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Sample records for type pelizaeus-merzbacher disease

  1. Neurogenetics of Pelizaeus-Merzbacher disease.

    Science.gov (United States)

    Osório, M Joana; Goldman, Steven A

    2018-01-01

    Pelizaeus-Merzbacher disease (PMD) is an X-linked disorder caused by mutations in the PLP1 gene, which encodes the proteolipid protein of myelinating oligodendroglia. PMD exhibits phenotypic variability that reflects its considerable genotypic heterogeneity, but all forms of the disease result in central hypomyelination associated with early neurologic dysfunction, progressive deterioration, and ultimately death. PMD has been classified into three major subtypes, according to the age of presentation: connatal PMD, classic PMD, and transitional PMD, combining features of both connatal and classic forms. Two other less severe phenotypes were subsequently described, including the spastic paraplegia syndrome and PLP1-null disease. These disorders may be associated with duplications, as well as with point, missense, and null mutations within the PLP1 gene. A number of clinically similar Pelizaeus-Merzbacher-like disorders (PMLD) are considered in the differential diagnosis of PMD, the most prominent of which is PMLD-1, caused by misexpression of the GJC2 gene encoding connexin-47. No effective therapy for PMD exists. Yet, as a relatively pure central nervous system hypomyelinating disorder, with limited involvement of the peripheral nervous system and little attendant neuronal pathology, PMD is an attractive therapeutic target for neural stem cell and glial progenitor cell transplantation, efforts at which are now underway in a number of centers internationally. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Magnetic resonance imaging in Pelizaeus-Merzbacher disease

    International Nuclear Information System (INIS)

    Journel, H.; Roussey, M.; Allaire, C.; Le Marec, B.; Gandon, Y.; Carsin, M.

    1987-01-01

    Pelizaeus-Merzbacher's disease is a progressive encephalopathy with demyelination of the cerebral white matter. The diagnosis cannot be made on clinical or biological grounds: pathological investigation is necessary to confirm tigroid demyelination. CT scanning failure to visualize this type of anomaly but detection is now possible with the advent of magnetic resonance imaging (MRI). The authors studied the case of a boy who, at the age of 8 presented with symptoms characeristic of the disease, rotatory nystagmus, progressive encephalopathy, and inherited X-linked recessive traits. Magnetic resonance imaging revealed a high signal in the supra-tentorial white matter and the usual contrast was inverted. The authors believe that MRI can make an important contribution to the diagnosis of the disease. (orig.)

  3. Genetics Home Reference: Pelizaeus-Merzbacher disease

    Science.gov (United States)

    ... condition worsens, affected children develop spasticity leading to joint deformities (contractures) that restrict movement. Individuals with connatal ... Topic: Leukodystrophies Health Topic: Neurologic Diseases Health Topic: Neuromuscular Disorders Genetic and Rare Diseases Information Center (1 ...

  4. Proton MR spectroscopy in connatal Pelizaeus-Merzbacher disease

    International Nuclear Information System (INIS)

    Spalice, A.; Parisi, P.; Iannetti, P.; Popolizio, T.; Scarabino, T.

    2000-01-01

    Background. Pelizaeus-Merzbacher disease (PMD) is a rare dysmyelinating disorder characterised by early pendular nystagmus, often rotatory and muscular hypotonia with subsequent ataxia, spasticity and mental retardation. Various point mutations or duplications in the PLP gene on the X chromosome are responsible for PMD in the majority of patients. Autosomal recessive inheritance, particularly in the connatal form, cannot be excluded. Three different forms of the disease have been identified based on their onset, progression and severity of myelin pathology indicated by MRI features.Objective. To determine if MR spectroscopy is useful in the diagnosis of the connatal form of PMD.Materials and methods. Proton MR spectroscopy was performed on two children with connatal PMD.Results. Our patients showed a markedly decreased peak of Cho. This alteration is well represented by quantitative analysis of the NAA-to-Cho ratio, which is the most important ratio affected. A significant decrease of the Cho-to-Cr ratio is also present. In the connatal form of PMD, global lack of myelination may be relevant, as demonstrated by a significant Cho peak reduction.Conclusions. Proton MR spectroscopy may be of diagnostic value in metabolic and destructive disorders of the brain. A greater number of patients with connatal PMD is needed in order to elucidate the significance of reduction of the Cho peak. (orig.)

  5. Magnetic resonance in Pelizaeus Merzbacher disease: findings in three brothers presenting the connatal variant

    International Nuclear Information System (INIS)

    Saez, J.; Perez, F.; Fuster, M.J.; Marti, L.

    1997-01-01

    Pelizaeus Merzbacher disease is a rare hereditary disorder of the white matter that is characterized by nystagmic eye movements, head shaking and severe psychomotor retardation. We report the MR findings in three brothers presenting the connatal variant of the disease, which is characterized by a diffuse increase in signal intensity on T2-weighted sequences, involving the white matter of the CNS. (Author) 10 refs

  6. Therapy of Pelizaeus-Merzbacher disease in mice by feeding a cholesterol-enriched diet.

    Science.gov (United States)

    Saher, Gesine; Rudolphi, Fabian; Corthals, Kristina; Ruhwedel, Torben; Schmidt, Karl-Friedrich; Löwel, Siegrid; Dibaj, Payam; Barrette, Benoit; Möbius, Wiebke; Nave, Klaus-Armin

    2012-07-01

    Duplication of PLP1 (proteolipid protein gene 1) and the subsequent overexpression of the myelin protein PLP (also known as DM20) in oligodendrocytes is the most frequent cause of Pelizaeus-Merzbacher disease (PMD), a fatal leukodystrophy without therapeutic options. PLP binds cholesterol and is contained within membrane lipid raft microdomains. Cholesterol availability is the rate-limiting factor of central nervous system myelin synthesis. Transgenic mice with extra copies of the Plp1 gene are accurate models of PMD. Dysmyelination followed by demyelination, secondary inflammation and axon damage contribute to the severe motor impairment in these mice. The finding that in Plp1-transgenic oligodendrocytes, PLP and cholesterol accumulate in late endosomes and lysosomes (endo/lysosomes), prompted us to further investigate the role of cholesterol in PMD. Here we show that cholesterol itself promotes normal PLP trafficking and that dietary cholesterol influences PMD pathology. In a preclinical trial, PMD mice were fed a cholesterol-enriched diet. This restored oligodendrocyte numbers and ameliorated intracellular PLP accumulation. Moreover, myelin content increased, inflammation and gliosis were reduced and motor defects improved. Even after onset of clinical symptoms, cholesterol treatment prevented disease progression. Dietary cholesterol did not reduce Plp1 overexpression but facilitated incorporation of PLP into myelin membranes. These findings may have implications for therapeutic interventions in patients with PMD.

  7. A duplicated PLP gene causing Pelizaeus-Merzbacher disease detected by comparative multiplex PCR

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, K.; Sugiyama, N.; Kawanishi, C. [Yokohama City Univ., Yokohama (Japan)] [and others

    1996-07-01

    Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder caused by abnormalities in the proteolipid protein (PLP) gene, which is essential for oligodendrocyte differentiation and CNS myelin formation. Although linkage analysis has shown the homogeneity at the PLP locus in patients with PMD, exonic mutations in the PLP gene have been identified in only 10% - 25% of all cases, which suggests the presence of other genetic aberrations, including gene duplication. In this study, we examined five families with PMD not carrying exonic mutations in PLP gene, using comparative multiplex PCR (CM-PCR) as a semiquantitative assay of gene dosage. PLP gene duplications were identified in four families by CM-PCR and confirmed in three families by densitometric RFLP analysis. Because a homologous myelin protein gene, PMP22, is duplicated in the majority of patients with Charcot-Marie-Tooth 1A, PLP gene overdosage may be an important genetic abnormality in PMD and affect myelin formation. 38 ref., 5 figs., 2 tabs.

  8. Unusual Presentation of Pelizaeus-Merzbacher Disease: Female Patient with Deletion of the Proteolipid Protein 1 Gene

    Directory of Open Access Journals (Sweden)

    Teva Brender

    2015-01-01

    Full Text Available Pelizaeus-Merzbacher disease (PMD is neurodegenerative leukodystrophy caused by dysfunction of the proteolipid protein 1 (PLP1 gene on Xq22, which codes for an essential myelin protein. As an X-linked condition, PMD primarily affects males; however there have been a small number of affected females reported in the medical literature with a variety of different mutations in this gene. No affected females to date have a deletion like our patient. In addition to this, our patient has skewed X chromosome inactivation which adds to her presentation as her unaffected mother also carries the mutation.

  9. A novel PLP1 mutation associated with optic nerve enlargement in two siblings with Pelizaeus-Merzbacher disease: A new MRI finding.

    Science.gov (United States)

    Pavlidou, Efterpi; Ramachandran, Vijaya; Govender, Veronica; Wilson, Clare; Das, Rini; Vlachou, Victoria; Pavlou, Evangelos; Saggar, Anand; Mankad, Kshitij; Kinali, Maria

    2017-03-01

    Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked disorder characterized by hypomyelination of the Central Nervous System due to mutations in the PLP1 gene. Certain mutations of the PLP1 gene correlate with specific clinical phenotypes and neuroimaging findings. We herein report a novel mutation of the PLP1 gene in two siblings with PMD associated with a rare and protean neuroimaging finding of optic nerve enlargement. To the best of our knowledge this is the first time that this novel mutation H133P of PLP1 gene is identified and clinically associated with optic nerve enlargement in PMD patients. Copyright © 2016 The Japanese Society of Child Neurology. All rights reserved.

  10. Genetics Home Reference: Pelizaeus-Merzbacher-like disease type 1

    Science.gov (United States)

    ... scale (dysmetria), tremors that occur mainly during movement (intention tremors), and head and neck tremors (titubation). People ... Available from http://www.ncbi.nlm.nih.gov/books/NBK470716/ Citation on PubMed Orthmann-Murphy JL, Freidin ...

  11. Involvement of ER Stress in Dysmyelination of Pelizaeus-Merzbacher Disease with PLP1 Missense Mutations Shown by iPSC-Derived Oligodendrocytes

    Directory of Open Access Journals (Sweden)

    Yuko Numasawa-Kuroiwa

    2014-05-01

    Full Text Available Pelizaeus-Merzbacher disease (PMD is a form of X-linked leukodystrophy caused by mutations in the proteolipid protein 1 (PLP1 gene. Although PLP1 proteins with missense mutations have been shown to accumulate in the rough endoplasmic reticulum (ER in disease model animals and cell lines transfected with mutant PLP1 genes, the exact pathogenetic mechanism of PMD has not previously been clarified. In this study, we established induced pluripotent stem cells (iPSCs from two PMD patients carrying missense mutation and differentiated them into oligodendrocytes in vitro. In the PMD iPSC-derived oligodendrocytes, mislocalization of mutant PLP1 proteins to the ER and an association between increased susceptibility to ER stress and increased numbers of apoptotic oligodendrocytes were observed. Moreover, electron microscopic analysis demonstrated drastically reduced myelin formation accompanied by abnormal ER morphology. Thus, this study demonstrates the involvement of ER stress in pathogenic dysmyelination in the oligodendrocytes of PMD patients with the PLP1 missense mutation.

  12. In vitro and in vivo plasmalogen replacement evaluations in rhizomelic chrondrodysplasia punctata and Pelizaeus-Merzbacher disease using PPI-1011, an ether lipid plasmalogen precursor

    Directory of Open Access Journals (Sweden)

    Wood Paul L

    2011-10-01

    Full Text Available Abstract Background Childhood peroxisomal disorders and leukodystrophies are devastating diseases characterized by dysfunctional lipid metabolism. Plasmalogens (ether glycerophosphoethanolamine lipids are decreased in these genetic disorders. The biosynthesis of plasmalogens is initiated in peroxisomes but completed in the endoplasmic reticulum. We therefore undertook a study to evaluate the ability of a 3-substituted, 1-alkyl, 2-acyl glyceryl ether lipid (PPI-1011 to replace plasmalogens in rhizomelic chrondrodysplasia punctata type 1 (RCDP1 and rhizomelic chrondrodysplasia punctata type 2 (RCDP2 lymphocytes which possess peroxisomal mutations culminating in deficient plasmalogen synthesis. We also examined plasmalogen synthesis in Pelizaeus-Merzbacher disease (PMD lymphocytes which possess a proteolipid protein-1 (PLP1 missense mutation that results in abnormal PLP1 folding and it's accumulation in the endoplasmic reticulum (ER, the cellular site of the last steps in plasmalogen synthesis. In vivo incorporation of plasmalogen precursor into tissue plasmalogens was also evaluated in the Pex7 mouse model of plasmalogen deficiency. Results In both RCDP1 and RCDP2 lymphocytes, PPI-1011 repleted the target ethanolamine plasmalogen (PlsEtn16:0/22:6 in a concentration dependent manner. In addition, deacylation/reacylation reactions resulted in repletion of PlsEtn 16:0/20:4 in both RCDP1 and RCDP2 lymphocytes, repletion of PlsEtn 16:0/18:1 and PlsEtn 16:0/18:2 in RCDP2 lymphocytes, and partial repletion of PlsEtn 16:0/18:1 and PlsEtn 16:0/18:2 in RCDP1 lymphocytes. In the Pex7 mouse, oral dosing of labeled PPI-1011 demonstrated repletion of tissue levels of the target plasmalogen PlsEtn 16:0/22:6 with phospholipid remodeling also resulting in significant repletion of PlsEtn 16:0/20:4 and PlsEtn 16:0/18:1. Metabolic conversion of PPI-1011 to the target plasmalogen was most active in the liver. Conclusions Our data demonstrate that PPI-1011 is activated

  13. A severe connatal form of Pelizaeus Merzbacher disease in a Czech boy caused by a novel mutation (725C>A, Ala242Glu) at the 'jimpy(msd) codon' in the PLP gene.

    Science.gov (United States)

    Seeman, Pavel; Paderova, Katerina; Benes, Vladimir; Sistermans, Erik A

    2002-02-01

    Pelizaeus Merzbacher disease (PMD) is an X-linked recessive disorder of the central nervous system myelination caused by mutations involving the proteolipid protein gene (PLP). Early nystagmus and developmental delay, progressive pyramidal, cerebellar and dystonic signs as well as white matter changes in brain MRI are typical for PMD. The PLP gene can be affected by two major types of mutations. A duplication of the whole PLP gene is the most common mutation and results usually in the milder classical phenotype, whereas point mutations in PLP gene often result in the rarer and more severe connatal form of PMD. The PLP protein is a higly conserved across species and is identical in human, mouse and rat. We describe a 13-year-old Czech boy with an early and severe developmental delay. His maternal uncle died at the age of one year and was also early and severely psychomotoricly retarded. The patient was the first child of healthy unrelated parents born after an uneventful pregnancy and delivery in 1988. Hyperbilirubinemia and bronchopneumonia and early stridor complicated his neonatal period. Diffuse hypotonia, nystagmus, psychomotor retardation, visual and hearing impairment have been observed in the patient since the age of 6 weeks. White matter abnormalities, cortical and periventricular atrophy were detected by MRI at the age of 6 and 11 years, respectively. Despite these signs and results an accurate clinical diagnosis was unclear until the age of 11 years. Last neurological examination in 1999 showed no nystagmus anymore, but extremely dystrophic limbs, truncal deformation, due to severe scoliosis, tetraplegia with hyperreflexia in C5C7 and areflexia L2S2 and positive pyramidal signs. The boy had no visual or speech contact. DNA tests followed the clinical suspicion for PMD. At first, duplication of PLP gene was excluded by quantitative comparative PCR. Direct sequencing of PLP gene detected a novel mutation in exon 6, a missense mutation 725C-->A (Ala242Glu

  14. Modeling the Mutational and Phenotypic Landscapes of Pelizaeus-Merzbacher Disease with Human iPSC-Derived Oligodendrocytes

    DEFF Research Database (Denmark)

    Nevin, Zachary S.; Factor, Daniel C.; Karl, Robert T.

    2017-01-01

    in humans. Attempts to identify a common pathogenic process underlying PMD have been complicated by an incomplete understanding of PLP1 dysfunction and limited access to primary human oligodendrocytes. To address this, we generated panels of human induced pluripotent stem cells (hiPSCs) and hi...... individual and shared defects in PLP1 mRNA expression and splicing, oligodendrocyte progenitor development, and oligodendrocyte morphology and capacity for myelination. These observations enabled classification of PMD subgroups by cell-intrinsic phenotypes and identified a subset of mutations for targeted...... treatment approaches for subsets of individuals. More broadly, this study demonstrates the versatility of a hiPSC-based panel spanning the mutational heterogeneity within a single disease and establishes a widely applicable platform for genotype-phenotype correlation and drug screening in any human myelin...

  15. Familial Case of Pelizaeus-Merzbacher Disorder Detected by Oligoarray Comparative Genomic Hybridization: Genotype-to-Phenotype Diagnosis

    Directory of Open Access Journals (Sweden)

    Kimia Najafi

    2017-01-01

    Full Text Available Introduction. Pelizaeus-Merzbacher disease (PMD is an X-linked recessive hypomyelinating leukodystrophy characterized by nystagmus, spastic quadriplegia, ataxia, and developmental delay. It is caused by mutation in the PLP1 gene. Case Description. We report a 9-year-old boy referred for oligoarray comparative genomic hybridization (OA-CGH because of intellectual delay, seizures, microcephaly, nystagmus, and spastic paraplegia. Similar clinical findings were reported in his older brother and maternal uncle. Both parents had normal phenotypes. OA-CGH was performed and a 436 Kb duplication was detected and the diagnosis of PMD was made. The mother was carrier of this 436 Kb duplication. Conclusion. Clinical presentation has been accepted as being the mainstay of diagnosis for most conditions. However, recent developments in genetic diagnosis have shown that, in many congenital and sporadic disorders lacking specific phenotypic manifestations, a genotype-to-phenotype approach can be conclusive. In this case, a diagnosis was reached by universal genomic testing, namely, whole genomic array.

  16. UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

    Science.gov (United States)

    2018-03-15

    Adrenoleukodystrophy; Batten Disease; Mucopolysaccharidosis II; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Neimann Pick Disease; Pelizaeus-Merzbacher Disease; Sandhoff Disease; Tay-Sachs Disease; Brain Diseases, Metabolic, Inborn; Alpha-Mannosidosis; Sanfilippo Mucopolysaccharidoses

  17. Genetics Home Reference: CLN8 disease

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    ... about four to six times per year. By middle age, seizures become even less frequent. In addition to ... What is precision medicine? What is newborn screening? New Pages RAB18 deficiency Depression Pelizaeus-Merzbacher-like disease ...

  18. Genetics Home Reference: essential thrombocythemia

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    ... splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia. Nat Genet. 1998 Jan;18(1):49-52. ... deficiency Depression Pelizaeus-Merzbacher-like disease type 1 All New & ...

  19. Hypomyelinating Leukodystrophy due to HSPD1 Mutations

    DEFF Research Database (Denmark)

    Kusk, Maria Schioldan; Damgaard, Bodil; Risom, Lotte

    2016-01-01

    The hypomyelinating leukodystrophies (HMLs) encompass the X-linked Pelizaeus-Merzbacher disease (PMD) caused by PLP1 mutations and known as the classical form of HML as well as Pelizaeus-Merzbacher-like disease (PMLD) (Online Mendelian Inheritance in Man [OMIM] 608804 and OMIM 260600) due to GJC2...

  20. Genetics Home Reference: beta-propeller protein-associated neurodegeneration

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    ... signs and symptoms, affected individuals can live into middle age. Death may result from complications of dementia or ... What is precision medicine? What is newborn screening? New Pages RAB18 deficiency Depression Pelizaeus-Merzbacher-like disease ...

  1. Genetics Home Reference: ADCY5-related dyskinesia

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    ... and severity before stabilizing or even improving in middle age. Anxiety, fatigue, and other stress can temporarily increase ... What is precision medicine? What is newborn screening? New Pages RAB18 deficiency Depression Pelizaeus-Merzbacher-like disease ...

  2. Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders

    Science.gov (United States)

    2017-11-15

    Hurler Syndrome (MPS I); Hurler-Scheie Syndrome; Hunter Syndrome (MPS II); Sanfilippo Syndrome (MPS III); Krabbe Disease (Globoid Leukodystrophy); Metachromatic Leukodystrophy (MLD); Adrenoleukodystrophy (ALD and AMN); Sandhoff Disease; Tay Sachs Disease; Pelizaeus Merzbacher (PMD); Niemann-Pick Disease; Alpha-mannosidosis

  3. Concise Review

    DEFF Research Database (Denmark)

    Osorio, M. Joana; Rowitch, David H.; Tesar, Paul

    2017-01-01

    Pelizaeus-Merzbacher disease (PMD) is an X-linked disorder caused by mutation in the proteolipid protein-1 (PLP1) gene, which encodes the proteolipid protein of myelinating oligodendroglia. PMD exhibits phenotypic variability that reflects its considerable genotypic heterogeneity, but all forms o...

  4. Longitudinal Study of Neurodegenerative Disorders

    Science.gov (United States)

    2018-01-31

    MLD; Krabbe Disease; ALD; MPS I; MPS II; MPS III; Vanishing White Matter Disease; GM3 Gangliosidosis; PKAN; Tay-Sachs Disease; NP Deficiency; Osteopetrosis; Alpha-Mannosidosis; Sandhoff Disease; Niemann-Pick Diseases; MPS IV; Gaucher Disease; GAN; GM1 Gangliosidoses; Morquio Disease; S-Adenosylhomocysteine Hydrolase Deficiency; Batten Disease; Pelizaeus-Merzbacher Disease; Leukodystrophy; Lysosomal Storage Diseases; Purine Nucleoside Phosphorylase Deficiency; Multiple Sulfatase Deficiency Disease

  5. Metabolic disorders with typical alterations in MRI

    International Nuclear Information System (INIS)

    Warmuth-Metz, M.

    2010-01-01

    The classification of metabolic disorders according to the etiology is not practical for neuroradiological purposes because the underlying defect does not uniformly transform into morphological characteristics. Therefore typical MR and clinical features of some easily identifiable metabolic disorders are presented. Canavan disease, Pelizaeus-Merzbacher disease, Alexander disease, X-chromosomal adrenoleukodystrophy and adrenomyeloneuropathy, mitochondrial disorders, such as MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) and Leigh syndrome as well as L-2-hydroxyglutaric aciduria are presented. (orig.) [de

  6. Metabolic disorders with typical alterations in MRI; Stoffwechselstoerungen mit typischen Veraenderungen im MRT

    Energy Technology Data Exchange (ETDEWEB)

    Warmuth-Metz, M. [Klinikum der Universitaet Wuerzburg, Abteilung fuer Neuroradiologie, Wuerzburg (Germany)

    2010-09-15

    The classification of metabolic disorders according to the etiology is not practical for neuroradiological purposes because the underlying defect does not uniformly transform into morphological characteristics. Therefore typical MR and clinical features of some easily identifiable metabolic disorders are presented. Canavan disease, Pelizaeus-Merzbacher disease, Alexander disease, X-chromosomal adrenoleukodystrophy and adrenomyeloneuropathy, mitochondrial disorders, such as MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) and Leigh syndrome as well as L-2-hydroxyglutaric aciduria are presented. (orig.) [German] Die Einteilung von Stoffwechselstoerungen nach ihrer Aetiologie ist fuer den diagnostischen Neuroradiologen nicht sinnvoll, da sich aus der zugrunde liegenden Stoerung keine Rueckschluesse auf die zu erwartende MR-Morphologie ziehen lassen. Deshalb sollen anhand typischer bildmorphologischer Veraenderungen in Zusammenschau mit den jeweiligen klinischen Charakteristika einige leicht einzuordnende Stoffwechselstoerungen dargestellt werden. Es handelt sich um den Morbus Canavan, Morbus Pelizaeus-Merzbacher, Morbus Alexander, die X-chromosomal vererbte Adrenoleukodystrophie und Adrenomyeloneuropathie, die mitochondrialen Stoerungen MELAS (mitochondriale Enzephalomyopathie, Laktazidose und Stroke-like-Episoden) und Leigh-Syndrom sowie die L-2-Hydroxyglutarazidurie. (orig.)

  7. Glycogen Storage Disease Type IV

    DEFF Research Database (Denmark)

    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...

  8. Type I Glycogen Storage Disease

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    ... 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 ...

  9. Le leucodistrofie: aspetti clinici e quadri con Tomografia Computerizzata e con Risonanza Magnetica

    International Nuclear Information System (INIS)

    Magnaldi, S.

    1991-01-01

    Leukodystrophies are inherited white matter diseases due to abnormalities occurring in myelin synthesis and/or maintenance. The most common types of these rare childhood conditions are represented by adrenoleukodystrophy, metachromatic leukodystrophy, Canavan's, Alexander's, Krabbe's, and Pelizaeus-Merzbacher's diseases. Most of them are lethal during childhood, with the exception of the adrenoleukodystrophy-adrenomyeloneuropathy complex, which sometimes, during its early phases, may be cured with a dietary therapy. The aims of this paper are: 1) the description of inheritance factors, pathogenesis, pathological and clinical findings of each of the most frequent childhood leukodystrophies; 2) the description of the most common patterns of these conditions on CT and MR imaging; 3) the evaluation of the diagnostic capabilities of these two imaging techniques and the comparison of their results. Finally, some of the therapies suggested for the mild forms of these conditions are discussed. The evaluation of leukodystrophic patients with CT and MR imaging shows both imaging modalities to have high sensitivity, thanks to the detection of abnormally myelinated areas, which appear hypodense on CT and Hypertense on T2-weighted MR images. Frequently, both imaging modalities exhibit high specificity as well: they allow a differential diagnosis between the different types through the demonstration of their location in the early stages and of their mode of spread. The most typical example is represented by adrenoleukodystrophy, which is the most common type of leukodystrophy: the frequent occipito-parietal onset and the anterior and caudal progression allow a correct diagnosis to be made on CT and MR images in most cases. The comparison between CT and MR findings demonstrates a slight superiority of the latter: multiplanarity and high contrast resolution make MR imaging more sensitive than CT in the detection of the both caudal spread and involvement of optic and acoustic

  10. Connexin: a potential novel target for protecting the central nervous system?

    Directory of Open Access Journals (Sweden)

    Hong-yan Xie

    2015-01-01

    Full Text Available Connexin subunits are proteins that form gap junction channels, and play an important role in communication between adjacent cells. This review article discusses the function of connexins/hemichannels/gap junctions under physiological conditions, and summarizes the findings regarding the role of connexins/hemichannels/gap junctions in the physiological and pathological mechanisms underlying central nervous system diseases such as brain ischemia, traumatic brain and spinal cord injury, epilepsy, brain and spinal cord tumor, migraine, neuroautoimmune disease, Alzheimer′s disease, Parkinson′s disease, X-linked Charcot-Marie-Tooth disease, Pelizaeus-Merzbacher-like disease, spastic paraplegia and maxillofacial dysplasia. Connexins are considered to be a potential novel target for protecting the central nervous system.

  11. Hib Disease (Haemophilus Influenzae Type b)

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    ... 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 ...

  12. Type I Glycogen Storage Disease

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    ... 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 ...

  13. Type I Glycogen Storage Disease

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    ... 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 ...

  14. Types of Neglected Tropical Diseases

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    ... 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 ...

  15. Insulin and Alzheimer disease: type 3 diabetes?

    Directory of Open Access Journals (Sweden)

    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.

  16. Type gaucher disease: radiographic and MRI manifestations

    International Nuclear Information System (INIS)

    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

  17. Genetics Home Reference: glycogen storage disease type VII

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    ... 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 ...

  18. Genetics Home Reference: glycogen storage disease type IV

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    ... 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 ...

  19. Pregnancies in glycogen storage disease type Ia

    NARCIS (Netherlands)

    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

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

    International Nuclear Information System (INIS)

    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.)

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

    Directory of Open Access Journals (Sweden)

    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

  2. Molecular Genetic Analysis of the PLP1 Gene in 38 Families with PLP1-related disorders: Identification and Functional Characterization of 11 Novel PLP1 Mutations

    Directory of Open Access Journals (Sweden)

    Marchiani Valentina

    2011-06-01

    Full Text Available Abstract Background The breadth of the clinical spectrum underlying Pelizaeus-Merzbacher disease and spastic paraplegia type 2 is due to the extensive allelic heterogeneity in the X-linked PLP1 gene encoding myelin proteolipid protein (PLP. PLP1 mutations range from gene duplications of variable size found in 60-70% of patients to intragenic lesions present in 15-20% of patients. Methods Forty-eight male patients from 38 unrelated families with a PLP1-related disorder were studied. All DNA samples were screened for PLP1 gene duplications using real-time PCR. PLP1 gene sequencing analysis was performed on patients negative for the duplication. The mutational status of all 14 potential carrier mothers of the familial PLP1 gene mutation was determined as well as 15/24 potential carrier mothers of the PLP1 duplication. Results and Conclusions PLP1 gene duplications were identified in 24 of the unrelated patients whereas a variety of intragenic PLP1 mutations were found in the remaining 14 patients. Of the 14 different intragenic lesions, 11 were novel; these included one nonsense and 7 missense mutations, a 657-bp deletion, a microdeletion and a microduplication. The functional significance of the novel PLP1 missense mutations, all occurring at evolutionarily conserved residues, was analysed by the MutPred tool whereas their potential effect on splicing was ascertained using the Skippy algorithm and a neural network. Although MutPred predicted that all 7 novel missense mutations would be likely to be deleterious, in silico analysis indicated that four of them (p.Leu146Val, p.Leu159Pro, p.Thr230Ile, p.Ala247Asp might cause exon skipping by altering exonic splicing elements. These predictions were then investigated in vitro for both p.Leu146Val and p.Thr230Ile by means of RNA or minigene studies and were subsequently confirmed in the case of p.Leu146Val. Peripheral neuropathy was noted in four patients harbouring intragenic mutations that altered RNA

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

    Science.gov (United States)

    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.

  4. Peripheral artery disease in type II diabetes

    International Nuclear Information System (INIS)

    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)

  5. HLA Typing and Celiac Disease in Moroccans

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    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.

  6. Celiac disease in type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    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.

  7. Niemann-Pick disease type C

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Coexistence of coeliac disease and type 1 diabetes

    OpenAIRE

    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.

  10. Periodontal disease in type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    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)

  11. Niemann-Pick disease type C

    Directory of Open Access Journals (Sweden)

    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

  12. Radiographic findings in type 3 b Gaucher disease

    International Nuclear Information System (INIS)

    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

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

    NARCIS (Netherlands)

    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

  14. Immune dysfunction in Niemann?Pick disease type C

    OpenAIRE

    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 ...

  15. Very early disease manifestations of macular telangiectasia type 2

    NARCIS (Netherlands)

    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

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

    International Nuclear Information System (INIS)

    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

  17. A probable new type of osteopenic bone disease

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  18. A probable new type of osteopenic bone disease

    International Nuclear Information System (INIS)

    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.)

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

    DEFF Research Database (Denmark)

    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...

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

    Science.gov (United States)

    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.

  1. Basal Cell Carcinoma in Type 2 Segmental Dariers Disease

    International Nuclear Information System (INIS)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    NARCIS (Netherlands)

    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

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

    International Nuclear Information System (INIS)

    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

    NARCIS (Netherlands)

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    LENUS (Irish Health Repository)

    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.

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

    LENUS (Irish Health Repository)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    African Journals Online (AJOL)

    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.

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

    LENUS (Irish Health Repository)

    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.

  13. Charcot-Marie-Tooth disease type 1A

    DEFF Research Database (Denmark)

    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...

  14. Exercise intolerance in Glycogen Storage Disease Type III

    DEFF Research Database (Denmark)

    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...

  15. The spectrum of leukodystrophies in children: Experience at a tertiary care centre from North India

    Directory of Open Access Journals (Sweden)

    Sheffali Gulati

    2016-01-01

    Full Text Available Objective: The objective of this study is to retrospectively collect and then describe the clinico-radiographical profile of confirmed cases of leukodystrophy who presented over a 5-year period to a tertiary care teaching hospital in North India. Materials and Methods: The case records of 80 confirmed cases of leukodystrophy were reviewed and the cases have been described in terms of their clinical presentation and neuroimaging findings. Results: The cases have been grouped into five categories: Hypomyelinating, demyelinating, disorders with vacuolization, cystic, and miscellaneous. The commonest leukodystrophies are megalencephalic leukoencephalopathy with subcortical cysts (MLC, Pelizaeus-Merzbacher disease (PMD, and metachromatic leukodystrophy (MLD. A notable proportion of hypomyelinating disorders were uncharacterized. Conclusions: Leukodystrophies at this point of time have no definite cure. They have a progressively downhill clinical course. Early diagnosis is imperative for appropriate genetic counseling. A simplified approach to diagnose common leukodystrophies has also been provided. It is important to develop a registry, which can provide valuable epidemiological data to prioritize research in this field, which has many unanswered questions.

  16. A microhomology-mediated break-induced replication model for the origin of human copy number variation.

    Directory of Open Access Journals (Sweden)

    P J Hastings

    2009-01-01

    Full Text Available Chromosome structural changes with nonrecurrent endpoints associated with genomic disorders offer windows into the mechanism of origin of copy number variation (CNV. A recent report of nonrecurrent duplications associated with Pelizaeus-Merzbacher disease identified three distinctive characteristics. First, the majority of events can be seen to be complex, showing discontinuous duplications mixed with deletions, inverted duplications, and triplications. Second, junctions at endpoints show microhomology of 2-5 base pairs (bp. Third, endpoints occur near pre-existing low copy repeats (LCRs. Using these observations and evidence from DNA repair in other organisms, we derive a model of microhomology-mediated break-induced replication (MMBIR for the origin of CNV and, ultimately, of LCRs. We propose that breakage of replication forks in stressed cells that are deficient in homologous recombination induces an aberrant repair process with features of break-induced replication (BIR. Under these circumstances, single-strand 3' tails from broken replication forks will anneal with microhomology on any single-stranded DNA nearby, priming low-processivity polymerization with multiple template switches generating complex rearrangements, and eventual re-establishment of processive replication.

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

    Science.gov (United States)

    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.

  18. The clinical management of Type 2 Gaucher disease.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  20. Pulmonary Arterial Hypertension in Glycogen Storage Disease Type I

    Directory of Open Access Journals (Sweden)

    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.

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

    NARCIS (Netherlands)

    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

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

    NARCIS (Netherlands)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Asymptomatic coronary artery disease in Type-2 diabetes

    International Nuclear Information System (INIS)

    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)

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

    Science.gov (United States)

    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.

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

    NARCIS (Netherlands)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    Science.gov (United States)

    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".

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    Science.gov (United States)

    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.

  17. Nondiabetic renal disease in patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    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.

  18. Genetic homogeneity of autoimmune polyglandular disease type I

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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

  20. Egg consumption, cardiovascular diseases and type 2 diabetes

    DEFF Research Database (Denmark)

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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 ...

  3. Toward tailored disease management for type 2 diabetes.

    Science.gov (United States)

    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.

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

    OpenAIRE

    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,...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    International Nuclear Information System (INIS)

    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.)

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  16. Glycogen storage disease type III: modified Atkins diet improves myopathy.

    Science.gov (United States)

    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.

  17. Disease management programs in type 2 diabetes: quality of care.

    Science.gov (United States)

    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.

  18. Increased expression of vascular endothelin type B and angiotensin type 1 receptors in patients with ischemic heart disease

    DEFF Research Database (Denmark)

    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...

  19. Overweight, insulin resistance and type II diabetes in type I Gaucher disease patients in relation to enzyme replacement therapy

    NARCIS (Netherlands)

    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

  20. Detection of type 1 prion protein in variant Creutzfeldt-Jakob disease

    NARCIS (Netherlands)

    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

  1. Geographical Overlapping of Obesity, Heart Disease, and Type 2 Diabetes

    Centers for Disease Control (CDC) Podcasts

    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.

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

    Science.gov (United States)

    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.

  3. Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European Study on Glycogen Storage Disease Type 1

    NARCIS (Netherlands)

    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

  4. 1H MR spectroscopy of the basal ganglia in childhood: a semiquantitative analysis

    International Nuclear Information System (INIS)

    Lam, W.W.M.; Zhao, H.; Berry, G.T.; Kaplan, P.; Gibson, J.; Kaplan, B.S.

    1998-01-01

    Proton MR spectra of the basal ganglia were obtained from 28 patients, 24 male and 14 female, median age 16.3 months (5 weeks to 31 years). They included 17 patients with normal MRI of the basal ganglia without metabolic disturbance (control group) and 11 patients with various metabolic diseases: one case each of high serum sodium and high serum osmolarity, cobalamin C deficiency, Leigh disease, Galloway-Mowat syndrome, Pelizaeus-Merzbacher disease, hemolytic-uremic syndrome and Wilson disease and two cases of Alagille syndrome and methylmalonic acidemia with abnormal MRI of the basal ganglia or blood or urine analysis (abnormal group). The MR spectrum was measured by using STEAM. The MR-visible water content of the region of interest was obtained. Levels of myoinositol, choline, creatine and N -acetylaspartate were measured using a semiquantitative approach, with absolute reference calibration. In the control group, there was a gradual drop of water content over the first year of life; N -acetylaspartate, creatine and myoinositol levels showed no significant change with age, in contrast to the occipital, parietal and cerebellar regions. Choline showed a gradual decrease for the first 2 years of life and then remained fairly constant. In the abnormal group the water content was not significantly different. N -Acetylaspartate was decreased in patients with high serum sodium and high serum osmolarity, cobalamin C deficiency, Leigh disease and one case of methylmalonic acidemia. Decreased creatine was also found in Leigh disease, and decreased choline in Galloway-Mowat syndrome and Wilson disease. Myoinositol was elevated in the patient with abnormally high serum sodium, and decreased in the hemolytic-uremic syndrome. (orig.)

  5. Haemophilus influenzae Type b disease among Amish children in Pennsylvania: reasons for persistent disease.

    Science.gov (United States)

    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.

  6. Retrospective study of diseases and associated pneumonia type ...

    African Journals Online (AJOL)

    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 ...

  7. Retrospective study of diseases and associated pneumonia type ...

    African Journals Online (AJOL)

    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 ...

  8. Validating the Type D personality construct in Chinese patients with coronary heart disease

    DEFF Research Database (Denmark)

    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...

  9. Correlation between the coping behavior and types of attitude to the disease in patients with coronary heart disease

    Directory of Open Access Journals (Sweden)

    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.

  10. Type D personality and health status in cardiovascular disease populations

    DEFF Research Database (Denmark)

    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...

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

    Science.gov (United States)

    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.

  12. Geographical Overlapping of Obesity, Heart Disease, and Type 2 Diabetes

    Centers for Disease Control (CDC) Podcasts

    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.

  13. Genetics Home Reference: glycogen storage disease type I

    Science.gov (United States)

    ... 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 ...

  14. An Acoustic Study of the Relationships among Neurologic Disease, Dysarthria Type, and Severity of Dysarthria

    Science.gov (United States)

    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…

  15. 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.

    Science.gov (United States)

    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.

  16. Screening for Addison's disease in patients with type 1 diabetes mellitus and recurrent hypoglycaemia

    Science.gov (United States)

    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

  17. Screening for Addison's disease in patients with type 1 diabetes mellitus and recurrent hypoglycaemia.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  19. Bone- and bone marrow scintigraphy in Gaucher disease type 1

    International Nuclear Information System (INIS)

    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

  20. Negative affectivity and social inhibition in cardiovascular disease: evaluating type-D personality and its assessment using item response theory.

    Science.gov (United States)

    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.

  1. Extraosseous manifestation of Gaucher's disease type I: MR and histological appearance

    International Nuclear Information System (INIS)

    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.)

  2. Type 1 diabetes mellitus, coeliac disease, and lymphoma: a report of four cases.

    LENUS (Irish Health Repository)

    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.

  3. Compromised quality of life in patients with both Type 1 diabetes mellitus and coeliac disease.

    Science.gov (United States)

    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.

  4. 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

    Directory of Open Access Journals (Sweden)

    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.

  5. Apparent diffusion coefficient vale of the brain in patients with Gaucher's disease type II and type III

    International Nuclear Information System (INIS)

    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.)

  6. [Progressive pulmonary hypertension in a patient with type 1 Gaucher disease].

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  8. MIXED HYALINE VASCULAR AND PLASMA CELL TYPE CASTLEMAN’S DISEASE: REPORT OF A CASE

    Directory of Open Access Journals (Sweden)

    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.

  9. Phenotype/genotype correlations in Gaucher disease type 1: Clinical and therapeutic implications

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. '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

    NARCIS (Netherlands)

    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

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

  13. A patient with common glycogen storage disease type Ib mutations without neutropenia or neutrophil dysfunction

    NARCIS (Netherlands)

    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.

  14. Cardiovascular risk factors and diseases precede oral hypoglycaemic therapy in patients with type 2 diabetes mellitus

    NARCIS (Netherlands)

    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

  15. Non alcoholic fatty liver disease in a Nigerian population with type II ...

    African Journals Online (AJOL)

    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 ...

  16. Female-type fibrocystic disease with papillary hyperplasia in a male breast.

    Science.gov (United States)

    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.

  17. Risk factors and treatment of pediatric chronic diseases : Type 1 diabetes, asthma and allergy

    NARCIS (Netherlands)

    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

  18. The hidden Niemann-Pick type C patient : Clinical niches for a rare inherited metabolic disease

    NARCIS (Netherlands)

    Hendriksz, Christian J.; Anheim, Mathieu; Bauer, Peter; Bonnot, Olivier; Chakrapani, Anupam; Corvol, Jean-Christophe; de Koning, Tom J.; Degtyareva, Anna; Dionisi-Vici, Carlo; Doss, Sarah; Duning, Thomas; Giunti, Paola; Iodice, Rosa; Johnston, Tracy; Kelly, Dierdre; Kluenemann, Hans-Hermann; Lorenzl, Stefan; Padovani, Alessandro; Pocovi, Miguel; Synofzik, Matthis; Terblanche, Alta; Bergh, Florian Then; Topcu, Meral; Tranchant, Christine; Walterfang, Mark; Velten, Christian; Kolb, Stefan A.

    2017-01-01

    Background: Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to

  19. Compromised quality of life in patients with both Type 1 diabetes mellitus and coeliac disease

    NARCIS (Netherlands)

    Bakker, S.; Pouwer, F.; Tushuizen, M.E.; Hoogma, R.P.; Mulder, C.J.; Simsek, S.

    2013-01-01

    Aims 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

  20. Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms

    NARCIS (Netherlands)

    Visser, Jeroen; Rozing, Jan; Sapone, Anna; Lammers, Karen; Fasano, Alessio; Fromm, M; Schulzke, JD

    2009-01-01

    Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on celiac disease (CD), an autoimmune enteropathy, and type I diabetes (TID), a hyperglycosaemia caused by a destructive autoimmune

  1. Shared and Distinct Genetic Variants in Type 1 Diabetes and Celiac Disease

    NARCIS (Netherlands)

    Smyth, Deborah J.; Plagnol, Vincent; Walker, Neil M.; Cooper, Jason D.; Downes, Kate; Yang, Jennie H. M.; Howson, Joanna M. M.; Stevens, Helen; McManus, Ross; Wijmenga, Cisca; Heap, Graham A.; Dubois, Patrick C.; Clayton, David G.; Hunt, Karen A.; van Heel, David A.; Todd, John A.

    2008-01-01

    Background: Two inflammatory disorders, type 1 diabetes and celiac disease, cosegregate in populations, suggesting a common genetic origin. Since both diseases are associated with the HLA class II genes on chromosome 6p21, we tested whether non-HLA loci are shared. Methods: We evaluated the

  2. Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data.

    Directory of Open Access Journals (Sweden)

    Anna Gerasimova

    Full Text Available Genome-wide association studies (GWASs identify single nucleotide polymorphisms (SNPs that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease.

  3. Differences Characteristics Patients Diabetes Mellitus Type 2 with and without Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Nindara Citra Aquarista

    2017-04-01

    Full Text Available Diabetes mellitus is the third highest Non-Communicable Diseases (NCDs, which causes death in Indonesia.The incidence of coronary heart disease in diabetes mellitus is high, 65% of people with diabetes mellitus die due to coronary heart disease and stroke. The purpose of this study is to analyze the differences in the characteristics of Diabetes mellitus type 2 in patients with and without coronary heart disease in Haji General Hospital Surabaya year 2016. This research uses observational analysis with cross sectional study design. The subject of the study is the incidence of diabetes Mellitus type 2 with and without coronary heart disease with undergoing outpatient treatment at Haji General Hospital Surabaya year 2016. The Samples were taken by fixed-disease sampling method with 42 people as the samples. The data analysis uses Chi Square test. The results show for the independent variables that have the most significant difference inHaji General Hospital Surabaya year 2016 is smoking behavior (p = 0.00; PR = 7.85; 95% CI = 2.09 to 29.50 and hypertension (p = 0,002; PR = 3.51; 95% CI = 1.42 to 8.67. In conclusion, the smoking behavior and hypertension can lead to complications of coronary heart disease for patients with type in Diabetes Mellitus type 2 in Haji General Hospital year 2016. It needs awareness to check blood pressure regularly and eliminate the smoking habit as the prevention of complications of coronary heart disease for patients with diabetes mellitus type 2. Keywords: diabetes mellitus type 2, coronary hearth disease.

  4. Plasma glucosylceramide and ceramide in type 1 Gaucher disease patients: correlations with disease severity and response to therapeutic intervention

    NARCIS (Netherlands)

    Groener, J. E. M.; Poorthuis, B. J. H. M.; Kuiper, S.; Hollak, C. E. M.; Aerts, J. M. F. G.

    2008-01-01

    The concentrations of plasma glucosylceramide (GlcCer) and ceramide (Cer) were determined in a cohort of type 1 Gaucher disease patients. In plasma of untreated patients, GlcCer concentrations were on average 3-fold increased (median Gaucher: 17.5 nmol/ml, range: 6.5-45.5 (n=27); median control: 5.9

  5. Metabolic syndrome and incidence of type 2 diabetes in patients with manifest vascular disease

    NARCIS (Netherlands)

    Wassink, A.M.J.; Graaf, van der Y.; Soedamah-Muthu, S.S.; Spiering, W.; Visseren, F.L.J.

    2008-01-01

    Risk reduction in patients with clinically manifest vascular disease focuses on preventing new vascular events and not on prevention of type 2 diabetes. However, given the common pathophysiological pathways involved in the development of atherosclerosis and type 2 diabetes, it is probable that

  6. Effects of Probiotic Yogurt Consumption on Cardiovascular Disease Risk Factors in Subjects with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    F mohammadi

    2015-02-01

    Conclusion: Consumption of probiotic yogurt improved lipid profile and some inflammatory biomarkers in patients with type 2 diabetes. Also, probiotic yogurt caused significant decrease in HbA1c. It is suggested that probiotic yogurt may be used as an adjunct therapy to reduce the cardiovascular disease risk factors in type 2 diabetes mellitus patients

  7. Use of modified cornstarch therapy to extend fasting in glycogen storage disease types Ia and Ib

    NARCIS (Netherlands)

    Correia, Catherine E.; Bhattacharya, Kaustuv; Lee, Philip J.; Shuster, Jonathan J.; Theriaque, Douglas W.; Shankar, Meena N.; Smit, G. Peter A.; Weinstein, David A.

    2008-01-01

    Background: Type I glycogen storage disease (GSD) is caused by a deficiency of glucose-6-phosphatase resulting in severe fasting hypoglycemia. Objective: We compared the efficacy of a new modified starch with the currently used cornstarch therapy in patients with type Ia and Ib GSD. Design: This was

  8. Type VIII collagen is elevated in diseases associated with angiogenesis and vascular remodeling

    DEFF Research Database (Denmark)

    Hansen, N. U. B.; Willumsen, N.; Bülow Sand, Jannie Marie

    2016-01-01

    Objectives Type VIII collagen is involved in angiogenesis and remodeling of arteries. We hypothesized that type VIII collagen was upregulated in diseases associated with vascular remodeling, e.g. pulmonary fibrosis and cancer. In this paper we present the development and validation of a competitive...

  9. Apparent diffusion coefficient vale of the brain in patients with Gaucher's disease type II and type III

    Energy Technology Data Exchange (ETDEWEB)

    Abdel Razek, Ahmed Abdel Khalek; Abd El-Gaber, Nahed [Mansoura Faculty of Medicine, Department of Diagnostic Radiology, Mansoura (Egypt); Abdalla, Ahmed; Fathy, Abeer [Mansoura Faculty of Medicine, Department of Pediatric, Mansoura (Egypt); Azab, Ahmed [Mansoura Faculty of Medicine, Department of Neurology, Mansoura (Egypt); Rahman, Ashraf Abdel [Radiology Unit of Pediatric Hospital, Mansoura (Egypt)

    2009-11-15

    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{sup 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.)

  10. Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II

    NARCIS (Netherlands)

    A.G.A. Bijvoet (Agnes); A.J.J. Reuser (Arnold); H. van Hirtum (Hans); M.A. Kroos (Marian); E.H. van de Kamp; O. Schoneveld; P. Visser (Pim); J.P. Brakenhoff (Just); M. Weggeman (Miranda); E.J.J.M. van Corven (Emiel); A.T. van der Ploeg (Ans)

    1999-01-01

    textabstractPompe's disease or glycogen storage disease type II (GSDII) belongs to the family of inherited lysosomal storage diseases. The underlying deficiency of acid alpha-glucosidase leads in different degrees of severity to glycogen storage in heart, skeletal

  11. Induced Pluripotent Stem Cells for Disease Modeling and Evaluation of Therapeutics for Niemann-Pick Disease Type A.

    Science.gov (United States)

    Long, Yan; Xu, Miao; Li, Rong; Dai, Sheng; Beers, Jeanette; Chen, Guokai; Soheilian, Ferri; Baxa, Ulrich; Wang, Mengqiao; Marugan, Juan J; Muro, Silvia; Li, Zhiyuan; Brady, Roscoe; Zheng, Wei

    2016-12-01

    : Niemann-Pick disease type A (NPA) is a lysosomal storage disease caused by mutations in the SMPD1 gene that encodes acid sphingomyelinase (ASM). Deficiency in ASM function results in lysosomal accumulation of sphingomyelin and neurodegeneration. Currently, there is no effective treatment for NPA. To accelerate drug discovery for treatment of NPA, we generated induced pluripotent stem cells from two patient dermal fibroblast lines and differentiated them into neural stem cells. The NPA neural stem cells exhibit a disease phenotype of lysosomal sphingomyelin accumulation and enlarged lysosomes. By using this disease model, we also evaluated three compounds that reportedly reduced lysosomal lipid accumulation in Niemann-Pick disease type C as well as enzyme replacement therapy with ASM. We found that α-tocopherol, δ-tocopherol, hydroxypropyl-β-cyclodextrin, and ASM reduced sphingomyelin accumulation and enlarged lysosomes in NPA neural stem cells. Therefore, the NPA neural stem cells possess the characteristic NPA disease phenotype that can be ameliorated by tocopherols, cyclodextrin, and ASM. Our results demonstrate the efficacies of cyclodextrin and tocopherols in the NPA cell-based model. Our data also indicate that the NPA neural stem cells can be used as a new cell-based disease model for further study of disease pathophysiology and for high-throughput screening to identify new lead compounds for drug development. Currently, there is no effective treatment for Niemann-Pick disease type A (NPA). To accelerate drug discovery for treatment of NPA, NPA-induced pluripotent stem cells were generated from patient dermal fibroblasts and differentiated into neural stem cells. By using the differentiated NPA neuronal cells as a cell-based disease model system, α-tocopherol, δ-tocopherol, and hydroxypropyl-β-cyclodextrin significantly reduced sphingomyelin accumulation in these NPA neuronal cells. Therefore, this cell-based NPA model can be used for further study of

  12. Prediction of First Cardiovascular Disease Event in Type 1 Diabetes Mellitus: The Steno Type 1 Risk Engine.

    Science.gov (United States)

    Vistisen, Dorte; Andersen, Gregers Stig; Hansen, Christian Stevns; Hulman, Adam; Henriksen, Jan Erik; Bech-Nielsen, Henning; Jørgensen, Marit Eika

    2016-03-15

    Patients with type 1 diabetes mellitus are at increased risk of developing cardiovascular disease (CVD), but they are currently undertreated. There are no risk scores used on a regular basis in clinical practice for assessing the risk of CVD in type 1 diabetes mellitus. From 4306 clinically diagnosed adult patients with type 1 diabetes mellitus, we developed a prediction model for estimating the risk of first fatal or nonfatal CVD event (ischemic heart disease, ischemic stroke, heart failure, and peripheral artery disease). Detailed clinical data including lifestyle factors were linked to event data from validated national registers. The risk prediction model was developed by using a 2-stage approach. First, a nonparametric, data-driven approach was used to identify potentially informative risk factors and interactions (random forest and survival tree analysis). Second, based on results from the first step, Poisson regression analysis was used to derive the final model. The final CVD prediction model was externally validated in a different population of 2119 patients with type 1 diabetes mellitus. During a median follow-up of 6.8 years (interquartile range, 2.9-10.9) a total of 793 (18.4%) patients developed CVD. The final prediction model included age, sex, diabetes duration, systolic blood pressure, low-density lipoprotein cholesterol, hemoglobin A1c, albuminuria, glomerular filtration rate, smoking, and exercise. Discrimination was excellent for a 5-year CVD event with a C-statistic of 0.826 (95% confidence interval, 0.807-0.845) in the derivation data and a C-statistic of 0.803 (95% confidence interval, 0.767-0.839) in the validation data. The Hosmer-Lemeshow test showed good calibration (P>0.05) in both cohorts. This high-performing CVD risk model allows for the implementation of decision rules in a clinical setting. © 2016 American Heart Association, Inc.

  13. Four Gaucher disease type II patients with three novel mutations: a single centre experience from Turkey.

    Science.gov (United States)

    Bulut, Fatma Derya; Kör, Deniz; Şeker-Yılmaz, Berna; Hergüner, Özlem; Ceylaner, Serdar; Özkınay, Ferda; Kılavuz, Sebile; Önenli-Mungan, Neslihan

    2018-04-14

    Gaucher disease is the most common lysosomal storage disorder due to glucosylceramidase enzyme deficiency. There are three subtypes of the disease. Neurological involvement accompanies visceral and haematological findings only in type II and type III Gaucher patients. Type II is the acute progressive neuronopathic form which is the most severe and rare subtype. Clinical findings are recognized prenatally or in the first months of life and followed by death within the first two years of age. Among our 81 Gaucher patients, we identified 4 (4,9%) type II patients in our metabolic centre. This rate is significantly higher than the rate reported in the literature (Gaucher patients with three novel mutations and one perinatal lethal form with generalized ichthyosis which is a very rare disorder. Additionally, we would like to highlight the phenotypic heterogeneity not only between the subtypes, also even in the same type.

  14. Adult onset glycogen storage disease type II (adult onset Pompe disease): report and magnetic resonance images of two cases

    International Nuclear Information System (INIS)

    Del Gaizo, Andrew; Banerjee, Sima; Terk, Michael

    2009-01-01

    Glycogen storage disease type II (GSDII), also referred to as Pompe disease or acid maltase deficiency, is a rare inherited condition caused by a deficiency in acid alpha-glucosidase (GAA) enzyme activity. The condition is often classified by age of presentation, with infantile and late onset variants (Laforet et al. J Neurology 55:1122-8, 2000). Late onset tends to present with progressive proximal muscle weakness and respiratory insufficiency (Winkel et al. J Neurology 252:875-84, 2005). We report two cases of biopsy confirmed adult onset GSDII, along with key Magnetic Resonance (MR) images. (orig.)

  15. Habitual coffee consumption and risk of type 2 diabetes, ischemic heart disease, depression and Alzheimer's disease: a Mendelian randomization study.

