple endocrine neoplasia (Men) consisting of an unusual combination of an insulin-producing islet cell tumour and an adrenal adenoma is reported. CT clearly demonstrated the adrenal mass whereas the pancreatic lesion remained questionable. Conversely angiography located the pancreatic tumour but the adrenal findings were subtle. (orig.)

  18. Shared genetic regulatory networks for cardiovascular disease and type 2 diabetes in multiple populations of diverse ethnicities in the United States.

    Le Shu

    2017-09-01

    Full Text Available Cardiovascular diseases (CVD and type 2 diabetes (T2D are closely interrelated complex diseases likely sharing overlapping pathogenesis driven by aberrant activities in gene networks. However, the molecular circuitries underlying the pathogenic commonalities remain poorly understood. We sought to identify the shared gene networks and their key intervening drivers for both CVD and T2D by conducting a comprehensive integrative analysis driven by five multi-ethnic genome-wide association studies (GWAS for CVD and T2D, expression quantitative trait loci (eQTLs, ENCODE, and tissue-specific gene network models (both co-expression and graphical models from CVD and T2D relevant tissues. We identified pathways regulating the metabolism of lipids, glucose, and branched-chain amino acids, along with those governing oxidation, extracellular matrix, immune response, and neuronal system as shared pathogenic processes for both diseases. Further, we uncovered 15 key drivers including HMGCR, CAV1, IGF1 and PCOLCE, whose network neighbors collectively account for approximately 35% of known GWAS hits for CVD and 22% for T2D. Finally, we cross-validated the regulatory role of the top key drivers using in vitro siRNA knockdown, in vivo gene knockout, and two Hybrid Mouse Diversity Panels each comprised of >100 strains. Findings from this in-depth assessment of genetic and functional data from multiple human cohorts provide strong support that common sets of tissue-specific molecular networks drive the pathogenesis of both CVD and T2D across ethnicities and help prioritize new therapeutic avenues for both CVD and T2D.

  19. Glycogen Storage Disease Type IV

    Bendroth-Asmussen, Lisa; Aksglaede, Lise; Gernow, Anne B

    2016-01-01

    molecular genetic analyses confirmed glycogen storage disease Type IV with the finding of compound heterozygosity for 2 mutations (c.691+2T>C and c.1570C>T, p.R524X) in the GBE1 gene. We conclude that glycogen storage disease Type IV can cause early miscarriage and that diagnosis can initially be made...

  20. Neurofibromatosis type 1 and multiple sclerosis: Genetically related ...

    Neurofibromatosis type I (NF1) is an autosomal dominant disorder with involvement of both the cutaneous and nervous systems. Patients are susceptible to neurological complication in the form of tumors of the brain and spinal cord. Multiple sclerosis (MS) is a chronic autoimmune disease that affects the myelinated axons ...

  1. Type I Glycogen Storage Disease

    ... Legacy Society Make Gifts of Stock Donate Your Car Personal Fundraising Partnership & Support Share Your Story Spread the Word Give While You Shop Contact Us Donate Now Glycogen Storage Disease Type ...

  2. On Multiple Polynomials of Capelli Type

    S.Y. Antonov

    2016-03-01

    Full Text Available This paper deals with the class of Capelli polynomials in free associative algebra F{Z} (where F is an arbitrary field, Z is a countable set generalizing the construction of multiple Capelli polynomials. The fundamental properties of the introduced Capelli polynomials are provided. In particular, decomposition of the Capelli polynomials by means of the same type of polynomials is shown. Furthermore, some relations between their T -ideals are revealed. A connection between double Capelli polynomials and Capelli quasi-polynomials is established.

  3. Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    Tonelli, Francesco; Giudici, Francesco; Giusti, Francesca; Brandi, Maria Luisa

    2012-01-01

    We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present

  4. Operation characteristics of a multiple type MCFC

    Kuroe, S.; Kamo, T. [Hitachi Research Lab., Hitachi, Ltd., Ibaraki-ken (Japan); Fujimura, H.; Kahara, T. [Hitachi, Ltd., Ibaraki-ken (Japan)

    1996-12-31

    Multiple type structure of MCFC of which the separator of the cell is divided by four element cells has been studied. For the stable operation of this type cell, the effect of gas flow rate and temperature distribution on the cell voltage should be clear. In order to clarify these characteristics, a small sized mimic model has been made and tested. The flow rate distribution for the four element cells were varied and cell voltage and temperature distribution were measured for each cell. The decrease in cell voltage and the increase in maximum temperature became remarkable when the apparent utilization factor for one element cell became over 100%. The calculated results agreed fairly good with test results.

  5. T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis

    Hedegaard, Chris J; Krakauer, Martin; Bendtzen, Klaus

    2008-01-01

    Autoreactive T cells are thought to play an essential role in the pathogenesis of multiple sclerosis (MS). We examined the stimulatory effect of human myelin basic protein (MBP) on mononuclear cell (MNC) cultures from 22 patients with MS and 22 sex-matched and age-matched healthy individuals, and...

  6. Multiple endocrine neoplasia type 2: achievements and current challenges

    Andreas Machens

    2012-01-01

    Full Text Available Incremental advances in medical technology, such as the development of sensitive hormonal assays for routine clinical care, are the drivers of medical progress. This principle is exemplified by the creation of the concept of multiple endocrine neoplasia type 2, encompassing medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism, which did not emerge before the early 1960s. This review sets out to highlight key achievements, such as joint biochemical and DNA-based screening of individuals at risk of developing multiple endocrine neoplasia type 2, before casting a spotlight on current challenges which include: (i ill-defined upper limits of calcitonin assays for infants and young children, rendering it difficult to implement the biochemical part of the integrated DNA-based/biochemical concept; (ii our increasingly mobile society in which different service providers are caring for one individual at various stages in the disease process. With familial relationships disintegrating as a result of geographic dispersion, information about the history of the origin family may become sketchy or just unavailable. This is when DNA-based gene tests come into play, confirming or excluding an individual's genetic predisposition to multiple endocrine neoplasia type 2 even before there is any biochemical or clinical evidence of the disease. However, the unrivaled molecular genetic progress in multiple endocrine neoplasia type 2 does not come without a price. Screening may uncover unknown gene sequence variants representing either harmless polymorphisms or pathogenic mutations. In this setting, functional characterization of mutant cells in vitro may generate helpful ancillary evidence with regard to the pathogenicity of gene variants in comparison with established mutations.

  7. Type I Gaucher disease: extraosseous extension of skeletal disease

    Poll, L.W.; Koch, J.A.; Moedder, U.; Dahl, S. vom; Haeussinger, D.; Sarbia, M.; Niederau, C.

    2000-01-01

    Objective. To investigate the frequency and morphology of extraosseous extension in patients with Gaucher disease type I.Design and patients. MRI examinations of the lower extremities were analyzed in 70 patients with Gaucher disease type I. Additionally, the thoracic spine and the midface were investigated on MRI in two patients.Results. Four cases are presented in which patients with Gaucher disease type I and severe skeletal involvement developed destruction or protrusion of the cortex with extraosseous extension into soft tissues. In one patient, Gaucher cell deposits destroyed the cortex of the mandible and extended into the masseter muscle. In the second patient, multiple paravertebral masses with localized destruction of the cortex were apparent in the thoracic spine. In the third and fourth patient, cortical destruction with extraosseous tissue extending into soft tissues was seen in the lower limbs.Conclusions. Extraosseous extension is a rare manifestation of Gaucher bone disease. While an increased risk of cancer, especially hematopoietic in origin, is known in patients with Gaucher disease, these extraosseous benign manifestations that may mimic malignant processes should be considered in the differential diagnosis of extraosseous extension into soft tissues. A narrow neck of tissue was apparent in all cases connecting bone and extraosseous extensions. (orig.)

  8. Graves′ disease allied with multiple pheochromocytoma

    Brahim Housni

    2013-01-01

    Full Text Available Pheochromocytoma is an uncommon cause of high blood pressure touching adults. The combination of severe hypertension in the triad of headache, sweating, and tachycardia should suggest this diagnosis; this clinical picture is similar to that of hyperthyroidism. We report the case of a 22-year-old patient with multiple pheochromocytoma associated with Graves′ disease revealed by malignant hypertension and discussed the difficulties of the diagnosis and the treatment approach.

  9. [Embryo-fetal diseases in multiple pregnancies].

    Colla, F; Alba, E; Grio, R

    2001-04-01

    Embryo-fetal diseases are the consequence of prenatal (progenetic and metagenetic or environmental) and intranatal (of a traumatic, infective, toxic nature) pathological factors. In multiple pregnancies this complex etiopathogenesis also includes an altered didymous embriogenesis. This study aimed to evaluate the pathologies affecting the fetus in multiple pregnancy, a special biological situation leading to the potential onset of severe fetal and neonatal damage. The authors studied 205 patients with multiple pregnancies, including 199 bigeminal, 5 trigeminal and 1 quadrigeminal, admitted to the Department B of the Obstetrics and Gynecological Clinic of Turin University between 1989-1999. Possible embyro-fetal damage was examined using a chronological criterion: namely following the development of the multiple fetuses from the zygotic to the neonatal phase. Pregnancies were biamniotic bichorionic in 54% of cases, biamniotic monochorionic in 45% and monochorionic monoamniotic in 1%. There were a total of 154 (79.38%) premature births out of 194 and neonatal birth weight was always SGA (small for gestational age). 66.84% of newborns were LBW (<2500 g) and 7.14% were VLBW (<1500 g). Fetal mortality (2.29%) was higher than early neonatal mortality (1.53%). Perinatal mortality (3.82%) was three times higher than in all neonates from the same period (1.03%). The severe embryo-fetal and neonatal damage found in multiple pregnancies is a clinical reality that calls for adequate diagnostic and therapeutic measures, and above all specific medical and social prevention to limit maternal pathogenic risks.

  10. Hib Disease (Haemophilus Influenzae Type b)

    ... Fitness Diseases & Conditions Infections Drugs & Alcohol School & Jobs Sports Expert Answers (Q&A) Staying Safe Videos for Educators Search English Español Hib Disease (Haemophilus Influenzae Type b) KidsHealth / For Teens / Hib Disease (Haemophilus Influenzae ...

  11. A rare presentation of multiple endocrine neoplasia (MEN type 2A syndrome

    Elroy Patrick Weledji

    2016-02-01

    Full Text Available Peptic ulcer disease may be a manifestation of symptomatic primary hyperparathyroidism. A case of an intractable complicated peptic ulcer disease secondary to hypercalcaemia from multiple endocrine neoplasia type 2A is presented. Hypercalcaemia should always be excluded as a cause of recurrent, or complicated peptic ulcer disease.

  12. Symptom profiles of subsyndromal depression in disease clusters of diabetes, excess weight, and progressive cerebrovascular conditions: a promising new type of finding from a reliable innovation to estimate exhaustively specified multiple indicators–multiple causes (MIMIC models

    Francoeur RB

    2016-12-01

    Full Text Available Richard B Francoeur School of Social Work, Adelphi University, Garden City, NY, USA Abstract: Addressing subsyndromal depression in cerebrovascular conditions, diabetes, and obesity reduces morbidity and risk of major depression. However, depression may be masked because self-reported symptoms may not reveal dysphoric (sad mood. In this study, the first wave (2,812 elders from the New Haven Epidemiological Study of the Elderly (EPESE was used. These population-weighted data combined a stratified, systematic, clustered random sample from independent residences and a census of senior housing. Physical conditions included progressive cerebrovascular disease (CVD; hypertension, silent CVD, stroke, and vascular cognitive impairment [VCI] and co-occurring excess weight and/or diabetes. These conditions and interactions (clusters simultaneously predicted 20 depression items and a latent trait of depression in participants with subsyndromal (including subthreshold depression (11≤ Center for Epidemiologic Studies Depression Scale [CES-D] score ≤27. The option for maximum likelihood estimation with standard errors that are robust to non-normality and non-independence in complex random samples (MLR in Mplus and an innovation created by the author were used for estimating unbiased effects from latent trait models with exhaustive specification. Symptom profiles reveal masked depression in 1 older males, related to the metabolic syndrome (hypertension–overweight–diabetes; silent CVD–overweight; and silent CVD–diabetes and 2 older females or the full sample, related to several diabetes and/or overweight clusters that involve stroke or VCI. Several other disease clusters are equivocal regarding masked depression; a couple do emphasize dysphoric mood. Replicating findings could identify subgroups for cost-effective screening of subsyndromal depression. Keywords: depression, diabetes, overweight, cerebrovascular disease, hypertension, metabolic

  13. Scintigraphic Evaluation of Multiple Endocrine Neoplasia Type 2 ( MEN Type 2 )

    Lee, Jae Tae; Lee, Kyu Bo; Whang, Kee Suk; Kim, Bo Wan; Lee, In Kyu

    1991-01-01

    Multiple endocrine neoplasia type 2 (MEN type 2, Sipple's syndrome) is a rare disorder characterized by the association of medullary carcinoma of the thyroid, parathyroid hyperplasia and can be diagnosed in early stage of the disease by meticulous screening tests of the family. This case report describes the location and categorization of tumors using 99m Tc-pertechnetate, I -NaI, 99m Tc-pentavalent(V) DMSA, 131 I -MIBG scans in two cases of MEN type 2 occurred in a 32 year old women and her 29-year old brother. In MEN type 2, we think, combined use of 99m Tc-(V)-DMSA, 99m Tc-pertechnetate and 1 '3 1 I -MIBG may be useful for the categorization of tumor mass lesions and planning appropriate therapy.

  14. Type I Glycogen Storage Disease

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  15. Type I Glycogen Storage Disease

    ... the most common form of glycogen storage disease, accounting for 25% of all cases. It is an ... Links Videos Webinars About ALF OVERVIEW Programs About Liver Disease Ask the Experts People ALF ...

  16. Primary Hyperparathyroidism in Patients with Multiple Endocrine Neoplasia Type 1

    Grzegorz Piecha

    2010-01-01

    Full Text Available Primary hyperparathyroidism may occur as a part of an inherited syndrome in a combination with pancreatic endocrine tumours and/or pituitary adenoma, which is classified as Multiple Endocrine Neoplasia type 1 (MEN-1. This syndrome is caused by a germline mutation in MEN-1 gene encoding a tumour-suppressor protein, menin. Primary hyperparathyroidism is the most frequent clinical presentation of MEN-1, which usually appears in the second decade of life as an asymptomatic hypercalcemia and progresses through the next decades. The most frequent clinical presentation of MEN-1-associated primary hyperparathyroidism is bone demineralisation and recurrent kidney stones rarely followed by chronic kidney disease. The aim of this paper is to present the pathomechanism, screening procedures, diagnosis, and management of primary hyperparathyroidism in the MEN-1 syndrome. It also summarises the recent advances in the pharmacological therapy with a new group of drugs—calcimimetics.

  17. Types of Neglected Tropical Diseases

    ... Trichuriasis (whipworm disease) Contracted by ingesting soil or vegetables contaminated with feces containing whipworm eggs, trichuriasis can cause dehydration and anemia and impair growth and cognition. Content ...

  18. Insulin and Alzheimer disease: type 3 diabetes?

    Andrés Jagua Gualdrón

    2007-01-01

    Full Text Available Alzheimer Disease is a neurodegenerative disease of central nervous system whose incidence will increase in next years. Recent investigations relate alzheimer with insulin signaling defects in neurons. Is alzheimer Disease a type 3 diabetes? In this communication write a brief article about evidences from this alzheimer‘s disease model.

  19. Pure spinal multiple sclerosis: A possible novel entity within the multiple sclerosis disease spectrum.

    Schee, Jie Ping; Viswanathan, Shanthi

    2018-05-01

    We identified five female patients retrospectively with relapsing short-segment partial myelitis whose clinical and paraclinical features were suggestive of cord involvement of multiple sclerosis (MS)-type albeit not rigidly fulfilling the 2017 McDonald criteria. Notably, these patients had not developed any typical MS-like brain lesions despite repeated neuroimaging assessments over years. Comprehensive work-up for differential diagnoses of MS and other causes of transverse myelitis particularly neuromyelitis optica spectrum disorders had been consistently negative on longitudinal follow-up. Thus, we postulate a possible entity of pure spinal MS which may represent a novel forme fruste within the MS disease spectrum.

  20. Multiple pathogenic proteins implicated in neuronopathic Gaucher disease mice.

    Xu, You-hai; Xu, Kui; Sun, Ying; Liou, Benjamin; Quinn, Brian; Li, Rong-hua; Xue, Ling; Zhang, Wujuan; Setchell, Kenneth D R; Witte, David; Grabowski, Gregory A

    2014-08-01

    Gaucher disease, a prevalent lysosomal storage disease (LSD), is caused by insufficient activity of acid β-glucosidase (GCase) and the resultant glucosylceramide (GC)/glucosylsphingosine (GS) accumulation in visceral organs (Type 1) and the central nervous system (Types 2 and 3). Recent clinical and genetic studies implicate a pathogenic link between Gaucher and neurodegenerative diseases. The aggregation and inclusion bodies of α-synuclein with ubiquitin are present in the brains of Gaucher disease patients and mouse models. Indirect evidence of β-amyloid pathology promoting α-synuclein fibrillation supports these pathogenic proteins as a common feature in neurodegenerative diseases. Here, multiple proteins are implicated in the pathogenesis of chronic neuronopathic Gaucher disease (nGD). Immunohistochemical and biochemical analyses showed significant amounts of β-amyloid and amyloid precursor protein (APP) aggregates in the cortex, hippocampus, stratum and substantia nigra of the nGD mice. APP aggregates were in neuronal cells and colocalized with α-synuclein signals. A majority of APP co-localized with the mitochondrial markers TOM40 and Cox IV; a small portion co-localized with the autophagy proteins, P62/LC3, and the lysosomal marker, LAMP1. In cultured wild-type brain cortical neural cells, the GCase-irreversible inhibitor, conduritol B epoxide (CBE), reproduced the APP/α-synuclein aggregation and the accumulation of GC/GS. Ultrastructural studies showed numerous larger-sized and electron-dense mitochondria in nGD cerebral cortical neural cells. Significant reductions of mitochondrial adenosine triphosphate production and oxygen consumption (28-40%) were detected in nGD brains and in CBE-treated neural cells. These studies implicate defective GCase function and GC/GS accumulation as risk factors for mitochondrial dysfunction and the multi-proteinopathies (α-synuclein-, APP- and Aβ-aggregates) in nGD. © The Author 2014. Published by Oxford University

  1. Molecular diagnosis of multiple endocrine neoplasia type 2A ...

    Molecular diagnosis of multiple endocrine neoplasia type 2A. RJ Pegoraro, DJ Hacking, RH Buck, L Rom, PA Lanning, GMB Berger. Abstract. Objective. To identify by means of genetic analyses individuals who are at risk of developing medullary thyroid cancer that is a component of multiple endocrine neoplasia. Subjects.

  2. Multiple symmetrical lipomatosis (Madelung's disease) - a case report

    Vieira, Marcelo Vasconcelos; Abreu, Marcelo de; Furtado, Claudia Dietz; Silveira, Marcio Fleck da; Furtado, Alvaro Porto Alegre; Genro, Carlos Horacio; Grazziotin, Rossano Ughini

    2001-01-01

    Multiple symmetrical lipomatosis (Madelung's disease) is a rare disorder characterized by deep accumulation of fat tissue, involving mainly the neck, shoulders and chest. This disease is associated with heavy alcohol intake and it is more common in men of Mediterranean origin. This disease can cause severe aesthetic deformities and progressive respiratory dysfunction. We report a case of a patient with multiple symmetrical lipomatosis and describe the clinical and radiological features of this disorder. (author)

  3. Multiple sclerosis and other white matter diseases

    Zimmerman, R.A.

    1991-01-01

    The diagnosis of multiple sclerosis (MS) by computerized tomography and nuclear magnetic resonance are shown, including the examination of cerebral spinal fluid. Lymphocytic, foamy histiocytic perivascular cuffing, degenerated oligodendrocytes, and microglia proliferation with relative axonal sparing are presented. In the latter stage of the chronic MS plaque there is sclerosis with microcystic formation with complete demyelination and organization. (author)

  4. Multiple modes of impulsivity in Parkinson's disease.

    Cristina Nombela

    Full Text Available Cognitive problems are a major factor determining quality of life of patients with Parkinson's disease. These include deficits in inhibitory control, ranging from subclinical alterations in decision-making to severe impulse control disorders. Based on preclinical studies, we proposed that Parkinson's disease does not cause a unified disorder of inhibitory control, but rather a set of impulsivity factors with distinct psychological profiles, anatomy and pharmacology. We assessed a broad set of measures of the cognitive, behavioural and temperamental/trait aspects of impulsivity. Sixty adults, including 30 idiopathic Parkinson's disease patients (Hoehn and Yahr stage I-III and 30 healthy controls, completed a neuropsychological battery, objective behavioural measures and self-report questionnaires. Univariate analyses of variance confirmed group differences in nine out of eleven metrics. We then used factor analysis (principal components method to identify the structure of impulsivity in Parkinson's disease. Four principal factors were identified, consistent with four different mechanisms of impulsivity, explaining 60% of variance. The factors were related to (1 tests of response conflict, interference and self assessment of impulsive behaviours on the Barrett Impulsivity Scale, (2 tests of motor inhibitory control, and the self-report behavioural approach system, (3 time estimation and delay aversion, and (4 reflection in hypothetical scenarios including temporal discounting. The different test profiles of these four factors were consistent with human and comparative studies of the pharmacology and functional anatomy of impulsivity. Relationships between each factor and clinical and demographic features were examined by regression against factor loadings. Levodopa dose equivalent was associated only with factors (2 and (3. The results confirm that impulsivity is common in Parkinson's disease, even in the absence of impulse control disorders, and

  5. Imaging Finding of Multiple Endocrine Neoplasia Type 1: Case Report

    Yum, Tae Jun; Cho, Hee Woo

    2012-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited syndrome with characteristic clinical and radiological manifestations. Many reports on MEN1 have been published; however, no cases of radiologically diagnosed MEN1 have been reported. Therefore, we report on a radiologically diagnosed case of MEN1 with clinical symptoms of gastroduodenal ulcer.

  6. Nuclear Receptors and Multiple Endocrine Neoplasia type 1 (MEN1)

    Dreijerink, K.M.A.

    2009-01-01

    Multiple Endocrine Neoplasia type 1 (MEN1) is an inherited syndrome that is characterized by the occurrence of tumours of the parathyroid glands, gastroenteropancreatic tumours, pitui-tary gland adenomas, as well as adrenal adenomas and neuro-endocrine tumours, often at a young age. MEN1 tumours can

  7. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    Nell, Sjoerd; van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Borel Rinkes, Inne H. M.; Vriens, Menno R.; Valk, Gerlof D.

    2015-01-01

    An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore, blood

  8. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    Nell, S.; Leeuwaarde, R.S. van; Pieterman, C.R.; Laat, J.M. de; Hermus, A.R.M.M.; Dekkers, O.M.; Herder, W.W. de; Horst-Schrivers, A.N. van der; Drent, M.L.; Bisschop, P.H.; Havekes, B.; Rinkes, I.H.; Vriens, M.R.; Valk, G.D.

    2015-01-01

    CONTEXT: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

  9. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    Nell, Sjoerd; Van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Rinkes, Inne H. M. Borel; Vriens, Menno R.; Valk, Gerlof D.

    2015-01-01

    Context: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

  10. No effect of season of birth on risk of type 1diabetes, cancer, schizophrenia and ischemic heart disease, while some variations may be seen for pneumonia and multiple sclerosis

    Streym, Súsanna við; Rejnmark, Lars; Mosekilde, Leif

    2013-01-01

    Background: The risk of type 1 diabetes (T1DM), infections, cancer, schizophrenia and multiple sclerosis (MS) has been associated with environmental factors including vitamin D status. Results: No associations between season of birth and risk of MS were seen in the 1940 cohort or the 1996 cohort...... of birth as a proxy variable for vitamin D status (summer: April– September and winter: October–March). Conclusion: MS and pneumonia in young subjects may be related to season of birth and thus maternal vitamin D exposure. Low sunlight exposure in the winter time leading to low vitamin D levels during......1DM before 10 y, infection, any type of cancer, schizophrenia and myocardial infarction. In the 1977 cohort the risk of pneumonia was significantly lower among those born in the summer compared with the winter at any age (HR 0.91, 95% CI 0.85–0.97, p

  11. Multiple Epiphyseal Dysplasia (MED: A Rare Type of Skeletal Dysplasia

    Mohammad Imnul Islam

    2012-06-01

    Full Text Available Multiple epiphyseal dysplasia (MED is a congenital disorder of skeletal development that primarily affects the ends of long bones, causing progressive joint and bone inflammation and short stature. Mutations in several genes are responsible for pathogenesis of this disease. We are reporting a case of MED who presented with the complaints of multiple swelling of the joints which was associated with pain during movement for last seven years. The patient had flexion deformity of all the affected joints along with restriction of movement. These were associated with kyphosis, pectus carnitum, knock-knee and short stature. Radiological findings were suggestive of MED. Counseling was done with the parents regarding the etiology, progression and outcome of the disease.DOI: http://dx.doi.org/10.3329/bsmmuj.v5i1.11025 BSMMU J 2012; 5(1:57-60 

  12. Type gaucher disease: radiographic and MRI manifestations

    Dong Yanqing; Li Kuncheng; Wang Yunzhao; Tian Ding

    1999-01-01

    Objective: To enhance the understanding of Gaucher disease (GD) type I bone involvement on imaging findings. Methods: The X-ray plain film and MRI findings of GD type I were reported, and literature reviewed. Results: The X-ray plain film of GD had characteristic change. The extent of bone involvement demonstrated could be depicted in longitudinal direction and the changes of marrow involvement on MRI. Conclusions: MRI is the best way to diagnose the bone involvement of GD

  13. Induced multiple disease resistance in wheat

    Borojevic, K.; Worland, A.J.

    1990-01-01

    Full text: The existence of genes suppressing resistance to leaf rust, stem rust and yellow rust in hexaploid wheat has been suggested. If such genes are deleted or inactivated, a more resistant variety may be obtained. In mutant lines of the wheat variety San Pastore, selected after treatment with 20,000 rad of gamma-rays, resistance to leaf rust, yellow rust, stem rust, and to some extent to Erysiphe graminis was determined. The mutants responded to infection by producing necrotic flecks in the presence of high level of disease inoculum. Similar flecks develop under stress condition. It is likely that the mother variety San Pastore carries genes for resistance which are masked by suppressor genes. Irradiation inactivates suppressors so that resistance genes which were previously masked are expressed. The first results of monosomic analysis indicate that chromosomes of groups 4 and 5 or possibly 7 may be critical for expression of resistance in the mutant lines. (author)

  14. Genetics Home Reference: glycogen storage disease type VII

    ... Home Health Conditions Glycogen storage disease type VII Glycogen storage disease type VII Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Glycogen storage disease type VII (GSDVII) is an inherited ...

  15. Genetics Home Reference: glycogen storage disease type IV

    ... Home Health Conditions Glycogen storage disease type IV Glycogen storage disease type IV Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Glycogen storage disease type IV (GSD IV) is an ...

  16. Multiple sclerosis or neurological manifestations of Celiac disease

    Vahid Shaygannejad

    2013-01-01

    Full Text Available Multiple sclerosis (MS and celiac disease (CD are considered to be T-cell-mediated autoimmune disease. We discuss about a known case of CD-showed relapsing - remitting neurological symptoms compatible with MS. In this rare co-occurrence subject, MS-CD patient, the interaction between MS - and CD-related inflammatory processes is open to discussion.

  17. Pregnancies in glycogen storage disease type Ia

    Martens, Danielle H. J.; Rake, Jan Peter; Schwarz, Martin; Ullrich, Kurt; Weinstein, David A.; Merkel, Martin; Sauer, Pieter J. J.; Smit, G. Peter A.

    OBJECTIVE: Reports on pregnancies in women with glycogen storage disease type Ia (GSD-Ia) are scarce. Because of improved life expectancy, pregnancy is becoming an important issue. We describe 15 pregnancies by focusing on dietary treatment, biochemical parameters, and GSD-Ia complications. STUDY

  18. PPARgamma in immunity and inflammation: cell types and diseases.

    Széles, Lajos; Töröcsik, Dániel; Nagy, László

    2007-08-01

    The lipid activated transcription factor, PPARgamma appears to have multiple functions in the immune system. There are several cell types expressing the receptor, most prominently antigen presenting cells, such as macrophages and dendritic cells. The receptor's activation leads to primary transcriptional activation of many, mostly lipid metabolism-related genes. However, gene regulation also occurs on immunity and inflammation-related genes. Key questions are: in what way lipid metabolism and immune regulation are connected and how activation and/or repression of gene expression may modulate inflammatory and anti-inflammatory responses and in what way can these be utilized in therapy. Here we provide a cell type and disease centric review on the role of this lipid activated transcription factor in the various cells of the immune system it is expressed in, and in some major inflammatory diseases such as atherosclerosis, inflammatory bowel disease and rheumatoid arthritis.

  19. Extranodal Rosai Dorfman disease in multiple sites: A case report

    Shim, Jong Joon; Kim, Ho Kyun; Shim, Jae Chan; Lee, Kyoung Eun; Lee, Ghi Jai; Suh, Jung Ho; Hong, Seong Woo; Lee, Hye Kyung [Seoul Paik Hospital/Inje Univ. College of Medicine, Seoul (Korea, Republic of)

    2012-07-15

    Rosai Dorfman disease involves an abnormal proliferation of histiocytes. This abnormal growth tends to occur within the lymph nodes, with occasional extranodal presentation. Rosai Dorfman disease is a rare disease, and the extranodal cases are even more uncommon. We report a rare case of extranodal Rosai Dorfman disease in multiple sites in a 56 year old male patient. Abdominopelvic CT revealed soft tissue attenuation masses, encasing both the renal pelvis and both ureters, as well as the thoracic vertebra. Following the neck sonography, both submandibular glands had an enlarged honey combed appearance. Although Rosai Dorfman disease is rare, it should be considered as a potential differential diagnosis when multiple sites involving soft tissue attenuation masses are observed with sonogram and CT.

  20. Glycogen storage disease type II (Pompe disease in children

    A. N. Semyachkina

    2014-01-01

    Full Text Available The paper gives the data available in the literature, which reflect the manifestations, diagnosis, and current treatments of the rare (orphan inherited disease glycogen storage disease type II or Pomp disease in children, as well as its classification. The infant form is shown to be most severe, resulting in death from cardiovascular or pulmonary failure generally within the first year of a child’s life. Emphasis is laid on major difficulties in the differential and true diagnosis of this severe disease. Much attention is given to the new pathogenetic treatment — genetically engineered enzyme replacement drug Myozyme®. The authors describe their clinical case of a child with the juvenile form of glycogen storage disease type II (late-onset Pompe disease. Particular emphasis is laid on the clinical symptoms of the disease and its diagnostic methods, among which the morphological analysis of a muscle biopsy specimen by light and electron microscopies, and enzyme and DNA diagnoses are of most importance. The proband was found to have significant lysosomal glycogen accumulation in the muscle biopsy specimen, reduced lymphocyte acid α-1,4-glucosidase activity to 4,2 nM/mg/h (normal value, 13,0—53,6 nM/mg/h, described in the HGMD missense mutation database from 1000 G>A p.Gly334er of the GAA in homozygous state, which verified the diagnosis of Pompe disease

  1. New type of cells with multiple chromosome rearrangements

    Aseeva, Elena A. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Snigiryova, Galina P. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Neverova, Anna L. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Bogomazova, Alexandra N.; Novitskaya, Natalia N.; Khazins, Eva D. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Domracheva, Elena V. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation)], E-mail: dom@blood.ru

    2010-04-15

    A comparative analysis of the distribution and the frequency of multiaberrant cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy) irradiated people was carried out. The highest MAC frequency was observed in people exposed to {alpha}-radiation (Pu, Rn) and in cosmonauts. This fact allows MAC to be considered as an indicator of a high-energy local exposure. A new type of cells with multiple chromosome rearrangements was discovered in the course of analysis of stable aberrations by the fluorescence in situ hybridization (FISH) method. The biological consequences of MAC formation and possibility of revealing the whole diversity of cells with multiple aberrations by means of modern molecular-cytogenetic methods are discussed.

  2. New type of cells with multiple chromosome rearrangements

    Aseeva, E.A.; Domracheva, E.V.; Neverova, A.L; Bogomazova, A.N.; Snigiryova, G.P.; Novitskaya, N.N.; Khazins, E.D.

    2008-01-01

    Full text: A comparative analysis of the distribution and the frequency of multiaberrant cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy) irradiated people was carried out. MAC were found in most of the examined groups and they were absent in the control population. A highest MAC frequency was observed in people exposed to alpha radiation (Pu, Ra). This fact allows MAC to be considered as an indicator of a high-energy local exposure. A new type of cells with multiple chromosome rearrangements was discovered in the course of analysis of stable aberrations by the FISH method. The biological consequences of MAC formation and possibility of revealing the whole diversity of cells with multiple aberrations by means of modern molecular-cytogenetic methods is discussed

  3. Youth experiences with multiple types of prejudice-based harassment.

    Bucchianeri, Michaela M; Gower, Amy L; McMorris, Barbara J; Eisenberg, Marla E

    2016-08-01

    Despite prejudice-based harassment's associations with serious physical and mental health risks, research examining multiple forms of harassment among children/adolescents is lacking. This study documents the prevalence of prejudice-based harassment (i.e., harassment on the basis of gender, race/ethnicity, weight or physical appearance, sexual orientation, and disability status) among a large, statewide, school-based Midwestern U.S. sample of 162,034 adolescents. Weight-/appearance-based harassment was most prevalent among both girls (25.3%) and boys (19.8%). Adolescents from certain vulnerable groups experienced higher rates of multiple types of harassment, even when controlling for other sociodemographic characteristics. Prejudice-based harassment experiences are prevalent among adolescent girls and boys. Differential rates of each type of harassment are reported across groups within the corresponding sociodemographic status (e.g., white female adolescents report a significantly lower rate of race-based harassment (4.8%), as compared to Native American (18.6%), mixed/other race (18.9%), Hispanic/Latina (21.5%), Asian/Pacific Islander (24.2%), or Black/African American (24.8%) female adolescents); but a pattern of cross-harassment also is evident, such that differences in prevalence of each harassment type emerge across a variety of statuses (e.g., disability-based harassment was statistically significantly higher among discordant heterosexual (12.7%), gay (13.0%), bisexual (15.3%), and unsure (15.3%) male adolescents than among heterosexual male (7.2%) adolescents). Adolescents from specific sociodemographic groups are particularly vulnerable to certain types of harassment. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  4. MRI of the spinocerebellar degeneration (multiple system atrophy, Holmes type, and Menzel-Joseph type)

    Mukai, Eiichiro; Makino, Naoki.

    1991-01-01

    We have analyzed MRI in 33 patients with several forms of spinocerebellar degeneration; 17 with multiple system atrophy, 10 with Holmes type, and 6 with Menzel-Joseph type. The MRIs were obtained using a 1.5-T GEMR System. Patients with multiple system atrophy demonstrated: atrophy of the brain stem, particularly basis pontis; decreased signal intensity of the white matter of pons; atrophy of the white matter of cerebellum; atrophy and decreased signal intensity of the putamen, particularly along their lateral and posterior portions; and atrophy of the cerebrum. Patients with Holmes type showed: atrophy of the cerebellum; atrophy of the vermis more than hemispheres; and nuclei of the cerebellum with no decreased intensity on T 2 -weighted sequences. Patients with Menzel-Joseph type demonstrated moderate atrophy of the brain stem and mild atrophy of the white matter of cerebellum. MRI is a useful diagnostic tool in the management of the spinocerebellar degeneration. (author)

  5. Thymoma (World Health Organization type B3) with neuroendocrine differentiation in multiple endocrine neoplasia type 1

    Tomita, Masaki; Ichiki, Nobuhiko; Ayabe, Takanori; Tanaka, Hiroyuki; Kataoka, Hiroaki; Nakamura, Kunihide

    2017-01-01

    Abstract Thymic epithelial tumors occur in 1?5% of patients with multiple endocrine neoplasia type 1 (MEN 1). Majority of these thymic epithelial tumors are thymic carcinoids and patients with thymoma in MEN 1 is rare. Furthermore, thymoma with neuroendocrine differentiation was also rarely reported. Herein, we report a 68-year-old man having type B3 thymoma with neuroendocrine differentiation in MEN 1 and to the best of our knowledge this is the first such case ever reported.

  6. Togetherness of the Multiple Diverticulosis of the First Part of the Duodenum with Neurofibromatosis Type I: A Case Report

    Ozgur Turk

    2014-04-01

    Full Text Available Duedonal diverticulosis is common in clinical practice. Most of duedonal diverticulosis is located at the second part of duodenum; incidence is reported as 67%, incidence of third and forth part is %20. Multiple diverticulosis of the first part of the duodenum is a rare case. There is not any knowledge togetherness of neurofibromatosis type 1 and duedonal diverticulosis. Here we reported incidentally diagnosed multiple diverticulosis of duodenum that is located in the first part in a neurofibromatosis type 1 patient with multiple neurofibromatosis nodules. Neurofibromatosis could affect various organs. Along the digestive system carcinoid tumors and neuroendocrine tumors are more encountered diseases. Endoscopic examinations and abdominal imaging may be useful for the diagnosis of gastrointestinal coexisting disease in neurofibromatosis type 1 . In conclusion neurofibromatosis type 1 could affect multiple systems and it should evaluate carefully.

  7. Assessment of Personality Types and Locus of Control in Multiple Sclerosis Patients

    Sh. Mazaheri

    2008-07-01

    Full Text Available Introduction & Objective: Multiple sclerosis (MS is an autoimmune disease with unknown cause. MS is one of the disabling neurologic diseases in adult especially young range that myelin part of central nervous system (CNS is destructed. The aim of this study was assessment of types A and B personality and internal and external locus of control in multiple sclerosis (MS patients and comparison of the results with control group.Materials & Methods: In a case-control study, 30 patients with MS and 30 normal persons as control group evaluated with neurological examination, Rotter locus of control test and Friedman-Rosenman questionnaire for detection of types A and B personality. We employed to analyze the results.Results: 43 percent and 57 percent of MS patients had internal and external locus of control respectively. 63 percent and 37 percent of MS patients had type A and B personality respectively. 60 percent and 40 percent of control group had internal and external locus of control respectively. 20 percent and 80 percent of control group had type A and B personality respectively. Difference between personality type in two groups was significant (P<0.01.Conclusions: In this study, MS patients had more type A personality in comparison to control group.

  8. [Type 3 Gaucher disease, also an adult disease?

    Leurs, A; Chepy, A; Detonellaere, C; Pascal, L; Gallois, P; Tran, T-A-C; Caillaud, C; Hatron, P-Y; Rose, C

    2018-03-30

    Gaucher disease is a genetic lysosomal storage disorder due to a glucocerebrosidase deficiency. Type 3, including neurological impairment, may have a specific phenotype in the context of the D409H mutation. We report the case of a 22-year-old woman who presented with Gaucher disease. Enzyme replacement therapy by imiglucerase was followed by rapid clinical and biological improvement. However, communication difficulties, which were initially attributed to the language barrier, revealed neurological impairment. After complementary assessment, the diagnosis of type 3 Gaucher disease was suspected. Gene analysis of the glucocerebrosidase showed a homozygous D409H mutation. This mutation results in calcified heart valves, corneal opacities, alteration of oculomotricity and hydrocephalus. The mild manifestation at onset and the late neurological involvement in the medical history make the diagnosis more difficult. This particular clinical phenotype deserves to be known in adult medicine departments. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  9. Capitalization of multiple intelligence types during the biology disciplines

    Mariana DUMITRU

    2010-05-01

    Full Text Available The study was conducted on a sample of children at the Lăpuş School with classes I-VIII, using the teaching/learning process of the biology disciplines. A key element in applying the theory of Multiple Intelligence in a classroom is knowing the intelligence profile of children. Differentiated teaching approach was designed based on the predominant types of intelligences. For this purpose we used various methods: questionnaire, observation of children as they are given various tasks, interview, development of projects, role play, the biographical method-personal history of child, analysis of activities' results (compositions, drawings, collages, portfolios, debates in pair-groups, and case studies. In child’s profile, (types of intelligences become qualities that we capitalize in training, designing different teaching approach depending on predominant types of intelligences. The results appeared without delay. After a school's year that we worked differently with the children, they have improved school performance and became more interested in the study of biological disciplines thus arousing their curiosity and respect towards life.

  10. Multiple primary cancer risk after therapy for Hodgkins's disease

    Brody, R.S.; Schottenfeld, D.; Reid, A.

    1977-01-01

    Forty-four antecedent, synchronous, and metachronous multiple primary cancers were identified among 41 patients who constituted 4.0% of 1028 patients initially treated for Hodgkin's disease during the years 1950--1954, 1960--1964, and 1968--1972. At 5 years post-therapy the cumulative probabilities of developing a multiple primary cancer for patients treated in 1950--1954, 1960--1964, and 1968--1972, were 1.14%, 1.48%, and 4.43%, respectively. At 10 years the cumulative probability of a multiple primary cancer was 2.54% for the 1950--1954 treatment group and 6.52% for the 1960--1964 treatment group. Among those patients 16-39 years of age, initially treated during the period 1960--1964, who had survived 6-10 years after receiving radiation plus single agent chemotherapy, we observed a significant 18-fold increase in the number of multiple primary cancers. A significant occurrence of two multiple primary cancers in a relatively small group of patients treated with chemotherapy only during the period 1968--1972 was also noted. Continued surveillance of patients extensively treated with combination chemotherapy and radiotherapy will enable assessment of the oncogenic potential of these modern therapeutic approaches to the management of Hodgkin's disease

  11. Peripheral artery disease in type II diabetes

    Ali, Z.; Ahmed, S.M.; Bhutto, A.R.; Chaudhry, A.; Munir, S.M.

    2012-01-01

    Objective: To determine the frequency of peripheral arterial disease (PAD) in type 2 diabetic patients. Study Design: Cross-sectional observational study. Place and Duration of Study: Diabetes Clinic, Medical Unit III, Jinnah Postgraduate Medical Centre, Karachi, from January to June 2010. Methodology:Three hundred and eighty seven (387) type II diabetic patients of either gender and any age were included. Patients with a previous history of trauma to the arterial vasculature, pregnancy and those who underwent in the study arterial graft procedures were excluded. Non-purposive convenient sampling technique was used to enroll patients in the study. PAD was diagnosed when ankle-brachial index (ABI) was less than 0.9. Ap-value of less than 0.05 was considered statistically significant. Results: Out of 387 studied patients, 128 were males (33.1%) and 259 were females (66.9%). Mean age was 52.22 +- 6.39 years. PAD was detected in 152 9.671 (22 - 76) years in the entire cohort. Mean duration of diabetes was 9.38 +- (39.28%) of the total study subjects. Thirty-one of 128 male patients (24.22%) had PAD disease while 121 out of 259 female patients (46.71%) had evidence of PAD (p = 0.001). Hypertension was a significantly associated factor (p = 0.002). Conclusion: A high frequency of PAD was observed in the diabetic population particularly with hypertension and more prevalent in females. (author)

  12. HLA Typing and Celiac Disease in Moroccans

    Daniela Piancatelli

    2017-01-01

    Full Text Available Genetic and environmental factors are responsible for differences in the prevalence of some diseases across countries. Human leukocyte antigen (HLA allele frequencies in North African populations show some differences in their distribution compared to Europeans, Mediterraneans, and sub-Saharans, and some specific alleles and haplotypes could be clinically relevant. Celiac disease (CD has been fast increasing in prevalence in North Africa; but few immunogenetic data are available for this area, in which a high prevalence of the disease has been described. In this report, we assess and discuss results of HLA class II (HLA-DQA1/DQB1/DRB1 typing in Moroccan patients with CD and compare them with a control population from Morocco—genetically well characterized—and with other North African, Mediterranean, and European populations. The classical HLA-DQ associations were confirmed in Moroccans with CD. The high frequency of DQ2.5 homozygosity (45.2% found in Moroccans with CD was noteworthy as compared with other populations (23%–32%. The genetic risk gradient for CD, identified by previous studies, has been confirmed in Moroccans with some differences, mainly concerning DQ8 genotypes. This study provides the immunogenetic framework of CD in Moroccans and confirms the need to learn more about associations with additional HLA and non-HLA genetic factors.

  13. Multiple sleep alterations in mice lacking cannabinoid type 1 receptors.

    Alessandro Silvani

    Full Text Available Cannabinoid type 1 (CB1 receptors are highly expressed in the brain and play a role in behavior control. Endogenous cannabinoid signaling is modulated by high-fat diet (HFD. We investigated the consequences of congenital lack of CB1 receptors on sleep in mice fed standard diet (SD and HFD. CB1 cannabinoid receptor knock-out (KO and wild-type (WT mice were fed SD or HFD for 4 months (n = 9-10 per group. Mice were instrumented with electroencephalographic (EEG and electromyographic electrodes. Recordings were performed during baseline (48 hours, sleep deprivation (gentle handling, 6 hours, sleep recovery (18 hours, and after cage switch (insomnia model paradigm, 6 hours. We found multiple significant effects of genotype on sleep. In particular, KO spent more time awake and less time in non-rapid-eye-movement sleep (NREMS and rapid-eye-movement sleep (REMS than WT during the dark (active period but not during the light (rest period, enhancing the day-night variation of wake-sleep amounts. KO had slower EEG theta rhythm during REMS. REMS homeostasis after sleep deprivation was less effective in KO than in WT. Finally, KO habituated more rapidly to the arousing effect of the cage-switch test than WT. We did not find any significant effects of diet or of diet x genotype interaction on sleep. The occurrence of multiple sleep alterations in KO indicates important roles of CB1 cannabinoid receptors in limiting arousal during the active period of the day, in sleep regulation, and in sleep EEG in mice.

  14. Teaching English Accepting Multiple Intelligence Types through Arts

    Ivana CIMERMANOVÁ

    2013-12-01

    Full Text Available The article discusses the importance of acceptance of the multiple intelligence types as one of the key factor influencing the (language teaching. It focuses mainly on the possibility to introduce art as a source of material for language teaching, providing a wide spectrum of possibilities to introduce different types of activities. The author understands art not only as a source for language teaching/learning but something more than that. For her, the art can be a source for presenting moral and aesthetic values and the material, which will develop learners as a complete personality. The art can bring ethics, culture, history to the language lesson and can help learners to understand the mentality and culture of the target language countr(ies more deeply. The paper is the case study done at the secondary school (1st graders, using some materials and preparing them for achieving the states aim, by the author. This study was a space to learn more about the students’ perception of task based approach, what gave them a chance to experience a shift from ‘teacher-centred’ learning to ‘learner centred’ lesson.

  15. Statin Induced Myopathy a Patient with Multiple Systemic Diseases

    Özgül Uçar

    2011-04-01

    Full Text Available Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins are the most successful class of drugs for the treatment of hypercholesterolaemia and dyslipidaemia. However, the popular profile of statins in terms of efficacy has been maligned by theiradverse effects. Statin induced myopathy, which can be seen at any time during the course of therapy, is a clinically important cause of statin intolerance and discontinuation. When a patient with multiple systemic diseases who use numerous medications represent with myalgia and muscle cramps, statin induced myopathy may not be remembered at first. We present a patient with multiple systemic diseases, alcohol and morphine abuse in whom myopathy developed. After exclusion of other etiologies, we concluded that myopathy was related to statin therapy.

  16. Integration of Multiple Genomic and Phenotype Data to Infer Novel miRNA-Disease Associations.

    Shi, Hongbo; Zhang, Guangde; Zhou, Meng; Cheng, Liang; Yang, Haixiu; Wang, Jing; Sun, Jie; Wang, Zhenzhen

    2016-01-01

    MicroRNAs (miRNAs) play an important role in the development and progression of human diseases. The identification of disease-associated miRNAs will be helpful for understanding the molecular mechanisms of diseases at the post-transcriptional level. Based on different types of genomic data sources, computational methods for miRNA-disease association prediction have been proposed. However, individual source of genomic data tends to be incomplete and noisy; therefore, the integration of various types of genomic data for inferring reliable miRNA-disease associations is urgently needed. In this study, we present a computational framework, CHNmiRD, for identifying miRNA-disease associations by integrating multiple genomic and phenotype data, including protein-protein interaction data, gene ontology data, experimentally verified miRNA-target relationships, disease phenotype information and known miRNA-disease connections. The performance of CHNmiRD was evaluated by experimentally verified miRNA-disease associations, which achieved an area under the ROC curve (AUC) of 0.834 for 5-fold cross-validation. In particular, CHNmiRD displayed excellent performance for diseases without any known related miRNAs. The results of case studies for three human diseases (glioblastoma, myocardial infarction and type 1 diabetes) showed that all of the top 10 ranked miRNAs having no known associations with these three diseases in existing miRNA-disease databases were directly or indirectly confirmed by our latest literature mining. All these results demonstrated the reliability and efficiency of CHNmiRD, and it is anticipated that CHNmiRD will serve as a powerful bioinformatics method for mining novel disease-related miRNAs and providing a new perspective into molecular mechanisms underlying human diseases at the post-transcriptional level. CHNmiRD is freely available at http://www.bio-bigdata.com/CHNmiRD.

  17. Integration of Multiple Genomic and Phenotype Data to Infer Novel miRNA-Disease Associations.

    Hongbo Shi

    Full Text Available MicroRNAs (miRNAs play an important role in the development and progression of human diseases. The identification of disease-associated miRNAs will be helpful for understanding the molecular mechanisms of diseases at the post-transcriptional level. Based on different types of genomic data sources, computational methods for miRNA-disease association prediction have been proposed. However, individual source of genomic data tends to be incomplete and noisy; therefore, the integration of various types of genomic data for inferring reliable miRNA-disease associations is urgently needed. In this study, we present a computational framework, CHNmiRD, for identifying miRNA-disease associations by integrating multiple genomic and phenotype data, including protein-protein interaction data, gene ontology data, experimentally verified miRNA-target relationships, disease phenotype information and known miRNA-disease connections. The performance of CHNmiRD was evaluated by experimentally verified miRNA-disease associations, which achieved an area under the ROC curve (AUC of 0.834 for 5-fold cross-validation. In particular, CHNmiRD displayed excellent performance for diseases without any known related miRNAs. The results of case studies for three human diseases (glioblastoma, myocardial infarction and type 1 diabetes showed that all of the top 10 ranked miRNAs having no known associations with these three diseases in existing miRNA-disease databases were directly or indirectly confirmed by our latest literature mining. All these results demonstrated the reliability and efficiency of CHNmiRD, and it is anticipated that CHNmiRD will serve as a powerful bioinformatics method for mining novel disease-related miRNAs and providing a new perspective into molecular mechanisms underlying human diseases at the post-transcriptional level. CHNmiRD is freely available at http://www.bio-bigdata.com/CHNmiRD.

  18. Sortilin and Its Multiple Roles in Cardiovascular and Metabolic Diseases

    Goettsch, Claudia; Kjølby, Mads Fuglsang; Aikawa, Elena

    2018-01-01

    Cardiovascular disease is a leading cause of morbidity and mortality in the Western world. Studies of sortilin's influence on cardiovascular and metabolic diseases goes far beyond the genome-wide association studies that have revealed an association between cardiovascular diseases and the 1p13...... locus that encodes sortilin. Emerging evidence suggests a significant role of sortilin in the pathogenesis of vascular and metabolic diseases; this includes type II diabetes mellitus via regulation of insulin resistance, atherosclerosis through arterial wall inflammation and calcification...... of sortilin's contributions to cardiovascular and metabolic diseases but focuses particularly on atherosclerosis. We summarize recent clinical findings that suggest that sortilin may be a cardiovascular risk biomarker and also discuss sortilin as a potential drug target....

  19. Celiac disease in type 1 diabetes mellitus

    Camarca Maria

    2012-03-01

    Full Text Available Abstract Celiac Disease (CD occurs in patients with Type 1 Diabetes (T1D ranging the prevalence of 4.4-11.1% versus 0.5% of the general population. The mechanism of association of these two diseases involves a shared genetic background: HLA genotype DR3-DQ2 and DR4-DQ8 are strongly associated with T1D, DR3-DQ2 with CD. The classical severe presentation of CD rarely occurs in T1D patients, but more often patients have few/mild symptoms of CD or are completely asymptomatic (silent CD. In fact diagnosis of CD is regularly performed by means of the screening in T1D patients. The effects of gluten-free diet (GFD on the growth and T1D metabolic control in CD/T1D patient are controversial. Regarding of the GFD composition, there is a debate on the higher glycaemic index of gluten-free foods respect to gluten-containing foods; furthermore GFD could be poorer of fibers and richer of fat. The adherence to GFD by children with CD-T1D has been reported generally below 50%, lower respect to the 73% of CD patients, a lower compliance being more frequent among asymptomatic patients. The more severe problems of GFD adherence usually occur during adolescence when in GFD non compliant subjects the lowest quality of life is reported. A psychological and educational support should be provided for these patients.

  20. Evaluation of prevalence of headache in Multiple Sclerosis patients before & after the disease

    H. Mozhdehipanah

    2017-08-01

    Full Text Available Background: Multiple Sclerosis disease is a chronic disease of nervous system which causes different symptoms. Although headache is not a major symptom of this disease, but a lot of patients suffer from it. To specify the prevalence of headache and its’ types has an important role in diagnose, treatment and improvement the quality of patients’ life. Objective: Our goal of this study was to determine the prevalence of headache in multiple sclerosis patients, before and after the diagnosis of this disease. Methods: This cross-sectional descriptive epidemiologic study was performed on 150 multiple sclerosis patients referred to the neurology clinic of Qazvin in 2015. Data were recorded by history taking & physical examination the existence of headache before the MS diagnosis and at the time of study was evaluated by the patients’ data. Findings: Among participants, prevalence of headache before the MS diagnosis was 40%, which increased to 64% after that (P<0.001. The most common type of headache, before and after the affection was tension headache, which formed 58.3% and 70.8% of all headaches, respectively. The average rate of headache in the group with headache, before and after the diagnosis of MS was 5.8 and 5.76 days in month, which calculated 2.32 and 3.68 days in month in all patients, respectively. Conclusion: Prevalence of headache increases in multiple sclerosis patients. Patients suffer from headache almost 13% of their life days.

  1. An improved early detection method of type-2 diabetes mellitus using multiple classifier system

    Zhu, Jia

    2015-01-01

    The specific causes of complex diseases such as Type-2 Diabetes Mellitus (T2DM) have not yet been identified. Nevertheless, many medical science researchers believe that complex diseases are caused by a combination of genetic, environmental, and lifestyle factors. Detection of such diseases becomes an issue because it is not free from false presumptions and is accompanied by unpredictable effects. Given the greatly increased amount of data gathered in medical databases, data mining has been used widely in recent years to detect and improve the diagnosis of complex diseases. However, past research showed that no single classifier can be considered optimal for all problems. Therefore, in this paper, we focus on employing multiple classifier systems to improve the accuracy of detection for complex diseases, such as T2DM. We proposed a dynamic weighted voting scheme called multiple factors weighted combination for classifiers\\' decision combination. This method considers not only the local and global accuracy but also the diversity among classifiers and localized generalization error of each classifier. We evaluated our method on two real T2DM data sets and other medical data sets. The favorable results indicated that our proposed method significantly outperforms individual classifiers and other fusion methods.

  2. Elevated interleukin-12 in progressive multiple sclerosis correlates with disease activity and is normalized by pulse cyclophosphamide therapy

    Comabella, M; Balashov, K; Issazadeh-Navikas, Shohreh

    1998-01-01

    Multiple sclerosis is postulated to be a Th1-type cell-mediated autoimmune disease. We investigated cytokine profiles in patients with progressive multiple sclerosis by using intracytoplasmic staining. We found increased IL-12 production by monocytes and increased IFN-gamma production by T cells...

  3. Multiple Observation Types Jointly Constrain Terrestrial Carbon and Water Cycles

    Raupach, M. R.; Haverd, V.; Briggs, P. R.; Canadell, J.; Davis, S. J.; Isaac, P. R.; Law, R.; Meyer, M.; Peters, G. P.; Pickett Heaps, C.; Roxburgh, S. H.; Sherman, B.; van Gorsel, E.; Viscarra Rossel, R.; Wang, Z.

    2012-12-01

    Information about the carbon cycle potentially constrains the water cycle, and vice versa. This paper explores the utility of multiple observation sets to constrain carbon and water fluxes and stores in a land surface model, and a resulting determination of the Australian terrestrial carbon budget. Observations include streamflow from 416 gauged catchments, measurements of evapotranspiration (ET) and net ecosystem production (NEP) from 12 eddy-flux sites, litterfall data, and data on carbon pools. The model is a version of CABLE (the Community Atmosphere-Biosphere-Land Exchange model), coupled with CASAcnp (a biogeochemical model) and SLI (Soil-Litter-Iso, a soil hydrology model including liquid and vapour water fluxes and the effects of litter). By projecting observation-prediction residuals onto model uncertainty, we find that eddy flux measurements provide a significantly tighter constraint on Australian continental net primary production (NPP) than the other data types. However, simultaneous constraint by multiple data types is important for mitigating bias from any single type. Results emerging from the multiply-constrained model are as follows (with all values applying over 1990-2011 and all ranges denoting ±1 standard error): (1) on the Australian continent, a predominantly semi-arid region, over half (0.64±0.05) of the water loss through ET occurs through soil evaporation and bypasses plants entirely; (2) mean Australian NPP is 2200±400 TgC/y, making the NPP/precipitation ratio about the same for Australia as the global land average; (3) annually cyclic ("grassy") vegetation and persistent ("woody") vegetation respectively account for 0.56±0.14 and 0.43±0.14 of NPP across Australia; (4) the average interannual variability of Australia's NEP (±180 TgC/y) is larger than Australia's total anthropogenic greenhouse gas emissions in 2011 (149 TgCeq/y), and is dominated by variability in desert and savannah regions. The mean carbon budget over 1990

  4. Próba ukierunkowania rehabilitacji u pacjentów ze stwardnieniem rozsianym w zależności od typu klinicznego choroby = The attempt conditions for the rehabilitation of patients with multiple sclerosis, depending on the type of clinical disease

    Wojciech Garczyński

    2016-07-01

    rednim czasie trwania choroby z podziałem na formy kliniczne (odpowiednio p<0,001 i p<0,01. Na podstawie testu Kruskala - Wallisa stwierdzono istotne statystycznie różnice w poziomie niewydolności ruchowej - EDSS (p<0,001, zmęczenia – MFIS (p<0,05, równowagi – EQUI SCALE (p<0,001 i niesprawności – MDST (p<0,01 w typach klinicznych stwardnienia rozsianego. WNIOSKI. 1. Poziom zmęczenia, zakres zaburzeń równowagi, poziom niewydolności ruchowej oraz niesprawności zależą od typu klinicznego SM. 2. Poziom objawów lękowych i depresyjnych nie wykazuje zróżnicowania pod względem typu klinicznego SM. 3. Pomimo występowania pewnego zróżnicowania poziomu wybranych funkcji fizycznych i społecznych zależnie od typu SM, trudnym wydaje się ukierunkowanie rehabilitacji w oparciu o te założenia.       INTRODUCTION. Multiple sclerosis (eng. Multiple sclerosis, MS is an inflammatory-demyelinating disease of the central nervous system, wherein the multifocal changes occur. Etiopathogenesis is related to genetics and immune. Lesions are characterized by rapid progression and are mainly found in the white matter, brainstem, cerebellum, spinal cord and optic nerve. In remission, remyelination occurs, following which the inflammation subsides. Multiple sclerosis can run with or without relapses. Clinical form of primary progressive (PPMS, multiple sclerosis occurring without relapses, other clinical forms: relapsing - remitting (RRMS, secondary progressive (SPMS and progressive - relapsing (PRMS are characterized by the appearance of relapses, a form of benign (BNMS may be present without relapses. OBJECTIVES. The main objective of this study was to examine correlations between the diversity of physical and social functions in patients with multiple sclerosis and the type and form of the disease. Possible to find such relations, in consequence,  would enable an early orientation of rehabilitation process for needs of patients with a particular type and form of the

  5. Morbillivirus v proteins exhibit multiple mechanisms to block type 1 and type 2 interferon signalling pathways.

    Senthil K Chinnakannan

    Full Text Available Morbilliviruses form a closely related group of pathogenic viruses which encode three non-structural proteins V, W and C in their P gene. Previous studies with rinderpest virus (RPV and measles virus (MeV have demonstrated that these non-structural proteins play a crucial role in blocking type I (IFNα/β and type II (IFNγ interferon action, and various mechanisms have been proposed for these effects. We have directly compared four important morbilliviruses, rinderpest (RPV, measles virus (MeV, peste des petits ruminants virus (PPRV and canine distemper virus (CDV. These viruses and their V proteins could all block type I IFN action. However, the viruses and their V proteins had varying abilities to block type II IFN action. The ability to block type II IFN-induced gene transcription correlated with co-precipitation of STAT1 with the respective V protein, but there was no correlation between co-precipitation of either STAT1 or STAT2 and the abilities of the V proteins to block type I IFN-induced gene transcription or the creation of the antiviral state. Further study revealed that the V proteins of RPV, MeV, PPRV and CDV could all interfere with phosphorylation of the interferon-receptor-associated kinase Tyk2, and the V protein of highly virulent RPV could also block the phosphorylation of another such kinase, Jak1. Co-precipitation studies showed that morbillivirus V proteins all form a complex containing Tyk2 and Jak1. This study highlights the ability of morbillivirus V proteins to target multiple components of the IFN signalling pathways to control both type I and type II IFN action.

  6. Multiple concurrent primary extramammary Paget’s disease

    Leelavathi Muthupalaniappen

    2016-11-01

    Full Text Available Extramammary Paget’s disease (EMPD is a rare malignant disorder of the skin, which was described in as early as the nineteenth century. EMPD usually occurs as a single lesion in the apocrine sweat gland–bearing skin with abundant hair follicles. Here, we present an elderly man who suffered from a non-resolving chronic genital pruritus for 8 months. Initially, he was managed for recurrent fungal infection and eczema. Later, a diagnosis of the rare condition multiple primary EMPD was made based on the histopathology findings and appropriate treatment was given.

  7. Genomic Physics. Multiple Laser Beam Treatment of Alzheimer's Disease

    Stefan, V. Alexander

    2014-03-01

    The synapses affected by Alzheimer's disease can be rejuvenated by the multiple ultrashort wavelength laser beams.[2] The guiding lasers scan the whole area to detect the amyloid plaques based on the laser scattering technique. The scanning lasers pinpoint the areas with plaques and eliminate them. Laser interaction is highly efficient, because of the focusing capabilities and possibility for the identification of the damaging proteins by matching the protein oscillation eigen-frequency with laser frequency.[3] Supported by Nikola Tesla Labs, La Jolla, California, USA.

  8. A Bayesian Hierarchical Model for Relating Multiple SNPs within Multiple Genes to Disease Risk

    Lewei Duan

    2013-01-01

    Full Text Available A variety of methods have been proposed for studying the association of multiple genes thought to be involved in a common pathway for a particular disease. Here, we present an extension of a Bayesian hierarchical modeling strategy that allows for multiple SNPs within each gene, with external prior information at either the SNP or gene level. The model involves variable selection at the SNP level through latent indicator variables and Bayesian shrinkage at the gene level towards a prior mean vector and covariance matrix that depend on external information. The entire model is fitted using Markov chain Monte Carlo methods. Simulation studies show that the approach is capable of recovering many of the truly causal SNPs and genes, depending upon their frequency and size of their effects. The method is applied to data on 504 SNPs in 38 candidate genes involved in DNA damage response in the WECARE study of second breast cancers in relation to radiotherapy exposure.

  9. A Case of Multiple Sclerosis and Celiac Disease

    H. Z. Batur-Caglayan

    2013-01-01

    Full Text Available Objectives. Multiple sclerosis (MS is an inflammatory autoimmune disorder of the central nervous system (CNS. Since a correlation between gluten intake and incidence of MS had been reported, the relationship of antigliadin antibodies and MS was debated. Case Report. We report the case of a 45-year-old female MS patient who is under interferon treatment. After seven years of monitoring, during her routine gastroenterological assessment, she was diagnosed with celiac disease. Conclusion. Beside the neurological manifestations that have been demonstrated in about 10% of celiac disease (CD patients, white-matter abnormalities in brain MRI are uncommon and controversial. But in the literature, MS seems to be associated with CD as in our patient. We suggest that MS patients with gastroenterological complaints should undergo an assessment for CD.

  10. Liver and Skin Histopathology in Adults with Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Type B)

    Thurberg, Beth L.; Wasserstein, Melissa P.; Schiano, Thomas; O’Brien, Fanny; Richards, Susan; Cox, Gerald F.; McGovern, Margaret M.

    2012-01-01

    Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disorder characterized by the pathologic accumulation of sphingomyelin in multiple cells types, and occurs most prominently within the liver, spleen and lungs, leading to significant clinical disease. Seventeen ASMD patients underwent a liver biopsy during baseline screening for a Phase 1 trial of recombinant human acid sphingomyelinase (rhASM) in adults with Niemann-Pick disease type B. Eleven of the 17 were enrolled in the trial...

  11. Prevalence of Diabetes Type 1 in Patients Suffered From Multiple Sclerosis

    Dayer

    2016-04-01

    Full Text Available Background Because IL2RA is considered a predisposing factor in the incidence of both type I diabetes and multiple sclerosis (MS, and considering that both are autoimmune diseases, some studies suggest a correlation between type I diabetes and MS. Objectives The aim of this study was to examine the prevalence of type I diabetes among people with MS. Patients and Methods The study subjects comprised 100 patients with MS from the Khuzestan multiple sclerosis center at rehabilitation school of Jundishapur University of Medical Sciences, whose diagnosis of MS had been confirmed by a specialist, and were not being treated with steroids. Subjects were selected from patients younger than 30 years old. After filling out an application form, 5 mL fasting venous blood and 5 mL after 2 hours were taken. The blood glucose level was measured with a kit (Zist Shimi using the enzymatic method. Results The mean age of the participants was 24.28 years. The rate of type I diabetes was equal to 4% of the total sample, while 18% of all patients had impaired fasting glucose. Conclusions Given the high level of impaired fasting glucose among patients in this study, it is likely that MS provides the basis for the incidence of glucose metabolism disorders. To prove this, further studies with larger sample sizes are required.

