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Sample records for fabry disease initiative

  1. [Fabry disease].

    Science.gov (United States)

    Boggio, Paula; Luna, Paula Carolina; Abad, María Eugenia; Larralde, Margarita

    2009-01-01

    Fabry disease is an uncommon, X-linked lysosomal storage disorder, caused by partial or complete deficiency of the enzyme a-galactosidase A. The defect leads to accumulation of uncleaved globotriaosylceramide on the vascular endothelium and visceral tissues, being the skin, heart, kidneys and central nervous system the most affected organs. We performed review of the literature related to the disease and emphasized that early recognition of angiokeratomas and hypohidrosis are key diagnostic signs of this serious disease. We also addressed the need of multidisciplinary assessment of these patients.

  2. Fabry disease in children

    DEFF Research Database (Denmark)

    Borgwardt, Line Gutte; Feldt-Rasmussen, U; Rasmussen, AK

    2013-01-01

    Fabry disease is a rare, multiorgan disease. The most serious complications involve the kidney, brain and heart. This study aims to assess the effect of enzyme replacement therapy (ERT) using agalsidase-beta in children with Fabry disease. We carried out a nationwide, descriptive and observational...... retrospective cohort study of 10 children (9-16 years at baseline), who underwent regular systematic investigations for 1-8 years after initiation of ERT with agalsidase-beta (Fabryzyme®, Genzyme). Ophthalmological, echocardiographic abnormalities and hypohidrosis were found at baseline and during the follow......-up period. Serious kidney, heart or brain involvement had not developed at the last follow-up examination. For the majority of the patients improvements were found concerning headache, acroparaesthesias and gastrointestinal pain during the follow-up period. The level of energy and physical activity also...

  3. Fabry Disease

    Science.gov (United States)

    ... Foundation National Organization for Rare Disorders (NORD) National Tay-Sachs and Allied Diseases Association See all related ... Foundation National Organization for Rare Disorders (NORD) National Tay-Sachs and Allied Diseases Association See all related ...

  4. Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease

    DEFF Research Database (Denmark)

    Biegstraaten, Marieke; Arngrímsson, Reynir; Barbey, Frederic;

    2015-01-01

    INTRODUCTION: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed...... to define European consensus recommendations for the initiation and cessation of ERT in patients with FD. METHODS: A Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15). Patient organization representatives were present at the meeting to give their views. Recommendations...

  5. Genetics Home Reference: Fabry disease

    Science.gov (United States)

    ... AJ, Germain DP, Goldman M, Grabowski G, Packman S, Wilcox WR. Fabry disease, an under-recognized multisystemic disorder: ... Sims K, Brodie SE, Pastores GM, Strotmann JM, Wilcox WR. Fabry disease: guidelines for the evaluation and ...

  6. Neurological manifestations in Fabry's disease

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Jensen, Troels Staehelin

    2007-01-01

    . Neurological symptoms, such as burning sensations (occasionally accompanied by acroparesthesia) and stroke, are among the first to appear, and occur in both male and female patients. A delay in establishing the diagnosis of Fabry's disease can cause unnecessary problems, especially now that enzyme replacement...... treatment is available to prevent irreversible organ damage. Females with Fabry's disease who present with pain have often been ignored and misdiagnosed because of the disorder's X-linked inheritance. This Review will stress the importance of recognizing neurological symptoms for the diagnosis of Fabry...

  7. Fabry disease simulating Crohn's ileitis.

    Science.gov (United States)

    Rubio, Carlos A; Villnow, Elizabeth; Sundelin, Birgitta; Eriksson, Elina; Dolapcsiev, Karoli; Björk, Jan; Befrits, Ragnar; Tengvar, Magnus; Iversen, Henrik

    2014-05-01

    Fabry disease is an inherited (X-linked) lysosomal storage disorder caused by deficiency of α-galactosidase A, leading to accumulation of globotriaosylceramide in various tissues. A 57-year-old male with a family history and laboratory findings of Fabry disease, was consulted for severe abdominal pain, undulating pyrexia, weight loss and diarrhea. The tentative clinical diagnosis of Crohn's ileitis was supported at computed tomographic examination, at laparotomy and at inspection of the resected ileal segment. Histology revealed chronic and acute inflammation, thick-walled occluded vessels, fibrosis and characteristic bi-refringent lamellar deposits of globotriaosylceramide and calcifications. Multi-nucleated giant cells contained phagocytized bi-refringent material. Transmission electron microscopy showed cells with irregular cytoplasmic bodies displaying distinctive zebra-like lamellar structures. It is submitted that the gastrointestinal phenotype of Fabry disease may concur with symptoms resembling abdominal Crohn's disease.

  8. Neurological manifestations in Fabry's disease

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Jensen, Troels Staehelin

    2007-01-01

    Fabry's disease is an X-linked lysosomal storage disorder caused by a defect in the gene that encodes the lysosomal enzyme alpha-galactosidase A. Symptoms arise because of accumulation of globotriaosylceramide in multiple organs, resulting in severely reduced quality of life and premature death....... Neurological symptoms, such as burning sensations (occasionally accompanied by acroparesthesia) and stroke, are among the first to appear, and occur in both male and female patients. A delay in establishing the diagnosis of Fabry's disease can cause unnecessary problems, especially now that enzyme replacement...

  9. Fabry disease and early stroke

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, U

    2011-01-01

    Fabry disease, an X-linked lysosomal storage disorder, results from deficient activity of the enzyme a-galactosidase A. Affected males with the classic phoenotype have acroparaesthesias, hypohidrosis, and corneal opacities in childhood and develop renal failure, cardiac hypertrophy or strokes...... in the third to fifth decade of life. Some female heterozygotes are asymptomatic, some as severely affected as males. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both genders. The mechanism is partly due to vascular endothelial...... accumulation of GL-3. White matter lesions on MRI occur. Both males and females can be safely treated with enzyme replacement; and thus screening for Fabry disease of young stroke populations should be considered. There are, however, no hard data of treatment effect on mortality and morbidity. The analyses...

  10. Fabry disease and early stroke

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, U

    2011-01-01

    Fabry disease, an X-linked lysosomal storage disorder, results from deficient activity of the enzyme α-galactosidase A. Affected males with the classic phoenotype have acroparaesthesias, hypohidrosis, and corneal opacities in childhood and develop renal failure, cardiac hypertrophy or strokes...... in the third to fifth decade of life. Some female heterozygotes are asymptomatic, some as severely affected as males. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both genders. The mechanism is partly due to vascular endothelial...... accumulation of GL-3. White matter lesions on MRI occur. Both males and females can be safely treated with enzyme replacement; and thus screening for Fabry disease of young stroke populations should be considered. There are, however, no hard data of treatment effect on mortality and morbidity. The analyses...

  11. Cochleovestibular Manifestations in Fabry Disease

    Directory of Open Access Journals (Sweden)

    Alberto Ciceran MD

    2016-09-01

    Full Text Available Fabry disease is a rare, X-linked lysosomal storage disorder resulting from deficient α-galactosidase A activity and globotriaosylceramide accumulation throughout the body. This accumulation leads to various clinical disorders, including inner ear lesions, with sensorineural hearing loss and dizziness. Although hearing loss is recognized in these patients, its incidence and natural history have not been characterized. Hearing disorders develop mainly in adulthood, and tinnitus may be an earlier symptom in Fabry disease. A significant incidence of mid- and high-frequency sensorineural hearing loss in affected males is commonly reported, whereas in female carriers, it is much less frequent. In addition, a high incidence of vestibular disorders with dizziness and chronic instability is also observed in these patients. The few studies about the effects of enzyme replacement therapy (ERT on cochleovestibular symptoms show controversial results. Based on the model of densely stained material accumulation in the inner ear, stria vascularis cell, and organ damage, an early indication of ERT may prevent hearing loss due to the reduction in substrate accumulation.

  12. Cochleovestibular Manifestations in Fabry Disease

    Directory of Open Access Journals (Sweden)

    Alberto Ciceran MD

    2016-09-01

    Full Text Available Fabry disease is a rare, X-linked lysosomal storage disorder resulting from deficient α-galactosidase A activity and globotriaosylceramide accumulation throughout the body. This accumulation leads to various clinical disorders, including inner ear lesions, with sensorineural hearing loss and dizziness. Although hearing loss is recognized in these patients, its incidence and natural history have not been characterized. Hearing disorders develop mainly in adulthood, and tinnitus may be an earlier symptom in Fabry disease. A significant incidence of mid- and high-frequency sensorineural hearing loss in affected males is commonly reported, whereas in female carriers, it is much less frequent. In addition, a high incidence of vestibular disorders with dizziness and chronic instability is also observed in these patients. The few studies about the effects of enzyme replacement therapy (ERT on cochleovestibular symptoms show controversial results. Based on the model of densely stained material accumulation in the inner ear, stria vascularis cell, and organ damage, an early indication of ERT may prevent hearing loss due to the reduction in substrate accumulation.

  13. Neurological manifestations in Fabry disease

    Institute of Scientific and Technical Information of China (English)

    Joseph Bruno Bidin Brooks; Yara Dadalti Fragoso

    2016-01-01

    Fabry disease (FD) is a rare, progressive, multisystem and highly debilitating disease. FD is an X-linked lysosome storage disorder that results in α-galactosidase A deifciency. The subsequent accumulation of glycosphingolipids is more evident in vascular endothelium and smooth-muscle cells. The resulting effect of the deposition is generalized inlfammation and vasculopathy, which can also affect the central and peripheral nervous system. FD progresses with kidney dysfunction, angiokeratoma of the skin, cardiomyopathy, cerebrovascular events and neurological disorders. In the present review, the neurological manifestations of FD are summarized with emphasis on cerebral vasculopathy, cochlear nerve dysfunction, psychiatric and cognitive symptoms, autonomic dysfunction and peripheral neuropathy. Enzyme replacement therapy is also discussed in the light of its more prominent effects when administered early in life, which make it essential to diagnose FD as soon as possible.

  14. Dermatologic Aspects of Fabry Disease

    Directory of Open Access Journals (Sweden)

    Paula C. Luna MD

    2016-09-01

    Full Text Available Isolated angiokeratomas (AKs are common cutaneous lesions, generally deemed unworthy of further investigation. In contrast, diffuse AKs should alert the physician to a possible diagnosis of Fabry disease (FD. Angiokeratomas often do not appear until adolescence or young adulthood. The number of lesions and the extension over the body increase progressively with time, so that generalization and mucosal involvement are frequent. Although rare, FD remains an important diagnosis to consider in patients with AKs, with or without familial history. Dermatologists must have a high index of suspicion, especially when skin features are associated with other earlier symptoms such as acroparesthesia, hypohidrosis, or heat intolerance. Once the diagnosis is established, prompt screening of family members should be performed. In all cases, a multidisciplinary team is necessary for the long-term follow-up and treatment.

  15. Vertebrobasilar Dolichoectasia in Fabry Disease

    Directory of Open Access Journals (Sweden)

    Juan Politei

    2014-06-01

    Full Text Available Introduction: Fabry disease (FD is a lysosomal storage disorder associated with marked cerebrovascular involvement. Conventional magnetic resonance imaging (MRI shows different abnormalities, like white matter lesions that may already be present at an early stage in the disease. Aim: To present observations from a series of brain MRIs performed among a cohort of patients with FD and the relationship of imaging abnormalities with the presence of cardiovascular risk factors (CVRFs. Methods: A total of 70 patients with FD (43 women were enrolled. The cardiac, renal, ophthalmic, and peripheral nerve functioning was assessed. The MRI evaluation included assessment for evidence of ischemia, microbleeds, pulvinar sign, Arnold-Chiari type 1 malformation, and vertebrobasilar dolichoectasia (VBD. The presence or absence of CVRFs was examined for all patients. Results: Renal involvement was found in 60%, cardiac compromise in 30%, cornea verticillata in 91.4%, and acroparesthesias in 87.1% of patients. Brain MRI analysis found evidence of cerebral ischemic injury in 25.9% of men and 30.2% of women. Vertebrobasilar dolichoectasia was observed in imaging from 55.5% of men and 34.8% of women. The logistic regression analysis adjusted for cardiovascular risks factors, using ischemia or VBD as a dependent variable, showed no statistically significant results. Discussion: Our results have demonstrated cerebrovascular involvement before the third decade in many patients with FD. This study is further evidence confirming that women are not just carriers of FD and should be followed clinically and evaluated comprehensively to monitor for disease burden and progression. Although silent brain ischemias in MRI should be included as a key feature for the diagnoses of FD, VBD is an earlier and frequent sign.

  16. Doença de Fabry Fabry disease

    Directory of Open Access Journals (Sweden)

    Paula Boggio

    2009-08-01

    Full Text Available A doença de Fabry é enfermidade de armazenamento lisossômico rara, ligada ao cromossomo-X, causada pela deficiência parcial ou completa da enzima alfagalactosidase A. O defeito resulta no acúmulo de globotriaosilceramida no endotélio vascular e tecidos viscerais, sendo a pele, o coração, os rins e o sistema nervoso central os mais afetados. As autoras realizam revisão da literatura relacionada a essa afecção e ressaltam que o reconhecimento precoce dos angioqueratomas e da hipoidrose constitui sinal-chave no diagnóstico dessa doença grave. Destacam também a necessidade de esses doentes serem avaliados por equipe multidisciplinar.Fabry disease is an uncommon, X-linked lysosomal storage disorder, caused by partial or complete deficiency of the enzyme a-galactosidase A. The defect leads to accumulation of uncleaved globotriaosylceramide on the vascular endothelium and visceral tissues, being the skin, heart, kidneys and central nervous system the most affected organs. We performed review of the literature related to the disease and emphasized that early recognition of angiokeratomas and hypohidrosis are key diagnostic signs of this serious disease. We also addressed the need of multidisciplinary assessment of these patients.

  17. Cognitive and Psychological Functioning in Fabry Disease

    Science.gov (United States)

    Sigmundsdottir, Linda; Tchan, Michel C.; Knopman, Alex A.; Menzies, Graham C.; Batchelor, Jennifer; Sillence, David O.

    2014-01-01

    Fabry disease is an X-linked lysosomal storage disorder which can result in renal, cardiac, and cerebrovascular disease. Patients are at increased risk of stroke and neuroimaging studies note cerebrovascular pathology. This study provides a cognitive profile of a cohort of individuals with Fabry disease and investigates the impact of pain, age, renal, cardiac, and cerebrovascular functioning on cognition and psychological functioning. Seventeen Fabry patients (12 males) with ages ranging 25 to 60 years (M = 46.6+11.8), and 15 age-matched healthy controls (M = 46.2+12.7) were administered a comprehensive neuropsychological battery. Fabry males demonstrated slower speed of information processing, reduced performance on measures of executive functions (verbal generation, reasoning, problem solving, perseveration), were more likely to show clinically significant reductions, and were more likely to report symptoms of anxiety and depression. Conversely, Fabry females performed at a similar level to controls. Correlational analyses indicated a link between cognitive and clinical measures of disease severity. PMID:25319043

  18. Fabry Disease in Families With Hypertrophic Cardiomyopathy

    DEFF Research Database (Denmark)

    Adalsteinsdottir, Berglind; Palsson, Runolfur; Desnick, Robert J

    2017-01-01

    BACKGROUND: The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by GLA(α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B...

  19. Fabry disease, respiratory symptoms, and airway limitation

    DEFF Research Database (Denmark)

    Svensson, Camilla Kara; Feldt-Rasmussen, Ulla; Backer, Vibeke

    2015-01-01

    abnormalities in patients with Fabry disease. Electron microscopy of lung biopsy and induced sputum show lamellar inclusion bodies (Zebra bodies) in the cytoplasm of cells in the airway wall. X-ray and CT scan have shown patchy ground-glass pulmonary infiltrations, fibrosis, and air trapping. Fibrosis diagnosed...

  20. Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry

    DEFF Research Database (Denmark)

    Wilcox, W.R.; Oliveira, J.P.; Hopkin, R.J.;

    2008-01-01

    Fabry disease (FD) is an X-linked lysosomal storage disease caused by alpha-galactosidase A deficiency. The Fabry Registry is a global clinical effort to collect longitudinal data on FD. In the past, most "carrier" females were usually thought to be clinically unaffected. A systematic effort has ...

  1. Multiple parapelvic cysts in Fabry disease.

    Science.gov (United States)

    Azancot, María A; Vila, Josefa; Domínguez, Carmen; Serres, Xavier; Espinel, Eugenia

    2016-01-01

    Fabry disease is an inherited, X-linked lysosomal storage disorder caused by deficiency of the enzyme alpha galactosidase A (alpha-GLA A), which leads to glycosphingolipid accumulation, mainly globotriaosylceramide, in tissues. Disease prevalence and the index of suspicion are both low, which tends to result in delayed diagnosis and treatment. We present the case of a male Fabry disease patient who manifested no angiokeratoma lesions but presented multiple parapelvic cysts and renal failure. The genetic study revealed an alpha-GLA A gene mutation that had not been recorded in the mutations registry. The de novo mutation was not found in his relatives and it was not transmitted to his offspring. The large number and peculiar appearance of the parapelvic cysts led to the diagnosis. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  2. Presymptomatic diagnosis of Fabry's disease

    DEFF Research Database (Denmark)

    Hasselbalch, Rasmus Bo; Madsen, Per Lav; Bundgaard, Henning;

    2016-01-01

    differential diagnoses in patients presenting with cardiac hypertrophy. In boys, onset has been reported in early childhood with complaints initially comprising neuropathic pain, reduced sweat production, and gastrointestinal symptoms. Later the cardiac, renal, and central nervous systems may become affected...

  3. Cardiac device implantation in Fabry disease

    Science.gov (United States)

    Sené, Thomas; Lidove, Olivier; Sebbah, Joel; Darondel, Jean-Marc; Picard, Hervé; Aaron, Laurent; Fain, Olivier; Zenone, Thierry; Joly, Dominique; Charron, Philippe; Ziza, Jean-Marc

    2016-01-01

    Abstract The incidence and predictive factors of arrhythmias and/or conduction abnormalities (ACAs) requiring cardiac device (CD) implantation are poorly characterized in Fabry disease (FD). The aim of our retrospective study was to determine the prevalence, incidence, and factors associated with ACA requiring CD implantation in a monocentric cohort of patients with confirmed FD who were followed up in a department of internal medicine and reference center for FD. Forty-nine patients (20M, 29F) were included. Nine patients (4M, 5F; 18%) had at least one episode of ACA leading to device therapy. Six patients (4M/2F) required a pacemaker (PM) for sinus node dysfunction (n = 4) or atrioventricular disease (n = 2). One female patient required an internal cardioverter-defibrillator (ICD) to prevent sudden cardiac death because of nonsustained ventricular tachycardia (nSVT). One female patient required PM-ICD for sinus node dysfunction and nSVT. One patient underwent CD implantation before the diagnosis of FD. The annual rate of CD implantation was estimated at 1.90 per 100 person years. On univariate analysis at the end of the follow-up period, the factors associated with ACAs requiring CD implantation were as follows: delayed diagnosis of FD, delayed initiation of enzyme replacement therapy, age at the last follow-up visit, and severe multiorgan phenotype (hypertrophic cardiomyopathy, chronic kidney disease, and/or sensorineural hearing loss). On multivariate analysis, age at diagnosis of FD and age at the last follow-up visit were independently associated with an increased risk of ACAs requiring CD (P sudden death in patients with FD, regular monitoring is mandatory, especially in patients with a late diagnosis of FD and/or with a severe phenotype. Regular Holter ECGs, therapeutic education of patients, and deliverance of an emergency card including a phenotype summary are crucial in the care of FD patients. Available guidelines for device therapy and the

  4. Prognostic Indicators of Renal Disease Progression in Adults with Fabry Disease: Natural History Data from the Fabry Registry

    NARCIS (Netherlands)

    C. Wanner; J.P. Oliveira; A. Ortiz; M. Mauer; D.P. Germain; G.E. Linthorst; A.L. Serra; L. Marodi; R. Mignani; B. Cianciaruso; B. Vujkovac; R. Lemay; D. Beitner-Johnson; S. Waldek; D.G. Warnock

    2010-01-01

    Background and objectives: These analyses were designed to characterize renal disease progression in untreated adults with Fabry disease. Design, setting, participants, & measurements: Data from the Fabry Registry for 462 untreated adults (121 men and 341 women) who had at least two estimated GFR (e

  5. Fabry's disease and psychosis: causality or coincidence?

    Science.gov (United States)

    Gairing, S; Wiest, R; Metzler, S; Theodoridou, A; Hoff, P

    2011-01-01

    A 21-year-old female with Fabry's disease (FD) presented acute psychotic symptoms such as delusions, auditory hallucinations and formal thought disorders. Since the age of 14, she had suffered from various psychiatric symptoms increasing in frequency and intensity. We considered the differential diagnoses of prodromal symptoms of schizophrenia and organic schizophrenia-like disorder. Routine examinations including cognitive testing, electroencephalography and structural magnetic resonance imaging revealed no pathological findings. Additional structural and functional imaging demonstrated a minor CNS involvement of FD, yet without functional limitations. In summary our examination results support the thesis that in the case of our patient a mere coincidence of FD and psychotic symptoms is more likely than a causal connection.

  6. Involvement of dorsal root ganglia in Fabry's disease.

    Science.gov (United States)

    Gadoth, N; Sandbank, U

    1983-08-01

    Bouts of shooting pain along the extremities are common in the early stages of Fabry's disease. No pathological explanation has been advanced to clarify the mechanism of such pain. In the present case neuronal storage of glycolipid was confined to dorsal root ganglia neurones only. It is suggested that this may explain the shooting pain in Fabry's disease. In hereditary sensory radicular neuropathy, familial dysautonomia, and tabes dorsalis, changes in dorsal root ganglia cells cause similar clinical signs and thus it may be concluded that shooting pains in Fabry's disease may be caused by damage to dorsal root ganglia neurones.

  7. Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy

    Science.gov (United States)

    Fall, Brent; Scott, C. Ronald; Mauer, Michael; Shankland, Stuart; Pippin, Jeffrey; Jefferson, Jonathan A.; Wallace, Eric; Warnock, David; Najafian, Behzad

    2016-01-01

    Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other kidney cell types in Fabry patients. Podocyte injury occurs early in age, and is progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase in Fabry patients and correlate with clinical severity of Fabry nephropathy. Urine specimens from 39 Fabry patients and 24 healthy subjects were evaluated for podocyturia. Most of the Fabry patients and many healthy subjects had podocyturia. The number of podocytes per gram of urine creatinine (UPodo/g Cr) was 3.6 fold greater in Fabry patients (3,741 ± 2796; p = 0.001) than healthy subjects (1,040 ± 972). Fabry patients with normoalbuminuria and normoproteinuria had over 2-fold greater UPodo/g Cr than healthy subjects (p = 0.048). UPodo/gCr was inversely related to eGFR in male patients (r = -0.69, p = 0.003). UPodo/gCr was directly related to urine protein creatinine ratio (r = 0.33; p = 0.04) in all Fabry patients. These studies confirm increased podocyturia in Fabry disease, even when proteinuria and albuminuria are absent. Podocyturia correlates with clinical severity of Fabry nephropathy, and potentially may be of prognostic value. PMID:27992580

  8. Autonomic skin responses in females with Fabry disease

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Bach, Flemming W.; Feldt-Rasmussen, Ulla

    2009-01-01

    dysfunction. This study examined peripheral autonomic nerve function in 19 female patients with Fabry disease and 19 sex and age-matched controls by measuring (1) sweat production following acetylcholine challenge; (2) the sympathetically mediated vasoconstrictor responses to inspiratory gasp, stress......, and the cold pressor test; and (3) cutaneous blood flow following capsaicin. The vasoconstrictor response to inspiratory gasp was increased in Fabry patients compared to controls (p = 0.03), while the response to cold and mental stress did not change. Female patients with Fabry disease had a reduced sweat...

  9. Fabry disease: recent advances in pathology, diagnosis, treatment and monitoring

    Directory of Open Access Journals (Sweden)

    Hoffmann Björn

    2009-10-01

    Full Text Available Abstract Background In Fabry disease (α-galactosidase A deficiency accumulation of Globotriaosylceramide (Gb3 leads to progressive organ failure and premature death. The introduction of enzyme replacement therapy (ERT was the beginning of a new era in this disorder, and has prompted a broad range of research activities. This review aims to summarize recent developments and progress with high impact for Fabry disease. Methods A Pubmed analysis was performed using the search terms "Fabry disease", "Anderson-Fabry disease", "alpha-galactosidase A" and "Gb3". Of the given publications by 31st January 2009 only original articles recently published in peer reviewed journals were included for this review. Case reports were included only when they comprised a new aspect. In addition we included relevant conference abstracts when the results had not already been published as original articles. Results Apart from Gb3-accumulation cellular and organ specific damages may be related also to inflammatory and immunological consequences. It will be interesting whether this may lead to new therapeutic strategies in the treatment of Fabry disease. Since newborn screening is still difficult in Fabry disease, detection of patients in populations at risk is of great importance. Undiagnosed patients with Fabry disease may still be found in cohorts of subjects with renal diseases, cardiomyopathy and TIA or stroke. Efforts should be undertaken to identify these individuals and initialise ERT in order to hault disease progression. It has also been demonstrated that Gb3-accumulation leads to pre-clinical damages and it is believed that early treatment may be the only possibility so far to prevent irreversible organ damage.

  10. Arterial Wall Properties and Womersley Flow in Fabry Disease

    Directory of Open Access Journals (Sweden)

    Dimitriadis Emilios

    2002-01-01

    Full Text Available Abstract Background Fabry disease is an X-linked recessive lysosomal storage disease resulting in the cellular accumulation of globotriaosylceramide particularly globotriaosylceramide. The disease is characterized by a dilated vasculopathy with arterial ectasia in muscular arteries and arterioles. Previous venous plethysomographic studies suggest enhanced endothelium-dependent vasodilation in Fabry disease indicating a functional abnormality of resistance vessels. Methods We examined the mechanical properties of the radial artery in Fabry disease, a typical fibro-muscular artery. Eight control subjects and seven patients with Fabry disease had a right brachial arterial line placed allowing real time recording of intra-arterial blood pressure. Real time B-mode ultrasound recordings of the right radial artery were obtained simultaneously allowing calculation of the vessel wall internal and external diameter, the incremental Young's modulus and arterial wall thickness. By simultaneously measurement of the distal index finger-pulse oximetry the pulse wave speed was calculated. From the wave speed and the internal radial artery diameter the volume flow was calculated by Womersley analysis following truncation of the late diastolic phase. Results No significant difference was found between Fabry patients and controls for internal or external arterial diameters, the incremental Young's modulus, the arterial wall thickness, the pulse wave speed and the basal radial artery blood flow. Further, no significant difference was found for the radial artery blood flow in response to intra-arterial acetylcholine or sodium nitroprusside. Both drugs however, elevated the mean arterial flow. Conclusions The current study suggests that no structural or mechanical abnormality exists in the vessel wall of fibro-muscular arteries in Fabry disease. This may indicate that a functional abnormality downstream to the conductance vessels is the dominant feature in

  11. A case of minimal change disease in a Fabry patient.

    Science.gov (United States)

    Zarate, Yuri A; Patterson, Larry; Yin, Hong; Hopkin, Robert J

    2010-03-01

    Fabry disease is an X-linked lysosomal storage disorder caused by mutations of the GLA gene and deficiency in alpha-galactosidase A activity. Glycosphingolipids accumulation causes renal injury that manifests early during childhood as tubular dysfunction and later in adulthood as proteinuria and renal insufficiency. Nephrotic syndrome as the first evidence of Fabry-related kidney damage is rare. We report the case of a teenager with known Fabry disease and normal renal function who developed acute nephrotic syndrome. He was found to have typical glycosphingolipids accumulation with no other findings suggestive of alternative causes of nephrotic syndrome on kidney biopsy. After treatment with enzyme replacement therapy and oral steroids, he went into complete remission from nephrotic syndrome, a response that is atypical for Fabry disease patients who develop heavy proteinuria as a result of longstanding disease and chronic renal injury. The nephrotic syndrome in this patient appears to have developed secondary to minimal change disease. We recommend considering immunotherapy in addition to enzyme replacement therapy in those patients with confirmed Fabry disease and acute nephrotic syndrome with clinical and microscopic findings suggestive of minimal change disease.

  12. Copious Podocyturia without Proteinuria and with Normal Renal Function in a Young Adult with Fabry Disease

    Science.gov (United States)

    Trimarchi, H.; Canzonieri, R.; Muryan, A.; Schiel, A.; Forrester, M.; Karl, A.; Lombi, F.; Andrews, J.; Pomeranz, V.; Rengel, T.; Zotta, E.

    2015-01-01

    The time for starting a patient with Fabry disease on enzyme replacement therapy is still a matter of debate, particularly when no overt classical clinical signs or symptoms are present. With respect to Fabry nephropathy, a dual problem coexists: the reluctance of many nephrologists to start enzyme replacement infusion until signs of renal disease appear as the appearance of proteinuria or an elevation in serum creatinine and the lack of validated biomarkers of early renal damage. In this regard, proteinuria is nowadays considered as an early and appropriate marker of kidney disease and of cardiovascular morbidity and mortality. However, in this report we demonstrate that podocyturia antedates the classical appearance of proteinuria and could be considered as an even earlier biomarker of kidney damage. Podocyturia may be a novel indication for the initiation of therapy in Fabry disease. PMID:26064721

  13. Copious Podocyturia without Proteinuria and with Normal Renal Function in a Young Adult with Fabry Disease

    Directory of Open Access Journals (Sweden)

    H. Trimarchi

    2015-01-01

    Full Text Available The time for starting a patient with Fabry disease on enzyme replacement therapy is still a matter of debate, particularly when no overt classical clinical signs or symptoms are present. With respect to Fabry nephropathy, a dual problem coexists: the reluctance of many nephrologists to start enzyme replacement infusion until signs of renal disease appear as the appearance of proteinuria or an elevation in serum creatinine and the lack of validated biomarkers of early renal damage. In this regard, proteinuria is nowadays considered as an early and appropriate marker of kidney disease and of cardiovascular morbidity and mortality. However, in this report we demonstrate that podocyturia antedates the classical appearance of proteinuria and could be considered as an even earlier biomarker of kidney damage. Podocyturia may be a novel indication for the initiation of therapy in Fabry disease.

  14. Screening, diagnosis, and management of patients with Fabry disease

    DEFF Research Database (Denmark)

    Schiffmann, Raphael; Hughes, Derralynn A; Linthorst, Gabor E

    2017-01-01

    Patients with Fabry disease (FD) are at a high risk for developing chronic kidney disease and cardiovascular disease. The availability of specific but costly therapy has elevated the profile of this rare condition. This KDIGO conference addressed controversial areas in the diagnosis, screening, a...

  15. Fabry disease - current treatment and new drug development.

    Science.gov (United States)

    Motabar, Omid; Sidransky, Ellen; Goldin, Ehud; Zheng, Wei

    2010-07-23

    Fabry disease is a rare inherited lysosomal storage disorder caused by a partial or complete deficiency of α-galactosidase A (GLA), resulting in the storage of excess cellular glycosphingolipids. Enzyme replacement therapy is available for the treatment of Fabry disease, but it is a costly, intravenous treatment. Alternative therapeutic approaches, including small molecule chaperone therapy, are currently being explored. High throughput screening (HTS) technologies can be utilized to discover other small molecule compounds, including non-inhibitory chaperones, enzyme activators, molecules that reduce GLA substrate, and molecules that activate GLA gene promoters. This review outlines the current therapeutic approaches, emerging treatment strategies, and the process of drug discovery and development for Fabry disease.

  16. A case of Fabry's disease with congenital agammaglobulinemia.

    Science.gov (United States)

    Lee, Ki-Yeol; Jeon, Su-Young; Hong, Jin-Woo; Kim, Sung-Eun; Song, Ki-Hoon; Kim, Young-Hun; Kim, Ki-Ho

    2011-07-01

    Fabry's disease is an X-linked lysosomal storage disorder caused by abnormalities in the α-galactosidase A (GLA) gene, which leads to a GLA deficiency and to the intracellular deposition of globotriaosylceramide (Gb3) within vascular endothelium and other tissues. It manifests as progressive multiple organ dysfunctions caused by the deposition of Gb3. On the other hand, congenital agammaglobulinemia is usually caused by mutations in Bruton's tyrosine kinase (Btk) gene with X-linked dominence, suppresses B cell maturation, and causes recurrent pyogenic infections. In former reports, the distance between the loci in the Xq22 region of the human X chromosome was found to be about 69 kilobases. A 23-yr-old man diagnosed with congenital agammaglobulinemia at age 5, showed typical clinical and laboratory and histopathological findings of Fabry's disease. The genetic basis of this combination of the two syndromes was studied in this patient. Here, we report a case of Fabry's disease with congenital agammaglobulinemia.

  17. Fabry disease, a complex pathology not easy to diagnose

    Directory of Open Access Journals (Sweden)

    Paolo Colomba

    2015-12-01

    Full Text Available Fabry disease is a multisystemic lysosomal storage disorder, inherited in an X-linked manner. It is a defect of metabolism of the glycosphingolipids, due to the reduction or absence of the activity of lysosomal enzyme α-galactosidase A. This reduction of activity causes the storage of globotriaosylceramide and derivatives in the lysosomes, triggering a cascade of cellular events, mainly in vascular endothelium. These events are the responsible for the systemic clinical manifestations and the renal, cardiac and cerebrovascular complications, or a combination of them. The symptomatology can lead to the premature death of patient between the fourth or fifth decade of life. The first symptoms can occur at different ages, generally in childhood, with different severity and course. Fabry disease is suspected on the basis of clinical and anamnestic-familial data, and it is confirmed by enzymatic and genetic assays. However, Fabry disease could be a pathology more complex than previously considered, and the diagnostic tests that are currently in use could be not always sufficient to confirm the clinical diagnosis. Probably, other factors could be also involved in the onset of symptomatology. In the last years, the knowledge of the disease is considerably increased but other studies are necessary to make a prompt and reliable diagnosis. An early diagnosis of Fabry disease is essential for the beginning of the enzyme replacement therapy, which can contribute to arrest its progression and improve the quality of life of patients.

  18. Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry

    Science.gov (United States)

    Ortiz, Alberto; Abiose, Ademola; Bichet, Daniel G; Cabrera, Gustavo; Charrow, Joel; Germain, Dominique P; Hopkin, Robert J; Jovanovic, Ana; Linhart, Aleš; Maruti, Sonia S; Mauer, Michael; Oliveira, João P; Patel, Manesh R; Politei, Juan; Waldek, Stephen; Wanner, Christoph; Yoo, Han-Wook; Warnock, David G

    2016-01-01

    Background Agalsidase β is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low α-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase β cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a ‘lag time’ to clinical benefit after initiating agalsidase β treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase β. Methods The incidence of severe clinical events (renal failure, cardiac events, stroke, death) was studied in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received agalsidase β (average dose 1 mg/kg every 2 weeks) for up to 5 years. Results The incidence of all severe clinical events was 111 per 1000 person-years (95% CI 84 to 145) during the first 6 months. After 6 months, the incidence decreased and remained stable within the range of 40–58 events per 1000 patient-years. The largest decrease in incidence rates was among male patients and those aged ≥40 years when agalsidase β was initiated. Conclusions Contrary to the expected increased incidence of severe clinical events with time, adult patients with Fabry disease had decreased incidence of severe clinical events after 6 months treatment with agalsidase β 1 mg/kg every 2 weeks. Trial registration number NCT00196742. PMID:26993266

  19. Magnetic resonance spectroscopy in patients with Fabry and Gaucher disease

    Energy Technology Data Exchange (ETDEWEB)

    Gruber, S., E-mail: stephan@nmr.at [Department of Radiology, MR-Centre of Excellence, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Bogner, W. [Department of Radiology, MR-Centre of Excellence, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Stadlbauer, A. [MR Physics Group, Department of Radiology, Landesklinikum St. Poelten (Austria); Krssak, M. [Department of Radiology, MR-Centre of Excellence, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Bodamer, O. [Department of Pediatrics, Medical University of Vienna (Austria)

    2011-08-15

    Objective: Fabry and Gaucher diseases are rare progressive inherited disorders of glycosphingolipid metabolism that affect multiple organ systems. The aim of this study was to investigate evidence for metabolic changes in the central nervous system involvement using proton magnetic resonance spectroscopic imaging. Methods: Seven Fabry and eight Gaucher patients were included into this study. A two-dimensional, spectroscopic imaging method with an ultra-short echo-time of 11 ms was used at a 3 T whole body magnet. Absolute metabolic values were retrieved using internal water scaling. Results were compared, with sex- and age-matched controls. Results: In contrast to previous findings, absolute and relative metabolite values of N-acetyl-aspartate (NAA) or NAA/Creatine (Cr), Cr, Choline (Cho) or Cho/Cr and myo-Inositol (mI) or mI/Cr revealed no, differences between Fabry and Gaucher Type 1 (GD1) patients and controls. Average values were, 10.22, 6.32, 2.15 and 5.39 mMol/kg wet weight for NAA, Cr, Cho and mI, respectively. In this study, we found significantly decreasing NAA/Cho with increasing age in all three groups (Fabry, GD1, patients and healthy controls) (between 5 and 8% per decade). Conclusions: There were no changes of the quantified metabolites detected by MRS in normal appearing white matter. This study shows the importance of sex- and age-matched controls.

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

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    Kultigin Turkmen

    2016-12-01

    Full Text Available Background/Aims: Fabry disease is a treatable cause of chronic kidney disease (CKD characterized by a genetic deficiency of α-galactosidase A. European Renal Best Practice (ERBP recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. Methods: This prospective study assessed α-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. Results: Three (all males of 313 CKD patients (0.95% were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%, tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%, heat intolerance (71%, and abdominal pain (57%. The most frequent manifestations in female patients were fatigue and cornea verticillata (50%, and tinnitus, vertigo and angiokeratoma (25%. Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever. Conclusions: The prevalence of Fabry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin.

  1. Fabry disease presenting with sudden hearing loss and otosclerosis: a case report

    Directory of Open Access Journals (Sweden)

    Felisati Giovanni

    2012-04-01

    Full Text Available Abstract Introduction Fabry disease is an X-linked lysosomal storage disorder resulting in a multiple-system disorder with a wide spectrum of physical signs and symptoms, predominantly affecting the central and peripheral nervous systems, skin, heart, kidneys, and eyes. Case presentation We describe the case of a 26-year-old European Caucasian man who had Fabry disease and who presented with episodic sudden unilateral hearing loss and was treated with glucocorticoids, pentoxifylline, hyperbaric oxygen, and fluoride because of concomitant audiometric evidence of otosclerosis. This case demonstrates the partial and transient beneficial effect of standard treatment for sudden hearing loss not related to Fabry disease and analyzes the possible connection between typical Fabry disease inner-ear lesions and otosclerosis. Whereas hearing loss has been described in connection with Fabry disease, otosclerosis-associated hearing loss in Fabry disease has not yet been described. Conclusions Although progressive hearing loss in patients with Fabry disease seems to be influenced by replacement therapy, few data concerning treatment of sudden hearing loss are available. The lack of literature concerning the pathogenesis of the otological involvement in Fabry disease makes it impossible to identify a connection between the latter and otosclerosis. Therefore, this report may help to reinforce the importance of a thorough evaluation of hearing in patients with Fabry disease and may be of help with therapeutic decision-making.

  2. Avascular necrosis of bilateral femoral heads in a patient with Fabry's disease.

    LENUS (Irish Health Repository)

    O'Neill, Francis

    2012-07-13

    The underlying cause of avascular necrosis (AVN) of the femoral head is often not apparent. We report the case of a 26 year old builder with a four month history of bilateral hip pain, and a diagnosis of bilateral femoral head avascular necrosis. Fabry\\'s disease was identified as the probable cause. Since 2001, enzyme replacement therapy for Fabry\\'s disease has become available, with a potential to influence the disease process, and this is of potential importance to clinicians treating AVN.

  3. Upregulation of inward rectifying currents and Fabry disease neuropathy.

    Science.gov (United States)

    Geevasinga, Nimeshan; Tchan, Michel; Sillence, David; Vucic, Steve

    2012-12-01

    Peripheral neuropathy and neuropathic pain are common clinical manifestations of Fabry disease (FD). Although the mechanisms underlying the development of sensory neuropathy remain to be fully elucidated, a chronic ischemic process was proposed. Consequently, this study utilized axonal excitability techniques to gain further insights into the pathophysiological mechanisms underlying the development of FD neuropathy. Median motor and sensory axonal excitability studies were undertaken in 13 FD patients and results were compared to 19 healthy subjects. A "fanning-in" of threshold electrotonus, suggestive of membrane depolarization, was evident only in motor axons in FD patients. In contrast, the sensory axons exhibited a lower threshold in FD (p < 0.05) and a significantly increased hyperpolarizing current/threshold (I/V) gradient (FD 0.48 ± 0.03; controls, 0.31 ± 0.02, p < 0.001), which correlated with clinical scores of disease severity (Rho = 0.65, p < 0.05), neuropathy (Rho = 0.54, p < 0.05) and neuropathic pain (Rho = 0.56, p < 0.05). These findings indicate that upregulation of I(h) , rather than ischemia, may underlie the sensory symptoms and possibly development of neuropathy in FD. Modulation of sensory I(h) may prove therapeutically useful in Fabry disease.

  4. Analysis of Placental Tissue in Fabry Disease With and Without Enzyme Replacement Therapy

    NARCIS (Netherlands)

    M.G. Bouwman; C.E.M. Hollak; M.A. van den Bergh Weerman; F.A. Wijburg; G.E. Linthorst

    2010-01-01

    There are only a few reports on the histology of placental tissue of pregnancies from mothers with Fabry disease. Fabry disease is a lysosomal disorder caused by alpha-galactosidase A deficiency. Extensive glycosphingolipid (GSL) accumulation in fetal and maternal placenta tissue obtained from a Fab

  5. The coincidence of IgA nephropathy and Fabry disease

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    Maixnerová Dita

    2013-01-01

    Full Text Available Abstract Background IgA nephropathy (IgAN is the most common glomerulonephritis, which may also coexist with other diseases. We present two patients with an unusual coincidence of IgAN and Fabry disease (FD. Case presentation A 26 year-old man underwent a renal biopsy in February 2001. Histopathology showed very advanced IgAN and vascular changes as a result of hypertension. Because of his progressive renal insufficiency the patient began hemodialysis in August 2001. By means of the blood spot test screening method the diagnosis of FD was suspected. Low activity of alpha-galactosidase A in the patient’s plasma and leukocytes and DNA analysis confirmed the diagnosis of FD. Enzyme replacement therapy started in July 2004. Then the patient underwent kidney transplantation in November 2005. Currently, his actual serum creatinine level is 250 μmol/l. Other organ damages included hypertrophic cardiomyopathy, neuropathic pain and febrile crisis. After enzyme replacement therapy, myocardial hypertrophy has stabilized and other symptoms have disappeared. No further progression of the disease has been noted. The other patient, a 30 year-old woman, suffered from long-term hematuria with a good renal function. Recently, proteinuria (2.6 g/day appeared and a renal biopsy was performed. Histopathology showed IgAN with remarkably enlarged podocytes. A combination of IgAN and a high suspicion of FD was diagnosed. Electron microscopy revealed dense deposits in paramesangial areas typical for IgAN and podocytes with inclusive zebra bodies and myelin figures characteristic of FD. FD was confirmed by the decreased alpha-galactosidase A activity in plasma and leukocytes and by DNA and RNA analysis. Enzyme replacement therapy and family screening were initiated. Conclusions Our results emphasize the role of complexity in the process of diagnostic evaluation of kidney biopsy samples. Electron microscopy represents an integral part of histopathology, and genetic

  6. Enfermedad de Fabry: Comunicación de ocho casos Fabry disease: Report of eight cases

    Directory of Open Access Journals (Sweden)

    M Palombo

    2011-12-01

    Full Text Available La Enfermedad de Fabry (EF constituye una alteración hereditaria del metabolismo de los glicoesfingolípidos, debida a la deficiencia parcial o completa de la enzima alfa-galactosidasa A. Es una enfermedad de transmisión genética ligada a X, que afecta universalmente a todas las etnias humanas con una incidencia comunicada de 1 cada 100.000 nacimientos, aunque es probable que esta cifra subestime la real prevalencia de la enfermedad, especialmente por el gran número de casos no diagnosticados. La EF se manifiesta en su forma más florida, en varones homocigotas que carecen completamente de actividad alfa-galactosidasa A, provocando una miríada de alteraciones, incluyendo anomalías renales (proteinuria progresiva e insuficiencia renal, cardiovasculares (cardiopatías, arritmias, accidentes cerebrovasculares, neurológicas (dolor acral y abdominal, y cocleo-vestibulares, entre las más importantes. Sin embargo, la afectación cutánea constituye la alteración más específica de la enfermedad y es en general, la que conduce a la sospecha diagnóstica. La EF no tratada reduce francamente la expectativa de vida de acuerdo a la severidad de la afectación renal y cardiovascular, si bien la terapia con reemplazo enzimático puede modificar e incluso detener el curso de la enfermedad. En 2010, una paciente de 28 años oriunda de la Provincia de Santa Fe, consultó porangioqueratomas, que condujeron al diagnóstico de enfermedad de Fabry. Desde entonces hemos estudiado y tratado a toda la familia, con ocho casos confirmados a la fecha y otros tantos en evaluación.Fabry disease (Online Mendelian Inheritance in Man No. 301500 is an X-linked inherited condition due to absence or reduction of ɑ galactosidase activity in lysosomes that results in accumulation of globotriaosylceramide and related neutral glycosphingolipids (storage disorder. It is estimated to occur in 1 in 40.000 to 117.000 live male births, although a more recent screening study in

  7. [Treatment of Fabry disease: Successes, failures, and expectations].

    Science.gov (United States)

    Lidove, Olivier; Barbey, Frédéric; Joly, Dominique

    2016-04-01

    Fabry disease, an X-linked lysosomal storage disease, results from α-galactosidase A deficiency. Two different recombinant enzyme treatments (algalsidase alpha agalsidase beta) have been available since 2001 to treat a disease that affects not only men but also women. Enzyme replacement therapy promotes cell clearance of susbtrate, and improves some clinical parameters (heart, kidney damage, pain, quality of life). However, there is no proven efficacy to date on central nervous system lesions, on cardiac morbidity and mortality, nor on renal damage beyond a certain stage (proteinuria>1g/day and/or estimated glomerular filtration rate<60mL/min/1.73m(2)). In this review, we discuss the potential benefit of an early intervention, the vascular protective measures to be associated with enzyme therapy and their rationale, and some alternative treatments under development, such as chaperones and substrate molecules inhibitors.

  8. Fabry disease in genetic counseling practice: recommendations of the National Society of Genetic Counselors.

    Science.gov (United States)

    Bennett, Robin L; Hart, Kimberly A; O'Rourke, Erin; Barranger, John A; Johnson, Jack; MacDermot, Kay D; Pastores, Gregory M; Steiner, Robert D; Thadhani, Ravi

    2002-04-01

    The objective of this document is to provide health care professionals with recommendations for genetic counseling and testing of individuals with a suspected or confirmed diagnosis of Fabry disease, with a family history of Fabry disease, and those identified as female carriers of Fabry disease. These recommendations are the opinions of a multicenter working group of genetic counselors, medical geneticists, and other health professionals with expertise in Fabry disease counseling, as well as an individual with Fabry disease who is a founder of a Fabry disease patient advocacy group in the United States. The recommendations are U.S. Preventive Task Force Class III, and they are based on clinical experience, a review of pertinent English-language articles, and reports of expert committees. This document reviews the genetics of Fabry disease, the indications for genetic testing and interpretation of results, psychosocial considerations, and references for professional and patient resources. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a healthcare provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations.

  9. Screening, diagnosis, and management of patients with Fabry disease: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference.

    Science.gov (United States)

    Schiffmann, Raphael; Hughes, Derralynn A; Linthorst, Gabor E; Ortiz, Alberto; Svarstad, Einar; Warnock, David G; West, Michael L; Wanner, Christoph

    2017-02-01

    Patients with Fabry disease (FD) are at a high risk for developing chronic kidney disease and cardiovascular disease. The availability of specific but costly therapy has elevated the profile of this rare condition. This KDIGO conference addressed controversial areas in the diagnosis, screening, and management of FD, and included enzyme replacement therapy and nonspecific standard-of-care therapy for the various manifestations of FD. Despite marked advances in patient care and improved overall outlook, there is a need to better understand the pathogenesis of this glycosphingolipidosis and to determine the appropriate age to initiate therapy in all types of patients. The need to develop more effective specific therapies was also emphasized.

  10. [Atypical symptoms of Fabry's disease: sudden bilateral deafness, lymphoedema and Lown-Ganong-Levine syndrome].

    Science.gov (United States)

    Undas, Anetta; Ryś, Donata; Wegrzyn, Wojciech; Musiał, Jacek

    2002-11-01

    A 40-year-old man with Fabry disease, confirmed by decreased leukocyte alpha-galactosidase A activity in 2001, complained of sudden bilateral deafness, as evidenced by clinical history and audiometry. Magnetic resonance of the brain revealed features typical of Fabry disease. Other clinical manifestations of the disease included: angiokeratoma, mild proteinuria with normal renal function, lymphoedema of the lower limbs, pre-excitation syndrome, myocardial hypertrophy.

  11. [Fabry's disease: an example of cardiorenal syndrome type 5].

    Science.gov (United States)

    Villa, Gianluca; Romagnoli, Stefano; Sharma, Aashish; Ronco, Claudio

    2017-03-01

    Fabry's disease (FD) is a severe congenital metabolic disorder characterized by the deficient activity of lysosomal exoglycohydrolase alpha-galactosidase, characterized by glycosphingolipid deposition in several cells, such as capillary endothelial cells, renal, cardiac, and nerve cells. As a systemic disease leading to a contemporaneous myocardial and renal dysfunction, FD might be an example of cardiorenal syndrome type 5 (CRS-5). Kidney damage is commonly characterized by proteinuria, isosthenuria and altered tubular function when occurs at the second-third decade, azotemia and end-stage renal disease in third-fifth decade. Beyond the irreversible glomerular, tubular and vascular damages, the podocytes foot process effacement is the major cause of kidney dysfunction. Myocardial damage is usually observed with right and left ventricular hypertrophy, arrhythmias (due to sinus node and conduction system impairment), diastolic dysfunction, congestive heart failure, myocardial ischemia, fibrosis and cardiac death. The enzymatic replacement therapy is essential for the management of FD, as well as the control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors- and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statins to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias). Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

  12. Clinical prodromes of neurodegeneration in Anderson-Fabry disease

    Science.gov (United States)

    Hughes, Derralynn; Milligan, Alan; Richfield, Linda; Reichmann, Heinz; Mehta, Atul; Schapira, Anthony H.V.

    2015-01-01

    Objective: To estimate the prevalence of prodromal clinical features of neurodegeneration in patients with Anderson-Fabry disease (AFD) in comparison to age-matched controls. Methods: This is a single-center, prospective, cross-sectional study in 167 participants (60 heterozygous females and 50 hemizygous males with genetically confirmed AFD, 57 age-matched controls) using a clinical screening program consisting of structured interview, quantitative tests of motor function, and assessments of cognition, depression, olfaction, orthostatic intolerance, pain, REM sleep behavior disorder, and daytime sleepiness. Results: In comparison to age-matched controls (mean age 48.3 years), patients with AFD (mean age 49.0 years) showed slower gait and transfer speed, poorer fine manual dexterity, and lower hand speed, which was independent of focal symptoms due to cerebrovascular disease. Patients with AFD were more severely affected by depression, pain, and daytime sleepiness and had a lower quality of life. These motor and nonmotor manifestations significantly correlated with clinical disease severity. However, patients with AFD did not reveal extrapyramidal motor features or signs of significant cognitive impairment, hyposmia, orthostatic intolerance, or REM sleep behavior disorder, which commonly precede later neurodegenerative disease. In our cohort, there were no differences in neurologic manifestations of AFD between heterozygous females and hemizygous males. Conclusions: Aside from cerebrovascular manifestations and small fiber neuropathy, AFD results in a distinct neurologic phenotype comprising poorer motor performance and specific nonmotor features. In contrast to functional loss of glucocerebrosidase in Gaucher disease, α-galactosidase deficiency in AFD is not associated with a typical cluster of clinical features prodromal for neurodegenerative diseases, such as Parkinson disease. PMID:25762709

  13. High Variability of Fabry Disease Manifestations in an Extended Italian Family

    Directory of Open Access Journals (Sweden)

    Giuseppe Cammarata

    2015-01-01

    Full Text Available Fabry disease (FD is an inherited metabolic disorder caused by partial or full inactivation of the lysosomal hydrolase α-galactosidase A (α-GAL. The impairment of α-GAL results in the accumulation of undegraded glycosphingolipids in lysosomes and subsequent cell and microvascular dysfunctions. This study reports the clinical, biochemical, and molecular characterization of 15 members of the same family. Eight members showed the exonic mutation M51I in the GLA gene, a disease-causing mutation associated with the atypical phenotype. The clinical history of this family highlights a wide phenotypic variability, in terms of involved organs and severity. The phenotypic variability of two male patients is not related to differences in α-GAL enzymatic activity: though both have no enzymatic activity, the youngest shows severe symptoms, while the eldest is asymptomatic. It is noticeable that for two female patients with the M51I mutation the initial clinical diagnosis was different from FD. One of them was diagnosed with Familial Mediterranean Fever, the other with Multiple Sclerosis. Overall, this study confirms that the extreme variability of the clinical manifestations of FD is not entirely attributable to different mutations in the GLA gene and emphasizes the need to consider other factors or mechanisms involved in the pathogenesis of Fabry Disease.

  14. Fabry disease in Spain. Description of Spanish patients and a comparison with other European countries using data from the Fabry Outcome Survey (FOS)

    OpenAIRE

    Barba Romero, Miguel Angel; Rivera Gallego, Alberto; Pintos Morell, Guillem

    2011-01-01

    Abstract Aims: Fabry disease (FD) is an X chromosome-linked transmitted lysosomal storage disorder due to the deficient activity of enzyme ?-galactosidase A. This leads to accumulation of neutral glycosphingolipids associated with organ involvement and premature death. We report the clinical characteristics of Spanish patients enrolled on the Fabry Outcome Survey (FOS; an international multicentre registry for the disease) and also compare these data with those from the rest of Eur...

  15. Gaucher disease and Fabry disease: new markers and insights in pathophysiology for two distinct glycosphingolipidoses.

    Science.gov (United States)

    Ferraz, Maria J; Kallemeijn, Wouter W; Mirzaian, Mina; Herrera Moro, Daniela; Marques, Andre; Wisse, Patrick; Boot, Rolf G; Willems, Lianne I; Overkleeft, H S; Aerts, J M

    2014-05-01

    Gaucher disease (GD) and Fabry disease (FD) are two relatively common inherited glycosphingolipidoses caused by deficiencies in the lysosomal glycosidases glucocerebrosidase and alpha-galactosidase A, respectively. For both diseases enzyme supplementation is presently used as therapy. Cells and tissues of GD and FD patients are uniformly deficient in enzyme activity, but the two diseases markedly differ in cell types showing lysosomal accumulation of the glycosphingolipid substrates glucosylceramide and globotriaosylceramide, respectively. The clinical manifestation of Gaucher disease and Fabry disease is consequently entirely different and the response to enzyme therapy is only impressive in the case of GD patients. This review compares both glycosphingolipid storage disorders with respect to similarities and differences. Presented is an update on insights regarding pathophysiological mechanisms as well as recently available biochemical markers and diagnostic tools for both disorders. Special attention is paid to sphingoid bases of the primary storage lipids in both diseases. The value of elevated glucosylsphingosine in Gaucher disease and globotriaosylsphingosine in Fabry disease for diagnosis and monitoring of disease is discussed as well as the possible contribution of the sphingoid bases to (patho)physiology. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.

  16. Agalsidase benefits renal histology in young patients with Fabry disease.

    Science.gov (United States)

    Tøndel, Camilla; Bostad, Leif; Larsen, Kristin Kampevold; Hirth, Asle; Vikse, Bjørn Egil; Houge, Gunnar; Svarstad, Einar

    2013-01-01

    The effect of early-onset enzyme replacement therapy on renal morphologic features in Fabry disease is largely unknown. Here, we evaluated the effect of 5 years of treatment with agalsidase alfa or agalsidase beta in 12 consecutive patients age 7-33 years (median age, 16.5 years). We performed renal biopsies at baseline and after 5 years of enzyme replacement therapy; 7 patients had additional biopsies after 1 and 3 years. After a median of 65 months, biopsy findings from all patients showed total clearance of glomerular endothelial and mesangial cell inclusions, and findings from 2 patients showed complete clearance of inclusions from epithelial cells of the distal tubule. The 4 patients who received the highest dose of agalsidase exhibited substantial clearance of podocyte inclusions, and the youngest patient had nearly complete clearance of these inclusions. Linear regression analysis showed a highly significant correlation between podocyte globotriaocylceramide clearance and cumulative agalsidase dose (r=0.804; P=0.002). Microalbuminuria normalized in five patients. In summary, long-term enzyme replacement therapy in young patients can result in complete globotriaocylceramide clearance of mesangial and glomerular endothelial cells across all dosage regimens, and clearance of podocyte inclusions is dose-dependent.

  17. Measuring patient experiences in Fabry disease: validation of the Fabry-specific Pediatric Health and Pain Questionnaire (FPHPQ

    Directory of Open Access Journals (Sweden)

    Ramaswami Uma

    2012-09-01

    Full Text Available Abstract Introduction Common symptoms for children with Anderson-Fabry Disease (FD such as acroparaesthesia and gastrointestinal manifestations can only be objectively assessed in patients using a valid instrument. To date, no such instrument exists. Methods A preliminary 40-item measure of symptoms and experience with FD, the Fabry-specific Paediatric Health and Pain Questionnaire (FPHPQ was developed, but lacked a formal assessment of its measurement properties. The FPHPQ was used in the Fabry Outcome Survey (FOS, a registry for all patients with a confirmed diagnosis of FD who are receiving agalsidase alfa, or are treatment naïve and who are managed by physicians participating in FOS. After an item analysis to explore how items performed and combined into domains, a battery of psychometric analyses was performed to assess the measurement properties of this new instrument. Results Eighty-seven children (ages 4-18 years completed the questionnaire. Twenty-three items in three subscales of the questionnaire emerged: pain associated with heat or exertion, pain associated with cold, and abdominal pain and fatigue symptoms. Internal consistency reliability for all three subscales was good (Cronbach alpha ≥ 0.84. Reliability was equally high for all age groups (4-7, 8-12, and 13-18. Test-retest reliability was high for all three subscales (intraclass correlation coefficient ≥ 0.74. Construct validity was demonstrated by moderate correlation with brief pain inventory (BPI, KINDL, and EQ-5D. Known group validity showed all subscales were able to discriminate between Fabry disease severity groups as classified by above or below median of the FOS MSSI (Mainz Severity Score Index grade. The heat or exertion subscale was responsive to change in symptoms between responders and non-responders as defined by change in EQ-5D index scores between the first and second visit. Conclusions Preliminary results indicate that the measurement properties

  18. Plasma globotriaosylsphingosine: diagnostic value and relation to clinical manifestations of Fabry disease.

    Science.gov (United States)

    Rombach, S M; Dekker, N; Bouwman, M G; Linthorst, G E; Zwinderman, A H; Wijburg, F A; Kuiper, S; Vd Bergh Weerman, M A; Groener, J E M; Poorthuis, B J; Hollak, C E M; Aerts, J M F G

    2010-09-01

    Fabry disease is an X-linked lysosomal storage disorder due to deficiency of alpha-Galactosidase A, causing accumulation of globotriaosylceramide and elevated plasma globotriaosylsphingosine (lysoGb3). The diagnostic value and clinical relevance of plasma lysoGb3 concentration was investigated. All male and adult female patients with classical Fabry disease could be discerned by an elevated plasma lysoGb3. In young pre-symptomatic Fabry heterozygotes, lysoGb3 levels can be normal. Individuals carrying the R112H and P60L mutations, without classical Fabry symptoms, showed no elevated plasma lysoGb3. Multiple regression analysis showed that there is no correlation of plasma lysoGb3 concentration with total disease severity score in Fabry males. However, plasma lysoGb3 concentration did correlate with white matter lesions (odds ratio: 6.1 per 100 nM lysoGb3 increase (95% CI: 1.4-25.9, p=0.015). In females, plasma lysoGb3 concentration correlated with overall disease severity. Furthermore, plasma lysoGb3 level was related to left ventricular mass (19.5+/-5.5 g increase per 10 nM lysoGb3 increase; p=0.001). In addition, it was assessed whether lifetime exposure to lysoGb3 correlates with disease manifestations. Male Fabry patients with a high lysoGb3 exposure (>10,000 U), were moderately or severely affected, only one mildly. Female patients with a low exposure (1000 U showed disease complications. Plasma lysoGb3 is useful for the diagnosis of Fabry disease. LysoGb3 is an independent risk factor for development of cerebrovascular white matter lesions in male patients and left ventricular hypertrophy in females. Disease severity correlates with exposure to plasma lysoGb3.

  19. Neuro-Otological and Peripheral Nerve Involvement in Fabry Disease

    Science.gov (United States)

    Carmona, Sergio; Weinschelbaum, Romina; Pardal, Ana; Marchesoni, Cintia; Zuberbuhler, Paz; Acosta, Patricia; Cáceres, Guillermo; Kisinovsky, Isaac; Bayón, Luciana; Reisin, Ricardo

    2017-01-01

    Fabry disease (FD) is an X-linked lysosomal storage disease, with multisystemic glycosphingolipids deposits. Neuro-otological involvement leading to hearing loss and vestibular dysfunctions has been described, but there is limited information about the frequency, site of lesion, or the relationship with peripheral neuropathy. The aim was to evaluate the presence of auditory and vestibular symptoms, and assess neurophysiological involvement of the VIII cranial nerve, correlating these findings with clinical and neurophysiological features of peripheral neuropathy. We studied 36 patients with FD with a complete neurological and neuro-otological evaluation including nerve conduction studies, quantitative sensory testing (to evaluate small fiber by warm and cold threshold detection and cold and heat pain), vestibular evoked myogenic potentials, videonistagmography, audiometry and brainstem auditory evoked potentials. Neuro-otologic symptoms included hearing loss (22.2%), vertigo (27.8%) or both (25%). An involvement of either cochlear or vestibular function was identified in most patients (75%). In 70% of our patients the involvement of both cochlear and vestibular function could not be explained by a neural or vascular mechanism. Small fiber neuropathy was identified in 77.7%. There were no significant associations between neuro-otological and QST abnormalities. Neuro-otologic involvement is frequent and most likely under-recognized in patients with FD. It lacks a specific neural or vascular pattern, suggesting multi-systemic, end organ damage. Small fiber neuropathy is an earlier manifestation of FD, but there is no correlation between the development of neuropathy and neuro-otological abnormalities. PMID:28794847

  20. Positron Emission Tomography and Magnetic Resonance Imaging of the Brain in Fabry Disease

    DEFF Research Database (Denmark)

    Korsholm, Kirsten; Feldt-Rasmussen, Ulla; Granqvist, Henrik;

    2015-01-01

    risk of cerebrovascular disease at a young age in addition to heart and kidney failure. OBJECTIVE: The objective of this study was to assess brain function and structure in the Danish cohort of patients with Fabry disease in a prospective way using 18-fluoro-deoxyglucose (F-18 FDG) positron emission....... CONCLUSION: Our data indicated that, in patients with Fabry disease, MRI is the preferable clinical modality--if applicable--when monitoring cerebral status, as no additional major brain-pathology was detected with FDG-PET.......BACKGROUND: Fabry disease is a rare metabolic glycosphingolipid storage disease caused by deficiency of the lysosomal enzyme α-galactosidase A--leading to cellular accumulation of globotriasylceramide in different organs, vessels, tissues, and nerves. The disease is associated with an increased...

  1. Fabry Disease: A Turkish Case with a Novel Mutation and Dermatological Manifestations

    Directory of Open Access Journals (Sweden)

    Neslihan Onenli Mungan

    2015-03-01

    Full Text Available Fabry disease is a rare, X-linked disease, caused by the deficiency of lysosomal and #945;-galactosidase. Clinical fetaures are; acroparesthesia, unexplained fever, hypohidrosis and angiokeratomas. Untreated cases die early from cardiac complications, renal insuffiency or stroke. Currently there is no cure for Fabry disease, enzyme replacement therapy is the only choice in this progressive disease. A 9-year-old boy admitted to the Dermatology Clinic with reddish papular skin lesions, joint pain and anhydrosis. Hystological examination of the skin biopsy revealed angiokeratoma. There was no renal dysfunction or proteinuria. Biochemical confirmation of Fabry disease was made by determining the deficient leukocyte and #945;-galactosidase activity. Subsequently, the patient's molecular analysis was identified a novel nonsense mutation c. 785G>T in the GLA gene. Enzyme replacement therapy with agalsidase beta was started. He is on enzyme replacement therapy for 8 years, significant improvement was obtained in severity and frequency of pain crisis and fatigue. We report this case to emphasize the importance of early diagnosis of Fabry disease restricted to dermatological findings, especially before renal and cardiac involvement occurs, while enzyme replacement therapy is now available. Also this patient is one of the first Fabry patients under enzyme replacement therapy in Turkey. [Cukurova Med J 2015; 40(Suppl 1: 156-160

  2. Fabry disease mimicking hypertrophic cardiomyopathy: genetic screening needed for establishing the diagnosis in women

    DEFF Research Database (Denmark)

    Havndrup, Ole; Christiansen, Michael; Stoevring, Birgitte

    2010-01-01

    AIMS: Fabry disease, an X-linked storage disorder caused by defective lysosomal enzyme alpha-galactosidase A activity, may resemble sarcomere-gene-associated hypertrophic cardiomyopathy (HCM). The 'cardiac variant' of Fabry disease which only affects the heart may be missed unless specifically...... tested for. METHODS AND RESULTS: We evaluated 90 consecutively recruited HCM probands and their relatives. Probands without sarcomere-gene mutations were tested for alpha-galactosidase A gene (GLA) mutations. Of the 90 families, 31 (34%) had sarcomere gene mutations and were therefore excluded...... without sarcomere gene mutations. GLA mutations were found in 3/90 (3%) of HCM families and in 2/20 (10%) of females without sarcomere-gene mutations. None of the probands presented other indices of Fabry disease. This, in combination with putative reversibility of cardiac changes by enzyme replacement...