    Science.gov (United States)

    Kwok, Man Ki; Leung, Gabriel M; Schooling, C Mary

    2016-11-15

    Observationally, coffee is inversely associated with type 2 diabetes mellitus (T2DM), depression and Alzheimer's disease, but not ischemic heart disease (IHD). Coffee features as possibly protective in the 2015 Dietary Guidelines for Americans. Short-term trials suggest coffee has neutral effect on most glycemic traits, but raises lipids and adiponectin. To clarify we compared T2DM, depression, Alzheimer's disease, and IHD and its risk factors by genetically predicted coffee consumption using two-sample Mendelian randomization applied to large extensively genotyped case-control and cross-sectional studies. Childhood cognition was used as a negative control outcome. Genetically predicted coffee consumption was not associated with T2DM (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.76 to 1.36), depression (0.89, 95% CI 0.66 to 1.21), Alzheimer's disease (1.17, 95% CI 0.96 to 1.43), IHD (0.96, 95% CI 0.80 to 1.14), lipids, glycemic traits, adiposity or adiponectin. Coffee was unrelated to childhood cognition. Consistent with observational studies, coffee was unrelated to IHD, and, as expected, childhood cognition. However, contrary to observational findings, coffee may not have beneficial effects on T2DM, depression or Alzheimer's disease. These findings clarify the role of coffee with relevance to dietary guidelines and suggest interventions to prevent these complex chronic diseases should be sought elsewhere.

  16. Late-Onset Glycogen Storage Disease Type II (Pompe's Disease) with a Novel Mutation: A Malaysian Experience.

    Science.gov (United States)

    Fu Liong, Hiew; Abdul Wahab, Siti Aishah; Yakob, Yusnita; Lock Hock, Ngu; Thong, Wong Kum; Viswanathan, Shanthi

    2014-01-01

    Pompe's disease (acid maltase deficiency, glycogen storage disease type II) is an autosomal recessive disorder caused by a deficiency of lysosomal acid α-1,4-glucosidase, resulting in excessive accumulation of glycogen in the lysosomes and cytoplasm of all tissues, most notably in skeletal muscles. We present a case of adult-onset Pompe's disease with progressive proximal muscles weakness over 5 years and respiratory failure on admission, requiring prolonged mechanical ventilation. Electromyography showed evidence of myopathic process with small amplitudes, polyphasic motor unit action potentials, and presence of pseudomyotonic discharges. Muscle biopsy showed glycogen-containing vacuoles in the muscle fibers consistent with glycogen storage disease. Genetic analysis revealed two compound heterozygous mutations at c.444C>G (p.Tyr148∗) in exon 2 and c.2238G>C (p.Trp746Cys) in exon 16, with the former being a novel mutation. This mutation has not been reported before, to our knowledge. The patient was treated with high protein diet during the admission and subsequently showed good clinical response to enzyme replacement therapy with survival now to the eighth year. Conclusion. In patients with late-onset adult Pompe's disease, careful evaluation and early identification of the disease and its treatment with high protein diet and enzyme replacement therapy improve muscle function and have beneficial impact on long term survival.

  17. Late-Onset Glycogen Storage Disease Type II (Pompe’s Disease with a Novel Mutation: A Malaysian Experience

    Directory of Open Access Journals (Sweden)

    Hiew Fu Liong

    2014-01-01

    Full Text Available Pompe’s disease (acid maltase deficiency, glycogen storage disease type II is an autosomal recessive disorder caused by a deficiency of lysosomal acid α-1,4-glucosidase, resulting in excessive accumulation of glycogen in the lysosomes and cytoplasm of all tissues, most notably in skeletal muscles. We present a case of adult-onset Pompe’s disease with progressive proximal muscles weakness over 5 years and respiratory failure on admission, requiring prolonged mechanical ventilation. Electromyography showed evidence of myopathic process with small amplitudes, polyphasic motor unit action potentials, and presence of pseudomyotonic discharges. Muscle biopsy showed glycogen-containing vacuoles in the muscle fibers consistent with glycogen storage disease. Genetic analysis revealed two compound heterozygous mutations at c.444C>G (p.Tyr148* in exon 2 and c.2238G>C (p.Trp746Cys in exon 16, with the former being a novel mutation. This mutation has not been reported before, to our knowledge. The patient was treated with high protein diet during the admission and subsequently showed good clinical response to enzyme replacement therapy with survival now to the eighth year. Conclusion. In patients with late-onset adult Pompe’s disease, careful evaluation and early identification of the disease and its treatment with high protein diet and enzyme replacement therapy improve muscle function and have beneficial impact on long term survival.

  18. Toward molecular pathogenesis of an autoimmune disease: Refined genetic mapping of autoimmune polyglandular disease type I (APECED)

    Energy Technology Data Exchange (ETDEWEB)

    Aaltonen, J.; Bjoerses, P.; Peltonen, L. [National Public Health Institute, Helsinki (Finland)] [and others

    1994-09-01

    Autoimmune reactions encoupled to many human diseases are still only partially understood. Unravelling the molecular pathogenesis of inherited diseases with a strong autoimmune component in their clinical expression could help to dissect individual components in the molecular background of abnormal immune response. One such genetic disorder is autosomal recessive autoimmune polyglandular disease type I (PGD I), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, MIM 240300). The disease is especially enriched in the genetically isolated population of Finland and we have assigned the APECED locus to human chromosome 21q22.3 in 14 Finnish families by linkage analyses. The best positional lod score of 6.49 was observed with marker D21S49. Based on the history of the Finns, the gene pool of this population clearly demonstrates the consequences of a founder effect and consequent isolation. In the Finnish population, we can take advantage of linkage disequilibrium and allelic association studies to more precisely define the critical DNA region for our disease gene of interest than would be possible by linkage analyses alone. We are now able to define the chromosomal region of interest between two flanking markers locating 1 cM apart. Linkage disequilibrium is observed with three of the markers used in the analyses and this suggests a distance of less than 500 kb to the disease locus, well approachable with molecular cloning techniques. Overlapping YAC and cosmid clones spanning our region of interest will facilitate the cloning of APECED gene in the near future.

  19. Dietary patterns and the risk of obesity, type 2 diabetes mellitus, cardiovascular diseases, asthma, and neurodegenerative diseases.

    Science.gov (United States)

    Medina-Remón, Alexander; Kirwan, Richard; Lamuela-Raventós, Rosa M; Estruch, Ramón

    2018-01-22

    Diet and lifestyle play a significant role in the development chronic diseases; however the full complexity of this relationship is not yet understood. Dietary pattern investigation, which reflects the complexity of dietary intake, has emerged as an alternative and complementary approach for examining the association between diet and chronic diseases. Literature on this association has largely focused on individual nutrients, with conflicting outcomes, but individuals consume a combination of foods from many groups that form dietary patterns. Our objective was to systematically review the current findings on the effects of dietary patterns on chronic diseases. In this review, we describe and discuss the relationships between dietary patterns, such as the Mediterranean, the Dietary Approach to Stop Hypertension, Prudent, Seventh-day Adventists, and Western, with risk of obesity, type-2 diabetes mellitus, cardiovascular diseases, asthma, and neurodegenearive diseases. Evidence is increasing from both observational and clinical studies that plant-based dietary patterns, which are rich in fruits, vegetables, and whole grains, are valuable in preventing various chronic diseases, whereas a diet high in red and processed meat, refined grains and added sugar seems to increase said risk. Dietary pattern analysis might be especially valuable to the development and evaluation of food-based dietary guidelines.

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

    DEFF Research Database (Denmark)

    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...

  1. Cataplexy leading to the diagnosis of Niemann-Pick disease type C.

    Science.gov (United States)

    Smit, Liesbeth S; Lammers, Gert Jan; Catsman-Berrevoets, Coriene E

    2006-07-01

    Cataplexy in childhood is a rare and often misdiagnosed symptom. It is described as a brief episode of bilateral loss of muscle tone with intact consciousness, triggered by a variety of strong emotions and in particular with unexpected laughter. This report presents a 9-year old male with progressive cerebellar and pyramidal symptoms and a cognitive decline since the age of 4. His recently developed "drop attacks" on laughter were recognized as cataplexy and led to the diagnosis of Niemann-Pick type C disease. With biochemical studies this diagnosis, a lysosomal storage disease, was confirmed. With cataplexy narcolepsy, Niemann-Pick type C disease, Norrie disease, Prader-Willi syndrome, and Coffin-Lowry syndrome are associated disorders. Recognition of cataplexy in children with concomitant neurologic symptoms may lead to an early and straight diagnosis of one of these disorders.

  2. Forgiveness and Personality Type among Men and Women Suffering from Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Elham Foroozandeh

    2014-07-01

    Full Text Available Background: Role of personality and some components of behaviors, traits and emotions as effective factors on coronary heart diseases (CHD were presented nearly 50 years ago with the concept of “type A” behavior, a compound of hostility, impatience, competitiveness and dominance. Later studies showed crucial role of other traits and behaviors like anger, introversion, depression and forgiveness. Objective: The aim of this study was to compare personality type and forgiveness in the patients suffering from cardiovascular diseases based on gender. Materials and method: The cross sectional study was designed and sample was collected from men and women referred to cardiologists (within the age range of 23-75 years old from the patients of Shahid Rajaee Heart Hospital of Tehran, Iran from December 2010 to March 2011. Total 87 subjects were selected using random method. The study subjects were given two questionnaires: personality type A (with two factors: TA1, pathologic behaviors of type A personality and TA2, non pathologic behaviors of type A personality and Interpersonal Forgiveness Inventory (IFI, with three subscales namely reestablishment of relationship, control of revenge and realistic perception. Data were analyzed using SPSS software. Results: Mean(±SD age of men was 50.5±11.6 years (n=33 and 55.7±14.4 years in women (n=54. Mean duration of suffering from cardiovascular diseases in men was 7.8 years and in women was 9.10 years. The study found high mean scores of type A pathologic but not non pathologic type A among women compared to men (p<0.038 and no statistically significant differences in forgiveness subscales. Conclusion: The study revealed significant difference between women and men suffering from cardiovascular disease in pathologic type A (TA1 and negative relationship between pathologic type A and forgiveness.

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

    International Nuclear Information System (INIS)

    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

    Energy Technology Data Exchange (ETDEWEB)

    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. Nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus and its association with cardiovascular disease.

    Science.gov (United States)

    Vanjiappan, Sivabal; Hamide, Abdoul; Ananthakrishnan, Ramesh; Periyasamy, Senthilkumar Gandhipuram; Mehalingam, Vadivelan

    2018-01-31

    Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver disease that ranges from hepatic steatosis to non-alcoholic steatohepatitis. Obesity and diabetes mellitus are the prime risk factors for NAFLD. The aim of this study was to find out the prevalence of NAFLD among patients with type 2 diabetes mellitus and to detect the association of NAFLD with cardiovascular disease in them. Prospective observational study. The study was conducted on 300 patients with type 2 diabetes mellitus attending the outpatient department of a tertiary care teaching hospital. All patients underwent hepatic ultrasonography to look for hepatic steatosis. Among the 300 patients, 124 were divided into NAFLD and non-NAFLD groups based on the ultrasound findings. These patients were subjected to electrocardiogram, 2D echocardiogram, carotid intima media thickness (CIMT) measurement and ankle brachial pressure index measurement along with measurement of markers of oxidative stress. Hepatic steatosis was present in 61% of diabetic patients in this study. Cardiovascular disease was not found to be significantly associated in diabetic patients with NAFLD. However, cardiovascular risk factors like CIMT, high sensitivity c-reactive protein (hs-CRP) and malondialdehyde (MDA) were elevated in these patients. hs-CRP and MDA levels were found to be significantly associated with the severity of NAFLD. There is a high prevalence of NAFLD in type 2 diabetic patients. No correlation was detected between the presence of NAFLD and cardiovascular disease in them; although there was an association between cardiovascular risk factors and NAFLD. Copyright © 2018. Published by Elsevier Ltd.

  6. Type a niemann-pick disease. Description of three cases with delayed myelination.

    Science.gov (United States)

    D'Amico, A; Sibilio, M; Caranci, F; Bartiromo, F; Taurisano, R; Balivo, F; Melis, D; Parenti, G; Cirillo, S; Elefante, R; Brunetti, A

    2008-06-03

    We describe three patients with type A Niemann-Pick disease (NPD-A). NPD-A is an autosomal recessive neuronal storage disease classified among the sphingolipidoses, characterized by accumulation of sphingomyelin in various tissues and in the brain. Magnetic Resonance imaging (MRI) of our three patients showed a marked delay of myelination with frontal atrophy. Few descriptions of this MRI pattern of delayed myelination have been published to date.

  7. Impaired Autophagy in the Lipid-Storage Disorder Niemann-Pick Type C1 Disease

    OpenAIRE

    Sarkar, Sovan; Carroll, Bernadette; Buganim, Yosef; Maetzel, Dorothea; Ng, Alex H.M.; Cassady, John P.; Cohen, Malkiel A.; Chakraborty, Souvik; Wang, Haoyi; Spooner, Eric; Ploegh, Hidde; Gsponer, Joerg; Korolchuk, Viktor I.; Jaenisch, Rudolf

    2013-01-01

    Autophagy dysfunction has been implicated in misfolded protein accumulation and cellular toxicity in several diseases. Whether alterations in autophagy also contribute to the pathology of lipid-storage disorders is not clear. Here, we show defective autophagy in Niemann-Pick type C1 (NPC1) disease associated with cholesterol accumulation, where the maturation of autophagosomes is impaired because of defective amphisome formation caused by failure in SNARE machinery, whereas the lysosomal prot...

  8. Hematopoietic stem cell transplantation in Niemann-Pick disease type B monitored by chitotriosidase activity.

    Science.gov (United States)

    Quarello, Paola; Spada, Marco; Porta, Francesco; Vassallo, Elena; Timeus, Fabio; Fagioli, Franca

    2018-02-01

    Here, we report a patient with Niemann-Pick disease type B, with early severe onset of disease and pulmonary involvement, treated with hematopoietic stem cell transplant (HSCT) from a bone marrow matched unrelated donor. We confirm that HSCT is feasible and potentially beneficial for patients with severe phenotype. Noteworthy, we discussed the potential usefulness of the activity of peripheral chitotriosidase for the longitudinal evaluation of HSCT success and effectiveness. © 2017 Wiley Periodicals, Inc.

  9. The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death

    DEFF Research Database (Denmark)

    Almdal, Thomas; Scharling, Henrik; Jensen, Jan Skov

    2004-01-01

    BACKGROUND: Epidemiological studies have reported that patients with type 2 diabetes mellitus (DM) have increased mortality and morbidity from cardiovascular diseases, independent of other risk factors. However, most of these studies have been performed in selected patient groups. The purpose...... of death was increased 1.5 to 2 times. CONCLUSIONS: In persons with type 2 DM, the risk of having an incident myocardial infarction or stroke is increased 2- to 3-fold and the risk of death is increased 2-fold, independent of other known risk factors for cardiovascular diseases....

  10. Adult Niemann-Pick disease type B with myositis ossificans: a case report

    Directory of Open Access Journals (Sweden)

    Russka Shumnalieva

    2016-07-01

    Full Text Available Niemann-Pick Disease (NPD is a rare autosomal recessive lysosomal lipid storage disorder. The disease is caused by gene mutations that affect the metabolism of sphingolipids. The dysfunctions cause sphingomyelin to accumulate in different organs. NPD includes forms with low and high levels of sphingomyelin. We report a case of a 34 year-old man with a family history of NPD type B who presented with hepatosplenomegaly, neurological deficiency, bone abnormalities, and myositis ossificans. The clinical, biochemical, and imaging data confirmed the combined diagnosis of NPD type B with myositis ossificans.

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

    DEFF Research Database (Denmark)

    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...

  12. Karl Jaspers on the disease entity: Kantian ideas and Weberian ideal types.

    Science.gov (United States)

    Walker, Chris

    2014-09-01

    Jaspers' nosology is indebted to Immanuel Kant's theory of knowledge. He drew the distinction of form and content from the Transcendental Analytic of Kant's Critique of Pure Reason. The distinction is universal to all knowledge, including psychopathology. Individual experience is constituted by a form or category of the Understanding to give a determinate or knowable object classified into the generic type of a real disease entity. The application of form and content is limited by the boundaries of experience. Beyond this boundary are wholes whose conception requires Ideas of reason drawn from the Transcendental Dialectic. Wholes are regulated by Ideas of reason to give an object or schema of the Idea collected into ideal types of an ideal typical disease entity. Jaspers drew ideal types from Max Weber's social theory. He anticipated that, as knowledge advanced, ideal typical disease entities would become real disease entities. By 1920, this had been the destiny of general paralysis as knowledge of its neuropathology, serology and microbiology emerged. As he presented the final edition of General Psychopathology in 1946, Jaspers was anticipating the transition of schizophrenia from ideal typical to real disease entity. Almost 70 years later, with knowledge of its aetiology still unclear, schizophrenia remains marooned as an ideal typical disease entity - still awaiting that crucial advance! © The Author(s) 2014.

  13. Deep lateral wall orbital decompression following strabismus surgery in patients with Type II ophthalmic Graves' disease.

    Science.gov (United States)

    Ellis, Michael P; Broxterman, Emily C; Hromas, Alan R; Whittaker, Thomas J; Sokol, Jason A

    2018-01-10

    Surgical management of ophthalmic Graves' disease traditionally involves, in order, orbital decompression, followed by strabismus surgery and eyelid surgery. Nunery et al. previously described two distinct sub-types of patients with ophthalmic Graves' disease; Type I patients exhibit no restrictive myopathy (no diplopia) as opposed to Type II patients who do exhibit restrictive myopathy (diplopia) and are far more likely to develop new-onset worsening diplopia following medial wall and floor decompression. Strabismus surgery involving extra-ocular muscle recession has, in turn, been shown to potentially worsen proptosis. Our experience with Type II patients who have already undergone medial wall and floor decompression and strabismus surgery found, when additional decompression is necessary, deep lateral wall decompression (DLWD) appears to have a low rate of post-operative primary-gaze diplopia. A case series of four Type II ophthalmic Graves' disease patients, all of whom had already undergone decompression and strabismus surgery, and went on to develop worsening proptosis or optic nerve compression necessitating further decompression thereafter. In all cases, patients were treated with DLWD. Institutional Review Board approval was granted by the University of Kansas. None of the four patients treated with this approach developed recurrent primary-gaze diplopia or required strabismus surgery following DLWD. While we still prefer to perform medial wall and floor decompression as the initial treatment for ophthalmic Graves' disease, for proptosis following consecutive strabismus surgery, DLWD appears to be effective with a low rate of recurrent primary-gaze diplopia.

  14. Relationship of adiponectin level with lipid profile in type-2 diabetic men with coronary heart disease

    International Nuclear Information System (INIS)

    Durrani, S.; Jan, M.R.; Shah, J.; Khan, M.A.

    2015-01-01

    Cerebro-vascular disease is a commonest long term complication of type-2 diabetes mellitus. The study was done to determine concentration of serum adiponectin and lipid profile in type-2 diabetic men with coronary heart disease (CHD) in the region of Khyber Pakhtunkhwa (KPK), and to find possible relationship between them. Methods: This was a cross-sectional study comprising of randomly selected thirty six healthy adult males and thirty six type-2 diabetic males with coronary heart disease. Their fasting blood samples were analysed for serum adiponectin, fasting blood glucose, glycosylated haemoglobin and lipid profile which included total cholesterol (T-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). The relationship of adiponectin with other variables in type-2 diabetic men with coronary heart disease was determined with Pearson correlations coefficient (r). Results: Type-2 diabetic males with coronary heart disease when compared to healthy males showed significantly low levels of serum adiponectin (p=<0.001) and HDL-C (p=<0.001) and significantly high level of FBG (p=<0.001), HbA1c (p=<0.001), TC (p=<0.05), TG (p=<0.05) and LDL-C (p=<0.05). Serum adiponectin level showed a significant negative correlation with FBG (r = -0.332; p= 0.04), HbA1c (r = -0.818; p=<0.01) and TG (r = -0.640; p=<0.01) in type-2 diabetic men with coronary heart disease. Adiponectin showed a significant positive association with HDL-C in controls (r = 0.948; p=<0.01) and patients of type-2 diabetes with CHD (r = 0.650; p=<0.01). Conclusion: Serum adiponectin concentration is markedly decreased in patients of type-2 diabetes with coronary heart disease. Hypoadiponectinemia is related with deranged lipid profile, i.e., high TG and low HDL-C levels in type-2 diabetic men with CHD. Moreover, adiponectin is associated positively with HDL-C and negatively with HbA1c and TG levels in the studied population. (author)

  15. Long-term Hyperglycemia Naturally Induces Dental Caries but Not Periodontal Disease in Type 1 and Type 2 Diabetic Rodents.

    Science.gov (United States)

    Nakahara, Yutaka; Ozaki, Kiyokazu; Matsuura, Tetsuro

    2017-11-01

    Periodontal disease (PD) in patients with diabetes is described as the sixth complication of diabetes. We have previously shown that diabetes increases dental caries, and carious inflammation might have a strong effect on the adjacent periodontal tissue in diabetic rodent models. However, the possibility that hyperglycemia may induce PD in diabetic animals could not be completely eliminated. The goal of this study was to confirm the presence of PD in diabetic animal models by preventing carious inflammation with fluoride administration. F344 rats injected with alloxan (type 1 diabetic model) and db/db mice (type 2 diabetic model) were given either tap water alone or tap water containing fluoride. A cariostatic effect of fluoride was evident in the diabetic animals. Meanwhile, fluoride treatment drastically attenuated periodontal inflammation in addition to preventing dental caries. Furthermore, with fluoride treatment, periodontitis was notably nonexistent in the periodontal tissue surrounding the normal molars, whereas the caries-forming process was clearly observed in the teeth that were enveloped with persistent periodontitis, suggesting that enhanced periodontal inflammation might have been derived from the dental caries in the diabetic rodents rather than from the PD. In conclusion, long-term hyperglycemia naturally induces dental caries but not PD in type 1 and type 2 diabetic rodents. © 2017 by the American Diabetes Association.

  16. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease

    DEFF Research Database (Denmark)

    Pfeffer, Marc A; Burdmann, Emmanuel A; Chen, Chao-Yin

    2009-01-01

    BACKGROUND: Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately...... tested. METHODS: In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin...... assigned to darbepoetin alfa and 496 patients assigned to placebo (Pchronic kidney disease...

  17. Osteoprotegerin and coronary artery disease in type 2 diabetic patients with microalbuminuria

    DEFF Research Database (Denmark)

    Reinhard, Henrik; Nybo, Mads; Hansen, Peter R

    2011-01-01

    Plasma osteoprotegerin (P-OPG) is an independent predictor of cardiovascular disease in diabetic and other populations. OPG is a bone-related glycopeptide produced by vascular smooth muscle cells and increased P-OPG may reflect arterial damage. We investigated the correlation between P-OPG and co......-OPG and coronary artery disease (CAD) in asymptomatic type 2 diabetic patients with microalbuminuria.......Plasma osteoprotegerin (P-OPG) is an independent predictor of cardiovascular disease in diabetic and other populations. OPG is a bone-related glycopeptide produced by vascular smooth muscle cells and increased P-OPG may reflect arterial damage. We investigated the correlation between P...

  18. CD64: An Attractive Immunotherapeutic Target for M1-type Macrophage Mediated Chronic Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Olusiji A. Akinrinmade

    2017-09-01

    Full Text Available To date, no curative therapy is available for the treatment of most chronic inflammatory diseases such as atopic dermatitis, rheumatoid arthritis, or autoimmune disorders. Current treatments require a lifetime supply for patients to alleviate clinical symptoms and are unable to stop the course of disease. In contrast, a new series of immunotherapeutic agents targeting the Fc γ receptor I (CD64 have emerged and demonstrated significant clinical potential to actually resolving chronic inflammation driven by M1-type dysregulated macrophages. This subpopulation plays a key role in the initiation and maintenance of a series of chronic diseases. The novel recombinant M1-specific immunotherapeutics offer the prospect of highly effective treatment strategies as they have been shown to selectively eliminate the disease-causing macrophage subpopulations. In this review, we provide a detailed summary of the data generated, together with the advantages and the clinical potential of CD64-based targeted therapies for the treatment of chronic inflammatory diseases.

  19. Winter circulation weather types and hospital admissions for respiratory diseases in Galicia, Spain.

    Science.gov (United States)

    Royé, D; Taboada, J J; Martí, A; Lorenzo, M N

    2016-04-01

    The link between various pathologies and atmospheric conditions has been a constant topic of study over recent decades in many places across the world; knowing more about it enables us to pre-empt the worsening of certain diseases, thereby optimizing medical resources. This study looked specifically at the connections in winter between respiratory diseases and types of atmospheric weather conditions (Circulation Weather Types, CWT) in Galicia, a region in the north-western corner of the Iberian Peninsula. To do this, the study used hospital admission data associated with these pathologies as well as an automatic classification of weather types. The main result obtained was that weather types giving rise to an increase in admissions due to these diseases are those associated with cold, dry weather, such as those in the east and south-east, or anticyclonic types. A second peak was associated with humid, hotter weather, generally linked to south-west weather types. In the future, this result may help to forecast the increase in respiratory pathologies in the region some days in advance.

  20. Winter circulation weather types and hospital admissions for respiratory diseases in Galicia, Spain

    Science.gov (United States)

    Royé, D.; Taboada, J. J.; Martí, A.; Lorenzo, M. N.

    2016-04-01

    The link between various pathologies and atmospheric conditions has been a constant topic of study over recent decades in many places across the world; knowing more about it enables us to pre-empt the worsening of certain diseases, thereby optimizing medical resources. This study looked specifically at the connections in winter between respiratory diseases and types of atmospheric weather conditions (Circulation Weather Types, CWT) in Galicia, a region in the north-western corner of the Iberian Peninsula. To do this, the study used hospital admission data associated with these pathologies as well as an automatic classification of weather types. The main result obtained was that weather types giving rise to an increase in admissions due to these diseases are those associated with cold, dry weather, such as those in the east and south-east, or anticyclonic types. A second peak was associated with humid, hotter weather, generally linked to south-west weather types. In the future, this result may help to forecast the increase in respiratory pathologies in the region some days in advance.

  1. Tc-99m-sestamibi scintigraphy in gaucher disease, type 1

    International Nuclear Information System (INIS)

    Park, Chan H.; Pai, Moon S.; Ha, Man J.; Yoon, S. N.; Kim, S.; Whang, K. H.; Kim, Hyun J.

    1999-01-01

    Gaucher disease is an autosomal recessive disorder characterized by lysosomal glycolipid storage in reticuloendothelial cells due to the deficiency of lysosomal enzyme, acid-glucosidase. Type 1 is one of the three subtypes of Gaucher disease and is manifested by a chronic and progressive involvement of the spleen, liver, bone marrow and other visceral organs. This study was done to see imaging feasibility of bone marrow involvement of Gaucher cells using sestamibi. Five patients with Gaucher disease, type I (M:F=4:1, age range: 9-25) underwent a simultaneous anterior and posterior whole body scan as well as spot views of the lower extremities as needed in 10-20 min following the IV administration of 0.2 mCi/kg of Tc-99m-sestamibi. Control group consisted of 10 patients with osteosarcoma, simple bone cyst, nonossifying fibroma, osteoid osteoma, exostosis and neuroblastoma ( M: F=9:1, age range: 2-20, mean : 12.1) and sestamibi images of the group were obtained as in Gaucher cases. For in vitro evaluation, Gaucher cells were isolated from the splenectomy specimen. The cells were incubated in media containing sestamibi for 10, 29, 30 min. After washing the cells twice with saline, cell labeling was checked by external counting. Control group depicted no appreciable sestamibi uptake in the lower extremities while 5 patients with Gaucher disease, type I revealed variable degrees of sestamibi uptake. It was difficult to assess vertebral activities due to hepatosplenomegaly. Ioslated Gaucher cells took up sestamibi supported by an increasing external counting in proportion to incubation time. There was sestamibi uptake in the lower extremities involved by Gaucher disease, type I, which was distinctly different from the control group. Also in vitro study revealed sestamibi uptake in Gaucher cells. On the basis of these results, we believe, it may be possible to evaluate enzyme replacement therapy in Gaucher disease, type I, utilizing sestamibi scintiscan

  2. Tc-99m-sestamibi scintigraphy in gaucher disease, type 1

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chan H.; Pai, Moon S.; Ha, Man J.; Yoon, S. N.; Kim, S.; Whang, K. H.; Kim, Hyun J. [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)

    1999-07-01

    Gaucher disease is an autosomal recessive disorder characterized by lysosomal glycolipid storage in reticuloendothelial cells due to the deficiency of lysosomal enzyme, acid-glucosidase. Type 1 is one of the three subtypes of Gaucher disease and is manifested by a chronic and progressive involvement of the spleen, liver, bone marrow and other visceral organs. This study was done to see imaging feasibility of bone marrow involvement of Gaucher cells using sestamibi. Five patients with Gaucher disease, type I (M:F=4:1, age range: 9-25) underwent a simultaneous anterior and posterior whole body scan as well as spot views of the lower extremities as needed in 10-20 min following the IV administration of 0.2 mCi/kg of Tc-99m-sestamibi. Control group consisted of 10 patients with osteosarcoma, simple bone cyst, nonossifying fibroma, osteoid osteoma, exostosis and neuroblastoma ( M: F=9:1, age range: 2-20, mean : 12.1) and sestamibi images of the group were obtained as in Gaucher cases. For in vitro evaluation, Gaucher cells were isolated from the splenectomy specimen. The cells were incubated in media containing sestamibi for 10, 29, 30 min. After washing the cells twice with saline, cell labeling was checked by external counting. Control group depicted no appreciable sestamibi uptake in the lower extremities while 5 patients with Gaucher disease, type I revealed variable degrees of sestamibi uptake. It was difficult to assess vertebral activities due to hepatosplenomegaly. Ioslated Gaucher cells took up sestamibi supported by an increasing external counting in proportion to incubation time. There was sestamibi uptake in the lower extremities involved by Gaucher disease, type I, which was distinctly different from the control group. Also in vitro study revealed sestamibi uptake in Gaucher cells. On the basis of these results, we believe, it may be possible to evaluate enzyme replacement therapy in Gaucher disease, type I, utilizing sestamibi scintiscan.

  3. A quantitative comparison of plaque types in Alzheimer's disease and senile dementia of the Lewy body type.

    Science.gov (United States)

    McKenzie, J E; Edwards, R J; Gentleman, S M; Ince, P G; Perry, R H; Royston, M C; Roberts, G W

    1996-01-01

    In a previous study we reported no difference in the overall beta-amyloid protein (beta AP) load between Alzheimer's disease (AD) and senile dementia of the Lewy body type (SDLT). However, it is possible that differences in the morphology of beta AP plaque types exist, analogous to the differences in cytoskeletal pathology found in these two disorders. We have carried out a quantitative image analysis of plaque subtypes in the temporal lobe of AD (n = 8), SDLT (n = 9) and control (n = 11) cases. Measurements of beta AP load and plaque density were consistently higher in AD and SDLT than in controls. When AD and SDLT cases were compared no differences were seen in either the density or relative proportions of classic and diffuse plaques. Based on these results we suggest that the variation in the clinical course of these diseases reflects differences in the cytoskeletal pathology, whereas the final stages of profound dementia common to both disorders is associated with the deposition of beta AP.

  4. Novel insertion mutation in a non-Jewish Caucasian type 1 Gaucher disease patient

    Energy Technology Data Exchange (ETDEWEB)

    Choy, F.Y.M.; Humphries, M.L. [Univ. of Victoria, British Columbia (Canada); Ferreira, P. [Univ. of Alberta, Edmonton (Canada)

    1997-01-20

    Gaucher disease is the most prevalent lysosomal storage disorder. It is autosomal recessive, resulting in lysosomal glucocerebrosidase deficiency. Three clinical forms of Gaucher disease have been described: type 1 (nonneuronopathic), type 2 (acute neuronopathic), and type 3 (subacute neuronopathic). We performed PCR-thermal cycle sequence analysis of glucocerebrosidase genomic DNA and identified a novel mutation in a non-Jewish type 1 Gaucher disease patient. It is a C insertion in exon 3 at cDNA nucleotide position 122 and genomic nucleotide position 1626. This mutation causes a frameshift and, subsequently, four of the five codons immediately downstream of the insertion were changed while the sixth was converted to a stop codon, resulting in premature termination of protein translation. The 122CC insertion abolishes a Cac81 restriction endonuclease cleavage site, allowing a convenient and reliable method for detection using RFLP analysis of PCR-amplified glucocerebrosidase genomic DNA. The mutation in the other Gaucher allele was found to be an A{r_arrow}G substitution at glucocerebrosidase cDNA nucleotide position 1226 that so far has only been reported among type 1 Gaucher disease patients. Since mutation 122CC causes a frameshift and early termination of protein translation, it most likely results in a meaningless transcript and subsequently no residual glucocerebrosidase enzyme activity. We speculate that mutation 122CC may result in a worse prognosis than mutations associated with partial activity. When present in the homozygous form, it could be a lethal allele similar to what has been postulated for the other known insertion mutation, 84GG. Our patient, who is a compound heterozygote 122CC/1226G, has moderately severe type 1 Gaucher disease. Her clinical response to Ceredase{reg_sign} therapy that began 31 months ago has been favorable, though incomplete. 30 refs., 3 figs., 2 tabs.

  5. Dose-response relationships for enzyme replacement therapy with imiglucerase/alglucerase in patients with Gaucher disease type 1

    NARCIS (Netherlands)

    Grabowski, Gregory A.; Kacena, Katherine; Cole, J. Alexander; Hollak, Carla E. M.; Zhang, Lin; Yee, John; Mistry, Pramod K.; Zimran, Ari; Charrow, Joel; vom Dahl, Stephan

    2009-01-01

    Purpose: To determine whether enzyme therapy with imiglucerase/ alglucerase demonstrates dose-response relationships with doses and disease parameters used in routine clinical practice for Gaucher disease type 1 patients. Methods: Analyses included all patients with Gaucher disease type 1 on enzyme

  6. Targeting the Immunogenetic Diseases with the Appropriate HLA Molecular Typing: Critical Appraisal on 2666 Patients Typed in One Single Centre

    Directory of Open Access Journals (Sweden)

    M. Guarene

    2013-01-01

    Full Text Available We compared the immunogenetic data from 2666 patients affected by HLA-related autoimmune diseases with those from 4389 ethnically matched controls (3157 cord blood donors CBD, 1232 adult bone marrow donors BMD, to verify the appropriateness of HLA typing requests received in the past decade. The frequency of HLA-B*27 phenotype was 10.50% in 724 ankylosing spondylitis, 16.80% in 125 uveitis (3.41% BMD, 4.24% CBD, P<0.0001; HLA-B*51 allele was 15.57% in 212 Behçet’s disease (12.91% BMD, 9.88% CBD, P<0.0001; the HLA-DRB1-rheumatoid arthritis (RA shared epitope was 13.72% in 554 RA (10.85% BMD, 13.48% CBD, P=0.016; the carriers of almost one of HLA-DQB1 susceptibility alleles were 84.91% in 795 celiac disease (CD and 59.37% in 256 insulin-dependent diabetes mellitus (IDDM (46.06% in 875 CBD, 42.75% in 662 BMD P<0.0001. Overall, our results show that the HLA marker frequencies were higher in patients than controls, but lower than expected from the literature data (excluding CD and IDDM and demonstrate that, in complex immunogenetic conditions, a substantial number of genetic analyses are redundant and inappropriate, burdening to the public health costs. For this reason, we suggest the Italian Scientific Society of Immunogenetics to establish guidelines to improve the appropriateness of typing requests.

  7. Anaplastic Large-Cell Lymphoma in a Child with Type I Diabetes and Unrecognised Coeliac Disease

    Directory of Open Access Journals (Sweden)

    Jemima Sharp

    2012-01-01

    Full Text Available Screening for coeliac disease is recommended for children from certain risk groups, with implications for diagnostic procedures and dietetic management. The risk of a malignant complication in untreated coeliac disease is not considered high in children. We present the case of a girl with type I diabetes who developed weight loss, fatigue, and inguinal lymphadenopathy. Four years before, when she was asymptomatic, a screening coeliac tTG test was positive, but gluten was not eliminated from her diet. Based on clinical examination, a duodenal biopsy, and an inguinal lymph node biopsy were performed, which confirmed both coeliac disease and an anaplastic large-cell lymphoma. HLA-typing demonstrated that she was homozygous for HLA-DQ8, which is associated with higher risk for celiac disease, more severe gluten sensitivity, and diabetes susceptibility. She responded well to chemotherapy and has been in remission for over 4 years. She remains on a gluten-free diet. This is the first case reporting the association of coeliac disease, type I diabetes, and anaplastic large-cell lymphoma in childhood. The case highlights the malignancy risk in a genetically predisposed individual, and the possible role of a perpetuated immunologic response by prolonged gluten exposure.

  8. HLA Typing and Histopathologic Features of Patients with Celiac Disease-A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Gulay Ceylan

    2014-12-01

    Full Text Available Aim: Celiac disease is the most common defect of nutrition intolerance. There is an increased sensitivity to the glutene. It is inherited multifactorial, because of this, genetic and enviromental factors are important in the evaluation. The existence of specific human leukocyte antigen alleles coding especially DQ2 and DQ8 are important at the diagnosis of celiac disease. In this study, it is aimed to determine human leukocyte antigens allel distribution for celiac disease in patients with chronic diarrhea, abdominal pain and similar symptomes. Material and Method: The prevalance of human leukocyte antigens of 40 patients applied to our laboratory were searched using polimerase chain reaction-sequence specific primer method. Marsh classification of the patients were also performed by a pathologist. Results: We determined human leukocyte antigens in 95% of the patients. The most common antigens were DQA1*0501 and DQB1*0201. The combination of DQA1*0501 and DRB1*04 was the least. According to Marsh classification, Grade 2 Marsh Type 4 hypoplastic was the most common type. Discussion: The human leukocyte antigen typing is helpful for the clinicians at the progression of the celiac disease and at the prediction of the tendency to the disease.

  9. Neurological signs in relation to type of cerebrovascular disease in vascular dementia

    NARCIS (Netherlands)

    Staekenborg, S.S.; van der Flier, W.M.; van Straaten, E.C.W.; Lane, R.; Barkhof, F.; Scheltens, P.

    2008-01-01

    BACKGROUND AND PURPOSE - The aim of this study was to describe the prevalence of a number of neurological signs in a large population of patients with vascular dementia (VaD) and to compare the relative frequency of specific neurological signs dependent on type of cerebrovascular disease. METHODS -

  10. Long-term clinical outcomes in type 1 Gaucher disease following 10 years of imiglucerase treatment

    NARCIS (Netherlands)

    Weinreb, Neal J.; Goldblatt, Jack; Villalobos, Jacobo; Charrow, Joel; Cole, J. Alexander; Kerstenetzky, Marcelo; vom Dahl, Stephan; Hollak, Carla

    2013-01-01

    We studied the effect of long-term alglucerase/imiglucerase (Ceredase®/Cerezyme®, Genzyme, a Sanofi company, Cambridge, MA, USA) treatment on hematological, visceral, and bone manifestations of Gaucher disease type 1 (GD1). The International Collaborative Gaucher Group (ICGG) Gaucher Registry

  11. Social inhibition and emotional distress in patients with coronary artery disease : The type D personality construct

    NARCIS (Netherlands)

    Timmermans, I.A.L.; Versteeg, H.; Duijndam, S.N.C.; Graafmans, C.; Polak, P.; Denollet, J.K.

    2018-01-01

    We examined the validity of the social inhibition component of Type D, its distinctiveness from negative affectivity, and value regarding emotional distress as measured with the DS14 in 173 coronary artery disease patients. In dimensional analysis, social inhibition and negative affectivity emerged

  12. Biotypes and ScM types of isolates of Streptococcus canis from diseased and healthy cats.

    Science.gov (United States)

    Timoney, J F; Velineni, S; Ulrich, B; Blanchard, P

    2017-04-08

    Lancefield group G Streptococcus canis is a component of the normal urogenital and pharyngeal flora of the cat. It is also frequently implicated in epizootics of severe disease in closed cat colonies and animal shelters. Given the importance of S canis as a feline pathogen and relative lack of published information on characteristics potentially associated with virulence, the authors have compared isolates from healthy and diseased cats in New York and California using fermentation profiles (biotype) and ScM sequences. With few exceptions, isolates associated with disease were biotype 1. Four alleles of scm were identified of which type 1 dominated in diseased cats. Type 4 allelic variants were found only in healthy cats and all but one were biotype 2. Type 2 and 3 alleles showed extensive N-terminal variation suggesting a plasminogen-binding site as found on the type 1 allele was absent. Cat antisera to ScM were opsonobactericidal, and these potentially protective antibodies increased during convalescence. British Veterinary Association.

  13. Hand involvement in children with Charcot-Marie-Tooth disease type 1A

    NARCIS (Netherlands)

    Burns, Joshua; Bray, Paula; Cross, Lauren A.; North, Kathryn N.; Ryan, Monique M.; Ouvrier, Robert A.

    2008-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A), a demyelinating neuropathy characterised by progressive length-dependent muscle weakness and atrophy, is thought to affect the foot and leg first followed some time later by hand weakness and dysfunction. We aimed to characterise hand Strength, function

  14. Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease

    NARCIS (Netherlands)

    Song, Ci; Burgess, Stephen; Eicher, John D.; O'Donnell, Christopher J.; Johnson, Andrew D.; Huang, Jie; Sabater-Lleal, Maria; Asselbergs, Folkert W.; Tregouet, David-Alexandre; Shin, So Youn; Ding, Jingzhong; Baumert, Jens; Oudot-Mellakh, Tiphaine; Folkersen, Lasse; Smith, Nicholas L.; Williams, Scott M; Ikram, Mohammad Arfan; Kleber, Marcus E.; Becker, Diane M.; Truong, Vinh; Mychaleckyj, Josyf C.; Tang, Weihong; Yang, Qiong; Sennblad, Bengt; Moore, Jason H; Williams, Frances M.K.; Dehghan, Abbas; Silbernagel, Günther; Schrijvers, Elisabeth M.C.; Smith, Shelly; Karakas, Mahir; Tofler, Geoffrey H.; Silveira, Angela; Navis, Gerjan J.; Lohman, Kurt; Chen, Ming Huei; Peters, Annette; Goel, Anuj; Hopewell, Jemma C.; Chambers, John C.; Saleheen, Danish; Lundmark, Per; Psaty, Bruce M.; Strawbridge, Rona J.; Boehm, Bernhard O.; Carter, Angela M.; Meisinger, Christa; Peden, John F.; Bis, Joshua C.; McKnight, Barbara; Öhrvik, John; Taylor, Kent D.; Franzosi, Maria Grazia; Seedorf, Udo; Collins, Rory; Franco-Cereceda, Anders; Syvänen, Ann-Christine; Goodall, Alison H.; Yanek, Lisa R.; Cushman, Mary; Müller-Nurasyid, Martina; Folsom, Aaron R.; Basu, Saonli; Matijevic, Nena; van Gilst, Wiek H.; Kooner, Jaspal S.; Danesh, John; Clarke, Robert; Meigs, James B; Kathiresan, Sekar; Reilly, Muredach P; Klopp, Norman; Harris, Tamara B.; Winkelmann, Bernhard R.; Grant, Peter J.; Hillege, Hans L.; Watkins, Hugh; Spector, Timothy D; Becker, Lewis C; Tracy, Russell P.; März, Winfried; Uitterlinden, Andre G; Eriksson, Per; Cambien, Francois; Morange, Pierre Emmanuel; Koenig, Wolfgang; Soranzo, Nicole; van der Harst, Pim; Liu, Yongmei; Hamsten, Anders; Ehret, Georg B.; Munroe, Patricia B.; Rice, Kenneth M.; Bochud, Murielle; Chasman, Daniel I.; Smith, Albert V.; Tobin, Martin D; Verwoert, Germaine C; Hwang, Shih-Jen; Pihur, Vasyl; Vollenweider, Peter; O'Reilly, Paul F.; Amin, Najaf; Bragg-Gresham, Jennifer L.; Teumer, Alexander; Glazer, Nicole L.; Launer, Lenore J.; Zhao, Jing Hua; Aulchenko, Yurii S.; Heath, Simon; Sõber, Siim; Parsa, Afshin; Luan, Jian'an; Arora, Pankaj; Zhang, Feng; Lucas, Gavin; Hicks, Andrew A.; Jackson, Anne U.; Tanaka, Toshiko; Wild, Sarah H.; Rudan, Igor; Igl, Wilmar; Milaneschi, Yuri; Parker, Alex N.; Fava, Cristiano; Fox, Ervin R.; Kumari, Meena; Go, Min Jin; Linda Kao, Wen Hong; Sjögren, Marketa; Vinay, D. G.; Alexander, Myriam; Tabara, Yasuharu; Shaw-Hawkins, Sue; Whincup, Peter H.; Shi, Gang; Kuusisto, Johanna; Tayo, Bamidele O.; Seielstad, Mark; Sim, Xueling; Nguyen, Khanh Dung Hoang; Lehtimäki, Terho; Matullo, Giuseppe; Wu, Ying; Gaunt, Tom R.; Onland-Moret, N. Charlotte; Cooper, Matthew N.; Platou, Carl G P; Org, Elin; Hardy, Rebecca; Dahgam, Santosh; Palmen, Jutta; Vitart, Veronique; Braund, Peter S; Kuznetsova, Tatiana; Uiterwaal, Cuno S.P.M.; Adeyemo, Adebowale; Palmas, Walter R.; Campbell, Harry; Ludwig, Barbara; Tomaszewski, Maciej; Tzoulaki, Ioanna; Palmer, Nicholette D.; Aspelund, Thor; Garcia, Melissa; Chang, Yen Pei C.; O'Connell, Jeffrey R.; Steinle, Nanette I.; Grobbee, Diederick E.; Arking, Dan E.; Kardia, Sharon L. R.; Morrison, Alanna C.; Hernandez, Dena G.; Najjar, Samer; McArdle, Wendy L.; Hadley, David; Brown, Morris J; Connell, John M; Hingorani, Aroon D.; Day, Ian N M; Lawlor, Debbie A.; Beilby, John P.; Lawrence, Robert W.; Ongen, Halit; Dreisbach, Albert W; Li, Yali; Young, J. Hunter; Kähönen, Mika; Viikari, Jorma S.; Adair, Linda S.; Lee, Nanette R.; Olden, Matthias; Pattaro, Cristian; Hoffman Bolton, Judith A.; Köttgen, Anna; Bergmann, Sven; Mooser, Vincent; Chaturvedi, Nish; Frayling, Timothy M.; Islam, Muhammad; Jafar, Tazeen H.; Erdmann, Jeanette; Kulkarni, Smita R.; Bornstein, Stefan R.; Grässler, Jürgen; Groop, Leif C.; Voight, Benjamin F; Kettunen, Johannes; Howard, Philip; Taylor, Andrew; Guarrera, Simonetta; Ricceri, Fulvio; Emilsson, Valur; Plump, Andrew; Barroso, Inês; Khaw, Kay Tee; Weder, Alan B.; Hunt, Steven C.; Sun, Yan V.; Bergman, Richard N.; Collins, Francis S.; Bonnycastle, Lori L.; Scott, Laura J; Stringham, Heather M.; Peltonen, Leena; Perola, Markus; Vartiainen, Erkki; Brand, Stefan Martin; Staessen, Jan A.; Wang, Thomas J.; Burton, Paul R.; Artigas, Maria Soler; Dong, Yanbin; Snieder, Harold; Wang, Xiaoling; Zhu, Haidong; Lohman, Kurt; Rudock, Megan E.; Heckbert, Susan R; Wiggins, Kerri L.; Doumatey, Ayo; Shriner, Daniel; Veldre, Gudrun; Viigimaa, Margus; Kinra, Sanjay; Prabhakaran, Dorairaj; Tripathy, Vikal; Langefeld, Carl D.; Rosengren, Annika; Thelle, Dag S.; Corsi, Anna Maria; Singleton, Andrew; Forrester, Terrence; Hilton, Gina; McKenzie, Colin A.; Salako, Tunde; Iwai, Naoharu; Kita, Yoshikuni; Ogihara, Toshio; Ohkubo, Takayoshi; Okamura, Tomonori; Ueshima, Hirotsugu; Umemura, Satoshi; Eyheramendy, Susana; Meitinger, Thomas; Wichmann, H-Erich; Cho, Yoon Shin; Kim, Hyung Lae; Lee, Jong-Young; Scott, James; Sehmi, Joban S.; Zhang, Weihua; Hedblad, Bo; Nilsson, Peter M.; Smith, George Davey; Wong, Andrew; Narisu, Narisu; Stančáková, Alena; Raffel, Leslie J.; Yao, Jie; Schwartz, Stephen M.; Arfan Ikram, M.; Longstreth, W.T. jr.; Mosley, Thomas H; Seshadri, Sudha; Shrine, Nick R.G.; Wain, Louise V.; Morken, Mario A.; Swift, Amy J.; Laitinen, Jaana; Prokopenko, Inga; Zitting, Paavo; Cooper, Jackie A.; Humphries, Steve E.; Rasheed, Asif; Bakker, Stephan J. L.; Janipalli, Charles S.; Mani, K. Radha; Yajnik, Chittaranjan S.; Mattace-Raso, Francesco U.S.; Oostra, Ben A.; Demirkan, Ayse; Isaacs, Aaron; Rivadeneira, Fernando; Lakatta, Edward G; Orru, Marco; Scuteri, Angelo; Ala-Korpela, Mika; Kangas, Antti J.; Lyytikäinen, Leo-Pekka; Soininen, Pasi; Tukiainen, Taru; Würtz, Peter; Ong, Rick Twee Hee; Dörr, Marcus; Kroemer, Heyo K; Völker, Uwe; Völzke, Henry; Galan, Pilar; Hercberg, Serge; Lathrop, Mark; Zelenika, Diana; Deloukas, Panos; Mangino, Massimo; Zhai, Guangju; Meschia, James F.; Nalls, Michael A.; Sharma, Pankaj; Terzic, Janos; Kumar, M. V.Kranthi; Denniff, Matthew; Zukowska-Szczechowska, Ewa; Wagenknecht, Lynne E.; Fowkes, F. Gerald R.; Charchar, Fadi J; Schwarz, Peter E. H.; Hayward, Caroline; Guo, Xiuqing; Rotimi, Charles N.; Bots, Michiel L.; Brand, Eva; Samani, Nilesh J.; Polasek, Ozren; Talmud, Philippa J.; Nyberg, Fredrik; Kuh, Diana; Laan, Maris; Hveem, Kristian; Palmer, Lyle J.; van der Schouw, Yvonne T.; Casas, Juan P.; Mohlke, Karen L.; Vineis, Paolo; Raitakari, Olli T.; Ganesh, Santhi K.; Wong, Tien-Yin; Shyong Tai, E.; Cooper, Richard S.; Laakso, Markku; Rao, Dabeeru C.; Morris, Richard W.; Dominiczak, Anna F.; Kivimaki, Mika; Marmot, Michael G.; Miki, Tetsuro; Chandak, Giriraj R.; Coresh, Josef; Navis, Gerjan J.; Salomaa, Veikko; Han, Bok-Ghee; Zhu, Xiaofeng; Melander, Olle; Ridker, Paul M.; Bandinelli, Stefania; Gyllensten, Ulf B.; Wright, Alan F.; Wilson, James F.; Ferrucci, Luigi; Farrall, Martin; Tuomilehto, Jaakko; Pramstaller, Peter P.; Elosua, Roberto; Sijbrands, Eric J. G.; Altshuler, David; Loos, Ruth J. F.; Gieger, Christian; Meneton, Pierre; Wareham, Nicholas J.; Gudnason, Vilmundur; Rotter, Jerome I.; Rettig, Rainer; Uda, Manuela; Strachan, David P.; Witteman, Jacqueline C M; Hartikainen, Anna-Liisa; Beckmann, Jacques S.; Boerwinkle, Eric; Vasan, Ramachandran S; Boehnke, Michael; Larson, Martin G.; Järvelin, Marjo-Riitta; Abecasis, Gonçalo R.; Chakravarti, Aravinda; Elliott, Paul; Van Duijn, Cornelia M.; Newton-Cheh, Christopher; Levy, Daniel; Caulfield, Mark J.; Johnson, Toby; van der Lugt, Aad; Shuldiner, Alan R.; Hofman, Albert; Kraja, Aldi T.; Uitterlinden, Andre G; Ziegler, Andreas; Newman, Anne B; Schillert, Arne; Oostra, Ben A.; Thorsson, Bolli; Mitchell, Braxton D.; Fox, Caroline S.; White, Charles C.; Ballantyne, Christie; Van Duijn, Cornelia M.; Herrington, David M.; O'Leary, Daniel H.; Siscovick, David S.; Couper, David J; Halperin, Eran; Stoegerer, Eva Maria; Ernst, Florian; Krestin, Gabriel P.; Homuth, Georg; Heiss, Gerardo; Usala, Gianluca; Eiriksdottir, Gudny; Shen, Haiqing; Erich Wichmann, H.; Schmidt, Helena; Borecki, Ingrid B.; Markus, Hugh S.; Witteman, Jacqueline C.; Lüdemann, Jan; Huffman, Jennifer E.; Murabito, Joanne M.; Thiery, Joachim; Seissler, Jochen; Massaro, Joseph M.; Polak, Joseph F.; Cunningham, Julie; North, Kari E.; Petrovic, Katja E; Rice, Kenneth M.; Adrienne Cupples, L.; Bielak, Lawrence F.; Launer, Lenore J.; de Andrade, Mariza; Feitosa, Mary F.; Kavousi, Maryam; Sitzer, Matthias; Oudkerk, Matthijs; Province, Michael A.; Nalls, Michael A.; Franceschini, Nora; Peyser, Patricia A.; Wolf, Philip A.; Zhang, Qunyuan; Wild, Philipp S; Schnabel, Renate B.; D'Agostino, Ralph B.; Chilukoti, Ravi Kumar; Schmidt, Reinhold; Sanna, Serena; Demissie, Serkalem; Sigurdsson, Sigurdur; Blankenberg, Stefan; Bevan, Steve; Elias-Smale, Suzette E.; Zeller, Tanja; Illig, Thomas; Münzel, Thomas; Howard, Timothy D.; Hoffmann, Udo; Schminke, Ulf; Nambi, Vijay; Post, Wendy S.; Rathmann, Wolfgang; Li, Xia; Cheng, Yu Ching

    2017-01-01

    Background--Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association

  15. Aspirin in the prevention of cardiovascular disease in type 2 diabetes

    NARCIS (Netherlands)

    Hovens, Marcel Maria Christiaan

    2010-01-01

    In the first of this thesis, results are summarized of a randomised crossover trial on the effects of aspirin on markers of inflammation, coagulation and number of endothelial progenitor cells in type 2 diabetic patients without cardiovascular disease. In the second part, results of two systematic

  16. Type IIIb glycogen storage disease associated with end-stage cirrhosis and hepatocellular carcinoma

    NARCIS (Netherlands)

    Haagsma, EB; Smit, GPA; NiezenKoning, KE; Gouw, ASH; Meerman, L; Slooff, MJH

    Type III glycogen storage disease (GSD) is a disorder of carbohydrate metabolism caused by a deficiency of debranching enzyme. Different subtypes with different clinical pictures have been recognized. During childhood and early adulthood, the symptoms generally regress, and normal adulthood appears

  17. Development of a Suspicion Index to aid diagnosis of Niemann-Pick disease type C

    NARCIS (Netherlands)

    Wijburg, F. A.; Sedel, F.; Pineda, M.; Hendriksz, C. J.; Fahey, M.; Walterfang, M.; Patterson, M. C.; Wraith, J. E.; Kolb, S. A.

    2012-01-01

    Objectives: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive lysosomal lipid storage disorder that is invariably fatal. NP-C diagnosis can be delayed for years due to heterogeneous presentation; adult-onset NP-C can be particularly difficult to diagnose. We developed a Suspicion

  18. Plasma chitotriosidase and CCL18: Early biochemical surrogate markers in type B Niemann-Pick disease

    NARCIS (Netherlands)

    Brinkman, J.; Wijburg, F. A.; Hollak, C. E.; Groener, J. E.; Verhoek, M.; Scheij, S.; Aten, J.; Boot, R. G.; Aerts, J. M.