  12. Prognostic clinical and molecular biomarkers of renal disease in type 2 diabetes

    Pena, Michelle J; de Zeeuw, Dick; Mischak, Harald

    2015-01-01

    biomarkers address the predictive performance of novel biomarker panels in addition to the classical panel in type 2 diabetes. However, the prospective studies conducted so far have small sample sizes, are insufficiently powered and lack external validation. Adequately sized validation studies of multiple......Diabetic kidney disease occurs in ∼ 25-40% of patients with type 2 diabetes. Given the high risk of progressive renal function loss and end-stage renal disease, early identification of patients with a renal risk is important. Novel biomarkers may aid in improving renal risk stratification...... and metabolomics biomarkers. We focus on multiple biomarker panels since the molecular processes of renal disease progression in type 2 diabetes are heterogeneous, rendering it unlikely that a single biomarker significantly adds to clinical risk prediction. A limited number of prospective studies of multiple...

  13. Multiple gastrointestinal stromal tumors in type I neurofibromatosis: a pathologic and molecular study.

    Yantiss, Rhonda K; Rosenberg, Andrew E; Sarran, Lisa; Besmer, Peter; Antonescu, Cristina R

    2005-04-01

    Multiple gastrointestinal stromal tumors typically occur in familial form associated with KIT receptor tyrosine kinase or platelet-derived growth factor receptor-alpha (PDGFRA) germline mutations, but may also develop in the setting of type 1 neurofibromatosis. The molecular abnormalities of gastrointestinal stromal tumors arising in neurofibromatosis have not been extensively studied. We identified three patients with type 1 neuro-fibromatosis and multiple small intestinal stromal tumors. Immunostains for CD117, CD34, desmin, actins, S-100 protein, and keratins were performed on all of the tumors. DNA was extracted from representative paraffin blocks from separate tumor nodules in each case and subjected to a nested polymerase chain reaction, using primers for KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18, followed by direct sequencing. The mean patient age was 56 years (range: 37-86 years, male/female ratio: 2/1). One patient had three tumors, one had five, and one had greater than 10 tumor nodules, all of which demonstrated histologic features characteristic of gastrointestinal stromal tumors and stained strongly for CD117 and CD34. One patient died of disease at 35 months, one was disease free at 12 months and one was lost to follow-up. DNA extracts from 10 gastrointestinal stromal tumors (three from each of two patients and four from one patient) were subjected to polymerase chain reactions and assessed for mutations. All of the tumors were wild type for KIT exons 9, 13, and 17 and PDGFRA exons 12 and 18. Three tumors from one patient had identical point mutations in KIT exon 11, whereas the other tumors were wild type at this locus. We conclude that, although most patients with type 1 neurofibromatosis and gastrointestinal stromal tumors do not have KIT or PDGFRA mutations, KIT germline mutations might be implicated in the pathogenesis of gastrointestinal stromal tumors in some patients.

  14. Niemann-Pick disease type C

    Vanier, Marie T

    2010-01-01

    Abstract Niemann-Pick C disease (NP-C) is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1/120 000 live births. The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. The neurological involvement defines the disease severity in most patients but is typically preceded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno- or hepatosplenomegaly in...

  15. Impact of Age and Antibody Type on Progression From Single to Multiple Autoantibodies in Type 1 Diabetes Relatives.

    Bosi, Emanuele; Boulware, David C; Becker, Dorothy J; Buckner, Jane H; Geyer, Susan; Gottlieb, Peter A; Henderson, Courtney; Kinderman, Amanda; Sosenko, Jay M; Steck, Andrea K; Bingley, Polly J

    2017-08-01

    Islet autoantibodies are markers of type 1 diabetes, and an increase in number of autoantibodies detected during the preclinical phase predicts progression to overt disease. To refine the effect of age in relation to islet antibody type on progression from single to multiple autoantibodies in relatives of people with type 1 diabetes. We examined 994 relatives with normal glucose tolerance who were positive for a single autoantibody, followed prospectively in the TrialNet Pathway to Prevention. Antibodies to glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated antigen 2, and zinc transporter 8 and islet cell antibodies were tested every 6 to 12 months. The primary outcome was confirmed development of multiple autoantibodies. Age was categorized as <8 years, 8 to 11 years, 12 to 17 years, and ≥18 years, and optimal age breakpoints were identified by recursive partitioning analysis. After median follow-up of 2 years, 141 relatives had developed at least one additional autoantibodies. Five-year risk was inversely related to age, but the pattern differed by antibody type: Relatives with GADA showed a gradual decrease in risk over the four age groups, whereas relatives with IAA showed a sharp decrease above age 8 years. Recursive partitioning analysis identified age breakpoints at 14 years in relatives with GADA and at 4 years in relatives with IAA. In relatives with IAA, spread of islet autoimmunity is largely limited to early childhood, whereas immune responses initially directed at glutamic acid decarboxylase can mature over a longer period. These differences have important implications for monitoring these patients and for designing prevention trials. Copyright © 2017 Endocrine Society

  16. Characteristics of the Danish families with multiple endocrine neoplasia type 1

    Jäger, Anne Charlotte; Friis-Hansen, Lennart; Hansen, Thomas v.O.

    2006-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is caused by autosomal dominantly inherited mutations in the MEN1 gene. Here, we report 25 MEN1 mutations - of which 12 are novel - found in 36 Danish families with MEN1 or variant MEN1 disease. Furthermore, one FIHP family was found to have an earlier...... reported mutation. The mutations were predominantly found in exons 9 and 10 encoding the C-terminal part of menin. Seven of the mutations were missense mutations, changing conserved residues. Furthermore screening of 93 out of 153 consecutive patients with primary hyperparathyroidism (pHPT) identified five...... mutation carriers. Two of these belonged to known MEN1 families, whereas the only MEN1-related disease in the other three was pHPT. Screening of 96 consecutive patients with fore-/midgut endocrine tumours revealed five mutation carries out of 28 patients with sporadic gastrinomas, whereas no mutations were...

  17. Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1

    Marcel Cerqueira Cesar Machado

    Full Text Available Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and

  18. Internal tremor in Parkinson's disease, multiple sclerosis, and essential tremor.

    Cochrane, Graham D; Rizvi, Syed; Abrantes, Ana; Crabtree, Brigid; Cahill, Jonathan; Friedman, Joseph H

    2015-10-01

    Internal tremor (IT) is a poorly recognized symptom that has been described in Parkinson's disease (PD). Described as a feeling of tremor in the extremities or trunk without actual movement, ITs are not debilitating but can be bothersome to patients. The origin of the sensation is unknown., and ITs may be prevalent in other diseases than PD. The present study sought to expand knowledge about IT by confirming their presence in PD, and determining their prevalence in Multiple Sclerosis (MS), and Essential Tremor (ET). A survey was developed in order to determine the prevalence of IT in PD, MS, and ET and to learn what associations with various disease characteristics were present. The survey was administered to 89 consecutive PD, 70 MS, and 11 ET patients. ITs were found to be a prevalent symptom in all three disorders (32.6% of PD, 35.9% of MS, and 54.5% of ET subjects reported experiencing ITs). ITs were found to be associated both with the subjects' perceived levels of anxiety and the presence of visible tremors. ITs appear to be a common symptom in all three disorders studied. These results need to be confirmed and compared to appropriate control populations. Copyright © 2015. Published by Elsevier Ltd.

  19. Lupus erythematosus, thyroiditis, alopecia areata and vitiligo – A multiple autoimmune syndrome type 3 case presentation

    Alin Laurentiu Tatu

    2017-04-01

    Full Text Available The combination of at least three autoimmune diseases in the same patient has defined as multiple autoimmune syndrome (MAS. Abnormalities of T cell-mediated immunity and humoral immunity have been described previously in the literature. Aims of work were to investigate the 22 years old patient with lupus erythematosus for three years and autoimune thyroiditis for one year, regardind other possible autoimmune conditions and to establish a treatment to control the diseases. The clinical exam revealed some circular hairless patches on the beard appeared about three months ago and white depigmented disseminated areas started one month ago and the laboratory investigations were performed. The modified laboratory findings were total IgE 530 UI/mL, Anti-SSA (anti-RO antibodies> 200 IU/mL, SSB negative, Antinuclear antibodies (ANA positive and fine speckled, Lupus anticoagulant testing positive, Anti-thyroid peroxidase antibodies 951 UI/ml, TSH 4,7 µUI/mL. The diagnosis of multiple autoimmune syndrome(MAS type 3 including Lupus erythematosus, autoimune Thyroiditis, Alopecia Areata and Vitiligo was established. Endocrine autoimmunities are associated with autoantibodies that react to specific antigens, whereas patients with collagen diseases synthesize immunoglobulins that recognize nonorgan-specific cellular targets, such as nucleoproteins and nucleic acids. Cellular autoimmunity is important in the pathogenesis MAS. The existence of one autoimmune disorder helps lead to the discovery of other autoimmune conditions.

  20. Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease

    Scarpa, Maurizio; Almássy, Zsuzsanna; Beck, Michael

    2011-01-01

    Mucopolysaccharidosis type II (MPS II) is a rare, life-limiting, X-linked recessive disease characterised by deficiency of the lysosomal enzyme iduronate-2-sulfatase. Consequent accumulation of glycosaminoglycans leads to pathological changes in multiple body systems. Age at onset, signs and symp......Mucopolysaccharidosis type II (MPS II) is a rare, life-limiting, X-linked recessive disease characterised by deficiency of the lysosomal enzyme iduronate-2-sulfatase. Consequent accumulation of glycosaminoglycans leads to pathological changes in multiple body systems. Age at onset, signs...... paediatricians, specialist nurses, otorhinolaryngologists, orthopaedic surgeons, ophthalmologists, cardiologists, pneumologists, anaesthesiologists, neurologists, physiotherapists, occupational therapists, speech therapists, psychologists, social workers, homecare companies and patient societies. Take...

  1. SEXUALLY TRANSMITTED DISEASES - HISTORY, TYPES, PREVALENCE, EPIDEMIOLOGY

    Valentin Irmov

    2017-12-01

    Full Text Available Sexually transmitted infections affect persons of active sex and cause serious consequences for the human organism, society and the generation. They spread sporadically, epidemically, and in some of them there are pandemics. For example, humanity is currently in a third viral hepatitis pandemic and a first AIDS pandemic. Another group of diseases can also be transmitted through sexual contact, but this is not the main mode of transmission. Such are salmonellosis, amoebiasis, influenza, various causes of meningitis and pneumonia. Despite being sexually transmitted, this is not a major and almost irrelevant way of transmitting the infection. Therefore, the diseases themselves are not included in the group of sexually transmitted diseases.

  2. Visual field impairment captures disease burden in multiple sclerosis.

    Ortiz-Perez, Santiago; Andorra, Magí; Sanchez-Dalmau, Bernardo; Torres-Torres, Rubén; Calbet, David; Lampert, Erika J; Alba-Arbalat, Salut; Guerrero-Zamora, Ana M; Zubizarreta, Irati; Sola-Valls, Nuria; Llufriu, Sara; Sepúlveda, María; Saiz, Albert; Villoslada, Pablo; Martinez-Lapiscina, Elena H

    2016-04-01

    Monitoring disease burden is an unmeet need in multiple sclerosis (MS). Identifying patients at high risk of disability progression will be useful for improving clinical-therapeutic decisions in clinical routine. To evaluate the role of visual field testing in non-optic neuritis eyes (non-ON eyes) as a biomarker of disability progression in MS. In 109 patients of the MS-VisualPath cohort, we evaluated the association between visual field abnormalities and global and cognitive disability markers and brain and retinal imaging markers of neuroaxonal injury using linear regression models adjusted for sex, age, disease duration and use of disease-modifying therapies. We evaluated the risk of disability progression associated to have baseline impaired visual field after 3 years of follow-up. Sixty-two percent of patients showed visual field defects in non-ON eyes. Visual field mean deviation was statistically associated with global disability; brain (normalized brain parenchymal, gray matter volume and lesion load) and retinal (peripapillary retinal nerve fiber layer thickness and macular ganglion cell complex thickness) markers of neuroaxonal damage. Patients with impaired visual field had statistically significative greater disability, lower normalized brain parenchymal volume and higher lesion volume than patients with normal visual field testing. MS patients with baseline impaired VF tripled the risk of disability progression during follow-up [OR = 3.35; 95 % CI (1.10-10.19); p = 0.033]. The association of visual field impairment with greater disability and neuroaxonal injury and higher risk of disability progression suggest that VF could be used to monitor MS disease burden.

  3. Designed multiple ligands in metabolic disease research: from concept to platform.

    Gattrell, W; Johnstone, C; Patel, S; Smith, C Sambrook; Scheel, A; Schindler, M

    2013-08-01

    Type 2 diabetes mellitus (T2DM) is a multifactorial disease, and drug monotherapy typically results in unsatisfactory treatment outcomes for patients. Even when used in combination, existing therapies lack efficacy in the long term. Designed multiple ligands (DMLs) are compounds developed to modulate multiple targets relevant to a disease. DMLs offer the potential to yield greater efficacy over monotherapies, either by modulating different biological pathways, or by boosting a single one. However, examples of DMLs progressing into clinical trials, or onto the market are rare; DML drug discovery is challenging, and perceived by some to be almost impossible. Nevertheless, with the judicious selection of biological targets, both from a biological and chemical perspective, it is possible to develop drug-like DMLs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Genetic homogeneity of autoimmune polyglandular disease type I

    Bjoerses, P.; Aaltonen, J.; Vikman, A. [Univ. of Helsinki (Finland)] [and others

    1996-10-01

    Autoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease (MIM 240300) characterized by hypoparathyroidism, primary adrenocortical failure, and chronic mucocutaneous candidiasis. The disease is highly prevalent in two isolated populations, the Finnish population and the Iranian Jewish one. Sporadic cases have been identified in many other countries, including almost all European countries. The APECED locus has previously been assigned to chromosome 21q22.3 by linkage analyses in 14 Finnish families. Locus heterogeneity is a highly relevant question in this disease affecting multiple tissues and with great phenotypic diversity. To solve this matter, we performed linkage and haplotype analyses on APECED families rising from different populations. Six microsatellite markers on the critical chromosomal region of 2.6 cM on 21q22.3 were analyzed. Pair-wise linkage analyses revealed significant LOD scores for all these markers, maximum LOD score being 10.23. The obtained haplotype data and the geographic distribution of the great-grandparents of the Finnish APECED patients suggest the presence of one major, relatively old mutation responsible for {approximately}90% of the Finnish cases. Similar evidence for one founder mutation was also found in analyses of Iranian Jewish APECED haplotypes. These haplotypes, however, differed totally from the Finnish ones. The linkage analyses in 21 non-Finnish APECED families originating from several European countries provided independent evidence for linkage to the same chromosomal region on 21q22.3 and revealed no evidence for locus heterogeneity. The haplotype analyses of APECED chromosomes suggest that in different populations APECED is due to a spectrum of mutations in a still unknown gene on chromosome 21. 21 refs., 3 figs., 3 tabs.

  5. 'CM 88' - A multiple disease resistant chickpea mutant variety

    Haq, M.A.; Hassan, Mahmudul; Sadiq, M.

    2001-01-01

    Full text: Chickpea is the most important grain legume crop of Pakistan. Ascochyta blight (Ascochyta rabiei) and Fusarium wilt (Fusarium oxysporum F. sp cicer) are most serious diseases, having the potential to devastate a crop. A multiple disease resistant and high yielding mutant CM 88 has been developed through 100 Gy gamma irradiation treatment of variety 'C 727'. This was once a widely grown and popular variety, which lost its resistance to Ascochyta and was replaced. The selection of mutants was performed in the M2 generation grown in the Ascochyta blight nursery and sixteen mutants were selected. In the subsequent generations CM 88 proved resistant to both Ascochyta blight and Fusarium wilt, and exhibited superiority in agronomic characteristics. CM 88 was also tested for many years in the various yield trials on research stations and farmers fields throughout the country. In these trials it out yielded both the parent and standard varieties. The mutant CM 88 has been approved by the Punjab Seed Council on 27 October 1994 for general cultivation in the Punjab Province, especially the Thal area which accounts for more than 70% of the area under chickpea cultivation. (author)

  6. [Disease concept, etiology and mechanisms of multiple sclerosis].

    Kira, Jun-Ichi

    2014-11-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system(CNS). MS is assumed to be caused by a complex interplay between genes and environments. Autoimmune mechanisms targeting CNS myelin has long been proposed, yet it has not been proved. Th17 cells producing interleukin-17 and Th1 cells producing interferon-gamma are postulated to play major roles in initiating inflammation while regulatory T cell functions are dampened. The forth nationwide survey of MS in Japan revealed that MS prevalence showed four-folds increase over 30 years and the increase was especially prominent in female. Thus, westernized life style and improved sanitation are suspected to increase MS susceptibility. Genome-wide association studies in Western MS patients disclosed more than 100 disease-susceptibility genes, most of which are immune-related genes. It therefore supports immune-mediated mechanisms to be operative. Detailed magnetic resonance imaging studies revealed an early atrophy of the cerebral gray matter where T cell infiltration is pathologically scarce. Therefore, neurodegenerative process also takes place in the early course beside neuroinflammation.

  7. Existence and multiplicity of solutions for divergence type elliptic equations

    Lin Zhao

    2011-03-01

    Full Text Available We establish the existence and multiplicity of weak solutions of a problem involving a uniformly convex elliptic operator in divergence form. We find one nontrivial solution by the mountain pass lemma, when the nonlinearity has a $(p-1$-superlinear growth at infinity, and two nontrivial solutions by minimization and mountain pass when the nonlinear term has a $(p-1$-sublinear growth at infinity.

  8. Clinical Holistic Medicine: The Patient with Multiple Diseases

    Søren Ventegodt

    2005-01-01

    Full Text Available In clinical practice, patients can present with many different diseases, often both somatic and mental. Holistic medicine will try to see the diseases as a whole, as symptoms of a more fundamental imbalance in the state of being. The holistic physician must help the patient to recover existence and a good relationship with self. According to the life mission theory, theory of character, and holistic process theory of healing, recovering the purpose of life (the life mission is essential for the patient to regain life, love, and trust in order to find happiness and realize the true purpose of life. We illustrate the power of the holistic medical approach with a case study of an invalidated female artist, aged 42 years, who suffered from multiple severe health problems, many of which had been chronic for years. She had a combination of neurological disturbances (tinnitus, migraine, minor hallucinations, immunological disturbances (recurrent herpes simplex, phlegm in the throat, fungal infection in the crotch, hormonal disturbances (14 days of menstruation in each cycle, muscle disturbances (neck tensions, mental disturbances (tendency to cry, inferiority feeling, mild depression, desolation, anxiety, abdominal complaints, hemorrhoids, and more. The treatment was a combined strategy of improving the general quality of life, recovering her human character and purpose of life (“renewing the patients life energy”, “balancing her global information system”, and processing the local blockages, thus healing most of her many different diseases in a treatment using 30 h of intense holistic therapy over a period of 18 months.

  9. CpG Type A Induction of an Early Protective Environment in Experimental Multiple Sclerosis

    James Crooks

    2017-01-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is an inflammatory, demyelinating disease of the CNS that mimics human multiple sclerosis (MS, and it is thought to be driven by Th1 and Th17 myelin-reactive cells. Although adaptive immunity is clearly pivotal in the pathogenesis of EAE, with an essential role of CD4+ T cells, little is known of early, innate responses in this experimental setting. CpG-rich oligodeoxynucleotides (ODNs, typically found in microbial genomes, are potent activators of TLR9 in plasmacytoid dendritic cells (pDCs. In this study, we compared the effects of two types of CpG, namely, type A and type B, on EAE. We found that treatment with CpG type A ODN (CpG-A, known to induce high amounts of IFN-α in pDCs, significantly reduced disease severity in EAE, relative to controls (12.63±1.86 versus 23.49±1.46, resp.; p=0.001. Treatment also delayed onset of neurological deficits and reduced spinal cord demyelination, while increasing the percentage of splenic regulatory (Foxp3+ CD4+ T cells. CpG-A likewise reduced the levels of IL-17 and IFN-γ in the CNS. Mechanistic insight into those events showed that CpG-A promoted a regulatory phenotype in pDCs. Moreover, adoptive transfer of pDCs isolated from CpG-A-treated mice inhibited CNS inflammation and induced disease remission in acute-phase EAE. Our data thus identify a link between TLR9 activation by specific ligands and the induction of tolerance via innate immunity mechanisms.

  10. Coexistence of coeliac disease and type 1 diabetes

    Szaflarska-Popławska, Anna

    2014-01-01

    There is a selective review of the literature concerning the coexistence of coeliac disease and type 1 diabetes mellitus. This review focuses on the principles of serological tests towards coeliac disease in patients with type 1 diabetes mellitus and metabolic control measures as a result of a gluten-free diet.

  11. Genetic diagnosis of a Chinese multiple endocrine neoplasia type ...

    However, different families with MEN 2A due to the same RET mutation often have significant variability inthe clinical exhibition of disease and aggressiveness of the MTC, which implies additional genetic loci exsit beyondRET coding region. Whole genome sequencing (WGS) greatly expands the breadth of screening from ...

  12. Empirical validation of the Horowitz Multiple Systemic Infectious Disease Syndrome Questionnaire for suspected Lyme disease.

    Citera, Maryalice; Freeman, Phyllis R; Horowitz, Richard I

    2017-01-01

    Lyme disease is spreading worldwide, with multiple Borrelia species causing a broad range of clinical symptoms that mimic other illnesses. A validated Lyme disease screening questionnaire would be clinically useful for both providers and patients. Three studies evaluated such a screening tool, namely the Horowitz Multiple Systemic Infectious Disease Syndrome (MSIDS) Questionnaire. The purpose was to see if the questionnaire could accurately distinguish between Lyme patients and healthy individuals. Study 1 examined the construct validity of the scale examining its factor structure and reliability of the questionnaire among 537 individuals being treated for Lyme disease. Study 2 involved an online sample of 999 participants, who self-identified as either healthy (N=217) or suffering from Lyme now (N=782) who completed the Horowitz MSIDS Questionnaire (HMQ) along with an outdoor activity survey. We examined convergent validity among components of the scale and evaluated discriminant validity with the Big Five personality characteristics. The third study compared a sample of 236 patients with confirmed Lyme disease with an online sample of 568 healthy individuals. Factor analysis results identified six underlying latent dimensions; four of these overlapped with critical symptoms identified by Horowitz - neuropathy, cognitive dysfunction, musculoskeletal pain, and fatigue. The HMQ showed acceptable levels of internal reliability using Cronbach's coefficient alpha and exhibited evidence of convergent and divergent validity. Components of the HMQ correlated more highly with each other than with unrelated traits. The results consistently demonstrated that the HMQ accurately differentiated those with Lyme disease from healthy individuals. Three migratory pain survey items (persistent muscular pain, arthritic pain, and nerve pain/paresthesias) robustly identified individuals with verified Lyme disease. The results support the use of the HMQ as a valid, efficient, and low

  13. Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases

    Bordoloi, Devivasha; Padmavathi, Ganesan; Monisha, Javadi; Roy, Nand Kishor; Prasad, Sahdeo

    2016-01-01

    Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in 1949 in Nature and the first clinical trial was reported in The Lancet in 1937. Although the current database indicates almost 9000 publications on curcumin, until 1990 there were less than 100 papers published on this nutraceutical. At the molecular level, this multitargeted agent has been shown to exhibit anti‐inflammatory activity through the suppression of numerous cell signalling pathways including NF‐κB, STAT3, Nrf2, ROS and COX‐2. Numerous studies have indicated that curcumin is a highly potent antimicrobial agent and has been shown to be active against various chronic diseases including various types of cancers, diabetes, obesity, cardiovascular, pulmonary, neurological and autoimmune diseases. Furthermore, this compound has also been shown to be synergistic with other nutraceuticals such as resveratrol, piperine, catechins, quercetin and genistein. To date, over 100 different clinical trials have been completed with curcumin, which clearly show its safety, tolerability and its effectiveness against various chronic diseases in humans. However, more clinical trials in different populations are necessary to prove its potential against different chronic diseases in humans. This review's primary focus is on lessons learnt about curcumin from clinical trials. Linked Articles This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc PMID:27638428

  14. Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases.

    Kunnumakkara, Ajaikumar B; Bordoloi, Devivasha; Padmavathi, Ganesan; Monisha, Javadi; Roy, Nand Kishor; Prasad, Sahdeo; Aggarwal, Bharat B

    2017-06-01

    Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in 1949 in Nature and the first clinical trial was reported in The Lancet in 1937. Although the current database indicates almost 9000 publications on curcumin, until 1990 there were less than 100 papers published on this nutraceutical. At the molecular level, this multitargeted agent has been shown to exhibit anti-inflammatory activity through the suppression of numerous cell signalling pathways including NF-κB, STAT3, Nrf2, ROS and COX-2. Numerous studies have indicated that curcumin is a highly potent antimicrobial agent and has been shown to be active against various chronic diseases including various types of cancers, diabetes, obesity, cardiovascular, pulmonary, neurological and autoimmune diseases. Furthermore, this compound has also been shown to be synergistic with other nutraceuticals such as resveratrol, piperine, catechins, quercetin and genistein. To date, over 100 different clinical trials have been completed with curcumin, which clearly show its safety, tolerability and its effectiveness against various chronic diseases in humans. However, more clinical trials in different populations are necessary to prove its potential against different chronic diseases in humans. This review's primary focus is on lessons learnt about curcumin from clinical trials. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. © 2016 The British Pharmacological Society.

  15. In vitro RBE-LET dependence for multiple particle types

    Sørensen, Brita Singers; Overgaard, Jens; Bassler, Niels

    2011-01-01

    Background. In vitro RBE values for various high LET radiation types have been determined for many different cell types. Occasionally it is criticized that RBE for a given endpoint cannot be single-value dependent on LET alone, but also on particle species, due to the different dose deposition...... profiles on microscopic scale. Hence LET is not sufficient as a predictor of RBE, and this is one of the motivations for development of radiobiological models which explicitly depend on the detailed particle energy spectrum of the applied radiation field. The aim of the present study is to summarize...... the available data in the literature regarding the dependency of RBE on LET for different particles. Method. As RBE is highly dependent on cell type and endpoint, we discriminated the RBE-LET relationship for the three investigated cell lines and at the same endpoint (10% survival in colony formation). Data...

  16. Multiple systemic embolism in infective endocarditis underlying in Barlow's disease.

    Yu, Ziqing; Fan, Bing; Wu, Hongyi; Wang, Xiangfei; Li, Chenguang; Xu, Rende; Su, Yangang; Ge, Junbo

    2016-08-11

    Systemic embolism, especially septic embolism, is a severe complication of infective endocarditis (IE). However, concurrent embolism to the brain, coronary arteries, and spleen is very rare. Because of the risk of hemorrhage or visceral rupture, anticoagulants are recommended only if an indication is present, e.g. prosthetic valve. Antiplatelet therapy in IE is controversial, but theoretically, this therapy has the potential to prevent and treat thrombosis and embolism in IE. Unfortunately, clinical trial results have been inconclusive. We describe a previously healthy 50-year-old man who presented with dysarthria secondary to bacterial endocarditis with multiple cerebral, coronary, splenic, and peripheral emboli; antibiotic therapy contributed to the multiple emboli. Emergency splenectomy was performed, with subsequent mitral valve repair. Pathological examination confirmed mucoid degeneration and mitral valve prolapse (Barlow's disease) as the underlying etiology of the endocardial lesion. Continuous antibiotics were prescribed, postoperatively. Transthoracic echocardiography at 1.5, 3, and 6 months after the onset of his illness showed no severe regurgitation, and there was no respiratory distress, fever, or lethargy during follow-up. Although antibiotic use in IE carries a risk of septic embolism, these drugs have bactericidal and antithrombotic benefits. It is important to consider that negative blood culture and symptom resolution do not confirm complete elimination of bacteria. However, vegetation size and Staphylococcus aureus infection accurately predict embolization. It is also important to consider that bacteria can be segregated from the microbicide when embedded in platelets and fibrin. Therefore, antimicrobial therapy with concurrent antiplatelet therapy should be considered carefully.

  17. Periodontal disease in type 2 diabetes mellitus

    Haseeb, M.; Khawaja, K.I.; Ataullah, K.; Munir, M.B.; Fatima, A.

    2012-01-01

    Objective: To determine the periodontal status in well controlled and poorly controlled type 2 diabetic patients compared with normal healthy individuals. Methodology: Forty well controlled and forty poorly controlled type 2 diabetic subjects having good oral hygiene (scored according to simplified oral hygiene index) were compared with a control group of forty normal healthy individuals. Probing depth (PD), gingival recession (GR), and attachment loss (AL) were recorded to obtain the periodontal status of each tooth, using a Michigan probe '0' with Williams marking. Glycemic control was evaluated by glycated Hb value. Using ANOVA and independent sample t-test, mean probing depth and attachment loss in each tooth type (incisors, canines, premolars and molars) were compared. Results: Mean age of diabetic subjects was 58.86 +- 6.21 years and that of control group was 56.92 +- 6.91 years; 60% were females. Probing depth was greater in patients with poorly controlled diabetes compared to well controlled diabetic patients and non-diabetic controls (4.21 mm vs. 3.72 mm and 2.93 mm respectively, p 0.05). Number of sites and mean percentage of sites with attachment loss of greater or equal to 4 and greater or equal to 6 mm was also significantly higher in poorly controlled diabetes compared to the control group (p < 0.05 and p < 0.001 respectively). Conclusion: Periodontal status as estimated by probing depth and degree of attachment loss deteriorates significantly with poor glycemic control in diabetes. (author)

  18. Established and novel disease-modifying treatments in multiple sclerosis.

    Cross, A H; Naismith, R T

    2014-04-01

    Multiple sclerosis (MS) is a presumed autoimmune disorder of the central nervous system, resulting in inflammatory demyelination and axonal and neuronal injury. New diagnostic criteria that incorporate magnetic resonance imaging have resulted in earlier and more accurate diagnosis of MS. Several immunomodulatory and immunosuppressive therapeutic agents are available for relapsing forms of MS, which allow individualized treatment based upon the benefits and risks. Disease-modifying therapies introduced in the 1990s, the beta-interferons and glatiramer acetate, have an established track record of efficacy and safety, although they require administration via injection. More recently, monoclonal antibodies have been engineered to act through specific mechanisms such as blocking alpha-4 integrin interactions (natalizumab) or lysing cells bearing specific markers, for example CD52 (alemtuzumab) or CD20 (ocrelizumab and ofatumumab). These agents can be highly efficacious, but sometimes have serious potential complications (natalizumab is associated with progressive multifocal leukoencephalopathy; alemtuzumab is associated with the development of new autoimmune disorders). Three new oral therapies (fingolimod, teriflunomide and dimethyl fumarate, approved for MS treatment from 2010 onwards) provide efficacy, tolerability and convenience; however, as yet, there are no long-term postmarketing efficacy and safety data in a general MS population. Because of this lack of long-term data, in some cases, therapy is currently initiated with the older, safer injectable medications, but patients are monitored closely with the plan to switch therapies if there is any indication of a suboptimal response or intolerance or lack of adherence to the initial therapy. For patients with MS who present with highly inflammatory and potentially aggressive disease, the benefit-to-risk ratio may support initiating therapy using a drug with greater potential efficacy despite greater risks (e

  19. Niemann-Pick disease type C

    Vanier Marie T

    2010-06-01

    Full Text Available Abstract Niemann-Pick C disease (NP-C is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1/120 000 live births. The broad clinical spectrum ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease. The neurological involvement defines the disease severity in most patients but is typically preceded by systemic signs (cholestatic jaundice in the neonatal period or isolated spleno- or hepatosplenomegaly in infancy or childhood. The first neurological symptoms vary with age of onset: delay in developmental motor milestones (early infantile period, gait problems, falls, clumsiness, cataplexy, school problems (late infantile and juvenile period, and ataxia not unfrequently following initial psychiatric disturbances (adult form. The most characteristic sign is vertical supranuclear gaze palsy. The neurological disorder consists mainly of cerebellar ataxia, dysarthria, dysphagia, and progressive dementia. Cataplexy, seizures and dystonia are other common features. NP-C is transmitted in an autosomal recessive manner and is caused by mutations of either the NPC1 (95% of families or the NPC2 genes. The exact functions of the NPC1 and NPC2 proteins are still unclear. NP-C is currently described as a cellular cholesterol trafficking defect but in the brain, the prominently stored lipids are gangliosides. Clinical examination should include comprehensive neurological and ophthalmological evaluations. The primary laboratory diagnosis requires living skin fibroblasts to demonstrate accumulation of unesterified cholesterol in perinuclear vesicles (lysosomes after staining with filipin. Pronounced abnormalities are observed in about 80% of the cases, mild to moderate alterations in the remainder ("variant" biochemical phenotype. Genotyping of patients is useful to confirm the diagnosis in the latter patients and essential for future prenatal diagnosis. The differential

  20. 75 FR 62487 - Compassionate Allowances for Cardiovascular Disease and Multiple Organ Transplants, Office of the...

    2010-10-12

    ...] Compassionate Allowances for Cardiovascular Disease and Multiple Organ Transplants, Office of the Commissioner... cardiovascular disease and multiple organ transplants, as well as topics covered at the hearing by: (1) e-mail... considering ways to quickly identify diseases and other serious medical conditions that obviously meet the...

  1. Heterogeneous pattern of bone disease in adult type 1 Gaucher disease: clinical and pathological correlates.

    van Dussen, L; Lips, P; van Essen, H W; Hollak, C E M; Bravenboer, N

    2014-09-01

    Gaucher disease (GD) is a lysosomal storage disorder characterized by accumulation of glucosylceramide in macrophages, so-called Gaucher cells, as a result of a deficiency of the lysosomal enzyme glucocerebrosidase. Bone complications are an important cause of morbidity of GD and are thought to result from imbalance in bone remodeling. Bone manifestations among GD patients demonstrate a large variation including increased osteoclastic bone resorption, low bone formation and osteonecrosis. The purpose of the current case series is to describe the histological features observed in undecalcified bone samples, obtained from three GD patients, and evaluate the relationship with clinical features in these patients. Bone fragments were obtained from three adult type 1 GD patients with variable degrees of bone disease during orthopedic surgery. Specimens were embedded without prior decalcification in methylmethacrylate and prepared for histology according to standardized laboratory procedures. Histology revealed a heterogeneous pattern of bone involvement. High cellularity of bone marrow, abundant presence of Gaucher cells (GCs) and high turnover were observed in a patient with a history of multiple bone complications, while minimal bone turnover and few GCs were detected in the mildest affected patient in this series. An intermediate picture with relatively low bone turnover and a substantial amount of Gaucher cells was demonstrated in the third, moderately affected patient. No gross abnormalities in three biochemical markers of bone turnover (osteocalcin, N-terminal propeptide of type 1 procollagen and type 1 collagen C-terminal telopeptide) were noted. Plastic embedding and subsequent Goldner and TRAP staining offered a unique possibility to study bone histological findings in GD. Our data show that bone manifestations in GD may vary both clinically as well as histologically and bone disease in GD will likely require a personalized approach. Copyright © 2014 Elsevier

  2. Cell elasticity with altered cytoskeletal architectures across multiple cell types.

    Grady, Martha E; Composto, Russell J; Eckmann, David M

    2016-08-01

    The cytoskeleton is primarily responsible for providing structural support, localization and transport of organelles, and intracellular trafficking. The structural support is supplied by actin filaments, microtubules, and intermediate filaments, which contribute to overall cell elasticity to varying degrees. We evaluate cell elasticity in five different cell types with drug-induced cytoskeletal derangements to probe how actin filaments and microtubules contribute to cell elasticity and whether it is conserved across cell type. Specifically, we measure elastic stiffness in primary chondrocytes, fibroblasts, endothelial cells (HUVEC), hepatocellular carcinoma cells (HUH-7), and fibrosarcoma cells (HT 1080) subjected to two cytoskeletal destabilizers: cytochalasin D and nocodazole, which disrupt actin and microtubule polymerization, respectively. Elastic stiffness is measured by atomic force microscopy (AFM) and the disruption of the cytoskeleton is confirmed using fluorescence microscopy. The two cancer cell lines showed significantly reduced elastic moduli values (~0.5kPa) when compared to the three healthy cell lines (~2kPa). Non-cancer cells whose actin filaments were disrupted using cytochalasin D showed a decrease of 60-80% in moduli values compared to untreated cells of the same origin, whereas the nocodazole-treated cells showed no change in elasticity. Overall, we demonstrate actin filaments contribute more to elastic stiffness than microtubules but this result is cell type dependent. Cancer cells behaved differently, exhibiting increased stiffness as well as stiffness variability when subjected to nocodazole. We show that disruption of microtubule dynamics affects cancer cell elasticity, suggesting therapeutic drugs targeting microtubules be monitored for significant elastic changes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Integration of Multiple Contractors with Performance Type of Contracts

    BURDGE, L.F.

    2000-01-01

    The management practices, procedures, and processes that are suited to managing Management and Operation (MandO) type of contracts at Department of Energy (DOE) sites, which were cost reimbursement with award fee, are not well suited to managing contracts where fee is determined by performance metrics. Thus a different style of management, requiring substantial revamping of the management process, is needed. This shift in philosophy also requires a dramatic shift in culture. This paper will describe how these changes are being managed at the River Protection Project (RPP), located at the DOE's Hanford Site in Washington State, one of DOE's largest and highest risk environmental clean-up project

  4. Cognitive Impairments in Multiple System Atrophy of the Cerebellar Type

    Hyun J. Hong

    2011-05-01

    Full Text Available Background and Purpose We investigated the cognitive profiles in a large sample of patients with multiple system atrophy-cerebellar ataxia (MSA-C and compared directly them in patients with clinical diagnosis of probable MSA-C without dementia and control subjects with intact cognition. Methods We prospectively enrolled 26 patients with clinical diagnosis of probable MSA-C. All patients underwent a standardized neuropsychological test of the Seoul Neuropsychological Screening Battery. Results The score of Korean version of the Mini- Mental State Examination was significantly lower in patients with MSA-C (27.2 ± 2.5 than in control subjects (28.9 ± 1.0, p = 0.003. Patients with MSA-C showed a significantly worse performance in visuospatial function, 3 words recall, verbal immediate, delayed and recognition memory, visual delayed memory, phonemic and sementic Controlled Oral Word Association Test, and ideomotor praxis (p < 0.05. Conclusions Patients with MSA-C show more severe and more widespread cognitive dysfunctions than controls. Our results also indicate that cognitive dysfunction in patients with MCA-C is suggestive of disruption of the cerebellocortical circuits.

  5. Influence of Disease and Patient Characteristics on Daratumumab Exposure and Clinical Outcomes in Relapsed or Refractory Multiple Myeloma

    Yan, Xiaoyu; Clemens, Pamela L; Puchalski, Thomas

    2018-01-01

    OBJECTIVE: The aim of this study was to understand the influence of disease and patient characteristics on exposure to daratumumab, an immunoglobulin Gκ (IgGκ) monoclonal antibody, and clinical outcomes in relapsed or refractory multiple myeloma (MM). PATIENTS AND METHODS: Baseline myeloma type, ...

  6. The Functions of Type I and Type II Natural Killer T (NKT) Cells in Inflammatory Bowel Diseases

    Liao, Chia-Min; Zimmer, Michael I.; Wang, Chyung-Ru

    2013-01-01

    CD1d-restricted natural killer T (NKT) cells are a distinct subset of T cells that rapidly produce an array of cytokines upon activation and play a critical role in regulating various immune responses. NKT cells are classified into two groups based on differences in T cell receptor (TCR) usage. Type I NKT cells have an invariant TCRα-chain and are readily detectable by α-galactosylceramide (α-GalCer)-loaded CD1d tetramers. Type II NKT cells have a more diverse TCR repertoire and cannot be directly identified. Both types of NKT cells as well as multiple CD1d-expressing cell types are present in the intestine and their interactions are likely to be modulated by pathogenic and commensal microbes, which in turn contribute to the intestinal immune responses in health and disease. Indeed, in several animal models of inflammatory bowel disease (IBD), Type I NKT cells have been shown to make both protective and pathogenic contributions to disease. In contrast, in human patients suffering from ulcerative colitis (UC), and a mouse model in which both CD1d expression and the frequency of Type II NKT cells are increased, Type II NKT cells appear to promote intestinal inflammation. In this review, we summarize present knowledge on the antigen recognition, activation and function of NKT cells with a particular focus on their role in IBD, and discuss factors that may influence the functional outcome of NKT cell responses in intestinal inflammation. PMID:23518808

  7. An improved early detection method of type-2 diabetes mellitus using multiple classifier system

    Zhu, Jia; Xie, Qing; Zheng, Kai

    2015-01-01

    The specific causes of complex diseases such as Type-2 Diabetes Mellitus (T2DM) have not yet been identified. Nevertheless, many medical science researchers believe that complex diseases are caused by a combination of genetic, environmental

  8. Generation of multiple cell types in Bacillus subtilis.

    Lopez, Daniel; Vlamakis, Hera; Kolter, Roberto

    2009-01-01

    Bacillus subtilis is a Gram-positive bacterium that is well known for its ability to differentiate into metabolically inactive spores that are highly resistant to environmental stresses. In fact, populations of genetically identical B. subtilis comprise numerous distinct cell types. In addition to spores, cells can become genetically competent, motile, produce extracellular matrix or degradative enzymes, or secrete toxins that allow them to cannibalize their neighbors. Many of the cell fates listed above appear to be mutually exclusive. In this review, we discuss how individual cells within a population control their gene expression to ensure that proper regulation of differentiation occurs. These different cell fates are regulated by an intricate network that relies primarily on the activity of three major transcriptional regulators: Spo0A, DegU, and ComK. While individual cells must choose distinct cell fates, the population as a whole exhibits a spectrum of phenotypes whose diversity may increase fitness.

  9. Methadone ameliorates multiple-low-dose streptozotocin-induced type 1 diabetes in mice

    Amirshahrokhi, K.; Dehpour, A.R.; Hadjati, J.; Sotoudeh, M.; Ghazi-Khansari, M.

    2008-01-01

    Type 1 diabetes is an autoimmune disease characterized by inflammation of pancreatic islets and destruction of β cells by the immune system. Opioids have been shown to modulate a number of immune functions, including T helper 1 (Th1) and T helper 2 (Th2) cytokines. The immunosuppressive effect of long-term administration of opioids has been demonstrated both in animal models and humans. The aim of this study was to determine the effect of methadone, a μ-opioid receptor agonist, on type 1 diabetes. Administration of multiple low doses of streptozotocin (STZ) (MLDS) (40mg/kg intraperitoneally for 5 consecutive days) to mice resulted in autoimmune diabetes. Mice were treated with methadone (10mg/kg/day subcutaneously) for 24days. Blood glucose, insulin and pancreatic cytokine levels were measured. Chronic methadone treatment significantly reduced hyperglycemia and incidence of diabetes, and restored pancreatic insulin secretion in the MLDS model. The protective effect of methadone can be overcome by pretreatment with naltrexone, an opioid receptor antagonist. Also, methadone treatment decreased the proinflammatory Th1 cytokines [interleukin (IL)-1β, tumor necrosis factor-α and interferon-γ] and increased anti-inflammatory Th2 cytokines (IL-4 and IL-10). Histopathological observations indicated that STZ-mediated destruction of β cells was attenuated by methadone treatment. It seems that methadone as an opioid agonist may have a protective effect against destruction of β cells and insulitis in the MLDS model of type 1 diabetes

  10. High frequency of multiple HPV types in cervical specimens from Danish women

    Mejlhede, Nina; Bonde, Jesper; Fomsgaard, Anders

    2009-01-01

    distribution among cervical specimens from more than 1000 Danish women. We also examined the HPV type distribution and the frequency of single and multiple HPV types for specimens from 113 women who underwent conization and were diagnosed with cervical intraepithelial neoplasia grade II or worse (CIN2+). Using...... microarray technology, we found that 49% of the HPV-positive patients were infected with multiple HPV types. Among the CIN2+ diagnosed women, this frequency was 41%. The most frequently found high-risk HPV type was HPV-16, which was found in 25% of the HPV-positive cervical specimens. Among the HPV positive...... CIN2+ diagnosed women, 48% were HPV-16 positive. Women younger than 30 years of age had a higher frequency of multiple infections (61%) than women older than 30 years (39%). We conclude that cervical infection with multiple HPV types is common among women in all age groups and among women...

  11. Multiple recycling of NdFeB-type sintered magnets

    Zakotnik, M. [Department of Metallurgy and Materials, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom)], E-mail: miha.zakotnik@gmail.com; Harris, I.R.; Williams, A.J. [Department of Metallurgy and Materials, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom)

    2009-02-05

    Some fully dense, sintered NdFeB-type magnets (employed in VCM disc drives) have been subjected to a recycling process using the hydrogen decrepitation (HD) process. After a brief milling treatment, the powder was aligned, pressed and re-sintered and this procedure was repeated four times with a progressive fall in the density and in the magnetic properties. The chemical analysis indicated that this was due to the progressive oxidation of the Nd-rich material and to some Nd loss by evaporation. The procedure was then repeated but with the addition (blending) of a fine powder of neodymium hydride after the first cycle. It was found that the addition of 1 at.% of neodymium at each stage was sufficient to maintain the density and the magnetic properties of the recycled magnets up to and including the 4th cycle. Inductively coupled plasma (ICP) and metallographic analysis indicated that the neodymium hydride additions compensated for the neodymium loss due to evaporation and to oxidation so that the proportion of Nd-rich material remained approximately constant. The additional amount of Nd{sub 2}O{sub 3} in the blended recycled magnets appeared to inhibit grain growth on the 3rd and 4th cycles when compared to that of the unblended magnets. The next challenge is to see if the process can be scaled-up to an industrial scale.

  12. A Systematic Review and Meta-Analysis of Strength Training in Individuals With Multiple Sclerosis Or Parkinson Disease

    Cruickshank, Travis M.; Reyes, Alvaro R.; Ziman, Melanie R.

    2015-01-01

    Abstract Strength training has, in recent years, been shown to be beneficial for people with Parkinson disease and multiple sclerosis. Consensus regarding its utility for these disorders nevertheless remains contentious among healthcare professionals. Greater clarity is required, especially in regards to the type and magnitude of effects as well as the response differences to strength training between individuals with Parkinson disease or multiple sclerosis. This study examines the effects, magnitude of those effects, and response differences to strength training between patients with Parkinson disease or multiple sclerosis. A comprehensive search of electronic databases including Physiotherapy Evidence Database scale, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL was conducted from inception to July 2014. English articles investigating the effect of strength training for individuals with neurodegenerative disorders were selected. Strength training trials that met the inclusion criteria were found for individuals with Parkinson disease or multiple sclerosis. Individuals with Parkinson disease or multiple sclerosis were included in the study. Strength training interventions included traditional (free weights/machine exercises) and nontraditional programs (eccentric cycling). Included articles were critically appraised using the Physiotherapy Evidence Database scale. Of the 507 articles retrieved, only 20 articles met the inclusion criteria. Of these, 14 were randomized and 6 were nonrandomized controlled articles in Parkinson disease or multiple sclerosis. Six randomized and 2 nonrandomized controlled articles originated from 3 trials and were subsequently pooled for systematic analysis. Strength training was found to significantly improve muscle strength in people with Parkinson disease (15%–83.2%) and multiple sclerosis (4.5%–36%). Significant improvements in mobility (11.4%) and disease progression were also reported in people

  13. Radiographic findings in type 3 b Gaucher disease

    Hill, S.C.; Damaska, B.M.; Tsokos, M.; Kreps, C.; Brady, R.O.; Barton, N.W.

    1996-01-01

    The purpose of this paper is to describe the radiographic findings in type 3 b Gaucher disease, a chronic neuronopathic form of the illness with severe systemic manifestations. Between 1980 and 1985 17 consecutive patients were evaluated with radiography of the chest, long bones and spine, CT of the head and chest, abdominal sonography, and MRI of the head, abdomen and spine. Clinical manifestations were severe, and led to death from hepatic, pulmonary or cardiac failure in nine patients. Type 3 b Gaucher disease shares the same spectrum of radiographic findings observed in type 1 disease, but the systemic manifestations are more severe. Pulmonary infiltrates, thoracic lymph node enlargement, vertebral compression fractures and osteonecrosis of the long bones occur much more frequently in patients with type 3 b disease. (orig.). With 7 figs., 2 tabs

  14. Study of the brain glucose metabolism in different stage of mixed-type multiple system atrophy

    Wang Ying; Zhang Benshu; Cai Li; Zhang Meiyun; Gao Shuo

    2014-01-01

    Objective: To investigate the brain glucose metabolism in different stage of mixed-type multiple system atrophy (MSA). Methods: Forty-six MSA patients with cerebellar or Parkinsonian symptoms and 18 healthy controls with similar age as patients were included. According to the disease duration,the patients were divided into three groups: group 1 (≤ 12 months, n=14), group 2 (13-24 months, n=13), group 3 (≥ 25 months, n=19). All patients and controls underwent 18 F-FDG PET/CT brain imaging. To compare metabolic distributions between different groups, SPM 8 software and two-sample t test were used for image data analysis. When P<0.005, the result was considered statistically significant. Results: At the level of P<0.005, the hypometabolism in group 1 (all t>3.49) was identified in the frontal lobe, lateral temporal lobe, insula lobe, anterior cingulate cortex, caudate nucleus and anterior cerebellar hemisphere. The regions of hypometabolism extended to posterolateral putamen and part of posterior cerebellar hemisphere in group 2 (all t>3.21). In group 3, the whole parts of putamen and cerebellar hemisphere were involved as hypometabolism (all t>4.08). In addition to the hypometabolism regions, there were also stabled hypermetabolism regions mainly in the parietal lobe, medial temporal lobe and the thalamus in all patient groups (all t>3.27 in group 1, all t>3.02 in group 2,all t>3.30 in group 3). Conclusions: Disease duration is closely related to the FDG metabolism in the MSA patients. Frontal lobe, lateral temporal lobe, anterior cingulate cortex and caudate nucleus can be involved at early stage of the disease. Putaminal hypometabolism begins in its posterolateral part. Cerebellar hypometabolism occurs early at its anterior part. Besides, thalamus shows hypermetabolism in the whole duration. 18 F-FDG metabolic changes of brain can reflect the development of mixed-type MSA. (authors)

  15. OAS1: a multiple sclerosis susceptibility gene that influences disease severity.

    O'Brien, M

    2012-02-01

    BACKGROUND: Type 1 interferons upregulate oligoadenylate synthetase 1 (OAS1). A single nucleotide polymorphism (SNP) in exon 7 of OAS1 results in differential RNAseL enzyme activity, the A allele coding for a truncated form with low activity and the G conferring high activity. We hypothesized that OAS1 genotypes would influence both susceptibility to multiple sclerosis (MS) and disease activity with the AA genotype being overrepresented and the GG genotype underrepresented in relapsing-remitting MS (RRMS) with increased disease activity. METHODS: We examined OAS1 genotype distribution in 401 patients with MS, 394 healthy controls, and 178 patients with RRMS receiving interferon-beta (IFNbeta) assessed as 1) having no or minimal disease activity on IFNbeta, 2) having disease activity despite IFNbeta, and 3) 65 patients with RRMS with highly active disease. RESULTS: The OAS1 genotype distribution differed between patients with MS and controls (p = 0.000003), with lower frequency of GG homozygotes in patients with MS (6%) compared with controls (17%). In relation to disease severity, 34 (32%) patients with no or minimal disease activity on IFNbeta had the AA and 8 (8%) the GG genotype; of patients with disease activity despite IFNbeta, 27 (51%) were AA, while only 1 (2%) was GG (p = 0.03). Median time to first relapse on IFNbeta was 24 months in patients with RRMS with AA genotype and 33 months with AG or GG genotype (p = 0.04). The GG genotype was absent in 65 patients with highly active RRMS (p = 0.03). CONCLUSIONS: A functional OAS1 SNP, AA genotype, confers susceptibility to MS and the GG genotype may protect against increased disease activity.

  16. Preimplantation genetic diagnosis for a patient with multiple endocrine neoplasia type 1: case report.

    Lima, Aline Dt; Alves, Vanessa R; Rocha, Andressa R; Martinhago, Ana C; Martinhago, Ciro; Donadio, Nilka; Dzik, Artur; Cavagna, Mario; Gebrim, Luiz H

    2018-03-01

    Preimplantation genetic diagnosis was carried out for embryonic analysis in a patient with multiple endocrine neoplasia type 1 (MEN1). This is a rare autosomal-dominant cancer syndrome and the patients with MEN1 are characterized by the occurrence of tumors in multiple endocrine tissues, associated with germline and somatic inactivating mutations in the MEN1 gene. This case report documents a successful preimplantation genetic diagnosis (PGD) involving a couple at-risk for MEN1 syndrome, with a birth of a healthy infant. The couple underwent a cycle of controlled ovarian stimulation and intracytoplasmic sperm injection (ICSI). Embryos were biopsied at the blastocyst stage and cryopreserved; we used PCR-based DNA analysis for PGD testing. Only one of the five embryos analyzed for MEN1 syndrome was unaffected. This embryo was thawed and transferred following endometrial preparation. After positive βHCG test; clinical pregnancy was confirmed by ultrasound, and a healthy infant was born. PGD for single gene disorders has been an emerging therapeutic tool for couples who are at risk of passing a genetic disease on to their offspring.

  17. Increased basal glucose production in type 1 Gaucher's disease

    Corssmit, E. P.; Hollak, C. E.; Endert, E.; van Oers, M. H.; Sauerwein, H. P.; Romijn, J. A.

    1995-01-01

    To evaluate the metabolic effects of Gaucher's disease, glucose metabolism and parameters of fat metabolism were studied by indirect calorimetry and primed continuous infusion of [3-3H]glucose in seven clinically stable untreated patients with type 1 Gaucher's disease and in seven healthy matched

  18. Immune dysfunction in Niemann?Pick disease type C

    Platt, Nick; Speak, Annelise O.; Colaco, Alexandria; Gray, James; Smith, David A.; Williams, Ian M.; Wallom, Kerri?Lee; Platt, Frances M.

    2015-01-01

    Abstract Lysosomal storage diseases are inherited monogenic disorders in which lysosome function is compromised. Although individually very rare, they occur at a collective frequency of approximately one in five thousand live births and usually have catastrophic consequences for health. The lysosomal storage diseases Niemann?Pick disease type C (NPC) is caused by mutations predominantly in the lysosomal integral membrane protein NPC1 and clinically presents as a progressive neurodegenerative ...

  19. Results of early thyroidectomy for medullary thyroid carcinoma in children with multiple endocrine neoplasia type 2.

    Telander, R L; Zimmerman, D; van Heerden, J A; Sizemore, G W

    1986-12-01

    Children with multiple endocrine neoplasia type 2 (MEN2) often develop medullary carcinoma of the thyroid (MCT) or its precursor, C-cell hyperplasia. Survival results are improved if malignancy is diagnosed early from the results of plasma immunoreactive calcitonin (iCT) measurement. The effect of early detection and thyroidectomy in children with MEN2 syndrome was determined by reviewing the experience between 1975 and 1985. Seventeen children with MEN2 who were 12 years old or younger underwent a total thyroidectomy for MCT or C-cell hyperplasia. iCT was measured in all patients preoperatively and postoperatively. Of the 17 children, 14 (82%) had MEN2a and 3 (18%) had MEN2b. There were 14 (82%) female and three (18%) male patients; their mean age was 6.97 years (range 1.5 to 12 years). In all patients, the diagnosis of MCT was made from initial elevated levels of iCT after stimulation with pentagastrin. Three patients had clinical evidence of disease preoperatively. All patients underwent a total thyroidectomy and lymph nodes were removed from the central zone; a neck dissection was performed in the three with clinically obvious disease. MCT with C-cell hyperplasia was found in 11 children and C-cell hyperplasia alone in six. Of the 11 with carcinoma, eight had bilateral disease and three unilateral. Six children had bilateral C-cell hyperplasia. All 17 children were alive and feeling well at the time of this report; however, three had evidence of metastatic disease according to iCT measurements. None of the children had recurrent nerve injuries; one had evidence of hypoparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Novel multiple endocrine neoplasia type 1 variations in patients with sporadic primary hyperparathyroidism

    S Birla

    2016-01-01

    Full Text Available Background and Objectives: Primary hyperparathyroidism (PHPT can occur either as a sporadic case or in association with syndromes such as multiple endocrine neoplasia. Multiple endocrine neoplasia type 1 (MEN1 is a rare autosomal-dominant disease resulting from mutations in MEN1 gene encoding a 621 amino acid long tumor suppressor protein “menin.” We report here the results of MEN1 screening in 31 patients diagnosed with sporadic PHPT. Materials and Methods: Diagnosis of sporadic PHPT was made when blood urea and serum creatinine were normal, serum parathyroid hormone was high, and parathyroid enlargement could be localized on ultrasound and/or parathyroid scan. A total of 31 patients and 50 healthy volunteers were recruited for molecular analysis after taking informed consent. Results: Major symptoms at presentation were bone pain, fatigue, muscle weakness, and renal stones. Molecular genetic analysis revealed the presence of two novel intronic variations, c. 913-79T>A and c. 784-129T>A which by human splicing finder are predicted to cause potential alteration of splicing by either activating an intronic cryptic acceptor site or converting a conserved exonic splicing silencer sequence to an exonic splicing enhancer site. Apart from these, two reported polymorphisms rs144677807 and rs669976 were seen only in patients and none of the controls. Other reported polymorphisms rs2071313 and rs654440 were identified both in controls and patients. Conclusions: This is the first study of MEN1 gene screening in sporadic PHPT in India reporting on the clinical and genetic findings, wherein two novel intronic variations c. 913-79T>A and c. 784-129T>A were identified showing their possible role in disease causation.

  1. Very early disease manifestations of macular telangiectasia type 2

    Issa, P.C.; Heeren, T.F.C.; Kupitz, E.H.; Holz, F.G.; Berendschot, T.T.J.M.

    Background: To report very early morphologic and functional alterations in patients with macular telangiectasia type 2. Methods: Patients with asymmetric disease manifestations, in whom retinal alterations characteristic for macular telangiectasia type 2 were present in one but not in the apparently

  2. Autosomic dominant type II Osteopetrosis (Albers-Schonberg disease)

    Zambrano, Angela R; Salamanca, Juan C; Ospino, Benjamin

    2003-01-01

    The osteopetrosis type II or albers-schonberg disease is an infrequent disease secondary to the decrease in the bone resorption. The osteoclast is the principal cell involved in the disease. The osteopetrosis is characterized by few symptoms and it also has a benign course, but may further develop medullar insufficiency. We report a case of a young patient that initially shows, thrombocytopenia and bone pain with increase in the bone density, suggestive of osteopetrosis type II. The x ray exam was conclusive of osteopetrosis

  3. A probable new type of osteopenic bone disease

    Widhe, Torulf L. [Department of Orthopaedics, Huddinge University Hospital (Sweden)

    2002-06-01

    A probable new type of osteopenic bone disease in two sisters and one female cousin is described. In infancy, the radiological findings were osteopenia, coxa vara, periosteal cloaking, bowing of the long bones, and flaring of the metaphyses. During growth, spinal pathology developed with compression of the vertebral bodies and scoliosis in one girl and kyphosis in another. All three children had genu valgum and two developed severe S-shaped bowing of the tibiae. Growth was stunted. Inheritance of this disorder is probably recessive. Type I and III collagen biosynthesis was normal. This condition is probably a hitherto undescribed form of osteogenesis imperfecta type III or a new bone disease. (orig.)

  4. A probable new type of osteopenic bone disease

    Widhe, Torulf L.

    2002-01-01

    A probable new type of osteopenic bone disease in two sisters and one female cousin is described. In infancy, the radiological findings were osteopenia, coxa vara, periosteal cloaking, bowing of the long bones, and flaring of the metaphyses. During growth, spinal pathology developed with compression of the vertebral bodies and scoliosis in one girl and kyphosis in another. All three children had genu valgum and two developed severe S-shaped bowing of the tibiae. Growth was stunted. Inheritance of this disorder is probably recessive. Type I and III collagen biosynthesis was normal. This condition is probably a hitherto undescribed form of osteogenesis imperfecta type III or a new bone disease. (orig.)

  5. Healthcare resource use and costs associated with chronic kidney disease in US private insurance patients with multiple myeloma.

    Bhowmik, Debajyoti; Song, Xue; Intorcia, Michele; Kent, Shia T; Shi, Nianwen

    2018-01-01

    Objectives Within a median 1.2 years after patients have an initial diagnosis with multiple myeloma, up to 61% were diagnosed with renal impairment and 50% were diagnosed with chronic kidney disease. This study estimated economic burden associated with chronic kidney disease in multiple myeloma patients in the US. Methods In this retrospective cohort study, patients ≥18 years old with ≥1 inpatient or ≥ 2 outpatient multiple myeloma diagnoses between 1 January 2008 and 31 March 2015 were identified from MarketScan® Commercial and Medicare Supplemental Databases. Chronic kidney disease patients had ≥1 diagnosis of chronic kidney disease Stages 1-5 (first chronic kidney disease diagnosis date = index date) on or after the first multiple myeloma diagnosis, and were propensity score matched 1:1 to multiple myeloma patients without chronic kidney disease, end-stage renal disease, dialysis, or other type of chronically impaired renal function. All patients had ≥six-month continuous enrollment prior to index date and were followed for ≥one month from index date until the earliest of inpatient death, end of continuous enrollment, or end of the study period (30 September 2015). The per-patient per-year healthcare resource utilization and costs were measured during follow-up. Costs were total reimbursed amount in 2016 US dollars. Results A total of 2541 multiple myeloma patients with chronic kidney disease stages 1-5 and 2541 matched controls met the study criteria and were respectively 69.3 and 69.6 years, 54.5% and 55.3% men, and had 572.2 and 533.4 mean days of follow up. Compared to controls, chronic kidney disease patients had significantly (all P chronic kidney disease, end-stage renal disease, or dialysis had $78,455 ( P chronic kidney disease in patients with multiple myeloma was estimated to be between $34,754 and $78,455 per-patient per-year. Given its substantial clinical and economic impact, preservation of renal function is important in

  6. Multiple solid pilocytic astrocytomas in cerebleiium with neurofibromatosis type: A case report

    Choi, Seo Young; Kim, Myung Soon; Kim, Young Ju

    2014-01-01

    Pilocytic astrocytoma usually has a classic imaging manifestation of a solitary, cyst-like mass with a strong contrast-enhancing mural nodule. There is only one published report so far of multiple solid and cyst type pilocytic astrocytomas in the cerebellum in neurofibromatosis type 1 (NF1) patient from the United States in 2007. We report a case of pilocytic astrocytoma presenting with only solid, multiple pilocytic astrocytomas in the cerebellum in NF1 patient.

  7. Role of thalamic diffusion for disease differentiation between multiple sclerosis and ischemic cerebral small vessel disease

    Oeztoprak, Bilge; Oeztoprak, Ibrahim; Salk, Ismail; Topalkara, Kamil; Erkoc, Mustafa F.

    2015-01-01

    Cerebral small vessel disease (CSVD) and multiple sclerosis (MS) both harbor multiple, T2-hyperintense white matter lesions on conventional magnetic resonance imaging (MRI).We aimed to determine the microstructural changes via diffusion-weighted imaging (DWI) in normal appearing thalami. We hypothesized that the apparent diffusion coefficient (ADC) values would be different in CSVD and MS, since the extent of arterial involvement is different in these two diseases. DWI was performed for 50 patients with CSVD and 35 patients with MS along with gender- and age-matched controls whose conventional MRI revealed normal findings. DWI was done with 1.5 Tesla MR devices using echo planar imaging (EPI) for b = 0, 1000 s/mm 2 . ADC values were obtained from the thalami which appeared normal on T2-weighted and FLAIR images. Standard oval regions of interest (ROIs) of 0.5 cm 2 which were oriented parallel to the long axis of the thalamus were used for this purpose. The mean ADC value of the thalamus was (0.99 ± 0.16) x 10 -3 mm 2 /s in patients with CSVD, whereas the mean ADC value was (0.78 ± 0.06) x 10 -3 mm 2 /s in the control group. The mean ADC value was significantly higher in patients with CSVD compared to the controls (p < 0.001). The mean ADC values of the thalamus were (0.78 ± 0.08) x 10 -3 mm 2 /s in MS patients, and (0.75 ± 0.08) x 10 -3 mm 2 /s in the control group, which are not significantly different (p > 0.05). Our study revealed a difference in the diffusion of the thalami between CSVD and MS. DWI may aid in the radiological disease differentiation. (orig.)

  8. Role of thalamic diffusion for disease differentiation between multiple sclerosis and ischemic cerebral small vessel disease

    Oeztoprak, Bilge; Oeztoprak, Ibrahim; Salk, Ismail [Cumhuriyet University School of Medicine, Department of Radiology, Sivas (Turkey); Topalkara, Kamil [Bayindir Hospital, Department of Neurology, Ankara (Turkey); Erkoc, Mustafa F. [Bozok University School of Medicine, Department of Radiology, Yozgat (Turkey)

    2015-04-01

    Cerebral small vessel disease (CSVD) and multiple sclerosis (MS) both harbor multiple, T2-hyperintense white matter lesions on conventional magnetic resonance imaging (MRI).We aimed to determine the microstructural changes via diffusion-weighted imaging (DWI) in normal appearing thalami. We hypothesized that the apparent diffusion coefficient (ADC) values would be different in CSVD and MS, since the extent of arterial involvement is different in these two diseases. DWI was performed for 50 patients with CSVD and 35 patients with MS along with gender- and age-matched controls whose conventional MRI revealed normal findings. DWI was done with 1.5 Tesla MR devices using echo planar imaging (EPI) for b = 0, 1000 s/mm{sup 2}. ADC values were obtained from the thalami which appeared normal on T2-weighted and FLAIR images. Standard oval regions of interest (ROIs) of 0.5 cm{sup 2} which were oriented parallel to the long axis of the thalamus were used for this purpose. The mean ADC value of the thalamus was (0.99 ± 0.16) x 10{sup -3} mm{sup 2}/s in patients with CSVD, whereas the mean ADC value was (0.78 ± 0.06) x 10{sup -3} mm{sup 2}/s in the control group. The mean ADC value was significantly higher in patients with CSVD compared to the controls (p < 0.001). The mean ADC values of the thalamus were (0.78 ± 0.08) x 10{sup -3} mm{sup 2}/s in MS patients, and (0.75 ± 0.08) x 10{sup -3} mm{sup 2}/s in the control group, which are not significantly different (p > 0.05). Our study revealed a difference in the diffusion of the thalami between CSVD and MS. DWI may aid in the radiological disease differentiation. (orig.)