  3. Receptor-mediated endocytosis of α-galactosidase A in human podocytes in Fabry disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Nielsen, Rikke; Larsen, Jakob Vejby;

    2011-01-01

    Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocy...

  4. Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Nielsen, Rikke; Larsen, Jakob Vejby;

    2011-01-01

    Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocy...

  5. [Fabry disease: clinic and enzymatic diagnosis of homozygous and heterozygous. New therapeutic prospects].

    Science.gov (United States)

    Peces, R; Olea, T

    2002-01-01

    Fabry disease is an X-linked recessive lysosomal storage disorder caused by a partial or complete deficiency of alpha-galactosidase A. Intracellular accumulation of globotriaosylceramide, the glycolipid substrate of this enzyme, leads to severe painful neuropathy with progressive renal, cardiovascular, and cerebrovascular dysfunction and early death. Men are predominantly affected but many female carriers have similar clinical involvement, including increased risk of stroke. Physical stigmata, such as angiokeratomas in skin and mucous membranes and characteristic benign corneal abnormalities, facilitate identification of Fabry disease. The finding of a marked decreased activity of (alpha-galactosidase A in plasma, white blood cells or cultured skin fibroblasts confirms the diagnosis. Treatment thus far has been symptomatic only. Etiology-based therapies are being developed that include enzyme replacement therapy, gene therapy, and substrate deprivation. The recently completed double-blind, placebo-controlled trials of intravenous infusions of (alpha-galactosidase A in patients with Fabry disease demonstrated the safety and efficacy of this treatment. We report a family with Fabry disease composed of hemicygous and heterocygous. The propositus developed chronic renal failure and received a cadaver renal transplant, which remained with adequate renal function during 15 years.

  6. Substrate reduction augments the efficacy of enzyme therapy in a mouse model of Fabry disease.

    Directory of Open Access Journals (Sweden)

    John Marshall

    Full Text Available Fabry disease is an X-linked glycosphingolipid storage disorder caused by a deficiency in the activity of the lysosomal hydrolase α-galactosidase A (α-gal. This deficiency results in accumulation of the glycosphingolipid globotriaosylceramide (GL-3 in lysosomes. Endothelial cell storage of GL-3 frequently leads to kidney dysfunction, cardiac and cerebrovascular disease. The current treatment for Fabry disease is through infusions of recombinant α-gal (enzyme-replacement therapy; ERT. Although ERT can markedly reduce the lysosomal burden of GL-3 in endothelial cells, variability is seen in the clearance from several other cell types. This suggests that alternative and adjuvant therapies may be desirable. Use of glucosylceramide synthase inhibitors to abate the biosynthesis of glycosphingolipids (substrate reduction therapy, SRT has been shown to be effective at reducing substrate levels in the related glycosphingolipidosis, Gaucher disease. Here, we show that such an inhibitor (eliglustat tartrate, Genz-112638 was effective at lowering GL-3 accumulation in a mouse model of Fabry disease. Relative efficacy of SRT and ERT at reducing GL-3 levels in Fabry mouse tissues differed with SRT being more effective in the kidney, and ERT more efficacious in the heart and liver. Combination therapy with ERT and SRT provided the most complete clearance of GL-3 from all the tissues. Furthermore, treatment normalized urine volume and uromodulin levels and significantly delayed the loss of a nociceptive response. The differential efficacies of SRT and ERT in the different tissues indicate that the combination approach is both additive and complementary suggesting the possibility of an improved therapeutic paradigm in the management of Fabry disease.

  7. Functional and structural nerve fiber findings in heterozygote patients with Fabry disease

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Bach, Flemming Winther; Feldt-Rasmussen, Ulla;

    2009-01-01

    recently disease manifestations in female carriers of Fabry disease have been questioned. To explore the frequency of symptoms and the functional and structural involvement of the nervous system in female patients we examined the presence of pain, manifestations of peripheral neuropathy and nerve density...... in skin biopsies in 19 female patients with Fabry disease and 19 sex- and age-matched controls. Diaries, quantitative sensory testing, neurophysiologic tests and skin biopsies were performed. Daily pain was present in 63% of patients, with a median VAS score of 4.0. Tactile detection threshold...... and pressure pain threshold were lower and cold detection thresholds increased in patients. Sensory nerve action potential amplitude and maximal sensory conduction velocity were not different, whereas there was a highly significant reduction in intraepidermal nerve fiber density. We found no correlation...

  8. Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

    Energy Technology Data Exchange (ETDEWEB)

    Baptista, Ana, E-mail: baptista-ana@hotmail.com; Magalhães, Pedro; Leão, Sílvia; Carvalho, Sofia; Mateus, Pedro; Moreira, Ilídio [Centro Hospitalar de Trás-os-Montes e Alto Douro, Unidade de Vila Real (Portugal)

    2015-08-15

    Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m{sup 2} for women or ≥ 116 g/m{sup 2} for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. A total of 47 patients with a mean left ventricular mass index of 141.1 g/m{sup 2} (± 28.5; 99.2 to 228.5 g/m{sup 2}] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5)

  9. Altered dynamics of a lipid raft associated protein in a kidney model of Fabry disease.

    Science.gov (United States)

    Labilloy, Anatália; Youker, Robert T; Bruns, Jennifer R; Kukic, Ira; Kiselyov, Kirill; Halfter, Willi; Finegold, David; do Monte, Semiramis Jamil Hadad; Weisz, Ora A

    2014-02-01

    Accumulation of globotriaosylceramide (Gb3) and other neutral glycosphingolipids with galactosyl residues is the hallmark of Fabry disease, a lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A (α-gal A). These lipids are incorporated into the plasma membrane and intracellular membranes, with a preference for lipid rafts. Disruption of raft mediated cell processes is implicated in the pathogenesis of several human diseases, but little is known about the effects of the accumulation of glycosphingolipids on raft dynamics in the context of Fabry disease. Using siRNA technology, we have generated a polarized renal epithelial cell model of Fabry disease in Madin-Darby canine kidney cells. These cells present increased levels of Gb3 and enlarged lysosomes, and progressively accumulate zebra bodies. The polarized delivery of both raft-associated and raft-independent proteins was unaffected by α-gal A knockdown, suggesting that accumulation of Gb3 does not disrupt biosynthetic trafficking pathways. To assess the effect of α-gal A silencing on lipid raft dynamics, we employed number and brightness (N&B) analysis to measure the oligomeric status and mobility of the model glycosylphosphatidylinositol (GPI)-anchored protein GFP-GPI. We observed a significant increase in the oligomeric size of antibody-induced clusters of GFP-GPI at the plasma membrane of α-gal A silenced cells compared with control cells. Our results suggest that the interaction of GFP-GPI with lipid rafts may be altered in the presence of accumulated Gb3. The implications of our results with respect to the pathogenesis of Fabry disease are discussed.

  10. Renal histology before and after effective enzyme replacement therapy in a patient with classical Fabry's disease.

    Science.gov (United States)

    Hirashio, S; Taguchi, T; Naito, T; Maki, K; Ogata, S; Taniyama, K; Taniguchi, Y; Yorioka, N

    2009-05-01

    A 38-year-old man underwent renal biopsy because of proteinuria. It revealed swelling and vacuolation of glomerular epithelial cells, as well as myelin-like structures characteristic of Fabry's disease. Detection of decreased plasma activity of alpha-galactosidase A confirmed the diagnosis. Enzyme replacement therapy was provided with recombinant agalsidase-beta, resulting in improvement of his symptoms. When renal biopsy was repeated, specific staining for globotriaosylceramide showed that renal deposits were decreased by enzyme therapy.

  11. Anderson-Fabry, the histrionic disease: from genetics to clinical management

    Directory of Open Access Journals (Sweden)

    Franco Cecchi

    2013-02-01

    Full Text Available Anderson-Fabry disease (AFD is an Xlinked lysosomal storage disorder of glycosphingolipid catabolism, due to deficiency or absence of a galactosidase A (α-gal A enzyme. The disease may affect males and females, the latter with an average 10 years delay. Metabolites storage (mostly Gb3 and lyso-Gb3 leads to progressive cellular and multiorgan dysfunction, with either early and late onset variable clinical manifestations that usually reduce quality of life and life expectancy. Heart and kidney failure, stroke and sudden death are the most devastating complications. AFD is always been considered a very rare disease, although new epidemiologic data, based on newborn screening, showed that AFD prevalence is probably underestimated and much higher than previously reported, especially for late-onset atypical phenotypes. Currently, the diagnosis may be easier and simpler by evaluating α-gal A enzyme activity and genetic analysis for GLA gene mutations on dried blood spot. While a marked α-gal A deficiency leads to diagnosis of AFD in hemizygous males, the molecular analysis is mandatory in heterozygous females. However, referral to a center with an expert multidisciplinary team is highly advisable, in order to ensure careful management and treatment of patients, based also on accurate molecular and biochemical data interpretation. While long-term efficacy of enzyme replacement therapy (ERT in advanced stage is still debated, increasing evidence shows greater efficacy of early treatment initiation. Concomitant, organ-specific therapy is also needed. New treatment approaches, such as chemical chaperone therapy, alone or in combination with ERT, are currently under investigation. The present review illustrates the major features of the disease, focusing also on biochemical and genetic aspects.

  12. Home infusion program for Fabry disease: experience with agalsidase alfa in Argentina

    Directory of Open Access Journals (Sweden)

    Isaac Kisinovsky

    2013-02-01

    Full Text Available Fabry disease is an X-linked lysosomal storage disorder caused by inherited deficiency of the enzyme α-galactosidase A. Enzyme replacement treatment using agalsidase alfa significantly reduces pain, improves cardiac function and quality of life, and slows renal deterioration. Nevertheless, it is a life-long treatment which requires regular intravenous infusions and entails a great burden for patients. Our objective was to evaluate retrospectively the safety and tolerability of the home infusion of agalsidase alfa in patients with Fabry disease in Argentina. We evaluated all the patients with Fabry disease who received home infusion with agalsidase alfa 0.2 mg/kg between January 2005 and June 2011. The program included 87 patients; 51 males (mean age: 30 years and 36 females (mean age: 34 years. A total of 5229 infusions (mean: 59 per patient; range: 1-150 were administered. A total of 5 adverse reactions were seen in 5 patients (5.7% of patients and 0.9% of the total number of infusions. All were mild in severity and resolved by reducing the rate of infusion and by using antihistaminics. All these 5 patients were positive for IgG antibodies, but none of them presented IgE antibodies and none suffered an anaphylactic shock. In our group 18 patients were switched from agalsidase beta to agalsidase alfa without complications. Home infusion with agalsidase alfa is safe, well tolerated and is associated to high compliance.

  13. Fabry disease : Baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry

    NARCIS (Netherlands)

    Eng, C. M.; Fletcher, J.; Wilcox, W. R.; Waldek, S.; Scott, C. R.; Sillence, D. O.; Breunig, F.; Charrow, J.; Germain, D. P.; Nicholls, K.; Banikazemi, M.

    2007-01-01

    The Fabry Registry is a global observational research platform established to define outcome data on the natural and treated course of this rare disorder. Participating physicians submit structured longitudinal data to a centralized, confidential database. This report describes the baseline demograp

  14. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease

    DEFF Research Database (Denmark)

    Hughes, Derralynn A; Nicholls, Kathleen; Shankar, Suma P

    2017-01-01

    therapy (ERT), stabilises specific mutant (amenable) forms of α-Gal to facilitate normal lysosomal trafficking. METHODS: The main objective of the 18-month, randomised, active-controlled ATTRACT study was to assess the effects of migalastat on renal function in patients with Fabry disease previously...... ventricular mass index decreased significantly with migalastat treatment (-6.6 g/m(2) (-11.0 to -2.2)); there was no significant change with ERT. Predefined renal, cardiac or cerebrovascular events occurred in 29% and 44% of patients in the migalastat and ERT groups, respectively. Plasma...... globotriaosylsphingosine remained low and stable following the switch from ERT to migalastat. PROs were comparable between groups. Migalastat was generally safe and well tolerated. CONCLUSIONS: Migalastat offers promise as a first-in-class oral monotherapy alternative treatment to intravenous ERT for patients with Fabry...

  15. COMPUTER ASSISTED RETINAL VESSEL TORTUOSITY EVALUATION IN NOVEL MUTATION FABRY DISEASE: Towards New Prognostic Markers.

    Science.gov (United States)

    San Román, Irene; Rodríguez, María-Elena; Caporossi, Orsola; Zoppetti, Claudia; Sodi, Andrea; Mecocci, Alessandro; López, David; Rodríguez, Beatriz; Gimeno, Juan-Ramón

    2017-03-01

    Fabry disease is a rare lysosomal storage disorder with systemic involvement. The authors report on a large Fabry family with GLA p.M187R mutation and exhaustive ophthalmologic assessment. Comprehensive systemic evaluation and genetic diagnosis were performed. Ophthalmologic evaluation included intraocular pressure/visual acuity measurement, refractometry, slit lamp examination, retinography, and optical coherence tomography. Three parameters quantified retinal vessel tortuosity: sum of angle metrics, product of angle distance, and triangular index. Calculations were semiautomatized using dedicated software. Ten individuals (2 males and 8 females) were described. Seventy-five percent had retinal vessel tortuosity. One hundred percent had cornea verticillata. Perimacular vessels were predominantly involved. The correlation between the right and left eye tortuosity measurements was very tight. A significant correlation between retinal vessel tortuosity and systemic severity measured by general Mainz Severity Score Index (MSSI), renal MSSI, and neurological MSSI but no cardiac MSSI was observed. Right sum of angle metrics value was an independent statistical predictor of the general-MSSI score in presence of age. p.M187R mutation causes a severe systemic and ophthalmologic phenotype, in both male and female patients. Semiautomatic assessment of retinal vessel tortuosity is an objective and reproducible tool. All three parameters of tortuosity are closely associated with Fabry severity scores. Studies of larger series are being awaited to establish the role of retinal vessel tortuosity as a noninvasive marker of disease progression.

  16. Skin-impedance in Fabry Disease: A prospective, controlled, non-randomized clinical study

    Directory of Open Access Journals (Sweden)

    Lidicker Jeffrey R

    2008-11-01

    Full Text Available Abstract Background We previously demonstrated improved sweating after enzyme replacement therapy (ERT in Fabry disease using the thermo-regularity sweat and quantitative sudomotor axon reflex tests. Skin-impedance, a measure skin-moisture (sweating, has been used in the clinical evaluation of burns and pressure ulcers using the portable dynamic dermal impedance monitor (DDIM system. Methods We compared skin impedance measurements in hemizygous patients with Fabry disease (22 post 3-years of bi-weekly ERT and 5 ERT naive and 22 healthy controls. Force compensated skin-moisture values were used for statistical analysis. Outcome measures included 1 moisture reading of the 100th repetitive reading, 2 rate of change, 3 average of 60–110th reading and 4 overall average of all readings. Results All outcome measures showed a significant difference in skin-moisture between Fabry patients and control subjects (p Conclusion The instrument portability, ease of its use, a relatively short time required for the assessment, and the fact that DDIM system was able to detect the difference in skin-moisture renders the instrument a useful clinical tool.

  17. Evaluación de pacientes con enfermedad de Fabry en la Argentina Evaluation of patients with Fabry disease in Argentina

    Directory of Open Access Journals (Sweden)

    2010-02-01

    Full Text Available La enfermedad de Fabry es un desorden lisosomal de transmisión ligada al cromosoma X debida al déficit de la enzima alfa galactosidasa A, con acumulación multisistémica de globotriaosilceramida y compromiso neurológico, gastrointestinal, cardíaco, renal, dermatológico y oftalmológico. Estudios recientes indican que las mujeres heterocigotas desarrollan síntomas similares a los de los varones, pero no existen en nuestro país datos comparativos respecto de la frecuencia relativa de manifestaciones clínicas, edad de inicio y gravedad entre hombres y mujeres con enfermedad de Fabry. Identificamos 59 pacientes adultos sintomáticos con enfermedad de Fabry: 32 varones (edad media: 34.8 años y 27 mujeres (edad media: 46.6 años. El diagnóstico se hizo por estudios enzimáticos en los hombres y genéticos en las mujeres. Se evaluó la frecuencia y la gravedad de las manifestaciones de la enfermedad. Las manifestaciones más frecuentes fueron acroparestesias, angioqueratomas, hipohidrosis y córnea verticilada; las tres primeras fueron estadísticamente más frecuentes en hombres, en los cuales la gravedad de estos síntomas fue significativamente mayor. Proteinuria e hipertrofia ventricular izquierda fueron hallazgos frecuentes tanto en hombres como en mujeres. Hubo una latencia prolongada entre la edad del inicio y la del diagnóstico de 14 años para varones y 30 para mujeres. La enfermedad de Fabry es una enfermedad subdiagnosticada y potencialmente letal que afecta a ambos sexos. La existencia de reemplazo enzimático obliga a identificar precozmente los síntomas y signos sugestivos de la enfermedad para realizar un diagnóstico y tratamiento precoces.Fabry disease is an X- linked lysosomal disorder due to deficient activity of the enzyme alpha galactosidase A which leads to multisystemic storage of globotriaosylceramide with neurologic, gastrointestinal, cardiac, renal, skin and ophtalmological involvement. Recent studies indicate

  18. Morphological features of iPS cells generated from Fabry disease skin fibroblasts using Sendai virus vector (SeVdp).

    Science.gov (United States)

    Kawagoe, Shiho; Higuchi, Takashi; Otaka, Manami; Shimada, Yohta; Kobayashi, Hiroshi; Ida, Hiroyuki; Ohashi, Toya; Okano, Hirotaka J; Nakanishi, Mahito; Eto, Yoshikatsu

    2013-08-01

    We generated iPS cells from human dermal fibroblasts (HDFs) of Fabry disease using a Sendai virus (SeVdp) vector; this method has been established by Nakanishi et al. for pathogenic evaluation. We received SeVdp vector from Nakanishi and loaded it simultaneously with four reprogramming factors (Klf4, Oct4, Sox2, and c-Myc) to HDFs of Fabry disease; subsequently, we observed the presence of human iPS-like cells. The Sendai virus nucleocapsid protein was not detected in the fibroblasts by RT-PCR analysis. Additionally, we confirmed an undifferentiated state, alkaline phosphatase staining, and the presence of SSEA-4, TRA-1-60, and TRA-1-81. Moreover, ultrastructural features of these iPS cells included massive membranous cytoplasmic bodies typical of HDFs of Fabry disease. Thus, we successfully generated human iPS cells from HDFs of Fabry disease that retained the genetic conditions of Fabry disease; also, these abnormal iPS cells could not be easily differentiated into mature cell types such as neuronal cells, cardiomyocytes, etc. because of a massive accumulation of membranous cytoplasmic bodies in lysosomes, possibly the persistent damages of intracellular architecture.

  19. Uric Acid as a Marker of Mortality and Morbidity in Fabry Disease.

    Science.gov (United States)

    Rob, Daniel; Marek, Josef; Dostálová, Gabriela; Goláň, Lubor; Linhart, Aleš

    2016-01-01

    Serum uric acid (UA) elevation is common in patients with cardiovascular, renal and metabolic diseases. However, no study to date has analysed the role of UA in Fabry disease (FD). To evaluate the association between serum UA levels and mortality and morbidity in FD. We conducted a post-hoc analysis of a prospectively followed-up cohort of 124 patients with genetically proven FD. Serum UA levels were acquired at baseline; clinical events and mortality were assessed during regular visits every 6 to 12 months. The primary endpoint was a composite of multiple secondary outcomes: all-cause mortality, adverse cardiovascular events, progression of renal dysfunction and stroke or transient ischaemic attack (TIA). Predictive value was assessed using the Cox proportional hazards model and the Kaplan Meyer estimator. During follow-up of 7.4 ± 3.7 years, 64 (52%) patients reached the primary combined endpoint. Overall, UA levels were significantly associated with combined outcome (p < 0.001) and remained independently associated after correcting for age, sex and estimated glomerular filtration rate (hazard ratio [HR] per 20 μmol/l increase 1.09, 95% confidence interval [95%CI] (1.00-1.19), p = 0.04). UA was associated with overall mortality in univariate analysis (p = 0.021); however, the association did not reach statistical significance after multivariate correction (HR per 20 μmol/l increase 1.07 95%CI 0.93-1.25, p = 0.32). Higher UA levels were also associated with cardiac adverse outcomes, progression of left ventricular hypertrophy and progression of renal dysfunction (ps < 0.001). No association was observed between UA levels and stroke or TIA (p = 0.323). Increased serum UA levels may represent an independent risk factor for adverse clinical outcomes in Fabry patients and are associated with all-cause mortality. UA is a widely available and cheap biomarker that may improve risk stratification of Fabry patients in clinical practice.

  20. The right ventricle in Fabry disease: natural history and impact of enzyme replacement therapy.

    Science.gov (United States)

    Niemann, Markus; Breunig, Frank; Beer, Meinrad; Herrmann, Sebastian; Strotmann, Jörg; Hu, Kai; Emmert, Andrea; Voelker, Wolfram; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

    2010-12-01

    Storage of globotriaosylceramides is present in the left and right ventricles of patients with Fabry disease. Improvement of left ventricular morphology and function during enzyme replacement therapy (ERT) has previously been reported. To analyse the effects of long term ERT on right ventricular morphology and function. This was a prospective follow-up of 75 genetically confirmed consecutive Fabry patients for 3.1±1.8 years. According to treatment guidelines the natural history was followed in 18 patients, whereas 57 patients received ERT. Standard echocardiography, strain rate imaging for regional deformation of the right and left ventricle, and magnetic resonance tomography with late enhancement (LE) imaging for the detection of fibrosis were all performed at yearly intervals. Right ventricular hypertrophy was evident in 53 patients (71%) at baseline. A significant positive correlation was found between left and right ventricular wall thickness (r=0.76; pright ventricle. Patients with LE in the left ventricle presented with the lowest right ventricular deformation properties. In contrast to the left ventricle, there was no change in right ventricular wall thickness (baseline 6.9±1.6 mm vs follow-up 6.7±1.5 mm; p=0.44) or systolic strain rate (2.2±0.7/s vs 2.1±0.8/s; p=0.31) during follow-up with ERT. The degree of right ventricular involvement in Fabry disease is related to the left ventricular cardiomyopathy stage. ERT seems to have no direct impact on right ventricular morphology and function.

  1. Therapy of Fabry disease with pharmacological chaperones: from in silico predictions to in vitro tests

    Directory of Open Access Journals (Sweden)

    Cammisa Marco

    2011-10-01

    Full Text Available Abstract Background Fabry disease is a rare disorder caused by a large variety of mutations in the gene encoding lysosomal alpha-galactosidase. Many of these mutations are unique to individual families. Fabry disease can be treated with enzyme replacement therapy, but a promising novel strategy relies on small molecules, so called "pharmacological chaperones", which can be administered orally. Unfortunately only 42% of genotypes respond to pharmacological chaperones. Results A procedure to predict which genotypes responsive to pharmacological chaperones in Fabry disease has been recently proposed. The method uses a position-specific substitution matrix to score the mutations. Using this method, we have screened public databases for predictable responsive cases and selected nine representative mutations as yet untested with pharmacological chaperones. Mutant lysosomal alpha galactosidases were produced by site directed mutagenesis and expressed in mammalian cells. Seven out of nine mutations responded to pharmacological chaperones. Nineteen other mutations that were tested with pharmacological chaperones, but were not included in the training of the predictive method, were gathered from literature and analyzed in silico. In this set all five mutations predicted to be positive were responsive to pharmacological chaperones, bringing the percentage of responsive mutations among those predicted to be positive and not used to train the classifier to 86% (12/14. This figure differs significantly from the percentage of responsive cases observed among all the Fabry mutants tested so far. Conclusions In this paper we provide experimental support to an "in silico" method designed to predict missense mutations in the gene encoding lysosomal alpha galactosidase responsive to pharmacological chaperones. We demonstrated that responsive mutations can be predicted with a low percentage of false positive cases. Most of the mutations tested to validate the method

  2. Long Term Treatment with Enzyme Replacement Therapy in Patients with Fabry Disease.

    Science.gov (United States)

    Oder, Daniel; Nordbeck, Peter; Wanner, Christoph

    2016-01-01

    Anderson-Fabry disease is a potentially life-threatening hereditary lysosomal storage disorder taking origin in over 1,000 known pathogenic mutations in the alpha-galactosidase A encoding gene. Over the past 15 years, intravenous replacement therapy of the deficient alpha agalsidase A enzyme has been well-established retarding the progression of a multisystemic disease and organ involvement. Despite this innovative treatment approach, premature deaths still do occur. The response to enzyme replacement therapy (ERT) varies considerably and appears to depend on gender, genotype (classic or later onset/non-classic), stage of disease or age and agalsidase inhibition by anti-agalsidase antibodies. Early ERT treatment at young age, a personalized approach, and adjunctive therapies for specific disease manifestations appear to impact on prognosis and are currently favored with the expectance of more effective intravenous and oral treatments in the short future.

  3. Accidente cerebro-vascular en la enfermedad de Fabry: Algo más que una simple estenosis Stroke in Fabry disease: More than a simple stenosis

    Directory of Open Access Journals (Sweden)

    Juan Manuel Politei

    2006-10-01

    Full Text Available Se analiza la evidencia existente a la fecha sobre los mecanismos fisiopatológicos que pueden generar accidentes cerebrovasculares en la enfermedad de Fabry. Esta entidad es el resultado de la deficiencia de a-galactosidasa A, lo que resulta en depósito patológico de glicoesfingilípidos en distintas poblaciones celulares. Asociados a la insuficiencia renal y cardíaca, los accidentes cerebrovasculares pueden derivar en la muerte de los pacientes. Durante mucho tiempo el único mecanismo generador de daño vascular informado fue la oclusión vascular por depósito lipídico a nivel endotelial. En la actualidad se describen otros mecanismos. El advenimiento de la terapia de reemplazo enzimático ha generado gran expectativa en cuanto la posibilidad de reversión de estos mecanismos. Si bien la evidencia es escasa y son necesarios más estudios a largo plazo, algunos informes demuestran que luego de meses, el tratamiento ha logrado revertir algunos de los mecanismos implicados.The objective is to analyze the updated evidence on the physiopathological mechanisms that can generate cerebrovascular damage in Fabry disease. Fabry disease is the result of the deficiency of a-galactosidasa A, which causes pathological storage of glycosphingolipids, in different cells. Associated to renal and cardiac insufficiency, cerebrovascular complications can derive in the death of the patients. During a long time the only reported mechanism was the vascular occlusion by deposit of lipids at endothelial level. At the present time, other mechanisms are postulated. The arrival of enzyme replacement therapy has generated great expectation on the possibility of reversion of these alterations. Although the evidence is scarce and more long term studies are necessary, some reports demonstrate that after months, the treatment has managed to revert some of the mechanisms involved.

  4. Expert opinion on temporary treatment recommendations for Fabry disease during the shortage of enzyme replacement therapy (ERT)

    NARCIS (Netherlands)

    G.E. Linthorst; D.P. Germain; C.E.M. Hollak; D. Hughes; A. Rolfs; C. Wanner; A. Mehta

    2011-01-01

    The shortage of enzyme for treatment of Fabry disease has caused anxiety among patients, physicians and governments. Following a request from the European Medicines Agency, consensus was reached on the temporary prioritization of patients for treatment based on disease severity and potential reversi

  5. Social-adaptive and psychological functioning of patients affected by Fabry disease.

    Science.gov (United States)

    Laney, Dawn Alyssia; Gruskin, Daniel J; Fernhoff, Paul M; Cubells, Joseph F; Ousley, Opal Y; Hipp, Heather; Mehta, Ami J

    2010-12-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of alpha-galactosidase A. In addition to the debilitating physical symptoms of FD, there are also under-recognized and poorly characterized psychiatric features. As a first step toward characterizing psychiatric features of FD, we administered the Achenbach adult self report questionnaire to 30 FD patients and the Achenbach adult behavior checklist questionnaire to 28 partners/parents/friends of FD patients. Data from at least one of the questionnaires were available on 33 subjects. Analysis focused on social-adaptive functioning in various aspects of daily life and on criteria related to the Diagnostic and statistical manual of mental disorders IV (DSM-IV). Adaptive functioning scale values, which primarily measure social and relationship functioning and occupational success, showed that eight FD patients (six female and two male) had mean adaptive functioning deficits as compared to population norms. Greater rates of depression (P personality (P Individuals affected by Fabry disease exhibited social-adaptive functioning deficits that were significantly correlated with anxiety, depression, antisocial behavior, and AD/H problems in a sampling of our male and female patients aged between 18 years and 59 years.

  6. Enzyme replacement therapy for Fabry disease: some answers but more questions

    Directory of Open Access Journals (Sweden)

    Majid Alfadhel

    2011-02-01

    Full Text Available Majid Alfadhel1, Sandra Sirrs21Division of Biochemical Diseases, Department of Paediatrics, BC Children’s and Women’s Hospital, University of British Columbia, Vancouver, BC, Canada; 2Adult Metabolic Diseases Clinic, Division of Endocrinology, Department of Medicine, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Vancouver, BC, CanadaAbstract: Fabry disease (FD is a multisystem, X-linked disorder of glycosphingolipid metabolism caused by enzyme deficiency of α-galactosidase A. Affected patients have symptoms including acroparesthesias, angiokeratomas, and hypohidrosis. More serious manifestations include debilitating pain and gastrointestinal symptoms, proteinuria and gradual deterioration of renal function leading to end-stage renal disease, hypertrophic cardiomyopathy, and stroke. Heterozygous females may have symptoms as severe as males with the classic phenotype. Before 2001, treatment of patients with FD was supportive. The successful development of enzyme replacement therapy (ERT has been a great advancement in the treatment of patients with FD and can stabilize renal function and cardiac size, as well as improve pain and quality of life of patients with FD. In this review, we have provided a critical appraisal of the literature on the effects of ERT for FD. This analysis shows that data available on the treatment of FD are often derived from studies which are not controlled, rely on surrogate markers, and are of insufficient power to detect differences on hard clinical endpoints. Further studies of higher quality are needed to answer the questions that remain concerning the efficacy of ERT for FD.Keywords: Fabry disease, agalsidase α, agalsidase β, Replagal, Fabrazyme, critical appraisal, evidence-based medicine

  7. Kidney transplantation from a mother with unrecognized Fabry disease to her son with low α-galactosidase A activity: A 14-year follow-up without enzyme replacement therapy.

    Science.gov (United States)

    Odani, Keiko; Okumi, Masayoshi; Honda, Kazuho; Ishida, Hideki; Tanabe, Kazunari

    2016-07-01

    We report a case of kidney transplantation from mother to son, both of whom were likely to have had an unrecognized renal variant phenotype of Fabry disease. The patient was a 54-year-old man, with an unknown primary cause of end stage renal disease. He had no notable past medical history, other than end stage renal disease. He underwent living-related kidney transplantation from his mother at age 40 years. Foam cells in the glomeruli were identified on histology assessment of a 0-hour allograft biopsy, with zebra bodies identified in the glomerular visceral epithelial cells by electron microscopy. These findings were indicative of Fabry disease in the donated kidney. As a definitive diagnosis of Fabry's disease could not be confirmed, enzyme replacement therapy was not initiated. Thirteen years after kidney transplantation, the patient underwent left nephrectomy for a left renal tumour, with pathological findings of clear cell carcinoma, foam cells and zebra bodies in the native kidney. Detailed examinations identified low α-galactosidase A activity and mutation of the α-Gal A gene, confirming a diagnosis of a renal variant phenotype of Fabry disease. Histology of several allograft biopsies performed over the 14 years from the time of kidney transplantation revealed only moderate interstitial fibrosis and tubular atrophy, with no evidence of disease progression on electron microscopy, despite the presence of zebra bodies in the glomerular visceral epithelial cells.

  8. Monitoring renal function in children with Fabry disease: comparisons of measured and creatinine-based estimated glomerular filtration rate

    NARCIS (Netherlands)

    C. Tondel; U. Ramaswami; K.M. Aakre; F. Wijburg; M. Bouwman; E. Svarstad

    2010-01-01

    Methods. Eighty-two examinations were done in 42 children (24 boys, 18 girls) with Fabry disease from three different centres. The mean age was 12.3 years. GFR was measured with iohexol, Cr-51-EDTA or iothalamate, and the mean mGFR was 108 ml/min/1.73 m(2). Results. The widely used original Schwartz

  9. Recommendations for the inclusion of Fabry disease as a rare febrile condition in existing algorithms for fever of unknown origin.

    Science.gov (United States)

    Manna, Raffaele; Cauda, Roberto; Feriozzi, Sandro; Gambaro, Giovanni; Gasbarrini, Antonio; Lacombe, Didier; Livneh, Avi; Martini, Alberto; Ozdogan, Huri; Pisani, Antonio; Riccio, Eleonora; Verrecchia, Elena; Dagna, Lorenzo

    2017-07-19

    Fever of unknown origin (FUO) is a rather rare clinical syndrome representing a major diagnostic challenge. The occurrence of more than three febrile attacks with fever-free intervals of variable duration during 6 months of observation has recently been proposed as a subcategory of FUO, Recurrent FUO (RFUO). A substantial number of patients with RFUO have auto-inflammatory genetic fevers, but many patients remain undiagnosed. We hypothesize that this undiagnosed subgroup may be comprised of, at least in part, a number of rare genetic febrile diseases such as Fabry disease. We aimed to identify key features or potential diagnostic clues for Fabry disease as a model of rare genetic febrile diseases causing RFUO, and to develop diagnostic guidelines for RFUO, using Fabry disease as an example of inserting other rare diseases in the existing FUO algorithms. An international panel of specialists in recurrent fevers and rare diseases, including internists, infectious disease specialists, rheumatologists, gastroenterologists, nephrologists, and medical geneticists convened to review the existing diagnostic algorithms, and to suggest recommendations for arriving at accurate diagnoses on the basis of available literature and clinical experience. By combining specific features of rare diseases with other diagnostic considerations, guidelines have been designed to raise awareness and identify rare diseases among other causes of FUO. The proposed guidelines may be useful for the inclusion of rare diseases in the diagnostic algorithms for FUO. A wide spectrum of patients will be needed to validate the algorithm in different clinical settings.

  10. One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease

    Science.gov (United States)

    Najafian, Behzad; Tøndel, Camilla; Svarstad, Einar; Sokolovkiy, Alexey; Smith, Kelly; Mauer, Michael

    2016-01-01

    Fabry nephropathy is associated with progressive accumulation of globotriaosylceramide (GL3) in podocytes. Reducing this GL3 burden may reduce podocyte injury. Sensitive methods to quantify podocyte GL3 content may determine whether a given strategy can benefit podocytes in Fabry disease. We developed an unbiased electron microscopic stereological method to estimate the average volume of podocytes and their GL3 inclusions in 6 paired pre- and post-enzyme replacement therapy (ERT) biopsies from 5 men with Fabry disease. Podocyte GL3 content was regularly reduced (average 73%) after 11–12 months of ERT. This was not detectable using a semi-quantitative approach. Parallel to GL3 reduction, podocytes became remarkably smaller (average 63%). These reductions in podocyte GL3 content or size were not significantly correlated with changes in foot process width (FPW). However, FPW after ERT was significantly correlated with the magnitude of the decrease in podocyte GL3 content from baseline to 11–12 months of ERT. Also podocytes exocytosed GL3 inclusions, a phenomenon correlated with their reduction in their GL3 content. Demonstrable after11–12 months, reduction in podocyte GL3 content allows for early assessment of treatment efficacy and shorter clinical trials in Fabry disease. PMID:27081853

  11. Multicomponent nanoparticles as nonviral vectors for the treatment of Fabry disease by gene therapy

    Directory of Open Access Journals (Sweden)

    Ruiz de Garibay AP

    2012-10-01

    Full Text Available Aritz Pérez Ruiz de Garibay, Diego Delgado, Ana del Pozo-Rodríguez, María Ángeles Solinís, Alicia Rodríguez GascónPharmacokinetics, Nanotechnology and Gene Therapy Group, Pharmacy Faculty, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, SpainPurpose: Gene-mediated enzyme replacement is a reasonable and highly promising approach for the treatment of Fabry disease (FD. The objective of the present study was to demonstrate the potential applications of solid lipid nanoparticle (SLN-based nonviral vectors for the treatment of FD.Methods: SLNs containing the pR-M10-αGal A plasmid that encodes the α-Galactosidase A (α-Gal A enzyme were prepared and their in vitro transfection efficacy was studied in Hep G2 cells. We also studied the cellular uptake of the vectors and the intracellular disposition of the plasmid.Results: The enzymatic activity of the cells treated with the vectors increased significantly relative to the untreated cells, regardless of the formulation assayed. When the SLNs were prepared with protamine or dextran and protamine, the activity of the α-Gal A enzyme by the transfected Hep G2 cells increased up to 12-fold compared to that of untreated cells.Conclusion: With this work we have revealed in Hep G2 cells the ability of a multicomponent system based on SLNs to act as efficient nonviral vectors to potentially correct low α-Gal A activity levels in FD with gene therapy.Keywords: solid lipid nanoparticles, Fabry disease, nonviral vectors, gene therapy

  12. Impaired Left Atrial Function in Fabry Disease: A Longitudinal Speckle-Tracking Echocardiography Study.

    Science.gov (United States)

    Pichette, Maxime; Serri, Karim; Pagé, Maude; Di, Lu Zhao; Bichet, Daniel G; Poulin, Frédéric

    2017-02-01

    Fabry disease (FD) is characterized by the accumulation of sphingolipids in multiple organs, including the left atrium. It is uncertain if the left atrial (LA) reservoir, conduit, and contractile functions evaluated by speckle-tracking echocardiography are affected in Fabry cardiomyopathy and whether enzyme replacement therapy can improve LA function. In this retrospective cohort study, LA strain, strain rates, and phasic LA volumes were studied in 50 patients with FD and compared with values in 50 healthy control subjects. All three LA phasic functions were altered. Peak positive strain (reservoir function) was 38.9 ± 14.9% versus 46.5 ± 10.9% (P = .004), and late diastolic strain (contractile function) was 12.6 ± 5.9% versus 15.6 ± 5.3% (P = .010). In 15 patients who started enzyme replacement therapy during the study, most of the LA parameters improved at 1-year follow-up (peak positive strain from 32.0 ± 13.5% to 38.0 ± 13.5%, P = .006), whereas there was a trend toward deterioration in 15 patients who never received treatment (peak positive strain from 47.3 ± 10.8% to 41.3 ± 9.3%, P = .058). Nine patients with FD (21%) experienced new-onset atrial fibrillation or stroke during 4-year follow-up. By univariate analysis, peak positive strain and early diastolic strain demonstrated significant associations with clinical events, surpassing conventional echocardiographic parameters and clinical characteristics. LA reservoir, conduit, and contractile functions by speckle-tracking echocardiography were all affected in FD. Enzyme replacement therapy improved LA function. LA strain parameters were associated with atrial fibrillation and stroke. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

  13. Characterization of Early Disease Status in Treatment-Naive Male Paediatric Patients with Fabry Disease Enrolled in a Randomized Clinical Trial

    Science.gov (United States)

    Wijburg, Frits A.; Bénichou, Bernard; Bichet, Daniel G.; Clarke, Lorne A.; Dostalova, Gabriela; Fainboim, Alejandro; Fellgiebel, Andreas; Forcelini, Cassiano; An Haack, Kristina; Hopkin, Robert J.; Mauer, Michael; Najafian, Behzad; Scott, C. Ronald; Shankar, Suma P.; Thurberg, Beth L.; Tøndel, Camilla; Tylki-Szymańska, Anna; Ramaswami, Uma

    2015-01-01

    Trial Design This analysis characterizes the degree of early organ involvement in a cohort of oligo-symptomatic untreated young patients with Fabry disease enrolled in an ongoing randomized, open-label, parallel-group, phase 3B clinical trial. Methods Males aged 5–18 years with complete α-galactosidase A deficiency, without symptoms of major organ damage, were enrolled in a phase 3B trial evaluating two doses of agalsidase beta. Baseline disease characteristics of 31 eligible patients (median age 12 years) were studied, including cellular globotriaosylceramide (GL-3) accumulation in skin (n = 31) and kidney biopsy (n = 6; median age 15 years; range 13–17 years), renal function, and glycolipid levels (plasma, urine). Results Plasma and urinary GL-3 levels were abnormal in 25 of 30 and 31 of 31 patients, respectively. Plasma lyso-GL-3 was elevated in all patients. GL-3 accumulation was documented in superficial skin capillary endothelial cells (23/31 patients) and deep vessel endothelial cells (23/29 patients). The mean glomerular filtration rate (GFR), measured by plasma disappearance of iohexol, was 118.1 mL/min/1.73 m2 (range 90.4–161.0 mL/min/1.73 m2) and the median urinary albumin/creatinine ratio was 10 mg/g (range 4.0–27.0 mg/g). On electron microscopy, renal biopsy revealed GL-3 accumulation in all glomerular cell types (podocytes and parietal, endothelial, and mesangial cells), as well as in peritubular capillary and non-capillary endothelial, interstitial, vascular smooth muscle, and distal tubules/collecting duct cells. Lesions indicative of early Fabry arteriopathy and segmental effacement of podocyte foot processes were found in all 6 patients. Conclusions These data reveal that in this small cohort of children with Fabry disease, histological evidence of GL-3 accumulation, and cellular and vascular injury are present in renal tissues at very early stages of the disease, and are noted before onset of microalbuminuria and development of

  14. [Globosides as key players in the pathophysiology of Shiga toxin-associated acute kidney failure and Fabry disease].

    Science.gov (United States)

    Porubsky, S

    2014-11-01

    Globosides and their isomeric counterparts isoglobosides belong to the class of neutral glycosphingolipids with an as yet undefined physiological function. In the pathogenesis of human diseases, globosides play an important role as cellular receptors for Shiga toxins which are produced by certain strains of S. dysenteriae and E. coli. In order to elucidate the pathogenesis of Shiga toxin-associated kidney failure, we studied human kidney biopsies and animal models. Our work showed that in patients suffering from Shiga toxin-elicited kidney failure, no complement activation could be demonstrated by immunohistochemical analysis of kidney biopsies. Therefore, complement activation is unlikely to play a major role in mediating thrombotic microangiopathy on exposure to Shiga toxin. Moreover, analysis of the human biopsies and of a murine model of Shiga toxin-associated disease pinpointed acute tubular damage as an important and previously neglected contributor to acute kidney failure in patients infected with Shiga toxin-producing E. coli. Furthermore, globosides play a decisive role in the pathogenesis of Fabry disease which results from a decreased or absent activity of the lysosomal enzyme α-galactosidase A. The results on transgenic mice showed that in vital organs, such as the heart, kidneys and liver, it was possible to revert the phenotype of Fabry disease by eliminating the synthesis of globosides. This implicates that substrate reduction therapy through inhibition of globosides might represent a new therapeutic option for Fabry disease, all the more so as globosides seem to be dispensable.

  15. Postmortem diagnosis of Fabry disease with acromegaly and a unique vasculopathy.

    Science.gov (United States)

    Takao, Masaki; Mori, Taisuke; Orikasa, Hideki; Oh, Haengphil; Suzuki, Kinuko; Koto, Atsuo; Yamazaki, Kazuto

    2007-09-01

    A 44-year-old Japanese man with elevated growth hormone levels and gradual deterioration of mental and renal function was admitted to the hospital. With his deteriorated general condition and renal failure, the patient developed pulmonary thromboembolism and died of respiratory failure. Autopsy examination was conducted, which revealed abnormal accumulation or intracytoplasmic storage of lipid-rich material in the small blood vessels, kidney, heart, and nervous system. After postmortem pathologic studies, including light-microscopic histochemistry, electron microscopy, and biochemical analysis of the stored lipid contents, a final diagnosis of Fabry disease was made. Histopathologic examination revealed a unique vasculopathy characterized by the presence of abnormal intracytoplasmic lipid inclusions and vascular remodeling. With regard to the clinical presentation of acromegaly, hyperplasia but not adenomatous transformation of the acidophils of the anterior pituitary gland with immunohistochemical detection of growth hormone within the cells was noted. In this case, the complication of acromegaly with hyperplasia of the acidophilic cells of the anterior pituitary gland and the unique vasculopathy causing significant organ failure, mainly of the kidney, heart, and central nervous systems, possibly as a result of microcirculatory failure, are considered to be not incidental findings but to be intimately involved in the pathogenesis of Farby disease.

  16. The attenuated/late onset lysosomal storage disorders: Therapeutic goals and indications for enzyme replacement treatment in Gaucher and Fabry disease.

    Science.gov (United States)

    Hollak, Carla E M; Weinreb, Neal J

    2015-03-01

    Enzyme replacement therapies have been developed and authorized for commercial use for six different lysosomal storage disorders. For Gaucher disease, Fabry disease and mucopolysaccharidosis type 1, disease-specific treatments have been available for more than a decade. Although long term follow-up data are still sparse, therapeutic goals for patients with Gaucher disease and Fabry disease have been formulated and published for both adults and children. Without adaptation or modification, these goals are often applied in clinical research and in routine patient care across the entire phenotypic spectrum of disease, although in practice, patients commonly manifest high variability in clinical presentation and course of the illness. In this context, establishing goals for the follow-up and treatment of late onset/attenuated phenotypes is particularly challenging. In this chapter, we review current therapeutic goals for Gaucher disease and Fabry disease and discuss approaches for those with attenuated disease manifestations.

  17. Fabry disease in patients with hypertrophic cardiomyopathy: a practical approach to diagnosis.

    Science.gov (United States)

    Seo, Jiwon; Kim, Minji; Hong, Geu-Ru; Kim, Dae-Seong; Son, Jang-Won; Cho, In Jeong; Shim, Chi Young; Chang, Hyuk-Jae; Ha, Jong-Won; Chung, Namsik

    2016-09-01

    This study aimed to develop a new set of screening criteria that is easily applicable and highly sensitive for the detection of patients at high risk of Fabry disease (FD) among hypertrophic cardiomyopathy (HCM) patients. We prospectively studied 273 consecutive unrelated patients who were referred to HCM clinic for unknown left ventricular hypertrophy. Among the 273 patients, we selected 65 high-risk patients who fulfilled at least one of our newly proposed screening criteria. All 273 patients were assayed for plasma α-galactosidase A (α-GAL A) activity. The new screening criteria were: (1) atypical HCM, (2) history or presence of documented arrhythmia, (3) short PR interval defined as <120 ms on electrocardiogram, and (4) symptoms of autonomic dysfunction. From this screening study, three unrelated patients (4.6%; 2 females and 1 male) were newly diagnosed with FD using α-GAL A activity and mutation analysis of the GLA gene. Using the screening method based on the newly proposed criteria, the prevalence of FD in our HCM population was 4.6% if at least one criterion was met and 18.8% if ⩾3 criteria were met. Therefore, our proposed criteria are easily applicable and highly sensitive for classifying patients at high risk of FD from HCM patients.

  18. Persistent increase in cardiac troponin I in Fabry disease: a case report

    Directory of Open Access Journals (Sweden)

    Schneider Christian

    2011-01-01

    Full Text Available Abstract Background Hypertrophic cardiomyopathy is a frequent manifestation in Fabry disease (FD - an X-linked lysosomal storage disorder caused by reduced activity of the enzyme α-galactosidase A. In FD an elevation of specific cardiac biomarkers, such as cardiac troponin I (cTNI has been reported in case of clinical manifestation suggestive of myocardial ischemia. In diagnosing acute myocardial infarction cTNI is considered the most reliable parameter. Case Presentation In the referred case we present a 59 years old female patient with the diagnosis of FD presenting with persistently increased cTNI level (lowest value 0.46 ng/ml, highest value 0.69 ng/ml; normal range Conclusions Our case report demonstrates a persistent cTNI release in FD with cardiac involvement. Proving the persistence in a symptom free interval, it might be related to a direct damage of myocytes. In FD cTNI could serve as a beneficial long term parameter providing new perspectives for screening strategies.

  19. Corpus callosum involvement: a useful clue for differentiating Fabry disease from multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Cocozza, Sirio; Olivo, Gaia; Pontillo, Giuseppe; Ugga, Lorenzo; De Rosa, Dario; Imbriaco, Massimo; Brunetti, Arturo; Tedeschi, Enrico [University ' ' Federico II' ' , Department of Advanced Biomedical Sciences, Naples (Italy); Riccio, Eleonora; Migliaccio, Silvia; Pisani, Antonio [University ' ' Federico II' ' , Department of Public Health, Nephrology Unit, Naples (Italy); Russo, Camilla [University ' ' Federico II' ' , Department of Advanced Biomedical Sciences, Naples (Italy); Feriozzi, Sandro [Belcolle Hospital, Nephrology and Dialysis Department, Viterbo (Italy); Veroux, Massimiliano [University Hospital of Catania, Department of Medical and Surgical Sciences and Advanced Technologies, Catania (Italy); Battaglia, Yuri [St. Anna Hospital-University, Department of Specialized Medicine, Division of Nephrology and Dialysis, Ferrara (Italy); Concolino, Daniela [University Magna Graecia, Department of Pediatrics, Catanzaro (Italy); Pieruzzi, Federico [University of Milano-Bicocca, Nephrology Unit, Milan (Italy); Tuttolomondo, Antonino [University of Palermo, Internal Medicine, DiBiMIS, Palermo (Italy); Caronia, Aurelio [Triolo Zancia Care Home, Palermo (Italy); Russo, Cinzia Valeria; Lanzillo, Roberta; Brescia Morra, Vincenzo [University ' ' Federico II' ' , Department of Neurosciences and Reproductive and Odontostomatological Sciences, Naples (Italy)

    2017-06-15

    Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS. In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms. WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion. FD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options. (orig.)

  20. Mutational analysis of the GLA gene in Mexican families with Fabry disease

    Indian Academy of Sciences (India)

    BIANCA ETHEL GUTIÉRREZ-AMAVIZCA; ANDREAS GAL; ROCÍO ORTÍZ-OROZCO; ULRICH ORTH; ERNESTO PRADO MONTES DE OCA; JAIME PAUL GUTIÉRREZ-AMAVIZCA; LUIS E. FIGUERA

    2017-03-01

    Fabry disease (FD) is a lysosomal storage disorder, which develops due to a deficiency in the hydrolytic enzyme, α-galactosidase A (α-Gal A). Alpha-Gal A hydrolyzes glycosphingolipid globotriaosylceramide (Gb3), and an α-Gal Adeficiency leads to Gb3 accumulation in tissues and cells in the body. This pathology is likely to involve multiple systems, but it is generally considered to affect primarily vascular endothelium. In this study, we investigated mutations in the GLA gene, which encodes α-Gal A, in Mexican families with FD. We included seven probands with FD that carried known mutations. We analysed pedigrees of the probands, and performed molecular screening in 65 relatives with the potential of carrying a GLA mutation. Five mutations (P40S, IVS4+4, G328V, R363H, R404del) were detected in seven unrelated Mexican familieswith the classic FD phenotype. Of the 65 relatives examined, 42 (64.6%) had a GLA gene mutation. In summary, among seven Mexican probands with FD, 65 relatives were at risk of carrying a known GLA mutation, and molecular screening identified 42 individuals with the mutation. Thus, our findings showed that it is important to perform molecular analysis in families with FD to detect mutations and to provide accurate diagnoses for individuals that could be affected.

  1. Two-dimensional speckle tracking as a non-invasive tool for identification of myocardial fibrosis in Fabry disease.

    Science.gov (United States)

    Krämer, Johannes; Niemann, Markus; Liu, Dan; Hu, Kai; Machann, Wolfram; Beer, Meinrad; Wanner, Christoph; Ertl, Georg; Weidemann, Frank

    2013-06-01

    This cross-sectional study aimed to analyse myocardial deformation in patients with Fabry disease (FD) in order to evaluate speckle tracking as a method for non-invasive determination of myocardial fibrosis. Myocardial fibrosis is common in Fabry cardiomyopathy and is associated with disease progression and severe prognosis. In 101 consecutive Fabry patients (39.8 ± 12.9 years; 42 males), the quantitative measurement of myocardial fibrosis with magnetic resonance imaging was compared with regional myocardial deformation assessed by speckle-tracking imaging. Patients were analysed in relation to per cent of late-enhancement (LE)-positive areas of left-ventricular (LV) mass. Fifty-two patients (51%) displayed LE with a mean volume of 1.2 ± 1.8% of total LV mass. Predominantly basal lateral and posterior segments were affected. Patients with LE had lower global systolic longitudinal strain than those without (LE -14.8 ± 3.5% and -18.9 ± 2.1%, respectively; P speckle tracking, was predominantly caused by basal posterior (P = 0.049) and lateral (P = 0.005) segments and global systolic strain correlated with the amount of LE (r = 0.543; P 2%, n = 22) showed the lowest deformation values (-5.9 ± 8.4%) in basal postero-lateral segments when compared with those with mild (Speckle tracking can be used as a tool for the indirect evaluation of LE in FD.

  2. Globotriaosylsphingosine accumulation and not alpha-galactosidase-A deficiency causes endothelial dysfunction in Fabry disease.

    Directory of Open Access Journals (Sweden)

    Mehdi Namdar

    Full Text Available BACKGROUND: Fabry disease (FD is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA resulting in the accumulation of globotriaosylsphingosine (Gb3 in a variety of tissues. While GLA deficiency was always considered as the fulcrum of the disease, recent attention shifted towards studying the mechanisms through which Gb3 accumulation in vascular cells leads to endothelial dysfunction and eventually multiorgan failure. In addition to the well-described macrovascular disease, FD is also characterized by abnormalities of microvascular function, which have been demonstrated by measurements of myocardial blood flow and coronary flow reserve. To date, the relative importance of Gb3 accumulation versus GLA deficiency in causing endothelial dysfunction is not fully understood; furthermore, its differential effects on cardiac micro- and macrovascular endothelial cells are not known. METHODS AND RESULTS: In order to assess the effects of Gb3 accumulation versus GLA deficiency, human macro- and microvascular cardiac endothelial cells (ECs were incubated with Gb3 or silenced by siRNA to GLA. Gb3 loading caused deregulation of several key endothelial pathways such as eNOS, iNOS, COX-1 and COX-2, while GLA silencing showed no effects. Cardiac microvascular ECs showed a greater susceptibility to Gb3 loading as compared to macrovascular ECs. CONCLUSIONS: Deregulation of key endothelial pathways as observed in FD vasculopathy is likely caused by intracellular Gb3 accumulation rather than deficiency of GLA. Human microvascular ECs, as opposed to macrovascular ECs, seem to be affected earlier and more severely by Gb3 accumulation and this notion may prove fundamental for future progresses in early diagnosis and management of FD patients.

  3. Angiotensinogen promoter and angiotensinogen II receptor type 1 gene polymorphisms and incidence of ischemic stroke and neurologic phenotype in Fabry disease.

    Science.gov (United States)

    Altarescu, Gheona; Haim, Shimon; Elstein, Deborah

    2013-11-01

    Stroke and/or white matter lesions (WMLs) are significant in Fabry disease. Polymorphisms of angiotensinogen (AGT), AGT Promoter and angiotensinogen II receptor type 1 (AGTR1) are correlated with WMLs. We compared AGT. AGT Promoter and AGTR1 genotypes to stroke incidence, Fabry-specific [Mainz Severity Score Index (MSSI)] severity score, and neurologic sub-score (n-MSSI). Sixty-three Fabry patients and 49 matched controls plus historic controls were genotyped. Institutional Review Board approval was received. Results. C and/or CC alleles of AGT Promoter and AGTR1 were significantly correlated with stroke and n-MSSI. Findings are suggestive of role of AGT Promoter and AGTR1 genotypes in Fabry phenotypes.

  4. Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel

    Directory of Open Access Journals (Sweden)

    Sommer Claudia

    2011-05-01

    Full Text Available Abstract Background Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen. Methods An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain. Results We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e.g., angiokeratoma, corneal opacities and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients. Conclusions Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with

  5. Lentivector Iterations and Pre-Clinical Scale-Up/Toxicity Testing: Targeting Mobilized CD34+ Cells for Correction of Fabry Disease

    Directory of Open Access Journals (Sweden)

    Ju Huang

    2017-06-01

    Full Text Available Fabry disease is a rare lysosomal storage disorder (LSD. We designed multiple recombinant lentivirus vectors (LVs and tested their ability to engineer expression of human α-galactosidase A (α-gal A in transduced Fabry patient CD34+ hematopoietic cells. We further investigated the safety and efficacy of a clinically directed vector, LV/AGA, in both ex vivo cell culture studies and animal models. Fabry mice transplanted with LV/AGA-transduced hematopoietic cells demonstrated α-gal A activity increases and lipid reductions in multiple tissues at 6 months after transplantation. Next we found that LV/AGA-transduced Fabry patient CD34+ hematopoietic cells produced even higher levels of α-gal A activity than normal CD34+ hematopoietic cells. We successfully transduced Fabry patient CD34+ hematopoietic cells with “near-clinical grade” LV/AGA in small-scale cultures and then validated a clinically directed scale-up transduction process in a GMP-compliant cell processing facility. LV-transduced Fabry patient CD34+ hematopoietic cells were subsequently infused into NOD/SCID/Fabry (NSF mice; α-gal A activity corrections and lipid reductions were observed in several tissues 12 weeks after the xenotransplantation. Additional toxicology studies employing NSF mice xenotransplanted with the therapeutic cell product demonstrated minimal untoward effects. These data supported our successful clinical trial application (CTA to Health Canada and opening of a “first-in-the-world” gene therapy trial for Fabry disease.

  6. PrEFiNe Plan: Strategic plan for Fabry diseases in Nephrology.

    Science.gov (United States)

    Del Pino, M D; Ortiz, A; Torra, R; Hernandez, D

    2016-01-01

    Renal failure is one of the main causes of death in patients with Fabry disease (FD). Due to the low prevalence of FD, delayed diagnosis and misdiagnosis, often the correct diagnosis is made when organ damage is already present. Early recognition of the disease would allow the prevention of severe complications and the premature death of patients with FD. We present here the PrEFiNE project, which includes a wide spectrum of activities with the aim of improve knowledge and diagnosis of FD. The project is sponsored by Shire Iberia (http://shireiberica.com/) From January 2016 to the end of 2017 several activities will be carried out, starting with a survey to evaluate current FD knowledge among nephrologists; in addition some studies to assess prevalence of this disease will be performed. One study will include patients receiving dialysis, another study will cover kidney transplant patients, and a pilot study in chronic kidney disease in stage 3-5 predialysis. Also planned is a pharmacoeconomic study to focus on burden of FD. At the same time medical education activities will be conducted both on line and on site. Plan for dissemination will include medical publications and diffusion to media. PrEFiNE Project will finish with the publication of a compilation book on FD in Nephrology including all planned activities and proposing recommendations based on results and detected unmet needs. PrEfiNE Plan will be coordinated by severa scientific committees, one at national level and 10 other regionals comittees, tha will be responsible to ensure the maximum scientific quality of proposed activities. An advisory board will supervise the project. PrEfiNE project will evaluate an action plan focused on improving FD knowledge to make necessary recommendations for an early recognition of the disease. In addition will generate a plan to improve previously undetected needs. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights

  7. Non-invasive determination of myocardial lipid content in Fabry disease by {sup 1}H-MR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Petritsch, B.; Koestler, H.; Machann, W.; Horn, M.; Weng, A.M.; Goltz, J.P.; Hahn, D.; Beer, M. [Universitaetsklinikum Wuerzburg (Germany). Inst. fuer Roentgendiagnostik im ZOM; Niemann, M.; Weidemann, F.; Wanner, C. [Universitaetsklinikum Wuerzburg (Germany). Medizinische Klinik I

    2012-11-15

    Purpose: In Fabry disease (FD), a progressive deposition of sphingolipids is reported in different organs. The present study applied {sup 1}H magnetic resonance spectroscopy (MRS) to investigate the myocardial lipid content in FD. Materials and Methods: In patients (PTS, n = 15) with genetically proven FD, {sup 1}H MRS of the heart was acquired in the same examination as routine cardiac cine and late enhancement MR imaging. Healthy volunteers (n = 11) without history of cardiac disease served as control (CTL). Myocardial triglycerides in vivo were quantified in {sup 1}H MRS. Left ventricular (LV) ejection fraction (EF) and late enhancement were assessed for the determination of LV systolic function, and onset or absence of myocardial fibrosis. Results: All {sup 1}H MRS revealed resonances for intramyocardial triglycerides. Clinical parameters, e.g. EF (PTS 64 {+-} 2 % vs. CTL 61 {+-} 1 %) were similar in PTS and CTL or showed a non-significant trend (LV mass). Apart from a single patient with elevated myocardial triglycerides, no significant impact of Fabry disease on the triglyceride/water resonance ratio (PTS 0.47 {+-} 0.11 vs. CTL 0.52 {+-} 0.11 %) was observed in our patient cohort. Conclusion: A comprehensive cardiac evaluation of morphology, function as well as metabolism in Fabry PTS with suspected cardiac involvement is feasible in a single examination. No significant effect of myocardial triglyceride deposition could be observed in patients. The remarkably high myocardial triglyceride content in one patient with advanced FD warrants further studies in PTS with an extended history of the disease. (orig.)

  8. Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch-2-Year Follow-Up.

    Science.gov (United States)

    Lenders, Malte; Canaan-Kühl, Sima; Krämer, Johannes; Duning, Thomas; Reiermann, Stefanie; Sommer, Claudia; Stypmann, Jörg; Blaschke, Daniela; Üçeyler, Nurcan; Hense, Hans-Werner; Brand, Stefan-Martin; Wanner, Christoph; Weidemann, Frank; Brand, Eva

    2016-03-01

    Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3-0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C-based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and Pswitch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used.

  9. Alpha-Galactosidase A p.A143T, a non-Fabry disease-causing variant

    OpenAIRE

    Lenders, Malte; Weidemann, Frank; Kurschat, Christine; Canaan-Kühl, Sima; Duning, Thomas; Stypmann, Jörg; Schmitz, Boris; Reiermann, Stefanie; Krämer, Johannes; Blaschke, Daniela; Wanner, Christoph; Brand, Stefan-Martin; Brand, Eva

    2016-01-01

    Background Fabry disease (FD) is an X-linked multisystemic disorder with a heterogeneous phenotype. Especially atypical or late-onset type 2 phenotypes present a therapeutical dilemma. Methods To determine the clinical impact of the alpha-Galactosidase A (GLA) p.A143T/ c.427G > A variation, we retrospectively analyzed 25 p.A143T patients in comparison to 58 FD patients with other missense mutations. Results p.A143T patients suffering from stroke/ transient ischemic attacks had slightly decrea...

  10. Long-term enzyme replacement therapy is associated with reduced proteinuria and preserved proximal tubular function in women with Fabry disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Birn, Henrik; Bibby, Bo M;

    2014-01-01

    BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficiency of α-galactosidase A (α-Gal A) causes intracellular accumulations of globotriaosylceramide (GL-3) and related glycosphingolipids in all organs, including the kidney, often leading...... to end-stage renal failure. In women with Fabry disease, accumulation of GL-3 in the glomerular podocytes and other renal cells induces progressive, proteinuric nephropathy, but not as severe as in men. Enzyme replacement therapy (ERT) with recombinant α-Gal A reduces cellular GL-3 deposits in podocytes...

  11. Oftalmopatía fabry : nuevos marcadores pronósticos para una enfermedad sistémica= Fabry ophthalmopathy: new prognostic markers for a systemic disease

    OpenAIRE

    2016-01-01

    INTRODUCCIÓN: La enfermedad de Fabry es un raro error innato del metabolismo de los glicoesfingolípidos perteneciente al grupo más numeroso de las enfermedades por depósito lisosomal, las lipidosis. Se estima una prevalencia de 1/40000 varones. Sigue un patrón de herencia dominante ligado a X y se origina por mutaciones en el gen GLA (Xq221). Estas mutaciones resultan en una enzima lisosomal α-galactosidasa-A (AGA) con actividad deficiente. El depósito ubícuo de moléculas glicolipídicas...