    2005-01-01

    Type B Niemann-Pick disease (NPD) is a nonneuronopathic lysosomal storage disorder which is characterized by accumulation of sphingomyelin-laden macrophages. The availability of plasma markers for storage cells may be of great value in facilitating therapeutic decisions. Given the similarity of the

  19. Cardiovascular disease morbidity and mortality in patients with type 1 diabetes mellitus: management strategies

    NARCIS (Netherlands)

    Soedamah-Muthu, S.S.; Stehouwer, C.D.A.

    2005-01-01

    There is an increased risk of cardiovascular disease (CVD) mortality and morbidity in patients with type 1 diabetes mellitus compared with the general population as shown by epidemiologic studies measuring cardiovascular endpoints, as well as by autopsy, angiographic, and coronary calcification

  20. Cardiovascular disease morbidity and mortality in patients with type 1 diabetes mellitus: Management Strategies

    NARCIS (Netherlands)

    Soedamah-Muthu, S.S.; Stehouwer, C.D.A.

    2005-01-01

    There is an increased risk of cardiovascular disease (CVD) mortality and morbidity in patients with type 1 diabetes mellitus compared with the general population as shown by epidemiologic studies measuring cardiovascular endpoints, as well as by autopsy, angiographic, and coronary calcification

  1. A convenient diagnostic function test of peripheral blood neutrophils in glycogen storage disease type Ib

    NARCIS (Netherlands)

    Verhoeven, A.J.; Visser, G; Van Zwieten, R; Gruszczynska, B; Poll-The, DWEET; Smit, GPA

    Neutrophils from patients suffering from glycogen storage disease type To (GSD-Ib) show several defects, one of which is a decreased rate of glucose utilization. In this study, we established experimental conditions to show the stimulation of the neutrophil respiratory burst by extracellular

  2. Genetic Risk Score Modelling for Disease Progression in New-Onset Type 1 Diabetes Patients

    DEFF Research Database (Denmark)

    Brorsson, Caroline A; Nielsen, Lotte B; Andersen, Marie-Louise

    2016-01-01

    Genome-wide association studies (GWAS) have identified over 40 type 1 diabetes risk loci. The clinical impact of these loci on β-cell function during disease progression is unknown. We aimed at testing whether a genetic risk score could predict glycemic control and residual β-cell function in type...... 1 diabetes (T1D). As gene expression may represent an intermediate phenotype between genetic variation and disease, we hypothesized that genes within T1D loci which are expressed in islets and transcriptionally regulated by proinflammatory cytokines would be the best predictors of disease...... constructed a genetic risk score based on the cumulative number of risk alleles carried in children with newly diagnosed T1D. With each additional risk allele carried, HbA1c levels increased significantly within first year after diagnosis. Network and gene ontology (GO) analyses revealed that several...

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

    Science.gov (United States)

    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.

  4. The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into "Old" Diseases.

    Science.gov (United States)

    Harsch, Igor Alexander; Konturek, Peter Christopher

    2018-04-17

    The investigation of the human microbiome is the most rapidly expanding field in biomedicine. Early studies were undertaken to better understand the role of microbiota in carbohydrate digestion and utilization. These processes include polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production. Recent research has demonstrated that the intricate axis between gut microbiota and the host metabolism is much more complex. Gut microbiota—depending on their composition—have disease-promoting effects but can also possess protective properties. This review focuses on disorders of metabolic syndrome, with special regard to obesity as a prequel to type 2 diabetes, type 2 diabetes itself, and type 1 diabetes. In all these conditions, differences in the composition of the gut microbiota in comparison to healthy people have been reported. Mechanisms of the interaction between microbiota and host that have been characterized thus far include an increase in energy harvest, modulation of free fatty acids—especially butyrate—of bile acids, lipopolysaccharides, gamma-aminobutyric acid (GABA), an impact on toll-like receptors, the endocannabinoid system and “metabolic endotoxinemia” as well as “metabolic infection.” This review will also address the influence of already established therapies for metabolic syndrome and diabetes on the microbiota and the present state of attempts to alter the gut microbiota as a therapeutic strategy.

  5. A case of improved hearing with cochlear implantation in Gaucher disease type 1.

    Science.gov (United States)

    Endo, Shiori; Mizuta, Kunihiro; Yamatodani, Takashi; Nakanishi, Hiroshi; Hosokawa, Kumiko; Misawa, Kiyoshi; Hosokawa, Seiji; Mineta, Hiroyuki

    2018-06-01

    Gaucher disease is a lysosomal storage disorder that is caused by congenital defective function of the enzyme glucocerebrosidase. Glucocerebroside that is not hydrolyzed by glucocerebrosidase mainly accumulates in the reticular tissue. We describe a Japanese boy with Gaucher disease type 1 who developed bilateral profound sensorineural hearing loss within approximately 4years. We performed cochlear implantation initially on his right ear and again on his left ear 5 months later. The cochlear implants were successfully utilized with a speech discrimination score of 95% on a Japanese sentence recognition test. There are many reports of central hearing loss in Gaucher disease type 2 or 3. However, to the best of our knowledge, this is the first report of profound inner ear hearing loss with Gaucher disease. It also appears to be the first record of cochlear implantation for Gaucher disease. Cochlear implants may be useful for sensorineural hearing loss in patients with Gaucher disease without neurological symptoms other than hearing loss. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Reporting diet-related health issues through newspapers: portrayal of cardiovascular disease and Type 2 diabetes.

    Science.gov (United States)

    Hellyer, Nicole Elizabeth; Haddock-Fraser, Janet

    2011-02-01

    This study identifies (i) the extent to which newsprint media communicate to their readers the lifestyle factors associated with the development of cardiovascular disease and Type 2 diabetes and (ii) newspaper portrayal of social determinants affecting onset of disease. A content analysis of five leading UK national newspapers and their Sunday equivalents was conducted over a 3-month period between January and March 2008. This study shows that cardiovascular disease had much higher press interest than Type 2 diabetes. 'Middle-market' and 'Quality' papers had higher levels of reporting than the 'Popular' press, but the patterns were more complex when the comprehensiveness of reporting was measured within each article. Social determinants affecting disease onset were poorly reported by newspapers, supporting similar research conducted in other countries. This research identifies that there is potential for newspapers to improve their reporting of lifestyle diseases, by including individual and social determinants of disease onset. Lower social classes who read the popular press receive the lowest frequency of reporting and could benefit most from this information. While the research identifies that newspapers are missing the potential to actively communicate and reinforce government health policy, it recognises that the commercial context of the print media may counter such behaviour.

  7. Chronic Kidney Disease and Associated Cardiovascular Risk Factors in Chinese with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Qing-Lin Lou

    2012-12-01

    Full Text Available BackgroundTo determine the frequency of chronic kidney disease (CKD and its associated risk factors in Chinese type 2 diabetic patients, we conducted a cross-sectional study in Nanjing, China, in the period between January 2008 and December 2009.MethodsPatients with type 2 diabetes under the care by Jiangsu Province Official Hospital, Nanjing, China were invited for assessment. CKD was defined as the presence of albuminuria or estimated glomerular filtration rate <60 mL/min/1.73 m2. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥30 mg/g.ResultsWe recruited 1,521 urban Chinese patients with type 2 diabetes (mean age, 63.9±12.0 years. The frequency of CKD and albuminuria was 31.0% and 28.9%, respectively. After adjusted by age and sex, hypertension, anemia and duration of diabetes were significantly associated with CKD with odds ratio (95% confidence interval being 1.93 (1.28 to 2.93, 1.70 (1.09 to 2.64, and 1.03 (1.00 to 1.06, respectively.ConclusionIn conclusion, CKD was common in the urban Nanjing Chinese with type 2 diabetes. Strategies to prevent or delay progression of kidney disease in diabetes should be carried out at the early disease course of type 2 diabetes.

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

    DEFF Research Database (Denmark)

    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...

  9. Characteristics of coronary artery disease in symptomatic type 2 diabetic patients: evaluation with CT angiography

    Directory of Open Access Journals (Sweden)

    Zhu Zhi-yu

    2010-11-01

    Full Text Available Abstract Background Coronary artery disease (CAD is a common and severe complication of type 2 diabetes mellitus (DM. The aim of this study is to identify the features of CAD in diabetic patients using coronary CT angiography (CTA. Methods From 1 July 2009 to 20 March 2010, 113 consecutive patients (70 men, 43 women; mean age, 68 ± 10 years with type 2 DM were found to have coronary plaques on coronary CTA. Their CTA data were reviewed, and extent, distribution and types of plaques and luminal narrowing were evaluated and compared between different sexes. Results In total, 287 coronary vessels (2.5 ± 1.1 per patient and 470 segments (4.2 ± 2.8 per patient were found to have plaques, respectively. Multi-vessel disease was more common than single vessel disease (p p p p p = 0.855. Extent of CAD, types of plaques and luminal narrowing were not significantly different between male and female diabetic patients. Conclusions Coronary CTA depicted a high plaque burden in patients with type 2 DM. Plaques, which were mainly calcified, were more frequently detected in the proximal segment of the LAD artery, and increased attention should be paid to the significant prevalence of obstructive stenosis. In addition, DM reduced the sex differential in CT findings of CAD.

  10. Episodes of breathlessness: types and patterns - a qualitative study exploring experiences of patients with advanced diseases.

    Science.gov (United States)

    Simon, Steffen T; Higginson, Irene J; Benalia, Hamid; Gysels, Marjolein; Murtagh, Fliss Em; Spicer, James; Bausewein, Claudia

    2013-06-01

    Despite the high prevalence and impact of episodic breathlessness, information about characteristics and patterns is scarce. To explore the experience of patients with advanced disease suffering from episodic breathlessness, in order to describe types and patterns. Qualitative design using in-depth interviews with patients suffering from advanced stages of chronic heart failure, chronic obstructive pulmonary disease, lung cancer or motor neurone disease. As part of the interviews, patients were asked to draw a graph to illustrate typical patterns of breathlessness episodes. Interviews were tape-recorded, transcribed verbatim and analysed using Framework Analysis. The graphs were grouped according to their patterns. Fifty-one participants (15 chronic heart failure, 14 chronic obstructive pulmonary disease, 13 lung cancer and 9 motor neurone disease) were included (mean age 68.2 years, 30 of 51 men, mean Karnofsky 63.1, mean breathlessness intensity 3.2 of 10). Five different types of episodic breathlessness were described: triggered with normal level of breathlessness, triggered with predictable response (always related to trigger level, e.g. slight exertion causes severe breathlessness), triggered with unpredictable response (not related to trigger level), non-triggered attack-like (quick onset, often severe) and wave-like (triggered or non-triggered, gradual onset). Four patterns of episodic breathlessness could be identified based on the graphs with differences regarding onset and recovery of episodes. These did not correspond with the types of breathlessness described before. Patients with advanced disease experience clearly distinguishable types and patterns of episodic breathlessness. The understanding of these will help clinicians to tailor specific management strategies for patients who suffer from episodes of breathlessness.

  11. Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links

    Directory of Open Access Journals (Sweden)

    Salvatore De Rosa

    2018-01-01

    Full Text Available Type 2 diabetes mellitus (DM is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD, which could lead to heart failure through a variety of mechanisms, including myocardial infarction and chronic pressure overload. Pathogenetic mechanisms, mainly linked to hyperglycemia and chronic sustained hyperinsulinemia, include changes in metabolic profiles, intracellular signaling pathways, energy production, redox status, increased susceptibility to ischemia, and extracellular matrix remodeling. The close relationship between type 2 DM and CVD has led to the common soil hypothesis, postulating that both conditions share common genetic and environmental factors influencing this association. However, although the common risk factors of both CVD and type 2 DM, such as obesity, insulin resistance, dyslipidemia, inflammation, and thrombophilia, can be identified in the majority of affected patients, less is known about how these factors influence both conditions, so that efforts are still needed for a more comprehensive understanding of this relationship. The genetic, epigenetic, and environmental backgrounds of both type 2 DM and CVD have been more recently studied and updated. However, the underlying pathogenetic mechanisms have seldom been investigated within the broader shared background, but rather studied in the specific context of type 2 DM or CVD, separately. As the precise pathophysiological links between type 2 DM and CVD are not entirely understood and many aspects still require elucidation, an integrated description of the genetic, epigenetic, and environmental influences involved in the concomitant development of both diseases is of paramount importance to shed new light on the interlinks between type 2 DM and CVD. This review addresses the current knowledge of overlapping genetic and epigenetic aspects in type 2 DM and CVD, including microRNAs and long non-coding RNAs, whose

  12. Iron storage in liver, bone marrow and splenic Gaucheroma reflects residual disease in type 1 Gaucher disease patients on treatment.

    Science.gov (United States)

    Regenboog, Martine; Bohte, Anneloes E; Akkerman, Erik M; Stoker, Jaap; Hollak, Carla E M

    2017-11-01

    Gaucher disease (GD) is a lysosomal storage disorder characterized by the storage of glycosphingolipids in macrophages. Despite effective therapy, residual disease is present in varying degrees and may be associated with late complications, such as persistent bone or liver disease and increased cancer risk. Gaucher macrophages are capable of storing iron and locations of residual disease may thus be detectable with iron imaging. Forty type 1 GD (GD1) patients and 40 matched healthy controls were examined using a whole-body magnetic resonance imaging protocol consisting of standard sequences, allowing analysis of iron content per organ, expressed as R2* (Hz). Median R2* values were significantly elevated in GD1 patients as compared to healthy controls in liver [41 Hz (range 29-165) vs. 38 Hz (range 28-53), P Gaucher lesions known as Gaucheroma were found to have increased R2* values. R2* values of liver, spleen and vertebral bone marrow strongly correlated with serum ferritin levels. GD1 patients with persistent hyperferritinaemia demonstrate increased iron levels in liver and bone marrow, which may carry a risk for liver fibrosis and cancer. © 2017 John Wiley & Sons Ltd.

  13. Incidence of invasive Haemophilus influenzae type b disease in Italian children

    International Nuclear Information System (INIS)

    Tozzi, Alberto E.; Salmaso, Stefania; Atti, Marta L. Ciofi degli; Panei, Pietro; Anemona, Alessandra; Scuderi, Gabriella; Wassilak, Steven G.F.

    1997-01-01

    To estimate the incidence of Haemophilus influenzae type b (Hib) invasive disease in Italian infants we performed a prospective study in a cohort of newborns enrolled for a randomized trial on safety and efficacy of three pertussis vaccines and followed for onset of serious disease or pertussis. The overall cumulative incidence observed in 15,601 children was 51.3/100,000 for all invasive Hib infections and 38.4/100,000 for Hib meningitis, over 27 months of observation. The incidence density of all invasive Hib diseases was 28.7/100,000 person-years, while meningitis occurred with an incidence of 21.5/100,000 person-years. Among the eight cases detected, six were meningitis, one sepsis, and one cellulitis. The child with sepsis died. The incidence and epidemiology of invasive Hib disease in Italy are comparable to those reported from other European countries. Cost-benefit analyses are needed for planning Italian vaccination policy

  14. Gaucher disease types 1 and 3: Phenotypic characterization of large populations from the ICGG Gaucher Registry.

    Science.gov (United States)

    Grabowski, Gregory A; Zimran, Ari; Ida, Hiroyuki

    2015-07-01

    Study of the natural history of Gaucher disease has revealed marked phenotypic variation. Correlations to genotypes could provide insight into individual susceptibility to varying disease severity, which may impact whole-life medical care, reproductive decisions, and therapeutic choices for affected families. Importantly, pre-symptomatic or prospective interventions or the use of therapies with significant risk require accurate risk-benefit analyses based on the prognosis for individual patients. The body of international data held within the International Collaborative Gaucher Group (ICGG) Gaucher Registry provides an unprecedented opportunity to characterize the phenotypes of Gaucher disease types 1 and 3 and to appreciate demographic and ethnic factors that may influence phenotypes. The diversity of GBA gene mutations from patients with Gaucher disease represented in the ICGG Gaucher Registry database and in the literature provides the basis for initial genotype/phenotype correlations, the outcomes of which are summarized here. © 2015 Wiley Periodicals, Inc.

  15. Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases

    DEFF Research Database (Denmark)

    Gusev, Alexander; Lee, S Hong; Trynka, Gosia

    2014-01-01

    Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common...... diseases to partition the heritability explained by genotyped SNPs (hg(2)) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach...... partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of hg(2) from imputed SNPs (5.1× enrichment...

  16. Perceptions of risk of coronary heart disease among people living with type 2 diabetes mellitus.

    Science.gov (United States)

    Ammouri, Ali Ahmad; Abu Raddaha, Ahmad H; Natarajan, Jansi; D'Souza, Melba Sheila

    2018-02-01

    Our aim is to assess perception of risk of developing coronary heart disease and to examine its associations with individuals' characteristics and health behaviours among Omani people with type 2 diabetes mellitus (T2DM). Evaluating perceptions of being at risk of developing a disease may give insight into health promotion behaviours. People with diabetes are at high risk of coronary heart disease. The management of diabetes mellitus should include prevention and control of coronary heart disease. A cross-sectional correlational study was conducted. A convenience sample of 160 adults with T2DM was invited to participate in this study between November 2014 and March 2015. Descriptive and regression analyses were performed to examine associations between study variables. Perception of risk of developing coronary heart disease was significantly associated with low educational level (β = 0.191, P diabetes mellitus (β = 0.200, P healthy diet more frequently. Teaching people with T2DM about the risk of developing coronary heart disease is essential as it could motivate them to perform health promotion behaviours, which may assist in controlling and reducing coronary heart disease. © 2017 John Wiley & Sons Australia, Ltd.

  17. Periodontal disease and type I diabetes mellitus: Associations with glycemic control and complications

    Directory of Open Access Journals (Sweden)

    Ajita Meenawat

    2013-01-01

    Full Text Available Objective: The aim of the study was to evaluate periodontal health status in patients diagnosed with type 1 diabetes mellitus (DM1 and to establish a correlation between metabolic control and periodontal health status. Materials and Methods: Periodontal health parameters namely plaque index (PI, gingival index (GI, probing pocket depth (PPD and clinical attachment loss (CAL were recorded in 28 patients diagnosed with type 1 diabetes mellitus (DM1 and 20 healthy controls. Diabetes history was recorded based on the information provided by the physician and it included date of diagnosis, duration, age of diagnosis, latest values of glycosylated haemoglobin and existing diabetic complications. Statistical analysis was performed to evaluate the relationship between periodontal parameters and degree of metabolic control, the duration of the disease and the appearance of complications. Results: The periodontal health in the diabetic group was compromised and they had greater bleeding index (P < 0.001, probing pocket depth (P < 0.001 and clinical attachment level (P = 0.001. Patients diagnosed for diabetes for shorter duration of time (4-7 years showed bleeding index-disease severity correlation to be 1.760 ΁ 0.434. Conclusion: Periodontal disease was more evident in type 1 diabetes mellitus patients and periodontal inflammation is greatly increased in subjects with longer disease course, poor metabolic control and diabetic complications.

  18. Type two innate lymphoid cells; the Janus cells in health and disease

    Science.gov (United States)

    Maazi, Hadi; Akbari, Omid

    2017-01-01

    Summary Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2 and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by costimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. PMID:28658553

  19. Type two innate lymphoid cells: the Janus cells in health and disease.

    Science.gov (United States)

    Maazi, Hadi; Akbari, Omid

    2017-07-01

    Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2, and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity, and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by co-stimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. McArdle disease does not affect skeletal muscle fibre type profiles in humans

    Directory of Open Access Journals (Sweden)

    Tertius Abraham Kohn

    2014-11-01

    Full Text Available Patients suffering from glycogen storage disease V (McArdle disease were shown to have higher surface electrical activity in their skeletal muscles when exercising at the same intensity as their healthy counterparts, indicating more muscle fibre recruitment. To explain this phenomenon, this study investigated whether muscle fibre type is shifted towards a predominance in type I fibres as a consequence of the disease. Muscle biopsies from the Biceps brachii (BB (n = 9 or Vastus lateralis (VL (n = 8 were collected over a 13-year period from male and female patients diagnosed with McArdle disease, analysed for myosin heavy chain (MHC isoform content using SDS-PAGE, and compared to healthy controls (BB: n = 3; VL: n = 10. All three isoforms were expressed and no difference in isoform expression in VL was found between the McArdle patients and healthy controls (MHC I: 33±19% vs. 43±7%; MHC IIa: 52±9% vs. 40±7%; MHC IIx: 15±18% vs. 17±9%. Similarly, the BB isoform content was also not different between the two groups (MHC I: 33±14% vs. 30±11%; MHC IIa: 46±17% vs. 39±5%; MHC IIx: 21±13% vs. 31±14%. In conclusion, fibre type distribution does not seem to explain the higher surface EMG in McArdle patients. Future studies need to investigate muscle fibre size and contractility of McArdle patients.

  1. Eliglustat tartrate for the treatment of adults with type 1 Gaucher disease

    Directory of Open Access Journals (Sweden)

    Bennett LL

    2015-08-01

    Full Text Available Lunawati L Bennett, Kelsey TurcotteSchool of Pharmacy, Union University, Jackson, TN, USA Abstract: The purpose of this article is to review eliglustat tartrate, a substrate reduction therapy, for the treatment of Gaucher disease type 1 (GD1. GD is an rare inborn error of metabolism caused by accumulation of lipid substrates such as glucosylceramide within the monocyte-macrophage system that affects the body by causing enlargement of the spleen and liver, destruction of bone, and abnormalities of the lungs and blood, such as anemia, thrombocytopenia, and leukopenia. GD is classified into three types: GD1, a chronic and non-neuronopathic disease accounting for 95% of GD cases; and types 2 and 3 (GD2 GD3 which are more progressive diseases with no approved drugs available at this time. Treatment options for GD1 include enzyme replacement therapy and substrate reduction therapy. Eliglustat works by inhibiting UDP-glucosylceramide synthase, the first enzyme that catalyzes the biosynthesis of glycosphingolipids, thus reducing the load of glucosylceramide influx into the lysosome. Eliglustat was approved by the US Food and Drug Administration after three Phase I, two Phase II, and two Phase III clinical trials. The dose of eliglustat is 84 mg twice a day or once daily depending on the cytochrome P450 2D6 genotype of the patient. Keywords: Gaucher disease, glucocerebrosidase, glucosylceramide synthase, eliglustat tartrate, substrate reduction therapy

  2. Relationships between Diet, Alcohol Preference, and Heart Disease and Type 2 Diabetes among Americans.

    Directory of Open Access Journals (Sweden)

    Michael K Adjemian

    Full Text Available Although excessive alcohol consumption is a recognized cause of morbidity and mortality, many studies have linked moderate alcohol consumption to improved cardiovascular health and a lower risk of Type 2 Diabetes (T2D. Self-reported alcohol and diet data used to generate these results suffer from measurement error due to recall bias. We estimate the effects of diet, alcohol, and lifestyle choices on the prevalence and incidence of cardiovascular disease and T2D among U.S. adults using a nationally representative cohort of households with scanner data representing their food-at-home, alcohol, and tobacco purchases from 2007-2010, and self-reported health surveys for the same study participants from 2010-2012. Multivariate regression models were used to identify significant associations among purchase data and lifestyle/demographic factors with disease prevalence in 2010, and with incidence of new disease from 2011-2012. After controlling for important confounders, respondents who purchased moderate levels of wine were 25% less likely than non-drinkers to report heart disease in 2010. However, no alcohol-related expenditure variables significantly affected the likelihood of reporting incident heart disease from 2011-2012. In contrast, many types of alcohol-related purchases were associated with a lower prevalence of T2D, and respondents who purchased the greatest volumes of wine or beer--but not liquor--were less likely to report being diagnosed with T2D in 2011-2012 than non-drinkers.

  3. Periodontal disease in children and adolescents with type 1 diabetes in Serbia.

    Science.gov (United States)

    Dakovic, Dragana; Pavlovic, Milos D

    2008-06-01

    The purpose of this study was to evaluate periodontal health in young patients with type 1 diabetes mellitus in Serbia. Periodontal disease was clinically assessed and compared in 187 children and adolescents (6 to 18 years of age) with type 1 diabetes mellitus and 178 control subjects without diabetes. Children and adolescents with type 1 diabetes mellitus had significantly more plaque, gingival inflammation, and periodontal destruction than control subjects. The main risk factors for periodontitis were diabetes (odds ratio [OR] = 2.78; 95% confidence interval [CI]: 1.42 to 5.44), bleeding/plaque ratio (OR = 1.25; 95% CI: 1.06 to 1.48), and age (OR = 1.10; 95% CI: 1.01 to 1.21). In case subjects, the number of teeth affected by periodontal destruction was associated with mean hemoglobin A1c (regression coefficient 0.17; P = 0.026), duration of diabetes (regression coefficient 0.19; P = 0.021), and bleeding/plaque ratio (regression coefficient 0.17; P = 0.021). Compared to children and adolescents without diabetes, periodontal disease is more prevalent and widespread in children and adolescents with type 1 diabetes mellitus and depends on the duration of disease, metabolic control, and the severity of gingival inflammation. Gingival inflammation in young patients with diabetes is more evident and more often results in periodontal destruction.

  4. Adult onset Niemann-Pick type C disease: A clinical, neuroimaging and molecular genetic study.

    Science.gov (United States)

    Battisti, Carla; Tarugi, Patrizla; Dotti, Maria Teresa; De Stefano, Nicola; Vattimo, Angelo; Chierichetti, Francesea; Calandra, Sebastiano; Federico, Antonio

    2003-11-01

    We report on a patient with adult-onset Niemann-Pick type C (NPC) disease, carrying the mutations P1007 and I1061T in the NPC1 gene, presenting with marked psychiatric changes followed by dystonia and cognitive impairment. Filipin staining, single photon emission computed tomography perfusional, positron emission tomography metabolic, conventional magnetic resonance imaging, and magnetic resonance spectroscopy findings suggested a pathophysiological correlation with phenotype expression. This case expands the clinical and genetic spectrum of the rare adult-onset NPC disease phenotype.

  5. Cross-talk between amyloidogenic proteins in type-2 diabetes and Parkinson’s disease

    OpenAIRE

    Horvath, Istvan; Wittung-Stafshede, Pernilla

    2016-01-01

    Protein assembly into ordered so-called amyloid fibers is a process that promotes several neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease (PD). Also type-2 diabetes (T2D) is a disease involving amyloid formation, although it occurs in the pancreas. Since the protein that forms amyloids in PD, α-synuclein (aS), is also expressed in the pancreas, we investigated whether it could affect aggregation of the peptide involved in T2D, and vice versa. Using in vitro methods an...

  6. Evaluation of central nervous system in patients with glycogen storage disease type 1a.

    Science.gov (United States)

    Aydemir, Yusuf; Gürakan, Figen; Saltık Temizel, İnci Nur; Demir, Hülya; Oğuz, Kader Karlı; Yalnızoğlu, Dilek; Topçu, Meral; Özen, Hasan; Yüce, Aysel

    2016-01-01

    We aimed to evaluate structure and functions of central nervous system (CNS) in children with glycogen storage disease (GSD) type 1a. Neurological examination, psychometric tests, electroencephalography (EEG), magnetic resonance imaging (MRI), visual evoked potentials (VEP) and brainstem auditory evoked potentials (BAEP) were performed. The results were compared between patients with good and poor metabolic control and healthy children. Twenty-three patients with GSD type 1a were studied. Twelve patients were in poor metabolic control group and 11 patients in good metabolic control group. Five patients had intellectual disability, 10 had EEG abnormalities, seven had abnormal VEP and two had abnormal BAEP results. MRI was abnormal in five patients. There was significant correlation between the number of hypoglycemic attacks and MRI abnormalities. Central nervous system may be affected in GSD type 1a even in patients with normal neurologic examination. Accumulation of abnormal results in patients with poor metabolic control supports the importance of metabolic control in GSD type 1a.

  7. Prevalence of cardiovascular disease and evaluation of standard of care in type 2 diabetes

    DEFF Research Database (Denmark)

    Rungby, Jorgen; Schou, Morten; Warrer, Per

    2017-01-01

    -density lipoprotein cholesterol was 2.0 mmol/l. Conclusion: In a nationwide database survey in primary care, the prevalence of CVD in patients with type 2 diabetes was high (21.4%). Standard of care was largely in accordance with national guidelines. Identification of eligible patients is possible with existing......Objective: Cardiovascular disease (CVD) complicates type 2 diabetes. Empagliflozin and liraglutide have demonstrated improved survival in patients with type 2 diabetes and established CVD. We assessed prevalence and standard of care of patients with type 2 diabetes and established CVD managed.......6% were women. Mean estimated glomerular filtration rate was 68.2 ml/min, and 22.2% had microalbuminuria or macroalbuminuria. Standard of care was fair: mean glycated hemoglobin was 52.3 mmol/mol (Diabetes Control and Complications Trial=6.9%), mean blood pressure was 131.4/75.7 mmHg, and mean low...

  8. Predictors of dropout in the German disease management program for type 2 diabetes.

    Science.gov (United States)

    Fullerton, Birgit; Erler, Antje; Pöhlmann, Boris; Gerlach, Ferdinand M

    2012-01-10

    To improve and assess the effectiveness of disease management programs (DMPs), it is critical to understand how many people drop out of disease management programs and why. We used routine data provided by a statutory health insurance fund from the regions North Rhine, North Wurttemberg and Hesse. As part of the German DMP for type 2 diabetes, the insurance fund received regular documentation of all members participating in the program. We followed 10,989 patients who enrolled in the DMP between July 2004 and December 2005 until the end of 2007 to study how many patients dropped out of the program. Dropout was defined based on the discontinuation of program documentation on a particular patient, excluding situations in which the patient died or left the insurance fund. Predictors of dropout, assessed at the time of program enrolment, were explored using logistic regression analysis. 5.5% of the patients dropped out of the disease management program within the observation period. Predictors of dropout at the time of enrolment were: region; retirement status; the number of secondary diseases; presence of a disabling secondary disease; doctor's recommendations to stop smoking or to seek nutritional counselling; and the completion and outcome of the routine foot and eye exams. Different trends of dropout were observed among retired and employed patients: retired patients of old age, who possibly drop out of the program due to other health care priorities and employed people of younger age who have not yet developed many secondary diseases, but were recommended to change their lifestyle. Overall, dropout rates for the German disease management programs for type 2 diabetes were low compared to other studies. Factors assessed at the time of program enrolment were predictive of later dropout and should be further studied to provide information for future program improvements.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. [Cathepsin K as a biomarker of bone involvement in type 1 Gaucher disease].

    Science.gov (United States)

    Bobillo Lobato, Joaquín; Durán Parejo, Pilar; Núñez Vázquez, Ramiro J; Jiménez Jiménez, Luis M

    2015-10-05

    Gaucher disease is an inherited disorder caused by deficit of acid β-glucocerebrosidase, responsible for the degradation of glucosylceramide to ceramide and glucose. Although the disorder is primarily hematologic, bone is the second most commonly affected structure. Cathepsin K (CATK) is an enzyme involved in bone remodelling process. It has been proposed that determination of its serum concentrations may provide additional information to other biomarkers. The study included 20 control subjects and 20 Gaucher type 1 patients from Andalusia and Extremadura regions. We analyzed the biomarkers of bone remodelling: the bone alkaline phosphatase (B-ALP), the N-terminal propeptide of type 1 procollagen (P1NP), the β carboxyterminal telopeptide of type 1 collagen (CTx) and the CATK through electrochemiluminescence and immunoassay techniques. There is an increase in levels of CATK, CATK/P1NP and CATK/B-ALP ratios in type 1 Gaucher patients compared to the control group. Considering the existence of skeletal manifestations in the patient group, the CATK and CATK/P1NP ratio showed higher levels in patients with bone damage compared to those without it. Although imaging studies are the gold standard for monitoring bone disease in type 1 Gaucher patients, the utility of CATK should be considered as a possible indicator of bone damage in these patients. Furthermore, this parameter can be used in the monitoring of the treatment of bone pathology. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  13. The absence of later wave components in auditory brainstem responses as an initial manifestation of type 2 Gaucher disease.

    Science.gov (United States)

    Okubo, Yusuke; Goto, Masahiro; Sakakibara, Hiroshi; Terakawa, Toshiro; Kaneko, Takashi; Miyama, Sahoko

    2014-12-01

    Type 2 Gaucher disease is the most severe neuronopathic form of Gaucher disease and is characterized by severe neurodegeneration with brainstem involvement and organ failure. Prediction or diagnosis of type 2 Gaucher disease before the development of neurological complications is difficult. A 5-month-old female infant presented with deafness without other neurological abnormalities. Auditory brainstem response analysis revealed the absence of later wave components. Two months later, muscular rigidity became evident, followed by the development of opisthotonus and strabismus. Rapid progression of splenomegaly led to the diagnosis of type 2 Gaucher disease. Abnormal auditory brainstem response findings may already exist before the development of severe brainstem abnormalities such as muscular rigidity and opisthotonus in type 2 Gaucher disease. When patients present with deafness and absent later wave components on auditory brainstem response, type 2 Gaucher disease should be included in the differential diagnosis even in the absence of other neurological abnormalities. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age?

    Science.gov (United States)

    Firneisz, Gábor

    2014-07-21

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.

  15. Management goals for type 1 Gaucher disease: An expert consensus document from the European working group on Gaucher disease.

    Science.gov (United States)

    Biegstraaten, M; Cox, T M; Belmatoug, N; Berger, M G; Collin-Histed, T; Vom Dahl, S; Di Rocco, M; Fraga, C; Giona, F; Giraldo, P; Hasanhodzic, M; Hughes, D A; Iversen, P O; Kiewiet, A I; Lukina, E; Machaczka, M; Marinakis, T; Mengel, E; Pastores, G M; Plöckinger, U; Rosenbaum, H; Serratrice, C; Symeonidis, A; Szer, J; Timmerman, J; Tylki-Szymańska, A; Weisz Hubshman, M; Zafeiriou, D I; Zimran, A; Hollak, C E M

    2018-02-01

    Gaucher Disease type 1 (GD1) is a lysosomal disorder that affects many systems. Therapy improves the principal manifestations of the condition and, as a consequence, many patients show a modified phenotype which reflects manifestations of their disease that are refractory to treatment. More generally, it is increasingly recognised that information as to how a patient feels and functions [obtained by patient- reported outcome measurements (PROMs)] is critical to any comprehensive evaluation of treatment. A new set of management goals for GD1 in which both trends are reflected is needed. To this end, a modified Delphi procedure among 25 experts was performed. Based on a literature review and with input from patients, 65 potential goals were formulated as statements. Consensus was considered to be reached when ≥75% of the participants agreed to include that specific statement in the management goals. There was agreement on 42 statements. In addition to the traditional goals concerning haematological, visceral and bone manifestations, improvement in quality of life, fatigue and social participation, as well as early detection of long-term complications or associated diseases were included. When applying this set of goals in medical practice, the clinical status of the individual patient should be taken into account. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Association of Lyme Disease and Schizoaffective Disorder, Bipolar Type: Is it Inflammation Mediated?

    Science.gov (United States)

    Mattingley, David William; Koola, Maju Mathew

    2015-01-01

    Lyme disease has been reported to be associated with various psychiatric presentations. Borreliaburgdorferi (Bb) can present with symptoms similar to schizophrenia and bipolar disorder. It has been suggested that inflammation incurred during the Bb infection leads to neurodegenerative changes that result in schizophrenia-like presentations. We report a case of a 41-year-old male with a past history of Bb infection who presents with psychosis. Later in the course of his hospitalization, he developed mood symptoms and was diagnosed with schizoaffective disorder, bipolar type. This case highlights the diagnosis and treatment of a patient with the unique presentation of schizoaffective disorder, bipolar type in the setting of previous Bb infection.

  17. Childhood BMI and Adult Type 2 Diabetes, Coronary Artery Diseases, Chronic Kidney Disease, and Cardiometabolic Traits: A Mendelian Randomization Analysis.

    Science.gov (United States)

    Geng, Tingting; Smith, Caren E; Li, Changwei; Huang, Tao

    2018-05-01

    To test the causal effect of childhood BMI on adult cardiometabolic diseases using a Mendelian randomization analysis. We used 15 single nucleotide polymorphisms as instrumental variables for childhood BMI to test the causal effect of childhood BMI on cardiometabolic diseases using summary-level data from consortia. We found that a 1-SD increase in childhood BMI (kg/m 2 ) was associated with an 83% increase in risk of type 2 diabetes (odds ratio [OR] 1.83 [95% CI 1.46, 2.30]; P = 2.5 × 10 -7 ) and a 28% increase in risk of coronary artery disease (CAD) (OR 1.28 [95% CI 1.17, 1.39]; P = 2.1 × 10 -8 ) at the Bonferroni-adjusted level of significance ( P BMI was associated with a 0.587-SD increase in adulthood BMI (kg/m 2 ), a 0.062-SD increase in hip circumference (cm), a 0.602-SD increase in waist circumference (cm), a 0.111 pmol/L increase in log fasting insulin, a 0.068 increase in log-transformed HOMA of ß-cell function (%), a 0.126 increase in log-transformed HOMA of insulin resistance (%), and a 0.109-SD increase in triglyceride (mg/dL) but a 0.138-SD decrease in HDL (mg/dL) in adults at the Bonferroni-adjusted level of significance ( P BMI was associated with increased risk of type 2 diabetes and CAD in adult life. These results provide evidence supportive of a causal association between childhood BMI and these outcomes. © 2018 by the American Diabetes Association.

  18. The increasing role of monoamine oxidase type B inhibitors in Parkinson's disease therapy.

    Science.gov (United States)

    Elmer, Lawrence W; Bertoni, John M

    2008-11-01

    The role of monoamine oxidase type B inhibitors in the treatment of Parkinson's disease has expanded with the new monoamine oxidase B inhibitor rasagiline and a new formulation, selegiline oral disintegrating tablets. As primary therapy in early disease monoamine oxidase B inhibitors reduce motor disability and delay the need for levodopa. In more advanced disease requiring levodopa, adjunctive monoamine oxidase B inhibitors reduce 'off' time and may improve gait and freezing. Rasagiline and selegiline oral disintegrating tablets may reduce the safety risks associated with the amfetamine and methamfetamine metabolites of conventional oral selegiline while retaining or improving therapeutic efficacy. Articles were identified by searches of PubMed and searches on the Internet and reviewed. All articles and other referenced materials were retrieved using the keywords 'Parkinson's disease', 'treatment' and 'monoamine oxidase B inhibitor' and were published between 1960 and 2007, with older references selected for historical significance. Only papers published in English were reviewed. Accumulating data support the use of monoamine oxidase B inhibitors as monotherapy for early and mild Parkinson's disease and as adjunctive therapy for more advanced Parkinson's disease with levodopa-associated motor fluctuations. The recently released monoamine oxidase B inhibitor rasagiline and a new formulation, selegiline oral disintegrating tablets, have potential advantages over conventional oral selegiline.

  19. Crosstalk between type II NKT cells and T cells leads to spontaneous chronic inflammatory liver disease.

    Science.gov (United States)

    Weng, Xiufang; He, Ying; Visvabharathy, Lavanya; Liao, Chia-Min; Tan, Xiaosheng; Balakumar, Arjun; Wang, Chyung-Ru

    2017-10-01

    Natural killer T (NKT) cells are CD1d-restricted innate-like T cells that modulate innate and adaptive immune responses. Unlike the well-characterized invariant/type I NKT cells, type II NKT cells with a diverse T cell receptor repertoire are poorly understood. This study defines the pathogenic role of type II NKT cells in the etiology of chronic liver inflammation. Transgenic mice with the Lck promoter directing CD1d overexpression on T cells in Jα18 wild-type (Lck-CD1dTgJα18 + ; type I NKT cell sufficient) and Jα18-deficient (Lck-CD1dTgJα18 o , type I NKT cell deficient) mice were analyzed for liver pathology and crosstalk between type II NKT cells and conventional T cells. CD1d expression on T cells in peripheral blood samples and liver sections from autoimmune hepatitis patients and healthy individuals were also examined. Lck-CD1dTgJα18 o and Lck-CD1dTgJα18 + mice developed similar degrees of liver pathology resembling chronic autoimmune hepatitis in humans. Increased CD1d expression on T cells promoted the activation of type II NKT cells and other T cells. This resulted in T h 1-skewing and impaired T h 2 cytokine production in type II NKT cells. Dysfunction of type II NKT cells was accompanied by conventional T cell activation and pro-inflammatory cytokine production, leading to a hepatic T/B lymphocyte infiltration, elevated autoantibodies and hepatic injury in Lck-CD1dTg mice. A similar mechanism could be extended to humans as CD1d expression is upregulated on activated human T cells and increased presence of CD1d-expressing T cells was observed in autoimmune hepatitis patients. Our data reveals enhanced crosstalk between type II NKT cells and conventional T cells, leading to a T h 1-skewed inflammatory milieu, and consequently, to the development of chronic autoimmune liver disease. Lay summary: CD1d overexpression on T cells enhances crosstalk between type II NKT cells and T cells, resulting in their aberrant activation and leading to the

  20. Oral hypoglycaemic agents, insulin resistance and cardiovascular disease in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hemmingsen, Bianca; Lund, Søren S; Wetterslev, Jørn

    2009-01-01

    This article is a narrative review of the current evidence of the effects on cardiovascular disease (CVD) of oral hypoglycaemic agents that increase insulin sensitivity in patients with type 2 diabetes (T2D). In overweight T2D patients, metformin has been demonstrated to reduce CVD risk, and this......This article is a narrative review of the current evidence of the effects on cardiovascular disease (CVD) of oral hypoglycaemic agents that increase insulin sensitivity in patients with type 2 diabetes (T2D). In overweight T2D patients, metformin has been demonstrated to reduce CVD risk......, and this beneficial effect may be conserved with the combination of metformin and insulin treatment. However, the effect of glitazones on CVD is uncertain. There is conflicting evidence from large randomized trials to support a protective effect against CVD of lowering blood glucose per se but a systematic review...

  1. A de novo SOX10 mutation causing severe type 4 Waardenburg syndrome without Hirschsprung disease.

    Science.gov (United States)

    Sznajer, Yves; Coldéa, Cristina; Meire, Françoise; Delpierre, Isabelle; Sekhara, Tayeb; Touraine, Renaud L

    2008-04-15

    Type 4 Waardenburg syndrome represents a well define entity caused by neural crest derivatives anomalies (melanocytes, intrinsic ganglion cells, central, autonomous and peripheral nervous systems) leading, with variable expressivity, to pigmentary anomalies, deafness, mental retardation, peripheral neuropathy, and Hirschsprung disease. Autosomal dominant mode of inheritance is prevalent when Sox10 gene mutation is identified. We report the natural history of a child who presented with synophrys, vivid blue eye, deafness, bilateral complete semicircular canals agenesis with mental retardation, subtle signs for peripheral neuropathy and lack of Hirschsprung disease. SOX10 gene sequencing identified "de novo" splice site mutation (c.698-2A > C). The present phenotype and the genotype findings underline the wide spectrum of SOX10 gene implication in unusual type 4 Waardenburg syndrome patient. Copyright 2008 Wiley-Liss, Inc.

  2. Changing practice: red blood cell typing by molecular methods for patients with sickle cell disease.

    Science.gov (United States)

    Casas, Jessica; Friedman, David F; Jackson, Tannoa; Vege, Sunitha; Westhoff, Connie M; Chou, Stella T

    2015-06-01

    Extended red blood cell (RBC) antigen matching is recommended to limit alloimmunization in patients with sickle cell disease (SCD). DNA-based testing to predict blood group phenotypes has enhanced availability of antigen-negative donor units and improved typing of transfused patients, but replacement of routine serologic typing for non-ABO antigens with molecular typing for patients has not been reported. This study compared the historical RBC antigen phenotypes obtained by hemagglutination methods with genotype predictions in 494 patients with SCD. For discrepant results, repeat serologic testing was performed and/or investigated by gene sequencing for silent or variant alleles. Seventy-one typing discrepancies were identified among 6360 antigen comparisons (1.1%). New specimens for repeat serologic testing were obtained for 66 discrepancies and retyping agreed with the genotype in 64 cases. One repeat Jk(b-) serologic phenotype, predicted Jk(b+) by genotype, was found by direct sequencing of JK to be a silenced allele, and one N typing discrepancy remains under investigation. Fifteen false-negative serologic results were associated with alleles encoding weak antigens or single-dose Fy(b) expression. DNA-based RBC typing provided improved accuracy and expanded information on RBC antigens compared to hemagglutination methods, leading to its implementation as the primary method for extended RBC typing for patients with SCD at our institution. © 2015 AABB.

  3. The relationship between disease activity, quality of life, and personality types in rheumatoid arthritis and ankylosing spondylitis patients.

    Science.gov (United States)

    Donisan, T; Bojincă, V C; Dobrin, M A; Bălănescu, D V; Predețeanu, D; Bojincă, M; Berghea, F; Opriș, D; Groșeanu, L; Borangiu, A; Constantinescu, C L; Ionescu, R; Bălănescu, A R

    2017-07-01

    We hypothesized that clinical outcomes might be influenced by personality type (A, B, C, D) in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). One hundred ninety-four patients (104 with RA, 90 with AS) participated in a questionnaire study. We evaluated health-related quality of life (HRQoL) using the Medical Outcome Study Short-Form 36 (SF-36), personality type A/B with the Jenkins Activity Survey, type C with the State-Trait Anger Expression Inventory Anger-in Scale, type D with the Type D Personality Scale, and disease activity with Disease Activity Score with 28 joints for RA and Bath Ankylosing Spondylitis Disease Activity Index for AS. We used Pearson's correlation coefficient, independent samples t tests, and multivariate analyses of variance. In the RA group, type D personality was significantly correlated with 7/12 SF-36 components. AS patients with type D personality had deficits in all SF-36 subscales. Type D was related with higher disease activity in RA and AS. Both RA and AS type C patients had more active disease forms and negatively affected HRQoL subscales. In the RA group, type A personality did not correlate with HRQoL, but it positively influenced pain visual analog scale scores. In AS patients, type A personality was linked with higher HRQoL and with less active disease. Type C and type D personality types were correlated with decreased HRQoL and higher disease activity in RA and AS patients. Type A personality was associated with less active disease and higher HRQoL in AS patients and with less pain in RA patients.

  4. Niemann-Pick type C disease: molecular mechanisms and potential therapeutic approaches

    OpenAIRE

    Rosenbaum, Anton I.; Maxfield, Frederick R.

    2011-01-01

    Cholesterol is an important lipid of mammalian cells. Its unique physicochemical properties modulate membrane behavior and it serves as the precursor for steroid hormones, oxysterols and vitamin D. Cholesterol is effluxed from the late endosomes/lysosomes via the concerted action of at least two distinct proteins: Niemann-Pick C1 and Niemann-Pick C2. Mutations in these two proteins manifest as Niemann-Pick type C disease – a very rare, usually fatal, autosomal, recessive, neurovisceral, lysos...

  5. Disease awareness in myotonic dystrophy type 1: an observational cross-sectional study

    OpenAIRE

    Baldanzi, Sigrid; Bevilacqua, Francesca; Lorio, Rita; Volpi, Leda; Simoncini, Costanza; Petrucci, Antonio; Cosottini, Mirco; Massimetti, Gabriele; Tognoni, Gloria; Ricci, Giulia; Angelini, Corrado; Siciliano, Gabriele

    2016-01-01

    Background Myotonic dystrophy type 1 (Steinert?s disease or DM1), the most common form of autosomal dominant muscular dystrophy in adults, is a multisystem disorder, affecting skeletal muscle as well as eyes, heart, gastrointestinal tract, endocrine system, and central nervous system, finally responsible of increasing disabilities and secondary social consequences. To date, DM1-related brain involvement represents a challenging field of research. It is well known that DM1 patients frequently ...

  6. Recognition of lysophosphatidylcholine by type II NKT cells and protection from an inflammatory liver disease.

    Science.gov (United States)

    Maricic, Igor; Girardi, Enrico; Zajonc, Dirk M; Kumar, Vipin

    2014-11-01

    Lipids presented by the MHC class I-like molecule, CD1d, are recognized by NK T (NKT) cells, which can be broadly categorized into two subsets. The well-characterized type I NKT cells express a semi-invariant TCR and can recognize both α- and β-linked glycolipids, whereas type II NKT cells are less well studied, express a relatively diverse TCR repertoire, and recognize β-linked lipids. Recent structural studies have shown a distinct mode of recognition of a self-glycolipid sulfatide bound to CD1d by a type II NKT TCR. To further characterize Ag recognition by these cells, we have used the structural data and screened other small molecules able to bind to CD1d and activate type II NKT cells. Using plate-bound CD1d and APC-based Ag presentation assay, we found that phospholipids such as lysophosphatidylcholine (LPC) can stimulate the sulfatide-reactive type II NKT hybridoma Hy19.3 in a CD1d-dependent manner. Using plasmon resonance studies, we found that this type II NKT TCR binds with CD1d-bound LPC with micromolar affinities similar to that for sulfatide. Furthermore, LPC-mediated activation of type II NKT cells leads to anergy induction in type I NKT cells and affords protection from Con A-induced hepatitis. These data indicate that, in addition to self-glycolipids, self-lysophospholipids are also recognized by type II NKT cells. Because lysophospholipids are involved during inflammation, our findings have implications for not only understanding activation of type II NKT cells in physiological settings, but also for the development of immune intervention in inflammatory diseases. Copyright © 2014 by The American Association of Immunologists, Inc.

  7. New susceptibility loci associated with kidney disease in type 1 diabetes

    DEFF Research Database (Denmark)

    Sandholm, Niina; Salem, Rany M; McKnight, Amy Jayne

    2012-01-01

    Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion...... mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ~2...... SNP in the ERBB4 gene (rs7588550, P = 2.1 × 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN....

  8. Infantile Type Sandhoff Disease with Striking Brain MRI Findings and a Novel Mutation

    International Nuclear Information System (INIS)

    Beker-Acay, Mehtap; Elmas, Muhsin; Koken, Resit; Unlu, Ebru; Bukulmez, Aysegul

    2016-01-01

    Sandhoff disease is an autosomal recessive disorder caused by β-hexosaminidase deficiency in which the ganglioside GM2 and other glycolipids accumulate intracellularly within lysosomes. This process results in progressive motor neuron manifestations, death from respiratory failure and infections in infantiles. This report presents a 22-month-old girl with infantile type Sandhoff disease that was hospitalized for generalized seizures and psychomotor retardation. She was diagnosed with a genetically proven novel mutation and by demonstrating it’s specific imaging findings. Determination of spesific changes in neuroimaging which are initial findings for GM2 gangliosidosis is important from the point of diagnosis and follow-up in infants suspected of having a neurodegenerative disease

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

    Directory of Open Access Journals (Sweden)

    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.

  10. PREVALENCE OF MEIBOMIAN GLAND DISEASE IN TYPE II DIABETIC PATIENTS & ITS CLINICAL PRESENTATIONS

    Directory of Open Access Journals (Sweden)

    Reshma Pathan

    2015-01-01

    Full Text Available AIMS : To study the prevalence of the meibomian gland disease in typ e 2 diabetic patients and its clinical presentations. SETTING AND DESIGN : A hospital based cross sectional descriptive study of 100 type 2 diabetic patients attending a medical college was conducted. METHODS : Detailed diabetic history was recorded. Assessment of ocular surface i.e. the lid margins , conjunctiva , corneal surface was done via slit lamp biomicroscopy. Meibomian gland disease (MGD severity was assessed by the quality and expressibility of the meibomian secretion. Dry eye tests like schir mer’s test and tear film breakup time were done. STATISTICAL ANALYSIS USED : SPSS statistical software version 17 was used. RESULTS : 56% of the patients out of 100 diabetic patients had MGD. The most common symptom was burning (46.9% , followed by dryness ( 23.5% , 5.6% had conjunctival injection , 7.14% had corneal erosions , 25% had mucus debris , 53.65% had dry eye which was statistically significant (p=0.001 , 56.25% males and 72.2% females had the disease which was not statistically significant. CONCLUSION : The prevalence of Meibomian gland disease in the diabetic population was 56% which is more than the general population prevalence. Apart from other disorders diabetics are also more prone for ocular surface diseases like Meibomian gland disease. MGD is an important pre disposer for severe diseases like Dry eye in this subgroup of patients which can lead to complications like conjunctival keratinisations , corneal erosions and perforations. Careful examination of these patients for ocular surface disease and prompt treatment is required.

  11. CLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial

    Science.gov (United States)

    Background Circadian rhythms regulate key biological processes influencing metabolic pathways. Dysregulation is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Circadian rhythms are generated by a transcriptional autoregulatory feedback loop involving core clock genes. CLOCK...

  12. Eliglustat tartrate for the treatment of adults with type 1 Gaucher disease.

    Science.gov (United States)

    Bennett, Lunawati L; Turcotte, Kelsey

    2015-01-01

    The purpose of this article is to review eliglustat tartrate, a substrate reduction therapy, for the treatment of Gaucher disease type 1 (GD1). GD is an rare inborn error of metabolism caused by accumulation of lipid substrates such as glucosylceramide within the monocyte-macrophage system that affects the body by causing enlargement of the spleen and liver, destruction of bone, and abnormalities of the lungs and blood, such as anemia, thrombocytopenia, and leukopenia. GD is classified into three types: GD1, a chronic and non-neuronopathic disease accounting for 95% of GD cases; and types 2 and 3 (GD2 GD3) which are more progressive diseases with no approved drugs available at this time. Treatment options for GD1 include enzyme replacement therapy and substrate reduction therapy. Eliglustat works by inhibiting UDP-glucosylceramide synthase, the first enzyme that catalyzes the biosynthesis of glycosphingolipids, thus reducing the load of glucosylceramide influx into the lysosome. Eliglustat was approved by the US Food and Drug Administration after three Phase I, two Phase II, and two Phase III clinical trials. The dose of eliglustat is 84 mg twice a day or once daily depending on the cytochrome P450 2D6 genotype of the patient.

  13. Oxidative Stress Parameters in Saliva and Its Association with Periodontal Disease and Types of Bacteria.

    Science.gov (United States)

    Almerich-Silla, Jose Manuel; Montiel-Company, Jose María; Pastor, Sara; Serrano, Felipe; Puig-Silla, Miriam; Dasí, Francisco

    2015-01-01

    To determine the association between oxidative stress parameters with periodontal disease, bleeding, and the presence of different periodontal bacteria. A cross-sectional study in a sample of eighty-six patients, divided into three groups depending on their periodontal status. Thirty-three with chronic periodontitis, sixteen with gingivitis, and thirty-seven with periodontal healthy as control. Oxidative stress biomarkers (8-OHdG and MDA), total antioxidant capacity (TAOC), and the activity of two antioxidant enzymes (GPx and SOD) were determined in saliva. Subgingival plaque samples were obtained from the deepest periodontal pocket and PCR was used to determine the presence of the 6 fimA genotypes of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, and Treponema denticola. Periodontal disease was found to be associated with increased oxidative stress parameter levels. These levels rose according to the number and type of different periodontal bacteria found in the periodontal pockets. The presence of different types of periodontal bacteria is predictive independent variables in linear regresion models of oxidative stress parameters as dependent variable, above all 8-OHdG. Oxidative stress parameter levels are correlated with the presence of different types of bacteria. Determination of these levels and periodontal bacteria could be a potent tool for controlling periodontal disease development.

  14. Muscle fiber type proportion and size is not altered in mcardle disease.

    Science.gov (United States)

    Henning, Franclo; Cunninghame, Carol Anne; Martín, Miguel Angel; Rubio, Juan Carlos; Arenas, Joaquín; Lucia, Alejandro; HernáNdez-Laín, Aurelio; Kohn, Tertius Abraham

    2017-06-01

    McArdle disease is a metabolic myopathy that presents with exercise intolerance and episodic rhabdomyolysis. Excessive muscle recruitment has also been shown to be present during strenuous exercise, suggesting decreased power output. These findings could potentially be explained by either impaired contractility, decreased fiber size, or altered fiber type proportion. However, there is a paucity of data on the morphological features seen on muscle histology. We examined muscle biopsies of patients with McArdle disease from a Spanish cohort and compared the findings with healthy controls. We found no significant difference in the fiber type proportion or mean fiber size between McArdle patients and controls in the biceps brachii or vastus lateralis muscles. No alterations in muscle fiber type proportion or size were found on muscle histology of patients with McArdle disease. Future research should focus on assessment of muscle fiber contractility to investigate the functional impairment. Muscle Nerve 55: 916-918, 2017. © 2016 Wiley Periodicals, Inc.