  9. Breeding of Yangfumai No.5 with multiple disease resistance

    He Zhentian; Chen Xiulan; Zhang Rong; Wang Jianhua; Wang Jinrong

    2013-01-01

    To control the damage of wheat yellow mosaic disease and powdery mildew, new wheat cultivar with high-yield, disease-resistant was bred. Yangfumai 9311 with yellow mosaic disease resistant was used as donor parent to backcross with recurrent parent Yangmai 11, and combined with conventional breeding techniques and irradiation methods, a new wheat variety Yangfumai No.5 was developed and registered in 2011. Yangfumai No.5 with resistance of yellow mosaic disease and powdery mildew is suitable to grow in the Yangtze River region. (authors)

  10. Radiological surveillance in multiple endocrine neoplasia type 1: a double-edged sword?

    Ruth Therese Casey

    2017-03-01

    Full Text Available Context: Multiple endocrine neoplasia type 1 (MEN1 is a hereditary condition characterised by the predisposition to hyperplasia/tumours of endocrine glands. MEN1-related disease, moreover, malignancy related to MEN1, is increasingly responsible for death in up to two-thirds of patients. Although patients undergo radiological and biochemical surveillance, current recommendations for radiological monitoring are based on non-prospective data with little consensus or evidence demonstrating improved outcome from this approach. Here, we sought to determine whether cumulative radiation exposure as part of the recommended radiological screening programme posed a distinct risk in a cohort of patients with MEN1.Patients and study design: A retrospective review of 43 patients with MEN1 attending our institution between 2007 and 2015 was performed. Demographic and clinical information including phenotype was obtained for all patients. We also obtained details regarding all radiological procedures performed as part of MEN1 surveillance or disease localisation. An estimated effective radiation dose (ED for each individual patient was calculated.Results: The mean ED for the total patient cohort was 121 mSv, and the estimated mean lifetime risk of cancer secondary to radiation exposure was 0.49%. Patients with malignant neuroendocrine tumours (NETS had significantly higher ED levels compared to patients without metastatic disease (P < 0.0022.Conclusions: In MEN1, radiological surveillance is associated with clinically significant exposure to ionising radiation. In patients with MEN1, multi-modality imaging strategies designed to minimise this exposure should be considered.

  11. Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies

    George, Michaela F; Briggs, Farren B S; Shao, Xiaorong

    2016-01-01

    associated with disease severity after accounting for cohort, sex, age at onset, and HLA-DRB1*15:01. After restricting analyses to cases with disease duration ≥10 years, associations were null (p value ≥0.05). No SNP was associated with disease severity after adjusting for multiple testing. CONCLUSIONS......OBJECTIVE: We investigated the association between 52 risk variants identified through genome-wide association studies and disease severity in multiple sclerosis (MS). METHODS: Ten unique MS case data sets were analyzed. The Multiple Sclerosis Severity Score (MSSS) was calculated using the Expanded...

  12. Ion torrent personal genome machine sequencing for genomic typing of Neisseria meningitidis for rapid determination of multiple layers of typing information.

    Vogel, Ulrich; Szczepanowski, Rafael; Claus, Heike; Jünemann, Sebastian; Prior, Karola; Harmsen, Dag

    2012-06-01

    Neisseria meningitidis causes invasive meningococcal disease in infants, toddlers, and adolescents worldwide. DNA sequence-based typing, including multilocus sequence typing, analysis of genetic determinants of antibiotic resistance, and sequence typing of vaccine antigens, has become the standard for molecular epidemiology of the organism. However, PCR of multiple targets and consecutive Sanger sequencing provide logistic constraints to reference laboratories. Taking advantage of the recent development of benchtop next-generation sequencers (NGSs) and of BIGSdb, a database accommodating and analyzing genome sequence data, we therefore explored the feasibility and accuracy of Ion Torrent Personal Genome Machine (PGM) sequencing for genomic typing of meningococci. Three strains from a previous meningococcus serogroup B community outbreak were selected to compare conventional typing results with data generated by semiconductor chip-based sequencing. In addition, sequencing of the meningococcal type strain MC58 provided information about the general performance of the technology. The PGM technology generated sequence information for all target genes addressed. The results were 100% concordant with conventional typing results, with no further editing being necessary. In addition, the amount of typing information, i.e., nucleotides and target genes analyzed, could be substantially increased by the combined use of genome sequencing and BIGSdb compared to conventional methods. In the near future, affordable and fast benchtop NGS machines like the PGM might enable reference laboratories to switch to genomic typing on a routine basis. This will reduce workloads and rapidly provide information for laboratory surveillance, outbreak investigation, assessment of vaccine preventability, and antibiotic resistance gene monitoring.

  13. Perspectives and experiences of Dutch multiple sclerosis patients and multiple sclerosis-specialized neurologists on injectable disease-modifying treatment

    Visser, Leo H.; Heerings, Marco A.; Jongen, Peter J.; van der Hiele, Karin

    2016-01-01

    Background: The adherence to treatment with injectable disease-modifying drugs (DMDs) in multiple sclerosis (MS) may benefit from adequate information provision and management of expectations. The communication between patients and physicians is very important in this respect. The current study

  14. Design optimization of offshore wind farms with multiple types of wind turbines

    Feng, Ju; Shen, Wen Zhong

    2017-01-01

    Most studies on offshore wind farm design assume a uniform wind farm, which consists of an identical type of wind turbines. In order to further reduce the cost of energy, we investigate the design of non-uniform offshore wind farms, i.e., wind farms with multiple types of wind turbines and hub-he...

  15. Comorbidity between chronic obstructive pulmonary disease and type 2 diabetes

    Meteran, Howraman; Backer, Vibeke; Kyvik, Kirsten Ohm

    2015-01-01

    BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and is associated with several systemic diseases, such as type 2 diabetes. It has been suggested that comorbidity between COPD and type 2 diabetes is due to shared genetic factors. AIM: To examine...... the relationship between type 2 diabetes and chronic bronchitis and COPD in adult twins, and to examine to what extent comorbidity between these diseases is explained by shared genetic or environmental factors. METHODS: Questionnaire data on chronic bronchitis and hospital discharge data on diagnosed COPD in 13.......5 vs. 2.3%), OR = 1.57 (1.10-2.26), p = 0.014, and in individuals with diagnosed COPD than in those without the diagnosis (6.6 vs. 2.3%), OR = 2.62 (1.63-4.2), p chronic...

  16. Role of Type 2 Innate Lymphoid Cells in Allergic Diseases.

    Cosmi, Lorenzo; Liotta, Francesco; Maggi, Laura; Annunziato, Francesco

    2017-09-11

    The adaptive immune response orchestrated by type 2 T helper (Th2) lymphocytes, strictly cooperates with the innate response of group 2 innate lymphoid cells (ILC2), in the protection from helminths infection, as well as in the pathogenesis of allergic disease. The aim of this review is to explore the pathogenic role of ILC2 in different type 2-mediated disorders. Recent studies have shown that epithelial cell-derived cytokines and their responding cells, ILC2, play a pathogenic role in bronchial asthma, chronic rhinosinusitis, and atopic dermatitis. The growing evidences of the contribution of ILC2 in the induction and maintenance of allergic inflammation in such disease suggest the possibility to target them in therapy. Biological therapies blocking ILC2 activation or neutralizing their effector cytokines are currently under evaluation to be used in patients with type 2-dominated diseases.

  17. Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease

    Shroff, Geeta

    2016-01-01

    Case series Patient: Male, 42 ? Female, 30 Final Diagnosis: Human embryonic stem cells showed good therapeutic potential for treatment of multiple sclerosis with lyme disease Symptoms: Fatigue ? weakness in limbs Medication: ? Clinical Procedure: Human embryonic stem cells transplantation Specialty: Transplantology Objective: Rare disease Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause dela...

  18. Basal Cell Carcinoma in Type 2 Segmental Dariers Disease

    Robertson, L.; Sauder, M. B.

    2012-01-01

    Dariers disease (DD), also known as Keratosis Follicularis or Dariers-White disease, is a rare disorder of keratinisation. DD can present as a generalized autosomal dominant condition as well as a localized or segmental post zygotic condition (Vasquez et al., 2002). Clinical features of DD include greasy, warty papules and plaques on seborrhoeic areas, dystrophic nails, palmo-plantar pits, and papules on the dorsum of the hands and feet. Objective. We report a case of basal cell carcinoma developing in a patient with type 2 segmental DD. Conclusion. According to the current literature, Type 2 segmental disease is a rare presentation of Dariers disease with only 8 previous cases reported to date. In addition, non melanoma skin cancer (NMSC) arising from DD is rarely reported; however, there may be an association between DD and risk of carcinogenesis.

  19. Basal Cell Carcinoma in Type 2 Segmental Darier's Disease

    Lynne Robertson

    2012-01-01

    Full Text Available Background. Darier's disease (DD, also known as Keratosis Follicularis or Darier-White disease, is a rare disorder of keratinization. DD can present as a generalized autosomal dominant condition as well as a localized or segmental postzygotic condition (Vázquez et al., 2002. Clinical features of DD include greasy, warty papules and plaques on seborrheic areas, dystrophic nails, palmo-plantar pits, and papules on the dorsum of the hands and feet. Objective. We report a case of basal cell carcinoma developing in a patient with type 2 segmental DD. Conclusion. According to the current literature, Type 2 segmental disease is a rare presentation of Darier's disease with only 8 previous cases reported to date. In addition, nonmelanoma skin cancer (NMSC arising from DD is rarely reported; however, there may be an association between DD and risk of carcinogenesis.

  20. Multiple Locus Variable-Number Tandem-Repeat and Single-Nucleotide Polymorphism-Based Brucella Typing Reveals Multiple Lineages in Brucella melitensis Currently Endemic in China

    Mingjun Sun

    2017-12-01

    Full Text Available Brucellosis is a worldwide zoonotic disease caused by Brucella spp. In China, brucellosis is recognized as a reemerging disease mainly caused by Brucella melitensis specie. To better understand the currently endemic B. melitensis strains in China, three Brucella genotyping methods were applied to 110 B. melitensis strains obtained in past several years. By MLVA genotyping, five MLVA-8 genotypes were identified, among which genotypes 42 (1-5-3-13-2-2-3-2 was recognized as the predominant genotype, while genotype 63 (1-5-3-13-2-3-3-2 and a novel genotype of 1-5-3-13-2-4-3-2 were second frequently observed. MLVA-16 discerned a total of 57 MLVA-16 genotypes among these Brucella strains, with 41 genotypes being firstly detected and the other 16 genotypes being previously reported. By BruMLSA21 typing, six sequence types (STs were identified, among them ST8 is the most frequently seen in China while the other five STs were firstly detected and designated as ST137, ST138, ST139, ST140, and ST141 by international multilocus sequence typing database. Whole-genome sequence (WGS-single-nucleotide polymorphism (SNP-based typing and phylogenetic analysis resolved Chinese B. melitensis strains into five clusters, reflecting the existence of multiple lineages among these Chinese B. melitensis strains. In phylogeny, Chinese lineages are more closely related to strains collected from East Mediterranean and Middle East countries, such as Turkey, Kuwait, and Iraq. In the next few years, MLVA typing will certainly remain an important epidemiological tool for Brucella infection analysis, as it displays a high discriminatory ability and achieves result largely in agreement with WGS-SNP-based typing. However, WGS-SNP-based typing is found to be the most powerful and reliable method in discerning Brucella strains and will be popular used in the future.

  1. Beyond PrPres type 1/Type 2 dichotomy in Creutzfeldt-Jakob disease

    Uro-Coste, E.; Cassard, H.; Simon, S.; Lugan, S.; Bilheude, J.M.; Perret-Liaudet, A.; Ironside, J.E.; Haik, S.; Basset-Leobon, C.; Lacroux, C.; Peoch, K.; Streichenberger, N.; Langeveld, J.P.M.; Head, M.W.; Grassi, J.; Hauw, J.J.; Schelcher, F.; Delisle, M.B.; Andreoletti, O.

    2008-01-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrPres) identified on Western blotting (type 1 or type 2). These biochemically distinct

  2. Epstein-Barr virus and disease activity in multiple sclerosis

    D. Buljevac (Dragan); H.Z. Flach (Zwenneke); J. Groen (Jan); P.A. van Doorn (Pieter); F.G.A. van der Meché (Frans); R.Q. Hintzen (Rogier); W.C.J. Hop (Wim); A.D.M.E. Osterhaus (Albert); G.J.J. van Doornum (Gerard)

    2005-01-01

    textabstractOBJECTIVES: To study in relapsing-remitting (RR) multiple sclerosis (MS) whether exacerbations and brain activity as measured by magnetic resonance imaging (MRI) are associated with plasma levels of anti-Epstein Barr (EBV) antibodies and EBV DNA. METHODS: This was a prospective study

  3. Infantile Refsum's disease: biochemical findings suggesting multiple peroxisomal dysfunction

    Poll-The, B. T.; Saudubray, J. M.; Ogier, H.; Schutgens, R. B.; Wanders, R. J.; Schrakamp, G.; van den Bosch, H.; Trijbels, J. M.; Poulos, A.; Moser, H. W.

    1986-01-01

    Infantile Refsum's disease was diagnosed in three male patients, presenting with facial dysmorphia, retinitis pigmentosa, neurosensory hearing loss, hepatomegaly, osteopenia and delayed growth and psychomotor development. An elevated plasma phytanic acid concentration and a deficient phytanic acid

  4. Gallstone disease and type-2 diabetes mellitus-the link

    Olokoba, A.B.; Bojuwoye, B.J.; Olokoba, K.B.; Braimoh, K.T.; Inikori, A.K.

    2007-01-01

    To determine the factors predisposing patients with type-2 diabetes mellitus to gallstone disease. One hundred type 2 diabetic patients and 100 age and gender-matched controls underwent real time ultrasonography to study factors predisposing patients with type 2 diabetes mellitus to gallstone disease. The age, gender, body mass index (BMI), duration of diabetes mellitus and serum lipids were determined in the individuals enrolled for the study. Fifteen percent of the diabetic patients had ultrasound evidence of gallstone disease as compared to 7% in non-diabetic controls. There was a steady increase in the incidence of gallstone disease in diabetic patients with age with a peak incidence in the seventh decade i.e. 60-69 years, and a decline in the eighth decade i.e. 70 - 79 years. The average age of the diabetic patients with gallstone disease - 59.1+ 9.5 years was significantly higher than in those without gallstone disease - 51.8 + 10.5 years (p 0.014). The mean duration of disease in the diabetic patients with gallstone disease was 5.0 + 4.9 years compared with 4.5 + 3.8 years in the diabetic patients without gallstone disease (p=0.772). The mean serum cholesterol and triglyceride levels - 4.3 + 1.3 mmol/L and 1.5 + 0.8 mmol/L respectively in the diabetic patients with gallstone disease was higher than in those without gallstone disease - 3.4 + 0.5 mmol/L (p=0.0941) and 1.4 + 0.7 mmol/L (p=0.712) respectively. The mean body mass index for the diabetic patients with gallstone disease was 26.2 + 5.5 kg /m 2 compared with 25.7 + 6.7 kg/m2 in those without gallstone disease (p=0.755) . Increasing age is a risk factor for gallstone disease in diabetic patients. Hyperlipidaemia, female gender, heavier weight and a longer duration of diabetes mellitus appear to be associated risk factors. (author)

  5. Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib : Results of the European Study on Glycogen Storage Disease Type I

    Visser, G; Rake, JP; Fernandes, J; Labrune, P; Leonard, JV; Moses, S; Ullrich, K; Smit, GPA

    Objective: To investigate the incidence, the severity, and the course of neutropenia, neutrophil dysfunction, and inflammatory bowel disease (IBD) in glycogen storage disease (GSD) type Ib. Method: As part of a collaborative European Study on GSD type I, a retrospective registry was established in

  6. An architecture model for multiple disease management information systems.

    Chen, Lichin; Yu, Hui-Chu; Li, Hao-Chun; Wang, Yi-Van; Chen, Huang-Jen; Wang, I-Ching; Wang, Chiou-Shiang; Peng, Hui-Yu; Hsu, Yu-Ling; Chen, Chi-Huang; Chuang, Lee-Ming; Lee, Hung-Chang; Chung, Yufang; Lai, Feipei

    2013-04-01

    Disease management is a program which attempts to overcome the fragmentation of healthcare system and improve the quality of care. Many studies have proven the effectiveness of disease management. However, the case managers were spending the majority of time in documentation, coordinating the members of the care team. They need a tool to support them with daily practice and optimizing the inefficient workflow. Several discussions have indicated that information technology plays an important role in the era of disease management. Whereas applications have been developed, it is inefficient to develop information system for each disease management program individually. The aim of this research is to support the work of disease management, reform the inefficient workflow, and propose an architecture model that enhance on the reusability and time saving of information system development. The proposed architecture model had been successfully implemented into two disease management information system, and the result was evaluated through reusability analysis, time consumed analysis, pre- and post-implement workflow analysis, and user questionnaire survey. The reusability of the proposed model was high, less than half of the time was consumed, and the workflow had been improved. The overall user aspect is positive. The supportiveness during daily workflow is high. The system empowers the case managers with better information and leads to better decision making.

  7. [Cardiovascular disease in patients with type 1 and type 2 diabetes in Spain].

    Ortega, Emilio; Amor, Antonio J; Rojo-Martínez, Gemma; Castell, Conxa; Giménez, Marga; Conget, Ignacio

    2015-09-21

    To describe the prevalence of cardiovascular disease (CVD) in type 1 diabetes (T1DM) and to compare it with that observed in type 2 diabetes (T2DM) and normal population in Spain. Cross-sectional study (18-70 years-old). Information on CVD was available from a nurse-administered questionnaire (Di@bet.es Study, NORMAL=3,430, T2DM=312) and from a physician reporting form (T1DM=1,382). Differences in the crude and adjusted prevalence of coronary heart (CHD), cerebrovascular (CNSD), peripheral vascular (PVD) and overall CV (CVD) disease were investigated between T1DM vs. NORMAL, and T1DM vs. T2DM groups. We found differences in age, body mass index, proportion of women, dyslipemia and antihypertensive medication between T1DM vs. NORMAL and T1DM vs. T2DM (all P<.001). Smoking prevalence was not different between T1DM vs. T2DM and it was lower in T1DM compared to NORMAL (P<.0001). The percentage of CHD, CNSD, PVD, and overall CVD in T1DM vs. NORMAL was 3.0 vs. 2.5 (P=.31), 0.70 vs. 1.10 (P=.22), 2.61 vs. 0.20 (P<.0001), and 5.1 vs. 3.44 (P<.01), respectively. The prevalence in T2DM (vs. T1DM) was 11.3 (P<.0001), 3.5 (P<.0001), 4.2 (P=.13), and 17% (P<.0001), respectively. Multiple logistic regression adjusted models showed a higher prevalence of CHD (odds ratio [OR] 2.27, 95% confidence interval [95% CI] 1.41-3.67), PVD (OR 15.35, 95% CI 5.61-42.04), and overall CVD (OR 2.32, 95% CI 1.55-3.46), but not for CNSD (OR 0.49, 95% CI 0.19-1.27) in T1DM compared to NORMAL. No differences were found between T1DM and T2DM. We found a higher prevalence of CVD in a Mediterranean population of T1DM individuals compared with non-diabetic subjects. This prevalence was similar to that observed in T2DM. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  8. Bowen's Disease Associated With Two Human Papilloma Virus Types.

    Eftekhari, Hojat; Gharaei Nejad, Kaveh; Azimi, Seyyede Zeinab; Rafiei, Rana; Mesbah, Alireza

    2017-09-01

    Bowen's disease (BD) is an epidermal in-situ squamous cell carcinoma (SCC). Most Human Papilloma Viruses (HPV)-positive lesions in Bowen's disease are localized to the genital region or distal extremities (periungual sites) in which HPV type-16 is frequently detected. Patient was a 64-year-old construction worker for whom we detected 2 erythematous psoriasiform reticular scaly plaques on peri-umbilical and medial knee. Biopsy established the diagnosis of Bowen's disease and polymerase chain reaction assay showed HPV-6, -18 co-infection. Patient was referred for surgical excision.

  9. [Multicentric hyaline vascular Castleman's disease. A POEMS type variant].

    Gracia-Ramos, Abraham Edgar; Cruz-Domínguez, María del Pilar; Vera-Lastra, Olga Lidia

    2013-01-01

    Castleman's disease is an atypical lymphoproliferative disorder which may be compatible with paraneoplastic manifestations of POEMS syndrome. a 53 year old man with a history of type 2 diabetes, hypothyroidism and Addison's disease presented with numbness and weakness in limbs, dyspnea, skin hardening, Raynaud's phenomenon, weight loss and fatigue. A physical exam showed tachypnea, generalized cutaneous hyperpigmentation and skin hardening of extremities, muscle weakness, hypoesthesia and hyporeflexia. Laboratory showed hyperprolactinemia, low testosterone, hypothyroidism and Addison's disease. Electrophoresis of proteins showed polyclonal hypergammaglobulinemia. Somatosensory evoked potentials reported peripheral neuropathy and severe axonal polyneuropathy by electromyography. Chest X-rays showed bilateral reticular infiltrates and mediastinal widening. An echocardiogram displayed moderate pulmonary hypertension. Skin biopsy had no evidence of scleroderma. CT reported axillar, mediastinal and retroperitoneal nodes. The mediastinal lesion biopsy reported hyaline vascular Castleman's disease, multicentric variety. He was treated with rituximab. the case meet criteria for multicentric hyaline vascular Castleman's disease, POEMS variant, treated with rituximab.

  10. Findings of Optical Coherence Tomography of Retinal Nerve Fiber Layer in Two Common Types of Multiple Sclerosis

    Gholamali Yousefipour

    2016-06-01

    Full Text Available Multiple sclerosis (MS is the most prevalent disease caused by the inflammatory demyelinating process that causes progressive nervous system degeneration over the time. Optical Coherence Tomography (OCT is a non-invasive optical imaging technology, which can measure the thickness of retinal nerve fiber layer as well as the diameter of the macula. The purpose of the study is evaluation OCT findings in two common types of multiple sclerosis. For doing the cross-sectional study, 63 patients with two prevalent types of multiple sclerosis (35 patients with Relapse Remitting Multiple Sclerosis (RRMS and 28 patients with Secondary Progressive Multiple Sclerosis (SPMS were evaluated for 6 months. Exclusion criteria of the study were a history of optic neuritis, suffering from diabetes mellitus, hypertension, ocular disease, and the presence of other neurologic degenerative diseases. Then, the thickness of retinal nerve fiber layer (RNFL, as well as thickness and volume of the macula, were measured in the patients using OCT technology. The disability rate of patients was evaluated according to Expanded Disability Status Scale (EDSS. Finally, data was analyzed by means of SPSS software. Overall, 35 patients with RRMS (with mean age of 32.37+10.01, average disease period of 3.81+3.42 and mean EDSS of 1.84+0.45 and 28 patients with SPMS (with mean age of 39.21+9.33, average disease period of 11.32+5.87 and mean EDSS of 5.12+1.46 were assessed and compared in terms of retinal nerve fiber layer and size and thickness of macula. In all of these sections, the thicknesses were smaller in SPMS patients than patients with RRMS. But, there was a significant difference in total thickness (81.82µm versus 96.03µm with P=0.04 and thickness of temporal sector (54.5 µm versus 69.34 µm with P=0.04 of retinal nerve fiber layer and macular size at the superior sector of external ring (1.48 mm³ versus 1.58 mm³ with P=0.03, and nasal sector of external ring surrounding

  11. Exercise and disease progression in multiple sclerosis: can exercise slow down the progression of multiple sclerosis?

    Dalgas, Ulrik; Stenager, Egon

    2012-01-01

    studies evaluating the effects on clinical outcome measures, (2) cross-sectional studies evaluating the relationship between fitness status and MRI findings, (3) cross-sectional and longitudinal studies evaluating the relationship between exercise/physical activity and disability/relapse rate and, finally......, (4) longitudinal exercise studies applying the experimental autoimmune encephalomyelitis (EAE) animal model of MS. Data from intervention studies evaluating disease progression by clinical measures (1) do not support a disease-modifying effect of exercise; however, MRI data (2), patient-reported data...... (3) and data from the EAE model (4) indicate a possible disease-modifying effect of exercise, but the strength of the evidence limits definite conclusions. It was concluded that some evidence supports the possibility of a disease-modifying potential of exercise (or physical activity) in MS patients...

  12. Multiple endocrine diseases in cats: 15 cases (1997-2008).

    Blois, Shauna L; Dickie, Erica L; Kruth, Stephen A; Allen, Dana G

    2010-08-01

    The objective of this retrospective study was to characterize a population of cats from a tertiary care center diagnosed with multiple endocrine disorders, including the specific disorders and time intervals between diagnosis of each disorder. Medical records of 15 cats diagnosed with more than one endocrine disorder were reviewed. The majority of cats were domestic shorthairs, and the mean age at the time of diagnosis of the first disorder was 10.3 years. The most common combination of disorders was diabetes mellitus and hyperthyroidism. Two cats had concurrent diabetes mellitus and hyperadrenocorticism, one cat had concurrent central diabetes insipidus and diabetes mellitus. A mean of 25.7 months elapsed between diagnoses of the first and second endocrine disorder, but this was variable. This study suggests the occurrence of multiple endocrine disorders is uncommon in cats. Copyright 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

  13. Edaravone alleviates Alzheimer's disease-type pathologies and cognitive deficits.

    Jiao, Shu-Sheng; Yao, Xiu-Qing; Liu, Yu-Hui; Wang, Qing-Hua; Zeng, Fan; Lu, Jian-Jun; Liu, Jia; Zhu, Chi; Shen, Lin-Lin; Liu, Cheng-Hui; Wang, Ye-Ran; Zeng, Gui-Hua; Parikh, Ankit; Chen, Jia; Liang, Chun-Rong; Xiang, Yang; Bu, Xian-Le; Deng, Juan; Li, Jing; Xu, Juan; Zeng, Yue-Qin; Xu, Xiang; Xu, Hai-Wei; Zhong, Jin-Hua; Zhou, Hua-Dong; Zhou, Xin-Fu; Wang, Yan-Jiang

    2015-04-21

    Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.

  14. Autoimmune disease prevalence in a multiple sclerosis cohort in Argentina.

    Farez, Mauricio F; Balbuena Aguirre, María E; Varela, Francisco; Köhler, Alejandro A; Correale, Jorge

    2014-01-01

    Background. Comorbid autoimmune diseases in MS patients have been studied extensively with controversial results. Moreover, no such data exists for Latin-American MS patients. Methods. We conducted a case-control study aimed to establish the prevalence of autoimmune disorders in a cohort of Argentinean MS patients. Results. There were no significant differences in autoimmune disease prevalence in MS patients with respect to controls. The presence of one or more autoimmune disorders did not increase risk of MS (OR 0.85, 95% CI 0.6-1.3). Discussion. Our results indicate absence of increased comorbid autoimmune disease prevalence in MS patients, as well as of increased risk of MS in patients suffering from other autoimmune disorders.

  15. Multiple sclerosis care: an integrated disease-management model.

    Burks, J

    1998-04-01

    A disease-management model must be integrated, comprehensive, individual patient focused and outcome driven. In addition to high quality care, the successful model must reduce variations in care and costs. MS specialists need to be intimately involved in the long-term care of MS patients, while not neglecting primary care issues. A nurse care manager is the "glue" between the managed care company, health care providers and the patient/family. Disease management focuses on education and prevention, and can be cost effective as well as patient specific. To implement a successful program, managed care companies and health care providers must work together.

  16. Charcot-Marie-Tooth disease complicating type 2 diabetes.

    Win, Htet Htet Ne

    2012-02-01

    Although both conditions are relatively common, there are very few descriptions of type 2 diabetes mellitus coexisting with Charcot-Marie-Tooth disease (CMT). This case report and literature review describes a 53-year-old Irish man who presented with type 2 diabetes and significant neuropathy, and who was subsequently diagnosed with CMT type 1A. This case report will also discuss how to differentiate diabetic neuropathy from a progressive hereditary neuropathy and how coexistence aggravates the progression of neuropathy thus necessitating early diagnosis.

  17. Charcot-marie-tooth disease complicating type 2 diabetes.

    Win, Htet Htet Ne

    2011-07-01

    Although both conditions are relatively common, there are very few descriptions of type 2 diabetes mellitus coexisting with Charcot-Marie-Tooth disease (CMT). This case report and literature review describes a 53-year-old Irish man who presented with type 2 diabetes and significant neuropathy, and who was subsequently diagnosed with CMT type 1A. This case report will also discuss how to differentiate diabetic neuropathy from a progressive hereditary neuropathy and how coexistence aggravates the progression of neuropathy thus necessitating early diagnosis.

  18. Autologous Graft versus Host Disease: An Emerging Complication in Patients with Multiple Myeloma

    Anu Batra

    2014-01-01

    Full Text Available Autologous graft versus host disease (autoGVHD is a rare transplant complication with significant morbidity and mortality. It has been hypothesized that patients with multiple myeloma might be predisposed to autoGVHD through dysregulation of the immune response resulting from either their disease, the immunomodulatory agents (IMiDs used to treat it, or transplant conditioning regimen. Hematopoietic progenitor cell (HPC products were available from 8 multiple myeloma patients with biopsy-proven autoGVHD, 16 matched multiple myeloma patients who did not develop autoGVHD, and 7 healthy research donors. The data on number of transplants prior to developing autoGVHD, mobilization regimens, exposure to proteasome inhibitors, use of IMiDs, and class I human leukocyte antigen types (HLA A and B were collected. The HPC products were analyzed by flow cytometry for expression of CD3, CD4, CD8, CD25, CD56, and FoxP3. CD3+ cell number was significantly lower in autoGVHD patients compared to unaffected controls (P=0.047. On subset analysis of CD3+ cells, CD8+ cells (but not CD4+ cells were found to be significantly lower in patients with autoGVHD (P=0.038. HLA-B55 expression was significantly associated with development of autoGVHD (P=0.032. Lower percentages of CD3+ and CD8+ T-cells and HLA-B55 expression may be predisposing factors for developing autoGVHD in myeloma.

  19. The saccadic and neurological deficits in type 3 Gaucher disease.

    William Benko

    Full Text Available Our objective was to characterize the saccadic eye movements in patients with type 3 Gaucher disease (chronic neuronopathic in relationship to neurological and neurophysiological abnormalities. For approximately 4 years, we prospectively followed a cohort of 15 patients with Gaucher type 3, ages 8-28 years, by measuring saccadic eye movements using the scleral search coil method. We found that patients with type 3 Gaucher disease had a significantly higher regression slope of duration vs amplitude and peak duration vs amplitude compared to healthy controls for both horizontal and vertical saccades. Saccadic latency was significantly increased for horizontal saccades only. Downward saccades were more affected than upward saccades. Saccade abnormalities increased over time in some patients reflecting the slowly progressive nature of the disease. Phase plane plots showed individually characteristic patterns of abnormal saccade trajectories. Oculo-manual dexterity scores on the Purdue Pegboard test were low in virtually all patients, even in those with normal cognitive function. Vertical saccade peak duration vs amplitude slope significantly correlated with IQ and with the performance on the Purdue Pegboard but not with the brainstem and somatosensory evoked potentials. We conclude that, in patients with Gaucher disease type 3, saccadic eye movements and oculo-manual dexterity are representative neurological functions for longitudinal studies and can probably be used as endpoints for therapeutic clinical trials.ClinicalTrials.gov NCT00001289.

  20. Type 1 diabetes mellitus and atopic diseases in children.

    Ehab

    Nancy S. Elbarbary. Assistant Professor of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Background. Diabetes mellitus type 1 (T1DM) is a complex disease resulting from the interplay of genetic, epigenetic, and environmental factors.1 Worldwide,. T1DM epidemic represents an increasing global.

  1. Acute type II cryoglobulinaemic vasculitis mimicking atherosclerotic peripheral vascular disease.

    Saeed, A

    2012-01-31

    Atherosclerotic peripheral vascular disease is a common presenting cause for digital ischaemia in life long smokers. Acute severe Type II Cryoglobulinaemic vasculitis is a rare yet important cause, which may present with similar clinical features and which if undiagnosed may be rapidly fatal. Following the instigation of therapy with intravenous methylprednisolone and cyclophosphamide this patient made an excellent recovery.

  2. Charcot-Marie-Tooth disease type 1A

    Hertz, Jens Michael; Børglum, A D; Brandt, C A

    1994-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant peripheral neuropathy associated with a DNA duplication on chromosome 17p11.2-p12 in the majority of cases. Most of the sporadic cases are due to a de novo duplication. We have screened for this duplication in 11 Danish patients...

  3. Exercise intolerance in Glycogen Storage Disease Type III

    Preisler, Nicolai; Pradel, Agnès; Husu, Edith

    2013-01-01

    Myopathic symptoms in Glycogen Storage Disease Type IIIa (GSD IIIa) are generally ascribed to the muscle wasting that these patients suffer in adult life, but an inability to debranch glycogen likely also has an impact on muscle energy metabolism. We hypothesized that patients with GSD IIIa can...

  4. The clinical management of Type 2 Gaucher disease.

    Weiss, Karin; Gonzalez, Ashley; Lopez, Grisel; Pedoeim, Leah; Groden, Catherine; Sidransky, Ellen

    2015-02-01

    Gaucher disease, the inherited deficiency of the enzyme glucocerebrosidase, is the most common of the lysosomal storage disorders. Type 2 Gaucher disease, the most severe and progressive form, manifests either prenatally or in the first months of life, followed by death within the first years of life. The rarity of the many lysosomal storage disorders makes their diagnosis a challenge, especially in the newborn period when the focus is often on more prevalent illnesses. Thus, a heightened awareness of the presentation of these rare diseases is necessary to ensure their timely consideration. This review, designed to serve as a guide to physicians treating newborns and infants with Gaucher disease, discusses the presenting manifestations of Type 2 Gaucher disease, the diagnostic work-up, associated genotypes and suggestions for management. We also address the ethical concerns that may arise with this progressive and lethal disorder, since currently available treatments may prolong life, but do not impact the neurological manifestations of the disease. Published by Elsevier Inc.

  5. Parathyroid mitogenic activity in plasma from patients with familial multiple endocrine neoplasia type 1

    Brandi, M.L.; Aurbach, G.D.; Fitzpatrick, L.A.; Quarto, R.; Spiegel, A.M.; Bliziotes, M.M.; Norton, J.A.; Doppman, J.L.; Marx, S.J.

    1986-01-01

    Hyperplasia of the parathyroid glands is a central feature of familial multiple endocrine neoplasia type 1. We used cultured bovine parathyroid cells to test for mitogenic activity in plasma from patients with this disorder. Normal plasma stimulated [ 3 H]thymidine incorporation, on the average, to the same extent as it was stimulated in a plasma-free control culture. This contrasted with the results of the tests with plasma from patients with familial multiple endocrine neoplasia type 1, in which parathyroid mitogenic activity increased 2400 percent over the control value (P less than 0.001). Plasma from these patients also stimulated the proliferation of bovine parathyroid cells in culture, whereas plasma from normal subjects inhibited it. Parathyroid mitogenic activity in plasma from the patients with familial multiple endocrine neoplasia type 1 was greater than that in plasma from patients with various other disorders, including sporadic primary hyperparathyroidism (with adenoma, hyperplasia, or cancer of the parathyroid), sporadic primary hypergastrinemia, sporadic pituitary tumor, familial hypocalciuric hypercalcemia, and multiple endocrine neoplasia type 2 (P less than 0.05). Parathyroid mitogenic activity in the plasma of patients with familial multiple endocrine neoplasia type 1 persisted for up to four years after total parathyroidectomy. The plasma also had far more mitogenic activity in cultures of parathyroid cells than did optimal concentrations of known growth factors or of any parathyroid secretagogue. This mitogenic activity had an apparent molecular weight of 50,000 to 55,000. We conclude that primary hyperparathyroidism in familial multiple endocrine neoplasia type 1 may have a humoral cause

  6. [An adult form of type-I. Gaucher's disease].

    Múzes, G; Pitlik, E; Gohér, A; Somogyi, A; Tulassay, Z

    2000-03-26

    A young woman with no previous history of any diseases was admitted for further evaluation of a mild thrombocytopenia she has had for some months. No signs of bleeding have so far occurred. Physical examination was normal except for a moderately enlarged spleen. Routine investigations showed lower platelet count. There was no laboratory evidence of disease conditions with autoimmune/inflammatory or hematologic origin. Bone marrow aspirate indicated Gaucher's-like cells raising the suspicion of Gaucher's disease. This was further supported by electron microscopic demonstration of Gaucher's bodies (with the characteristic tubular structures) in crista biopsy specimens. However, definitive diagnosis was obtained by verifying deficient lysosomal glucosylceramide-beta-D-glucosidase activity in peripheral blood leukocytes. Upon the absence of neurologic involvement the patient was typical for the adult form or type-1 Gaucher's disease.

  7. Pulmonary Arterial Hypertension in Glycogen Storage Disease Type I

    Rachel D. Torok MD

    2017-05-01

    Full Text Available Pulmonary arterial hypertension (PAH is a rare and highly fatal disease that has been reported in 8 patients with glycogen storage disease type I (GSDI. We describe an additional case of an acute presentation of PAH in a 14-year-old patient with GSDI, which was successfully treated with inhaled nitric oxide and sildenafil. We investigated the incidence of PAH in 28 patients with GSDI on routine echocardiography and found no evidence of PAH and no significant cardiac abnormalities. This study highlights that PAH is a rare disease overall, but our case report and those previously described suggest an increased incidence in patients with GSDI. Should cardiopulmonary symptoms develop, clinicians caring for patients with GSDI should have a high degree of suspicion for acute PAH and recognize that prompt intervention can lead to survival in this otherwise highly fatal disease.

  8. Adipokines and Non-Alcoholic Fatty Liver Disease: Multiple Interactions

    Timon E. Adolph

    2017-07-01

    Full Text Available Accumulating evidence links obesity with low-grade inflammation which may originate from adipose tissue that secretes a plethora of pro- and anti-inflammatory cytokines termed adipokines. Adiponectin and leptin have evolved as crucial signals in many obesity-related pathologies including non-alcoholic fatty liver disease (NAFLD. Whereas adiponectin deficiency might be critically involved in the pro-inflammatory state associated with obesity and related disorders, overproduction of leptin, a rather pro-inflammatory mediator, is considered of equal relevance. An imbalanced adipokine profile in obesity consecutively contributes to metabolic inflammation in NAFLD, which is associated with a substantial risk for developing hepatocellular carcinoma (HCC also in the non-cirrhotic stage of disease. Both adiponectin and leptin have been related to liver tumorigenesis especially in preclinical models. This review covers recent advances in our understanding of some adipokines in NAFLD and associated HCC.

  9. Light chain deposition disease in multiple myeloma: MR imaging features correlated with histopathological findings

    Baur, A.; Staebler, A.; Reiser, M.; Lamerz, R.; Bartl, R.

    1998-01-01

    The clinical, histopathological, and imaging findings on MRI of a 56-year-old woman with light chain deposition disease occurring in multiple myeloma are presented. Light chain deposition disease is a variant of multiple myeloma with distinct clinical and histological characteristics. MRI of this patient also revealed an infiltration pattern in the bone marrow distinct from that of typical multiple myeloma. Multiple small foci of low signal intensity were present on T1- and T2-weighted spin echo and STIR images, corresponding to conglomerates of light chains in bone marrow biopsy. Contrast-enhanced T1-weighted spin echo images show diffuse enhancement of 51% over all vertebral bodies, with a minor enhancement of the focal conglomerates of light chains. Light chain deposition disease in multiple myeloma should be added to the list of those few entities with normal radiographs and discrete low-signal marrow lesions on T1- and T2-weighted spin echo pulse sequences. (orig.)

  10. Surgical approach in patients with hyperparathyroidism in multiple endocrine neoplasia type 1: total versus partial parathyroidectomy

    Francesco Tonelli

    2012-01-01

    Full Text Available Usually, primary hyperparathyroidism is the first endocrinopathy to be diagnosed in patients with multiple endocrine neoplasia type 1, and is also the most common one. The timing of the surgery and strategy in multiple endocrine neoplasia type 1/hyperparathyroidism are still under debate. The aims of surgery are to: 1 correct hypercalcemia, thus preventing persistent or recurrent hyperparathyroidism; 2 avoid persistent hypoparathyroidism; and 3 facilitate the surgical treatment of possible recurrences. Currently, two types of surgical approach are indicated: 1 subtotal parathyroidectomy with removal of at least 3-3 K glands; and 2 total parathyroidectomy with grafting of autologous parathyroid tissue. Transcervical thymectomy must be performed with both of these procedures. Unsuccessful surgical treatment of hyperparathyroidism is more frequently observed in multiple endocrine neoplasia type 1 than in sporadic hyperparathyroidism. The recurrence rate is strongly influenced by: 1 the lack of a pre-operative multiple endocrine neoplasia type 1 diagnosis; 2 the surgeon's experience; 3 the timing of surgery; 4 the possibility of performing intra-operative confirmation (histologic examination, rapid parathyroid hormone assay of the curative potential of the surgical procedure; and, 5 the surgical strategy. Persistent hyperparathyroidism seems to be more frequent after subtotal parathyroidectomy than after total parathyroidectomy with autologous graft of parathyroid tissue. Conversely, recurrent hyperparathyroidism has a similar frequency in the two surgical strategies. To plan further operations, it is very helpful to know all the available data about previous surgery and to undertake accurate identification of the site of recurrence.

  11. Whole-Body MRI versus PET in assessment of multiple myeloma disease activity.

    Shortt, Conor P

    2009-04-01

    The purpose of this study was to compare FDG PET; whole-body MRI; and the reference standard, bone marrow aspiration and biopsy, to determine the best imaging technique for assessment of disease activity in multiple myeloma.

  12. A minimal unified model of disease trajectories captures hallmarks of multiple sclerosis

    Kannan, Venkateshan; Kiani, Narsis A.; Piehl, Fredrik; Tegner, Jesper

    2017-01-01

    Multiple Sclerosis (MS) is an autoimmune disease targeting the central nervous system (CNS) causing demyelination and neurodegeneration leading to accumulation of neurological disability. Here we present a minimal, computational model involving

  13. Consensus guidelines for management of glycogen storage disease type 1b - European Study on Glycogen Storage Disease Type 1

    Visser, G; Rake, JP; Labrune, P; Leonard, JV; Moses, S; Ullrich, K; Wendel, U; Smit, GPA

    2002-01-01

    Life expectancy in glycogen storage disease type 1 (GSD-1) has improved considerably. Its relative rarity implies that no metabolic centre has experience of large series of patients and therefore experience with long-term management and follow-up at each centre is limited. There is wide variation in

  14. Guidelines for management of glycogen storage disease type I - European study on glycogen storage disease type I (ESGSD I)

    Rake, JP; Visser, G; Labrune, P; Leonard, JV; Ullrich, K; Smit, GPA

    2002-01-01

    Life-expectancy in glycogen storage disease type I (GSD I) has improved considerably. Its relative rarity implies that no metabolic centre has experience of large series of patients and experience with long-term management and follow-up at each centre is limited. There is wide variation in methods

  15. Association of Multiple Melanocytic Naevi with Education, Sex and Skin Type. A Northern Finland Birth Cohort 1966 Study with 46 Years Follow-up.

    Sinikumpu, Suvi-Päivikki; Huilaja, Laura; Jokelainen, Jari; Auvinen, Juha; Timonen, Markku; Tasanen, Kaisa

    2017-02-08

    Having multiple melanocytic naevi (sex, socioeconomic status (education) in childhood and adulthood, skin type and sunbathing habits. The prevalence of multiple melanocytic naevi was 11.6% (223/1,930). Higher education (odds ratio (OR) 2.11, 95% confidence interval (95% CI) 1.51-2.96), male sex (OR 1.48, 95% CI 1.07-2.06), sun-sensitive skin type (OR 2.09, 95% CI 1.34-3.27) and regular use of sunscreen (OR 2.03, 95% CI 1.23-3.37) were associated with increased risk of multiple naevi. Inflammatory skin diseases decreased (OR 0.49, 95 CI% 0.33-0.72) the risk of multiple naevi. In conclusion, several risk factors were found for multiple naevi among adults living in high latitudes, in Northern Finland.

  16. Diagnosis of Alzheimer's disease and multiple infarct dementia by tomographic imaging of iodine-123 IMP

    Cohen, M.B.; Graham, L.S.; Lake, R.

    1986-01-01

    Tomographic imaging of the brain was performed using a rotating slant hole collimator and [ 123 I]N-isopropyl p-iodoamphetamine (IMP) in normal subjects (n = 6) and patients with either Alzheimer's disease (n = 5) or multiple infarct dementia (n = 3). Four blinded observers were asked to make a diagnosis from the images. Normal subjects and patients with multiple infarct dementia were correctly identified. Alzheimer's disease was diagnosed in three of the five patients with this disease. One patient with early Alzheimer's disease was classified as normal by two of the four observers. Another patient with Alzheimer's disease had an asymmetric distribution of IMP and was incorrectly diagnosed as multiple infarct dementia by all four observers. Limited angle tomography of the cerebral distribution of 123 I appears to be a useful technique for the evaluation of demented patients

  17. Type IX Collagen Gene Mutations Can Result in Multiple Epiphyseal Dysplasia That Is Associated With Osteochondritis Dissecans and a Mild Myopathy

    Jackson, Gail C.; Marcus-Soekarman, Dominique; Stolte-Dijkstra, Irene; Verrips, Aad; Taylor, Jacqueline A.; Briggs, Michael D.

    Multiple epiphyseal dysplasia (MED) is a clinically variable and genetically heterogeneous disease that is characterized by mild short stature and early onset osteoarthritis. Autosomal dominant forms are caused by mutations in the genes that encode type IX collagen, cartilage oligomeric matrix

  18. Type IX collagen gene mutations can result in multiple epiphyseal dysplasia that is associated with osteochondritis dissecans and a mild myopathy.

    Jackson, G.C.; Marcus-Soekarman, D.; Stolte-Dijkstra, I.; Verrips, A.; Taylor, J.A.; Briggs, M.D.

    2010-01-01

    Multiple epiphyseal dysplasia (MED) is a clinically variable and genetically heterogeneous disease that is characterized by mild short stature and early onset osteoarthritis. Autosomal dominant forms are caused by mutations in the genes that encode type IX collagen, cartilage oligomeric matrix

  19. The VLT-FLAMES Tarantula Survey. XXII. Multiplicity properties of the B-type stars

    Dunstall, P.R.; Dufton, P.L.; Sana, H.; Evans, C.J.; Howarth, I.D.; Simón-Díaz, S.; de Mink, S.E.; Langer, N.; Maíz Apellániz, J.; Taylor, W.D.

    2015-01-01

    We investigate the multiplicity properties of 408 B-type stars observed in the 30 Doradus region of the Large Magellanic Cloud with multi-epoch spectroscopy from the VLT-FLAMES Tarantula Survey (VFTS). We use a cross-correlation method to estimate relative radial velocities from the helium and metal

  20. Strong convergence of an extragradient-type algorithm for the multiple-sets split equality problem.

    Zhao, Ying; Shi, Luoyi

    2017-01-01

    This paper introduces a new extragradient-type method to solve the multiple-sets split equality problem (MSSEP). Under some suitable conditions, the strong convergence of an algorithm can be verified in the infinite-dimensional Hilbert spaces. Moreover, several numerical results are given to show the effectiveness of our algorithm.

  1. A new multiplicity formula for the Weyl modules of type A

    Ye Jiachen; Zhou Zhongguo

    2003-08-01

    A monomial basis and a filtration of subalgebras for the universal enveloping algebra U(g) of a complex simple Lie algebra g l of type A I is given in this note. In particular, a new multiplicity formula for the Weyl module V(λ) of U(g l ) is obtained in this note. (author)

  2. Prevalence of Gastroesophageal Reflux Disease in Type II Diabetes Mellitus

    Huihui Sun

    2014-01-01

    Full Text Available Background/Aims. Patients with type II diabetes mellitus (DM were known to have higher prevalence of gastroesophageal reflux disease (GERD in the Western countries, but data on the impact of GERD on DM patients in our country are scarce. The aim of this study was to evaluate the prevalence of GERD in type II DM patients in Shanghai, China, and to explore its possible risk factors. Methods. 775 type II DM cases were randomly collected. Reflux Disease Questionnaire (RDQ was used to check the presence of GERD. Patients’ characteristics, laboratory data, face-to-face interview, nerve conduction study, and needle electromyogram (EMG test were analyzed. Results. 16% patients were found with typical GERD symptoms. Pathophysiological factors such as peripheral neuropathy, metabolism syndrome, and obesity were found to have no significant differences between GERD and non-GERD type II DM patients in the present study. Conclusion. The prevalence of GERD in type II DM patients is higher than that in adult inhabitants in Shanghai, China. No difference in pathophysiological factors, such as peripheral neuropathy, and metabolism syndrome was found in DM-GERD patients, suggesting that further study and efforts are needed to explore deeper the potential risk factors for the high prevalence rate of GERD in DM patients.

  3. Multiple endocrine diseases in dogs: 35 cases (1996-2009).

    Blois, Shauna L; Dickie, Erica; Kruth, Stephen A; Allen, Dana G

    2011-06-15

    To characterize a population of dogs from a tertiary care center with 2 or more endocrine disorders, including the specific disorders and time intervals between diagnosis of each disorder. Retrospective case series. 35 dogs with 2 or more endocrine disorders. Medical records were reviewed, and the following was recorded: clinical signs, physical examination findings, and the results of CBC, serum biochemical analysis, urinalysis, aerobic bacterial culture of urine samples, endocrine testing, diagnostic imaging, and necropsy. 35 dogs with more than 1 endocrine disorder were identified. Seventy-seven percent (27/35) of the dogs were male, and the mean age at the time of diagnosis of the first endocrinopathy was 7.9 years. Miniature Schnauzer was the most common breed. Twenty-eight of 35 (80%) dogs had 2 disorders; 7 (20%) had 3 disorders. The most common combinations of disorders included diabetes mellitus and hyperadrenocorticism in 57.1 % (20/35) of dogs; hypoadrenocorticism and hypothyroidism in 22.9% (8/35) of dogs; and diabetes mellitus and hypothyroidism in 28.6% (10/35) of dogs. A mean of 14.5 months elapsed between diagnosis of the first and second endocrine disorders, whereas there was a mean of 31.1 months between diagnosis of the first and third endocrine disorders. Results suggested that the occurrence of multiple endocrine disorders was uncommon in dogs. The most common combinations of endocrine disorders in this population of dogs were diabetes mellitus and hyperadrenocorticism, followed by hypoadrenocorticism and hypothyroidism.

  4. Multiple Frequencies in the Basal Ganglia in Parkinson's Disease

    Clare M. Davidson

    2015-01-01

    Full Text Available In recent years, the authors have developed what appears to be a very successful phenomenological model for analyzing the role of deep brain stimulation (DBS in alleviating the symptoms of Parkinson's disease. In this paper, we extend the scope of the model by using it to predict the generation of new frequencies from networks tuned to a specific frequency, or indeed not self-oscillatory at all. We have discussed two principal cases: firstly where the constituent systems are coupled in an excitatory-excitatory fashion, which we designate by ``+/+''; and secondly where the constituent systems are coupled in an excitatory-inhibitory fashion, which we designate ``+/-''. The model predicts that from a basic system tuned to tremor frequency we can generate an unlimited range of frequencies. We illustrate in particular, starting from systems which are initially non-oscillatory, that when the coupling coefficient exceeds a certain value, the system begins to oscillate at an amplitude which increases with the coupling strength. Another very interesting feature, which has been shown by colleagues of ours to arise through the coupling of complicated networks based on the physiology of the basal ganglia, can be illustrated by the root locus method which shows that increasing and decreasing frequencies of oscillation, existing simultaneously, have the property that their geometric mean remains substantially constant as the coupling strength is varied. We feel that with the present approach, we have provided another tool for understanding the existence and interaction of pathological oscillations which underlie, not only Parkinson's disease, but other conditions such as Tourette's syndrome, depression and epilepsy.

  5. Asymptomatic coronary artery disease in Type-2 diabetes

    Ahmed, S.S.F.; Othman, S.; Meo, S.A.

    2009-01-01

    Objective: To select a subgroup of type-2 diabetics with two additional pre specified risk factors to see that whether there is any benefit of screening such patients. Methodology: Five hundred twenty six patients were sent for treadmill stress test or thallium scan. Those who had abnormal results were advised coronary angiography. The angiographically proven CAD was correlated with various risk factors to find the relationship between the disease and variables. Results: Two hundred thirty five (48%) patients had abnormal results and among them 158 (67%)underwent coronary angiography. Among these 21% had evidence of CAD. Coronary artery bypass grafting (CABG) was performed in 35(33%) patients, catheter based intervention (PCI) in 44(40%) patients and 30(27%) patients were not suitable for intervention. Duration of diabetes, smoking, diabetic retinopathy, albuminuria, and peripheral vascular disease were significant predictor of asymptomatic CAD. Conclusion: This study has demonstrated strong relationship between risk factors and asymptomatic CAD in type 2 diabetics. (author)

  6. [Type 2 diabetes mellitus and chronic kidney disease].

    Ponťuch, Peter

    The number of type 2 diabetic patients is increasing world-wide and a prediction of prevalence of chronic kidney disease up to 2025 in European diabetic population is alarming. Albuminuria and estimated glomerular filtration rate are cardinal biochemical parameters in diagnostics of diabetic nephropathy. Following diagnostic methods are also used: renal ultrasonography, ophthalmoscopy and in not clarified cases renal biopsy. Long-term optimal glycemic control, efficient antihypertensive treatment by angiotensin converting enzyme inhibitor, or angiotensin receptor blocker and recommended protein intake is a cornerstone of therapy. The research is presently focused on new pathophysiological mechanisms, as analysis of genome, microRNA, kidney injury biomarkers and proteomes.Key words: chronic kidney disease - type 2 diabetes mellitus.

  7. Activity of glucocerebrosidase in extracts of different cell types from type 1 Gaucher disease patients

    Sa Miranda, M. C.; Aerts, J. M.; Pinto, R.; Fontes, A.; de Lacerda, L. W.; van Weely, S.; Barranger, J.; Tager, J. M.

    1990-01-01

    Glucocerebrosidase activity in extracts of leukocytes, Epstein-Barr virus transformed lymphocytes and fibroblasts from Portuguese Type 1 Gaucher disease patients was studied. The residual glucocerebrosidase activity in all extracts from patients was less than 25% if measured in the presence of bile

  8. Type 2 diabetes mellitus in the pathophysiology of Alzheimer's disease

    Aparecida Marcelino de Nazareth

    Full Text Available ABSTRACT Both Alzheimer's disease (AD and type 2 diabetes mellitus (DM are two common forms of disease worldwide and many studies indicate that people with diabetes, especially DM, are at higher risk of developing AD. AD is characterized by progressive cognitive decline and accumulation of β-amyloid (Aβ forming senile plaques. DM is a metabolic disorder characterized by hyperglycemia in the context of insulin resistance and relative lack of insulin. Both diseases also share common characteristics such as loss of cognitive function and inflammation. Inflammation resulting from Aβ further induces production of Aβ1-42 peptides. Inflammation due to overnutrition induces insulin resistance and consequently DM. Memory deficit and a decrease in GLUT4 and hippocampal insulin signaling have been observed in animal models of insulin resistance. The objective of this review was to show the shared characteristics of AD and DM.

  9. Bone turnover markers in patients with type 1 Gaucher disease

    Gaetano Giuffrida

    2012-11-01

    Full Text Available Bone complications occur frequently in Gaucher disease (GD and reduce the quality of life of these patients. Skeletal involvement is an important indication for treatment to ameliorate symptoms and reduce the risk of irreversible and debilitating disease. Bone biomarkers have been used to assess disease status and the response to therapy in a number of bone disorders. Here, we examine the literature for evidence of abnormalities in bone turnover markers in patients with type 1 GD to assess whether they might be useful for the assessment of bone involvement in GD. We have found that bone biomarkers in GD show highly variable results which do not currently support their routine use for clinical assessment of bone status, as an indication for therapy initiation, or for monitoring the response to therapy. A greater understanding of bone markers and their relation to the bone manifestations of GD is required.

  10. Mild thrombocytopenia as presenting symptom of type 1 Gauchers's disease.

    Müzes, G; Pitlik, E; Somogyi, A; Tulassay, Z

    2001-06-01

    A young woman was examined for a mild thrombocytopenia which was present for some months. No signs of bleeding had so far occurred. Physical examination was normal except for a moderately enlarged spleen. Laboratory investigations showed a low platelet count. There was no evidence of an autoimmune or hematologic disease. Bone narrow aspirate indicated Gaucher's-like cells raising the suspicion of Gaucher's disease. This was further supported by electron microscopic demonstration of Gaucher's bodies in crista biopsy specimens. However, the definitive diagnosis was obtained by verifying deficient lysosomal glucosylceramide-beta-D-glucosidase activity in peripheral blood leukocytes. Upon the absence of neurologic involvement the patient was typical for the adult-onset or type 1 form of Gaucher's disease.

  11. A familial case of segregation of motor sensory neuropathy type 1B with multiple exostoses in monozygous twins

    V. P. Fedotov

    2015-01-01

    Full Text Available Hereditary motor-sensory neuropathy (MIM 118200 is a rare genetic variant of myelinopathy with autosomal-dominant type of inheritance. Multiple exostosis bones are signs of multiple exostoses chondrodysplasia, genetically heterogeneous form of systemic bone disease with an autosomal dominant mode of inheritance. The combination of two rare autosomal dominant diseases, affecting bone and peripheral nervous system in a pair of monozygotic twins and their father in one family, belongs to a unique clinical observations: since early childhood twins presented sharp reduction of the conduction velocity in all investigated motor nerves (>10 times together with multiple exostosis bone, confirmed by x-ray with a relatively benign course. Similar manifestations were detected in the patients father. DNA analysis confirmed the presence of 2 separate mutations in 2 different genes, с.389А>G/N gene MPZ and c.678С>А/N EXT2 gene that was inherited autosomal dominant manner, independently of each members of the same family.

  12. Familial disseminated plaque type porokeratosis with multiple horns and squamous cell carcinoma involving anal skin

    Sarma Nilendu

    2009-01-01

    Full Text Available Porokeratosis is a disorder of keratinization showing a well-defined lesion with a hyperkeratotic ridge on the border that contains the coronoid lamella. We report familial (autosomal dominant with reduced penetrance disseminated plaque type (Mibelli′s type porokeratosis in a father and son. In the father, there were multiple horns and a large squamous cell carcinoma in a large lesion over the perianal region that reached up to the squamo-columnar junction of the anal mucosa and even invaded the anal sphincteric muscles. Disseminated lesions of the Mibelli′s type, development of horns, and malignancy in this unusual location have not been previously reported.

  13. Multiple disease resistance to fungal and oomycete pathogens using a recombinant inbred line population in pepper

    Incorporating disease resistance into cultivars is a primary focus of modern breeding programs. Resistance to pathogens is often introgressed from landrace or wild individuals with poor fruit quality into commercial-quality cultivars. Sites of multiple disease resistance (MDR) are regions or “hotspo...

  14. Health-related needs of people with multiple chronic diseases: differences and underlying factors.

    Hopman, P.; Schellevis, F.G.; Rijken, M.

    2016-01-01

    Purpose: To examine the health-related needs of people with multiple chronic diseases in the Netherlands compared to people with one chronic disease, and to identify different subgroups of multimorbid patients based on differences in their health problems. Methods: Participants were 1092 people with

  15. Speech and Pause Characteristics Associated with Voluntary Rate Reduction in Parkinson's Disease and Multiple Sclerosis

    Tjaden, Kris; Wilding, Greg

    2011-01-01

    The primary purpose of this study was to investigate how speakers with Parkinson's disease (PD) and Multiple Sclerosis (MS) accomplish voluntary reductions in speech rate. A group of talkers with no history of neurological disease was included for comparison. This study was motivated by the idea that knowledge of how speakers with dysarthria…

  16. The immunoregulatory role of type I and type II NKT cells in cancer and other diseases

    Terabe, Masaki; Berzofsky, Jay A.

    2014-01-01

    NKT cells are CD1d-restricted T cells that recognize lipid antigens. They also have been shown to play critical roles in the regulation of immune responses. In the immune responses against tumors, two subsets of NKT cells, type I and type II, play opposing roles and cross-regulate each other. As members of both the innate and adaptive immune systems, which form a network of multiple components, they also interact with other immune components. Here we discuss the function of NKT cells in tumor immunity and their interaction with other regulatory cells, especially CD4+CD25+Foxp3+ regulatory T cells. PMID:24384834

  17. Default mode network links to visual hallucinations: A comparison between Parkinson's disease and multiple system atrophy.

    Franciotti, Raffaella; Delli Pizzi, Stefano; Perfetti, Bernardo; Tartaro, Armando; Bonanni, Laura; Thomas, Astrid; Weis, Luca; Biundo, Roberta; Antonini, Angelo; Onofrj, Marco

    2015-08-01

    Studying default mode network activity or connectivity in different parkinsonisms, with or without visual hallucinations, could highlight its roles in clinical phenotypes' expression. Multiple system atrophy is the archetype of parkinsonism without visual hallucinations, variably appearing instead in Parkinson's disease (PD). We aimed to evaluate default mode network functions in multiple system atrophy in comparison with PD. Functional magnetic resonance imaging evaluated default mode network activity and connectivity in 15 multiple system atrophy patients, 15 healthy controls, 15 early PD patients matched for disease duration, 30 severe PD patients (15 with and 15 without visual hallucinations), matched with multiple system atrophy for disease severity. Cortical thickness and neuropsychological evaluations were also performed. Multiple system atrophy had reduced default mode network activity compared with controls and PD with hallucinations, and no differences with PD (early or severe) without hallucinations. In PD with visual hallucinations, activity and connectivity was preserved compared with controls and higher than in other groups. In early PD, connectivity was lower than in controls but higher than in multiple system atrophy and severe PD without hallucinations. Cortical thickness was reduced in severe PD, with and without hallucinations, and correlated only with disease duration. Higher anxiety scores were found in patients without hallucinations. Default mode network activity and connectivity was higher in PD with visual hallucinations and reduced in multiple system atrophy and PD without visual hallucinations. Cortical thickness comparisons suggest that functional, rather than structural, changes underlie the activity and connectivity differences. © 2015 International Parkinson and Movement Disorder Society.

  18. Clinical and Genetic Analysis of Multiple Endocrine Neoplasia Type 1-Related Primary Hyperparathyroidism in Chinese.

    Jing Kong

    Full Text Available Multiple endocrine neoplasia type 1-related primary hyperparathyroidism (MHPT differs in many aspects from sporadic PHPT (SHPT. The aims of this study were to summarize the clinical features and genetic background of Chinese MHPT patients and compare the severity of the disease with those of SHPT.A total of 40 MHPT (27 sporadic, 7 families and 169 SHPT cases of Chinese descent were retrospectively analyzed. X-rays and ultrasound were used to assess the bone and urinary system. Dual energy x-ray absorptiometry (DXA were performed to measure bone mineral density (BMD. Besides direct sequencing of the MEN1 and CDKN1B genes, multiplex ligation-dependent probe amplification (MLPA was used to screen gross deletion for the MEN1 gene.Compared with SHPT patients, MHPT patients showed lower prevalence of typical X-ray changes related to PHPT (26.3% vs. 55.7%, P = 0.001 but higher prevalence of urolithiasis/renal calcification (40.2% vs. 60.0%, P = 0.024. MHPT patients showed higher phosphate level (0.84 vs. 0.73mmol/L, P<0.05 but lower ALP (103.0 vs. 174.0U/L, P<0.001 and PTH (4.0 vs. 9.8×upper limit, P<0.001 levels than SHPT patients. There were no significant differences in BMD Z-scores at the lumbar spine and femoral neck between the two groups. Mutations in the MEN1 gene were detected in 27 MHPT cases. Among the nine novel mutations were novel, one of them involved the deletion of exon 5 and 6.MHPT patients experienced more common kidney complications but less skeletal issues, and a milder biochemical manifestation compared with SHPT patients. MEN1 mutation detection rate was 79.4% and 9 of the identified mutations were novel.

  19. Multiple long bone cysts revealed by MRI in trichorhinophalangeal syndrome type II predisposing to pathological fractures

    Konala, Praveen; Cassar-Pullicino, Victor N. [The Robert Jones and Agnes Hunt Orthopaedic Hospital, Department of Radiology, Oswestry (United Kingdom); Kiely, Nigel [The Robert Jones and Agnes Hunt Orthopaedic Hospital, Department of Orthopaedic Surgery, Oswestry (United Kingdom); Noakes, Charlotte [Oxford University Hospital, The Oxford Genetics Laboratories, Oxford (United Kingdom); Blair, Edward [Oxford University Hospital, Department of Clinical Genetics, Oxford (United Kingdom)

    2017-07-15

    Trichorhinophalangeal syndrome type II is a rare genetic disorder with the few published case reports mainly reporting the radiographic skeletal manifestations. There are no published imaging reports of long bone cysts involving multiple bones in this condition. We report a unique case of bone cysts involving multiple long bones detected with MRI in a patient with trichorhinophalangeal syndrome type II complicated by a subsequent pathological fracture. It is possible that the bone cysts are a previously undescribed feature of this syndrome; however, the evidence is insufficient to establish a definite association. Chromosomal abnormality identified in this patient is consistent with trichorhinophalangeal syndrome type II with no unusual features. Although the nature of these bone cysts is unclear, they are one of the causes of the known increased fracture risk observed in this syndrome. (orig.)