  12. Home infusion program for Fabry disease: experience with agalsidase alfa in Argentina Programa de infusión domiciliaria para la enfermedad de Fabry: experiencia con agalsidasa alfa en la Argentina

    Directory of Open Access Journals (Sweden)

    Isaac Kisinovsky

    2013-02-01

    Full Text Available Fabry disease is an X-linked lysosomal storage disorder caused by inherited deficiency of the enzyme α-galactosidase A. Enzyme replacement treatment using agalsidase alfa significantly reduces pain, improves cardiac function and quality of life, and slows renal deterioration. Nevertheless, it is a life-long treatment which requires regular intravenous infusions and entails a great burden for patients. Our objective was to evaluate retrospectively the safety and tolerability of the home infusion of agalsidase alfa in patients with Fabry disease in Argentina. We evaluated all the patients with Fabry disease who received home infusion with agalsidase alfa 0.2 mg/kg between January 2005 and June 2011. The program included 87 patients; 51 males (mean age: 30 years and 36 females (mean age: 34 years. A total of 5229 infusions (mean: 59 per patient; range: 1-150 were administered. A total of 5 adverse reactions were seen in 5 patients (5.7% of patients and 0.9% of the total number of infusions. All were mild in severity and resolved by reducing the rate of infusion and by using antihistaminics. All these 5 patients were positive for IgG antibodies, but none of them presented IgE antibodies and none suffered an anaphylactic shock. In our group 18 patients were switched from agalsidase beta to agalsidase alfa without complications. Home infusion with agalsidase alfa is safe, well tolerated and is associated to high compliance.La enfermedad de Fabry es un trastorno de almacenamiento lisosomal hereditario ligado al cromosoma X ocasionado por el déficit de la enzima alfa galactosidasa A. La terapia de reemplazo enzimático utilizando agalsidasa alfa reduce significativamente el dolor, mejora la función cardíaca y la calidad de vida y enlentece el deterioro renal. Sin embargo, es un tratamiento de por vida que requiere infusiones intravenosas regulares y supone una gran carga para los pacientes. Nuestro objetivo fue evaluar retrospectivamente la

  13. Right ventricular involvement in patients with Fabry's disease and the effect of enzyme replacement therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wuest, W. [Universitaetsklinikum Erlangen (Germany). Radiologisches Inst.; Machann, W.; Koestler, H.; Hahn, D.; Beer, M. [Universitaetsklinikum Wuerzburg (Germany). Inst. fuer Roentgendiagnostik; Breunig, F.; Weidemann, F.; Wanner, C. [Universitaetsklinikum Wuerzburg (Germany). Medizinische Klinik I

    2011-11-15

    According to echocardiography reports, Fabry cardiomyopathy not only affects the left ventricle (LV) but also the right ventricle (RV). Until now no MRI studies about the effect of enzyme replacement therapy (ERT) on the RV are available. We evaluated the effect of ERT on the RV. In this prospective trial 14 patients with genetically proven Fabry's disease were examined using a 1.5 T MR scanner before ERT and after 13 {+-} 1 months of ERT. All patients underwent cardiac MR imaging and the RV/LV cardiac morphology and function were analyzed. At baseline examination the values were as follows: RV mass 31 {+-} 6 g/m{sup 2}, end-diastolic volume (EDV) 88 {+-} 13 ml/m{sup 2}, end-systolic volume (ESV) 39 {+-} 9 ml/m{sup 2}, stroke volume (SV) 49 {+-} 7 ml/m{sup 2} and ejection fraction (EF) 56 {+-} 5 %. The RV mass and EDV decreased significantly after 13 {+-} 1 months on ERT (mass 27 {+-} 7 g/m{sup 2}, p < 0.05, EDV 76 {+-} 24 ml/m{sup 2}, p < 0.05), with no significant change of ESV (33 {+-} 13 ml/m{sup 2}), SV (43 {+-} 12 ml/m{sup 2}) and EF (57 {+-} 7 %). The LV mass (102 {+-} 26 g/m{sup 2} vs. 94 {+-} 27 g/m{sup 2}, p < 0.05), EDV (76 {+-} 13 ml/m{sup 2} vs. 66 {+-} 22 ml/m{sup 2}, p < 0.05) and ESV (29 {+-} 9 ml/m{sup 2} vs. 23 {+-} 9 ml/m{sup 2}, p < 0.05) decreased significantly while the EF (64 {+-} 7 % vs. 66 {+-} 5 %; p < 0.05) increased significantly. Besides the known beneficial effect on the LV, ERT improves RV mass and EDV. (orig.)

  14. Co-existence of Phenylketonuria and Fabry disease on a 3 year-old boy: case report

    Directory of Open Access Journals (Sweden)

    Bonapace Giuseppe

    2010-05-01

    Full Text Available Abstract Background The co-existence of two genetically distinct metabolic disorders in the same patient has rarely been reported. Phenylketonuria (PKU is an inborn error of the metabolism resulting from a phenylalanine hydroxylase deficiency. Fabry disease (FD is an X-linked lysosomal storage disorder due to a deficiency of the enzyme alpha-galactosidase A. Case presentation We report a case of a 3 year- old boy affected by classic PKU and FD, both confirmed by molecular data. The FD was suspected at the age of 21 months on the presence of non-specific GI symptoms (severe abdominal pain and periodically appearance of not specific episodes of gastroenteritis apparently non related to PKU. Conclusion This is the first report of co-existence of FD and PKU, two different congenital inborn of metabolism and in consideration of the prevalence of each disease this chance association is a very unusual event. The co-existence of this diseases made very difficult the correct interpretation of clinical symptoms as lack of appetite, severe abdominal pain and non-specific gastroenteritis episodes. Furthermore, this case report helps to define the early clinical phenotype of FD.

  15. Pedigree analysis of Mexican families with Fabry disease as a powerful tool for identification of heterozygous females.

    Science.gov (United States)

    Gutiérrez-Amavizca, B E; Orozco-Castellanos, R; R Padilla-Gutiérrez, J; Valle, Y; Figuera, L E

    2014-08-28

    Fabry disease (FD) is an X-linked lysosomal storage disease caused by α-galactosidase A deficiency; in contrast to other X-linked diseases, heterozygous females can be as affected as men. The construction and analysis of a family pedigree is a powerful tool to aid clinicians in diagnosis, establishment of inheritance pattern, and early detection of potentially affected relatives. The present study highlights the importance of pedigree analysis in families with FD for identifying other possibly affected relatives and investigating the clinical manifestations. This clinical report included 12 Mexican index cases with confirmed FD diagnosis. We constructed and analyzed their pedigree, and diagnosed FD in 24 affected relatives. Clinical features were similar to those reported for other populations. Pedigree analysis further identified an additional 30 women as possible carriers. We conclude that pedigree construction and analysis is a useful tool to help physicians detect and diagnose relatives at risk for FD, particularly heterozygous females, so that they can receive genetic counseling and early treatment. Mexican families with FD were similar to other populations reported in the literature, and our findings confirmed that heterozygous females can have signs and symptoms ranging from subtle manifestations to the classical severe presentation described in males.

  16. Initiation of Parkinson's disease treatment.

    Science.gov (United States)

    Reichmann, Heinz

    2008-09-01

    Parkinson therapy should be commenced as soon as patients feel impaired by motor or other symptoms. Recently it has been stated, however, to start treatment immediately after the diagnosis of PD has been made, in order to offer some neuroprotection to active dopaminergic neurons and to prevent deleterious compensatory mechanisms in dopaminergic cells. The selection of the medication depends on the state of the disease, the clinical symptoms, concomitant diseases and age. In de novo patients, most guidelines, including those of the German Neurological Society, advocate to start with a dopamine agonist. In my opinion, initial treatment with a MAO-B-inhibitor and subsequent combination with a long-acting dopamine agonist may be even more promising with regard to neuroprotection, modification of the disease, avoidance of dyskinesia and good motor improvement.

  17. Identification of an Allosteric Binding Site on Human Lysosomal Alpha-Galactosidase Opens the Way to New Pharmacological Chaperones for Fabry Disease

    Science.gov (United States)

    den-Haan, Helena; Pérez-Sánchez, Horacio; Del Prete, Rosita; Liguori, Ludovica; Cimmaruta, Chiara; Lukas, Jan; Andreotti, Giuseppina

    2016-01-01

    Personalized therapies are required for Fabry disease due to its large phenotypic spectrum and numerous different genotypes. In principle, missense mutations that do not affect the active site could be rescued with pharmacological chaperones. At present pharmacological chaperones for Fabry disease bind the active site and couple a stabilizing effect, which is required, to an inhibitory effect, which is deleterious. By in silico docking we identified an allosteric hot-spot for ligand binding where a drug-like compound, 2,6-dithiopurine, binds preferentially. 2,6-dithiopurine stabilizes lysosomal alpha-galactosidase in vitro and rescues a mutant that is not responsive to a mono-therapy with previously described pharmacological chaperones, 1-deoxygalactonojirimycin and galactose in a cell based assay. PMID:27788225

  18. Fabry disease: a study of 6 hemizygous men and 5 heterozygous women with emphasis on dermatologic manifestations.

    Science.gov (United States)

    Larralde, Margarita; Boggio, Paula; Amartino, Hernán; Chamoles, Néstor

    2004-12-01

    To determine the significance of the dermatologic and systemic abnormalities found in 11 patients with Fabry disease (FD) which is an X-linked lysosomal storage disorder caused by the partial or complete deficiency of the alpha-galactosidase A enzyme. This defect leads to the accumulation of uncleaved glycosphingolipids throughout vascular endothelium and visceral tissues. Case series. Pediatric Dermatology Division, Ramos Mejia Hospital (primary care center) and Laboratory of Neurochemistry (referral center for metabolic diseases). Eleven patients with FD were studied: 6 hemizygous men (mean age, 23.0 years) and 5 heterozygous women (mean age, 49.4 years). Mucocutaneous angiokeratomas (AKs) were found in 5 (83%) of 6 hemizygotes and 4 (80%) of 5 heterozygotes. The AKs appeared at an average age of 13 years, affecting predominantly genitalia, back, elbows, and other frequently traumatized areas. All the hemizygotes and none of the heterozygotes suffered from hypohidrosis. Angiokeratomas on the trunk and oral mucosa without sweat abnormalities were detected in 80% of heterozygous women. All hemizygotic men presented with acral pain in childhood. We emphasize the value of early recognition of AKs and hypohidrosis as diagnostic clues to FD, a severe and progressive disorder.

  19. Rapid preparation of (3R,4S,5R) polyhydroxylated pyrrolidine-based libraries to discover a pharmacological chaperone for treatment of Fabry disease.

    Science.gov (United States)

    Cheng, Wei-Chieh; Wang, Jen-Hon; Yun, Wen-Yi; Li, Huang-Yi; Hu, Jia-Ming

    2017-01-27

    The rapid discovery of a pharmacological chaperone toward human α-Gal A for the treatment of Fabry disease is described. Two polyhydroxylated pyrrolidines with the (3R,4S,5R) configuration pattern underwent rapid substituent diversity by conjugating the primary aminomethyl moiety of each with a variety of carboxylic acids to generate two libraries (2 × 60 members). Our bioevaluation results showed one member with the (2R,3R,4S,5R) configuration pattern and bearing a 5-cyclohexylpentanoyl group as a substituent moiety possessed sufficient chaperoning capability to rescue α-Gal A activity in the lymphocyte of the N215S Fabry patient-derived cell line and other α-Gal A mutants in COS7 cells.

  20. Comprehensive clinical evaluation of a large Spanish family with Anderson-Fabry disease, novel GLA mutation and severe cardiac phenotype.

    Science.gov (United States)

    San Román-Monserrat, Irene; Moreno-Flores, Victoria; López-Cuenca, David; Rodríguez-González-Herrero, Elena; Guillén-Navarro, Encarna; Rodríguez-González-Herrero, Beatriz; Alegría-Fernández, Marisol; Poza-Cisneros, Gabriela; Piñero-Fernández, Juan A; Sornichero-Martínez, Javier; Gimeno-Blanes, Juan R

    2014-06-06

    Fabry disease is an X-linked multisystemic lysosomal-storage condition. We describe a large family with a novel GLA mutation: p.M187R/g7219 T>G. Anamnesis/physical-exam, blood/urine analysis, α-Gal-A activity and/or genetic study of at-risk individuals and multidisciplinary evaluation in confirmed cases. 4 males and 13 heterozygous-females displayed the mutation. Cardiac/renal/neurological disease was diagnosed at a mean age of 41/29/39 years in males and 51/56/46 years in females. Onset mean age was 20 years versus 42 years. 9/15 had cardiomyopathy. Delta wave suggestive of accessory pathway was identified in 1 male and 2 females. 1 female had cardiac arrest (ventricular fibrillation, 61 years). 2 females and 1 male died suddenly (63, 64 and 57 years). Cardiac-subscore of Mainz Severity-Score-Index was severe for males and females over 40 years. 4/15(26%) developed early renal disease. 2 males needed dialysis. 1 male died at 69 years in spite of kidney-heart transplant. We describe the largest genetically confirmed Spanish family using multidisciplinary evaluation and MSSI calculation. The novel mutation p.M187R/g7219 T>G is associated with a particularly malignant cardiac phenotype in males and females over 40 years. Severity was higher than that of the largest Spanish FOS-cohort. Short-PR with delta is being reported for the first time. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  1. Patients affected with Fabry disease have an increased incidence of progressive hearing loss and sudden deafness: an investigation of twenty-two hemizygous male patients

    Directory of Open Access Journals (Sweden)

    Chassaing Augustin

    2002-10-01

    Full Text Available Abstract Background Fabry disease (FD, OMIM 301500 is an X-linked inborn error of glycosphingolipid metabolism due to the deficient activity of alpha-galactosidase A, a lysosomal enzyme. While the progressive systemic deposition of uncleaved glycosphingolipids throughout the body is known to have protean clinical manifestations, few data are available regarding the cochlear involvement. Methods We non-invasively investigated cochlear functions in 22 consecutive hemizygous males (age 19–64 years, mean 39 affected with classic FD. Conventional audiometry, tympanometry, ABR audiometry, otoacoustic emissions were performed in all patients, together with medical history record and physical examination as part of an exhaustive baseline evaluation prior to enzyme replacement therapy. Results A total of 12 patients (54.5% with classic FD were found to have abnormal audition. Five patients had progressive hearing loss and seven patients (32% experienced sudden deafness. In addition, a hearing loss on high-tone frequencies was found in 7 out of the 10 remaining patients without clinical impairment, despite their young age at time of examination. The incidence of hearing loss appeared significantly increased in FD patients with kidney failure (P tinnitus aurium was also found in six patients (27%. Conclusion This is the first evidence of a high incidence of both progressive hearing loss and sudden deafness in a cohort of male patients affected with classic Fabry disease. The exact pathophysiologic mechanism(s of the cochlear involvement deserves further studies.

  2. Lysosome-associated protein 1 (LAMP-1) and lysosome-associated protein 2 (LAMP-2) in a larger family carrier of Fabry disease.

    Science.gov (United States)

    Pereira, Ester M; do Monte, Semiramis J H; do Nascimento, Fernando F; de Castro, Jose A F; Sousa, Jackeline L M; Filho, Henrique C S A L C; da Silva, Raimundo N; Labilloy, Anatália; Monte Neto, José T; da Silva, Adalberto S

    2014-02-15

    This study investigated the potential relationship between the expression levels of lysosome-associated membrane proteins (LAMP) 1 and 2 and responses to enzyme replacement therapy (ERT) in the members of a single family with Fabry disease (FD). LAMP levels were assessed by flow cytometry in leukocytes from 17 FD patients who received an eight-month course of ERT course and 101 healthy individuals. We found that phagocytic cells from the FD patients had higher expression levels of both LAMP-1 and LAMP-2, relative to the levels in phagocytes from the healthy controls (p=0.001). Furthermore, the LAMP-1 and LAMP-2 levels in phagocytes from the FD carriers continuously decreased with ERT administration to reach levels similar to those in healthy controls. We suggest that LAMP-1 and LAMP-2 could be used as additional markers with which to assess ERT effectiveness in FD.

  3. Initial daytime and nighttime SOFDI observations of thermospheric winds from Fabry-Perot Doppler shift measurements of the 630-nm OI line-shape profile

    Directory of Open Access Journals (Sweden)

    A. J. Gerrard

    2011-09-01

    Full Text Available In this paper we present both night and day thermospheric wind observations made with the Second-generation, Optimized, Fabry-Perot Doppler Imager (SOFDI, a novel triple-etalon Fabry-Perot interferometer (FPI designed to make 24-h measurements of thermospheric winds from OI 630-nm emission. These results were obtained from the northeastern United States and from under the magnetic equator at Huancayo, Peru and demonstrate the current instrument capability for measurements of Doppler shifts for either night or day. We found the uncertainties in the measurements agree with expected values based upon forward modeling calculations; nighttime wind components having an uncertainty of ~20-m s−1 at 30-min resolution and daytime wind components having an uncertainty of ~70-m s−1 at 20-min resolution. The nighttime uncertainties are typically larger than those seen with traditional single-etalon FPIs, which occur at the cost of being able to achieve daytime measurements. The thermospheric wind measurements from Huancayo replicate recently reported CHAMP zonal winds and are in disagreement with current empirical wind climatologies. In addition, we discuss the incorporation of how multiple point heads in the SOFDI instrument will allow for unique studies of gravity wave activity in future measurements.

  4. Investigation of multiple organ involvement in Fabry disease%法布里病患者多器官病变的临床特点分析

    Institute of Scientific and Technical Information of China (English)

    张巍; 康曼德; 赵亚雯; 李凡; 舒俊龙; 左越焕; 刘靖; 黄一宁; 袁云

    2015-01-01

    Objective To investigate incidence and clinical features of multiple organ involvement in Chinese patients with Fabry disease.Methods We collected 151 patients of 31 families with Fabry disease,all of whom were confirmed by classic pathology,decreased α-galactosidase A activity or GLA mutation from the year of 2011 to 2014 in Department of Neurology,Peking University First Hospital.The clinical data included incidence and onset of neuralgia,renal dysfunction,heart disease,hypertension and cerebral stroke.We calculate the incidence of these symptoms and analyze their gender difference using chisquare with SPSS 17.0 software.Results Among 31 families with Fabry disease,151 patients (82 males and 69 females) were affected,including 91 patients (60.26%) with neuralgia,62 patients (41.06%) with renal disease,33 patients (21.85%) with heart disease,33 patients (21.85%) with hypertension,and 21 patients (13.91%) with cerebral stroke.The peak incidence of neuralgia was from 10 to 20 years old,followed by renal disease from 30 to 40 years old,heart disease and stroke from 40 to 50 years old.There is no peak period for hypertension.Except for males with higher incidence of renal dysfunction than females (P < 0.05),there were no gender difference in the incidence of other organ involvement.Conclusion The incidence and onset of multiple organ dysfunction in Chinese patients with Fabry disease displayed special regularity.Gender difference appeared only in renal disease.%目的 总结我国法布里病患者多器官病变的发生率和临床表现特点.方法 收集北京大学第一医院神经内科2001-2014年依据病理改变、α-半乳糖苷酶活性A测定和GLA基因突变检查确诊的31个法布里病家系发病者的临床资料,统计其神经痛、肾脏病变、心脏病变、高血压病和脑卒中的发生率和起病时间,使用SPSS 17.0统计软件对男女患者不同器官损害的发生率进行x2检验,比较男女患者上述

  5. PERIANAL DISEASE AS INITIAL MANIFESTATION OF CROHN’S DISEASE

    Directory of Open Access Journals (Sweden)

    Gaurav Shireesh Babar

    2017-06-01

    Full Text Available BACKGROUND Crohn’s disease is a chronic inflammatory disease, which involves almost all parts of body. Perianal manifestations maybe the initial presentation in these patients, but usually includes other systemic manifestations along with it. This study was conducted to determine presence of perianal disease as the initial manifestation in otherwise asymptomatic Crohn’s patients. MATERIALS AND METHODS This study was conducted in Department of Gastroenterology in a tertiary care hospital. All patients presenting with perianal manifestations were evaluated with colonoscopy and other imaging (in selected cases to identify Crohn’s disease. RESULTS A total of 46 patients were evaluated for perianal disease, out of which 3 patients (6.5% had evidence of Crohn’s disease in colonoscopy. Major presentation in these patients were skin tags (n=27, 58.6%, anal fissures (n=15, 32.6% and fistula (n=4, 8.6%. The major symptoms were pain in perianal region (n=38, 82.6%, bleeding PR (n=23, 50%, anal pruritus (n=8, 17.3% and mucus discharge PR (n=7, 15.2%. CONCLUSION Perianal disease maybe the initial presentation in Crohn’s disease. Judicious evaluation of these perianal lesions helps in early diagnosis of Crohn’s disease.

  6. Anti-BlyS antibody reduces the immune reaction against enzyme and enhances the efficacy of enzyme replacement therapy in Fabry disease model mice.

    Science.gov (United States)

    Sato, Yohei; Ida, Hiroyuki; Ohashi, Toya

    2017-02-02

    Formation of antibodies against a therapeutic enzyme is an important complication during enzyme replacement therapy (ERT) for lysosomal storage diseases. Fabry disease (FD) is caused by a deficiency of alpha-galactosidase (GLA), which results in the accumulation of globotriaosylceramide (GL-3). We have shown immune tolerance induction (ITI) during ERT in FD model mice by using an anti-B lymphocyte stimulator (anti-BlyS) antibody (belimumab). A single dose of the anti-BlyS antibody temporarily lowered the percentage of B cells and IgG antibody titer against recombinant human GLA. Administration of a low maintenance dose of the anti-BlyS antibody suppressed the B cell population and immunotolerance was induced in 20% of mice, but antibody formation could not be prevented. We then increased the maintenance dose of the anti-BlyS antibody and immunotolerance was induced in 50% of mice. Therapeutic enzyme distribution and clearance of GL-3 were also enhanced by a high maintenance dose of the anti-BlyS antibody.

  7. The Southern Cone Initiative against Chagas disease.

    Science.gov (United States)

    Schofield, C J; Dias, J C

    1999-01-01

    Chagas disease (also known as American trypanosomiasis) is now ranked as the most serious parasitic disease of the Americas, with an economic impact far outranking the combined effects of other parasitic diseases such as malaria, schistosomiasis and leishmaniasis. Although the chronic infection remains virtually incurable, transmission can be halted by eliminating the domestic insect vectors and screening blood donors to avoid transfusional transmission. In line with this strategy, governments of the six Southern Cone countries (Argentina, Bolivia, Brazil, Chile, Paraguay and Uruguay) launched in 1991 an ambitious initiative to control Chagas disease through elimination of the main vector, Triatoma infestans, and large-scale screening of blood donors. Now at its mid-point, the programme has achieved remarkable success, with transmission halted over vast areas of the previously endemic regions. Well over 2 million rural houses have been sprayed to eliminate T. infestans, and the programme has already shown significant economic rates of return in addition to the medical and social benefits.

  8. The Large Phenotypic Spectrum of Fabry Disease Requires Graduated Diagnosis and Personalized Therapy: A Meta-Analysis Can Help to Differentiate Missense Mutations

    Directory of Open Access Journals (Sweden)

    Valentina Citro

    2016-12-01

    Full Text Available Fabry disease is caused by mutations in the GLA gene and is characterized by a large genotypic and phenotypic spectrum. Missense mutations pose a special problem for graduating diagnosis and choosing a cost-effective therapy. Some mutants retain enzymatic activity, but are less stable than the wild type protein. These mutants can be stabilized by small molecules which are defined as pharmacological chaperones. The first chaperone to reach clinical trial is 1-deoxygalactonojirimycin, but others have been tested in vitro. Residual activity of GLA mutants has been measured in the presence or absence of pharmacological chaperones by several authors. Data obtained from transfected cells correlate with those obtained in cells derived from patients, regardless of whether 1-deoxygalactonojirimycin was present or not. The extent to which missense mutations respond to 1-deoxygalactonojirimycin is variable and a reference table of the results obtained by independent groups that is provided with this paper can facilitate the choice of eligible patients. A review of other pharmacological chaperones is provided as well. Frequent mutations can have residual activity as low as one-fourth of normal enzyme in vitro. The reference table with residual activity of the mutants facilitates the identification of non-pathological variants.

  9. The Large Phenotypic Spectrum of Fabry Disease Requires Graduated Diagnosis and Personalized Therapy: A Meta-Analysis Can Help to Differentiate Missense Mutations

    Science.gov (United States)

    Citro, Valentina; Cammisa, Marco; Liguori, Ludovica; Cimmaruta, Chiara; Lukas, Jan; Cubellis, Maria Vittoria; Andreotti, Giuseppina

    2016-01-01

    Fabry disease is caused by mutations in the GLA gene and is characterized by a large genotypic and phenotypic spectrum. Missense mutations pose a special problem for graduating diagnosis and choosing a cost-effective therapy. Some mutants retain enzymatic activity, but are less stable than the wild type protein. These mutants can be stabilized by small molecules which are defined as pharmacological chaperones. The first chaperone to reach clinical trial is 1-deoxygalactonojirimycin, but others have been tested in vitro. Residual activity of GLA mutants has been measured in the presence or absence of pharmacological chaperones by several authors. Data obtained from transfected cells correlate with those obtained in cells derived from patients, regardless of whether 1-deoxygalactonojirimycin was present or not. The extent to which missense mutations respond to 1-deoxygalactonojirimycin is variable and a reference table of the results obtained by independent groups that is provided with this paper can facilitate the choice of eligible patients. A review of other pharmacological chaperones is provided as well. Frequent mutations can have residual activity as low as one-fourth of normal enzyme in vitro. The reference table with residual activity of the mutants facilitates the identification of non-pathological variants. PMID:27916943

  10. Fabry-Perot interferometers

    CERN Document Server

    Mora-Hernandez, G

    1988-01-01

    This book describes the Fabry-Perot interferometer and its variants as well as its use, optimisation and applications. The author begins with an historical perspective on the development of the instrument. Because of the quantitative uses of the device, the text tends to be mostly mathematical in its treatment. However, there is also much practical detail on the use and optimization of the Fabry-Perot interferometer and discussion of its classical uses (such as in metrology) and its contemporary applications (such as in lasers). In addition the book contains a comprehensive bibliography summarizing the extensive literature on the subject. This book will appeal both to high-resolution practitioners, such as spectroscopists, and to the laser community, since the Fabrv-Perot is not only an integral part of the laser but is also usea to characterize its optical and spectroscopic behaviour.

  11. First experience of simultaneous PET/MRI for the early detection of cardiac involvement in patients with Anderson-Fabry disease

    Energy Technology Data Exchange (ETDEWEB)

    Nappi, Carmela; Altiero, Michele; Imbriaco, Massimo; Giudice, Caterina Anna; Spinelli, Letizia; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Nicolai, Emanuele; Aiello, Marco; Diomiaiuti, Claudio Tommaso [IRCCS SDN, Naples (Italy); Pisani, Antonio [University Federico II, Department of Public Health, Naples (Italy)

    2015-03-26

    Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder associated with severe multiorgan dysfunction and premature death. Early diagnosis and treatment strategies play a key role in patient outcome. We investigated the potential role of hybrid PET/MR imaging in the assessment of early cardiac involvement in AFD patients. Thirteen AFD patients without cardiac symptoms and with normal left ventricular function underwent simultaneous cardiac PET/MR imaging after administration of {sup 18}F-FDG. Cardiac FDG uptake was quantified by measuring the standardized uptake value in 17 myocardial segments in each subject. The coefficient of variation (COV, i.e. the standard deviation divided by the average) of the uptake of the 17 segments was calculated as an index of heterogeneity in the heart. Six patients exhibited focal late gadolinium enhancement (LGE) indicating intramyocardial fibrosis, and four of these also had positive short inversion time inversion recovery (STIR) sequences. All patients with LGE and positive STIR MR images showed focal FDG uptake in the corresponding myocardial segments indicating inflammation. Of the seven patients with negative LGE and STIR images, five showed homogeneous FDG cardiac uptake and two showed heterogeneous FDG uptake. The COV was significantly greater in patients with focal FDG uptake (0.25 ± 0.02) than in those without (0.14 ± 0.07, p < 0.01). PET/MR imaging is clinically feasible for the early detection of cardiac involvement in patients with AFD. Further studies evaluating the role of hybrid PET/MR imaging in management of the disease in larger patient populations are warranted. (orig.)

  12. The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies

    Science.gov (United States)

    Ferreira, Susana; Ortiz, Alberto; Germain, Dominique P.; Viana-Baptista, Miguel; Gomes, António Caldeira; Camprecios, Marta; Fenollar-Cortés, Maria; Gallegos-Villalobos, Ángel; Garcia, Diego; García-Robles, José Antonio; Egido, Jesús; Gutiérrez-Rivas, Eduardo; Herrero, José Antonio; Mas, Sebastián; Oancea, Raluca; Péres, Paloma; Salazar-Martín, Luis Manuel; Solera-Garcia, Jesús; Alves, Helena; Garman, Scott C.; Oliveira, João Paulo

    2015-01-01

    Summary Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue – GLA p.(Arg118Cys) –, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands’ close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease, since the allelic frequency in stroke patients was 0.0087 (p=0.0185 vs the general population). The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for “rare” condition. PMID:25468652

  13. Relationship between left ventricular diastolic function and myocardial sympathetic denervation measured by {sup 123}I-meta-iodobenzylguanidine imaging in Anderson-Fabry disease

    Energy Technology Data Exchange (ETDEWEB)

    Spinelli, Letizia; Giudice, Caterina Anna; Imbriaco, Massimo; Trimarco, Bruno; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Pellegrino, Teresa [Institute of Biostructure and Bioimaging, National Council of Research, Naples (Italy); Pisani, Antonio; Riccio, Eleonora [University Federico II, Department of Public Health, Naples (Italy); Salvatore, Marco [IRCCS SDN, Naples (Italy)

    2016-04-15

    Whether cardiac sympathetic nervous function abnormalities may be present in patients with Anderson-Fabry disease (AFD) remains unexplored. We investigated the relationship between left ventricular (LV) function and cardiac sympathetic nervous function in patients with AFD. Twenty-five patients (12 men, mean age 43 ± 13 years) with genetically proved AFD and preserved LV ejection fraction and ten age and gender-matched control subjects underwent speckle tracking echocardiography and {sup 123}I-meta-iodobenzylguanidine (MIBG) imaging from which early and late heart to mediastinum (H/M) ratios and myocardial washout rate values were calculated. In AFD patients, a significant correlation between late H/M ratio and LV mass index (r = -61, p = 0.001), left atrial volume (r = -0.72, p < 0.001), systolic pulmonary artery pressure (r = -0.75, p < 0.001), and early diastolic untwisting rate (r = -0.66, p < 0.001) was found. Ten AFD patients exhibited a late H/M ratio below two fold standard deviation of control subjects (≤1.75). Patients showing late H/M ratio ≤ 1.75 had significantly higher LV mass index, relative wall thickness, left atrial volume and systolic pulmonary artery pressure, lower systolic longitudinal strain and an early diastolic untwisting rate compared to patients with late H/M ratio > 1.75. At multivariable linear regression analysis, early diastolic untwisting rate was the only independent predictor of late H/M ratio ≤ 1.75 (odds ratio 1.15, 95 % confidence interval 1.07-1.31, p < 0.05). The present findings provide the first demonstration of a cardiac sympathetic derangement in AFD patients with preserved LV ejection fraction, which is mostly related to LV diastolic dysfunction. (orig.)

  14. Variations in plasma and urinary lipids in response to enzyme replacement therapy for Fabry disease patients by nanoflow UPLC-ESI-MS/MS.

    Science.gov (United States)

    Byeon, Seul Kee; Kim, Jin Yong; Lee, Jin-Sung; Moon, Myeong Hee

    2016-03-01

    A deficiency of α-galactosidase A causes Fabry disease (FD) by disrupting lipid metabolism, especially trihexosylceramide (THC). Enzyme replacement therapy (ERT) is clinically offered to FD patients in an attempt to lower the accumulated lipids. Studies on specific types of lipids that are directly or indirectly altered by FD are very scarce, even though they are crucial in understanding the biological process linked to the pathogenesis of FD. We performed a comprehensive lipid profiling of plasma and urinary lipids from FD patients with nanoflow liquid chromatography electrospray-ionization tandem mass spectrometry (nLC-ESI-MS/MS) and identified 129 plasma and 111 urinary lipids. Among these, lipids that exhibited alternations (>twofold) in patients were selected as targets for selected reaction monitoring (SRM)-based high-speed quantitation using nanoflow ultra-performance LC-ESI-MS/MS (nUPLC-ESI-MS/MS) and 31 plasma and 26 urinary lipids showed significant elevation among FD patients. Higher percentages of sphingolipids (SLs; 48% for plasma and 42% for urine) were highly elevated in patients; whereas, a smaller percentage of phospholipids (PLs; 15% for plasma and 13% for urine) were significantly affected. Even though α-galactosidase A is reported to affect THC only, the results show that other classes of lipids (especially SLs) are changed as well, indicating that FD not only alters metabolism of THC but various classes of lipids too. Most lipids showing significant increases in relative amounts before ERT decreased after ERT, but overall, ERT influenced plasma lipids more than urinary lipids.

  15. Safety and pharmacodynamic effects of a pharmacological chaperone on α-galactosidase A activity and globotriaosylceramide clearance in Fabry disease: report from two phase 2 clinical studies

    Directory of Open Access Journals (Sweden)

    Germain Dominique P

    2012-11-01

    Full Text Available Abstract Background Fabry disease (FD is a genetic disorder resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A, which leads to globotriaosylceramide (GL-3 accumulation in multiple tissues. We report on the safety and pharmacodynamics of migalastat hydrochloride, an investigational pharmacological chaperone given orally at 150 mg every-other-day. Methods Two open-label uncontrolled phase 2 studies of 12 and 24 weeks (NCT00283959 and NCT00283933 in 9 males with FD were combined. At multiple time points, α-Gal A activity and GL-3 levels were quantified in blood cells, kidney and skin. GL-3 levels were also evaluated through skin and renal histology. Results Compared to baseline, increased α-Gal A activity of at least 50% was demonstrated in blood, skin and kidney in 6 of 9 patients. Patients’ increased α-Gal A activities paralleled the α-Gal A increases observed in vitro in HEK-293 cells transfected with the corresponding mutant form of the enzyme. The same 6 patients who demonstrated increases of α-Gal A activity also had GL-3 reduction in skin, urine and/or kidney, and had α-Gal A mutations that responded in transfected cells incubated with the drug. The 3 patients who did not show a consistent response in vivo had α-Gal A mutations that did not respond to migalastat HCl in transfected cells. Migalastat HCl was well tolerated. Conclusions Migalastat HCl is a candidate pharmacological chaperone that provides a novel genotype-specific treatment for FD. It enhanced α-Gal A activity and resulted in GL-3 substrate decrease in patients with responsive GLA mutations. Phase 3 studies are ongoing. Trial registration Clinicaltrial.gov: NCT00283959 and NCT00283933

  16. Klinefelter syndrome with fabry disease--a case of nondisjunction of the X-chromosome with sex-linked recessive mutation.

    Science.gov (United States)

    Sadick, Victoria J; Fietz, Michael J; Tchan, Michel C; Kovoor, Pramesh; Thomas, Liza; Sadick, Norman

    2014-12-01

    A 52 year-old male with Klinefelter syndrome presented with chest tightness and rapid atrial fibrillation with hypotension. His echocardiogram demonstrated symmetrical left ventricular hypertrophy with minimal diastolic dysfunction. Subsequent investigations confirmed the diagnosis of Fabry cardiomyopathy. This is the first reported case of Klinefelter syndrome with homozygous sex-linked recessive mutation presenting primarily with cardiac manifestation.

  17. Enzyme replacement therapy for Anderson-Fabry disease: A complementary overview of a Cochrane publication through a linear regression and a pooled analysis of proportions from cohort studies.

    Science.gov (United States)

    El Dib, Regina; Gomaa, Huda; Ortiz, Alberto; Politei, Juan; Kapoor, Anil; Barreto, Fellype

    2017-01-01

    Anderson-Fabry disease (AFD) is an X-linked recessive inborn error of glycosphingolipid metabolism caused by a deficiency of alpha-galactosidase A. Renal failure, heart and cerebrovascular involvement reduce survival. A Cochrane review provided little evidence on the use of enzyme replacement therapy (ERT). We now complement this review through a linear regression and a pooled analysis of proportions from cohort studies. To evaluate the efficacy and safety of ERT for AFD. For the systematic review, a literature search was performed, from inception to March 2016, using Medline, EMBASE and LILACS. Inclusion criteria were cohort studies, patients with AFD on ERT or natural history, and at least one patient-important outcome (all-cause mortality, renal, cardiovascular or cerebrovascular events, and adverse events) reported. The pooled proportion and the confidence interval (CI) are shown for each outcome. Simple linear regressions for composite endpoints were performed. 77 cohort studies involving 15,305 participants proved eligible. The pooled proportions were as follows: a) for renal complications, agalsidase alfa 15.3% [95% CI 0.048, 0.303; I2 = 77.2%, p = 0.0005]; agalsidase beta 6% [95% CI 0.04, 0.07; I2 = not applicable]; and untreated patients 21.4% [95% CI 0.1522, 0.2835; I2 = 89.6%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; b) for cardiovascular complications, agalsidase alfa 28% [95% CI 0.07, 0.55; I2 = 96.7%, p<0.0001]; agalsidase beta 7% [95% CI 0.05, 0.08; I2 = not applicable]; and untreated patients 26.2% [95% CI 0.149, 0.394; I2 = 98.8%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; and c) for cerebrovascular complications, agalsidase alfa 11.1% [95% CI 0.058, 0.179; I2 = 70.5%, p = 0.0024]; agalsidase beta 3.5% [95% CI 0.024, 0.046; I2 = 0%, p = 0.4209]; and untreated patients 18.3% [95% CI 0.129, 0.245; I2 = 95% p < 0.0001]. Effect differences favored agalsidase beta

  18. Fourier Transform Fabry-Perot Interferometer

    Science.gov (United States)

    Snell, Hilary E.; Hays, Paul B.

    1992-01-01

    We are developing a compact, rugged, high-resolution remote sensing instrument with wide spectral scanning capabilities. This relatively new type of instrument, which we have chosen to call the Fourier-Transform Fabry-Perot Interferometer (FT-FPI), is accomplished by mechanically scanning the etalon plates of a Fabry-Perot interferometer (FPI) through a large optical distance while examining the concomitant signal with a Fourier-transform analysis technique similar to that employed by the Michelson interferometer. The FT-FPI will be used initially as a ground-based instrument to study near-infrared atmospheric absorption lines of trace gases using the techniques of solar absorption spectroscopy. Future plans include modifications to allow for measurements of trace gases in the stratosphere using spectral lines at terahertz frequencies.

  19. Recommendations on reintroduction of agalsidase Beta for patients with fabry disease in europe, following a period of shortage

    DEFF Research Database (Denmark)

    Linthorst, Gabor E; Burlina, Alessandro P; Cecchi, Franco;

    2012-01-01

    The interruption of the manufacturing process of agalsidase beta has led to a worldwide shortage of this drug. In the EU, nearly all patients initially reduced their agalsidase beta dose, and many of these switched to agalsidase alfa (Replagal Shire HGT). The clinical consequences of this period...... of drug shortage need to be further evaluated. A gradual increase of agalsidase beta supply is now expected. This implies that patients could resume or even commence agalsidase beta treatment. Guidance for prioritization of patients is needed to support equitable distribution of agalsidase beta to EU...

  20. Initial Staging of Hodgkin’s Disease

    Science.gov (United States)

    Chiaravalloti, Agostino; Danieli, Roberta; Caracciolo, Cristiana Ragano; Travascio, Laura; Cantonetti, Maria; Gallamini, Andrea; Guazzaroni, Manlio; Orlacchio, Antonio; Simonetti, Giovanni; Schillaci, Orazio

    2014-01-01

    Abstract The objective of this study was to compare the diagnostic accuracy of positron emission tomography/low-dose computed tomography (PET/ldCT) versus the same technique implemented by contrast-enhanced computed tomography (ceCT) in staging Hodgkin’s disease (HD). Forty patients (18 men and 22 women, mean age 30 ± 9.6) with biopsy-proven HD underwent a PET/ldCT study for initial staging including an unenhanced low-dose computed tomography for attenuation correction with positron emission tomography acquisition and a ceCT, performed at the end of the PET/ldCT scan, in the same exam session. A detailed datasheet was generated for illness locations for separate imaging modality comparison and then merged in order to compare the separate imaging method results (PET/ldCT and ceCT) versus merged results positron emission tomography/contrast-enhanced computed tomography (PET/ceCT). The nodal and extranodal lesions detected by each technique were then compared with follow-up data that served as the reference standard. No significant differences were found at staging between PET/ldCT and PET/ceCT in our series. One hundred and eighty four stations of nodal involvement have been found with no differences in both modalities. Extranodal involvement was identified in 26 sites by PET/ldCT and in 28 by PET/ceCT. We did not find significant differences concerning the stage (Ann Arbor). Our study shows a good concordance and conjunction between PET/ldCT and ceCT in both nodal and extranodal sites in the initial staging of HD, suggesting that PET/ldCT could suffice in most of these patients. PMID:25121354

  1. Clinical and magnetic resonance imaging studies of Anderson-Fabry disease: 2 cases report%表现为早发缺血性卒中的Fabry病二例

    Institute of Scientific and Technical Information of China (English)

    李小璇; 王璐; 张赟; 张巍; 洪道俊; 王朝霞; 高惠珍; 袁云

    2011-01-01

    Objective To report 2 cases of Fabry disease with early-onset ischemic stroke and investigate the clinical and image features. Methods The 2 patients developed dizziness, diplopia and progressive memory decline at 32 and 25 years of age respectively. The α-galactosidase A (GLA)activity was 4. 3 U in case 1 and 1. 0 U in case 2 ( normal range 100-500 U). Skin biopsy showed numerous membrane bounded osmiophilic laminar material in vascular smooth muscle cells and endothelial cells. GLA gene analysis revealed GLA exon 7 1033-1034 TC del in case 1 and GLA exon 3 466G > A in case 2. The 2 patients were evaluated by Mainz severity score index (MSSI) and cranial MRI. Results The general MSSI was 32 in case 1 and 16 in case 2, with the highest score of neurological score ( 11 and 14). Both cases showed multifocal infarcts in bilateral cerebellum, occipital lobe, basal ganglia, which were hypointensity on T1 WI and hyperintensity on T2WI. There were hyperintensity changes in the pulvinar and basal ganglia on T1 WI in case 2. Conclusions Cerebral ischemic stroke could appear as initial symptoms in Fabry disease,which predominantly involved the posterior circulation. There might be no dilation of basal-vertebral artery.%目的 报道以早发缺血性卒中为主要表现的2例Fabry病,分析其卒中表现规律和影像学改变特点.方法 2例Fabry病患者分别在32岁和25岁出现头晕和突发视物成双,伴随记忆力下降.α-半乳糖苷酶活性在例1为4.3 U,例2为1.0 U(正常值100~500 U).皮肤病理检查发现血管平滑肌细胞和内皮细胞内充满膜性包裹的板层样小体.α-半乳糖苷酶基因检查显示例1的7号外显子存在1033-1034 TC del突变,而例2存在3号外显子c.466G>A突变.对2例患者进行美茵滋严重度评分(MSSI)和头MRI检查.结果 例1的MSSI总分为32,其中神经系统评分最高(11分),例2的总分为16,其中神经系统评分最高(14分).MRI均表现为双侧小脑、枕叶、基

  2. Genetic Disorders with Dyshidrosis: Ectodermal Dysplasia, Incontinentia Pigmenti, Fabry Disease, and Congenital Insensitivity to Pain with Anhidrosis.

    Science.gov (United States)

    Wataya-Kaneda, Mari

    2016-01-01

    Sweating is regulated by various neurohormonal mechanisms. A disorder in any part of the sweating regulatory pathways, such as the thermal center, neurotransmitters in the central to peripheral nerve, innervation of periglandular neurotransmission, and sweat secretion in the sweat gland itself, induces dyshidrosis. Therefore, hereditary disorders with dyshidrosis result from a variety of causes. These diseases have characteristic symptoms derived from each pathogenesis besides dyshidrosis. The information in this chapter is useful for the differential diagnosis of representative genetic disorders with dyshidrosis. © 2016 S. Karger AG, Basel.

  3. Genetic Screening of Mutations Associated with Fabry Disease in a Nationwide Cohort of Juvenile Idiopathic Arthritis Patients

    Science.gov (United States)

    Gonçalves, Maria J.; Mourão, Ana F.; Martinho, António; Simões, Olívia; Melo-Gomes, José; Salgado, Manuel; Estanqueiro, Paula; Ribeiro, Célia; Brito, Iva; Fonseca, João E.; Canhão, Helena

    2017-01-01

    Fabry’s disease (FD) is a lysosomal storage disorder associated with an alpha-galactosidase A deficiency. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients with established diagnosis is unknown, but as musculoskeletal pain may be an important complaint at presentation, misdiagnosed cases are anticipated. With this study, we aim to calculate the frequency of FD-associated mutations in a cohort of JIA patients. Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded in the Portuguese rheumatic diseases register (http://Reuma.pt). Molecular genetic testing to detect GLA gene mutations was performed. After the multiplex polymerase chain reactions technique for DNA amplification, direct sequencing of the complete sequence of GLA gene was completed. From a cohort of 292 patients with JIA (188 females, 104 males), mutations were identified in 5 patients (all female). Four patients had the mutation D313Y, a rare GLA variant, which is associated with low enzymatic levels in plasma, but normal lysosomal levels. One patient presented the missense mutation R118C, which was previously described in Mediterranean patients with FD. This is the first screening of FD mutations in a cohort of JIA patients. No “classic” pathogenic FD mutations were reported. The late-onset FD-associated mutation, R118C, was found in a frequency of 0.34% (1/292). PMID:28299312

  4. Holographic Fabry-Perot spectrometer.

    Science.gov (United States)

    Martínez-Matos, O; Rodrigo, José A; Vaveliuk, P; Calvo, M L

    2011-02-15

    We propose a spectrum analyzer based on the properties of a hologram recorded with the field transmitted by a Fabry-Perot etalon. The spectral response of this holographic Fabry-Perot spectrometer (HFPS) is analytically investigated in the paraxial approximation and compared with a conventional Fabry-Perot etalon of similar characteristics. We demonstrate that the resolving power is twice increased and the free spectral range (FSR) is reduced to one-half. The proposed spectrometer could improve the operational performance of the etalon because it can exhibit high efficiency and it would be insensible to environmental conditions such as temperature and vibrations. Our analysis also extends to another variant of the HFPS based on holographic multiplexing of the transmitted field of a Fabry-Perot etalon. This device increases the FSR, keeping the same HFPS performance.

  5. End-Stage Renal Disease (ESRD) Quality Initiative

    Data.gov (United States)

    U.S. Department of Health & Human Services — The End Stage Renal Disease (ESRD) Quality Initiative promotes ongoing CMS strategies to improve the quality of care provided to ESRD patients. This initiative...

  6. Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with Fabry disease

    Science.gov (United States)

    Goláň, Lubor; Goker-Alpan, Ozlem; Holida, Myrl; Kantola, Ikka; Klopotowski, Mariusz; Kuusisto, Johanna; Linhart, Aleš; Musial, Jacek; Nicholls, Kathleen; Gonzalez-Rodriguez, Derlis; Sharma, Reena; Vujkovac, Bojan; Chang, Peter; Wijatyk, Anna

    2015-01-01

    Purpose Efficacy and safety of agalsidase alfa at 0.2 mg/kg weekly were compared with 0.2 mg/kg every other week (EOW). Exploratory analyses were performed for 0.4 mg/kg weekly. Patients and methods This was a 53-week, Phase III/IV, multicenter, open-label study (NCT01124643) in treatment-naïve adults (≥18 years) with Fabry disease. Inclusion criteria were left ventricular hypertrophy at baseline, defined as left ventricular mass indexed to height >50 g/m2.7 for males and >47 g/m2.7 for females. Primary endpoint was reduction of left ventricular mass indexed to height as assessed by echocardiography. Secondary endpoints included cardiac (peak oxygen consumption, 6-minute walk test, Minnesota Living with Heart Failure Questionnaire, New York Heart Association classification), renal (Modification of Diet in Renal Disease, estimated glomerular filtration rate), and biomarker (plasma globotriaosylceramide) assessments. Safety endpoints were adverse events and anti–agalsidase alfa antibodies. Results Twenty patients were randomized to 0.2 mg/kg EOW (mean age, 50.3 years; 70% male), 19 to 0.2 mg/kg weekly (51.8 years; 53% male), and 5 to 0.4 mg/kg weekly (49.4 years; 40% male). The mean change in left ventricular mass indexed to height by Week 53 in the 0.2-mg/kg EOW and weekly groups was 3.2 g/m2.7 and 0.5 g/m2.7, with no significant difference between groups. No clinically meaningful changes by Week 53 were found within or between the 0.2-mg/kg groups for peak oxygen consumption, 6-minute walk test, or Minnesota Living with Heart Failure Questionnaire. Two patients in each group improved by ≥1 New York Heart Association classification. No significant differences were found between 0.2 mg/kg EOW and weekly for mean change in estimated glomerular filtration rate (−1.21 mL/min/1.73 m2 vs −3.32 mL/min/1.73 m2) or plasma globotriaosylceramide (−1.05 nmol/mL vs −2.13 nmol/mL), respectively. Infusion-related adverse events were experienced by 25% and 21% in the

  7. The prevalent deep intronic c. 639+919 G>A GLA mutation causes pseudoexon activation and Fabry disease by abolishing the binding of hnRNPA1 and hnRNP A2/B1 to a splicing silencer

    DEFF Research Database (Denmark)

    Palhais, Bruno; Dembic, Maja; Sabaratnam, Rugivan;

    2016-01-01

    with the ESS is also able to inhibit inclusion of an unrelated pseudoexon in the FGB gene, and that also in the FGB context inactivation of the ESS by the c.639+919 G>A mutation causes pseudoexon activation, underscoring the universal nature of the ESS. Finally, we demonstrate that splice switching......Fabry disease is an X-linked recessive inborn disorder of the glycosphingolipid metabolism, caused by total or partial deficiency of the lysosomal α-galactosidase A enzyme due to mutations in the GLA gene. The prevalent c.639+919 G>A mutation in GLA leads to pathogenic insertion of a 57bp...... pseudoexon sequence from intron 4, which is responsible for the cardiac variant phenotype. In this study we investigate the splicing regulatory mechanism leading to GLA pseudoexon activation. Splicing analysis of GLA minigenes revealed that pseudoexon activation is influenced by cell-type. We demonstrate...

  8. Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with Fabry disease

    Directory of Open Access Journals (Sweden)

    Goláň L

    2015-07-01

    Full Text Available Lubor Goláň,1 Ozlem Goker-Alpan,2 Myrl Holida,3 Ikka Kantola,4 Mariusz Klopotowski,5 Johanna Kuusisto,6 Aleš Linhart,1 Jacek Musial,7 Kathleen Nicholls,8 Derlis Gonzalez-Rodriguez,9 Reena Sharma,10 Bojan Vujkovac,11 Peter Chang,12 Anna Wijatyk12 1First Faculty of Medicine, Department of Cardiovascular Medicine, Charles University, Prague, Czech Republic; 2Lysosomal Research and Treatment Unit, Fairfax, VA, USA; 3Stead Family Department of Pediatrics, Division of Medical Genetics, University of Iowa Hospitals and Clinics, Iowa City, IA, USA; 4Division of Medicine, Turku University Hospital, Turku, Finland; 5Institute of Cardiology, Warsaw, Poland; 6Department of Medicine, Center for Medicine and Clinical Research, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland; 7Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland; 8Department of Nephrology, Royal Melbourne Hospital and the University of Melbourne, VIC, Australia; 9Instituto Privado de Hematologia E Investigacion Clinica (IPHIC, Asuncion, Paraguay; 10Salford Royal NHS Foundation Trust, Salford, UK; 11General Hospital Slovenj Gradec, Slovenj Gradec, Slovenia; 12Shire, Lexington, MA, USA Purpose: Efficacy and safety of agalsidase alfa at 0.2 mg/kg weekly were compared with 0.2 mg/kg every other week (EOW. Exploratory analyses were performed for 0.4 mg/kg weekly.Patients and methods: This was a 53-week, Phase III/IV, multicenter, open-label study (NCT01124643 in treatment-naïve adults (≥18 years with Fabry disease. Inclusion criteria were left ventricular hypertrophy at baseline, defined as left ventricular mass indexed to height >50 g/m2.7 for males and >47 g/m2.7 for females. Primary endpoint was reduction of left ventricular mass indexed to height as assessed by echocardiography. Secondary endpoints included cardiac (peak oxygen consumption, 6-minute walk test, Minnesota Living with Heart Failure Questionnaire, New

  9. Computer-assisted initial diagnosis of rare diseases

    Directory of Open Access Journals (Sweden)

    Rui Alves

    2016-07-01

    Full Text Available Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient’s symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80% and sensitivity (≥99%, and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers.

  10. Computer-assisted initial diagnosis of rare diseases

    Science.gov (United States)

    Piñol, Marc; Vilaplana, Jordi; Teixidó, Ivan; Cruz, Joaquim; Comas, Jorge; Vilaprinyo, Ester; Sorribas, Albert

    2016-01-01

    Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient’s symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers. PMID:27547534

  11. Computer-assisted initial diagnosis of rare diseases.

    Science.gov (United States)

    Alves, Rui; Piñol, Marc; Vilaplana, Jordi; Teixidó, Ivan; Cruz, Joaquim; Comas, Jorge; Vilaprinyo, Ester; Sorribas, Albert; Solsona, Francesc

    2016-01-01

    Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient's symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers.

  12. WHO Initiative to Estimate the Global Burden of Foodborne Diseases

    DEFF Research Database (Denmark)

    Havelaar, Arie H.; Cawthorne, Amy; Angulo, Fred

    2013-01-01

    appropriate, evidence-informed priorities in the area of food safety. MethodsThe Initiative aims to provide estimates on the global burden of foodborne diseases by age, sex, and region; strengthen country capacity for conducting burden of foodborne disease assessments in parallel with food safety policy...... of foodborne diseases, based on national and international studies. Systematic reviews to support estimates of the incidence and mortality of food-related diseases are being completed. Results will be used to update and refine global burden estimates for relevant food-related hazards, in the context of other...

  13. Disease management strategy: initiative links pharmaceutical and mental health data.

    Science.gov (United States)

    Docherty, J P

    1996-02-01

    The emphasis in healthcare is shifting to practical applications of medical knowledge for the provision of more cost-effective care. This requires greater linkages among clinical information systems across multiple organizations. This article describes new initiatives in disease management to link the traditionally separate data systems fo pharmaceutical, behavioral and general medical care. The potential for improved patient care is highlighted. The author is an expert consultant for a large pharmaceutical manufacturer's disease state management initiative, and has an extensive leadership background in many segments of the behavioral healthcare industry.

  14. Preeclampsia or initial diagnosis of chronic renal disease during pregnancy.

    Science.gov (United States)

    Iavazzo, C; Kalmantis, K; Bozemberg, T; Ntziora, F; Ioakeimidis, A; Paschalinopoulos, D

    2008-01-01

    An unusual case of early nephrotic syndrome without hypertension which slightly resolved after delivery is documented. Renal biopsy was performed postpartum and the diagnosis was focal and segmental glomerulosclerosis with moderate chronic renal changes. It is questioned whether the case was due to preeclampsia or was the initial diagnosis of chronic renal disease which was made during pregnancy. The role of renal biopsy in such cases is briefly discussed (Tab. 2, Ref. 15). Full Text (Free, PDF) www.bmj.sk.

  15. The pilot European Alzheimer's Disease Neuroimaging Initiative of the European Alzheimer's Disease Consortium

    DEFF Research Database (Denmark)

    Frisoni, G.B.; Henneman, W.J.; Weiner, M.W.

    2008-01-01

    BACKGROUND: In North America, the Alzheimer's Disease Neuroimaging Initiative (ADNI) has established a platform to track the brain changes of Alzheimer's disease. A pilot study has been carried out in Europe to test the feasibility of the adoption of the ADNI platform (pilot E-ADNI). METHODS: Sev...

  16. Vascular Tortuosities of the Upper Eyelid: A New Clinical Finding in Fabry Patient Screening

    Directory of Open Access Journals (Sweden)

    Langis Michaud

    2013-01-01

    Full Text Available Purpose. To report a new clinical finding related to Fabry disease. Methods. Fabry subjects were enrolled in the study, matched for age and sex with healthy individuals as a control group. This is a prospective review of all upper lid pictures taken for every subject at their last visit. A 4-step grading scale is proposed to classify this new entity. Results. Group A (Fabry comprised 16 males and 22 females, aged 40 (±14 years on average. Group B (control comprised 7 males and 8 females, aged 37 (±12 Vessels tortuosity was identified on the external superior lid in 36 of the Fabry patients (94.7%, while none of the subjects in group B showed similar vessels tortuosity. In addition, microaneurysms (MAs were found in 10/38 group A subjects while none in group B presented a similar finding. The differences are highly significant. Conclusion. This paper proposes that blood vessels tortuosity on the upper eyelid be recognized as a new clinical entity for inclusion among the classic ocular manifestations of Fabry’s disease. Without evidence of any negative impact, it should be considered a benign sign contributing to evidence of suspected Fabry disease.

  17. Alzheimer's Disease Neuroimaging Initiative 2 Clinical Core: Progress and plans.

    Science.gov (United States)

    Aisen, Paul S; Petersen, Ronald C; Donohue, Michael; Weiner, Michael W

    2015-07-01

    This article reviews the current status of the Clinical Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI), and summarizes planning for the next stage of the project. Clinical Core activities and plans were synthesized based on discussions among the Core leaders and external advisors. The longitudinal data in ADNI-2 provide natural history data on a clinical trials population and continue to inform refinement and standardization of assessments, models of trajectories, and clinical trial methods that have been extended into sporadic preclinical Alzheimer's disease (AD). Plans for the next phase of the ADNI project include maintaining longitudinal follow-up of the normal and mild cognitive impairment cohorts, augmenting specific clinical cohorts, and incorporating novel computerized cognitive assessments and patient-reported outcomes. A major hypothesis is that AD represents a gradually progressive disease that can be identified precisely in its long presymptomatic phase, during which intervention with potentially disease-modifying agents may be most useful. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  18. Distributed Fabry-Perot Measurement System

    Institute of Scientific and Technical Information of China (English)

    WENG Jian-hua

    2003-01-01

    The theoretic analysis indicates that if the lengths of the cascaded and paralleled Fabry-Perot sensors are properly selected, the crosstalk can be well restricted.And the experiment simulation results agree with that of the theoretic analysis.

  19. A Novel Rapid MALDI-TOF-MS-Based Method for Measuring Urinary Globotriaosylceramide in Fabry Patients

    Science.gov (United States)

    Alharbi, Fahad J.; Geberhiwot, Tarekegn; Hughes, Derralynn A.; Ward, Douglas G.

    2016-04-01

    Fabry disease is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A, resulting in the accumulation of glycosphingolipids in various organs. Globotriaosylceramide (Gb3) and its isoforms and analogues have been identified and quantified as biomarkers of disease severity and treatment efficacy. The current study aimed to establish rapid methods for urinary Gb3 extraction and quantitation. Urine samples from 15 Fabry patients and 21 healthy control subjects were processed to extract Gb3 by mixing equal volumes of urine, methanol containing an internal standard, and chloroform followed by sonication and centrifugation. Thereafter, the lower phase was analyzed by MALDI-TOF MS and the relative peak areas of the internal standard and four major species of Gb3 determined. The results showed high reproducibility with intra- and inter-assay coefficients variation of 9.9% and 13.7%, respectively. The limit of detection was 0.15 ng/μL and the limit of quantitation was 0.30 ng/μL. Total urinary Gb3 levels in both genders of classic Fabry patients were significantly higher than in healthy controls (p < 0.0001). Gb3 levels in Fabry males were higher than in Fabry females (p = 0.08). We have established a novel assay for urinary total Gb3 that takes less than 15 min from start to finish.

  20. Inhibition of Intermediate-Conductance Calcium-Activated K Channel (KCa3.1) and Fibroblast Mitogenesis by α-Linolenic Acid and Alterations of Channel Expression in the Lysosomal Storage Disorders, Fabry Disease, and Niemann Pick C

    Science.gov (United States)

    Oliván-Viguera, Aida; Lozano-Gerona, Javier; López de Frutos, Laura; Cebolla, Jorge J.; Irún, Pilar; Abarca-Lachen, Edgar; García-Malinis, Ana J.; García-Otín, Ángel Luis; Gilaberte, Yolanda; Giraldo, Pilar; Köhler, Ralf

    2017-01-01

    The calcium/calmodulin-gated KCa3.1 channel regulates normal and abnormal mitogenesis by controlling K+-efflux, cell volume, and membrane hyperpolarization-driven calcium-entry. Recent studies suggest modulation of KCa3.1 by omega-3 fatty acids as negative modulators and impaired KCa3.1 functions in the inherited lysosomal storage disorder (LSD), Fabry disease (FD). In the first part of present study, we characterize KCa3.1 in murine and human fibroblasts and test the impact of omega-3 fatty acids on fibroblast proliferation. In the second, we study whether KCa3.1 is altered in the LSDs, FD, and Niemann-Pick disease type C (NPC). Our patch-clamp and mRNA-expression studies on murine and human fibroblasts show functional expression of KCa3.1. KCa currents display the typical pharmacological fingerprint of KCa3.1: Ca2+-activation, potentiation by the positive-gating modulators, SKA-31 and SKA-121, and inhibition by TRAM-34, Senicapoc (ICA-17043), and the negative-gating modulator, 13b. Considering modulation by omega-3 fatty acids we found that α-linolenic acid (α-LA) and docosahexanenoic acid (DHA) inhibit KCa3.1 currents and strongly reduce fibroblast growth. The α-LA-rich linseed oil and γ-LA-rich borage oil at 0.5% produce channel inhibition while α-LA/γ-LA-low oils has no anti-proliferative effect. Concerning KCa3.1 in LSD, mRNA expression studies, and patch-clamp on primary fibroblasts from FD and NPC patients reveal lower KCa3.1-gene expression and membrane expression than in control fibroblasts. In conclusion, the omega-3 fatty acid, α-LA, and α-LA/γ-LA-rich plant oils, inhibit fibroblast KCa3.1 channels and mitogenesis. Reduced fibroblast KCa3.1 functions are a feature and possible biomarker of cell dysfunction in FD and NPC and supports the concept that biased lipid metabolism is capable of negatively modulating KCa3.1 expression. PMID:28197106

  1. Acute Warfarin Toxicity as Initial Manifestation of Metastatic Liver Disease

    Directory of Open Access Journals (Sweden)

    Varalaxmi Bhavani Nannaka

    2016-01-01

    Full Text Available Near complete infiltration of the liver secondary to metastasis from the head and neck cancer is a rare occurrence. The prognosis of liver failure associated with malignant infiltration is extremely poor; the survival time of patients is extremely low. We present a case of acute warfarin toxicity as initial manifestation of metastatic liver disease. Our patient is a 64-year-old woman presenting with epigastric pain and discomfort, found to have unrecordable International Normalized Ratio. She rapidly deteriorated with acute respiratory failure requiring mechanical ventilation, profound shock requiring high dose vasopressor infusion, severe coagulopathy, worsening liver enzymes with worsening of lactic acidosis and severe metabolic abnormalities, and refractory to aggressive supportive care and died in less than 48 hours. Autopsy revealed that >90% of the liver was replaced by tumor masses.