  15. Regeneration of different plant functional types in a Masson pine forest following pine wilt disease.

    Science.gov (United States)

    Hu, Guang; Xu, Xuehong; Wang, Yuling; Lu, Gao; Feeley, Kenneth J; Yu, Mingjian

    2012-01-01

    Pine wilt disease is a severe threat to the native pine forests in East Asia. Understanding the natural regeneration of the forests disturbed by pine wilt disease is thus critical for the conservation of biodiversity in this realm. We studied the dynamics of composition and structure within different plant functional types (PFTs) in Masson pine forests affected by pine wilt disease (PWD). Based on plant traits, all species were assigned to four PFTs: evergreen woody species (PFT1), deciduous woody species (PFT2), herbs (PFT3), and ferns (PFT4). We analyzed the changes in these PFTs during the initial disturbance period and during post-disturbance regeneration. The species richness, abundance and basal area, as well as life-stage structure of the PFTs changed differently after pine wilt disease. The direction of plant community regeneration depended on the differential response of the PFTs. PFT1, which has a higher tolerance to disturbances, became dominant during the post-disturbance regeneration, and a young evergreen-broad-leaved forest developed quickly after PWD. Results also indicated that the impacts of PWD were dampened by the feedbacks between PFTs and the microclimate, in which PFT4 played an important ecological role. In conclusion, we propose management at the functional type level instead of at the population level as a promising approach in ecological restoration and biodiversity conservation.

  16. Peculiarities of clinical course of gastroesophageal reflux disease in patients with type 2 diabetes and obesity

    Directory of Open Access Journals (Sweden)

    Andreeva E.l.

    2017-12-01

    Full Text Available Aim: to study the clinical course of gastroesophageal reflux disease (GERD in patients with type 2 diabetes and evaluation of the parameters of the esophagus 24-hour pH-metry. Material and Methods. In the examination of patients with GERD, three groups of patients were selected for 50 people each. The first group includes patients with GERD with combined course of obesity and type 2 diabetes (mean age 54.6±2.73 year; 32 females and 18 males. The second group included patients with GERD against obesity (mean age 42.3±2.11 year; 30 females and 20 males. The control group consisted of patients with GERD without excess body weight and concomitant pathology (average age43.6±2.11 year; 29 females and 21 males. In addition to collecting complaints and anamnesis, the patients and the control group underwent a 24-hour pH-metric study of the esophagus according to a conventional method. Results. Patients suffering from GERD in the background of type 2 diabetes have a clinically asymptomatic or asymptomatic course; there is a significant increase in the daily pH-metry, indicating a more pronounced nature of the changes. Conclusion. Patients suffering from GERD in the background of type 2 diabetes require a comprehensive examination of the upper digestive tract to identify GERD, even if there are no complaints characteristic of the disease.

  17. Detection of Motor Impairment in Parkinson's Disease Via Mobile Touchscreen Typing.

    Science.gov (United States)

    Arroyo-Gallego, Teresa; Ledesma-Carbayo, Maria Jesus; Sanchez-Ferro, Alvaro; Butterworth, Ian; Mendoza, Carlos S; Matarazzo, Michele; Montero, Paloma; Lopez-Blanco, Roberto; Puertas-Martin, Veronica; Trincado, Rocio; Giancardo, Luca

    2017-09-01

    Mobile technology is opening a wide range of opportunities for transforming the standard of care for chronic disorders. Using smartphones as tools for longitudinally tracking symptoms could enable personalization of drug regimens and improve patient monitoring. Parkinson's disease (PD) is an ideal candidate for these tools. At present, evaluation of PD signs requires trained experts to quantify motor impairment in the clinic, limiting the frequency and quality of the information available for understanding the status and progression of the disease. Mobile technology can help clinical decision making by completing the information of motor status between hospital visits. This paper presents an algorithm to detect PD by analyzing the typing activity on smartphones independently of the content of the typed text. We propose a set of touchscreen typing features based on a covariance, skewness, and kurtosis analysis of the timing information of the data to capture PD motor signs. We tested these features, both independently and in a multivariate framework, in a population of 21 PD and 23 control subjects, achieving a sensitivity/specificity of 0.81/0.81 for the best performing feature and 0.73/0.84 for the best multivariate method. The results of the alternating finger-tapping, an established motor test, measured in our cohort are 0.75/0.78. This paper contributes to the development of a home-based, high-compliance, and high-frequency PD motor test by analysis of routine typing on touchscreens.

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

    DEFF Research Database (Denmark)

    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...

  19. Validating the Type D personality construct in Chinese patients with coronary heart disease.

    Science.gov (United States)

    Yu, Doris S F; Thompson, David R; Yu, Cheuk Man; Pedersen, Susanne S; Denollet, Johan

    2010-08-01

    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. Type D discrepancies in depression/anxiety, among Chinese patients with CHD. Patients with CHD (N=326) completed the Chinese version of the DS14. The NEO Five Factor Inventory (NEO-FFI), Hospital Anxiety and Depression Scale (HADS), and Stress Symptom Checklist (SSC) were administered to subsamples to establish construct and discriminant validity. Administration of the DS14, HADS, and SSC was repeated at 1 month after hospital discharge in 66 patients, and stability of the DS14 was examined in another subsample of 100 patients. The theoretical structure of the Type D construct in the Chinese culture was supported (chi(2)/df=2.89, root mean square error of approximation=0.08, normal fit index=0.91, non-normal fit index=0.91, comparative fit index=0.93). The Negative Affectivity (NA) and Social Inhibition (SI) subscales of the DS14 in the entire sample were internally consistent (Cronbach's alpha=0.89/0.81), measured stable traits (3-month test-retest ICC=0.76/0.74), and correlated significantly with the neuroticism (NA/neuroticism, r=0.78, Ppersonality was 31%. Type D was not related to transient emotional states. However, Chinese patients with a Type D personality were at increased concurrent risk of anxiety (P=.002) and depression (P=.016). Type D personality is a cross-culturally valid construct, is associated with an increased risk of anxiety and depression, and deserves prompt attention in estimating the prognostic risk of Chinese CHD patients. Copyright 2010 Elsevier Inc. All rights reserved.

  20. Clinical potential of eliglustat tartrate in the treatment of type 1 Gaucher disease

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    Kaplan P

    2014-05-01

    Full Text Available Paige KaplanLysosomal Disorders Center, Section of Metabolic Diseases, Children's Hospital of Philadelphia, Philadelphia, PA, USAAbstract: Nonneuropathic type 1 Gaucher disease is an autosomal recessive inherited disease caused by the deficiency or absence of beta glucocerebrosidase (beta glucosidase. The highest prevalence of type 1 is in Ashkenazi Jews, but it affects all ethnic groups. It manifests at any age but is seen predominantly in the first two decades. The phenotype is characterized by painless splenomegaly and secondary hypersplenism (low hemoglobin concentration and low platelet and white blood cell counts. Symptoms and signs include splenomegaly; chronic fatigue, frequent nose bleeds, prolonged bleeding, and/or bruising; hepatomegaly; bone pain, bone destruction and low bone density; and poor growth in childhood and delayed pubertal development. Current treatment with intravenous enzyme replacement has been generally successful. However, oral treatments have been developed because enzyme replacement is time-consuming and invasive, and intravenous infusions are not universally available for patients who live far from medical centers or home infusion nurses. Furthermore, it may become difficult to access veins after repeated infusions. Orally administered substrate reduction is a newer treatment approach. The aim is to limit the synthesis of the substrate, glucosylceramide. The residual intrinsic enzyme, acting alone or with recombinant enzyme, can then completely catabolize the smaller amounts of glucosylceramide that are transported into lysosomes. Eliglustat tartrate is a new specific inhibitor of glucosylceramide synthase. Phase III trials in humans have been completed. Eliglustat tartrate has been shown to be efficacious and safe in adult humans. The results are as good or better compared with intravenous replacement with regard to reductions in spleen and liver enlargement and improvements in hemoglobin concentrations, platelet

  1. Pseudo (Platelet-type von Willebrand disease in pregnancy: a case report

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    Grover Neetu

    2013-01-01

    Full Text Available Abstract Background Pseudo (platelet-type-von Willebrand disease is a rare autosomal dominant bleeding disorder caused by an abnormal function of the glycoprotein lb protein; the receptor for von Willebrand factor. This leads to an increased removal of VWF multimers from the circulation as well as platelets and this results in a bleeding diathesis. Worldwide, less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD. Case presentation We describe the management of platelet type von Willebrand disease in pregnancy of a 26 year old Caucasian primigravida. The initial diagnosis was made earlier following a significant haemorrhage post tonsillectomy several years prior to pregnancy. The patient was managed under a multidisciplinary team which included obstetricians, haematologists, anaesthetists and neonatologists. Care plans were made for the ante- natal, intra-partum and post-partum periods in partnership with the patient. The patient’s platelet count levels dropped significantly during the antenatal period. This necessitated the active exclusion of other causes of thrombocytopenia in pregnancy. A vaginal delivery was desired and plans were made for induction of labour at 38 weeks of gestation with platelet cover in view of the progressive fall of the platelet count. The patient however went into spontaneous labour on the day of induction. She was transfused two units of platelets before delivery. She had an unassisted vaginal delivery of a healthy baby. The successful antenatal counselling has encouraged the diagnosis of the same condition in her mother and sister. We found this to be a particularly interesting case as well as challenging to manage due to its rarity. Psuedo von Willebrand disease in pregnancy can be confused with a number of other differential diagnoses, such as gestational thrombocutopenia, idiopathatic thrombocytopenia, thrombotic thrombocytopenic purpura and pre-eclampsia; all need consideration

  2. Prevalence of a positive family history of type 2 diabetes in women with polycystic ovarian disease.

    Science.gov (United States)

    Fox, R

    1999-12-01

    The known association between insulin resistance and polycystic ovarian disease (PCOD) has been studied by determination of the prevalence of a positive family history of diabetes in a consecutive series of oligomenorrheic women with polycystic ovaries and eumenorrheic women with normal ovaries who served as controls. A significantly greater proportion of the families of the patients with PCOD had at least one member affected by type 2 diabetes (39.1% of the PCOD group and 7.6% of the controls; p PCOD had an increased prevalence of type 2 diabetes within their families. Paternal and maternal family members affected were in similar proportions, there being no evidence of preferential transmission through the female line in this study. The increased prevalence of type 2 diabetes in the families of women with polycystic ovaries is further evidence for the association between PCOD and insulin resistance, and provides a possible explanation for the familial nature of the ovarian disorder.

  3. Microvascular disease during pregnancy in type 1 diabetes is associated with ambulatory arterial stiffness

    DEFF Research Database (Denmark)

    Tjessem, Ingvild; Al-Far, Hanine M; Fuglsang, Jens

    2017-01-01

    Objectives: The objective of this study was to evaluate the association between the ambulatory arterial stiffness index (AASI) and markers of microvascular disease during pregnancy in women with type 1 diabetes. Study design: A total of 151 women with type 1 diabetes mellitus were recruited...... during pregnancy in women with type 1 diabetes. Together with the flattened circadian rhythm this indicates a pregnancy-related functional change in the vascular bed....... for repeat 24-h BP recordings thrice during pregnancy and once three months post partum. Fifty women without diabetes served as controls. The AASI and pulse pressure (PP) were computed from blood pressure recordings. Repeated measures analysis of variance was used for comparison between groups during...

  4. Parenting goals: predictors of parent involvement in disease management of children with type 1 diabetes.

    Science.gov (United States)

    Robinson, Elizabeth M; Iannotti, Ronald J; Schneider, Stefan; Nansel, Tonja R; Haynie, Denise L; Sobel, Douglas O

    2011-09-01

    The purpose of this study was to develop a measure of diabetes-specific parenting goals for parents of children with type 1 diabetes and to examine whether parenting goals predict a change in parenting involvement in disease management. An independent sample of primary caretakers of 87 children aged 10 to 16 years with type 1 diabetes completed the measure of parenting goals (diabetes-specific and general goals); both parent and child completed measures of parent responsibility for diabetes management at baseline and 6 months. Parents ranked diabetes-specific parenting goals as more important than general parenting goals, and rankings were moderately stable over time. Parenting goals were related to parent responsibility for diabetes management. The relative ranking of diabetes-specific parenting goals predicted changes in parent involvement over 6 months, with baseline ranking of goals predicting more parental involvement at follow-up. Parenting goals may play an important role in family management of type 1 diabetes.

  5. Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases.

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    Rong Chen

    Full Text Available Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may

  6. The role of monocytes and monocyte-derived dendritic cells in type 1 diabetes mellitus and autoimmune thyroid disease

    NARCIS (Netherlands)

    W.K. Lam-Tse

    2003-01-01

    textabstractType 1 diabetes mellitus (DM1) and autoimmune thyroid disease (AITD) are organ specific autoimmune diseases in which the immune system is directed against the ß cells and the thyrocytes respectively. The etio-pathogenesis of organ-specific or endocrine autoimmune diseases is complex,

  7. The treatment of gastroesophageal reflux disease in menopausal women suffering from diabetes mellitus type II

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    Semikina Т.М.

    2016-12-01

    Full Text Available Purpose: to develop criteria for the selection of optimal tactics of supporting treatment of nonerosive gastroesophageal reflux disease with proton pump inhibitors in menopausal women suffering from diabetes mellitus type II. Material and Methods. 186 patients aged 45-59 who suffer from gastroesophageal reflux disease have been followed up, 46 of which suffer from diabetes mellitus type II as well. The climacteric syndrome's morbidity has been assessed in accordance with the modified menopause index; the level of glycated hemoglobin has been measured by the Abbott analyzer produced in the USA. Results. It is established that irrespective of the supporting treatment, the gastroesophageal reflux disease remittance was shorter in direct proportion with increase of the HbA1c level and the value of the modified menopause index in menopausal women suffering from diabetes mellitus type II. Conclusion. When the climacteric syndrome was mild or moderate, taking 20 mg Omeprazole once a day and "on demand" has comparable results, therefore this group of women prefer the "on demand" regimen as it lowers the risk of osteoporosis progression and further bone fracture. Taking 20 mg Omeprazole once a day, every other day, and "on demand" allows the disease remittance to prolong for a year and longer in less than 30% of women suffering from severe climacteric syndrome and having HbA1c>9.0%; however, this number may grow up to 70% of women in case they follow medical advice and reduce their carbohydrate input to 11 carbohydrate units and less.

  8. Prevalence of anemia in patients with type 1 and type 2 diabetes mellitus with chronic renal disease

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    Sergey A. Martynov

    2017-12-01

    Full Text Available Background. Diabetes mellitus (DM is a non-infectious disease with a high prevalence worldwide and is one of the most common causes of diabetic kidney disease (DKD. Anaemia is a well-known complication of chronic kidney disease (CKD and has been estimated to affect one in three adults with DM. Aims. To evaluate the prevalence and severity of anaemia among patients with DKD and to compare the distribution of anaemia among patients with diabetic and non-diabetic CKD. Methods. A total of 2,015 patients with DM [n = 807 with type 1 DM (T1DM; n = 1,208 with type 2 DM (T2DM] and 244 patients with biopsy-proven chronic glomerulonephritis (CGN were selected. Patients with glomerular filtration rate (GFR of <15 ml/min/1,73 m2 (stage 5 CKD and treated by erythropoietin-stimulating agents and/or iron medication were not included. The presence of anaemia was defined as haemoglobin (Hb of <130 g/l in men and <120 g/l in woman. GFR was calculated using the MDRD formula. CKD stages were defined based on stages 1–4 of CKD by KDOQI and KDIGO guidelines: stage 1 (GFR ≥ 90 ml/min/1.73 m2; stage 2 (GFR 60–89 ml/min/1.73 m2; stage 3 (GFR 30–59 ml/min/1.73 m2; stage 3a (45–59 ml/min/1.73 m2; stage 3b (GFR 30–44 ml/min/1.73 m2; stage 4 (GFR 15–29 ml/min/1.73 m2. Results. Rates of anaemia were higher among patients with DM and DKD (38.8% and 22.6% for T1DM and T2DM, respectively than diabetic patients without DKD (16.6% and 11.5%, respectively. Prevalence of anaemia by CKD stage increased from 23.3% in stage 1 to 80% in stage 4 among patients with T1DM, and from 16.9% to 81 % among patients with T2DM. The prevalence of anaemia was also higher among protoeinuric patients (53.9% and 34.4% for T1DM and T2DM, respectively relative to microalbuminuric patients (29.4% and 17.6%, respectively. Anaemia prevalence was significantly greater in DKD due to T1DM (53.9% than in CGN (19.7, and the rates did not differ based on stages of CKD. Conclusions. We found a two

  9. Medical care of type 2 diabetes in German disease management programmes: a population-based evaluation.

    Science.gov (United States)

    Stark, Reneé G; Schunk, Michaela V; Meisinger, Christine; Rathmann, Wolfgang; Leidl, Reiner; Holle, Rolf

    2011-05-01

    Type 2 diabetes disease management programmes (DDMPs) are offered by German social health insurance to promote healthcare consistent with evidence-based medical guidelines. The aim of this study was to compare healthcare quality and medical endpoints between diabetes management programme participants and patients receiving usual care designated as controls. All patients with type 2 diabetes (age range: 36-81) in a cross-sectional survey of a cohort study, performed by the Cooperative Health Research in the Region of Augsburg, received a self-administered questionnaire regarding their diabetes care. Physical examination and laboratory tests were also performed. The analysis only included patients with social health insurance and whose participation status in a diabetes disease management program was validated by the primary physician (n = 166). Regression analyses, adjusting for age, sex, education, diabetes duration, baseline waist circumference and clustering regarding primary physician were conducted. Evaluation of healthcare processes showed that those in diabetes disease management programmes (n = 89) reported medical examination of eyes and feet and medical advice regarding diet [odds ratio (OR): 2.39] and physical activity (OR: 2.87) more frequently, received anti-diabetic medications (OR: 3.77) and diabetes education more often (OR: 2.66) than controls. Both groups had satisfactory HbA(1c) control but poor low-density lipoprotein cholesterol control. Blood pressure goals (management programmes (OR: 2.21). German diabetes disease management programmes are associated with improved healthcare processes and blood pressure control. Low-density lipoprotein cholesterol control must be improved for all patients with diabetes. Further research will be required to assess the long-term effects of this diabetes disease management programme. Copyright © 2011 John Wiley & Sons, Ltd.

  10. Development of a Coronary Heart Disease Risk Prediction Model for Type 1 Diabetes: The Pittsburgh CHD in Type 1 Diabetes Risk Mode

    NARCIS (Netherlands)

    Zgibor, J.C.; Ruppert, K.; Orchard, T.J.; Soedamah-Muthu, S.S.; Fuller, J.H.; Chaturvedi, N.; Roberts, M.S.

    2010-01-01

    Aim - To create a coronary heart disease (CHD) risk prediction model specific to type 1 diabetes. Methods - Development of the model used data from the Pittsburgh Epidemiology of Diabetes Complications Study (EDC). EDC subjects had type 1 diabetes diagnosed between 1950 and 1980, received their

  11. MRI bone marrow findings in 63 patients with type I Gaucher's disease

    Energy Technology Data Exchange (ETDEWEB)

    Poll, L.W. [Berufsgenossenschaftliche Unfallklinik Duisburg GmbH (Germany). Abt. Radiologie; Willers, R. [Duesseldorf Univ. (Germany). Zentrum fuer Information, Kommunikation und Medientechnologie; Haeussinger, D. [Universitaetsklinikum Duesseldorf (Germany). Klinik fuer Gastroenterologie, Hepatologie und Infektiologie; Moedder, U. [Universitaetsklinikum Duesseldorf (Germany). Inst. fuer Radiologie; Dahl, S. vom [St.-Franziskus-Hospital Koeln, Akademisches Lehrkrankenhaus der Koeln Univ. (Germany). Klinik fuer Innere Medizin.

    2010-11-15

    Purpose: To determine whether MR bone marrow findings in Gaucher patients may help to identify patients at high risk of developing severe Gaucher bone complications exemplified by avascular necrosis (AVN) of the femoral head. Materials and Methods: MR images were obtained in 63 Type I Gaucher patients through a standard protocol using coronal T1 and T2-weighted sequences of the lower extremities. The location and extent of infiltrated marrow was established using a semi-quantitative MRI scoring method (Duesseldorf Gaucher score, DGS) and the morphological pattern of bone marrow involvement determined (whether homogeneous type A or non-homogeneous type B). The active marrow process with bone edema and AVN of the femoral head were also analyzed. Results: Bone marrow involvement was observed in femoral sites more than in tibial sites. A high DGS was significantly correlated with type B morphology and femoral AVN (both p < 0.0001). Splenectomized patients showed a significantly higher Duesseldorf Gaucher score and type B morphology than non-splenectomized patients (both p < 0.05). AVN was seen in 46 % of patients with type B morphology versus 3 % in type A morphology (p < 0.0001). DGS and morphology of bone marrow involvement were not significantly correlated with active marrow processes. Conclusion: Type B marrow morphology and extensive marrow packing were significantly associated with AVN of the femoral head (both p < 0.0001). These patterns are considered predictive and may be employed in a disease management context to alert physicians to the need for urgent therapeutic measures. (orig.)

  12. MRI bone marrow findings in 63 patients with type I Gaucher's disease

    International Nuclear Information System (INIS)

    Poll, L.W.; Willers, R.; Haeussinger, D.; Moedder, U.; Dahl, S. vom

    2010-01-01

    Purpose: To determine whether MR bone marrow findings in Gaucher patients may help to identify patients at high risk of developing severe Gaucher bone complications exemplified by avascular necrosis (AVN) of the femoral head. Materials and Methods: MR images were obtained in 63 Type I Gaucher patients through a standard protocol using coronal T1 and T2-weighted sequences of the lower extremities. The location and extent of infiltrated marrow was established using a semi-quantitative MRI scoring method (Duesseldorf Gaucher score, DGS) and the morphological pattern of bone marrow involvement determined (whether homogeneous type A or non-homogeneous type B). The active marrow process with bone edema and AVN of the femoral head were also analyzed. Results: Bone marrow involvement was observed in femoral sites more than in tibial sites. A high DGS was significantly correlated with type B morphology and femoral AVN (both p < 0.0001). Splenectomized patients showed a significantly higher Duesseldorf Gaucher score and type B morphology than non-splenectomized patients (both p < 0.05). AVN was seen in 46 % of patients with type B morphology versus 3 % in type A morphology (p < 0.0001). DGS and morphology of bone marrow involvement were not significantly correlated with active marrow processes. Conclusion: Type B marrow morphology and extensive marrow packing were significantly associated with AVN of the femoral head (both p < 0.0001). These patterns are considered predictive and may be employed in a disease management context to alert physicians to the need for urgent therapeutic measures. (orig.)

  13. Risk factors for periodontal diseases among Yemeni type II diabetic patients. A case-control study.

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    Anas Shamala

    2017-08-01

    Full Text Available Background: Chronic periodontal diseases are one of diabetes mellitus complications. The present study aims to compare the periodontal status of type II diabetic patients to a control group and assess the role of risk factors in both groups. Materials and methods: A case-control study was conducted of 270 individuals (132 type II diabetics and 138 non-diabetics. Full mouth periodontal examination including plaque index, gingival bleeding, gingival recession, clinical attachment loss (CAL, tooth mobility, furcation involvement and the number of missing teeth. The case group was subdivided according to glycosylated hemoglobin (HbA1c status (poorly controlled HbA1c >8 and well controlled HbA1c≤8 Likewise, the duration of diabetes mellitus as short or long duration (DM≤10 or >10. The diabetic group was also subdivided according to smoking and Khat chewing habits. Result: The severity of periodontal disease among type II diabetic patients were significantly higher compared to the control group regarding the plaque index 2.6 (1.6-4.3, bleeding on probing 3.5 (2.3-13.0, gingival recession 2.0 (1.2-3.4, furcation involvement 4.0 (2.3-6.7, clinical attachment loss 5.7 (3.1-10.5, tooth mobility 2.0 (1.2-3.4, and number of missing teeth 4.4 (2.3-8.5. In addition, poorly controlled type II DM and long duration had higher CAL and number of missing teeth than well-controlled DM and short duration. No significant differences were found between smokers/nonsmokers and Khat chewers/non-chewers among the diabetic group. Conclusion: Type II diabetic patients have severe periodontal destruction and tooth loss compared to non-diabetic people and there were no differences within the diabetic group in regards to smoking and Khat chewing habits.

  14. "PREVALENCE OF AUTOANTIBODIES TO THYROID PEROXIDASE AND AUTOIMMUNE THYROID DISEASE IN TYPE I DIABETES MELLITUS"

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    H. Moayeri A. Rabbani

    2004-09-01

    Full Text Available Type I diabetes mellitus (DM is frequently associated with autoimmune thyroid disease (ATD. Association of ATD and type I DM has been described with varying frequencies but there is still debate about the situation in the Iranian population. We investigated the prevalence of anti thyroid peroxidase (anti-TPO antibodies and ATD in children and adolescents with type I DM. A total of 145 patients with type I DM were participated in this study. They were screened for anti-TPO antibodies and TSH levels. Signs and symptoms of hypothyroidism and hyperthyroidism and the presence of goiter were sought. A group of 50 healthy unrelated girls and boys aged 11-16 years served as controls. Anti-TPO antibodies were found in 34 (23.4% diabetic patients and 1 subject (2% in the control group (P<0.001. Frequency of anti TPO antibodies was significantly higher in girls than boys (P<0.05. We failed to show any significant correlation between thyroid autoimmunity and duration of DM. We found that younger patients at diagnosis are more likely to be anti-TPO negative (P<0.001. Out of 145 diabetic patients, 32 (22% had visible goiter. Subclinical hypothyroidism, hypothyroidism and thyrotoxicosis occurred in 1, 9 and 1 patients, respectively. Visible goiter was found in 2 subjects (4% of the control group, but all of them were euthyroid. In conclusion, the evaluation of thyroid autoimmunity in type I diabetic patients may improve the diagnosis of thyroid disease in early stages. Yearly examination of anti-TPO antibodies allows identifying diabetic patients with thyroid autoimmunity.

  15. [Celiac disease in a group of children and adolescents with type 1 diabetes mellitus].

    Science.gov (United States)

    Brandt, Katia G; Silva, Giselia A P; Antunes, Margarida M C

    2004-12-01

    To know the prevalence of celiac disease (CD) in a group of children and adolescents with type I diabetes mellitus. A cross sectional study was conducted at the Instituto Materno Infantil de Pernambuco (IMIP) in March 2000. The sample consisted of 19 children and adolescents with type I diabetes mellitus that had the human anti-tissue transglutaminase antibodies assessed using kits from the Eurospital Laboratory. In case of positive results it was realized small intestine biopsy to confirm the diagnosis. For the calculation of the prevalence of CD it was considered the number of patients with serum positive histological alterations of the mucous membrane of the small intestine compatible with CD. Four patients presented serum positivity for human anti-tissue transglutaminase antibodies with a serum prevalence of 21% (4/19). Out of these four subjects, three who accomplished small intestine biopsy presented histological alterations compatible with CD. The prevalence of CD in this group was 15.8% (3/19). The prevalence of CD in this study group was high, suggesting that those with type I diabetes mellitus should be led as a group of high risk to develop this disease.

  16. In Vivo Assessment of Neurodegeneration in Type C Niemann-Pick Disease by IDEAL-IQ.

    Science.gov (United States)

    Guo, Ruo-Mi; Li, Qing-Ling; Luo, Zhong-Xing; Tang, Wen; Jiao, Ju; Wang, Jin; Kang, Zhuang; Chen, Shao-Qiong; Zhang, Yong

    2018-01-01

    To noninvasively assess the neurodegenerative changes in the brain of patients with Niemann-Pick type C (NPC) disease by measuring the lesion tissue with the iterative decomposition of water and fat with echo asymmetry and least square estimation-iron quantification (IDEAL-IQ). Routine brain MRI, IDEAL-IQ and 1 H-proton magnetic resonance spectroscopy ( 1 H-MRS, served as control) were performed on 12 patients with type C Niemann-Pick disease (4 males and 8 females; age range, 15-61 years; mean age, 36 years) and 20 healthy subjects (10 males and 10 females; age range, 20-65 years; mean age, 38 years). The regions with lesion and the normal appearing regions (NARs) of patients were measured and analyzed based on the fat/water signal intensity on IDEAL-IQ and the lipid peak on 1 H-MRS. Niemann-Pick type C patients showed a higher fat/water signal intensity ratio with IDEAL-IQ on T2 hyperintensity lesions and NARs (3.7-4.9%, p IQ instead of 1 H-MRS. The findings of this study suggested that IDEAL-IQ may be useful as a noninvasive and objective method in the evaluation of patients with NPC; additionally, IDEAL-IQ can be used to quantitatively measure the brain parenchymal adipose content and monitor patient follow-up after treatment of NPC.

  17. Prevalence and clinical profile of celiac disease in children with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Rajesh Joshi

    2015-01-01

    Full Text Available Objective: To determine the prevalence of celiac disease (CD in children with type 1 diabetes mellitus (TIDM in follow-up in a Tertiary Care Referral Centre in Western India and to describe the clinical features indicative of CD in screened patients of TIDM. Study Design: In this single center observational cross-sectional study, 71 children who were diagnosed with TIDM were subjected to screening for CD with tissue transglutaminase antibody testing. Those who tested positive were offered intestinal biopsy for the confirmation of diagnosis. Clinical profiles of both groups of patients were compared and manifestations of CD were delineated. Results: The study revealed the prevalence of CD (based on serology in children with Type 1 diabetes as 15.49%. The prevalence of biopsy-confirmed CD was 7.04%. Of the diagnosed CD patients, one-third were symptomatic at the time of screening while the majority was asymptomatic. The major clinical features indicative of CD were intestinal symptoms, anemia, rickets, and short stature. Autoimmune thyroid disease was prevalent in 29.6% of the patients with TIDM followed by CD. Conclusions: The high prevalence of CD in children with Type 1 diabetes emphasizes the need for routine screening programs to be in place for these high-risk populations. The clinical profile of patients with CD further elaborates the indicators of CD and the need to screen for them.

  18. The prevalence and extent of gastroesophageal reflux disease correlates to the type of lung transplantation.

    Science.gov (United States)

    Fisichella, Piero Marco; Davis, Christopher S; Shankaran, Vidya; Gagermeier, James; Dilling, Daniel; Alex, Charles G; Kovacs, Elizabeth J; Joehl, Raymond J; Love, Robert B

    2012-02-01

    Evidence is increasingly convincing that lung transplantation is a risk factor of gastroesophageal reflux disease (GERD). However, it is still not known if the type of lung transplant (unilateral, bilateral, or retransplant) plays a role in the pathogenesis of GERD. The records of 61 lung transplant patients who underwent esophageal function tests between September 2008 and May 2010, were retrospectively reviewed. These patients were divided into 3 groups based on the type of lung transplant they received: unilateral (n=25); bilateral (n=30), and retransplant (n=6). Among these groups we compared: (1) the demographic characteristics (eg, sex, age, race, and body mass index); (2) the presence of Barrett esophagus, delayed gastric emptying, and hiatal hernia; and (3) the esophageal manometric and pH-metric profile. Distal and proximal reflux were more prevalent in patients with bilateral transplant or retransplant and less prevalent in patients after unilateral transplant, regardless of the cause of their lung disease. The prevalence of hiatal hernia, Barrett esophagus, and the manometric profile were similar in all groups of patients. Although our data show a discrepancy in prevalence of GERD in patients with different types of lung transplantation, we cannot determine the exact cause for these findings from this study. We speculate that the extent of dissection during the transplant places the patients at risk for GERD. On the basis of the results of this study, a higher level of suspicion of GERD should be held in patients after bilateral or retransplantation.

  19. Neurofibromatosis type 1 and the "elephant man's" disease: the confusion persists: an ethnographic study.

    Science.gov (United States)

    Legendre, Claire-Marie; Charpentier-Côté, Catherine; Drouin, Régen; Bouffard, Chantal

    2011-02-09

    In 1986, two Canadian geneticists had demonstrated that Joseph Merrick, better known as the Elephant Man, suffered from the Proteus syndrome and not from neurofibromatosis type 1 (NF1), as was alleged by dermatologist Parkes in 1909. Despite this and although the two diseases differ at several levels: prevalence, diagnostic criteria, clinical manifestations and transmission, the confusion between NF1 and the "elephant man's" disease continues in medical and social representations by current linguistic usage, and in some media reports. With this article, we want to 1) document the persistence and extent of this fallacy, 2) identify certain critical factors that contribute to its persistence, and 3) evaluate its impact on the health and well being of patients with NF1 and their family members. Participant observation in the course of an ethnographic study on intergenerational dialogue between individuals with neurofibromatosis and their parents - Analysis of the scientific literature and of pinpoint articles in the print and online news media. Our findings show that because physicians have little knowledge about NF1, several print and online news media and a lot of physicians continue to make the confusion between NF1 and the disease the "elephant man". This misconception contributes to misinformation about the disease, feeding prejudices against affected patients, exacerbating the negative impacts of the disease on their quality of life, their cognitive development, their reproductive choices, as well as depriving them of proper care and appropriate genetic counseling. If family physicians and pediatricians were properly informed about the disease, they could refer their patients with NF1 to NF clinics and to specialists. Thus, patients and their family members would benefit from better-tailored clinical management of their cases, perhaps even optimal management. [corrected

  20. Neurofibromatosis type 1 and the "elephant man's" disease: the confusion persists: an ethnographic study.

    Directory of Open Access Journals (Sweden)

    Claire-Marie Legendre

    2011-02-01

    Full Text Available In 1986, two Canadian geneticists had demonstrated that Joseph Merrick, better known as the Elephant Man, suffered from the Proteus syndrome and not from neurofibromatosis type 1 (NF1, as was alleged by dermatologist Parkes in 1909. Despite this and although the two diseases differ at several levels: prevalence, diagnostic criteria, clinical manifestations and transmission, the confusion between NF1 and the "elephant man's" disease continues in medical and social representations by current linguistic usage, and in some media reports. With this article, we want to 1 document the persistence and extent of this fallacy, 2 identify certain critical factors that contribute to its persistence, and 3 evaluate its impact on the health and well being of patients with NF1 and their family members.Participant observation in the course of an ethnographic study on intergenerational dialogue between individuals with neurofibromatosis and their parents - Analysis of the scientific literature and of pinpoint articles in the print and online news media.Our findings show that because physicians have little knowledge about NF1, several print and online news media and a lot of physicians continue to make the confusion between NF1 and the disease the "elephant man". This misconception contributes to misinformation about the disease, feeding prejudices against affected patients, exacerbating the negative impacts of the disease on their quality of life, their cognitive development, their reproductive choices, as well as depriving them of proper care and appropriate genetic counseling.If family physicians and pediatricians were properly informed about the disease, they could refer their patients with NF1 to NF clinics and to specialists. Thus, patients and their family members would benefit from better-tailored clinical management of their cases, perhaps even optimal management. [corrected

  1. A nanotechnological approach to the management of Alzheimer disease and type 2 diabetes.

    Science.gov (United States)

    Alam, Qamre; ZubairAlam, Mohammad; Karim, Sajjad; Gan, Siew H; Kamal, Mohammad A; Jiman-Fatani, Asif; Damanhouri, Ghazi A; Abuzenadah, Adel M; Chaudhary, Adeel G; Haque, Absarul

    2014-04-01

    Alzheimer's disease (AD) and type 2 diabetes (T2D) are both prevalent in older individuals and have gained significant attention due to alarming rates of increase. The high incidences of these diseases pose a great socioeconomic burden and cause major public health concerns worldwide. A number of studies have established potential links between AD and T2D, supporting the hypothesis that T2D is linked with an increased risk of AD and that controlling diabetes could have a positive impact on the prevention of AD. At present, both diseases lack precise diagnostic approaches for early intervention and effective cure. Further, the currently available diagnostic tools for AD screening are insufficiently sensitive and robust for preventive measures. Although several drugs are used for the treatment of both these diseases, none of these drugs offers complete remission of the disease, merely symptomatic relief. Moreover, these drugs have limited efficacy because of problems such as conventional drug delivery systems beyond the blood brain barrier, a lack of target specificity and diminished potency. From this perspective, the emerging field of nanotechnology has offered new techniques and tools to overcome these challenges. In this review, we discuss the direct and indirect limitations of existing therapies and describe alternative potential nanotechnological approaches that could be utilized to overcome these limitations. New insight in the field of nanomedicine is necessary for early diagnosis, the development of novel drug therapies, the action of drugs and prevention, as well as for gaining an in-depth understanding of the complex biology of both diseases.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Comparison of the clinical course of Japanese MM1-type sporadic Creutzfeldt-Jakob disease between subacute spongiform encephalopathy and panencephalopathic-type.

    Science.gov (United States)

    Iwasaki, Yasushi; Tatsumi, Shinsui; Mimuro, Maya; Kitamoto, Tetsuyuki; Yoshida, Mari

    2014-06-01

    Approximately half of Japanese sporadic Creutzfeldt-Jakob disease (sCJD) cases show panencephalopathic-type (PE-type) pathology, which is a rare subtype in North Americans and Europeans. Until now, the differences in the clinical course between subacute spongiform encephalopathy (SSE) cases and PE-type cases have been unclear. To investigate the clinical course of both subtypes, clinical findings from 42 Japanese MM1-type sCJD cases (20 SSE cases and 22 PE-type cases) were retrospectively evaluated by statistical analysis. No significant differences could be found regarding age at disease onset, the period between disease onset and first observation of myoclonus, the period between disease onset and the first observation of periodic sharp-wave complexes on electroencephalogram, or the period between disease onset and progression to the akinetic mutism state - whereas total disease duration and the period between the akinetic mutism state and death were significantly longer in PE-type cases. The prolonged disease duration was induced by the extended survival period in the akinetic mutism state. There was a statistically significant difference between the two series regarding performance of tube-feeding, but no statistically significant difference regarding performance of tracheotomy or gastrostomy. None of the cases received mechanical ventilation. We speculate that the most crucial factor of the prolonged survival period of Japanese sCJD cases, particularly in the PE-type, is that the introduction of tube-feeding in the akinetic mutism state leads to the stabilization of the patient's general condition. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. The early life origin theory in the development of cardiovascular disease and type 2 diabetes.

    Science.gov (United States)

    Lindblom, Runa; Ververis, Katherine; Tortorella, Stephanie M; Karagiannis, Tom C

    2015-04-01

    Life expectancy has been examined from a variety of perspectives in recent history. Epidemiology is one perspective which examines causes of morbidity and mortality at the population level. Over the past few 100 years there have been dramatic shifts in the major causes of death and expected life length. This change has suffered from inconsistency across time and space with vast inequalities observed between population groups. In current focus is the challenge of rising non-communicable diseases (NCD), such as cardiovascular disease and type 2 diabetes mellitus. In the search to discover methods to combat the rising incidence of these diseases, a number of new theories on the development of morbidity have arisen. A pertinent example is the hypothesis published by David Barker in 1995 which postulates the prenatal and early developmental origin of adult onset disease, and highlights the importance of the maternal environment. This theory has been subject to criticism however it has gradually gained acceptance. In addition, the relatively new field of epigenetics is contributing evidence in support of the theory. This review aims to explore the implication and limitations of the developmental origin hypothesis, via an historical perspective, in order to enhance understanding of the increasing incidence of NCDs, and facilitate an improvement in planning public health policy.

  5. Functional mechanism of neuroprotection by inhibitors of type B monoamine oxidase in Parkinson's disease.

    Science.gov (United States)

    Naoi, Makoto; Maruyama, Wakako

    2009-08-01

    Neuroprotective therapy has been proposed for age-related neurodegenerative disorders, including Parkinson's disease. Inhibitors of type B monoamine oxidase (MAOB-Is), rasagiline and (-)deprenyl, are the most promising candidate neuroprotective drugs. Clinical trials of rasagiline in patients with Parkinson's disease suggest that rasagiline may have some disease-modifying effects. Results using animal and cellular models have proved that the MAOB-Is protect neurons by the intervention of 'intrinsic' mitochondrial apoptotic cascade and the induction of prosurvival antiapoptotic Bcl-2 and neurotrophic factors. Rasagiline-related MAOB-Is prevent mitochondrial permeability transition induced by various insults and activation of subsequent apoptotic cascades: cytochrome c release, casapase activation, and condensation and fragmentation of nuclear DNA. MAOB-Is increase transcription of prosurvival genes through activating the nuclear transcription factor-(NF) system. Rasagiline increases the protein and mRNA levels of GDNF in dopaminergic SH-SY5Y cells, whereas (-)deprenyl increases those of BDNF. Systemic administration of (-)deprenyl and rasagiline increases these neurotrophic factors in the cerebrospinal fluid from patients with Parkinson's disease and nonhuman primates. This review presents recent advances in our understanding of the neuroprotection offered by MAOB-Is and possible evaluation of neuroprotective efficacy in clinical samples is discussed.

  6. Impaired Autophagy in the Lipid-Storage Disorder Niemann-Pick Type C1 Disease

    Directory of Open Access Journals (Sweden)

    Sovan Sarkar

    2013-12-01

    Full Text Available Autophagy dysfunction has been implicated in misfolded protein accumulation and cellular toxicity in several diseases. Whether alterations in autophagy also contribute to the pathology of lipid-storage disorders is not clear. Here, we show defective autophagy in Niemann-Pick type C1 (NPC1 disease associated with cholesterol accumulation, where the maturation of autophagosomes is impaired because of defective amphisome formation caused by failure in SNARE machinery, whereas the lysosomal proteolytic function remains unaffected. Expression of functional NPC1 protein rescues this defect. Inhibition of autophagy also causes cholesterol accumulation. Compromised autophagy was seen in disease-affected organs of Npc1 mutant mice. Of potential therapeutic relevance is that HP-β-cyclodextrin, which is used for cholesterol-depletion treatment, impedes autophagy, whereas stimulating autophagy restores its function independent of amphisome formation. Our data suggest that a low dose of HP-β-cyclodextrin that does not perturb autophagy, coupled with an autophagy inducer, may provide a rational treatment strategy for NPC1 disease.

  7. Oxidative Stress: A Pathogenic Mechanism for Niemann-Pick Type C Disease

    Directory of Open Access Journals (Sweden)

    Mary Carmen Vázquez

    2012-01-01

    Full Text Available Niemann-Pick type C (NPC disease is a neurovisceral atypical lipid storage disorder involving the accumulation of cholesterol and other lipids in the late endocytic pathway. The pathogenic mechanism that links the accumulation of intracellular cholesterol with cell death in NPC disease in both the CNS and the liver is currently unknown. Oxidative stress has been observed in the livers and brains of NPC mice and in different NPC cellular models. Moreover, there is evidence of an elevation of oxidative stress markers in the serumof NPC patients. Recent evidence strongly suggests that mitochondrial dysfunction plays an important role in NPC pathogenesis and that mitochondria could be a significant source of oxidative stress in this disease. In this context, the accumulation of vitamin E in the late endosomal/lysosomal compartments in NPC could lead to a potential decrease of its bioavailability and could be another possible cause of oxidative damage. Another possible source of reactive species in NPC is the diminished activity of different antioxidant enzymes. Moreover, because NPC is mainly caused by the accumulation of free cholesterol, oxidized cholesterol derivatives produced by oxidative stress may contribute to the pathogenesis of the disease.

  8. Impaired autophagy in the lipid-storage disorder Niemann-Pick type C1 disease.

    Science.gov (United States)

    Sarkar, Sovan; Carroll, Bernadette; Buganim, Yosef; Maetzel, Dorothea; Ng, Alex H M; Cassady, John P; Cohen, Malkiel A; Chakraborty, Souvik; Wang, Haoyi; Spooner, Eric; Ploegh, Hidde; Gsponer, Joerg; Korolchuk, Viktor I; Jaenisch, Rudolf

    2013-12-12

    Autophagy dysfunction has been implicated in misfolded protein accumulation and cellular toxicity in several diseases. Whether alterations in autophagy also contribute to the pathology of lipid-storage disorders is not clear. Here, we show defective autophagy in Niemann-Pick type C1 (NPC1) disease associated with cholesterol accumulation, where the maturation of autophagosomes is impaired because of defective amphisome formation caused by failure in SNARE machinery, whereas the lysosomal proteolytic function remains unaffected. Expression of functional NPC1 protein rescues this defect. Inhibition of autophagy also causes cholesterol accumulation. Compromised autophagy was seen in disease-affected organs of Npc1 mutant mice. Of potential therapeutic relevance is that HP-β-cyclodextrin, which is used for cholesterol-depletion treatment, impedes autophagy, whereas stimulating autophagy restores its function independent of amphisome formation. Our data suggest that a low dose of HP-β-cyclodextrin that does not perturb autophagy, coupled with an autophagy inducer, may provide a rational treatment strategy for NPC1 disease. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Role of σ1 Receptors in Learning and Memory and Alzheimer's Disease-Type Dementia.

    Science.gov (United States)

    Maurice, Tangui; Goguadze, Nino

    2017-01-01

    The present chapter will review the role of σ 1 receptor in learning and memory and neuroprotection , against Alzheimer's type dementia. σ 1 Receptor agonists have been tested in a variety of pharmacological and pathological models of learning impairments in rodents these last past 20 years. Their anti-amnesic effects have been explained by the wide-range modulatory role of σ 1 receptors on Ca 2+ mobilizations, neurotransmitter responses, and particularly glutamate and acetylcholine systems, and neurotrophic factors. Recent observations from genetic and pharmacological studies have shown that σ 1 receptor can also be targeted in neurodegenerative diseases, and particularly Alzheimer's disease . Several compounds, acting partly through the σ 1 receptor, have showed effective neuroprotection in transgenic mouse models of Alzheimer's disease . We will review the data and discuss the possible mechanisms of action, particularly focusing on oxidative stress and mitochondrial integrity, trophic factors and a novel hypothesis suggesting a functional interaction between the σ 1 receptor and α 7 nicotinic acetylcholine receptor. Finally, we will discuss the pharmacological peculiarities of non-selective σ 1 receptor ligands, now developed as neuroprotectants in Alzheimer's disease , and positive modulators, recently described and that showed efficacy against learning and memory deficits.

  10. Haemophilus influenzae type b disease in Auckland children during the Hib vaccination era: 1995-2009.

    Science.gov (United States)

    Leung, Bonnie; Taylor, Susan; Drinkovic, Dragana; Roberts, Sally; Carter, Phil; Best, Emma

    2012-11-09

    To characterise Haemophilus influenzae type b (Hib) invasive disease in the era of Hib vaccination, in children of the greater Auckland region of New Zealand. Identification of sterile site culture positive Hib via the Auckland hospital laboratories databases and national laboratory surveillance database in the time period; 1995 to 2009. There were a total of 26 cases in the Auckland Region. Over the 15-year period, the annual incidence of invasive Hib disease was 0.61 per 100,000 (95% CI: 0.4-0.9) for children aged under 15 years and 1.65 per 100,000 (95% CI: 1.1-2.5) for children aged under 5 years. Ninety-two percent were under 5 years and 54% were under 1 year. Sixty percent of the children were of Maori and Pacific ethnicity. The predominant diagnosis was meningitis, accounting for 15 cases (60%). There were no fatalities. Forty-eight percent of affected children were completely unimmunised with the Hib vaccine which has been fully funded on the National Immunisation Schedule since 1994. Since the introduction of the Hib vaccine, the disease rates have greatly reduced in the Auckland region. Although ethnic disparities have improved amongst the cases that occur, immunisation rates in cases are low and infants remain most at risk. Current emphasis on intensifying immunisation programmes to achieve higher vaccination rates and timeliness of delivery will help in efforts to achieve elimination of the disease in New Zealand.

  11. Role of gut microbiota in obesity, type 2 diabetes and Alzheimer's disease.

    Science.gov (United States)

    Naseer, Muhammad I; Bibi, Fehmida; Alqahtani, Mohammed H; Chaudhary, Adeel G; Azhar, Esam I; Kamal, Mohammad A; Yasir, Muhammad

    2014-03-01

    In recent years, there is a growing interest in research to investigate the importance of gut microbiome in health and diseases. This opens a new area of research for the role of microbial flora of the human gut in inflammation, energy homeostasis, pathogenesis of obesity and other associated disorders. Recent studies propose association of the gut microbiome with development of obesity and metabolic syndromes, such as type 2 diabetes mellitus (T2DM). The T2DM is a metabolic disease that is mainly caused by obesity-linked insulin resistance. The vascular effects of obesity appears to play a role in the development of Alzheimer's disease (AD) that is one of the rapidly growing diseases of a late stage of life all over the world. Studies from both humans and mice models have been demonstrated the engagement of gut microbial flora in the pathogenesis of obesity and host metabolism. The aim of this review is to discuss the current findings that may explain the cascade of gut microbial flora participation in the development of obesity, T2DM and further initiation of AD. In addition, the available data regarding the mechanisms that have been proposed to elucidate the role of gut microbiota in weight gain and possible cause of T2DM and AD have been examined.

  12. Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms

    Science.gov (United States)

    Visser, Jeroen; Rozing, Jan; Sapone, Anna; Lammers, Karen; Fasano, Alessio

    2010-01-01

    Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on celiac disease (CD), an autoimmune enteropathy, and type 1 diabetes (T1D), a hyperglycosaemia caused by a destructive autoimmune process targeting the insulin-producing pancreatic islet cells. Even if environmental factors and genetic susceptibility are clearly involved in the pathogenesis of autoimmunity, for most autoimmune disorders there is no or little knowledge about the causing agent or genetic makeup underlying the disease. In this respect, CD represents a unique autoimmune disorder because a close genetic association with HLA-DQ2 or HLA-DQ8 haplotypes and, more importantly, the environmental trigger (the gliadin fraction of gluten-containing grains wheat, barley, and rye) are known. Conversely, the trigger for autoimmune destruction of pancreatic ß cells in T1D is unclear. Interestingly, recent data suggest that gliadin is also involved in the pathogenesis of T1D. There is growing evidence that increased intestinal permeability plays a pathogenic role in various autoimmune diseases including CD and T1D. Therefore, we hypothesize that besides genetic and environmental factors, loss of intestinal barrier function is necessary to develop autoimmunity. In this review, each of these components will be briefly reviewed. PMID:19538307

  13. Charcot-Marie-Tooth disease type 1A: morphological phenotype of the 17p duplication versus PMP22 point mutations

    NARCIS (Netherlands)

    Gabreëls-Festen, A. A.; Bolhuis, P. A.; Hoogendijk, J. E.; Valentijn, L. J.; Eshuis, E. J.; Gabreëls, F. J.

    1995-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) or hereditary motor and sensory neuropathy type Ia (HMSN type Ia) is an autosomal dominant demyelinating polyneuropathy, which may result from duplications as large as 1.5 Mb on chromosome 17p 11.2-p12 encompassing the gene for the peripheral myelin

  14. Safety and Efficacy of Liraglutide in Patients With Type 2 Diabetes and End-Stage Renal Disease

    DEFF Research Database (Denmark)

    Idorn, Thomas; Knop, Filip K; Jørgensen, Morten B

    2016-01-01

    OBJECTIVE: To evaluate parameters related to safety and efficacy of liraglutide in patients with type 2 diabetes and dialysis-dependent end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS: Twenty-four patients with type 2 diabetes and ESRD and 23 control subjects with type 2 diabetes...

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

    Science.gov (United States)

    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.

  16. MAVS is not a Likely Susceptibility Locus for Addison's Disease and Type 1 Diabetes.

    Science.gov (United States)

    Zurawek, Magdalena; Fichna, Marta; Kazimierska, Marta; Fichna, Piotr; Dzikiewicz-Krawczyk, Agnieszka; Przybylski, Grzegorz; Ruchala, Marek; Nowak, Jerzy

    2017-06-01

    Mitochondrial antiviral signaling (MAVS) protein is an intracellular adaptor molecule, downstream of viral sensors, retinoid acid-inducible gene I (RIG-I)-like receptors (RLRs). Impaired antiviral cell signaling might contribute to autoimmunity. Studies have recently shown variations in genes encoding RLRs as risk factors for autoimmune diseases. We investigated whether MAVS coding polymorphisms are associated with Addison's disease (AD) and type 1 diabetes (T1D) in Polish population. We genotyped 140 AD, 532 T1D patients and 600 healthy controls for MAVS rs17857295, rs7262903, rs45437096 and rs7269320. Genotyping was performed by TaqMan assays. Distribution of the MAVS genotypes and alleles did not reveal significant differences between patients and controls (p > 0.05). This analysis did not indicate the association of the MAVS locus with susceptibility to AD and T1D.

  17. Celiac Disease and Pediatric Type 1 Diabetes: Diagnostic and Treatment Dilemmas

    Directory of Open Access Journals (Sweden)

    Daneman Denis

    2010-05-01

    Full Text Available Abstract Despite the advent of sensitive and specific serologic testing, routine screening for celiac disease (CD in diabetic populations may not be universal practice, and many clinicians struggle to find the optimal approach to managing CD in pediatric Type 1 diabetes (T1D patients. While some clinicians advocate screening for CD in all patients with T1D, others are unsure whether this is warranted. The diagnosis of patients who present with symptomatic CD, including malabsorption and obvious pathology upon biopsy, remains straightforward, with improvements noted on a gluten-free diet. Many patients identified by screening, however, tend to be asymptomatic. Evidence is inconclusive as to whether the benefits of screening and potentially treating asymptomatic individuals outweigh the harms of managing a population already burdened with a serious illness. This review focuses on current knowledge of CD in children and youth with T1D, highlighting important elements of the disease's pathophysiology, epidemiology, clinical presentation, and diagnostic challenges.

  18. Prevalence of celiac disease autoimmunity in children with type 1 diabetes

    DEFF Research Database (Denmark)

    Adlercreutz, Emma H; Svensson, Jannet; Hansen, Dorte

    2015-01-01

    OBJECTIVES: The aim was to determine the prevalence of celiac disease autoimmunity in children with type 1 diabetes (T1D) diagnosed in Denmark and Sweden. METHODS: A total of 662 Swedish children with T1D were matched with 1080 Danish children with T1D and 309 healthy children from Sweden and 283...... was equally distributed among 89 children with T1D positive for both IgAG-DGP/tTG and IgG-tTG. CONCLUSION: The discrepancy in levels of IgAG-DGP/tTG and IgG-tTG between Swedish and Danish T1D cohorts was independent of HLA and suggests that regional variations in comorbidity of celiac disease in T1D is caused...

  19. Cognitive decline in patients with Alzheimer's disease, vascular dementia and senile dementia of Lewy body type.

    Science.gov (United States)

    Ballard, C; Patel, A; Oyebode, F; Wilcock, G

    1996-05-01

    One hundred and twenty-four patients with DSM-III-R dementia were assessed with a standardized battery which included the Geriatric Mental State Schedule, the History and Aetiology Schedule, the Secondary Dementia Schedule and the CAMCOG. Patients with Alzheimer's disease, vascular dementia and senile dementia of Lewy body type (SDLT) all had a similar degree of cognitive impairment at the time of the baseline interview. Patients with Alzheimer's disease and vascular dementia each experienced a mean decline of 27 points in patients with SDLT. Patients with SDLT had a significantly greater decline of verbal fluency than both the other groups. Women were significantly more impaired than men at the time of the baseline assessment but experienced a similar decline during the year of follow-up.

  20. Evaluation of an indirect ELISA for detection and typing of foot-and-mouth disease virus

    International Nuclear Information System (INIS)

    Prado, J.A.