  20. [Psychological distress of children with progressive diseases and multiple disabilities: A crossed analysis].

    Perifano, A; Scelles, R

    2015-09-01

    In this paper, we present the results of research conducted on the psychological distress of lysosomal-disease-affected children. Lysosomal diseases are rare genetic diseases most often leading to severe disabilities, both psychological and physiological. As frequently reported by their relatives, affected children experience nervous breakdowns, which are sometimes treated with antidepressant prescriptions. However, mental impairment as well physical disabilities can prevent children from making their pain noticed and identified by their relatives. This raises a new research question: when disabilities are severe, how should the psychological distress of affected children be identified? Recent studies on the care of children with multiple disabilities (San Salavadour 2000; Scelles 2003; Camelio 2006; Pautrel, 2009) have used the children's family and caregivers to access their feelings, considered to be translators of children's feelings because they understand their nonverbal language (Camelio, 2006). Using this methodology, four parents from the French not-for-profit association called "VML" (Vaincre les maladies lysosomales) and four professionals were involved in semi-structured interviews. The goal of these interviews was to identify signs of possible psychological suffering, the context in which those signs were expressed, the meaning and the value attributed to it by the family and caregivers, and the reaction as well as an evaluation of that reaction. Thirteen children were involved, 12 of whom were described as having shown signs of psychological distress. Six lysosomal diseases were represented. Two types of signs were reported: active signs (e.g., agitation, screaming, crying) and passive signs (e.g., no communication, withdrawal, lack of facial expression). Most of the time, passive signs were interpreted by the family and caregivers as evidence of deep psychological distress. The meanings of both types of sign were the following: fear, anxiety

  1. Association of IgA multiple myeloma with pre-existing disease

    Schafer, A.I.; Miller, J.B.

    1979-01-01

    A retrospective analysis of 153 patients with multiple myeloma was performed for evaluation of the possible significance of pre-existing disease. 37% of the group had no significant antecedent disorder. The most common prior illnesses were peptic ulcer disease and gallbladder disease. Of 12 patients in the group who had prior biliary tract disease and for whom immunoelectrophoretic studies were available, eight (66.7%) had IgA paraproteins. This figure is statistically higher than the 14.1% of prevalence of IgA paraproteins in those myeloma patients without biliary disease. We conclude that prior inflammatory gastrointestinal, pulmonary, and, particularly, biliary disease may be implicated in the pathogenesis of the IgA subset of multiple myeloma.

  2. Prevalence of single and multiple HPV types in cervical carcinomas in Jakarta, Indonesia.

    Schellekens, Maaike C; Dijkman, Anneke; Aziz, Mohammad Farid; Siregar, Budiningsih; Cornain, Santoso; Kolkman-Uljee, Sandra; Peters, Lex A W; Fleuren, Gert Jan

    2004-04-01

    Cervical cancer is the second most frequently occurring type of cancer in women worldwide. A persistent infection with high-risk human papillomavirus (HPV) is a necessary causal factor in cervical carcinogenesis. The distribution of HPV types in populations has been studied worldwide. In Indonesia, however, few data are available describing the prevalence of HPV. Cervical carcinoma is the most common female cancer in Indonesia and causes high morbidity and mortality figures. With HPV vaccination studies in progress, it is important to map the HPV status of a population that would benefit greatly from future prevention programs. We tested 74 cervical cancer specimens from consecutive, newly diagnosed cervical cancer patients in the outpatient clinic of the Dr. Cipto Mangunkusumo Hospital, Jakarta. After additional staining, the formalin-fixed, paraffin-embedded tissue samples were histologically classified. HPV presence and genotype distribution were determined by SPF10 polymerase chain reaction and line probe assay. HPV DNA of 12 different HPV types was detected in 96% of the specimens. The three most common types were 16 (44%), 18 (39%) and 52 (14%). In 14% of the specimens, multiple HPV types were present. The multiple HPV types were significantly more prevalent among adenosquamous carcinomas in comparison with squamous cell carcinoma or adenocarcinoma (P = 0.014). Distribution of HPV types in Indonesia with a more prominent role for HPV 18 is slightly different from that in other parts of the world. The high amount of multiple HPV infections found in adenosquamous carcinomas may prompt further research on the pathogenesis of this type of cervical tumours.

  3. Value of multiple risk factors in predicting coronary artery disease

    Zhu Zhengbin; Zhang Ruiyan; Zhang Qi; Yang Zhenkun; Hu Jian; Zhang Jiansheng; Shen Weifeng

    2008-01-01

    Objective: This study sought to assess the relationship between correlative comprehension risk factors and coronary arterial disease and to build up a simple mathematical model to evaluate the extension of coronary artery lesion in patients with stable angina. Methods: A total of 1024 patients with chest pain who underwent coronary angiography were divided into CAD group(n=625)and control group(n=399) based on at least one significant coronary artery narrowing more than 50% in diameter. Independent risk factors for CAD were evaluated and multivariate logistic regression model and receiver-operating characteristic(ROC) curves were used to estimate the independent influence factor for CAD and built up a simple formula for clinical use. Results: Multivariate regression analysis revealed that UACR > 7.25 μg/mg(OR=3.6; 95% CI 2.6-4.9; P 20 mmol/L(OR=3.2; 95% CI 2.3-4.4; P 2 (OR=2.3; 95% CI 1.4-3.8; P 2.6 mmol/L (OR 2.141; 95% CI 1.586-2.890; P 7.25 μg/mg + 1.158 x hsCRP > 20 mmol/L + 0.891 GFR 2 + 0.831 x LVEF 2.6 mmol/L + 0.676 x smoking history + 0.594 x male + 0.459 x diabetes + 0.425 x hypertension). Area under the curve was 0.811 (P < 0.01), and the optimal probability value for predicting severe stage of CAD was 0.977 (sensitivity 49.0%, specificity 92.7% ). Conclusions: Risk factors including renal insufficiency were the main predictors for CAD. The logistic regression model is the non-invasive method of choice for predicting the extension of coronary artery lesion in patients with stable agiana. (authors)

  4. Interpersonal traits change as a function of disease type and severity in degenerative brain diseases.

    Sollberger, Marc; Neuhaus, John; Ketelle, Robin; Stanley, Christine M; Beckman, Victoria; Growdon, Matthew; Jang, Jung; Miller, Bruce L; Rankin, Katherine P

    2011-07-01

    Different degenerative brain diseases result in distinct personality changes as a result of divergent patterns of brain damage; however, little is known about the natural history of these personality changes throughout the course of each disease. To investigate how interpersonal traits change as a function of degenerative brain disease type and severity. Using the Interpersonal Adjective Scales, informant ratings of retrospective premorbid and current scores for dominance, extraversion, warmth and ingenuousness were collected annually for 1 to 4 years on 188 patients (67 behavioural variant frontotemporal dementia (bvFTD), 40 semantic dementia (SemD), 81 Alzheimer's disease (AD)) and 65 older healthy controls. Using random coefficient models, interpersonal behaviour scores at very mild, mild or moderate-to-severe disease stages were compared within and between patient groups. Group-level changes from premorbid personality occurred as a function of disease type and severity, and were apparent even at a very mild disease stage (Clinical Dementia Rating=0.5) for all three diseases. Decreases in interpersonal traits were associated with emotional affiliation (ie, extraversion, warmth and ingenuousness) and more rigid interpersonal behaviour differentiated bvFTD and SemD patients from AD patients. Specific changes in affiliative interpersonal traits differentiate degenerative brain diseases even at a very mild disease stage, and patterns of personality change differ across bvFTD, SemD and AD with advancing disease. This study describes the typical progression of change of interpersonal traits in each disease, improving the ability of clinicians and caregivers to predict and plan for symptom progression.

  5. Quantification of whole-body bradykinesia in Parkinson's disease participants using multiple inertial sensors.

    Memar, Sara; Delrobaei, Mehdi; Pieterman, Marcus; McIsaac, Kenneth; Jog, Mandar

    2018-04-15

    Bradykinesia (slowness of movement) is a common motor symptom of Parkinson's disease (PD) that can severely affect quality of life for those living with the disease. Assessment and treatment of PD motor symptoms largely depends on clinical scales such as the Unified Parkinson's Disease Rating Scale (UPDRS). However, such clinical scales rely on the visual assessment by a human observer, naturally resulting in inter-rater variability. Although previous studies have developed objective means for measuring bradykinesia in PD patients, their evaluation was restricted by the type of movement and number of joints assessed. These studies failed to provide a more comprehensive, whole-body evaluation capable of measuring multiple joints simultaneously. This study utilizes wearable inertial measurement units (IMUs) to quantify whole-body movements, providing novel bradykinesia indices for walking (WBI) and standing up from a chair (sit-to-stand; SBI). The proposed bradykinesia indices include the joint angles at both upper and lower limbs and trunk motion to compute a complete, objective score for whole body bradykinesia. Thirty PD and 11 age-matched healthy control participants were recruited for the study. The participants performed two standard walking tasks that involved multiple body joints in the upper and lower limbs. The WBI and SBI successfully identified differences between control and PD participants. The indices also effectively identified differences within the PD population, distinguishing participants assessed with (ON) and without (OFF) levodopa; the gold-standard of treatment for PD. The goal of this study is to provide health professionals with an objective score for whole body bradykinesia by simultaneously measuring the upper and lower extremities along with truncal movement. This method demonstrates potential to be used in conjunction with current clinical standards for motor symptom assessment, and may also be promising for the remote assessment of PD

  6. Association of Chronic Kidney Disease and Cerebral Small Vessel Disease with Cognitive Impairment in Elderly Patients with Type 2 Diabetes

    Toshitaka Umemura

    2013-07-01

    Full Text Available Background/Aims: In recent years, the relationship between chronic kidney disease (CKD and cognitive impairment has been attracting attention. Cerebral small vessel disease (SVD is also associated with an increased risk of cognitive impairment. However, it is still unknown whether CKD markers are associated with cognitive impairment independently of SVD in elderly diabetic patients. Methods: Seventy-nine type 2 diabetic patients (mean age, 76.0 years were enrolled in the present study. CKD was defined as the presence of albuminuria and/or a low estimated glomerular filtration rate (eGFR 2. SVD was evaluated by the presence and severity of silent brain infarcts (SBIs and white matter lesions (WMLs on brain magnetic resonance imaging. Neuropsychological tests were assessed using four validated cognitive instruments. Results: In multiple linear regression analyses, albuminuria was associated with worse modified Stroop Color Word scores (β = 0.284, p = 0.017 and low eGFR was associated with reduced Digit Symbol Substitution scores (β = -0.224, p = 0.026 after adjustment for age, sex, education years, diabetes duration, hypertension, multiple SBIs, and advanced WMLs. In contrast, there were no significant associations between CKD markers and Mini-Mental State Examination or Word Recall scores. Conclusion: Our findings suggest that albuminuria and low eGFR are associated with frontal lobe dysfunction independently of SVD in elderly type 2 diabetic patients.

  7. Disease Type- and Status-Specific Alteration of CSF Metabolome Coordinated with Clinical Parameters in Inflammatory Demyelinating Diseases of CNS.

    Soo Jin Park

    Full Text Available Central nervous system (CNS inflammatory demyelinating diseases (IDDs are a group of disorders with different aetiologies, characterized by inflammatory lesions. These disorders include multiple sclerosis (MS, neuromyelitis optica spectrum disorder (NMOSD, and idiopathic transverse myelitis (ITM. Differential diagnosis of the CNS IDDs still remains challenging due to frequent overlap of clinical and radiological manifestation, leading to increased demands for new biomarker discovery. Since cerebrospinal fluid (CSF metabolites may reflect the status of CNS tissues and provide an interfacial linkage between blood and CNS tissues, we explored multi-component biomarker for different IDDs from CSF samples using gas chromatography mass spectrometry-based metabolite profiling coupled to multiplex bioinformatics approach. We successfully constructed the single model with multiple metabolite variables in coordinated regression with clinical characteristics, expanded disability status scale, oligoclonal bands, and protein levels. The multi-composite biomarker simultaneously discriminated four different immune statuses (a total of 145 samples; 54 MS, 49 NMOSD, 30 ITM, and 12 normal controls. Furthermore, systematic characterization of transitional metabolic modulation identified relapse-associated metabolites and proposed insights into the disease network underlying type-specific metabolic dysfunctionality. The comparative analysis revealed the lipids, 1-monopalmitin and 1-monostearin were common indicative for MS, NMOSD, and ITM whereas fatty acids were specific for the relapse identified in all types of IDDs.

  8. Common Fixed Points of Generalized Rational Type Cocyclic Mappings in Multiplicative Metric Spaces

    Mujahid Abbas

    2015-01-01

    Full Text Available The aim of this paper is to present fixed point result of mappings satisfying a generalized rational contractive condition in the setup of multiplicative metric spaces. As an application, we obtain a common fixed point of a pair of weakly compatible mappings. Some common fixed point results of pair of rational contractive types mappings involved in cocyclic representation of a nonempty subset of a multiplicative metric space are also obtained. Some examples are presented to support the results proved herein. Our results generalize and extend various results in the existing literature.

  9. Patterns and correlates of co-occurrence among multiple types of child maltreatment

    Kim, Kihyun; Mennen, Ferol E.; Trickett, Penelope K.

    2017-01-01

    This study examined the patterns and correlates of the types of maltreatment experienced by adolescents aged 9–12, participating in an ongoing longitudinal study on the impact of neglect on children’s development. Using case record abstraction, the study compared the child protection classification and findings from the case record abstraction with regard to the rates of four types of maltreatment (i.e. physical, sexual, emotional abuse and neglect) as well as co-occurrence across multiple types of maltreatment. Next, the study examined the frequently observed patterns of child maltreatment. Finally, the study investigated whether aspects of caretaker functioning and the detailed incident characteristics in the cases of neglect differed by the number of different types of maltreatment the children experienced. Results showed significant discrepancies between the Child Protective Service classification and case record abstraction. Child Protective Service classification considerably underestimated the rate of co-occurrence across multiple types of maltreatment. Neglect accompanied by physical and emotional abuse was the most common form. Some of the caretaker functioning variables distinguished the number of types of maltreatment. Based on the findings, future-research directions and practice implication were discussed. PMID:29225485

  10. Features of Coping with Disease in Iranian Multiple Sclerosis Patients: a Qualitative Study.

    Dehghani, Ali; Dehghan Nayeri, Nahid; Ebadi, Abbas

    2018-03-01

    Introduction: Coping with disease is of the main components improving the quality of life in multiple sclerosis patients. Identifying the characteristics of this concept is based on the experiences of patients. Using qualitative research is essential to improve the quality of life. This study was conducted to explore the features of coping with the disease in patients with multiple sclerosis. Method: In this conventional content analysis study, eleven multiple sclerosis patients from Iran MS Society in Tehran (Iran) participated. Purposive sampling was used to select participants. Data were gathered using semi structured interviews. To analyze data, a conventional content analysis approach was used to identify meaning units and to make codes and categories. Results: Results showed that features of coping with disease in multiple sclerosis patients consists of (a) accepting the current situation, (b) maintenance and development of human interactions, (c) self-regulation and (d) self-efficacy. Each of these categories is composed of sub-categories and codes that showed the perception and experience of patients about the coping with disease. Conclusion: Accordingly, a unique set of features regarding features of coping with the disease were identified among the patients with multiple sclerosis. Therefore, working to ensure the emergence of, and subsequent reinforcement of these features in MS patients can be an important step in improving the adjustment and quality of their lives.

  11. [Diabetes and autoimmune diseases: prevalence of celiac disease in children and adolescents with type 1 diabetes].

    Mont-Serrat, Camila; Hoineff, Claudio; Meirelles, Ricardo M R; Kupfer, Rosane

    2008-12-01

    Determine the prevalence of celiac disease in children and adolescents with type 1 diabetes mellitus (DM1) in attendance in Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE). Blood samples were analyzed in 120 children and adolescents with DM1 from IEDE Diabetes Clinic for the IgA antitissue-transglutaminase antibody and dosage of the seric IgA. Those with positive serology were guided for upper endoscopy with small-bowel biopsy to confirm the celiac disease. The antibody was positive in 3 of the 120 patients. The small-bowel biopsy was confirmatory in all of the positive patients, leading to a prevalence of celiac disease of 2.5% in the studied group. The prevalence of celiac disease is increased in children and adolescents with DM1 when compared with normality. As most are asymptomatic, it is recommended periodical screening of celiac disease in children with DM1.

  12. Multiple pharmacy use and types of pharmacies used to obtain prescriptions.

    Look, Kevin A; Mott, David A

    2013-01-01

    To evaluate trends and patterns in the prevalence of multiple pharmacy use (MPU) and to describe the number and types of pharmacies used by multiple pharmacy users from 2003 to 2009. Retrospective, cross-sectional, descriptive study. United States from 2003 to 2009. 89,941 responses to the Medical Expenditure Panel Survey over 7 years. Analysis of respondent pharmacy use behaviors. Annual use of more than one pharmacy and number and types of pharmacies used. MPU among patients using medications increased significantly during the study period (from 36.4% [95% CI 35.2-37.6] in 2003 to 43.2% [41.9-44.4] in 2009)-a relative increase of 18.7% ( P = 0.01). Multiple pharmacy users used between 2 and 17 different pharmacies per year to obtain prescription medications. Although approximately 70% of multiple pharmacy users used only two pharmacies, the proportion using three or more pharmacies increased from 24.1% (22.5-25.7) in 2003 to 29.1% (27.4-30.8) in 2009. Mail service pharmacy use had the largest relative increase among multiple pharmacy users during the study period (27.2%), and MPU was nearly twice as high (75%) among mail service users compared with non-mail service users. MPU is common on a national level and has increased greatly in recent years. Patient use of pharmacies that have the potential to share medication information electronically is low among multiple pharmacy users, suggesting increased workload for pharmacists and potential medication safety concerns. This has important implications for pharmacists, as it potentially impedes their ability to maintain accurate medication profiles for patients.

  13. Complex lipid trafficking in Niemann-Pick disease type C.

    Vanier, Marie T

    2015-01-01

    Niemann-Pick disease type C (NPC) is an atypical lysosomal storage disease resulting from mutations in one of two genes, either NPC1 or NPC2. Although a neurovisceral disorder, it is above all a neurodegenerative disease in the vast majority of patients. Not an enzyme deficiency, it is currently conceived as a lipid trafficking disorder. Impaired egress of cholesterol from the late endosomal/lysosomal (LE/L) compartment is a specific and key element of the pathogenesis, but other lipids, more specially sphingolipids, are also involved, and there are indications for further abnormalities. The full function of the NPC1 and NPC2 proteins is still unclear. This review provides a reappraisal of lipid storage and lysosomal enzymes activities in tissues/cells from NPC patients and animal models. It summarizes the current knowledge on the NPC1 and NPC2 proteins and their function in transport of cholesterol within the late endosomal-lysosomal compartment, with emphasis on differences between systemic organs and the brain; it also discusses regulation by membrane lipids of the NPC2-mediated cholesterol trafficking, interplay between cholesterol and sphingomyelin, the metabolic origin of glycosphingolipids stored in brain, and the putative role of free sphingoid bases in pathogenesis. Brief mention is finally made of diseases affecting other genes that were very recently shown to impact the "NPC pathway".

  14. Atuoradiographic detection of multiple sclerosis plaques with an ω3 (peripheral type benzodiazepine) binding site radiogland

    HAUW, J.J.; Sazdovitch, V.; Cornu, P.; Dubois, A.; Benavides, J.; Mac Kenzie, E.; Scatton, B.

    1989-01-01

    In Multiple Sclerosis (MS), the presence of monocyte-macrophages and microglial cells in active plaques is a constant feature. They are numerous at the border of active lesions where they constiture, with other cell types such as lymphocytes and oligodendrocytes the so-called flial wall. Monocyte-macrophages and microglial cells are thought to be directly involved in the process of demyelination. Some macrophages laden with meylin degradation products are also seen in the center of the plaqie, often located in the perivascular cuffs. In addition, astrocytic gliosis occurs in the center of the plaques. As all these cell types are richly endowed with ω3 sites, the feasibility of using ω3 site autoradiagraphy to detect the demyelination plaques in the brain of post-mortem cases of Multiple Sclerosis has been investigated. (Author). 8 refs

  15. Continued Kinematic and Photometric Investigations of Hierarchical Solar-type Multiple Star Systems

    Roberts, Lewis C. Jr.; Marinan, Anne D. [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena CA 91109 (United States); Tokovinin, Andrei [Cerro Tololo Inter-American Observatory, Casilla 603, La Serena (Chile); Mason, Brian D., E-mail: lewis.c.roberts@jpl.nasa.gov [U.S. Naval Observatory, 3450 Massachusetts Avenue, NW, Washington, DC 20392-5420 (United States)

    2017-03-01

    We observed 15 of the solar-type binaries within 67 pc of the Sun previously observed by the Robo-AO system in the visible, with the PHARO near-infrared camera and the PALM-3000 adaptive optics system on the 5 m Hale telescope. The physical status of the binaries is confirmed through common proper motion and detection of orbital motion. In the process, we detected a new candidate companion to HIP 95309. We also resolved the primary of HIP 110626 into a close binary, making that system a triple. These detections increase the completeness of the multiplicity survey of the solar-type stars within 67 pc of the Sun. Combining our observations of HIP 103455 with archival astrometric measurements and RV measurements, we are able to compute the first orbit of HIP 103455, showing that the binary has a 68 year period. We place the components on a color–magnitude diagram and discuss each multiple system individually.

  16. A novel multi-item joint replenishment problem considering multiple type discounts.

    Ligang Cui

    Full Text Available In business replenishment, discount offers of multi-item may either provide different discount schedules with a single discount type, or provide schedules with multiple discount types. The paper investigates the joint effects of multiple discount schemes on the decisions of multi-item joint replenishment. In this paper, a joint replenishment problem (JRP model, considering three discount (all-unit discount, incremental discount, total volume discount offers simultaneously, is constructed to determine the basic cycle time and joint replenishment frequencies of multi-item. To solve the proposed problem, a heuristic algorithm is proposed to find the optimal solutions and the corresponding total cost of the JRP model. Numerical experiment is performed to test the algorithm and the computational results of JRPs under different discount combinations show different significance in the replenishment cost reduction.

  17. MRI findings in patients with multiple lacunar infarcts manifesting hyperactive-type delirium

    Arahata, Yutaka; Motegi, Yoshimasa; Furuse, Masahiro; Watanabe, Masaki; Takahashi, Akira.

    1994-01-01

    MRI studies were carried out on 69 patients with multiple lacunar infarcts: 32 had hyperactive-type delirium and the other 37 were non-delirious controls. Between the two groups, there were no statistically significant differences in mean age and sex distribution. In the corona radiata and basal ganglia, the number of infarcts did not differ between the two groups. However, the extent of thalamic infarcts and periventricular hyperintensity (PVH), the maximal width of the third ventricle and Evans' ratio among the delirious patients were significantly larger than those in the controls. In conclusion, thalamic lesions and diffuse advanced PVH may have an intimate correlation in the development of hyperactive-type delirium in patients with multiple lacunar infarcts. (author)

  18. MRI findings in patients with multiple lacunar infarcts manifesting hyperactive-type delirium

    Arahata, Yutaka; Motegi, Yoshimasa; Furuse, Masahiro (Nakatsugawa Municipal General Hospital, Gifu (Japan)); Watanabe, Masaki; Takahashi, Akira

    1994-04-01

    MRI studies were carried out on 69 patients with multiple lacunar infarcts: 32 had hyperactive-type delirium and the other 37 were non-delirious controls. Between the two groups, there were no statistically significant differences in mean age and sex distribution. In the corona radiata and basal ganglia, the number of infarcts did not differ between the two groups. However, the extent of thalamic infarcts and periventricular hyperintensity (PVH), the maximal width of the third ventricle and Evans' ratio among the delirious patients were significantly larger than those in the controls. In conclusion, thalamic lesions and diffuse advanced PVH may have an intimate correlation in the development of hyperactive-type delirium in patients with multiple lacunar infarcts. (author).

  19. Identification of multiple HPV types on spermatozoa from human sperm donors

    Kaspersen, Maja D; Larsen, Peter B; Ingerslev, Hans Jakob

    2011-01-01

    Human papillomaviruses (HPV) may cause sexually transmitted disease. High-risk types of HPV are involved in the development of cervical cell dysplasia, whereas low-risk types may cause genital condyloma. Despite the association between HPV and cancer, donor sperm need not be tested for HPV...... according to European regulations. Consequently, the potential health risk of HPV transmission by donor bank sperm has not been elucidated, nor is it known how HPV is associated with sperm. The presence of 35 types of HPV was examined on DNA from semen samples of 188 Danish sperm donors using a sensitive...

  20. A simplified approach for evaluating multiple test outcomes and multiple disease states in relation to the exercise thallium-201 stress test in suspected coronary artery disease

    Pollock, S.G.; Watson, D.D.; Gibson, R.S.; Beller, G.A.; Kaul, S.

    1989-01-01

    This study describes a simplified approach for the interpretation of electrocardiographic and thallium-201 imaging data derived from the same patient during exercise. The 383 patients in this study had also undergone selective coronary arteriography within 3 months of the exercise test. This matrix approach allows for multiple test outcomes (both tests positive, both negative, 1 test positive and 1 negative) and multiple disease states (no coronary artery disease vs 1-vessel vs multivessel coronary artery disease). Because this approach analyzes the results of 2 test outcomes simultaneously rather than serially, it also negates the lack of test independence, if such an effect is present. It is also demonstrated that ST-segment depression on the electrocardiogram and defects on initial thallium-201 images provide conditionally independent information regarding the presence of coronary artery disease in patients without prior myocardial infarction. In contrast, ST-segment depression on the electrocardiogram and redistribution on the delayed thallium-201 images may not provide totally independent information regarding the presence of exercise-induced ischemia in patients with or without myocardial infarction

  1. Using Multiple Types of Studies in Systematic Reviews of Health Care Interventions – A Systematic Review

    Peinemann, Frank; Tushabe, Doreen Allen; Kleijnen, Jos

    2013-01-01

    Background A systematic review may evaluate different aspects of a health care intervention. To accommodate the evaluation of various research questions, the inclusion of more than one study design may be necessary. One aim of this study is to find and describe articles on methodological issues concerning the incorporation of multiple types of study designs in systematic reviews on health care interventions. Another aim is to evaluate methods studies that have assessed whether reported effects differ by study types. Methods and Findings We searched PubMed, the Cochrane Database of Systematic Reviews, and the Cochrane Methodology Register on 31 March 2012 and identified 42 articles that reported on the integration of single or multiple study designs in systematic reviews. We summarized the contents of the articles qualitatively and assessed theoretical and empirical evidence. We found that many examples of reviews incorporating multiple types of studies exist and that every study design can serve a specific purpose. The clinical questions of a systematic review determine the types of design that are necessary or sufficient to provide the best possible answers. In a second independent search, we identified 49 studies, 31 systematic reviews and 18 trials that compared the effect sizes between randomized and nonrandomized controlled trials, which were statistically different in 35%, and not different in 53%. Twelve percent of studies reported both, different and non-different effect sizes. Conclusions Different study designs addressing the same question yielded varying results, with differences in about half of all examples. The risk of presenting uncertain results without knowing for sure the direction and magnitude of the effect holds true for both nonrandomized and randomized controlled trials. The integration of multiple study designs in systematic reviews is required if patients should be informed on the many facets of patient relevant issues of health care

  2. Multiple Endocrine Neoplasia Type 1 (MEN1) and Pituitary Adenoma Predisposition (PAP) in Northern Finland

    Vierimaa, O. (Outi)

    2008-01-01

    Abstract Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome characterized by parathyroid, gastroenteropancreatic and pituitary neuroendocrine tumours. In Northern Finland, two founder mutations of the MEN1 gene (1466del12, 1657insC) accounting for the majority of the MEN1 cases, have common ancestors born in the 18th and 19th centuries, respectively. Three small clusters of familial pituitary adenoma have also been detected, two of which could be linked by genealogy to a ...

  3. CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis

    Sellebjerg, Finn; Madsen, Hans O; Jensen, Claus V

    2000-01-01

    Chemokines and matrix metalloproteinases (MMPs) appear to be crucial in leukocyte recruitment to the central nervous system in multiple sclerosis (MS). CCR5 delta32, a truncated allele of the CC chemokine receptor CCR5 gene encoding a non-functional receptor, did not confer protection from MS. CCR5...... delta32 was, however, associated with a lower risk of recurrent clinical disease activity. High CSF levels of MMP-9 activity were also associated with recurrent disease activity. These results directly link intrathecal inflammation to disease activity in patients with MS, suggesting that treatments...... targeting CCR5 or treatment with MMP inhibitors may attenuate disease activity in MS...

  4. A case of disseminated hydatid disease by surgery involving multiple organs

    Asli Tanrivermis Sayit

    2014-09-01

    Full Text Available Hydatid disease is the most common parasitic infection in the world, and is caused by the parasite Echinococcus granulosus. The most common site of this disease is the liver (75%, followed by the lungs, kidney, bones, and brain. Multiple abdominal organ and peritoneal involvement can also be seen in some cases. The dissemination of hydatid cyst disease can develop spontaneously or secondary to trauma or surgery. Here, we present the case of a 69-year-old man with multiple cyst hydatidosis, who underwent surgery for acute appendicitis approximately 20 years previously. Computed tomography of the abdomen shows the multiple active and inactive cystic lesions in the liver, spleen, right kidney, and mesentery. This patient required surgery several times, as well as medical treatment, after the rupture of a mesenteric hydatid cyst during the appendectomy. Combined anthelmintic treatment was recommended to the patient who refused further surgical treatment.

  5. Beyond PrPres Type 1/Type 2 Dichotomy in Creutzfeldt-Jakob Disease

    Simon, Stéphanie; Lugan, Séverine; Bilheude, Jean-Marc; Perret-Liaudet, Armand; Ironside, James W.; Haik, Stéphane; Basset-Leobon, Christelle; Lacroux, Caroline; Peoch', Katell; Streichenberger, Nathalie; Langeveld, Jan; Head, Mark W.; Grassi, Jacques; Hauw, Jean-Jacques; Schelcher, Francois; Delisle, Marie Bernadette; Andréoletti, Olivier

    2008-01-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrPres) identified on Western blotting (type 1 or type 2). These biochemically distinct PrPres types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrPres in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrPres and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrPSc) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrPres were identified. Despite this, the other two biochemical assays found that PrPSc from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrPSc subgroups were identified that correlated with the current sCJD clinico-pathological classification. In iCJD, four similar biochemical clusters were observed, but these did not correlate to any particular PRNP 129 polymorphism or western blot PrPres pattern. The identification of four different PrPSc biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrPres isoform provides an alternative biochemical definition of PrPSc diversity and new insight in the perception of Human TSE agents variability. PMID:18389084

  6. Evolution of high yielding chickpea varieties, having improved plant type and disease resistance, through induced mutations

    Sadiq, M.; Hussan, M.; Haq, M.A.

    1989-01-01

    The breeding programme on the use of induced mutations, in chickpea for genetic variability for better plant type, grain yield and disease resistance has been started. The chickpea mutant variety is one of the leading varieties being extensively grown throughout Pakistan and has played its role in stabilizing the chickpea production in the country. Four chickpea varieties were treated, each with two dosed of gamma rays. The main purpose of the mutagenic treatment of these varieties/cultivars, was induce multiple resistance. (A.B.)

  7. The co-occurrence of multiple sclerosis and type 1 diabetes: shared aetiologic features and clinical implication for MS aetiology.

    Tettey, Prudence; Simpson, Steve; Taylor, Bruce V; van der Mei, Ingrid A F

    2015-01-15

    We reviewed the evidence for the co-occurrence of type 1 diabetes mellitus (T1D) and multiple sclerosis (MS), and assessed the clinical significance of this association and the shared aetiological features of the two diseases. T1D and MS contribute considerably to the burden of autoimmune diseases in young adults. The co-occurrence of MS and T1D has been reported by a number of studies, suggesting that the two conditions share one or more aetiological components. Both conditions have been associated with distinct human leukocyte antigen (HLA) haplotypes but share a number of similarities in clinical, epidemiological and immunological features, leading to suggestions of possible common mechanisms of development. While underlying genetic factors may be important for the co-occurrence of both conditions, some evidence suggests that environmental factors such as vitamin D deficiency may also modulate an individual's risk for the development of both conditions. Evidence on whether the co-occurrence of the two autoimmune conditions will affect the disease course and severity of MS is merely absent. Further studies need to be conducted to ascertain whether the neuropathology associated with T1D might influence the disease course and contribute to the severity of MS. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. E4 antibodies facilitate detection and type-assignment of active HPV infection in cervical disease.

    Heather Griffin

    Full Text Available High-risk human papillomavirus (HPV infections are the cause of nearly all cases of cervical cancer. Although the detection of HPV DNA has proved useful in cervical diagnosis, it does not necessarily predict disease presence or severity, and cannot conclusively identify the causative type when multiple HPVs are present. Such limitations may be addressed using complementary approaches such as cytology, laser capture microscopy, and/or the use of infection biomarkers. One such infection biomarker is the HPV E4 protein, which is expressed at high level in cells that are supporting (or have supported viral genome amplification. Its distribution in lesions has suggested a role in disease staging. Here we have examined whether type-specific E4 antibodies may also allow the identification and/or confirmation of causal HPV-type. To do this, type-specific polyclonal and monoclonal antibodies against three E4 proteins (HPV-16, -18, and -58 were generated and validated by ELISA and western blotting, and by immunohistochemistry (IHC staining of epithelial rafts containing these individual HPV types. Type-specific detection of HPV and its associated disease was subsequently examined using formalin-fixed paraffin-embedded cervical intra-epithelial neoplasias (CIN, (n = 247 and normal controls (n = 28. All koilocytotic CIN1 lesions showed type-specific E4 expression of their respective HPV types. Differences were noted amongst E4 expression patterns in CIN3. HPV-18 E4 was not detected in any of the 6 HPV-18 DNA-positive CIN3 lesions examined, whereas in HPV-16 and -58 CIN3, 28/37 (76% and 5/9 (55.6% expressed E4 respectively, usually in regions of epithelial differentiation. Our results demonstrate that type-specific E4 antibodies can be used to help establish causality, as may be required when multiple HPV types are detected. The unique characteristics of the E4 biomarker suggest a role in diagnosis and patient management particularly when used in combination.

  9. Hemolytic disease of the fetus and newborn due to multiple maternal antibodies.

    Markham, Kara Beth; Rossi, Karen Q; Nagaraja, Haikady N; O'Shaughnessy, Richard W

    2015-07-01

    The objective of the study was to determine whether women with combinations of red blood cell antibodies are more likely to develop significant hemolytic disease of the fetus and newborn than those with single antibodies. A retrospective exposure cohort study was conducted of pregnant women with red blood cell antibodies. The development of significant hemolytic disease of the fetus and newborn was then compared between patients with single antibodies and those with multiple antibodies. Data analysis was limited to pregnancies delivering since the year 2000. Thirteen percent of the patients referred to our program had multiple red blood cell antibodies. Odds of developing significant hemolytic disease of the fetus and newborn for patients with anti-Rh(D) combined with at least 1 additional red blood cell antibody were 3.65 times the odds for women with anti-Rh(D) antibodies in isolation (95% confidence interval, 1.84-7.33). In the setting of multiple antibodies including anti-Rh(D), Rh-positive fetuses/neonates have an increased odds of developing significant hemolytic disease even if the fetus is negative for the other corresponding red blood cell antigen. Women with multiple red blood cell antibodies are more likely to develop significant hemolytic disease of the fetus and newborn than those with a single antibody especially in the presence of anti-(Rh)D. This pathophysiology may suggest a more aggressive immune response in women who develop more than 1 red blood cell antibody. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Glycogen storage disease type I: clinical and laboratory profile

    Berenice L. Santos

    2014-12-01

    Full Text Available OBJECTIVES: To characterize the clinical, laboratory, and anthropometric profile of a sample of Brazilian patients with glycogen storage disease type I managed at an outpatient referral clinic for inborn errors of metabolism. METHODS: This was a cross-sectional outpatient study based on a convenience sampling strategy. Data on diagnosis, management, anthropometric parameters, and follow-up were assessed. RESULTS: Twenty-one patients were included (median age 10 years, range 1-25 years, all using uncooked cornstarch therapy. Median age at diagnosis was 7 months (range, 1-132 months, and 19 patients underwent liver biopsy for diagnostic confirmation. Overweight, short stature, hepatomegaly, and liver nodules were present in 16 of 21, four of 21, nine of 14, and three of 14 patients, respectively. A correlation was found between height-for-age and BMI-for-age Z-scores (r = 0.561; p = 0.008. CONCLUSIONS: Diagnosis of glycogen storage disease type I is delayed in Brazil. Most patients undergo liver biopsy for diagnostic confirmation, even though the combination of a characteristic clinical presentation and molecular methods can provide a definitive diagnosis in a less invasive manner. Obesity is a side effect of cornstarch therapy, and appears to be associated with growth in these patients.

  11. Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm.

    Giovannoni, Gavin

    2018-06-01

    The treatment of multiple sclerosis is evolving rapidly with 11 classes of disease-modifying therapies (DMTs). This article provides an overview of a new classification system for DMTs and treatment paradigm for using these DMTs effectively and safely. A summary of research into the use of more active approaches to early and effective treatment of multiple sclerosis with defined treatment targets of no evident disease activity (NEDA). New insights are discussed that is allowing the field to begin to tackle more advanced multiple sclerosis, including people with multiple sclerosis using wheelchairs. However, the need to modify expectations of what can be achieved in more advanced multiple sclerosis are discussed; in particular, the focus on neuronal systems with reserve capacity, for example, upper limb, bulbar and visual function. The review describes a new more active way of managing multiple sclerosis and concludes with a call to action in solving the problem of slow adoption of innovations and the global problem of untreated, or undertreated, multiple sclerosis.

  12. [Effects of nutritional status on the multiple sclerosis disease: systematic review].

    Ródenas Esteve, Irene; Wanden-Berghe, Carmina; Sanz-Valero, Javier

    2018-01-19

    To review the available scientific literature about the effects of nutritional status on the multiple sclerosis disease. A systematic review of the scientific literature in the Medline (PubMed), Scopus, Cochrane Library and Web of Science databases through November 2016. Search equation: ("Multiple Sclerosis"[Mesh] OR "Multiple Sclerosis"[Title/Abstract] OR "Disseminated Sclerosis"[Title/Abstract] OR "Multiple Sclerosis Acute Fulminating"[Title/Abstract]) AND ("Nutritional Status"[Mesh] OR "Nutritional Status"[Title/Abstract] OR "Nutrition Status"[Title/Abstract]). The quality of the selected articles was discussed using the STROBE questionnaire. The search was completed through experts inquiry and additional review of the bibliographic references included in the selected papers. The concordance between authors (Kappa index) had to be higher than 80% for inclusion in this review. Of the 160 references recovered, after applying inclusion and exclusion criteria, 29 articles were selected for review. Concordance between evaluators was 100.00%. The most studies established vitamin D levels. Others focused their research on finding out which nutrient deficits might be related to the multiple sclerosis development. Vitamin D may influence multiple sclerosis improvement. Sunlight and physical activity would be important factors, with nutritional status, in the course of this disease. It is necessary to produce new specific works that will delve into the subject to find out more about the relationship between nutritional status and multiple sclerosis.

  13. Complex heterogeneous tissue constructs containing multiple cell types prepared by inkjet printing technology.

    Xu, Tao; Zhao, Weixin; Zhu, Jian-Ming; Albanna, Mohammad Z; Yoo, James J; Atala, Anthony

    2013-01-01

    This study was designed to develop a versatile method for fabricating complex and heterogeneous three-dimensional (3D) tissue constructs using simultaneous ink-jetting of multiple cell types. Human amniotic fluid-derived stem cells (hAFSCs), canine smooth muscle cells (dSMCs), and bovine aortic endothelial cells (bECs), were separately mixed with ionic cross-linker calcium chloride (CaCl(2)), loaded into separate ink cartridges and printed using a modified thermal inkjet printer. The three cell types were delivered layer-by-layer to pre-determined locations in a sodium alginate-collagen composite located in a chamber under the printer. The reaction between CaCl(2) and sodium alginate resulted in a rapid formation of a solid composite gel and the printed cells were anchored in designated areas within the gel. The printing process was repeated for several cycles leading to a complex 3D multi-cell hybrid construct. The biological functions of the 3D printed constructs were evaluated in vitro and in vivo. Each of the printed cell types maintained their viability and normal proliferation rates, phenotypic expression, and physiological functions within the heterogeneous constructs. The bioprinted constructs were able to survive and mature into functional tissues with adequate vascularization in vivo. These findings demonstrate the feasibility of fabricating complex heterogeneous tissue constructs containing multiple cell types using inkjet printing technology. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. A minimal unified model of disease trajectories captures hallmarks of multiple sclerosis

    Kannan, Venkateshan

    2017-03-29

    Multiple Sclerosis (MS) is an autoimmune disease targeting the central nervous system (CNS) causing demyelination and neurodegeneration leading to accumulation of neurological disability. Here we present a minimal, computational model involving the immune system and CNS that generates the principal subtypes of the disease observed in patients. The model captures several key features of MS, especially those that distinguish the chronic progressive phase from that of the relapse-remitting. In addition, a rare subtype of the disease, progressive relapsing MS naturally emerges from the model. The model posits the existence of two key thresholds, one in the immune system and the other in the CNS, that separate dynamically distinct behavior of the model. Exploring the two-dimensional space of these thresholds, we obtain multiple phases of disease evolution and these shows greater variation than the clinical classification of MS, thus capturing the heterogeneity that is manifested in patients.

  15. [Oral diseases in auto-immune polyendocrine syndrome type 1].

    Proust-Lemoine, Emmanuelle; Guyot, Sylvie

    2017-09-01

    Auto-immune polyendocrine syndrome type 1 (APS1) also called Auto-immune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) is a rare monogenic childhood-onset auto-immune disease. This autosomal recessive disorder is caused by mutations in the auto-immune regulator (AIRE) gene, and leads to autoimmunity targeting peripheral tissues. There is a wide variability in clinical phenotypes in patients with APSI, with auto-immune endocrine and non-endocrine disorders, and chronic mucocutaneous candidiasis. These patients suffer from oral diseases such as dental enamel hypoplasia and candidiasis. Both are frequently described, and in recent series, enamel hypoplasia and candidiasis are even the most frequent components of APS1 together with hypoparathyroidism. Both often occur during childhood (before 5 years old for canrdidiasis, and before 15 years old for enamel hypoplasia). Oral candidiasis is recurrent all life long, could become resistant to azole antifungal after years of treatment, and be carcinogenic, leading to severe oral squamous cell carcinoma. Oral components of APS1 should be diagnosed and rigorously treated. Dental enamel hypoplasia and/or recurrent oral candidiasis in association with auto-immune diseases in a young child should prompt APS1 diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Discontinuing disease-modifying therapy in progressive multiple sclerosis: can we stop what we have started?

    Lonergan, Roisin

    2012-02-01

    Disease-modifying therapy is ineffective in disabled patients (Expanded Disability Status Scale [EDSS] > 6.5) with secondary progressive multiple sclerosis (MS) without relapses, or in primary progressive MS. Many patients with secondary progressive MS who initially had relapsing MS continue to use disease-modifying therapies. The enormous associated costs are a burden to health services. Regular assessment is recommended to guide discontinuation of disease-modifying therapies when no longer beneficial, but this is unavailable to many patients, particularly in rural areas. The objectives of this study are as follows: 1. To observe use of disease-modifying therapies in patients with progressive multiple sclerosis and EDSS > 6.5. 2. To examine approaches used by a group of international MS experts to stopping-disease modifying therapies in patients with secondary progressive MS without relapses. During an epidemiological study in three regions of Ireland (southeast Dublin city, and Wexford and Donegal Counties), we recorded details of disease-modifying therapies in patients with progressive MS and EDSS > 6.5. An e-questionnaire was sent to 26 neurologists with expert knowledge of MS, asking them to share their approach to stopping disease-modifying therapies in patients with secondary progressive MS. Three hundred and thirty-six patients were studied: 88 from southeast Dublin, 99 from Wexford and 149 from Donegal. Forty-four had EDSS > 6.5: 12 were still using disease-modifying therapies. Of the surveyed neurologists, 15 made efforts to stop disease-modifying therapies in progressive multiple sclerosis, but most did not insist. A significant proportion (12 of 44 patients with progressive MS and EDSS > 6.5) was considered to be receiving therapy without benefit. Eleven of the 12 were from rural counties, reflecting poorer access to neurology services. The costs of disease-modifying therapies in this group (>170,000 euro yearly) could be re-directed towards development

  17. Klinefelter's Syndrome with Seizure, Pseudohypoparathyroidism Type Ib and Multiple Endocrine Dysfunctions

    Chwen-Yi Yang

    2005-12-01

    Full Text Available Klinefelter's syndrome is rarely associated with hypocalcemia, especially pseudohypoparathyroidism (PHP type Ib. We describe a case of Klinefelter's syndrome associated with seizure, PHP type Ib and multiple endocrine dysfunctions. A 19-year-old Taiwanese male was admitted due to seizures with loss of consciousness. He had been diagnosed with Klinefelter's syndrome with seizure disorder and hypocalcemia 3 months previously. Physical examination revealed eunuchoidism but no osteodystrophy, while laboratory data revealed severe hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone. Chromosomal study showed 47, XXY. Osteoporosis was found on chest and abdominal radiography. Dense calcification in the cerebrum and cerebellum was shown on brain computed tomography and magnetic resonance imaging. Elevation of the patient's serum calcium level was noted after vitamin D and calcium carbonate supplements were given. Klinefelter's syndrome is rarely associated with PHP type Ib; our patient's hypocalcemia improved after long-term aggressive treatment.

  18. Prevalence of Convergence Insufficiency-Type Symptomatology in Parkinson's Disease.

    Law, Caroline; Chriqui, Estefania; Kergoat, Marie-Jeanne; Leclerc, Bernard-Simon; Panisset, Michel; Irving, Elizabeth L; Postuma, Ronald B; Chouinard, Sylvain; Kergoat, Hélène

    2017-09-01

    Individuals with Parkinson's disease (PD) often present with visual symptoms (e.g., difficulty in reading, double vision) that can also be found in convergence insufficiency (CI). Our objective was to estimate the prevalence of CI-type visual symptomatology in individuals with PD, in comparison with controls. Participants ≥50 years with (n=300) and without (n=300) PD were recruited. They were administered the Convergence Insufficiency Symptom Survey (CISS-15) over the phone. A score of ≥21 on the CISS-15, considered positive for CI-type symptomatology, served as the cutoff. Data from individuals (n=87 with, n=94 without PD) who were approached but who reported having a known oculovisual condition were analysed separately. Student's t test and chi-square at the 0.05 level were employed for statistical significance. A total of 29.3% of participants with versus 7.3% without PD presented with a score of ≥21 on the CISS-15 (p=0.001). Of the participants having a known oculovisual condition, 39.1% with versus 19.1% without PD presented with a score of ≥21 on the CISS-15 (p=0.01). The prevalence of CI-type visual symptoms is higher in individuals with versus without PD whether or not they have a coexisting oculovisual condition. These results suggest that PD per se places individuals with the disease at greater risk of visual symptomatology. These results further underline the importance of providing regular eye exams for individuals with PD.

  19. Influence of Multiple Infection and Relatedness on Virulence: Disease Dynamics in an Experimental Plant Population and Its Castrating Parasite

    Buono, Lorenza; López-Villavicencio, Manuela; Shykoff, Jacqui A.; Snirc, Alodie; Giraud, Tatiana

    2014-01-01

    The level of parasite virulence, i.e., the decrease in host's fitness due to a pathogen, is expected to depend on several parameters, such as the type of the disease (e.g., castrating or host-killing) and the prevalence of multiple infections. Although these parameters have been extensively studied theoretically, few empirical data are available to validate theoretical predictions. Using the anther smut castrating disease on Silene latifolia caused by Microbotryum lychnidis-dioicae, we studied the dynamics of multiple infections and of different components of virulence (host death, non-recovery and percentage of castrated stems) during the entire lifespan of the host in an experimental population. We monitored the number of fungal genotypes within plants and their relatedness across five years, using microsatellite markers, as well as the rates of recovery and host death in the population. The mean relatedness among genotypes within plants remained at a high level throughout the entire host lifespan despite the dynamics of the disease, with recurrent new infections. Recovery was lower for plants with multiple infections compared to plants infected by a single genotype. As expected for castrating parasites, M. lychnidis-dioicae did not increase host mortality. Mortality varied across years but was generally lower for plants that had been diseased the preceding year. This is one of the few studies to have empirically verified theoretical expectations for castrating parasites, and to show particularly i) that castrated hosts live longer, suggesting that parasites can redirect resources normally used in reproduction to increase host lifespan, lengthening their transmission phase, and ii) that multiple infections increase virulence, here in terms of non-recovery and host castration. PMID:24892951

  20. Fisetin Acts on Multiple Pathways to Reduce the Impact of Age and Disease on CNS Function

    Maher, Pamela

    2017-01-01

    It is becoming increasingly clear that neurological diseases are multi-factorial involving disruptions in multiple cellular systems. Thus, while each disease has its own initiating mechanisms and pathologies, certain common pathways appear to be involved in most, if not all, neurological diseases described to date. Thus, it is unlikely that modulating only a single factor will be effective at either preventing disease development or slowing disease progression. A better approach is to identify small (fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also activate key neurotrophic factor signaling pathways. In addition, it has anti-inflammatory activity against microglial cells and inhibits the activity of lipoxygenases, thereby reducing the production of pro-inflammatory eicosanoids and their by-products. This wide range of actions suggests that fisetin has the ability to reduce the impact of age-related neurological diseases on brain function. PMID:25961687

  1. Genomic screening for dissection of a complex disease: The multiple sclerosis phenotype

    Haines, J.L.; Bazyk, A.; Gusella, J.F. [Massachusetts General Hospital, Boston, MA (United States)] [and others

    1994-09-01

    Application of positional cloning to diseases with a complex etiology is fraught with problems. These include undefined modes of inheritance, heterogeneity, and epistasis. Although microsatellite markers now make genotyping the genome a straightforward task, no single analytical method is available to efficiently and accurately use these data for a complex disease. We have developed a multi-stage genomic screening strategy which uses a combination of non-parametric approaches (Affected Pedigree Member (APM) linkage analysis and robust sib pair analysis (SP)), and the parametric lod score approach (using four different genetic models). To warrant follow-up, a marker must have two or more of: a nominal P value of 0.05 or less on the non-parametric tests, or a lod score greater than 1.0 for any model. Two adjacent markers each fulfilling one criterion are also considered for follow-up. These criteria were determined both by simulation studies and our empirical experience in screening a large number of other disorders. We applied this approach to multiple sclerosis (MS), a complex neurological disorder with a strong but ill-defined genetic component. Analysis of the first 91 markers from our screen of 55 multiplex families found 5 markers which met the SP criteria, 13 markers which met the APM criteria, and 8 markers which met the lod score criteria. Five regions (on chromosomes 2, 4, 7, 14, and 19) met our overall criteria. However, no single method identified all of these regions, suggesting that each method is sensitive to various (unknown) influences. The chromosome 14 results were not supported by follow-up typing and analysis of markers in that region, but the chromosome 19 results remain well supported. Updated screening results will be presented.

  2. Nondiabetic renal disease in patients with type 2 diabetes

    Ikram Mami

    2017-01-01

    Full Text Available Diabetic nephropathy (DN is one of the major complications of type 2 diabetes mellitus (T2DM. The diagnosis of DN is mostly clinical. Kidney biopsy is indicated only if nondiabetic renal disease (NDRD is suspected. This study is aimed to assess the prevalence of NDRD and to determine predictor and prognostic factors of DN, NDRD. It was a retrospective analytic study including T2DM patients in whom renal biopsies were performed at our department from 1988 to 2014. Seventy-five patients were included. Mean age was 52.7 years with sex ratio at 1.56. Renal biopsy findings were isolated NDRD in 33 cases, NDRD superimposed on DN in 24 cases, and isolated DN in 18 cases. Most common NDRD found were focal segmental glomerulosclerosis (21% and membranous nephropathy (19%. Multivariate analysis showed that the absence of ischemic heart disease [odds ratio (OR = 0.178, 95% confidence interval (CI = 0.041–0.762], absence of peripheral vascular disease (OR = 0.173, 95% CI = 0.045–0.669, and presence of hematuria (OR = 7.200, 95%CI = 0.886–58.531 were independent predictors of NDRD. 24 patients reached end-stage renal disease 55% in DN group, 16% in DN associated to NDRD group, and 30% in NDRD group. The prevalence of NDRD found in our study confirmed usefulness of renal biopsy in patients with T2DM, especially in those without degenerative complications, hypertension, and insulin therapy.

  3. Multiple sclerosis masquerading as Alzheimer-type dementia: Clinical, radiological and pathological findings.

    Tobin, W O; Popescu, B F; Lowe, V; Pirko, I; Parisi, J E; Kantarci, K; Fields, J A; Bruns, M B; Boeve, B F; Lucchinetti, C F

    2016-04-01

    We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology. Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex. Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry. © The Author(s), 2015.

  4. Serological prevalence of celiac disease in Brazilian population of multiple sclerosis, neuromyelitis optica and myelitis.

    de Oliveira, Pérola; de Carvalho, Daniel Rocha; Brandi, Ivar Viana; Pratesi, Riccardo

    2016-09-01

    Comorbidity of celiac disease with demyelinating diseases of the central nervous system has been reported since the 1960s. The objective of this study was to determine the serological prevalence of celiac disease in the largest series of patients diagnosed with multiple sclerosis, neuromyelitis optica, or myelitis. A prevalence study was conducted with patients evaluated at Sarah Network of Rehabilitation Hospitals between March 2012 and September 2013. They were previously diagnosed with multiple sclerosis, neuromyelitis optica, or idiopathic myelitis. The serum levels of antibodies against tissue transglutaminase and endomysium were assessed. Of the 379 patients evaluated, 249 (65.70%) were diagnosed with multiple sclerosis, 37 (9.56%) with neuromyelitis optica, and 96 (24.54%) with idiopathic myelitis. Two patients (0.53%), one with multiple sclerosis and other with myelitis, tested positive for both antibodies. Our study do not confirm the relationship between celiac serological antibodies with multiple sclerosis, neuromyelitis optica and inflammatory myelitis of an unknown etiology. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Metformin in Patients With Type 2 Diabetes and Kidney Disease

    Inzucchi, Silvio E.; Lipska, Kasia J.; Mayo, Helen; Bailey, Clifford J.; McGuire, Darren K.

    2015-01-01

    IMPORTANCE Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis. OBJECTIVE To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. EVIDENCE ACQUISITION In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial. RESULTS Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus

  6. Improved double-multiple streamtube model for the Darrieus-type vertical axis wind turbine

    Berg, D. E.

    Double streamtube codes model the curved blade (Darrieus-type) vertical axis wind turbine (VAWT) as a double actuator fish arrangement (one half) and use conservation of momentum principles to determine the forces acting on the turbine blades and the turbine performance. Sandia National Laboratories developed a double multiple streamtube model for the VAWT which incorporates the effects of the incident wind boundary layer, nonuniform velocity between the upwind and downwind sections of the rotor, dynamic stall effects and local blade Reynolds number variations. The theory underlying this VAWT model is described, as well as the code capabilities. Code results are compared with experimental data from two VAWT's and with the results from another double multiple streamtube and a vortex filament code. The effects of neglecting dynamic stall and horizontal wind velocity distribution are also illustrated.

  7. Superficial Type of Multiple Basal Cell Carcinomas: Detailed Comparative Study of Its Dermoscopic and Histopathological Findings

    Hirofuji, A.; Takiguchi, K.; Nakamura, K.; Kuramochi, A.; Tsuchida, T.; Arai, E.; Shimizu, M.

    2011-01-01

    We investigated in detail the dermoscopic and histopathological findings in a case of a superficial type of multiple basal cell carcinomas (BCCs). These multiple lesions (occurring in the chest, neck, and back) showed three different findings, respectively. Dermoscopy of the erythematous and brown-colored patch on the anterior chest showed spoke wheel areas, and the histopathological cross-section revealed vertical spoke wheel structures. In the black- and brown-colored patch at the neck, the dermatoscopy showed a maple leaf-like structure, which was in accordance with the strengthening of the histological lateral connection of the lesion. The brown-colored patch of the lateral back histologically showed irregularly enlarged spoke wheel-like areas with peripheral increased melanin pigments, which correlated with the dark black color of dermoscopic maple leaf-like areas. The vertical spoke wheel areas by dermatoscopy revealed a horizontal spoke wheel structure by histopathology

  8. Superficial Type of Multiple Basal Cell Carcinomas: Detailed Comparative Study of Its Dermoscopic and Histopathological Findings

    Akiko Hirofuji

    2011-01-01

    Full Text Available We investigated in detail the dermoscopic and histopathological findings in a case of a superficial type of multiple basal cell carcinomas (BCCs. These multiple lesions (occurring in the chest, neck, and back showed three different findings, respectively. Dermoscopy of the erythematous and brown-colored patch on the anterior chest showed spoke wheel areas, and the histopathological cross-section revealed vertical spoke wheel structures. In the black- and brown-colored patch at the neck, the dermatoscopy showed a maple leaf-like structure, which was in accordance with the strengthening of the histological lateral connection of the lesion. The brown-colored patch of the lateral back histologically showed irregularly enlarged spoke wheel-like areas with peripheral increased melanin pigments, which correlated with the dark black color of dermoscopic maple leaf-like areas. The vertical spoke wheel areas by dermatoscopy revealed a horizontal spoke wheel structure by histopathology.

  9. Terahertz optical-Hall effect for multiple valley band materials: n-type silicon

    Kuehne, P.; Hofmann, T.; Herzinger, C.M.; Schubert, M.

    2011-01-01

    The optical-Hall effect comprises generalized ellipsometry at long wavelengths on samples with free-charge carriers placed within external magnetic fields. Measurement of the anisotropic magneto-optic response allows for the determination of the free-charge carrier properties including spatial anisotropy. In this work we employ the optical-Hall effect at terahertz frequencies for analysis of free-charge carrier properties in multiple valley band materials, for which the optical free-charge carrier contributions originate from multiple Brillouin-zone conduction or valence band minima or maxima, respectively. We investigate exemplarily the room temperature optical-Hall effect in low phosphorous-doped n-type silicon where free electrons are located in six equivalent conduction-band minima near the X-point. We simultaneously determine their free-charge carrier concentration, mobility, and longitudinal and transverse effective mass parameters.

  10. Multiple schwannomas of cauda equine in the absence of von Recklinghausen's disease

    Kayaoglu, Cetin R.; Sengul, G.; Aydin, Ismail H.

    2007-01-01

    Multiple schwannomas in the absence of neurofibromatosis is rarely reported in the literature. We present a 56-year-old female with a history of severe leg and back pain on the left side for one year. Magnetic resonance imaging revealed 4 schwannomas located in the cauda equine in the absence of von Recklinghausen's disease. (author)

  11. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy

    Coles, Alasdair J; Twyman, Cary L; Arnold, Douglas L

    2012-01-01

    The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment....

  12. Feasibility of large-scale deployment of multiple wearable sensors in Parkinson's disease

    Silva de Lima, A.L.; Hahn, T.; Evers, L.J.W.; Vries, N.M. de; Cohen, E.; Afek, M.; Bataille, L.; Daeschler, M.; Claes, K.; Boroojerdi, B.; Terricabras, D.; Little, M.A.; Baldus, H.; Bloem, B.R.; Faber, M.J.

    2017-01-01

    Wearable devices can capture objective day-to-day data about Parkinson's Disease (PD). This study aims to assess the feasibility of implementing wearable technology to collect data from multiple sensors during the daily lives of PD patients. The Parkinson@home study is an observational, two-cohort

  13. Comparison of Intelligibility Measures for Adults with Parkinson's Disease, Adults with Multiple Sclerosis, and Healthy Controls

    Stipancic, Kaila L.; Tjaden, Kris; Wilding, Gregory

    2016-01-01

    Purpose: This study obtained judgments of sentence intelligibility using orthographic transcription for comparison with previously reported intelligibility judgments obtained using a visual analog scale (VAS) for individuals with Parkinson's disease and multiple sclerosis and healthy controls (K. Tjaden, J. E. Sussman, & G. E. Wilding, 2014).…

  14. Perceptual Measures of Speech from Individuals with Parkinson's Disease and Multiple Sclerosis: Intelligibility and beyond

    Sussman, Joan E.; Tjaden, Kris

    2012-01-01

    Purpose: The primary purpose of this study was to compare percent correct word and sentence intelligibility scores for individuals with multiple sclerosis (MS) and Parkinson's disease (PD) with scaled estimates of speech severity obtained for a reading passage. Method: Speech samples for 78 talkers were judged, including 30 speakers with MS, 16…

  15. Egg consumption, cardiovascular diseases and type 2 diabetes

    Geiker, Nina Rica Wium; Lytken Larsen, Mogens; Dyerberg, Jørn

    2018-01-01

    Eggs are rich in nutrients and a source of essential fatty- and amino acids, and the food item with highest cholesterol content. Since the 1970s dietary recommendations have advised limiting egg intake to 2-4 a week for the healthy population, and in those diagnosed with cardiovascular disease (CVD......) and type 2 diabetes (T2D) an even more restricted consumption. The aim of the present paper was to assess the recommendation to lower the dietary intake of cholesterol and especially the intake of egg to reduce the risk of CVD and T2D. We performed three web-based literature searches on human studies...... (observational and interventional) published within the past 10 years during spring 2015. High-quality intervention studies have found nonsignificant effects of increasing the consumption of eggs on risk markers for CVD and T2D in healthy subjects and subjects with T2D. The risk associations found...

  16. Peripheral Arterial Disease in Patients with Type 2 Diabetes Mellitus

    Sang Youl Rhee

    2015-08-01

    Full Text Available Peripheral arterial disease (PAD in patients with type 2 diabetes mellitus (T2DM exhibits broad clinical characteristics and various consequences and is known as one of the major macrovascular complications of T2DM. Atherosclerosis is recognized as the most direct and important cause of PAD, but acute or chronic limb ischemia may be the result of various risk factors. In light of the increasing number of patients who undergo peripheral vascular procedures, the number of subjects who are exposed to the risks for PAD and related complications is increasing. In this review, we will discuss the clinical and epidemiological characteristics of PAD, as well as the clinical significance of PAD in T2DM subjects.

  17. All about Your Risk for Prediabetes, Type 2 Diabetes, and Heart Disease

    Toolkit No. 1 All About Your Risk for Prediabetes, Type 2 Diabetes, and Heart Disease What does prediabetes have to do with type 2 diabetes and heart disease? When you have prediabetes, your blood glucose (sugar) levels are higher than ...

  18. Liver and Skin Histopathology in Adults with Acid Sphingomyelinase Deficiency (Niemann-Pick Disease Type B)

    Thurberg, Beth L.; Wasserstein, Melissa P.; Schiano, Thomas; O’Brien, Fanny; Richards, Susan; Cox, Gerald F.; McGovern, Margaret M.

    2012-01-01

    Acid sphingomyelinase deficiency (ASMD) is a lysosomal storage disorder characterized by the pathologic accumulation of sphingomyelin in multiple cells types, and occurs most prominently within the liver, spleen and lungs, leading to significant clinical disease. Seventeen ASMD patients underwent a liver biopsy during baseline screening for a Phase 1 trial of recombinant human acid sphingomyelinase (rhASM) in adults with Niemann-Pick disease type B. Eleven of the 17 were enrolled in the trial and each received a single dose of rhASM and underwent a repeat liver biopsy on Day 14. Biopsies were evaluated for fibrosis, sphingomyelin accumulation and macrophage infiltration by light and electron microscopy. When present, fibrosis was periportal and pericellular, predominantly surrounding affected Kupffer cells. Two baseline biopsies exhibited frank cirrhosis. Sphingomyelin was localized to isolated Kupffer cells in mildly affected biopsies and was present in both Kupffer cells and hepatocytes in more severely affected cases. Morphometric quantification of sphingomyelin storage in liver biopsies ranged from 4–44% of the microscopic field. Skin biopsies were also performed at baseline and Day 14 in order to compare the sphingomyelin distribution in a peripheral tissue to that of liver. Sphingomyelin storage was present at lower levels in multiple cell types of the skin, including dermal fibroblasts, macrophages, vascular endothelial cells, vascular smooth muscle cells and Schwann cells. This Phase 1 trial of rhASM in adults with ASMD provided a unique opportunity for a prospective assessment of hepatic and skin pathology in this rare disease and their potential usage as pharmacodynamic biomarkers. PMID:22613999

  19. Neurofibromatosis Type 1 Diagnosed in a Child Based on Multiple Juvenile Xanthogranulomas and Juvenile Myelomonocytic Leukemia

    Jans, Sune R R; Schomerus, Eckhard; Bygum, Anette

    2015-01-01

    An association between juvenile xanthogranuloma (JXG), neurofibromatosis type 1 (NF1), and juvenile myelomonocytic leukemia (JMML) has been described in the literature but has only been documented in approximately 20 cases. We diagnosed a patient with NF1 at 25 months of age, before any cutaneous...... with chemotherapy and allogenic bone marrow transplantation. With increased awareness, patients with JXG and NF1 who develop symptoms possibly related to JMML, such as paleness, skin bleeding, cough, unexplained fever, and hepatosplenomegaly, should be further evaluated. We also emphasize that multiple JXG lesions...

  20. Prognostic Classification Factors Associated With Development of Multiple Autoantibodies, Dysglycemia, and Type 1 Diabetes?A Recursive Partitioning Analysis

    Xu, Ping; Krischer, Jeffrey P.

    2016-01-01

    OBJECTIVE To define prognostic classification factors associated with the progression from single to multiple autoantibodies, multiple autoantibodies to dysglycemia, and dysglycemia to type 1 diabetes onset in relatives of individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS Three distinct cohorts of subjects from the Type 1 Diabetes TrialNet Pathway to Prevention Study were investigated separately. A recursive partitioning analysis (RPA) was used to determine the risk classes. Clini...