  2. Characterization of Fabry mice treated with recombinant adeno-associated virus 2/8-mediated gene transfer

    Directory of Open Access Journals (Sweden)

    Choi Jin-Ok

    2010-04-01

    Full Text Available Abstract Background Enzyme replacement therapy (ERT with α-galactosidase A (α-Gal A is currently the most effective therapeutic strategy for patients with Fabry disease, a lysosomal storage disease. However, ERT has limitations of a short half-life, requirement for frequent administration, and limited efficacy for patients with renal failure. Therefore, we investigated the efficacy of recombinant adeno-associated virus (rAAV vector-mediated gene therapy for a Fabry disease mouse model and compared it with that of ERT. Methods A pseudotyped rAAV2/8 vector encoding α-Gal A cDNA (rAAV2/8-hAGA was prepared and injected into 18-week-old male Fabry mice through the tail vein. The α-Gal A expression level and globotriaosylceramide (Gb3 levels in the Fabry mice were examined and compared with Fabry mice with ERT. Immunohistochemical and ultrastructural studies were conducted. Results Treatment of Fabry mice with rAAV2/8-hAGA resulted in the clearance of accumulated Gb3 in tissues such as liver, spleen, kidney, heart, and brain with concomitant elevation of α-Gal A enzyme activity. Enzyme activity was elevated for up to 60 weeks. In addition, expression of the α-Gal A protein was identified in the presence of rAAV2/8-hAGA at 6, 12, and 24 weeks after treatment. α-Gal A activity was significantly higher in the mice treated with rAAV2/8-hAGA than in Fabry mice that received ERT. Along with higher α-Gal A activity in the kidney of the Fabry mice treated with gene therapy, immunohistochemical studies showed more α-Gal A expression in the proximal tubules and glomerulus, and less Gb3 deposition in Fabry mice treated with this gene therapy than in mice given ERT. The α-gal A gene transfer significantly reduced the accumulation of Gb3 in the tubules and podocytes of the kidney. Electron microscopic analysis of the kidneys of Fabry mice also showed that gene therapy was more effective than ERT. Conclusions The rAAV2/8-hAGA mediated α-Gal A gene

  3. Deep Vein Thrombosis as Initial Manifestation of Whipple Disease

    Directory of Open Access Journals (Sweden)

    Mônica Souza de Miranda Henriques

    2016-11-01

    Full Text Available Introduction: Wipple disease (WD is a rare chronic disease caused by the bacillus Tropheryma whipplei. Constitutive, rheumatologic, gastrointestinal, cardiac, cerebral, lymphatic, cutaneous, and ophthalmological signs are possible systemic symptoms. However, thrombotic manifestations are rarely described as “stroke-like syndrome” or arterial thrombosis. Diagnosis is based on clinical manifestations and pathological examination. Laboratory findings may include anemia, leukocytosis, and thrombocytosis. Objective: We report a case of venous thrombosis as initial manifestation of WD. Case Report: We describe the case of a 53-year-old male with iliofemoral vein thrombosis followed by intermittent diarrhea, loss of appetite, abdominal distension, and bloating. A mild malnutrition state with a weight loss of 13 kg, pallor (+/4 +, presence of lower-limb edema (+/4 +, and hypertympanic distended abdomen occurred. Laboratory tests on admission revealed anemia, positive inflammatory activity tests, and normal coagulation. Endoscopic examination showed villous edema with white dotted infiltrates in the second duodenal portion and intestinal lymphangiectasia in the terminal ileum. Pathological examination revealed numerous macrophages with positive periodic acid-Schiff inclusions. Venous Doppler ultrasound showed extensive deep thrombosis on the left lower limb and recanalization of the femoral vein in the right lower limb. The patient was treated with ceftriaxone and enoxaparin sodium, which led to an improvement of gastrointestinal and thrombosis symptoms. Comments: Hypercoagulability, endothelial damage, vasculitis, and blood stasis are present in T. whipplei infection, which are associated with the activation of inflammatory mechanisms as well as procoagulant and thromboembolic events. WD should be part of the differential diagnosis of diseases that cause venous thrombosis of unknown origin.

  4. Development of a disease registry for autoimmune bullous diseases: initial analysis of the pemphigus vulgaris subset.

    Science.gov (United States)

    Shah, Amit Aakash; Seiffert-Sinha, Kristina; Sirois, David; Werth, Victoria P; Rengarajan, Badri; Zrnchik, William; Attwood, Kristopher; Sinha, Animesh A

    2015-01-01

    Pemphigus vulgaris (PV) is a rare, potentially life threatening, autoimmune blistering skin disease. The International Pemphigus and Pemphigoid Foundation (IPPF) has recently developed a disease registry with the aim to enhance our understanding of autoimmune bullous diseases with the long-term goal of acquiring information to improve patient care. Patients were recruited to the IPPF disease registry through direct mail, e-mail, advertisements, and articles in the IPPF-quarterly, -website, -Facebook webpage, and IPPF Peer Health Coaches to complete a 38-question survey. We present here the initial analysis of detailed clinical information collected on 393 PV patients. We report previously unrecognized gender differences in terms of lesion location, autoimmune comorbidity, and delay in diagnosis. The IPPF disease registry serves as a useful resource and guide for future clinical investigation.

  5. Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients

    NARCIS (Netherlands)

    B.E. Smid; S.M. Rombach; J.M.F.G. Aerts; S. Kuiper; M. Mirzaian; H.S. Overkleeft; B.J.H.M. Poorthuis; C.E.M. Hollak; J.E.M. Groener; G.E. Linthorst

    2011-01-01

    ABSTRACT: BACKGROUND: Enzyme replacement therapy is currently the only approved therapy for Fabry disease. From June 2009 on, viral contamination of Genzyme's production facility resulted in a worldwide shortage of agalsidase beta leading to involuntary dose reductions (approved dose 1 mg/kg/eow, re

  6. Rebleeding after initial endoscopic hemostasis in peptic ulcer disease.

    Science.gov (United States)

    Hong, Mi Jin; Lee, Sun-Young; Kim, Jeong Hwan; Sung, In-Kyung; Park, Hyung Seok; Shim, Chan Sup; Jin, Choon Jo

    2014-10-01

    Endoscopic hemostasis is the first-line treatment for upper gastrointestinal bleeding (UGIB). Although several factors are known to be risk factors for rebleeding, little is known about the use of antithrombotics. We tried to verify whether the use of antithrombotics affects rebleeding rate after a successful endoscopic hemostasis for peptic ulcer disease (PUD). UGIB patients who underwent successful endoscopic hemostasis were included. Rebleeding was diagnosed when the previously treated lesion bled again within 30 days of the initial episode. Of 522 UGIB patients with PUD, rebleeding occurred in 93 patients (17.8%). The rate of rebleeding was higher with aspirin medication (P=0.006) and after a long endoscopic hemostasis (P<0.001). Of all significant variables, procedure time longer than 13.5 min was related to the rate of rebleeding (OR, 2.899; 95% CI, 1.768-4.754; P<0.001) on the logistic regression analysis. The rate of rebleeding after endoscopic hemostasis for PUD is higher in the patients after a long endoscopic hemostasis. Endoscopic hemostasis longer than 13.5 min is related to rebleeding after a successful endoscopic hemostasis for PUD.

  7. Chinese patients with Huntington's disease initially presenting with spinocerebellar ataxia.

    Science.gov (United States)

    Dong, Y; Sun, Y-M; Liu, Z-J; Ni, W; Shi, S-S; Wu, Z-Y

    2013-04-01

    Recent studies have described Huntington's disease (HD) patients with atypical onset of ataxia. Symptoms in these patients can overlap with those of spinocerebellar ataxia (SCA). We retrospectively examined clinical data for 82 HD probands and found 7 had initially been clinically diagnosed as SCA cases. Clinical features in these patients were further investigated and the number of CAG repeats in the huntingtin (HTT) gene was determined by direct sequencing. Genetic screenings for SCAs in the 7 patients were all negative. By contrast, HTT was heterozygous in each patient. The distribution of CAG number in the 7 patients was statistically the same as that in the other 75 patients. Each of 7 HD patients had presented with atypical onset of ataxia. The mean time from onset to HTT genetic testing was 5.6 ± 5.52 years. Three of the patients developed chorea, but the others did not. Our observations confirm the clinical heterogeneity of HD in Han Chinese. Based on these findings, testing for HTT expansions should be considered for clinically diagnosed SCA patients who test negatively in genetic screening of SCA genes.

  8. To differentiate Alzheimer's disease earlier: introduction of Alzheimer's Disease Neuroimaging Initiative (ADNI

    Directory of Open Access Journals (Sweden)

    Zhi-gang QI

    2014-04-01

    Full Text Available Alzheimer's disease (AD brought about much pressure in modern aging society both economically and psychologically, so it is meaningful to carry out AD research. Being considered as the most successful multi-center, inter-disciplinary and longitudinal research in AD field, Alzheimer's Disease Neuroimaging Initiative (ADNI has obtained outstanding achievements. In this review, we attempt to introduce the research plan of ADNI project for reference. doi: 10.3969/j.issn.1672-6731.2014.04.003

  9. Neurological aspects of Gaucher and Fabry disease

    NARCIS (Netherlands)

    Biegstraaten, M.

    2011-01-01

    Momenteel zijn er meer dan vijftig stapelingsziekten bekend, waarvan de ernst zeer uiteen loopt. Sommige aandoeningen worden gekenmerkt door ernstige mentale retardatie, neurologische problemen en overlijden op kinderleeftijd; andere vormen hebben nauwelijks een lagere levensverwachting. Ook in de l

  10. 78 FR 15015 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panels (SEP): Initial Review

    Science.gov (United States)

    2013-03-08

    ... Activities for Avian Influenza and other Zoonotic Diseases, FOA CK13-002, initial review. Correction: The... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry. Elaine L....

  11. 以慢性肾炎综合征为主要表现的Fabry病2例报道并文献复习%Fabry disease with chronic nephritis syndrome as the main manifestation and literature study:2 cases report

    Institute of Scientific and Technical Information of China (English)

    廖武琼; 李典耕; 谢大洋; 陈仆; 李清刚; 陈香美

    2015-01-01

    Objective To investigate the clinical manifestation and renal pathology of Fabry disease which characteri zed with chronic nephritis syndrome as the main manifestation. Methods Retrospectively review the 2 cases of Fabry disease, which characterized as chronic nephritis syndrome as the main manifestation, the clinical signs and pathology were analyzed, and review of the relevant literature to master the methods of diagnosis and treatment. Results One case was male patient, the other was female patient, and onset age was 46 years old and 44 years old, 2 cases showed proteinuria, hematuria, hyperten-sion, and no characteristic of extra-renal manifestations. Under the light microscope, glomerular sclerosis rates were 30. 8%and 32. 1% respectively, significant swelling of glomerular podocytes, visible vacuoles formed in the cytoplasm, renal tubular multifocal atrophic were found. Dense and irregular osmiophilic myelin bodies also can be found. There is no effective cure methods for Fabry disease, combined with renal damage, the treatment mainly was to protect the kidney function, reducing protein, control symptom, the main medicine are ARB, such as losartan potassium, leflunomide. Conclusion Fabry disease is a rare genetic chromosome X diseases, renal damage is one of the most common clinical manifestation, under microscopic osmiophilic myelin bodies is the pathological finding, symptomatic treatment with enzyme replacement therapy are the main treatment, and combined with the genetics of appropriate intervention to block the genetics of the disease.%目的:探讨以慢性肾炎综合征为主要表现的Fabry病临床表现和肾脏病理学特点。方法回顾性分析收治的以慢性肾炎综合征为主要表现的Fabry病2例,分析其临床体征及病理学特征,同时复习相关文献掌握其诊断及治疗方法。结果男女患者各1例,发病年龄分别为46岁和44岁,2例均表现为蛋白尿、血尿、高血压,而无特征性的肾外表现

  12. Disease management. A global cost-containing initiative?

    Science.gov (United States)

    Bloor, K; Maynard, A

    2000-06-01

    Disease management has been marketed by healthcare industry providers as a way of improving resource allocation in healthcare and containing costs. However, to achieve improved efficiency in healthcare requires the guidelines and protocols in the disease management process to be based on sound evidence of effectiveness and cost effectiveness. This has not always been the case. The approach itself has an inadequate evidence base in terms of randomised controlled trials, other rigorous methods of evaluation and the results of economic evaluation. Disease management can be viewed as an attempt by pharmaceutical companies to undertake forward vertical integration into other parts of the healthcare process. This could reduce uncertainty for purchasers and reduce transaction costs, thereby potentially facilitating both healthcare expenditure control and efficiency. However, such cost savings may be outweighed by a concentration of power in disease management (pharmaceutical) companies, and the exploitation of such power to inflate expenditure and misallocate resources. Disease management must be appraised with care.

  13. The molecular initiation and subsequent acquisition of disease ...

    African Journals Online (AJOL)

    Interactions between disease resistance (R) genes in plants and their ... salicylic acid, and reactive oxygen intermediates prior to upregulation of R genes. The physiological role of these molecules in plant resistance to pathogens is beginning ...

  14. 78 FR 60878 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2013-10-02

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... and Disease Prevention Research Centers, Funding Opportunity Announcement (FOA) DP14-001, initial... Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: Times and Dates 8...

  15. 78 FR 9055 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial review

    Science.gov (United States)

    2013-02-07

    ... Activities for Avian Influenza and other Zoonotic Diseases, FOA CK13-002, initial review. In accordance with... Interface Activities for Avian Influenza and other Zoonotic Diseases, FOA CK13-002''. Contact Person for... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention...

  16. An Archetype Semi-Ring Fabry-Perot (SRFP) Resonator

    Science.gov (United States)

    Taghavi-Larigani, Shervin; VanZyl, Jakob

    2009-01-01

    We introduce and demonstrate the generation of a novel resonator, termed Semi-Ring Fabry-Perot (SRFP), that exhibits unique features, such as, its use of one plane mirror, allowing the SRFP to be easily fabricated as a symmetrical device. In addition to its unique features, it exhibits advantages of ring and Fabry-Perot resonators: 1) compared to a ring resonator that only allows a transmitted intensity, the Semi-Ring Fabry-Perot (SRFP) supports standing waves, allowing both a reflected and transmitted intensity; 2) the reflected light spectrum of the SRFP resonator is much narrower than similar Fabry-Perot, implying higher finesse.

  17. The role of air pollutants in initiating liver disease.

    Science.gov (United States)

    Kim, Jong Won; Park, Surim; Lim, Chae Woong; Lee, Kyuhong; Kim, Bumseok

    2014-06-01

    Recent episodes of severe air pollution in eastern Asia have been reported in the scientific literature and news media. Therefore, there is growing concern about the systemic effects of air pollution on human health. Along with the other well-known harmful effects of air pollution, recently, several animal models have provided strong evidence that air pollutants can induce liver toxicity and act to accelerate liver inflammation and steatosis. This review briefly describes examples where exposure to air pollutants was involved in liver toxicity, focusing on how particulate matter (PM) or carbon black (CB) may be translocated from lung to liver and what liver diseases are closely associated with these air pollutants.

  18. Surveying quality of life in patients with Fabry disease by the SF-36 scale%SF-36量表评估Fabry病患者生活质量的研究

    Institute of Scientific and Technical Information of China (English)

    欧阳彦; 潘晓霞; 王朝晖; 沈平雁; 王伟铭; 任红; 张文; 陈楠

    2014-01-01

    Objective To test the availability of the SF-36 scale for the Chinese patient with Fabry disease (FD),the quality of life(QOL) and its probable influence factors were analyzed.Methods The data were obtained from 50 healthy volunteers and 57 patients with FD enrolled in nephrology department of Ruijin hospital from Jan,2003 to Jan,2013.The SF-36 scale was used to evaluate the QOL of patients and to compare the difference between the patients and controls.Furthermore,the influencing factors were estimated by multiple linear regressions.Results Between the patients and controls,the differences of 8 dimensionalitiy's scores had statistical significance,which claimed that the reaction was sensitive.Especially,in the patient group,the Pearson correlation coefficient among each domain of the SF-36 was lower than its Cronbach's α coefficient (0.934),which indicated good internal consistency reliability.The two common factors were much the same to the theory assume,which illustrated the construct validity was available.Even the acceptability of the patient' group at 100% proved the scale was appropriate for patients with FD.In addition,in rolephysical (RP) and bodily pain (BP),the scores of the male patients were less than the females (P <0.01),declared that the QOL of the males was inferior to the females.In the physical function (PF) and the mental health (MH),the scores of the patients with angiokeratoma were less than the group without it,so the patients who had evident clinical symptoms more likely contributed to depression.Using multiple linear regression,age,gender and clinical types were chosen into regression equation by stepwise regression,and the main potential predictor was age.Conclusions The SF-36 scale applies to evaluate the QOL of patients with FD.It is critical to concern and manage the QOL of FD patients,especially in their mental health aspect.%目的 调查中国Fabry病患者生存质量(quality of life,QOL),分析其可能的影响因

  19. 77 FR 25181 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-04-27

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and..., Cholera And HIV/AIDS Response, GH12-003, initial review. In accordance with Section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention...

  20. Small-fibre neuropathy in female Fabry patients: reduced allodynia and skin blood flow after topical capsaicin

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Feldt-Rasmussen, Ulla; Rasmussen, Åse K.;

    2006-01-01

    affected. Recently, attention has been drawn to female patients whether they also show signs of nerve involvement. An early sign of the disease is painful small-fibre neuropathy. The aim of this study was to evaluate a small-fibre dysfunction in female Fabry patients by using capsaicin applied topically....... The response to capsaicin was evaluated by laser Doppler imaging. We found that the female Fabry patients had a significantly smaller increase in blood flow (p = 0.0003) after capsaicin application. The area of static mechanical allodynia and dynamic mechanical hyperalgesia was also significantly smaller (p...

  1. A high resolution scanning fabry-perot for OSIRIS

    Directory of Open Access Journals (Sweden)

    A. Bernal

    2007-01-01

    Full Text Available Following the directives of the workshop on the interferometric mode of OSIRIS, the Mexican team has received support to ac- quire a scanning Fabry-Perot interferometer for OSIRIS. In this presentation we will try to define which Fabry-Perot will be selected as well as which filters need to be acquired. We will also discuss the acquisition software

  2. Immunohistochemical diagnosis of Fabry nephropathy and localisation of globotriaosylceramide deposits in paraffin-embedded kidney tissue sections.

    Science.gov (United States)

    Valbuena, Carmen; Leitão, Dina; Carneiro, Fátima; Oliveira, João Paulo

    2012-02-01

    Fabry disease (FD) is a rare X-linked lysosomal storage disorder of glycosphingolipids, mostly globotriaosylceramide (Gb3). Proteinuric chronic kidney disease develops frequently, and recognition of Fabry nephropathy on a kidney biopsy may be the first clue to the underlying diagnosis. Since the accumulated glycosphingolipids are largely extracted by the paraffin-embedding procedure, the most characteristic feature of Fabry nephropathy on routine light microscopy (LM) is nonspecific cell vacuolization. To test whether residual Gb3 in kidney tissue might be exploited for the specific diagnosis of Fabry nephropathy, paraffin-embedded kidney biopsies of nine FD patients (one boy, four men, four women) and of a female carrier of a mild genetic mutation, with no evidence of Fabry nephropathy, were immunostained with an anti-Gb3 antibody. The adult biopsies were additionally co-stained with a lysosomal marker (anti-lysosomal-associated membrane protein 2 (anti-LAMP2) antibody). The distribution of Gb3 deposits was scored per cell type and compared to the histological scorings of glycosphingolipid inclusions on semi-thin sections. FD patients had residual Gb3 in all types of glomerular, tubular, interstitial and vascular kidney cells. The highest expression of LAMP2 was seen in tubular cells, but there were no meaningful associations between LAMP2 expression and prevalence of Gb3 deposits on different kidney cell types. The histological scorings of glycosphingolipid inclusions were relatively higher than the corresponding immunohistochemical scorings of Gb3 deposits. In the mildly affected female, Gb3 expression was limited to tubular cells, a pattern similar to controls. Gb3 immunostaining allows the specific diagnosis of Fabry nephropathy even in kidney biopsies routinely processed for LM.

  3. Lower extremity necrotizing fasciitis: A unique initial presentation of Crohn's disease

    Directory of Open Access Journals (Sweden)

    Anna Weiss

    2015-09-01

    Full Text Available Crohn's disease is a disease of the bowel, typically presenting with diarrhea, weight loss, and abdominal pain. Complications such as abscesses, fistulas, and strictures may require surgical intervention. We would like to report a patient with Crohn's disease who presented for the first time with left lower extremity necrotizing fasciitis. There are very few reports of necrotizing fasciitis in Crohn's disease as the initial presentation.

  4. CSF biomarkers associated with disease heterogeneity in early Parkinson's disease: the Parkinson's Progression Markers Initiative study.

    Science.gov (United States)

    Kang, Ju-Hee; Mollenhauer, Brit; Coffey, Christopher S; Toledo, Jon B; Weintraub, Daniel; Galasko, Douglas R; Irwin, David J; Van Deerlin, Vivianna; Chen-Plotkin, Alice S; Caspell-Garcia, Chelsea; Waligórska, Teresa; Taylor, Peggy; Shah, Nirali; Pan, Sarah; Zero, Pawel; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Tanner, Caroline M; Simuni, Tanya; Singleton, Andrew; Toga, Arthur W; Chowdhury, Sohini; Trojanowski, John Q; Shaw, Leslie M

    2016-06-01

    The development of biomarkers to predict the progression of Parkinson's disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson's Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1-42 (Aβ1-42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1-42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1-42, or highest t-tau/Aβ1-42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1-42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance.

  5. Ophthalmic experience over 10 years in an observational nationwide Danish cohort of Fabry patients with access to enzyme replacement

    DEFF Research Database (Denmark)

    Fledelius, Hans C.; Sandfeld, Lisbeth; Rasmussen, Åse Krogh

    2015-01-01

    PURPOSE: Enzyme replacement therapy (ERT) was offered from year 2001 to patients with Fabry disease. The ophthalmic experience was analysed, as part of a general 10-year status. METHODS: A retrospective observational series comprising 39 patients (25 females, 14 males) closely followed by the end...

  6. An economic Fabry-Perot wavelength reference

    Science.gov (United States)

    Fżrész, Gábor; Glenday, Alex; Latham, Christian

    2014-07-01

    Precision radial velocity (PRV) measurements are key in studying exoplanets, and so are wavelength calibrators in PRV instruments. ThAr lamps offer an affordable but somewhat limited solution for the visible passband. Laser frequency combs are ideal calibrators, except the (still) narrow wavelength coverage and large price tag. White light Fabry-Perot (FP) calibrators offer frequency-comb like properties in a more affordable and less complicated package1. Using a commercial solid FP etalon and off-the shelf components we have constructed an economic FP calibrator suitable for observatories on a smaller budget.

  7. 78 FR 17411 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2013-03-21

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Evaluation of Malaria Control and Elimination Activities, FOA GH13-005, initial review. In accordance with... and Prevention (CDC) announces the aforementioned meeting: Time and Date: 11:00 a.m.-3:00 p.m., May...

  8. Protocol and methodology of the Stroke in Young Fabry Patients (sifap1) study: a prospective multicenter European study of 5,024 young stroke patients aged 18-55 years.

    LENUS (Irish Health Repository)

    Rolfs, Arndt

    2011-01-01

    Stroke in the young has not been thoroughly investigated with most previous studies based on a small number of patients from single centers. Furthermore, recent reports indicate that Fabry disease may be a significant cause for young stroke. The primary aim of our study was to determine the prevalence of Fabry disease in young stroke patients, while the secondary aim was to describe patterns of stroke in young patients.

  9. Degree of host susceptibility in the initial disease outbreak influences subsequent epidemic spread.

    Science.gov (United States)

    Severns, Paul M; Estep, Laura K; Sackett, Kathryn E; Mundt, Christopher C

    2014-12-01

    Disease epidemics typically begin as an outbreak of a relatively small, spatially explicit population of infected individuals (focus), in which disease prevalence increases and rapidly spreads into the uninfected, at-risk population. Studies of epidemic spread typically address factors influencing disease spread through the at-risk population, but the initial outbreak may strongly influence spread of the subsequent epidemic.We initiated wheat stripe rust Puccinia striiformis f. sp. tritici epidemics to assess the influence of the focus on final disease prevalence when the degree of disease susceptibility differed between the at-risk and focus populations.When the focus/at-risk plantings consisted of partially genetic resistant and susceptible cultivars, final disease prevalence was statistically indistinguishable from epidemics produced by the focus cultivar in monoculture. In these experimental epidemics, disease prevalence was not influenced by the transition into an at-risk population that differed in disease susceptibility. Instead, the focus appeared to exert a dominant influence on the subsequent epidemic.Final disease prevalence was not consistently attributable to either the focus or the at-risk population when focus/at-risk populations were planted in a factorial set-up with a mixture (~28% susceptible and 72% resistant) and susceptible individuals. In these experimental epidemics, spatial heterogeneity in disease susceptibility within the at-risk population appeared to counter the dominant influence of the focus.Cessation of spore production from the focus (through fungicide/glyphosate application) after 1.3 generations of stripe rust spread did not reduce final disease prevalence, indicating that the focus influence on disease spread is established early in the epidemic.Synthesis and applications. Our experiments indicated that outbreak conditions can be highly influential on epidemic spread, even when disease resistance in the at-risk population is

  10. Interleukin-18 deteriorates Fabry cardiomyopathy and contributes to the development of left ventricular hypertrophy in Fabry patients with GLA IVS4+919 G>A mutation

    Science.gov (United States)

    Huang, Wei-Lin; Chou, Shih-Jie; Chang, Wei-Chao; Chang, Yuh-Lih; Leu, Hsin-Bang; Chen, Kuan-Hsuan; Wang, Kang-Ling; Lai, Ying-Hsiu; Liu, Yung-Yang; Lu, Kai-Hsi; Li, Hsin-Yang; Sung, Yen-Jen; Jong, Yuh-Jyh; Chen, Yann-Jang; Chen, Chung-Hsuan; Yu, Wen-Chung

    2016-01-01

    Rationale A high incidence of GLA IVS4+919 G>A mutation in patients with Fabry disease of the later-onset cardiac phenotype, has been reported in Taiwan. However, suitable biomarkers or potential therapeutic surrogates for Fabry cardiomyopathy (FC) in such patients under enzyme replacement treatment (ERT) remain unknown. Objective Using FC patients carrying IVS4+919 G>A mutation, we constructed an induced pluripotent stem cell (iPSC)-based disease model to investigate the pathogenetic biomarkers and potential therapeutic targets in ERT-treated FC. Results and methods The iPSC-differentiated cardiomyocytes derived from FC-patients (FC-iPSC-CMs) carried IVS4+919 G>A mutation recapitulating FC characteristics, including low α-galactosidase A enzyme activity, cellular hypertrophy, and massive globotriaosylceramide accumulation. Microarray analysis revealed that interleukin-18 (IL-18), a pleiotropic cytokine involved in various myocardial diseases, was the most highly upregulated marker in FC-iPSC-CMs. Meanwhile, IL-18 levels were found to be significantly elevated in the culture media of FC-iPSC-CMs and patients’ sera. Notably, the serum IL-18 levels were highly paralleled with the progression of left ventricular hypertrophy in Fabry patients receiving ERT. Finally, using FC-iPSC-CMs as in vitro FC model, neutralization of IL-18 with specific antibodies combined with ERT synergistically reduced the secretion of IL-18 and the progression of cardiomyocyte hypertrophy in FC-iPSC-CMs. Conclusion Our data demonstrated that cardiac IL-18 and circulating IL-18 are involved in the pathogenesis of FC and LVH. IL-18 may be a novel marker for evaluating ERT efficacy, and targeting IL-18 might be a potential adjunctive therapy combined with ERT for the treatment of advanced cardiomyopathy in FC patients with IVS4+919 G>A mutation. PMID:27888626

  11. Effects of auditory cues on gait initiation and turning in patients with Parkinson's disease.

    Science.gov (United States)

    Gómez-González, J; Martín-Casas, P; Cano-de-la-Cuerda, R

    2016-12-08

    To review the available scientific evidence about the effectiveness of auditory cues during gait initiation and turning in patients with Parkinson's disease. We conducted a literature search in the following databases: Brain, PubMed, Medline, CINAHL, Scopus, Science Direct, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Library Plus, CENTRAL, Trip Database, PEDro, DARE, OTseeker, and Google Scholar. We included all studies published between 2007 and 2016 and evaluating the influence of auditory cues on independent gait initiation and turning in patients with Parkinson's disease. The methodological quality of the studies was assessed with the Jadad scale. We included 13 studies, all of which had a low methodological quality (Jadad scale score≤2). In these studies, high-intensity, high-frequency auditory cues had a positive impact on gait initiation and turning. More specifically, they 1) improved spatiotemporal and kinematic parameters; 2) decreased freezing, turning duration, and falls; and 3) increased gait initiation speed, muscle activation, and gait speed and cadence in patients with Parkinson's disease. We need studies of better methodological quality to establish the Parkinson's disease stage in which auditory cues are most beneficial, as well as to determine the most effective type and frequency of the auditory cue during gait initiation and turning in patients with Parkinson's disease. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Burning Tongue as Initial Presentation of Celiac Disease in an Elderly Woman: A Case Report.

    Science.gov (United States)

    Sherman, Andrea; Zamulko, Alla

    2016-06-01

    There are few reports in the literature where celiac disease presents with tongue manifestations, although atypical presentations of celiac disease are not uncommon. This case report highlights an atypical presentation of celiac disease in an elderly female. Our patient presented to clinic with complaints of a burning tongue for the past two years as well as occasional loose stools and fatigue. Work-up revealed iron deficiency anemia, zinc deficiency and an abnormal celiac panel. Complete symptom improvement was noted by 10 weeks into the initiation of a gluten free diet. Celiac disease can present at any age and should be considered as a differential in findings of malabsorption and gastrointestinal symptoms.

  13. Fabry-Perot resonance of water waves.

    Science.gov (United States)

    Couston, Louis-Alexandre; Guo, Qiuchen; Chamanzar, Maysamreza; Alam, Mohammad-Reza

    2015-10-01

    We show that significant water wave amplification is obtained in a water resonator consisting of two spatially separated patches of small-amplitude sinusoidal corrugations on an otherwise flat seabed. The corrugations reflect the incident waves according to the so-called Bragg reflection mechanism, and the distance between the two sets controls whether the trapped reflected waves experience constructive or destructive interference within the resonator. The resulting amplification or suppression is enhanced with increasing number of ripples and is most effective for specific resonator lengths and at the Bragg frequency, which is determined by the corrugation period. Our analysis draws on the analogous mechanism that occurs between two partially reflecting mirrors in optics, a phenomenon named after its discoverers Charles Fabry and Alfred Perot.

  14. Line-imaging Fabry-Perot interferometer

    Energy Technology Data Exchange (ETDEWEB)

    Mathews, A.R.; Warnes, R.H.; Hemsing, W.F.; Whittemore, G.R.

    1990-01-01

    A method for measuring the velocity history of a line element on a shock-loaded solid has been demonstrated. Light from single-frequency laser is focused through a cylindrical lens to a line on a moving target. The return Doppler-shifted image is passed through a Fabry-Perot interferometer. Because only specific combinations of incident light angle and frequency can pass through the interferometer the output is an incomplete image of the moving target appearing as a set of fringes. This image is focused onto an electronic streak camera and swept in time. The fringe pattern changes with time as the target surface moves, allowing determination of velocity for each point on the target that forms a fringe. Because the velocity can only be measured at the fringe positions, it is necessary to use an interpolating polynomial to obtain a continuous function of time and velocity along the sampled lien. 9 refs., 7 figs.

  15. The many facets of the Fabry-Perot

    CERN Document Server

    Sanchez-Soto, Luis L; Leuchs, Gerd

    2016-01-01

    We address the response, both in amplitude and intensity, of a Fabry-Perot from a variety of viewpoints. These complementary pictures conspire to achieve a comprehensive and consistent theory of the operation of this system.

  16. Predictors of time to initiation of symptomatic therapy in early Parkinson's disease.

    Science.gov (United States)

    Simuni, Tanya; Long, Jeffrey D; Caspell-Garcia, Chelsea; Coffey, Christopher S; Lasch, Shirley; Tanner, Caroline M; Jennings, Danna; Kieburtz, Karl D; Marek, Kenneth

    2016-07-01

    To determine clinical and biological variables that predict time to initiation of symptomatic therapy in de novo Parkinson's disease patients. Parkinson's Progression Markers Initiative is a longitudinal case-control study of de novo, untreated Parkinson's disease participants at enrolment. Participants contribute a wide range of motor and non-motor measures, including biofluids and imaging biomarkers. The machine learning method of random survival forests was used to examine the ability of baseline variables to predict time to initiation of symptomatic therapy since study enrollment (baseline). There were 423 PD participants enrolled in PPMI and 33 initial baseline variables. Cross-validation results showed that the three-predictor subset of disease duration (time from diagnosis to enrollment), the modified Schwab and England activities of daily living scale, and the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score modestly predicted time to initiation of symptomatic therapy (C = 0.70, pseudo-R (2) = 0.13). Prediction using the three variables was similar to using the entire set of 33. None of the biological variables increased accuracy of the prediction. A prognostic index for time to initiation of symptomatic therapy was created using the linear and nonlinear effects of the three top variables based on a post hoc Cox model. Our findings using a novel machine learning method support previously reported clinical variables that predict time to initiation of symptomatic therapy. However, the inclusion of biological variables did not increase prediction accuracy. Our prognostic index constructed, based on the group-level survival curve can provide an indication of the risk of initiation of ST for PD patients based on functions of the three top predictors.

  17. Pulmonary Nodules as an Initial Manifestation of Behçet's Disease

    DEFF Research Database (Denmark)

    Malekmohammad, M; Emamifar, A

    2014-01-01

    Behçet's disease (BD) is a systemic vasculopathy, characterized by recurrent oral aphthae, genital ulcers, uveitis, and skin lesions. Although vascular involvement, including venous and arteries of any size, is a usual manifestation, cases with pulmonary thrombosis as the initial symptom are not ......Behçet's disease (BD) is a systemic vasculopathy, characterized by recurrent oral aphthae, genital ulcers, uveitis, and skin lesions. Although vascular involvement, including venous and arteries of any size, is a usual manifestation, cases with pulmonary thrombosis as the initial symptom...

  18. The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

    OpenAIRE

    Weiner, MW; Veitch, DP; Aisen, PS; Beckett, LA; Cairns, NJ; Green, RC; Harvey, D.; Jack, CR; Jagust, W.; Morris, JC; Petersen, RC; Salazar, J.; Saykin, AJ; Shaw, LM; Toga, AW

    2017-01-01

    © 2016 the Alzheimer's Association Introduction The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. Methods ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connec...

  19. Effect of Three Cueing Devices for People with Parkinson’s disease with Gait Initiation Difficulties

    OpenAIRE

    Mccandless, Paula; Evans, Brenda Joy; Janssen, Jessica; Selfe, James; Churchill, Andrew; Richards,James

    2015-01-01

    Background: Freezing of gait (FOG) remains one of the most common debilitating aspects of Parkinson’s disease and has been linked to injuries, falls and reduced quality of life. Although commercially available portable cueing devices exist claiming to assist with overcoming freezing; their immediate effectiveness in overcoming gait initiation failure currently unknown. This study investigated the effects of three different types of cueing device in people with Parkinson’s disease who experien...

  20. Integrating gut microbiota immaturity and disease-discriminatory taxa to diagnose the initiation and severity of shrimp disease.

    Science.gov (United States)

    Xiong, Jinbo; Zhu, Jinyong; Dai, Wenfang; Dong, Chunming; Qiu, Qiongfen; Li, Chenghua

    2017-04-01

    Increasing evidence has emerged a tight link among the gut microbiota, host age and health status. This osculating interplay impedes the definition of gut microbiome features associated with host health from that in developmental stages. Consequently, gut microbiota-based prediction of health status is promising yet not well established. Here we firstly tracked shrimp gut microbiota (N = 118) over an entire cycle of culture; shrimp either stayed healthy or progressively transitioned into severe disease. The results showed that the gut microbiota were significantly distinct over shrimp developmental stages and disease progression. Null model and phylogenetic-based mean nearest taxon distance (MNTD) analyses indicated that deterministic processes that governed gut community became less important as the shrimp aged and disease progressed. The predicted gut microbiota age (using the profiles of age-discriminatory bacterial species as independent variables) fitted well (r = 0.996; P shrimp, but sharply decreased when disease emerged. By distinguishing between age- and disease- discriminatory taxa, we developed a model, bacterial indicators of shrimp health status, to diagnose disease from healthy subjects with 91.5% accuracy. Notably, the relative abundances of the bacterial indicators were indicative for shrimp disease severity. These findings, in aggregate, add our understanding on the gut community assembly patterns over shrimp developmental stages and disease progression. In addition, shrimp disease initiation and severity can be accurately diagnosed using gut microbiota immaturity and bacterial indicators. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  1. Adolescence and Later Life Disease Burden: Quantifying the Contribution of Adolescent Tobacco Initiation From Longitudinal Cohorts.

    Science.gov (United States)

    Viner, Russell M; Hargreaves, Dougal S; Motta, Janaina Vieira Dos Santos; Horta, Bernardo; Mokdad, Ali H; Patton, George

    2017-08-01

    Adolescence is a time of initiation of behaviors leading to noncommunicable diseases (NCDs). We use tobacco to illustrate a novel method for assessing the contribution of adolescence to later burden. Data on initiation of regular smoking during adolescence (10-19 years) and current adult smoking were obtained from the 1958 British Birth Cohort, the U.S. National Longitudinal Study of Adolescent Health (Add Health), the Pelotas 1982 Birth Cohort, and the Victorian Adolescent Health Cohort Study. We estimated an "adolescent attributable fraction" (AAF) by calculating the proportion of persisting adult daily smoking initiated 155 countries using contemporary surveillance data. In the 1958 British Birth Cohort, 81.6% of daily smokers at age 50 years initiated adolescent initiation. The adjusted AAF was 69.1. Proportions of smokers initiating Adolescent Health Cohort Study; and 70.9%, 5.8%, and 56.9% in Pelotas males and 89.9%, 6.4%, and 75.9% in females. Initiation adolescent smoking initiation to adult smoking burden is high, suggesting a need to formulate and implement effective actions to reduce smoking initiation in adolescents. Similar trends in other NCD risks suggest that adolescents will be central to future efforts to control NCDs. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  2. When to Initiate Disease-Modifying Drugs for Relapsing Remitting Multiple Sclerosis in Adults?

    Directory of Open Access Journals (Sweden)

    Mona Alkhawajah

    2011-01-01

    Full Text Available For patients with Relapsing Remitting Multiple Scierosis Beta Interfaerons and Glatiramer Acetate were the first to be licensed for treatment. This review deals with one major question: when to initiate therapy? Through exploring the unique characteristics of the disease and treatement we suggest an approach that should be helpful in the process of decision-making.

  3. Dietary patterns are associated with disease risk among participants in the women's health initiative observational study

    Science.gov (United States)

    Coronary heart disease (CHD) is the leading cause of death in women. A nested case-control study tested whether dietary patterns predicted CHD events among 1224 participants in the Women’s Health Initiative-Observational Study (WHI-OS) with centrally confirmed CHD, fatal or nonfatal myocardial infar...

  4. The Alzheimer’s Disease Neuroimaging Initiative Informatics Core: A Decade in Review

    Science.gov (United States)

    Toga, Arthur W.; Crawford, Karen L.

    2015-01-01

    The Informatics Core of the Alzheimer’s Diseases Neuroimaging Initiative (ADNI) has coordinated data integration and dissemination for a continually growing and complex dataset in which both data contributors and recipients span institutions, scientific disciplines and geographic boundaries. This article provides an update on the accomplishments and future plans. PMID:26194316

  5. Incidence and initial disease course of inflammatory bowel diseases in 2011 in Europe and Australia

    DEFF Research Database (Denmark)

    Vegh, Z; Burisch, J.; Pedersen, N.

    2014-01-01

    in the ECCO-EpiCom 2011 inception cohort. Patients' data regarding disease type, socio-demographic factors, extraintestinal manifestations and therapy were entered into the Web-based EpiCom database, www.ecco-epicom.eu. RESULTS: A total of 711 adult patients were diagnosed during the inclusion year 2011, 178...

  6. Initial Disease Course and Treatment in an Inflammatory Bowel Disease Inception Cohort in Europe

    DEFF Research Database (Denmark)

    Burisch, Johan; Pedersen, Natalia; Cukovic-Cavka, Silvja

    2014-01-01

    BACKGROUND: The EpiCom cohort is a prospective, population-based, inception cohort of inflammatory bowel disease (IBD) patients from 31 European centers covering a background population of 10.1 million. The aim of this study was to assess the 1-year outcome in the EpiCom cohort. METHODS: Patients...

  7. Chronic granulomatous otitis externa as an initial presentation of cutaneous Crohn disease.

    Science.gov (United States)

    Raynor, Eileen M

    2014-08-01

    In the limited number of Crohn disease cases involving the head and neck, there is a predilection for mucosal surfaces and rare reports of involvement in the postauricular region. To our knowledge, in all previously reported cases involving the head and neck, the patients had a known diagnosis of Crohn disease. This case describes a 10-year-old boy with a history of psoriasis and psoriasiform dermatitis who presented with bilateral chronic granulomatous otitis externa, obliteration of the external auditory canal, and fissuring, resulting in separation of the lobule from the preauricular skin. Pathologic examination results were consistent with granulomatous dermatitis concerning for cutaneous Crohn disease, and a subsequent gastroenterologic workup confirmed the diagnosis of Crohn disease. This is a report of chronic granulomatous otitis as the initial presentation of cutaneous Crohn disease in a child.

  8. Spirometry utilisation among Danish adults initiating medication targeting obstructive lung disease

    DEFF Research Database (Denmark)

    Koefoed, Mette

    2015-01-01

    with pharmacotherapy targeting obstructive lung disease and only few have additional tests conducted, although the predictive value of respiratory symptoms for diagnosing obstructive lung disease has proven to be low. Spirometry is recommended as the gold standard for confirming obstructive lung disease, and testing...... can also rule out airway obstruction in patients with respiratory symptoms caused by other illnesses, such as heart failure or lung cancer. Initiating medication for obstructive lung disease without spirometry entails the risk of these patients experiencing unnecessary delay in the diagnostic process......-infectious dyspnoea, chronic cough and wheezing are common symptoms in the population. Patients often present with these symptoms in general practice and have a high probability of having obstructive lung diseases. However, there is an indication that the majority of these patients are treated empirically...

  9. Spirometry utilisation among Danish adults initiating medication targeting obstructive lung disease

    DEFF Research Database (Denmark)

    Koefoed, Mette

    2015-01-01

    with pharmacotherapy targeting obstructive lung disease and only few have additional tests conducted, although the predictive value of respiratory symptoms for diagnosing obstructive lung disease has proven to be low. Spirometry is recommended as the gold standard for confirming obstructive lung disease, and testing...... and being exposed to unnecessary economic costs and medication risks. The literature has indicated that many users of medication targeting obstructive lung medication have not had spirometry performed and do not actually have obstructive lung disease. This potential quality gap needs to be assessed. Also......, in order to target interventions enhancing earlier spirometry utilisation among patients initiating medication targeting obstructive lung disease, improved knowledge on patient and practice factors associated with spirometry testing is needed. AIMS: Among first time users of obstructive lung medication we...

  10. High precision optical fiber Fabry-Perot sensor for gas pressure detection

    Science.gov (United States)

    Mao, Yan; Tong, Xing-lin

    2013-09-01

    An optical fiber Fabry-Perot (F-P) sensor with quartz diaphragm for gas pressure testing was designed and fabricated. It consisted of single-mode fiber, hollow glass tube and quartz diaphragm. It uses the double peak demodulation to obtain the initialized cavity length. The variety of cavity length can be calcultated by the single peak demodulation after changing the gas pressure. The results show that the sensor is small in size, whose sensitivity is 19 pm/kPa in the range of the 10 ~ 260 kPa gas pressure. And it has good linearity and repeatability.

  11. Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases

    Science.gov (United States)

    Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

    2016-01-01

    Context There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Objective Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and “others”). Methods We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Results Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and “true” effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. Conclusion The differences in reliability

  12. The GREGOR Fabry-P\\'erot Interferometer

    CERN Document Server

    Puschmann, K G; Kneer, F; Erdogan, N Al; Balthasar, H; Bauer, S M; Beck, C; González, N Bello; Collados, M; Hahn, T; Hirzberger, J; Hofmann, A; Louis, R E; Nicklas, H; Okunev, O; Pillet, V Martínez; Popow, E; Seelemann, T; Volkmer, R; Wittmann, A D; Woche, M

    2012-01-01

    The GREGOR Fabry-P\\'erot Interferometer (GFPI) is one of three first-light instruments of the German 1.5-meter GREGOR solar telescope at the Observatorio del Teide, Tenerife, Spain. The GFPI uses two tunable etalons in collimated mounting. Thanks to its large-format, high-cadence CCD detectors with sophisticated computer hard- and software it is capable of scanning spectral lines with a cadence that is sufficient to capture the dynamic evolution of the solar atmosphere. The field-of-view (FOV) of 50" x 38" is well suited for quiet Sun and sunspot observations. However, in the vector spectropolarimetric mode the FOV reduces to 25" x 38". The spectral coverage in the spectroscopic mode extends from 530-860 nm with a theoretical spectral resolution R of about 250,000, whereas in the vector spectropolarimetric mode the wavelength range is at present limited to 580-660 nm. The combination of fast narrow-band imaging and post-factum image restoration has the potential for discovery science concerning the dynamic Su...

  13. The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

    Energy Technology Data Exchange (ETDEWEB)

    Weiner, Michael W. [Dept. of Veterans Affairs Medical Center, San Francisco, CA (United States); Univ. of California, San Francisco, CA (United States); Veitch, Dallas P. [Dept. of Veterans Affairs Medical Center, San Francisco, CA (United States); Aisen, Paul S. [Univ. of Southern California, San Diego, CA (United States); Beckett, Laurel A. [Univ. of California, Davis, CA (United States); Cairns, Nigel J. [Washington Univ. School of Medicine, St. Louis, MO (United States); Green, Robert C. [Brigham and Women' s Hospital and Harvard Medical School, Boston, MA (United States); Harvey, Danielle [Univ. of California, Davis, CA (United States); Jack, Clifford R. [Mayo Clinic, Rochester, MN (United States); Jagust, William [Univ. of California, Berkeley, CA (United States); Morris, John C. [Univ. of Southern California, San Diego, CA (United States); Petersen, Ronald C. [Mayo Clinic, Rochester, MN (United States); Salazar, Jennifer [Univ. of Southern California, San Diego, CA (United States); Saykin, Andrew J. [Indiana Univ. School of Medicine, Indianapolis, IN (United States); Shaw, Leslie M. [Eli Lilly and Company, Indianapolis, IN (United States); Toga, Arthur W. [Univ. of Southern California, Los Angeles, CA (United States); Trojanowski, John Q. [Univ. of Pennsylvania, Philadelphia, PA (United States)

    2016-12-05

    Overall, the goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning will be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition. Multimodal analyses will provide insight into AD pathophysiology and disease progression. Finally, ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments.

  14. The influence of age at disease onset on disease activity and disability: results from the Ontario Best Practices Research Initiative.

    Science.gov (United States)

    Ruban, T N; Jacob, B; Pope, J E; Keystone, E C; Bombardier, C; Kuriya, B

    2016-03-01

    This study aims to compare characteristics between late-onset rheumatoid arthritis (RA) and young-onset RA and determine the association between age at disease onset and disease severity. We cross-sectionally studied 971 patients at the time of entry into the Ontario Best Practices Research Initiative, a registry of RA patients followed up in routine care. We restricted patients to ≤5 years of disease duration. Late-onset RA was defined as an onset ≥60 years of age and young-onset RA <60 years. Group differences were compared, and multivariate linear regression models were used to test the influence of age at onset on Disease Activity Score in 28 Joints with erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), and Health Assessment Questionnaire (HAQ) scores. The swollen joint count (6.2 vs. 5.3), acute phase reactants (C-reactive protein (CRP) 17.4 vs. 11.8 mg/L, ESR 30.6 vs. 21.5 mm/h), and comorbidity burden were higher in late-onset RA compared to young-onset RA (p < 0.01). Mean DAS28-ESR (4.6 vs. 4.3) and HAQ (1.2 vs. 1.1) scores were higher in late-onset RA patients (p < 0.05). Late-onset RA patients received more initial disease-modifying antirheumatic drug (DMARD) monotherapy and corticosteroids in comparison to greater DMARD/biologic combination therapy in young-onset RA patients (p < 0.05). Adjusted multivariate analyses showed that late-onset RA was independently associated with higher mean DAS28-ESR and HAQ scores, but not CDAI. Late-onset RA patients have greater disease activity that may contribute to disability early in the disease course. Despite this, initial treatment consists of less combination DMARD and biologic use in late-onset RA patients. This may have implications for future response to therapy and development of joint damage, disability, and comorbidities in this group.

  15. Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

    Science.gov (United States)

    Ioset, Jean-Robert; Chang, Shing

    2011-09-01

    The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

  16. Cardiac lesions and initial laboratory data in Kawasaki disease: a nationwide survey in Japan.

    Science.gov (United States)

    Kuwabara, Masanari; Yashiro, Mayumi; Kotani, Kazuhiko; Tsuboi, Satoshi; Ae, Ryusuke; Nakamura, Yosikazu; Yanagawa, Hiroshi; Kawasaki, Tomisaku

    2015-01-01

    Cardiac lesions, such as coronary dilatation, aneurysms, narrowing, myocardial infarction, and valvular lesions, sometimes occur in Kawasaki disease, but most studies have only evaluated cardiac lesions in the later phase of the disease. This study was undertaken to clarify the related factors between cardiac lesions and laboratory data in the initial phase of Kawasaki disease. We conducted a cross-sectional study using data for 26 691 patients from the 22nd nationwide survey of Kawasaki disease in Japan, the observation period of which was from January 2011 through December 2012. We excluded patients with recurrent Kawasaki disease and who were more than seven days from the start of symptoms at admission. We analyzed 23 155 cases (13 353 boys; mean age: 923 ± 734 days) with available laboratory data for white blood cell count, platelet count, serum albumin, and C-reactive protein (CRP). Cardiac lesions were detected in 984 cases (656 boys and 328 girls); lesions were classified as coronary dilatation (764 cases), coronary aneurysm (40), giant coronary aneurysm (6), coronary narrowing (3), and valvular lesions (204). The significant related factors of initial coronary dilatation were male sex (odds ratio [OR] 1.73), older age (OR per 100 days increase 1.03), higher platelet count (OR per 10 000 cells/µL increase 1.006), lower albumin (OR per 1 g/dL increase 0.66), and higher CRP (OR per 1 mg/dL increase 1.02). The factors related to coronary aneurysm were higher platelet count (OR 1.01) and lower albumin (OR 0.34). No factors were significantly related to giant coronary aneurysm. The related factors of valvular lesions were age (OR 0.98), and higher CRP (OR 1.05). Clinicians should consider male sex, older age, higher platelet count, lower albumin levels, and higher CRP levels when assessing risk of cardiac lesions in the initial phase of Kawasaki disease.

  17. Coagulopathy as initial manifestation of concomitant celiac disease and cystic fibrosis: a case report

    Directory of Open Access Journals (Sweden)

    Zdraveska Nikolina

    2011-03-01

    Full Text Available Abstract Introduction Celiac disease and cystic fibrosis have many common manifestations, such as malabsorption, steatorrhea and growth failure, and were for many years recognized as one clinical entity. Since their recognition as two separate diseases, their co-existence in a patient has been described sporadically; around 20 cases have been described in the literature. Taking into consideration the incidences of the two diseases, the chance of them occurring together is one in 2,000,000 in the general population. Case presentation We describe the case of a five-year-old boy of Turkish ethnicity with both celiac disease and cystic fibrosis, who presented initially with a skin hemorrhage. The diagnosis of celiac disease was made with a positive serum anti-tissue transglutaminase antibody test and the presence of HLA-DQ2 heterodimer, and confirmed on histology with small intestinal villous atrophy. A positive sweat test confirmed the diagnosis of associated cystic fibrosis. To the best of our knowledge there has been no previous report of this rare presentation of associated celiac disease and cystic fibrosis. Conclusion The clinical significance of this case is the consideration of malabsorption with both celiac disease and cystic fibrosis in patients who present with unexplained coagulopathy.

  18. The Alzheimer's disease neuroimaging initiative: perspectives of the Industry Scientific Advisory Board.

    Science.gov (United States)

    Schmidt, Mark E; Siemers, Eric; Snyder, Peter J; Potter, William Z; Cole, Patricia; Soares, Holly

    2010-05-01

    The Industry Scientific Advisory Board (ISAB) consists of representatives from the private companies and nonprofit foundations participating as sponsors of Alzheimer's Disease Neuroimaging Initiative (ADNI). Currently 21 companies are represented including pharmaceutical, imaging, and biotech concerns, and two foundations including the Alzheimer's Association. ISAB members meet regularly by teleconference or face-to-face at ADNI meetings and participate in the ADNI Core groups, all administered and organized by the Foundation for the National Institutes of Health. ISAB 'deliverables' include dissemination of information to sponsors, assisting in scientific review of protocols and results, initiation and consideration of "add-on" studies and analyses, and generation of consensus positions on industry priorities and concerns. Although positioned as an advisory body, ISAB also actively contributes to the ADNI mission of identifying biomarkers of disease progression.

  19. Oromandibular Dyskinesia as the Initial Manifestation of Late-Onset Huntington Disease

    Directory of Open Access Journals (Sweden)

    Dong-Seok Oh

    2011-10-01

    Full Text Available Huntington’s disease (HD is a neurodegenerative disorder characterized by a triad of choreoathetosis, dementia and dominant inheritance. The cause of HD is an expansion of CAG trinucleotide repeats in the HD gene. Typical age at onset of symptoms is in the 40s, but the disorder can manifest at any time. Late-onset (≥ 60 years HD is clinically different from other adult or juvenile onset HD and characterized by mild motor problem as the initial symptoms, shorter disease duration, frequent lack of family history, and relatively low CAG repeats expansion. We report a case of an 80-year-old female with oromandibular dyskinesia as an initial manifestation of HD and 40 CAG repeats.

  20. Infliximab as the First Retreatment in Patients with Kawasaki Disease Resistant to Initial Intravenous Immunoglobulin.

    Science.gov (United States)

    Youn, Youngmin; Kim, Jisoo; Hong, Young Mi; Sohn, Sejung

    2016-04-01

    Forty-three patients with Kawasaki disease who were resistant to initial intravenous immunoglobulin (IVIG) were randomized to receive either a second dose of IVIG (n = 32) or an infliximab (n = 11). With IVIG retreatment 21 patients (65.6%) responded, and with infliximab 10 patients (90.9%) responded. The infliximab group had shorter duration of fever and fewer days of hospitalization. Coronary artery outcomes and adverse events were similar.

  1. Two cases of possible neuro-Sweet disease with meningoencephalitis as the initial manifestation

    OpenAIRE

    Go Makimoto; Yasuhiro Manabe; Chizuru Yamakawa; Daiki Fujii; Yasuko Ikeda-Sakai; Hisashi Narai; Nobuhiko Omori; Koji Abe

    2012-01-01

    We report 2 cases that were considered to be neuro-Sweet disease. They initially manifested with meningoencephalitis and no skin lesions, and rapidly improved with corticosteroid therapy. In both cases, patients complained of meningitic symptoms such as fever and headache, and HLA-B54 and -Cw1 turned out to be positive over the clinical course. Cerebrospinal fluid analysis showed increased levels of lymphocytes and protein. In case #1, fluid-attenuated inversion recovery (FLAIR), magnetic res...

  2. Vascular and Alzheimer's disease markers independently predict brain atrophy rate in Alzheimer's Disease Neuroimaging Initiative controls.

    Science.gov (United States)

    Barnes, Josephine; Carmichael, Owen T; Leung, Kelvin K; Schwarz, Christopher; Ridgway, Gerard R; Bartlett, Jonathan W; Malone, Ian B; Schott, Jonathan M; Rossor, Martin N; Biessels, Geert Jan; DeCarli, Charlie; Fox, Nick C

    2013-08-01

    This study assessed relationships among white matter hyperintensities (WMH), cerebrospinal fluid (CSF), Alzheimer's disease (AD) pathology markers, and brain volume loss. Subjects included 197 controls, 331 individuals with mild cognitive impairment (MCI), and 146 individuals with AD with serial volumetric 1.5-T MRI. CSF Aβ1-42 (n = 351) and tau (n = 346) were measured. Brain volume change was quantified using the boundary shift integral (BSI). We assessed the association between baseline WMH volume and annualized BSI, adjusting for intracranial volume. We also performed multiple regression analyses in the CSF subset, assessing the relationships of WMH and Aβ1-42 and/or tau with BSI. WMH burden was positively associated with BSI in controls (p = 0.02) but not MCI or AD. In multivariable models, WMH (p = 0.003) and Aβ1-42 (p = 0.001) were independently associated with BSI in controls; in MCI Aβ1-42 (p brain atrophy in the context of AD pathology in pre-dementia stages.

  3. Impact of the Alzheimer’s Disease Neuroimaging Initiative, 2004 to 2014

    Science.gov (United States)

    Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Cedarbaum, Jesse; Donohue, Michael C.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Shaw, Leslie; Thompson, Paul M.; Toga, Arthur W.; Trojanowski, John Q.

    2015-01-01

    Introduction The Alzheimer’s Disease Neuroimaging Initiative (ADNI) was established in 2004 to facilitate the development of effective treatments for Alzheimer’s disease (AD) by validating biomarkers for AD clinical trials. Methods We searched for ADNI publications using established methods. Results ADNI has (1) developed standardized biomarkers for use in clinical trial subject selection and as surrogate outcome measures; (2) standardized protocols for use across multiple centers; (3) initiated worldwide ADNI; (4) inspired initiatives investigating traumatic brain injury and post-traumatic stress disorder in military populations, and depression, respectively, as an AD risk factor; (5) acted as a data-sharing model; (6) generated data used in over 600 publications, leading to the identification of novel AD risk alleles, and an understanding of the relationship between biomarkers and AD progression; and (7) inspired other public-private partnerships developing biomarkers for Parkinson’s disease and multiple sclerosis. Discussion ADNI has made myriad impacts in its first decade. A competitive renewal of the project in 2015 would see the use of newly developed tau imaging ligands, and the continued development of recruitment strategies and outcome measures for clinical trials. PMID:26194320

  4. Calibrating echelle spectrographs with Fabry-Perot etalons

    CERN Document Server

    Bauer, Florian F; Reiners, Ansgar

    2015-01-01

    Over the past decades hollow-cathode lamps have been calibration standards for spectroscopic measurements. Advancing to cm/s radial velocity precisions with the next generation of instruments requires more suitable calibration sources with more lines and less dynamic range problems. Fabry-Perot interferometers provide a regular and dense grid of lines and homogeneous amplitudes making them good candidates for next generation calibrators. We investigate the usefulness of Fabry-Perot etalons in wavelength calibration, present an algorithm to incorporate the etalon spectrum in the wavelength solution and examine potential problems. The quasi periodic pattern of Fabry-Perot lines is used along with a hollow-cathode lamp to anchor the numerous spectral features on an absolute scale. We test our method with the HARPS spectrograph and compare our wavelength solution to the one derived from a laser frequency comb. The combined hollow-cathode lamp/etalon calibration overcomes large distortion (50 m/s) in the wavelengt...

  5. [A case of Wilson's disease in an elderly patient initially diagnosed with NASH].

    Science.gov (United States)

    Seishima, Jun; Sakai, Yoshio; Kitahara, Noriaki; Kitamura, Kazuya; Arai, Kuniaki; Kagaya, Takashi; Yamashita, Tatsuya; Mizukoshi, Eishiro; Honda, Masao; Kaneko, Shuichi

    2015-02-01

    A 62-year-old female was admitted to our hospital for examination of icterus and thrombocytopenia. She had a history of diabetes mellitus (under treatment), and liver cirrhosis was evident on abdominal CT. Because she was clinically obese and had no past history of alcohol consumption, the initial diagnosis was NASH. However, subsequent MRI findings and normal serum transaminase levels were not consistent with this diagnosis. We then performed additional examinations, including liver biopsy, measurements of serum Cu and ceruloplasmin concentrations, and measurement of urinary Cu secretion, which resulted in a diagnosis of Wilson's disease. It is necessary to include Wilson's disease in the differential diagnosis of NASH in cases of unidentified liver disease even among elderly patients.

  6. Sterile pyuria as the initial finding in a case with Kawasaki disease

    Directory of Open Access Journals (Sweden)

    Bahar Büyükkaragöz

    2015-09-01

    Full Text Available Kawasaki disease is a multisystemic vasculitis of pediatric age group. Early diagnosis and treatment is crucial as coronary artery aneurysms may develop in 20-25% of untreated cases in the 2nd-3rd weeks of the disease. The most common urinary finding in the active period is sterile pyuria; which is believed to be a sign of a more severe systemic inflammation. In this study, a 3.5 year old boy who admitted with high fever was presented. As he had pyuria and elevated acute phase reactants, antibiotic treatment was started with a pre-diagnosis of acute pyelonephritis. Later, with the persistence of fever, detection of a negative urine culture result and emergence of dermal, mucosal and conjunctival changes, incomplete Kawasaki disease (KD was diagnosed. In conclusion, it should be remembered that prolonged fever with sterile pyuria can be the initial findings in KD; before the emergence of typical lesions.

  7. Carpal spasm in a girl as initial presentation of celiac disease: a case report.

    Science.gov (United States)

    Ramosaj-Morina, Atifete; Keka-Sylaj, A; Hasbahta, V; Baloku-Zejnullahu, A; Azemi, M; Zunec, R

    2017-09-04

    Celiac disease is an immune-mediated disorder elicited by ingestion of gluten in genetically susceptible persons. This disorder is characterized by specific histological changes of the small intestine mucosa resulting in malabsorption. This case was written up as it was an unusual and dramatic presentation of celiac disease. We report the case of a 3-year-old Albanian girl who presented at our clinic with carpal spasms and hand paresthesia. A physical examination at admission revealed a relatively good general condition and body weight of 10.5 kg (10 percentile). Carpal spasms and paresthesias of her extremities were present. Neuromuscular irritability was demonstrated by positive Chvostek and Trousseau signs. Blood tests showed severe hypocalcemia with a total serum calcium of 1.2 mmol/L (normal range 2.12 to 2.55 mmol/L), ionized calcium of 0.87 (normal range 1.11 to 1.30 mmol/L), and 24-hour urine calcium excretion of 9.16 mmol (normal range female celiac disease was performed: antigliadin immunoglobulin A, anti-tissue transglutaminase, and anti-endomysial immunoglobulin A antibodies were positive. A duodenal biopsy revealed lymphocyte infiltration, crypt hyperplasia, and villous atrophy compatible with celiac disease grade IIIb according to the Marsh classification. Following the diagnosis of celiac disease, human leukocyte antigen typing was performed, giving a definite diagnosis of celiac disease. She was started on a gluten-free diet. Due to failure to follow a gluten-free diet, episodes of carpal spasms appeared again. Unfortunately, at the age of 7 years she presents with delayed psychophysical development. Although hypocalcemia is a common finding in celiac disease, hypocalcemic carpal spasm is a rare initial manifestation of the disease. Therefore, the possibility of celiac disease should be considered in patients with repeated carpal spasms that seem unduly difficult to treat. This should be evaluated even in the absence of gastrointestinal

  8. Attenuation of disease phenotype through alternative translation initiation in low-penetrance retinoblastoma.

    Science.gov (United States)

    Sánchez-Sánchez, Francisco; Ramírez-Castillejo, Carmen; Weekes, Daniel B; Beneyto, Magdalena; Prieto, Félix; Nájera, Carmen; Mittnacht, Sibylle

    2007-02-01

    Hereditary predisposition to retinoblastoma (RB) is caused by germline mutations in the retinoblastoma 1 (RB1) gene and transmits as an autosomal dominant trait. In the majority of cases disease develops in greater than 90% of carriers. However, reduced penetrance with a large portion of disease-free carrier is seen in some families. Unambiguous identification of the predisposing mutation in these families is important for accurate risk prediction in relatives and their genetic counseling but also provides conceptual information regarding the relationship between the RB1 genotype and the disease phenotype. In this study we report a novel mutation detected in 10 individuals of an extended family, only three of whom are affected by RB disease. The mutation comprises a 23-basepair (bp) duplication in the first exon of RB1 (c.43_65dup) producing a frameshift in exon 1 and premature chain termination in exon 2. Mutations resulting in premature chain termination classically are associated with high penetrance disease, as message translation may not generate functional product and nonsense mediated RNA decay (NMD) frequently eliminates the mutant transcript. However, appreciable NMD does not follow from the mutation described here and transcript expression in tissue culture cells and translation in vitro reveals that alternative in-frame translation start sites involving Met113 and possibly Met233 are used to generate truncated RB1 products (pRB94 and pRB80), known and suspected to exhibit tumor suppressor activity. These results strongly suggest that modulation of disease penetrance in this family is achieved by internal translation initiation. Our observations provide the first example for rescue of a chain-terminating mutation in RB1 through alternative translation initiation.

  9. Time Delay Properties of a Fabry-Perot Interferometer

    Institute of Scientific and Technical Information of China (English)

    YUAN Shi; MAN Wei-Ning; YU Jin; GAO Jin-Yue

    2001-01-01

    The time delay properties of a Fabry-Perot interferometer are investigated. We found that the group velocity of light through a Fabry-Perot interferometer can be reduced to 10-4 of the light speed in vacuum and the time delay is 210ns, when the reflectivity is 0.999 and the distance between two mirrors is 1 cm. The system is analogous to the recently proposed one-dimensional photonic band-gap structures with a defect [Zhu et al. Opt.Commun. 174(2000)139].