    1998-01-01

    An indirect enzyme linked immunosorbent assay (ELISA) kit was used for diagnosis of foot-and-mouth disease virus (FMDV) types O1, A23, C3 which occurred in Rio Grande do Sul State, Southern Brazil during 1984-1994. The samples were randomly selected and tested by ELISA, Complement Fixation Test (CFT) and in tissue culture. Out of 106 samples 78 (73,5%) were positive by ELISA and 39 (36,8%) were found positive in CFT, when original suspensions were used. Once these samples were inoculated onto tissue culture both tests gave similar results, although ELISA picked up more positive samples during the 1st passage in tissue culture. The negative samples (16) included in this study were negative in all tests. The ELISA was more sensitive than and as specific as CFT. ELISA and tissue culture together were shown to be a better system for detection of foot-and-mouth disease virus antigen than CFT. (author)

  1. Skeletal muscle metabolism is impaired during exercise in glycogen storage disease type III

    DEFF Research Database (Denmark)

    Preisler, Nicolai; Laforêt, Pascal; Madsen, Karen Lindhardt

    2015-01-01

    /kg/min (p = 0.024). Fructose ingestion improved exercise tolerance in the patients. CONCLUSION: Similar to patients with McArdle disease, in whom muscle glycogenolysis is also impaired, GSDIIIa is associated with a reduced skeletal muscle oxidation of carbohydrates and a compensatory increase in fatty acid......OBJECTIVE: Glycogen storage disease type IIIa (GSDIIIa) is classically regarded as a glycogenosis with fixed weakness, but we hypothesized that exercise intolerance in GSDIIIa is related to muscle energy failure and that oral fructose ingestion could improve exercise tolerance in this metabolic...... myopathy. METHODS: We challenged metabolism with cycle-ergometer exercise and measured substrate turnover and oxidation rates using stable isotope methodology and indirect calorimetry in 3 patients and 6 age-matched controls on 1 day, and examined the effect of fructose ingestion on exercise tolerance...

  2. Unrealistic pessimism about risk of coronary heart disease and stroke in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Asimakopoulou, Koula G.; Skinner, T. Chas; Spimpolo, Jennifer

    2008-01-01

    and rated their mood about these risks using a self-report measure. Using an objective risk calculator, they were then told their actual risk of CHD and stroke and their mood was re-assessed. Results: Patients' estimates of their risk of CHD/stroke were grossly inflated. A negative relationship between...... disease risk and mood was also seen where higher risk of actual and perceived CHD/stroke was related to worse mood. A positive relationship between mood and extent of perceptual error was further observed; the more inaccurate patients' perceptions of CHD/stroke risk were, the better their mood. Mood......Objective: We examined the accuracy of type 2 diabetes (T2D) patients' risk estimates of developing coronary heart disease (CHD)/having a stroke as a consequence of diabetes and their mood about these risks. Methods: Patients reported their perceived risks of developing CHD/having a stroke...

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

    Science.gov (United States)

    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

  4. Anorexia nervosa of the restrictive type and celiac disease in adolescence

    Directory of Open Access Journals (Sweden)

    Nacinovich R

    2017-05-01

    Full Text Available Renata Nacinovich,1 Lucio Tremolizzo,2 Fabiola Corbetta,1 Elisa Conti,2 Francesca Neri,1 Monica Bomba1 1Child and Adolescent Mental Health Department, 2Neurology Unit and Lab of Neurobiology, San Gerardo Hospital, School of Medicine and Surgery and Milan Center for Neuroscience (Neuro-MI, University of Milano-Bicocca, Monza, Italy Background: Anorexia nervosa (AN is usually present in adolescence with symptoms partially overlapping celiac disease (CD, but the relationship between these two conditions has received little attention in the literature. The aim of this work was to explore this relationship, considering if CD could be associated with specific baseline AN-related clinical features. Methods: In this retrospective study, 82 adolescent female out- and inpatients with AN of the restrictive type (ANr, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, were recruited. CD diagnosis and related serology were recorded, including tissue transglutaminase type-2 antibodies, endomysial antibodies, and antibodies against deamidated forms of gliadin peptides. Eating disorder inventory-3, Children’s Depression Inventory, body mass index, age, and disease duration data recorded at the time of blood withdrawal were also obtained from each patient. Results: Five (6.1% subjects presented a CD disorder associated with AN: none of the collected psychometric measures was significantly correlated with any CD-related parameter or characterized as a specific subgroup. Conclusion: CD diagnosis or serology does not relate to ANr clinical or demographic characteristics. However, a slight increase in prevalence with respect to the general population might be hypothesized and possibly elucidated by further studies with an appropriate design. Keywords: anorexia nervosa, celiac disease, adolescence, celiac disease antibody, gluten

  5. HLA DRB1*03 as a possible common etiology of schizophrenia, Graves' disease, and type 2 diabetes.

    Science.gov (United States)

    Sayeh, Aicha; Ben Cheikh, Cheker; Mardessi, Ali; Mrad, Meriem; Nsiri, Brahim; Oumaya, Abdelaziz; Fekih-Mrissa, Najiba

    2017-01-01

    Autoimmune diseases and schizophrenia share many common features. Association studies confirm a shared genetic association in the human leukocyte antigen (HLA) region between schizophrenia and most autoimmune diseases. To our knowledge, the simultaneous syndromes of Graves' disease (GD) and type 2 diabetes (T2D) in schizophrenia are rare in Tunisia. We report a case of a 42-year-old woman admitted to the department of psychiatry for an acute relapse of chronic schizophrenia. Her medical history revealed that she was followed for Graves' disease and for a type 2 diabetes mellitus. A low-resolution HLA typing was performed by polymerase chain reaction sequence-specific primer (PCR-SSP) techniques according to determine the patient's haplotype. Our study suggests that the HLA DRB1*03 allele may explain a common etiology underlying the co-morbidity of Graves' disease, type 2 diabetes, and schizophrenia in our patient.

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

    International Nuclear Information System (INIS)

    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. Diabetes Mellitus Type 2 and Non-alcoholic Fatty Liver Disease. The Effects of Metformin

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    V.I. Pankiv

    2013-08-01

    Full Text Available Diabetes mellitus (DM type 2 in clinical practice is often associated with non-alcoholic fatty liver disease (NAFLD, which has a number of clinical and morphological forms and develops in patients who do not abuse alcohol. The combination of DM type 2 and NAFLD is associated not only with a high risk of developing liver cirrhosis and hepatocellular carcinoma in these patients. Although all aspects of the etiology of NAFLD is not fully known, it is points to the role of insulin resistance in its development. This concept has facilitated a number of clinical studies using metformin as the insulin sensitizer in insulin-resistant patients with NAFLD. The findings emphasize the importance of metformin in the treatment of NAFLD in combination with a hypocaloric diet and the control of body weight. It is also reported about other tissue effects of metformin in NAFLD.

  8. Rare co-occurrence of osteogenesis imperfecta type I and autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Hoefele, Julia; Mayer, Karin; Marschall, Christoph; Alberer, Martin; Klein, Hanns-Georg; Kirschstein, Martin

    2016-11-01

    There are several clinical reports about the co-occurrence of autosomal dominant polycystic kidney disease (ADPKD) and connective tissue disorders. A simultaneous occurrence of osteogenesis imperfecta (OI) type I and ADPKD has not been observed so far. This report presents the first patient with OI type I and ADPKD. Mutational analysis of PKD1 and COL1A1 in the index patient revealed a heterozygous mutation in each of the two genes. Mutational analysis of the parents indicated the mother as a carrier of the PKD1 mutation and the father as a carrier of the COL1A1 mutation. The simultaneous occurrence of both disorders has an estimated frequency of 3.5:100 000 000. In singular cases, ADPKD can occur in combination with other rare disorders, e.g. connective tissue disorders.

  9. Elevated fasting plasma cortisol is associated with ischemic heart disease and its risk factors in people with type 2 diabetes: the Edinburgh type 2 diabetes study.

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    Reynolds, Rebecca M; Labad, Javier; Strachan, Mark W J; Braun, Anke; Fowkes, F Gerry R; Lee, Amanda J; Frier, Brian M; Seckl, Jonathan R; Walker, Brian R; Price, Jackie F

    2010-04-01

    Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the metabolic syndrome, but whether circulating cortisol levels predict cardiovascular end points is less clear. People with type 2 diabetes are at increased cardiovascular disease risk and thus are suitable to study associations of plasma cortisol with cardiovascular risk. We aimed to assess whether altered HPA axis activity was associated with features of the metabolic syndrome and ischemic heart disease in people with type 2 diabetes. We conducted a cross-sectional cohort study in the general community, including 919 men and women aged 67.9 (4.2) yr with type 2 diabetes (the Edinburgh Type 2 Diabetes Study). We measured fasting morning plasma cortisol. Associations between cortisol levels, features of the metabolic syndrome, obesity, and ischemic heart disease were determined. Elevated plasma cortisol levels were associated with raised fasting glucose and total cholesterol levels (P cortisol levels were associated with prevalent ischemic heart disease (>800 vs. cortisol is also associated with a greater prevalence of ischemic heart disease, independent of conventional risk factors. Understanding the role of cortisol in the pathogenesis of ischemic heart disease merits further exploration.

  10. Renoprotective effects of thiazides combined with loop diuretics in patients with type 2 diabetic kidney disease.

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    Hoshino, Taro; Ookawara, Susumu; Miyazawa, Haruhisa; Ito, Kiyonori; Ueda, Yuichiro; Kaku, Yoshio; Hirai, Keiji; Mori, Honami; Yoshida, Izumi; Tabei, Kaoru

    2015-04-01

    Type 2 diabetic kidney disease (DKD) is frequently accompanied by uncontrollable hypertension due to the sodium sensitivity inherent in DKD and to diuretic-resistant edema. In general, diuretics are effective in treating this condition, but thiazide diuretics are thought to be innocuous in advanced chronic kidney disease (CKD). We examined the renoprotective effects of combination therapy with thiazides and loop diuretics in type 2 DKD patients with CKD stage G4 or G5. This study included 11 patients with type 2 DKD and an estimated glomerular filtration rate (eGFR) diuretics. Each patient received additional hydrochlorothiazide (HCTZ) therapy, which was continued for more than 12 months. We examined clinical parameters including blood pressure (BP), proteinuria, and eGFR before and after the addition of HCTZ. Patients received a 13.6 ± 3.8 mg/day dose of HCTZ in addition to loop diuretics (azosemide: 120 mg/day in 6 cases, 60 mg/day in 3 cases and furosemide: 80 mg/day in 1 case, 120 mg/day in 1 case). Side effects of HCTZ were not observed in all patients. After the addition of HCTZ therapy, systolic and diastolic blood pressures (S-BP, D-BP) as well as proteinuria significantly decreased (S-BP: at 6 months, p diuretics improves BP levels, and decreases proteinuria even in advanced stage type 2 DKD patients with severe edema. The addition of HCTZ therapy was not found to negatively affect the change in eGFR in the present study.

  11. Type I interferon induction is detrimental during infection with the Whipple's disease bacterium, Tropheryma whipplei.

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    Khatoun Al Moussawi

    2010-01-01

    Full Text Available Macrophages are the first line of defense against pathogens. Upon infection macrophages usually produce high levels of proinflammatory mediators. However, macrophages can undergo an alternate polarization leading to a permissive state. In assessing global macrophage responses to the bacterial agent of Whipple's disease, Tropheryma whipplei, we found that T. whipplei induced M2 macrophage polarization which was compatible with bacterial replication. Surprisingly, this M2 polarization of infected macrophages was associated with apoptosis induction and a functional type I interferon (IFN response, through IRF3 activation and STAT1 phosphorylation. Using macrophages from mice deficient for the type I IFN receptor, we found that this type I IFN response was required for T. whipplei-induced macrophage apoptosis in a JNK-dependent manner and was associated with the intracellular replication of T. whipplei independently of JNK. This study underscores the role of macrophage polarization in host responses and highlights the detrimental role of type I IFN during T. whipplei infection.

  12. Early manifestations of type 1 Gaucher disease in presymptomatic children diagnosed after parental carrier screening.

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    Yang, Amy C; Bier, Louise; Overbey, Jessica R; Cohen-Pfeffer, Jessica; Desai, Khyati; Desnick, Robert J; Balwani, Manisha

    2017-06-01

    The overall published experience with pediatric type 1 Gaucher disease (GD1) has been based on ascertainment through clinical presentation of the disease. We describe the longitudinal follow-up in a presymptomatic pediatric cohort. The cohort includes children diagnosed with GD1, either prenatally or postnatally by molecular genetic testing, and followed for clinical care at our center from 1998 to 2016. All patients' parents were GBA mutation carriers identified through carrier screening programs. Longitudinal clinical, laboratory, and imaging data were obtained through chart review. Thirty-eight patients aged 1-18 years (mean at last visit 6.9 ± 4.1 years) were followed, including 32 p.N409S homozygotes and 6 p.N409S/p.R535H compound heterozygotes. At the last evaluation, a minority had hematological (5%), bone (15%), or linear growth (19%) issues. Only 12% had splenomegaly and 74% had moderate hepatomegaly. Chitotriosidase activity varied widely (6-5,640 nmol/hour/ml) and generally increased with age. Pediatric Gaucher severity scores (GSS) remained stable and within the mild-disease range for most (95%). Treatment for progressive disease during this period was recommended for four children. Most children with the p.N409S/p.N409S and p.N409S/p.R535H GD1 genotypes have minimal disease manifestations and progression during childhood and can be monitored using limited assessments. Those with other mutations may require additional monitoring. These data are valuable for newborn screening and counseling.Genet Med advance online publication 13 October 2016.

  13. Characterisation of aggression in Huntington's disease: rates, types and antecedents in an inpatient rehabilitation setting.

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    Brown, Anahita; Sewell, Katherine; Fisher, Caroline A

    2017-10-01

    To systematically review aggression in an inpatient Huntington's cohort examining rates, types and antecedents. Although the prevalence of aggression in Huntington's disease is high, research into this problematic behaviour has been limited. Few studies have investigated the nature of aggressive behaviour in Huntington's disease or antecedents that contribute to its occurrence. A systematic, double-coded, electronic medical file audit. The electronic hospital medical records of 10 people with Huntington's disease admitted to a brain disorders unit were audited for a 90-day period using the Overt Aggression Scale-Modified for Neurorehabilitation framework, yielding 900 days of clinical data. Nine of 10 clients exhibited aggression during the audit period. Both verbal (37·1%) aggression and physical aggression were common (33·8%), along with episodes of mixed verbal and physical aggression (15·2%), while aggression to objects/furniture was less prevalent (5·5%). The most common antecedent was physical guidance with personal care, far exceeding any other documented antecedents, and acting as the most common trigger for four of the nine clients who exhibited aggression. For the remaining five clients, there was intraindividual heterogeneity in susceptibility to specific antecedents. In Huntington's sufferers at mid- to late stages following disease onset, particular care should be made with personal care assistance due to the propensity for these procedures to elicit an episode of aggression. However, given the degree of intraindividual heterogeneity in susceptibility to specific antecedents observed in the present study, individualised behaviour support plans and sensory modulation interventions may be the most useful in identifying triggers and managing aggressive episodes. Rates of aggression in Huntington's disease inpatients can be high. Knowledge of potential triggers, such as personal care, is important for nursing and care staff, so that attempts can be

  14. Prevalence of autoantibodies in the course of Gaucher disease type 1: A multicenter study comparing Gaucher disease patients to healthy subjects.

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    Serratrice, Christine; Bensalah, Nesma; Penaranda, Guillaume; Bardin, Nathalie; Belmatoug, Nadia; Masseau, Agathe; Rose, Christian; Lidove, Olivier; Camou, Fabrice; Maillot, François; Leguy, Vanessa; Magy-Bertrand, Nadine; Marie, Isabelle; Cherin, Patrick; Bengherbia, Monia; Carballo, Sebastian; Boucraut, José; Serratrice, Jacques; Berger, Marc; Verrot, Denis

    2018-01-01

    Type 1 Gaucher disease may be related to the presence of autoantibodies. Their clinical significance is questioned. Primary endpoint was to compare the prevalence of autoantibodies in type 1 Gaucher disease patients with healthy subjects, seeking correlations with autoimmune characteristics. Secondary endpoints were to determine whether patients with autoantibodies reported autoimmunity-related symptoms and if genotype, splenectomy or treatment influenced autoantibodies presence. Type 1 Gaucher disease patients and healthy volunteers were included in this national multicenter exploratory study. Autoantibodies presence was compared in both groups and assessed regarding to genotype, splenectomy, Gaucher disease treatment and autoimmunity-related symptoms. Twenty healthy subjects and 40 type 1 Gaucher disease patients were included. Of the studied group: 15 patients undergone splenectomy, 37 were treated either with enzyme replacement therapy (34) or with substrate reduction therapy (3), 25 were homozygous/heterozygous for the N370S mutation. In type 1 Gaucher disease group (studied group), 52% had positive autoantibodies versus 26% in control group. Antiphospholipid antibodies were more frequent in the studied group (30% vs. 5%), but without correlation to thrombosis, osteonecrosis or bone infarcts. In the studied group, antinuclear antibodies were more frequent (25% vs. 16%). None of the patients with autoantibodies had clinical manifestations of autoimmune diseases. Autoantibodies were not correlated with treatment, genotype, or splenectomy, except for anticardiolipid, more frequent in splenectomized patients. In type 1 Gaucher disease, autoantibodies were more frequent compared to a healthy population. However, they were not associated with an increased prevalence of clinical active autoimmune diseases. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  15. A new framework for evaluating the health impacts of treatment for Gaucher disease type 1

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    Michael L. Ganz

    2017-02-01

    Full Text Available Abstract Background The Disease Severity Scoring System (DS3 is a validated measure for evaluating Gaucher disease type 1 (GD1 severity. We developed a new framework, consisting of health states, transition probabilities between those states, and preferences for those states (utilities based on the DS3 to predict long-term outcomes of patients starting treatment. We defined nine mutually exclusive (alive health states based on three DS3 categories: mild (0 ≤ DS3 ≤ 3.5 without symptoms of bone disease; mild with bone pain, mild with severe skeletal complications (SSC defined as lytic lesions, avascular necrosis, or fracture; moderate (3.5 < DS3 ≤ 6.5 without SSC; moderate with SSC; marked (6.5 < DS3 ≤ 9.5 without SSC; marked with SSC; severe (9.5 < DS3 ≤ 19 without SSC; and severe with SSC. Health-state transition probabilities and utilities were estimated from a longitudinal sample of patients with GD1 who started enzyme replacement therapy (the DS3 Score Study. Age dependent GD1-specific mortality was derived from published data. We used a Markov state-transition model to illustrate how to estimate time spent in each health state. Results The average predicted utilities for each health state ranged from 0.76 for mild disease with no clinical symptoms of bone disease to 0.52 with severe disease with SSC. Transition probabilities depended on disease severity (DS3 score at treatment initiation and whether patients had undergone a total splenectomy or had an intact spleen/partial splenectomy prior to starting treatment. Patients who started treatment with intact or residual spleens spent more time in better health states than those who started treatment with total splenectomy. Conclusions This new framework, which is based on the DS3, can be used to project the long-term outcomes of GD1 patients starting treatment. The framework could also be used to compare the long-term outcomes of different GD1 treatment options. Trial

  16. A Review of Haptoglobin Typing Methods for Disease Association Study and Preventing Anaphylactic Transfusion Reaction

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    Dae-Hyun Ko

    2013-01-01

    Full Text Available Haptoglobin, the product of the gene, is a glycoprotein involved in the scavenging of free hemoglobin. Haptoglobin levels increase or decrease in response to various acquired conditions, and they are also influenced by genetic predisposition. There were 2 major alleles, and , and 1 minor allele, . Many researchers have attempted to study the haptoglobin types and their association with disease; however, no definitive conclusions have been reached yet. It is reported that patients who are genetically deficient in haptoglobin are at risk of anaphylaxis against blood components containing haptoglobin. Haptoglobin genotypes also affect the reference intervals of haptoglobin levels. Many studies have attempted to establish simple and accurate typing methods. In this paper, we have broadly reviewed several methods for haptoglobin typing—phenotyping, Southern blotting, conventional PCR, real-time PCR, and loop-mediated isothermal amplification. We discuss their characteristics, clinical applications, and limitations. The phenotyping methods are time consuming and labor intensive and not designed to detect patients harboring . The rapid and robust haptoglobin genotyping may help in preventing fatal anaphylactic reactions and in establishing the relationships between the haptoglobin phenotypes and diseases.

  17. Olfactory deficits in Niemann-Pick type C1 (NPC1 disease.

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    Marina Hovakimyan

    Full Text Available BACKGROUND: Niemann-Pick type C disease (NPC is a rare autosomal recessive lipid storage disease characterized by progressive neurodegeneration. As only a few studies have been conducted on the impact of NPC on sensory systems, we used a mutant mouse model (NPC1(-/- to examine the effects of this disorder to morphologically distinct regions of the olfactory system, namely the olfactory epithelium (OE and olfactory bulb (OB. METHODOLOGY/PRINCIPAL FINDINGS: For structural and functional analysis immunohistochemistry, electron microscopy, western blotting, and electrophysiology have been applied. For histochemistry and western blotting, we used antibodies against a series of neuronal and glia marker proteins, as well as macrophage markers. NPC1(-/- animals present myelin-like lysosomal deposits in virtually all types of cells of the peripheral and central olfactory system. Especially supporting cells of the OE and central glia cells are affected, resulting in pronounced astrocytosis and microgliosis in the OB and other olfactory cortices. Up-regulation of Galectin-3, Cathepsin D and GFAP in the cortical layers of the OB underlines the critical role and location of the OB as a possible entrance gate for noxious substances. Unmyelinated olfactory afferents of the lamina propria seem less affected than ensheathing cells. Supporting the structural findings, electro-olfactometry of the olfactory mucosa suggests that NPC1(-/- animals exhibit olfactory and trigeminal deficits. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a pronounced neurodegeneration and glia activation in the olfactory system of NPC1(-/-, which is accompanied by sensory deficits.

  18. Vestibular function in patients with Niemann-Pick type C disease.

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    Bremova, Tatiana; Krafczyk, Siegbert; Bardins, Stanislavs; Reinke, Jörg; Strupp, Michael

    2016-11-01

    We investigated whether vestibular dysfunction may cause or contribute to postural imbalance and falls in patients with Niemann-Pick type C disease (NP-C). Eight patients with NP-C disease and 20 healthy controls were examined using the video-based head impulse test (vHIT) and caloric irrigation to investigate horizontal canal function as well as ocular- and cervical vestibular evoked myogenic potentials (o- and cVEMP), and binocular subjective visual vertical estimation (SVV) for otolith function, and static posturography. There were no significant differences in vestibulo-ocular gain, caloric excitability, o-/cVEMP measures or SVV between the two groups. Posturographic total sway path (tSP) and root mean square (RMS) were significantly higher in NP-C than in controls in 3 out of 4 conditions. The Romberg quotient (RQ) to assess the amount of visual stabilization was significantly lower in the NP-C than in the HC group. In contrast to other inherited metabolic disorders, such as Morbus Gaucher type 3, we did not find any evidence for an impairment of canal or otolith function in patients with NP-C as their cause of postural imbalance. Since RQ was low in NP-C patients, indicating proper sensory input, the observed increased postural sway is most likely due to a cerebellar dysfunction in NP-C, which may therefore, explain postural imbalance.

  19. Inhibition of type I NKT cells by retinoids or following sulfatide-mediated activation of type II NKT cells attenuates alcoholic liver disease

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    Maricic, Igor; Sheng, Huiming; Marrero, Idania; Seki, Ehikiro; Kisseleva, Tatiana; Chaturvedi, Som; Molle, Natasha; Mathews, K. Stephanie; Gao, Bin; Kumar, Vipin

    2015-01-01

    Innate immune mechanisms leading to liver injury following chronic alcohol ingestion are poorly understood. Natural killer T (NKT) cells, enriched in the liver and comprised of at least two distinct subsets, type I and type II, recognize different lipid antigens presented by CD1d molecules. We have investigated whether differential activation of NKT cell subsets orchestrates inflammatory events leading to alcoholic liver disease (ALD). We found that following chronic plus binge feeding of Lieber-DeCarli liquid diet in male C57BL/6 mice, type I but not type II NKT cells are activated leading to recruitment of inflammatory Gr-1highCD11b+ cells into liver. A central finding is that liver injury following alcohol feeding is dependent upon type I NKT cells. Thus liver injury is significantly inhibited in Jα18−/− mice deficient in type I NKT cells as well as following their inactivation by sulfatide-mediated activation of type II NKT cells. Furthermore we have identified a novel pathway involving all-trans retinoic acid (ATRA) and its receptor RARγ signaling that inhibits type I NKT cells and consequently ALD. A semi-quantitative PCR analysis of hepatic gene expression of some of the key proinflammatory molecules shared in human disease indicated that their upregulation in ALD is dependent upon type I NKT cells. Conclusion Type I but not type II NKT cells become activated following alcohol feeding. Type I NKT cells-induced inflammation and neutrophil recruitment results in liver tissue damage while type II NKT cells protect from injury in ALD. Inhibition of type I NKT cells by retinoids or by sulfatide prevents ALD. Since the CD1d pathway is highly conserved between mice and humans, NKT cell subsets might be targeted for potential therapeutic intervention in ALD. PMID:25477000

  20. Prenatal-Onset Niemann–Pick Type C Disease with Nonimmune Hydrops Fetalis

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    Ozge Surmeli-Onay

    2013-10-01

    Full Text Available Niemann–Pick type C (NPC; OMIM 257219 disease is a neurodegenerative lysosomal storage disorder characterized by accumulation of unesterified cholesterol in the lysosomal/late endosomal system. This autosomal recessive disorder occurs in approximately 1/150,000 births. The broad clinical spectrum ranges from a prenatal severe presentation to an adult-onset chronic neurodegenerative disease. Data about prenatal presentation of NPC are limited. A female newborn was born at 342 weeks' gestation with a birth weight of 3070 g, and transferred to the Neonatal Intensive Care Unit because of nonimmune hydrops fetalis (NIHF and respiratory distress. On admission, a physical examination revealed skin edema, mild respiratory distress, and abdominal distention due to massive ascites. Hepatosplenomegaly and cholestasis increased progressively and bleeding diathesis occurred. Results of an abdominal ultrasonography showed hepatosplenomegaly and segmental multicystic dysplastic left kidney. Foamy cells with a lysosomal phospholipid storage pattern compatible with NPC were found in the bone marrow smear. Cultured fibroblasts showed a strongly elevated filipin staining (classical NPC cellular phenotype, establishing the diagnosis of NPC. The infant died on the 52nd day of life because of respiratory distress due to lung involvement of NPC, massive ascites, and progressive liver failure. Results of an autopsy showed multiorgan storage disease involving the liver, spleen, lymph nodes, thymus, lungs, and brain. Here, we present a preterm infant with NIHF as a sign of severe prenatal-onset NPC and review the literature.

  1. Dietary gluten and the development of celiac disease and type 1 diabetes

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    Ciacci C

    2016-04-01

    Full Text Available Carolina Ciacci, Fabiana Zingone Department of Medicine and Surgery, Celiac Center, University of Salerno, Fisciano, Italy Abstract: The objective of this study was to perform a review of the present knowledge on the epidemiology and pathogenesis of the association between celiac disease (CD and type 1 diabetes mellitus (T1DM. Results from this review show that the estimated prevalence rate of CD in T1DM ranges from 4% to 11.5%, which seems higher in children than in adults, while there is no sex predominance in the prevalence of CD in T1DM. On the basis of the previous literature, screening for CD should be considered at diabetes diagnosis in all subjects and again within 2 and 5 years after diagnosis, even in the absence of symptoms. The anti-islet antibodies detection test, instead, is not recommended in CD, just as in the general population, except for CD patients having a relative with T1DM. Both genes and environmental factors seem to play a role in this association. HLADQ2 has been found to be the most frequent allele in the patients with both CD and T1DM, while gluten may be considered the trigger that induces the production of autoantibodies and the development, in genetically predisposed individuals, of both diseases. Keywords: diabetes, celiac disease, genetics, environmental, epidemiological

  2. Structure and Dynamics of RNA Repeat Expansions That Cause Huntington's Disease and Myotonic Dystrophy Type 1.

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    Chen, Jonathan L; VanEtten, Damian M; Fountain, Matthew A; Yildirim, Ilyas; Disney, Matthew D

    2017-07-11

    RNA repeat expansions cause a host of incurable, genetically defined diseases. The most common class of RNA repeats consists of trinucleotide repeats. These long, repeating transcripts fold into hairpins containing 1 × 1 internal loops that can mediate disease via a variety of mechanism(s) in which RNA is the central player. Two of these disorders are Huntington's disease and myotonic dystrophy type 1, which are caused by r(CAG) and r(CUG) repeats, respectively. We report the structures of two RNA constructs containing three copies of a r(CAG) [r(3×CAG)] or r(CUG) [r(3×CUG)] motif that were modeled with nuclear magnetic resonance spectroscopy and simulated annealing with restrained molecular dynamics. The 1 × 1 internal loops of r(3×CAG) are stabilized by one-hydrogen bond (cis Watson-Crick/Watson-Crick) AA pairs, while those of r(3×CUG) prefer one- or two-hydrogen bond (cis Watson-Crick/Watson-Crick) UU pairs. Assigned chemical shifts for the residues depended on the identity of neighbors or next nearest neighbors. Additional insights into the dynamics of these RNA constructs were gained by molecular dynamics simulations and a discrete path sampling method. Results indicate that the global structures of the RNA are A-form and that the loop regions are dynamic. The results will be useful for understanding the dynamic trajectory of these RNA repeats but also may aid in the development of therapeutics.

  3. [Myasthenia gravis, Graves-Basedow disease and other autoimmune diseases in patient with diabetes type 1 - APS-3 case report, therapeutic complications].

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    Klenczar, Karolina; Deja, Grażyna; Kalina-Faska, Barbara; Jarosz-Chobot, Przemysława

    2017-01-01

    Diabetes type 1(T1D) is the most frequent form of diabetes in children and young people, which essence is autoimmune destruction of pancreatic B cells islet. Co-occurrence of other autoimmune diseases is observed in children with T1D, the most often are: Hashimoto disease or coeliac disease. We report the case of the patient, who presents coincidence of T1D with other rare autoimmune diseases such as: Graves - Basedow disease, myasthenia gravis, vitiligo and IgA deficiency. All mentioned diseases significantly complicated both endocrine and diabetic treatment of our patient and they negatively contributed her quality of life. The clinical picture of the case allows to recognize one of the autoimmune polyendocrine syndromes: APS-3 and is associated with still high risk of developing another autoimmune disease. © Polish Society for Pediatric Endocrinology and Diabetology.

  4. New susceptibility loci associated with kidney disease in type 1 diabetes.

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    Niina Sandholm

    2012-09-01

    Full Text Available Diabetic kidney disease, or diabetic nephropathy (DN, is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D. Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS of T1D DN comprising ~2.4 million single nucleotide polymorphisms (SNPs imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 × 10(-8 and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 × 10(-9. Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1 pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 × 10(-7, a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

  5. Musculoskeletal Disease in MDA5-Related Type I Interferonopathy: A Mendelian Mimic of Jaccoud's Arthropathy.

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    de Carvalho, Luciana Martins; Ngoumou, Gonza; Park, Ji Woo; Ehmke, Nadja; Deigendesch, Nikolaus; Kitabayashi, Naoki; Melki, Isabelle; Souza, Flávio Falcäo L; Tzschach, Andreas; Nogueira-Barbosa, Marcello H; Ferriani, Virgínia; Louzada-Junior, Paulo; Marques, Wilson; Lourenço, Charles M; Horn, Denise; Kallinich, Tilmann; Stenzel, Werner; Hur, Sun; Rice, Gillian I; Crow, Yanick J

    2017-10-01

    To define the molecular basis of a multisystem phenotype with progressive musculoskeletal disease of the hands and feet, including camptodactyly, subluxation, and tendon rupture, reminiscent of Jaccoud's arthropathy. We identified 2 families segregating an autosomal-dominant phenotype encompassing musculoskeletal disease and variable additional features, including psoriasis, dental abnormalities, cardiac valve involvement, glaucoma, and basal ganglia calcification. We measured the expression of interferon (IFN)-stimulated genes in the peripheral blood and skin, and undertook targeted Sanger sequencing of the IFIH1 gene encoding the cytosolic double-stranded RNA (dsRNA) sensor melanoma differentiation-associated protein 5 (MDA-5). We also assessed the functional consequences of IFIH1 gene variants using an in vitro IFNβ reporter assay in HEK 293T cells. We recorded an up-regulation of type I IFN-induced gene transcripts in all 5 patients tested and identified a heterozygous gain-of-function mutation in IFIH1 in each family, resulting in different substitutions of the threonine residue at position 331 of MDA-5. Both of these variants were associated with increased IFNβ expression in the absence of exogenous dsRNA ligand, consistent with constitutive activation of MDA-5. These cases highlight the significant musculoskeletal involvement that can be associated with mutations in MDA-5, and emphasize the value of testing for up-regulation of IFN signaling as a marker of the underlying molecular lesion. Our data indicate that both Singleton-Merten syndrome and neuroinflammation described in the context of MDA-5 gain-of-function constitute part of the same type I interferonopathy disease spectrum, and provide possible novel insight into the pathology of Jaccoud's arthropathy. © 2017, American College of Rheumatology.

  6. Anticipatory guidance in type 2 diabetes to improve disease management; next steps after basal insulin.

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    Johnson, Eric L; Frias, Juan P; Trujillo, Jennifer M

    2018-03-23

    The alarming rise in the number of people living with type 2 diabetes (T2D) presents primary care physicians with increasing challenges associated with long-term chronic disease care. Studies have shown that the majority of patients are not achieving or maintaining glycemic goals, putting them at risk of a wide range of diabetes-related complications. Disease- and self-management programs have been shown to help patients improve their glycemic control, and are likely to be of particular benefit for patients with diabetes dealing with these issues. Anticipatory guidance is an individualized, proactive approach to patient education and counseling by a health-care professional to support patients in better coping with problems before they arise. It has been shown to improve disease outcomes in a variety of chronic conditions, including diabetes. While important at all stages, anticipatory guidance may be of particular importance during changes in treatment regimens, and especially during transition to, and escalation of, insulin-based regimens. The aim of this article is to provide advice to physicians on anticipatory guidance for basal-insulin dosing, focusing on appropriate basal-insulin-dose increase and prevention of potentially deleterious basal-insulin doses, so called overbasalization. It also provides an overview of new treatment options for patients with T2D who are not well controlled on basal-insulin therapy, fixed-ratio combinations of basal insulin and glucagon-like peptide-1 receptor agonists, and advice on the type of anticipatory guidance needed to ensure safe and appropriate switching to these therapies.

  7. High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients

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    R. Rozenberg

    2006-09-01

    Full Text Available Gaucher disease (GD, the most prevalent lysosome storage disorder, presents an autosomal recessive mode of inheritance. It is a paradigm for therapeutic intervention in medical genetics due to the existence of effective enzyme replacement therapy. We report here the analysis of GD in 262 unrelated Brazilian patients, carried out in order to establish the frequency of the most common mutations and to provide prognostic information based on genotype-phenotype correlations. Among 247 type 1 GD patients, mutation N370S was detected in 47% of all the alleles, but N370S/N370S homozygosity was found in only 10% of the patients, a much lower frequency than expected, suggesting that most individuals presenting this genotype may not receive medical attention. Recombinant alleles were detected at a high frequency: 44% of the chromosomes bearing mutation L444P had other mutations derived from the pseudogene sequence, present in 25% of patients. Three neuronopathic type 2 patients were homozygous for L444P, all presenting additional mutations (E326K or recombinant alleles that probably lead to the more severe phenotypes. Six children, classified as type 1 GD patients, had a L444P/L444P genotype, showing that neuronopathic symptoms may only manifest later in life. This would indicate the need for a higher treatment dose during enzyme replacement therapy. Finally, mutation G377S was present in 4 homozygous type 1 patients and also in compound heterozygosity in 5 (42% type 3 patients. These findings indicate that G377S cannot be unambiguously classified as mild and suggest an allele-dose effect for this mutation.

  8. Risk of development of chronic kidney disease in patients with type 2 diabetes having metabolic syndrome

    International Nuclear Information System (INIS)

    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)

  9. Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway.

    Science.gov (United States)

    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

  10. Protective effect of catechin in type I Gaucher disease cells by reducing endoplasmic reticulum stress

    International Nuclear Information System (INIS)

    Lee, Yea-Jin; Kim, Sung-Jo; Heo, Tae-Hwe

    2011-01-01

    Highlights: → Catechin reduces the expression level of ER stress marker protein in type I Gaucher disease cells. → Catechin induces the proliferation rate of GD cells similar levels to normal cells. → Catechin improves wound healing activity. → Catechin-mediated reductions in ER stress may be associated with enhanced cell survival. → We identified catechin as a protective agent against ER stress in GD cells. -- Abstract: Gaucher disease (GD) is the most common lysosomal storage disorder (LSD) and is divided into three phenotypes, I, II, and III. Type I is the most prevalent form and has its onset in adulthood. The degree of endoplasmic reticulum (ER) stress is one of the factors that determine GD severity. It has recently been reported that antioxidants reduce ER stress and apoptosis by scavenging the oxidants that cause oxidative stress. For this report, we investigated the possibility that catechin can act on type I GD patient cells to alleviate the pathogenic conditions of GD. We treated GD cells with catechin and examined the expression level of GRP78/BiP (an ER stress marker) by western blots and fluorescence microscopy, the proliferation rate of GD cells, and scratch-induced wound healing activity. Our results show that catechin reduces the expression level of GRP78/BiP, leads to cell proliferation rates of GD cells similar levels to normal cells, and improves wound healing activity. We conclude that catechin protects against ER stress in GD cells and catechin-mediated reductions in ER stress may be associated with enhanced cell survival.

  11. Protective effect of catechin in type I Gaucher disease cells by reducing endoplasmic reticulum stress

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yea-Jin [Department of Biotechnology, Hoseo University, Baebang, Asan, Chungnam, 336-795 (Korea, Republic of); Kim, Sung-Jo, E-mail: sungjo@hoseo.edu [Department of Biotechnology, Hoseo University, Baebang, Asan, Chungnam, 336-795 (Korea, Republic of); Heo, Tae-Hwe, E-mail: thhur92@catholic.ac.kr [College of Pharmacy, The Catholic University of Korea, Bucheon 420-743 (Korea, Republic of)

    2011-09-23

    Highlights: {yields} Catechin reduces the expression level of ER stress marker protein in type I Gaucher disease cells. {yields} Catechin induces the proliferation rate of GD cells similar levels to normal cells. {yields} Catechin improves wound healing activity. {yields} Catechin-mediated reductions in ER stress may be associated with enhanced cell survival. {yields} We identified catechin as a protective agent against ER stress in GD cells. -- Abstract: Gaucher disease (GD) is the most common lysosomal storage disorder (LSD) and is divided into three phenotypes, I, II, and III. Type I is the most prevalent form and has its onset in adulthood. The degree of endoplasmic reticulum (ER) stress is one of the factors that determine GD severity. It has recently been reported that antioxidants reduce ER stress and apoptosis by scavenging the oxidants that cause oxidative stress. For this report, we investigated the possibility that catechin can act on type I GD patient cells to alleviate the pathogenic conditions of GD. We treated GD cells with catechin and examined the expression level of GRP78/BiP (an ER stress marker) by western blots and fluorescence microscopy, the proliferation rate of GD cells, and scratch-induced wound healing activity. Our results show that catechin reduces the expression level of GRP78/BiP, leads to cell proliferation rates of GD cells similar levels to normal cells, and improves wound healing activity. We conclude that catechin protects against ER stress in GD cells and catechin-mediated reductions in ER stress may be associated with enhanced cell survival.

  12. Type 1 Diabetes TrialNet: A Multifaceted Approach to Bringing Disease-Modifying Therapy to Clinical Use in Type 1 Diabetes.

    Science.gov (United States)

    Bingley, Polly J; Wherrett, Diane K; Shultz, Ann; Rafkin, Lisa E; Atkinson, Mark A; Greenbaum, Carla J

    2018-04-01

    What will it take to bring disease-modifying therapy to clinical use in type 1 diabetes? Coordinated efforts of investigators involved in discovery, translational, and clinical research operating in partnership with funders and industry and in sync with regulatory agencies are needed. This Perspective describes one such effort, Type 1 Diabetes TrialNet, a National Institutes of Health-funded and JDRF-supported international clinical trials network that emerged from the Diabetes Prevention Trial-Type 1 (DPT-1). Through longitudinal natural history studies, as well as trials before and after clinical onset of disease combined with mechanistic and ancillary investigations to enhance scientific understanding and translation to clinical use, TrialNet is working to bring disease-modifying therapies to individuals with type 1 diabetes. Moreover, TrialNet uses its expertise and experience in clinical studies to increase efficiencies in the conduct of trials and to reduce the burden of participation on individuals and families. Herein, we highlight key contributions made by TrialNet toward a revised understanding of the natural history of disease and approaches to alter disease course and outline the consortium's plans for the future. © 2018 by the American Diabetes Association.

  13. A study of type and intensity of disease infecting banana plants Musa sp at Tegalagung village Semanding subdistrict

    Directory of Open Access Journals (Sweden)

    Supiana Dian Nurtjahyani

    2014-12-01

    Full Text Available Diseases affecting banana plants are very detrimental to farmers as these can lower production and economic income. The purpose of this study was to determine the type and intensity of the disease affecting banana plants. This research was an observational analytic study that observe and analyze condition or symptoms of diseases affecting banana plants in Tegalagung village, Semanding subdistrict, Tuban as many as 38 samples. Parameters observed were type of disease and measure intensity of the disease, data obtained were analyzed descriptively. Based on the symptoms that occurred on the leaves, the study found four disease types affecting banana plant that were fusarium wilt, bacterial wilt (Blood, Sigatoka leaf spot and stunting disease. The diseases intensity were 50% of Fusarium wilt; 26,66% of bacterial wilt (Blood; 26.32% of Sigatoka leaf spot and 15.38% of stunting disease. Conclusion of the study, the highest intensity of the disease that attacks banana plants is Fusarium wilt as high as 50%.

  14. Functional state of the cardiorespiratory system of women with postmastectomy syndrome with different types of attitude to the disease

    Directory of Open Access Journals (Sweden)

    Yuriy Briskin

    2015-08-01

    Full Text Available Purpose: to determine the peculiarities of the functional state of cardiorespiratory system in women with postmastectomy syndrome with different types of attitude to the disease. Material and Methods: analysis of the literature and empirical data; rheography, spirography, the definition of the type of attitude to the disease of personality questionnaires of Institute of Behtereva; methods of mathematical statistics. 115 women with postmastectomy syndrome on clinical stage of rehabilitation were involved in this study. Results: in women with intra- and interpsychic types of attitude to the disease decreased reserve capacity of the cardiovascular and respiratory systems respectively. Conclusions: It was proved that women with a rational relationship to the type of disease show significantly better results of the cardiovascular system compared to interpsychic and intrapsychic.

  15. Mitochondrial GSH replenishment as a potential therapeutic approach for Niemann Pick type C disease

    Directory of Open Access Journals (Sweden)

    Sandra Torres

    2017-04-01

    Full Text Available Niemann Pick type C (NPC disease is a progressive lysosomal storage disorder caused by mutations in genes encoding NPC1/NPC2 proteins, characterized by neurological defects, hepatosplenomegaly and premature death. While the primary biochemical feature of NPC disease is the intracellular accumulation of cholesterol and gangliosides, predominantly in endolysosomes, mitochondrial cholesterol accumulation has also been reported. As accumulation of cholesterol in mitochondria is known to impair the transport of GSH into mitochondria, resulting in mitochondrial GSH (mGSH depletion, we investigated the impact of mGSH recovery in NPC disease. We show that GSH ethyl ester (GSH-EE, but not N-acetylcysteine (NAC, restored the mGSH pool in liver and brain of Npc1-/- mice and in fibroblasts from NPC patients, while both GSH-EE and NAC increased total GSH levels. GSH-EE but not NAC increased the median survival and maximal life span of Npc1-/- mice. Moreover, intraperitoneal therapy with GSH-EE protected against oxidative stress and oxidant-induced cell death, restored calbindin levels in cerebellar Purkinje cells and reversed locomotor impairment in Npc1-/- mice. High-resolution respirometry analyses revealed that GSH-EE improved oxidative phosphorylation, coupled respiration and maximal electron transfer in cerebellum of Npc1-/- mice. Lipidomic analyses showed that GSH-EE treatment had not effect in the profile of most sphingolipids in liver and brain, except for some particular species in brain of Npc1-/- mice. These findings indicate that the specific replenishment of mGSH may be a potential promising therapy for NPC disease, worth exploring alone or in combination with other options.

  16. Treatment of cataplexy in Niemann-Pick disease type C with the use of miglustat.

    Science.gov (United States)

    Zarowski, Marcin; Steinborn, Barbara; Gurda, Barbara; Dvorakova, Lenka; Vlaskova, Hana; Kothare, Sanjeev V

    2011-01-01

    Cataplexy is the sudden muscle weakness brought on by strong emotions, particularly joking, laughter, or anger. Cataplexy may involve only certain group of muscles or the entire voluntary musculature. In rare cases, symptoms of cataplexy can be seen during the course of some inherited diseases (Niemann-Pick type C (NPC), Prader-Willi syndrome, myotonic dystrophy, Norrie disease). We report the successful use of miglustat, a reversible inhibitor of the enzyme glucosylceramide synthase, approved for use in Gaucher's disease, and which catalyses the first step in the biosynthesis of most glycosphingolipid, in a boy with NPC with cataplexy. A 9-year-old boy was admitted for assessments of frequent "drop attacks" while laughing. The filipin fluorescence tests of cultured skin fibroblasts revealed massive accumulation of unesterified cholesterol, confirming the diagnosis of NPC disease. Molecular studies confirmed the diagnosis of NPC too. After approval from the bioethics committee, miglustat was initiated on the child at 100mg three times a day. Cataplectic attacks disappeared completely after 6 months on treatment, and patient continues to be in remission from the cataplectic attacks at 16 months follow-up. There was no further progression of neurological signs or symptoms or splenomegaly, with some improvement in cognitive function as well as social, affective and attention problems, up-gaze, and gait. Miglustat was well tolerated with no side effects observed. In summary, this is the first report of miglustat treatment of cataplexy in NPC. Long-term follow-up for continuing efficacy and tolerability in a larger cohort with NPC is needed to substantiate our observation. © 2010 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  17. Characterization of a canine model of glycogen storage disease type IIIa

    Directory of Open Access Journals (Sweden)

    Haiqing Yi

    2012-11-01

    Glycogen storage disease type IIIa (GSD IIIa is an autosomal recessive disease caused by deficiency of glycogen debranching enzyme (GDE in liver and muscle. The disorder is clinically heterogeneous and progressive, and there is no effective treatment. Previously, a naturally occurring dog model for this condition was identified in curly-coated retrievers (CCR. The affected dogs carry a frame-shift mutation in the GDE gene and have no detectable GDE activity in liver and muscle. We characterized in detail the disease expression and progression in eight dogs from age 2 to 16 months. Monthly blood biochemistry revealed elevated and gradually increasing serum alanine transaminase (ALT, aspartate transaminase (AST and alkaline phosphatase (ALP activities; serum creatine phosphokinase (CPK activity exceeded normal range after 12 months. Analysis of tissue biopsy specimens at 4, 12 and 16 months revealed abnormally high glycogen contents in liver and muscle of all dogs. Fasting liver glycogen content increased from 4 months to 12 months, but dropped at 16 months possibly caused by extended fibrosis; muscle glycogen content continually increased with age. Light microscopy revealed significant glycogen accumulation in hepatocytes at all ages. Liver histology showed progressive, age-related fibrosis. In muscle, scattered cytoplasmic glycogen deposits were present in most cells at 4 months, but large, lake-like accumulation developed by 12 and 16 months. Disruption of the contractile apparatus and fraying of myofibrils was observed in muscle at 12 and 16 months by electron microscopy. In conclusion, the CCR dogs are an accurate model of GSD IIIa that will improve our understanding of the disease progression and allow opportunities to investigate treatment interventions.

  18. Non-diabetic renal disease in patients with type-2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Sonia Yaqub

    2012-01-01

    Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage renal disease in diabetics worldwide, yet most patients with type-2 diabetes mellitus are not formally evaluated with a renal biopsy. The diagnosis is almost always based on clinical grounds. A wide spectrum of non-diabetic renal disease (NDRD is reported to occur in patients with type-2 diabetes. It has been estimated that up to one-third of all diabetic patients who present with proteinuria are suffering from NDRD. The aim of this analysis was to evaluate the prevalence and etiology of NDRD in patients with type-2 diabetes. We retrospectively reviewed the medical records of patients with type-2 diabetes who underwent kidney biopsy on clinical suspicion of NDRD (absence of diabetic retinopathy and/or neuropathy; short duration of diabetes, i.e. less than five years from January 2003 through December 2007 at the Aga Khan University Hospital, Karachi. Based on the biopsy findings, patients were grouped as Group-I, isolated NDRD; Group-II, NDRD with underlying DN; and Group-III, isolated DN. Of 68 patients studied, 75% were males and the mean age was 56 years. The mean duration of diabetes was nine years. Group-I included 34 patients (52%, Group-II included 11 patients (17% and Group-III included 23 patients (31%. Among the Group-I patients, the mean age was 56 years (41-77 years. The most common NDRDs were acute interstitial nephritis (32%, diffuse proliferative glomerulonephritis (17%; membranous nephropathy (12% and crescentic glomerulonephritis (12%. Among Group-II, the mean age was 60 years (46-71 years, and the most common lesion was interstitial nephritis superimposed on underlying DN (63% cases. Among Group-III, the mean age was 53 years (42- 80 years. The mean proteinuria was 5, 6.3 and 7.3 g/24 h of urine collection in Groups I, II and III, respectively (P = NS. The mean duration of diabetes was 7.3, 11.7 and 10.7 years in Groups I, II and III, respectively. The duration of

  19. Diet and kidney disease in high-risk individuals with type 2 diabetes mellitus.

    Science.gov (United States)

    Dunkler, Daniela; Dehghan, Mahshid; Teo, Koon K; Heinze, Georg; Gao, Peggy; Kohl, Maria; Clase, Catherine M; Mann, Johannes F E; Yusuf, Salim; Oberbauer, Rainer

    2013-10-14

    Type 2 diabetes mellitus and associated chronic kidney disease (CKD) have become major public health problems. Little is known about the influence of diet on the incidence or progression of CKD among individuals with type 2 diabetes. To examine the association between (healthy) diet, alcohol, protein, and sodium intake, and incidence or progression of CKD among individuals with type 2 diabetes. All 6213 individuals with type 2 diabetes without macroalbuminuria from the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) were included in this observational study. Recruitment spanned from January 2002 to July 2003, with prospective follow-up through January 2008. Chronic kidney disease was defined as new microalbuminuria or macroalbuminuria or glomerular filtration rate decline of more than 5% per year at 5.5 years of follow-up. We assessed diet using the modified Alternate Healthy Eating Index (mAHEI). The analyses were adjusted for known risk factors, and competing risk of death was considered. After 5.5 years of follow-up, 31.7% of participants had developed CKD and 8.3% had died. Compared with participants in the least healthy tertile of mAHEI score, participants in the healthiest tertile had a lower risk of CKD (adjusted odds ratio [OR], 0.74; 95% CI, 0.64-0.84) and lower risk of mortality (OR, 0.61; 95% CI, 0.48-0.78). Participants consuming more than 3 servings of fruits per week had a lower risk of CKD compared with participants consuming these food items less frequently. Participants in the lowest tertile of total and animal protein intake had an increased risk of CKD compared with participants in the highest tertile (total protein OR, 1.16; 95% CI, 1.05-1.30). Sodium intake was not associated with CKD. Moderate alcohol intake reduced the risk of CKD (OR, 0.75; 95% CI, 0.65-0.87) and mortality (OR, 0.69; 95% CI, 0.53-0.89). A healthy diet and moderate intake of alcohol may decrease the incidence or progression of CKD

  20. Non-diabetic renal disease in patients with type 2 diabetes: a single centre study.

    Science.gov (United States)

    Fan, Jian-Zhen; Wang, Rong

    2018-04-01

    Non-diabetic renal disease (NDRD) has been widely known in diabetic patients. The clinical differentiation between diabetic nephropathy (DN) and NDRD is still not so clear and effective. To analyse the pathological characteristics and distribution of renal injury in selected type 2 diabetic patients. Comparison between DN and NDRD in clinical characteristics, to find important predictors for NDRD. To conduct retrospective analysis of clinical, laboratory and pathohistological data of type 2 diabetic patients in whom renal biopsies were performed from March 2010 to September 2014 in Shandong Provincial Hospital affiliated to Shandong University (n = 88). According to the findings of renal biopsy, the incidences of DN, NDRD and DN complicated with NDRD were 20.46, 72.73 and 6.82% respectively. The most common NDRD found were: membranous nephropathy, followed by IgA nephropathy and focal segmental glomerulosclerosis. In multivariate logistic-analysis, fasting blood glucose (odds ratio (OR) 0.714; 95% confidence interval (CI) = 0.543-0.939; P = 0.016) and absence of diabetic retinopathy (OR 18.602; 95% CI = 2.176-159.018; P = 0.003) were independent predictors of NDRD. This study confirmed a considerably high prevalence of NDRD in type 2 diabetic patients with renal injury. As some cases of NDRD are readily treatable or remittable, we should consider renal biopsy in selected diabetic patients with renal involvement, especially in those with effective blood glucose control and the absence of diabetic retinopathy. © 2017 Royal Australasian College of Physicians.

  1. Borna disease virus nucleoprotein inhibits type I interferon induction through the interferon regulatory factor 7 pathway

    International Nuclear Information System (INIS)

    Song, Wuqi; Kao, Wenping; Zhai, Aixia; Qian, Jun; Li, Yujun; Zhang, Qingmeng; Zhao, Hong; Hu, Yunlong; Li, Hui; Zhang, Fengmin

    2013-01-01

    Highlights: •IRF7 nuclear localisation was inhibited by BDV persistently infected. •BDV N protein resistant to IFN induction both in BDV infected OL cell and N protein plasmid transfected OL cell. •BDV N protein is related to the inhibition of IRF7 nuclear localisation. -- Abstract: The expression of type I interferon (IFN) is one of the most potent innate defences against viral infection in higher vertebrates. Borna disease virus (BDV) establishes persistent, noncytolytic infections in animals and in cultured cells. Early studies have shown that the BDV phosphoprotein can inhibit the activation of type I IFN through the TBK1–IRF3 pathway. The function of the BDV nucleoprotein in the inhibition of IFN activity is not yet clear. In this study, we demonstrated IRF7 activation and increased IFN-α/β expression in a BDV-persistently infected human oligodendroglia cell line following RNA interference-mediated BDV nucleoprotein silencing. Furthermore, we showed that BDV nucleoprotein prevented the nuclear localisation of IRF7 and inhibited endogenous IFN induction by poly(I:C), coxsackie virus B3 and IFN-β. Our findings provide evidence for a previously undescribed mechanism by which the BDV nucleoprotein inhibits type I IFN expression by interfering with the IRF7 pathway

  2. A case of stiff-person syndrome, type 1 diabetes, celiac disease and dermatitis herpetiformis.

    LENUS (Irish Health Repository)

    O'Sullivan, Eoin P

    2009-05-01

    Antibodies against glutamic acid decarboxylase (GAD) are involved in the pathophysiology of stiff-person syndrome (SPS) and type 1 diabetes. GAD catalyses the conversion of glutamate to gamma-aminobutyric acid (GABA). GABA acts as a neurotransmitter between neurones, while in pancreatic beta cells it plays an integral role in normal insulin secretion, hence the clinical presentation of muscular spasms in SPS and insulin deficiency in diabetes. Despite this apparent major overlap in pathophysiology, SPS only rarely occurs in individuals with type 1 diabetes. We report the case of a 41-year-old man presenting with a simultaneous diagnosis of both these conditions. His case is unusual in that it is the first reported case in the literature of these conditions occurring in someone with celiac disease (CD) and dermatitis herpetiformis. We discuss why SPS and type 1 diabetes co-exist in only a minority of cases and speculate on the underlying mechanism of the association with CD and dermatitis herpetiformis in our patient.