  1. Toward tailored disease management for type 2 diabetes.

    Elissen, Arianne M J; Duimel-Peeters, Inge G P; Spreeuwenberg, Cor; Spreeuwenberg, Marieke; Vrijhoef, Hubertus J M

    2012-10-01

    To assess the differentiated effects of population-based disease management programs (DMPs) for type 2 diabetes on intermediary clinical outcomes in The Netherlands. Data covering a period from 20 to 24 months between January 2008 and December 2010 were collected from 18 Dutch care groups (primary care provider networks that have bundled payment contracts for delivery of diabetes DMPs). Meta-analysis and meta-regression methods were used to conduct differentiated analyses of these programs' effects over time on 4 clinical indicators: glycated hemoglobin, lowdensity lipoprotein, systolic blood pressure, and body mass index. Heterogeneous average results were stratified according to various patient and process characteristics to investigate whether differences in these features could explain variation in outcomes. Between 56% and 71% of patients (N = 105,056) had valid first- and second-year measurements of the study outcomes. Although average changes in these measures over time were small, stratified analyses demonstrated that clinically relevant improvements were achieved in patients with poor first-year health values. Interactions with age, disease duration, comorbidity, and smoking status were not consistent across outcomes; nonetheless, heterogeneity in results decreased considerably when simultaneously correcting for known patient characteristics. Positive effects tended to diminish with longer length of follow-up, while greater measurement frequency was associated with improved results, especially in patients with poor health. Our data suggest that tailored disease management, in which not only evidencebased guidelines but also patient characteristics directly determine care processes, including self-management support, has great potential to improve the cost-effectiveness of current chronic care delivery.

  2. Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

    Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B.; Lee, Young Mok; Chou, Janice Y.; Byrne, Barry J.; Correia, Catherine E.; Mah, Cathryn S.; Weinstein, David A.; Conlon, Thomas J.

    2011-01-01

    A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size,...

  3. Central nervous system infectious diseases mimicking multiple sclerosis: recognizing distinguishable features using MRI

    Antonio Jose da Rocha

    2013-09-01

    Full Text Available The current diagnostic criteria for multiple sclerosis (MS confirm the relevant role of magnetic resonance imaging (MRI, supporting the possibility of characterizing the dissemination in space (DIS and the dissemination in time (DIT in a single scan. To maintain the specificity of these criteria, it is necessary to determine whether T2/FLAIR visible lesions and the gadolinium enhancement can be attributed to diseases that mimic MS. Several diseases are included in the MS differential diagnosis list, including diseases with exacerbation, remitting periods and numerous treatable infectious diseases, which can mimic the MRI features of MS. We discuss the most relevant imaging features in several infectious diseases that resemble MS and examine the primary spatial distributions of lesions and the gadolinium enhancement patterns related to MS. Recognizing imaging "red flags" can be useful for the proper diagnostic evaluation of suspected cases of MS, facilitating the correct differential diagnosis by assessing the combined clinical, laboratory and MR imaging information.

  4. ɑ-Synuclein strains and seeding in Parkinson's disease, incidental Lewy body disease, dementia with Lewy bodies and multiple system atrophy: similarities and differences.

    Peelaerts, W; Bousset, L; Baekelandt, V; Melki, R

    2018-04-27

    Several age-related neurodegenerative disorders are characterized by the deposition of aberrantly folded endogenous proteins. These proteins have prion-like propagation and amplification properties but so far appear nontransmissible between individuals. Because of the features they share with the prion protein, PrP, the characteristics of pathogenic protein aggregates in several progressive brain disorders, including different types of Lewy body diseases (LBDs), such as Parkinson's disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies (DLB), have been actively investigated. Even though the pleomorphic nature of these syndromes might suggest different underlying causes, ɑ-synuclein (ɑSyn) appears to play an important role in this heterogeneous group of diseases (the synucleinopathies). An attractive hypothesis is that different types of ɑSyn protein assemblies have a unique and causative role in distinct synucleinopathies. We will discuss the recent research progress on ɑSyn assemblies involved in PD, MSA and DLB; their behavior as strains; current spreading hypotheses; their ability to seed centrally and peripherally; and their implication for disease pathogenesis.

  5. Impact of smoking on disease severity in patients with plaque type psoriasis

    Nuriye Kayıran

    2015-12-01

    Full Text Available Background and Design: Psoriasis is a chronic enflammatory systemic disease involving skin, scalp, nails and joints and is characterized by remission and activation periods. Although the etiopathogenesis of psoriasis has not been fully elucidated, many genetic and environmental factors are believed to have a role in the development of the disease. Obesity, smoking, family history of psoriasis, repetitive physical traumas and stress are the factors thought to affect the severity and progress of the disease. In this study, we aimed to investigate the effects of smoking on the clinical severity of psoriasis in patients with chronic plaque psoriasis. Materials and Methods: Three hundred outpatients with chronic plaque-type psoriasis were enrolled in the study. Data on age, gender, family history, smoking history, educational status, history of chronic illness, and psoriasis area severity index (PASI scores were recorded for each patient. The effects of these factors on PASI were evaluated. Results: Current smokers, never smokers and former smokers were compared in terms of disease severity. The median PASI values of current smokers and never smokers were compared. The mean PASI value was statistically significantly higher in smokers (p=0.049. In multiple logistic regression analysis, it was detected that the risk of moderate and severe disease increased by male sex 2 times, by family history 2.3 times, and by smoking period above 20 years, 10 times. In smokers of more than 1 pack a day, this risk further increased. Conclusion: On the basis of these data, it may be concluded that smoking affects the severity of disease significantly. In addition to amount of daily cigarette consumption, smoking period was shown to have an effect on the severity of disease. Elimination of risk factors such as smoking, which appears to increase the severity of diseases, may be helpful in the management of psoriasis.

  6. A Case of Autoimmune Polyglandular Syndrome (APS) Type II with Hypothyroidism, Hypoadrenalism, and Celiac Disease - A Rare Combination.

    Lakhotia, Manoj; Pahadia, Hans Raj; Kumar, Harish; Singh, Jagdish; Tak, Sandeep

    2015-04-01

    Autoimmune Polyglandular syndrome (APS) are rare condition characterised by presence of immune dysfunction of two or more endocrine glands and other non-endocrine organs. APS is divided into 2 major subtypes based on age of presentation, pattern of disease combinations and mode of inheritance. APS 1(juvenile) usually manifest in early adolescence or in infancy. It is characterised by multiple endocrinal deficiency with mucocutaneous candidiasis and ectodermal dystrophy. Of the endocrine diseases, hypoparathyroidism form an important component followed by Addison's disease, type 1A diabetes, hypogonadism and thyroid disease. On the other hand APS II usually manifest in 3rd or 4th decade of life with female preponderance. Endocrine diseases commonly include autoimmune thyroid disease (graves or autoimmune thyroiditis), type 1A diabetes, and Addison's disease. Hypoparathyroidism is of rare occurrence and there is no mucocutaneous candidiasis. We report here a case of APS type II in a 29-year-old male who initially presented with hypothyroidism, which was soon followed by Addison's disease. The involvement of thyroid gland preceding the involvement of adrenal is of rare occurrence. The patient also had celiac disease which makes the combination further uncommon.

  7. Type 3 Diabetes Mellitus: A Novel Implication of Alzheimers Disease.

    Leszek, Jerzy; Trypka, Elzbieta; Tarasov, Vadim V; Ashraf, Ghulam Md; Aliev, Gjumrakch

    2017-01-01

    The brain of patients with Alzheimer disease (AD) showed the evidence of reduced expression of insulin and neuronal insulin receptors, as compared with those of age-matched controls. This event gradually and certainly leads to a breakdown of the entire insulin-signaling pathway, which manifests insulin resistance. This in turn affects brain metabolism and cognitive functions, which are the bestdocumented abnormalities in AD. These observations led Dr. de la Monte and her colleagues to suggest that AD is actually a neuroendocrine disorder that resembles type 2 diabetes mellitus. The truth would be more complex with understanding the role of low-density lipoprotein receptor-related protein 1, Aβ derived diffusible ligands, and advanced glycation end products. However, now it known as "brain diabetes" and is called type 3 diabetes mellitus (T3DM). This review provides an overview of "brain diabetes" focusing on the reason why the phenomenon is called T3DM. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Assessment of Type I Interferon Signaling in Pediatric Inflammatory Disease.

    Rice, Gillian I; Melki, Isabelle; Frémond, Marie-Louise; Briggs, Tracy A; Rodero, Mathieu P; Kitabayashi, Naoki; Oojageer, Anthony; Bader-Meunier, Brigitte; Belot, Alexandre; Bodemer, Christine; Quartier, Pierre; Crow, Yanick J

    2017-02-01

    Increased type I interferon is considered relevant to the pathology of a number of monogenic and complex disorders spanning pediatric rheumatology, neurology, and dermatology. However, no test exists in routine clinical practice to identify enhanced interferon signaling, thus limiting the ability to diagnose and monitor treatment of these diseases. Here, we set out to investigate the use of an assay measuring the expression of a panel of interferon-stimulated genes (ISGs) in children affected by a range of inflammatory diseases. A cohort study was conducted between 2011 and 2016 at the University of Manchester, UK, and the Institut Imagine, Paris, France. RNA PAXgene blood samples and clinical data were collected from controls and symptomatic patients with a genetically confirmed or clinically well-defined inflammatory phenotype. The expression of six ISGs was measured by quantitative polymerase chain reaction, and the median fold change was used to calculate an interferon score (IS) for each subject compared to a previously derived panel of 29 controls (where +2 SD of the control data, an IS of >2.466, is considered as abnormal). Results were correlated with genetic and clinical data. Nine hundred ninety-two samples were analyzed from 630 individuals comprising symptomatic patients across 24 inflammatory genotypes/phenotypes, unaffected heterozygous carriers, and controls. A consistent upregulation of ISG expression was seen in 13 monogenic conditions (455 samples, 265 patients; median IS 10.73, interquartile range (IQR) 5.90-18.41), juvenile systemic lupus erythematosus (78 samples, 55 patients; median IS 10.60, IQR 3.99-17.27), and juvenile dermatomyositis (101 samples, 59 patients; median IS 9.02, IQR 2.51-21.73) compared to controls (78 samples, 65 subjects; median IS 0.688, IQR 0.427-1.196), heterozygous mutation carriers (89 samples, 76 subjects; median IS 0.862, IQR 0.493-1.942), and individuals with non-molecularly defined autoinflammation (89 samples, 69

  9. Laser-Bioplasma Interaction: The Blood Type Transmutation Induced by Multiple Ultrashort Wavelength Laser Beams

    Stefan, V. Alexander

    2015-11-01

    The interaction of ultrashort wavelength multi laser beams with the flowing blood thin films leads to the transmutation of the blood types A, B, and AB into O type. This is a novel mechanism of importance for the transfusion medicine. Laser radiation is in resonance with the eigen-frequency modes of the antigen proteins and forces the proteins to parametrically oscillate until they get kicked out from the surface. The stripping away of antigens is done by the scanning-multiple-lasers of a high repetition rate in the blue-purple frequency domain. The guiding-lasers are in the red-green frequency domain. The laser force, (parametric interaction with the antigen eigen-oscillation), upon the antigen protein molecule must exceed its weight. The scanning laser beam is partially reflected as long as the antigen(s) is not eliminated. The process of the protein detachment can last a few minutes. Supported by Nikola Tesla Labs., Stefan University.

  10. Patterns of cervical coinfection with multiple human papilloma virus types in a screening population in Denmark

    Goldman, Bryan; Rebolj, Matejka; Rygaard, Carsten

    2013-01-01

    Patterns of cervical human papillomavirus (HPV) infection suggest that HPV genotypes are not independent of each other. This may be explained by risk factors common to all HPV infections, but type-specific biological factors may also play a role. This raises the question of whether widespread use...... of the quadrivalent vaccine (covering HPV6, 11, 16, 18) may indirectly affect the prevalence of any non-vaccine types. Routine screening samples from 5014 Danish women were tested for 35 HPV genotypes (including 13 high-risk) using the Genomica CLART(®) HPV2 kit, which is a low-density microarray based on PCR...... amplification. Simulation studies were performed both under independence between genotypes and under a common dependence structure as would arise from common risk factors, and simulation results were compared to observed coinfection patterns. Overall HPV prevalence was 37.4%, with multiple infections in 17...

  11. Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

    Hahner Stefanie

    2008-07-01

    Full Text Available Abstract Background Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from β-cell autoimmunity. Methods We investigated the role of the -2221Msp(C/T and -23HphI(A/T polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317, Addison's disease (AD, n = 107 or Hashimoto's thyroiditis (HT, n = 61], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62 as well as in healthy controls (HC, n = 275. Results T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T and "AA" -23HphI(A/T polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively. The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion We demonstrate that the allele "C" of the -2221Msp(C/T and "A" -23HphI(A/T insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.

  12. Payment for multiple forest benefits alters the effect of tree disease on optimal forest rotation length.

    Macpherson, Morag F; Kleczkowski, Adam; Healey, John R; Hanley, Nick

    2017-04-01

    Forests deliver multiple benefits both to their owners and to wider society. However, a wave of forest pests and pathogens is threatening this worldwide. In this paper we examine the effect of disease on the optimal rotation length of a single-aged, single rotation forest when a payment for non-timber benefits, which is offered to private forest owners to partly internalise the social values of forest management, is included. Using a generalisable bioeconomic framework we show how this payment counteracts the negative economic effect of disease by increasing the optimal rotation length, and under some restrictive conditions, even makes it optimal to never harvest the forest. The analysis shows a range of complex interactions between factors including the rate of spread of infection and the impact of disease on the value of harvested timber and non-timber benefits. A key result is that the effect of disease on the optimal rotation length is dependent on whether the disease affects the timber benefit only compared to when it affects both timber and non-timber benefits. Our framework can be extended to incorporate multiple ecosystem services delivered by forests and details of how disease can affect their production, thus facilitating a wide range of applications.

  13. Imaging of multiple myeloma and related monoclonal plasma cell diseases. An update

    Weber, Marc-Andre; Delorme, Stefan; Hillengass, Jens

    2014-01-01

    Multiple myeloma is a hematologic disorder characterized by the infiltration and proliferation of monoclonal plasma cells mainly in the bone marrow. The main symptoms are hypercalcemia, renal impairment, cytopenia/anemia and bone disease - summarized as CRAB-criteria. Symptomatic multiple myeloma is consistently preceded by asymptomatic premalignant stages called monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Staging of multiple myeloma is based on the measurement of the monoclonal protein in serum and urine as well as the assessment of impairment of hematopoiesis, renal function and mineralized bone. In the last decade the development of novel therapeutic agents has led to an increase in response rates and survival time of patients with multiple myeloma, which further stresses the value of response assessment by imaging. Cross sectional imaging like MRI and CT is currently replacing conventional radiological surveys in the initial work-up and follow-up of patients with monoclonal plasma cell diseases. The added value of MRI is to improve initial staging by unraveling a diffuse infiltration of bone marrow by plasma cells, a focal pattern or a combination of both. Furthermore, a complete remission of myeloma confirmed by MRI and CT goes along with a better prognosis compared to a complete response based only on serological parameters.

  14. Ferguson Smith type multiple keratoacanthomas and a keratoacanthoma centrifugum marginatum in a woman from Japan.

    Kato, N; Ito, K; Kimura, K; Shibata, M

    2003-10-01

    We report a case of multiple keratoacanthomas on the sun-exposed skin of a 37-year-old woman from Japan. She had experienced 4 similar episodes of evolution and involution of multiple keratoacanthomas during a period of 10 years since she was 27 years old. She was given the diagnosis of Ferguson Smith type keratoacanthoma. This is the seventh Japanese case of Ferguson Smith type keratoacanthoma described in detail in the literature. In addition, the patient was found to have an annular, coral reef-like eruption on the front of her neck, which was diagnosed as a keratoacanthoma centrifugum marginatum. A combination of different variants of keratoacanthoma in 1 patient is uncommon, and only 2 patients with the same combination of lesions, as that seen in our patient, have been reported. Our patient was treated by a relatively low dose (0.5 mg/kg body weight) of etretinate. Both variants of keratoacanthoma showed good response to the treatment. Effectiveness of etretinate for treating keratoacanthoma centrifugum marginatum has only been reported in a few cases. Our patient had no relapse during a period of 15 months after cessation of etretinate treatment.

  15. Design of PH-based accelerated life testing plans under multiple-stress-type

    Elsayed, E.A.; Zhang Hao

    2007-01-01

    Accelerated life testing (ALT) is used to obtain failure time data quickly under high stress levels in order to predict product life performance under design stress conditions. Most of the previous work on designing ALT plans is focused on the application of a single stress. However, as components or products become more reliable due to technological advances, it becomes more difficult to obtain significant amount of failure data within reasonable amount of time using single stress only. Multiple-stress-type ALTs have been employed as a means of overcoming such difficulties. In this paper, we design optimum multiple-stress-type ALT plans based on the proportional hazards model. The optimum combinations of stresses and their levels are determined such that the variance of the reliability estimate of the product over a specified period of time is minimized. The use of the model is illustrated using numerical example, and sensitivity analysis shows that the resultant optimum ALT plan is robust to the deviation in model parameters

  16. Neurogenic bowel dysfunction in patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson's disease

    Richard A Awad

    2011-01-01

    Exciting new features have been described concerning neurogenic bowel dysfunction, including interactions between the central nervous system, the enteric nervous system, axonal injury, neuronal loss, neurotransmission of noxious and non-noxious stimuli, and the fields of gastroenterology and neurology. Patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson's disease present with serious upper and lower bowel dysfunctions characterized by constipation, incontinence, gastrointestinal motor dysfunction and altered visceral sensitivity. Spinal cord injury is associated with severe autonomic dysfunction, and bowel dysfunction is a major physical and psychological burden for these patients. An adult myelomeningocele patient commonly has multiple problems reflecting the multisystemic nature of the disease. Multiple sclerosis is a neurodegenerative disorder in which axonal injury, neuronal loss, and atrophy of the central nervous system can lead to permanent neurological damage and clinical disability. Parkinson's disease is a multisystem disorder involving dopaminergic, noradrenergic, serotoninergic and cholinergic systems, characterized by motor and non-motor symptoms. Parkinson's disease affects several neuronal structures outside the substantia nigra, among which is the enteric nervous system. Recent reports have shown that the lesions in the enteric nervous system occur in very early stages of the disease, even before the involvement of the central nervous system. This has led to the postulation that the enteric nervous system could be critical in the pathophysiology of Parkinson's disease, as it could represent the point of entry for a putative environmental factor to initiate the pathological process. This review covers the data related to the etiology, epidemiology, clinical expression, pathophysiology, genetic aspects, gastrointestinal motor dysfunction, visceral sensitivity, management, prevention and prognosis of neurogenic bowel

  17. Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks.

    Xiaoke Ma

    2015-06-01

    Full Text Available Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways. Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment. Currently, there is a lack of computational methods that enable analysis of multiple gene networks, each of which exhibits differential activity compared to the network of the baseline/healthy condition. We describe the iMDM algorithm to identify both unique and shared gene modules across multiple differential co-expression networks, termed M-DMs (multiple differential modules. We applied iMDM to a time-course RNA-Seq dataset generated using a murine heart failure model generated on two genotypes. We showed that iMDM achieves higher accuracy in inferring gene modules compared to using single or multiple co-expression networks. We found that condition-specific M-DMs exhibit differential activities, mediate different biological processes, and are enriched for genes with known cardiovascular phenotypes. By analyzing M-DMs that are present in multiple conditions, we revealed dynamic changes in pathway activity and connectivity across heart failure conditions. We further showed that module dynamics were correlated with the dynamics of disease phenotypes during the development of heart failure. Thus, pathway dynamics is a powerful measure for understanding pathogenesis. iMDM provides a principled way to dissect the dynamics of gene pathways and its relationship to the dynamics of disease phenotype. With the exponential growth of omics data, our method can aid in generating systems-level insights into disease progression.

  18. Distribution patterns of infection with multiple types of human papillomaviruses and their association with risk factors.

    Sara Soto-De Leon

    Full Text Available BACKGROUND: Infection with multiple types of human papillomavirus (HPV is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1,810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. PRINCIPAL FINDINGS: The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%, while this risk decreased in women who had given birth more than 4 times (-31.1%, or were of mestizo (-24.6% or black (-40.9% ethnicity. CONCLUSIONS: According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2-4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies.

  19. Stem Cell Physics. Multiple-Laser-Beam Treatment of Parkinson's Disease

    Stefan, V.

    2013-03-01

    A novel method for the treatment of Parkinson's disease is proposed. Pluripotent stem cells are laser cultured, using ultrashort wavelength, (around 0.1 micron-ultraviolet radiation-with intensities of a few mW/cm2) , multiple laser beams.[2] The multiple-energy laser photons[3] interact with the neuron DNA molecules to be cloned. The laser created dopaminergic substantia nigra neurons can be, (theoretically), laser transplanted, (a higher focusing precision as compared to a syringe method), into the striatum or substantia nigra regions of the brain, or both. Supported by Nikola Tesla Labs, Stefan University.

  20. High accuracy prediction of beta-turns and their types using propensities and multiple alignments.

    Fuchs, Patrick F J; Alix, Alain J P

    2005-06-01

    We have developed a method that predicts both the presence and the type of beta-turns, using a straightforward approach based on propensities and multiple alignments. The propensities were calculated classically, but the way to use them for prediction was completely new: starting from a tetrapeptide sequence on which one wants to evaluate the presence of a beta-turn, the propensity for a given residue is modified by taking into account all the residues present in the multiple alignment at this position. The evaluation of a score is then done by weighting these propensities by the use of Position-specific score matrices generated by PSI-BLAST. The introduction of secondary structure information predicted by PSIPRED or SSPRO2 as well as taking into account the flanking residues around the tetrapeptide improved the accuracy greatly. This latter evaluated on a database of 426 reference proteins (previously used on other studies) by a sevenfold crossvalidation gave very good results with a Matthews Correlation Coefficient (MCC) of 0.42 and an overall prediction accuracy of 74.8%; this places our method among the best ones. A jackknife test was also done, which gave results within the same range. This shows that it is possible to reach neural networks accuracy with considerably less computional cost and complexity. Furthermore, propensities remain excellent descriptors of amino acid tendencies to belong to beta-turns, which can be useful for peptide or protein engineering and design. For beta-turn type prediction, we reached the best accuracy ever published in terms of MCC (except for the irregular type IV) in the range of 0.25-0.30 for types I, II, and I' and 0.13-0.15 for types VIII, II', and IV. To our knowledge, our method is the only one available on the Web that predicts types I' and II'. The accuracy evaluated on two larger databases of 547 and 823 proteins was not improved significantly. All of this was implemented into a Web server called COUDES (French acronym

  1. Glycogen storage disease type I: clinical and laboratory profile

    Berenice L. Santos

    2014-11-01

    Full Text Available Objectives: To characterize the clinical, laboratory, and anthropometric profile of a sample of Brazilian patients with glycogen storage disease type I managed at an outpatient referral clinic for inborn errors of metabolism. Methods: This was a cross-sectional outpatient study based on a convenience sampling strategy. Data on diagnosis, management, anthropometric parameters, and follow-up were assessed. Results: Twenty-one patients were included (median age 10 years, range 1–25 years, all using uncooked cornstarch therapy. Median age at diagnosis was 7 months (range, 1–132 months, and 19 patients underwent liver biopsy for diagnostic confirmation. Overweight, short stature, hepatomegaly, and liver nodules were present in 16 of 21, four of 21, nine of 14, and three of 14 patients, respectively. A correlation was found between height-for-age and BMI-for-age Z-scores (r = 0.561; p = 0.008. Conclusions: Diagnosis of glycogen storage disease type I is delayed in Brazil. Most patients undergo liver biopsy for diagnostic confirmation, even though the combination of a characteristic clinical presentation and molecular methods can provide a definitive diagnosis in a less invasive manner. Obesity is a side effect of cornstarch therapy, and appears to be associated with growth in these patients. Resumo: Objetivos: Caracterizar o perfil clínico, laboratorial e antropométrico de uma amostra de pacientes brasileiros com doença de depósito de glicogênio tipo I tratados em um ambulatório de referência para erros inatos do metabolismo. Métodos: Este foi um estudo ambulatorial transversal com base em uma estratégia de amostragem de conveniência. Foram avaliados os dados com relação ao diagnóstico, tratamento, parâmetros antropométricos e acompanhamento. Resultados: Foram incluídos 21 pacientes (idade média de 10 anos, faixa 1-25 anos de idade, e todos se encontravam em terapia de amido de milho cru. A idade média na época do diagn

  2. T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.

    van Langelaar, Jamie; van der Vuurst de Vries, Roos M; Janssen, Malou; Wierenga-Wolf, Annet F; Spilt, Isis M; Siepman, Theodora A; Dankers, Wendy; Verjans, Georges M G M; de Vries, Helga E; Lubberts, Erik; Hintzen, Rogier Q; van Luijn, Marvin M

    2018-05-01

    Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients. T helper memory populations single- and double-positive for C-C chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were functionally assessed in blood and/or cerebrospinal fluid from a total of 59 patients with clinically isolated syndrome, 35 untreated patients and 24 natalizumab-treated patients with relapsing-remitting multiple sclerosis, and nine patients with end-stage multiple sclerosis. Within the clinically isolated syndrome group, 23 patients had a second attack within 1 year and 26 patients did not experience subsequent attacks during a follow-up of >5 years. Low frequencies of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3-) effector memory populations in blood strongly associated with a rapid diagnosis of clinically definite multiple sclerosis. In cerebrospinal fluid of clinically isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like Th17 effector memory cells were abundant and showed increased production of interferon-gamma and granulocyte macrophage colony-stimulating factor compared to paired CCR6+ and CCR6-CD8+ T cell populations and their blood equivalents after short-term culturing. Their local enrichment was confirmed ex vivo using cerebrospinal fluid and brain single-cell suspensions. Across all pro-inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4

  3. Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis.

    Calvo-Barreiro, Laura; Eixarch, Herena; Montalban, Xavier; Espejo, Carmen

    2018-02-01

    The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated. This review highlights animal studies in which commensal microbiota modulation was tested in EAE, as well as the mechanisms of action and influence of the commensal microbiota not only in the local milieu but also in the innate and adaptive immune system and the CNS. Regarding human research, this review focuses on studies that show how the commensal microbiota might act as a pathogenic environmental risk factor by directing immune responses towards characteristic pathogenic profiles of MS. We speculate how specific microbiome signatures could be obtained and used as potential pathogenic events and biomarkers for the clinical course of MS. Finally, we review recently published and ongoing clinical trials in MS patients regarding the immunomodulatory properties exerted by some microorganisms. Because MS is a complex disease with a large variety of associated environmental risk factors, we suggest that current treatments combined with strategies that modulate the commensal microbiota would constitute a broader immunotherapeutic approach and improve the clinical outcome for MS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. MR imaging in adults with Gaucher disease type I: evulation of marrow involvement and disease activity

    Hermann, G. (Dept. of Radiology, Mount Sinai Medical Center, City Univ. of New York, NY (United States)); Shaprio, R.S. (Dept. of Radiology, Mount Sinai Medical Center, City Univ. of New York, NY (United States)); Abdelwahab, I.F. (Dept. of Radiology, Mount Sinai Medical Center, City Univ. of New York, NY (United States)); Grabowski, G. (Dept. of Pediatrics, Mount Sinai Medical Center, City Univ. of New York, NY (United States))

    1993-05-01

    An investigation was conducted to determine the usefulness of magnetic resonance imaging (MRI) in the evaluation of bone marrow involvement in patients with Gaucher disease type I. T1- and T2-weighted images were obtained of the lower extremities of 29 adult patients. Patients were classified into one of three groups based on marrow signal patterns on T1- and T2-weighted images as well as change in signal intensity from T1- to T2-weighted images. An increase in signal intensity from T1- to T2-weighted images was the criterion for an 'active process' within the bone marrow. Classification of the 29 patients produced the following results: Group A: Normal, 4 patients; group B: Marrow infiltration, 16 patients; group C: Marrow infiltration plus active marrow process, 9 patients. Correlation with clinical findings revealed that all nine patients with evidence of an active marrow process on MRI (group C) had acute bone pain. Conversely, only one of the remaining 20 patients (groups A and B) had bone pain. There was no correlation between disease activity and findings on conventional radiographs. We conclude the MRI provides an excellent noninvasive assessment of the extent and activity of marrow involvement in type I Gaucher disease. (orig.)

  5. MR imaging in adults with Gaucher disease type I: evulation of marrow involvement and disease activity

    Hermann, G.; Shaprio, R.S.; Abdelwahab, I.F.; Grabowski, G.

    1993-01-01

    An investigation was conducted to determine the usefulness of magnetic resonance imaging (MRI) in the evaluation of bone marrow involvement in patients with Gaucher disease type I. T1- and T2-weighted images were obtained of the lower extremities of 29 adult patients. Patients were classified into one of three groups based on marrow signal patterns on T1- and T2-weighted images as well as change in signal intensity from T1- to T2-weighted images. An increase in signal intensity from T1- to T2-weighted images was the criterion for an 'active process' within the bone marrow. Classification of the 29 patients produced the following results: Group A: Normal, 4 patients; group B: Marrow infiltration, 16 patients; group C: Marrow infiltration plus active marrow process, 9 patients. Correlation with clinical findings revealed that all nine patients with evidence of an active marrow process on MRI (group C) had acute bone pain. Conversely, only one of the remaining 20 patients (groups A and B) had bone pain. There was no correlation between disease activity and findings on conventional radiographs. We conclude the MRI provides an excellent noninvasive assessment of the extent and activity of marrow involvement in type I Gaucher disease. (orig.)

  6. Antecedents of Coping with the Disease in Patients with Multiple Sclerosis: A Qualitative Content Analysis.

    Dehghani, Ali; Dehghan Nayeri, Nahid; Ebadi, Abbas

    2017-01-01

    Due to many physical and mental disorders that occur in multiple sclerosis patients, identifying the factors affecting coping based on the experiences of patients using qualitative study is essential to improve their quality of life. This study was conducted to explore the antecedents of coping with the disease in patients with multiple sclerosis. This is a qualitative study conducted on 11 patients with multiple sclerosis in 2015 in Tehran, Iran. These patients were selected based on purposive sampling. Data were collected using semi-structured and in-depth interviews and coded. These data were analyzed using the conventional content analysis. The rigor of qualitative data using the criteria proposed by Guba and Lincoln were assessed. Five main categories were revealed: (1) social support, (2) lenience, (3) reliance on faith, (4) knowledge of multiple sclerosis and modeling, and (5) economic and environmental situation. Each category had several distinct sub-categories. The results of this study showed that coping with multiple sclerosis is a complex, multidimensional and contextual concept that is affected by various factors in relation to the context of Iran. The findings of the study can provide the healthcare professionals with deeper recognition and understanding of these antecedents to improve successful coping in Iranian patients suffering from multiple sclerosis.

  7. The neutrophil-to-lymphocyte ratio as disease actvity marker in multiple sclerosis and optic neuritis

    Bisgaard, A K; Pihl-Jensen, G; Frederiksen, J L

    2017-01-01

    BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). The neutrophil-to-lymphocyte ratio (NLR) has been identified as a disease activity marker in several diseases. We aim to evaluate the significance of the NLR in the different subtypes of MS......, optic neuritis (ON) and in relation to disease activity and Expanded Disability Status Scale (EDSS). METHODS: We included 378 patients and 813 healthy controls (HC) from The Nordic Reference Interval Project 2000 (NORIP). Complete blood count, demographic and clinical data from patients were evaluated...... between NLR and time of blood sampling. Logistic regression models were constructed for EDSS ≥ 4.0 as outcome. RESULTS: The NLR was significantly higher (p higher NLR (p

  8. Multiple Sclerosis and autoimmune diseases: clinical cases and review of the literature

    A. Protti

    2011-09-01

    Full Text Available Multiple sclerosis (MS, the most frequent demyelinating disease in adults, is thought to be an autoimmune disease. Symptoms and signs observed in MS reflect lesions present mainly in the white matter of the central nervous system (CNS. The diagnosis remains difficult, at least concerning presenting symptoms, because of their low specificity. Diagnosis criteria are usually based on dissemination of signs in time and space, evoked potentials, findings of magnetic resonance imaging, results of cerebrospinal fluid examination, and the exclusion of other diagnosis possibly explaining the clinical signs. However, no clinical and paraclinical investigation can distinguish with certainity MS from other conditions such as autoimmune or inflammatory diseases predominantly affecting the central nervous system. These other disorders include systemic lupus erythematosus, antiphospholipid syndrome, Behcet disease, Sjogren syndrome, sarcoidosis and vasculitides. We present four clinical cases showing the difficulty in reaching a proper diagnosis...

  9. Impulse control disorders are associated with multiple psychiatric symptoms in Parkinson's disease.

    Jaakkola, Elina; Kaasinen, Valtteri; Siri, Chiara; Martikainen, Kirsti; Cilia, Roberto; Niemelä, Solja; Joutsa, Juho

    2014-01-01

    Impulse control disorders can have serious adverse consequences to the life of a patient with Parkinson's disease. Although impulse control disorders are common, a possible psychiatric comorbidity has not been fully characterized. The aim of this study was to investigate the psychiatric symptoms exhibited by Parkinson's disease patients with impulse control disorders. The study was conducted as a postal survey to patients in the registry of the Finnish Parkinson Association. A total of 290 Parkinson's disease patients were evaluated for impulse control disorders using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease. Psychiatric symptoms were systematically screened using the Symptom Checklist 90. We found that 108 of the evaluated patients had one or more impulse control disorders. Patients with impulse control disorders had markedly higher scores for symptoms of psychoticism (Bonferroni corrected p disorder (p impulse control disorders. Impulse control disorders were shown to be independently associated with these symptoms. Patients with multiple impulse control disorders had higher scores for depression and obsessive-compulsive symptoms when compared with patients that exhibited only one impulse control disorder. COUNCLUSIONS: Our results confirm the previous observations that impulse control disorders in Parkinson's disease are linked with multiple psychiatric symptoms, including psychoticism, interpersonal sensitivity, obsessive-compulsive symptoms and depression. Clinicians treating these patients should acknowledge the concomitant psychiatric symptoms.

  10. [Retinopathy of prematurity in multiple births: risk analysis for plus disease].

    García-Serrano, J L; Ramírez-García, M C; Piñar-Molina, R

    2009-04-01

    To analyze the risk factors associated with plus disease in retinopathy of prematurity (ROP). Over a period of 8.5 years we carried out a prospective study of ROP in twins and triplets. Fifty-four multiple-birth infants with low birth weight (large area of avascular retina, low gestational age, low birth weight, a patent ductus arteriosus, length of mechanical ventilation, adverse events increase, low 5 min Apgar scores and poor postnatal weight gain (in the first 4 to 6 weeks of life). Using multiple logistic regression, only the grade of ROP (OR: 5.5; p disease gained an average 3.9 +/- 3.1 g/day in the first 6 weeks of life, compared to a mean of 11.84 +/- 8.3 g/day for those without plus disease (p < 0.0001). Advanced ROP stages and poor weight gain were the most significant factors associated with plus disease. Twins who gained weight at more than 7 g/day in the first 4-6 weeks of life had a significantly reduced risk of plus disease. A good weight gain is an effective strategy against avoidable blindness due to ROP.

  11. CD4 T cell activation and disease activity at onset of multiple sclerosis

    Jensen, J; Langkilde, Annika Reynberg; Fenst, C

    2004-01-01

    We studied CD4 T cell activation in patients with clinically isolated syndromes (CIS) suggesting an initial attack of multiple sclerosis. The percentage of blood CD26+ CD4 T cells was increased in these patients, and correlated with magnetic resonance imaging disease activity and clinical disease...... severity. In contrast, the percentage of CD25+ CD4 T cells in cerebrospinal fluid correlated negatively with the cerebrospinal fluid concentration of myelin basic protein and the presence of IgG oligoclonal bands. These results suggest that distinct systemic and intrathecal T cell activation states...

  12. Immunological cross-reactivity to multiple autoantigens in patients with liver kidney microsomal type 1 autoimmune hepatitis.

    Choudhuri, K; Gregorio, G V; Mieli-Vergani, G; Vergani, D

    1998-11-01

    We describe two patients with liver kidney microsomal antibody type 1 (LKM1)-positive autoimmune hepatitis (AIH) with associated endocrinopathies. The first patient had insulin-dependent diabetes (IDDM), and the second patient had Addison's disease and hypoparathyroidism, and is also positive for islet cell antibodies, without overt diabetes. To account for the existence of multiple endocrinopathy in these patients, we investigated whether there is sequence similarity between the target of LKM1 antibodies, cytochrome P4502D6 (CYP2D6), and other human proteins, and if so, whether this structural similarity produces a detectable cross-reactive immune response. Our database search identified two proteins, carboxypeptidase H, an autoantigen in insulin-dependent diabetes, and 21-hydroxylase, the major autoantigen in Addison's disease, that share sequence similarity to the second major LKM1 epitope on CYP2D6. We tested the reactivity of sera from these patients to the homologous regions of the three autoantigens using an enzyme-linked immunosorbent assay (ELISA). The cut-off for positivity was established by testing sera from 22 healthy children. To determine the significance of reactivity to the peptide homologues of the three autoantigens, we investigated 16 additional patients with LKM1 AIH and 20 children with chronic hepatitis B virus infection as pathological controls. We found that reactivity to the second major epitope of CYP2D6 is significantly associated with reactivity to the homologous regions of carboxypeptidase H (CPH) and 21-hydroxylase (21-OHase) in patients with LKM1 AIH, and that this simultaneous recognition is cross-reactive. We suggest that a cross-reactive immune response between homologous autoantigens may contribute to the development of multiple endocrinopathies in LKM1 AIH.

  13. The need for a disease-specific prospective pregnancy registry for multiple sclerosis (MS).

    Alwan, Sura; Chambers, Christina D; Armenti, Vincent T; Sadovnick, A Dessa

    2015-01-01

    Multiple sclerosis (MS) is the most commonly acquired neurological disorder affecting young adults of reproductive age with an approximately 3:1 female to male ratio. Although pregnancy is not contraindicated in MS, data are limited regarding pregnancy outcome among MS patients, and the safety or risk to the fetus associated with most maternal MS treatments, such as disease modifying therapies (DMTs), during pregnancy is unknown. We review available epidemiological and registry data on MS and pregnancy and discuss the need to initiate a North American Multiple Sclerosis Pregnancy Registry that will prospectively identify pregnancies in women with MS, obtain information on the disease, and its treatment during gestation and lactation and follow the children to determine their health status. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Sleep disorders in Charcot-Marie-Tooth disease type 1.

    Boentert, Matthias; Knop, Katharina; Schuhmacher, Christine; Gess, Burkhard; Okegwo, Angelika; Young, Peter

    2014-03-01

    Obstructive sleep apnoea (OSA) and restless legs syndrome (RLS) have been reported in Charcot-Marie-Tooth disease (CMT) type 1A and axonal subtypes of CMT, respectively. The aim of this case-control study was to investigate both prevalence and severity of OSA, RLS and periodic limb movements in sleep (PLMS) in adult patients with genetically proven CMT1. 61 patients with CMT1 and 61 insomnic control subjects were matched for age, sex, and Body Mass Index. Neurological disability in patients with CMT was assessed using the Functional Disability Scale (FDS). RLS diagnosis was based on a screening questionnaire and structured clinical interviews. All participants underwent overnight polysomnography. OSA was present in 37.7% of patients with CMT1 and 4.9% of controls (psleep quality. In addition to known risk factors, CMT may predispose to OSA. RLS is highly prevalent not only in axonal subtypes of CMT but also in primarily demyelinating subforms of CMT. PLMS are common in CMT1, but do not significantly impair sleep quality.

  15. Dynamic load mitigation using dissipative elastic metamaterials with multiple Maxwell-type oscillators

    Alamri, Sagr; Li, Bing; Tan, K. T.

    2018-03-01

    Dissipative elastic metamaterials have attracted increased attention in recent times. This paper presents the development of a dissipative elastic metamaterial with multiple Maxwell-type resonators for stress wave attenuation. The mechanism of the dissipation effect on the vibration characteristics is systematically investigated by mass-spring-damper models with single and dual resonators. Based on the parameter optimization, it is revealed that a broadband wave attenuation region (stopping band) can be obtained by properly utilizing interactions from resonant motions and viscoelastic effects of the Maxwell-type oscillators. The relevant numerical verifications are conducted for various cases, and excellent agreement between the numerical and theoretical frequency response functions is shown. The design of this dissipative metamaterial system is further applied for dynamic load mitigation and blast wave attenuation. Moreover, the transient response in the continuum model is designed and analyzed for more robust design. By virtue of the bandgap merging effect induced by the Maxwell-type damper, the transient blast wave can be almost completely suppressed in the low frequency range. A significantly improved performance of the proposed dissipative metamaterials for stress wave mitigation is verified in both time and frequency domains.

  16. Glycogen storage disease type Ia in canines: a model for human metabolic and genetic liver disease.

    Specht, Andrew; Fiske, Laurie; Erger, Kirsten; Cossette, Travis; Verstegen, John; Campbell-Thompson, Martha; Struck, Maggie B; Lee, Young Mok; Chou, Janice Y; Byrne, Barry J; Correia, Catherine E; Mah, Cathryn S; Weinstein, David A; Conlon, Thomas J

    2011-01-01

    A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including "lactic acidosis", larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

  17. Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

    Andrew Specht

    2011-01-01

    Full Text Available A canine model of Glycogen storage disease type Ia (GSDIa is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

  18. Staphylococcus cohnii as a cause of multiple brain abscesses in Weber-Christian disease.

    Yamashita, Satoshi; Yonemura, Kiminobu; Sugimoto, Ryoko; Tokunaga, Makoto; Uchino, Makoto

    2005-11-15

    We report a patient with multiple brain abscesses due to Staphylococcus cohnii. While these brain abscesses markedly responded to the antibiotics, this patient was subsequently suffered from subcutaneous inflammatory nodules in the adipose tissue, which diagnosed him as having Weber-Christian disease (WCD). This is the first report that subcutaneous inflammatory nodules in the adipose tissue, which lead the diagnosis of WCD, followed multiple brain abscesses. To our knowledge, S. cohnii has not yet been reported to cause multiple brain abscesses in humans. Although the etiology of WCD is unknown, an immune mechanism has been implicated in the pathogenesis. Therefore, we should notice that patients with WCD could be immunocompromised hosts with a higher risk to suffer from severe opportunistic infections.

  19. The white band disease type II pathogen in Puerto Rico

    D. L Gil-Agudelo

    2006-12-01

    Full Text Available The white band disease type I (WBD-I epizootic event of the early 1980’s resulted in significant changes in the structure and composition of coral communities throughout the wider Caribbean. The disease decimated populations of acroporid corals throughout their geographic distribution and it is still affecting the surviving and recovering populations of these corals in a number of localities in the wider Caribbean. The putative pathogen for this syndrome (WBD-I was never identified. A second pattern of white band was described later as white band type II (WBD-II. A potential pathogen named Vibrio charchariae was identified but Koch’s postulates were never fulfilled. In this work, we present results of a preliminary approach to confirm the identity of the pathogen of WBD-II. During the fall months of 2004, samples of Acropora cervicornis with signs of WBD-II were collected from a small population in Mario reef, an isolated patch reef off La Parguera, southwest coast of Puerto Rico. Bacteria extracted from these samples were isolated in TCBS agar, grown in Glycerol Seawater agar, and then used to inoculate separated, healthy-looking colonies of the same population in the same reef. Isolation, culture, and inoculations of bacteria were conducted under controlled conditions within hours of collection, and no microorganisms that were not already in the reef community were introduced with these experiments. Some of the newly inoculated colonies developed the disease signs within 24 hr. These were subsequently sampled and bacterial re-isolated to be identified, thus complying with the first steps to fulfill Koch ’s postulates for this disease. Rates of advance of the disease signs varied between 0.5 and 2 cm/day. Preliminary analyses indicated that the potential cause of WBD-II is a Vibrio species very close to Vibrio harveyi, a synonymy of V. charchariae. All inoculated coral colonies that developed the signs of WBD-II, behaved as the naturally

  20. Exploration of machine learning techniques in predicting multiple sclerosis disease course

    Zhao, Yijun; Healy, Brian C.; Rotstein, Dalia; Guttmann, Charles R. G.; Bakshi, Rohit; Weiner, Howard L.; Brodley, Carla E.; Chitnis, Tanuja

    2017-01-01

    Objective To explore the value of machine learning methods for predicting multiple sclerosis disease course. Methods 1693 CLIMB study patients were classified as increased EDSS?1.5 (worsening) or not (non-worsening) at up to five years after baseline visit. Support vector machines (SVM) were used to build the classifier, and compared to logistic regression (LR) using demographic, clinical and MRI data obtained at years one and two to predict EDSS at five years follow-up. Results Baseline data...

  1. Multiple endocrine neoplasia phenocopy revealed as a co-occurring neuroendocrine tumor and familial hypocalciuric hypercalcemia type 3

    Hovden, Silje; Jespersen, Marie Louise; Nissen, Peter H

    2016-01-01

    Familial hypocalciuric hypercalcemia type 3 should be considered as differential diagnosis in patients with suspected primary hyperparathyroidism and/or suspected multiple neoplasia syndrome, as correct diagnosis will spare the patients for going through multiple futile parathyroidectomies...... and for the worry of being diagnosed with a cancer susceptibility syndrome....

  2. 47 CFR 2.924 - Marketing of electrically identical equipment having multiple trade names and models or type...

    2010-10-01

    ... Authorizations § 2.924 Marketing of electrically identical equipment having multiple trade names and models or... 47 Telecommunication 1 2010-10-01 2010-10-01 false Marketing of electrically identical equipment having multiple trade names and models or type numbers under the same FCC Identifier. 2.924 Section 2.924...

  3. A decision tree for differentiating multiple system atrophy from Parkinson's disease using 3-T MR imaging.

    Nair, Shalini Rajandran; Tan, Li Kuo; Mohd Ramli, Norlisah; Lim, Shen Yang; Rahmat, Kartini; Mohd Nor, Hazman

    2013-06-01

    To develop a decision tree based on standard magnetic resonance imaging (MRI) and diffusion tensor imaging to differentiate multiple system atrophy (MSA) from Parkinson's disease (PD). 3-T brain MRI and DTI (diffusion tensor imaging) were performed on 26 PD and 13 MSA patients. Regions of interest (ROIs) were the putamen, substantia nigra, pons, middle cerebellar peduncles (MCP) and cerebellum. Linear, volumetry and DTI (fractional anisotropy and mean diffusivity) were measured. A three-node decision tree was formulated, with design goals being 100 % specificity at node 1, 100 % sensitivity at node 2 and highest combined sensitivity and specificity at node 3. Nine parameters (mean width, fractional anisotropy (FA) and mean diffusivity (MD) of MCP; anteroposterior diameter of pons; cerebellar FA and volume; pons and mean putamen volume; mean FA substantia nigra compacta-rostral) showed statistically significant (P decision tree. Threshold values were 14.6 mm, 21.8 mm and 0.55, respectively. Overall performance of the decision tree was 92 % sensitivity, 96 % specificity, 92 % PPV and 96 % NPV. Twelve out of 13 MSA patients were accurately classified. Formation of the decision tree using these parameters was both descriptive and predictive in differentiating between MSA and PD. • Parkinson's disease and multiple system atrophy can be distinguished on MR imaging. • Combined conventional MRI and diffusion tensor imaging improves the accuracy of diagnosis. • A decision tree is descriptive and predictive in differentiating between clinical entities. • A decision tree can reliably differentiate Parkinson's disease from multiple system atrophy.

  4. PCA-based bootstrap confidence interval tests for gene-disease association involving multiple SNPs

    Xue Fuzhong

    2010-01-01

    Full Text Available Abstract Background Genetic association study is currently the primary vehicle for identification and characterization of disease-predisposing variant(s which usually involves multiple single-nucleotide polymorphisms (SNPs available. However, SNP-wise association tests raise concerns over multiple testing. Haplotype-based methods have the advantage of being able to account for correlations between neighbouring SNPs, yet assuming Hardy-Weinberg equilibrium (HWE and potentially large number degrees of freedom can harm its statistical power and robustness. Approaches based on principal component analysis (PCA are preferable in this regard but their performance varies with methods of extracting principal components (PCs. Results PCA-based bootstrap confidence interval test (PCA-BCIT, which directly uses the PC scores to assess gene-disease association, was developed and evaluated for three ways of extracting PCs, i.e., cases only(CAES, controls only(COES and cases and controls combined(CES. Extraction of PCs with COES is preferred to that with CAES and CES. Performance of the test was examined via simulations as well as analyses on data of rheumatoid arthritis and heroin addiction, which maintains nominal level under null hypothesis and showed comparable performance with permutation test. Conclusions PCA-BCIT is a valid and powerful method for assessing gene-disease association involving multiple SNPs.

  5. Homocyst(e)ine and risk of cardiovascular disease in the multiple risk factor intervention trial.

    Evans, R W; Shaten, B J; Hempel, J D; Cutler, J A; Kuller, L H

    2000-01-01

    A nested case-control study was undertaken involving men participating in the Multiple Risk Factor Intervention Trial (MRFIT). Serum samples from 712 men, stored for upto 20 years, were analysed for homocyst(e)ine. Cases involved non-fatal myocardial infractions, identified through the active phase of the study, which ended on February 28, 1982, and deaths due to coronary heart disease, monitored through 1990. The non-fatal myocardial infarction occurred within 7 years of sample collection, whereas the majority of coronary heart disease deaths occurred more than 11 years after sample collection. Mean homocyst(e)ine concentrations were in the expected range and did not differ significantly between case patients and control subjects: myocardial infarction cases, 12.6 micromol/L; myocardial infarction controls, 13.1 micromol/L; coronary heart disease death cases, 12.8 micromol/L; and coronary heart disease controls, 12.7 micromol/L. Odds ratios versus quartile 1 for coronary heart disease deaths and myocardial infarctions combined were as follows: quartile 2, 1.03; quartile 3, 0.84; and quartile 4, 0.92. Thus, in this prospective study, no association of homocyst(e)ine concentration with heart disease was detected. Homocyst(e)ine levels were weakly associated with the acute-phase (C-reactive) protein. These results are discussed with respect to the suggestion that homocyst(e)ine is an independent risk factor for heart disease.

  6. Failure to demonstrate human T cell lymphotropic virus type I in multiple sclerosis patients

    Fugger, L; Morling, N; Ryder, L P

    1990-01-01

    The polymerase chain reaction (PCR) technique was employed in searching for human T cell lymphotropic virus type I (HTLV-I) gag, env and pol sequences in samples of DNA prepared from two HTLV-I seropositive patients with tropical spastic paraparesis (TSP), the Swedish multiple sclerosis (MS......) patients who recently have been reported to be PCR-positive for HTLV-I gag and env sequences, and eight healthy individuals. Precautions were taken in order to reduce the risk of cross-contamination in the PCR. In the two TSP patients strong signals were obtained with gag, env and pol amplification primers...... data do not confirm the presence of HTLV-I sequences in MS patients....

  7. Magnetic resonance imaging perfusion is associated with disease severity and activity in multiple sclerosis

    Sowa, Piotr [Oslo University Hospital, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo (Norway); Owren Nygaard, Gro [Oslo University Hospital, Department of Neurology, Oslo (Norway); Bjoernerud, Atle [Intervention Center, Oslo University Hospital, Oslo (Norway); University of Oslo, Department of Physics, Oslo (Norway); Gulowsen Celius, Elisabeth [Oslo University Hospital, Department of Neurology, Oslo (Norway); University of Oslo, Institute of Health and Society, Faculty of Medicine, Oslo (Norway); Flinstad Harbo, Hanne [University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo (Norway); Oslo University Hospital, Department of Neurology, Oslo (Norway); Kristiansen Beyer, Mona [Oslo University Hospital, Department of Radiology and Nuclear Medicine, Oslo (Norway); Oslo and Akershus University College of Applied Sciences, Department of Life Sciences and Health, Oslo (Norway)

    2017-07-15

    The utility of perfusion-weighted imaging in multiple sclerosis (MS) is not well investigated. The purpose of this study was to compare baseline normalized perfusion measures in subgroups of newly diagnosed MS patients. We wanted to test the hypothesis that this method can differentiate between groups defined according to disease severity and disease activity at 1 year follow-up. Baseline magnetic resonance imaging (MRI) including a dynamic susceptibility contrast perfusion sequence was performed on a 1.5-T scanner in 66 patients newly diagnosed with relapsing-remitting MS. From the baseline MRI, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps were generated. Normalized (n) perfusion values were calculated by dividing each perfusion parameter obtained in white matter lesions by the same parameter obtained in normal-appearing white matter. Neurological examination was performed at baseline and at follow-up approximately 1 year later to establish the multiple sclerosis severity score (MSSS) and evidence of disease activity (EDA). Baseline normalized mean transit time (nMTT) was lower in patients with MSSS >3.79 (p = 0.016), in patients with EDA (p = 0.041), and in patients with both MSSS >3.79 and EDA (p = 0.032) at 1-year follow-up. Baseline normalized cerebral blood flow and normalized cerebral blood volume did not differ between these groups. Lower baseline nMTT was associated with higher disease severity and with presence of disease activity 1 year later in newly diagnosed MS patients. Further longitudinal studies are needed to confirm whether baseline-normalized perfusion measures can differentiate between disease severity and disease activity subgroups over time. (orig.)

  8. Magnetic resonance imaging perfusion is associated with disease severity and activity in multiple sclerosis

    Sowa, Piotr; Owren Nygaard, Gro; Bjoernerud, Atle; Gulowsen Celius, Elisabeth; Flinstad Harbo, Hanne; Kristiansen Beyer, Mona

    2017-01-01

    The utility of perfusion-weighted imaging in multiple sclerosis (MS) is not well investigated. The purpose of this study was to compare baseline normalized perfusion measures in subgroups of newly diagnosed MS patients. We wanted to test the hypothesis that this method can differentiate between groups defined according to disease severity and disease activity at 1 year follow-up. Baseline magnetic resonance imaging (MRI) including a dynamic susceptibility contrast perfusion sequence was performed on a 1.5-T scanner in 66 patients newly diagnosed with relapsing-remitting MS. From the baseline MRI, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps were generated. Normalized (n) perfusion values were calculated by dividing each perfusion parameter obtained in white matter lesions by the same parameter obtained in normal-appearing white matter. Neurological examination was performed at baseline and at follow-up approximately 1 year later to establish the multiple sclerosis severity score (MSSS) and evidence of disease activity (EDA). Baseline normalized mean transit time (nMTT) was lower in patients with MSSS >3.79 (p = 0.016), in patients with EDA (p = 0.041), and in patients with both MSSS >3.79 and EDA (p = 0.032) at 1-year follow-up. Baseline normalized cerebral blood flow and normalized cerebral blood volume did not differ between these groups. Lower baseline nMTT was associated with higher disease severity and with presence of disease activity 1 year later in newly diagnosed MS patients. Further longitudinal studies are needed to confirm whether baseline-normalized perfusion measures can differentiate between disease severity and disease activity subgroups over time. (orig.)

  9. Free energy landscape and multiple folding pathways of an H-type RNA pseudoknot.

    Yunqiang Bian

    Full Text Available How RNA sequences fold to specific tertiary structures is one of the key problems for understanding their dynamics and functions. Here, we study the folding process of an H-type RNA pseudoknot by performing a large-scale all-atom MD simulation and bias-exchange metadynamics. The folding free energy landscapes are obtained and several folding intermediates are identified. It is suggested that the folding occurs via multiple mechanisms, including a step-wise mechanism starting either from the first helix or the second, and a cooperative mechanism with both helices forming simultaneously. Despite of the multiple mechanism nature, the ensemble folding kinetics estimated from a Markov state model is single-exponential. It is also found that the correlation between folding and binding of metal ions is significant, and the bound ions mediate long-range interactions in the intermediate structures. Non-native interactions are found to be dominant in the unfolded state and also present in some intermediates, possibly hinder the folding process of the RNA.

  10. Aptamer-based hydrogel barcodes for the capture and detection of multiple types of pathogenic bacteria.

    Xu, Yueshuang; Wang, Huan; Luan, Chengxin; Liu, Yuxiao; Chen, Baoan; Zhao, Yuanjin

    2018-02-15

    Rapid and sensitive diagnosing hematological infections based on the separation and detection of pathogenic bacteria in the patient's blood is a significant challenge. To address this, we herein present a new barcodes technology that can simultaneously capture and detect multiple types of pathogenic bacteria from a complex sample. The barcodes are poly (ethylene glycol) (PEG) hydrogel inverse opal particles with characteristic reflection peak codes that remain stable during bacteria capture on their surfaces. As the spherical surface of the particles has ordered porous nanostructure, the barcodes can provide not only more surface area for probe immobilization and reaction, but also a nanopatterned platform for highly efficient bioreactions. In addition, the PEG hydrogel scaffold could decrease the non-specificity adsorption by its anti-adhesive effect, and the decorated aptamer probes in the scaffolds could increase the sensitivity, reliability, and specificity of the bacteria capture and detection. Moreover, the tagged magnetic nanoparticles in the PEG scaffold could impart the barcodes with controllable movement under magnetic fields, which can be used to significantly increase the reaction speed and simplify the processing of the bioassays. Based on the describe barcodes, it was demonstrated that the bacteria could be captured and identified even at low bacterial concentrations (100 CFU mL -1 ) within 2.5h, which is effectively shortened in comparison with the "gold standard" in clinic. These features make the barcodes ideal for capturing and detecting multiple bacteria from clinical samples for hematological infection diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Multiple types of motives don't multiply the motivation of West Point cadets.

    Wrzesniewski, Amy; Schwartz, Barry; Cong, Xiangyu; Kane, Michael; Omar, Audrey; Kolditz, Thomas

    2014-07-29

    Although people often assume that multiple motives for doing something will be more powerful and effective than a single motive, research suggests that different types of motives for the same action sometimes compete. More specifically, research suggests that instrumental motives, which are extrinsic to the activities at hand, can weaken internal motives, which are intrinsic to the activities at hand. We tested whether holding both instrumental and internal motives yields negative outcomes in a field context in which various motives occur naturally and long-term educational and career outcomes are at stake. We assessed the impact of the motives of over 10,000 West Point cadets over the period of a decade on whether they would become commissioned officers, extend their officer service beyond the minimum required period, and be selected for early career promotions. For each outcome, motivation internal to military service itself predicted positive outcomes; a relationship that was negatively affected when instrumental motives were also in evidence. These results suggest that holding multiple motives damages persistence and performance in educational and occupational contexts over long periods of time.

  12. A full scope nuclear power plant simulator for multiple reactor types with virtual control panels

    Yonezawa, Hisanori; Ueda, Hiroki; Kato, Takahisa

    2017-01-01

    This paper summarizes a full scope nuclear power plant simulator for multiple reactor types with virtual control panels which Toshiba developed and delivered. After the Fukushima DAIICHI nuclear power plants accident, it is required that all the people who are engaged in the design, manufacturing, operation, maintenance, management and regulation for the nuclear power plant should learn the wide and deep knowledge about the nuclear power plant design including the severe accident. For this purpose, the training with a full scope simulator is one of the most suitable ways. However the existing full scope simulators which are consist of the control panels replica of the referenced plants are costly and they are hard to remodel to fit to the real plant of the latest condition. That's why Toshiba developed and delivered the new concept simulator system which covers multiple referenced plants even though they have different design like BWR and PWR. The control panels of the simulator are made by combining 69 large Liquid Crystal Display (LCD) panels with touch screen instead of a control panel replica of referenced plant. The screen size of the each panel is 42 inches and 3 displays are arranged in tandem for one unit and 23 units are connected together. Each panel displays switches, indicators, recorders and lamps with the Computer Graphics (CG) and trainees operate them with touch operations. The simulator includes a BWR and a PWR simulator model, which enable trainees to learn the wide and deep knowledge about the nuclear power plant of BWR and PWR reactor types. (author)

  13. Heterogeneity in Red Wine Polyphenolic Contents Differentially Influences Alzheimer's Disease-type Neuropathology and Cognitive Deterioration

    Ho, Lap; Chen, Ling Hong; Wang, Jun; Zhao, Wei; Talcott, Stephen T.; Ono, Kenjiro; Teplow, David; Humala, Nelson; Cheng, Alice; Percival, Susan S.; Ferruzzi, Mario; Janle, Elsa; Dickstein, Dara L.; Pasinetti, Giulio Maria

    2009-01-01

    We recently found that moderate consumption of two unrelated red wines generate from different grape species, a Cabernet Sauvignon and a muscadine wine that are characterized by distinct component composition of polyphenolic compounds, significantly attenuated the development of Alzheimer's disease (AD)-type brain pathology and memory deterioration in a transgenic AD mouse model. Interestingly, our evidence suggests that the two red wines attenuated AD phenotypes through independent mechanisms. In particular, we previously found that treatment with Cabernet Sauvignon reduced the generation of AD-type amyloid-β (Aβ) peptides. In contrast, evidence from our present study suggests that muscadine treatment attenuates Aβ neuropathology and Aβ-related cognitive deterioration in Tg2576 mice by interfering with the oligomerization of Aβ molecules to soluble high-molecular-weight Aβ oligomer species that are responsible for initiating a cascade of cellular events resulting in cognitive decline. Collectively, our observations suggest that distinct polyphenolic compounds from red wines may be bioavailable at the organism level and beneficially modulate AD phenotypes through multiple Aβ-related mechanisms. Results from these studies suggest the possibility of developing a “combination” of dietary polyphenolic compounds for AD prevention and/or therapy by modulating multiple Aβ-related mechanisms. PMID:19158422

  14. Wave interactions with multiple semi-immersed Jarlan-type perforated breakwaters

    Elbisy, Moussa S.

    2017-06-01

    This study examines wave interactions with multiple semi-immersed Jarlan-type perforated breakwaters. A numerical model based on linear wave theory and an eigenfunction expansion method has been developed to study the hydrodynamic characteristics of breakwaters. The numerical results show a good agreement with previous analytical results and experimental data for limiting cases of double partially immersed impermeable walls and double and triple Jarlan-type breakwaters. The wave transmission coefficient C T; reflection coefficient C R, and energy dissipation coefficient C E coefficients and the horizontal wave force exerted on the front and rear walls are examined. The results show that C R reaches the maximum value when B/L = 0.46 n while it is smallest when B/L=0.46 n+0.24 ( n=0, 1, 2,...). An economical triple semi-immersed Jarlan-type perforated breakwater can be designed with B/L = 0.25 and C R and C T ranging from 0.25 to 0.32 by choosing a relative draft d/h of 0.35 and a permeability parameter of the perforated front walls being 0.5 for an incident wave number kh nearly equal to 2.0. The triple semi-immersed Jarlan-type perforated breakwaters with significantly reduced C R, will enhance the structure's wave absorption ability, and lead to smaller wave forces compared with the double one. The proposed model may be used to predict the response of a structure in the preliminary design stage for practical engineering.

  15. Utilization of dimethyl fumarate and related molecules for treatment of multiple sclerosis, cancer, and other diseases

    Azzam Maghazachi

    2016-07-01

    Full Text Available Several drugs have been approved for treatment of multiple sclerosis. Dimethyl fumarate (DMF is utilized as an oral drug to treat this disease and is proven to be potent with less side effects than several other drugs. On the other hand, monomethyl fumarate (MMF, a related compound has not been examined in greater details although it has the potential as a therapeutic drug for multiple sclerosis and other diseases. The mechanism of action of DMF or MMF is related to their ability to enhance the antioxidant pathways and to inhibit reactive oxygen species. However, other mechanisms have also been described which include effects on monocytes, dendritic cells, T cells, and natural killer cells. It is also reported that DMF might be useful for treating psoriasis, asthma, aggressive breast cancers, hematopoeitic tumors, inflammatory bowel disease, intracerebral hemorrhage, osteoarthritis, chronic pancreatitis, and retinal ischemia. In this article we will touch on some of these diseases with an emphasis on the effects of DMF and MMF on various immune cells.

  16. Multiple Fractures in Patient with Graves' Disease Accompanied by Isolated Hypogonadotropic Hypogonadism.

    Yi, Hyon-Seung; Kim, Ji Min; Ju, Sang Hyeon; Lee, Younghak; Kim, Hyun Jin; Kim, Koon Soon

    2016-02-01

    Isolated hypogonadotropic hypogonadism (IHH) is known to decrease bone mineral density due to deficiency of sex steroid hormone. Graves' disease is also an important cause of secondary osteoporosis. However, IHH does not preclude the development of primary hyperthyroidism caused by Graves' disease, leading to more severe osteoporosis rapidly. Here, we describe the first case of 35-year-old Asian female patient with IHH accompanied by Graves' disease and osteoporosis-induced multiple fractures. Endocrine laboratory findings revealed preserved anterior pituitary functions except for secretion of gonadotropins and showed primary hyperthyroidism with positive autoantibodies. Sella magnetic resonance imaging showed slightly small sized pituitary gland without mass lesion. Dual energy X-ray absorptiometry revealed severe osteoporosis in lumbar spine and femur neck of the patient. Plain film radiography of the pelvis and shoulder revealed a displaced and nondisplaced fracture, respectively. After surgical fixation with screws for the femoral fracture, the patient was treated with antithyroid medication, calcium, and vitamin D until now and has been recovering fairly well. We report a patient of IHH with Graves' disease and multiple fractures that is a first case in Korea.

  17. Absence of Multiple Sclerosis and Demyelinating Diseases among Lacandonians, a Pure Amerindian Ethnic Group in Mexico

    Jose Flores

    2012-01-01

    Full Text Available Multiple Sclerosis (MS is a highly polymorphic disease characterized by different neurologic signs and symptoms. In MS, racial and genetic factors may play an important role in the geographic distribution of this disease. Studies have reported the presence of several protective alleles against the development of autoimmune disorders. In the case of MS, however, they help define MS as a complex disease, and confirm the importance of environmental agents as an independent variable not associated with ethnicity. We carried out an on-site epidemiological study to confirm the absence of MS or NMO among Lacandonians, a pure Amerindian ethnic group in Mexico. We administered a structured interview to 5,372 Lacandonians to assess by family background any clinical data consistent with the presence of a prior demyelinating event. Every participating subject underwent a comprehensive neurological examination by a group of three members of the research team with experience in the diagnosis and treatment of demyelinating disorders to detect clinical signs compatible with a demyelinating disease. We did not find any clinical signs compatible with multiple sclerosis among study participants.