  10. Perturbations of ground support alter posture and locomotion coupling during step initiation in Parkinson's disease.

    Science.gov (United States)

    Rogers, Mark W; Hilliard, Marjorie Johnson; Martinez, Katherine M; Zhang, Yunhui; Simuni, Tanya; Mille, Marie-Laure

    2011-02-01

    During the initiation of stepping, anticipatory postural adjustments (APAs) for lateral weight transfer and propulsion normally precede the onset of locomotion. In Parkinson's disease (PD), impaired step initiation typically involves altered APA ground force production with delayed step onset and deficits in stepping performance. If, as in stance and gait, sensory information about lower limb load is important for the control of stepping, then perturbations influencing loading conditions could affect the step initiation process. This study investigated the influence of changes in lower limb loading during step initiation in patients with PD and healthy control subjects. Participants performed rapid self-triggered step initiation with the impending single stance limb positioned over a pneumatically actuated platform. In perturbation trials, the stance limb ground support surface was either moved vertically downward (DROP) or upward (ELEVATE) by 1.5 cm shortly after the onset of the APA phase. Overall, PD patients demonstrated a longer APA duration, longer time to first step onset, and slower step speed than controls. In both groups, the DROP perturbation reinforced the intended APA kinetic changes for lateral weight transfer and resulted in a significant reduction in APA duration, increase in peak amplitude, and earlier time to first step onset compared with other conditions. During ELEVATE trials that opposed the intended weight transfer forces both groups rapidly adapted their stepping to preserve standing stability by decreasing step length and duration, and increasing step height and foot placement laterally. The findings suggested that sensory information associated with limb load and/or foot pressure modulates the spatial and temporal parameters of posture and locomotion components of step initiation in interaction with a centrally generated feedforward mode of neural control. Moreover, impaired step initiation in PD may at least acutely be enhanced by

  11. Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients

    Directory of Open Access Journals (Sweden)

    Hollak Carla EM

    2011-10-01

    Full Text Available Abstract Background Enzyme replacement therapy is currently the only approved therapy for Fabry disease. From June 2009 on, viral contamination of Genzyme's production facility resulted in a worldwide shortage of agalsidase beta leading to involuntary dose reductions (approved dose 1 mg/kg/eow, reduced dose 0.5 mg/kg/m, or switch to agalsidase alpha (administered dose 0.2 mg/kg/eow. An assessment report from the European Medicines Agency (EMA raised serious concerns about an increase in adverse events at lower dosages of agalsidase beta. We determined the influence of the shortage on clinical event incidence and the most sensitive biochemical marker (lysoGb3 in Dutch Fabry patients. Methods The incidence of clinical events per person per year was calculated from start of agalsidase beta treatment until the shortage, and was compared to the incidence of clinical events during the shortage period. In addition, plasma lysoGb3, eGFR, quality of life (SF-36 and brief pain inventory (BPI questionnaires were analysed. Results All thirty-five Dutch Fabry patients using agalsidase beta (17 males were included. Mean clinical event incidence was unchanged: 0.15 events per person per year before versus 0.15 during the shortage (p = 0.68. In total 28 clinical events occurred in 14 patients during 4.6 treatment years, compared to 7 events in 6 patients during the 1.3 year shortage period. eGFR and BPI scores were not significantly altered. Two SF-36 subscales were significantly but minimally reduced in females. In males, lysoGb3 increased with a median of 8.1 nM (range 2.5 - 29.2 after 1 year of shortage (p = 0.001. Increases in lysoGb3 were found in both patients switching to agalsidase alpha and on a reduced agalsidase beta dose. Antibody status, treatment duration or clinical event incidence showed no clear correlation to lysoGb3 increases. Conclusions No increase in clinical event incidence was found in the adult Dutch Fabry cohort during the agalsidase

  12. Use of combination antihypertensive therapy initiation in older Americans without prevalent cardiovascular disease.

    Science.gov (United States)

    Li, Xiaojuan; Camelo Castillo, Wendy; Stürmer, Til; Pate, Virginia; Gray, Christine L; Simpson, Ross J; Setoguchi, Soko; Hanson, Laura C; Jonsson Funk, Michele

    2014-09-01

    To describe new users of antihypertensive medications and identify predictors of combination therapy initiation in older Americans. Retrospective observational cohort study. Population-based study using U.S. Medicare fee-for-service healthcare claims (2007-2010). Medicare beneficiaries aged 65 and older with no recent diagnoses, procedures, or medications for cardiovascular disease who newly initiated an antihypertensive therapy (n = 275,493; 210,605 initiated monotherapy, 64,888 initiated combination therapy). Multivariable Poisson regression was used to assess factors associated with initiation of combination therapy versus monotherapy, including participant characteristics, prescriber characteristics, and participant encounters with the healthcare system. Initiation of combination therapy increased from 21.9% in 2007 to 24.7% in 2010. The most frequently initiated combinations were angiotensin-converting enzyme inhibitors with thiazide (29.7%) and angiotensin II receptor antagonists with thiazide (18.7%). Blacks (prevalence ratio (PR) = 1.48, 95% confidence interval (CI) = 1.45-1.51 vs. whites), individuals seeing a generalist (PR = 1.10, 95% CI = 1.07-1.14), individuals seeing more than one doctor (PR = 3.38, 95% CI = 3.33-3.44), and participants with no pharmacy claims in the previous 6 months (PR = 1.34, 95% CI = 1.30-1.37 vs. ≥3 unique drug classes) were more likely to initiate combination therapy, whereas those who had more outpatient visits in the previous 12 months were less likely to initiate combination therapy (per five visits, PR = 0.82, 95% CI = 0.80-0.83). Nearly one in four new users of antihypertensive medications aged 65 and older started treatment with combination therapy. Blacks, individuals living in the south, and those with fewer outpatient physician office visits were more likely to initiate combination therapy. Further research is needed to determine whether this approach to managing hypertension is being well targeted to individuals who

  13. A Precision Medicine Initiative for Alzheimer's disease: the road ahead to biomarker-guided integrative disease modeling.

    Science.gov (United States)

    Hampel, H; O'Bryant, S E; Durrleman, S; Younesi, E; Rojkova, K; Escott-Price, V; Corvol, J-C; Broich, K; Dubois, B; Lista, S

    2017-04-01

    After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single 'magic bullet' drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine. It is hypothesized that deconstructing AD into multiple genetic and biological subsets existing within this heterogeneous target population will provide an effective PM strategy for treating individual patients with the specific agent(s) that are likely to work best based on the specific individual biological make-up. The Alzheimer's Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience. It is hypothesized that successful realization of PM in AD and other neurodegenerative diseases will result in breakthrough therapies, such as in oncology, with optimized safety profiles, better responder rates and treatment responses, particularly through biomarker-guided early preclinical disease-stage clinical trials.

  14. Autopsy-confirmed hippocampal-sparing Alzheimer's disease with delusional jealousy as initial manifestation.

    Science.gov (United States)

    Fujishiro, Hiroshige; Iritani, Shuji; Hattori, Miho; Sekiguchi, Hirotaka; Matsunaga, Shinji; Habuchi, Chikako; Torii, Youta; Umeda, Kentaro; Ozaki, Norio; Yoshida, Mari; Fujita, Kiyoshi

    2015-09-01

    Alzheimer's disease (AD) is clinically characterized by gradual onset over years with worsening of cognition. The initial and most prominent cognitive deficit is commonly memory dysfunction. However, a subset of AD cases has less hippocampal atrophy than would be expected relative to the predominance of cortical atrophy. These hippocampal-sparing cases have distinctive clinical features, including the presence of focal cortical clinical syndromes. Given that previous studies have indicated that severe hippocampal atrophy corresponds to prominent loss of episodic memory, it is likely that memory impairment is initially absent in hippocampal-sparing AD cases. Here, we report on a patient with an 8-year history of delusional jealousy with insidious onset who was clinically diagnosed as possible AD and pathologically confirmed to have AD with relatively preserved neurons in the hippocampus. This patient had delusional jealousy with a long pre-dementia stage, which initially was characterized by lack of memory impairment. Head magnetic resonance imaging findings showed preserved hippocampal volume with bilateral enlarged ventricles and mild-to-moderate cortical atrophy. Head single-photon emission computed tomography revealed severely decreased regional cerebral blood flow in the right temporal lobe. The resolution of the delusion was attributed to pharmacotherapy by an acetylcholinesterase inhibitor, suggesting that the occurrence of delusional jealousy was due to the disease process of AD. Although the neural basis of delusional jealousy remains unclear, this hippocampal-sparing AD case may be classified as an atypical presentation of AD.

  15. Non-infectious environmental antigens as a trigger for the initiation of an autoimmune skin disease.

    Science.gov (United States)

    Qian, Ye; Culton, Donna A; Jeong, Joseph S; Trupiano, Nicole; Valenzuela, Jesus G; Diaz, Luis A

    2016-09-01

    Pemphigus represents a group of organ specific autoimmune blistering disorders of the skin mediated by pathogenic autoantibodies with well-defined antigenic targets. While most of these diseases are sporadic, endemic forms of disease do exist. The endemic form of pemphigus foliaceus (also known as fogo selvagem, FS) exhibits epidemiological features that suggest exposure to hematophagous insect bites are a possible precipitating factor of this autoimmune disease, and provides a unique opportunity to study how environmental factors contribute to autoimmune disease development. FS patients and healthy individuals from endemic regions show an autoreactive IgM response that starts in early childhood and becomes restricted to IgG4 autoantibodies in FS patients. In searching for triggering environmental antigens, we have found that IgG4 and IgE autoantibodies from FS patients cross-react with a salivary antigen from sand flies. The presence of these cross-reactive antibodies and antibody genetic analysis confirming that these antibodies evolve from the same naïve B cells provides compelling evidence that this non-infectious environmental antigen could be the initial target of the autoantibody response in FS. Consequently, FS serves as an ideal model to study the impact of environmental antigens in the development of autoimmune disease.

  16. Meningococcal disease in the Asia-Pacific region: Findings and recommendations from the Global Meningococcal Initiative.

    Science.gov (United States)

    Borrow, Ray; Lee, Jin-Soo; Vázquez, Julio A; Enwere, Godwin; Taha, Muhamed-Kheir; Kamiya, Hajime; Kim, Hwang Min; Jo, Dae Sun

    2016-11-21

    The Global Meningococcal Initiative (GMI) is a global expert group that includes scientists, clinicians, and public health officials with a wide range of specialties. The purpose of the Initiative is to promote the global prevention of meningococcal disease (MD) through education, research, and cooperation. The first Asia-Pacific regional meeting was held in November 2014. The GMI reviewed the epidemiology of MD, surveillance, and prevention strategies, and outbreak control practices from participating countries in the Asia-Pacific region.Although, in general, MD is underreported in this region, serogroup A disease is most prominent in low-income countries such as India and the Philippines, while Taiwan, Japan, and Korea reported disease from serogroups C, W, and Y. China has a mixed epidemiology of serogroups A, B, C, and W. Perspectives from countries outside of the region were also provided to provide insight into lessons learnt. Based on the available data and meeting discussions, a number of challenges and data gaps were identified and, as a consequence, several recommendations were formulated: strengthen surveillance; improve diagnosis, typing and case reporting; standardize case definitions; develop guidelines for outbreak management; and promote awareness of MD among healthcare professionals, public health officials, and the general public.

  17. Polio eradication initiative in Africa: influence on other infectious disease surveillance development

    Directory of Open Access Journals (Sweden)

    Cochi Stephen

    2002-12-01

    Full Text Available Abstract Background The World Health Organization (WHO and partners are collaborating to eradicate poliomyelitis. To monitor progress, countries perform surveillance for acute flaccid paralysis (AFP. The WHO African Regional Office (WHO-AFRO and the U.S Centers for Disease Control and Prevention are also involved in strengthening infectious disease surveillance and response in Africa. We assessed whether polio-eradication initiative resources are used in the surveillance for and response to other infectious diseases in Africa. Methods During October 1999-March 2000, we developed and administered a survey questionnaire to at least one key informant from the 38 countries that regularly report on polio activities to WHO. The key informants included WHO-AFRO staff assigned to the countries and Ministry of Health personnel. Results We obtained responses from 32 (84% of the 38 countries. Thirty-one (97% of the 32 countries had designated surveillance officers for AFP surveillance, and 25 (78% used the AFP resources for the surveillance and response to other infectious diseases. In 28 (87% countries, AFP program staff combined detection for AFP and other infectious diseases. Fourteen countries (44% had used the AFP laboratory specimen transportation system to transport specimens to confirm other infectious disease outbreaks. The majority of the countries that performed AFP surveillance adequately (i.e., non polio AFP rate = 1/100,000 children aged Conclusions Despite concerns regarding the targeted nature of AFP surveillance, it is partially integrated into existing surveillance and response systems in multiple African countries. Resources provided for polio eradication should be used to improve surveillance for and response to other priority infectious diseases in Africa.

  18. Mathematical model of Fabry-Perot cavity filter%WDM设计中的Fabry-Perot腔传递函数模型

    Institute of Scientific and Technical Information of China (English)

    孙雅东; 武良春

    2003-01-01

    作为WDM(Wave Division Multiplexing)一个重要的器件,Fabry-Perot腔的相关设计和算法不断更新.笔者提出一种新的数学模型:把Fabry-Perot作为系统的一个参数对待,将信号与系统的知识纳入Fabry-Perot腔中,用系统的方法(梅森公式)求解Fabry-Perot腔的传递函数,避免了繁琐的矩阵运算,这样易于理解和优化设计.

  19. Tics as an initial manifestation of juvenile Huntington's disease: case report and literature review.

    Science.gov (United States)

    Cui, Shi-Shuang; Ren, Ru-Jing; Wang, Ying; Wang, Gang; Chen, Sheng-Di

    2017-08-08

    Huntington's disease (HD) is an autosomal dominant disorder, typically characterized by chorea due to a trinucleotide repeat expansion in the HTT gene, although the clinical manifestations of patients with juvenile HD (JHD) are atypical. A 17-year-old boy with initial presentation of tics attended our clinic and his DNA analysis demonstrated mutation in the HTT gene (49 CAG repeats). After treatment, his symptoms improved. Furthermore, we performed literature review through searching the databases and summarized clinical features in 33 JHD patients. The most prevalent symptoms are ataxia, and two cases reported that tics as initial and prominent manifestation in JHD. Among them, 88% patients carried CAG repeats beyond 60 and most of them have family history. This case here illustrates the variable range of clinical symptoms of JHD and the necessity of testing for the HD mutation in young patients with tics with symptoms unable to be explained by Tourette's syndrome (TS).

  20. Pulmonary Nodules as an Initial Manifestation of Behçet’s Disease

    Directory of Open Access Journals (Sweden)

    M. Malekmohammad

    2014-01-01

    Full Text Available Behçet’s disease (BD is a systemic vasculopathy, characterized by recurrent oral aphthae, genital ulcers, uveitis, and skin lesions. Although vascular involvement, including venous and arteries of any size, is a usual manifestation, cases with pulmonary thrombosis as the initial symptom are not common in the absence of pulmonary artery aneurysm (PAA. This report describes a 36-year-old man with recurrent fever, nonmassive hemoptysis, and persistent cough with lung nodules in CT scan who had undergone open lung biopsy. On the basis of morphological findings, BD was suggested and more precise evaluation confirmed the diagnosis.

  1. A Fabry-Perot Solid Etalon for Teaching.

    Science.gov (United States)

    Bruce, P. J.; And Others

    1986-01-01

    Describes a solid etalon Fabry-Perot interferometer, discussing free spectral range, instrumental finesse, and temperature effects. Provides schematic of temperature control/display circuit. Explains use of 100 millimeter camera lens and 10 power micrometer eyepiece for resolving rings and measure diameters. (JM)

  2. A Coaxial Cable Fabry-Perot Interferometer for Sensing Applications

    Directory of Open Access Journals (Sweden)

    Ming Luo

    2013-11-01

    Full Text Available This paper reports a novel coaxial cable Fabry-Perot interferometer for sensing applications. The sensor is fabricated by drilling two holes half-way into a coaxial cable. The device physics was described. The temperature and strain responses of the sensor were tested. The measurement error was calculated and analyzed.

  3. Development of the Fabry-Perot Spectrometer Application

    Science.gov (United States)

    Browne, Kathryn

    2015-01-01

    Methane is a greenhouse gas with global warming effects 20 times more detrimental than carbon dioxide. Currently, only aircraft missions measure methane and do not provide continuous monitoring, This presentation will cover the Fabry-Perot spectrometer which will provide continuous monitoring of methane. It will also cover the development of the software used to extract and process the data the spectrometer collects.

  4. Gamma irradiation of Fabry-Perot interband cascade lasers

    Energy Technology Data Exchange (ETDEWEB)

    Myers, Tanya L.; Cannon, Bret D.; Brauer, Carolyn S.; Canedy, Chadwick L.; Kim, Chul Soo; Kim, Mijin; Merritt, Charles D.; Bewley, William W.; Vurgaftman, Igor; Meyer, Jerry R.

    2017-09-20

    Two Fabry-Perot interband cascade lasers (ICLs) were exposed to Cobalt-60 gamma rays for a dosage of 500 krad(Si) each, which is higher than is typically encountered in space applications. The ICLs do not show any significant changes in threshold current or slope efficiency, suggesting the suitability of ICLs for use in radiation environments.

  5. Silicon Carbide Mounts for Fabry-Perot Interferometers

    Science.gov (United States)

    Lindemann, Scott

    2011-01-01

    Etalon mounts for tunable Fabry- Perot interferometers can now be fabricated from reaction-bonded silicon carbide structural components. These mounts are rigid, lightweight, and thermally stable. The fabrication of these mounts involves the exploitation of post-casting capabilities that (1) enable creation of monolithic structures having reduced (in comparison with prior such structures) degrees of material inhomogeneity and (2) reduce the need for fastening hardware and accommodations. Such silicon carbide mounts could be used to make lightweight Fabry-Perot interferometers or could be modified for use as general lightweight optical mounts. Heretofore, tunable Fabry-Perot interferometer structures, including mounting hardware, have been made from the low-thermal-expansion material Invar (a nickel/iron alloy) in order to obtain the thermal stability required for spectroscopic applications for which such interferometers are typically designed. However, the high mass density of Invar structures is disadvantageous in applications in which there are requirements to minimize mass. Silicon carbide etalon mounts have been incorporated into a tunable Fabry-Perot interferometer of a prior design that originally called for Invar structural components. The strength, thermal stability, and survivability of the interferometer as thus modified are similar to those of the interferometer as originally designed, but the mass of the modified interferometer is significantly less than the mass of the original version.

  6. Variable Free Spectral Range Spherical Mirror Fabry-Perot Interferometer

    CERN Document Server

    Kerner, K; Yashchuk, V V; Budker, D; Kerner, Katherine; Rochester, Simon M.; Yashchuk, Valeriy V.

    2003-01-01

    A spherical Fabry-Perot interferometer with adjustable mirror spacing is used to produce interference fringes with frequency separation (c/2L)/N, N=2-15. The conditions for observation of these fringes are derived from the consideration of the eigenmodes of the cavity with high transverse indices.

  7. Initial and long-term costs of patients hospitalized with West Nile virus disease.

    Science.gov (United States)

    Staples, J Erin; Shankar, Manjunath B; Sejvar, James J; Meltzer, Martin I; Fischer, Marc

    2014-03-01

    There are no published data on the economic burden for specific West Nile virus (WNV) clinical syndromes (i.e., fever, meningitis, encephalitis, and acute flaccid paralysis [AFP]). We estimated initial hospital and lost-productivity costs from 80 patients hospitalized with WNV disease in Colorado during 2003; 38 of these patients were followed for 5 years to determine long-term medical and lost-productivity costs. Initial costs were highest for patients with AFP (median $25,117; range $5,385-$283,381) and encephalitis (median $20,105; range $3,965-$324,167). Long-term costs were highest for patients with AFP (median $22,628; range $624-$439,945) and meningitis (median $10,556; range $0-$260,748). Extrapolating from this small cohort to national surveillance data, we estimated the total cumulative costs of reported WNV hospitalized cases from 1999 through 2012 to be $778 million (95% confidence interval $673 million-$1.01 billion). These estimates can be used in assessing the cost-effectiveness of interventions to prevent WNV disease.

  8. The Vietnam Initiative on Zoonotic Infections (VIZIONS): A Strategic Approach to Studying Emerging Zoonotic Infectious Diseases.

    Science.gov (United States)

    Rabaa, Maia A; Tue, Ngo Tri; Phuc, Tran My; Carrique-Mas, Juan; Saylors, Karen; Cotten, Matthew; Bryant, Juliet E; Nghia, Ho Dang Trung; Cuong, Nguyen Van; Pham, Hong Anh; Berto, Alessandra; Phat, Voong Vinh; Dung, Tran Thi Ngoc; Bao, Long Hoang; Hoa, Ngo Thi; Wertheim, Heiman; Nadjm, Behzad; Monagin, Corina; van Doorn, H Rogier; Rahman, Motiur; Tra, My Phan Vu; Campbell, James I; Boni, Maciej F; Tam, Pham Thi Thanh; van der Hoek, Lia; Simmonds, Peter; Rambaut, Andrew; Toan, Tran Khanh; Van Vinh Chau, Nguyen; Hien, Tran Tinh; Wolfe, Nathan; Farrar, Jeremy J; Thwaites, Guy; Kellam, Paul; Woolhouse, Mark E J; Baker, Stephen

    2015-12-01

    The effect of newly emerging or re-emerging infectious diseases of zoonotic origin in human populations can be potentially catastrophic, and large-scale investigations of such diseases are highly challenging. The monitoring of emergence events is subject to ascertainment bias, whether at the level of species discovery, emerging disease events, or disease outbreaks in human populations. Disease surveillance is generally performed post hoc, driven by a response to recent events and by the availability of detection and identification technologies. Additionally, the inventory of pathogens that exist in mammalian and other reservoirs is incomplete, and identifying those with the potential to cause disease in humans is rarely possible in advance. A major step in understanding the burden and diversity of zoonotic infections, the local behavioral and demographic risks of infection, and the risk of emergence of these pathogens in human populations is to establish surveillance networks in populations that maintain regular contact with diverse animal populations, and to simultaneously characterize pathogen diversity in human and animal populations. Vietnam has been an epicenter of disease emergence over the last decade, and practices at the human/animal interface may facilitate the likelihood of spillover of zoonotic pathogens into humans. To tackle the scientific issues surrounding the origins and emergence of zoonotic infections in Vietnam, we have established The Vietnam Initiative on Zoonotic Infections (VIZIONS). This countrywide project, in which several international institutions collaborate with Vietnamese organizations, is combining clinical data, epidemiology, high-throughput sequencing, and social sciences to address relevant one-health questions. Here, we describe the primary aims of the project, the infrastructure established to address our scientific questions, and the current status of the project. Our principal objective is to develop an integrated approach to

  9. Electrical Changes in Resting, Exercise, and Holter Electrocardiography in Fabry Cardiomyopathy.

    Science.gov (United States)

    Krämer, Johannes; Nordbeck, Peter; Störk, Stefan; Ritter, Christian; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

    2015-10-27

    In Fabry cardiomyopathy, little is known about the interaction between its key feature of myocardial replacement fibrosis and changes in resting, Holter, and exercise electrocardiography (-ECG). Resting ECG, 24-h Holter ECG, and exercise ECG were performed in 95 patients (50 women) with Fabry disease, staged using cardiac magnetic resonance imaging to measure left ventricular fibrosis. With resting ECG, T alterations were seen in patients with cardiac fibrosis, while time intervals and rhythm were unchanged (except for a longer QRS duration in patients with severe fibrosis). All patients with severe fibrosis showed T inversion, ST alteration, or both. With Holter ECG, maximum and minimum heart rate did not differ with fibrosis severity. Patients without fibrotic tissue showed less ventricular premature beats (VPB) (median 5/24 h) compared to those with mild (median 11/24 h) or severe fibrosis (median 115/24 h; P 10 mmHg) occurred in some patients with no (3/41) or mild fibrosis (3/34) but not in patients with severe fibrosis (0/20; P Holter ECG. During exercise ECG, advanced cardiomyopathy is characterized by chronotropic incompetence with limitations on blood pressure and heart rate increase.

  10. [The control of the transmission by transfusion of Chagas' disease in the Southern Cone Initiative].

    Science.gov (United States)

    Dias, J C; Schofield, C J

    1998-01-01

    The Southern Cone Initiative against Chagas' disease, was launched in 1991. The aim was to interrupt the transmission of Chagas disease by elimination of domestic populations of the major vector, Triatoma infestans, and by improved screening of blood donors. As a result of these activities, a marked reduction in the risk of transfusional transmission can now be seen throughout the programme area. In addition to specific legislation concerning the quality of transfused blood, a series of national and regional reference laboratories have been set up with the help of PAHO in order to improve the quality of pre-transfusional serodiagnosis. Results indicate a progressive reduction in the overall infection prevalence of blood donors, and show that the age-prevalence curve has shifted towards older age-groups. In this paper we analyse the changes in infection prevalence in the Southern Cone countries, drawing attention to the situation in Bolivia which has the highest indices of infection and lowest levels of coverage by the control programme. In this situation chemoprophylaxis of blood prior to transfusion may be recommended in accordance with PAHO criteria. In the medium term however, interruption of human Chagas disease transmission may be expected over most of the Southern Cone region, as long as the control activities are continued and consolidated through effective epidemiological surveillance.

  11. Adrenal medullary transplantation to the caudate nucleus in Parkinson's disease. Initial clinical results in 18 patients.

    Science.gov (United States)

    Allen, G S; Burns, R S; Tulipan, N B; Parker, R A

    1989-05-01

    Results from a pilot study of adrenal medullary autotransplantation for Parkinson's disease are presented. Eighteen patients were studied; 12 were followed up for 1 year, and 6 were followed up for 6 months. Four of 12 patients showed distinct improvement in the signs and symptoms of their disease, as assessed using the Columbia Rating Scale, at 1 year; none showed distinct deterioration. The 6 patients who were followed up for only 6 months were an average of 20 years older and generally more severely affected. None distinctly improved. Morbidity was considered to be minor and transient among the first 12 patients, while 4 of the last 6 patients experienced alteration in mental status lasting as long as several months. This problem has led us to conclude that older patients with preexisting cognitive impairment should not be included in future studies until the benefits are more clearly established. However, we believe that the distinct and persistent improvement seen in some of the younger patients warrants the initiation of a well-designed, randomized, and controlled trial of adrenal medullary autotransplantation for the purpose of confirming these results and assessing the effect of the procedure on the natural progression of Parkinson's disease.

  12. Two cases of possible neuro-Sweet disease with meningoencephalitis as the initial manifestation

    Directory of Open Access Journals (Sweden)

    Go Makimoto

    2012-02-01

    Full Text Available We report 2 cases that were considered to be neuro-Sweet disease. They initially manifested with meningoencephalitis and no skin lesions, and rapidly improved with corticosteroid therapy. In both cases, patients complained of meningitic symptoms such as fever and headache, and HLA-B54 and -Cw1 turned out to be positive over the clinical course. Cerebrospinal fluid analysis showed increased levels of lymphocytes and protein. In case #1, fluid-attenuated inversion recovery (FLAIR, magnetic resonance imaging (MRI and diffusion-weighted images (DWI showed high-intensity signals in the right dorsal medulla oblongata, bilateral dorsal midbrain, and left thalamus. In case #2, FLAIR and DWI showed high-intensity signals in the bilateral cerebellar cortex and left caudate nucleus. Symptoms and MRI images were markedly improved in both cases after corticosteroid pulse therapy. According to published diagnostic criteria, these 2 cases were considered possible neuro-Sweet disease. These cases suggest that the combination of meningoencephalitis and HLA specificity is important to consider the possibility of neuro-Sweet disease, even without skin lesions.

  13. Two cases of possible neuro-Sweet disease with meningoencephalitis as the initial manifestation

    Science.gov (United States)

    Makimoto, Go; Manabe, Yasuhiro; Yamakawa, Chizuru; Fujii, Daiki; Ikeda-Sakai, Yasuko; Narai, Hisashi; Omori, Nobuhiko; Abe, Koji

    2012-01-01

    We report 2 cases that were considered to be neuro-Sweet disease. They initially manifested with meningoencephalitis and no skin lesions, and rapidly improved with corticosteroid therapy. In both cases, patients complained of meningitic symptoms such as fever and headache, and HLA-B54 and -Cw1 turned out to be positive over the clinical course. Cerebrospinal fluid analysis showed increased levels of lymphocytes and protein. In case #1, fluid-attenuated inversion recovery (FLAIR), magnetic resonance imaging (MRI) and diffusion-weighted images (DWI) showed high-intensity signals in the right dorsal medulla oblongata, bilateral dorsal midbrain, and left thalamus. In case #2, FLAIR and DWI showed high-intensity signals in the bilateral cerebellar cortex and left caudate nucleus. Symptoms and MRI images were markedly improved in both cases after corticosteroid pulse therapy. According to published diagnostic criteria, these 2 cases were considered possible neuro-Sweet disease. These cases suggest that the combination of meningoencephalitis and HLA specificity is important to consider the possibility of neuro-Sweet disease, even without skin lesions. PMID:22593809

  14. Long-term survival after initial hospital admission for peripheral arterial disease in the lower extremities

    Directory of Open Access Journals (Sweden)

    Grobbee DE

    2009-08-01

    Full Text Available Abstract Background As the population ages, peripheral arterial disease (PAD in the lower extremities will become a larger public health problem. Awareness in patients as well clinicians of the high risk of morbidity and mortality is important but seems currently low. Insights in absolute mortality risks following admission for PAD in the lower extremities can be useful to improve awareness as they are easy to interpret. Methods A nationwide cohort of 4,158 patients with an initial admission for PAD in the lower extremities was identified through linkage of the national hospital and population register in 1997 and 2000. Results Over 60% of 4,158 patients were men. 28 days, 1 year and 5 year mortality risk were 2.4%, 10.3% and 31.0% for men and 3.5%, 10.4% and 27.4% for women. Coronary heart disease and stroke were frequent cause of death. Five years mortality risk was higher for men compared to women (HR 1.36, 95% CI 1.21–1.53. Conclusion In conclusion, our findings demonstrate that, 5 year mortality risk is high, especially in men and comparable to that of patients admitted for acute myocardial infarction or ischemic stroke. Though, in general population the awareness of the severity of PAD in the lower extremities is significantly lower than that for any other cardiovascular disease and it seems that cardiovascular risk factor management for prevention in PAD patients is very modest.

  15. Cognitive function in chronic obstructive pulmonary disease: relationship to global initiative for chronic obstructive lung disease 2011 categories.

    Science.gov (United States)

    Tulek, Baykal; Atalay, Nart Bedin; Yildirim, Gulfem; Kanat, Fikret; Süerdem, Mecit

    2014-08-01

    Recently, comorbidities such as impaired cognitive function have been attracting more focus when considering the management of chronic obstructive pulmonary disease (COPD). Here we investigated the relationship between cognitive function and the categories given in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in 2011. Specifically, after controlling for non-COPD covariates, we assessed the clinical features that may be predictive of cognitive impairment in patients with COPD. We recruited 119 stable patients with mild to very severe COPD. We administered a broad array of standardized neuropsychological tests that assessed cognitive functions in the domains of attention, memory, psychomotor coordination and language. Cognitive scores were significantly different between patients falling within GOLD 2011 categories. Scores were lower in patients with high future risk compared with low future risk. In parallel, there were significant differences in cognitive function between COPD patient subgroups when patients were grouped according to the forced expiratory volume in 1 s, exacerbation history and C-reactive protein levels. After controlling for non-COPD predictors, only exacerbation history remained a significant predictor of cognitive scores. The number of exacerbation events in a year may be used as a predictor of cognitive impairment in patients with COPD. © 2014 Asian Pacific Society of Respirology.

  16. The pilot European Alzheimer’s Disease Neuroimaging Initiative (E-ADNI) of the European Alzheimer’s Disease Consortium

    Science.gov (United States)

    Frisoni, Giovanni B; Henneman, Wouter JP; Weiner, Michael W; Scheltens, Philip; Vellas, Bruno; Reynish, Emma; Hudecova, Jaroslava; Hampel, Harald; Burger, Katharina; Blennow, Kaj; Waldemar, Gunhild; Johannsen, Peter; Wahlund, Lars-Olof; Zito, Giancarlo; Rossini, Paolo M; Winblad, Bengt; Barkhof, Frederik

    2008-01-01

    Background In North-America, the Alzheimer’s Disease Neuroimaging Initiative (ADNI) has established a platform to track the brain changes of Alzheimer’s disease. A pilot study has been carried out in Europe to test the feasibility of the adoption of the ADNI platform (pilot E-ADNI). Methods Seven academic sites of the European Alzheimer’s Disease Consortium (EADC) enrolled 19 patients with MCI, 22 with AD, and 18 older healthy persons using the ADNI clinical and neuropsychological battery. ADNI compliant MR scans, CSF and blood samples were shipped to central repositories. Medial temporal atrophy (MTA) and white matter hyperintensities (WMH) were assessed by a single rater using visual rating scales. Results Recruitment rate was 3.5 subjects per month per site. The cognitive, behavioural and neuropsychological features of the European subjects were very similar to their US counterparts. 3D T1-weighted MRI sequences were successfully performed on all subjects and CSF samples obtained from 77%, 68%, and 83% of AD, MCI, and controls. Mean MTA score showed a significant increase from controls (left, right: 0.4, 0.3) to MCI (0.9, 0.8) to AD (2.3, 2.0), while mean WMH score did not differ among the three diagnostic groups (between 0.7 and 0.9). The distribution of both MRI markers was comparable to matched US ADNI subjects. Conclusions Academic EADC centres can adopt the ADNI platform to enrol MCI and AD patients and older controls with global cognitive and structural imaging features remarkably similar to those of the US ADNI. PMID:18631976

  17. Multivariate protein signatures of pre-clinical Alzheimer's disease in the Alzheimer's disease neuroimaging initiative (ADNI plasma proteome dataset.

    Directory of Open Access Journals (Sweden)

    Daniel Johnstone

    Full Text Available BACKGROUND: Recent Alzheimer's disease (AD research has focused on finding biomarkers to identify disease at the pre-clinical stage of mild cognitive impairment (MCI, allowing treatment to be initiated before irreversible damage occurs. Many studies have examined brain imaging or cerebrospinal fluid but there is also growing interest in blood biomarkers. The Alzheimer's Disease Neuroimaging Initiative (ADNI has generated data on 190 plasma analytes in 566 individuals with MCI, AD or normal cognition. We conducted independent analyses of this dataset to identify plasma protein signatures predicting pre-clinical AD. METHODS AND FINDINGS: We focused on identifying signatures that discriminate cognitively normal controls (n = 54 from individuals with MCI who subsequently progress to AD (n = 163. Based on p value, apolipoprotein E (APOE showed the strongest difference between these groups (p = 2.3 × 10(-13. We applied a multivariate approach based on combinatorial optimization ((α,β-k Feature Set Selection, which retains information about individual participants and maintains the context of interrelationships between different analytes, to identify the optimal set of analytes (signature to discriminate these two groups. We identified 11-analyte signatures achieving values of sensitivity and specificity between 65% and 86% for both MCI and AD groups, depending on whether APOE was included and other factors. Classification accuracy was improved by considering "meta-features," representing the difference in relative abundance of two analytes, with an 8-meta-feature signature consistently achieving sensitivity and specificity both over 85%. Generating signatures based on longitudinal rather than cross-sectional data further improved classification accuracy, returning sensitivities and specificities of approximately 90%. CONCLUSIONS: Applying these novel analysis approaches to the powerful and well-characterized ADNI dataset has identified sets of

  18. Vulvar and vaginal graft versus host disease: A healthcare clinic initiative

    Directory of Open Access Journals (Sweden)

    Naomi Van Dam

    2017-01-01

    Full Text Available Objective: In patients receiving bone marrow transplantation (BMT, their mucosa becomes altered and sclerotic changes in the female external genital organs occur. Although a few studies have specifically addressed vulvar and vaginal graft versus host disease (VVGvHD and its repercussions on the sexual health and quality of life of patients, VVGvHD can be overlooked by health practitioners. The objective of the study is to describe the initiation of a health care clinic specializing in VVGvHD in a general tertiary hospital. Methods: A VVGvHD clinic was founded as a part of BMT daycare in a joint initiative of the nursing staff and the medical director of the department and a gynecologist specializing in vulva and vaginal disease. Patients were assessed for vulvovaginal symptoms, such as dryness, burning, itching, pain to touch, pain during intercourse, and dysuria. These patients might be subsequently referred to the VVGvHD clinic according to their needs assessed by daycare nurses. Treatment guidelines were developed by the specialist gynecologist. Results: A total of 81 women aged 2–66 years (median age = 38 years visited the clinic from 2009 to 2015. Of these women, 70 received an allogeneic transplant and 11 underwent autologous transplantation before consultation in our clinic. VVGvHD was detected in 54% of the patients. Conclusions: The VVGvHD clinic was developed to fulfill the specific needs of female patients who underwent BMT. The pioneer clinic was founded as a joint effort of the multidisciplinary team. Evidence supporting the optimum treatment for this condition is insufficient. This was the main reason for performing this study to explore the clinic that was newly based in Israel. VVGvHD may be a fluctuating condition with frequent deterioration and improvement. Therefore, regular clinical examinations are necessary.

  19. Lighten Up: Specific Postural Instructions Affect Axial Rigidity and Step Initiation in Patients With Parkinson's Disease.

    Science.gov (United States)

    Cohen, Rajal G; Gurfinkel, Victor S; Kwak, Elizabeth; Warden, Amelia C; Horak, Fay B

    2015-10-01

    Parkinson's disease (PD) is associated with stooped postural alignment, increased postural sway, and reduced mobility. The Alexander Technique (AT) is a mindfulness-based approach to improving posture and mobility by reducing muscular interference while maintaining upward intentions. Evidence suggests that AT can reduce disability associated with PD, but a mechanism for this effect has not yet been established. We investigated whether AT-based instructions reduce axial rigidity and increase upright postural alignment, and whether these instructions have different effects on postural alignment, axial rigidity, postural sway, and mobility than effort-based instructions regarding posture. Twenty subjects with PD practiced 2 sets of instructions and then attempted to implement both approaches (as well as a relaxed control condition) during quiet standing and step initiation. The "Lighten Up" instructions relied on AT principles of reducing excess tension while encouraging length. The "Pull Up" instructions relied on popular concepts of effortful posture correction. We measured kinematics, resistance to axial rotation, and ground reaction forces. Both sets of experimental instructions led to increases in upright postural alignment relative to the control condition. Only the Lighten Up instructions led to reduced postural sway, reduced axial postural tone, greater modifiability of tone, and a smoother center of pressure trajectory during step initiation, possibly indicating greater movement efficiency. Mindful movement approaches such as AT may benefit balance and mobility in subjects with PD by acutely facilitating increased upright postural alignment while decreasing rigidity. © The Author(s) 2015.

  20. Recovery from Multiple APAs Delays Gait Initiation in Parkinson’s Disease

    Science.gov (United States)

    Cohen, Rajal G.; Nutt, John G.; Horak, Fay B.

    2017-01-01

    Background: Freezing of gait in Parkinson’s disease (PD) has been linked with deficits in inhibitory control, but causal mechanisms are not established. Freezing at gait initiation (start hesitation) is often accompanied by multiple anticipatory postural adjustments (APAs). If inhibition deficits contribute to freezing by interfering with ability to inhibit initial weight shifts in the wrong direction, then PD subjects should experience more episodes of multiple APAs than healthy controls (HCs) do. If inhibition deficits contribute to freezing by interfering with ability to release a previously inhibited step following multiple APAs, then step onset following multiple APAs should be delayed more in people with PD than in HCs. Methods: Older adults with PD and HC subjects rapidly initiated stepping in response to a light cue in blocks of simple (SRT) and choice (CRT) conditions. We recorded kinematics and ground reaction forces, and we administered the Stroop task to assess inhibitory control. Results: Multiple APAs were more common in CRT than SRT conditions but were equally common in HC and PD subjects. Step onsets were delayed in both conditions and further delayed in trials with multiple APAs, except for HC subjects in SRT trials. Poor Stroop performance correlated with many multiple APAs, late step onset, and rearward position of center of mass (COM) at cue presentation. Forward motion of the COM during the APA was higher in trials with multiple APAs than in trials with single APAs, especially in CRT trials and in PD subjects without self-reported freezing. Conclusion: Start hesitation is not caused by multiple APAs per se, but may be associated with difficulty recovering from multiple APAs, due to difficulty releasing a previously inhibited step. PMID:28261073

  1. Periodic fever in MVK deficiency: a patient initially diagnosed with incomplete Kawasaki disease.

    Science.gov (United States)

    Thors, Valtyr S; Vastert, Sebastiaan J; Wulffraat, Nico; van Royen, Annet; Frenkel, Joost; de Sain-van der Velden, Monique; de Koning, Tom J

    2014-02-01

    Mevalonate kinase deficiency (MKD) is a rare autosomal recessive disorder causing 1 of 2 phenotypes, hyperimmunoglobulin D syndrome and mevalonic aciduria, presenting with recurrent fever episodes, often starting in infancy, and sometimes evoked by stress or vaccinations. This autoinflammatory disease is caused by mutations encoding the mevalonate kinase (MVK) gene and is classified in the group of periodic fever syndromes. There is often a considerable delay in the diagnosis among pediatric patients with recurrent episodes of fever. We present a case of an 8-week-old girl with fever of unknown origin and a marked systemic inflammatory response. After excluding infections, a tentative diagnosis of incomplete Kawasaki syndrome was made, based on the finding of dilated coronary arteries on cardiac ultrasound and fever, and she was treated accordingly. However, the episodes of fever recurred, and alternative diagnoses were considered, which eventually led to the finding of increased excretion of mevalonic acid in urine. The diagnosis of MKD was confirmed by mutation analysis of the MVK gene. This case shows that the initial presentation of MKD can be indistinguishable from incomplete Kawasaki syndrome. When fever recurs in Kawasaki syndrome, other (auto-)inflammatory diseases must be ruled out to avoid inappropriate diagnostic procedures, ineffective interventions, and treatment delay.

  2. Frequencies of initial gait disturbances and falls in 100 Wilson's disease patients.

    Science.gov (United States)

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

    2015-10-01

    Wilson's disease (WD) is an inherited copper metabolism disorder. Gait disturbances may present with both extrapyramidal and cerebellar patterns. The frequencies of particular types of gait abnormalities have not been established; thus, the aim of the present study was to determine the occurrence of initial gait disturbances among our neurological WD patients. We analyzed 103 WD patients with neurological features at the time of diagnosis, between 2005 and 2014. The neurological and gait assessments were based on the Unified Wilson's Disease Score Scale (UWDRS), from which, we distinguished three main patterns of gait: dystonic, ataxic, or Parkinsonian. All types of gait impairment were assessed using four stages of severity (0=normal, 4=severe). We also obtained each patient's history of falls. Three patients had severe dystonia of limbs and were unable to stand or walk. Gait abnormalities were noted in 59% (59/100) of the remaining group of patients. The most common observed pattern was ataxic gait (45%; 27/59), which presented as impaired tandem in most cases. A mixed gait impairment was observed in 25% (15/59) of patients (ataxic, dystonic, and Parkinsonian, n=8; ataxic and Parkinsonian, n=7), a Parkinsonian gait in 18% (11/59), and a dystonic gait in 10% (6/59) of patients. Falls were noted in 35% of patients, but were occasionally observed in most cases. Gait disturbances are frequent in WD, and reflect the involvement of many brain structures.

  3. Predicting episodic memory performance using different biomarkers: results from Argentina-Alzheimer’s Disease Neuroimaging Initiative

    Science.gov (United States)

    Russo, María Julieta; Cohen, Gabriela; Chrem Mendez, Patricio; Campos, Jorge; Nahas, Federico E; Surace, Ezequiel I; Vazquez, Silvia; Gustafson, Deborah; Guinjoan, Salvador; Allegri, Ricardo F; Sevlever, Gustavo

    2016-01-01

    Purpose Argentina-Alzheimer’s Disease Neuroimaging Initiative (Arg-ADNI) is the first ADNI study to be performed in Latin America at a medical center with the appropriate infrastructure. Our objective was to describe baseline characteristics and to examine whether biomarkers related to Alzheimer’s disease (AD) physiopathology were associated with worse memory performance. Patients and methods Fifteen controls and 28 mild cognitive impairment and 13 AD dementia subjects were included. For Arg-ADNI, all biomarker parameters and neuropsychological tests of ADNI-II were adopted. Results of positron emission tomography (PET) with fluorodeoxyglucose and 11C-Pittsburgh compound-B (PIB-PET) were available from all participants. Cerebrospinal fluid biomarker results were available from 39 subjects. Results A total of 56 participants were included and underwent baseline evaluation. The three groups were similar with respect to years of education and sex, and they differed in age (F=5.10, P=0.01). Mean scores for the baseline measurements of the neuropsychological evaluation differed significantly among the three groups at P0.1). Baseline amyloid deposition and left hippocampal volume separated the three diagnostic groups and correlated with the memory performance (P<0.001). Conclusion Cross-sectional analysis of baseline data revealed links between cognition, structural changes, and biomarkers. Follow-up of a larger and more representative cohort, particularly analyzing cerebrospinal fluid and brain biomarkers, will allow better characterization of AD in our country. PMID:27695331

  4. Executive functioning in daily life in Parkinson's disease: initiative, planning and multi-task performance.

    Directory of Open Access Journals (Sweden)

    Janneke Koerts

    Full Text Available Impairments in executive functioning are frequently observed in Parkinson's disease (PD. However, executive functioning needed in daily life is difficult to measure. Considering this difficulty the Cognitive Effort Test (CET was recently developed. In this multi-task test the goals are specified but participants are free in their approach. This study applies the CET in PD patients and investigates whether initiative, planning and multi-tasking are associated with aspects of executive functions and psychomotor speed. Thirty-six PD patients with a mild to moderate disease severity and thirty-four healthy participants were included in this study. PD patients planned and demonstrated more sequential task execution, which was associated with a decreased psychomotor speed. Furthermore, patients with a moderate PD planned to execute fewer tasks at the same time than patients with a mild PD. No differences were found between these groups for multi-tasking. In conclusion, PD patients planned and executed the tasks of the CET sequentially rather than in parallel presumably reflecting a compensation strategy for a decreased psychomotor speed. Furthermore, patients with moderate PD appeared to take their impairments into consideration when planning how to engage the tasks of the test. This compensation could not be detected in patients with mild PD.

  5. Clinical trial designs for rare diseases: Studies developed and discussed by the International Rare Cancers Initiative

    Science.gov (United States)

    Bogaerts, Jan; Sydes, Matthew R.; Keat, Nicola; McConnell, Andrea; Benson, Al; Ho, Alan; Roth, Arnaud; Fortpied, Catherine; Eng, Cathy; Peckitt, Clare; Coens, Corneel; Pettaway, Curtis; Arnold, Dirk; Hall, Emma; Marshall, Ernie; Sclafani, Francesco; Hatcher, Helen; Earl, Helena; Ray-Coquard, Isabelle; Paul, James; Blay, Jean-Yves; Whelan, Jeremy; Panageas, Kathy; Wheatley, Keith; Harrington, Kevin; Licitra, Lisa; Billingham, Lucinda; Hensley, Martee; McCabe, Martin; Patel, Poulam M.; Carvajal, Richard; Wilson, Richard; Glynne-Jones, Rob; McWilliams, Rob; Leyvraz, Serge; Rao, Sheela; Nicholson, Steve; Filiaci, Virginia; Negrouk, Anastassia; Lacombe, Denis; Dupont, Elisabeth; Pauporté, Iris; Welch, John J.; Law, Kate; Trimble, Ted; Seymour, Matthew

    2015-01-01

    Background The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. Settings The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional – usually randomised – clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed. Results The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design. Interpretation Trials can be designed using a wide array of possibilities. There is no ‘one size fits all’ solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases. PMID:25542058

  6. Initial clinical experience using the Echo Navigator~-system during structural heart disease interventions

    Institute of Scientific and Technical Information of China (English)

    Jan; Balzer; Tobias; Zeus; Katharina; Hellhammer; Verena; Veulemans; Silke; Eschenhagen; Eva; Kehmeier; Christian; Meyer; Tienush; Rassaf; Malte; Kelm

    2015-01-01

    AIM: To present our initial clinical experience using this innovative software solution for guidance of percutaneous structural heart disease interventions.METHODS: Left atrial appendage, atrial septal defect and paravalvular leak closure, transaortic valve repair and Mitra Clip procedures were performed in the catheter laboratory under fluoroscopic and echocardiographic guidance. The two-dimensional and three-dimensional images generated by the transesophageal echocardiography probe were interfaced with the fluoroscopic images in real-time using the Echo Navigator-system.RESULTS:The application of the novel image fusion technology was safe and led to a better appreciation of multimodality imaging guidance due to improved visualization of the complex relationship between catheter devices and anatomical structures.CONCLUSION:The Echo Navigator-system is a feasible and safe tool for guidance of interventional procedures in structural heart disease.This innovative technology may improve confidence of interventional cardiologists in targeting and positioning interventional devices in order to increase safety,accuracy,and efficacy of percutaneous interventions in the catheter laboratory.

  7. Diffusion-weighted MR imaging of kidneys in patients with chronic kidney disease: initial study

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xueqin; Fang, Wenqiang; Ling, Huawei; Chai, Weimin; Chen, Kemin [Ruijin Hospital Shanghai, Jiaotong University School of Medicine, Department of Radiology, Shanghai (China)

    2010-04-15

    To prospectively evaluate the feasibility of diffusion-weighted (DW) magnetic resonance (MR) imaging in the assessment of renal function in patients with chronic kidney disease (CKD). Seventy-two healthy volunteers and 43 patients underwent coronal echo-planar DW MR imaging of the kidneys with a single breath-hold time of 16 s. The patients were grouped according to five stages as indicated by the K/DOQI CKD (kidney disease outcome quality initiative). The apparent diffusion coefficient (ADC) value of the kidneys was calculated with high b values (b = 500 s/mm{sup 2}). The ADC values were compared between patients and healthy volunteers, and among different stages. For statistical analysis, Student's t tests, ANOVA, Pearson's correlation tests, and Spearman's correlation tests were used. No difference between the cortex and medulla could be observed on DW images of all volunteers. Patients with CKD had significantly lower renal ADC (t = -4.383, P = 0.000) than volunteers. The ADC values of kidneys were significantly lower than normal at most stages of CKD, except CKD1. There was a negative correlation between the ADCs and serum creatinine (sCr) level (P = 0.000) amongst the patients. Diffusion-weighted MR imaging is feasible in the assessment of renal function, especially in the detection of early stage renal failure of CKD. (orig.)

  8. Brain collection, standardized neuropathologic assessment, and comorbidity in Alzheimer's Disease Neuroimaging Initiative 2 participants.

    Science.gov (United States)

    Franklin, Erin E; Perrin, Richard J; Vincent, Benjamin; Baxter, Michael; Morris, John C; Cairns, Nigel J

    2015-07-01

    The Alzheimer's Disease Neuroimaging Initiative Neuropathology Core (ADNI-NPC) facilitates brain donation, ensures standardized neuropathologic assessments, and maintains a tissue resource for research. The ADNI-NPC coordinates with performance sites to promote autopsy consent, facilitate tissue collection and autopsy administration, and arrange sample delivery to the NPC, for assessment using National Institute on Aging-Alzheimer's Association neuropathologic diagnostic criteria. The ADNI-NPC has obtained 45 participant specimens, and neuropathologic assessments have been completed in 36 to date. Challenges in obtaining consent at some sites have limited the voluntary autopsy rate to 58%. Among assessed cases, clinical diagnostic accuracy for Alzheimer disease (AD) is 97%; however, 58% of cases show neuropathologic comorbidities. Challenges facing autopsy consent and coordination are largely resource related. The neuropathologic assessments indicate that ADNI's clinical diagnostic accuracy for AD is high; however, many AD cases have comorbidities that may impact the clinical presentation, course, and imaging and biomarker results. These neuropathologic data permit multimodal and genetic studies of these comorbidities to improve diagnosis and provide etiologic insights. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  9. Single-SectionFabry-Perot Mode-Locked Semiconductor Lasers

    Directory of Open Access Journals (Sweden)

    Weiguo Yang

    2011-01-01

    Full Text Available We present a review of the theoretical models and experimental verification of the single-section Fabry-Perot mode-locked semiconductor lasers based on multiple-spatial-mode (MSM coupling. The mode-locked operation at the repetition rates of 40 GHz and higher and the pulse width of a few picoseconds are confirmed by the intensity autocorrelation, the fast photo detection and RF spectrum, and the optical spectral interference measurement of ultrafast pulse. The spatial mode coupling theory of single-section Fabry-Perot mode-locked semiconductor lasers is also reviewed, and the results are compared with the experimental observations. The small signal modulation response of these lasers, which exhibits high-frequency responses well beyond the relaxation oscillation resonance limit, is also modeled theoretically, and the simulation is verified by the experimental measurements.

  10. Transforming Fabry-Perot resonances into a Tamm mode

    CERN Document Server

    Durach, Maxim

    2012-01-01

    We propose a novel photonic structure composed of metal nanolayer, Bragg mirror and metal nanolayer. The structure supports resonances that are transitional between Fabry-Perot and Tamm modes. When the dielectric contrast of the DBR is removed these modes are a pair of conventional Fabry-Perot resonances. They spectrally merge into a Tamm mode at high contrast. Such behavior differs from the results for structures supporting Tamm modes reported earlier. The optical properties of the structure in the frequency range of the DBR stop band, including highly beneficial 50% transmittivity through thick structures, are determined by the introduced in the paper hybrid resonances. The results can find a wide range of photonic applications.

  11. Curvature sensor based on a Fabry-Perot interferometer

    Science.gov (United States)

    Monteiro, Catarina; Ferreira, Marta S.; Kobelke, Jens; Schuster, Kay; Bierlich, Jörg; Frazão, Orlando

    2016-05-01

    A curvature sensor based on a Fabry-Perot interferometer is proposed. A capillary tube of silica is fusion spliced between two single mode fibers, producing a Fabry-Perot cavity. The light propagates in air, when passing through the capillary tube. Two different cavities are subjected to curvature and temperature. The cavity with shorter length shows insensitivity to both measurands. The larger cavity shows two operating regions for curvature measurement, where a linear response is shown, with a maximum sensitivity of 18.77pm/m-1 for the high curvature radius range. When subjected to temperature, the sensing head produces a similar response for different curvature radius, with a sensitivity of 0.87pm/°C.

  12. CSF biomarkers associated with disease heterogeneity in early Parkinson’s disease: the Parkinson’s Progression Markers Initiative study

    Science.gov (United States)

    Kang, Ju-Hee; Mollenhauer, Brit; Coffey, Christopher S.; Toledo, Jon B.; Weintraub, Daniel; Galasko, Douglas R.; Irwin, David J.; Van Deerlin, Vivianna; Chen-Plotkin, Alice S.; Caspell-Garcia, Chelsea; Waligórska, Teresa; Taylor, Peggy; Shah, Nirali; Pan, Sarah; Zero, Pawel; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Tanner, Caroline M.; Simuni, Tanya; Singleton, Andrew; Toga, Arthur W.; Chowdhury, Sohini; Trojanowski, John Q.; Shaw, Leslie M.

    2016-01-01

    The development of biomarkers to predict the progression of Parkinson’s disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson’s Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1–42 (Aβ1–42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1–42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1–42, or highest t-tau/Aβ1–42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1–42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance. PMID:27021906

  13. Time of Initiating Enzyme Replacement Therapy Affects Immune Abnormalities and Disease Severity in Patients with Gaucher Disease

    Science.gov (United States)

    Ioanou, Chidima; Plassmeyer, Matthew; Ryherd, Mark; Kozhaya, Lina; Austin, Lauren; Abidoglu, Cem; Unutmaz, Derya; Alpan, Oral; Goker-Alpan, Ozlem

    2016-01-01

    Gaucher disease (GD) patients often present with abnormalities in immune response that may be the result of alterations in cellular and/or humoral immunity. However, how the treatment and clinical features of patients impact the perturbation of their immunological status remains unclear. To address this, we assessed the immune profile of 26 GD patients who were part of an enzyme replacement therapy (ERT) study. Patients were evaluated clinically for onset of GD symptoms, duration of therapy and validated outcome measures for ERT. According to DS3 disease severity scoring system criteria, they were assigned to have mild, moderate or severe GD. Flow cytometry based immunophenotyping was performed to analyze subsets of T, B, NK, NKT and dendritic cells. GD patients showed multiple types of immune abnormalities associated to T and B lymphocytes with respect to their subpopulations as well as memory and activation markers. Skewing of CD4 and CD8 T cell numbers resulting in lower CD4/CD8 ratio and an increase in overall T cell activation were observed. A decrease in the overall B cells and an increase in NK and NKT cells were noted in the GD patients compared to controls. These immune alterations do not correlate with GD clinical type or level of biomarkers. However, subjects with persistent immune alterations, especially in B cells and DCs correlate with longer delay in initiation of ERT (ΔTX). Thus, while ERT may reverse some of these immune abnormalities, the immune cell alterations become persistent if therapy is further delayed. These findings have important implications in understanding the immune disruptions before and after treatment of GD patients. PMID:27942037

  14. Intrinsic functional component analysis via sparse representation on Alzheimer's disease neuroimaging initiative database.

    Science.gov (United States)

    Jiang, Xi; Zhang, Xin; Zhu, Dajiang

    2014-10-01

    Alzheimer's disease (AD) is the most common type of dementia (accounting for 60% to 80%) and is the fifth leading cause of death for those people who are 65 or older. By 2050, one new case of AD in United States is expected to develop every 33 sec. Unfortunately, there is no available effective treatment that can stop or slow the death of neurons that causes AD symptoms. On the other hand, it is widely believed that AD starts before development of the associated symptoms, so its prestages, including mild cognitive impairment (MCI) or even significant memory concern (SMC), have received increasing attention, not only because of their potential as a precursor of AD, but also as a possible predictor of conversion to other neurodegenerative diseases. Although these prestages have been defined clinically, accurate/efficient diagnosis is still challenging. Moreover, brain functional abnormalities behind those alterations and conversions are still unclear. In this article, by developing novel sparse representations of whole-brain resting-state functional magnetic resonance imaging signals and by using the most updated Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, we successfully identified multiple functional components simultaneously, and which potentially represent those intrinsic functional networks involved in the resting-state activities. Interestingly, these identified functional components contain all the resting-state networks obtained from traditional independent-component analysis. Moreover, by using the features derived from those functional components, it yields high classification accuracy for both AD (94%) and MCI (92%) versus normal controls. Even for SMC we can still have 92% accuracy.

  15. MR findings of neuro-Behcet's disease: initial and follow-up changes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Beom; Chang, Ki Hyun; Kim, Hong Dae [College of Medicine, Hallym University, Seoul (Korea, Republic of); Han, Moon Hee; Kang, Heung Sik; Lee, Joon Woo; Yu, In Kyu [College of Medicine and the Institute of Radiation Medicine, Seoul National University, Seoul (Korea, Republic of); Seong, Su Ok [Cheonju St. Mary' s Hospital, Cheongju (Korea, Republic of); Kim, Hyung Seok [Cheju Medical Center, Cheju (Korea, Republic of)

    2000-08-01

    To evaluate the MR findings of neuro{sub B}ehcet's disease, and changes occurring during follow up. Brain MR imaging was performed in 19 patients in whom neuro-Behcet's disease had been clinically diagnosed. After treatment with corticosteroids and immunosuppressive agents, 23 follow-up MR images were obtained in 12 patients, and a total of 42 MR images were retrospectively reviewed by two radiologists. Of the 19 patients, 17 (89%) had parenchymal lesions, and the other two had dural venous sinus thrombosis. Among the 17 patients with parenchymal lesions, three showed leptomeningeal enhancement. A total of 72 parenchymal lesions were detected on initial MR images; 55 (76%) were patchy or nodular in shape and the lesion of the internal capsule appeared linear. Seventeen lesions (24%) in 12 patients were confluent. In order of frequency, the involved sites were the pons, midbrain, thalamus, basal ganglia, internal capsule, and frontal lobe. Thirteen lesions of 39 lesions detected on postcontrast images were enhanced, and a mass effect was seen in the area of 16 parenchymal lesions. Associated findings were microhemorrhage of the brain in two patients and spinal cord involvement in one. On short-term follow-up images obtained 1 week to 2 months after intensive treatment during the acute stage of the illness, the leptomeningeal enhancement seen in three patients had decreased and most parenchymal lesions showed improvement. Long-term follow-up images obtained 3 months to 3 years late showed that parenchymal lesions had relapsed in five patients, and brainstem atrophy had developed or progressed in five others. The most characteristic MR finding of neuro-Behcet's disease is multiple non-hemorrhagic lesions involving the brainstem. Leptomeningeal enhancement and dural venous sinus thrombosis may also be noted. On follow-up MR, the lesions may show either improvement or aggravation, and brainstem atrophy is not uncommon. (author)

  16. The current situation of meningococcal disease in Latin America and updated Global Meningococcal Initiative (GMI) recommendations.

    Science.gov (United States)

    Sáfadi, Marco Aurélio P; O'Ryan, Miguel; Valenzuela Bravo, Maria Teresa; Brandileone, Maria Cristina C; Gorla, Maria Cecília O; de Lemos, Ana Paula S; Moreno, Gabriela; Vazquez, Julio A; López, Eduardo L; Taha, Muhamed-Kheir; Borrow, Ray

    2015-11-27

    The Global Meningococcal Initiative (GMI) was established in 2009 and comprises an international team of scientists, clinicians, and public health officials with expertise in meningococcal disease (MD). Its primary goal is to promote global prevention of MD through education, research, international cooperation, and developing recommendations that include decreasing the burden of severe disease. The group held its first roundtable meeting with experts from Latin American countries in 2011, and subsequently proposed several recommendations to reduce the regional burden of MD. A second roundtable meeting was convened with Latin American representatives in June 2013 to reassess MD epidemiology, vaccination strategies, and unmet needs in the region, as well as to update the earlier recommendations. Special emphasis was placed on the emergence and spread of serogroup W disease in Argentina and Chile, and the control measures put in place in Chile were a particular focus of discussions. The impact of routine meningococcal vaccination programs, notably in Brazil, was also evaluated. There have been considerable improvements in MD surveillance systems and diagnostic techniques in some countries (e.g., Brazil and Chile), but the lack of adequate infrastructure, trained personnel, and equipment/reagents remains a major barrier to progress in resource-poor countries. The Pan American Health Organization's Revolving Fund is likely to play an important role in improving access to meningococcal vaccines in Latin America. Additional innovative approaches are needed to redress the imbalance in expertise and resources between countries, and thereby improve the control of MD. In Latin America, the GMI recommends establishment of a detailed and comprehensive national/regional surveillance system, standardization of laboratory procedures, adoption of a uniform MD case definition, maintaining laboratory-based surveillance, replacement of polysaccharide vaccines with conjugate

  17. Neuro-Behcet's disease: initial and follow-up MR imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chan Sung; Choi, Sun Seob; Lee, Ha Jong; Ha, Dong Ho; Lee, Yong Il [Donga Medical Center, Pusan (Korea, Republic of)

    1998-09-01

    The purpose of this study was to evaluate initial and follow-up MR imaging(MRI) findings of neuro-Behcet's disease. MRI of seven clinically diagnosed cases of neuro-Behcet's disease were retrospectively analysed in terms of involved site, pattern, signal intensity, contrast enhancement pattern and changes seen on follow-up. Using a 0.35T or 1.0T unit T2-and T1-weighted spin-echocontrast-enhanced images were obtained in six patients. Follow-up MRI after steroid therapy lastion between two weeks and 16 months was performed in six patients. Lesions involved the midbrain(6/7), pons(5/7), thalamus(4/7), medulla oblongata(3/7), tegmentum(3/7), internal capsule(3/7), middle cerebellar peduncle(2/7), dentate nucleus(1/7), basal ganglia(1/7) and temporal lobe(1/7). They were 1-3cm in size, and their shape was ill-defined and patchy. Inhomogeneous high and low signal-intensity was seen on T2-weighted and T1-weighted images, respectively. In two of six cases there was focal mild patchy enhancement. Euring follow-up lasting for between two weeks and 16 months after steroid therapy, the lesions decreased in extent(n=3D5) or disappeared(n=3D1), and in the brainstem, focal brain atrophy occurred in three cases. Although MRI findings of neuro-Behcet's disease are nonspecific, common involvement of the brainstem, tegmentum and internal capsule, as well as improvement on follow-up MRI, may be helpful diagnostic indicators of this condition.=20.

  18. Interstitial lung disease in anti-synthetase syndrome: Initial and follow-up CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Debray, Marie-Pierre, E-mail: marie-pierre.debray@bch.aphp.fr [AP-HP, Bichat-Claude Bernard Hospital, Department of Radiology, 46, rue Henri Huchard, 75877 Paris Cedex 18 (France); Borie, Raphael, E-mail: raphael.borie@bch.aphp.fr [AP-HP, Bichat-Claude Bernard Hospital, Department of Pneumology A and Centre de Compétence Maladies Pulmonaires rares, DHU Fire 46, rue Henri Huchard, 75877 Paris Cedex 18 (France); Inserm, U1152, Paris (France); Revel, Marie-Pierre, E-mail: marie-pierre.revel@htd.aphp.fr [AP-HP, Cochin Hospital, Department of Radiology, 27, Rue du Fg Saint Jacques, 75679 Paris Cedex 14 (France); Naccache, Jean-Marc, E-mail: jean-marc.naccache@tnn.aphp.fr [AP-HP, Avicenne Hospital, Department of Pneumology and Centre de Compétence Maladies Pulmonaires rares, Bobigny (France); AP-HP, Tenon Hospital, Department of Pneumology and Centre de Compétence Maladies Pulmonaires rares, 4, rue de la Chine, 75020 Paris (France); Khalil, Antoine, E-mail: antoine.khalil@tnn.aphp.fr [AP-HP, Tenon Hospital, Department of Radiology, 4, rue de la Chine, 75020 Paris (France); Toper, Cécile, E-mail: cecile.toper@gmail.com [AP-HP, Tenon Hospital, Department of Pneumology and Centre de Compétence Maladies Pulmonaires rares, 4, rue de la Chine, 75020 Paris (France); Israel-Biet, Dominique, E-mail: dominique.israel-biet@egp.aphp.fr [Université Paris Descartes and AP-HP, Department of Pneumology, Georges Pompidou European Hospital, 20, rue Leblanc, 75015 Paris (France); and others

    2015-03-15

    Purpose: To describe the initial and follow-up CT features of interstitial lung disease associated with anti-synthetase syndrome (AS-ILD). Materials and methods: Two independent thoracic radiologists retrospectively analysed thin-section CT images obtained at diagnosis of AS-ILD in 33 patients (17 positive for anti-Jo1, 13 for anti-PL12, and three for anti-PL7 antibodies). They evaluated the pattern, distribution and extent of the CT abnormalities. They also evaluated the change in findings during follow-up (median 27 months; range 13–167 months) in 26 patients. Results: At diagnosis, ground-glass opacities (100%), reticulations (87%) and traction bronchiectasis (76%) were the most common CT findings. Consolidations were present in 45% of patients. A non-specific interstitial pneumonia (NSIP), organizing pneumonia (OP) or mixed NSIP-OP CT pattern were observed in 15 out of 33 (45%), seven out of 33 (21%) and eight out of 33 (24%) patients, respectively, whereas the CT pattern was indeterminate in three patients. During follow-up, consolidations decreased or disappeared in 11 out of 12 patients (92%), among which seven within the first 6 months, but honeycombing progressed or appeared in ten out of 26 patients (38%) and overall disease extent increased in nine out of 26 patients (35%). Conclusion: CT features at diagnosis of AS-ILD mainly suggest NSIP and OP, isolated or in combination. Consolidations decrease or disappear in most cases but the disease may progress to fibrosis in more than one third of patients.