  3. Recurrent hypoglycaemia in type-1 diabetes mellitus may unravel the association with Addison's disease: a case report.

    Science.gov (United States)

    Passanisi, Stefano; Timpanaro, Tiziana; Lo Presti, Donatella; Caruso-Nicoletti, Manuela

    2014-09-12

    Primary adrenocortical insufficiency or Addison's disease is caused by a progressive destruction of the adrenal cortex, resulting into a reduction of glucocorticoids, mineralocorticoids, and androgens. Autoimmune Addison's disease is the most common etiological form, accounting for about 80% of all cases. We describe the case of a 16-year-old Caucasian boy affected by type-1 diabetes mellitus and autoimmune thyroiditis, who experienced recurrent hypoglycaemia as presenting symptom of Addison's disease. Hypoglycaemia is not a common presenting feature of Addison's disease, both in patients with type-1 diabetes mellitus and in non-diabetic patients. However, hypoglycaemia may occur in association with primary and secondary glucocorticoid deficiency as a result of an enhanced insulin sensitivity. Hypoglycaemia is the most common acute complication of insulin therapy in patients with type-1 diabetes mellitus. Addison's disease has been described in approximately 0.5% of patients with type-1 diabetes mellitus, being more frequent in females and occurring in middle-aged patients. An association among type-1 diabetes mellitus, autoimmune thyroiditis, and Addison's disease is found in the "Schmidt's syndrome", a rare disorder that may occur in the paediatric age. Our case suggests that the presence of Addison's disease should be taken into consideration in patients with type-1 diabetes mellitus and frequent episodes of hypoglycaemia. We wish to highlight that there are no specific indications to screen for the association between Addison's disease and type-1 diabetes mellitus, although an early diagnosis of Addison's disease in diabetic patients would prevent the morbidity and potential mortality of this association.

  4. Impact of Education on Disease Knowledge and Glycaemic Control Among Type 2 Diabetic Patients in Family Practice

    Directory of Open Access Journals (Sweden)

    Samira Herenda

    2007-08-01

    Full Text Available In patients with diabetes type 2, good knowledge about disease often doesn’t follow appropriate behavior in their life. Therefore, we wanted to find out basic level of disease knowledge and glycemic control among type 2 diabetic patients, and after that impact of passive and intensive education on knowledge and glycemic control. Starting with 130 participants, 91 patients with type 2 diabetes, from four family medicine services in Tuzla Canton, completed six months education about their disease. Disease Knowledge Test of Michigan Diabetes Training and Research Center was used to evaluate knowledge about diabetes and glycaemic control was assessed by HbAic. Participants were tested at the beginning of survey, after 3 months of passive education and additional 3 months of intensive one. Basic test showed good knowledge of participants (score 8,3 out of 15, improved knowledge after passive education (score 9,23 and intensive one (11,19 (P<0,0001. Demographic characteristics of patients (age, sex, living area, level of education, duration of disease and type of treatment had no influence on disease knowledge and glycaemic control during education. Generally, patient education improved significantly glycaemic control by HbA1c reduction 0,45% (P=0,011 without significant differences between passive and intensive one. Education of patients improves both disease knowledge and glycaemic control among type 2 diabetic patients.

  5. Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease

    DEFF Research Database (Denmark)

    Zhao, Wei; Rasheed, Asif; Tikkanen, Emmi

    2017-01-01

    To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for ...

  6. Niemann-Pick disease, type B with TRAP-positive storage cells and secondary sea blue histiocytosis

    Directory of Open Access Journals (Sweden)

    R. Saxena

    2009-09-01

    Full Text Available We present 2 cases of Niemann Pick disease, type B with secondary sea-blue histiocytosis. Strikingly, in both cases the Pick cells were positive for tartrate resistant acid phosphatase, a finding hitherto described only in Gaucher cells. This report highlights the importance of this finding as a potential cytochemical diagnostic pitfall in the diagnosis of Niemann Pick disease.

  7. Pathogenesis of type 2 diabetes and cardiovascular disease in South Asians : effects of dietary interventions on metabolism and cardiovascular function

    NARCIS (Netherlands)

    Bakker, Leontine Erica Henriëtte

    2015-01-01

    People of South Asian origin have an increased risk of developing type 2 diabetes (T2D) and cardiovascular disease (CVD) compared to people of Western European descent. Not only is the prevalence of these diseases higher in South Asians, they also occur at a younger age and lower BMI, and have a

  8. HLA-DQ genetic risk gradient for type 1 diabetes and celiac disease in northwestern Mexico.

    Science.gov (United States)

    Mejía-León, M E; Ruiz-Dyck, K M; Calderón de la Barca, A M

    2015-01-01

    Type 1 diabetes (T1D) and celiac disease (CD) are the 2 most common autoimmune childhood diseases that share their HLA-DQ2 and DQ8 genetic origin. There has currently been an increase in both diseases worldwide. In children from the low-population State of Sonora (15 inhabitants/km(2)) in north-western Mexico, there is no information on their genetic risk or the distribution of the related alleles in the general population. To compare the HLA-DQ allele frequency in a representative sample of newborns from Sonora with that of T1D and CD patients to determine the risk gradient, and to identify the presence of celiac autoimmunity in the T1D group. The study included 397 Sonoran newborns, with 44 cases of T1D, and 25 CD cases. The CD and T1D cases were clinically diagnosed by specialists at the Hospital Infantil del Estado de Sonora, and the autoantibodies were determined by ELISA. Whole blood was collected, gDNA was extracted, and HLA-DQ2 and DQ8 were typed by PCR-SSP. The risk gradient was calculated by comparing the allele frequencies of the cases with those of the newborns. The Sonoran HLA-DQ risk heterodimer proportion was 16.1% for HLA-DQ2 and 13.6% for HLA-DQ8, with an HLA-DQ2:HLA-DQ8 ratio of 1.2:1. The DQ8/DQ2 genotype represented a 1:14 risk for T1D, whereas the DQ8/DQB1*0201 combination showed a 1:6 risk for CD. The prevalence of CD autoimmunity in T1D children was 7%. The Sonoran population has a distinctive HLA-DQ allele distribution due to its ancestry. The HLA-DQ8 combinations with DQ2 or one of its alleles conferred the highest risk for both diseases, and T1D and CD frequently appear together. Copyright © 2015 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

  9. Spotlight on taliglucerase alfa in the treatment of pediatric patients with type 1 Gaucher disease

    Directory of Open Access Journals (Sweden)

    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

  10. EFFECTIVENESS AND SAFETY OF VELAGLUCERASE ALFA IN TREATMENT OF GAUCHER DISEASE TYPE 1 (ACCORDING TO INTERNATIONAL STUDIES

    Directory of Open Access Journals (Sweden)

    O. S. Gundobina

    2014-01-01

    Full Text Available The article is dedicated to modern approaches to treatment of Gaucher’s disease. The authors list the primary aspects of the disease and present data on the origin and introduction of pathogenetic enzyme replacement therapy to clinical practice. Review of international clinical studies demonstrates high effectiveness and safety of long-term enzyme replacement therapy with velaglucerase alfa in patients with confirmed type I Gaucher’s disease

  11. Congenital genetic inborn errors of metabolism presenting as an adult or persisting into adulthood: neuroimaging in the more common or recognizable disorders.

    Science.gov (United States)

    Krishna, Shri H; McKinney, Alexander M; Lucato, Leandro T

    2014-04-01

    Numerous congenital-genetic inborn errors of metabolism (CIEMs) have been identified and characterized in detail within recent decades, with promising therapeutic options. Neuroimaging is becoming increasingly utilized in earlier stages of CIEMs, and even in asymptomatic relatives of patients with a CIEM, so as to monitor disease progress and treatment response. This review attempts to summarize in a concise fashion the neuroimaging findings of various CIEMs that may present in adulthood, as well as those that may persist into adulthood, whether because of beneficial therapy or a delay in diagnosis. Notably, some of these disorders have neuroimaging findings that differ from their classic infantile or early childhood forms, whereas others are identical to their early pediatric forms. The focus of this review is their appearance on routine magnetic resonance imaging sequences, with some basic attention to the findings of such CIEMs on specialized neuroimaging, based on recent or preliminary research. The general classes of disorders covered in this complex review are: peroxisomal disorders (adrenoleukodystrophy), lysosomal storage disorders (including metachromatic leukodystrophy, Krabbe or globoid cell leukodystrophy, Fabry, Niemann-Pick, GM1, GM2, Gaucher, mucopolysaccharidoses, and Salla diseases), mitochondrial disorders (including mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes, myoclonic epilepsy with ragged red fibers, Leigh disease, and Kearns-Sayre syndrome), urea cycle disorders, several organic acidemias (including phenylketonuria, maple syrup urine disease, 3-hydroxy-3-methylglutaryl colyase deficiency, glutaric acidurias, methylmalonic academia, proprionic academia, 3-methylglucatonic aciduria, and 2-hydroxyglutaric acidurias), cytoskeletal or transporter molecule defects (including Alexander or fibrinoid leukodystrophy, proteolipid protein-1 defect or Pelizaeus Merzbacher, Wilson, and Huntington diseases), and several

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

    Science.gov (United States)

    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.

  13. DISEASES

    DEFF Research Database (Denmark)

    Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi

    2015-01-01

    Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition...... of human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should...... not stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases...

  14. The association between cardiovascular disease and type 2 diabetes in adults with atopic dermatitis

    DEFF Research Database (Denmark)

    Thyssen, J P; Halling-Overgaard, A-S; Andersen, Y M F

    2017-01-01

    databases. Data extraction was done by two independent reviewers. We found a total of 2,855 citations, of which 53 were considered relevant based on title and abstract. Sixteen publications were included in the qualitative analysis, of which 13 were also included in a quantitative meta-analysis of crude...... 0.83-1.56), but a positive association was observed with angina pectoris (OR 1.73; 95% CI 1.27-2.37). Meta-analysis on adjusted data gave similar results. While adults with AD in some populations have increased prevalence of cardiovascular risk factors, such as obesity and smoking, it is unlikely......Recent studies examining the association between atopic dermatitis (AD) and cardiovascular disease (CVD) and type 2 diabetes have shown inconsistent results. We compared the risk of CVD and diabetes between adult patients with and without AD by searching the Pubmed, Embase, and Web of Science...

  15. Phenotype Variation in Human Immunodeficiency virus Type 1 Transmission and Disease Progression

    Directory of Open Access Journals (Sweden)

    Mariangela Cavarelli

    2009-01-01

    Full Text Available Human immunodeficiency virus type I (HIV-1 infects target cells through interaction with the CD4 molecule and chemokine receptors, mainly CCR5 and CXCR4. Viral isolates can be phenotypically classified based on the co-receptor they utilize to infect target cells. Thus, R5 and X4 virus use respectively CCR5 and CXCR4, whereas R5X4 virus can use either CCR5 or CXCR4. This review describes the central role played by co-receptor expression and usage for HIV-1 cell tropism, transmission and pathogenesis. We discuss various hypotheses proposed to explain the preferential transmission of R5 viruses and the mechanisms driving the change of HIV-1 co-receptor usage in the course of infection. Recent insights in the intrinsic variability of R5 viruses and their role in influencing disease progression in both adults and children are also discussed.

  16. Phenotype variation in human immunodeficiency virus type 1 transmission and disease progression.

    Science.gov (United States)

    Cavarelli, Mariangela; Scarlatti, Gabriella

    2009-01-01

    Human immunodeficiency virus type I (HIV-1) infects target cells through interaction with the CD4 molecule and chemokine receptors, mainly CCR5 and CXCR4. Viral isolates can be phenotypically classified based on the co-receptor they utilize to infect target cells. Thus, R5 and X4 virus use respectively CCR5 and CXCR4, whereas R5X4 virus can use either CCR5 or CXCR4. This review describes the central role played by co-receptor expression and usage for HIV-1 cell tropism, transmission and pathogenesis. We discuss various hypotheses proposed to explain the preferential transmission of R5 viruses and the mechanisms driving the change of HIV-1 co-receptor usage in the course of infection. Recent insights in the intrinsic variability of R5 viruses and their role in influencing disease progression in both adults and children are also discussed.

  17. Potatoes and risk of obesity, type 2 diabetes, and cardiovascular disease in apparently healthy adults

    DEFF Research Database (Denmark)

    Borch, Daniel; Juul-Hindsgaul, Nicole; Veller, Mette

    2016-01-01

    BACKGROUND: Potatoes have been related to increased risks of obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD) mainly because of their high glycemic index. OBJECTIVE: We conducted a systematic review to evaluate the relation between intake of potatoes and risks of obesity, T2D......, and measured adiposity (body weight, body mass index, or waist circumference), cases of T2D, cases of cardiovascular events, or risk markers thereof. RESULTS: In total, 13 studies were deemed eligible; 5 studies were related to obesity, 7 studies were related to T2D, and one study was related to CVD. Only....... CONCLUSIONS: The identified studies do not provide convincing evidence to suggest an association between intake of potatoes and risks of obesity, T2D, or CVD. French fries may be associated with increased risks of obesity and T2D although confounding may be present. In this systematic review, only...

  18. Increased salivary oxidative stress parameters in patients with type 2 diabetes: Relation with periodontal disease.

    Science.gov (United States)

    Arana, Carlos; Moreno-Fernández, Ana María; Gómez-Moreno, Gerardo; Morales-Portillo, Cristóbal; Serrano-Olmedo, Isabel; de la Cuesta Mayor, M Carmen; Martín Hernández, Tomás

    2017-05-01

    The aim of this study was to determine whether there are differences in salivary oxidative stress between patients with diabetes mellitus type 2 (DM2) and healthy non-diabetic patients, and whether this oxidative stress is associated with the presence of periodontal disease in diabetic patients. This observational study included 70 patients divided into three groups according to metabolic control levels: 19 non-diabetic patients (control group); 24 patients with good metabolic control (HbA1c7%). The following oxidative stress parameters were measured in all subjects: glutathione peroxidase (GPx), glutathione reductase (GRd), reduced glutathione (GSH) and oxidized glutathione (GSSG). Periodontal health was determined by means of the community periodontal index (CPI) recommended by the WHO. The diabetic group with good metabolic control showed a significant increase in GPx and GRd activity in comparison with the control group (Pperiodontal health. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Peripheral vascular disease is associated with reduced glycosuria in newly diagnosed type 2 diabetic patients

    DEFF Research Database (Denmark)

    Olivarius, Niels de Fine; Holstein-Rathlou, N H; Siersma, V

    2004-01-01

    was 65.2 years. Urinary glucose concentration (UGC) was determined quantitatively in a freshly voided morning urine specimen. RESULTS: The over-all prevalence of peripheral vascular disease (PVD) was 16.5%. Bivariately, high values of UGC were associated with low prevalence of PVD (p...). The predictive value of PVD--together with HbA1c, glomerular filtration rate (GFR) and 10 other possible predictors--was confirmed in a logistic regression analysis with glycosuria (Y/N) as outcome variable (p=0.0004). CONCLUSION: Surprisingly, type 2 diabetic patients with PVD tend not to have glycosuria...... as compared to patients without PVD. PVD may be indicative of generalized atherosclerotic lesions in the major vessels, including the renal arteries. This could lead to a lowering of GFR and thereby of the amount of glucose filtered. Assuming no, or only a minor direct effect of PVD on tubular function...

  20. Mitochondrial dysfunction in calf muscles of patients with combined peripheral arterial disease and diabetes type 2

    DEFF Research Database (Denmark)

    Lindegaard Pedersen, Brian; Bækgaard, Niels; Quistorff, Bjørn

    2017-01-01

    BACKGROUND: This study elucidate the effects on muscle mitochondrial function in patients suffering from combined peripheral arterial disease (PAD) and type 2 diabetes (T2D) and the relation to patient symptoms and treatment. METHODS: Near Infra Red Spectroscopy (NIRS) calf muscle exercise tests...... were conducted on Forty subjects, 15 (PAD), 15 (PAD+T2D) and 10 healthy age matched controls (CTRL) recruited from the vascular outpatient clinic at Gentofte County Hospital, Denmark. Calf muscle biopsies (~ 80 mg) (Gastrocnemius and Anterior tibial muscles) were sampled and mitochondrial function...... group. This was confirmed by a ~30% reduction in oxygen consumption in the muscle biopsy tests for the PAD+T2D compared to the PAD group (P

  1. Compromised cortical bone compartment in type 2 diabetes mellitus patients with microvascular disease

    DEFF Research Database (Denmark)

    Shanbhogue, Vikram Vinod; Hansen, Stinus; Nielsen, Morten Frost Munk

    2016-01-01

    OBJECTIVE AND DESIGN: Patients with type 2 diabetes mellitus (T2D) have an increased fracture risk despite a normal or elevated bone mineral density (BMD). The aim of this cross-sectional in vivo study was to assess parameters of peripheral bone microarchitecture, estimated bone strength and bone...... remodeling in T2D patients with and without diabetic microvascular disease (MVD+ and MVD- respectively) and to compare them with healthy controls. METHODS: Fifty-one T2D patients (MVD+ group: n=25) were recruited from Funen Diabetic Database and matched for age, sex and height with 51 healthy subjects. High...... deficits are not a characteristic of all T2D patients but of a subgroup characterized by the presence of microvascular complications. Whether this influences fracture rates in these patients needs further investigation....

  2. Plasma copeptin as marker of cardiovascular disease in asymptomatic type 2 diabetes patients

    DEFF Research Database (Denmark)

    Bar-Shalom, Dana; Poulsen, Mikael K; Rasmussen, Lars M

    2014-01-01

    Recently, copeptin was found associated with cardiovascular disease (CVD) and all-cause mortality in type 2 diabetes mellitus (T2DM) patients treated in primary care. This study aimed to evaluate whether plasma copeptin correlated to CVD in asymptomatic T2DM patients intensively investigated....... A variety of clinical investigations were performed, including blood pressure measurements, carotid intima media thickness evaluation and myocardial perfusion scintigraphy. Blood sample analyses included copeptin measurements. Median plasma copeptin concentrations were similar in the T2DM group...... for sub-clinical CVD. A total of 302 T2DM patients referred to the Diabetes Clinic at Odense University Hospital, Denmark, entered the study. None of the patients had known or suspected CVD. As a control group, 30 healthy adults were recruited from the DanRisk study - a random sample of middle-aged Danes...

  3. Miglustat therapy in the French cohort of paediatric patients with Niemann-Pick disease type C

    Directory of Open Access Journals (Sweden)

    Héron Bénédicte

    2012-06-01

    Full Text Available Abstract Background Niemann-Pick disease type C (NP-C is a rare neurovisceral lysosomal lipid storage disease characterized by progressive neurological deterioration. Published data on the use of miglustat in paediatric patients in clinical practice settings are limited. We report findings from a prospective open-label study in the French paediatric NP-C cohort. Methods Data on all paediatric NP-C patients treated with miglustat in France between October 2006 and December 2010 were compiled. All patients had a confirmed diagnosis of NP-C, and received miglustat therapy according to manufacturer’s recommendations. Pre-treatment and follow-up assessments were conducted according to a standardized protocol. Results Twenty children were enrolled; 19 had NPC1 gene mutations and 1 had NPC2 gene mutations. The median age at diagnosis was 1.5 years, and the median age at miglustat initiation was 6.0 years. Eight NPC1 patients had the early-infantile, eight had the late-infantile, and three had the juvenile-onset forms of NP-C. A history of hepatosplenomegaly and/or other cholestatic symptoms was recorded in all 8 early-infantile onset patients, 3/8 late-infantile patients, and 1/3 juvenile onset patients. Brain imaging indicated white matter abnormalities in most patients. The median (range duration of miglustat therapy was 1.3 (0.6–2.3 years in early-infantile, 1.0 (0.8–5.0 year in late-infantile, and 1.0 (0.6–2.5 year in juvenile onset patients. NP-C disability scale scores indicated either stabilization or improvement of neurological manifestations in 1/8, 6/8, and 1/3 NPC1 patients in these subgroups, respectively. There were no correlations between brain imaging findings and disease course. Mild-to-moderate gastrointestinal disturbances were frequent during the first 3 months of miglustat therapy, but were easily managed with dietary modifications and/or anti-propulsive medication. Conclusions Miglustat can improve or stabilize neurological

  4. Metabolic syndrome and the development of vascular disease and type 2 diabetes in high-risk patients

    NARCIS (Netherlands)

    Wassink, A.M.J.

    2009-01-01

    Abdominal obesity and its associated insulin resistance play a key role in the clustering of vascular risk factors, known as Metabolic Syndrome. Subjects with Metabolic Syndrome are at increased risk for the development of both type 2 diabetes and cardiovascular disease. Type 2 diabetes and

  5. Early myocardial impairment in type 1 diabetes patients without known heart disease assessed with tissue Doppler echocardiography

    DEFF Research Database (Denmark)

    Jensen, Magnus Thorsten; Søgaard, Peter; Andersen, Henrik Ullits

    2016-01-01

    PURPOSE: Cardiovascular disease is the most common cause of mortality in type 1 diabetes; patients with albuminuria are at greatest risk. We investigated myocardial function and premature myocardial impairment in type 1 diabetes patients with and without albuminuria compared to controls. METHODS:...

  6. Role of pH in determining the cell-type-specific residual activity of glucocerebrosidase in type 1 Gaucher disease

    NARCIS (Netherlands)

    van Weely, S.; van den Berg, M.; Barranger, J. A.; Sa Miranda, M. C.; Tager, J. M.; Aerts, J. M.

    1993-01-01

    The properties of control and 370Asn-->Ser glucocerebrosidase, the frequently encountered mutated form of the enzyme in type 1 Gaucher disease, were studied in vitro as well as in situ. The catalytic properties of purified 370Asn-->Ser glucocerebrosidase were highly dependent on the assay

  7. Co-existence of scrapie prion protein types 1 and 2 in sporadic Creutzfeldt-Jakob disease: its effect on the phenotype and prion-type characteristics

    NARCIS (Netherlands)

    Cali, I.; Castellani, R.; Alshekhlee, A.; Cohen, Y.; Blevins, J.; Yuan, J.; Langeveld, J.P.M.; Parchi, P.; Safar, J.G.; Zou, W.Q.; Gambetti, P.

    2009-01-01

    Five phenotypically distinct subtypes have been identified in sporadic Creutzfeldt-Jakob disease (sCJD), based on the methionine/valine polymorphic genotype of codon 129 of the prion protein (PrP) gene and the presence of either one of the two protease K-resistant scrapie prion protein (PrPSc) types

  8. Patients with type 1 Gaucher disease in Spain: A cross-sectional evaluation of health status.

    Science.gov (United States)

    Giraldo, Pilar; Pérez-López, Jordi; Núñez, Ramiro; de la Puebla, Rafael Fernández; Luño, Elisa; Saura-Grau, Salvador; Bureo, Juan Carlos; Plaza, Sylvia; de la Serna, Javier

    2016-01-01

    A multicentre, cross-sectional epidemiological survey was conducted to describe the health status of patients with type 1 Gaucher disease (GD1) in Spain. Patient data were collected retrospectively from clinical records. Therapeutic goals for seven clinical parameters were chosen as primary outcome measures. 108 GD1 patients (mean age 44.8 years; 53% male) were recruited from 28 hospitals. Ninety-five patients (88%) were receiving treatment for GD1. Hemoglobin concentration was the therapeutic goal with the highest level of achievement, being met by 105 of 108 patients (97%), followed by the goals for liver volume (86/98 patients; 88%), spleen volume (67/77 patients; 87%) and platelet count (81/108 patients; 75%). The goal for bone mineral density (BMD) was met by 48 of 75 patients (64%), and the goal for quality of life was met by 65 of 103 patients (63%). Bone pain was the parameter with the lowest level of achievement (goal met by 50/94 patients; 53%). The clinical information most often missing from patient records was the BMD Z-score (missing for 31% of patients). These data suggest that most Spanish GD1 patients have good control over hematological and visceral parameters, but there is a need to improve monitoring and treatment of GD-related bone disease. Copyright © 2015. Published by Elsevier Inc.

  9. Early-onset Alzheimer's disease: nonamnestic subtypes and type 2 AD.

    Science.gov (United States)

    Mendez, Mario F

    2012-11-01

    Patients with Alzheimer's disease (AD), the most prevalent neurodegenerative dementia, are usually elderly; however, ∼4-5% develop early-onset AD (EOAD) with onset before age 65. Most EOAD is sporadic, but about 5% of patients with EOAD have an autosomal dominant mutation such as Presenilin 1, Presenilin 2, or alterations in the Amyloid Precursor Protein gene. Although most Alzheimer's research has concentrated on older, late-onset AD (LOAD), there is much recent interest and research in EOAD. These recent studies indicate that EOAD is a heterogeneous disorder with significant differences from LOAD. From 22-64% of EOAD patients have a predominant nonamnestic syndrome presenting with deficits in language, visuospatial abilities, praxis, or other non-memory cognition. These nonamnestic patients may differ in several ways from the usual memory or amnestic patients. Patients with nonamnestic EOAD compared to typical amnestic AD have a more aggressive course, lack the apolipoprotein Eɛ4 (APOE ɛ4) susceptibility gene for AD, and have a focus and early involvement of non-hippocampal areas of brain, particularly parietal neocortex. These differences in the EOAD subtypes indicate differences in the underlying amyloid cascade, the prevailing pathophysiological theory for the development of AD. Together the results of recent studies suggest that nonamnestic subtypes of EOAD constitute a Type 2 AD distinct from the usual, typical disorder. In sum, the study of EOAD can reveal much about the clinical heterogeneity, predisposing factors, and neurobiology of this disease. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

  10. Recent development and gene therapy for glycogen storage disease type Ia.

    Science.gov (United States)

    Chou, Janice Y; Kim, Goo-Young; Cho, Jun-Ho

    2017-09-01

    Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC) that is expressed primarily in the liver, kidney, and intestine. G6Pase-α catalyzes the hydrolysis of glucose-6-phosphate (G6P) to glucose and phosphate in the terminal step of gluconeogenesis and glycogenolysis, and is a key enzyme for endogenous glucose production. The active site of G6Pase-α is inside the endoplasmic reticulum (ER) lumen. For catalysis, the substrate G6P must be translocated from the cytoplasm into the ER lumen by a G6P transporter (G6PT). The functional coupling of G6Pase-α and G6PT maintains interprandial glucose homeostasis. Dietary therapies for GSD-Ia are available, but cannot prevent the long-term complication of hepatocellular adenoma that may undergo malignant transformation to hepatocellular carcinoma. Animal models of GSD-Ia are now available and are being exploited to both delineate the disease more precisely and develop new treatment approaches, including gene therapy.

  11. Renal sonographic findings of type I glycogen storage disease in infancy and early childhood

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chun-Chen; Lin, Shuan-Pei [Mackay Memorial Hospital, Department of Pediatrics, Taipei (Taiwan); Tsai, Jeng-Daw; Lee, Hung-Chang [Mackay Memorial Hospital, Department of Pediatrics, Taipei (Taiwan); Taipei Medical University, Department of Pediatrics, Taipei (Taiwan)

    2005-08-01

    Type I glycogen storage disease (GSD-I) is an inherited disorder affecting glycogenolysis and gluconeogenesis. The characteristic manifestations are hepatomegaly, hypoglycemia, hyperlacticacidemia, hyperuricemia, and hyperlipidemia. Renal disease is regarded as a long-term complication and is reported mainly in older patients. We report the renal manifestations and renal ultrasonographic findings of GSD-I in infancy and early childhood in order to assess the role of renal sonography in the diagnosis of GSD-I. We retrospectively reviewed our hospital's database for patients with GSD-I from January 1993 to September 2004. The records of five patients were reviewed for this study. These five patients were diagnosed when they were younger than 3 years old. Data extracted from the charts included the initial extrarenal and renal manifestations, laboratory data, and imaging studies. We analyzed the indications for, and results of, renal sonography. In addition to the clinical presentations and laboratory abnormalities, all five children had nephromegaly and increased echogenicity on ultrasonography on their first visit, although only a minor degree of tubular dysfunction was noted clinically. Three of these five patients had nephrocalcinosis or renal stones or both. Hyperechoic large kidneys, nephrocalcinosis, and renal stones are common in GSD-I. They can be present in early infancy. Abnormalities on renal sonography might suggest GSD-I in a patient with suspected inborn errors of metabolism. (orig.)

  12. Progressive neurologic and somatic disease in a novel mouse model of human mucopolysaccharidosis type IIIC

    Directory of Open Access Journals (Sweden)

    Sara Marcó

    2016-09-01

    Full Text Available Mucopolysaccharidosis type IIIC (MPSIIIC is a severe lysosomal storage disease caused by deficiency in activity of the transmembrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT that catalyses the N-acetylation of α-glucosamine residues of heparan sulfate. Enzyme deficiency causes abnormal substrate accumulation in lysosomes, leading to progressive and severe neurodegeneration, somatic pathology and early death. There is no cure for MPSIIIC, and development of new therapies is challenging because of the unfeasibility of cross-correction. In this study, we generated a new mouse model of MPSIIIC by targeted disruption of the Hgsnat gene. Successful targeting left LacZ expression under control of the Hgsnat promoter, allowing investigation into sites of endogenous expression, which was particularly prominent in the CNS, but was also detectable in peripheral organs. Signs of CNS storage pathology, including glycosaminoglycan accumulation, lysosomal distension, lysosomal dysfunction and neuroinflammation were detected in 2-month-old animals and progressed with age. Glycosaminoglycan accumulation and ultrastructural changes were also observed in most somatic organs, but lysosomal pathology seemed most severe in liver. Furthermore, HGSNAT-deficient mice had altered locomotor and exploratory activity and shortened lifespan. Hence, this animal model recapitulates human MPSIIIC and provides a useful tool for the study of disease physiopathology and the development of new therapeutic approaches.

  13. A case of variant biochemical phenotype of Niemann-Pick disease type C accompanying savant syndrome.

    Science.gov (United States)

    Hamatani, Mio; Jingami, Naoto; Uemura, Kengo; Nakasone, Naoe; Kinoshita, Hisanori; Yamakado, Hodaka; Ninomiya, Haruaki; Takahashi, Ryosuke

    2016-06-22

    A 40-year-old man was referred to our hospital because of vertical supranuclear gaze palsy, frequent sudden loss of muscle tonus and ataxia for several years. He had a history of prolonged neonatal jaundice. He was given a diagnosis of autism in his childhood, followed by a diagnosis of schizophrenia in his teenage. He also developed a savant skill of calendar calculating. (123)I-IMP-SPECT showed decreased cerebral blood flow in the left frontotemporal lobe as often seen in savant syndrome. Although genetic analysis of NPC1 and NPC2 revealed no pathogenic mutation, filipin staining of cultured fibroblasts from his biopsied skin revealed a certain amount of intracellular cholesterol storage pattern, indicating a variant biochemical phenotype of Niemann-Pick disease type C (NPC). The diagnosis of adulthood onset NPC is difficult and challenging, especially for neurologists, because the symptoms and signs are not as clear as those in the classical childhood onset NPC and this subtype is not yet widely known. However, the diagnosis can be made by a combination of filipin staining of fibroblast and/or gene analysis. As a disease-specific therapy for NPC has been approved in Japan, the diagnosis of NPC is of significance.

  14. Gpnmb Is a Potential Marker for the Visceral Pathology in Niemann-Pick Type C Disease.

    Directory of Open Access Journals (Sweden)

    André R A Marques

    Full Text Available Impaired function of NPC1 or NPC2 lysosomal proteins leads to the intracellular accumulation of unesterified cholesterol, the primary defect underlying Niemann-Pick type C (NPC disease. In addition, glycosphingolipids (GSLs accumulate in lysosomes as well. Intralysosomal lipid accumulation triggers the activation of a set of genes, including potential biomarkers. Transcript levels of Gpnmb have been shown to be elevated in various tissues of an NPC mouse model. We speculated that Gpnmb could serve as a marker for visceral lipid accumulation in NPC disease. We report that Gpnmb expression is increased at protein level in macrophages in the viscera of Npc1nih/nih mice. Interestingly, soluble Gpnmb was also found to be increased in murine and NPC patient plasma. Exposure of RAW264.7 macrophages to the NPC-phenotype-inducing drug U18666A also upregulated Gpnmb expression. Inhibition of GSL synthesis with the glucosylceramide synthase (GCS inhibitor N-butyl-1-deoxynojirimycin prevented U18666A-induced Gpnmb induction and secretion. In summary, we show that Gpnmb is upregulated in NPC mice and patients, most likely due to GSL accumulation.

  15. Glycogen storage disease type Ia: linkage of glucose, glycogen, lactic acid, triglyceride, and uric acid metabolism.

    Science.gov (United States)

    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.

  16. Impact of type 1 diabetes mellitus and celiac disease on nutrition and quality of life.

    Science.gov (United States)

    Nunes-Silva, J G; Nunes, V S; Schwartz, R P; Mlss Trecco, S; Evazian, D; Correa-Giannella, M L; Nery, M; Queiroz, M S

    2017-01-09

    Type 1 diabetes mellitus (T1DM) and celiac disease (CD) are autoimmune diseases and have similar genetic patterns. T1DM treatment is based on diet, physical activity and insulin therapy, whereas CD depends on dietary changes with restriction of wheat, rye and barley. The aim of the study was to evaluate the quality of life (QoL) of individuals with the association of T1DM and CD, to characterize their nutritional status and to compare it with those with only one disease and healthier controls. Sixty patients controlled by sex, age and body mass index (BMI) were stratified by previous diagnosis in: T1DM and CD (DMCD group); T1DM (DM group); CD (CD group); or healthy participants (HC). The SF-36 questionnaire was applied to assess psychological well being and results were compared with glycemic control and presence of complications related to diabetes, adhesion to gluten-free diet (GFD). Nutritional status and body mass composition were determined by BMI, waist circumference, bioimpedance, general laboratory tests and whole-body densitometry. The time of diagnosis of T1DM was similar between DMCD and DM groups; however, the duration of CD was significantly higher in the CD group compared with DMCD. The SF-36 analysis revealed statistically significant differences between DM and HC groups in two domains: general health (P=0.042) and energy/vitality (P=0.012). QoL was also correlated with compliance to a GFD, and scores were similar in both groups: DMCD and CD. Forty percent of individuals in the CD group had visceral fat area above 100 cm 2 , as opposed to 20% in the other groups. Individuals of DMCD group had similar scores to DM, CD and HC on QoL, as well as on their nutritional status and bone metabolism. Thereby, we should conclude that the association of T1DM and CD did not deteriorate their health status.

  17. Direct costs associated with chronic kidney disease among type 2 diabetic patients in India

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    K Satyavani

    2014-01-01

    Full Text Available The aim of this study was to estimate the direct costs of medical care among hospitalized type 2 diabetic patients with chronic kidney disease (CKD. A total of 209 (M:F, 133:76 patients were divided into groups based on the severity of kidney disease. Group 1 subjects had undergone renal transplantation (n = 12, group 2 was CKD patients on hemodialysis (n = 45, group 3 was patients with CKD, prior to end-stage renal disease (ESRD (n = 66, and group 4 (n = 86 consisted of subjects without any complications. Details about expenditure per hospitalization, length of stay during admission, direct medical and nonmedical cost, expenditure for the previous two years, and source of bearing the expenditure were recorded in a questionnaire. Diabetic patients with CKD prior to ESRD spend more per hospitalization than patients without any complications. [Median ₹ 12,664 vs. 3,214]. The total median cost of CKD patients on hemodialysis was significantly higher than other CKD patients (INR 61,170 vs. 12,664. The median cost involved in kidney transplantation was ₹ 392,920. The total expenditure for hospital admissions in two years was significantly higher for dialysis than transplantation. Patients on hemodialysis or kidney transplantation tend to stay longer as inpatient admissions. The source of funds for the expenditure was mainly personal savings (46%. The expenditure on hospital admissions for CKD was considerably higher, and so, there is a need to develop a protocol on a cost-effective strategy for the treatment of CKD.

  18. The hidden Niemann-Pick type C patient: clinical niches for a rare inherited metabolic disease.

    Science.gov (United States)

    Hendriksz, Christian J; Anheim, Mathieu; Bauer, Peter; Bonnot, Olivier; Chakrapani, Anupam; Corvol, Jean-Christophe; de Koning, Tom J; Degtyareva, Anna; Dionisi-Vici, Carlo; Doss, Sarah; Duning, Thomas; Giunti, Paola; Iodice, Rosa; Johnston, Tracy; Kelly, Dierdre; Klünemann, Hans-Hermann; Lorenzl, Stefan; Padovani, Alessandro; Pocovi, Miguel; Synofzik, Matthis; Terblanche, Alta; Then Bergh, Florian; Topçu, Meral; Tranchant, Christine; Walterfang, Mark; Velten, Christian; Kolb, Stefan A

    2017-05-01

    Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups ("clinical niches") have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes. Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included. Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches. Several clinical niches have been identified that harbor patients at increased risk of NP-C.

  19. Human T-lymphotropic virus type 1 infection and disease in Spain.

    Science.gov (United States)

    de Mendoza, Carmen; Caballero, Estrella; Aguilera, Antonio; Requena, Silvia; de Lejarazu, Raúl Ortiz; Pirón, María; González, Rocío; Jiménez, Ana; Roc, Lourdes; Treviño, Ana; Benito, Rafael; Fernández-Alonso, Miriam; Aguinaga, Aitziber; Rodríguez, Carmen; García-Costa, Juan; Blanco, Lidia; Ramos, José M; Calderón, Enrique; Eirós, José M; Sauleda, Silvia; Barreiro, Pablo; Soriano, Vicente

    2017-07-31

    : Human T-lymphotropic virus type 1 (HTLV-1) infection is a neglected disease despite roughly 15 million people are chronically infected worldwide. Lifelong less than 10% of carriers develop life-threatening diseases, mostly a subacute myelopathy known as tropical spastic paraparesis (TSP) and a lymphoproliferative disorder named adult T-cell leukemia (ATL). HTLV-1 is efficiently transmitted perinatally (breastfeeding), sexually (more from men to women) and parenterally (transfusions, injection drug user (IDU), and transplants). To date there is neither prophylactic vaccine nor effective antiviral therapy. A total of 327 cases of HTLV-1 infection had been reported at the HTLV-1 Spanish registry until December 2016, of whom 34 had been diagnosed with TSP and 25 with ATL. Overall 62% were Latin American immigrants and 13% were persons of African origin. The incidence of HTLV-1 in Spain has remained stable for nearly a decade with 20-25 new cases yearly. Of the 21 newly diagnosed HTLV-1 cases during year 2016, one was a native Spaniard pregnant woman, and four presented with symptomatic disease, including three with ATL and one with TSP. Underdiagnosis of HTLV-1 in Spain must be high (iceberg model), which may account for the disproportionate high rate of symptomatic cases (almost 20%) and the late recognition of preventable HTLV-1 transmissions in special populations, such as newborns and transplant recipients. Our current estimate is of 10 000 persons living with HTLV-1 infection in Spain. Given the large flux of immigrants and visitors from HTLV-1 endemic regions to Spain, the expansion of HTLV-1 screening policies is warranted. At this time, it seems worth recommending HTLV testing to all donor/recipient organ transplants and pregnant women regardless place of birth. Although current leukoreduction procedures largely prevent HTLV-1 transmission by blood transfusions, HTLV testing of all first-time donors should be cost-effective contributing to unveil

  20. Dual Blockade of the Renin-angiotensin-aldosterone System in Type 2 Diabetic Kidney Disease

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    Yan-Huan Feng

    2016-01-01

    Full Text Available Objective: To examine the efficacy and safety of dual blockade of the renin-angiotensin-aldosterone system (RAAS among patients with type 2 diabetic kidney disease. Data Sources: We searched the major literature repositories, including the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE, for randomized clinical trials published between January 1990 and October 2015 that compared the efficacy and safety of the use of dual blockade of the RAAS versus the use of monotherapy, without applying any language restrictions. Keywords for the searches included "diabetic nephropathy," "chronic kidney disease," "chronic renal insufficiency," "diabetes mellitus," "dual therapy," "combined therapy," "dual blockade," "renin-angiotensin system," "angiotensin-converting enzyme inhibitor," "angiotensin-receptor blocker," "aldosterone blockade," "selective aldosterone blockade," "renin inhibitor," "direct renin inhibitor," "mineralocorticoid receptor blocker," etc. Study Selection: The selected articles were carefully reviewed. We excluded randomized clinical trials in which the kidney damage of patients was related to diseases other than diabetes mellitus. Results: Combination treatment with an angiotensin-converting enzyme inhibitor supplemented by an angiotensin II receptor blocking agent is expected to provide a more complete blockade of the RAAS and a better control of hypertension. However, existing literature has presented mixed results, in particular, related to patient safety. In view of this, we conducted a comprehensive literature review in order to explain the rationale for dual blockade of the RAAS, and to discuss the pros and cons. Conclusions: Despite the negative results of some recent large-scale studies, it may be immature to declare that the dual blockade is a failure because of the complex nature of the RAAS surrounding its diversified functions and utility. Further trials are warranted to study the combination therapy as an

  1. Cerebral hemodynamics in adult ischemic-type patients with moyamoya disease compared with those of atherothrombotic middle cerebral artery occlusion

    International Nuclear Information System (INIS)

    Idei, Masaru; Yamane, Kanji; Nishida, Masahiro; Manabe, Kazufumi; Yokota, Akira

    2005-01-01

    We measured regional cerebral blood flow (rCBF) in adult ischemic-type patients with moyamoya disease and in patients with atherothrombotic middle cerebral artery occlusion (MCAO) to investigate cerebral hemodynamics in adult ischemic-type of moyamoya disease. In this study we measured rCBF and regional cerebro-vascular response (rCVR) using acetazolamide by Xe-non-enhanced CT. Our subjects consisted of 15 adult ischemic-type patients with moyamoya disease and 27 atherothrombotic stroke patients with proximal occlusion of the middle cerebral artery. The region of inter est was conducted in the anterior cerebral artery, middle cerebral artery and posterior cerebral artery territories as well as basal ganglia regions. rGBF was preserved in all regions of patients with moyamoya disease. However, rCVR severely decreased in the anterior circulation territory in patients with moyamoya disease compared with those of MCAO. These results suggest that rCBF in the anterior circulation territory of adult ischemic-type patients with moyamoya disease is preserved by vasodilation of the cerebral arteries, while cerebral hemodynamic reserve capacity is severely reduced. The results indicated that basal moyamoya vessels are dilated. These findings may be one of the reasons why stroke occurs more frequently in adult than child patients with moyamoya disease. (author)

  2. Apolipoprotein E Gene Polymorphism and Its Association with Cardiovascular Heart Disease Risk Factors in Type 2 Diabetes Mellitus

    OpenAIRE

    Amani Ashari; Julia Omar; Arif Hashim; Shahrul Hamid

    2016-01-01

    Apolipoprotein E (APOE) gene polymorphism has influence on serum lipids which relates to cardiovascular risk. The purpose of this study was to determine the frequency distribution of APOE alleles among Malaysian Type 2 Diabetes Mellitus (DM) patients with and without coronary artery disease (CAD) and their association with serum lipid profiles. A total of 115 patients were recruited in which 78 patients had Type 2 DM without CAD and 37 patients had Type 2 DM with CAD. The APOE polymorphism wa...

  3. Validity of Type D personality in Iceland: association with disease severity and risk markers in cardiac patients

    OpenAIRE

    Svansdottir, Erla; Karlsson, Hrobjartur D.; Gudnason, Thorarinn; Olason, Daniel T.; Thorgilsson, Hordur; Sigtryggsdottir, Unnur; Sijbrands, Eric J.; Pedersen, Susanne S.; Denollet, Johan

    2011-01-01

    textabstractType D personality has been associated with poor prognosis in cardiac patients. This study investigated the validity of the Type D construct in Iceland and its association with disease severity and health-related risk markers in cardiac patients. A sample of 1,452 cardiac patients completed the Type D scale (DS14), and a subgroup of 161 patients completed measurements for the five-factor model of personality, emotional control, anxiety, depression, stress and lifestyle factors. Th...

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

    Science.gov (United States)

    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

  5. Platelet oxidative stress and its relationship with cardiovascular diseases in type 2 diabetes mellitus patients.

    Science.gov (United States)

    El Haouari, Mohammed

    2017-10-05

    Enhanced platelet activation and thrombosis are linked to various cardiovascular diseases. Among other mechanisms, oxidative stress seems to play a pivotal role in platelet hyperactivity. Indeed, upon stimulation by physiological agonists, human platelets generate and release several types of reactive oxygen species (ROS) such as O2-, H2O2 or OH- , further amplifying the platelet activation response via various signalling pathways, including, formation of isoprostanes, Ca2+ mobilization and NO inactivation. Furthermore, excessive platelet ROS generation, incorporation of free radicals from environment and/or depletion of antioxidants induce pro-oxidant, pro-inflammatory and platelet hyperaggregability effects, leading to the incidence of cardiovascular events. Here, we review the current knowledge regarding the effect of oxidative stress on platelet signaling pathways and its implication in CVD such as type 2 diabetes mellitus. We also summarize the role of natural antioxidants included in vegetables, fruits and medicinal herbs in reducing platelet function via an oxidative stress-mediated mechanism. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Coronary Artery Disease Alters Ventricular Repolarization Dynamics in Type 2 Diabetes

    Science.gov (United States)

    Vrtovec, Bojan; Sinkovec, Matjaz; Starc, Vito; Radovancevic, Branislav; Schlegel, Todd T.

    2005-01-01

    Ventricular repolarization dynamics (VRD) is an important predictor of outcome in diabetes. We examined the potential impact of coronary artery disease (CAD) on VRD in type 2 diabetic patients. We recorded 5-min high-resolution resting electrocardiograms (ECG) in 38 diabetic patients undergoing elective coronary angiography, and in 38 age- and gender- matched apparently healthy subjects (Controls). Using leads I and II, time-domain indices of VRD were calculated. Coronary angiography was regarded as positive if a 350% stenosis was found. Angiography was positive in 21 diabetic patients (55%). Patients with CAD had a significantly higher degree of VRD than Controls (SDNN(QT): 15.81+/-7.22 ms vs. 8.94+/-6.04 ms; P <0.001, rMSSD(QT): 21.02k7.07 ms vs. 11.18k7.45 ms; P <0.001). VRD in diabetic patients with negative angiograms did not differ from VRD in Controls (SDNN(QT): 8.94+/-6.04 ms vs. 7.44+/-5.72 ms; P=0.67, rMSSD(QT): 11.18+/-7.45 ms vs. 10.22+/-5.35 ms; P=O. 82). CAD increases VRD in patients with type 2 diabetes. Therefore, changes in ventricular repolarization in diabetic patients may be due to silent CAD rather than to diabetes per se.

  7. Type IV collagen as marker of fibrosis in nonalcoholic liver disease

    Directory of Open Access Journals (Sweden)

    Alvina Alvina

    2016-02-01

    Full Text Available Currently nonalcoholic fatty liver disease (NAFLD and nonalcoholic steatohepatitis (NASH are medical problems associated with the increasing prevalence of diabetes mellitus, obesity, hypertension and hypertriglyceridemia, usually designated as the metabolic syndrome associated with insulin resistance. One study demonstrated an increase in NAFLD prevalence of around 17-33% and in NASH prevalence of 5.7-16.5%. NAFLD comprises a range of mild to severe conditions, from simple steatosis to steatohepatitis, hepatic fibrosis and cirrhosis. The diagnosis of hepatic fibrosis is important for prognosis, stratification for treatment, and monitoring of treatment efficacy. Ultrasonography (USG is a simple method for detecting fatty infiltrates in the liver. USG has a sensitivity of 82-89% and a specificity of 93%, but cannot differentiate between hepatic steatosis and fibrosis. The gold standard for evaluation of hepatic fibrosis is liver biopsy, which however is a painful and invasive procedure. Currently determination of serum type IV collagen has been suggested as an alternative to liver biopsy among the non-invasive methods for evaluation of hepatic fibrosis, as its serum concentration is closely correlated with advanced hepatic fibrosis in NASH. Type IV collagen is one of the components of basement membrane and its serum concentration is indicative of degradation of the extracellular matrix.

  8. Type IV collagen as marker of fibrosis in nonalcoholic liver disease

    Directory of Open Access Journals (Sweden)

    Alvina

    2010-08-01

    Full Text Available Currently nonalcoholic fatty liver disease (NAFLD and nonalcoholic steatohepatitis (NASH are medical problems associated with the increasing prevalence of diabetes mellitus, obesity, hypertension and hypertriglyceridemia, usually designated as the metabolic syndrome associated with insulin resistance. One study demonstrated an increase in NAFLD prevalence of around 17-33% and in NASH prevalence of 5.7-16.5%. NAFLD comprises a range of mild to severe conditions, from simple steatosis to steatohepatitis, hepatic fibrosis and cirrhosis. The diagnosis of hepatic fibrosis is important for prognosis, stratification for treatment, and monitoring of treatment efficacy. Ultrasonography (USG is a simple method for detecting fatty infiltrates in the liver. USG has a sensitivity of 82-89% and a specificity of 93%, but cannot differentiate between hepatic steatosis and fibrosis. The gold standard for evaluation of hepatic fibrosis is liver biopsy, which however is a painful and invasive procedure. Currently determination of serum type IV collagen has been suggested as an alternative to liver biopsy among the non-invasive methods for evaluation of hepatic fibrosis, as its serum concentration is closely correlated with advanced hepatic fibrosis in NASH. Type IV collagen is one of the components of basement membrane and its serum concentration is indicative of degradation of the extracellular matrix.

  9. Prognostic value of uric acid in patients with Type 2 diabetes mellitus and coronary artery disease.

    Science.gov (United States)

    Ndrepepa, Gjin; Braun, Siegmund; King, Lamin; Cassese, Salvatore; Tada, Tomohisa; Fusaro, Massimiliano; Hadamitzky, Martin; Haase, Hans-Ullrich; Schömig, Albert; Kastrati, Adnan

    2013-02-01

    Studies investigating the prognostic role of UA (uric acid) in patients with Type 2 diabetes mellitus have given conflicting findings. We undertook the present study to assess the association between UA and outcome in patients with Type 2 diabetes mellitus and CAD (coronary artery disease). The study included 3705 patients with diabetes mellitus and angiography-proven CAD. UA was measured before coronary angiography. The primary outcome was 1-year all-cause mortality. The UA concentration [median (25th-75th quartiles)] was 6.44 mg/dl (5.40-7.70 mg/dl). There were 264 deaths (7.1%) during follow-up: 45 deaths in patients of the first UA quartile, 43 deaths in patients of the second UA quartile, 51 deaths in patients of the third UA quartile and 125 deaths in patients of the fourth UA quartile {Kaplan-Meier estimates of mortality, 5.1, 4.8, 5.6 and 14.0% respectively; unadjusted HR (hazard ratio), 2.81 [95% CI (confidence interval), 2.21-3.58]; Ppower of the model regarding prediction of all-cause mortality [absolute and relative IDI (integrated discrimination improvement) 0.034 and 20.5% respectively; Pdiabetes mellitus and confirmed CAD, elevated levels of UA predict mortality independently of known cardiovascular risk factors.

  10. CLINICAL PROFILE OF PATTERN OF DYSLIPIDAEMIA AND ISCHAEMIC HEART DISEASE IN TYPE II DIABETES MELLITUS PATIENTS

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    Atul Vijayrao Rajkondawar

    2017-07-01

    Full Text Available BACKGROUND The present research was undertaken to study the pattern of dyslipidaemia and varied clinical manifestations of ischaemic heart disease, its risk factors in type 2 diabetes mellitus patients. Diabetes Mellitus (DM has become major public health problem in India. It is not only increasing in morbidity and mortality, but also decreases the quality of life. Also, disease and its complications are causing heavy economic burden for patients suffering from it.1,2 Diabetes is endemic globally with increasing prevalence in both developing and developed countries. Diabetes is a major cause of mortality, but several studies indicate that it is likely underreported as a cause of death. A recent estimate suggested that diabetes was the fifth leading cause of death worldwide and was responsible for almost 3 million deaths annually (1.7-5.2% of all deaths. MATERIALS AND METHODS A total of 100 patients attending the outpatient department or admitted to medical wards, ICU of tertiary care centre and fulfilling the inclusion criteria were evaluated clinically. A baseline Electrocardiogram (ECG was taken in all cases irrespective of clinical evidence of cardiac involvement. Patients with normal ECG pattern were further evaluated by Treadmill Testing (TMT or stress test for subclinical cardiac involvement. Risk factor evaluation was done in all cases. RESULTS Prevalence of IHD was found to be 41% with a male predominance (1.067:1. Evaluation of risk factors has shown its strong association with IHD. Incidence of IHD was high when low HDL (P 25 had negatively significant association with IHD in type 2 diabetics (P=0.072. Smoking was not statistically associated (P=0.577 and in male alcoholics, IHD had positive association with alcohol (P=0.193. CONCLUSION The current study points out that there exists an increased incidence of ischaemic heart disease in diabetics with few, but not all risk factors contributing to it. Early detection, optimal glycaemic

  11. Diffusion Magnetic Resonance Imaging Patterns in Metabolic and Toxic Brain Disorders

    Energy Technology Data Exchange (ETDEWEB)

    Sener, R.N. [Ege Univ. Hospital, Bornova, Izmir (Turkey). Dept. of Radiology

    2004-08-01

    Purpose: To evaluate metabolic and toxic brain disorders that manifest with restricted, elevated, or both restricted and elevated diffusion patterns on diffusion magnetic resonance imaging (MRI). Material and Methods: Echo-planar diffusion MRI examinations were obtained in 34 pediatric patients with metabolic and toxic brain disorders proved by appropriate laboratory studies. The MRI unit operated at 1.5T with a gradient strength of 30 mT/meter, and a rise time of 600 s. b=1000 s/mm{sup 2} images and apparent diffusion coefficient (ADC) maps with ADC values were studied. Results: Three patterns were observed: 1. A restricted diffusion pattern (high signal on b=1000 s/mm{sup 2} images and low ADC values); 2. an elevated diffusion pattern (normal signal on b=1000 s/mm2 images and high ADC values); and 3. a mixed pattern (coexistent restricted and increased diffusion patterns in the same patient). Disorders manifesting with a restricted diffusion pattern included metachromatic leukodystrophy (n=2), phenylketonuria (n=3), maple syrup urine disease (intermediate form) (n=1), infantile neuroaxonal dystrophy (n=1), Leigh (n=2), Wilson (n=3), and Canavan disease (n=1). Disorders with an elevated diffusion pattern included phenylketonuria (n=1), adrenoleukodystrophy (n=1), merosin-deficient congenital muscular dystrophy (n=2), mucopolysaccharidosis (n=2), Lowe syndrome (n=1), Leigh (n=2), Alexander (n=1), Pelizaeus-Merzbacher (n=1), and Wilson (n=3) disease. Disorders with a mixed pattern included L-2 hydroxyglutaric aciduria (n=2), non-ketotic hyperglycinemia (n=1), infantile neuroaxonal dystrophy (n=2), maple syrup urine disease (n=1), and Leigh (n=1) disease. Conclusion: The findings suggested that the three different diffusion patterns reflect the histopathological changes associated with the disorders and different stages of a particular disorder. It is likely that the restricted diffusion pattern corresponds to abnormalities related to myelin, and the elevated

  12. Diffusion Magnetic Resonance Imaging Patterns in Metabolic and Toxic Brain Disorders

    International Nuclear Information System (INIS)

    Sener, R.N.