  18. Glycogen storage disease type III: modified Atkins diet improves myopathy.

    Mayorandan, Sebene; Meyer, Uta; Hartmann, Hans; Das, Anibh Martin

    2014-11-28

    Frequent feeds with carbohydrate-rich meals or continuous enteral feeding has been the therapy of choice in glycogen storage disease (Glycogenosis) type III. Recent guidelines on diagnosis and management recommend frequent feedings with high complex carbohydrates or cornstarch avoiding fasting in children, while in adults a low-carb-high-protein-diet is recommended. While this regimen can prevent hypoglycaemia in children it does not improve skeletal and heart muscle function, which are compromised in patients with glycogenosis IIIa. Administration of carbohydrates may elicit reactive hyperinsulinism, resulting in suppression of lipolysis, ketogenesis, gluconeogenesis, and activation of glycogen synthesis. Thus, heart and skeletal muscle are depleted of energy substrates. Modified Atkins diet leads to increased blood levels of ketone bodies and fatty acids. We hypothesize that this health care intervention improves the energetic balance of muscles. We treated 2 boys with glycogenosis IIIa aged 9 and 11 years with a modified Atkins diet (10 g carbohydrate per day, protein and fatty acids ad libitum) over a period of 32 and 26 months, respectively. In both patients, creatine kinase levels in blood dropped in response to Atkins diet. When diet was withdrawn in one of the patients he complained of chest pain, reduced physical strength and creatine kinase levels rapidly increased. This was reversed when Atkins diet was reintroduced. One patient suffered from severe cardiomyopathy which significantly improved under diet. Patients with glycogenosis IIIa benefit from an improved energetic state of heart and skeletal muscle by introduction of Atkins diet both on a biochemical and clinical level. Apart from transient hypoglycaemia no serious adverse effects were observed.

  19. Disease management programs in type 2 diabetes: quality of care.

    Berthold, Heiner K; Bestehorn, Kurt P; Jannowitz, Christina; Krone, Wilhelm; Gouni-Berthold, Ioanna

    2011-06-01

    To determine whether disease management programs (DMPs) for type 2 diabetes mellitus (T2DM) can improve some processes of care and intermediate outcomes. Two cross-sectional registries of patients with T2DM were used for data extraction before (previous cohort) and after (recent cohort) introduction of DMPs in Germany (N = 78,110). In the recent cohort, 15,293 patients were treated within the DMPs and 9791 were not. Processes of care, medications, and intermediate outcomes (achievement of treatment targets for low-density lipoprotein [LDL] cholesterol, blood pressure, and glycosylated hemoglobin [A1C]) were analyzed using multi- variable, multilevel logistic regression, adjusting for patient case-mix and physician-level clustering to derive odds ratios and 95% confidence intervals (CIs). Availability of structured diabetes education and of lipid, blood pressure, and A1C measurements increased over time. In DMP patients, availability was significantly higher for blood pressure and A1C but not for lipid measurements. Prescription of angiotensin-converting enzyme inhibitors, oral antidiabetic drugs, and insulin increased over time and was more common in DMP patients. Statin prescription increased over time but was not influenced by DMP status. Intermediate outcomes improved over time, but DMPs had no influence on intermediate outcomes except for reaching LDL cholesterol targets (odds ratio 1.12 [95% CI 1.06, 1.19] in favor of DMPs). While there may be some unmeasured confounding, our data suggest that improvement in processes of care by DMPs, as implemented in Germany, only partially translates into improvement of intermediate outcomes.

  20. Infectious Bursal Disease Virus-Host Interactions: Multifunctional Viral Proteins that Perform Multiple and Differing Jobs

    Yao Qin

    2017-01-01

    Full Text Available Infectious bursal disease (IBD is an acute, highly contagious and immunosuppressive poultry disease caused by IBD virus (IBDV. The consequent immunosuppression increases susceptibility to other infectious diseases and the risk of subsequent vaccination failure as well. Since the genome of IBDV is relatively small, it has a limited number of proteins inhibiting the cellular antiviral responses and acting as destroyers to the host defense system. Thus, these virulence factors must be multifunctional in order to complete the viral replication cycle in a host cell. Insights into the roles of these viral proteins along with their multiple cellular targets in different pathways will give rise to a rational design for safer and effective vaccines. Here we summarize the recent findings that focus on the virus–cell interactions during IBDV infection at the protein level.

  1. Characterization of annual disease progression of multiple sclerosis patients: A population-based study

    Freilich, Jonatan; Manouchehrinia, Ali; Trusheim, Mark

    2017-01-01

    Previous research characterizing factors influencing multiple sclerosis (MS) disease progression has typically been based on time to disease milestones (Kaplan-Meier, Cox hazard regression, etc.). A limitation of these methods is the handling of the often large groups of patients not reaching...... the milestone. To characterize clinical factors influencing MS disease progression as annual transitions from each Expanded Disability Status Scale (EDSS). The annual progression of 11,964 patients from the Swedish MS Registry was analysed with 10 multinomial logistic regressions, that is, one for transition...... from each full EDSS with explanatory variables age, sex, age at onset, time in current EDSS, highest prior EDSS, MS course and treatment. All factors (except sex) investigated had statistically significant impacts on transitions from at least one EDSS. However, significance and size of the effect...

  2. Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease

    Dimitrijevic, Ivan; Edvinsson, Lars; Chen, Qingwen

    2009-01-01

    expression in subcutaneous arteries from patients with different degrees of ischemic heart disease. METHODS: Subcutaneous arteries were obtained, by biopsy from the abdomen, from patients undergoing coronary artery bypass graft (CABG) surgery because of ischemic heart disease (n = 15), patients with angina...... pectoris without established myocardial infarction (n = 15) and matched cardiovascular healthy controls (n = 15). Endothelin type A (ETA) and type B (ETB), and angiotensin type 1 (AT1) and type 2 (AT2) receptors expression and function were examined using immunohistochemistry, Western blot and in vitro...

  3. Analysis of Brassica oleracea early stage abiotic stress responses reveals tolerance in multiple crop types and for multiple sources of stress.

    Beacham, Andrew M; Hand, Paul; Pink, David Ac; Monaghan, James M

    2017-12-01

    Brassica oleracea includes a number of important crop types such as cabbage, cauliflower, broccoli and kale. Current climate conditions and weather patterns are causing significant losses in these crops, meaning that new cultivars with improved tolerance of one or more abiotic stress types must be sought. In this study, genetically fixed B. oleracea lines belonging to a Diversity Fixed Foundation Set (DFFS) were assayed for their response to seedling stage-imposed drought, flood, salinity, heat and cold stress. Significant (P ≤ 0.05) variation in stress tolerance response was found for each stress, for each of four measured variables (relative fresh weight, relative dry weight, relative leaf number and relative plant height). Lines tolerant to multiple stresses were found to belong to several different crop types. There was no overall correlation between the responses to the different stresses. Abiotic stress tolerance was identified in multiple B. oleracea crop types, with some lines exhibiting resistance to multiple stresses. For each stress, no one crop type appeared significantly more or less tolerant than others. The results are promising for the development of more environmentally robust lines of different B. oleracea crops by identifying tolerant material and highlighting the relationship between responses to different stresses. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  4. Comparison of Statistical Algorithms for the Detection of Infectious Disease Outbreaks in Large Multiple Surveillance Systems

    Farrington, C. Paddy; Noufaily, Angela; Andrews, Nick J.; Charlett, Andre

    2016-01-01

    A large-scale multiple surveillance system for infectious disease outbreaks has been in operation in England and Wales since the early 1990s. Changes to the statistical algorithm at the heart of the system were proposed and the purpose of this paper is to compare two new algorithms with the original algorithm. Test data to evaluate performance are created from weekly counts of the number of cases of each of more than 2000 diseases over a twenty-year period. The time series of each disease is separated into one series giving the baseline (background) disease incidence and a second series giving disease outbreaks. One series is shifted forward by twelve months and the two are then recombined, giving a realistic series in which it is known where outbreaks have been added. The metrics used to evaluate performance include a scoring rule that appropriately balances sensitivity against specificity and is sensitive to variation in probabilities near 1. In the context of disease surveillance, a scoring rule can be adapted to reflect the size of outbreaks and this was done. Results indicate that the two new algorithms are comparable to each other and better than the algorithm they were designed to replace. PMID:27513749

  5. Optimized GF(2k) ONB type I multiplier architecture based on the Massey-Omura multiplication pattern

    Fournaris, A P; Koufopavlou, O

    2005-01-01

    Multiplication in GF(2 k ) finite fields is becoming rapidly a very promising solution for fast, small, efficient binary algorithms designed for hardware applications. GF(2 k ) finite fields defined over optimal normal bases (ONB) can be very advantageous in term of gates number and multiplication time delay. Many ONB multipliers works have been proposed that use the Massey-Omura multiplication pattern. In this paper, a method for designing type I optimal normal basis multipliers and an optimal normal basis (ONB) type I multiplier hardware architecture is proposed that, through parallelism and pairing categorization of the ONB multiplication table matrix, achieves very interesting results in terms of gate number and multiplication time delay

  6. Three novel, multiple recombinant types of species of human mastadenovirus D (HAdV-D 73, 74 & 75) isolated from diarrhoeal faeces of immunocompromised patients.

    Hage, Elias; Dhingra, Akshay; Liebert, Uwe G; Bergs, Sandra; Ganzenmueller, Tina; Heim, Albert

    2017-11-02

    Species D is the largest of the seven species of human mastadenoviruses (HAdV), but few of its multiple types are associated with asevere disease, e.g. epidemic keratoconjunctivitis. Many other types are hardly ever associated with significant diseases in immunocompetent patients, but have been isolated from the diarrhoeal faeces of terminal AIDS patients suggesting their role as opportunistic pathogens. Three novel HAdV-D strains were isolated from the faeces of three immunocompromised adult patients (clinical diagnoses: lymphoma, myelodysplastic syndrome and AIDS CDC3B, respectively). These strains were not typeable by imputed serology of the hexon and fibre gene and therefore complete genomic sequences were generated by next-generation sequencing (NGS). All three strains were multiple recombinants and fulfilled the criteria for designation as types 73, 74 and 75 with the penton/hexon/fibre genotype codes P67H45F27, P70H74F51 and P75H26F29, respectively. A novel genomic backbone and also a novel hexon neutralization epitope sequence were discovered in type 74, and a novel penton sequence in type 75. At the complete genome level, types 73, 74 and 75 were closely related neither to each other nor to type 70, which was previously isolated in the same region. However, these four HAdV-D types were closely related to each other in single genes and gene regions, e.g. penton, E1 and E4 due to recombination events in their phylogeny. In conclusion, regional co-circulation of opportunistic HAdV-D types facilitated co- and super-infections, which are essential for homologous recombination, and thus resulted in the evolution of novel genotypes by lateral gene transfer.

  7. Overweight, insulin resistance and type II diabetes in type I Gaucher disease patients in relation to enzyme replacement therapy

    Langeveld, M.; de Fost, M.; Aerts, J. M. F. G.; Sauerwein, H. P.; Hollak, C. E. M.

    2008-01-01

    Type I Gaucher disease, a lysosomal storage disorder is associated with metabolic abnormalities such as high resting energy expenditure, low circulating adiponectin and peripheral insulin resistance. Treatment with enzyme replacement therapy (enzyme therapy) leads to a decrease in resting energy

  8. Detection of type 1 prion protein in variant Creutzfeldt-Jakob disease

    Yull, H.M.; Ritchie, D.L.; Langeveld, J.P.M.; Zijderveld, van F.G.; Bruce, M.E.; Ironside, J.W.; Head, M.W.

    2006-01-01

    Molecular typing of the abnormal form of the prion protein (PrPSc) has come to be regarded as a powerful tool in the investigation of the prion diseases. All evidence thus far presented indicates a single PrPSc molecular type in variant Creutzfeldt-Jakob disease (termed type 2B), presumably

  9. Human endogenous retroviruses and multiple sclerosis: innocent bystanders or disease determinants?

    Antony, Joseph M; Deslauriers, Andre M; Bhat, Rakesh K; Ellestad, Kristofer K; Power, Christopher

    2011-02-01

    Human endogenous retroviruses (HERVs) constitute 5-8% of human genomic DNA and are replication incompetent despite expression of individual HERV genes from different chromosomal loci depending on the specific tissue. Several HERV genes have been detected as transcripts and proteins in the central nervous system, frequently in the context of neuroinflammation. The HERV-W family has received substantial attention in large part because of associations with diverse syndromes including multiple sclerosis (MS) and several psychiatric disorders. A HERV-W-related retroelement, multiple sclerosis retrovirus (MSRV), has been reported in MS patients to be both a biomarker as well as an effector of aberrant immune responses. HERV-H and HERV-K have also been implicated in MS and other neurological diseases but await delineation of their contributions to disease. The HERV-W envelope-encoded glycosylated protein, syncytin-1, is encoded by chromosome 7q21 and exhibits increased glial expression within MS lesions. Overexpression of syncytin-1 in glia induces endoplasmic reticulum stress leading to neuroinflammation and the induction of free radicals, which damage proximate cells. Syncytin-1's receptor, ASCT1 is a neutral amino acid transporter expressed on glia and is suppressed in white matter of MS patients. Of interest, antioxidants ameliorate syncytin-1's neuropathogenic effects raising the possibility of using these agents as therapeutics for neuroinflammatory diseases. Given the multiple insertion sites of HERV genes as complete and incomplete open reading frames, together with their differing capacity to be expressed and the complexities of individual HERVs as both disease markers and bioactive effectors, HERV biology is a compelling area for understanding neuropathogenic mechanisms and developing new therapeutic strategies. 2010 Elsevier B.V. All rights reserved.

  10. Geographical Overlapping of Obesity, Heart Disease, and Type 2 Diabetes

    2017-10-09

    This podcast features Kayla Smurthwaite, an undergraduate student at Australian National University in Canberra, Australia, and one of the winners of PCD’s 2017 Student Research Paper Contest. Kayla answers questions about her winning research and what impact her study has on chronic disease prevention and public health.  Created: 10/9/2017 by Preventing Chronic Disease (PCD), National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/9/2017.

  11. Analysis of multiple types of human cells subsequent to bioprinting with electrospraying technology.

    Xin, Yu; Chai, Gang; Zhang, Ting; Wang, Xiangsheng; Qu, Miao; Tan, Andy; Bogari, Melia; Zhu, Ming; Lin, Li; Hu, Qingxi; Liu, Yuanyuan; Zhang, Yan

    2016-12-01

    The aim of the present study was to investigate bioprinting with electrospraying technology using multiple types of human cell suspensions as bio-ink, in order to lay the initial foundations for the application of the bioprinting technology in tissue engineering. In the current study, six types of human cells were selected and cultured, including human fibroblasts, human adipose-derived stem cells (hADSCs), human periodontal ligament cells (HPDLCs), adult human retinal pigment epithelial cells (ARPE-19), human umbilical vascular endothelial cells (HUVECs) and human gastric epithelial cell line (GES-1). Each cell type was divided into two groups, the experimental and control group. All the experimental group cells were electrosprayed using an electrospraying printer (voltage, 15 kV; flow rate, 150 µl/min) and collected in a petri dish placed 15 cm away from the needle (needle diameter, 0.5 mm). Subsequently, cell viability was detected by flow cytometry with a Live/Dead Viability kit. In addition, the cell morphological characteristics were observed with a phase-contrast microscope after 6 h of culturing in order to obtain adherent cells, while cell proliferation was analyzed using a Cell Counting Kit-8 assay. The control groups, without printing, were subjected to the same procedures as the experimental groups. The results of the cell viability and proliferation assays indicated a statistically significant difference after printing between the experiments and control groups only for the hADSCs (P0.05). In addition, there were no observable differences between all experimental and the control groups at any examined time point in the terms of cell morphological characteristics. In conclusion, bioprinting based on electrospraying technology demonstrated no distinct negative effect on cell vitality, proliferation and morphology in the present study, and thus the application of this novel technology to cell printing may provide a promising method in tissue engineering.

  12. Cat-scratch disease presenting as multiple hepatic lesions: case report and literature review.

    Baptista, Mariana Andrade; Lo, Denise Swei; Hein, Noely; Hirose, Maki; Yoshioka, Cristina Ryoka Miyao; Ragazzi, Selma Lopes Betta; Gilio, Alfredo Elias; Ferronato, Angela Esposito

    2014-01-01

    Although infectious diseases are the most prevalent cause of fevers of unknown origin (FUO), this diagnosis remains challenging in some pediatric patients. Imaging exams, such as computed tomography (CT) are frequently required during the diagnostic processes. The presence of multiple hypoattenuating scattered images throughout the liver associated with the history of cohabitation with cats should raise the suspicion of the diagnosis of cat-scratch disease (CSD), although the main etiologic agent of liver abscesses in childhood is S taphylococcus aureus . Differential diagnosis by clinical and epidemiological data with Bartonella henselae is often advisable. The authors report the case of a boy aged 2 years and 9 months with 16-day history of daily fever accompanied by intermittent abdominal pain. Physical examination was unremarkable. Abdominal ultrasound performed in the initial work up was unrevealing, but an abdominal CT that was performed afterwards disclosed multiple hypoattenuating hepatic images compatible with the diagnosis of micro abscesses. Initial antibiotic regimen included cefotaxime, metronidazole, and oxacillin. Due to the epidemiology of close contact with kittens, diagnosis of CSD was considered and confirmed by serologic tests. Therefore, the initial antibiotics were replaced by clarithromycin orally for 14 days followed by fever defervescence and clinical improvement. The authors call attention to this uncommon diagnosis in a child presenting with FUO and multiple hepatic images suggestive of micro abscesses.

  13. Cat-scratch disease presenting as multiple hepatic lesions: case report and literature review

    Mariana Andrade Baptista

    2014-06-01

    Full Text Available Although infectious diseases are the most prevalent cause of fevers of unknown origin (FUO, this diagnosis remains challenging in some pediatric patients. Imaging exams, such as computed tomography (CT are frequently required during the diagnostic processes. The presence of multiple hypoattenuating scattered images throughout the liver associated with the history of cohabitation with cats should raise the suspicion of the diagnosis of cat-scratch disease (CSD, although the main etiologic agent of liver abscesses in childhood is Staphylococcus aureus. Differential diagnosis by clinical and epidemiological data with Bartonella henselae is often advisable. The authors report the case of a boy aged 2 years and 9 months with 16-day history of daily fever accompanied by intermittent abdominal pain. Physical examination was unremarkable. Abdominal ultrasound performed in the initial work up was unrevealing, but an abdominal CT that was performed afterwards disclosed multiple hypoattenuating hepatic images compatible with the diagnosis of micro abscesses. Initial antibiotic regimen included cefotaxime, metronidazole, and oxacillin. Due to the epidemiology of close contact with kittens, diagnosis of CSD was considered and confirmed by serologic tests. Therefore, the initial antibiotics were replaced by clarithromycin orally for 14 days followed by fever defervescence and clinical improvement. The authors call attention to this uncommon diagnosis in a child presenting with FUO and multiple hepatic images suggestive of micro abscesses.

  14. Comparison between cerebral ischemia disease and multiple sclerosis by using MR diffusion tensor imaging

    Lou Xin; Cai Youquan; Ma Lin; Cai Jianming

    2007-01-01

    Objective: To assess the value of MR diffusion tensor imaging (DTI) in the differentiation between the patients with cerebral ischemia disease and multiple sclerosis. Methods: MR diffusion tensor imaging was performed in thirty-two patients with internal carotid artery stenosis ≥70% and eighteen patients with clinical diagnosed multiple sclerosis. Fractional anisotropy (FA) value of the germ, splenium, body of the corpus callosum, and the white matter of the frontal and occipital lobe were measured respectively, and independent-sample t-test statistical analysis was performed. Results: The FA value was decreased obviously in the anterior and posterior body and splenium of the corpus callosumin the MS patients compared with the ICA severe stenosis patients (0.67 ± 0.12 vs. 0.75 ± 0.05, t=3.443, P 0.05; 0.34 ± 0.08 vs. 0.34 ± 0.05, t=0.137, P> 0.05; 0.29 ± 0.06 vs. 0.40 ± 0.06, t=5.449, P>0.05). Conclusion: DTI can noninvasive detect the potential disorder of corpus callosum in vivo, thus providing useful information to differentiate the cerebral ischemia disease from multiple sclerosis. (authors)

  15. Variation in type and frequency of diagnostic imaging during trauma care across multiple time points by patient insurance type

    Bell, Nathaniel; Repáraz, Laura; Fry, William R.; Smith, R. Stephen; Luis, Alejandro

    2016-01-01

    Research has shown that uninsured patients receive fewer radiographic studies during trauma care, but less is known as to whether differences in care are present among other insurance groups or across different time points during hospitalization. Our objective was to examine the number of radiographic studies administered to a cohort of trauma patients over the entire hospital stay as well as during the first 24-hours of care. Patient data were obtained from an American College of Surgeons (ACS) verified Level I Trauma Center between January 1, 2011 and December 31, 2012. We used negative binomial regression to construct relative risk (RR) ratios for type and frequency of radiographic imaging received among persons with Medicare, Medicaid, no insurance, or government insurance plans in reference to those with commercial indemnity plans. The analysis was adjusted for patient age, sex, race/ethnicity, injury severity score, injury mechanism, comorbidities, complications, hospital length of stay, and Intensive Care Unit (ICU) admission. A total of 3621 records from surviving patients age > =18 years were assessed. After adjustment for potential confounders, the expected number of radiographic studies decreased by 15 % among Medicare recipients (RR 0.85, 95 % CI 0.78–0.93), 11 % among Medicaid recipients (0.89, 0.81–0.99), 10 % among the uninsured (0.90, 0.85–0.96) and 19 % among government insurance groups (0.81, 0.72–0.90), compared with the reference group. This disparity was observed during the first 24-hours of care among patients with Medicare (0.78, 0.71–0.86) and government insurance plans (0.83, 0.74–0.94). Overall, there were no differences in the number of radiographic studies among the uninsured or among Medicaid patients during the first 24-hours of care compared with the reference group, but differences were observed among the uninsured in a sub-analysis of severely injured patients (ISS > 15). Both uninsured and insured patients treated at a

  16. The self-management experience of patients with type 2 diabetes and chronic kidney disease: A qualitative study.

    Shirazian, Shayan; Crnosija, Natalie; Weinger, Katie; Jacobson, Alan M; Park, Joonho; Tanenbaum, Molly L; Gonzalez, Jeffrey S; Mattana, Joseph; Hammock, Amy C

    2016-03-01

    The purpose of this study was to explore views related to the self-management of type 2 diabetes and chronic kidney disease. We conducted three semi-structured focus groups in participants with type 2 diabetes and chronic kidney disease. Interviews were transcribed, coded, and analyzed using thematic analysis. Credibility was supported through triangulation of data sources and the use of multiple investigators from different disciplines. Twenty-three adults participated. Three major themes were identified: emotional reactions to health state, the impact of family dynamics on self-management, and the burden of self-management regimens. Family dynamics were found to be a barrier and support to self-management, while complicated self-management regimens were found to be a barrier. Additionally, participants expressed several emotional reactions related to their CKD status, including regret related to having developed CKD and distress related both to their treatment regimens and the future possibility of dialysis. This exploratory study of patients with type 2 diabetes and chronic kidney disease describes barriers and supports to self-management and emotional reactions to chronic kidney disease status. Future research should confirm these findings in a larger population and should include family members and/or health care providers to help further define problems with self-management in patients with type 2 diabetes and chronic kidney disease. © The Author(s) 2015.

  17. BDNF val66met polymorphism affects aging of multiple types of memory.

    Kennedy, Kristen M; Reese, Elizabeth D; Horn, Marci M; Sizemore, April N; Unni, Asha K; Meerbrey, Michael E; Kalich, Allan G; Rodrigue, Karen M

    2015-07-01

    The BDNF val66met polymorphism (rs6265) influences activity-dependent secretion of brain-derived neurotrophic factor in the synapse, which is crucial for learning and memory. Individuals homozygous or heterozygous for the met allele have lower BDNF secretion than val homozygotes and may be at risk for reduced declarative memory performance, but it remains unclear which types of declarative memory may be affected and how aging of memory across the lifespan is impacted by the BDNF val66met polymorphism. This cross-sectional study investigated the effects of BDNF polymorphism on multiple indices of memory (item, associative, prospective, subjective complaints) in a lifespan sample of 116 healthy adults aged 20-93 years. Advancing age showed a negative effect on item, associative and prospective memory, but not on subjective memory complaints. For item and prospective memory, there were significant age×BDNF group interactions, indicating the adverse effect of age on memory performance across the lifespan was much stronger in the BDNF met carriers than for the val homozygotes. BDNF met carriers also endorsed significantly greater subjective memory complaints, regardless of age, and showed a trend (pmemory performance compared to val homozygotes. These results suggest that genetic predisposition to the availability of brain-derived neurotrophic factor, by way of the BDNF val66met polymorphism, exerts an influence on multiple indices of episodic memory - in some cases in all individuals regardless of age (subjective memory and perhaps associative memory), in others as an exacerbation of age-related differences in memory across the lifespan (item and prospective memory). This article is part of a Special Issue entitled Memory & Aging. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Imaging Surrogates of Disease Activity in Neuromyelitis Optica Allow Distinction from Multiple Sclerosis.

    Matthews, Lucy; Kolind, Shannon; Brazier, Alix; Leite, Maria Isabel; Brooks, Jonathan; Traboulsee, Anthony; Jenkinson, Mark; Johansen-Berg, Heidi; Palace, Jacqueline

    2015-01-01

    Inflammatory demyelinating lesions of the central nervous system are a common feature of both neuromyelitis optica and multiple sclerosis. Despite this similarity, it is evident clinically that the accumulation of disability in patients with neuromyelitis optica is relapse related and that a progressive phase is very uncommon. This poses the question whether there is any pathological evidence of disease activity or neurodegeneration in neuromyelitis optica between relapses. To investigate this we conducted a longitudinal advanced MRI study of the brain and spinal cord in neuromyelitis optica patients, comparing to patients with multiple sclerosis and controls. We found both cross-sectional and longitudinal evidence of diffusely distributed neurodegenerative surrogates in the multiple sclerosis group (including thalamic atrophy, cervical cord atrophy and progressive widespread diffusion and myelin water imaging abnormalities in the normal appearing white matter) but not in those with neuromyelitis optica, where localised abnormalities in the optic radiations of those with severe visual impairment were noted. In addition, between relapses, there were no new silent brain lesions in the neuromyelitis optica group. These findings indicate that global central nervous system neurodegeneration is not a feature of neuromyelitis optica. The work also questions the theory that neurodegeneration in multiple sclerosis is a chronic sequela to prior inflammatory and demyelinating pathology, as this has not been found to be the case in neuromyelitis optica where the lesions are often more destructive.

  19. Imaging Surrogates of Disease Activity in Neuromyelitis Optica Allow Distinction from Multiple Sclerosis.

    Lucy Matthews

    Full Text Available Inflammatory demyelinating lesions of the central nervous system are a common feature of both neuromyelitis optica and multiple sclerosis. Despite this similarity, it is evident clinically that the accumulation of disability in patients with neuromyelitis optica is relapse related and that a progressive phase is very uncommon. This poses the question whether there is any pathological evidence of disease activity or neurodegeneration in neuromyelitis optica between relapses. To investigate this we conducted a longitudinal advanced MRI study of the brain and spinal cord in neuromyelitis optica patients, comparing to patients with multiple sclerosis and controls. We found both cross-sectional and longitudinal evidence of diffusely distributed neurodegenerative surrogates in the multiple sclerosis group (including thalamic atrophy, cervical cord atrophy and progressive widespread diffusion and myelin water imaging abnormalities in the normal appearing white matter but not in those with neuromyelitis optica, where localised abnormalities in the optic radiations of those with severe visual impairment were noted. In addition, between relapses, there were no new silent brain lesions in the neuromyelitis optica group. These findings indicate that global central nervous system neurodegeneration is not a feature of neuromyelitis optica. The work also questions the theory that neurodegeneration in multiple sclerosis is a chronic sequela to prior inflammatory and demyelinating pathology, as this has not been found to be the case in neuromyelitis optica where the lesions are often more destructive.

  20. The importance of studying sex differences in disease: The example of multiple sclerosis.

    Golden, Lisa C; Voskuhl, Rhonda

    2017-01-02

    To date, scientific research has often focused on one sex, with assumptions that study of the other sex would yield similar results. However, many diseases affect males and females differently. The sex of a patient can affect the risk for both disease susceptibility and progression. Such differences can be brought to the laboratory bench to be investigated, potentially bringing new treatments back to the clinic. This method of research, known as a "bedside to bench to bedside" approach, has been applied to studying sex differences in multiple sclerosis (MS). Females have greater susceptibly to MS, while males have worse disease progression. These two characteristics of the disease are influenced by the immune system and the nervous system, respectively. Thus, sex differences in each system must be studied. Personalized medicine has been at the forefront of research recently, and studying sex differences in disease fits with this initiative. This review will discuss the known sex differences in MS and highlight how investigating them can lead to new insights and potential treatments for both men and women. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Multiple contemporary arterial dissection in Ehlers-Danlos syndrome type IV

    Anna Rocci

    2015-03-01

    Full Text Available We report a case of multiple spontaneous arteries dissection in a 52-year-old female; the patient had a relevant family history of vascular complications and typical features so we hypothesized vascular Ehlers-Danlos syndrome (EDS that was confirmed by genetic analysis of COL3A1 gene. We adopted a conservative approach: the patient was treated with heparin in the acute phase followed by aspirin and then celiprolol was started on the basis of a recent trial that demonstrates a reduction in arterial events in EDS patient treated. A careful follow-up was done with Doppler ultrasound and computed tomography scan, as non-invasive diagnostic techniques are preferred in these patients, and no other vascular symptomatic events have occurred. We tested all living relatives: half of them had COL3A1 mutation, they were referred to another center specialized in rare diseases and EDS for long-term follow-up and genetic counseling. This case demonstrates as a careful evaluation of clinical signs, clinical history of the patient and his family has allowed a definitive diagnosis, proper management of the patient during the acute event and in terms of prophylaxis of recurrence.

  2. On the construction of elliptic Chudnovsky-type algorithms for multiplication in large extensions of finite fields

    Ballet, Stéphane; Bonnecaze, Alexis; Tukumuli, Mila

    2013-01-01

    International audience; We indicate a strategy in order to construct bilinear multiplication algorithms of type Chudnovsky in large extensions of any finite field. In particular, using the symmetric version of the generalization of Randriambololona specialized on the elliptic curves, we show that it is possible to construct such algorithms with low bilinear complexity. More precisely, if we only consider the Chudnovsky-type algorithms of type symmetric elliptic, we show that the symmetric bil...

  3. Design and performance of multiple effect basin type solar still; Basin-taju koyo fukugogata taiyonetsu joryuki no kaihatsu

    Tanaka, H; Nosoko, T; Nagata, T [Univ. of the Ryukyus, Okinawa (Japan)

    1997-11-25

    A seawater desalinating still was devised, which utilizes solar heat and combines a basin type still with a multiple effect type still. The devised still has a triangular cross section, has a seawater basin at its bottom, wherein the slope facing the sun has a double glass window, and the other slope is arranged with a multiple effect still (three-step effect system). The sun light that has permeated the double glass window heats and evaporates seawater on the basin. Majority of the generated steam is condensed at the lower face of a lowermost partition of the multiple effect section, and its latent heat evaporates the seawater contained in a wick on the rear side. The steam is condensed at the lower face of the second partition, this action is repeated sequentially to upper plates, and the heat is discharged finally into the surrounding air from the uppermost face of the multiple effect section. Seawater is supplied from the upper part onto the wick in each partition, which is evaporated, condensed and recovered at the lower part. The condensate is recovered at the lower part of each plate. The construction is simpler than the conventional downward indirect heating multiple effect type still, and the distilling efficiency is improved by 30%. Technological difficulty in the upward direct heating multiple effect type still can also be improved. 6 refs., 6 figs., 2 tabs.

  4. Infections in patients with multiple sclerosis: Implications for disease-modifying therapy.

    Celius, E G

    2017-11-01

    Patients with multiple sclerosis have an increased risk of infections compared to the general population. The increased risk has been described for decades and is not alone attributed to the use of disease-modifying drugs, but secondary to the disability. The introduction of more potent immunomodulatory drugs may cause an additional challenge, and depending on the mechanism of action, a treatment-induced increased risk of bacterial, viral, fungal or parasitic infections is observed. The choice of treatment in the individual patient with infections and multiple sclerosis must be guided by the drugs' specific mechanism of action, the drug-specific risk of infection and comorbidities. Increased monitoring and follow-up through treatment registries is warranted to increase our understanding and thereby improve management. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European Study on Glycogen Storage Disease Type 1

    Visser, G.; Rake, J.P.; Labrune, P.; Leonard, J.V.; Moses, S.; Ullrich, K.; Wendel, U.; Groenier, K.H.; Smit, G.P.

    2002-01-01

    Patients with glycogen storage disease type 1b (GSD-1b) have neutropenia and neutrophil dysfunction that predispose to frequent infections and inflammatory bowel disease (IBD), for which granulocyte colony-stimulating factor (GCSF) is given. To investigate the use and the value of GCSF treatment in

  6. Digital dashboard design using multiple data streams for disease surveillance with influenza surveillance as an example.

    Cheng, Calvin K Y; Ip, Dennis K M; Cowling, Benjamin J; Ho, Lai Ming; Leung, Gabriel M; Lau, Eric H Y

    2011-10-14

    Great strides have been made exploring and exploiting new and different sources of disease surveillance data and developing robust statistical methods for analyzing the collected data. However, there has been less research in the area of dissemination. Proper dissemination of surveillance data can facilitate the end user's taking of appropriate actions, thus maximizing the utility of effort taken from upstream of the surveillance-to-action loop. The aims of the study were to develop a generic framework for a digital dashboard incorporating features of efficient dashboard design and to demonstrate this framework by specific application to influenza surveillance in Hong Kong. Based on the merits of the national websites and principles of efficient dashboard design, we designed an automated influenza surveillance digital dashboard as a demonstration of efficient dissemination of surveillance data. We developed the system to synthesize and display multiple sources of influenza surveillance data streams in the dashboard. Different algorithms can be implemented in the dashboard for incorporating all surveillance data streams to describe the overall influenza activity. We designed and implemented an influenza surveillance dashboard that utilized self-explanatory figures to display multiple surveillance data streams in panels. Indicators for individual data streams as well as for overall influenza activity were summarized in the main page, which can be read at a glance. Data retrieval function was also incorporated to allow data sharing in standard format. The influenza surveillance dashboard serves as a template to illustrate the efficient synthesization and dissemination of multiple-source surveillance data, which may also be applied to other diseases. Surveillance data from multiple sources can be disseminated efficiently using a dashboard design that facilitates the translation of surveillance information to public health actions.

  7. Relationship between contrast sensitivity test and disease severity in multiple sclerosis patients.

    Soler García, A; González Gómez, A; Figueroa-Ortiz, L C; García-Ben, A; García-Campos, J

    2014-09-01

    To assess the importance of the Pelli-Robson contrast sensitivity test in multiple sclerosis patients according to the Expanded Disability Status Scale (EDSS). A total of 62 patients with multiple sclerosis were included in a retrospective study. Patients were enrolled from the Neurology Department to Neuroophthalmology at Virgen de la Victoria Hospital. Patients were classified into 3 groups according to EDSS: group A) lower than 1.5, group B) between 1.5 and 3.5 and group C) greater than 3.5. Visual acuity and monocular and binocular contrast sensitivity were performed with Snellen and Pelli-Robson tests respectively. Twelve disease-free control participants were also recruited. Correlations between parameter changes were analyzed. The mean duration of the disease was 81.54±35.32 months. Monocular and binocular Pelli-Robson mean values in the control group were 1.82±0.10 and 1.93±0.43 respectively, and 1.61±0.29 and 1.83±0.19 in multiple sclerosis patients. There were statistically significant differences in the monocular analysis for a level of significance P<.05. Mean monocular and binocular Pelli-Robson values in relation to gravity level were, in group A: 1.66±0.24 and 1.90±0.98, group B: 1.64±0.21 and 1.82±0.16, and group C: 1.47±0.45 and 1.73±0.32 respectively. Group differences were statistically significant in both tests: P=.05 and P=.027. Monocular and binocular contrast discrimination analyzed using the Pelli-Robson test was found to be significantly lower when the severity level, according EDSS, increases in multiple sclerosis patients. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  8. Multiple sclerosis: patients’ information sources and needs on disease symptoms and management

    Albert I Matti

    2010-06-01

    Full Text Available Albert I Matti1, Helen McCarl2, Pamela Klaer2, Miriam C Keane1, Celia S Chen11Department of Ophthalmology, Flinders Medical Centre and Flinders University, Bedford Park, SA, Australia; 2The Multiple Sclerosis Society of South Australia and Northern Territory, Klemzig, SA, AustraliaObjective: To investigate the current information sources of patients with multiple sclerosis (MS in the early stages of their disease and to identify patients’ preferred source of information. The relative amounts of information from the different sources were also compared.Methods: Participants at a newly diagnosed information session organized by the Multiple Sclerosis Society of South Australia were invited to complete a questionnaire. Participants were asked to rate on a visual analog scale how much information they had received about MS and optic neuritis from different information sources and how much information they would like to receive from each of the sources.Results: A close to ideal amount of information is being provided by the MS society and MS specialist nurses. There is a clear deficit between what information patients are currently receiving and the amount of information they actually want from various sources. Patients wish to receive significantly more information from treating general practitioners, eye specialists, neurologists, and education sessions. Patients have identified less than adequate information received on optic neuritis from all sources.Conclusion: This study noted a clear information deficit regarding MS from all sources. This information deficit is more pronounced in relation to optic neuritis and needs to be addressed in the future.Practice implications: More patient information and counselling needs to be provided to MS patients even at early stages of their disease, especially in relation to management of disease relapse.Keywords: information sources, information needs, MS patients, optic neuritis

  9. One For All? Hitting multiple Alzheimer’s Disease targets with one drug

    Rebecca Ellen Hughes

    2016-04-01

    Full Text Available Alzheimer’s disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs. Intended as a introduction for non-experts, this review describes the key multi-target drug design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch and also the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer’s Disease are rasagiline, originally developed for the treatment of Parkinson’s Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic.

  10. Growth Hormone and Disease Severity in Early Stage of Multiple Sclerosis

    M. Gironi

    2013-01-01

    Full Text Available Evidence suggests that neurohormones such as GH and IGF-I are involved in the neuroreparative processes in multiple sclerosis (MS. GH and IGF-I blood levels in naïve MS patients with different disease courses were investigated in this study. Serum GH and IGF-I in untreated MS patients (n=64, healthy controls (HC, n=62, and patients affected by other neurological diseases (OND, n=46 were evaluated with a solid-phase-enzyme-labeled-chemiluminescent-immunometric assay. No differences were detected in GH across MS, OND, and HC (MS=0.87±1.32 ng/mL; OND=1.66±3.7; and HC=1.69±3.35; P=0.858 when considering gender, disease duration, and disease course. However, GH was lower (P=0.007 in patients with more severe disease (expanded disability scale score, EDSS≥4.0 compared with milder forms (EDSS<4. IGF-I l did not differ across the 3 groups (P=0.160, as far as concern disease course, disability, and gender were. Lower IGF-I levels were detected in subjects older than 50 years compared to younger ones for all 3 groups. Lower GH was detected in patients with more severe MS, and age was confirmed as the main factor driving IGF-I levels in all subjects. These findings, relying on the natural course of the disease, could help in shedding lights on the mechanisms involved in autoreparative failure associated with poorer prognosis in MS.

  11. Analysis of risk factors in obese patients with coronary artery disease, with and without diabetes mellitus type two

    Vasić Danjela

    2014-01-01

    Full Text Available Diabetes mellitus type 2 is one of the leading chronic diseases in the world and in our country, which is an important risk factor for development of cardiovascular morbidity and mortality. Objective. The aim of this research was making the estimation of risk factors in the etiology of coronary heart disease in obese patients with diabetes mellitus type 2. The study included 82 obese patients, of which 52 with diabetes mellitus and 30 without diabetes mellitus, in all of them coronary artery disease proven by coronary angiography. All were examined by clinical examination, laboratory tests and echocardiography. Based on the test results we found that the distribution of risk factors such as hypertension, family burden coronary artery disease, smoking, alcohol intake was the same in the obese patients with diabetes mellitus, and of those without diabetes mellitus. Echocardiography showed significantly larger left ventricle, lower ejection fraction, larger left atrium and significant mitral regurgitation. Also, in a group of patients with diabetes mellitus, there was significantly higher number of patients with multiple vessel coronary disease. Despite the small sample, we can conclude that the present of diabetes mellitus in obese patients is crucial for severe forms of coronary artery disease. Severity is expressed through significant structural and functional changes in the left ventricle and the number of diseased coronary arteries.

  12. Haemophilus influenzae Type b disease among Amish children in Pennsylvania: reasons for persistent disease.

    Fry, A M; Lurie, P; Gidley, M; Schmink, S; Lingappa, J; Fischer, M; Rosenstein, N E

    2001-10-01

    To identify reservoirs of Haemophilus influenzae type b (Hib) pharyngeal carriage and assess barriers to vaccination among 2 Amish communities in Pennsylvania. We investigated recent cases, performed community surveys for Hib vaccination coverage and pharyngeal carriage, and administered a questionnaire assessing vaccination knowledge and attitudes to 298 members of 2 Amish communities (A and B) in Pennsylvania and, as a comparison group, 136 non-Amish family members who participated in state immunization clinics. From December 1999 to February 2000, 8 cases of invasive Hib disease occurred among children who were 5 years of age or younger in Pennsylvania. Six of the case-patients were from Amish communities. None of the children had been vaccinated. Among children who were 5 years of age or younger, Hib vaccine coverage was low in the 2 Amish communities: A (9 [28%] of 32) and B (3 [7%] of 41) compared with the non-Amish group (19 [95%] of 20). Hib carriage prevalence was higher in both Amish communities than in the non-Amish group (A: 3%; B: 8%; non-Amish: 0%). More households in community B had 1 or more Hib carriers than in community A (8 [28%] of 29 vs 3 [9%] of 32). Among Amish parents who did not vaccinate their children, only 25% (13 of 51) identified either religious or philosophical objections as a factor; 51% (26 of 51) reported that vaccinating was not a priority compared with other activities of daily life. Seventy-three percent (36 of 49) would vaccinate their children if vaccination were offered locally. Undervaccinated communities in the United States still exist and allow circulation of Hib strains, resulting in disease among susceptible children. Identification of undervaccinated populations, such as the Amish, and targeted education and vaccination campaigns are essential to achieving elimination of Hib disease.

  13. Designing Kerr interactions using multiple superconducting qubit types in a single circuit

    Elliott, Matthew; Joo, Jaewoo; Ginossar, Eran

    2018-02-01

    The engineering of Kerr interactions is of great interest for processing quantum information in multipartite quantum systems and for investigating many-body physics in a complex cavity-qubit network. We study how coupling multiple different types of superconducting qubits to the same cavity modes can be used to modify the self- and cross-Kerr effects acting on the cavities and demonstrate that this type of architecture could be of significant benefit for quantum technologies. Using both analytical perturbation theory results and numerical simulations, we first show that coupling two superconducting qubits with opposite anharmonicities to a single cavity enables the effective self-Kerr interaction to be diminished, while retaining the number splitting effect that enables control and measurement of the cavity field. We demonstrate that this reduction of the self-Kerr effect can maintain the fidelity of coherent states and generalised Schrödinger cat states for much longer than typical coherence times in realistic devices. Next, we find that the cross-Kerr interaction between two cavities can be modified by coupling them both to the same pair of qubit devices. When one of the qubits is tunable in frequency, the strength of entangling interactions between the cavities can be varied on demand, forming the basis for logic operations on the two modes. Finally, we discuss the feasibility of producing an array of cavities and qubits where intermediary and on-site qubits can tune the strength of self- and cross-Kerr interactions across the whole system. This architecture could provide a way to engineer interesting many-body Hamiltonians and be a useful platform for quantum simulation in circuit quantum electrodynamics.

  14. Human immunodeficiency virus-like particles activate multiple types of immune cells

    Sailaja, Gangadhara; Skountzou, Ioanna; Quan, Fu-Shi; Compans, Richard W.; Kang, Sang-Moo

    2007-01-01

    The rapid spread of human immunodeficiency virus (HIV) worldwide makes it a high priority to develop an effective vaccine. Since live attenuated or inactivated HIV is not likely to be approved as a vaccine due to safety concerns, HIV virus like particles (VLPs) offer an attractive alternative because they are safe due to the lack of a viral genome. Although HIV VLPs have been shown to induce humoral and cellular immune responses, it is important to understand the mechanisms by which they induce such responses and to improve their immunogenicity. We generated HIV VLPs, and VLPs containing Flt3 ligand (FL), a dendritic cell growth factor, to target VLPs to dendritic cells, and investigated the roles of these VLPs in the initiation of adaptive immune responses in vitro and in vivo. We found that HIV-1 VLPs induced maturation of dendritic cells and monocyte/macrophage populations in vitro and in vivo, with enhanced expression of maturation markers and cytokines. Dendritic cells pulsed with VLPs induced activation of splenocytes resulting in increased production of cytokines. VLPs containing FL were found to increase dendritic cells and monocyte/macrophage populations in the spleen when administered to mice. Administration of VLPs induced acute activation of multiple types of cells including T and B cells as indicated by enhanced expression of the early activation marker CD69 and down-regulation of the homing receptor CD62L. VLPs containing FL were an effective form of antigen in activating immune cells via dendritic cells, and immunization with HIV VLPs containing FL resulted in enhanced T helper type 2-like immune responses

  15. Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

    Pessoa de Magalhães, Roberto J.; Vidriales, María-Belén; Paiva, Bruno; Fernandez-Gimenez, Carlos; García-Sanz, Ramón; Mateos, Maria-Victoria; Gutierrez, Norma C.; Lecrevisse, Quentin; Blanco, Juan F; Hernández, Jose; de las Heras, Natalia; Martinez-Lopez, Joaquin; Roig, Monica; Costa, Elaine Sobral; Ocio, Enrique M.; Perez-Andres, Martin; Maiolino, Angelo; Nucci, Marcio; De La Rubia, Javier; Lahuerta, Juan-Jose; San-Miguel, Jesús F.; Orfao, Alberto

    2013-01-01

    Multiple myeloma remains largely incurable. However, a few patients experience more than 10 years of relapse-free survival and can be considered as operationally cured. Interestingly, long-term disease control in multiple myeloma is not restricted to patients with a complete response, since some patients revert to having a profile of monoclonal gammopathy of undetermined significance. We compared the distribution of multiple compartments of lymphocytes and dendritic cells in the bone marrow and peripheral blood of multiple myeloma patients with long-term disease control (n=28), patients with newly diagnosed monoclonal gammopathy of undetermined significance (n=23), patients with symptomatic multiple myeloma (n=23), and age-matched healthy adults (n=10). Similarly to the patients with monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma, patients with long-term disease control showed an expansion of cytotoxic CD8+ T cells and natural killer cells. However, the numbers of bone marrow T-regulatory cells were lower in patients with long-term disease control than in those with symptomatic multiple myeloma. It is noteworthy that B cells were depleted in patients with monoclonal gammopathy of undetermined significance and in those with symptomatic multiple myeloma, but recovered in both the bone marrow and peripheral blood of patients with long-term disease control, due to an increase in normal bone marrow B-cell precursors and plasma cells, as well as pre-germinal center peripheral blood B cells. The number of bone marrow dendritic cells and tissue macrophages differed significantly between patients with long-term disease control and those with symptomatic multiple myeloma, with a trend to cell count recovering in the former group of patients towards levels similar to those found in healthy adults. In summary, our results indicate that multiple myeloma patients with long-term disease control have a constellation of unique immune changes

  16. Multiple reaction monitoring assay based on conventional liquid chromatography and electrospray ionization for simultaneous monitoring of multiple cerebrospinal fluid biomarker candidates for Alzheimer's disease.

    Choi, Yong Seok; Lee, Kelvin H

    2016-03-01

    Alzheimer's disease (AD) is the most common type of dementia, but early and accurate diagnosis remains challenging. Previously, a panel of cerebrospinal fluid (CSF) biomarker candidates distinguishing AD and non-AD CSF accurately (>90 %) was reported. Furthermore, a multiple reaction monitoring (MRM) assay based on nano liquid chromatography tandem mass spectrometry (nLC-MS/MS) was developed to help validate putative AD CSF biomarker candidates including proteins from the panel. Despite the good performance of the MRM assay, wide acceptance may be challenging because of limited availability of nLC-MS/MS systems in laboratories. Thus, here, a new MRM assay based on conventional LC-MS/MS is presented. This method monitors 16 peptides representing 16 (of 23) biomarker candidates that belonged to the previous AD CSF panel. A 30-times more concentrated sample than the sample used for the previous study was loaded onto a high capacity trap column, and all 16 MRM transitions showed good linearity (average R(2) = 0.966), intra-day reproducibility (average coefficient of variance (CV) = 4.78 %), and inter-day reproducibility (average CV = 9.85 %). The present method has several advantages such as a shorter analysis time, no possibility of target variability, and no need for an internal standard.

  17. Spinal tumours in neurofibromatosis type 1: an MRI study of frequency, multiplicity and variety

    Thakkar, S.D.; Mautner, V.F.; Feigen, U.

    1999-01-01

    In neurofibromatosis type 1 (NF1) spinal tumours cause neurological symptoms in about 2 % of patients. Among over 1400 patients with NF1 we saw symptomatic spinal tumours in 23 (1.6 %). MRI of the entire spinal canal was obtained in 54 patients aged 5-56 years with NF1. The number, site, morphology and signal characteristics of the spinal tumours were recorded and analysed. There were 24 patients with symptoms such as sensory impairment or paralysis; 30 patients had no neurological deficits. Of the 24 symptomatic patients, 23 (96 %) had spinal tumours, while we saw spinal tumours in 12 (40 %) of the 30 patients without neurological deficits. No spinal segment was preferred in symptomatic or asymptomatic patients. Most intraspinal extramedullary tumours were primarily extradural and intraforaminal. MRI showed intramedullary tumours in 3 patients (6 %), intraspinal extramedullary tumours in 18 (33 %) and intraforaminal tumours in 31 (57 %). Only neurological deficits in patients with NF1 should prompt further diagnostic clarification. In patients with neurological symptoms there may be a multiplicity of masses in the spinal canal, which can lead to difficulties in attaching symptoms to a certain tumour. In patients who do not satisfy the NIH criteria, it can be a helpful observation that spinal tumours in NF1 are primarily intraforaminal, extending into the spinal canal, while in NF2 they are mostly intraspinal intradural tumours. (orig.)

  18. Impact of Co-Channel Interference on the Outage Performance Under Multiple Type II Relay Environments

    Choi, Seyeong; Alouini, Mohamed-Slim; Nam, Sung Sik

    2017-01-01

    In this paper, through an exact analysis of the outage probability, we investigate the impact of co-channel interference (CCI) on the outage performance of type II (or user equipment) relay under multiple-relay environments considering the selection combining-based relay selection scheme with the decode-and-forward protocol. We consider the signal to interference plus noise ratio (SINR) over both independent and identically distributed and independent but non-identically distributed fading channels. To fully take into account the effect of CCI, we adopt a more practical parameter such as the CCI coefficient. The major difficulty in the analysis resides in the determination of the statistics of the output SINR. To settle this problem, we first present the general but relatively simplified expressions for the statistics and then the related outage probability in closed-form. Furthermore, to consider more practical scenario, based on the fact that the number of participating relays can be random, we investigate the average outage probability by averaging the number of participating relays.

  19. Multiple zebrafish atoh1 genes specify a diversity of neuronal types in the zebrafish cerebellum.

    Kidwell, Chelsea U; Su, Chen-Ying; Hibi, Masahiko; Moens, Cecilia B

    2018-06-01

    A single Atoh1 basic-helix-loop-helix transcription factor specifies multiple neuron types in the mammalian cerebellum and anterior hindbrain. The zebrafish genome encodes three paralagous atoh1 genes whose functions in cerebellum and anterior hindbrain development we explore here. With use of a transgenic reporter, we report that zebrafish atoh1c-expressing cells are organized in two distinct domains that are separated both by space and developmental time. An early isthmic expression domain gives rise to an extracerebellar population in rhombomere 1 and an upper rhombic lip domain gives rise to granule cell progenitors that migrate to populate all four granule cell territories of the fish cerebellum. Using genetic mutants we find that of the three zebrafish atoh1 paralogs, atoh1c and atoh1a are required for the full complement of granule neurons. Surprisingly, the two genes are expressed in non-overlapping granule cell progenitor populations, indicating that fish use duplicate atoh1 genes to generate granule cell diversity that is not detected in mammals. Finally, live imaging of granule cell migration in wildtype and atoh1c mutant embryos reveals that while atoh1c is not required for granule cell specification per se, it is required for granule cells to delaminate and migrate away from the rhombic lip. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Type 2 diabetes-related variants influence the risk of developing multiple myeloma

    Ríos, Rafael; Lupiañez, Carmen Belén; Campa, Daniele

    2015-01-01

    Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence...... genetic information (area under the curve (AUC)=0.645 vs AUC=0.629; P=4.05×10(-) (06)). A gender-stratified analysis also revealed a significant gender effect modification for ADAM30rs2641348 and NOTCH2rs10923931 variants (Pinteraction=0.001 and 0.0004, respectively). Men carrying the ADAM30rs2641348C...... carrying the KCNQ1rs2237892T allele or the CDKN2A-2Brs2383208G/G, IGF1rs35767T/T and MADDrs7944584T/T genotypes had a significantly increased risk of MM (odds ratio (OR)=1.32-2.13) whereas those carrying the KCNJ11rs5215C, KCNJ11rs5219T and THADArs7578597C alleles or the FTOrs8050136A/A and LTArs1041981C...

  1. Optimal placement of multiple types of communicating sensors with availability and coverage redundancy constraints

    Vecherin, Sergey N.; Wilson, D. Keith; Pettit, Chris L.

    2010-04-01

    Determination of an optimal configuration (numbers, types, and locations) of a sensor network is an important practical problem. In most applications, complex signal propagation effects and inhomogeneous coverage preferences lead to an optimal solution that is highly irregular and nonintuitive. The general optimization problem can be strictly formulated as a binary linear programming problem. Due to the combinatorial nature of this problem, however, its strict solution requires significant computational resources (NP-complete class of complexity) and is unobtainable for large spatial grids of candidate sensor locations. For this reason, a greedy algorithm for approximate solution was recently introduced [S. N. Vecherin, D. K. Wilson, and C. L. Pettit, "Optimal sensor placement with terrain-based constraints and signal propagation effects," Unattended Ground, Sea, and Air Sensor Technologies and Applications XI, SPIE Proc. Vol. 7333, paper 73330S (2009)]. Here further extensions to the developed algorithm are presented to include such practical needs and constraints as sensor availability, coverage by multiple sensors, and wireless communication of the sensor information. Both communication and detection are considered in a probabilistic framework. Communication signal and signature propagation effects are taken into account when calculating probabilities of communication and detection. Comparison of approximate and strict solutions on reduced-size problems suggests that the approximate algorithm yields quick and good solutions, which thus justifies using that algorithm for full-size problems. Examples of three-dimensional outdoor sensor placement are provided using a terrain-based software analysis tool.

  2. Impact of Co-Channel Interference on the Outage Performance Under Multiple Type II Relay Environments

    Choi, Seyeong

    2017-11-15

    In this paper, through an exact analysis of the outage probability, we investigate the impact of co-channel interference (CCI) on the outage performance of type II (or user equipment) relay under multiple-relay environments considering the selection combining-based relay selection scheme with the decode-and-forward protocol. We consider the signal to interference plus noise ratio (SINR) over both independent and identically distributed and independent but non-identically distributed fading channels. To fully take into account the effect of CCI, we adopt a more practical parameter such as the CCI coefficient. The major difficulty in the analysis resides in the determination of the statistics of the output SINR. To settle this problem, we first present the general but relatively simplified expressions for the statistics and then the related outage probability in closed-form. Furthermore, to consider more practical scenario, based on the fact that the number of participating relays can be random, we investigate the average outage probability by averaging the number of participating relays.

  3. T regulatory cells are markers of disease activity in multiple sclerosis patients.

    Dacia Dalla Libera

    Full Text Available FoxP3⁺ Treg cells are believed to play a role in the occurrence of autoimmunity and in the determination of clinical recurrences. Contradictory reports are, however, available describing frequency and function of Treg cells during autoimmune diseases. We examined, by both polychromatic flow cytometry, and real-time RT-PCR, several Treg markers in peripheral blood mononuclear cells from patients with multiple sclerosis (MS, an autoimmune disease affecting the central nervous system. We found that Tregs, as defined by CD25, CD39, FoxP3, CTLA4, and GITR expression, were significantly decreased in stable MS patients as compared to healthy donors, but, surprisingly, restored to normal levels during an acute clinical attack. We conclude that Treg cells are not involved in causing clinical relapses, but rather react to inflammation in the attempt to restore homeostasis.

  4. Retrospective study of diseases and associated pneumonia type ...

    ADEYEYE

    2014-09-05

    Sep 5, 2014 ... The causes and types of pneumonia in dogs have not been accorded due attention in Nigeria. It is imperative to ... records while the specific type of pneumonia was by histopathology of selected lungs tissues, using standard techniques. .... compromised immunity or those associated with stress due to early ...

  5. Retrospective study of diseases and associated pneumonia type ...

    The causes and types of pneumonia in dogs have not been accorded due attention in Nigeria. It is imperative to investigate the incidence and type of pneumonia commonly observed during post-mortem at the Department of Veterinary Pathology arm of the Veterinary Teaching Hospital, Ibadan, Nigeria. This investigation ...

  6. Nontypeable pneumococci can be divided into multiple cps types, including one type expressing the novel gene pspK.

    Park, In Ho; Kim, Kyung-Hyo; Andrade, Ana Lucia; Briles, David E; McDaniel, Larry S; Nahm, Moon H

    2012-01-01

    Although virulence of Streptococcus pneumoniae is associated with its capsule, some pathogenic S. pneumoniae isolates lack capsules and are serologically nontypeable (NT). We obtained 64 isolates that were identified as NT "pneumococci" (i.e., bacteria satisfying the conventional definition but without the multilocus sequence typing [MLST]-based definition of S. pneumoniae) by the traditional criteria. All 64 were optochin sensitive and had lytA, and 63 had ply. Twelve isolates had cpsA, suggesting the presence of a conventional but defective capsular polysaccharide synthesis (cps) locus. The 52 cpsA-negative isolates could be divided into three null capsule clades (NCC) based on aliC (aliB-like ORF1), aliD (aliB-like ORF2), and our newly discovered gene, pspK, in their cps loci. pspK encodes a protein with a long alpha-helical region containing an LPxTG motif and a YPT motif known to bind human pIgR. There were nine isolates in NCC1 (pspK(+) but negative for aliC and aliD), 32 isolates in NCC2 (aliC(+) aliD(+) but negative for pspK), and 11 in NCC3 (aliD(+) but negative for aliC and pspK). Among 52 cpsA-negative isolates, 41 were identified as S. pneumoniae by MLST analysis. All NCC1 and most NCC2 isolates were S. pneumoniae, whereas all nine NCC3 and two NCC2 isolates were not S. pneumoniae. Several NCC1 and NCC2 isolates from multiple individuals had identical MLST and cps regions, showing that unencapsulated S. pneumoniae can be infectious among humans. Furthermore, NCC1 and NCC2 S. pneumoniae isolates could colonize mice as well as encapsulated S. pneumoniae, although S. pneumoniae with an artificially disrupted cps locus did not. Moreover, an NCC1 isolate with pspK deletion did not colonize mice, suggesting that pspK is critical for colonization. Thus, PspK may provide pneumococci a means of surviving in the nasopharynx without capsule. IMPORTANCE The presence of a capsule is critical for many pathogenic bacteria, including pneumococci. Reflecting the

  7. Effectiveness of Multiple Daily Injections or Continuous Subcutaneous Insulin Infusion for Children with Type 1 Diabetes Mellitus in Clinical Practice

    Chun-xiu Gong

    2014-01-01

    Full Text Available Aims. To determine whether multiple daily injections (MDIs or continuous subcutaneous insulin infusion (CSII contributes to better glucose control in children with different type 1 diabetes duration. Methods. Subjects were grouped according to early (≤1 year after disease onset; 1A or late (1–3 years after onset; 2A MDIs/CSII treatment initiation. Corresponding control groups (1B, 2B received insulin injections twice daily. Results. HbA1c levels were consistently lower in group 1A than in group 1B (6 months (T2: 7.37% versus 8.21%; 12 months (T3: 7.61% versus 8.41%; 24/36 months (T4/T5: 7.61% versus 8.72%; all P<0.05, but were lower in group 2A than in group 2B only at T2 (8.36% versus 9.19%; P=0.04. Levels were lower in group 1A than in group 2A when disease duration was matched (7.61% versus 8.49%; P<0.05. Logistic regression revealed no correlation between HbA1c level and MDIs/CSII therapy. HbA1c levels were only negatively related to insulin dosage. Conclusions. Blood glucose control was better in patients receiving MDIs/CSII than in those receiving conventional treatment. Early MDIs/CSII initiation resulted in prolonged maintenance of low HbA1c levels compared with late initiation. MDIs/CSII therapy should be combined with comprehensive management.

  8. Assessment of Depression, Anxiety, Quality of Life, and Coping in Long-Standing Multiple Endocrine Neoplasia Type 2 Patients.

    Rodrigues, Karine C; Toledo, Rodrigo A; Coutinho, Flavia L; Nunes, Adriana B; Maciel, Rui M B; Hoff, Ana O; Tavares, Marcos C; Toledo, Sergio P A; Lourenço, Delmar M

    2017-05-01

    Data on psychological harm in multiple endocrine neoplasia type 2 (MEN2) are scarce. The aim of this study was to assess anxiety, depression, quality of life, and coping in long-standing MEN2 patients. Patients were 43 adults (age ≥18 years) with clinical and genetic diagnosis of MEN2 and long-term follow-up (10.6 ± 8.2 years; range 1-33 years). This was a cross-sectional study with qualitative and quantitative psychological assessment using semi-directed interviews and HADS, EORTC QLQ C30, and MINI-MAC scales. Adopting clinical criteria from 2015 ATA Guidelines on MEN2, biochemical cure (39%; 16/41), persistence/recurrence (61%; 25/41), and stable chronic disease (22/41) of medullary thyroid carcinoma (MTC) were scored. Pheochromocytoma affected 19 (44%) patients, with previous adrenalectomy in 17 of them. Overall, anxiety (42%; mean score 11 ± 2.9; range 8-18; anxiety is defined as a score ≥8) and depression (26%; mean score 11 ± 3.8; range 8-20; depression is defined as a score ≥8) symptoms were frequent. Patients who transmitted RET mutations to a child had higher scores for weakness-discouragement/anxious preoccupation and lower scores for cognitive, emotional, and physical functioning (p emotional functioning were noticed in 33 patients who were well-informed about their disease (p stress-inducing factors had lower scores for fighting spirit and cognitive functioning and higher scores for insomnia and dyspnea (p stress-inducing factors, and cure) interfering positively or negatively with the results of the psychometrics scales. The active investigation of these factors and the applied psychological assessment protocol are useful to identify MEN2 patients requiring psychological assistance.

  9. Risk of development of chronic kidney disease in patients with type 2 diabetes having metabolic syndrome

    Moin, S.; Gondal, G.M.G.

    2008-01-01

    To measure the relation of creatinine clearance in type-2 diabetic patients with different components of metabolic syndrome and to quantify the relationship of frequency of incident CKD with increasing number of metabolic syndrome components while controlling for age, gender and duration of diabetes. Cross-sectional descriptive study. Patients having type-2 Diabetes for more than 5 years were enrolled. Information regarding age, gender, duration of diabetes, type of diabetes, treatment taking, complete fasting lipid profile, fasting blood glucose, Body Mass Index (BMI), 24 hours urinary proteins and creatinine clearance, co-existent risk factors like hypertension and ischemic heart disease was taken. Patients were divided into groups having one to all five metabolic syndrome traits. Progressive increase in the metabolic syndrome traits was compared with decline in creatinine clearance. Pearson correlation test and multiple logistic regression were applied to determine correlation with significance at r and p <0.05. Out of 104 evaluated female and male patients, 70% had hypertension, ischemic heart disease and a family history of diabetes. While 20% had normal creatinine clearance, 37% had a creatinine clearance between 60-90 ml/min, 19% had a creatinine clearance of 30-59 ml/min, 18% had a creatinine clearance of less than 30 ml/min and 10% were already in stage 5 CKD. The decline in renal function was more severe in subjects evaluated who had a higher number of features of the metabolic syndrome. Age was the only significant determinant of development of CKD (p=0.05). The renal function progressively declined with 3 or more features of the metabolic syndrome. (author)

  10. Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway.