  19. Optical power equalization using Fabry-Perot semiconductor optical amplifier

    Institute of Scientific and Technical Information of China (English)

    Yun Ling; Kun Qiu; Wei Zhang; Ying Pang

    2006-01-01

    A novel scheme of optical power equalization based on Fabry-Perot semiconductor optical amplifier (FPSOA) is proposed. Because of the gain characteristic of FP-SOA, real-time controlling mechanism according to input optical power is aborted in the scheme. The simulations show that 10-dB pulse peak power variation can be clamped in less than i dB. The influences of injecting current, pulse periods, and pulse width are discussed.

  20. Validation of Alzheimer's disease CSF and plasma biological markers: the multicentre reliability study of the pilot European Alzheimer's Disease Neuroimaging Initiative (E-ADNI)

    DEFF Research Database (Denmark)

    Buerger, Katharina; Frisoni, Giovanni; Uspenskaya, Olga

    2009-01-01

    BACKGROUND: Alzheimer's Disease Neuroimaging Initiatives ("ADNI") aim to validate neuroimaging and biochemical markers of Alzheimer's disease (AD). Data of the pilot European-ADNI (E-ADNI) biological marker programme of cerebrospinal fluid (CSF) and plasma candidate biomarkers are reported. METHODS...

  1. Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat

    DEFF Research Database (Denmark)

    Germain, Dominique P; Hughes, Derralynn A; Nicholls, Kathleen

    2016-01-01

    a significant treatment effect: 13 of 32 patients (41%) who received migalastat and 9 of 32 patients (28%) who received placebo had a response at 6 months (P=0.30). Among patients with suitable mutant α-galactosidase who received migalastat for up to 24 months, the annualized changes from baseline...

  2. Fabry's Disease: Case Series and Review of Literature

    African Journals Online (AJOL)

    case series of five patient's along with the review of literature is presented here. Keywords: ... underwent a renal transplant biopsy to ascertain the cause of ... A 16-year-old male presented in March 2002 with a fever of unknown origin and splenomegaly. ... There was no evidence of tuft necrosis/crescent formation or.

  3. Optical layout for a 10m Fabry-P\\'erot Michelson interferometer with tunable stability

    CERN Document Server

    Gräf, Christian; Lück, Harald; Willke, Benno; Strain, Kenneth A; Goßler, Stefan; Danzmann, Karsten

    2011-01-01

    The sensitivity of high-precision interferometric measurements can be limited by Brownian noise within dielectric mirror coatings. This occurs, for instance, in the optical resonators of gravitational wave detectors where the noise can be reduced by increasing the laser beam size. However, the stability of the resonator and its optical performance often impose a limit on the maximally feasible beam size. In this article we describe the optical design of a 10\\,m Fabry-P\\'erot Michelson interferometer with tunable stability. Our design will allow us to carry out initial commissioning with arm cavities of high stability, while afterwards the arm cavity length can be increased stepwise towards the final, marginally stable configuration. Requiring only minimal hardware changes, with respect to a comparable "static" layout, the proposed technique will not only enable us to explore the stability limits of an optical resonator with realistic mirrors exhibiting inevitable surface imperfections, but also the opportunit...

  4. The Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception

    Science.gov (United States)

    Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Liu, Enchi; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Schmidt, Mark E.; Shaw, Leslie; Shen, Li; Siuciak, Judith A.; Soares, Holly; Toga, Arthur W.; Trojanowski, John Q.

    2014-01-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD, and 200 normal control subjects; $67 million funding was provided by both the public and private sectors, including the National Institute on Aging, 13 pharmaceutical companies, and 2 foundations that provided support through the Foundation for the National Institutes of Health. This article reviews all papers published since the inception of the initiative and summarizes the results as of February 2011. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimers Dis 2006;9(Suppl 3):151–3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities, including MRI, [18F]-fluorodeoxyglucose-PET, CSF biomarkers, and clinical tests; (4) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects, and are leading candidates

  5. The Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception

    Science.gov (United States)

    Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Liu, Enchi; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Schmidt, Mark E.; Shaw, Leslie; Siuciak, Judith A.; Soares, Holly; Toga, Arthur W.; Trojanowski, John Q.

    2012-01-01

    The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic and biochemical biomarkers for the early detection and tracking of Alzheimer’s disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD and 200 normal controls and $67 million funding was provided by both the public and private sectors including the National Institutes on Aging, thirteen pharmaceutical companies and two Foundations that provided support through the Foundation for NIH (FNIH). This article reviews all papers published since the inception of the initiative and summarizes the results as of February, 2011. The major accomplishments of ADNI have been 1) the development of standardized methods for clinical, magnetic resonance imaging (MRI) and positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in a multi-center setting; 2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control, MCI and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β amyloid (Aβ) cascade [1] and tau mediated neurodegeneration hypotheses for AD while brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; 3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities including MRI, FDG-PET, CSF biomarkers and clinical tests; 4) the development of methods for the early detection of AD. CSF biomarkers, Aβ42 and tau as well as amyloid PET may reflect the earliest steps in AD pathology in mildly or even non-symptomatic subjects and are leading candidates for the detection of AD in its preclinical stages; 5) the improvement of clinical trial efficiency through the identification of subjects most

  6. Prevalence and variation of Chronic Kidney Disease in the Irish health system: initial findings from the National Kidney Disease Surveillance Programme.

    LENUS (Irish Health Repository)

    Stack, Austin G

    2014-01-01

    Chronic Kidney Disease (CKD) is a major non-communicable chronic disease that is associated with adverse clinical and economic outcomes. Passive surveillance systems are likely to improve efforts for prevention of chronic kidney disease (CKD) and inform national service planning. This study was conducted to determine the overall prevalence of CKD in the Irish health system, assess period trends and explore patterns of variation as part of a novel surveillance initiative.

  7. Fabry-Perot腔滤波器的数学模型%The Mathematical Model of the Fabry-Perot Filter

    Institute of Scientific and Technical Information of China (English)

    齐永兴; 陈树强; 刘元安; 钱宗珏; 赵国谦

    2004-01-01

    将信号与系统的知识应用于Fabry-Perot(FP)腔滤波器的分析和设计中,避免了繁琐的矩阵运算,而且FP腔滤波器同整个系统紧密地联系在一起,使其成为一个以传递函数为特征的器件,更易于理解和优化设计.

  8. Initial diagnosis and management of chronic obstructive pulmonary disease in Australia: views from the coal face.

    Science.gov (United States)

    Bereznicki, Bonnie; Walters, Haydn; Walters, Julia; Peterson, Gregory; Bereznicki, Luke

    2017-07-01

    Early diagnosis and management can mitigate the long-term morbidity and mortality of chronic obstructive pulmonary disease (COPD). To gain insights into the initial diagnostic process and early management of COPD by Australian general practitioners (GP). A random sample of Australian GP was invited to complete a postal survey, which assessed familiarity with and use of contemporary practice guidelines, diagnostic criteria and management preferences for COPD. A total of 233 GP completed the survey. While most GP based a COPD diagnosis on smoking history (94.4%), symptoms (91.0%) and spirometry (88.8%), only 39.9% of respondents recorded a formal diagnosis of COPD after the patient's first symptomatic presentation. Tiotropium was the preferred treatment in 77.3% of GP for the initial management of COPD, while only 27.5% routinely recommended pulmonary rehabilitation. GP routinely recorded patients' smoking status and offered smoking cessation advice, but the timing of this advice varied. Less than half of the respondents routinely used COPD management guidelines or tools and resources provided by the Australian Lung Foundation. There is scope for major improvement in GP familiarity with and use of COPD management guidelines and readily available tools and resources. Some systematic issues were highlighted in the Australian primary care setting, such as a reactive and relatively passive and delayed approach to diagnosis, potentially delayed smoking cessation advice and underutilisation of pulmonary rehabilitation. There is an urgent need to devise strategies for improving patient outcomes in COPD using resources that are readily available. © 2017 Royal Australasian College of Physicians.

  9. 78 FR 56236 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2013-09-12

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC) announces the... Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry. Elaine L....

  10. 78 FR 24751 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2013-04-26

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC) announces the... Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry. Elaine L....

  11. About the J-GRID (Japan Initiative for Global Research Network on Infectious Diseases).

    Science.gov (United States)

    Nagai, Yoshiyuki

    2014-06-01

    Since infectious diseases heed no national borders, international research collaboration across borders must be enhanced. The Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan launched the J-GRID program in the fiscal year (FY) 2005, which consists of the two elements; (1) the construction of collaboration centers in Asian and African countries on a reciprocal basis between a Japanese university/institution and an overseas partner university/institution and (2) the networking of those collaboration centers and setting up its headquarters at RIKEN. J-GRID initiated with 5 collaboration centers in 3 Asian countries has expanded to include 13 centers in 8 countries (6 in Asia and 2 in Africa). The aims of J-GRID include conducting high quality research on infectious diseases of regional and global importance, advancing relevant technologies and developing human resources in the field. In this way, J-GRID is expected to contribute to the public health of the host countries, Japan and the rest of the world. After the completion of the first start-up phase, Term I (2005-2009), J-GRID has stepped up its activity for the second step-up phase, Term II (2010-2014). While the first term was just like an incubation period, the second term should be the exponential growth phase, maximizing its research activities. Indeed, J-GRID is now generating remarkable research outcomes with an increasing number of publications. The mid-term evaluation made by the MEXT in FY2012 commended J-GRID as an ideal model to demonstrate Japan's leadership, in science and technology, and strongly recommended its extension in years to come after Term II terminates in FY 2014.

  12. Hypercortisolemia and glucocorticoid receptor-signaling insufficiency in Alzheimer's disease initiation and development.

    Science.gov (United States)

    Notarianni, Elena

    2013-09-01

    The cause and mechanism of development of Alzheimer' s disease (AD) remain unexplained. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, denoted by adrenal cortisol hypersecretion, is a recognised feature of the condition but generally disregarded as causative, due to lack of association between AD and other hypercortisolemic states. However, a meta-analysis of published studies suggests a need for reappraisal. A specific circadian rhythm of cortisol hypersecretion pertains at mild-to-moderate AD stages, entailing increased levels at the circadian peak from a low nadir. This is in contrast to the continuously elevated levels that are characteristic of other hypercortisolemic states, e.g. Cushing' s disease or major depression. This previously overlooked detail provides a starting premise here: that equating the form of hypercortisolism in AD with that in other states is inappropriate, as phasic and chronic elevation elicit different neuroendocrine effects. Theoretical implications are discussed in this review. Given the capacity of glucocorticoids and corticotropin-releasing hormone to induce AD-associated pathologies, I suggest a role for circadian cortisol hypersecretion in the initiation of sporadic AD; and propose a temporal mechanism for AD development featuring neuroinflammation- mediated suppression of central glucocorticoid receptor (GR) signaling. This latter may represent a critical phase in AD development, where the density of functional GR is proposed to underlie the "cognitive reserve". Supporting evidence for this mechanism is drawn from the brain regional locations of AD neuropathologies, and from risk factors for AD development (aging, ApoE-4 genotype, and hypertension). Thus, it is argued that basal hypercortisolemia merits further scrutiny regarding AD causation and development.

  13. Risk Factors in the Initial Presentation of Specific Cardiovascular Disease Syndromes

    Science.gov (United States)

    2013-03-03

    Heart Diseases; Cardiovascular Diseases; Acute Myocardial Infarction; Unstable Angina; Chronic Stable Angina; Ischemic Stroke; Cerebrovascular Accident; Subarachnoid Hemorrhage; Transient Ischemic Attack; Abdominal Aortic Aneurysm; Peripheral Arterial Disease; Sudden Coronary Death; Ventricular Arrhythmia; Sudden Death; Cardiac Arrest; Heart Failure

  14. Initial circulatory response to active standing in Parkinson's disease without typical orthostatic hypotension

    Directory of Open Access Journals (Sweden)

    Guillermo Delgado

    2014-03-01

    Full Text Available While the circulatory response to orthostatic stress has been already evaluated in Parkinson's disease patients without typical orthostatic hypotension (PD-TOH, there is an initial response to the upright position which is uniquely associated with active standing (AS. We sought to assess this response and to compare it to that seen in young healthy controls (YHC. Method In 10 PD-TOH patients (8 males, 60±7 years, Hoehn and Yahr ≤3 the changes in systolic blood pressure (SBP and heart rate that occur in the first 30 seconds (sec of standing were examined. Both parameters were non-invasively and continuously monitored using the volume-clamp method by Peñáz and the Physiocal criteria by Wesseling. The choice of sample points was prompted by the results of previous studies. These sample points were compared to those of 10 YHC (8 males, 32±8 years. Results The main finding of the present investigation was an increased time between the AS onset and SBP overshoot in PD-TOH group (24±4 vs. 19±3 sec; p<0.05. Conclusion This delay might reflect a prolonged latency in the baroreflex-mediated vascular resistance response, but more studies are needed to confirm this preliminary hypothesis.

  15. A Novel Chemically Modified Curcumin Reduces Severity of Experimental Periodontal Disease in Rats: Initial Observations

    Directory of Open Access Journals (Sweden)

    Muna S. Elburki

    2014-01-01

    Full Text Available Tetracycline-based matrix metalloproteinase- (MMP- inhibitors are currently approved for two inflammatory diseases, periodontitis and rosacea. The current study addresses the therapeutic potential of a novel pleiotropic MMP-inhibitor not based on an antibiotic. To induce experimental periodontitis, endotoxin (LPS was repeatedly injected into the gingiva of rats on one side of the maxilla; the contralateral (control side received saline injections. Two groups of rats were treated by daily oral intubation with a chemically modified curcumin, CMC 2.24, for two weeks; the control groups received vehicle alone. After sacrifice, gingiva, blood, and maxilla were collected, the jaws were defleshed, and periodontal (alveolar bone loss was quantified morphometrically and by μ-CT scan. The gingivae were pooled per experimental group, extracted, and analyzed for MMPs (gelatin zymography; western blot and for cytokines (e.g., IL-1β; ELISA; serum and plasma samples were analyzed for cytokines and MMP-8. The LPS-induced pathologically excessive bone loss was reduced to normal levels based on either morphometric (P=0.003 or μ-CT (P=0.008 analysis. A similar response was seen for MMPs and cytokines in the gingiva and blood. This initial study, on a novel triketonic zinc-binding CMC, indicates potential efficacy on inflammatory mediators and alveolar bone loss in experimental periodontitis and warrants future therapeutic and pharmacokinetic investigations.

  16. 77 FR 28392 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-05-14

    ... Motor Vehicle Injury Research, FOA CE12-006, initial review. In accordance with Section 10(a)(2) of the...-related Motor Vehicle Injury Research, FOA CE12-006, initial review.'' Contact Person for More...

  17. 76 FR 51985 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2011-08-19

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and..., National Center for Chronic Disease Prevention and Health Promotion, CDC, 4770 Buford Highway, NE... meetings and other committee management activities, for both the Centers for Disease Control and...

  18. 76 FR 32213 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP); Initial Review

    Science.gov (United States)

    2011-06-03

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and..., Hepatitis and Sexually Transmitted Diseases Prevention, CDC, 1600 Clifton Road, NE., Mailstop E-60, Atlanta... and Prevention and the Agency for Toxic Substances and Disease Registry. Dated: May 25, 2011. Elaine...

  19. 76 FR 49771 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2011-08-11

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC) announces the..., National Center for Chronic Disease Prevention and Health Promotion, CDC, 4770 Buford Highway,...

  20. 78 FR 19489 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2013-04-01

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention... management activities, for both the Centers for Disease Control and Prevention and the Agency for...

  1. 76 FR 28438 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2011-05-17

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and...), the Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: Time and....S.P.H., Director, Extramural Research Program Office, National Center for Chronic Disease...

  2. 76 FR 28437 - Disease, Disability, and Injury Prevention and Control Special Interest Project (SIP): Initial...

    Science.gov (United States)

    2011-05-17

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC..., Director, Extramural Research Program Office, National Center for Chronic Disease Prevention and...

  3. 78 FR 19490 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panels (SEP): Initial Review

    Science.gov (United States)

    2013-04-01

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... activities, for both the Centers for Disease Control and Prevention and the Agency for Toxic Substances and... Disease Control and Prevention. BILLING CODE 4163-18-P...

  4. 76 FR 28437 - Disease, Disability, and Injury Prevention and Control Special Interest Projects (SIPs): Initial...

    Science.gov (United States)

    2011-05-17

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC...., Director, Extramural Research Program Office, National Center for Chronic Disease Prevention and...

  5. 78 FR 25743 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2013-05-02

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control and Prevention (CDC... both the Centers for Disease Control and Prevention and the Agency for Toxic Substances and...

  6. 78 FR 19490 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2013-04-01

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... and Prevention and the Agency for Toxic Substances and Disease Registry. Dana Redford, Acting Director, Management Analysis and Services Office, Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  7. 76 FR 45575 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2011-07-29

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and..., Extramural Programs, National Center for HIV, Hepatitis and Sexually Transmitted Diseases Prevention, CDC... management activities, for both the Centers for Disease Control and Prevention and the Agency for...

  8. 78 FR 22268 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panels (SEP): Initial Review

    Science.gov (United States)

    2013-04-15

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and...; Strengthening Disease Prevention Research Capacity for Public Health Action in Guatemala and the Central...; Strengthening Disease Prevention Research Capacity for Public Health Action in Guatemala and the...

  9. 78 FR 732 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2013-01-04

    ..., Surveillance, and Control of Vector-Borne and Zoonotic Infectious Diseases in Uganda, Funding Opportunity... Control of Vector- Borne and Zoonotic Infectious Diseases in Uganda, FOA CK13-001.'' Contact Person for... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention...

  10. Initially unrecognised group A streptococcal pelvic inflammatory disease in a postmenopausal woman.

    Science.gov (United States)

    Kouijzer, I J E; Polderman, F N; Bekers, E M; Bloks, P H C J; Schneeberger, P M; de Jager, C P C

    2014-11-01

    Invasive group A streptococcal infection is a severe disease with high mortality. Invasive group A streptococcal infection may arise after pelvic inflammatory disease. Pelvic inflammatory disease in postmenopausal women is rare. Here, we report a unique case of a postmenopausal woman with fatal invasive group A streptococcal infection due to pelvic inflammatory disease and an extraordinary course of diagnosis.

  11. 77 FR 5026 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-02-01

    ... University of Alabama Birmingham, February 28, 2012 to advise and make recommendations to the Disease... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control...

  12. Influence of cavity loss on an extrinsic Fabry-Perot cavity intensity-based pressure sensor.

    Science.gov (United States)

    Lű, Tao

    2015-09-01

    We present an extrinsic Fabry-Perot cavity intensity-based pressure sensor that mainly comprises a single-mode fiber end and an elastic monocrystalline silicon layer bonded to a silicon diaphragm. We investigated the influence of cavity loss on the performance indexes (PIS) of the intensity-based extrinsic Fabry-Perot cavity optical fiber pressure sensor. A buffer unit made of three incompressible oil cavities attenuated outside pressure and transformed pressure information into cavity length microchange information. Experimental results indicated that, under center quadrature-points within the linear regions of adjacent fringes, for an applied 40 kPa external pressure, cavity length was modulated by pressures of 69.9 kPa-109.9 kPa, 150.1 kPa-190 kPa, 220.1 kPa-259.9 kPa, and 279.9 kPa-319.9 kPa, output intensity ranges increased as 1 μW, 1.02 μW, 1.03 μW, and 1.05 μW, sensitivity increased as 0.01909 μW/kPa, 0.01986 μW/kPa, 0.02127 μW/kPa, and 0.02387 μW/kPa, but linearity degraded, as indicated by the standard deviation of linear fits of 0.02607, 0.02664, 0.02935, and 0.04879 due to cavity loss. Furthermore, the pressure ranges within the same quarter period decreased as 40 kPa, 37.45 kPa, 32.4 kPa, and 30.15 kPa. Consequently, the same lengths of linear regions within adjacent fringes of an approximately sinusoidal curve corresponded to different measurement ranges, linearities, and sensitivities. Initial cavity length must be chosen to optimize both signal strength and the PIS studied here in manufacturing this type sensor.

  13. A Fabry-Perot interferometer system for high-speed velocity measurement

    NARCIS (Netherlands)

    Cheng, L.K.; Bruinsma, A.J.A.; Prinse, W.C.; Smorenburg, C.

    1997-01-01

    The Fabry-Perot Velocity Interferometer System (F-PVIS) is designed and built for measuring the Doppler shift of light by recording positional changes in the interferometric pattern behind the Fabry-Perot interferometer. The velocity of a surface can be deduced from the Doppler shift which is caused

  14. Wide-angle spectral imaging using a Fabry-Perot interferometer

    NARCIS (Netherlands)

    Strauch, M.; Livshits, I.L.; Bociort, F.; Urbach, H.P.

    2015-01-01

    We show that wide-angle spectral imaging can be achieved with compact and cost-effective devices using Fabry-Pérot interferometers. Designs with a full field of view of 90°, in which the Fabry-Pérot interferometer is mounted either in front of an imaging lens system or behind a telecentric lens syst

  15. A Fabry-Perot interferometer system for high-speed velocity measurement

    NARCIS (Netherlands)

    Cheng, L.K.; Bruinsma, A.J.A.; Prinse, W.C.; Smorenburg, C.

    1997-01-01

    The Fabry-Perot Velocity Interferometer System (F-PVIS) is designed and built for measuring the Doppler shift of light by recording positional changes in the interferometric pattern behind the Fabry-Perot interferometer. The velocity of a surface can be deduced from the Doppler shift which is caused

  16. Fever of unknown origin and leukemoid reaction as initial presentation of adult-onset Still's disease.

    Science.gov (United States)

    Pardo-Cabello, Alfredo José; Manzano-Gamero, Victoria; Javier-Martínez, Rosario

    2014-01-01

    Adult Still's Disease has been reported as cause of Fever of Unknown Origin. Leukocytosis has been described as a common haematological abnormality in Adult Still's Disease. In some rare cases, leukemoid reaction has been reported associated to Still's Disease. We report the case of Adult Still's Disease presenting as Fever of Unknown Origin and leukemoid reaction in a patient with Down Syndrome. The patient needed high dosage of corticosteroids to control the disease and haematological findings.

  17. Recent publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing progress toward improved AD clinical trials.

    Science.gov (United States)

    Weiner, Michael W; Veitch, Dallas P; Aisen, Paul S; Beckett, Laurel A; Cairns, Nigel J; Green, Robert C; Harvey, Danielle; Jack, Clifford R; Jagust, William; Morris, John C; Petersen, Ronald C; Saykin, Andrew J; Shaw, Leslie M; Toga, Arthur W; Trojanowski, John Q

    2017-04-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the over 400 publications using ADNI data during 2014 and 2015. We used standard searches to find publications using ADNI data. (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses. Models of prion-like spreading of Aβ pathology along WM tracts predict known patterns of cortical Aβ deposition and declines in glucose metabolism; (7) New AD risk and protective gene loci have been identified using biologically informed approaches; (8) Cognitively normal and mild cognitive impairment (MCI) subjects are heterogeneous and include groups typified not only by "classic" AD pathology but also by normal biomarkers, accelerated decline, and suspected non-Alzheimer's pathology; (9) Selection of subjects at risk of imminent decline on the basis of one or more pathologies improves the power of clinical trials; (10) Sensitivity of cognitive outcome measures to early changes in cognition has been improved and

  18. Left Ventricular Geometry and Blood Pressure as Predictors of Adverse Progression of Fabry Cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Johannes Krämer

    Full Text Available In spite of several research studies help to describe the heart in Fabry disease (FD, the cardiomyopathy is not entirely understood. In addition, the impact of blood pressure and alterations in geometry have not been systematically evaluated.In 74 FD patients (mean age 36±12 years; 45 females the extent of myocardial fibrosis and its progression were quantified using cardiac magnetic-resonance-imaging with late enhancement technique (LE. Results were compared to standard echocardiography complemented by 2D-speckle-tracking, 3D-sphericity-index (SI and standardized blood pressure measurement. At baseline, no patient received enzyme replacement therapy (ERT. After 51±24 months, a follow-up examination was performed.Systolic blood pressure (SBP was higher in patients with vs. without LE: 123±17 mmHg vs. 115±13 mmHg; P = 0.04. A positive correlation was found between SI and the amount of LE-positive myocardium (r = 0.51; P<0.001 indicating an association of higher SI in more advanced stages of the cardiomyopathy. SI at baseline was positively associated with the increase of LE-positive myocardium during follow-up. The highest SBP (125±19 mmHg and also the highest SI (0.32±0.05 was found in the subgroup with a rapidly increasing LE (ie, ≥0.2% per year; n = 16; P = 0.04. Multivariate logistic regression analysis including SI, SBP, EF, left ventricular volumes, wall thickness and NT-proBNP adjusted for age and sex showed SI as the most powerful parameter to detect rapid progression of LE (AUC = 0.785; P<0.05.LV geometry as assessed by the sphericity index is altered in relation to the stage of the Fabry cardiomyopathy. Although patients with FD are not hypertensive, the SBP has a clear impact on the progression of the cardiomyopathy.

  19. Holographic liquid crystal polarization grating with Fabry-Perot structure.

    Science.gov (United States)

    Sakamoto, Moritsugu; Yamaguchi, Haruki; Noda, Kohei; Sasaki, Tomoyuki; Kawatsuki, Nobuhiro; Ono, Hiroshi

    2016-03-15

    A holographic liquid crystal polarization grating with a Fabry-Perot structure was developed. Because of its resonant structure, the device offers high levels of control of the diffraction properties of incident-polarized light beams, depending on the resonance conditions. The diffracted light beams are emitted in both the reflection and transmission directions, and the device thus works as a multibranch polarization grating with double optical paths, unlike a conventional polarization grating. These device features were experimentally demonstrated and were also explained theoretically.

  20. Review: Research progress on Fabry-Perot resonator antenna

    Institute of Scientific and Technical Information of China (English)

    Zhen-guo LIU; Zhi-chen GE; Xi-yuan CHEN

    2009-01-01

    The Fabry-Perot resonator (FPR) antenna has found wide applications in microwave and millimeter waves and recently attracted considerable interest, in this paper, a summary of planar and cylindrical structures, analytic models and research development is presented, and a comparison between these structures and analytic models is made, showing that such analytic models as the FP cavity mode, electromagnetic band gap (EBG) defect mode, transmission line mode, and leaky-wave mode are consistent when applied to analyze this type of resonator antenna. Some interesting topics under recent research, including dual or multi-band, improvement of gain bandwidth, low profile and beam control, are surveyed.

  1. A stable fiber-based Fabry-Perot cavity

    CERN Document Server

    Steinmetz, T; Colombe, Y; Hunger, D; Hänsch, T W; Warburton, R J; Reichel, J

    2006-01-01

    We report the development of a fiber-based, tunable optical cavity with open access. The cavity is of the Fabry-Perot type and is formed with miniature spherical mirrors positioned on the end of single- or multi-mode optical fibers by a transfer technique which involves lifting a high-quality mirror from a smooth convex substrate, either a ball lens or micro-lens. The cavities typically have a finesse of $\\sim 1,000$ and a mode volume of 600 $\\mu$m$^3$. We demonstrate the detection of small ensembles of cold Rb atoms guided through such a cavity on an atom chip.

  2. Experimental measurement of photothermal effect in Fabry-Perot cavities

    CERN Document Server

    De Rosa, M L; Cerdonio, M; Pinard, M; Marin, F

    2002-01-01

    We report the experimental observation of the photothermal effect. The measurements are performed by modulating the laser power absorbed by the mirrors of two high-finesse Fabry-Perot cavities. The results are very well described by a recently proposed theoretical model [M. Cerdonio, L. Conti, A. Heidmann and M. Pinard, Phys. Rev. D 63 (2001) 082003], confirming the correctness of such calculations. Our observations and quantitative characterization of the photothermal effect demonstrate its critical importance for high sensitivity interferometric displacement measurements, as those necessary for gravitational wave detection.

  3. 77 FR 4048 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-01-26

    ... Dengue Epidemiology, Outcomes, and Prevention in Sentinel Surveillance and Research Sites in Puerto Rico... to ``Evaluation of Dengue Epidemiology, Outcomes and Prevention in Sentinel Surveillance and Research... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention...

  4. A Supranuclear Disorder of Ocular Motility as a Rare Initial Presentation of Motor Neurone Disease.

    Science.gov (United States)

    Yu-Wai-Man, C; Petheram, K; Davidson, A W; Williams, T; Griffiths, P G

    2011-01-01

    A case is described of motor neurone disease presenting with an ocular motor disorder characterised by saccadic intrusions, impaired horizontal and vertical saccades, and apraxia of eyelid opening. The occurrence of eye movement abnormalities in motor neurone disease is discussed.

  5. Initial cognitive response to cholinesterase inhibitors and subsequent long-term course in patients with mild Alzheimer's disease

    NARCIS (Netherlands)

    Droogsma, Erika; van Asselt, Dieneke; Diekhuis, Marjolein; Veeger, Nic; van der Hooft, Cornelis; De Deyn, Peter Paul

    Background: Some guidelines recommend to discontinue treatment with cholinesterase inhibitors (ChEIs) in patients with Alzheimer's disease (AD) without an initial response to ChEI treatment. Evidence supporting this recommendation, however, is limited. This study aimed to investigate the relation

  6. Dietary Patterns Predict Subsequent Coronary Heart Disease Risk In Postmenopausal Women : The Women’s Health Initiative Observational Cohort Study

    Science.gov (United States)

    Background: Evidence suggests that dietary patterns predispose to the development of coronary heart disease (CHD). The relationship between dietary patterns and CHD risk was assessed in postmenopausal women participating in the Women’s Health Initiative Observational Study (WHI-OS). Methods: Case-co...

  7. 77 FR 20822 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-04-06

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Emerging Vector- Borne Zoonotic Pathogens in Indonesia, Funding Opportunity Announcement (FOA) CK12-002... both the Centers for Disease Control and Prevention and the Agency for Toxic Substances and...

  8. 77 FR 12844 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-03-02

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Emerging Vector- Borne Zoonotic Pathogens in Indonesia, Funding Opportunity Announcement (FOA) CK12-002..., for both the Centers for Disease Control and Prevention and the Agency for Toxic Substances...

  9. 77 FR 5257 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-02-02

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Emerging Vector Borne Zoonotic Pathogens in Indonesia, Funding Opportunity Announcement (FOA), CK12-002...), the Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: Time...

  10. 77 FR 25180 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-04-27

    ... Dengue Epidemiology, Outcomes, and Prevention in Sentinel Surveillance and Research Sites in Puerto Rico... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... meetings and other committee management activities, for both the Centers for Disease Control and...

  11. Initially unrecognised group A streptococcal pelvic inflammatory disease in a postmenopausal woman

    NARCIS (Netherlands)

    Kouijzer, I.J.; Polderman, F.N.; Bekers, E.M.; Bloks, P.H.; Schneeberger, P.M.; Jager, C.P. de

    2014-01-01

    Invasive group A streptococcal infection is a severe disease with high mortality. Invasive group A streptococcal infection may arise after pelvic inflammatory disease. Pelvic inflammatory disease in postmenopausal women is rare. Here, we report a unique case of a postmenopausal woman with fatal

  12. 78 FR 78966 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2013-12-27

    ..., Prevention, and Treatment of Influenza and Other Respiratory Infections in a Malaria- Endemic Area of Malawi... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... Disease Control and Prevention (CDC) announces the aforementioned meeting: Time and Date: 1:00 p.m.-3:00...

  13. Effect of an Oral Adsorbent, AST-120, on Dialysis Initiation and Survival in Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Shingo Hatakeyama

    2012-01-01

    Full Text Available The oral adsorbent AST-120 has the potential to delay dialysis initiation and improve survival of patients on dialysis. We evaluated the effect of AST-120 on dialysis initiation and its potential to improve survival in patients with chronic kidney disease. The present retrospective pair-matched study included 560 patients, grouped according to whether or not they received AST-120 before dialysis (AST-120 and non-AST-120 groups. The cumulative dialysis initiation free rate and survival rate were compared by the Kaplan-Meier method. Multivariate analysis was used to determine the impact of AST-120 on dialysis initiation. Our results showed significant differences in the 12- and 24-month dialysis initiation free rate (P<0.001, although no significant difference was observed in the survival rate between the two groups. In conclusion, AST-120 delays dialysis initiation in chronic kidney disease (CKD patients but has no effect on survival. AST-120 is an effective therapy for delaying the progression of CKD.

  14. Influence of socioeconomic and demographic status on spirometry testing in patients initiating medication targeting obstructive lung disease

    DEFF Research Database (Denmark)

    Koefoed, Mette M; Søndergaard, Jens; Christensen, René Depont;

    2013-01-01

    a possible association between education, income, labour market affiliation, cohabitation status and having spirometry performed when initiating medication targeting obstructive pulmonary disease. METHODS: We conducted a population-based cohort study. Danish national registers were linked, retrieving data...... on prescriptions, spirometry testing, socioeconomic and demographic variables in all first time users of medication targeting obstructive lung disease in 2008. RESULTS: A total of 37,734 persons were included and approximately half of the cohort had spirometry performed. Among medication users under 65 years...... spirometry performed among men (OR = 0.78, CI = 0.69-0.88). CONCLUSION: Social inequity in spirometry testing among patients initiating medication targeting obstructive lung disease was confirmed in this study. Increased focus on spirometry testing among elderly men living alone, among the unemployed...

  15. 可调Fabry-Perot腔滤波器结构%On the Structure of Fabry-Perot Tunable Optical Filter

    Institute of Scientific and Technical Information of China (English)

    于多多

    2006-01-01

    设计了C波段可调光纤Fabry-Perot腔光滤波器,并对其进行了参数特性及影响因素的分析.器件在较宽的自由光谱区内有良好的滤光特性,可调谐范围广,优于绝大部分其他类型的光滤波器,并且具有较高的精细度特性.

  16. 光纤Fabry-Perot腔振动传感器%Fiber Optical Fabry-Perot Vibration Sensor

    Institute of Scientific and Technical Information of China (English)

    江毅; 刘莉

    2003-01-01

    用频谱分析的方法对光纤Fabry-Perot腔传感器的输出信号进行解调.在正弦振动条件下,用干涉信号的3次谐波与基次波的功率比直接计算出振动幅度,可以简单地解调出信号.这一技术能够满足工程中精度要求不是很高的场合应用.

  17. Error analysis of Fabry-Perot Filter%Fabry-Perot滤光器的误差分析

    Institute of Scientific and Technical Information of China (English)

    常亮; 刘忠

    2007-01-01

    本文介绍了影响Fabry-Perot滤光器性能的几个重要因素,并对其产生的误差进行了分析,主要有相位误差,温度变化对系统产生的误差,光线入射角度偏移所带来的误差以及平板平行度误差和平板面形精度对系统的影响等.

  18. Nurse-initiated telephone follow-ups of patients with chronic obstructive pulmonary disease do not reduce readmission rates but support disease management: A randomised controlled trial

    DEFF Research Database (Denmark)

    Karlsson, Marie Lavesen; Ladelund, Steen; Just, Addie

    2016-01-01

    of disease management were completed. Readmission and death were recorded on days 30 and 84. Results: There was no significant difference in readmission rates, but significant differences in patients’ assessment of own perception of managing dyspnoea, lung symptoms, ability to react to signs of exacerbation......Introduction: Readmissions reduce quality of life and increase mortality. Furthermore, disease severity and shortened length of stay make it difficult to support disease management during admission. The aim of this study was to explore whether telephone follow-up after discharge may reduce...... readmission rates, lower mortality and improve disease management in patients with chronic obstructive pulmonary disease (COPD). 
Methods: This was a randomised controlled trial (n = 224) with nurse-initiated telephone intervention after discharge. On day 30, questionnaires about health status and perceptions...

  19. Fiber-coupled short Fabry-Perot resonators

    Energy Technology Data Exchange (ETDEWEB)

    Stone, J.; Marcuse, D. (AT and T Bell Labs., Holmdel, NJ (USA))

    1989-05-01

    Fabry-Perot resonators intended as filters in wavelength-multiplexed optical communications systems may have to be very short (on the order of 10 {mu}m) in order to increase their free spectral range. Short, yet tunable cavities can be designed as air gaps between two fibers placed in close proximity with highly reflecting mirrors deposited on their ends. However, an air-gap resonator with plane mirrors between closely spaced fiber ends may yield low throughout because of the poor match between the modes of typical single-mode fibers and the resonant mode in the air-gap cavity. The throughput can be improved by confining the resonant mode by means of a hollow dielectric tube placed inside the resonator. This paper compares short fiber-coupled Fabry-Parot resonators with and without an inserted hollow dielectric waveguide and derives expressions for their transmission losses. The authors show that the throughput of both types of resonator can be improved significantly by using a special fiber with large mode size to couple to the resonator. The special fiber is then spliced to a conventional single-mode fiber. They conclude that the resonator with an inserted hollow dielectric waveguide offers increased throughput for resonators with high finesse.

  20. Transforming Fabry-Pérot resonances into a Tamm mode

    Science.gov (United States)

    Durach, Maxim; Rusina, Anastasia

    2012-12-01

    We propose an optical structure composed of two metal nanolayers enclosing a distributed Bragg reflector (DBR) mirror. The structure is an open photonic system whose bound modes are coupled to external radiation. We apply the special theoretical treatment based on inversion symmetry of the structure to classify its resonances. We show that the structure supports resonances transitional between Fabry-Pérot modes and Tamm plasmons. When the dielectric contrast of the DBR is removed these modes are a pair of conventional Fabry-Pérot resonances. They spectrally merge into a Tamm mode at high contrast. The optical properties of the structure in the frequency range of the DBR stop band, including highly beneficial 50% transmittivity through thick structures with sub-skin-depth metal films, are determined by the hybrid quasinormal modes of the open nonconservative structure under consideration. The results can find a broad range of applications in photonics and optoelectronics, including the possibility of coherent control over optical fields in the class of structures similar to the one proposed here.

  1. Hydrocarbon gas detection with microelectromechanical Fabry-Perot interferometer

    Science.gov (United States)

    Mannila, Rami; Tuohiniemi, Mikko; Mäkynen, Jussi; Näkki, Ismo; Antila, Jarkko

    2013-05-01

    VTT Technical Research Centre of Finland has developed microelectromechanical (MEMS) Fabry-Perot interferometer (FPI) for hydrocarbon measurements. Fabry-Perot interferometer is a structure where is two highly reflective surfaces separated by a tunable air gap. The MEMS FPI is a monolithic device, i.e. it is made entirely on one substrate in a batch process, without assembling separate pieces together. The gap is adjusted by moving the upper mirror with electrostatic force, so there are no actual moving parts. The manufactured MEMS FPIs have been characterized. The tuning wavelength range of the MEMS FPI is 2.8-3.5 μm and its spectral resolution is 50-60 nm. VTT has designed and manufactured a handheld size demonstrator device based on the technology presented in this abstract. This device demonstrates gas detecting by measuring cigarette lighter gas and various plastic materials transmission spectra. The demonstrator contains light source, gas cell, MEMS FPI, detector and control electronics. It is connected to a laptop by USB connection, additional power supply or connection is not needed.

  2. Spirometry utilisation among Danish adults initiating medication targeting obstructive lung disease

    DEFF Research Database (Denmark)

    Koefoed, Mette

    2015-01-01

    with pharmacotherapy targeting obstructive lung disease and only few have additional tests conducted, although the predictive value of respiratory symptoms for diagnosing obstructive lung disease has proven to be low. Spirometry is recommended as the gold standard for confirming obstructive lung disease, and testing...... prescriptions for medication targeting obstructive lung disease are registered. All spirometry tests provided to the patient cohort in the time period 2007-2010 were extracted from the Danish National Health Service Register and the Danish National Patient Register and we assessed if patients had a spirometry...

  3. Disease progression model for Clinical Dementia Rating–Sum of Boxes in mild cognitive impairment and Alzheimer’s subjects from the Alzheimer’s Disease Neuroimaging Initiative

    Directory of Open Access Journals (Sweden)

    Samtani MN

    2014-05-01

    Full Text Available Mahesh N Samtani, Nandini Raghavan, Gerald Novak, Partha Nandy, Vaibhav A Narayan On behalf of the Alzheimer’s disease Neuroimaging Initiative Janssen Research and Development, LLC, Raritan, New Jersey, USA Background: The objective of this analysis was to develop a nonlinear disease progression model, using an expanded set of covariates that captures the longitudinal Clinical Dementia Rating Scale–Sum of Boxes (CDR–SB scores. These were derived from the Alzheimer’s disease Neuroimaging Initiative ADNI-1 study, of 301 Alzheimer’s disease and mild cognitive impairment patients who were followed for 2–3 years. Methods: The model describes progression rate and baseline disease score as a function of covariates. The covariates that were tested fell into five groups: a hippocampal volume; b serum and cerebrospinal fluid (CSF biomarkers; c demographics and apolipoprotein Epsilon 4 (ApoE4 allele status; d baseline cognitive tests; and e disease state and comedications. Results: Covariates associated with baseline disease severity were disease state, hippocampal volume, and comedication use. Disease progression rate was influenced by baseline CSF biomarkers, Trail-Making Test part A score, delayed logical memory test score, and current level of impairment as measured by CDR–SB. The rate of disease progression was dependent on disease severity, with intermediate scores around the inflection point score of 10 exhibiting high disease progression rate. The CDR–SB disease progression rate in a typical patient, with late mild cognitive impairment and mild Alzheimer’s disease, was estimated to be approximately 0.5 and 1.4 points/year, respectively. Conclusions: In conclusion, this model describes disease progression in terms of CDR–SB changes in patients and its dependency on novel covariates. The CSF biomarkers included in the model discriminate mild cognitive impairment subjects as progressors and nonprogressors. Therefore, the model may

  4. Rheumatoid arthritis patients with continued low disease activity have similar outcomes over 10 years, regardless of initial therapy.

    Science.gov (United States)

    Bergstra, Sytske Anne; Landewé, Robert B M; Huizinga, Tom W J; Allaart, Cornelia F

    2017-10-01

    To compare 10-year disease outcomes of RA patients who have continuous low disease activity and are on MTX with or without initial combination therapy with infliximab or prednisone and SSZ. Recent-onset RA patients from the Behandel Strategieen (BeSt) (Dutch acronym for Treatment Strategies) study with 10 years of follow-up were analysed. Treatment was tightly controlled, targeted at DAS ⩽ 2.4. The selected patients had low disease activity from 6 months until 10 years and therefore did not intensify treatment. Patients were grouped into those receiving MTX monotherapy and those receiving initial combination therapy. Between-group differences over time were compared, using (generalized) linear mixed model analyses, for the outcomes DAS, HAQ, ESR, visual analogue scale patient global health, percentage of patients in (drug-free) remission and percentage of patients with Sharp/van der Heijde score progression ⩾5. At 10 years, 28/247 (11%) patients on MTX monotherapy (some tapered to drug free) had continued DAS ⩽ 2.4 compared with 68/261 (26%) patients on combination therapy (all tapered to monotherapy or drug free). No between-group differences in continuous responders were found over time, except for a higher percentage of patients in drug-free remission after MTX monotherapy. Significant group-time interactions were found for DAS, ESR and visual analogue scale patient global health, but the results seem clinically negligible. More patients achieved continuous low disease activity on initial prednisone or infliximab combination therapy than on initial MTX monotherapy, but there appeared to be no additional benefits. Regardless of induction therapy, patients with continuous low disease activity have similar long-term outcomes, with only a higher proportion of patients in drug-free remission after MTX monotherapy.

  5. 77 FR 291 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-01-04

    ... Positive Persons, Funding Opportunity Announcement (FOA), PS12-001, initial review. In accordance with... HIV Prevention with Positive Persons, FOA PS12-001.'' Contact Person for More Information:...

  6. 78 FR 9926 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2013-02-12

    ... Incentive- based Smoking Cessation for Pregnant Women, FOA DP 13-003, initial review. In accordance with... applications received in response to ``Cost-Benefit of Incentive-based Smoking Cessation for Pregnant...

  7. 77 FR 28393 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-05-14

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and..., Cholera and HIV/AIDS Response, FOA GH12-001, and Research and Technical Assistance for Public Health Laboratories in Haiti to Support Post Earthquake Reconstruction, Cholera and HIV/AIDS Response, FOA...

  8. 77 FR 14806 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-03-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and..., Prevention and Treatment of Influenza and Other Respiratory Infections in Ghana, Studies at the...

  9. 77 FR 4047 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-01-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and..., Prevention and Treatment of Influenza and Other Respiratory Infections in Ghana, IP12- 001, Studies at...

  10. Lack of spirometry use in Danish patients initiating medication targeting obstructive lung disease

    DEFF Research Database (Denmark)

    Koefoed, Mette; Christensen, René Depont; Søndergaard, Jens;

    2012-01-01

    Research indicates that a large proportion of patients using medication targeting obstructive lung disease have no history of spirometry testing.......Research indicates that a large proportion of patients using medication targeting obstructive lung disease have no history of spirometry testing....

  11. Towards reframing health service delivery in Uganda: the Uganda Initiative for Integrated Management of Non-Communicable Diseases

    Directory of Open Access Journals (Sweden)

    Jeremy I. Schwartz

    2015-01-01

    Full Text Available Background: The burden of non-communicable diseases (NCDs in low- and middle-income countries (LMICs is accelerating. Given that the capacity of health systems in LMICs is already strained by the weight of communicable diseases, these countries find themselves facing a double burden of disease. NCDs contribute significantly to morbidity and mortality, thereby playing a major role in the cycle of poverty, and impeding development. Methods: Integrated approaches to health service delivery and healthcare worker (HCW training will be necessary in order to successfully combat the great challenge posed by NCDs. Results: In 2013, we formed the Uganda Initiative for Integrated Management of NCDs (UINCD, a multidisciplinary research collaboration that aims to present a systems approach to integrated management of chronic disease prevention, care, and the training of HCWs. Discussion: Through broad-based stakeholder engagement, catalytic partnerships, and a collective vision, UINCD is working to reframe integrated health service delivery in Uganda.

  12. Towards reframing health service delivery in Uganda: the Uganda Initiative for Integrated Management of Non-Communicable Diseases.

    Science.gov (United States)

    Schwartz, Jeremy I; Dunkle, Ashley; Akiteng, Ann R; Birabwa-Male, Doreen; Kagimu, Richard; Mondo, Charles K; Mutungi, Gerald; Rabin, Tracy L; Skonieczny, Michael; Sykes, Jamila; Mayanja-Kizza, Harriet

    2015-01-01

    The burden of non-communicable diseases (NCDs) in low- and middle-income countries (LMICs) is accelerating. Given that the capacity of health systems in LMICs is already strained by the weight of communicable diseases, these countries find themselves facing a double burden of disease. NCDs contribute significantly to morbidity and mortality, thereby playing a major role in the cycle of poverty, and impeding development. Integrated approaches to health service delivery and healthcare worker (HCW) training will be necessary in order to successfully combat the great challenge posed by NCDs. In 2013, we formed the Uganda Initiative for Integrated Management of NCDs (UINCD), a multidisciplinary research collaboration that aims to present a systems approach to integrated management of chronic disease prevention, care, and the training of HCWs. Through broad-based stakeholder engagement, catalytic partnerships, and a collective vision, UINCD is working to reframe integrated health service delivery in Uganda.

  13. Fiber Current Sensor Based on Fabry-Perot%基于光纤Fabry-Perot的电流传感器

    Institute of Scientific and Technical Information of China (English)

    刘京诚; 姚小芳; 陈小强; 刘俊

    2007-01-01

    利用光纤抗电磁干扰、绝缘性好, 体积小等特性,提出一种新型的光纤电流传感器. 该传感器将悬臂梁结构和光纤Fabry-Perot相结合,基于材料力学理论和电磁感应原理,利用Fabry-Perot干涉仪原理来实现对电流的测量. 在解调方式上采用了相位解调法,分析了该传感器的工作原理及光纤F-P的测量原理,建立了光纤F-P腔的数学模型,推导出电流检测理论公式,并进行了相关实验,证明该电流传感器具有绝缘性好、结构简单、灵敏度高等优点.

  14. Points to consider for reporting, screening for and preventing selected comorbidities in chronic inflammatory rheumatic diseases in daily practice : a EULAR initiative

    NARCIS (Netherlands)

    Baillet, Athan; Gossec, Laure; Carmona, Loreto; de Wit, Maarten; van Eijk-Hustings, Yvonne; Bertheussen, Heidi; Alison, Kent; Toft, Mette; Kouloumas, Marios; Ferreira, Ricardo J. O.; Oliver, Susan; Rubbert-Roth, Andrea; van Assen, Sander; Dixon, William G.; Finckh, Axel; Zink, Angela; Kremer, Joel; Kvien, Tore K.; Nurmohamed, Michael; van der Heijde, Desiree; Dougados, Maxime

    2016-01-01

    In chronic inflammatory rheumatic diseases, comorbidities such as cardiovascular diseases and infections are suboptimally prevented, screened for and managed. The objective of this European League Against Rheumatism (EULAR) initiative was to propose points to consider to collect comorbidities in pat

  15. Focused ion beam post-processing of optical fiber Fabry-Perot cavities for sensing applications.

    Science.gov (United States)

    André, Ricardo M; Pevec, Simon; Becker, Martin; Dellith, Jan; Rothhardt, Manfred; Marques, Manuel B; Donlagic, Denis; Bartelt, Hartmut; Frazão, Orlando

    2014-06-01

    Focused ion beam technology is combined with chemical etching of specifically designed fibers to create Fabry-Perot interferometers. Hydrofluoric acid is used to etch special fibers and create microwires with diameters of 15 μm. These microwires are then milled with a focused ion beam to create two different structures: an indented Fabry-Perot structure and a cantilever Fabry-Perot structure that are characterized in terms of temperature. The cantilever structure is also sensitive to vibrations and is capable of measuring frequencies in the range 1 Hz - 40 kHz.

  16. A novel Michelson Fabry-Perot hybrid interference sensor based on the micro-structured fiber

    Science.gov (United States)

    Zhang, Yaxun; Zhang, Yu; Wang, Zhenzhen; Liu, Zhihai; Wei, Yong; Zhao, Enming; Yang, Xinghua; Zhang, Jianzhong; Yang, Jun; Yuan, Libo

    2016-09-01

    We propose and demonstrate a novel Michelson Fabry-Perot hybrid fiber interference sensor. By integrating a Michelson interferometer in a two-core fiber and a Fabry-Perot interferometer in a micro silica-capillary, we produce the Michelson Fabry-Perot hybrid interference sensor. Owing to the structure characteristic of the micro-structured fiber, this hybrid fiber interference sensor can achieve the measurement of the axial strain and radial bending simultaneously. The measurement sensitivity of the axial train is 0.015 nm/με and the measurement sensitivity of the radial bending is 1.393 nm/m-1.

  17. Two-Color Fabry-Perot Laser Diode with THz Primary Mode Spacing

    CERN Document Server

    O'Brien, S; Buckley, K; Fehse, R; Amann, A; O'Reilly, E P; Barry, L P; Anandarajah, P; Patchell, J; O'Gorman, J

    2006-01-01

    A class of multiwavelength Fabry-Perot lasers is introduced where the spectrum is tailored through a non-periodic patterning of the cavity effective index. The cavity geometry is obtained using an inverse scattering approach and can be designed such that the spacing of discrete Fabry-Perot lasing modes is limited only by the bandwidth of the inverted gain medium. A specific two-color semiconductor laser with a mode spacing in the THz regime is designed, and measurements are presented demonstrating the simultaneous oscillation of the two wavelengths. The extension of the Fabry-Perot laser concept described presents significant new possibilities in laser cavity design.

  18. Fabry-perot multilayers for enhancing the diffraction efficiency of ion-implanted gratings.

    Science.gov (United States)

    Escoubas, L; Flory, F O; Lemarchand, F; Drouard, E; Roux, L; Tisserand, S; Albrand, G

    2001-04-01

    Enhancement of the free-space diffraction efficiency of gratings made by titanium-ion implantation is demonstrated both theoretically and experimentally. Indeed, by insertion of a grating into a multilayer dielectric Fabry-Perot cavity, the diffraction efficiency can be increased to as much as 24 times that of a single grating. The sensitivity of the diffraction efficiency to the optogeometrical parameters of the grating or of the Fabry-Perot cavity is discussed. Moreover, a process for performance of a phase grating inside a Fabry-Perot cavity is described, and experimental results concerning efficiency measurements are compared with computed values for various grating periods.

  19. Fabry-Perot Diaphragm Fiber Optic Sensor (DFOS for Acoustic Detection

    Directory of Open Access Journals (Sweden)

    Yan SUN

    2007-10-01

    Full Text Available A diaphragm fiber optic sensor (DFOS solely based on Fabry-Perot multiple beam interference has been designed and fabricated with micro-electric mechanical system (MEMS technology. The silicon diaphragm with an embossed center was designed with an interference gap width kept accurately. The DFOS was verified to be a truly and purely Fabry-Perot device via a critical test. Parallel testing with a Piezoelectric (PZT sensor showed that the DFOS had high sensitivity. The Fabry-Perot DFOS also demonstrated excellent performance in on-line monitoring of Partial Discharge (PD in power transformers.

  20. [Efficacy of metformin as initial therapy in patients with coronary artery disease and diabetes type 2].

    Science.gov (United States)

    Lavrenko, A V; Kutsenko, L A; Solokhina, I L; Rasin, M S; Kaĭdashev, I P

    2011-01-01

    The use of metformin during the first month of treatment of patients with coronary artery disease and diabetes type 2 led to the decrease of insulin resistance and reduced activity of systemic inflammation (significant decrease in the concentrations of IL-1, IL-6, IL-8 and TNF-alpha). Reduced activity of systemic inflammation had a beneficial effect on the course of coronary artery disease (significant decrease in the functional class of stable angina). Type 2 diabetes appears to be quite successfully modifiable risk factor for coronary artery disease by the adequate controls.

  1. Abnormalities of the First Three Steps of Gait Initiation in Patients with Parkinson's Disease with Freezing of Gait

    Directory of Open Access Journals (Sweden)

    Yohei Okada

    2011-01-01

    Full Text Available The purpose of this study was to investigate abnormalities of the first three steps of gait initiation in patients with Parkinson's disease (PD with freezing of gait (FOG. Ten PD patients with FOG and 10 age-matched healthy controls performed self-generated gait initiation. The center of pressure (COP, heel contact positions, and spatiotemporal parameters were estimated from the vertical pressures on the surface of the force platform. The initial swing side of gait initiation was consistent among the trials in healthy controls but not among the trials in PD patients. The COP and the heel contact position deviated to the initial swing side during the first step, and the COP passed medial to each heel contact position during the first two steps in PD patients. Medial deviation of the COP from the first heel contact position had significant correlation with FOG questionnaire item 5. These findings indicate that weight shifting between the legs is abnormal and that medial deviation of the COP from the first heel contact position sensitively reflects the severity of FOG during the first three steps of gait initiation in PD patients with FOG.

  2. A US database study characterizing patients initiating a budesonide–formoterol combination versus tiotropium bromide as initial maintenance therapy for chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Kern DM

    2014-07-01

    Full Text Available David M Kern,1 Setareh A Williams,2 Ozgur Tunceli,1 Catrin Wessman,3 Siting Zhou,1 Ned Pethick,2 Hanaa Elhefni,2 Frank Trudo2 1HealthCore Inc., 2AstraZeneca, Wilmington, DE, USA; 3AstraZeneca, Mölndal, Sweden Objective: To compare clinical and demographic characteristics, resource utilization and costs of chronic obstructive pulmonary disease (COPD patients prior to initiating budesonide–formoterol combination (BFC or tiotropium-maintenance therapy. Materials and methods: This cross-sectional study used claims-based diagnosis to identify COPD patients in the HealthCore Integrated Research Database who initiated BFC or tiotropium therapy between March 1, 2009 and January 31, 2012 (intake period; the index date was defined as the initial prescription fill for either agent. Patients diagnosed with respiratory tract cancer or receiving inhaled corticosteroids/long-acting β2-adrenergic agonists or tiotropium in 12 months prior to index date were excluded. Categorical variables were evaluated with Χ2 tests; mean cost differences were evaluated using γ-regression. Results: Overall, 6,940 BFC and 10,831 tiotropium patients were identified. The BFC group was younger (mean age 64 versus 67 years, with a greater proportion of females (54% versus 51%. BFC-treated patients had more comorbid respiratory conditions, including asthma (25% versus 13%, but fewer comorbid cardiovascular conditions, including atherosclerosis (7% versus 10% and myocardial infarction (4% versus 6%. A greater proportion of BFC patients received prior respiratory medication, including oral corticosteroids (46% versus 35% and short-acting β2-agonists (44% versus 35%. Tiotropium-treated patients had a greater mean number of COPD-related outpatient visits (4.6 versus 4.1. BFC-treated patients had lower total all-cause ($17,259 versus $17,926 and COPD-related ($1,718 versus $1,930 health care costs, driven by lower all-cause and COPD-related inpatient expenditures. Conclusion

  3. 7-T MRI in Cerebrovascular Diseases : Challenges to Overcome and Initial Results

    NARCIS (Netherlands)

    Harteveld, Anita A; van der Kolk, Anja G; Zwanenburg, Jaco J M; Luijten, Peter R; Hendrikse, J

    2016-01-01

    Magnetic resonance imaging (MRI) plays a key role in the investigation of cerebrovascular diseases. Compared with computed tomography (CT) and digital subtraction angiography (DSA), its advantages in diagnosing cerebrovascular pathology include its superior tissue contrast, its ability to visualize

  4. Controversies in Neurology: why monoamine oxidase B inhibitors could be a good choice for the initial treatment of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Reichmann Heinz

    2011-09-01

    Full Text Available Abstract Background Early initiation of pharmacotherapy in Parkinson's disease (PD is nowadays widely advocated by experts since the delay of treatment has shown to be associated with a significant deterioration of health related quality of life in affected patients. Due to marked advances in PD treatment during the last decades, physicians are nowadays fortunately equipped with a variety of substances that can effectively ameliorate emerging motor symptoms of the disease, among them levodopa, dopamine agonists and monoamine oxidase type B (MAO-B inhibitors. Despite numerous drug intervention trials in early PD, there is however still ongoing controversy among neurologists which substance to use for the initial treatment of the disease. Discussion In multiple studies, MAO-B inhibitors, such as selegiline and rasagiline, have shown to provide mild symptomatic effects, delay the need for levodopa, and to reduce the incidence of motor fluctuations. Although their symptomatic efficacy is inferior compared to dopamine agonists and levodopa, MAO-B inhibitors undoubtedly have fewer side effects and are easy to administer. In contrary to their competitors, MAO-B inhibitors may furthermore offer a chance for disease modification, which so far remains a major unmet need in the management of PD and eventually makes them ideal candidates for the early treatment of the disease. Summary MAO-B inhibitors may constitute a preferable therapeutic option for early PD, mainly due to their favourable safety profile and their putative neuroprotective capabilities. Since the symptomatic effects of MAO-B inhibitors are comparatively mild, dopamine agonists and levodopa should however be considered for initial treatment in those PD patients, in whom robust and immediate symptomatic relief needs to be prioritized.

  5. 77 FR 25485 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-04-30

    ... for Preventing Violence and Violence Related Injury, Funding Opportunity Announcement (FOA) CE12-002..., Management Analysis and Services Office, CDC, pursuant to Public Law 92-463. Matters to be Discussed: The... to ``Research Grants for Preventing Violence and Violence Related Injury, FOA CE12-002, initial...

  6. 77 FR 39497 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-07-03

    ... Projects (SIPs): Nutrition and Obesity Policy Research and Evaluation Network (NOPREN)--Coordinating Center, SIP12-061 and Nutrition and Obesity Policy Research and Evaluation Network (NOPREN)--Collaborating... initial review, discussion, and evaluation of applications received in response to ``Nutrition and Obesity...

  7. 77 FR 21778 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Science.gov (United States)

    2012-04-11

    ... Testing of a Clinic-Based Intervention to Increase Dual Protection against Unintended Pregnancy and STDs among High Risk Female Teens, FOA DP12- 001, initial review. In accordance with Section 10(a)(2) of the... Testing of a Clinic-Based Intervention to Increase Dual Protection against Unintended Pregnancy and...

  8. Frosted branch angiitis, neuroretinitis as initial ocular manifestation in Behçet disease

    Directory of Open Access Journals (Sweden)

    Abdullah Al-Mujaini

    2011-01-01

    Full Text Available Behçet disease is an idiopathic, multisystem disorder characterized by recurrent episodes of orogenital ulceration and vasculitis of the veins and arteries of all calibers. Ocular involvement may affect the conjunctiva, sclera, uveal tract, vitreous, blood vessels, and retina. Many theories have pointed toward an autoimmune response behind its pathogenesis, which may be triggered by exposure to an infectious agent. Frosted branch angiitis is characterized by vascular inflammation, sheathing, retinal edema, and retinal hemorrhages. The disease may be idiopathic in a majority of the cases or may be associated with ocular and systemic pathology. Association between Behηet disease, Frosted branch angiitis, and neuroretinitis is not reported in literature. This uncommon combination reflects the varied systemic and ocular manifestations in Behηet disease, especially in patients who are not diagnosed and treated in time. We hereby report a case of bilateral frosted branch angiitis and neuroretinitis in a young male from Middle-east, suffering from Behçet disease.

  9. Fabry-Perot Observations of HH 1/2

    Directory of Open Access Journals (Sweden)

    A. Riera

    2005-01-01

    Full Text Available Presentamos nuevas observaciones Fabry-Perot del sistema HH1/2 en la l nea de H. Se han obtenidos los perfiles de las l neas, y los mapas de velocidad radial y de dispersi n de velocidades a partir de los canales de velocidad de los objetos HH 1 y HH 2. La distribuci on espacial de la velocidad radial de ambos objetos (HH 1, HH 2 presenta material desplazado al rojo hacia la fuente, y material desplazado al azul alej ndose de la fuente. Un modelo que contempla la presencia de emisi n directa+dispersada con tres condensaciones emisoras reproduce cualitativamente la distribuci n espacial de la velocidad radial y de la dispersi n de velocidades de HH 2.

  10. Millimeter-long fiber Fabry-Perot cavities.

    Science.gov (United States)

    Ott, Konstantin; Garcia, Sebastien; Kohlhaas, Ralf; Schüppert, Klemens; Rosenbusch, Peter; Long, Romain; Reichel, Jakob

    2016-05-01

    We demonstrate fiber Fabry-Perot (FFP) cavities with concave mirrors that can be operated at cavity lengths as large as 1.5 mm without significant deterioration of the finesse. This is achieved by using a laser dot machining technique to shape spherical mirrors with ultralow roughness and employing single-mode fibers with large mode area for good mode matching to the cavity. Additionally, in contrast to previous FFPs, these cavities can be used over an octave-spanning frequency range with adequate coatings. We also show directly that shape deviations caused by the fiber's index profile lead to a finesse decrease as observed in earlier attempts to build long FFP cavities, and show a way to overcome this problem.

  11. Fiber Fabry-Perot interferometer for curvature sensing

    Science.gov (United States)

    Monteiro, Catarina S.; Ferreira, Marta S.; Silva, Susana O.; Kobelke, Jens; Schuster, Kay; Bierlich, Jörg; Frazão, Orlando

    2016-07-01

    A curvature sensor based on an Fabry-Perot (FP) interferometer was proposed. A capillary silica tube was fusion spliced between two single mode fibers, producing an FP cavity. Two FP sensors with different cavity lengths were developed and subjected to curvature and temperature. The FP sensor with longer cavity showed three distinct operating regions for the curvature measurement. Namely, a linear response was shown for an intermediate curvature radius range, presenting a maximum sensitivity of 68.52 pm/m-1. When subjected to temperature, the sensing head produced a similar response for different curvature radii, with a sensitivity varying from 0.84 pm/°C to 0.89 pm/°C, which resulted in a small cross-sensitivity to temperature when the FP sensor was subjected to curvature. The FP cavity with shorter length presented low sensitivity to curvature.