    2004-01-01

    Purpose: To evaluate metabolic and toxic brain disorders that manifest with restricted, elevated, or both restricted and elevated diffusion patterns on diffusion magnetic resonance imaging (MRI). Material and Methods: Echo-planar diffusion MRI examinations were obtained in 34 pediatric patients with metabolic and toxic brain disorders proved by appropriate laboratory studies. The MRI unit operated at 1.5T with a gradient strength of 30 mT/meter, and a rise time of 600 s. b=1000 s/mm 2 images and apparent diffusion coefficient (ADC) maps with ADC values were studied. Results: Three patterns were observed: 1. A restricted diffusion pattern (high signal on b=1000 s/mm 2 images and low ADC values); 2. an elevated diffusion pattern (normal signal on b=1000 s/mm2 images and high ADC values); and 3. a mixed pattern (coexistent restricted and increased diffusion patterns in the same patient). Disorders manifesting with a restricted diffusion pattern included metachromatic leukodystrophy (n=2), phenylketonuria (n=3), maple syrup urine disease (intermediate form) (n=1), infantile neuroaxonal dystrophy (n=1), Leigh (n=2), Wilson (n=3), and Canavan disease (n=1). Disorders with an elevated diffusion pattern included phenylketonuria (n=1), adrenoleukodystrophy (n=1), merosin-deficient congenital muscular dystrophy (n=2), mucopolysaccharidosis (n=2), Lowe syndrome (n=1), Leigh (n=2), Alexander (n=1), Pelizaeus-Merzbacher (n=1), and Wilson (n=3) disease. Disorders with a mixed pattern included L-2 hydroxyglutaric aciduria (n=2), non-ketotic hyperglycinemia (n=1), infantile neuroaxonal dystrophy (n=2), maple syrup urine disease (n=1), and Leigh (n=1) disease. Conclusion: The findings suggested that the three different diffusion patterns reflect the histopathological changes associated with the disorders and different stages of a particular disorder. It is likely that the restricted diffusion pattern corresponds to abnormalities related to myelin, and the elevated diffusion pattern

  13. Gaucher disease type I: assessment of basal metabolic rate in patients from southern Brazil.

    Science.gov (United States)

    Doneda, Divair; Lopes, André L; Oliveira, Alvaro R; Netto, Cristina B; Moulin, Cileide C; Schwartz, Ida V D

    2011-01-15

    Gaucher disease (GD) is characterized by clinical heterogeneity and is associated with metabolic abnormalities such as increased resting energy expenditure. To assess the basal metabolic rate (BMR) of patients with GD type I followed at the Gaucher Disease Reference Center of Rio Grande do Sul, Brazil. Fourteen patients (male=6) and 14 healthy controls matched by gender, age and body mass index (BMI) were included in the study. The nutritional status of patients was assessed by BMI. The BMR was measured by indirect calorimetry. In two patients, it was possible to perform BMR in the pre- and the post-treatment periods. Mean age and BMI of patients and controls were, respectively, 32.8 ± 17.6 and 32.1 ± 16.6 years and 23.3 ± 3.1 and 22.4 ± 3.1 kg/m(2). Twelve patients were receiving enzyme replacement therapy (ERT) with imiglucerase (mean duration of treatment=5.2 ± 4.3 years; mean dosage of imiglucerase=24.2 ± 7.3 UI/kg/inf). Five patients (36%) were overweight, and nine (64%) were normal weight. Mean BMR of patients on ERT was 27.1% higher than that of controls (p=0.007). There was no difference between the BMR of patients on ERT and not on ERT (n=4) (p=0.92). Comparing the BMR of patients on ERT and their controls with the BMR estimated by the Harris-Benedict equation, the BMR of patients was 6.3% higher than the estimated (p = 0.1), while the BMR of their controls was 17.0% lower than the estimated (p = 0.001). Most treated GD type I patients were normal weight. The patients including those on ERT showed higher BMR when compared to controls. Imiglucerase is probably unable to normalize the hypermetabolism presented by GD type I patients. Additional studies should be performed to confirm our findings. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Brain local and regional neuroglial alterations in Alzheimer's Disease: cell types, responses and implications.

    Science.gov (United States)

    Toledano, Adolfo; Álvarez, María-Isabel; Toledano-Díaz, Adolfo; Merino, José-Joaquín; Rodríguez, José Julio

    2016-01-01

    From birth to death, neurons are dynamically accompanied by neuroglial cells in a very close morphological and functional relationship. Three families have been classically considered within the CNS: astroglia, oligodendroglia and microglia. Many types/subtypes (including NGR2+ cells), with a wide variety of physiological and pathological effects on neurons, have been described using morphological and immunocytochemical criteria. Glio-glial, glio-neuronal and neuro-glial cell signaling and gliotransmission are phenomena that are essential to support brain functions. Morphofunctional changes resulting from the plasticity of all the glial cell types parallel the plastic neuronal changes that optimize the functionality of neuronal circuits. Moreover, neuroglia possesses the ability to adopt a reactive status (gliosis) in which, generally, new functions arise to improve and restore if needed the neural functionality. All these features make neuroglial cells elements of paramount importance when attempting to explain any physiological or pathological processes in the CNS, because they are involved in both, neuroprotection/neurorepair and neurodegeneration. There exist diverse and profound, regional and local, neuroglial changes in all involutive processes (physiological and pathological aging; neurodegenerative disorders, including Alzheimer ´s disease -AD-), but today, the exact meaning of such modifications (the modifications of the different neuroglial types, in time and place), is not well understood. In this review we consider the different neuroglial cells and their responses in order to understand the possible role they fulfill in pathogenesis, diagnosis and treatment (preventive or palliative) of AD. The existence of differentiated and/or concurrent pathogenic and neuro-protective/neuro-restorative astroglial and microglial responses is highlighted.

  15. Physical activity types and life expectancy with and without cardiovascular disease: the Rotterdam Study.

    Science.gov (United States)

    Dhana, Klodian; Koolhaas, Chantal M; Berghout, Mathilde A; Peeters, Anna; Ikram, M Arfan; Tiemeier, Henning; Hofman, Albert; Nusselder, Wilma; Franco, Oscar H

    2017-12-01

    We aimed to determine the contribution of specific physical activity (PA) types (i.e. walking, cycling, domestic work, sports and gardening) on total life expectancy (LE) and LE with and without cardiovascular disease (CVD). We constructed multistate life tables to calculate the effects of total PA and PA types on LE, among individuals older than 55 years from the Rotterdam Study. For the life table calculations, we used sex-specific prevalences, incident rates and hazard ratios for three transitions (healthy-to-CVD, healthy-to-death and CVD-to-death) by levels of PA and adjusted for confounders. High total PA was associated with gains in total and CVD-free LE. High cycling contributed to higher total LE in men (3.7 years) and women (2.1 years) and higher LE without CVD in men (3.1 years) and women (2.4 years). Total and CVD-free LE were increased by high domestic work in women (2.6 and 2.4 years, respectively) and high gardening in men (2.7 and 2.0 years, respectively). Higher PA levels are associated with increased LE and more years lived without CVD. Of the different PA types, cycling provided high effects in both men and women. Cycling could be more strongly encouraged in activity guidelines to maximize the population benefits of PA. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  16. Nut consumption, serum fatty acid profile and estimated coronary heart disease risk in type 2 diabetes.

    Science.gov (United States)

    Nishi, S K; Kendall, C W C; Bazinet, R P; Bashyam, B; Ireland, C A; Augustin, L S A; Blanco Mejia, S; Sievenpiper, J L; Jenkins, D J A

    2014-08-01

    Nut consumption has been associated with decreased risk of coronary heart disease (CHD) and type 2 diabetes which has been largely attributed to their healthy fatty acid profile, yet this has not been ascertained. Therefore, we investigated the effect of nut consumption on serum fatty acid concentrations and how these relate to changes in markers of glycemic control and calculated CHD risk score in type 2 diabetes. 117 subjects with type 2 diabetes consumed one of three iso-energetic (mean 475 kcal/d) supplements for 12 weeks: 1. full-dose nuts (50-100 g/d); 2. half-dose nuts with half-dose muffins; and 3. full-dose muffins. In this secondary analysis, fatty acid concentrations in the phospholipid, triacylglycerol, free fatty acid, and cholesteryl ester fractions from fasting blood samples obtained at baseline and week 12 were analyzed using thin layer and gas chromatography. Full-dose nut supplementation significantly increased serum oleic acid (OA) and MUFAs compared to the control in the phospholipid fraction (OA: P = 0.036; MUFAs: P = 0.024). Inverse associations were found with changes in CHD risk versus changes in OA and MUFAs in the triacylglycerol (r = -0.256, P = 0.011; r = -0.228, P = 0.024, respectively) and phospholipid (r = -0.278, P = 0.006; r = -0.260, P = 0.010, respectively) fractions. In the cholesteryl ester fraction, change in MUFAs was inversely associated with markers of glycemic control (HbA1c: r = -0.250, P = 0.013; fasting blood glucose: r = -0.395, P consumption increased OA and MUFA content of the serum phospholipid fraction, which was inversely associated with CHD risk factors and 10-year CHD risk. NCT00410722, clinicaltrials.gov. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Connective Tissue Reflex Massage for Type 2 Diabetic Patients with Peripheral Arterial Disease: Randomized Controlled Trial

    Science.gov (United States)

    Castro-Sánchez, Adelaida María; Moreno-Lorenzo, Carmen; Matarán-Peñarrocha, Guillermo A.; Feriche-Fernández-Castanys, Belen; Granados-Gámez, Genoveva; Quesada-Rubio, José Manuel

    2011-01-01

    The objective of this study was to evaluate the efficacy of connective tissue massage to improve blood circulation and intermittent claudication symptoms in type 2 diabetic patients. A randomized, placebo-controlled trial was undertaken. Ninety-eight type 2 diabetes patients with stage I or II-a peripheral arterial disease (PAD) (Leriche-Fontaine classification) were randomly assigned to a massage group or to a placebo group treated using disconnected magnetotherapy equipment. Peripheral arterial circulation was determined by measuring differential segmental arterial pressure, heart rate, skin temperature, oxygen saturation and skin blood flow. Measurements were taken before and at 30 min, 6 months and 1 year after the 15-week treatment. After the 15-week program, the groups differed (P < .05) in differential segmental arterial pressure in right lower limb (lower one-third of thigh, upper and lower one-third of leg) and left lower limb (lower one-third of thigh and upper and lower one-third of leg). A significant difference (P < .05) was also observed in skin blood flow in digits 1 and 4 of right foot and digits 2, 4 and 5 of left foot. ANOVA results were significant (P < .05) for right and left foot oxygen saturation but not for heart rate and temperature. At 6 months and 1 year, the groups differed in differential segmental arterial pressure in upper third of left and right legs. Connective tissue massage improves blood circulation in the lower limbs of type 2 diabetic patients at stage I or II-a and may be useful to slow the progression of PAD. PMID:19933770

  18. Connective Tissue Reflex Massage for Type 2 Diabetic Patients with Peripheral Arterial Disease: Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Adelaida María Castro-Sánchez

    2011-01-01

    Full Text Available The objective of this study was to evaluate the efficacy of connective tissue massage to improve blood circulation and intermittent claudication symptoms in type 2 diabetic patients. A randomized, placebo-controlled trial was undertaken. Ninety-eight type 2 diabetes patients with stage I or II-a peripheral arterial disease (PAD (Leriche-Fontaine classification were randomly assigned to a massage group or to a placebo group treated using disconnected magnetotherapy equipment. Peripheral arterial circulation was determined by measuring differential segmental arterial pressure, heart rate, skin temperature, oxygen saturation and skin blood flow. Measurements were taken before and at 30 min, 6 months and 1 year after the 15-week treatment. After the 15-week program, the groups differed (P<.05 in differential segmental arterial pressure in right lower limb (lower one-third of thigh, upper and lower one-third of leg and left lower limb (lower one-third of thigh and upper and lower one-third of leg. A significant difference (P<.05 was also observed in skin blood flow in digits 1 and 4 of right foot and digits 2, 4 and 5 of left foot. ANOVA results were significant (P<.05 for right and left foot oxygen saturation but not for heart rate and temperature. At 6 months and 1 year, the groups differed in differential segmental arterial pressure in upper third of left and right legs. Connective tissue massage improves blood circulation in the lower limbs of type 2 diabetic patients at stage I or II-a and may be useful to slow the progression of PAD.

  19. Imiglucerase in the management of Gaucher disease type 1: an evidence-based review of its place in therapy

    Science.gov (United States)

    Serratrice, Christine; Carballo, Sebastian; Serratrice, Jacques; Stirnemann, Jérome

    2016-01-01

    Introduction Gaucher disease is the first lysosomal disease to benefit from enzyme replacement therapy, thus serving as model for numerous other lysosomal diseases. Alglucerase was the first glucocerebrosidase purified from placental extracts, and this was then replaced by imiglucerase – a Chinese hamster ovary cell-derived glucocerebrosidase. Aim The aim was to review the evidence underlying the use of imiglucerase in Gaucher disease type 1 Evidence review Data from clinical trials and Gaucher Registries were analyzed. Conclusion Imiglucerase has been prescribed and found to have an excellent efficacy and safety profile. We report herein the evidence-based data published for 26 years justifying the use of imiglucerase. PMID:27790078

  20. The pathogenesis of Newcastle disease: A comparison of selected Newcastle disease virus wild-type strains and their infectious clones

    International Nuclear Information System (INIS)

    Wakamatsu, Nobuko; King, Daniel J.; Seal, Bruce S.; Samal, Siba K.; Brown, Corrie C.

    2006-01-01

    The effect of mutations of Newcastle disease virus (NDV) fusion (F) gene, hemagglutinin-neuraminidase (HN) gene, and phosphoprotein (P) gene and HN chimeras between the virulent Beaudette C and low virulence LaSota strains on pathogenesis and pathogenicity was examined in fully susceptible chickens. A virulent F cleavage site motif within a LaSota backbone increased pathogenicity and severity of clinical disease. A LaSota HN within a Beaudette C backbone decreased pathogenicity indices and disease severity. A Beaudette C HN within a LaSota backbone did not change either pathogenicity indices or severity of disease in chickens. Loss of glycosylation at site 4 of the HN or modified P gene of Beaudette C decreased pathogenicity indices and caused no overt clinicopathologic disease in chickens. Both pathogenicity indices and clinicopathologic examination demonstrated that the F, HN, and P genes of NDV collectively or individually can contribute to viral virulence

  1. Allelic heterogeneity in hereditary motor and sensory neuropathy type Ia (Charcot-Marie-Tooth disease type 1a)

    NARCIS (Netherlands)

    Hoogendijk, J. E.; Janssen, E. A.; Gabreëls-Festen, A. A.; Hensels, G. W.; Joosten, E. M.; Gabreëls, F. J.; Zorn, I.; Valentijn, L. J.; Baas, F.; Ongerboer de Visser, B. W.

    1993-01-01

    The most frequently found mutation in autosomal dominant hereditary motor and sensory neuropathy type I (HMSN I) is a large duplication on chromosome 17p11.2 containing probes VAW409R3, VAW412R3, and EW401. We investigated a family with severe features of HMSN I, and demonstrated the absence of this

  2. Effects of orally administered undenatured type II collagen against arthritic inflammatory diseases: a mechanistic exploration.

    Science.gov (United States)

    Bagchi, D; Misner, B; Bagchi, M; Kothari, S C; Downs, B W; Fafard, R D; Preuss, H G

    2002-01-01

    Arthritis afflicts approximately 43 million Americans or approximately 16.6% of the US population. The two most common and best known types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). A significant amount of scientific research has been done in attempts to explain what initiates forms of arthritis, how it is promoted and perpetuated and how to effectively intervene in the disease process and promote cartilage remodeling. Current pharmacological strategies mainly address immune suppression and antiinflammatory mechanisms and have had limited success. Recent research provides evidence that alterations in the three-dimensional configuration of glycoproteins are responsible for the recognition/response signaling that catalyzes T-cell attack. Oral administration of autoantigens has been shown to suppress a variety of experimentally induced autoimmune pathologies, including antigen-induced RA. The interaction between gut-associated lymphoid tissue in the duodenum and epitopes of orally administered undenatured type II collagen facilitates oral tolerance to the antigen and stems systemic T-cell attack on joint cartilage. Previous studies have shown that small doses of orally administered undenatured type II chicken collagen effectively deactivate killer T-cell attack. A novel glycosylated undenatured type II collagen material (UC-II) was developed to preserve biological activity. The presence of active epitopes in the UC-II collagen is confirmed by an enzyme-linked immunosorbent assay test and distinguishes this form from hydrolyzed or denatured collagen. Oral intake of small amounts of glycosylated UC-II presents active epitopes, with the correct three-dimensional structures, to Peyer's patches, which influences the signaling required for the development of immune tolerance. UC-II has demonstrated the ability to induce tolerance, effectively reducing joint pain and swelling in RA subjects. A pilot study was conducted for 42 days to evaluate the

  3. The potential usefulness of human leukocyte antigen typing for celiac disease screening: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Alicia Díaz-Redondo

    2015-07-01

    Full Text Available Background and aim: The presence of specific human leukocyte antigen-DQ2 and DQ8 seems to be necessary for celiac disease development, but the real contribution of its typing for screening is still uncertain. We aim to conduct a systematic review and meta-analysis of the diagnostic performance of human leukocyte antigen typing tests for celiac disease screening. Methods: Systematic review of published studies assessing accuracy of human leukocyte antigen DQ2 and DQ8 typing for the detection of celiac disease were selected. MEDLINE and EMBASE were searched from 1st January 2004 until 31st December 2013. Two independent researchers carried out selection and classification of studies, data extraction and analysis. Meta-analysis combining sensitivities, specificities and likelihood ratios of HLA-DQ2 and DQ8 for the diagnosis of celiac disease were carried out. Results: 6 studies including 1303 individuals were finally evaluated. Pooled sensitivity was 98% (95% confidence interval: 97-99. Overall specificity was 45% (95% confidence interval: 41-48. Regarding specificity, studies were heterogeneous and a subgroup analysis was done according to the type of population included. Overall negative likelihood ratio was 0.05 (0.03-0.09. Conclusions: Due to its great sensitivity and low negative likelihood ratio, human leukocyte antigen-DQ2/DQ8 typing would be an appropriate test for ruling out celiac disease in the general population suffering related symptoms, and even more in at risk population.

  4. Pharmacologic Treatment Assigned for Niemann Pick Type C1 Disease Partly Changes Behavioral Traits in Wild-Type Mice.

    Science.gov (United States)

    Schlegel, Victoria; Thieme, Markus; Holzmann, Carsten; Witt, Martin; Grittner, Ulrike; Rolfs, Arndt; Wree, Andreas

    2016-11-09

    Niemann-Pick Type C1 (NPC1) is an autosomal recessive inherited disorder characterized by accumulation of cholesterol and glycosphingolipids. Previously, we demonstrated that BALB/c-npc1 nih Npc1 -/- mice treated with miglustat, cyclodextrin and allopregnanolone generally performed better than untreated Npc1 -/- animals. Unexpectedly, they also seemed to accomplish motor tests better than their sham-treated wild-type littermates. However, combination-treated mutant mice displayed worse cognition performance compared to sham-treated ones. To evaluate effects of these drugs in healthy BALB/c mice, we here analyzed pharmacologic effects on motor and cognitive behavior of wild-type mice. For combination treatment mice were injected with allopregnanolone/cyclodextrin weekly, starting at P7. Miglustat injections were performed daily from P10 till P23. Starting at P23, miglustat was embedded in the chow. Other mice were treated with miglustat only, or sham-treated. The battery of behavioral tests consisted of accelerod, Morris water maze, elevated plus maze, open field and hot-plate tests. Motor capabilities and spontaneous motor behavior were unaltered in both drug-treated groups. Miglustat-treated wild-type mice displayed impaired spatial learning compared to sham- and combination-treated mice. Both combination- and miglustat-treated mice showed enhanced anxiety in the elevated plus maze compared to sham-treated mice. Additionally, combination treatment as well as miglustat alone significantly reduced brain weight, whereas only combination treatment reduced body weight significantly. Our results suggest that allopregnanolone/cyclodextrin ameliorate most side effects of miglustat in wild-type mice.

  5. Pharmacologic Treatment Assigned for Niemann Pick Type C1 Disease Partly Changes Behavioral Traits in Wild-Type Mice

    Directory of Open Access Journals (Sweden)

    Victoria Schlegel

    2016-11-01

    Full Text Available Niemann-Pick Type C1 (NPC1 is an autosomal recessive inherited disorder characterized by accumulation of cholesterol and glycosphingolipids. Previously, we demonstrated that BALB/c-npc1nihNpc1−/− mice treated with miglustat, cyclodextrin and allopregnanolone generally performed better than untreated Npc1−/− animals. Unexpectedly, they also seemed to accomplish motor tests better than their sham-treated wild-type littermates. However, combination-treated mutant mice displayed worse cognition performance compared to sham-treated ones. To evaluate effects of these drugs in healthy BALB/c mice, we here analyzed pharmacologic effects on motor and cognitive behavior of wild-type mice. For combination treatment mice were injected with allopregnanolone/cyclodextrin weekly, starting at P7. Miglustat injections were performed daily from P10 till P23. Starting at P23, miglustat was embedded in the chow. Other mice were treated with miglustat only, or sham-treated. The battery of behavioral tests consisted of accelerod, Morris water maze, elevated plus maze, open field and hot-plate tests. Motor capabilities and spontaneous motor behavior were unaltered in both drug-treated groups. Miglustat-treated wild-type mice displayed impaired spatial learning compared to sham- and combination-treated mice. Both combination- and miglustat-treated mice showed enhanced anxiety in the elevated plus maze compared to sham-treated mice. Additionally, combination treatment as well as miglustat alone significantly reduced brain weight, whereas only combination treatment reduced body weight significantly. Our results suggest that allopregnanolone/cyclodextrin ameliorate most side effects of miglustat in wild-type mice.

  6. Limited Effects of Type I Interferons on Kyasanur Forest Disease Virus in Cell Culture.

    Directory of Open Access Journals (Sweden)

    Bradley W M Cook

    2016-08-01

    Full Text Available The tick-borne flavivirus, Kyasanur Forest disease virus (KFDV causes seasonal infections and periodic outbreaks in south-west India. The current vaccine offers poor protection with reported issues of coverage and immunogenicity. Since there are no approved prophylactic therapeutics for KFDV, type I IFN-α/β subtypes were assessed for antiviral potency against KFDV in cell culture.The continued passage of KFDV-infected cells with re-administered IFN-α2a treatment did not eliminate KFDV and had little effect on infectious particle production whereas the IFN-sensitive, green fluorescent protein-expressing vesicular stomatitis virus (VSV-GFP infection was controlled. Further evaluation of the other IFN-α/β subtypes versus KFDV infection indicated that single treatments of either IFN-αWA and IFN-αΚ appeared to be more effective than IFN-α2a at reducing KFDV titres. Concentration-dependent analysis of these IFN-α/β subtypes revealed that regardless of subtype, low concentrations of IFN were able to limit cytopathic effects (CPE, while significantly higher concentrations were needed for inhibition of virion release. Furthermore, expression of the KFDV NS5 in cell culture before IFN addition enabled VSV-GFP to overcome the effects of IFN-α/β signalling, producing a robust infection.Treatment of cell culture with IFN does not appear to be suitable for KFDV eradication and the assay used for such studies should be carefully considered. Further, it appears that the NS5 protein is sufficient to permit KFDV to bypass the antiviral properties of IFN. We suggest that other prophylactic therapeutics should be evaluated in place of IFN for treatment of individuals with KFDV disease.

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

    Science.gov (United States)

    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.

  8. [Molecular and clinical characterization of Colombian patients suffering from type III glycogen storage disease].

    Science.gov (United States)

    Mantilla, Carolina; Toro, Mónica; Sepúlveda, María Elsy; Insuasty, Margarita; Di Filippo, Diana; López, Juan Álvaro; Baquero, Carolina; Navas, María Cristina; Arias, Andrés Augusto

    2018-05-01

    Type III glycogen storage disease (GSD III) is an autosomal recessive disorder in which a mutation in the AGL gene causes deficiency of the glycogen debranching enzyme. The disease is characterized by fasting hypoglycemia, hepatomegaly and progressive myopathy. Molecular analyses of AGL have indicated heterogeneity depending on ethnic groups. The full spectrum of AGL mutations in Colombia remains unclear. To describe the clinical and molecular characteristics of ten Colombian patients diagnosed with GSD III. We recruited ten Colombian children with a clinical and biochemical diagnosis of GSD III to undergo genetic testing. The full coding exons and the relevant exon-intron boundaries of the AGL underwent Sanger sequencing to identify mutation. All patients had the classic phenotype of the GSD III. Genetic analysis revealed a mutation p.Arg910X in two patients. One patient had the mutation p.Glu1072AspfsX36, and one case showed a compound heterozygosity with p.Arg910X and p.Glu1072AspfsX36 mutations. We also detected the deletion of AGL gene 3, 4, 5, and 6 exons in three patients. The in silico studies predicted that these defects are pathogenic. No mutations were detected in the amplified regions in three patients. We found mutations and deletions that explain the clinical phenotype of GSD III patients. This is the first report with a description of the clinical phenotype and the spectrum of AGL mutations in Colombian patients. This is important to provide appropriate prognosis and genetic counseling to the patient and their relatives.

  9. Clinical application of nuclear magnetic resonance imaging (resistive type) on cardiovascular disease

    International Nuclear Information System (INIS)

    Imai, Hitoshi; Yoshida, Katsuya; Watanabe, Shigeru; Masuda, Yoshiaki; Inagaki, Yoshiaki; Ikehira, Hiroo; Fukuda, Nobuo; Tateno, Yukio.

    1984-01-01

    In order to evaluate the usefulness of Nuclear Magnetic Resonance (NMR) imaging in diagnosing cardiovascular disease, 27 subjects were examined using a 0.1-Tesla resistive type (ASAHI MARK-J). In 10 normal subjects, four cardiac chambers, interventricular septum, aorta, pulmonary vessels and vena cava were clearly identified in NMR imaging. In two patients with old anteroseptal myocardial infarction, anteroseptal wall thinning and left ventricular aneurysm with mural thrombi were demonstrated. In two cases of antrolateral and posterolateral myocardial infarction, however, infarcted areas were not identified in NMR imaging. In one patient with congestive cardiomyopathy, enlarged left ventricle without hypertrophy was recognized. In two patients with hypertrophic obstructive cardiomyopathy, NMR imaging disclosed thickened left ventricular wall associated with its narrowed cavity. A mural thrombus in the right ventricle was distinctly visualized in one patient with cardio-vascular Behcet's disease. In two patients with mitral valve stenosis, enlarged left atrium with a mural thrombus was clearly demonstrated in both cross and longitudinal sections. In three patients with thoratic aortic aneurysm, local dilatation of aorta and mural thrombi were recognized. In four patients with dissecting aortic aneurysm, double channels with an intimal flap in the aorta were visualized in NMR imaging. Mean T 1 values and standard deviations of left ventricle, left ventricular wall, and thrombi were 593+-89, 341+-20, 316+-84 msec, respectively. Mean T 1 values of thrombi were ordinally shorter than those of left ventricule. But some thrombi which might be expected fresh had longer T 1 values. (J.P.N.)

  10. Geographical distribution of complement receptor type 1 variants and their associated disease risk.

    Directory of Open Access Journals (Sweden)

    Thaisa Lucas Sandri

    Full Text Available Pathogens exert selective pressure which may lead to substantial changes in host immune responses. The human complement receptor type 1 (CR1 is an innate immune recognition glycoprotein that regulates the activation of the complement pathway and removes opsonized immune complexes. CR1 genetic variants in exon 29 have been associated with expression levels, C1q or C3b binding and increased susceptibility to several infectious diseases. Five distinct CR1 nucleotide substitutions determine the Knops blood group phenotypes, namely Kna/b, McCa/b, Sl1/Sl2, Sl4/Sl5 and KCAM+/-.CR1 variants were genotyped by direct sequencing in a cohort of 441 healthy individuals from Brazil, Vietnam, India, Republic of Congo and Ghana.The distribution of the CR1 alleles, genotypes and haplotypes differed significantly among geographical settings (p≤0.001. CR1 variants rs17047660A/G (McCa/b and rs17047661A/G (Sl1/Sl2 were exclusively observed to be polymorphic in African populations compared to the groups from Asia and South-America, strongly suggesting that these two SNPs may be subjected to selection. This is further substantiated by a high linkage disequilibrium between the two variants in the Congolese and Ghanaian populations. A total of nine CR1 haplotypes were observed. The CR1*AGAATA haplotype was found more frequently among the Brazilian and Vietnamese study groups; the CR1*AGAATG haplotype was frequent in the Indian and Vietnamese populations, while the CR1*AGAGTG haplotype was frequent among Congolese and Ghanaian individuals.The African populations included in this study might have a selective advantage conferred to immune genes involved in pathogen recognition and signaling, possibly contributing to disease susceptibility or resistance.

  11. Mechanisms of disease: inflammasome activation and the development of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Ryan W. Grant

    2013-03-01

    Full Text Available Over the recent past, the importance of aberrant immune cell activation as one of the contributing mechanisms to the development of insulin-resistance and type 2 diabetes (T2D has been recognized. Among the panoply of pro-inflammatory cytokines that are linked to chronic metabolic diseases, new data suggests that interleukin-1β (IL-1β may play an important role in initiating and sustaining inflammation induced organ dysfunction in T2D. Therefore, factors that control secretion of bioactive IL-1β have therapeutic implications. In this regard, the identification of multiprotein scaffolding complexes, ‘inflammasomes’, has been a great advance in our understanding of this process. The secretion of bioactive IL-1β is predominantly controlled by activation of caspase-1 through assembly of a multiprotein scaffold, ‘inflammasome’ that is composed of NLRP3 (for nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 ASC (apoptosis associated speck-like protein containing a CARD and procaspase-1. The NLRP3 inflammasome appears to be an important sensor of metabolic dysregulation and controls obesity-associated insulin resistance and pancreatic beta cell dysfunction. Initial clinical proof of concept studies suggest that blocking IL-1β may favorably modulate factors related to development and treatment of T2D. However, this potential therapeutic approach remains to be fully substantiated through phase-II clinical studies. Here, we outline the new immunological mechanisms that link metabolic dysfunction to the emergence of chronic inflammation and discuss the opportunities and challenges of future therapeutic approaches to dampen NLRP3 inflammasome activation or IL-1β signaling for controlling type 2 diabetes.

  12. Systemic Correction of Murine Glycogen Storage Disease Type IV by an AAV-Mediated Gene Therapy.

    Science.gov (United States)

    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.

  13. Mucosal Expression of Type 2 and Type 17 Immune Response Genes Distinguishes Ulcerative Colitis From Colon-Only Crohn's Disease in Treatment-Naive Pediatric Patients.

    Science.gov (United States)

    Rosen, Michael J; Karns, Rebekah; Vallance, Jefferson E; Bezold, Ramona; Waddell, Amanda; Collins, Margaret H; Haberman, Yael; Minar, Phillip; Baldassano, Robert N; Hyams, Jeffrey S; Baker, Susan S; Kellermayer, Richard; Noe, Joshua D; Griffiths, Anne M; Rosh, Joel R; Crandall, Wallace V; Heyman, Melvin B; Mack, David R; Kappelman, Michael D; Markowitz, James; Moulton, Dedrick E; Leleiko, Neal S; Walters, Thomas D; Kugathasan, Subra; Wilson, Keith T; Hogan, Simon P; Denson, Lee A

    2017-05-01

    There is controversy regarding the role of the type 2 immune response in the pathogenesis of ulcerative colitis (UC)-few data are available from treatment-naive patients. We investigated whether genes associated with a type 2 immune response in the intestinal mucosa are up-regulated in treatment-naive pediatric patients with UC compared with patients with Crohn's disease (CD)-associated colitis or without inflammatory bowel disease (IBD), and whether expression levels are associated with clinical outcomes. We used a real-time reverse-transcription quantitative polymerase chain reaction array to analyze messenger RNA (mRNA) expression patterns in rectal mucosal samples from 138 treatment-naive pediatric patients with IBD and macroscopic rectal disease, as well as those from 49 children without IBD (controls), enrolled in a multicenter prospective observational study from 2008 to 2012. Results were validated in real-time reverse-transcription quantitative polymerase chain reaction analyses of rectal RNA from an independent cohort of 34 pediatric patients with IBD and macroscopic rectal disease and 17 controls from Cincinnati Children's Hospital Medical Center. We measured significant increases in mRNAs associated with a type 2 immune response (interleukin [IL]5 gene, IL13, and IL13RA2) and a type 17 immune response (IL17A and IL23) in mucosal samples from patients with UC compared with patients with colon-only CD. In a regression model, increased expression of IL5 and IL17A mRNAs distinguished patients with UC from patients with colon-only CD (P = .001; area under the receiver operating characteristic curve, 0.72). We identified a gene expression pattern in rectal tissues of patients with UC, characterized by detection of IL13 mRNA, that predicted clinical response to therapy after 6 months (odds ratio [OR], 6.469; 95% confidence interval [CI], 1.553-26.94), clinical response after 12 months (OR, 6.125; 95% CI, 1.330-28.22), and remission after 12 months (OR, 5

  14. Revisiting the Heidenhain Variant of Creutzfeldt-Jakob Disease: Evidence for Prion Type Variability Influencing Clinical Course and Laboratory Findings.

    Science.gov (United States)

    Baiardi, Simone; Capellari, Sabina; Ladogana, Anna; Strumia, Silvia; Santangelo, Mario; Pocchiari, Maurizio; Parchi, Piero

    2016-01-01

    The Heidenhain variant defines a peculiar clinical presentation of sporadic Creutzfeldt-Jakob disease (sCJD) characterized by isolated visual disturbances at disease onset and reflecting the early targeting of prions to the occipital cortex. Molecular and histopathological typing, thus far performed in 23 cases, has linked the Heidenhain variant to the MM1 sCJD type. To contribute a comprehensive characterization of cases with the Heidenhain variant, we reviewed a series of 370 definite sCJD cases. Eighteen patients (4.9%) fulfilled the selection criteria. Fourteen of them belonging to sCJD types MM1 or MM1+2C had a short duration of isolated visual symptoms and overall clinical disease, a high prevalence of periodic sharp-wave complexes in EEG, and a marked increase of cerebrospinal fluid proteins t-tau and 14-3-3 levels. In contrast, three cases of the MM 2C or MM 2+1C types showed a longer duration of isolated visual symptoms and overall clinical disease, non-specific EEG findings, and cerebrospinal fluid concentration below threshold for the diagnosis of "probable" CJD of both 14-3-3 and t-tau. However, a brain DWI-MRI disclosed an occipital cortical hyperintensity in the majority of examined cases of both groups. While confirming the strong linkage with the methionine genotype at the polymorphic codon 129 of the prion protein gene, our results definitely establish that the Heidenhain variant can also be associated with the MM 2C sCJD type in addition to the more common MM1 type. Likewise, our results highlight the significant differences in clinical evolution and laboratory findings between cases according to the dominant PrPSc type (type 1 versus type 2).

  15. Assay of the β-glucosidase activity with natural labelled and artificial substrates in leukocytes from homozygotes and heterozygotes with the Norrbottnian type (Type 3) of Gaucher disease

    International Nuclear Information System (INIS)

    Svennerholm, L.; Haakansson, G.; Dreborg, S.

    1980-01-01

    Leukocytes were isolated from 14 patients (7 males and 7 females) with Gaucher disease of the Norrbottnian type (Type 3), 32 obligate heterozygotes (16 males and 16 females) for this disease and 20 controls (10 males and 10 females). After collection, the cells were transported in dry ice to the laboratory, where they were assayed. The assays were repeated after the cells had been stored for 12 months. β-Glucosidase activity was assayed with D-[glucose-U- 14 C]glucosylceramide at pH 5.8 with Cutscum-Na-cholate as a detergent and 4-methylumbelliferyl-β-glucoside at pH 4.1 with Triton-Na-taurocholate as a detergent. The activities of two marker enzymes, 4-methylumbelliferyl-β-galactosidase and N-acetyl-β-glucosaminidase, were assayed in aliquots of the same leukocyte samples. (Auth.)

  16. Type II Natural Killer T (NKT) Cells And Their Emerging Role In Health And Disease

    Science.gov (United States)

    Dhodapkar, Madhav V.; Kumar, Vipin

    2016-01-01

    Natural killer T (NKT) cells recognize lipid antigens presented by a class I MHC-like molecule CD1d, a member of the CD1 family. While most of the initial studies on NKT cells focused on a subset with semi-invariant T cell receptor (TCR) termed iNKT cells, majority of CD1d-restricted lipid-reactive human T cells express diverse TCRs and are termed as type II NKT cells. These cells constitute a distinct population of circulating and tissue-resident effector T cells with immune-regulatory properties. They react to a growing list of self- as well as non-self lipid ligands, and share some properties with both iNKT as well as conventional T cells. Emerging body of evidence points to their role in the regulation of immunity to pathogens/tumors and in autoimmune/metabolic disorders. Improved understanding of the biology of these cells and the ability to manipulate their function may be of therapeutic benefit in diverse disease conditions. PMID:28115591

  17. Type II NKT Cells and Their Emerging Role in Health and Disease.

    Science.gov (United States)

    Dhodapkar, Madhav V; Kumar, Vipin

    2017-02-01

    NKT cells recognize lipid Ags presented by a class I MHC-like molecule CD1d, a member of the CD1 family. Although most initial studies on NKT cells focused on a subset with semi-invariant TCR termed invariant NKT cells, the majority of CD1d-restricted lipid-reactive human T cells express diverse TCRs and are termed type II NKT cells. These cells constitute a distinct population of circulating and tissue-resident effector T cells with immune-regulatory properties. They react to a growing list of self- as well as non-self-lipid ligands, and share some properties with both invariant NKT and conventional T cells. An emerging body of evidence points to their role in the regulation of immunity to pathogens/tumors and in autoimmune/metabolic disorders. An improved understanding of the biology of these cells and the ability to manipulate their function may be of therapeutic benefit in diverse disease conditions. Copyright © 2017 by The American Association of Immunologists, Inc.

  18. Review of Coconut “Lethal Yellowing” type diseases Diversity, variability and diagnosis

    Directory of Open Access Journals (Sweden)

    Dollet Michel

    2009-03-01

    Full Text Available Coconut palms (Cocos nucifera L. can be affected by several types of Lethal Yellowing (LY diseases worldwide. Some of the syndromes are caused by phytoplasmas, small bacteria that are impossible to detect by light microscopy. Amplification of a given gene of the phytoplasmas by polymerase chain reaction (PCR is the most convenient diagnosis method. The problem is that there are at least 28 “groups” of phytoplasmas and only one pair of primers -P1/P7- commonly used for PCR. As these primers belong to a very conserved gene, false positives are frequent. Consequently, alternative primers specific to one “strain” (or subgroup have to be used, such as LY-F/LY-R for the Caribbean LY, Rohde primers for LD Tanzania. Such specific primers are sometimes restrictive. Indeed, there is variability within each strain and the sequence of the primers has to be adapted to that variability. There are at least five LY subgroups. The subgroups can only be identified by restriction fragment length polymorphism or sequencing. In Africa, two subgroups of LY phytoplasmas have been identified so far.

  19. Increased Regenerative Capacity of the Olfactory Epithelium in Niemann–Pick Disease Type C1

    Directory of Open Access Journals (Sweden)

    Anja Meyer

    2017-04-01

    Full Text Available Niemann–Pick disease type C1 (NPC1 is a fatal neurovisceral lysosomal lipid storage disorder. The mutation of the NPC1 protein affects the homeostasis and transport of cholesterol and glycosphingolipids from late endosomes/lysosomes to the endoplasmic reticulum resulting in progressive neurodegeneration. Since olfactory impairment is one of the earliest symptoms in many neurodegenerative disorders, we focused on alterations of the olfactory epithelium in an NPC1 mouse model. Previous findings revealed severe morphological and immunohistochemical alterations in the olfactory system of NPC1−/− mutant mice compared with healthy controls (NPC1+/+. Based on immunohistochemical evaluation of the olfactory epithelium, we analyzed the impact of neurodegeneration in the olfactory epithelium of NPC1−/− mice and observed considerable loss of mature olfactory receptor neurons as well as an increased number of proliferating and apoptotic cells. Additionally, after administration of two different therapy approaches using either a combination of miglustat, 2-hydroxypropyl-β-cyclodextrin (HPβCD and allopregnanolone or a monotherapy with HPβCD, we recorded a remarkable reduction of morphological damages in NPC1−/− mice and an up to four-fold increase of proliferating cells within the olfactory epithelium. Numbers of mature olfactory receptor neurons doubled after both therapy approaches. Interestingly, we also observed therapy-induced alterations in treated NPC1+/+ controls. Thus, olfactory testing may provide useful information to monitor pharmacologic treatment approaches in human NPC1.

  20. Neuroimaging Findings in a Brain With Niemann–Pick Type C Disease

    Directory of Open Access Journals (Sweden)

    Jei-Yie Huang

    2011-08-01

    Full Text Available Niemann-Pick type C disease (NPC is a rare autosomal recessive lipid storage disorder caused by impaired cellular functions in processing and transporting low-density lipoprotein-cholesterol. In this report, we present magnetic resonance imaging (MRI, magnetic resonance spectrography (MRS and 18-fluoro-2-deoxyglucose positron emission tomography (PET imaging results for a 22-year-old male NPC patient. The patient's two MRI studies (at age 19 years and 22 years demonstrated progressive changes of brain atrophy that were more prominent at the frontal lobes, and hyperintense signals in bilateral parietal-occipital periventricular white matter. MRS (at age 19 years revealed no significant decrease in N-acetyl aspartate/choline ratio in the left frontal central white matter. PET (at age 22 years showed significant bilateral hypometabolism in the prefrontal cortex and dorsomedial thalamus, and hypermetabolism in the parietal-occipital white matter, lenticular nucleus of the basal ganglia, cerebellum and pons. The imaging findings noted by MRI, MRS and 18-fluoro-2-deoxyglucose PET offered a possible supplementary explanation for the clinical neurological symptoms of this NPC patient.

  1. The impact of different types of assistive devices on gait measures and safety in Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Anne D Kloos

    Full Text Available BACKGROUND: Gait and balance impairments lead to frequent falls and injuries in individuals with Huntington's disease (HD. Assistive devices (ADs such as canes and walkers are often prescribed to prevent falls, but their efficacy is unknown. We systematically examined the effects of different types of ADs on quantitative gait measures during walking in a straight path and around obstacles. METHODS: Spatial and temporal gait parameters were measured in 21 subjects with HD as they walked across a GAITRite walkway under 7 conditions (i.e., using no AD and 6 commonly prescribed ADs: a cane, a weighted cane, a standard walker, and a 2, 3 or 4 wheeled walker. Subjects also were timed and observed for number of stumbles and falls while walking around two obstacles in a figure-of-eight pattern. RESULTS: Gait measure variability (i.e., coefficient of variation, an indicator of fall risk, was consistently better when using the 4WW compared to other ADs. Subjects also walked the fastest and had the fewest number of stumbles and falls when using the 4WW in the figure-of-eight course. Subjects walked significantly slower using ADs compared to no AD both across the GAITRite and in the figure-of-eight. Measures reflecting gait stability and safety improved with the 4WW but were made worse by some other ADs.

  2. The impact of different types of assistive devices on gait measures and safety in Huntington's disease.

    Science.gov (United States)

    Kloos, Anne D; Kegelmeyer, Deborah A; White, Susan E; Kostyk, Sandra K

    2012-01-01

    Gait and balance impairments lead to frequent falls and injuries in individuals with Huntington's disease (HD). Assistive devices (ADs) such as canes and walkers are often prescribed to prevent falls, but their efficacy is unknown. We systematically examined the effects of different types of ADs on quantitative gait measures during walking in a straight path and around obstacles. Spatial and temporal gait parameters were measured in 21 subjects with HD as they walked across a GAITRite walkway under 7 conditions (i.e., using no AD and 6 commonly prescribed ADs: a cane, a weighted cane, a standard walker, and a 2, 3 or 4 wheeled walker). Subjects also were timed and observed for number of stumbles and falls while walking around two obstacles in a figure-of-eight pattern. Gait measure variability (i.e., coefficient of variation), an indicator of fall risk, was consistently better when using the 4WW compared to other ADs. Subjects also walked the fastest and had the fewest number of stumbles and falls when using the 4WW in the figure-of-eight course. Subjects walked significantly slower using ADs compared to no AD both across the GAITRite and in the figure-of-eight. Measures reflecting gait stability and safety improved with the 4WW but were made worse by some other ADs.

  3. Acoustically accessible window determination for ultrasound mediated treatment of glycogen storage disease type Ia patients

    Science.gov (United States)

    Wang, Shutao; Raju, Balasundar I.; Leyvi, Evgeniy; Weinstein, David A.; Seip, Ralf

    2012-10-01

    Glycogen storage disease type Ia (GSDIa) is caused by an inherited single-gene defect resulting in an impaired glycogen to glucose conversion pathway. Targeted ultrasound mediated delivery (USMD) of plasmid DNA (pDNA) to liver in conjunction with microbubbles may provide a potential treatment for GSDIa patients. As the success of USMD treatments is largely dependent on the accessibility of the targeted tissue by the focused ultrasound beam, this study presents a quantitative approach to determine the acoustically accessible liver volume in GSDIa patients. Models of focused ultrasound beam profiles for transducers of varying aperture and focal lengths were applied to abdomen models reconstructed from suitable CT and MRI images. Transducer manipulations (simulating USMD treatment procedures) were implemented via transducer translations and rotations with the intent of targeting and exposing the entire liver to ultrasound. Results indicate that acoustically accessible liver volumes can be as large as 50% of the entire liver volume for GSDIa patients and on average 3 times larger compared to a healthy adult group due to GSDIa patients' increased liver size. Detailed descriptions of the evaluation algorithm, transducer-and abdomen models are presented, together with implications for USMD treatments of GSDIa patients and transducer designs for USMD applications.

  4. A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

    DEFF Research Database (Denmark)

    van Zuydam, Natalie R; Ahlqvist, Emma; Sandholm, Niina

    2018-01-01

    complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined (T1D+T2D) GWAS was performed using complementary data available......Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight...... for subjects with T1D, which, with replication samples, involved up to 40,340 diabetic subjects (and 18,582 DKD cases).Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, p=4.5×10-8) associated with 'microalbuminuria' in European T2D cases. However, no replication...

  5. Glycemic control and periodontal disease in type 2 diabetes mellitus patients: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Vaibhav Tandon

    2015-01-01

    Full Text Available Introduction: Diabetes mellitus (DM is a chronic, noncommunicable disease with concomitant oral manifestations that impact on dental care. Aim: To determine the correlation between glycemic control and periodontitis among 35-45 years aged patients with DM type 2 (DM2. Materials and Methods: A convenient sample of 40 subjects aged 35-45 years with DM2 on oral medication were recruited for the study. Glycosylated, hemoglobin(HbA1c, probing pocket depth (PPD, gingival index (GI, plaque index (PI, and the relevant drug history were recorded. The data were analyzed using unpaired student t-test to compare the means of PPD, GI, PI between different HbA1c levels, gender, and duration of drug, and the Pearson correlation was used to find correlation between HbA1c and PPD, GI, PI, duration of drug. Results: With the increase in HbA1c values there was a significant rise in PPD, PI scores, and GI scores (P < 0.001. Diabetic males had a higher PPD, PI, and GI score as compared to females. With the increase in duration of the drug, there was an increase in PPD, which was found to be statistically nonsignificant. Conclusion: Patients are having poor glycemic level had more severe periodontitis as compared to patients having a fair glycemic level.

  6. The association of pioglitazone and urinary tract disease in type 2 diabetic Taiwanese: bladder cancer and chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Mei-Yueh Lee

    Full Text Available OBJECTIVE: Although studies have shown an association between pioglitazone and bladder cancer, the associated factors have not been identified. The aim of this study was to investigate the factors that may link pioglitazone to bladder cancer. MATERIALS AND METHODS: In total, 34,970 study subjects were identified from the National Health Insurance Research Database in 2003 with follow-up from 2005 to 2009. The demographic characteristics of patients who had used and had never used pioglitazone, including age, sex, diabetes duration, urinary tract disease, nephropathy, bladder cancer, and cumulative dose and duration of pioglitazone therapy, were analyzed using the χ2 test. Cox proportional hazard regression models were used to determine the independent effects of pioglitazone on bladder cancer and newly developed chronic kidney disease. RESULTS: Among 3,497 ever users and 31,473 never users of pioglitazone, the respective incident cases of bladder cancer were 12 (0.4% and 72 (0.2%, and for newly developed chronic kidney disease 245 (8.1% and 663 (2.3%, respectively. Ever use of pioglitazone [1.59(1.32-1.91], cumulative dose of pioglitazone 10,500 mg [1.34 (1.04-1.73], and duration of therapy 12 months [1.39 (1.09-1.76] were associated with the development of chronic kidney disease. CONCLUSIONS: There was no association of pioglitazone use with bladder cancer development, however, there was an association with an increased risk of newly developed chronic kidney disease.

  7. Higher prevalence of type 2 diabetes, metabolic syndrome and cardiovascular diseases in gypsies than in non-gypsies in Slovakia

    DEFF Research Database (Denmark)

    de Courten, Barbora; de Courten, Maximilian; Hanson, Robert L

    2003-01-01

    Gypsies (or Roma) recently experienced a transition from a traditional to a Westernized lifestyle. Although mortality in this population is 4-fold higher compared with non-Gypsies, very limited information is available on their morbidity especially with regard to non-communicable diseases. Our ai...... was to determine the prevalence of type 2 diabetes mellitus (T2DM), metabolic syndrome and cardiovascular diseases in Gypsies and non-Gypsies living in the same region of southern Slovakia....

  8. HLA typing using genome wide data reveals susceptibility types for infections in a psychiatric disease enriched sample.

    Science.gov (United States)

    Parks, Samuel; Avramopoulos, Dimitrios; Mulle, Jennifer; McGrath, John; Wang, Ruihua; Goes, Fernando S; Conneely, Karen; Ruczinski, Ingo; Yolken, Robert; Pulver, Ann E; Pearce, Brad D

    2018-05-01

    The infections Toxoplasma gondii (T. gondii), cytomegalovirus, and Herpes Simplex Virus Type 1 (HSV1) are common persistent infections that have been associated with schizophrenia and bipolar disorder. The major histocompatibility complex (MHC, termed HLA in humans) region has been implicated in these infections and these mental illnesses. The interplay of MHC genetics, mental illness, and infection has not been systematically examined in previous research. In a cohort of 1636 individuals, we used genome-wide association data to impute 7 HLA types (A, B, C, DRB1, DQA1, DQB1, DPB1), and combined this data with serology data for these infections. We used regression analysis to assess the association between HLA alleles, infections (individually and collectively), and mental disorder status (schizophrenia, bipolar disorder, controls). After Bonferroni correction for multiple comparisons, HLA C∗07:01 was associated with increased HSV1 infection among mentally healthy controls (OR 3.4, p = 0.0007) but not in the schizophrenia or bipolar groups (P > 0.05). For the multiple infection outcome, HLA B∗ 38:01 and HLA C∗12:03 were protective in the healthy controls (OR ≈ 0.4) but did not have a statistically-significant effect in the schizophrenia or bipolar groups. T. gondii had several nominally-significant positive associations, including the haplotypes HLA DRB∗03:01 ∼ HLA DQA∗05:01 ∼ HLA DQB∗02:01 and HLA B∗08:01 ∼ HLA C∗07:01. We identified HLA types that showed strong and significant associations with neurotropic infections. Since some of these associations depended on mental illness status, the engagement of HLA-related pathways may be altered in schizophrenia due to immunogenetic differences or exposure history. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. GLUT4 is reduced in slow muscle fibers of type 2 diabetic patients: is insulin resistance in type 2 diabetes a slow, type 1 fiber disease?

    DEFF Research Database (Denmark)

    Gaster, M; Staehr, P; Beck-Nielsen, H

    2001-01-01

    To gain further insight into the mechanisms underlying muscle insulin resistance, the influence of obesity and type 2 diabetes on GLUT4 immunoreactivity in slow and fast skeletal muscle fibers was studied. Through a newly developed, very sensitive method using immunohistochemistry combined...... with morphometry, GLUT4 density was found to be significantly higher in slow compared with fast fibers in biopsy specimens from lean and obese subjects. In contrast, in type 2 diabetic subjects, GLUT4 density was significantly lower in slow compared with fast fibers. GLUT4 density in slow fibers from diabetic...... was reduced to 77% in the obese subjects and to 61% in type 2 diabetic patients compared with the control subjects. We propose that a reduction in the fraction of slow-twitch fibers, combined with a reduction in GLUT4 expression in slow fibers, may reduce the insulin-sensitive GLUT4 pool in type 2 diabetes...

  10. Potential Biomarkers of Insulin Resistance and Atherosclerosis in Type 2 Diabetes Mellitus Patients with Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Sharifah Intan Qhadijah Syed Ikmal

    2013-01-01

    Full Text Available Type 2 diabetes mellitus patients with coronary artery disease have become a major public health concern. The occurrence of insulin resistance accompanied with endothelial dysfunction worsens the state of atherosclerosis in type 2 diabetes mellitus patients. The combination of insulin resistance and endothelial dysfunction leads to coronary artery disease and ischemic heart disease complications. A recognized biological marker, high-sensitivity C-reactive protein, has been used widely to assess the progression of atherosclerosis and inflammation. Along with coronary arterial damage and inflammatory processes, high-sensitivity C-reactive protein is considered as an essential atherosclerosis marker in patients with cardiovascular disease, but not as an insulin resistance marker in type 2 diabetes mellitus patients. A new biological marker that can act as a reliable indicator of both the exact state of insulin resistance and atherosclerosis is required to facilitate optimal health management of diabetic patients. Malfunctioning of insulin mechanism and endothelial dysfunction leads to innate immune activation and released several biological markers into circulation. This review examines potential biological markers, YKL-40, alpha-hydroxybutyrate, soluble CD36, leptin, resistin, interleukin-18, retinol binding protein-4, and chemerin, as they may play significant roles in insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease.

  11. Relationship between Proinflammatory and Antioxidant Proteins with the Severity of Cardiovascular Disease in Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Beatriz García-Fontana

    2015-04-01

    Full Text Available Type 2 diabetes mellitus patients are at significant risk of cardiovascular disease, however, the pathophysiology of these complications is complex and incompletely known in this population. The aim of this study was to compare the serum proteome of patients with type 2 diabetes mellitus presenting or not presenting cardiovascular disease with non-diabetic subjects to find essential proteins related to these cardiovascular complications. This cross-sectional study compares the serum proteome by a combination of protein depletion with 2D-DIGE (2-dimension Difference Gel Electrophoresis methodology. The proteins differentially expressed were identified by MALDI TOF/TOF (Matrix-assisted laser desorption/ionization and Time-Of-Flight ion detector or LC-MS/MS (Liquid Chromatography coupled to Mass-Mass Spectrometry. Type 2 diabetes mellitus patients with cardiovascular disease showed higher expression of plasma retinol binding protein and glutathione peroxidase-3 compared to those without cardiovascular disease and non-diabetic controls. These results show that proteins related to the inflammatory and redox state appear to play an important role in the pathogenesis of the cardiovascular disease in the type 2 diabetes mellitus patients.

  12. The self-management experience of patients with type 2 diabetes and chronic kidney disease: A qualitative study.

    Science.gov (United States)

    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.

  13. Nonalcoholic fatty liver disease is associated with aortic valve sclerosis in patients with type 2 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Stefano Bonapace

    Full Text Available BACKGROUND: Recent epidemiological data suggest that non-alcoholic fatty liver disease (NAFLD is closely associated with aortic valve sclerosis (AVS, an emerging risk factor for adverse cardiovascular outcomes, in nondiabetic and type 2 diabetic individuals. To date, nobody has investigated the association between NAFLD and AVS in people with type 2 diabetes, a group of individuals in which the prevalence of these two diseases is high. METHODS AND RESULTS: We recruited 180 consecutive type 2 diabetic patients without ischemic heart disease, valvular heart disease, hepatic diseases or excessive alcohol consumption. NAFLD was diagnosed by liver ultrasonography whereas AVS was determined by conventional echocardiography in all participants. In the whole sample, 120 (66.7% patients had NAFLD and 53 (29.4% had AVS. No patients had aortic stenosis. NAFLD was strongly associated with an increased risk of prevalent AVS (odds ratio [OR] 2.79, 95% CI 1.3-6.1, p<0.01. Adjustments for age, sex, duration of diabetes, diabetes treatment, body mass index, smoking, alcohol consumption, hypertension, dyslipidemia, hemoglobin A1c and estimated glomerular filtration rate did not attenuate the strong association between NAFLD and risk of prevalent AVS (adjusted-OR 3.04, 95% CI 1.3-7.3, p = 0.01. CONCLUSIONS: Our results provide the first demonstration of a positive and independent association between NAFLD and AVS in patients with type 2 diabetes mellitus.