    Fineran, Paul; Lloyd-Evans, Emyr; Lack, Nathan A; Platt, Nick; Davis, Lianne C; Morgan, Anthony J; Höglinger, Doris; Tatituri, Raju Venkata V; Clark, Simon; Williams, Ian M; Tynan, Patricia; Al Eisa, Nada; Nazarova, Evgeniya; Williams, Ann; Galione, Antony; Ory, Daniel S; Besra, Gurdyal S; Russell, David G; Brenner, Michael B; Sim, Edith; Platt, Frances M

    2016-11-18

    Tuberculosis remains a major global health concern. The ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including Mycobacterium tuberculosis , achieve long-term persistence within host cells. The mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. Host macrophages infected with persistent mycobacteria share phenotypic similarities with cells taken from patients suffering from Niemann-Pick Disease Type C (NPC), a rare lysosomal storage disease in which endocytic trafficking defects and lipid accumulation within the lysosome lead to cell dysfunction and cell death. We investigated whether these shared phenotypes reflected an underlying mechanistic connection between mycobacterial intracellular persistence and the host cell pathway dysfunctional in NPC. The induction of NPC phenotypes in macrophages from wild-type mice or obtained from healthy human donors was assessed via infection with mycobacteria and subsequent measurement of lipid levels and intracellular calcium homeostasis. The effect of NPC therapeutics on intracellular mycobacterial load was also assessed. Macrophages infected with persistent intracellular mycobacteria phenocopied NPC cells, exhibiting accumulation of multiple lipid types, reduced lysosomal Ca 2+ levels, and defects in intracellular trafficking. These NPC phenotypes could also be induced using only lipids/glycomycolates from the mycobacterial cell wall. These data suggest that persistent intracellular mycobacteria inhibit the NPC pathway, likely via inhibition of the NPC1 protein, and subsequently induce altered acidic store Ca 2+ homeostasis. Reduced lysosomal calcium levels may provide a mechanistic explanation for the reduced levels of phagosome-lysosome fusion in mycobacterial infection. Treatments capable of correcting defects in NPC mutant cells via modulation of host cell calcium were of benefit in promoting clearance of mycobacteria

  11. Validating the Type D personality construct in Chinese patients with coronary heart disease

    Yu, Doris S F; Thompson, David R; Yu, Cheuk Man

    2010-01-01

    Type D personality predicts poor prognosis in coronary heart disease (CHD) but little is known about Type D in non-Western cultures. We examined the (a) validity of the Type D construct and its assessment with the DS14 scale in the Chinese culture, (b) prevalence of Type D, and (c) gender vs. Typ...

  12. Multiple Observation Types Jointly Constrain Australian Terrestrial Carbon and Water Cycles

    Haverd, Vanessa; Raupach, Michael; Briggs, Peter; Canadell, Pep; Davis, Steven; Isaac, Peter; Law, Rachel; Meyer, Mick; Peters, Glenn; Pickett-Heaps, Christopher; Roxburgh, Stephen; Sherman, Bradford; van Gorsel, Eva; Viscarra Rossel, Raphael; Wang, Ziyuan

    2013-04-01

    Information about the carbon cycle potentially constrains the water cycle, and vice versa. This paper explores the utility of multiple observation sets to constrain carbon and water fluxes and stores in a land surface model, and a resulting determination of the Australian terrestrial carbon budget. Observations include streamflow from 416 gauged catchments, measurements of evapotranspiration (ET) and net ecosystem production (NEP) from 12 eddy-flux sites, litterfall data, and data on carbon pools. The model is a version of CABLE (the Community Atmosphere-Biosphere-Land Exchange model), coupled with CASAcnp (a biogeochemical model) and SLI (Soil-Litter-Iso, a soil hydrology model including liquid and vapour water fluxes and the effects of litter). By projecting observation-prediction residuals onto model uncertainty, we find that eddy flux measurements provide a significantly tighter constraint on Australian continental net primary production (NPP) than the other data types. However, simultaneous constraint by multiple data types is important for mitigating bias from any single type. Results emerging from the multiply-constrained model are as follows (with all values applying over 1990-2011 and all ranges denoting ±1 standard error): (1) on the Australian continent, a predominantly semi-arid region, over half (0.64±0.05) of the water loss through ET occurs through soil evaporation and bypasses plants entirely; (2) mean Australian NPP is 2200±400 TgC/y, making the NPP/precipitation ratio about the same for Australia as the global land average; (3) annually cyclic ("grassy") vegetation and persistent ("woody") vegetation respectively account for 0.56±0.14 and 0.43±0.14 of NPP across Australia; (4) the average interannual variability of Australia's NEP (±180 TgC/y) is larger than Australia's total anthropogenic greenhouse gas emissions in 2011 (149 TgCeq/y), and is dominated by variability in desert and savannah regions. The mean carbon budget over 1990

  13. Treatment and disease management of multiple sclerosis patients: A review for nurse practitioners.

    Roman, Cortnee; Menning, Kara

    2017-10-01

    This review discusses the role of the nurse practitioner (NP) in evaluating the clinical effects, potential side effects, and monitoring requirements for treatment options in multiple sclerosis (MS) and provides guidance on how to help patients understand these issues. A literature search was conducted on PubMed to identify publications on monitoring and disease management of MS patients. Additional resources included drug information web sites and package inserts. NPs play an active role in the management of MS patients via effective monitoring and communication throughout the patient's treatment regimen and disease course. In the shared decision-making model of MS treatment, NPs ensure that patients understand the implications of their disease-modifying therapies (DMTs). As patients move through treatments during the course of their disease, the importance of this role increases, and it is critical that NPs follow the guidelines in each medication's product label and take into account any potential lingering effects of prior medications. It is critical for NPs to promote patient adherence, to ensure that patients understand treatment side effects and monitoring requirements, and to take sequencing and reversibility implications of DMTs into account when making clinical decisions. ©2017 American Association of Nurse Practitioners.

  14. Osteogenesis Imperfecta with Celiac Disease and Type II Diabetes Mellitus Associated: Improvement with a Gluten-Free Diet

    Luis Rodrigo

    2012-01-01

    Full Text Available Osteogenesis imperfecta (OI is a genetic disease, with a connective tissue alteration, consisting in the presence of multiple spontaneous fractures or after minimal traumatism. Its association with other metabolic processes is rarely described. We present the clinical case of a female adult patient of 43 years. From her infancy, she has had multiple fractures, needing several surgical interventions, and she was diagnosed of OI type 2 at adolescence age. Due mainly to difficulties in walking remaining in wheel-chair in the last three years, she was overweight with morbid obesity (BMI=45.4 and had a type-II DM associated. She suffered from recurrent abdominal pain and chronic diarrhea and was diagnosed of celiac disease (CD with increased intraepithelial duodenal infiltration, being classified as lymphocytic enteritis, Marsh I type. She was put on a gluten-free diet (GFD, having lost 6 kg of weight after 6 months, with a good control of DM-II and presenting a significant clinical improvement. It is rewarding to search the presence of two coincidental metabolic diseases associated to OI, specially CD, because of the dramatic clinical benefit in the general found after putting on a GFD.

  15. Osteogenesis Imperfecta with Celiac Disease and Type II Diabetes Mellitus Associated: Improvement with a Gluten-Free Diet

    Rodrigo, Luis; Pérez-Martinez, Isabel

    2012-01-01

    Osteogenesis imperfecta (OI) is a genetic disease, with a connective tissue alteration, consisting in the presence of multiple spontaneous fractures or after minimal traumatism. Its association with other metabolic processes is rarely described. We present the clinical case of a female adult patient of 43 years. From her infancy, she has had multiple fractures, needing several surgical interventions, and she was diagnosed of OI type 2 at adolescence age. Due mainly to difficulties in walking remaining in wheel-chair in the last three years, she was overweight with morbid obesity (BMI = 45.4) and had a type-II DM associated. She suffered from recurrent abdominal pain and chronic diarrhea and was diagnosed of celiac disease (CD) with increased intraepithelial duodenal infiltration, being classified as lymphocytic enteritis, Marsh I type. She was put on a gluten-free diet (GFD), having lost 6 kg of weight after 6 months, with a good control of DM-II and presenting a significant clinical improvement. It is rewarding to search the presence of two coincidental metabolic diseases associated to OI, specially CD, because of the dramatic clinical benefit in the general found after putting on a GFD. PMID:22481956

  16. Financial burden is associated with worse health-related quality of life in adults with multiple endocrine neoplasia type 1.

    Peipert, Benjamin J; Goswami, Sneha; Helenowski, Irene; Yount, Susan E; Sturgeon, Cord

    2017-12-01

    Health-related quality of life and financial burden among patients with multiple endocrine neoplasia type 1 is poorly described. It is not known how financial burden influences health-related quality of life in this population. We hypothesized that the financial burden attributable to multiple endocrine neoplasia type 1 is associated with worse health-related quality of life. United States adults (≥18 years) with multiple endocrine neoplasia type 1 were recruited from the AMENSupport MEN online support group. Patient demographics, clinical characteristics, and financial burden were assessed via an online survey. The instrument Patient-Reported Outcomes Measurement Information System 29-item profile measure was used to assess health-related quality of life. Multivariable linear regression was used to identify significant variables in each Patient-Reported Outcomes Measurement Information System domain. Out of 1,378 members in AMENSupport, our survey link was accessed 449 times (33%). Of 153 US respondents who completed our survey, 84% reported financial burden attributable to multiple endocrine neoplasia type 1. The degree of financial burden had a linear relationship with worse health-related quality of life across all Patient-Reported Outcomes Measurement Information System domains (r = 0.36-0.55, P financial event(s). Borrowing money from friends/family (30%), unemployment (13%), and spending >$100/month out-of-pocket on prescription medications (46%) were associated consistently with impaired health-related quality of life (ß = 3.75-6.77, P times more likely to be unemployed and declare bankruptcy than the US population, respectively. This study characterizes the financial burden in patients with multiple endocrine neoplasia type 1. Individuals with multiple endocrine neoplasia type 1 report a high degree of financial burden, negative financial events, and unemployment. Each of these factors was associated with worse health-related quality of life

  17. Multiple-locus variable-number tandem repeat analysis for molecular typing of Aspergillus fumigatus

    Chermette René

    2010-12-01

    Full Text Available Abstract Background Multiple-locus variable-number tandem repeat (VNTR analysis (MLVA is a prominent subtyping method to resolve closely related microbial isolates to provide information for establishing genetic patterns among isolates and to investigate disease outbreaks. The usefulness of MLVA was recently demonstrated for the avian major pathogen Chlamydophila psittaci. In the present study, we developed a similar method for another pathogen of birds: the filamentous fungus Aspergillus fumigatus. Results We selected 10 VNTR markers located on 4 different chromosomes (1, 5, 6 and 8 of A. fumigatus. These markers were tested with 57 unrelated isolates from different hosts or their environment (53 isolates from avian species in France, China or Morocco, 3 isolates from humans collected at CHU Henri Mondor hospital in France and the reference strain CBS 144.89. The Simpson index for individual markers ranged from 0.5771 to 0.8530. A combined loci index calculated with all the markers yielded an index of 0.9994. In a second step, the panel of 10 markers was used in different epidemiological situations and tested on 277 isolates, including 62 isolates from birds in Guangxi province in China, 95 isolates collected in two duck farms in France and 120 environmental isolates from a turkey hatchery in France. A database was created with the results of the present study http://minisatellites.u-psud.fr/MLVAnet/. Three major clusters of isolates were defined by using the graphing algorithm termed Minimum Spanning Tree (MST. The first cluster comprised most of the avian isolates collected in the two duck farms in France, the second cluster comprised most of the avian isolates collected in poultry farms in China and the third one comprised most of the isolates collected in the turkey hatchery in France. Conclusions MLVA displayed excellent discriminatory power. The method showed a good reproducibility. MST analysis revealed an interesting clustering with a

  18. N-terminal pro-C-type natriuretic peptide in serum associated with bone destruction in patients with multiple myeloma

    Mylin, Anne K; Goetze, Jens P; Heickendorff, Lene

    2015-01-01

    AIM: To examine whether N-terminal proCNP concentrations in serum is associated with bone destruction in patients with multiple myeloma. MATERIALS & METHODS: N-terminal proCNP and biochemical bone markers were measured in 153 patients. Radiographic bone disease and skeletal-related events were...

  19. Correlation between the coping behavior and types of attitude to the disease in patients with coronary heart disease

    O. A. Zubareva

    2014-01-01

    Full Text Available The article represents the results of research of correlation between the coping behavior and types of attitude to the disease taking into account the emotional, behavioral and cognitive components in male patients with different types of acute coronary heart disease (acute myocardial infarction and unstable stenocardia. Recommendations for the elaborating of psychocorrectional program were given according to the analysis of the obtained data.

  20. Combined influence of multiple climatic factors on the incidence of bacterial foodborne diseases.

    Park, Myoung Su; Park, Ki Hwan; Bahk, Gyung Jin

    2018-01-01

    Information regarding the relationship between the incidence of foodborne diseases (FBD) and climatic factors is useful in designing preventive strategies for FBD based on anticipated future climate change. To better predict the effect of climate change on foodborne pathogens, the present study investigated the combined influence of multiple climatic factors on bacterial FBD incidence in South Korea. During 2011-2015, the relationships between 8 climatic factors and the incidences of 13 bacterial FBD, were determined based on inpatient stays, on a monthly basis using the Pearson correlation analyses, multicollinearity tests, principal component analysis (PCA), and the seasonal autoregressive integrated moving average (SARIMA) modeling. Of the 8 climatic variables, the combination of temperature, relative humidity, precipitation, insolation, and cloudiness was significantly associated with salmonellosis (Pclimatic factors. These findings indicate that the relationships between multiple climatic factors and bacterial FBD incidence can be valuable for the development of prediction models for future patterns of diseases in response to changes in climate. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Type D personality and health status in cardiovascular disease populations

    Versteeg, Henneke; Spek, Viola; Pedersen, Susanne S.

    2012-01-01

    Background: Knowledge of the factors associated with individual differences in patient-reported outcomes is essential to identify high-risk patients and improve secondary prevention. Design: In this meta-analysis, we examined the association between Type D personality and the individual differences...... in patient-reported physical and mental health status among cardiovascular patients. Methods: A computerized search of the literature through PUBMED and PsychINFO (from 1995 to May 2011) was performed and prospective studies were selected that analysed the association between Type D personality and health...... status in cardiovascular patients. Two separate meta-analyses were performed for the association of Type D personality with physical and mental health status, respectively. Results: Of all identified studies, ten studies met the selection criteria. The meta-analyses showed that Type D was associated...

  2. Logistic regression analysis of multiple noninvasive tests for the prediction of the presence and extent of coronary artery disease in men

    Hung, J.; Chaitman, B.R.; Lam, J.; Lesperance, J.; Dupras, G.; Fines, P.; Cherkaoui, O.; Robert, P.; Bourassa, M.G.

    1985-01-01

    The incremental diagnostic yield of clinical data, exercise ECG, stress thallium scintigraphy, and cardiac fluoroscopy to predict coronary and multivessel disease was assessed in 171 symptomatic men by means of multiple logistic regression analyses. When clinical variables alone were analyzed, chest pain type and age were predictive of coronary disease, whereas chest pain type, age, a family history of premature coronary disease before age 55 years, and abnormal ST-T wave changes on the rest ECG were predictive of multivessel disease. The percentage of patients correctly classified by cardiac fluoroscopy (presence or absence of coronary artery calcification), exercise ECG, and thallium scintigraphy was 9%, 25%, and 50%, respectively, greater than for clinical variables, when the presence or absence of coronary disease was the outcome, and 13%, 25%, and 29%, respectively, when multivessel disease was studied; 5% of patients were misclassified. When the 37 clinical and noninvasive test variables were analyzed jointly, the most significant variable predictive of coronary disease was an abnormal thallium scan and for multivessel disease, the amount of exercise performed. The data from this study provide a quantitative model and confirm previous reports that optimal diagnostic efficacy is obtained when noninvasive tests are ordered sequentially. In symptomatic men, cardiac fluoroscopy is a relatively ineffective test when compared to exercise ECG and thallium scintigraphy

  3. Glycogen storage disease type Ia: linkage of glucose, glycogen, lactic acid, triglyceride, and uric acid metabolism.

    Sever, Sakine; Weinstein, David A; Wolfsdorf, Joseph I; Gedik, Reyhan; Schaefer, Ernst J

    2012-01-01

    A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides >5000 mg/dL. The diagnosis of type 1A glycogen storage disease was made via the result of a liver biopsy, which showed increased glycogen and absent glucose-6-phosphatase enzyme activity. The patient was treated with dextrose administered orally, which was replaced by frequent feedings of cornstarch, which resulted in an improvement of her metabolic parameters. At age 18 years of age, she had marked hypertriglyceridemia (3860 mg/dL) and eruptive xanthomas and was treated with fenofibrate, atorvastatin, and fish oil. At age 29 years she was noted to have multiple liver adenomas, severe anemia, and hyperuricemia. Aggressive cornstarch therapy was commenced with a goal of maintaining her blood glucose levels >75 mg/dL and lactate levels triglycerides 179, high-density lipoprotein cholesterol 32, and calculated low-density lipoprotein cholesterol 154. Her weight was stable with a body mass index of 24.8 kg/m(2). Her liver adenomas had decreased in size, and her anemia and hyperuricemia had improved. She was homozygous for the R83C missense mutation in G6PC. Our data indicate that optimized metabolic control to maintain blood glucose levels >75 mg/dL is critical in the management of this disease. Copyright © 2012. Published by Elsevier Inc.

  4. New FDA-Approved Disease-Modifying Therapies for Multiple Sclerosis.

    English, Clayton; Aloi, Joseph J

    2015-04-01

    Interferon injectables and glatiramer acetate have served as the primary disease-modifying treatments for multiple sclerosis (MS) since their introduction in the 1990s and are first-line treatments for relapsing-remitting forms of MS (RRMS). Many new drug therapies were launched since early 2010, expanding the drug treatment options considerably in a disease state that once had a limited treatment portfolio. The purpose of this review is to critically evaluate the safety profile and efficacy data of disease-modifying agents for MS approved by the US Food and Drug Administration (FDA) from 2010 to the present and provide cost and available pharmacoeconomic data about each new treatment. Peer-reviewed clinical trials, pharmacoeconomic studies, and relevant pharmacokinetic/pharmacologic studies were identified from MEDLINE (January 2000-December 2014) by using the search terms multiple sclerosis, fingolimod, teriflunomide, alemtuzumab, dimethyl fumarate, pegylated interferon, peginterferon beta-1a, glatiramer 3 times weekly, and pharmacoeconomics. Citations from available articles were also reviewed for additional references. The databases publically available at www.clinicaltrials.gov and www.fda.gov were searched for unpublished studies or studies currently in progress. A total of 5 new agents and 1 new dosage formulation were approved by the FDA for the treatment of RRMS since 2010. Peginterferon beta-1a and high-dose glatiramer acetate represent 2 new effective injectable options for MS that reduce burden of administration seen with traditional interferon and low-dose glatiramer acetate. Fingolimod, teriflunomide, and dimethyl fumarate represent new oral agents available for MS, and their efficacy in reducing annualized relapse rates is 48% to 55%, 22% to 36.3%, and 44% to 53%, respectively, compared with placebo. Alemtuzumab is a biologic given over a 2-year span that reduced annualized relapse rates by 55% in treatment-naive patients and by 49% in patients

  5. The Multimorbidity Cluster Analysis Tool: Identifying Combinations and Permutations of Multiple Chronic Diseases Using a Record-Level Computational Analysis

    Kathryn Nicholson

    2017-12-01

    Full Text Available Introduction: Multimorbidity, or the co-occurrence of multiple chronic health conditions within an individual, is an increasingly dominant presence and burden in modern health care systems.  To fully capture its complexity, further research is needed to uncover the patterns and consequences of these co-occurring health states.  As such, the Multimorbidity Cluster Analysis Tool and the accompanying Multimorbidity Cluster Analysis Toolkit have been created to allow researchers to identify distinct clusters that exist within a sample of participants or patients living with multimorbidity.  Development: The Tool and Toolkit were developed at Western University in London, Ontario, Canada.  This open-access computational program (JAVA code and executable file was developed and tested to support an analysis of thousands of individual records and up to 100 disease diagnoses or categories.  Application: The computational program can be adapted to the methodological elements of a research project, including type of data, type of chronic disease reporting, measurement of multimorbidity, sample size and research setting.  The computational program will identify all existing, and mutually exclusive, combinations and permutations within the dataset.  An application of this computational program is provided as an example, in which more than 75,000 individual records and 20 chronic disease categories resulted in the detection of 10,411 unique combinations and 24,647 unique permutations among female and male patients.  Discussion: The Tool and Toolkit are now available for use by researchers interested in exploring the complexities of multimorbidity.  Its careful use, and the comparison between results, will be valuable additions to the nuanced understanding of multimorbidity.

  6. Multiple plasmid-borne virulence genes of Clavibacter michiganensis ssp. capsici critical for disease development in pepper.

    Hwang, In Sun; Oh, Eom-Ji; Kim, Donghyuk; Oh, Chang-Sik

    2018-02-01

    Clavibacter michiganensis ssp. capsici is a Gram-positive plant-pathogenic bacterium causing bacterial canker disease in pepper. Virulence genes and mechanisms of C. michiganensis ssp. capsici in pepper have not yet been studied. To identify virulence genes of C. michiganensis ssp. capsici, comparative genome analyses with C. michiganensis ssp. capsici and its related C. michiganensis subspecies, and functional analysis of its putative virulence genes during infection were performed. The C. michiganensis ssp. capsici type strain PF008 carries one chromosome (3.056 Mb) and two plasmids (39 kb pCM1 Cmc and 145 kb pCM2 Cmc ). The genome analyses showed that this bacterium lacks a chromosomal pathogenicity island and celA gene that are important for disease development by C. michiganensis ssp. michiganensis in tomato, but carries most putative virulence genes in both plasmids. Virulence of pCM1 Cmc -cured C. michiganensis ssp. capsici was greatly reduced compared with the wild-type strain in pepper. The complementation analysis with pCM1 Cmc -located putative virulence genes showed that at least five genes, chpE, chpG, ppaA1, ppaB1 and pelA1, encoding serine proteases or pectate lyase contribute to disease development in pepper. In conclusion, C. michiganensis ssp. capsici has a unique genome structure, and its multiple plasmid-borne genes play critical roles in virulence in pepper, either separately or together. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  7. Geographical Overlapping of Obesity, Heart Disease, and Type 2 Diabetes

    This podcast features Kayla Smurthwaite, an undergraduate student at Australian National University in Canberra, Australia, and one of the winners of PCD's 2017 Student Research Paper Contest. Kayla answers questions about her winning research and what impact her study has on chronic disease prevention and public health.

  8. Genetics Home Reference: glycogen storage disease type I

    ... resulting from uric acid crystals in the joints (gout), kidney disease, and high blood pressure in the ... particular ethnic groups? Genetic Changes Mutations in two genes, G6PC and SLC37A4 , cause GSDI. G6PC gene mutations ...

  9. An Acoustic Study of the Relationships among Neurologic Disease, Dysarthria Type, and Severity of Dysarthria

    Kim, Yunjung; Kent, Raymond D.; Weismer, Gary

    2011-01-01

    Purpose: This study examined acoustic predictors of speech intelligibility in speakers with several types of dysarthria secondary to different diseases and conducted classification analysis solely by acoustic measures according to 3 variables (disease, speech severity, and dysarthria type). Method: Speech recordings from 107 speakers with…

  10. Evidence for somatic gene conversion and deletion in bipolar disorder, Crohn's disease, coronary artery disease, hypertension, rheumatoid arthritis, type-1 diabetes, and type-2 diabetes.

    Ross, Kenneth Andrew

    2011-02-03

    During gene conversion, genetic information is transferred unidirectionally between highly homologous but non-allelic regions of DNA. While germ-line gene conversion has been implicated in the pathogenesis of some diseases, somatic gene conversion has remained technically difficult to investigate on a large scale. A novel analysis technique is proposed for detecting the signature of somatic gene conversion from SNP microarray data. The Wellcome Trust Case Control Consortium has gathered SNP microarray data for two control populations and cohorts for bipolar disorder (BD), cardiovascular disease (CAD), Crohn's disease (CD), hypertension (HT), rheumatoid arthritis (RA), type-1 diabetes (T1D) and type-2 diabetes (T2D). Using the new analysis technique, the seven disease cohorts are analyzed to identify cohort-specific SNPs at which conversion is predicted. The quality of the predictions is assessed by identifying known disease associations for genes in the homologous duplicons, and comparing the frequency of such associations with background rates. Of 28 disease/locus pairs meeting stringent conditions, 22 show various degrees of disease association, compared with only 8 of 70 in a mock study designed to measure the background association rate (P conversion could be a significant causative factor in each of the seven diseases. The specific genes provide potential insights about disease mechanisms, and are strong candidates for further study.

  11. Areal and volumetric Bone Mineral Density and risk of multiple types of fracture in older men

    Chalhoub, Didier; Orwoll, Eric S.; Cawthon, Peggy M.; Ensrud, Kristine E.; Boudreau, Robert; Greenspan, Susan; Newman, Anne B.; Zmuda, Joseph; Bauer, Douglas; Cummings, Steven; Cauley, Jane A.

    2016-01-01

    Although many studies have examined the association between low bone mineral density (BMD) and fracture risk in older men, none have simultaneously studied the relationship between multiple BMD sites and risk of different types of fractures. Using data from the Osteoporotic Fractures in Men study, we evaluated the association between areal BMD (aBMD) by dual-energy X-ray absorptiometry (DXA) and volumetric BMD (vBMD) by quantitative computed tomography (QCT) measurements, and different types of fractures during an average of 9.7 years of follow up. Men answered questionnaires about fractures every 4 months (>97% completions). Fractures were confirmed by centralized review of radiographic reports; pathological fractures were excluded. Risk of fractures was assessed at the hip, spine, wrist, shoulder, rib/chest/sternum, ankle/foot/toe, arm, hand/finger, leg, pelvis/coccyx, skull/face and any non-spine fracture. Age and race adjusted Cox proportional-hazards modeling was used to assess the risk of fracture in 3301 older men with both aBMD (at the femoral neck (FN) and lumbar spine) and vBMD (at the trabecular spine and FN, and cortical FN) measurements, with hazard ratios (HRs) expressed per standard deviation (SD) decrease. Lower FN and spine aBMD were associated with an increased risk of fracture at the hip, spine, wrist, shoulder, rib/chest/sternum, arm, and any non-spine fracture (statistically significant HRs per SD decrease ranged from 1.24 - 3.57). Lower trabecular spine and FN vBMD were associated with increased risk of most fractures with statistically significant HRs ranging between 1.27 and 3.69. There was a statistically significant association between FN cortical vBMD and fracture risk at the hip (HR=1.55) and spine sites (HR=1.26), but no association at other fracture sites. In summary, both lower aBMD and vBMD were associated with increased fracture risk. The stronger associations observed for trabecular vBMD than cortical vBMD may reflect the greater

  12. Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels

    Ma, Gang; Yu, Jiang; Xiao, Yue; Chan, Danny; Gao, Bo; Hu, Jianxin; He, Yongxing; Guo, Shengzhen; Zhou, Jian; Zhang, Lingling; Gao, Linghan; Zhang, Wenjuan; Kang, Yan; Cheah, Kathryn SE; Feng, Guoyin; Guo, Xizhi; Wang, Yujiong; Zhou, Cong-zhao; He, Lin

    2011-01-01

    Brachydactyly type A1 (BDA1), the first recorded Mendelian autosomal dominant disorder in humans, is characterized by a shortening or absence of the middle phalanges. Heterozygous missense mutations in the Indian Hedgehog (IHH) gene have been identified as a cause of BDA1; however, the biochemical consequences of these mutations are unclear. In this paper, we analyzed three BDA1 mutations (E95K, D100E, and E131K) in the N-terminal fragment of Indian Hedgehog (IhhN). Structural analysis showed that the E95K mutation changes a negatively charged area to a positively charged area in a calcium-binding groove, and that the D100E mutation changes the local tertiary structure. Furthermore, we showed that the E95K and D100E mutations led to a temperature-sensitive and calcium-dependent instability of IhhN, which might contribute to an enhanced intracellular degradation of the mutant proteins via the lysosome. Notably, all three mutations affected Hh binding to the receptor Patched1 (PTC1), reducing its capacity to induce cellular differentiation. We propose that these are common features of the mutations that cause BDA1, affecting the Hh tertiary structure, intracellular fate, binding to the receptor/partners, and binding to extracellular components. The combination of these features alters signaling capacity and range, but the impact is likely to be variable and mutation-dependent. The potential variation in the signaling range is characterized by an enhanced interaction with heparan sulfate for IHH with the E95K mutation, but not the E131K mutation. Taken together, our results suggest that these IHH mutations affect Hh signaling at multiple levels, causing abnormal bone development and abnormal digit formation. PMID:21537345

  13. Brucella Modulates Secretory Trafficking via Multiple Type IV Secretion Effector Proteins

    Myeni, Sebenzile; Child, Robert; Ng, Tony W.; Kupko, John J.; Wehrly, Tara D.; Porcella, Stephen F.; Knodler, Leigh A.; Celli, Jean

    2013-01-01

    The intracellular pathogenic bacterium Brucella generates a replicative vacuole (rBCV) derived from the endoplasmic reticulum via subversion of the host cell secretory pathway. rBCV biogenesis requires the expression of the Type IV secretion system (T4SS) VirB, which is thought to translocate effector proteins that modulate membrane trafficking along the endocytic and secretory pathways. To date, only a few T4SS substrates have been identified, whose molecular functions remain unknown. Here, we used an in silico screen to identify putative T4SS effector candidate proteins using criteria such as limited homology in other bacterial genera, the presence of features similar to known VirB T4SS effectors, GC content and presence of eukaryotic-like motifs. Using β-lactamase and CyaA adenylate cyclase reporter assays, we identified eleven proteins translocated into host cells by Brucella, five in a VirB T4SS-dependent manner, namely BAB1_0678 (BspA), BAB1_0712 (BspB), BAB1_0847 (BspC), BAB1_1671 (BspE) and BAB1_1948 (BspF). A subset of the translocated proteins targeted secretory pathway compartments when ectopically expressed in HeLa cells, and the VirB effectors BspA, BspB and BspF inhibited protein secretion. Brucella infection also impaired host protein secretion in a process requiring BspA, BspB and BspF. Single or combined deletions of bspA, bspB and bspF affected Brucella ability to replicate in macrophages and persist in the liver of infected mice. Taken together, these findings demonstrate that Brucella modulates secretory trafficking via multiple T4SS effector proteins that likely act coordinately to promote Brucella pathogenesis. PMID:23950720

  14. Thermoelectric material including a multiple transition metal-doped type I clathrate crystal structure

    Yang, Jihui [Lakeshore, CA; Shi, Xun [Troy, MI; Bai, Shengqiang [Shanghai, CN; Zhang, Wenqing [Shanghai, CN; Chen, Lidong [Shanghai, CN; Yang, Jiong [Shanghai, CN

    2012-01-17

    A thermoelectric material includes a multiple transition metal-doped type I clathrate crystal structure having the formula A.sub.8TM.sub.y.sub.1.sup.1TM.sub.y.sub.2.sup.2 . . . TM.sub.y.sub.n.sup.nM.sub.zX.sub.46-y.sub.1.sub.-y.sub.2.sub.- . . . -y.sub.n.sub.-z. In the formula, A is selected from the group consisting of barium, strontium, and europium; X is selected from the group consisting of silicon, germanium, and tin; M is selected from the group consisting of aluminum, gallium, and indium; TM.sup.1, TM.sup.2, and TM.sup.n are independently selected from the group consisting of 3d, 4d, and 5d transition metals; and y.sub.1, y.sub.2, y.sub.n and Z are actual compositions of TM.sup.1, TM.sup.2, TM.sup.n, and M, respectively. The actual compositions are based upon nominal compositions derived from the following equation: z=8q.sub.A-|.DELTA.q.sub.1|y.sub.1-|.DELTA.q.sub.2|y.sub.2- . . . -|.DELTA.q.sub.n|y.sub.n, wherein q.sub.A is a charge state of A, and wherein .DELTA.q.sub.1, .DELTA.q.sub.2, .DELTA.q.sub.n are, respectively, the nominal charge state of the first, second, and n-th TM.

  15. Multiple Restrictions of Human Immunodeficiency Virus Type 1 in Feline Cells▿

    Münk, Carsten; Zielonka, Jörg; Constabel, Hannelore; Kloke, Björn-Philipp; Rengstl, Benjamin; Battenberg, Marion; Bonci, Francesca; Pistello, Mauro; Löchelt, Martin; Cichutek, Klaus

    2007-01-01

    The productive replication of human immunodeficiency virus type 1 (HIV-1) occurs exclusively in defined cells of human or chimpanzee origin, explaining why heterologous animal models for HIV replication, pathogenesis, vaccination, and therapy are not available. This lack of an animal model for HIV-1 studies prompted us to examine the susceptibility of feline cells in order to evaluate the cat (Felis catus) as an animal model for studying HIV-1. Here, we report that feline cell lines harbor multiple restrictions with respect to HIV-1 replication. The feline CD4 receptor does not permit virus infection. Feline T-cell lines MYA-1 and FeT-1C showed postentry restrictions resulting in low HIV-1 luciferase reporter activity and low expression of viral Gag-Pol proteins when pseudotyped vectors were used. Feline fibroblastic CrFK and KE-R cells, expressing human CD4 and CCR5, were very permissive for viral entry and HIV-long terminal repeat-driven expression but failed to support spreading infection. KE-R cells displayed a profound block with respect to release of HIV-1 particles. In contrast, CrFK cells allowed very efficient particle production; however, the CrFK cell-derived HIV-1 particles had low specific infectivity. We subsequently identified feline apolipoprotein B-editing catalytic polypeptide 3 (feAPOBEC3) proteins as active inhibitors of HIV-1 particle infectivity. CrFK cells express at least three different APOBEC3s: APOBEC3C, APOBEC3H, and APOBEC3CH. While the feAPOBEC3C did not significantly inhibit HIV-1, the feAPOBEC3H and feAPOBEC3CH induced G to A hypermutations of the viral cDNA and reduced the infectivity ∼10- to ∼40-fold. PMID:17459941

  16. Historical Perspective and Risk of Multiple Neglected Tropical Diseases in Coastal Tanzania: Compositional and Contextual Determinants of Disease Risk.

    Armah, Frederick Ato; Quansah, Reginald; Luginaah, Isaac; Chuenpagdee, Ratana; Hambati, Herbert; Campbell, Gwyn

    2015-01-01

    In the past decade, research on neglected tropical diseases (NTDs) has intensified in response to the need to enhance community participation in health delivery, establish monitoring and surveillance systems, and integrate existing disease-specific treatment programs to control overlapping NTD burdens and detrimental effects. In this paper, we evaluated the geographical distribution of NTDs in coastal Tanzania. We also assessed the collective (compositional and contextual) factors that currently determine risks to multiple NTDs using a cross sectional survey of 1253 individuals in coastal Tanzania. The results show that the effect size in decreasing order of magnitude for non-binary predictors of NTD risks is as follows: NTD comorbidities > poverty > educational attainment > self-reported household quality of life > ethnicity. The multivariate analysis explained 95% of the variance in the relationship between NTD risks and the theoretically-relevant covariates. Compositional (biosocial and sociocultural) factors explained more variance at the neighbourhood level than at the regional level, whereas contextual factors, such as access to health services and household quality, in districts explained a large proportion of variance at the regional level but individually had modest statistical significance, demonstrating the complex interactions between compositional and contextual factors in generating NTD risks. NTD risks were inequitably distributed over geographic space, which has several important policy implications. First, it suggests that localities of high burden of NTDs are likely to diminish within statistical averages at higher (regional or national) levels. Second, it indicates that curative or preventive interventions will become more efficient provided they can be focused on the localities, particularly as populations in these localities are likely to be burdened by several NTDs simultaneously, further increasing the imperative of multi-disease

  17. Historical Perspective and Risk of Multiple Neglected Tropical Diseases in Coastal Tanzania: Compositional and Contextual Determinants of Disease Risk.

    Frederick Ato Armah

    Full Text Available In the past decade, research on neglected tropical diseases (NTDs has intensified in response to the need to enhance community participation in health delivery, establish monitoring and surveillance systems, and integrate existing disease-specific treatment programs to control overlapping NTD burdens and detrimental effects. In this paper, we evaluated the geographical distribution of NTDs in coastal Tanzania.We also assessed the collective (compositional and contextual factors that currently determine risks to multiple NTDs using a cross sectional survey of 1253 individuals in coastal Tanzania. The results show that the effect size in decreasing order of magnitude for non-binary predictors of NTD risks is as follows: NTD comorbidities > poverty > educational attainment > self-reported household quality of life > ethnicity. The multivariate analysis explained 95% of the variance in the relationship between NTD risks and the theoretically-relevant covariates. Compositional (biosocial and sociocultural factors explained more variance at the neighbourhood level than at the regional level, whereas contextual factors, such as access to health services and household quality, in districts explained a large proportion of variance at the regional level but individually had modest statistical significance, demonstrating the complex interactions between compositional and contextual factors in generating NTD risks.NTD risks were inequitably distributed over geographic space, which has several important policy implications. First, it suggests that localities of high burden of NTDs are likely to diminish within statistical averages at higher (regional or national levels. Second, it indicates that curative or preventive interventions will become more efficient provided they can be focused on the localities, particularly as populations in these localities are likely to be burdened by several NTDs simultaneously, further increasing the imperative of multi-disease

  18. One-Year Outcomes of an Integrated Multiple Sclerosis Disease Management Program.

    Groeneweg, Marti; Forrester, Sara H; Arnold, Beth; Palazzo, Lorella; Zhu, Weiwei; Yoon, Paul; Scearce, Tim

    2018-05-01

    Multiple sclerosis (MS) is associated with high total health care cost, the majority of which is attributable to medications. Patients with MS are less likely to experience relapses, emergency department (ED) visits, and hospitalizations when they are adherent to disease-modifying treatments. Disease management programs are hypothesized to improve medication adherence thereby improving clinical and economic outcomes. To evaluate the clinical and economic effects of a specialty pharmacy and chronic disease management program for patients with MS from a health plan perspective. This study was a retrospective analysis using prescription drug claims, medical claims, and electronic medical record information (2013-2015) 1 year before and after enrollment in the disease management program for members with 24 months of continuous health plan coverage. Medication adherence was calculated using proportion of days covered (PDC). Relapse rate was defined as an MS outpatient visit associated with a corticosteroid dispense within 7 days of the visit or an MS hospitalization. Disease progression was assessed using the Modified Expanded Disability Status Scale (mEDSS). Resource use included outpatient visits, ED visits, and hospitalizations. Cost information was collected as health plan-paid amount and was reported in 2013 U.S. dollars. The analysis included 377 patients (mean age 55 years, 76.4% female). After enrollment in the program, 78.7% of the study group had a PDC of ≥ 0.80 compared with 70.0% before enrollment (P management for patients with MS can increase the proportion of patients adherent to medication. The increase in health plan spend on MS medications is not offset by savings in health care resource utilization. This study was funded by Kaiser Permanente Washington Health Research Institute and Kaiser Permanente Washington Pharmacy Administration. The authors have no disclosures to report.

  19. Screening for Addison's disease in patients with type 1 diabetes mellitus and recurrent hypoglycaemia

    Likhari, Taruna; Magzoub, Saeed; Griffiths, Melanie J; Buch, Harit N

    2007-01-01

    Background Addison's disease may present with recurrent hypoglycaemia in subjects with type 1 diabetes mellitus. There are no data, however, on the prevalence of Addison's disease presenting with recurrent hypoglycaemia in patients with diabetes mellitus. Methods Three year retrospective study of diabetic patients with “unexplained” recurrent hypoglycaemia investigated with a short Synacthen test to exclude adrenocortical insufficiency. Results 95 patients with type 1 diabetes mellitus were studied. Addison's disease was identified as the cause of recurrent hypoglycaemia in one patient with type 1 diabetes mellitus. Conclusion Addison's disease is a relatively rare but remedial cause of recurrent hypoglycaemia in patients with type 1 diabetes mellitus. A low threshold for investigating patients with type 1 diabetes mellitus and recurrent hypoglycaemia to detect Addison's disease is therefore suggested. PMID:17551075

  20. Screening for Addison's disease in patients with type 1 diabetes mellitus and recurrent hypoglycaemia.

    Likhari, Taruna; Magzoub, Saeed; Griffiths, Melanie J; Buch, Harit N; Gama, R

    2007-06-01

    Addison's disease may present with recurrent hypoglycaemia in subjects with type 1 diabetes mellitus. There are no data, however, on the prevalence of Addison's disease presenting with recurrent hypoglycaemia in patients with diabetes mellitus. Three year retrospective study of diabetic patients with "unexplained" recurrent hypoglycaemia investigated with a short Synacthen test to exclude adrenocortical insufficiency. 95 patients with type 1 diabetes mellitus were studied. Addison's disease was identified as the cause of recurrent hypoglycaemia in one patient with type 1 diabetes mellitus. Addison's disease is a relatively rare but remedial cause of recurrent hypoglycaemia in patients with type 1 diabetes mellitus. A low threshold for investigating patients with type 1 diabetes mellitus and recurrent hypoglycaemia to detect Addison's disease is therefore suggested.

  1. Matrix-type multiple reciprocity boundary element method for solving three-dimensional two-group neutron diffusion equations

    Itagaki, Masafumi; Sahashi, Naoki.

    1997-01-01

    The multiple reciprocity boundary element method has been applied to three-dimensional two-group neutron diffusion problems. A matrix-type boundary integral equation has been derived to solve the first and the second group neutron diffusion equations simultaneously. The matrix-type fundamental solutions used here satisfy the equation which has a point source term and is adjoint to the neutron diffusion equations. A multiple reciprocity method has been employed to transform the matrix-type domain integral related to the fission source into an equivalent boundary one. The higher order fundamental solutions required for this formulation are composed of a series of two types of analytic functions. The eigenvalue itself is also calculated using only boundary integrals. Three-dimensional test calculations indicate that the present method provides stable and accurate solutions for criticality problems. (author)

  2. 99M-TC MIBI-an indicator of active disease in multiple myeloma

    Raluca Mititelu; Serban Ghita; Catalin Mazilu; George Marinescu

    2004-01-01

    Purpose: to evaluate the role of 99mTc-MIBI in the assessment of bone marrow involvement in patients with multiple myeloma and to demonstrate how different patterns of 99mTc-MIBI uptake are reflecting the activity of the disease. Material and method: 27 patients with documented MM were studied, 14M, 13 F, median age 62 years, range 31 - 78. 7 MPI (myocardial perfusion imaging) patients served as controle. Diagnosis and staging of the disease were based on standard criteria: 5 patients in stage I, 7 in stage II, 15 in stage III. The disease activity was determined by clinical and biological assessment and the aspect of bone marrow biopsy. 17 patients had active disease (2 patients in stage I, 4 in stage II, 11 in stage III), 10 patients had not' clinical and biological criteria of active disease. All patients included in the group of active disease underwent radiological examination, 99mTc-MDP whole-body scan and 99mTc-MIBI whole-body scan. MRI was performed in 5 patients with active disease (2 in stage I, 1 in stage II, 2 in stage lib - for evaluation of spine involvement. In the other group (patients with clinical and biological criteria of non-active disease), due to high cost of investigations, we performed whole-body 99mTc-MIBI scan, as the oncologist referred us the patient for monitoring therapeutic response. Whole-body 99mTc-MIBI scans were obtained 20 rain after iv injection of 740 MBq 99mTc-MIBI, in anterior and posterior views, with a dual-head gamma camera Philips -Axis. Results: In the group of patients with active disease (17 patients) we found three different patterns of pathologic 99mTc-MIBI uptake: focal uptake in different sites in 9 patients, diffuse uptake in 4, both focal and diffuse uptake in 3; no pathologic uptake was seen in 1 patient (probably due to overexpression of Pglycoprotein). In the other group, with non-active disease criteria (10 patients), we found normal aspect of 99mTc-MIBI uptake in 8 patients; 2 patients had diffuse increased

  3. [Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study].

    Ribeiro, Maria Estela Bellini; Del Roio Liberatore Junior, Raphael; Custodio, Rodrigo; Martinelli Junior, Carlos Eduardo

    2016-01-01

    To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes melito. 40 patients with type 1 diabetes melito (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15-40 patients have severe hypoglycemic events versus 5-40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  4. Multiple stress response of lowland stream benthic macroinvertebrates is dependent on habitat type

    Graeber, Daniel; Jensen, Tinna M.; Rasmussen, Jes

    2017-01-01

    Worldwide, lowland stream ecosystems are exposed to multiple anthropogenic stress due to the combination of water scarcity, eutrophication and fine sedimentation. The understanding of the effects of such multiple stress on stream benthic macroinvertebrates has been growing in the recent years...

  5. Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease.

    Shroff, Geeta

    2016-12-13

    BACKGROUND Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause delayed neurologic symptoms similar to those seen in Lyme disease (LD) patients. Thymus derived T-cells (myelin reactive) migrate to the blood brain barrier and stimulate an inflammatory cascade in the central nervous system. Cell based therapies play an important role in treating neurological diseases such as MS and LD. CASE REPORT Human embryonic stem cell (hESC) therapy was used to treat two patients with both MS and LD. The hESCs were administered via different routes including intramuscular, intravenous, and supplemental routes (e.g., deep spinal, caudal, intercostal through eye drops) to regenerate the injured cells. Both the patients showed remarkable improvement in their functional skills, overall stamina, cognitive abilities, and muscle strength. Furthermore, the improvement in the patients' conditions were assessed by magnetic resonance tractography and single photon emission computed tomography (SPECT). CONCLUSIONS Therapy with hESCs might emerge as an effective and safe treatment for patients with both MS and LD. Well-designed clinical trials and follow-up studies are needed to prove the long-term efficacy and safety of hESC therapy in the treatment of patients with MS and LD.

  6. Comparison of Multiple Chronic Obstructive Pulmonary Disease (COPD) Indices in Chinese COPD Patients.

    Zhang, Jinsong; Miller, Anastasia; Li, Yongxia; Lan, Qinqin; Zhang, Ning; Chai, Yanling; Hai, Bing

    2018-04-01

    Chronic obstructive pulmonary disease (COPD) is a serious chronic condition with a global impact. Symptoms of COPD include progressive dyspnea, breathlessness, cough, and sputum production, which have a considerable impact on the lives of patients. In addition to the human cost of living with COPD and the resulting death, COPD entails a huge economic burden on the Chinese population, with patients spending up to one-third of the average family income on COPD management in some regions is clinically beneficial to adopt preventable measures via prudent COPD care utilization, monetary costs, and hospitalizations. Toward this end, this study compared the relative effectiveness of six indices in predicting patient healthcare utilization, cost of care, and patient health outcome. The six assessment systems evaluated included the three multidimensional Body mass index, Obstruction, Dyspnea, Exercise capacity index, Dyspnea, Obstruction, Smoking, Exacerbation (DOSE) index, and COPD Assessment Test index, or the unidimensional measures that best predict the future of patient healthcare utilization, cost of care, and patient health outcome among Chinese COPD patients. Multiple linear regression models were created for each healthcare utilization, cost, and outcome including a single COPD index and the same group of demographic variables for each of the outcomes. We conclude that the DOSE index facilitates the prediction of patient healthcare utilization, disease expenditure, and negative clinical outcomes. Our study indicates that the DOSE index has a potential role beyond clinical predictions. Copyright©2018. The Korean Academy of Tuberculosis and Respiratory Diseases.

  7. Bone- and bone marrow scintigraphy in Gaucher disease type 1

    Mikosch, P.; Zitter, F.; Gallowitsch, H.J.; Lind, P.; Wuertz, F.; Mehta, A.B.; Hughes, D.A.

    2008-01-01

    Scintigraphy is a method for imaging metabolism and should be viewed as complimentary to morphological imaging. Bone and bone marrow scintigraphy can particularly contribute to the detection of focal disease in Gaucher disease. In bone crises it can discriminate within three days after pain onset between local infection and aseptic necrosis. A further advantage of bone- and bone marrow scintigraphy is the visualization of the whole skeleton within one setting. Whole body imaging for focal lesions might thus be an objective in GD, in particular in patients complaining of several painful sites. Direct imaging of bone marrow deposits in GD by MIBI scintigraphy might be of special interest in children in whom bone marrow undergoes a developmental conversion from red to yellow marrow in the ap-pendicular skeleton. MRI interpretation in young GD patients is thus difficult in order to estimate the exact amount and extent of bone marrow infiltration by Gaucher cells. 99mTc-MIBI scintigraphy with its direct visualization of lipid storage could thus add interesting additional information not shown with other methods including MRI. Although MRI is the most accepted imaging modality in assessing the skeletal status in GD, a selective use of scintigraphy for imaging bone and bone marrow may add information in the evaluation of patients with Gaucher disease

  8. Tailor-made rehabilitation approach using multiple types of hybrid assistive limb robots for acute stroke patients: A pilot study.

    Fukuda, Hiroyuki; Morishita, Takashi; Ogata, Toshiyasu; Saita, Kazuya; Hyakutake, Koichi; Watanabe, Junko; Shiota, Etsuji; Inoue, Tooru

    2016-01-01

    This article investigated the feasibility of a tailor-made neurorehabilitation approach using multiple types of hybrid assistive limb (HAL) robots for acute stroke patients. We investigated the clinical outcomes of patients who underwent rehabilitation using the HAL robots. The Brunnstrom stage, Barthel index (BI), and functional independence measure (FIM) were evaluated at baseline and when patients were transferred to a rehabilitation facility. Scores were compared between the multiple-robot rehabilitation and single-robot rehabilitation groups. Nine hemiplegic acute stroke patients (five men and four women; mean age 59.4 ± 12.5 years; four hemorrhagic stroke and five ischemic stroke) underwent rehabilitation using multiple types of HAL robots for 19.4 ± 12.5 days, and 14 patients (six men and eight women; mean age 63.2 ± 13.9 years; nine hemorrhagic stroke and five ischemic stroke) underwent rehabilitation using a single type of HAL robot for 14.9 ± 8.9 days. The multiple-robot rehabilitation group showed significantly better outcomes in the Brunnstrom stage of the upper extremity, BI, and FIM scores. To the best of the authors' knowledge, this is the first pilot study demonstrating the feasibility of rehabilitation using multiple exoskeleton robots. The tailor-made rehabilitation approach may be useful for the treatment of acute stroke.

  9. Prediction of beta-turns and beta-turn types by a novel bidirectional Elman-type recurrent neural network with multiple output layers (MOLEBRNN).

    Kirschner, Andreas; Frishman, Dmitrij

    2008-10-01

    Prediction of beta-turns from amino acid sequences has long been recognized as an important problem in structural bioinformatics due to their frequent occurrence as well as their structural and functional significance. Because various structural features of proteins are intercorrelated, secondary structure information has been often employed as an additional input for machine learning algorithms while predicting beta-turns. Here we present a novel bidirectional Elman-type recurrent neural network with multiple output layers (MOLEBRNN) capable of predicting multiple mutually dependent structural motifs and demonstrate its efficiency in recognizing three aspects of protein structure: beta-turns, beta-turn types, and secondary structure. The advantage of our method compared to other predictors is that it does not require any external input except for sequence profiles because interdependencies between different structural features are taken into account implicitly during the learning process. In a sevenfold cross-validation experiment on a standard test dataset our method exhibits the total prediction accuracy of 77.9% and the Mathew's Correlation Coefficient of 0.45, the highest performance reported so far. It also outperforms other known methods in delineating individual turn types. We demonstrate how simultaneous prediction of multiple targets influences prediction performance on single targets. The MOLEBRNN presented here is a generic method applicable in a variety of research fields where multiple mutually depending target classes need to be predicted. http://webclu.bio.wzw.tum.de/predator-web/.

  10. Low accuracy of tumor markers for diagnosing pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 patients

    de Laat, Joanne M.; Pieterman, Carolina R. C.; Weijmans, Maaike; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N. A.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Vriens, Menno R.; Valk, Gerlof D.

    2013-01-01

    Context: The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. Objective: The objective of the study was to assess the

  11. Low Accuracy of Tumor Markers for Diagnosing Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1 Patients

    de Laat, Joanne M.; Pieterman, Carolina R. C.; Weijmans, Maaike; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N. A.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Vriens, Menno R.; Valk, Gerlof D.

    2013-01-01

    Context: The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. Objective: The objective of the study was to assess the

  12. Teacher Subject Specialisms and Their Relationships to Learning Styles, Psychological Types and Multiple Intelligences: Implications for Course Development

    Perry, Chris; Ball, Ian

    2004-01-01

    This study explores issues in teacher education that increase our understanding of, and response to, the individual differences displayed by learners. A large undergraduate teacher education cohort provided evidence of the range and distribution of preferences in learning styles, psychological types and multiple intelligences. This information…

  13. Agreement between different input image types in brain atrophy measurement in multiple sclerosis using SIENAX and SIENA

    Neacsu, V.; Jasperse, B.; Korteweg, T.; Knol, D.L.; Valsasina, P.; Filippi, M.; Barkhof, F.; Rovaris, M.; Vrenken, H.

    2008-01-01

    Purpose: To investigate whether multiple sclerosis (MS) atrophy can be assessed by SIENA and SIENAX software using other image types from MS research protocols than T1-weighted images without contrast agent, which are not always available. Materials and Methods: We selected 46 MS patients with

  14. Assessing the feasibility of a web-based registry for multiple orphan lung diseases: the Australasian Registry Network for Orphan Lung Disease (ARNOLD) experience

    Casamento, K.; Laverty, A.; Wilsher, M.; Twiss, J.; Gabbay, E.; Glaspole, I.; Jaffe, A.

    2016-01-01

    Background We investigated the feasibility of using an online registry to provide prevalence data for multiple orphan lung diseases in Australia and New Zealand. Methods A web-based registry, The Australasian Registry Network of Orphan Lung Diseases (ARNOLD) was developed based on the existing British Paediatric Orphan Lung Disease Registry. All adult and paediatric respiratory physicians who were members of the Thoracic Society of Australia and New Zealand in Australia and New Zealand were s...

  15. Spotlight on taliglucerase alfa in the treatment of pediatric patients with type 1 Gaucher disease

    Gupta P

    2017-06-01

    Full Text Available Punita Gupta,1 Gregory M Pastores2 1Division of Genetics, Department of Pediatrics, St. Joseph’s Children’s Hospital, Paterson, New Jersey, USA; 2National Center for Inherited Metabolic Disorders, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland Abstract: Gaucher disease (GD is a heritable storage disorder caused by functional defects of the lysosomal acid β-glucosidase and the accumulation of glucosylceramide within macrophages, resulting in multiple organ dysfunction. There are three commercially available enzyme replacement therapy (ERT products for the treatment of GD type 1 (GD1: imiglucerase, velaglucerase alfa, and taliglucerase alfa. Imiglucerase and velaglucerase alfa are produced in different mammalian cell systems; imiglucerase requires postproduction deglycosylation to expose terminal α-mannose residues, which are required for mannose receptor-mediated uptake by target macrophages. These steps are critical to the success of ERT for the treatment of visceral and hematologic manifestations of GD. Taliglucerase alfa is the first US Food and Drug Administration-approved plant-cell-expressed recombinant human protein, using carrot root cell cultures. Furthermore, it does not require postproduction glycosidic modifications. It is indicated for treatment of adults with GD1 in the US, Israel, Australia, Canada, Chile, Brazil, and other countries, and it is additionally approved for the treatment of pediatric patients in the US, Australia, and Canada and for the treatment of hematologic manifestations in pediatric patients with Type 3 GD in Canada and other countries. Our review focuses on the role of taliglucerase alfa in the pediatric population. A literature search through PubMed (from 1995 up till November 2016 of English language articles was performed with the following terms: Gaucher disease, lysosomal storage disease, taliglucerase. Secondary and tertiary references were obtained by reviewing

  16. Negative affectivity and social inhibition in cardiovascular disease: evaluating type-D personality and its assessment using item response theory.

    Emons, Wilco H M; Meijer, Rob R; Denollet, Johan

    2007-07-01

    Individuals with increased levels of both negative affectivity (NA) and social inhibition (SI)-referred to as type-D personality-are at increased risk of adverse cardiac events. We used item response theory (IRT) to evaluate NA, SI, and type-D personality as measured by the DS14. The objectives of this study were (a) to evaluate the relative contribution of individual items to the measurement precision at the cutoff to distinguish type-D from non-type-D personality and (b) to investigate the comparability of NA, SI, and type-D constructs across the general population and clinical populations. Data from representative samples including 1316 respondents from the general population, 427 respondents diagnosed with coronary heart disease, and 732 persons suffering from hypertension were analyzed using the graded response IRT model. In Study 1, the information functions obtained in the IRT analysis showed that (a) all items had highest measurement precision around the cutoff and (b) items are most informative at the higher end of the scale. In Study 2, the IRT analysis showed that measurements were fairly comparable across the general population and clinical populations. The DS14 adequately measures NA and SI, with highest reliability in the trait range around the cutoff. The DS14 is a valid instrument to assess and compare type-D personality across clinical groups.

  17. Weyl Group Multiple Dirichlet Series Type A Combinatorial Theory (AM-175)

    Brubaker, Ben; Friedberg, Solomon

    2011-01-01

    Weyl group multiple Dirichlet series are generalizations of the Riemann zeta function. Like the Riemann zeta function, they are Dirichlet series with analytic continuation and functional equations, having applications to analytic number theory. By contrast, these Weyl group multiple Dirichlet series may be functions of several complex variables and their groups of functional equations may be arbitrary finite Weyl groups. Furthermore, their coefficients are multiplicative up to roots of unity, generalizing the notion of Euler products. This book proves foundational results about these series an

  18. CD40: Novel Association with Crohn's Disease and Replication in Multiple Sclerosis Susceptibility

    Alcina, Antonio; Teruel, María; Díaz-Gallo, Lina M.; Gómez-García, María; López-Nevot, Miguel A.; Rodrigo, Luis; Nieto, Antonio; Cardeña, Carlos; Alcain, Guillermo; Díaz-Rubio, Manuel; de la Concha, Emilio G.; Fernandez, Oscar; Arroyo, Rafael

    2010-01-01

    Background A functional polymorphism located at −1 from the start codon of the CD40 gene, rs1883832, was previously reported to disrupt a Kozak sequence essential for translation. It has been consistently associated with Graves' disease risk in populations of different ethnicity and genetic proxies of this variant evaluated in genome-wide association studies have shown evidence of an effect in rheumatoid arthritis and multiple sclerosis (MS) susceptibility. However, the protective allele associated with Graves' disease or rheumatoid arthritis has shown a risk role in MS, an effect that we aimed to replicate in the present work. We hypothesized that this functional polymorphism might also show an association with other complex autoimmune condition such as inflammatory bowel disease, given the CD40 overexpression previously observed in Crohn's disease (CD) lesions. Methodology Genotyping of rs1883832C>T was performed in 1564 MS, 1102 CD and 969 ulcerative colitis (UC) Spanish patients and in 2948 ethnically matched controls by TaqMan chemistry. Principal Findings The observed effect of the minor allele rs1883832T was replicated in our independent Spanish MS cohort [p = 0.025; OR (95% CI) = 1.12 (1.01–1.23)]. The frequency of the minor allele was also significantly higher in CD patients than in controls [p = 0.002; OR (95% CI) = 1.19 (1.06–1.33)]. This increased predisposition was not detected in UC patients [p = 0.5; OR (95% CI) = 1.04 (0.93–1.17)]. Conclusion The impact of CD40 rs1883832 on MS and CD risk points to a common signaling shared by these autoimmune conditions. PMID:20634952

  19. Thickening and enhancement of multiple cranial nerves in conjunction with cystic white matter lesions in early infantile Krabbe disease

    Beslow, Lauren A.; Boennemann, Carsten G. [Children' s Hospital of Philadelphia, Division of Neurology, Philadelphia, PA (United States); Schwartz, Erin S. [Children' s Hospital of Philadelphia, Division of Neuroradiology, Philadelphia, PA (United States)

    2008-06-15

    We present serial MR findings in a child ultimately diagnosed with the early infantile form of Krabbe disease. MR showed typical features of Krabbe disease including cerebellar and brainstem hyperintensity, periventricular and deep white matter hyperintensity, and cerebral atrophy. In addition, the combination of both enlargement and enhancement of multiple cranial nerves in conjunction with unusual cystic lesions adjacent to the frontal horns of the lateral ventricles was previously unreported and expands the spectrum of imaging findings in early Krabbe disease. (orig.)

  20. Extraosseous manifestation of Gaucher's disease type I: MR and histological appearance

    Poll, L.W.; Koch, J.A.; Moedder, U.

    2000-01-01

    Gaucher's disease type I is the most prevalent lysosomal storage disorder caused by an autosomal-recessive inherited deficiency of glucocerebrosidase activity with secondary accumulation of glucocerebrosides within the lysosomes of macrophages. The storage disorder produces a multisystem disease characterized by progressive visceral enlargement and gradual replacement of bone marrow with lipid-laden macrophages. Skeletal disease is a major source of disability in Gaucher's disease. Extraosseous extension of Gaucher cells is an extremely rare manifestation of skeletal Gaucher's disease. This is a report on the MRI and histopathological findings of an extraosseous Gaucher-cell extension into the midface in a patient with Gaucher's disease. (orig.)

  1. Interactions between SNPs affecting inflammatory response genes are associated with multiple myeloma disease risk and survival

    Nielsen, Kaspar René; Rodrigo-Domingo, Maria; Steffensen, Rudi

    2017-01-01

    The origin of multiple myeloma depends on interactions with stromal cells in the course of normal B-cell differentiation and evolution of immunity. The concept of the present study is that genes involved in MM pathogenesis, such as immune response genes, can be identified by screening for single......3L1 gene promoters. The occurrence of single polymorphisms, haplotypes and SNP-SNP interactions were statistically analyzed for association with disease risk and outcome following high-dose therapy. Identified genes that carried SNPs or haplotypes that were identified as risk or prognostic factors......= .005). The 'risk genes' were analyzed for expression in normal B-cell subsets (N = 6) from seven healthy donors and we found TNFA and IL-6 expressed both in naïve and in memory B cells when compared to preBI, II, immature and plasma cells. The 'prognosis genes' CHI3L1, IL-6 and IL-10 were differential...

  2. Patients’ satisfaction with and views about treatment with disease-modifying drugs in multiple sclerosis

    Caroline Vieira Spessotto

    2016-08-01

    Full Text Available ABSTRACT Objective The treatment of multiple sclerosis (MS with disease-modifying-drugs (DMDs is evolving and new drugs are reaching the market. Efficacy and safety aspects of the drugs are crucial, but the patients’ satisfaction with the treatment must be taken into consideration. Methods Individual interview with patients with MS regarding their satisfaction and points of view on the treatment with DMDs. Results One hundred and twenty eight patients attending specialized MS Units in five different cities were interviewed. Over 80% of patients were very satisfied with the drugs in use regarding convenience and perceived benefits. The only aspect scoring lesser values was tolerability. Conclusion Parameters for improving treatment in MS must include efficacy, safety, and patient satisfaction with the given DMD.

  3. Management of sleep disorders in Parkinson's disease and multiple system atrophy.

    Videnovic, Aleksandar

    2017-05-01

    Parkinson's disease (PD) and multiple system atrophy (MSA) are disorders associated with α synuclein-related neurodegeneration. Nonmotor symptoms are common hallmarks of these disorders, and disturbances of the sleep-wake cycle are among the most common nonmotor symptoms. It is only recently that sleep disturbances have received the attention of the medical and research community. Significant progress has been made in understanding the pathophysiology of sleep and wake disruption in alphasynucleinopathies during the past few decades. Despite these advancements, treatment options are limited and frequently associated with problematic side effects. Further studies that center on the development of novel treatment approaches are very much needed. In this article, the author discusses the current state of the management of disturbed sleep and alertness in PD and MSA. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  4. Effector stage CC chemokine receptor-1 selective antagonism reduces multiple sclerosis-like rat disease.

    Eltayeb, Sana; Sunnemark, Dan; Berg, Anna-Lena; Nordvall, Gunnar; Malmberg, Asa; Lassmann, Hans; Wallström, Erik; Olsson, Tomas; Ericsson-Dahlstrand, Anders

    2003-09-01

    We have studied the role of the chemokine receptor CCR1 during the effector stage of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in DA rats. In situ hybridization histochemistry revealed local production of the CCR1 ligands CCL3 (MIP-1 alpha) and CCL5 (RANTES), as well as large numbers of CCR1 and CCR5 expressing cells within inflammatory brain lesions. A low-molecular weight CCR1 selective antagonist potently abrogated both clinical and histopathological disease signs during a 5-day treatment period, without signs of peripheral immune compromise. Thus, we demonstrate therapeutic targeting of CCR1-dependent leukocyte recruitment to the central nervous system in a multiple sclerosis (MS)-like rat model.

  5. Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

    Erdas, Enrico; Mariotti, Stefano; Pomata, Mariano; Aste, Nicola; Pilloni, Luca; Nicolosi, Angelo; Licheri, Sergio; Cappai, Antonello; Mastinu, Marco; Cetani, Filomena; Pardi, Elena

    2012-01-01

    Diagnosis of multiple endocrine neoplasia type 1 (MEN1) is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT) in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21). The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99m Tc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well and shows no signs or symptoms of recurrence. Despite

  6. Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

    Erdas Enrico

    2012-12-01

    Full Text Available Abstract Background Diagnosis of multiple endocrine neoplasia type 1 (MEN1 is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. Case presentation The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21. The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99mTc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well

  7. Treatment patterns in disease-modifying therapy for patients with multiple sclerosis in the United States.

    Bonafede, Machaon M; Johnson, Barbara H; Wenten, Madé; Watson, Crystal

    2013-10-01

    Patients with multiple sclerosis (MS) whose disease activity is inadequately controlled with a platform therapy (interferon beta or glatiramer acetate [GA]) may switch to another platform therapy or escalate therapy to natalizumab or fingolimod, which were approved in the US in 2006 and 2010, respectively. The objective of this study was to describe treatment patterns in patients with multiple sclerosis (MS) in the United States who were followed for 2 years after initiating a disease-modifying therapy (DMT). A retrospective observational cohort study was conducted to examine treatment patterns of initial DMT use (on initial therapy for 2 years with and without gaps of ≥ 60 days, medication switching, and discontinuation) among patients with MS who initiated a platform therapy (interferon-β or glatiramer acetate) or natalizumab between January 1, 2007, and September 30, 2009; the first DMT claim was the index. Eligible patients were identified in the MarketScan Commercial and Medicare Supplemental databases based on continuous enrollment for 6 months before (preindex period) and 24 months after their index date, with a diagnosis of MS and no claim for a previous DMT in the 6-month preindex period. Demographics at index and clinical characteristics during the preindex period were also analyzed. A total of 6181 MS patients were included, with 5735 (92.8%) starting on platform therapy. Natalizumab initiators were more likely to stay on index therapy (32.3% vs 16.9%, P treatment gaps of ≥ 60 days (44.8% vs 55.3%, P treatment (13.9% vs 19.1%, P = 0.007) and took longer to switch (400.9 days vs 330.7 days, P treatment gaps, and switch less than platform initiators in the 2 years after treatment initiation. Switching between platform therapies is common despite evidence that MS patients on platform therapy may benefit from switching to natalizumab. © 2013 Elsevier HS Journals, Inc. All rights reserved.