  12. Fourier transform spectrometer based on Fabry-Perot interferometer.

    Science.gov (United States)

    Al-Saeed, Tarek A; Khalil, Diaa A

    2016-07-10

    We analyze the Fourier transform spectrometer based on a symmetric/asymmetric Fabry-Perot interferometer. In this spectrometer, the interferogram is obtained by recording the intensity as a function of the interferometer length. Then, we recover the spectrum by applying the discrete Fourier transform (DFT) directly on the interferogram. This technique results in spectral harmonic overlap and fictitious wavenumber components outside the original spectral range. For this purpose, in this work, we propose a second method to recover the spectrum. This method is based on expanding the DFT of the interferogram and the spectrum by a Haar or box function. By this second method, we recovered the spectrum and got rid of the fictitious spectral components and spectral harmonic overlap.

  13. Millimeter-long Fiber Fabry-Perot cavities

    CERN Document Server

    Ott, Konstantin; Kohlhaas, Ralf; Schüppert, Klemens; Rosenbusch, Peter; Long, Romain; Reichel, Jakob

    2016-01-01

    We demonstrate fiber Fabry-Perot (FFP) cavities with concave mirrors that can be operated at cavity lengths as large as 1.5mm without significant deterioration of the finesse. This is achieved by using a laser dot machining technique to shape spherical mirrors with ultralow roughness and employing single-mode fibers with large mode area for good mode matching to the cavity. Additionally, in contrast to previous FFPs, these cavities can be used over an octave-spanning frequency range with adequate coatings. We also show directly that shape deviations caused by the fiber's index profile lead to a finesse decrease as observed in earlier attempts to build long FFP cavities, and show a way to overcome this problem.

  14. A Fabry-Perot Microcavity for Diamond-Based Photonics

    CERN Document Server

    Janitz, Erika; Dimock, Mark; Bourassa, Alexandre; Sankey, Jack; Childress, Lilian

    2015-01-01

    Open Fabry-Perot microcavities represent a promising route for achieving a quantum electrodynamics (cavity-QED) platform with diamond-based emitters. In particular, they offer the opportunity to introduce high purity, minimally fabricated material into a tunable, high quality factor optical resonator. Here, we demonstrate a fiber-based microcavity incorporating a thick (> 10 {\\mu}m) diamond membrane with a finesse of 17,000, corresponding to a quality factor Q ~ $10^6$. Such minimally fabricated, thick samples can contain optically stable emitters similar to those found in bulk diamond. We observe modified microcavity spectra in the presence of the membrane, and develop analytic and numerical models to describe the effect of the membrane on cavity modes, including loss and coupling to higher-order transverse modes. We estimate that a Purcell enhancement of approximately 20 should be possible for emitters within the diamond in this device, and provide evidence that better diamond surface treatments and mirror ...

  15. Intrinsic Fabry-Perot optical fiber sensors and their multiplexing

    Science.gov (United States)

    Wang, Anbo

    2007-12-11

    An intrinsic Fabry-Perot optical sensor includes a thin film sandwiched between two fiber ends. When light is launched into the fiber, two reflections are generated at the two fiber/thin film interfaces due to a difference in refractive indices between the fibers and the film, giving rise to the sensor output. In another embodiment, a portion of the cladding of a fiber is removed, creating two parallel surfaces. Part of the evanescent fields of light propagating in the fiber is reflected at each of the surfaces, giving rise to the sensor output. In a third embodiment, the refractive index of a small portion of a fiber is changed through exposure to a laser beam or other radiation. Interference between reflections at the ends of the small portion give rise to the sensor output. Multiple sensors along a single fiber are multiplexed using an optical time domain reflectometry method.

  16. Photoacoustic imaging using an 8-beam Fabry-Perot scanner

    Science.gov (United States)

    Huynh, Nam; Ogunlade, Olumide; Zhang, Edward; Cox, Ben; Beard, Paul

    2016-03-01

    The planar Fabry Perot (FP) photoacoustic scanner has been shown to provide exquisite high resolution 3D images of soft tissue structures in vivo to depths up to approximately 10mm. However a significant limitation of current embodiments of the concept is low image acquisition speed. To increase acquisition speed, a novel multi-beam scanner architecture has been developed. This enables a line of equally spaced 8 interrogation beams to be scanned simultaneously across the FP sensor and the photoacoustic signals detected in parallel. In addition, an excitation laser operating at 200Hz was used. The combination of parallelising the detection and the high pulse repetition frequency (PRF) of the excitation laser has enabled dramatic reductions in image acquisition time to be achieved. A 3D image can now be acquired in 10 seconds and 2D images at video rates are now possible.

  17. Diffractively coupled Fabry-Perot resonator with power-recycling

    CERN Document Server

    Britzger, Michael; Kroker, Stefanie; Brückner, Frank; Burmeister, Oliver; Kley, Ernst-Bernhard; Tünnermann, Andreas; Danzmann, Karsten; Schnabel, Roman

    2011-01-01

    We demonstrate the optical coupling of two cavities without light transmission through a substrate. Compared to a conventional coupling component, that is a partially transmissive mirror, an all-reflective coupler avoids light absorption in the substrate and therefore associated thermal problems, and even allows the use of opaque materials with possibly favourable mechanical and thermal properties. Recently, the all-reflective coupling of two cavities with a low-efficiency 3-port diffraction grating was theoretically investigated. Such a grating has an additional (a third) port. However, it was shown that the additional port does not necessarily decrease the bandwidth of the coupled cavities. Such an all-reflective scheme for cavity coupling is of interest in the field of gravitational wave detection. In such detectors light that is resonantly enhanced inside the so-called power-recycling cavity is coupled to (kilometre-scale) Fabry-Perot resonators representing the arms of a Michelson interferometer. In orde...

  18. Fiber Fabry-Perot cavity with high finesse

    CERN Document Server

    Hunger, David; Colombe, Yves; Deutsch, Christian; Hänsch, Theodor W; Reichel, Jakob

    2010-01-01

    We have realized a fiber-based Fabry-Perot cavity with CO2 laser-machined mirrors. It combines very small size, high finesse F>=130000, small waist and mode volume, and good mode matching between the fiber and cavity modes. This combination of features is a major advance for cavity quantum electrodynamics (CQED), as shown in recent CQED experiments with Bose-Einstein condensates enabled by this cavity [Y. Colombe et al., Nature 450, 272 (2007)]. It should also be suitable for a wide range of other applications, including coupling to solid-state emitters, gas detection at the single-particle level, fiber-coupled single-photon sources and high-resolution optical filters with large stopband.

  19. Fiber Fabry-Perot interferometer for curvature sensing

    Science.gov (United States)

    Monteiro, Catarina S.; Ferreira, Marta S.; Silva, Susana O.; Kobelke, Jens; Schuster, Kay; Bierlich, Jörg; Frazão, Orlando

    2016-12-01

    A curvature sensor based on an Fabry-Perot (FP) interferometer was proposed. A capillary silica tube was fusion spliced between two single mode fibers, producing an FP cavity. Two FP sensors with different cavity lengths were developed and subjected to curvature and temperature. The FP sensor with longer cavity showed three distinct operating regions for the curvature measurement. Namely, a linear response was shown for an intermediate curvature radius range, presenting a maximum sensitivity of 68.52 pm/m-1. When subjected to temperature, the sensing head produced a similar response for different curvature radii, with a sensitivity varying from 0.84 pm/°C to 0.89 pm/°C, which resulted in a small cross-sensitivity to temperature when the FP sensor was subjected to curvature. The FP cavity with shorter length presented low sensitivity to curvature.

  20. Fabry-Perot enhanced Faraday rotation in graphene.

    Science.gov (United States)

    Ubrig, Nicolas; Crassee, Iris; Levallois, Julien; Nedoliuk, Ievgeniia O; Fromm, Felix; Kaiser, Michl; Seyller, Thomas; Kuzmenko, Alexey B

    2013-10-21

    We demonstrate that giant Faraday rotation in graphene in the terahertz range due to the cyclotron resonance is further increased by constructive Fabry-Perot interference in the supporting substrate. Simultaneously, an enhanced total transmission is achieved, making this effect doubly advantageous for graphene-based magneto-optical applications. As an example, we present far-infrared spectra of epitaxial multilayer graphene grown on the C-face of 6H-SiC, where the interference fringes are spectrally resolved and a Faraday rotation up to 0.15 radians (9°) is attained. Further, we discuss and compare other ways to increase the Faraday rotation using the principle of an optical cavity.

  1. Micromachined fiber optic Fabry-Perot underwater acoustic probe

    Science.gov (United States)

    Wang, Fuyin; Shao, Zhengzheng; Hu, Zhengliang; Luo, Hong; Xie, Jiehui; Hu, Yongming

    2014-08-01

    One of the most important branches in the development trend of the traditional fiber optic physical sensor is the miniaturization of sensor structure. Miniature fiber optic sensor can realize point measurement, and then to develop sensor networks to achieve quasi-distributed or distributed sensing as well as line measurement to area monitoring, which will greatly extend the application area of fiber optic sensors. The development of MEMS technology brings a light path to address the problems brought by the procedure of sensor miniaturization. Sensors manufactured by MEMS technology possess the advantages of small volume, light weight, easy fabricated and low cost. In this paper, a fiber optic extrinsic Fabry-Perot interferometric underwater acoustic probe utilizing micromachined diaphragm collaborated with fiber optic technology and MEMS technology has been designed and implemented to actualize underwater acoustic sensing. Diaphragm with central embossment, where the embossment is used to anti-hydrostatic pressure which would largely deflect the diaphragm that induce interferometric fringe fading, has been made by double-sided etching of silicon on insulator. By bonding the acoustic-sensitive diaphragm as well as a cleaved fiber end in ferrule with an outer sleeve, an extrinsic Fabry-Perot interferometer has been constructed. The sensor has been interrogated by quadrature-point control method and tested in field-stable acoustic standing wave tube. Results have been shown that the recovered signal detected by the sensor coincided well with the corresponding transmitted signal and the sensitivity response was flat in frequency range from 10 Hz to 2kHz with the value about -154.6 dB re. 1/μPa. It has been manifest that the designed sensor could be used as an underwater acoustic probe.

  2. Contacts to general practice and antidepressant treatment initiation after screening for anxiety and depression in patients with heart disease

    DEFF Research Database (Denmark)

    Larsen, Karen Kjær; Vestergaard, Claus Høstrup; Schougaard, Liv Marit Valen;

    2016-01-01

    Introduction Anxiety and depression are found in 20-30% of all persons with heart disease, and depression is known to impact mortality. This paper aimed to describe the effect of systematic screening of this population in terms of use of general practice, psychological therapy and antidepressant...... symptoms had more general practitioner (GP) contact rates than patients without anxiety or depressive symptoms both before and after the screening. Furthermore, patients with depressive symptoms increased their GP contact rate significantly in the first month after the screening, while...... this was not the case for patients with anxiety symptoms. Finally, patients with heart disease and anxiety or depressive symptoms more frequently initiated treatment with antidepressants than patients with heart disease without anxiety or depressive symptoms, whereas therapy sessions with a psychologist were rarely...

  3. Headache and focal neurologic signs following exposure to spicy aroma as an initial presentation of moyamoya disease

    Directory of Open Access Journals (Sweden)

    Bilal A. Siddiqui, A.B.

    2014-12-01

    Full Text Available Moyamoya disease is a condition of the cerebrovascular system that involves stenosis of the intracranial internal carotid arteries as well as their proximal branches, often leading to stroke in affected patients. Here we describe the case of a patient with headache and focal neurologic signs following exposure to a spicy aroma, who initially had a negative vascular work-up and a preliminary diagnosis of a complex migraine syndrome. She subsequently developed infarction of the left frontal lobe, and imaging studies revealed the diagnosis of moyamoya disease. She was treated with an encephalodurosynangiosis procedure, with notable improvement. This case highlights the importance of considering moyamoya disease in the differential diagnosis of patients presenting with headaches with aura.

  4. Regional Initiatives in Support of Surveillance in East Africa: The East Africa Integrated Disease Surveillance Network (EAIDSNet Experience

    Directory of Open Access Journals (Sweden)

    Maurice Ope

    2013-01-01

    Full Text Available The East African Integrated Disease Surveillance Network (EAIDSNet was formed in response to a growing frequency of cross-border malaria outbreaks in the 1990s and a growing recognition that fragmented disease interventions, coupled with weak laboratory capacity, were making it difficult to respond in a timely manner to the outbreaks of malaria and other infectious diseases. The East Africa Community (EAC partner states, with financial support from the Rockefeller Foundation, established EAIDSNet in 2000 to develop and strengthen the communication channels necessary for integrated cross-border disease surveillance and control efforts. The objective of this paper is to review the regional EAIDSNet initiative and highlight achievements and challenges in its implementation. Major accomplishments of EAIDSNet include influencing the establishment of a Department of Health within the EAC Secretariat to support a regional health agenda; successfully completing a regional field simulation exercise in pandemic influenza preparedness; and piloting a web-based portal for linking animal and human health disease surveillance. The strategic direction of EAIDSNet was shaped, in part, by lessons learned following a visit to the more established Mekong Basin Disease Surveillance (MBDS regional network. Looking to the future, EAIDSNet is collaborating with the East, Central and Southern Africa Health Community (ECSA-HC, EAC partner states, and the World Health Organization to implement the World Bank-funded East Africa Public Health Laboratory Networking Project (EAPHLNP. The network has also begun lobbying East African countries for funding to support EAIDSNet activities.

  5. Oral Campylobacter species: Initiators of a subgroup of inflammatory bowel disease?

    Science.gov (United States)

    Zhang, Li

    2015-08-21

    In recent years, a number of studies detected a significantly higher prevalence of Campylobacter species such as Campylobacter concisus (C. concisus) in intestinal biopsies and fecal samples collected from patients with inflammatory bowel disease (IBD) compared to controls. Most of these Campylobacter species are not of zoonotic origin but are human oral Campylobacter species. Bacterial species usually cause diseases in the location where they colonize. However, C. concisus and other oral Campylobacter species are associated with IBD occurring at the lower parts of the gastrointestinal tract, suggesting that these Campylobacter species may have unique virulence factors that are expressed in the lower parts of the gastrointestinal tract.

  6. Demonstrations Using a Fabry-Perot. I. Multiple-Slit Interference

    Science.gov (United States)

    Roychoudhuri, Chandrasekhar

    1975-01-01

    Describes a demonstration technique for showing multiple-slit interference patterns with the use of a Fabry-Perot etalon and a laser beam. A simple derivation of the analytical expression for such fringes is presented. (Author/CP)

  7. Fabry-Perot Based Ranging Interferometer Receiver for High Spectral Resolution Lidar Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Michigan Aerospace Corporation (MAC) is pleased to present the following Phase II proposal for a Fabry-Perot Based Interferometer Receiver for the High Spectral...

  8. A Novel Technique to Measure Gain Spectrum for Fabry-Pérot Semiconductor Lasers

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A novel gain measurement technique based on the integration of the measured amplified spontaneous emission spectrum multiplying a phase function over one longitudinal mode interval is proposed for Fabry-Perot semiconductor lasers.

  9. Sinusoidal Phase-Modulating Fabry-Perot Interferometer for Angular Displacement Measurement

    Institute of Scientific and Technical Information of China (English)

    Caini Zhang; Xiangzhao Wang

    2003-01-01

    In this paper, a sinusoidal phase-modulating Fabry-Perot interferometer is proposed to measure angular displacement.The usefulness of the interferometer is demonstrated by simulations and experiments.

  10. Compact High-Resolution Broad-Band Terahertz Fabry-Perot Spectrometer Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Our objective is to develop a compact scanning Fabry-Perot spectrometer, for satellite far-infrared astronomy and Earth remote sensing, that operates at wavelengths...

  11. Sinusoidal Phase-Modulating Fabry-Perot Interferometer for Angular Displacement Measurement

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    In this paper, a sinusoidal phase-modulating Fabry-Perot interferometer is proposed to measure angular displacement. The usefulness of the interferometer is demonstrated by simulations and experiments.

  12. Rugged Low Temperature Actuators for Tunable Fabry Perot Optical Filters Project

    Data.gov (United States)

    National Aeronautics and Space Administration — During our Phase I SBIR research, we propose to integrate a novel low-temperature large-strain actuator technology into Fabry-Perot optical filters. The resulting...

  13. Isolated ileal perforation in infancy: a lethal initial presentation of Hirschsprung’s disease

    Directory of Open Access Journals (Sweden)

    Fadi Iskandarani

    2017-06-01

    Full Text Available A rare case of ileal perforation, as a fatal initial presentation of total colonic aganglionosis (TCA in infancy is reported. A 10-week-old boy, was brought to the emergency department with symptoms of complicated intestinal obstruction. He looked ill, was lethargic, markedly dehydrated and had a severely distended abdomen. An abdominal X-ray revealed multiple air fluid levels seen in a distended small intestine. During exploratory laparotomy the ileum was massively dilated with distal segment perforation. Ileal perforation repair was performed. A totally collapsed microcolon was identified. Biopsies were taken from the high rectum, sigmoid and hepatic flexure. Appendectomy and ileostomy were performed. All biopsies, as well as the appendix, showed absence of ganglion cells. Despite this procedure the patient progressively deteriorated and later died due to sepsis. Ileal perforation in infants is a rare, but potentially fatal initial presentation of TCA. Early detection is essential to prevent life-threatening complications.

  14. National Studies as a Component of the World Health Organization Initiative to Estimate the Global and Regional Burden of Foodborne Disease

    NARCIS (Netherlands)

    Lake, Robin J; Devleesschauwer, Brecht; Nasinyama, George; Havelaar, Arie H; Kuchenmüller, Tanja; Haagsma, Juanita A; Jensen, Helen H; Jessani, Nasreen; Maertens de Noordhout, Charline; Angulo, Frederick J; Ehiri, John E; Molla, Lindita; Agaba, Friday; Aungkulanon, Suchunya; Kumagai, Yuko; Speybroeck, Niko

    2015-01-01

    BACKGROUND: The World Health Organization (WHO) initiative to estimate the global burden of foodborne diseases established the Foodborne Diseases Burden Epidemiology Reference Group (FERG) in 2007. In addition to global and regional estimates, the initiative sought to promote actions at a national l

  15. National studies as a component of the World Health Organization initiative to estimate the global and regional burden of foodborne disease

    NARCIS (Netherlands)

    R.J. Lake (Robin); B. Devleesschauwer (Brecht); G. Nasinyama (George); A.H. Havelaar (Arie H); T. Kuchenmüller (Tanja); J.A. Haagsma (Juanita); H.H. Jensen (Helen H.); N. Jessani (Nasreen); C.M. de Noordhout (Charline Maertens); F.J. Angulo (Frederick); J.E. Ehiri (John E.); L. Molla (Lindita); F. Agaba (Friday); S. Aungkulanon (Suchunya); Y. Kumagai (Yuko); N. Speybroeck (Niko)

    2015-01-01

    textabstractBackground: The World Health Organization (WHO) initiative to estimate the global burden of foodborne diseases established the Foodborne Diseases Burden Epidemiology Reference Group (FERG) in 2007. In addition to global and regional estimates, the initiative sought to promote actions at

  16. Development and initial validation of prescribing quality indicators for patients with chronic kidney disease

    NARCIS (Netherlands)

    Smits, Kirsten P J; Sidorenkov, Grigory; Bilo, Henk J G; Bouma, Margriet; van Ittersum, Frans J; Voorham, Jaco; Navis, Gerjan; Denig, Petra

    2016-01-01

    BACKGROUND: Quality assessment is a key element for improving the quality of care. Currently, a comprehensive indicator set for measuring the quality of medication treatment in patients with chronic kidney disease (CKD) is lacking. Our aim was to develop and validate a set of prescribing quality ind

  17. Development and initial validation of prescribing quality indicators for patients with chronic kidney disease

    NARCIS (Netherlands)

    Smits, Kirsten P J; Sidorenkov, Grigory; Bilo, Henk J G; Bouma, Margriet; van Ittersum, Frans J; Voorham, Jaco; Navis, Gerjan; Denig, Petra

    2016-01-01

    BACKGROUND: Quality assessment is a key element for improving the quality of care. Currently, a comprehensive indicator set for measuring the quality of medication treatment in patients with chronic kidney disease (CKD) is lacking. Our aim was to develop and validate a set of prescribing quality ind

  18. Wishes for the end of life in Huntington's Disease. Observations and reflections, initiated in The Netherlands

    NARCIS (Netherlands)

    Booij, Suzanne José

    2014-01-01

    Euthanasia and physicia-assisted suicide are possible in case of Huntington's Disease, also based on an advance directive. Requirements to make this possible are a sound and possibly longstanding physician-patient relationship. Secondly a thorough knowlegde of the requirements of due care is necessa

  19. Medication Knowledge : An Initial Step in Self-management for Youth With Inflammatory Bowel Disease

    NARCIS (Netherlands)

    Fishman, Laurie N.; Houtman, Dirk; van Groningen, Julia; Arnold, Janis; Ziniel, Sonja

    2011-01-01

    Objective: Adolescents with chronic illness need to develop skills to independently manage their own health. Knowledge of medication is an early step in this process. We explored which factors affect acquisition of medication knowledge in adolescents with inflammatory bowel disease (IBD). Patients a

  20. Dynamic hyperinflation during daily activities: does COPD global initiative for chronic obstructive lung disease stage matter?

    NARCIS (Netherlands)

    Hannink, J.D.C.; Helvoort, H.A.C. van; Dekhuijzen, P.N.R.; Heijdra, Y.F.

    2010-01-01

    BACKGROUND: One of the contributors to exercise limitation in COPD is dynamic hyperinflation. Although dynamic hyperinflation appears to occur during several exercise protocols in COPD and seems to increase with increasing disease severity, it is unknown whether dynamic hyperinflation occurs at diff

  1. Wishes for the end of life in Huntington's Disease. Observations and reflections, initiated in The Netherlands

    NARCIS (Netherlands)

    Booij, Suzanne José

    2014-01-01

    Euthanasia and physicia-assisted suicide are possible in case of Huntington's Disease, also based on an advance directive. Requirements to make this possible are a sound and possibly longstanding physician-patient relationship. Secondly a thorough knowlegde of the requirements of due care is

  2. Depression and Alzheimer's disease: is stress the initiating factor in a common neuropathological cascade?

    DEFF Research Database (Denmark)

    Aznar, Susana; Knudsen, Gitte M

    2011-01-01

    The existence of a high co-morbidity between Alzheimer's disease (AD) and depression has been known for a long time. More interesting though are recent studies indicating that depression and number of depressive episodes earlier in life is associated with increased risk of AD development. This su...

  3. Wishes for the end of life in Huntington's Disease. Observations and reflections, initiated in The Netherlands

    NARCIS (Netherlands)

    Booij, Suzanne José

    2014-01-01

    Euthanasia and physicia-assisted suicide are possible in case of Huntington's Disease, also based on an advance directive. Requirements to make this possible are a sound and possibly longstanding physician-patient relationship. Secondly a thorough knowlegde of the requirements of due care is necessa

  4. Potential savings of harmonising hospital and community formularies for chronic disease medications initiated in hospital.

    Directory of Open Access Journals (Sweden)

    Lauren Lapointe-Shaw

    Full Text Available BACKGROUND: Hospitals in Canada manage their formularies independently, yet many inpatients are discharged on medications which will be purchased through publicly-funded programs. We sought to determine how much public money could be saved on chronic medications if hospitals promoted the initiation of agents with the lowest outpatient formulary prices. METHODS: We used administrative databases for the province of Ontario to identify patients initiated on a proton pump inhibitor (PPI, angiotensin-converting enzyme (ACE inhibitor or angiotensin receptor blocker (ARB following hospital admission from April 1(st 2008-March 31(st 2009. We assessed the cost to the Ontario Drug Benefit Program (ODB over the year following initiation and determined the cost savings if prescriptions were substituted with the least expensive agent in each class. RESULTS: The cost for filling all PPI, ACE inhibitor and ARB prescriptions was $ 2.48 million, $968 thousand and $325 thousand respectively. Substituting the least expensive agent could have saved $1.16 million (47% for PPIs, $162 thousand (17% for ACE inhibitors and $14 thousand (4% for ARBs over the year following discharge. INTERPRETATION: In a setting where outpatient prescriptions are publicly funded, harmonising outpatient formularies with inpatient therapeutic substitution resulted in modest cost savings and may be one way to control rising pharmaceutical costs.

  5. [Management of patients with end-stage renal disease prior to initiation of renal replacement therapy in 2013 in France].

    Science.gov (United States)

    Tuppin, Philippe; Cuerq, Anne; Torre, Sylvie; Couchoud, Cécile; Fagot-Campagna, Anne

    2017-04-01

    This study evaluated the management of patients with end-stage renal disease prior to initiation of renal replacement therapy. Among the 51 million national health insurance general scheme beneficiaries (77% of the population), persons 18 years and older, starting dialysis or undergoing preemptive renal transplantation in 2013, were included in this study. Data were derived from the French national health insurance system (SNIIRAM). In this population of 6674 patients (median age: 68 years), 88% initiated renal replacement therapy by haemodialysis, 8% by peritoneal dialysis, and 4% by renal transplantation. During the year preceding initiation of dialysis, 76% of patients had been hospitalised with at least one diagnostic code for renal disease in 83% of cases, 16% had not received any reimbursements for serum creatinine assay and 32% had not seen a nephrologist; 87% were taking at least one antihypertensive drug (60% were taking at least a renin-angiotensin system inhibitor) and 30% were taking a combination of 4 or more classes of antihypertensive drugs. For patients initiating haemodialysis in a haemodialysis centre, 39% had undergone a procedure related to arteriovenous fistula and 10% had been admitted to an intensive care unit. This study, based on the available reimbursement data, shows that, despite frequent use of the health care system by this population, there is still room for improvement of screening and management of patients with end-stage renal disease and preparation for renal replacement therapy. Copyright © 2016 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.

  6. Vaccination against foot-and-mouth disease: do initial conditions affect its benefit?

    Directory of Open Access Journals (Sweden)

    Thibaud Porphyre

    Full Text Available When facing incursion of a major livestock infectious disease, the decision to implement a vaccination programme is made at the national level. To make this decision, governments must consider whether the benefits of vaccination are sufficient to outweigh potential additional costs, including further trade restrictions that may be imposed due to the implementation of vaccination. However, little consensus exists on the factors triggering its implementation on the field. This work explores the effect of several triggers in the implementation of a reactive vaccination-to-live policy when facing epidemics of foot-and-mouth disease. In particular, we tested whether changes in the location of the incursion and the delay of implementation would affect the epidemiological benefit of such a policy in the context of Scotland. To reach this goal, we used a spatial, premises-based model that has been extensively used to investigate the effectiveness of mitigation procedures in Great Britain. The results show that the decision to vaccinate, or not, is not straightforward and strongly depends on the underlying local structure of the population-at-risk. With regards to disease incursion preparedness, simply identifying areas of highest population density may not capture all complexities that may influence the spread of disease as well as the benefit of implementing vaccination. However, if a decision to vaccinate is made, we show that delaying its implementation in the field may markedly reduce its benefit. This work provides guidelines to support policy makers in their decision to implement, or not, a vaccination-to-live policy when facing epidemics of infectious livestock disease.

  7. Histopathological findings of extra-ileal manifestations at initial diagnosis of Crohn's disease-related ileitis.

    Science.gov (United States)

    Brown, Ian S; Miller, Gregory C; Bettington, Mark L; Rosty, Christophe

    2016-11-01

    Crohn's disease is a chronic inflammatory disorder that can affect any part of the gastrointestinal tract. Our objective was to review the histological findings in index biopsies from the terminal ileum and other gastro-intestinal tract sites of Crohn's disease patients prior any treatment and to compare them with the findings from patients with non-specific ileitis. A total of 111 consecutive Crohn's disease cases (55 females, median age 27 years) with extra-ileal biopsies were retrospectively selected. Upper gastrointestinal inflammatory changes were found in 68 % of gastric biopsies, 60 % of oesophageal biopsies and 43 % of duodenal biopsies with no significant difference in frequency between paediatric and adult cases. Crohn's colitis was more common in paediatric cases than adult cases (85 % versus 57 %). Granuloma in at least one extra-ileal site was observed in 40 %, more frequently in paediatric cases than in adults (78 vs 27 %). Compared with Crohn's disease cases, the group of 151 non-specific ileitis cases (75 females, median age 52 years) were more likely to have normal upper and lower gastrointestinal biopsies and to show less frequent crypt architectural changes in the terminal ileum. In summary, Crohn's disease ileitis is often associated with inflammation elsewhere in the gastrointestinal tract while non-specific ileitis was infrequently associated with inflammation elsewhere for both paediatric and adult patients. These findings support the role of systematic biopsies in multiple gastrointestinal sites to help distinguishing Crohn's ileitis from non-specific ileitis in paediatric and adult population.

  8. Engineering-reflected phase in Fabry-Perot sensors with resonant mirrors.

    Science.gov (United States)

    Gellineau, Antonio; Wong, Yu-Po; Solgaard, Olav

    2013-12-01

    Fabry-Perot cavities made with photonic crystal (PC) mirrors and other resonant structures exhibit nontraditional characteristics due to the strong wavelength dependence of their reflected phase. This Letter describes how engineering the phase of PC mirrors enables sensors that are tolerant to variations in laser center frequency and line width. Reflection spectra measurements of Fabry-Perot cavities made with PC mirrors were collected as a function of wavelength and cavity length, providing experimental verification of theory and simulations.

  9. Compact imaging spectrometer combining Fourier transform spectroscopy with a Fabry-Perot interferometer.

    Science.gov (United States)

    Pisani, Marco; Zucco, Massimo

    2009-05-11

    An imaging spectrometer based on a Fabry-Perot interferometer is presented. The Fabry-Perot interferometer scans the mirror distance up to contact and the intensity modulated light signal is transformed using a Fourier Transform based algorithm, as the Michelson based Fourier Transform Spectrometers does. The resulting instrument has the advantage of a compact, high numerical aperture, high luminosity hyperspectral imaging device. Theory of operation is described along with one experimental realization and preliminary results.

  10. Laparoscopic Assisted Surgery for Crohn's Disease an Initial Experience and Results

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The inflammatory process associated with Crohn's disease often makes dissection difficult, even in open surgery. The aim of this study was to assess the technical feasibility, safety and indication of laparoscopic assisted procedures performed in patients with Crohn's disease. Records of patients undergoing surgical operation for Crohn's disease from 1993 to 1998 at our hospital were reviewed. Intestinal resection was performed laparoscopically in 24 patients (LAP) and by open technique in 23 patients (OPEN). No significant differences existed as to age, gender, body-mass-index and previous surgery. In the laparoscopic group, seven operations (CON) were converted to open laparotomy (29 %) because of large inflammatory mass and/or fistula. The mean intraoperative blood loss was significantly higher in CON- and OPEN-groups than in LAP-group (P<0. 01 ). Major complications occurred only in one patient who underwent laparoscopic assisted high anterior resection. Patients who underwent laparoscopic operation tolerated p.o. liquids sooner than patients who underwent open surgery (median: 2 vs. 5 day, P<0. 05). Compared with the CON- and OPEN-groups, patients in LAP-group had lower analgesic requirements (median: 3 vs. 6 and 5 day, P<0. 01). The median postoperative length of stay was significantly shorter in LAP-group than in OPEN-group (median: 11 vs. 14 day, P<0. 05). Our study showed that LAP is technically feasible for Crohn's disease. The preoperative correct diagnosis and selection of indications are very important, because the laparoscopic mobilization and resection may be difficult or impossible in patients with large fixed masses, multiple complx fistulas, or recurrent Crohn'sdisease.

  11. Febrile cholestatic disease as an initial presentation of nodular lymphocyte-predominant Hodgkin lymphoma

    Institute of Scientific and Technical Information of China (English)

    Anna; Mrzljak; Slavko; Gasparov; Ika; Kardum-Skelin; Vesna; Colic-Cvrlje; Slobodanka; Ostojic; Kolonic

    2010-01-01

    Febrile cholestatic liver disease is an extremely unusual presentation of Hodgkin lymphoma(HL).The liver biopsy of a 40-year-old man with febrile episodes and cholestatic laboratory pattern disclosed an uncommon subtype of HL,a nodular lymphocyte-predominant HL(NLPHL).Liver involvement in the early stage of the usually indolent NLPHL's clinical course suggests an aggressiveness and unfavorable outcome.Emphasizing a liver biopsy early in the diagnostic algorithm enables accurate diagnosis and appropriate tre...

  12. Medication knowledge: an initial step in self-management for youth with inflammatory bowel disease.

    Science.gov (United States)

    Fishman, Laurie N; Houtman, Dirk; van Groningen, Julia; Arnold, Janis; Ziniel, Sonja

    2011-12-01

    Adolescents with chronic illness need to develop skills to independently manage their own health. Knowledge of medication is an early step in this process. We explored which factors affect acquisition of medication knowledge in adolescents with inflammatory bowel disease (IBD). Consecutive patients with IBD older than 10 years received a confidential survey at an outpatient visit including questions regarding medication name, dose, and adverse effects. Results were compared with the medical record. Demographic characteristics obtained included age, sex, disease duration, and type of IBD. Completed surveys were returned by 294 patients (65% of those approached). Overall, 95% of patients could name their medication and 54% could identify their correct dose. Of 95 patients receiving biologics, 88% could identify the medicine and 50% could report either dose or timing. Of 139 patients on immunomodulator therapy, 94% could name medicine and 68% reported correct dose. Sex, type, or duration of disease did not affect name or dose knowledge. Generally, older patients did not demonstrate better medication or dosage knowledge than younger patients, although there was a significant trend toward improved knowledge of side effects for older patients. However, knowledge is an early stage of self-management, yet many adolescents cannot report the dose of IBD medications, nor know the side effects of immunosuppression. This finding persists into late adolescence, which has ramifications for patients as they separate from parents for college or work.

  13. Mantle Cell Hyperplasia of Peripheral Lymph Nodes as Initial Manifestation of Sickle Cell Disease

    Science.gov (United States)

    Monabbati, Ahmad; Noori, Sadat; Safaei, Akbar; Ramzi, Mani; Eghbali, Seyedsajjad

    2016-01-01

    Sickle cell disease (SCD) is a well known hemoglobinopathy with usual manifestations including anemia, hyperbilirubinemia, and vasoocclusive complications. Despite presence of mild splenomegaly in early phase of the disease, lymphadenopathy is not an often finding of SCD. We introduce an undiagnosed case of SCD who presented in third decade of his life with multiple cervical lymphadenopathies and mild splenomegaly persistent for about five years. Histopathologic examination of the resected lymph nodes showed expansion of the mantle cell layers of secondary follicles as well as several monomorphic mantle cell nodules. To rule out possibility of a malignant process involving lymph nodes, an immunohistochemical panel was ordered which was in favor of benign mantle cell hyperplasia. Immunoglobulin gene rearrangement study showed no clonal bands and confirmed benign nature of the process. Respecting mild abnormalities on Complete Blood Count, peripheral blood smear was reviewed revealing some typical sickle red blood cells as well as rare nucleated red blood cells. Solubility test for hemoglobin (HB) S was positive. Hemoglobin electrophoresis confirmed diagnosis of homozygous HbS disease. PMID:27872769

  14. Mantle Cell Hyperplasia of Peripheral Lymph Nodes as Initial Manifestation of Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Ahmad Monabbati

    2016-01-01

    Full Text Available Sickle cell disease (SCD is a well known hemoglobinopathy with usual manifestations including anemia, hyperbilirubinemia, and vasoocclusive complications. Despite presence of mild splenomegaly in early phase of the disease, lymphadenopathy is not an often finding of SCD. We introduce an undiagnosed case of SCD who presented in third decade of his life with multiple cervical lymphadenopathies and mild splenomegaly persistent for about five years. Histopathologic examination of the resected lymph nodes showed expansion of the mantle cell layers of secondary follicles as well as several monomorphic mantle cell nodules. To rule out possibility of a malignant process involving lymph nodes, an immunohistochemical panel was ordered which was in favor of benign mantle cell hyperplasia. Immunoglobulin gene rearrangement study showed no clonal bands and confirmed benign nature of the process. Respecting mild abnormalities on Complete Blood Count, peripheral blood smear was reviewed revealing some typical sickle red blood cells as well as rare nucleated red blood cells. Solubility test for hemoglobin (HB S was positive. Hemoglobin electrophoresis confirmed diagnosis of homozygous HbS disease.

  15. The effect of Tai Chi exercise on gait initiation and gait performance in persons with Parkinson's disease.

    Science.gov (United States)

    Amano, Shinichi; Nocera, Joe R; Vallabhajosula, Srikant; Juncos, Jorge L; Gregor, Robert J; Waddell, Dwight E; Wolf, Steven L; Hass, Chris J

    2013-11-01

    Gait dysfunction and postural instability are two debilitating symptoms in persons with Parkinson's disease (PD). Tai Chi exercise has recently gained attention as an attractive intervention for persons with PD because of its known potential to reduce falls and improve postural control, walking abilities, and safety at a low cost. The purpose of this report is to investigate the effect of Tai Chi exercise on dynamic postural control during gait initiation and gait performance in persons with idiopathic PD, and to determine whether these benefits could be replicated in two different environments, as complementary projects. In these two separate projects, a total of 45 participants with PD were randomly assigned to either a Tai Chi group or a control group. The Tai Chi groups in both projects completed a 16-week Tai Chi exercise session, while the control groups consisted of either a placebo (i.e., Qi-Gong) or non-exercise group. Tai Chi did not significantly improve Unified Parkinson's Disease Rating Scale Part III score, selected gait initiation parameters or gait performance in either project. Combined results from both projects suggest that 16 weeks of class-based Tai Chi were ineffective in improving either gait initiation, gait performance, or reducing parkinsonian disability in this subset of persons with PD. Thus the use of short-term Tai Chi exercise should require further study before being considered a valuable therapeutic intervention for these domains in PD.

  16. Depression and Alzheimer's disease: is stress the initiating factor in a common neuropathological cascade?

    DEFF Research Database (Denmark)

    Aznar, Susana; Knudsen, Gitte M

    2011-01-01

    . This suggests the existence of common neuropathological mechanisms behind depression and AD. Here we propose that the brain changes associated with depressive episodes that compromise the brain's ability to cope with stress may constitute risk factors for development of AD. Furthermore, in individuals...... with a genetic linkage to depression, there may be an increased vulnerability towards the initiation of a detrimental neurodegenerative cascade. The following review will deal with the various observations reported within the different neurobiological systems known to be involved and affected in depression, like...

  17. Contraceptive Method Initiation: Using the Centers for Disease Control and Prevention Selected Practice Guidelines.

    Science.gov (United States)

    Wu, Wan-Ju; Edelman, Alison

    2015-12-01

    The US Selected Practice Recommendations is a companion document to the Medical Eligibility Criteria for Contraceptive Use that focuses on how providers can use contraceptive methods most effectively as well as problem-solve common issues that may arise. These guidelines serve to help clinicians provide contraception safely as well as to decrease barriers that prevent or delay a woman from obtaining a desired method. This article summarizes the Selected Practice Recommendations on timing of contraceptive initiation, examinations, and tests needed prior to starting a method and any necessary follow-up.

  18. A Study of the Chaos of Non-linear Fabry-Perot Resonator%含非线性介质Fabry-Perot腔混沌研究

    Institute of Scientific and Technical Information of China (English)

    袁圣付; 姜宗福

    2000-01-01

    根据混沌动力学的基本理论,计算了含非线性介质Fabry-Perot腔动力学方程在其参数下的Lyapunov指数分布图.利用Lyapunov指数和动力学特性的对应关系,分析出非线性Fabry-Perot腔在各种参数下的动力学特性、稳态参数区域面积和混沌转换机制.

  19. Influence of intensity loss in the cavity of a folded Fabry-Perot interferometer on interferometric signals.

    Science.gov (United States)

    Shyu, Lih-Horng; Chang, Chung-Ping; Wang, Yung-Cheng

    2011-06-01

    Fabry-Perot interferometer is often used for the micro-displacement, because of its common optical path structure being insensitive to the environmental disturbances. Recently, the folded Fabry-Perot interferometer has been investigated for displacement measurements in large ranges. The advantages of a folded Fabry-Perot interferometer are insensitive to the tilt angle and higher optical resolution. But the design of the optical cavity has become more and more complicated. For this reason, the intensity loss in the cavity will be an important parameter for the distribution of the interferometric intensity. To obtain a more accurate result of such interferometer utilized for displacement measurements, the intensity loss of the cavity in the fabricated folded Fabry-Perot interferometer and the modified equation of the folded Fabry-Perot interferometer will be described. According to the theoretical and experimental results, the presented model is available for the analysis of displacement measurements by a folded Fabry-Perot interferometer.

  20. Risk factors for late-stage HIV disease presentation at initial HIV diagnosis in Durban, South Africa.

    Directory of Open Access Journals (Sweden)

    Paul K Drain

    Full Text Available After observing persistently low CD4 counts at initial HIV diagnosis in South Africa, we sought to determine risk factors for late-stage HIV disease presentation among adults.We surveyed adults prior to HIV testing at four outpatient clinics in Durban from August 2010 to November 2011. All HIV-infected adults were offered CD4 testing, and late-stage HIV disease was defined as a CD4 count <100 cells/mm(3. We used multivariate regression models to determine the effects of sex, emotional health, social support, distance from clinic, employment, perceived barriers to receiving healthcare, and foregoing healthcare to use money for food, clothing, or housing ("competing needs to healthcare" on presentation with late-stage HIV disease.Among 3,669 adults screened, 830 were enrolled, newly-diagnosed with HIV and obtained a CD4 result. Among those, 279 (33.6% presented with late-stage HIV disease. In multivariate analyses, participants who lived ≥5 kilometers from the test site [adjusted odds ratio (AOR 2.8, 95% CI 1.7-4.7], reported competing needs to healthcare (AOR 1.7, 95% CI 1.2-2.4, were male (AOR 1.7, 95% CI 1.2-2.3, worked outside the home (AOR 1.5, 95% CI 1.1-2.1, perceived health service delivery barriers (AOR 1.5, 95% CI 1.1-2.1, and/or had poor emotional health (AOR 1.4, 95% CI 1.0-1.9 had higher odds of late-stage HIV disease presentation.Independent risk factors for late-stage HIV disease presentation were from diverse domains, including geographic, economic, demographic, social, and psychosocial. These findings can inform various interventions, such as mobile testing or financial assistance, to reduce the risk of presentation with late-stage HIV disease.

  1. 1,25-dihydroxyvitamin D3 conditioned CD11c+ dendritic cells are effective initiators of CNS autoimmune disease

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    Dario eBesusso

    2015-11-01

    Full Text Available Dendritic cells (DC play a crucial role in regulating T cell activation. Due to their capacity to shape the immune response, tolerogenic DC have been used to treat autoimmune diseases. In this study we examined whether 1,25 dihydroxyvitamin D3 conditioned bone marrow derived DC (VitD-BMDC were able to limit the development of autoimmune pathology in experimental autoimmune encephalomyelitis (EAE. We found that VitD-BMDC had lower expression of MHC class II and co-stimulatory molecules and were less effective at priming autoreactive T cells in-vitro. Using our recently described BMDC driven model of EAE, we demonstrated that VitD-BMDC had a significantly reduced ability to initiate EAE. We found that the impaired ability of VitD-BMDC to initiate EAE was not due to T cell tolerisation. Instead, we discovered that the addition of 1,25(OH2D3 to BMDC cultures resulted in a significant reduction in the proportion of CD11c+ cells. Purified CD11c+VitD-BMDC were significantly less effective at priming T cells in-vitro yet were similarly capable of initiating EAE as vehicle treated CD11c+BMDC. This study demonstrates that in-vitro assays of DC function can be a poor predictor of in-vivo behaviour and that CD11c+VitD-BMDC are highly effective initiators of an autopathogenic T cell response.

  2. 1,25-Dihydroxyvitamin D3-Conditioned CD11c+ Dendritic Cells are Effective Initiators of CNS Autoimmune Disease.

    Science.gov (United States)

    Besusso, Dario; Saul, Louise; Leech, Melanie D; O'Connor, Richard A; MacDonald, Andrew S; Anderton, Stephen M; Mellanby, Richard J

    2015-01-01

    Dendritic cells (DC) play a crucial role in regulating T cell activation. Due to their capacity to shape the immune response, tolerogenic DC have been used to treat autoimmune diseases. In this study, we examined whether 1,25 dihydroxyvitamin D3-conditioned bone marrow-derived DC (VitD-BMDC) were able to limit the development of autoimmune pathology in experimental autoimmune encephalomyelitis (EAE). We found that VitD-BMDC had lower expression of MHC class II and co-stimulatory molecules and were less effective at priming autoreactive T cells in vitro. Using our recently described BMDC-driven model of EAE, we demonstrated that VitD-BMDC had a significantly reduced ability to initiate EAE. We found that the impaired ability of VitD-BMDC to initiate EAE was not due to T cell tolerization. Instead, we discovered that the addition of 1,25(OH)2D3 to BMDC cultures resulted in a significant reduction in the proportion of CD11c+ cells. Purified CD11c+ VitD-BMDC were significantly less effective at priming T cells in vitro yet were similarly capable of initiating EAE as vehicle-treated CD11c+ BMDC. This study demonstrates that in vitro assays of DC function can be a poor predictor of in vivo behavior and that CD11c+ VitD-BMDC are highly effective initiators of an autopathogenic T cell response.

  3. Computed tomography, lymphography, and staging laparotomy: correlations in initial staging of Hodgkin disease

    Energy Technology Data Exchange (ETDEWEB)

    Castellino, R.A.; Hoppe, R.T.; Blank, N.; Young, S.W.; Neumann, C.; Rosenberg, S.A.; Kaplan, H.S.

    1984-07-01

    One hundred twenty-one patients with newly diagnosed, previously untreated Hodgkin disease underwent abdominal and pelvic computed tomographic (CT) scanning and bipedal lymphography. These studies were followed by staging laparotomy, which included biopsy of the liver, retroperitoneal and mesenteric lymph nodes, and splenectomy. Correlation of the results of the imaging studies with the histopathologic diagnoses revealed a small - but significant - increased accuracy of lymphography compared with CT in assessing the retroperitoneal lymph nodes. The theoretical advantages of CT scanning in detecting lymphomatous deposits in lymph nodes about the celiac axis and the mesentery, or in the liver and spleen, were not confirmed.

  4. The human secretome atlas initiative: implications in health and disease conditions.

    Science.gov (United States)

    Brown, Kristy J; Seol, Haeri; Pillai, Dinesh K; Sankoorikal, Binu-John; Formolo, Catherine A; Mac, Jenny; Edwards, Nathan J; Rose, Mary C; Hathout, Yetrib

    2013-11-01

    Proteomic analysis of human body fluids is highly challenging, therefore many researchers are redirecting efforts toward secretome profiling. The goal is to define potential biomarkers and therapeutic targets in the secretome that can be traced back in accessible human body fluids. However, currently there is a lack of secretome profiles of normal human primary cells making it difficult to assess the biological meaning of current findings. In this study we sought to establish secretome profiles of human primary cells obtained from healthy donors with the goal of building a human secretome atlas. Such an atlas can be used as a reference for discovery of potential disease associated biomarkers and eventually novel therapeutic targets. As a preliminary study, secretome profiles were established for six different types of human primary cell cultures and checked for overlaps with the three major human body fluids including plasma, cerebrospinal fluid and urine. About 67% of the 1054 identified proteins in the secretome of these primary cells occurred in at least one body fluid. Furthermore, comparison of the secretome profiles of two human glioblastoma cell lines to this new human secretome atlas enabled unambiguous identification of potential brain tumor biomarkers. These biomarkers can be easily monitored in different body fluids using stable isotope labeled standard proteins. The long term goal of this study is to establish a comprehensive online human secretome atlas for future use as a reference for any disease related secretome study. This article is part of a Special Issue entitled: An Updated Secretome.

  5. Pregnancy related breast diseases in a developing African country: Initial Sonographic Evaluation.

    Science.gov (United States)

    Adeniji-Sofoluwe, Adenike Temitayo; Obajimi, Gbolahan Oladele; Obajimi, Millicent Olubunmi

    2015-01-01

    Benign diseases are more common than malignant diseases in pregnant and lactating women. Fibroadenomas are the most commonly identified benign breast tumour in pregnant and lactating women. Pregnancy related breast cancer is defined as breast cancer that occurs during pregnancy or within 1 year of delivery. Its incidence is estimated at 1 in 3000 to 1 in 10 000 pregnancies. Several reproductive factors like age at menarche, age at menopause, age at full-term pregnancy, parity, age at any birth and spacing of pregnancies, breast feeding, characteristics of the menstrual cycle, infertility, spontaneous and induced abortions, characteristics of the menstrual cycle and infertility are some of the factors that have been incriminated as risk factors for breast cancer. We sought to describe the predominant breast pattern, sonographic array of pregnancy related breast diseases in women referred to the breast imaging unit in the department of Radiology at the University College Hospital, Ibadan south west Nigeria. Socio-demographic characteristics in these women were also evaluated. Archived images were reviewed and documented and data was analysed with SPSS version 17 and presented with descriptives. In this descriptive study, we retrospectively retrieved the sonomammographic records of 21 women (pregnant or lactating) referred to and imaged in the department of radiology, University college hospital Ibadan, between 2006 and 2013. Diagnostic breast sonograms performed by MO and ATS; Consultant radiologists with 7-10 years' experience utilized a 7-10 MHz transducer of the General electric GE Logiq P5 machine for the scans. Twenty-one women with ages between 22-42 years (Mean 31.4 ± 5.4 SD) pregnant or lactating were referred to the radiology department for sonomammographic evaluation. Majority of the women were in the 3rd decade. Referral was mainly (11) by family Physicians from the general outpatient clinic, 5 were self-referred, 2 from radiotherapy department, 2 from

  6. A CMOS millimeter-wave transceiver embedded in a semi-confocal Fabry-Perot cavity for molecular spectroscopy

    Science.gov (United States)

    Drouin, Brian J.; Tang, Adrian; Schlecht, Erich; Brageot, Emily; Gu, Q. Jane; Ye, Y.; Shu, R.; Frank Chang, Mau-chung; Kim, Y.

    2016-08-01

    The extension of radio frequency complementary metal oxide semiconductor (CMOS) circuitry into millimeter wavelengths promises the extension of spectroscopic techniques in compact, power efficient systems. We are now beginning to use CMOS millimeter devices for low-mass, low-power instrumentation capable of remote or in situ detection of gas composition during space missions. We have chosen to develop a Flygare-Balle type spectrometer, with a semi-confocal Fabry-Perot cavity to amplify the pump power of a mm-wavelength CMOS transmitter that is directly coupled to the planar mirror of the cavity. We have built a pulsed transceiver system at 92-105 GHz inside a 3 cm base length cavity and demonstrated quality factor up to 4680, allowing for modes with 20 MHz bandwidth, with a sufficient cavity amplification factor for mW class transmitters. This work describes the initial gas measurements and outlines the challenges and next steps.

  7. A CMOS millimeter-wave transceiver embedded in a semi-confocal Fabry-Perot cavity for molecular spectroscopy.

    Science.gov (United States)

    Drouin, Brian J; Tang, Adrian; Schlecht, Erich; Brageot, Emily; Gu, Q Jane; Ye, Y; Shu, R; Frank Chang, Mau-Chung; Kim, Y

    2016-08-21

    The extension of radio frequency complementary metal oxide semiconductor (CMOS) circuitry into millimeter wavelengths promises the extension of spectroscopic techniques in compact, power efficient systems. We are now beginning to use CMOS millimeter devices for low-mass, low-power instrumentation capable of remote or in situ detection of gas composition during space missions. We have chosen to develop a Flygare-Balle type spectrometer, with a semi-confocal Fabry-Perot cavity to amplify the pump power of a mm-wavelength CMOS transmitter that is directly coupled to the planar mirror of the cavity. We have built a pulsed transceiver system at 92-105 GHz inside a 3 cm base length cavity and demonstrated quality factor up to 4680, allowing for modes with 20 MHz bandwidth, with a sufficient cavity amplification factor for mW class transmitters. This work describes the initial gas measurements and outlines the challenges and next steps.

  8. A case of MCTD overlapped by Takayasu's arteritis, presenting Raynaud's phenomenon as the initial manifestation of both diseases.

    Science.gov (United States)

    Lim, Mie Jin; Kwon, Seong Ryul; Kim, Sang Gu; Park, Won

    2009-04-01

    Raynaud's phenomenon is characteristic three-phase color change of digits that occurs when hands are exposed to cold and subsequently rewarmed. Raynaud's phenomenon has many possible causes, but evaluation tends to focus on a few notorious etiologies, such as, connective tissue diseases. Thus, having reached a diagnosis, detailed physical exam to rule out other possible causes is often not performed. The authors present a case of mixed connective tissue disease (MCTD) and Takayasu's arteritis overlap in a woman, who showed Raynaud's phenomenon as an initial manifestation. She was first diagnosed as having MCTD, but her treatment did not improve the persistent Raynaud's phenomenon. Several years later, follow-up chest CT showed underlying Takayasu's arteritis and a subsequent physical examination revealed that typical abnormalities consistent with Takayasu's arteritis were present. The authors advocate thorough history taking and complete physical examinations on a routine basis to help unearth other underlying causes.

  9. Orbital Pseudotumor: Uncommon Initial Presentation of IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Teresa Carbone

    2015-01-01

    Full Text Available IgG4-related disease (IgG4-RD encompasses a group of fibroinflammatory conditions recognized in recent times. The main clinical features include variable degrees of tissue fibrosis, tumorlike expansions, perivascular lymphocytic infiltration rich in IgG4-positive plasma cells, and elevated serum IgG4. A case has been reported of an elderly patient with an unexplained unilateral exophthalmia; biopsy was performed and revealed lymphocytic infiltration, suggesting IgG4-RD. High serum levels of IgG4, in association with a good response to steroid therapy and to the exclusion of other diagnoses, confirmed the hypothesis of orbital pseudotumor by IgG4-RD.

  10. A prospective study of low fasting glucose with cardiovascular disease events and all-cause mortality: The Women's Health Initiative.

    Science.gov (United States)

    Mongraw-Chaffin, Morgana; LaCroix, Andrea Z; Sears, Dorothy D; Garcia, Lorena; Phillips, Lawrence S; Salmoirago-Blotcher, Elena; Zaslavsky, Oleg; Anderson, Cheryl A M

    2017-05-01

    While there is increasing recognition of the risks associated with hypoglycemia in patients with diabetes, few studies have investigated incident cause-specific cardiovascular outcomes with regard to low fasting glucose in the general population. We hypothesized that low fasting glucose would be associated with cardiovascular disease risk and all-cause mortality in postmenopausal women. To test our hypothesis, we used both continuous incidence rates and Cox proportional hazards models in 17,287 participants from the Women's Health Initiative with fasting glucose measured at baseline. Participants were separated into groups based on fasting glucose level: low (fasting glucose distribution exhibited evidence of a weak J-shaped association with heart failure and mortality that was predominantly due to participants with treated diabetes. Impaired and diabetic fasting glucose were positively associated with all outcomes. Associations for low fasting glucose differed, with coronary heart disease (HR=0.64 (0.42, 0.98)) significantly inverse; stroke (0.73 (0.48, 1.13)), combined cardiovascular disease (0.91 (0.73, 1.14)), and all-cause mortality (0.97 (0.79, 1.20)) null or inverse and not significant; and heart failure (1.27 (0.80, 2.02)) positive and not significant. Fasting glucose at the upper range, but not the lower range, was significantly associated with incident cardiovascular disease and all-cause mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Survival analysis of patients with clinical stages I or II Hodgkin's disease who have relapsed after initial treatment with radiotherapy alone

    DEFF Research Database (Denmark)

    Horwich, A; Specht, L; Ashley, S

    1997-01-01

    To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first...... relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial...... radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate...

  12. Subthalamic Stimulation Reduces Vowel Space at the Initiation of Sustained Production: Implications for Articulatory Motor Control in Parkinson's Disease.

    Science.gov (United States)

    Sidtis, John J; Alken, Amy G; Tagliati, Michele; Alterman, Ron; Van Lancker Sidtis, Diana

    2016-03-19

    Stimulation of the subthalamic nuclei (STN) is an effective treatment for Parkinson's disease, but complaints of speech difficulties after surgery have been difficult to quantify. Speech measures do not convincingly account for such reports. This study examined STN stimulation effects on vowel production, in order to probe whether DBS affects articulatory posturing. The objective was to compare positioning during the initiation phase with the steady prolongation phase by measuring vowel spaces for three "corner" vowels at these two time frames. Vowel space was measured over the initial 0.25 sec of sustained productions of high front (/i/), high back (/u/) and low vowels (/a/), and again during a 2 sec segment at the midpoint. Eight right-handed male subjects with bilateral STN stimulation and seven age-matched male controls were studied based on their participation in a larger study that included functional imaging. Mean values: age = 57±4.6 yrs; PD duration = 12.3±2.7 yrs; duration of DBS = 25.6±21.2 mos, and UPDRS III speech score = 1.6±0.7. STN subjects were studied off medication at their therapeutic DBS settings and again with their stimulators off, counter-balanced order. Vowel space was larger in the initiation phase compared to the midpoint for both the control and the STN subjects off stimulation. With stimulation on, however, the initial vowel space was significantly reduced to the area measured at the mid-point. For the three vowels, the acoustics were differentially affected, in accordance with expected effects of front versus back position in the vocal tract. STN stimulation appears to constrain initial articulatory gestures for vowel production, raising the possibility that articulatory positions normally used in speech are similarly constrained.

  13. Viral Genome-Linked Protein (VPg) Is Essential for Translation Initiation of Rabbit Hemorrhagic Disease Virus (RHDV).

    Science.gov (United States)

    Zhu, Jie; Wang, Binbin; Miao, Qiuhong; Tan, Yonggui; Li, Chuanfeng; Chen, Zongyan; Guo, Huimin; Liu, Guangqing

    2015-01-01

    Rabbit hemorrhagic disease virus (RHDV), the causative agent of rabbit hemorrhagic disease, is an important member of the caliciviridae family. Currently, no suitable tissue culture system is available for proliferating RHDV, limiting the study of the pathogenesis of RHDV. In addition, the mechanisms underlying RHDV translation and replication are largely unknown compared with other caliciviridae viruses. The RHDV replicon recently constructed in our laboratory provides an appropriate model to study the pathogenesis of RHDV without in vitro RHDV propagation and culture. Using this RHDV replicon, we demonstrated that the viral genome-linked protein (VPg) is essential for RHDV translation in RK-13 cells for the first time. In addition, we showed that VPg interacts with eukaryotic initiation factor 4E (eIF4E) in vivo and in vitro and that eIF4E silencing inhibits RHDV translation, suggesting the interaction between VPg and eIF4E is involved in RHDV translation. Our results support the hypothesis that VPg serves as a novel cap substitute during the initiation of RHDV translation.

  14. Viral Genome-Linked Protein (VPg Is Essential for Translation Initiation of Rabbit Hemorrhagic Disease Virus (RHDV.

    Directory of Open Access Journals (Sweden)

    Jie Zhu

    Full Text Available Rabbit hemorrhagic disease virus (RHDV, the causative agent of rabbit hemorrhagic disease, is an important member of the caliciviridae family. Currently, no suitable tissue culture system is available for proliferating RHDV, limiting the study of the pathogenesis of RHDV. In addition, the mechanisms underlying RHDV translation and replication are largely unknown compared with other caliciviridae viruses. The RHDV replicon recently constructed in our laboratory provides an appropriate model to study the pathogenesis of RHDV without in vitro RHDV propagation and culture. Using this RHDV replicon, we demonstrated that the viral genome-linked protein (VPg is essential for RHDV translation in RK-13 cells for the first time. In addition, we showed that VPg interacts with eukaryotic initiation factor 4E (eIF4E in vivo and in vitro and that eIF4E silencing inhibits RHDV translation, suggesting the interaction between VPg and eIF4E is involved in RHDV translation. Our results support the hypothesis that VPg serves as a novel cap substitute during the initiation of RHDV translation.

  15. Enhancing patient engagement in chronic disease self-management support initiatives in Australia: the need for an integrated approach.

    Science.gov (United States)

    Jordan, Joanne E; Briggs, Andrew M; Brand, Caroline A; Osborne, Richard H

    2008-11-17

    Although emphasis on the prevention of chronic disease is important, governments in Australia need to balance this with continued assistance to the 77% of Australians reported to have at least one long-term medical condition. Self-management support is provided by health care and community services to enhance patients' ability to care for their chronic conditions in a cooperative framework. In Australia, there is a range of self-management support initiatives that have targeted patients (most notably, chronic disease self-management education programs) and health professionals (financial incentives, education and training). To date, there has been little coordination or integration of these self-management initiatives to enhance the patient-health professional clinical encounter. If self-management support is to work, there is a need to better understand the infrastructure, systems and training that are required to engage the key stakeholders - patients, carers, health professionals, and health care organisations. A coordinated approach is required in implementing these elements within existing and new health service models to enhance uptake and sustainability.

  16. [A case of Creutzfeldt-Jakob disease presenting with arm levitation as an initial symptom].

    Science.gov (United States)

    Kamogawa, Kenji; Ninomiya, Satoko; Okuda, Shinya; Matsumoto, Yushi; Tomita, Hitomi; Okamoto, Kensho; Okuda, Bungo

    2014-01-01

    A 74-year-old, right handed man, developed insidiously with levitation and clumsiness of the right upper limb. His right arm tended to levitate spontaneously, when he was examined. He could put the elevated arm down on command, while the arm resumed to antigravity posture when his attention was diverted. His right arm also exhibited unwilled elevation when performing complex finger movements on the right side. He had a feeling of strangeness of the elevated limb, especially with the eyes closed. In addition to asymmetric limb-kinetic apraxia, combined sensations such as stereognosis were disturbed on the right side. Brain MRI showed high signal lesions predominantly in the left cerebral cortices and basal ganglia. SPECT with (123)I-IMP revealed asymmetric hypoperfusion, predominantly in the left medial frontal and parietal regions. Two months after the onset, levitation of the arm gradually disappeared, with the development of rapidly progressive dementia, frontal signs, dystonia and generalized myoclonus. The diagnosis of Creutzfeldt-Jakob disease (CJD) was made based on the clinical features and cerebrospinal fluid biomarkers. The early manifestation of the patient mimicked corticobasal degeneration which presents with arm levitation or alien hand syndrome. It is suggested that CJD can represent involuntary movements with higher brain dysfunction resembling corticobasal degeneration at the early stage of the illness. Although the underlying mechanism of arm levitation is still unknown, frontal disinhibition and parietal cortical sensory disturbance may contribute to the development of involuntary arm levitation in our patient.

  17. Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active α-Galactosidase A in Fabry Patients when Co-Administered with Infused Agalsidase.

    Directory of Open Access Journals (Sweden)

    David G Warnock

    Full Text Available Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder. The currently approved, biologics-based therapy for Fabry disease is enzyme replacement therapy (ERT with either agalsidase alfa (Replagal or agalsidase beta (Fabrazyme. Based on preclinical data, migalastat HCl in combination with agalsidase is expected to result in the pharmacokinetic (PK enhancement of agalsidase in plasma by increasing the systemic exposure of active agalsidase, thereby leading to increased cellular levels in disease-relevant tissues. This Phase 2a study design consisted of an open-label, fixed-treatment sequence that evaluated the effects of single oral doses of 150 mg or 450 mg migalastat HCl on the PK and tissue levels of intravenously infused agalsidase (0.2, 0.5, or 1.0 mg/kg in male Fabry patients. As expected, intravenous administration of agalsidase alone resulted in increased α-Gal A activity in plasma, skin, and peripheral blood mononuclear cells (PBMCs compared to baseline. Following co-administration of migalastat HCl and agalsidase, α-Gal A activity in plasma was further significantly increased 1.2- to 5.1-fold compared to agalsidase administration alone, in 22 of 23 patients (95.6%. Importantly, similar increases in skin and PBMC α-Gal A activity were seen following co-administration of migalastat HCl and agalsidase. The effects were not related to the administered migalastat HCl dose, as the 150 mg dose of migalastat HCl increased α-Gal A activity to the same extent as the 450 mg dose. Conversely, agalsidase had no effect on the plasma PK of migalastat. No migalastat HCl-related adverse events or drug-related tolerability issues were identified.ClinicalTrials.gov NCT01196871.

  18. Interactions between Global Health Initiatives and country health systems: the case of a neglected tropical diseases control program in Mali.

    Science.gov (United States)

    Cavalli, Anna; Bamba, Sory I; Traore, Mamadou N; Boelaert, Marleen; Coulibaly, Youssouf; Polman, Katja; Pirard, Marjan; Van Dormael, Monique

    2010-08-17

    Recently, a number of Global Health Initiatives (GHI) have been created to address single disease issues in low-income countries, such as poliomyelitis, trachoma, neonatal tetanus, etc.. Empirical evidence on the effects of such GHIs on local health systems remains scarce. This paper explores positive and negative effects of the Integrated Neglected Tropical Disease (NTD) Control Initiative, consisting in mass preventive chemotherapy for five targeted NTDs, on Mali's health system where it was first implemented in 2007. Campaign processes and interactions with the health system were assessed through participant observation in two rural districts (8 health centres each). Information was complemented by interviews with key informants, website search and literature review. Preliminary results were validated during feedback sessions with Malian authorities from national, regional and district levels. We present positive and negative effects of the NTD campaign on the health system using the WHO framework of analysis based on six interrelated elements: health service delivery, health workforce, health information system, drug procurement system, financing and governance. At point of delivery, campaign-related workload severely interfered with routine care delivery which was cut down or totally interrupted during the campaign, as nurses were absent from their health centre for campaign-related activities. Only 2 of the 16 health centres, characterized by a qualified, stable and motivated workforce, were able to keep routine services running and to use the campaign as an opportunity for quality improvement. Increased workload was compensated by allowances, which significantly improved staff income, but also contributed to divert attention away from core routine activities. While the campaign increased the availability of NTD drugs at country level, parallel systems for drug supply and evaluation requested extra efforts burdening local health systems. The campaign budget

  19. Optimal timing for initiation of biofeedback-assisted relaxation training in hospitalized coronary heart disease patients with sleep disturbances.