  14. Successful switch from enzyme replacement therapy to miglustat in an adult patient with type 1 Gaucher disease: a case report.

    Science.gov (United States)

    Giuffrida, Gaetano; Lombardo, Rita; Di Francesco, Ernesto; Parrinello, Laura; Di Raimondo, Francesco; Fiumara, Agata

    2016-11-08

    Gaucher disease is one of the most common lipid-storage disorders, affecting approximately 1 in 75,000 births. Enzyme replacement therapy with recombinant glucocerebrosidase is currently considered the first-line treatment choice for patients with symptomatic Gaucher disease type 1. Oral substrate reduction therapy is generally considered a second-line treatment option for adult patients with mild to moderate Gaucher disease type 1 who are unable or unwilling to receive lifelong intravenous enzyme infusions. The efficacy and safety of the oral substrate reduction therapy miglustat (Zavesca®) in patients with Gaucher disease type 1 have been established in both short-term clinical trials and long-term, open-label extension studies. Published data indicate that miglustat can be used as maintenance therapy in patients with stable Gaucher disease type 1 switched from previous enzyme replacement therapy. We report a case of a 44-year-old Caucasian man with Gaucher disease type 1 who was initially treated with enzyme replacement therapy but, owing to repeated cutaneous allergic reactions, had to be switched to miglustat after several attempts with enzyme replacement therapy. Despite many attempts, desensitization treatment did not result in improved toleration of imiglucerase infusions, and the patient became unwilling to continue with any intravenous enzyme replacement therapy. He subsequently agreed to switch to oral substrate reduction therapy with miglustat 100 mg twice daily titrated up to 100 mg three times daily over a short period. Long-term miglustat treatment maintained both hemoglobin and platelet levels within acceptable ranges over 8 years. The patient's spleen volume decreased, his plasma chitotriosidase levels stayed at reduced levels, and his bone mineral density findings have remained stable throughout follow-up. The patient's quality of life has remained satisfactory. Miglustat showed good gastrointestinal tolerability in this patient, and no

  15. Epicardial, pericardial and total cardiac fat and cardiovascular disease in type 2 diabetic patients with elevated urinary albumin excretion rate

    DEFF Research Database (Denmark)

    Christensen, Regitse H.; Von Scholten, Bernt J.; Hansen, Christian S.

    2017-01-01

    of 200 patients with type 2 diabetes and elevated urinary albumin excretion rate (UAER). Methods Cardiac adipose tissue was measured from baseline echocardiography. The composite endpoint comprised incident cardiovascular disease and all-cause mortality. Coronary artery calcium, carotid intima media.......7, p = 0.017) models. Cardiac adipose tissue (p = 0.033) was associated with baseline coronary artery calcium (model 1) and interleukin-8 (models 1-3, all p type 2 diabetes patients without coronary artery disease, high cardiac adipose tissue levels were associated...

  16. Correlation between serum Hcy content and coronary atherosclerosis severity in patients with H-type hypertension and coronary heart disease

    Directory of Open Access Journals (Sweden)

    Xiao-Mei Li

    2017-03-01

    Full Text Available Objective: To analyze the correlation between serum Hcy content and coronary atherosclerosis severity in patients with H-type hypertension and coronary heart disease. Methods: 48 patients with H-type hypertension and coronary heart disease were selected as observation group, and 57 patients with normal hypertension and coronary heart disease were selected as control group. Echocardiography was used to determine coronary lesion parameters, enzymelinked immunosorbent assay (ELISA was used to determine serum levels of homocysteine (Hcy and coronary heart disease-related indexes, and the correlation between Hcy levels and coronary heart disease was further analyzed. Results: Serum Hcy level of observation group was higher than that of control group (P<0.05, absolute GLPSS value and E/A value under echocardiography were less than those of control group while E-DT and E/e value were higher than those of control group (P<0.05; serum adiponectin (APN level was lower than that of control group while P-selectin, asymmetric dimethylarginine (ADMA, oxidized high-density lipoprotein (OX-HDL, MMP-2, MMP-9, lipoprotein-associated phospholipase A2 (Lp-PLA2 and Resistin levels were higher than those of control group (P<0.05; Hcy was negatively correlated with absolute GLPSS value, E/A value and APN level, and was positively correlated with E-DT value, E/e value as well as P-selectin, ADMA, OX-HDL, MMP-2, MMP-9, Lp- PLA2 and Resistin levels (P<0.05. Conclusions: There is direct correlation between serum Hcy levels and the severity of coronary heart disease in patients with H-type hypertension and coronary heart disease, it can be a reliable way to early screen for coronary heart disease and evaluate the illness, and it is also a new target of coronary heart disease intervention.

  17. Effect of the amount and type of dietary fat on cardiometabolic risk factors and risk of developing type 2 diabetes, cardiovascular diseases, and cancer

    DEFF Research Database (Denmark)

    Schwab, Ursula; Lauritzen, Lotte; Tholstrup, Tine

    2014-01-01

    of this systematic review (SR) was to assess the evidence of an effect of the amount and type of dietary fat on body weight (BW), risk factors, and risk of non-communicable diseases, that is, type 2 diabetes (T2DM), cardiovascular diseases (CVD), and cancer in healthy subjects or subjects at risk for these diseases...... suggestive. Evidence for a direct association between total fat intake and risk of T2DM was inconclusive, whereas there was limited-suggestive evidence from biomarker studies that LA is inversely associated with the risk of T2DM. However, there was limited-suggestive evidence in biomarker studies that odd......-chain SFA found in milk fat and fish may be inversely related to T2DM, but these associations have not been supported by controlled studies. The evidence for an association between dietary n-3 PUFA and T2DM was inconclusive. Evidence for effects of fat on major types of cancer was inconclusive regarding...

  18. Histological characterisation of visceral changes in a patient with type 2 Gaucher disease treated with enzyme replacement therapy.

    Science.gov (United States)

    Tezuka, Yuko; Fukuda, Mitsumasa; Watanabe, Shohei; Nakano, Takeshi; Okamoto, Kentaro; Kuzume, Kazuyo; Yano, Yoshiaki; Eguchi, Mariko; Ishimae, Minenori; Ishii, Eiichi; Miyazaki, Tatsuhiko

    2018-02-01

    Gaucher disease is a lysosomal storage disease caused by deficiency of glucocerebrosidase and accumulation of glucocerebroside. Three major sub-types have been described, type 2 is an acute neurological form that exhibits serious general symptoms and poor prognosis, compared with the other types. This case was a girl diagnosed with type 2 Gaucher disease at 12months of age who presented with poor weight gain from infancy, stridor, hypertonia, hepatosplenomegaly, trismus and an eye movement disorder. Enzyme replacement therapy (ERT) was administered, but she had frequent myoclonus and developmental regression. She needed artificial ventilation because of respiratory failure. She died at 11years of age. An autopsy demonstrated infiltrating CD68-positive large cells containing abundant lipids in alveoli, while in the liver, kidney and bone marrow CD68-positive cells were small and round. In the bone marrow, myelodysplastic changes were present without Gaucher cells. The infiltration of Gaucher cells in alveoli was marked, suggesting that ERT was relatively ineffective in pulmonary involvement, particularly intra-alveolar. Additional treatments are necessary to improve the neurological and pulmonary prognosis of type 2Gaucher disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Whole genome typing of the recently emerged Canadian serogroup W Neisseria meningitidis sequence type 11 clonal complex isolates associated with invasive meningococcal disease

    Directory of Open Access Journals (Sweden)

    Raymond S.W. Tsang

    2018-04-01

    Full Text Available Objectives: This study was performed to analyze the Canadian invasive serogroup W Neisseria meningitidis (MenW sequence type 11 (ST-11 clonal complex (CC isolates by whole genome typing and to compare Canadian isolates with similar isolates from elsewhere. Methods: Whole genome typing of 30 MenW ST-11 CC, 20 meningococcal group C (MenC ST-11 CC, and 31 MenW ST-22 CC isolates was performed on the Bacterial Isolate Genome Sequence database platform. Canadian MenW ST-11 CC isolates were compared with the 2000 MenW Hajj outbreak strain, as well as with MenW ST-11 CC from other countries. Results: Whole genome typing showed that the Canadian MenW ST-11 CC isolates were distinct from the traditional MenW ST-22 CC; they were not capsule-switched contemporary MenC strains that incorporated MenW capsules. While some recent MenW disease cases in Canada were caused by MenW ST-11 CC isolates showing relatedness to the 2000 MenW Hajj strain, many were non-Hajj isolates similar to current MenW ST-11 isolates found globally. Geographical and temporal variations in genotypes and surface protein antigen genes were found among the MenW ST-11 CC isolates. Conclusions: The current MenW ST-11 isolates did not arise by capsule switching from contemporary MenC ST-11 isolates. Both the Hajj-related and non-Hajj MenW ST-11 CC strains were associated with invasive meningococcal disease in Canada. Keywords: Neisseria meningitidis, Invasive meningococcal disease, Whole genome typing

  20. Association between tobacco consumption and periodontal diseases among type 2 diabetes mellitus patients

    Directory of Open Access Journals (Sweden)

    Shaikh Zakir Mahmud

    2016-01-01

    Conclusions: The relationship between smoking and chewing betel leaf and periodontal diseases provide strong evidence that tobacco products could be in a straight line responsible for developing periodontal diseases.

  1. Foot-and-mouth disease virus typing from foot-and-mouth outbreaks in the central provinces of Viet Nam

    International Nuclear Information System (INIS)

    Nguyen Luong Hien

    2000-01-01

    A total of 167 tissue samples were collected from Foot-and-mouth disease (FMD) infected animals from 57 FMD outbreaks to detect the sero-type of the FMD virus by the ELISA technique. The ELISA kit has been prepared and standardised by the World Reference Laboratory (WRL), UK and supplied under a Research Contract as part of an FAO/IAEA Co-ordinated Research Project. Eight tissue samples from cattle and one tissue sample from pig were sent to WRL for further study on the sero-type and to characterize the FMD viruses present in Viet Nam. The study was carried out from March 1996 to May 1998 in the central region of Viet Nam and the FMD type O virus was detected in these outbreaks only. The FMD type O virus from cattle and the FMD type O virus from pig are two distinct FMD type O viruses in Viet Nam. (author)

  2. [The German program for disease management guidelines: type 2 diabetes--diabetic retinopathy/maculopathy guideline 2006. Short review].

    Science.gov (United States)

    Ollenschläger, Günter; Kopp, Ina; Thole, Henning; Lelgemann, Monika

    2007-02-15

    In Germany, the first national consensus between six medical scientific associations on evidence-based recommendations for prevention and therapy of retinopathy/maculopathy in type 2 diabetes was reached in fall 2006. The recommendations' main sources are the NICE Retinopathy Guideline 2002, and existing German guidelines and reviews of recent scientific evidence. The article gives an overview on authors, sources, and key recommendations of the German National Disease Management Guideline Type 2 Diabetes-Retinopathy/Maculopathy 2006 (www.diabetes.versorgungsleitlinien.de).

  3. Occupational diseases in the Netherlands: incidence, type, consequences and risk factors: abstract and presentation

    NARCIS (Netherlands)

    Venema, A.; Steenbeek, R.; Dam, L. van; Vroome, E. de

    2017-01-01

    Objectives: Occupational diseases are common and result in a substantial disease burden and high sickness absence. Reliable data on the incidence and a better understanding of the risk factors will help to develop preventive measures. Methods: Several sources of measuring occupational diseases were

  4. Recommendations for the use of eliglustat in the treatment of adults with Gaucher disease type 1 in the United States.

    Science.gov (United States)

    Balwani, Manisha; Burrow, Thomas Andrew; Charrow, Joel; Goker-Alpan, Ozlem; Kaplan, Paige; Kishnani, Priya S; Mistry, Pramod; Ruskin, Jeremy; Weinreb, Neal

    2016-02-01

    In Gaucher disease, deficient activity of acid β-glucosidase results in accumulation of its substrates, glucosylceramide and glucosylsphingosine, within the lysosomes of cells primarily in the spleen, liver, bone marrow, and occasionally the lung. The multisystem disease is predominantly characterized by hepatosplenomegaly, anemia, thrombocytopenia, and skeletal disease. Enzyme replacement therapy with recombinant human acid β-glucosidase has been the first-line therapy for Gaucher disease type 1 for more than two decades. Eliglustat, a novel oral substrate reduction therapy, was recently approved in the United States and the European Union as a first-line treatment for adults with Gaucher disease type 1. Eliglustat inhibits glucosylceramide synthase, thereby decreasing production of the substrate glucosylceramide and reducing its accumulation. Although existing recommendations for the care of patients with Gaucher disease remain in effect, unique characteristics of eliglustat require additional investigation and monitoring. A panel of physicians with expertise in Gaucher disease and experience with eliglustat in the clinical trials provide guidance regarding the use of eliglustat, including considerations before starting therapy and monitoring of patients on eliglustat therapy. Copyright © 2015 Shire Development LLC. Published by Elsevier Inc. All rights reserved.

  5. Analysis of risk factors in obese patients with coronary artery disease, with and without diabetes mellitus type two

    Directory of Open Access Journals (Sweden)

    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.

  6. The Type 1 Diabetes - HLA Susceptibility Interactome - Identification of HLA Genotype-Specific Disease Genes for Type 1 Diabetes

    DEFF Research Database (Denmark)

    Brorsson, C.; Hansen, Niclas Tue; Bergholdt, R.

    2010-01-01

    Background: The individual contribution of genes in the HLA region to the risk of developing type 1 diabetes (T1D) is confounded by the high linkage disequilibrium (LD) in this region. Using a novel approach we have combined genetic association data with information on functional protein......-protein interactions to elucidate risk independent of LD and to place the genetic association into a functional context. Methodology/Principal Findings: Genetic association data from 2300 single nucleotide polymorphisms (SNPs) in the HLA region was analysed in 2200 T1D family trios divided into six risk groups based...... on HLA-DRB1 genotypes. The best SNP signal in each gene was mapped to proteins in a human protein interaction network and their significance of clustering in functional network modules was evaluated. The significant network modules identified through this approach differed between the six HLA risk groups...

  7. Negative affectivity in cardiovascular disease: Evaluating Type D personality assessment using item response theory

    NARCIS (Netherlands)

    Emons, Wilco H.M.; Meijer, R.R.; Denollet, Johan

    2007-01-01

    Objective: 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

  8. Clinical presentation and biochemical findings children with glycogen storage disease type 1A

    International Nuclear Information System (INIS)

    Saeed, A.; Suleman, H.; Arshad, H.

    2015-01-01

    To determine the clinical pattern of presentation and biochemical characteristics of glycogen storage disease (GSD) type 1a in children at a tertiary referral centre. Study Design: Descriptive/ cross sectional study. Place and Duration of Study: Department of Pediatric, division of Gastroenterology and Hepatology of the Children's hospital, Lahore over a period of 11 years. Patients and Methods: Confirmed cases of glycogen storage disease (clinical plus biochemical findings consistent with GSD 1a and proven on liver biopsy) were enrolled in this study from neonatal age till 18 years. Data was retrieved from files and electronic record for these cases. Diagnosis was made on the basis of history, clinical findings including hepatomegaly, hypertriglyceridemia, hypercholesterolemia, hypoglycemia and hyperuricemia (if present). Diagnosis was confirmed on liver biopsy. Patients with other storage disorders and benign and malignant tumours were excluded from the study. Results: Total patients included in the study were 360 with male to female ratio of 1.25:1. Median age at the time of diagnosis was 25.6 months (age range from one month to 18 years). Most common presentation was abdominal distension (83%) followed by failure to thrive (69%) and recurrent wheezing and diarrhoea (44%) each. Seizures were present in only 1/3rd of children. Other presentations included vomiting, respiratory distress, altered sensorium, nephrocalcinosis, epistaxis and hypothyroidism. Few patients around 11% presented with acute hepatitis and later were diagnosed as GSD. Significant hepatomegaly was evident in almost all patients but nephromegaly was present in only 5.5% patients. All children had marked hypertriglyceridemia but cholesterol levels were raised in 1/3rd of children. A large majority of children had deranged ALT more than 2 times of normal and around 38% children had marked anemia. Significant hypoglycemia and metabolic acidosis was documented in around 1/3rd of children

  9. Assessment of Bone Health in Patients With Type 1 Gaucher Disease Using Impact Microindentation.

    Science.gov (United States)

    Herrera, Sabina; Pérez-López, Jordi; Moltó-Abad, Marc; Güerri-Fernández, Roberto; Cabezudo, Elena; Novelli, Silvana; Esteve, Jordi; Hernández, Albert; Roig, Inmaculada; Solanich, Xavier; Prieto-Alhambra, Daniel; Nogués, Xavier; Díez-Pérez, Adolfo

    2017-07-01

    Gaucher disease (GD), one of the most common lysosomal disorders (a global population incidence of 1:50,000), is characterized by beta-glucocerebrosidase deficiency. Some studies have demonstrated bone infiltration in up to 80% of patients, even if asymptomatic. Bone disorder remains the main cause of morbidity in these patients, along with osteoporosis, avascular necrosis, and bone infarcts. Enzyme replacement therapy (ERT) has been shown to improve these symptoms. This cross-sectional study included patients with type 1 Gaucher disease (GD1) selected from the Catalan Study Group on GD. Clinical data were collected and a general laboratory workup was performed. Bone mineral density (BMD) was measured at the lumbar spine and hip using dual-energy X-ray absorptiometry (DXA). Patients with bone infarcts or any other focal lesion in the area of indentation visible on imaging were excluded. Bone Material Strength index (BMSi) was measured by bone impact microindentation using an Osteoprobe instrument. Analysis of covariance (ANCOVA) models were fitted to adjust for age, sex, weight, and height. Sixteen patients with GD1 and 29 age- and sex-matched controls were included. GD1 was associated with significantly lower BMSi (adjusted beta -9.30; 95% CI, -15.18 to -3.42; p = 0.004) and reduced lumbar BMD (adjusted beta -0.14; 95% CI, -0.22 to -0.06; p = 0.002) and total hip BMD (adjusted beta -0.09; 95% CI, -0.15 to -0.03; p = 0.006), compared to GD1-free controls. Chitotriosidase levels were negatively correlated with BMSi (linear R 2  = 51.6%, p = 0.004). Bone tissue mechanical characteristics were deteriorated in patients with GD1. BMSi was correlated with chitotriosidase, the marker of GD activity. Bone disorder requires special consideration in this group of patients, and microindentation could be an appropriate tool for assessing and managing their bone health. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone

  10. Decreased in vivo availability of the cannabinoid type 2 receptor in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Rawaha; Laere, Koen van [KU Leuven and University Hospitals Leuven, Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging, Leuven (Belgium); University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); Postnov, Andrey [KU Leuven and University Hospitals Leuven, Department of Imaging and Pathology, Nuclear Medicine and Molecular Imaging, Leuven (Belgium); National Research Nuclear University MEPhI, Moscow (Russian Federation); Bormans, Guy [KU Leuven, Laboratory for Radiopharmacy, Leuven (Belgium); Versijpt, Jan [University Hospital Brussels, Department of Neurology, Brussels (Belgium); Vandenbulcke, Mathieu [KU Leuven and University Hospitals Leuven, Old Age Psychiatry, Department of Psychiatry, Leuven (Belgium)

    2016-11-15

    The cannabinoid type 2 receptor (CB{sub 2}R) is expressed by immune cells such as monocytes and macrophages. In the brain, CB{sub 2}R is primarily found on microglia. CB{sub 2}R upregulation has been reported in animal models of Alzheimer's disease, with a preferential localization near amyloid beta (Aβ) plaques, and in patients post mortem. We performed in vivo brain imaging and kinetic modelling of the CB{sub 2}R tracer [{sup 11}C]NE40 in healthy controls (HC) and in patients with Alzheimer's disease (AD) to investigate whether higher CB{sub 2}R availability regionally colocalized to Aβ deposits is present in vivo. Dynamic 90-min [{sup 11}C]NE40 PET scans were performed in eight HC and nine AD patients with full kinetic modelling using arterial sampling and metabolite correction and partial volume correction. All AD patients received a static [{sup 11}C]PIB scan 40 min after injection. In four HC, a retest scan with [{sup 11}C]NE40 PET was performed within 9 weeks to investigate test-retest characteristics. [{sup 11}C]NE40 was metabolized quickly leading to 50 % of intact tracer 20 min after injection and 20 % at 90 min. A two-tissue kinetic model fitted most of the time-activity curves best; both binding potential (BP{sub ND}) and distribution volume (V{sub T}) parameters could be used. Brain uptake was generally low with an average K{sub 1} value of 0.07 ml/min/ml tissue. V{sub T} and BP{sub ND} were in the range of 0.7 - 1.8 and 0.6 - 1.6, respectively. Test values in HC were about 30 % for V{sub T} and BP{sub ND}. AD patients showed overall significantly lower CB{sub 2}R binding. No relationship was found between regional or global amyloid load and CB{sub 2}R availability. Kinetic modelling of [{sup 11}C]NE40 is possible with a two-tissue reversible model. In contrast to preclinical and post-mortem data, [{sup 11}C]NE40 PET shows lower CB{sub 2}R availability in vivo in AD patients, with no relationship to Aβ plaques. A possible explanation for

  11. Effect of alogliptin on hypertensive chronic kidney disease patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Amira Said

    2018-02-01

    Full Text Available Background Diabetes mellitus (DM is a leading cause of chronic kidney disease (CKD. The antihyperglycemic treatment options for patients with Type 2 DM are limited because of safety and tolerability concerns. Aims To retrospectively assess the effect of using Alogliptin; a dipeptidyl peptidase-4 inhibitor (DPP-4i along with conventional gliclazide: a sulphonylurea (SU on renal outcomes and glycaemic control in T2DM patients with mild CKD and hypertension. Methods A total of 76 patient records (38 males and 38 females of patient ages 40–60 were analysed from the kidney unit at Punjab Care hospital, Lahore, Pakistan. All patients had a confirmed history of T2DM with mild CKD and established hypertension. Eligible patients were divided into two groups of 38 individuals each. Group SU received gliclazide monotherapy (SU or Alogliptin (DPP-4i+gliclazide (SU add on therapy. All patients were followed up for 12 months. Results The alogliptin (DPP-4i plus gliclazide (SU add on therapy group, in comparison to the group only receiving gliclazide (SU, showed a significant difference in eGFR values. The mean±SD GFR values post 12 months were 74.8±0.31 (95%CI:74.8±0.09;74.7–74.9 and 76.1±0.25 (95%CI: 76.1±0.08;76.0-76.2 for SU vs. SU+DPP-4i, respectively, with mean calculated effect size of 1.6,. HbA1c, 1,5 AG and ipid profile values have significantly changed (p<0.05 while blood pressure values showed no change. The mean±SD systolic blood pressure readings post 12 months for for SU vs. SU+DPP-4i were 131.4±10.4 (95% CI 131.4±3.3;128.1– 134.7, and 131.8±9.9 (95%CI 131.8±3; 128.8–134.8, respectively. Conclusion In the present study, patients using alogliptin in addition to sulfonyl urea showed improved glycaemic control and lipid profile without increased occurrence of hypoglycaemia. We concluded that, DPP-4i inhibitors are safe treatment options for patients with type 2 diabetes and mild degree of renal impairment.

  12. Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat

    International Nuclear Information System (INIS)

    Kamath, Ravi S.; Lukina, Elena; Watman, Nora; Dragosky, Marta; Pastores, Gregory M.; Arreguin, Elsa Avila; Rosenbaum, Hanna; Zimran, Ari; Aguzzi, Rasha; Puga, Ana Cristina; Norfleet, Andrea M.; Peterschmitt, M.J.; Rosenthal, Daniel I.

    2014-01-01

    Eliglustat is an investigational oral substrate reduction therapy for Gaucher disease type 1 (GD1). Its skeletal effects were evaluated by prospective monitoring of bone mineral density (BMD), fractures, marrow infiltration by Gaucher cells, focal bone lesions, and infarcts during an open-label, multi-site, single-arm phase 2 trial (NCT00358150). Institutional review board approval and patient informed consent were obtained. Eliglustat (50 or 100 mg) was self-administered by mouth twice daily; 19 patients completed 4 years of treatment. All were skeletally mature (age range, 18-55 years). DXA and MRI assessments were conducted at baseline and annually thereafter. X-rays were obtained annually until month 24, and then every other year. Lumbar spine BMD increased significantly (p = 0.02; n = 15) by a mean (SD) of 9.9 % (14.2 %) from baseline to year 4; corresponding T-scores increased significantly (p = 0.01) from a mean (SD) of -1.6 (1.1) to -0.9 (1.3). Mean femur T-score remained normal through 4 years. Femur MRI showed that 10/18 (56 %) patients had decreased Gaucher cell infiltration compared to baseline; one patient with early improvement had transient worsening at year 4. There were no lumbar spine or femoral fractures and no reported bone crises during the study. At baseline, 8/19 (42 %) patients had focal bone lesions, which remained stable, and 7/19 (37 %) patients had bone infarctions, which improved in one patient by year 2. At year 4, one new asymptomatic, indeterminate bone lesion was discovered that subsequently resolved. Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1. (orig.)

  13. Ischaemic heart disease and glycaemic control in type-2 diabetes mellitus by questionnaire method

    International Nuclear Information System (INIS)

    Yathish, T.R.; Annamalai, N.; Shankar, V.

    2010-01-01

    Background: Various tests like Echocardiogram, Nuclear scan, Electron-beam computed tomography, Coronary angiography, and magnetic resonance angiography are available for diagnosis of ischemic heart disease (IHD). But most of these are expensive, invasive and cannot be afforded in developing countries. An attempt was made to study sensitivity, specificity, and predictive value of non-invasive technique like questionnaire method and compared with traditional clinical evaluation. This study compared diagnosis of angina made with the Rose uestionnaire to diagnosis by physician in type-2 diabetes mellitus and the effect of glycaemic control. Methods: A cross-sectional study was done from March 2005 to March 2006. Cases were collected from outpatients and inpatients visiting RL Jalappa hospital and SNR Hospital attached to Sri Devraj Urs Medical College Kolar, Karnataka, India. Glycosylated haemoglobin levels were estimated. Data on Rose questionnaire angina and physician diagnosed angina were collected and compared between groups of well controlled diabetics, poorly controlled diabetics and controls. The 12 lead Electrocardiogram was used to confirm the diagnosis. Results: The Rose questionnaire had 63.63% sensitivity, 97.5% specificity, 73% positive predictive value, and 96% negative predictive value. This study also showed the occurrence of IHD was higher in the poorly controlled diabetics (16.3%) as compared to well controlled diabetic patients (6%) and controls (5%) which were significant. Conclusions: The questionnaire diagnosis showed good sensitivity and high specificity as compared with diagnosis by physicians. The questionnaire method can be frequently used and incorporated in cardiovascular risk assessment and epidemiologic screening programs. (author)

  14. Long-term clinical outcomes in type 1 Gaucher disease following 10 years of imiglucerase treatment.

    Science.gov (United States)

    Weinreb, Neal J; Goldblatt, Jack; Villalobos, Jacobo; Charrow, Joel; Cole, J Alexander; Kerstenetzky, Marcelo; vom Dahl, Stephan; Hollak, Carla

    2013-05-01

    We studied the effect of long-term alglucerase/imiglucerase (Ceredase®/Cerezyme®, Genzyme, a Sanofi company, Cambridge, MA, USA) treatment on hematological, visceral, and bone manifestations of Gaucher disease type 1 (GD1). The International Collaborative Gaucher Group (ICGG) Gaucher Registry identified GD1 patients treated with alglucerase/imiglucerase who had dose and clinical data at first infusion and after 10 years of follow-up. Data for hemoglobin, platelet count, organ volumes, bone pain, and bone crisis were analyzed. Tests of the null hypothesis (no change from first infusion to 10 years) were performed using t tests for within-patient absolute change in continuous measurements and McNemar/chi-square tests for change in distributions using categorical values. An alpha level of 0.05 designated statistical significance. As of October 2011, 557 nonsplenectomized and 200 splenectomized patients met the inclusion criteria. The majority of GD1 patients had at least one N370S allele. Compared with nonsplenectomized patients at first infusion, splenectomized patients had lower percentages of anemia (26.0 % vs. 42.8 %) and thrombocytopenia (14.2 % vs. 76.3 %), similar percentages of moderate or severe hepatomegaly (81.2 % vs. 80.0 %), and higher percentages of bone pain (88.9 % vs. 52.4 %) and bone crises (38.3 % vs. 16.0 %). After 10 years, both groups showed significant (p < 0.05) improvements in mean hemoglobin levels, platelet count, liver, and spleen (nonsplenectomized) volumes, and bone crises. Initial dosing in both groups ranged from <15 U/kg to ≤90 U/kg every 2 weeks. After 10 years, the majority was receiving 15 to ≤45 U/kg every 2 weeks. Ten years of imiglucerase treatment results in sustainable improvements in all GD1 parameters.

  15. Gastrointestinal symptoms in children with type 1 diabetes screened for celiac disease.

    Science.gov (United States)

    Narula, Priya; Porter, Lesley; Langton, Josephine; Rao, Veena; Davies, Paul; Cummins, Carole; Kirk, Jeremy; Barrett, Timothy; Protheroe, Susan

    2009-09-01

    The association between celiac disease (CD) and type 1 diabetes mellitus (DM) is recognized. Most cases of CD in patients with DM are reported to be asymptomatic. The objectives of this study were to (1) compare and audit our practice with the published standards for screening for CD in children with DM, (2) characterize the children with DM and biopsy-confirmed CD, in terms of growth and gastrointestinal symptoms, and compare them with children with DM and negative celiac serology, and (3) document the effects of a gluten-free diet (GFD) after 1 year of gastrointestinal symptoms, growth, and insulin requirement. We performed a retrospective case-note review of 22 children with DM, positive celiac serology +/- biopsy-confirmed CD, and 50 children with DM and negative celiac serology. Twenty-two children (3.9% of the total diabetic population) had positive celiac serology on screening, with 17 (3%) having biopsy-confirmed CD. Ninety-four percent of the children had standardized celiac serology testing. At diagnosis of CD, 13 of the 17 biopsy-positive children (76.4%) had > or =1 gastrointestinal symptom. The frequency of gastrointestinal symptoms in negative celiac serology diabetic children was 6% (3 of 50) (P Symptoms resolved in all children after introduction of a GFD. A significant improvement in weight SD score (P = .008) and BMI SD score (P = .02) was noted in those compliant with a GFD after 1 year. Children with DM and CD have a higher frequency of gastrointestinal symptoms than their diabetic peers with negative celiac serology and are not truly asymptomatic. Institution of a GFD has a positive effect on nutritional status and symptom resolution in the short-term.

  16. The Statins in Prevention of Coronary Heart Diseases in Type 2 Diabetics

    Directory of Open Access Journals (Sweden)

    Bećir Heljić

    2009-02-01

    Full Text Available We aimed to determine whether the administration of statins to type 2 diabetics without pre-existing CHD reduced the incidence of CHD and their effects on cholesterol and CRP levels. All the participants were carefully interviewed, clinically examined, and laboratory tested to exclude conditions likely to provoke an inflammatory response that was an exclusion criterion. Exclusion criteria: Serious heart, liver or kidney problems, history of renal transplant, recent history of drug or alcohol abuse, HbA1c>10%, blood pressure >140/90mmHg, BMI >35 kg/m2, triglycerides >3,0mmol/dm3. 95 obese diabetics (mean age 60,9 years and BMI=31,59 kg/m2, diabetes duration more than 10 years without pre-existing CHD, were included in the analysis and were randomized to simvastatin (25 female and 20 male used 40 mg simvastatin daily or placebo (30 female and 20 male group. After six months, simvastatin significantly lowered CRP levels by 19%, (p<0,01, cholesterol levels by 18%, TG levels by 8%, LDL levels by 20% and VLDL levels by 17%, whereas there was no change with placebo. After one year the difference sustained between groups. Coronary events were rarely in the simvastatin group (6,6% than in the placebo group (14%. Coronary revascularizations were 4 in the placebo group and 1 in the simvastatin group. Rate of stroke was more often in the placebo group (18% than in the simvastatin group (8,8%. So, reduction of acute CHD events is for 7,4% in the simvastatin group. Positive correlation was between CRP and CVD (r=0,29. Statin therapy reduced the risk of coronary hearth disease in diabetics without CHD.

  17. Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat

    Energy Technology Data Exchange (ETDEWEB)

    Kamath, Ravi S. [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Fairfax Radiological Consultants, Fairfax, VA (United States); Lukina, Elena [Russian Academy of Medical Sciences, Moscow (Russian Federation); Watman, Nora [Hospital Ramos Mejia, Buenos Aires (Argentina); Dragosky, Marta [Instituto Mexicano del Seguro Social Hospital de Especialidades, Col. La Raza (Mexico); Pastores, Gregory M. [New York University, New York (United States); Yale University School of Medicine, New Haven, CT (United States); Arreguin, Elsa Avila [Instituto Argentino de Diagnostico y Tratamiento, Buenos Aires (Argentina); Rosenbaum, Hanna [Rambam Medical Center, Haifa (Israel); Zimran, Ari [Sha' are Zedek Hebrew University and Hadassah Medical School, Jerusalem (Israel); Aguzzi, Rasha [Genzyme, a Sanofi company, Cambridge, MA (United States); Alexion Pharmaceuticals, Cambridge, MA (United States); Puga, Ana Cristina; Norfleet, Andrea M.; Peterschmitt, M.J. [Genzyme, a Sanofi company, Cambridge, MA (United States); Rosenthal, Daniel I. [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Massachusetts General Hospital, Department of Radiology, Boston, MA (United States)

    2014-10-15

    Eliglustat is an investigational oral substrate reduction therapy for Gaucher disease type 1 (GD1). Its skeletal effects were evaluated by prospective monitoring of bone mineral density (BMD), fractures, marrow infiltration by Gaucher cells, focal bone lesions, and infarcts during an open-label, multi-site, single-arm phase 2 trial (NCT00358150). Institutional review board approval and patient informed consent were obtained. Eliglustat (50 or 100 mg) was self-administered by mouth twice daily; 19 patients completed 4 years of treatment. All were skeletally mature (age range, 18-55 years). DXA and MRI assessments were conducted at baseline and annually thereafter. X-rays were obtained annually until month 24, and then every other year. Lumbar spine BMD increased significantly (p = 0.02; n = 15) by a mean (SD) of 9.9 % (14.2 %) from baseline to year 4; corresponding T-scores increased significantly (p = 0.01) from a mean (SD) of -1.6 (1.1) to -0.9 (1.3). Mean femur T-score remained normal through 4 years. Femur MRI showed that 10/18 (56 %) patients had decreased Gaucher cell infiltration compared to baseline; one patient with early improvement had transient worsening at year 4. There were no lumbar spine or femoral fractures and no reported bone crises during the study. At baseline, 8/19 (42 %) patients had focal bone lesions, which remained stable, and 7/19 (37 %) patients had bone infarctions, which improved in one patient by year 2. At year 4, one new asymptomatic, indeterminate bone lesion was discovered that subsequently resolved. Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1. (orig.)

  18. Predictive properties of plasma amino acid profile for cardiovascular disease in patients with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Shinji Kume

    Full Text Available Prevention of cardiovascular disease (CVD is an important therapeutic object of diabetes care. This study assessed whether an index based on plasma free amino acid (PFAA profiles could predict the onset of CVD in diabetic patients. The baseline concentrations of 31 PFAAs were measured with high-performance liquid chromatography-electrospray ionization-mass spectrometry in 385 Japanese patients with type 2 diabetes registered in 2001 for our prospective observational follow-up study. During 10 years of follow-up, 63 patients developed cardiovascular composite endpoints (myocardial infarction, angina pectoris, worsening of heart failure and stroke. Using the PFAA profiles and clinical information, an index (CVD-AI consisting of six amino acids to predict the onset of any endpoints was retrospectively constructed. CVD-AI levels were significantly higher in patients who did than did not develop CVD. The area under the receiver-operator characteristic curve of CVD-AI (0.72 [95% confidence interval (CI: 0.64-0.79] showed equal or slightly better discriminatory capacity than urinary albumin excretion rate (0.69 [95% CI: 0.62-0.77] on predicting endpoints. A multivariate Cox proportional hazards regression analysis showed that the high level of CVD-AI was identified as an independent risk factor for CVD (adjusted hazard ratio: 2.86 [95% CI: 1.57-5.19]. This predictive effect of CVD-AI was observed even in patients with normoalbuminuria, as well as those with albuminuria. In conclusion, these results suggest that CVD-AI based on PFAA profiles is useful for identifying diabetic patients at risk for CVD regardless of the degree of albuminuria, or for improving the discriminative capability by combining it with albuminuria.

  19. Sirtuin signaling controls mitochondrial function in glycogen storage disease type Ia.

    Science.gov (United States)

    Cho, Jun-Ho; Kim, Goo-Young; Mansfield, Brian C; Chou, Janice Y

    2018-05-08

    Glycogen storage disease type Ia (GSD-Ia) deficient in glucose-6-phosphatase-α (G6Pase-α) is a metabolic disorder characterized by impaired glucose homeostasis and a long-term complication of hepatocellular adenoma/carcinoma (HCA/HCC). Mitochondrial dysfunction has been implicated in GSD-Ia but the underlying mechanism and its contribution to HCA/HCC development remain unclear. We have shown that hepatic G6Pase-α deficiency leads to downregulation of sirtuin 1 (SIRT1) signaling that underlies defective hepatic autophagy in GSD-Ia. SIRT1 is a NAD + -dependent deacetylase that can deacetylate and activate peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), a master regulator of mitochondrial integrity, biogenesis, and function. We hypothesized that downregulation of hepatic SIRT1 signaling in G6Pase-α-deficient livers impairs PGC-1α activity, leading to mitochondrial dysfunction. Here we show that the G6Pase-α-deficient livers display defective PGC-1α signaling, reduced numbers of functional mitochondria, and impaired oxidative phosphorylation. Overexpression of hepatic SIRT1 restores PGC-1α activity, normalizes the expression of electron transport chain components, and increases mitochondrial complex IV activity. We have previously shown that restoration of hepatic G6Pase-α expression normalized SIRT1 signaling. We now show that restoration of hepatic G6Pase-α expression also restores PGC-1α activity and mitochondrial function. Finally, we show that HCA/HCC lesions found in G6Pase-α-deficient livers contain marked mitochondrial and oxidative DNA damage. Taken together, our study shows that downregulation of hepatic SIRT1/PGC-1α signaling underlies mitochondrial dysfunction and that oxidative DNA damage incurred by damaged mitochondria may contribute to HCA/HCC development in GSD-Ia.

  20. Tryptophan hydroxylase type 2 variants modulate severity and outcome of addictive behaviors in Parkinson's disease.

    Science.gov (United States)

    Cilia, Roberto; Benfante, Roberta; Asselta, Rosanna; Marabini, Laura; Cereda, Emanuele; Siri, Chiara; Pezzoli, Gianni; Goldwurm, Stefano; Fornasari, Diego

    2016-08-01

    Impulse control disorders and compulsive medication intake may occur in a minority of patients with Parkinson's disease (PD). We hypothesize that genetic polymorphisms associated with addiction in the general population may increase the risk for addictive behaviors also in PD. Sixteen polymorphisms in candidate genes belonging to five neurotransmitter systems (dopaminergic, catecholaminergic, serotonergic, glutamatergic, opioidergic) and the BDNF were screened in 154 PD patients with addictive behaviors and 288 PD control subjects. Multivariate analysis investigated clinical and genetic predictors of outcome (remission vs. persistence/relapse) after 1 year and at the last follow-up (5.1 ± 2.5 years). Addictive behaviors were associated with tryptophan hydroxylase type 2 (TPH2) and dopamine transporter gene variants. A subsequent analysis within the group of cases showed a robust association between TPH2 genotype and the severity of addictive behaviors, which survived Bonferroni correction for multiple testing. At multivariate analysis, TPH2 genotype resulted the strongest predictor of no remission at the last follow-up (OR[95%CI], 7.4[3.27-16.78] and 13.2[3.89-44.98] in heterozygous and homozygous carriers, respectively, p medication dose reduction was not a predictor. TPH2 haplotype analysis confirmed the association with more severe symptoms and lower remission rates in the short- and the long-term (p addictive behaviors in PD, modulating the severity of symptoms and the rate of remission at follow-up. If confirmed in larger independent cohorts, TPH2 genotype may become a useful biomarker for the identification of at-risk individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Urine RAS components in mice and people with type 1 diabetes and chronic kidney disease.

    Science.gov (United States)

    Wysocki, Jan; Goodling, Anne; Burgaya, Mar; Whitlock, Kathryn; Ruzinski, John; Batlle, Daniel; Afkarian, Maryam

    2017-08-01

    The pathways implicated in diabetic kidney disease (DKD) are largely derived from animal models. To examine if alterations in renin-angiotensin system (RAS) in humans are concordant with those in rodent models, we measured concentration of angiotensinogen (AOG), cathepsin D (CTSD), angiotensin-converting enzyme (ACE), and ACE2 and enzymatic activities of ACE, ACE2, and aminopeptidase-A in FVB mice 13-20 wk after treatment with streptozotocin ( n = 9) or vehicle ( n = 15) and people with long-standing type 1 diabetes, with ( n = 37) or without ( n = 81) DKD. In streptozotocin-treated mice, urine AOG and CTSD were 10.4- and 3.0-fold higher than in controls, respectively ( P animals ( P animals ( P = 0.017). Compared with people without DKD, those with DKD had higher urine AOG (170 vs. 15 μg/g) and CTSD (147 vs. 31 μg/g). In people with DKD, urine ACE concentration was 1.8-fold higher (1.4 vs. 0.8 μg/g in those without DKD), while its enzymatic activity was 0.6-fold lower (1.0 vs. 1.6 × 10 9 RFU/g in those without DKD). Lower ACE activity, but not ACE protein concentration, was associated with ACE inhibitor (ACEI) treatment. After adjustment for clinical covariates, AOG, CTSD, ACE concentration, and ACE activity remained associated with DKD. In conclusion, in mice with streptozotocin-induced diabetes and in humans with DKD, urine concentrations and enzymatic activities of several RAS components are concordantly increased, consistent with enhanced RAS activity and greater angiotensin II formation. ACEI use was associated with a specific reduction in urine ACE activity, not ACE protein concentration, suggesting that it may be a marker of exposure to this widely-used therapy. Copyright © 2017 the American Physiological Society.

  2. Pharmacological benefits of selective modulation of cannabinoid receptor type 2 (CB2) in experimental Alzheimer's disease.

    Science.gov (United States)

    Jayant, Shalini; Sharma, Brij Mohan; Bansal, Rani; Sharma, Bhupesh

    2016-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that pervasively affects the population across the world. Currently, there is no effective treatment available for this and existing drugs merely slow the progression of cognitive function decline. Thus, massive effort is required to find an intended therapeutic target to overcome this condition. The present study has been framed to investigate the ameliorative role of selective modulator of cannabinoid receptor type 2 (CB2), 1-phenylisatin in experimental AD condition. We have induced experimental AD in mice by using two induction models viz., intracerebroventricular (i.c.v.) administration of streptozotocin (STZ) and aluminum trichloride (AlCl3)+d-galactose. Morris water maze (MWM) and attentional set shifting test (ASST) were used to assess learning and memory. Hematoxylin-eosin and Congo red staining were used to examine the structural variation in brain. Brain oxidative stress (thiobarbituric acid reactive substance and glutathione), nitric oxide levels (nitrites/nitrates), acetyl cholinesterase activity, myeloperoxidase and calcium levels were also estimated. i.c.v. STZ as well as AlCl3+d-galactose have impaired spatial and reversal learning with executive functioning, increased brain oxidative and nitrosative stress, cholinergic activity, inflammation and calcium levels. Furthermore, these agents have also enhanced the burden of Aβ plaque in the brain. Treatment with 1-phenylisatin and donepezil attenuated i.c.v. STZ as well as AlCl3+d-galactose induced impairment of learning-memory, brain biochemistry and brain damage. Hence, this study concludes that CB2 receptor modulation can be a potential therapeutic target for the management of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Celiac Disease Does Not Influence Fracture Risk in Young Patients with Type 1 Diabetes

    Science.gov (United States)

    Reilly, Norelle R; Lebwohl, Benjamin; Mollazadegan, Kaziwe; Michaëlsson, Karl; Green, Peter HR; Ludvigsson, Jonas F

    2015-01-01

    Objectives To examine the risk of any fractures in patients with both type 1 diabetes (T1D) and celiac disease (CD) vs patients with T1D only. Study design We performed a population-based cohort study. We defined T1D as individuals aged ≤30 years who had a diagnosis of diabetes recorded in the Swedish National Patient Register between 1964–2009. Individuals with CD were identified through biopsy report data between 1969–2008 from any of Sweden’s 28 pathology departments. Some 958 individuals had both T1D and CD and were matched for sex, age and calendar period with 4,598 reference individuals with T1D only. We then used a stratified Cox regression analysis, where CD was modeled as a time-dependent covariate, to estimate the risk of any fractures and osteoporotic fractures (hip, distal forearm, thoracic and lumbar spine, and proximal humerus) in patients with both T1D and CD compared with that in patients with T1D only. Results During follow-up, 12 patients with T1D and CD had a fracture (1 osteoporotic fracture). CD did not influence the risk of any fracture (adjusted Hazard Ratio=0.77; 95%CI=0.42–1.41) or osteoporotic fractures (adjusted Hazard Ratio=0.46; 95%CI=0.06–3.51) in patients with T1D. Stratification for time since CD diagnosis did not affect risk estimates. Conclusion Having a diagnosis of CD does not seem to influence fracture risk in young patients with T1D. Follow-up in this study was, however, too short to ascertain osteoporotic fractures which traditionally occur in old age. PMID:26589343

  4. Predictive Properties of Plasma Amino Acid Profile for Cardiovascular Disease in Patients with Type 2 Diabetes

    Science.gov (United States)

    Kume, Shinji; Araki, Shin-ichi; Ono, Nobukazu; Shinhara, Atsuko; Muramatsu, Takahiko; Araki, Hisazumi; Isshiki, Keiji; Nakamura, Kazuki; Miyano, Hiroshi; Koya, Daisuke; Haneda, Masakazu; Ugi, Satoshi; Kawai, Hiromichi; Kashiwagi, Atsunori; Uzu, Takashi; Maegawa, Hiroshi

    2014-01-01

    Prevention of cardiovascular disease (CVD) is an important therapeutic object of diabetes care. This study assessed whether an index based on plasma free amino acid (PFAA) profiles could predict the onset of CVD in diabetic patients. The baseline concentrations of 31 PFAAs were measured with high-performance liquid chromatography-electrospray ionization-mass spectrometry in 385 Japanese patients with type 2 diabetes registered in 2001 for our prospective observational follow-up study. During 10 years of follow-up, 63 patients developed cardiovascular composite endpoints (myocardial infarction, angina pectoris, worsening of heart failure and stroke). Using the PFAA profiles and clinical information, an index (CVD-AI) consisting of six amino acids to predict the onset of any endpoints was retrospectively constructed. CVD-AI levels were significantly higher in patients who did than did not develop CVD. The area under the receiver-operator characteristic curve of CVD-AI (0.72 [95% confidence interval (CI): 0.64–0.79]) showed equal or slightly better discriminatory capacity than urinary albumin excretion rate (0.69 [95% CI: 0.62–0.77]) on predicting endpoints. A multivariate Cox proportional hazards regression analysis showed that the high level of CVD-AI was identified as an independent risk factor for CVD (adjusted hazard ratio: 2.86 [95% CI: 1.57–5.19]). This predictive effect of CVD-AI was observed even in patients with normoalbuminuria, as well as those with albuminuria. In conclusion, these results suggest that CVD-AI based on PFAA profiles is useful for identifying diabetic patients at risk for CVD regardless of the degree of albuminuria, or for improving the discriminative capability by combining it with albuminuria. PMID:24971671

  5. Circumcision status and incident herpes simplex virus type 2 infection, genital ulcer disease, and HIV infection

    Science.gov (United States)

    Mehta, Supriya D.; Moses, Stephen; Parker, Corette B.; Agot, Kawango; Maclean, Ian; Bailey, Robert C.

    2013-01-01

    Objective We assessed the protective effect of medical male circumcision (MMC) against HIV, herpes simplex virus type 2 (HSV-2), and genital ulcer disease (GUD) incidence. Design Two thousand, seven hundred and eighty-seven men aged 18–24 years living in Kisumu, Kenya were randomly assigned to circumcision (n=1391) or delayed circumcision (n =1393) and assessed by HIV and HSV-2 testing and medical examinations during follow-ups at 1, 3, 6, 12, 18, and 24 months. Methods Cox regression estimated the risk ratio of each outcome (incident HIV, GUD, HSV-2) for circumcision status and multivariable models estimated HIV risk associated with HSV-2, GUD, and circumcision status as time-varying covariates. Results HIV incidence was 1.42 per 100 person-years. Circumcision was 62% protective against HIV [risk ratio =0.38; 95% confidence interval (CI) 0.22–0.67] and did not change when controlling for HSV-2 and GUD (risk ratio =0.39; 95% CI 0.23–0.69). GUD incidence was halved among circumcised men (risk ratio =0.52; 95% CI 0.37–0.73). HSV-2 incidence did not differ by circumcision status (risk ratio =0.94; 95% CI 0.70–1.25). In the multivariable model, HIV seroconversions were tripled (risk ratio =3.44; 95% CI 1.52–7.80) among men with incident HSV-2 and seven times greater (risk ratio =6.98; 95% CI 3.50–13.9) for men with GUD. Conclusion Contrary to findings from the South African and Ugandan trials, the protective effect of MMC against HIV was independent of GUD and HSV-2, and MMC had no effect on HSV-2 incidence. Determining the causes of GUD is necessary to reduce associated HIV risk and to understand how circumcision confers protection against GUD and HIV PMID:22382150

  6. Molecular Mechanisms for Herpes Simplex Virus Type 1 Pathogenesis in Alzheimer’s Disease

    Science.gov (United States)

    Harris, Steven A.; Harris, Elizabeth A.

    2018-01-01

    This review focuses on research in the areas of epidemiology, neuropathology, molecular biology and genetics that implicates herpes simplex virus type 1 (HSV-1) as a causative agent in the pathogenesis of sporadic Alzheimer’s disease (AD). Molecular mechanisms whereby HSV-1 induces AD-related pathophysiology and pathology, including neuronal production and accumulation of amyloid beta (Aβ), hyperphosphorylation of tau proteins, dysregulation of calcium homeostasis, and impaired autophagy, are discussed. HSV-1 causes additional AD pathologies through mechanisms that promote neuroinflammation, oxidative stress, mitochondrial damage, synaptic dysfunction, and neuronal apoptosis. The AD susceptibility genes apolipoprotein E (APOE), phosphatidylinositol binding clathrin assembly protein (PICALM), complement receptor 1 (CR1) and clusterin (CLU) are involved in the HSV lifecycle. Polymorphisms in these genes may affect brain susceptibility to HSV-1 infection. APOE, for example, influences susceptibility to certain viral infections, HSV-1 viral load in the brain, and the innate immune response. The AD susceptibility gene cholesterol 25-hydroxylase (CH25H) is upregulated in the AD brain and is involved in the antiviral immune response. HSV-1 interacts with additional genes to affect cognition-related pathways and key enzymes involved in Aβ production, Aβ clearance, and hyperphosphorylation of tau proteins. Aβ itself functions as an antimicrobial peptide (AMP) against various pathogens including HSV-1. Evidence is presented supporting the hypothesis that Aβ is produced as an AMP in response to HSV-1 and other brain infections, leading to Aβ deposition and plaque formation in AD. Epidemiologic studies associating HSV-1 infection with AD and cognitive impairment are discussed. Studies are reviewed supporting subclinical chronic reactivation of latent HSV-1 in the brain as significant in the pathogenesis of AD. Finally, the rationale for and importance of clinical

  7. Characterization of vascular lesions in pigs affected by porcine circovirus type 2-systemic disease.

    Science.gov (United States)

    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.

  8. Prevalence and Risk Factors of Gastroesophageal Reflux Disease in Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Jun Ouk Ha

    2016-06-01

    Full Text Available BackgroundGastrointestinal symptoms are common in patients with type 2 diabetes mellitus (T2DM. The prevalence of gastroesophageal reflux disease (GERD in Korea appears to be increasing. Some studies have shown that T2DM is a risk factor for symptomatic GERD. However, this possibility is still debated, and the pathogenesis of GERD in T2DM is not yet fully understood. The aim of this study was to analyze the prevalence and risk factors (including autonomic neuropathy of GERD in patients with T2DM.MethodsThis cross-sectional case-control study enrolled T2DM patients (n=258 and healthy controls (n=184. All participants underwent physical examinations and laboratory tests. We evaluated medical records and long-term diabetes complications, including peripheral and autonomic neuropathy in patients with T2DM. Esophagogastroduodenoscopy was performed in all patients. The Los Angeles (LA classification was used to grade GERD. GERD was defined as LA grade A (or higher or minimal change with GERD symptoms. GERD symptoms were examined using a frequency scale. Data were expressed as mean±standard error. Independent t-tests or chi-square tests were used to make comparisons between groups.ResultsThe prevalence of GERD (32.6% vs. 35.9%, P=0.266 and GERD symptoms (58.8% vs. 59.2%, P=0.503 was not significantly different between T2DM patients and controls. We found no significant differences between T2DM patients with GERD and T2DM patients without GERD with respect to diabetic complications, including autonomic neuropathy, peripheral neuropathy, duration of DM, and glucose control.ConclusionThe prevalence of GERD in patients with T2DM showed no difference from that of controls. GERD was also not associated with peripheral and cardiovascular autonomic neuropathy, age, or duration of DM in patients with T2DM.

  9. Quantitative measurement of duplicated DNA as a diagnostic test for Charcot-Marie-Tooth disease type 1a

    NARCIS (Netherlands)

    Hensels, G. W.; Janssen, E. A.; Hoogendijk, J. E.; Valentijn, L. J.; Baas, F.; Bolhuis, P. A.

    1993-01-01

    Charcot-Marie-Tooth disease type 1 (CMT1) is a hereditary motor and sensory neuropathy. The autosomal dominant subtype is often linked with a large duplication on chromosome 17p11.2. The gene encoding the peripheral myelin protein PMP 22 (the critical gene in this subtype of CMT1) is located within

  10. PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

    NARCIS (Netherlands)

    van Paassen, Barbara W.; van der Kooi, Anneke J.; van Spaendonck-Zwarts, Karin Y.; Verhamme, Camiel; Baas, Frank; de Visser, Marianne

    2014-01-01

    PMP22 related neuropathies comprise (1) PMP22 duplications leading to Charcot-Marie-Tooth disease type 1A (CMT1A), (2) PMP22 deletions, leading to Hereditary Neuropathy with liability to Pressure Palsies (HNPP), and (3) PMP22 point mutations, causing both phenotypes. Overall prevalence of CMT is

  11. Potential efficacy of enzyme replacement and substrate reduction therapy in three siblings with Gaucher disease type III

    NARCIS (Netherlands)

    Cox-Brinkman, J.; van Breemen, M. J.; van Maldegem, B. T.; Bour, L.; Donker, W. E.; Hollak, C. E. M.; Wijburg, F. A.; Aerts, J. M. F. G.

    2008-01-01

    We report three siblings with Gaucher disease type III, born between 1992 and 2004. During this period, new developments resulted in different potential therapies, changing clinical practice. The two eldest siblings received enzyme replacement therapy (ERT) from the age of 24 and 5 months

  12. Use of fluorquinolones is associated with a reduced risk of coronary heart disease in diabetes mellitus type 2 patients

    NARCIS (Netherlands)

    Erkens, JA; Klungel, OH; Herings, RMC; Stolk, RP; Spoelstra, JA; Grobbee, DE; Leufkens, HGM

    2002-01-01

    Aims The aim of the present study was to investigate whether use of specific antibiotic drugs