  8. Prescriptive Oriented Drug Analysis of Multiple Sclerosis Disease by LC-UV in Whole Human Blood.

    Suneetha, A; Rajeswari, Raja K

    2016-02-01

    As a polytherapy treatment, multiple sclerosis disease demands prescriptions with more than one drug. Polytherapy is sometimes rational for drug combinations chosen to minimize adverse effects. Estimation of drugs that are concomitantly administered in polytherapy is acceptable as it shortens the analytical timepoints and also the usage of biological matrices. In clinical phase trials, the withdrawal of biofluids is a critical issue for each analysis. Estimating all the coadminsitered drugs in a single shot will be more effective and economical for pharmaceuticals. A single, simple, rapid and sensitive high-performance liquid chromatography assay method has been developed with UV detection and fully validated for the quantification of 14 drugs (at random combinations) used in the treatment of multiple sclerosis disease. The set of combinations was based on prescriptions to patients. Separations were achieved on an X-Terra MS C18 (100 × 3.9 mm, 5 µm) column. The analytes were extracted from 50 µL aliquots of whole human blood with protein precipitation using acetonitrile. All the drugs were sufficiently stable during storage for 24 h at room temperature and for 23 days at 2-8°C. The percentage recoveries of all drugs were between 90 and 115%, with RSD values <10.6%. This method has been shown to be reproducible and sensitive and can be applied to clinical samples from pharmacokinetic studies and also a useful tool in studying the drug interaction studies. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Type 1 diabetes mellitus, coeliac disease, and lymphoma: a report of four cases.

    O'Connor, T M

    2012-02-03

    INTRODUCTION: Patients with Type 1 diabetes mellitus have a high prevalence of coeliac disease, symptoms of which are often mild, atypical, or absent. Untreated coeliac disease is associated with an increased risk of malignancy, particularly of lymphoma. We describe four patients with Type 1 diabetes mellitus and coeliac disease who developed lymphoma. CASE REPORTS: Two patients were male and two female. In three patients, coeliac disease and lymphoma were diagnosed simultaneously. Enteropathy-associated T cell lymphoma occurred in two patients, Hodgkin\\'s disease in one, and B cell lymphoma in one. Response to treatment was in general poor, and three patients died soon after the diagnosis of lymphoma was made. CONCLUSION: As the relative risk of lymphoma is reduced by a gluten-free diet, a high index of suspicion for coeliac disease should exist in all Type 1 diabetic patients with unexplained constitutional or gastrointestinal symptoms.

  10. Therapeutic compliance of first line disease-modifying therapies in patients with multiple sclerosis. COMPLIANCE Study.

    Saiz, A; Mora, S; Blanco, J

    2015-05-01

    Non-adherence to disease-modifying therapies (DMTs) in multiple sclerosis may be associated with reduced efficacy. We assessed compliance, the reasons for non-compliance, treatment satisfaction, and quality of life (QoL) of patients treated with first-line therapies. A cross-sectional, multicenter study was conducted that included relapsing multiple sclerosis patients. Compliance in the past month was assessed using Morisky-Green test. Seasonal compliance and reasons for non-compliance were assessed by an ad-hoc questionnaire. Treatment satisfaction and QoL were evaluated by means of TSQM and PRIMUS questionnaires. A total of 220 patients were evaluated (91% relapsing-remitting); the mean age was 39.1 years, 70% were female, and the average time under treatment was 5.4 years. Subcutaneous interferon (IFN) β-1b was used in 23% of the patients, intramuscular IFN β-1a in 21%, subcutaneous IFN β-1a in 37%, and with glatiramer acetate in 19%. The overall compliance was 75%, with no significant differences related to the therapy, and 81% did not report any seasonal variation. Compliant patients had significantly lower disability scores and time of diagnosis, and greater satisfaction with treatment and its effectiveness. Discomfort and flu-like symptoms were the most frequent reasons for non-compliance. The satisfaction and QoL were associated with less disability and number of therapeutic switches. The rate of compliance, satisfaction and QoL in multiple sclerosis patients under DMTs is high, especially for those newly diagnosed, less disabled, and with fewer therapeutic switches. Discomfort and flu-like symptoms associated with injected therapies significantly affect adherence. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  11. Validation of patient determined disease steps (PDDS) scale scores in persons with multiple sclerosis.

    Learmonth, Yvonne C; Motl, Robert W; Sandroff, Brian M; Pula, John H; Cadavid, Diego

    2013-04-25

    The Patient Determined Disease Steps (PDDS) is a promising patient-reported outcome (PRO) of disability in multiple sclerosis (MS). To date, there is limited evidence regarding the validity of PDDS scores, despite its sound conceptual development and broad inclusion in MS research. This study examined the validity of the PDDS based on (1) the association with Expanded Disability Status Scale (EDSS) scores and (2) the pattern of associations between PDDS and EDSS scores with Functional System (FS) scores as well as ambulatory and other outcomes. 96 persons with MS provided demographic/clinical information, completed the PDDS and other PROs including the Multiple Sclerosis Walking Scale-12 (MSWS-12), and underwent a neurological examination for generating FS and EDSS scores. Participants completed assessments of cognition, ambulation including the 6-minute walk (6 MW), and wore an accelerometer during waking hours over seven days. There was a strong correlation between EDSS and PDDS scores (ρ = .783). PDDS and EDSS scores were strongly correlated with Pyramidal (ρ = .578 &ρ = .647, respectively) and Cerebellar (ρ = .501 &ρ = .528, respectively) FS scores as well as 6 MW distance (ρ = .704 &ρ = .805, respectively), MSWS-12 scores (ρ = .801 &ρ = .729, respectively), and accelerometer steps/day (ρ = -.740 &ρ = -.717, respectively). This study provides novel evidence supporting the PDDS as valid PRO of disability in MS.

  12. Baseline predictors of persistence to first disease-modifying treatment in multiple sclerosis.

    Zettl, U K; Schreiber, H; Bauer-Steinhusen, U; Glaser, T; Hechenbichler, K; Hecker, M

    2017-08-01

    Patients with multiple sclerosis (MS) require lifelong therapy. However, success of disease-modifying therapies is dependent on patients' persistence and adherence to treatment schedules. In the setting of a large multicenter observational study, we aimed at assessing multiple parameters for their predictive power with respect to discontinuation of therapy. We analyzed 13 parameters to predict discontinuation of interferon beta-1b treatment during a 2-year follow-up period based on data from 395 patients with MS who were treatment-naïve at study onset. Besides clinical characteristics, patient-related psychosocial outcomes were assessed as well. Among patients without clinically relevant fatigue, males showed a higher persistence rate than females (80.3% vs 64.7%). Clinically relevant fatigue scores decreased the persistence rate in men and especially in women (71.4% and 51.2%). Besides gender and fatigue, univariable and multivariable analyses revealed further factors associated with interferon beta-1b therapy discontinuation, namely lower quality of life, depressiveness, and higher relapse rate before therapy initiation, while higher education, living without a partner, and higher age improved persistence. Patients with higher grades of fatigue and depressiveness are at higher risk to prematurely discontinue MS treatment; especially, women suffering from fatigue have an increased discontinuation rate. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Descriptive epidemiology of chronic liver disease in northeastern Italy: an analysis of multiple causes of death.

    Fedeli, Ugo; Schievano, Elena; Lisiero, Manola; Avossa, Francesco; Mastrangelo, Giuseppe; Saugo, Mario

    2013-10-10

    The analysis of multiple causes of death data has been applied in the United States to examine the population burden of chronic liver disease (CLD) and to assess time trends of alcohol-related and hepatitis C virus (HCV)-related CLD mortality. The aim of this study was to assess the mortality for CLD by etiology in the Veneto Region (northeastern Italy). Using the 2008-2010 regional archive of mortality, all causes registered on death certificates were extracted and different descriptive epidemiological measures were computed for HCV-related, alcohol-related, and overall CLD-related mortality. The crude mortality rate of all CLD was close to 40 per 100,000 residents. In middle ages (35 to 74 years) CLD was mentioned in about 10% and 6% of all deaths in males and females, respectively. Etiology was unspecified in about half of CLD deaths. In females and males, respectively, HCV was mentioned in 44% and 21% and alcohol in 11% and 26% of overall CLD deaths. A bimodal distribution with age was observed for HCV-related proportional mortality among females, reflecting the available seroprevalence data. Multiple causes of death analyses can provide useful insights into the burden of CLD mortality according to etiology among different population subgroups.

  14. Bilateral multiple cystic kidney disease and renal cortical abscess in a Boerboel

    A. M. Kitshoffa

    2011-04-01

    Full Text Available Cystic renal disease is rare in dogs and although infected renal cysts have been reported in humans, no report could be found in dogs. A 58 kg, 5-year-old, castrated, male Boerboel presented with weight loss, pyrexia, lethargy and vomiting, 20 months after an incident of haematuria was reported. The initial ultrasonographic diagnosis was bilateral multiple renal cysts of unknown aetiology. The cysts had significantly increased in size over the 20-month period and some contained echogenic specks which could be related to infection, normal cellular debris or haemorrhage. In both kidneys the renal contours were distorted (the left more than the right. The abnormal shape of the left kidney was largely due to multiple cysts and a large crescent-shaped septate mass on the cranial pole of the kidney. Aspirates of the septate mass were performed (left kidney and the cytology and culture were indicative of an abscess. It is suggested that the previous incident of haematuria provided a portal of entry for bacteria into the cysts resulting in renal cortical abscess formation.

  15. Evaluation of both perfusion and atrophy in multiple system atrophy of the cerebellar type using brain SPECT alone

    Matsuda, Hiroshi; Imabayashi, Etsuko; Kuji, Ichiei; Seto, Akira; Ito, Kimiteru; Kikuta, Daisuke; Yamada, Minoru; Shimano, Yasumasa; Sato, Noriko

    2010-01-01

    Partial volume effects in atrophied areas should be taken into account when interpreting brain perfusion single photon emission computed tomography (SPECT) images of neurodegenerative diseases. To evaluate both perfusion and atrophy using brain SPECT alone, we developed a new technique applying tensor-based morphometry (TBM) to SPECT. After linear spatial normalization of brain perfusion SPECT using 99m Tc-ethyl cysteinate dimer ( 99m Tc-ECD) to a Talairach space, high-dimension-warping was done using an original 99m Tc-ECD template. Contraction map images calculated from Jacobian determinants and spatially normalized SPECT images using this high-dimension-warping were compared using statistical parametric mapping (SPM2) between two groups of 16 multiple system atrophy of the cerebellar type (MSA-C) patients and 73 age-matched normal controls. This comparison was also performed in conventionally warped SPECT images. SPM2 demonstrated statistically significant contraction indicating local atrophy and decreased perfusion in the whole cerebellum and pons of MSA-C patients as compared to normal controls. Higher significance for decreased perfusion in these areas was obtained in high-dimension-warping than in conventional warping, possibly due to sufficient spatial normalization to a 99m Tc-ECD template in high-dimensional warping of severely atrophied cerebellum and pons. In the present high-dimension-warping, modification of tracer activity remained within 3% of the original tracer distribution. The present new technique applying TBM to brain SPECT provides information on both perfusion and atrophy at the same time thereby enhancing the role of brain perfusion SPECT

  16. Evaluation of both perfusion and atrophy in multiple system atrophy of the cerebellar type using brain SPECT alone

    Matsuda Hiroshi

    2010-08-01

    Full Text Available Abstract Background Partial volume effects in atrophied areas should be taken into account when interpreting brain perfusion single photon emission computed tomography (SPECT images of neurodegenerative diseases. To evaluate both perfusion and atrophy using brain SPECT alone, we developed a new technique applying tensor-based morphometry (TBM to SPECT. Methods After linear spatial normalization of brain perfusion SPECT using 99mTc-ethyl cysteinate dimer (99mTc-ECD to a Talairach space, high-dimension-warping was done using an original 99mTc-ECD template. Contraction map images calculated from Jacobian determinants and spatially normalized SPECT images using this high-dimension-warping were compared using statistical parametric mapping (SPM2 between two groups of 16 multiple system atrophy of the cerebellar type (MSA-C patients and 73 age-matched normal controls. This comparison was also performed in conventionally warped SPECT images. Results SPM2 demonstrated statistically significant contraction indicating local atrophy and decreased perfusion in the whole cerebellum and pons of MSA-C patients as compared to normal controls. Higher significance for decreased perfusion in these areas was obtained in high-dimension-warping than in conventional warping, possibly due to sufficient spatial normalization to a 99mTc-ECD template in high-dimensional warping of severely atrophied cerebellum and pons. In the present high-dimension-warping, modification of tracer activity remained within 3% of the original tracer distribution. Conclusions The present new technique applying TBM to brain SPECT provides information on both perfusion and atrophy at the same time thereby enhancing the role of brain perfusion SPECT

  17. Compromised quality of life in patients with both Type 1 diabetes mellitus and coeliac disease.

    Bakker, S F; Pouwer, F; Tushuizen, M E; Hoogma, R P; Mulder, C J; Simsek, S

    2013-07-01

    Type 1 diabetes mellitus and coeliac disease are two chronic illnesses associated with each other. Both diseases and their treatments can seriously impair quality of life. The objective of the present study was to investigate health-related quality of life in adult patients diagnosed with both Type 1 diabetes and coeliac disease and compare this with healthy control subjects and control subjects who have Type 1 diabetes only. A generic measure of health-related quality of life (RAND-36) and a measure of diabetes-specific quality of life (DQOL) questionnaires were sent to patients diagnosed with both Type 1 diabetes and coeliac disease. The control group consisted of patients with Type 1 diabetes without coeliac disease matched for age, gender and socio-economic status. Generic quality of life scores were compared with data from healthy Dutch control subjects. Fifty-seven patients with Type 1 diabetes and coeliac disease were included and no associations between clinical characteristics and quality of life were observed. Women reported a lower quality of life in social functioning, vitality and mental health than men (all P coeliac disease compared with patients with Type 1 diabetes. Compared with healthy control subjects, quality of life in patients with Type 1 diabetes and coeliac disease was significantly lower, particularly social functioning (Cohen's d = 0.76) and general health perception (Cohen's d = 0.86). The additional diagnosis of coeliac disease and treatment by gluten-free diet in adult patients with Type 1 diabetes has a considerable, negative impact on quality of life and diabetes-specific quality of life. Women are particularly affected and social functioning and general health perception is compromised. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  18. Evidence for somatic gene conversion and deletion in bipolar disorder, Crohn's disease, coronary artery disease, hypertension, rheumatoid arthritis, type-1 diabetes, and type-2 diabetes

    Ross Kenneth

    2011-02-01

    Full Text Available Abstract Background During gene conversion, genetic information is transferred unidirectionally between highly homologous but non-allelic regions of DNA. While germ-line gene conversion has been implicated in the pathogenesis of some diseases, somatic gene conversion has remained technically difficult to investigate on a large scale. Methods A novel analysis technique is proposed for detecting the signature of somatic gene conversion from SNP microarray data. The Wellcome Trust Case Control Consortium has gathered SNP microarray data for two control populations and cohorts for bipolar disorder (BD, cardiovascular disease (CAD, Crohn's disease (CD, hypertension (HT, rheumatoid arthritis (RA, type-1 diabetes (T1D and type-2 diabetes (T2D. Using the new analysis technique, the seven disease cohorts are analyzed to identify cohort-specific SNPs at which conversion is predicted. The quality of the predictions is assessed by identifying known disease associations for genes in the homologous duplicons, and comparing the frequency of such associations with background rates. Results Of 28 disease/locus pairs meeting stringent conditions, 22 show various degrees of disease association, compared with only 8 of 70 in a mock study designed to measure the background association rate (P -9. Additional candidate genes are identified using less stringent filtering conditions. In some cases, somatic deletions appear likely. RA has a distinctive pattern of events relative to other diseases. Similarities in patterns are apparent between BD and HT. Conclusions The associations derived represent the first evidence that somatic gene conversion could be a significant causative factor in each of the seven diseases. The specific genes provide potential insights about disease mechanisms, and are strong candidates for further study. Please see Commentary: http://www.biomedcentral.com/1741-7015/9/13/abstract.

  19. Decision aids for multiple-decision disease management as affected by weather input errors.

    Pfender, W F; Gent, D H; Mahaffee, W F; Coop, L B; Fox, A D

    2011-06-01

    Many disease management decision support systems (DSSs) rely, exclusively or in part, on weather inputs to calculate an indicator for disease hazard. Error in the weather inputs, typically due to forecasting, interpolation, or estimation from off-site sources, may affect model calculations and management decision recommendations. The extent to which errors in weather inputs affect the quality of the final management outcome depends on a number of aspects of the disease management context, including whether management consists of a single dichotomous decision, or of a multi-decision process extending over the cropping season(s). Decision aids for multi-decision disease management typically are based on simple or complex algorithms of weather data which may be accumulated over several days or weeks. It is difficult to quantify accuracy of multi-decision DSSs due to temporally overlapping disease events, existence of more than one solution to optimizing the outcome, opportunities to take later recourse to modify earlier decisions, and the ongoing, complex decision process in which the DSS is only one component. One approach to assessing importance of weather input errors is to conduct an error analysis in which the DSS outcome from high-quality weather data is compared with that from weather data with various levels of bias and/or variance from the original data. We illustrate this analytical approach for two types of DSS, an infection risk index for hop powdery mildew and a simulation model for grass stem rust. Further exploration of analysis methods is needed to address problems associated with assessing uncertainty in multi-decision DSSs.

  20. Association of Multiple Genetic Variants with the Extension and Severity of Coronary Artery Disease

    Simone Cristina Pinto Matheus Fischer

    2018-02-01

    Full Text Available Abstract Background: Metabolic syndrome (MS is a condition that, when associated with ischemic heart disease and cardiovascular events, can be influenced by genetic variants and determine more severe coronary atherosclerosis. Objectives: To examine the contribution of genetic polymorphisms to the extension and severity of coronary disease in subjects with MS and recent acute coronary syndrome (ACS. Methods: Patients (n = 116, 68% males aged 56 (9 years, with criteria for MS, were prospectively enrolled to the study during the hospitalization period after an ACS. Clinical and laboratory parameters, high-sensitivity C-reactive protein, thiobarbituric acid reactive substances, adiponectin, endothelial function, and the Gensini score were assessed. Polymorphisms of paraoxonase-1 (PON-1, methylenotetrahydrofolate reductase (MTHFR, endothelial nitric oxide synthase (ENOS, angiotensin-converting enzyme (ACE, angiotensin II type 1 receptor (AT1R, apolipoprotein C3 (APOC3, lipoprotein lipase (LPL were analysed by polymerase chain reaction (PCR technique, followed by the identification of restriction fragment length polymorphisms (RFLP, and a genetic score was calculated. Parametric and non-parametric tests were used, as appropriate. Significance was set at p < 0.05. Results: Polymorphisms of PON-1, MTHFR and ENOS were not in the Hardy-Weinberg equilibrium. The DD genotype of LPL was associated with higher severity and greater extension of coronary lesions. Genetic score tended to be higher in patients with Gensini score < P50 (13.7 ± 1.5 vs. 13.0 ± 1.6, p = 0.066, with an inverse correlation between genetic and Gensini scores (R = -0.194, p = 0.078. Conclusions: The LPL polymorphism contributed to the severity of coronary disease in patients with MS and recent ACS. Combined polymorphisms were associated with the extension of coronary disease, and the lower the genetic score the more severe the disease.

  1. Apparent diffusion coefficient vale of the brain in patients with Gaucher's disease type II and type III

    Abdel Razek, Ahmed Abdel Khalek; Abd El-Gaber, Nahed; Abdalla, Ahmed; Fathy, Abeer; Azab, Ahmed; Rahman, Ashraf Abdel

    2009-01-01

    The aim of this work is to assess the usefulness of apparent diffusion coefficient (ADC) value of the brain for diagnosis of patients with Gaucher's disease type II and type III. Prospective study was conducted upon 13 patients (nine boys and four girls aged 8 months-14 years: mean 6.1 years) with Gaucher's disease type II and III and for age-matched control group (n = 13). Diffusion-weighted magnetic resonance imaging using a single-shot echo-planar imaging with a diffusion-weighted factor b of 0, 500, and 1,000 s/mm 2 was done for all patients and volunteers. The ADC value was calculated in ten regions of the brain parenchyma and correlated with genotyping. There was significantly lower ADC value of the cortical frontal (P = 0.003), cortical temporal (P = 0.04), frontal subcortical white matter (P = 0.02), corticospinal tract (P = 0.001), cerebellum (P = 0.001), medulla (P = 0.002), and midbrain (P = 0.02) between patients and volunteers. There was significant difference in the ADC value of the frontal and temporal gray matter (P = 0.04 and 0.05, respectively) between patients with heterozygous and homozygous gene mutation. We concluded that ADC value is a new promising quantitative imaging parameter that can be used for the detection of brain abnormalities in patients with Gaucher's disease type II and type III and has a correlation with genotyping. (orig.)

  2. [Progressive pulmonary hypertension in a patient with type 1 Gaucher disease].

    Ponomarev, R V; Model, S V; Averbukh, O M; Gavrilov, A M; Galstyan, G M; Lukina, E A

    Gaucher disease is the most common form of hereditary enzymopathies combined into a group of lysosomal storage diseases. The basis for the disease is a hereditary deficiency of the activity of acid β-glucosidase, a lysosomal enzyme involved in the catabolism of lipids, which results in the accumulation of nonutilized cellular metabolism products in the macrophage lysosomes. The main clinical manifestations of type 1 Gaucher disease are cytopenia, hepatomegaly, and splenomegaly, and bone lesion. One of the atypical clinical manifestations of Gaucher disease is damage to the lungs with the development of pulmonary hypertension, which is usually considered within the underlying disease - the development of pneumosclerosis due to macrophage dysfunction. The paper describes a case of progressive pulmonary hypertension in a patient with type 1 Gaucher disease.

  3. Differences in early speech patterns between Parkinson variant of multiple system atrophy and Parkinson's disease.

    Huh, Young Eun; Park, Jongkyu; Suh, Mee Kyung; Lee, Sang Eun; Kim, Jumin; Jeong, Yuri; Kim, Hee-Tae; Cho, Jin Whan

    2015-08-01

    In Parkinson variant of multiple system atrophy (MSA-P), patterns of early speech impairment and their distinguishing features from Parkinson's disease (PD) require further exploration. Here, we compared speech data among patients with early-stage MSA-P, PD, and healthy subjects using quantitative acoustic and perceptual analyses. Variables were analyzed for men and women in view of gender-specific features of speech. Acoustic analysis revealed that male patients with MSA-P exhibited more profound speech abnormalities than those with PD, regarding increased voice pitch, prolonged pause time, and reduced speech rate. This might be due to widespread pathology of MSA-P in nigrostriatal or extra-striatal structures related to speech production. Although several perceptual measures were mildly impaired in MSA-P and PD patients, none of these parameters showed a significant difference between patient groups. Detailed speech analysis using acoustic measures may help distinguish between MSA-P and PD early in the disease process. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Heterogeneity in Multiple Sclerosis: Scratching the Surface of a Complex Disease

    Disanto, Giulio; Berlanga, Antonio J.; Handel, Adam E.; Para, Andrea E.; Burrell, Amy M.; Fries, Anastasia; Handunnetthi, Lahiru; De Luca, Gabriele C.; Morahan, Julia M.

    2011-01-01

    Multiple Sclerosis (MS) is the most common demyelinating disease of the central nervous system. Although the etiology and the pathogenesis of MS has been extensively investigated, no single pathway, reliable biomarker, diagnostic test, or specific treatment have yet been identified for all MS patients. One of the reasons behind this failure is likely to be the wide heterogeneity observed within the MS population. The clinical course of MS is highly variable and includes several subcategories and variants. Moreover, apart from the well-established association with the HLA-class II DRB1*15:01 allele, other genetic variants have been shown to vary significantly across different populations and individuals. Finally both pathological and immunological studies suggest that different pathways may be active in different MS patients. We conclude that these “MS subtypes” should still be considered as part of the same disease but hypothesize that spatiotemporal effects of genetic and environmental agents differentially influence MS course. These considerations are extremely relevant, as outcome prediction and personalised medicine represent the central aim of modern research. PMID:21197462

  5. Mutant lines of currant tomato, valuable germplasm with multiple disease resistance

    Govorova, G.F.; Khrustaleva, V.V.; Shcherbakov, V.K.

    1987-01-01

    Studies were carried out for two years on eight mutant lines of currant tomato at the Krymsk Experimental Breeding Station of the N.I. Vavilov All-Union Scientific Research Institute of Plant-Growing (VIR). The station is situated in an area of commercial field tomato growing (Krasnodar region). The mutant lines of currant tomato (VIR specimen No. k-4053) were obtained through chronic gamma-irradiation. A disease resistance evaluation of the mutants was carried out for Verticillium wilt (Verticillium albo-atrum Rein. and Berth.), for black bacterial spotting (Xanthomonas vesicatoria Dows.), for tobacco mosaic virus Nicotiana 1 Smith), for streak virus (Nicotiana 1), for the combination TMV with X and Y potato viruses, for cucumber virus (Cucumis 1), and also for top rot. Fifty plants of each mutant line were evaluated and checks were made three times in each season. A comparison of the currant tomato mutants with the standard tomato varieties demonstrates the better resistance shown by the mutant germplasm to the main pathogens. The degree to which some currant tomato mutants were affected by Verticillium was lower than that of the most VerticiIlium-resistant samples of tomato evaluated between 1975 and 1981. The mutants of currant tomato should therefore be of interest as germplasm in breeding tomatoes for improved multiple disease resistance

  6. Fertility, pregnancy and childbirth in patients with multiple sclerosis: impact of disease-modifying drugs.

    Amato, Maria Pia; Portaccio, Emilio

    2015-03-01

    In recent decades, pregnancy-related issues in multiple sclerosis (MS) have received growing interest. MS is more frequent in women than in men and typically starts during child-bearing age. An increasing number of disease-modifying drugs (DMDs) for the treatment of MS are becoming available. Gathering information on their influences on pregnancy-related issues is of crucial importance for the counselling of MS patients. As for the immunomodulatory drugs (interferons and glatiramer acetate), accumulating evidence points to the relative safety of pregnancy exposure in terms of maternal and foetal outcomes. In case of higher clinical disease activity before pregnancy, these drugs could be continued until conception. As for the 'newer' drugs (fingolimod, natalizumab, teriflunomide, dimethyl fumarate and alemtuzumab), the information is more limited. Whereas fingolimod and teriflunomide are likely associated with an increased risk of foetal malformations, the effects of natalizumab, dimethyl fumarate and alemtuzumab still need to be ascertained. This article provides a review of the available information on the use of DMDs during pregnancy, with a specific focus on fertility, foetal development, delivery and breast-feeding.

  7. Exploration of machine learning techniques in predicting multiple sclerosis disease course.

    Yijun Zhao

    Full Text Available To explore the value of machine learning methods for predicting multiple sclerosis disease course.1693 CLIMB study patients were classified as increased EDSS≥1.5 (worsening or not (non-worsening at up to five years after baseline visit. Support vector machines (SVM were used to build the classifier, and compared to logistic regression (LR using demographic, clinical and MRI data obtained at years one and two to predict EDSS at five years follow-up.Baseline data alone provided little predictive value. Clinical observation for one year improved overall SVM sensitivity to 62% and specificity to 65% in predicting worsening cases. The addition of one year MRI data improved sensitivity to 71% and specificity to 68%. Use of non-uniform misclassification costs in the SVM model, weighting towards increased sensitivity, improved predictions (up to 86%. Sensitivity, specificity, and overall accuracy improved minimally with additional follow-up data. Predictions improved within specific groups defined by baseline EDSS. LR performed more poorly than SVM in most cases. Race, family history of MS, and brain parenchymal fraction, ranked highly as predictors of the non-worsening group. Brain T2 lesion volume ranked highly as predictive of the worsening group.SVM incorporating short-term clinical and brain MRI data, class imbalance corrective measures, and classification costs may be a promising means to predict MS disease course, and for selection of patients suitable for more aggressive treatment regimens.

  8. The primary cilium as a multiple cellular signaling scaffold in development and disease

    Hyuk Wan Ko*

    2012-08-01

    Full Text Available Primary cilia, single hair-like appendage on the surface of themost mammalian cells, were once considered to be vestigialcellular organelles for a past century because of their tinystructure and unknown function. Although they lack ancestralmotility function of cilia or flagella, they share common groundwith multiciliated motile cilia and flagella on internal structuresuch as microtubule based nine outer doublets nucleated from thebase of mother centrioles called basal body. Making cilia,ciliogenesis, in cells depends on the cell cycle stage due to reuseof centrioles for cell division forming mitotic spindle pole (Mphase and assembling cilia from basal body (starting G1 phaseand maintaining most of interphase. Ciliary assembly requiredtwo conflicting processes such as assembly and disassembly andbalance between these two processes determines the length ofcilia. Both process required highly conserved transport system tosupply needed substance to grow tip of cilia and bring ciliaryturnover product back to the base of cilia using motor protein,kinesin and dynein, and transport protein complex, IFT particles.Disruption of ciliary structure or function causes multiple humandisorder called ciliopathies affecting disease of diverse ciliatedtissues ranging from eye, kidney, respiratory tract and brain.Recent explosion of research on the primary cilia and theirinvolvement on animal development and disease attracts scientificinterest on how extensively the function of cilia related to specificcell physiology and signaling pathway. In this review, I introducegeneral features of primary cilia and recent progress inunderstanding of the ciliary length control and signaling pathwaystransduced through primary cilia in vertebrates.

  9. Understanding disease processes in multiple sclerosis through magnetic resonance imaging studies in animal models

    Nabeela Nathoo

    2014-01-01

    Full Text Available There are exciting new advances in multiple sclerosis (MS resulting in a growing understanding of both the complexity of the disorder and the relative involvement of grey matter, white matter and inflammation. Increasing need for preclinical imaging is anticipated, as animal models provide insights into the pathophysiology of the disease. Magnetic resonance (MR is the key imaging tool used to diagnose and to monitor disease progression in MS, and thus will be a cornerstone for future research. Although gadolinium-enhancing and T2 lesions on MRI have been useful for detecting MS pathology, they are not correlative of disability. Therefore, new MRI methods are needed. Such methods require validation in animal models. The increasing necessity for MRI of animal models makes it critical and timely to understand what research has been conducted in this area and what potential there is for use of MRI in preclinical models of MS. Here, we provide a review of MRI and magnetic resonance spectroscopy (MRS studies that have been carried out in animal models of MS that focus on pathology. We compare the MRI phenotypes of animals and patients and provide advice on how best to use animal MR studies to increase our understanding of the linkages between MR and pathology in patients. This review describes how MRI studies of animal models have been, and will continue to be, used in the ongoing effort to understand MS.

  10. Prediction of orthostatic hypotension in multiple system atrophy and Parkinson disease

    Sun, Zhanfang; Jia, Dandan; Shi, Yuting; Hou, Xuan; Yang, Xiaosu; Guo, Jifeng; Li, Nan; Wang, Junling; Sun, Qiying; Zhang, Hainan; Lei, Lifang; Shen, Lu; Yan, Xinxiang; Xia, Kun; Jiang, Hong; Tang, Beisha

    2016-01-01

    Orthostatic hypotension (OH) is common in multiple system atrophy (MSA) and Parkinson disease (PD), generally assessed through a lying-to-standing orthostatic test. However, standing blood pressure may not be available due to orthostatic intolerance or immobilization for such patients. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were successively measured in supine, sitting, and standing positions in patients with MSA and PD. Receiver operating characteristic analysis was used to evaluate diagnostic performance of the drops of sitting SBP or DBP. OH and severe OH were respectively regarded as “gold standard”. The drops of SBP in standing position were associated with increased disease severity for MSA and correlated with age for PD. In MSA group, drops in sitting SBP ≥ 14 mmHg or DBP ≥ 6 mmHg had highest validity for prediction of OH, and drops in sitting SBP ≥ 18 mmHg or DBP ≥ 8 mmHg for severe OH. In PD group, drops in sitting SBP ≥ 10 mmHg or DBP ≥ 6 mmHg had highest validity for prediction of OH. The lying-to-sitting orthostatic test is an alternative method for detection of OH in MSA and PD, especially when standing BP could not be validly measured due to various reasons. PMID:26867507

  11. Ecosystem services capacity across heterogeneous forest types: understanding the interactions and suggesting pathways for sustaining multiple ecosystem services.

    Alamgir, Mohammed; Turton, Stephen M; Macgregor, Colin J; Pert, Petina L

    2016-10-01

    As ecosystem services supply from tropical forests is declining due to deforestation and forest degradation, much effort is essential to sustain ecosystem services supply from tropical forested landscapes, because tropical forests provide the largest flow of multiple ecosystem services among the terrestrial ecosystems. In order to sustain multiple ecosystem services, understanding ecosystem services capacity across heterogeneous forest types and identifying certain ecosystem services that could be managed to leverage positive effects across the wider bundle of ecosystem services are required. We sampled three forest types, tropical rainforests, sclerophyll forests, and rehabilitated plantation forests, over an area of 32,000m(2) from Wet Tropics bioregion, Australia, aiming to compare supply and evaluate interactions and patterns of eight ecosystem services (global climate regulation, air quality regulation, erosion regulation, nutrient regulation, cyclone protection, habitat provision, energy provision, and timber provision). On average, multiple ecosystem services were highest in the rainforests, lowest in sclerophyll forests, and intermediate in rehabilitated plantation forests. However, a wide variation was apparent among the plots across the three forest types. Global climate regulation service had a synergistic impact on the supply of multiple ecosystem services, while nutrient regulation service was found to have a trade-off impact. Considering multiple ecosystem services, most of the rehabilitated plantation forest plots shared the same ordination space with rainforest plots in the ordination analysis, indicating that rehabilitated plantation forests may supply certain ecosystem services nearly equivalent to rainforests. Two synergy groups and one trade-off group were identified. Apart from conserving rainforests and sclerophyll forests, our findings suggest two additional integrated pathways to sustain the supply of multiple ecosystem services from a

  12. Bisphenol A (BPA) aggravates multiple low-dose streptozotocin-induced Type 1 diabetes in C57BL/6 mice.

    Cetkovic-Cvrlje, Marina; Thinamany, Sinduja; Bruner, Kylie A

    2017-12-01

    Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disorder characterized by destruction of insulin-producing pancreatic β-cells. Whereas epidemiological data implicate environmental factors in the increasing incidence of T1D, their identity remains unknown. Though exposure to bisphenol A (BPA) has been associated with several disorders, no epidemiologic evidence has linked BPA exposure and T1D. The goal of this study was to elucidate diabetogenic potentials of BPA and underlying mechanisms in the context of T-cell immunity, in a multiple low-dose streptozotocin (MLDSTZ)-induced autoimmune mouse T1D model. C57BL/6 mice were orally exposed to 1 or 10 mg BPA/L starting at 4 wk of age; diabetes was induced at 9 wk of age with STZ. T-cell composition, function, and insulitis levels were studied at Days 11 and 50 during diabetes development (i.e. post-first STZ injection). Results showed both BPA doses increased diabetes incidence and affected T-cell immunity. However, mechanisms of diabetogenic action appeared divergent based on dose. Low-dose BPA fits a profile of an agent that exhibits pro-diabetogenic effects via T-cell immunomodulation in the early stages of disease development, i.e. decreases in splenic T-cell subpopulations [especially CD4 + T-cells] along with a trend in elevation of splenic T-cell formation of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6). In contrast, high-dose BPA did not affect T-cell populations and led to decreased levels of IFN-γ and TNF-α. Both treatments did not affect insulitis levels at the disease early stage, but aggravated it later on. By the study end, besides decreasing T-cell proliferative capacity, low-dose BPA did not affect other T-cell-related parameters, including cytokine secretion, comparable to the effects of high-dose BPA. In conclusion, this study confirmed BPA as a potential diabetogenic compound with immunomodulatory mechanisms of action - in the context of T-cell immunity - that seemed to be dose

  13. Real-Time PCR Typing of Escherichia coli Based on Multiple Single Nucleotide Polymorphisms--a Convenient and Rapid Method.

    Lager, Malin; Mernelius, Sara; Löfgren, Sture; Söderman, Jan

    2016-01-01

    Healthcare-associated infections caused by Escherichia coli and antibiotic resistance due to extended-spectrum beta-lactamase (ESBL) production constitute a threat against patient safety. To identify, track, and control outbreaks and to detect emerging virulent clones, typing tools of sufficient discriminatory power that generate reproducible and unambiguous data are needed. A probe based real-time PCR method targeting multiple single nucleotide polymorphisms (SNP) was developed. The method was based on the multi locus sequence typing scheme of Institute Pasteur and by adaptation of previously described typing assays. An 8 SNP-panel that reached a Simpson's diversity index of 0.95 was established, based on analysis of sporadic E. coli cases (ESBL n = 27 and non-ESBL n = 53). This multi-SNP assay was used to identify the sequence type 131 (ST131) complex according to the Achtman's multi locus sequence typing scheme. However, it did not fully discriminate within the complex but provided a diagnostic signature that outperformed a previously described detection assay. Pulsed-field gel electrophoresis typing of isolates from a presumed outbreak (n = 22) identified two outbreaks (ST127 and ST131) and three different non-outbreak-related isolates. Multi-SNP typing generated congruent data except for one non-outbreak-related ST131 isolate. We consider multi-SNP real-time PCR typing an accessible primary generic E. coli typing tool for rapid and uniform type identification.

  14. Cerebrovascular and hypertensive diseases as multiple causes of death in Brazil from 2004 to 2013.

    Villela, P B; Klein, C H; Oliveira, G M M

    2018-06-02

    The proportion of deaths attributed to hypertensive diseases (HYPDs) was only 50% of that registered for cerebrovascular diseases (CBVDs) in 2013 in Brazil. This article aims to evaluate mortality related to HYPDs and CBVDs as multiple causes of death, in Brazil from 2004 to 2013. Analysis of historical series of secondary data obtained from Brazilian official registries. Data about the deaths were obtained from the Mortality Information System of the Brazilian Ministry of Health, available on the DATASUS website. CBVDs and HYPDs were evaluated according to their mentions as the underlying cause of death or entry in any line of the death certificates (DCs), according to their International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes. When CBVDs were the underlying causes of death, HYPDs were mentioned in 40.9% of the DCs. When HYPDs were the underlying causes of death, CBVDs were mentioned in only 5.0%. When CBVDs were mentioned without HYPDs, they were selected as the underlying cause of death 74.4% of the time. When HYPDs were mentioned in DCs without CBVDs, HYPDs were selected 30.0% of the time. In 2004, the frequency of any mention of HYPDs relative to the frequency of HYPDs cited as underlying causes increased fourfold and was followed by a plateau until 2013. In contrast, the frequency of any mention of CBVDs relative to the frequency of CBVDs as underlying causes decreased in the same period. Because this study was based on DC records, it was limited by the way these documents were completed, which may have included lack of record of the causes related to the sequence that culminated in death. When deaths related to HYPDs were evaluated as multiple causes of death, they were mentioned up to four times more often than when they were selected as underlying causes of death. This reinforces the need for better control of hypertension to prevent deaths. Copyright © 2018 The Royal Society for Public Health. Published by

  15. Characterization of vascular lesions in pigs affected by porcine circovirus type 2-systemic disease.

    Resendes, A R; Segalés, J

    2015-05-01

    Vascular lesions and their association with porcine circovirus type 2 (PCV2) were evaluated in multiple organs from 10 pigs affected with PCV2-systemic disease (PCV2-SD). Animals had vascular lesions in multiple organs, consisting of lymphohistiocytic lymphangitis and/or phlebitis, mild to severe necrotizing arteritis, and thrombosis within splenic arterioles and choroid plexus capillaries. Variable amounts of PCV2 nucleic acid detected by in situ hybridization were present within endothelial cells, tunica media myocytes, and perivascular and/or intralesional inflammatory cell infiltrates. PCV2 nucleic acid was detected within endothelial cells of both lymphatic and blood vessels without lesions in the associated tissues. Necrotizing arteritis was principally present in lymph nodes and kidney and consisted of degeneration, necrosis, and pyknosis of myocytes, often with intracytoplasmic, brightly eosinophilic inclusion bodies that were strongly positive for PCV2 nucleic acid. Segmental or circumferential fibrinoid necrosis was mainly present in vessels of the lymph node, spleen, and choroid plexus and was variably associated with PCV2 nucleic acid. Severe lymphangitis associated with strong intralesional PCV2 labeling was frequently detected within the mesenteric and mediastinal lymph nodes and the lamina propria of the ileum. In most tissues, medium and large lymphatics and/or veins often had disruption of the intima and mild mononuclear inflammatory cell infiltration that was variably associated with PCV2 nucleic acid. The present study indicates that vasculitis is a frequent finding in natural cases of PCV2-SD and that PCV2 may have a direct cytopathic effect on tunica media myocytes of small- and medium-sized arteries as well as endothelium. © The Author(s) 2014.

  16. Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease

    Levitt DG

    2014-09-01

    Full Text Available David G Levitt,1 Michael D Levitt2 1Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, USA; 2Research Service, Veterans Affairs Medical Center, Minneapolis, MN, USAAbstract: Serum bilirubin measurements are commonly obtained for the evaluation of ill patients and to screen for liver disease in routine physical exams. An enormous research effort has identified the multiple mechanisms involved in the production and metabolism of conjugated (CB and unconjugated bilirubin (UB. While the qualitative effects of these mechanisms are well understood, their expected quantitative influence on serum bilirubin homeostasis has received less attention. In this review, each of the steps involved in bilirubin production, metabolism, hepatic cell uptake, and excretion is quantitatively examined. We then attempt to predict the expected effect of normal and defective function on serum UB and CB levels in health and disease states including hemolysis, extra- and intrahepatic cholestasis, hepatocellular diseases (eg, cirrhosis, hepatitis, and various congenital defects in bilirubin conjugation and secretion (eg, Gilbert's, Dubin–Johnson, Crigler–Najjar, Rotor syndromes. Novel aspects of this review include: 1 quantitative estimates of the free and total UB and CB in the plasma, hepatocyte, and bile; 2 detailed discussion of the important implications of the recently recognized role of the hepatic OATP transporters in the maintenance of CB homeostasis; 3 discussion of the differences between the standard diazo assay versus chromatographic measurement of CB and UB; 4 pharmacokinetic implications of the extremely high-affinity albumin binding of UB; 5 role of the enterohepatic circulation in physiologic jaundice of newborn and fasting hyperbilirubinemia; and 6 insights concerning the clinical interpretation of bilirubin measurements.Keywords: liver, conjugation, diazo, albumin, Rotor

  17. The Geomagnetic Field and Correlations with Multiple Sclerosis: A Possible Etiology of Disease

    Wade, Brett

    Multiple sclerosis (MS) is a complex autoimmune disease that results in a demyelinating process of the central nervous system. It is the most common, progressive, neurological disease affecting young adults, and there is no cure. A curious feature of MS is its distinct global prevalence with high rates of occurrence between 40 and 60 degrees latitude. While genetics may partially explain this phenomenon, studies have shown that the influence of genetics is modest. Many non-genetic variables, such as viruses, vitamin D, smoking, diet, hormones, etc., have been shown to be related to the expression of MS but none of these variables have been determined to be necessarily strong enough to exclude other factors. The geomagnetic field, which is a non-uniform, three dimensional entity which protects all living things from ionizing radiation, is suggested in this research to be related to global MS prevalence. This study hypothesized that either the total field, the vertical field, or the horizontal field strength of the geomagnetic field will be correlated with MS. Using secondary sources of prevalence studies (N=131) and geomagnetic data, the results supported all three hypotheses with the strongest correlation being an inverse relationship between the horizontal field and MS (r = -.607). The explanation for the inverse relationship being most strongly correlated with MS prevalence is explained by the fact that the horizontal aspect of the geomagnetic field has a protective effect from incoming cosmic radiation. Chronic exposure to high levels of background radiation can have deleterious health effects. This research suggests that living in areas of a weak horizontal field increases a person's exposure to ionizing radiation and therefore increases the risk for developing MS. While it was not the intention of this research, it became clear that an explanation which explained the results of this research and also attempted to unify the mechanisms of all non

  18. Modeling of cognitive impairment by disease duration in multiple sclerosis: a cross-sectional study.

    Anat Achiron

    Full Text Available BACKGROUND/AIMS: Large-scale population studies measuring rates and dynamics of cognitive decline in multiple sclerosis (MS are lacking. In the current cross-sectional study we evaluated the patterns of cognitive impairment in MS patients with disease duration of up to 30 years. METHODS: 1,500 patients with MS were assessed by a computerized cognitive battery measuring verbal and non-verbal memory, executive function, visual spatial perception, verbal function, attention, information processing speed and motor skills. Cognitive impairment was defined as below one standard deviation (SD and severe cognitive impairment as below 2SD for age and education matched healthy population norms. RESULTS: Cognitive performance in our cohort was poorer than healthy population norms. The most frequently impaired domains were information processing speed and executive function. MS patients with secondary-progressive disease course performed poorly compared with clinically isolated syndrome, relapsing-remitting and primary progressive MS patients. By the fifth year from disease onset, 20.9% of patients performed below the 1SD cutoff for impairment, p=0.005, and 6.0% performed below the 2SD cutoff for severe cognitive impairment, p=0.002. By 10 years from onset 29.3% and 9.0% of patients performed below the 1SD and 2SD cutoffs, respectively, p=0.0001. Regression modeling suggested that cognitive impairment may precede MS onset by 1.2 years. CONCLUSIONS: The rates of cognitive impairment in this large sample of MS patients were lower than previously reported and severe cognitive impairment was evident only in a relatively small group of patients. Cognitive impairment differed significantly from expected normal distribution only at five years from onset, suggesting the existence of a therapeutic window during which patients may benefit from interventions to maintain cognitive health.

  19. Cytokine profiling in the prefrontal cortex of Parkinson's Disease and Multiple System Atrophy patients.

    Rydbirk, Rasmus; Elfving, Betina; Andersen, Mille Dahl; Langbøl, Mia Aggergaard; Folke, Jonas; Winge, Kristian; Pakkenberg, Bente; Brudek, Tomasz; Aznar, Susana

    2017-10-01

    Parkinson's Disease (PD) and Multiple System Atrophy (MSA) are neurodegenerative diseases characterized neuropathologically by alpha-synuclein accumulation in brain cells. This accumulation is hypothesized to contribute to constitutive neuroinflammation, and to participate in the neurodegeneration. Cytokines, which are the main inflammatory signalling molecules, have been identified in blood and cerebrospinal fluid of PD patients, but studies investigating the human brain levels are scarce. It is documented that neurotrophins, necessary for survival of brain cells and known to interact with cytokines, are altered in the basal ganglia of PD patients. In regards to MSA, no major study has investigated brain cytokine or neurotrophin protein expression. Here, we measured protein levels of 18 cytokines (IL-2, 4-8, 10, 12, 13, 17, G-CSF, GM-CSF, IFN-γ, MCP-1, MIP-1α and 1β, TNF-α) and 5 neurotrophins (BDNF, GDNF, bFGF, PDGF-BB, VEGF) in the dorsomedial prefrontal cortex in brains of MSA and PD patients and control subjects. We found altered expression of IL-2, IL-13, and G-CSF, but no differences in neurotrophin levels. Further, in MSA patients we identified increased mRNA levels of GSK3β that is involved in neuroinflammatory pathways. Lastly, we identified increased expression of the neurodegenerative marker S100B, but not CRP, in PD and MSA patients, indicating local rather than systemic inflammation. Supporting this, in both diseases we observed increased MHC class II + and CD45 + positive cells, and low numbers of infiltrating CD3 + cells. In conclusion, we identified neuroinflammatory responses in PD and MSA which seems more widespread in the brain than neurotrophic changes. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Therapeutic molecules for multiple human diseases identified from pigeon pea (Cajanus cajan L. Millsp. through GC–MS and molecular docking

    Deepu Mathew

    2017-12-01

    Full Text Available Molecular mechanism behind the therapeutic potential of pigeon pea over the human diseases such as rheumatoid arthritis, breast cancer, type II diabetes, malaria, measles and sickle cell disease were revealed through docking of GC–MS identified phyto-compound ligands with candidate disease proteins. Of the 242 ligands, three dimensional structures of 47 compounds had to be drawn using ChemSketch and the remaining structures were retrieved from PubChem and docked with the active sites of candidate proteins. The molecules identified through docking were further subjected to ADMET analysis and promising drug candidates were identified for each disease. This paper presents a precise account of the chemoprofile of pigeon pea leaves, stems and seeds, interaction of these molecules with target proteins and suggests 26 highly potential molecules which are drug candidates for multiple human diseases. Pigeon pea seeds are especially proven as invaluable source for therapeutic molecules. Keywords: Breast cancer, Drug discovery, Herbal medicine, In silico, Malaria, Measles, Phyto-compounds, Rheumatoid arthritis, Sickle cell disease, Type II diabetes

  1. A Semi-Supervised Learning Algorithm for Predicting Four Types MiRNA-Disease Associations by Mutual Information in a Heterogeneous Network.

    Zhang, Xiaotian; Yin, Jian; Zhang, Xu

    2018-03-02

    Increasing evidence suggests that dysregulation of microRNAs (miRNAs) may lead to a variety of diseases. Therefore, identifying disease-related miRNAs is a crucial problem. Currently, many computational approaches have been proposed to predict binary miRNA-disease associations. In this study, in order to predict underlying miRNA-disease association types, a semi-supervised model called the network-based label propagation algorithm is proposed to infer multiple types of miRNA-disease associations (NLPMMDA) by mutual information derived from the heterogeneous network. The NLPMMDA method integrates disease semantic similarity, miRNA functional similarity, and Gaussian interaction profile kernel similarity information of miRNAs and diseases to construct a heterogeneous network. NLPMMDA is a semi-supervised model which does not require verified negative samples. Leave-one-out cross validation (LOOCV) was implemented for four known types of miRNA-disease associations and demonstrated the reliable performance of our method. Moreover, case studies of lung cancer and breast cancer confirmed effective performance of NLPMMDA to predict novel miRNA-disease associations and their association types.

  2. MIXED HYALINE VASCULAR AND PLASMA CELL TYPE CASTLEMAN’S DISEASE: REPORT OF A CASE

    F. Asgarani

    2006-05-01

    Full Text Available Castleman’s disease (angiofollicular lymphoid hyperplasia includes a heterogeneous group of lymphoproliferative disorders. The cause of this disease remains uncertain. There are two types of localized Castleman’s disease: the more common hyaline vascular and the plasma cell types. Mixed variant is an uncommon localized lesion in general population. The lesions can occur in any part of the body that contains lymphoid tissue, although seventy percent are found in the anterior mediastinum. We report a thirty years old boy with Castleman’s disease who presented with fever, anorexia, weight loss,sweating, anemia and abdominal mass. The histologic examination of the biopsy specimens revealed a mixed hyaline vascular and plasma cell type of Castleman’s disease.

  3. Phenotype/genotype correlations in Gaucher disease type 1: Clinical and therapeutic implications

    Sibille, A.; Eng, C.M.; Kim, S.J.; Pastores, G. (Mount Sinai School of Medicine, New York, NY (United States)); Grabowski, G.A. (Mount Sinai School of Medicine, New York, NY (United States) Univ. of Cincinnati, OH (United States))

    1993-06-01

    Gaucher disease is the most frequent lysosomal storage disease and the most prevalent genetic disease among Ashkenazi Jews. Gaucher disease type 1 is characterized by marked variability of the phenotype and by the absence of neuronopathic involvement. To test the hypothesis that this phenotypic variability was due to genetic compounds of several different mutant alleles, 161 symptomatic patients with Gaucher disease type 1 (> 90% Ashkenazi Jewish) were analyzed for clinical involvement, and their genotypes were determined. Qualitative and quantitative measures of disease involvement included age at onset of the disease manifestations, hepatic and splenic volumes, age at splenectomy, and severity of bony disease. High statistically significant differences (P < .005) were found in each clinical parameter in patients with the N370S/N370S genotype compared with those patients with the N370S/84GG, N370S/L444P, and N370/ genotypes. The symptomatic N370S homozygotes had onset of their disease two to three decades later than patients with the other genotypes. In addition, patients with the latter genotypes have much more severely involved livers, spleens, and bones and had a higher incidence of splenectomy at an earlier age. These predictive genotype analyses provide the basis for genetic care delivery and therapeutic recommendations in patients affected with Gaucher disease type 1. 38 refs., 1 fig., 4 tabs.

  4. 'Non-neuronopathic' Gaucher disease reconsidered. Prevalence of neurological manifestations in a Dutch cohort of type I Gaucher disease patients and a systematic review of the literature

    Biegstraaten, M.; van Schaik, I. N.; Aerts, J. M. F. G.; Hollak, C. E. M.

    2008-01-01

    Gaucher disease is a lysosomal storage disorder, which is classically divided into three types. Type I Gaucher disease is differentiated from types II and III disease by the absence of nervous system involvement. However, an increasing number of reports has emerged on neurological manifestations in

  5. An M/G/1 queue with multiple types of feedback and gated vacations

    O.J. Boxma (Onno); U. Yechiali

    1995-01-01

    textabstractThis paper considers a single-server queue with Poisson arrivals and multiple customer feedbacks. If the first service attempt of a newly arriving customer is not successful, he returns to the end of the queue for another service attempt, with a different service time distribution. He

  6. Seismic reflector imaging using internal multiples with Marchenko-type equations

    Slob, E.C.; Wapenaar, C.P.A.; Broggini, F.; Snieder, R.

    2014-01-01

    We present an imaging method that creates a map of reflection coefficients in correct one-way time with no contamination from internal multiples using purely a filtering approach. The filter is computed from the measured reflection response and does not require a background model. We demonstrate

  7. The Representation of Multiple Intelligences Types in the Top-Notch Series: A Textbook Evaluation

    Razmjoo, Seyyed Ayatollah; Jozaghi, Zahra

    2010-01-01

    This study aims at evaluating Top-Notch series through a checklist devised by the researchers based on the elements of the Multiple Intelligences (MI) theory proposed by Gardner (1998). With the shift from teacher-centered classrooms to learner-centered one, more and more research is needed to be done in the realm of students' need analysis. One…

  8. Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1

    Goudie, David R; D'Alessandro, Mariella; Merriman, Barry

    2011-01-01

    Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving......-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer....

  9. Effects of multiple training modalities in patients with Alzheimer’s disease: a pilot study

    Tai SY

    2016-11-01

    Full Text Available Shu-Yu Tai,1–4 Chia-Ling Hsu,5 Shu-Wan Huang,5 Tzu-Chiao Ma,6,7 Wen-Chien Hsieh,8,9 Yuan-Han Yang5,7,10,11 1Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, 2Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 3Department of Family Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, 4Research Center for Environmental Medicine, Kaohsiung Medical University, 5Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, 6Graduate Institute of Oral Health Sciences, Kaohsiung Medical University, 7Mentality Protection Center, Fo Guang Shan Compassion Foundation, 8Department of Social Work, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, 9Department of Sociology and Social Work, Kaohsiung Medical University, 10Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 11Department of and Master’s Program in Neurology, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan Objective: This pilot study investigated the effects of multiple training modalities on cognition, neuropsychiatric symptoms, caregivers’ burden, and quality of life in patients with Alzheimer’s disease (AD.Patients and methods: This intervention study was conducted in 24 patients with AD aged ≥65 years with a Clinical Dementia Rating (CDR score of 0.5–1. The patients were assigned to receive multiple training modalities (1 hour for each training: Tai Chi, calligraphy, and drawing over a 6-week period in either the experimental group (n=14 or the comparison group (n=10. A series of neuropsychological tests – namely the Traditional Chinese version Mini-Mental Status Examination, Cognitive Assessment Screening Instrument (CASI, Neuropsychiatric Inventory and the Neuropsychiatric Inventory Caregiver Distress Scale, and the Clinical Dementia

  10. Endovascular repair of multiple infrageniculate aneurysms in a patient with vascular type Ehlers-Danlos syndrome.

    Domenick, Natalie; Cho, Jae S; Abu Hamad, Ghassan; Makaroun, Michel S; Chaer, Rabih A

    2011-09-01

    Patients with vascular type Ehler-Danlos syndrome can develop aneurysms in unusual locations. We describe the case of a 33-year-old woman with vascular type Ehlers-Danlos syndrome who developed metachronous tibial artery aneurysms that were sequentially treated with endovascular means. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  11. Evolution of Late-type Galaxies in a Cluster Environment: Effects of High-speed Multiple Encounters with Early-type Galaxies

    Hwang, Jeong-Sun; Park, Changbom; Banerjee, Arunima; Hwang, Ho Seong

    2018-04-01

    Late-type galaxies falling into a cluster would evolve being influenced by the interactions with both the cluster and the nearby cluster member galaxies. Most numerical studies, however, tend to focus on the effects of the former with little work done on those of the latter. We thus perform a numerical study on the evolution of a late-type galaxy interacting with neighboring early-type galaxies at high speed using hydrodynamic simulations. Based on the information obtained from the Coma cluster, we set up the simulations for the case where a Milky Way–like late-type galaxy experiences six consecutive collisions with twice as massive early-type galaxies having hot gas in their halos at the closest approach distances of 15–65 h ‑1 kpc at the relative velocities of 1500–1600 km s‑1. Our simulations show that the evolution of the late-type galaxy can be significantly affected by the accumulated effects of the high-speed multiple collisions with the early-type galaxies, such as on cold gas content and star formation activity of the late-type galaxy, particularly through the hydrodynamic interactions between cold disk and hot gas halos. We find that the late-type galaxy can lose most of its cold gas after the six collisions and have more star formation activity during the collisions. By comparing our simulation results with those of galaxy–cluster interactions, we claim that the role of the galaxy–galaxy interactions on the evolution of late-type galaxies in clusters could be comparable with that of the galaxy–cluster interactions, depending on the dynamical history.

  12. Cannabis use in people with Parkinson's disease and Multiple Sclerosis: A web-based investigation.

    Kindred, John H; Li, Kaigang; Ketelhut, Nathaniel B; Proessl, Felix; Fling, Brett W; Honce, Justin M; Shaffer, William R; Rudroff, Thorsten

    2017-08-01

    Cannabis has been used for medicinal purpose for thousands of years; however the positive and negative effects of cannabis use in Parkinson's disease (PD) and Multiple Sclerosis (MS) are mostly unknown. Our aim was to assess cannabis use in PD and MS and compare results of self-reported assessments of neurological disability between current cannabis users and non-users. An anonymous web-based survey was hosted on the Michael J. Fox Foundation and the National Multiple Sclerosis Society webpages from 15 February to 15 October 2016. The survey collected demographic and cannabis use information, and used standardized questionnaires to assess neurological function, fatigue, balance, and physical activity participation. Analysis of variance and chi-square tests were used for the analysis. The survey was viewed 801 times, and 595 participants were in the final data set. Seventy-six percent and 24% of the respondents reported PD and MS respectively. Current users reported high efficacy of cannabis, 6.4 (SD 1.8) on a scale from 0 to 7 and 59% reported reducing prescription medication since beginning cannabis use. Current cannabis users were younger and less likely to be classified as obese (P Cannabis users reported lower levels of disability, specifically in domains of mood, memory, and fatigue (PCannabis may have positive impacts on mood, memory, fatigue, and obesity status in people with PD and MS. Further studies using clinically and longitudinally assessed measurements of these domains are needed to establish if these associations are causal and determine the long-term benefits and consequences of cannabis use in people with PD and MS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Psychosocial predictors of patient adherence to disease-modifying therapies for multiple sclerosis

    Alosaimi FD

    2017-03-01

    Full Text Available Fahad D Alosaimi,1 Alaa AlMulhem,2 Hanan AlShalan,2 Mohammad Alqazlan,3 Abdulgader Aldaif,4 Matthew Kowgier,5 Janooshsheya Balasundaram,6 Sanjeev Sockalingam6,7 1Department of Psychiatry, 2College of Medicine, King Saud University, 3Department of Mental Health, King Faisal Specialist Hospital and Research Centre, 4Department of Neurology, King Saud University, Riyadh, Saudi Arabia; 5Dalla Lana School of Public Health, University of Toronto, 6Centre for Mental Health, University Health Network, 7Department of Psychiatry, University of Toronto, Toronto, ON, Canada Objectives: Our aim was to identify the impact of psychosocial predictors, specifically relationship style, depressive symptoms, anxiety symptoms, cognitive impairment, and culture-specific disease beliefs, on treatment adherence for multiple sclerosis (MS patients.Methods: In this cross-sectional observational study, patients from two MS clinics in Saudi Arabia completed self-reported questionnaires focused on MS treatment adherence, physical symptom burden, relationship style, cultural beliefs, depressive symptoms, anxiety, and cognitive impairment.Results: A total of 163 MS patients participated, 81.6% of them were female, and the mean age of the patients was 31.6 years. Mean patient-reported adherence to their MS treatment regimen was 79.47%±25.26%. Multivariate linear regression analysis only identified patients’ belief that their MS was due to “supernatural” forces as being significantly negatively associated with MS medication adherence.Conclusion: This study demonstrates the importance of cultural interpretations to MS medication adherence in comparison to psychosocial factors. Education and family involvement in the treatment planning may address this issue and warrant further research. Keywords: multiple sclerosis, adherence, depression, attachment style, culture

  14. Simulation of a resonant-type ring magnet power supply with multiple resonant cells and energy storage chokes

    Kim, J.M.S.; Blackmore, E.W.; Reiniger, K.W.

    1992-01-01

    For the TRIUMF KAON Factory Booster Ring, a resonant-type magnet power supply has been proposed for the dipole magnet excitation. The Booster Ring magnet power supply system based on resonant circuits, coupled with distributed energy make-up networks, is a complex system, sensitive to many system parameters. When multiple resonant cells, each with its own energy make-up network, are connected in a ring, it is very difficult to derive closed-form solutions to determine the operating conditions of the power supply system. A meaningful way to understand and analyze such a complex system is to use a simulation tool. This paper presents the analysis of operating conditions of the resonant-type ring magnet power supply with multiple resonant cells, using the circuit simulation tool, SPICE. The focus of the study is on the effect of circuit parameter variations in energy storage chokes

  15. Systemic Correction of Murine Glycogen Storage Disease Type IV by an AAV-Mediated Gene Therapy.

    Yi, Haiqing; Zhang, Quan; Brooks, Elizabeth D; Yang, Chunyu; Thurberg, Beth L; Kishnani, Priya S; Sun, Baodong

    2017-03-01

    Deficiency of glycogen branching enzyme (GBE) causes glycogen storage disease type IV (GSD IV), which is characterized by the accumulation of a less branched, poorly soluble form of glycogen called polyglucosan (PG) in multiple tissues. This study evaluates the efficacy of gene therapy with an adeno-associated viral (AAV) vector in a mouse model of adult form of GSD IV (Gbe1 ys/ys ). An AAV serotype 9 (AAV9) vector containing a human GBE expression cassette (AAV-GBE) was intravenously injected into 14-day-old Gbe1 ys/ys mice at a dose of 5 × 10 11 vector genomes per mouse. Mice were euthanized at 3 and 9 months of age. In the AAV-treated mice at 3 months of age, GBE enzyme activity was highly elevated in heart, which is consistent with the high copy number of the viral vector genome detected. GBE activity also increased significantly in skeletal muscles and the brain, but not in the liver. The glycogen content was reduced to wild-type levels in muscles and significantly reduced in the liver and brain. At 9 months of age, though GBE activity was only significantly elevated in the heart, glycogen levels were significantly reduced in the liver, brain, and skeletal muscles of the AAV-treated mice. In addition, the AAV treatment resulted in an overall decrease in plasma activities of alanine transaminase, aspartate transaminase, and creatine kinase, and a significant increase in fasting plasma glucose concentration at 9 months of age. This suggests an alleviation of damage and improvement of function in the liver and muscles by the AAV treatment. This study demonstrated a long-term benefit of a systemic injection of an AAV-GBE vector in Gbe1 ys/ys mice.

  16. A patient with common glycogen storage disease type Ib mutations without neutropenia or neutrophil dysfunction

    Martens, DHJ; Kuijpers, TW; Maianski, NA; Rake, JP; Smit, GPA; Visser, G

    We describe a 16-year old boy with glycogen storage disease type Ib, homozygous for the common 1211-1212delCT mutation, who never experienced neutropenia, and did not suffer from frequent infections or inflammatory bowel disease. In addition, neutrophil function tests showed no abnormalities.

  17. Cardiovascular risk factors and diseases precede oral hypoglycaemic therapy in patients with type 2 diabetes mellitus

    Erkens, JA; Herings, RMC; Stolk, RP; Spoelstra, JA; Grobbee, DE; Leufkens, HGM

    Although patients with type 2 diabetes mellitus and cardiovascular disease share common risk factors, the link between these diseases remains largely unexplained. In this case-control study, the earlier use of cardiovascular drugs (before the diagnosis of diabetes) was investigated among cases with

  18. Non alcoholic fatty liver disease in a Nigerian population with type II ...

    Introduction: Worldwide, Non-alcoholic fatty liver disease (NAFLD) has become an important cause of chronic liver disease and cardiovascular morbidity, even more so in subjects with Type II Diabetes Mellitus (T2DM). The aim of this study was to determine the prevalence and risk factors of NAFLD in an African population ...

  19. Female-type fibrocystic disease with papillary hyperplasia in a male breast.

    Robertson, K E; Kazmi, S A; Jordan, L B

    2010-01-01

    Fibrocystic disease is a common benign finding in the female breast and often presents as a palpable mass. It is much less commonly found in the male breast. A case is reported of a young man with female-type fibrocystic disease associated with papillary hyperplasia in the right breast.

  20. Risk factors and treatment of pediatric chronic diseases : Type 1 diabetes, asthma and allergy

    Ahmadizar, F.

    2016-01-01

    Chronic diseases such as type 1 diabetes (T1DM) and asthma are leading causes of morbidity and mortality worldwide. The increase in the number of children with chronic diseases is a major concern. Early detection through improved screening and diagnostic tests, better diagnosis based on updated