    Science.gov (United States)

    Wang, Li-Na; Tao, Hong; Zhao, Yue; Zhou, Yu-Qiu; Jiang, Xiu-Rong

    2014-07-01

    Clinical studies have shown that biofeedback-assisted relaxation positively influences the treatment outcomes of sleep disturbance. However, there are only few studies reporting the timing of relaxation training initiation, and the relationships between the timing of initiation and the effectiveness of relaxation remain unclear. The aim of this study was to determine the optimal timing for initiating nurse-led biofeedback-assisted relaxation on hospitalized coronary heart disease patients with sleep disturbance. An experimental pretest and repeated posttest design was used to compare the effectiveness of nurse-led biofeedback-assisted relaxation. A total of 128 patients with coronary heart disease were randomly assigned to 1 of 4 groups: morning group, night group, morning-night group, or control group. Outcome measures included self-report of sleep-related indicators, the scores of the Pittsburgh Sleep Quality Index (PSQI) and the Zung's Self-rating Anxiety Scale (SAS), and the dosage of sleep medication used. A 2-way analysis of variance and a simple effect test were used to analyze the differences among the 4 groups. No significant differences could be detected at baseline. Compared with the control group, the nurse-led biofeedback-assisted relaxation yielded a greater benefit for patients in the 3 intervention groups. Group and time factors (pretest-protest) could explain the variation in the effectiveness of this program (main effect P sleep latency, experienced fewer awakenings, reported higher sleep quality, and used significantly fewer sleep medications than the morning group did (F = 32.97, P sleep quality and decrease the need for of sleep medications in hospitalized patients with sleep disturbance.

  20. Impact of subsequent metastases on costs and medical resource use for prostate cancer patients initially diagnosed with localized disease.

    Science.gov (United States)

    Li, Tracy T; Shore, Neal D; Mehra, Maneesha; Todd, Mary B; Saadi, Ryan; Leblay, Gaetan; Aggarwal, Jyoti; Griffiths, Robert I

    2017-09-15

    The impact of subsequent metastases on costs and medical resource use (MRU) for prostate cancer (PC) patients initially diagnosed with localized disease was estimated. Surveillance, Epidemiology, and End Results data, linked to Medicare (1999-2012), were used to identify 7482 patients diagnosed with subsequent metastases 12 months or more after the initial diagnosis of localized PC (cases), and they were matched to 25,709 localized PC patients without subsequent metastases (controls). Patients were followed for costs and MRU from 12 months before their index date (subsequent metastases or a matched date for controls) up to 12 months after it. Costs and MRU were stratified by the setting/type of care/service. Multivariate mixed effects regression analyses were used to construct and compare longitudinal trajectories of marginal predicted costs and predicted probabilities of MRU between cases and controls. Among the controls, predicted monthly costs remained relatively stable throughout the entire observation period (weighted mean per patient per month, $2746; range during 24 months, $2603-2858). In contrast, among the cases, costs increased from $2622 (95% confidence interval [CI], $2525-2719) 12 months before the diagnosis of subsequent metastases to $4767 (95% CI, $4623-4910) 1 month before the diagnosis of subsequent metastases, peaked during the month of metastases at $13,291 (95% CI, $13,148-13,435), and remained significantly higher than costs for the controls thereafter (eg, $4677 at + 12 months; 95% CI, $4549-4805). Costs and MRU increased across a wide range of settings/types, including inpatient, outpatient, home health, and hospice settings. In PC patients initially diagnosed with localized disease, a diagnosis of subsequent metastases is associated with substantially increased costs and MRU. Cancer 2017;123:3591-601. © 2017 American Cancer Society. © 2017 American Cancer Society.

  1. Ulinastatin, a urinary trypsin inhibitor, for the initial treatment of patients with Kawasaki disease: a retrospective study.

    Science.gov (United States)

    Kanai, Takashi; Ishiwata, Takahiro; Kobayashi, Tohru; Sato, Hiroki; Takizawa, Mari; Kawamura, Yoichi; Tsujimoto, Hiroshi; Nakatani, Keigo; Ishibashi, Naoko; Nishiyama, Mitsunori; Hatai, Yoshiho; Asano, Yuh; Kobayashi, Tomio; Takeshita, Seiichiro; Nonoyama, Shigeaki

    2011-12-20

    Markedly activated neutrophils or higher plasma levels of neutrophil elastase are involved in the poor response to intravenous immunoglobulin (IVIG) and the formation of coronary artery lesions (CAL) in patients with acute Kawasaki disease. We hypothesized that ulinastatin (UTI), by both direct and indirect suppression of neutrophils, would reduce the occurrence of CAL. We retrospectively analyzed the clinical records of patients with Kawasaki disease between 1998 and 2009. Three hundred sixty-nine patients were treated with a combination of UTI, aspirin, and IVIG as an initial treatment (UTI group), and 1178 were treated with a conventional initial treatment, and IVIG with aspirin (control group). The baseline characteristics did not demonstrate notable differences between the two groups. The occurrence of CAL was significantly lower in the UTI group than in the control group (3% versus 7%; crude odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25-0.86; P=0.01). The OR adjusted for sex, Gunma score (the predictive score for IVIG unresponsiveness), and dosage of initial IVIG (1 or 2 g/kg) was 0.32 (95% CI, 0.17-0.60; P<0.001). In addition, most CAL occurred in patients requiring additional rescue treatment and the proportion of those patients was significantly lower in the UTI group than in the control group (13% versus 22%; crude OR, 0.52; 95% CI, 0.38-0.73; P<0.001). The adjusted OR was 0.30 (95% CI, 0.20-0.44; P<0.001). UTI was associated with fewer patients requiring additional rescue treatment and reduction of CAL in this retrospective study.

  2. Enhanced expression of c-myc in hepatocytes promotes initiation and progression of alcoholic liver disease.

    Science.gov (United States)

    Nevzorova, Yulia A; Cubero, Francisco J; Hu, Wei; Hao, Fengjie; Haas, Ute; Ramadori, Pierluigi; Gassler, Nikolaus; Hoss, Mareike; Strnad, Pavel; Zimmermann, Henning W; Tacke, Frank; Trautwein, Christian; Liedtke, Christian

    2016-03-01

    Progression of alcoholic liver disease (ALD) can be influenced by genetic factors, which potentially include specific oncogenes and tumor suppressors. In the present study, we tested the hypothesis that aberrant expression of the proto-oncogene c-myc might exert a crucial role in the development of ALD. Expression of c-myc was measured in biopsies of patients with ALD by quantitative real-time PCR and immunohistochemistry. Mice with transgenic expression of c-myc in hepatocytes (alb-myc(tg)) and wild-type (WT) controls were fed either control or ethanol (EtOH) containing Lieber-DeCarli diet for 4weeks to induce ALD. Hepatic c-myc was strongly upregulated in human patients with advanced ALD and in EtOH-fed WT mice. Transcriptome analysis indicated deregulation of pathways involved in ER-stress, p53 signaling, hepatic fibrosis, cell cycle regulation, ribosomal synthesis and glucose homeostasis in EtOH-fed alb-myc(tg) mice. Transgenic expression of c-myc in hepatocytes with simultaneous EtOH-uptake led to early ballooning degeneration, increased liver collagen deposition and hepatic lipotoxicity, together with excessive CYP2E1-derived reactive oxygen species (ROS) production. Moreover, EtOH-fed alb-myc(tg) mice exhibited substantial changes in mitochondrial morphology associated with energy dysfunction. Pathway analysis revealed that elevated c-myc expression and ethanol uptake synergistically lead to strong AKT activation, Mdm2 phosphorylation and as a consequence to inhibition of p53. Expression of c-myc and EtOH-uptake synergistically accelerate the progression of ALD most likely due to loss of p53-dependent protection. Thus, c-myc is a new potential marker for the early detection of ALD and identification of risk patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  3. Analysis of a Parent-Initiated Social Media Campaign for Hirschsprung’s Disease

    Science.gov (United States)

    Wittmeier, Kristy; Holland, Cindy; Hobbs-Murison, Kendall; Crawford, Elizabeth; Beauchamp, Chad; Milne, Brodie; Morris, Melanie

    2014-01-01

    Background Social media can be particularly useful for patients or families affected by rare conditions by allowing individuals to form online communities across the world. Objective Our aim in this study was to conduct a descriptive and quantitative analysis of the use of a social media community for Hirschsprung’s Disease (HD). Methods In July 2011, a mother of a child with HD launched the “Shit Happens” campaign. The campaign uses social media (blogs, Twitter, and Facebook) to engage other families affected by HD. Internet analytics including Google Analytics and Facebook Insights were used to evaluate the reach and responsiveness of this campaign. Results On the day the HD campaign was launched, 387 people viewed the blog “Roo’s Journey”. Blog views have now exceeded 5400 views from 37 countries. The Facebook page extends to 46 countries, has an average post reach of 298 users, 1414 “likes”, and an overall reach of 131,032 users. The campaign has 135 Twitter followers and 344 tweets at the time of writing. The most common question posted on the Facebook page is related to treatment for extreme diaper rash. Responsiveness assessment demonstrated that within 2 hours of posting, a question could receive 143 views and 20 responses, increasing to 30 responses after 5 hours. Conclusions Social media networks are well suited to discussion, support, and advocacy for health-related conditions and can be especially important in connecting families affected by rare conditions. The HD campaign demonstrates the reach and responsiveness of a community that primarily relies on social media to connect families affected by HD. Although responsive, this community is currently lacking consistent access to evidence-based guidance for their common concerns. We will explore innovative consumer-researcher partnerships to offer a solution in future research. PMID:25499427

  4. Cause and Consequence: Mitochondrial Dysfunction Initiates and Propagates Neuronal Dysfunction, Neuronal Death and Behavioral Abnormalities in Age Associated Neurodegenerative Diseases

    Science.gov (United States)

    Gibson, Gary E.; Starkov, Anatoly; Blass, John P.; Ratan, Rajiv R.; Beal, M. Flint

    2009-01-01

    SUMMARY Age-related neurodegenerative diseases are associated with mild impairment of oxidative metabolism and accumulation of abnormal proteins. Within the cell, the mitochondria appears to be a dominant site for initiation and propagation of disease processes. Shifts in metabolism in response to mild metabolic perturbations may decrease the threshold for irreversible injury in response to ordinarily sub lethal metabolic insults. Mild impairment of metabolism accrue from and lead to increased reactive oxygen species (ROS). Increased ROS change cell signaling via post transcriptional and transcriptional changes. The cause and consequences of mild impairment of mitochondrial metabolism is one focus of this review. Many experiments in tissues from humans support the notion that oxidative modification of the α-ketoglutarate dehydrogenase complex (KGDHC) compromises neuronal energy metabolism and enhance ROS production in Alzheimer’s Disease (AD). These data suggest that cognitive decline in AD derives from the selective tricarboxylic acid (TCA) cycle abnormalities. By contrast in Huntington’s Disease (HD), a movement disorder with cognitive features distinct form AD, complex II + III abnormalities may dominate. These distinct mitochondrial abnormalities culminate in oxidative stress, energy dysfunction, and aberrant homeostasis of cytosolic calcium. Cytosolic calcium, elevations even only transiently, leads to hyperactivity of a number of enzymes. One calcium activated enzyme with demonstrated pathophysiological import in HD and AD is transglutaminase (TGase). TGase is a cross linking enzymes that can modulate transcrption, inactivate metabolic enzymes, and cause aggregation of critical proteins. Recent data indicate that TGase can silence expression of genes involved in compensating for metabolic stress. Altogether, our results suggest that increasing KGDHC via inhibition of TGase or via a host of other strategies to be described would be effective therapeutic

  5. Effective oral favipiravir (T-705 therapy initiated after the onset of clinical disease in a model of arenavirus hemorrhagic Fever.

    Directory of Open Access Journals (Sweden)

    Michelle Mendenhall

    2011-10-01

    Full Text Available Lassa and Junín viruses are the most prominent members of the Arenaviridae family of viruses that cause viral hemorrhagic fever syndromes Lassa fever and Argentine hemorrhagic fever, respectively. At present, ribavirin is the only antiviral drug indicated for use in treatment of these diseases, but because of its limited efficacy in advanced cases of disease and its toxicity, safer and more effective antivirals are needed.Here, we used a model of acute arenaviral infection in outbred guinea pigs based on challenge with an adapted strain of Pichindé virus (PICV to further preclinical development of T-705 (Favipiravir, a promising broad-spectrum inhibitor of RNA virus infections. The guinea pig-adapted passage 19 PICV was uniformly lethal with an LD(50 of ∼5 plaque-forming units and disease was associated with fever, weight loss, thrombocytopenia, coagulation defects, increases in serum aspartate aminotransferase (AST concentrations, and pantropic viral infection. Favipiravir (300 mg/kg/day, twice daily orally for 14 days was highly effective, as all animals recovered fully from PICV-induced disease even when therapy was initiated one week after virus challenge when animals were already significantly ill with marked fevers and thrombocytopenia. Antiviral activity and reduced disease severity was evidenced by dramatic reductions in peak serum virus titers and AST concentrations in favipiravir-treated animals. Moreover, a sharp decrease in body temperature was observed shortly after the start of treatment. Oral ribavirin was also evaluated, and although effective, the slower rate of recovery may be a sign of the drug's known toxicity.Our findings support further development of favipiravir for the treatment of severe arenaviral infections. The optimization of the experimental favipiravir treatment regimen in the PICV guinea pig model will inform critical future studies in the same species based on challenge with highly pathogenic arenaviruses

  6. Modified Fabry-Perot interferometric method for waveguide loss measurement.

    Science.gov (United States)

    Taebi, Sareh; Khorasaninejad, Mohammadreza; Saini, Simarjeet Singh

    2008-12-10

    An extension to the Fabry-Perot interferometric method is demonstrated to calculate the optical loss and the reflectivity for optical waveguides simultaneously. The method uses an excitation of the waveguide with a broadband amplified spontaneous emission source (a superluminescent diode in our case) and curve fitting to account for the change of input power, thereby simplifying the measurement procedure. The use of a broadband source as opposed to tunable lasers allows for simultaneous measurements over multiple wavelengths and decreased sensitivity to reflections in the cavity. Further, waveguides of different lengths are measured to calculate the optical loss and the reflectivity simultaneously. It is shown that, if the value for reflectivity is assumed, there could be a large error in the measurement of loss especially for short waveguides. Optical loss for ridge waveguides is measured and compared by using a tunable laser as the input source. The method can be used for a generic case where it is suspected that the input power changes during the measurement.

  7. Active Sensing with Fabry-Perot Infrared Interferometers

    Science.gov (United States)

    Huang, Jin; Gosangi, Rakesh; Gutierrez-Osuna, Ricardo

    2011-09-01

    In this article, we describe an active-sensing framework for infrared (IR) spectroscopy. The goal is to generate a sequence of wavelengths that best discriminates among chemicals. Unlike feature-selection strategies, the sequence is selected on-the-fly as the device acquires data. The framework models the problem as a Partially Observable Markov Decision Process (POMDP), which is solved by a greedy myopic algorithm. In previous work [1], we had applied this framework to temperature-modulated metal oxide sensor. Here, we adapt the framework to a tunable IR sensor based on Fabry-Perot interferometers (FPI). FPIs provide a low-cost alternative to traditional Fourier Transform Infrared Spectroscopy (FTIR), though at the expense of a narrower effective range and lower spectral resolution. Here, we first test whether the framework can scale up to large problems consisting 27 chemicals with 60 dimensions; our previous work on metal oxide sensors employed three chemicals and 7 dimensions. For this purpose, FPI spectra are simulated from FTIR. Then we validate the framework experimentally on 3 chemicals using a prototype instrument based on FPIs. These preliminary results are encouraging and indicate that the framework is able to solve classification problems of reasonable size.

  8. Optical fiber Fabry-Perot interferometer for microorganism growth detection

    Science.gov (United States)

    Liu, Xiaohui; Jiang, Mingshun; Sui, Qingmei; Luo, Shuyang; Geng, Xiangyi

    2016-07-01

    An optical fiber Fabry-Perot interferometer (FPI) based on hollow-core photonic crystal fiber (HCPCF) for microorganism growth detection is proposed and demonstrated. The FPI is formed by splicing both ends of a short section of HCPCF to SMFs and cleaving the SMF pigtail to a proper length. By measuring the fringe contrast of interference pattern, the refractive index (RI) changes of analyte during microorganism growth can be obtained. RI response of the sensor was investigated theoretically and experimentally. It shows linear response with sensitivity of -136 dB/RIU and good repeatability. Temperature response was also tested and the result confirms the low temperature cross-sensitivity of the sensor. Detection of yeast growth in liquid medium by the FPI sensor was conducted and the result shows the characteristic of typical yeast growth curve. With its advantages of high RI sensitivity, low temperature cross-sensitivity, capability for real-time measurement and so on, this FPI sensor has great potential in biosensing.

  9. Dielectric Fabry-Perot mirror coatings for infrared astronomy

    Science.gov (United States)

    Trauger, J.

    1984-01-01

    A number of Fabry-Perot (FP) coating designs have been developed specifically for IR astronomy. These have been optimized for uniform reflectance over five contiguous spectral ranges of particular astronomical interest between 1 and 5 microns. Wavelength coverage in individual designs is given by (maximum wavelength/minimum wavelength) greater than 1.4, over which reflective finesse is maintained near 35. Consideration has been made for the peculiar requirements of FP coatings. Visual alignment and testing of the FP has been made convenient by bringing the reflective finesse of the coating at 632.8 nm to the same value as the main IR reflection band. For example, a calcium fluoride FP can be aligned and tested at 632.8-nm He-Ne laser line, with the assurance of a corresponding finesse and spectral resolving power over its IR (3.6-5.1-micron) range. In addition, the FP can be used for IR spectroscopy while being simultaneously monitored and/or actively controlled at the laser wavelength. The potential for the coating itself to degrade the effective surface flatness of the FP through either mechanical stress or thickness nonuniformities is minimized by reducing to a minimum the number and thickness of coating layers. Several of these coatings have been fabricated and are actively in use at a number of observatories.

  10. Fabry-Perot Interferometer for Column CO2

    Science.gov (United States)

    Heaps, William S.; Kawa, Randolph; Bhartia, P. K. (Technical Monitor)

    2002-01-01

    Global atmospheric CO2 measurements are essential to resolving significant discrepancies in our understanding of the global carbon budget and, hence, humankind's role in global climate change. The science measurement requirements for CO2 are extremely demanding (precision approx. 0.3%). No atmospheric chemical species has ever been measured from space with this precision. We are developing a novel application of a Fabry-Perot interferometer to detect spectral absorption of reflected sunlight by CO2 and O2 in the atmosphere. Preliminary design studies indicate that the method will be able to achieve the sensitivity and signal-to-noise detection required to measure column CO2 at the target specification. The objective of this program is to construct a prototype instrument for deployment on an aircraft to test the instrument performance and our ability to retrieve the data in the real atmosphere. To date we have assembled a laboratory bench system to begin testing the optical and electronic components. We are also measuring signal and noise levels in actual sunlight to evaluate component performance.

  11. Fabry-Perot Interferometer for Column CO2: Airborne

    Science.gov (United States)

    Kawa, S. R.; Heaps, W. S.; Mao, J.; Andrews, A. E.; Burris, J. F.; Miodek, M.; Georgieva, E.

    2002-01-01

    Global atmospheric CO2 measurements are essential to resolving significant discrepancies in our understanding of the global carbon budget and, hence, humankind's role in global climate change. The science measurement requirements for CO2 are, however, extremely demanding (precision approximately 0.3%). We are developing a novel application of a Fabry-Perot interferometer to detect spectral absorption of reflected sunlight by CO2 and O2 in the atmosphere that should be able to achieve sufficient sensitivity and signal-to-noise to measure column CO2 at the target specification. We are currently constructing a prototype instrument for deployment on aircraft. The aircraft version will measure total column CO2 and CO2 below the aircraft as well as O2, which allows normalization of CO2 column amounts for varying surface height and pressure. This instrument will be a valuable asset in carbon budget field studies as well as a useful tool for evaluating existing and future space-based CO2 measurements. We will present the instrument concept, sensitivity calculations, and the results of testing a bench system in the laboratory and outdoors on the ground. We will also discuss our plan for deployment on the aircraft and potential flight applications to the CO2 budget problem.

  12. Demonstration of Fabry-Perot interferometric spectrometry technology

    Science.gov (United States)

    Petersen, T. V.; Makel, D. B.; Thurman, C.

    1993-06-01

    As rocket engine components experience wear or failure, anomalous materials may be entrained in the plume. Historically, visible plume anomalies have preceded many rocket engine failures, some of which have been catastrophic. Development of a small, rugged, high-speed, high resolution Fabry-Perot interferometer (FPI) based spectrometer capable of detecting the spectral signatures of eroding engine components during rocket engine test and/or flight operations is described. An operational plume spectrometer fabricated with miniaturized optics has been successfully tested. An extensive test series was conducted to define the limits of the spectrometer with respect to time-response and resolution. The data collected during testing were correlated with measurements obtained using sensitive ground equipment in order to benchmark the spectrometer's performance against a known device. The FPI demonstrated the reliability required for a flight instrument by functioning satisfactorily at or near the rocket engine test stand environment. Several of the optical components are interchangeable, allowing collection of a greater variety of plume signals. Also, the FPI's high resolution capabilities suggest it is suitable for application to both absorption and emission spectroscopy.

  13. Performance of a dual Fabry-Perot cavity refractometer.

    Science.gov (United States)

    Egan, Patrick F; Stone, Jack A; Hendricks, Jay H; Ricker, Jacob E; Scace, Gregory E; Strouse, Gregory F

    2015-09-01

    We have built and characterized a refractometer that utilizes two Fabry-Perot cavities formed on a dimensionally stable spacer. In the typical mode of operation, one cavity is held at vacuum, and the other cavity is filled with nitrogen gas. The differential change in length between the cavities is measured as the difference in frequency between two helium-neon lasers, one locked to the resonance of each cavity. This differential change in optical length is a measure of the gas refractivity. Using the known values for the molar refractivity and virial coefficients of nitrogen, and accounting for cavity length distortions, the device can be used as a high-resolution, multi-decade pressure sensor. We define a reference value for nitrogen refractivity as n-1=(26485.28±0.3)×10(-8) at p=100.0000  kPa, T=302.9190  K, and λ(vac)=632.9908  nm. We compare pressure determinations via the refractometer and the reference value to a mercury manometer.

  14. Equation of state measurements using single Fabry-Perot velocimeter

    Science.gov (United States)

    Saxena, A. K.; Kaushik, T. C.; Rawool, A. M.; Gupta, Satish C.

    2012-07-01

    Accurate measurement of projectile and free surface velocity of target is a crucial part of any high pressure physics experiments involving hyper velocity impact. Fabry Perot velocimeter (FPV) is a widely accepted technique for single surface velocity measurements. In the present work a possibility of using single FPV for two surface velocity measurements is experimentally explored. The laser light is launched in such a way that it illuminates both the surfaces under study and reflected light coming from the flyer as well as from the target is used to generate interference fringes. Therefore by recording fringe displacements due to Doppler shift in reflected light corresponding to movement of both the surfaces at different time instants, velocity profile of both target and projectile can be computed. This technique has been utilized for equation of state measurements of polyurethane based retro-reflective tape at 12 GPa and aluminum at 15 GPa. Measured peak particle velocities at the target-glass interface have been found in good agreement with the reported equation of state data.

  15. Health-related quality of life in different stages of chronic kidney disease and at initiation of dialysis treatment

    Directory of Open Access Journals (Sweden)

    Pagels Agneta A

    2012-06-01

    Full Text Available Abstract Objectives To evaluate health-related quality of life (HRQoL in patients in different stages of chronic kidney disease (CKD up to initiation of dialysis treatment and to explore possible correlating and influencing factors. Methods Cross-sectional design with 535 patients in CKD stages 2–5 and 55 controls assessed for HRQoL through SF-36 together with biomarkers. Results All HRQoL dimensions deteriorated significantly with CKD stages with the lowest scores in CKD 5. The largest differences between the patient groups were seen in ‘physical functioning’, ‘role physical’, ‘general health’ and in physical summary scores (PCS. The smallest disparities were seen in mental health and pain. Patients in CKD stages 2–3 showed significantly decreased HRQoL compared to matched controls, with differences of large magnitude - effect size (ES ≥ .80 - in ‘general health’ and PCS. Patients in CDK 4 demonstrated deteriorated scores with a large magnitude in ‘physical function’, ‘general health’ and PCS compared to the patients in CKD 2–3. Patients in CKD 5 demonstrated deteriorated scores with a medium sized magnitude (ES 0.5 – 0.79 in ‘role emotional’ and mental summary scores compared to the patients in CKD 4. Glomerular filtration rate Conclusions Having CKD implies impaired HRQoL, also in earlier stages of the disease. At the time for dialysis initiation HRQoL is substantially deteriorated. Co-existing conditions, such as inflammation and cardiovascular disease seem to be powerful predictors of impaired HRQoL in patients with CKD. Within routine renal care, strategies to improve function and well-being considering the management of co-existing conditions like inflammation and CVD need to be developed.

  16. Fabry-Perot干涉腔型光纤声发射传感器%Fiber-optic acoustic emission sensors with dual Fabry-Perot interferometric cavities

    Institute of Scientific and Technical Information of China (English)

    赵江海; 章小建

    2015-01-01

    设计了一种新型的双Fabry-Perot腔光纤传感器用于材料损伤引起的声发射信号检测.基于低细度Fabry-Perot腔多光束干涉原理,建立了光纤Fabry-Perot传感器检测声发射信号的数学模型.分析双Fabry-Perot腔正交点稳定工作机制,设计并制作了具有双Fabry-Perot腔结构的光纤声发射传感器来保持传感器正交点的稳定性.通过模拟AE信号检测与热应力干扰实验对设计的传感器进行了实验验证.实验一通过冲击振动与折断铅笔芯产生两类模拟声发射信号,使用商用的压电传感器和光纤传感器进行对比实验,结果表明光纤传感器能够成功检测到两类模拟声发射信号,灵敏度为12.9 nm,带宽达到30 kHz.实验二对传感器进行工作点稳定测试,结果表明双F-P腔的控制机制能够保证传感器工作在正交点,解决了传感器输出信号衰减的问题.

  17. Category learning in Alzheimer's disease and normal cognitive aging depends on initial experience of feature variability.

    Science.gov (United States)

    Phillips, Jeffrey S; McMillan, Corey T; Smith, Edward E; Grossman, Murray

    2017-04-01

    Semantic category learning is dependent upon several factors, including the nature of the learning task, as well as individual differences in the quality and heterogeneity of exemplars that an individual encounters during learning. We trained healthy older adults (n=39) and individuals with a diagnosis of Alzheimer's disease or Mild Cognitive Impairment (n=44) to recognize instances of a fictitious animal, a "crutter". Each stimulus item contained 10 visual features (e.g., color, tail shape) which took one of two values for each feature (e.g., yellow/red, curly/straight tails). Participants were presented with a series of items (learning phase) and were either told the items belonged to a semantic category (explicit condition) or were told to think about the appearance of the items (implicit condition). Half of participants saw learning items with higher similarity to an unseen prototype (high typicality learning set), and thus lower between-item variability in their constituent features; the other half learned from items with lower typicality (low typicality learning set) and higher between-item feature variability. After the learning phase, participants were presented with test items one at a time that varied in the number of typical features from 0 (antitype) to 10 (prototype). We examined between-subjects factors of learning set (lower or higher typicality), instruction type (explicit or implicit), and group (patients vs. elderly control). Learning in controls was aided by higher learning set typicality: while controls in both learning set groups demonstrated significant learning, those exposed to a high-typicality learning set appeared to develop a prototype that helped guide their category membership judgments. Overall, patients demonstrated more difficulty with category learning than elderly controls. Patients exposed to the higher-typicality learning set were sensitive to the typical features of the category and discriminated between the most and least

  18. Cognitive reserve and Aβ1-42 in mild cognitive impairment (Argentina-Alzheimer’s Disease Neuroimaging Initiative)

    Science.gov (United States)

    Harris, Paula; Fernandez Suarez, Marcos; Surace, Ezequiel I; Chrem Méndez, Patricio; Martín, María Eugenia; Clarens, María Florencia; Tapajóz, Fernanda; Russo, Maria Julieta; Campos, Jorge; Guinjoan, Salvador M; Sevlever, Gustavo; Allegri, Ricardo F

    2015-01-01

    Background The purpose of this study was to investigate the relationship between cognitive reserve and concentration of Aβ1-42 in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment, those with Alzheimer’s disease, and in control subjects. Methods Thirty-three participants from the Argentina-Alzheimer’s Disease Neuroimaging Initiative database completed a cognitive battery, the Cognitive Reserve Questionnaire (CRQ), and an Argentinian accentuation reading test (TAP-BA) as a measure of premorbid intelligence, and underwent lumbar puncture for CSF biomarker quantification. Results The CRQ significantly correlated with TAP-BA, education, and Aβ1-42. When considering Aβ1-42 levels, significant differences were found in CRQ scores; higher levels of CSF Aβ1-42 were associated with higher CRQ scores. Conclusion Reduced Aβ1-42 in CSF is considered as evidence of amyloid deposition in the brain. Previous results suggest that individuals with higher education, higher occupational attainment, and participation in leisure activities (cognitive reserve) have a reduced risk of developing Alzheimer’s disease. Our results support the notion that enhanced neural activity has a protective role in mild cognitive impairment, as evidenced by higher CSF Aβ1-42 levels in individuals with more cognitive reserve. PMID:26504392

  19. Initial evaluation of hepatic T1 relaxation time as an imaging marker of liver disease associated with autosomal recessive polycystic kidney disease (ARPKD).

    Science.gov (United States)

    Gao, Ying; Erokwu, Bernadette O; DeSantis, David A; Croniger, Colleen M; Schur, Rebecca M; Lu, Lan; Mariappuram, Jose; Dell, Katherine M; Flask, Chris A

    2016-01-01

    Autosomal recessive polycystic kidney disease (ARPKD) is a potentially lethal multi-organ disease affecting both the kidneys and the liver. Unfortunately, there are currently no non-invasive methods to monitor liver disease progression in ARPKD patients, limiting the study of potential therapeutic interventions. Herein, we perform an initial investigation of T1 relaxation time as a potential imaging biomarker to quantitatively assess the two primary pathologic hallmarks of ARPKD liver disease: biliary dilatation and periportal fibrosis in the PCK rat model of ARPKD. T1 relaxation time results were obtained for five PCK rats at 3 months of age using a Look-Locker acquisition on a Bruker BioSpec 7.0 T MRI scanner. Six three-month-old Sprague-Dawley (SD) rats were also scanned as controls. All animals were euthanized after the three-month scans for histological and biochemical assessments of bile duct dilatation and hepatic fibrosis for comparison. PCK rats exhibited significantly increased liver T1 values (mean ± standard deviation = 935 ± 39 ms) compared with age-matched SD control rats (847 ± 26 ms, p = 0.01). One PCK rat exhibited severe cholangitis (mean T1  = 1413 ms), which occurs periodically in ARPKD patients. The observed increase in the in vivo liver T1 relaxation time correlated significantly with three histological and biochemical indicators of biliary dilatation and fibrosis: bile duct area percent (R = 0.85, p = 0.002), periportal fibrosis area percent (R = 0.82, p = 0.004), and hydroxyproline content (R = 0.76, p = 0.01). These results suggest that hepatic T1 relaxation time may provide a sensitive and non-invasive imaging biomarker to monitor ARPKD liver disease.

  20. High-field MR imaging in pediatric congenital heart disease: Initial results

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Kim-Lien [David Geffen School of Medicine at UCLA, Division of Cardiology, VA Greater Los Angeles Healthcare System, Los Angeles, CA (United States); Khan, Sarah N.; Moriarty, John M.; Mohajer, Kiyarash; Renella, Pierangelo; Boechat, M.I.; Finn, J.P. [University of California at Los Angeles, Department of Radiological Sciences, Los Angeles, CA (United States); Satou, Gary [David Geffen School of Medicine at UCLA, Division of Pediatric Cardiology, Los Angeles, CA (United States); Ayad, Ihab; Patel, Swati [David Geffen School of Medicine at UCLA, Department of Anesthesia, Los Angeles, CA (United States)

    2014-08-03

    Comprehensive assessment of pediatric congenital heart disease (CHD) at any field strength mandates evaluation of both vascular and dynamic cardiac anatomy for which diagnostic quality contrast-enhanced magnetic resonance angiography (CEMRA) and cardiac cine are crucial. To determine whether high-resolution (HR) CEMRA and steady-state free precession (SSFP) cine can be performed reliably at 3.0 T in children with CHD and to compare the image quality to similar techniques performed at 1.5 T. Twenty-eight patients with a median age of 5 months and average weight 9.0 ± 7.8 kg with suspected or known CHD were evaluated at 3.0 T. SSFP cine (n = 86 series) and HR-CEMRA (n = 414 named vascular segments) were performed and images were scored for image quality and artifacts. The findings were compared to those of 28 patients with CHD of similar weight who were evaluated at 1.5 T. Overall image quality on HR-CEMRA was rated as excellent or good in 96% (397/414) of vascular segments at 3.0 T (k = 0.49) and in 94% (349/371) of vascular segments at 1.5 T (k = 0.36). Overall image quality of SSFP was rated excellent or good in 91% (78/86) of cine series at 3.0 T (k = 0.55) and in 81% (87/108) at 1.5 T (k = 0.47). Off-resonance artifact was common at both field strengths, varied over the cardiac cycle and was more prevalent at 3.0 T. At 3.0 T, off-resonance dark band artifact on SSFP cine was absent in 3% (3/86), mild in 69% (59/86), moderate in 27% (23/86) and severe in 1% (1/86) of images; at 1.5 T, dark band artifact was absent in 16% (17/108), mild in 69% (75/108), moderate in 12% (13/108) and severe in 3% (3/108) of cine images. The signal-to-noise ratio and contrast-to-noise ratio of both SSFP cine and HR-CEMRA images were significantly higher at 3.0 T than at 1.5 T (P < 0.001). Signal-to-noise ratio and contrast-to-noise ratio of high-resolution contrast-enhanced magnetic resonance angiography and SSFP cine were higher at 3.0 T than at 1.5 T. Artifacts on SSFP cine were

  1. Satisfaction with patient-doctor relationships in inflammatory bowel diseases: Examining patient-initiated change of specialist

    Institute of Scientific and Technical Information of China (English)

    Daniel R van Langenberg; Jane M Andrews

    2012-01-01

    AIM:To assess the reasons for,and factors associated with,patient-initiated changes in treating specialist in inflammatory bowel diseases (IBD).METHODS:Prospectively identified IBD patients (n =256) with ≥ 1 encounter at a metropolitan hospital were surveyed,including whether they had changed treating specialist and why.Negative reasons included loss of confidence,disagreement,and/or personality clash with the specialist.RESULTS:Of 162 respondents,70 (43%) had ever changed specialists; 30/70 (43%) for negative reasons,52/70 (74%) in the preceding year.Patients with negative reasons for changing (n =30) were younger (median,35.2 years vs 45.3 years),had higher IBD knowledge (median,5.0 years vs 4.0 years),yet had lower medication adherence and satisfaction scores (median,19.0 years vs 22.0 years,14.0 years vs 16.0 years respectively,Mann-Whitney tests,all P < 0.05),compared to all other responders (n =132).Patients with a recent change (for any reason) were more likely to have Crohn's disease,currently active disease,previous bowel resection and recent hospitalization [OR 2.6,95% CI (1.3-5.4),2.2 (1.0-4.7),5.56 (1.92-16.67),2.0(1.3-3.0),each P < 0.05].CONCLUSION:Changing specialist appears associated with patient-related (age,nonadherence) and contemporaneous disease-related factors (recent relapse) which,where modifiable,may enhance patient-doctor relationships and therefore quality of care.

  2. Increases in Recent HIV Testing Among Men Who Have Sex With Men Coincide With the Centers for Disease Control and Prevention's Expanded Testing Initiative

    Science.gov (United States)

    Cooley, Laura A.; Wejnert, Cyprian; Rose, Charles E.; Paz-Bailey, Gabriela; Taussig, Jennifer; Gern, Robert; Hoyte, Tamika; Salazar, Laura; White, Jianglan; Todd, Jeff; Bautista, Greg; Flynn, Colin; Sifakis, Frangiscos; German, Danielle; Isenberg, Debbie; Driscoll, Maura; Hurwitz, Elizabeth; Doherty, Rose; Wittke, Chris; Prachand, Nikhil; Benbow, Nanette; Melville, Sharon; Pannala, Praveen; Yeager, Richard; Sayegh, Aaron; Dyer, Jim; Sheu, Shane; Novoa, Alicia; Thrun, Mark; Al-Tayyib, Alia; Wilmoth, Ralph; Higgins, Emily; Griffin, Vivian; Mokotoff, Eve; MacMaster, Karen; Wolverton, Marcia; Risser, Jan; Rehman, Hafeez; Padgett, Paige; Bingham, Trista; Sey, Ekow Kwa; LaLota, Marlene; Metsch, Lisa; Forrest, David; Beck, Dano; Cardenas, Gabriel; Nemeth, Chris; Anderson, Bridget J.; Watson, Carol-Ann; Smith, Lou; Robinson, William T.; Gruber, DeAnn; Barak, Narquis; Murrill, Chris; Neaigus, Alan; Jenness, Samuel; Hagan, Holly; Reilly, Kathleen H.; Wendel, Travis; Cross, Helene; Bolden, Barbara; D'Errico, Sally; Wogayehu, Afework; Godette, Henry; Brady, Kathleen A.; Kirkland, Althea; Sifferman, Andrea; Miguelino-Keasling, Vanessa; Velasco, Al; Tovar, Veronica; Raymond, H. Fisher; De León, Sandra Miranda; Rolón-Colón, Yadira; Marzan, Melissa; Courogen, Maria; Jaenicke, Tom; Thiede, Hanne; Burt, Richard; Jia, Yujiang; Opoku, Jenevieve; Sansone, Marie; West, Tiffany; Magnus, Manya; Kuo, Irene

    2015-01-01

    According to National HIV Behavioral Surveillance system data, human immunodeficiency virus (HIV) testing increased among gay, bisexual, and other men who have sex with men from 2008 to 2011 in cities funded by the Centers for Disease Control and Prevention's Expanded Testing Initiative, suggesting that focused HIV testing initiatives might have positive effects. PMID:25352589

  3. Increases in Recent HIV Testing Among Men Who Have Sex With Men Coincide With the Centers for Disease Control and Prevention's Expanded Testing Initiative

    OpenAIRE

    2014-01-01

    According to National HIV Behavioral Surveillance system data, human immunodeficiency virus (HIV) testing increased among gay, bisexual, and other men who have sex with men from 2008 to 2011 in cities funded by the Centers for Disease Control and Prevention's Expanded Testing Initiative, suggesting that focused HIV testing initiatives might have positive effects.

  4. Periodontal Disease and Incident Cancer Risk among Postmenopausal Women: Results from the Women's Health Initiative Observational Cohort.

    Science.gov (United States)

    Nwizu, Ngozi N; Marshall, James R; Moysich, Kirsten; Genco, Robert J; Hovey, Kathleen M; Mai, Xiaodan; LaMonte, Michael J; Freudenheim, Jo L; Wactawski-Wende, Jean

    2017-08-01

    Background: Periodontal pathogens have been isolated from precancerous and cancerous lesions and also shown to promote a procarcinogenic microenvironment. Few studies have examined periodontal disease as a risk factor for total cancer, and none have focused on older women. We examined whether periodontal disease is associated with incident cancer among postmenopausal women in the Women's Health Initiative Observational Study.Methods: Our prospective cohort study comprised 65,869 women, ages 54 to 86 years. Periodontal disease information was obtained via self-report questionnaires administered between 1999 and 2003, whereas ascertainment of cancer outcomes occurred through September 2013, with a maximum follow-up period of 15 years. Physician-adjudicated incident total cancers were the main outcomes and site-specific cancers were secondary outcomes. HRs and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression. All analyses were conducted two-sided.Results: During a mean follow-up of 8.32 years, 7,149 cancers were identified. Periodontal disease history was associated with increased total cancer risk (multivariable-adjusted HR, 1.14; 95% CI, 1.08-1.20); findings were similar in analyses limited to 34,097 never-smokers (HR, 1.12; 95% CI, 1.04-1.22). Associations were observed for breast (HR, 1.13; 95% CI, 1.03-1.23), lung (HR, 1.31; 95% CI, 1.14-1.51), esophagus (HR, 3.28; 95% CI, 1.64-6.53), gallbladder (HR, 1.73; 95% CI, 1.01-2.95), and melanoma skin (HR, 1.23; 95% CI, 1.02-1.48) cancers. Stomach cancer was borderline (HR, 1.58; 95% CI, 0.94-2.67).Conclusions: Periodontal disease increases risk of total cancer among older women, irrespective of smoking, and certain anatomic sites appear to be vulnerable. Impact: Our findings support the need for further understanding of the effect of periodontal disease on cancer outcomes. Cancer Epidemiol Biomarkers Prev; 26(8); 1255-65. ©2017 AACR. ©2017 American Association for Cancer

  5. Two-dimensional photonic-crystal-based Fabry-Perot etalon.

    Science.gov (United States)

    Ho, Chong Pei; Pitchappa, Prakash; Kropelnicki, Piotr; Wang, Jian; Cai, Hong; Gu, Yuandong; Lee, Chengkuo

    2015-06-15

    We demonstrate the design, fabrication, and characterization of a polycrystalline-silicon-based photonic crystal Fabry-Perot etalon, which is aimed to work in the mid-infrared wavelengths. The highly reflective mirrors required in a Fabry-Perot etalon are realized by freestanding polycrystalline-silicon-based photonic crystal membranes with etched circular air holes. A peak reflection of 96.4% is observed at 3.60 μm. We propose a monolithic CMOS-compatible fabrication process to configure two such photonic crystal mirrors to be in parallel to form a Fabry-Perot etalon; a filtered transmission centered at 3.51 μm is observed. The quality factor measured is around 300, which is significantly higher than in existing works. This creates the possibility of using such devices for high-resolution applications such as gas sensing and hyperspectral imaging.

  6. Enhanced random lasing in ZnO nanocombs assisted by Fabry-Perot resonance.

    Science.gov (United States)

    Chen, Yungting; Chen, Yangfang

    2011-04-25

    The ultraviolet random lasing behavior of an ensemble of ZnO nanocombs has been demonstrated. It is found that the Fabry-Perot resonance induced by nanocomb geometry can greatly enhance random lasing action with a low threshold condition. Besides, the emission spectra exhibit few sharp lasing peaks with a full width at half maximum (FWHM) of less than 0.3 nm and a narrow background emission with a FWHM of about 5 nm. Cathodoluminescence mapping images are utilized to analyze the Fabry-Perot resonance phenomenon. The resonant effect on the lasing system is further confirmed by nanocombs with different resonant cavity lengths. The unique lasing behavior induced by the simultaneous occurrence of Fabry-Perot resonance and random laser action shown here may open up a new possibility for the creation of highly efficient light emitting devices.

  7. Distributed torsion sensor based on cascaded coaxial cable Fabry-Perot interferometers

    Science.gov (United States)

    Cheng, Baokai; Zhu, Wenge; Hua, Liwei; Liu, Jie; Li, Yurong; Nygaard, Runar; Xiao, Hai

    2016-07-01

    Cascaded coaxial cable Fabry-Perot interferometers (FPI) are studied and demonstrated for distributed torsion measurement. Multiple weak reflectors are implemented on a coaxial cable so that any two consecutive reflectors can form a Fabry-Perot cavity. By fixing the cable sensor in a helical form on a shaft, the distributed torsion of the shaft can be measured by the cascaded Fabry-Perot cavities. A test on a single section shows that the sensor has a linear response with a sensitivity of 1.834 MHz (rad/m)-1 in the range of twisted rate from 0 to 8.726 rad m-1. The distributed torsion sensing capability is useful in drilling process monitoring, structure health monitoring and machine failure detection.

  8. Improved spectral characteristics of 980 nm broad area slotted Fabry-Perot diode lasers

    Institute of Scientific and Technical Information of China (English)

    Gao Zhuo; Wang Jun; Xiong Cong; Liu Yuanyuan; Liu Suping; Ma Xiaoyu

    2012-01-01

    A novel broad area slotted Fabry-Perot diode laser is designed and fabricated.Using a new semianalytical method,we introduce effective refractive index perturbations in the form of etched slot features into a conventional 980 nm broad area Fabry-Perot cavity,and the spectral characteristics of the device are expected to be noticeably improved.A low density of slot features is formed by using standard optical lithography and inductively coupled plasma dry etching.The experimental results show that the full spectral width at half-maximum is less than 0.4 nm,meanwhile,the thermal shift of the emission spectrum is decreased from 0.26 to 0.07 nm/℃ over a temperature range of 10 to 60 ℃.The improved spectral characteristics of the device are proved to be attributed to such slotted Fabry-Perot laser structures.

  9. High Finesse Fiber Fabry-Perot Cavities: Stabilization and Mode Matching Analysis

    CERN Document Server

    Gallego, Jose; Alavi, Seyed Khalil; Alt, Wolfgang; Martinez-Dorantes, Miguel; Meschede, Dieter; Ratschbacher, Lothar

    2015-01-01

    Fiber Fabry-Perot cavities, formed by micro-machined mirrors on the end-facets of optical fibers, are used in an increasing number of technical and scientific applications, where they typically require precise stabilization of their optical resonances. Here, we study two different approaches to construct fiber Fabry-Perot resonators and stabilize their length for experiments in cavity quantum electrodynamics with neutral atoms. A piezo-mechanically actuated cavity with feedback based on the Pound-Drever-Hall locking technique is compared to a novel rigid cavity design that makes use of the high passive stability of a monolithic cavity spacer and employs thermal self-locking and external temperature tuning. Furthermore, we present a general analysis of the mode matching problem in fiber Fabry-Perot cavities, which explains the asymmetry in their reflective line shapes and has important implications for the optimal alignment of the fiber resonators. Finally, we discuss the issue of fiber-generated background ph...

  10. Lighten up: Specific postural instructions affect axial rigidity and step initiation in patients with Parkinson’s disease

    Science.gov (United States)

    Cohen, Rajal G.; Gurfinkel, Victor S.; Kwak, Elizabeth; Warden, Amelia C.; Horak, Fay B.

    2015-01-01

    Background Parkinson’s disease (PD) is associated with stooped postural alignment, increased postural sway, and reduced mobility. The Alexander Technique (AT) is a mindfulness-based approach to improving posture and mobility by reducing muscular interference while maintaining upward intentions. Evidence suggests that AT can reduce disability associated with PD, but a mechanism for this effect has not yet been established. Objective We investigated whether AT-based instructions reduce axial rigidity and increase upright postural alignment, and whether these instructions have different effects on postural alignment, axial rigidity, postural sway, and mobility than effort-based instructions regarding posture. Method Twenty subjects with PD practiced two sets of instructions and then attempted to implement both approaches (as well as a relaxed control condition) during quiet standing and step initiation. The ‘Lighten Up’ instructions relied on AT principles of reducing excess tension while encouraging length. The ‘Pull Up’ instructions relied on popular concepts of effortful posture correction. We measured kinematics, resistance to axial rotation, and ground reaction forces. Results Both sets of experimental instructions led to increases in upright postural alignment relative to the control condition. Only the Lighten Up instructions led to reduced postural sway, reduced axial postural tone, greater modifiability of tone, and a smoother center of pressure trajectory during step initiation, possibly indicating greater movement efficiency. Conclusion Mindful movement approaches such as AT may benefit balance and mobility in subjects with PD by acutely facilitating increased upright postural alignment while decreasing rigidity. PMID:25665828

  11. Possible Involvement of a Mitochondrial Translation Initiation Factor 3 Variant Causing Decreased mRNA Levels in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Anna Anvret

    2010-01-01

    Full Text Available Genes important for mitochondrial function have been implicated in Parkinson's disease (PD. Mitochondrial translation initiation factor 3 (MTIF3 is a nuclear encoded protein required for the initiation of complex formation on mitochondrial ribosomes. Dysfunction of MTIF3 may impair mitochondrial function and dopamine neurons appear to be particularly vulnerable to oxidative stress, which may relate to their degeneration in PD. An association was recently reported between the synonymous rs7669(C>T in MTIF3 and PD in a German case-control material. We investigated rs7669 in a Swedish Parkinson case-control material. The study revealed no significant association of the individual genotypes or alleles with PD. When comparing the combined TT/CT-genotypes versus the CC-genotype, we observed a significant association (P=.0473 with PD. We also demonstrated that the TT-genotype causes a significant decrease in MTIF3 mRNA expression compared to the CC-genotype (P=.0163. Our findings support the hypothesis that MTIF3 may be involved in the etiology of PD.

  12. Usual interstitial pneumonia preceding collagen vascular disease: a retrospective case control study of patients initially diagnosed with idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Masato Kono

    Full Text Available BACKGROUND: The aim of this study was to evaluate the cumulative incidence and the predictive factors for collagen vascular disease (CVD in patients initially diagnosed with idiopathic pulmonary fibrosis (IPF, and to examine the features of patients who then developed CVD. METHODS: This was a retrospective review of 111 consecutive patients with IPF diagnosed at our institution. None of the patients fulfilled any of the CVD criteria from the American College of Rheumatology (ACR within 6 months or more after the diagnosis of IPF. RESULTS: Ten patients (9.0% developed CVD during the follow-up period: four had rheumatoid arthritis (RA; four had microscopic polyangiitis (MPA; one had systemic sclerosis (SSc; and one had SSc and Sjogren's syndrome (SjS. The mean time until CVD diagnosis was 3.9 years. The cumulative incidences of CVD at 1, 5, and 10 years were 0.91%, 9.85%, and 15.5%, respectively. Patients who developed CVD were significantly younger, more likely to be women and had a better prognosis than those with IPF. Cox proportional hazards regression analysis showed that female sex and the presence of lymphoid aggregates with germinal centers were significantly associated with the occurrence of CVD in patients initially diagnosed with IPF. CONCLUSIONS: CVD is an important underlying condition in IPF, and shows better prognosis. The possibility of the development of CVD should remain a consideration in the follow-up of IPF.

  13. A phase II study of bortezomib plus prednisone for initial therapy of chronic graft-versus-host disease.

    Science.gov (United States)

    Herrera, Alex F; Kim, Haesook T; Bindra, Bhavjot; Jones, Kyle T; Alyea, Edwin P; Armand, Philippe; Cutler, Corey S; Ho, Vincent T; Nikiforow, Sarah; Blazar, Bruce R; Ritz, Jerome; Antin, Joseph H; Soiffer, Robert J; Koreth, John

    2014-11-01

    Chronic graft-versus-host disease (GVHD) induces significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Corticosteroids are standard initial therapy, despite limited efficacy and long-term toxicity. Based on our experience using bortezomib as effective acute GVHD prophylaxis, we hypothesized that proteasome-inhibition would complement the immunomodulatory effects of corticosteroids to improve outcomes in chronic GVHD (cGVHD). We undertook a single-arm phase II trial of bortezomib plus prednisone for initial therapy of cGVHD. Bortezomib was administered at 1.3 mg/m(2) i.v. on days 1, 8, 15, and 22 of each 35-day cycle for 3 cycles (15 weeks). Prednisone was dosed at .5 to 1 mg/kg/day, with a suggested taper after cycle 1. All 22 enrolled participants were evaluable for toxicity; 20 were evaluable for response. Bortezomib plus prednisone therapy was well tolerated, with 1 occurrence of grade 3 sensory peripheral neuropathy possibly related to bortezomib. The overall response rate at week 15 in evaluable participants was 80%, including 2 (10%) complete and 14 (70%) partial responses. The organ-specific complete response rate was 73% for skin, 53% for liver, 75% for gastrointestinal tract, and 33% for joint, muscle, or fascia involvement. The median prednisone dose decreased from 50 mg/day to 20 mg/day at week 15 (P prednisone for initial treatment of cGVHD is feasible and well tolerated. We observed a high response rate to combined bortezomib and prednisone therapy; however, in this single-arm study, we could not directly measure the impact of bortezomib. Proteasome inhibition may offer benefit in the treatment of cGVHD and should be further evaluated.

  14. Fiber Fabry-Perot interferometer with controllable temperature sensitivity.

    Science.gov (United States)

    Zhang, Xinpu; Peng, Wei; Zhang, Yang

    2015-12-01

    We proposed a fiber taper based on the Fabry-Perot (FP) interferometer structure with controllable temperature sensitivity. The FP interferometer is formed by inserting a segment of tapered fiber tip into the capillary and subsequently splicing the other end of the capillary to a single-mode fiber (SMF), the tapered fiber endface, and the spliced face form the FP cavity. Through controlling the inserted tapered fiber length, a series of FP interferometers were made. Because the inserted taper tip has the degree of freedom along the fiber axial, when the FP interferometer is subjected to temperature variation, the thermal expansion of the fiber taper tip will resist the FP cavity length change caused by the evolution of capillary length, and we can control the temperature sensitivity by adjusting the inserted taper length. In this structure, the equivalent thermal expansion coefficient of the FP interferometer can be defined; it was used to evaluate the temperature sensitivity of the FP interferometer, which provides an effective method to eliminate the temperature effect and to enhance other measurement accuracy. We fabricated the FP interferometers and calibrated their temperature characters by measuring the wavelength shift of the resonance dips in the reflection spectrum. In a temperature range of 50°C to 150°C, the corresponding temperature sensitivities can be controlled between 0 and 1.97 pm/°C when the inserted taper is between 75 and 160 μm. Because of its controllable temperature sensitivity, ease of fabrication, and low cost, this FP interferometer can meet different temperature sensitivity requirements in various application areas, especially in the fields which need temperature insensitivity.

  15. The benefit of consolidation radiotherapy to initial disease bulk in patients with advanced Hodgkin's disease who achieved complete remission after standard chemotherapy

    Directory of Open Access Journals (Sweden)

    Bayoumi Y

    2015-03-01

    Full Text Available Yasser Bayoumi,1,2 Abdulaziz Al-Homaidi,3 Syed Zaidi,3 Imran Tailor,3 Ibrahiem Motiabi,3 Nawal Alshehri,3 Assem Al-Ghazali,3 Samer Almudaibigh3 1Radiation Oncology, National Cancer Institute, Cairo University, Egypt; 2Radiation Oncology Department, 3Department of Haematology and Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia Background/purpose: The aim of this study was to evaluate the role of consolidation radiotherapy (RT in advanced-stage Hodgkin's disease (HD with initial bulky sites after radiological complete remission (CR or partial response (PR with positron emission tomography-negative (metabolic CR following standard chemotherapy (ABVD [Adriamycin, bleomycin, vinblastine, and dacarbazine] six to eight cycles. Patients and methods: Adult patients with advanced-stage HD treated at our institute during the period 2006 to 2012 were retrospectively evaluated. One hundred and ninety-two patients with initial bulky disease size (>7 cm who attained radiological CR/PR and metabolic CR were included in the analysis. One hundred and thirteen patients who received radiotherapy (RT as consolidation postchemotherapy (RT group were compared to 79 patients who did not receive RT (non-RT group. Disease-free (DFS and overall survival (OS rates were estimated using the Kaplan–Meier method and were compared according to treatment group by the log-rank tests at P ≤0.05 significance level. Results: The mean age of the cohort was 33 (range: 14 to 81 years. Eighty-four patients received involved-field radiation and 29 patients received involved-site RT. The RT group had worse prognostic factors compared to the non-RT group. Thirteen (12% relapses occurred in the RT group, and 19 (24% relapses occurred in the non-RT group. Nine patients (8% in the RT group died, compared to eleven patients (14% in the non-RT group. Second malignancies were seen in only five patients: three patients in the RT group compared to two

  16. Salvage of relapse of patients with Hodgkin's disease in clinical stages I or II who were staged with laparotomy and initially treated with radiotherapy alone. A report from the international database on Hodgkin's disease

    DEFF Research Database (Denmark)

    Specht, L.; Horwich, A.; Ashley, S.

    1994-01-01

    PURPOSE: To analyze presentation variables that might indicate a high or low likelihood of success of the treatment of patients relapsing after initial radiotherapy of Hodgkin's disease in clinical Stages I or II who were staged with laparotomy. METHODS AND MATERIALS: Data were analyzed on 681...... patients in the International Database on Hodgkin's Disease who were initially in clinical Stages I or II, who were staged with laparotomy, and who relapsed after initial treatment with irradiation alone. Factors analyzed for outcome after first relapse included initial stage, age, sex, histology...

  17. Neurodevelopment and brain growth in classic Menkes disease is influenced by age and symptomatology at initiation of copper treatment.

    Science.gov (United States)

    Kaler, Stephen G

    2014-10-01

    Menkes disease is an X-linked recessive disorder of brain copper metabolism caused by mutations in an essential mammalian copper transport gene, ATP7A. Untreated affected individuals suffer failure to thrive and neurodevelopmental delays that usually commence at 6-8 weeks of age. Death by age three years is typical. While provision of working copies of ATP7A to the brain by viral vectors is a promising strategy under development, the only treatment currently available is subcutaneous copper injections. These can normalize circulating blood levels and may replete brain copper depending on the molecular context, e.g., the severity of ATP7A mutation and potential presence of mosaicism. In this paper, we summarize somatic growth and neurodevelopmental outcomes for 60 subjects enrolled in a recently concluded phase I/II clinical trial of copper histidine for Menkes disease (ClinicalTrials.gov Identifier: NCT00001262). Primary outcomes indicate highly statistically significant improvements in gross motor, fine motor/adaptive, personal-social, and language neurodevelopment in the cohort of subjects who received early treatment prior to onset of symptoms (n=35). Correlating with these findings, quantitative parameters of somatic growth indicated statistically significant greater growth in head circumference for the initially asymptomatic group, whereas weight and height/length at age three years (or at time of death) did not differ significantly. Mortality at age 3 was higher (50%) in subjects older and symptomatic when treatment commenced compared to the asymptomatic group (28.6%). We conclude that early copper histidine for Menkes disease is safe and efficacious, with treatment outcomes influenced by the timing of intervention, and ATP7A mutation.

  18. High-temperature fiber-optic Fabry-Perot interferometric sensors

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Wenhui; Jiang, Yi; Gao, Ran, E-mail: bitjy@bit.edu.cn [School of Optoelectronics, Beijing Institute of Technology, Beijing 100081 (China); Liu, Yuewu [Key Laboratory for Mechanics in Fluid Solid Coupling Systems, Institute of Mechanics, Chinese Academy of Science, Beijing 100190 (China)

    2015-05-15

    A photonic crystal fiber (PCF) based high-temperature fiber-optic sensor is proposed and experimentally demonstrated. The sensor head is a Fabry-Perot cavity manufactured with a short section of endless single-mode photonic crystal fiber (ESM PCF). The interferometric spectrum of the Fabry-Perot interferometer is collected by a charge coupled device linear array based micro spectrometer. A high-resolution demodulation algorithm is used to interrogate the peak wavelengths. Experimental results show that the temperature range of 1200 °C and the temperature resolution of 1 °C are achieved.

  19. High-temperature fiber-optic Fabry-Perot interferometric sensors.

    Science.gov (United States)

    Ding, Wenhui; Jiang, Yi; Gao, Ran; Liu, Yuewu

    2015-05-01

    A photonic crystal fiber (PCF) based high-temperature fiber-optic sensor is proposed and experimentally demonstrated. The sensor head is a Fabry-Perot cavity manufactured with a short section of endless single-mode photonic crystal fiber (ESM PCF). The interferometric spectrum of the Fabry-Perot interferometer is collected by a charge coupled device linear array based micro spectrometer. A high-resolution demodulation algorithm is used to interrogate the peak wavelengths. Experimental results show that the temperature range of 1200 °C and the temperature resolution of 1 °C are achieved.

  20. Negative Goos-H(a)nchen Effect in Thin-Film Fabry-Perot Filter

    Institute of Scientific and Technical Information of China (English)

    LI Ming-Yu; LIU Xu; MA Xin; LI Yi-Yu; GU Pei-Fu

    2007-01-01

    We investigate the Goos-Hanchen effect of a Gaussian light beam reflected by the thin-film Fabry-Perot filter. It is shown that the Goos-Hanchen shift can be either negative or positive. The Gaussian-beam analysis and stationary phase method are introduced to calculate the lateral shift between the incident beam and the reflected beam at different wavelengths and to analyse the Goos-Hanchen effect in the thin-film Fabry-Perot filter. The effect of the incident beam diameter is also discussed.

  1. The Three-Arm Michelson-Fabry-Pérot Detector for Gravitational Waves

    Institute of Scientific and Technical Information of China (English)

    Chao-Guang Huang; Yong-Gui Li; Ning Zhu

    2016-01-01

    A three-arm Michelson-Fabry-Pérot detector for gravitational waves is designed.It consists of three Michelson Fabry-Pérot interferometers,one for each pair of arms.The new detector can be used to confirm whether the gravitational waves are in general relativity polarization states and to set the strong constraints on non-GR gravitational wave polarization states.By the new detectors,the angular resolution of sources can be improved significantly.With the new detector,it is easier to search for and confirm a gravitational wave signal in the observation data.

  2. Period Doubling in a Fabry-Perot Laser Diode Subject to Optical Pulse Injection

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yue-Peng; WANG Yun-Cai; ZHANG Ming-Jiang; AN Yi; WANG Ji-Long

    2007-01-01

    Experimental study and numerical simulations of the period doubling of injected optical pulses in Fabry-Perot laser diodes are presented. In our experiments, the period doubling is achieved within a wide input frequency range and the period doubling of the injected optical pulses with 6.32 GHz repetition rate is investigated in detail. The obtained experimental results indicate that period doubling occurs at an appropriate injected optical power level when the bias current of the Fabry-Perot laser diode is located in lower ranges. Moreover, the experimental observed features have been numerically demonstrated by using a coupled rate-equation model. Numerical simulations are consistent with the experimental results.

  3. Displacement-noise-free gravitational-wave detection with two Fabry-Perot cavities

    CERN Document Server

    Rakhubovsky, Andrey A

    2008-01-01

    We propose two detuned Fabry-Perot cavities, each pumped through both the mirrors, positioned in line as a toy model of the gravitational-wave (GW) detector free from displacement noise of the test masses. It is demonstrated that the noise of cavity mirrors can be completely excluded in a proper linear combination of the cavities output signals. This model is illustrated by a simplified round trip model (without Fabry-Perot cavities). We show that in low-frequency region the obtained displacement-noise-free response signal is stronger than the one of the interferometer recently proposed by S.Kawamura and Y.Chen.

  4. Model of Fabry-Pérot-type electromagnetic modes of a cylindrical nanowire

    DEFF Research Database (Denmark)

    Bordo, Vladimir

    2010-01-01

    The rigorous theory of normal electromagnetic modes of a cylindrical nanowire of finite length is developed. The exact integral equation which determines the solution of Maxwell's equations obeying the boundary conditions at the whole nanowire surface is derived. The nanowire normal (Fabry......-Pérot) modes are defined as non-trivial solutions of the source-free equation. The approach is considered in more detail for elongated nanowires whose length is much larger than their diameter. The resonance condition obtained for a single-mode nanowire resembles the formula for the Fabry-Pérot resonator...

  5. Fiber-Optic Anemometer Based on Silicon Fabry-Perot Interferometer

    Science.gov (United States)

    2015-11-05

    f, oo •• " • ~ OII Ct’ THIS f’ORM CANCELS AND SUPERSEOES All. P~EVIOUS \\I!:RSI Fiber-optic anemometer based on silicon Fabry-Pérot...monitoring, etc. In this paper, we propose a new anemometer which consists of a Fabry-Pérot interferometer (FPI) implemented using a thin silicon mounted...on the tip of an optical fiber. The anemometer takes advantage of the superior thermal and optical properties of silicon. Silicon is transparent to

  6. Decreased vibrational susceptibility of Fabry-Perot cavities via designs of geometry and structural support

    Institute of Scientific and Technical Information of China (English)

    Yang Tao; Li Wen-Bo; Zang Er-Jun; Chen Li-Sheng

    2007-01-01

    Ultra-stable optical cavities are widely used for laser frequency stabilization. In these experiments the laser performance relies on the length stability of the Fabry-Perot cavities. Vibration-induced deformation is one of the dominant factors that affect the stability of ultra-stable optical cavities. We have quantitatively analysed the elastic deformation of Fabry-Perot cavities with various shapes and mounting configurations. Our numerical result facilitates a novel approach for the design of ultra-stable cavities that are insensitive to vibrational perturbations. This approach can be applied to many experiments such as laser frequency stabilization, high-precision laser spectroscopy, and optical frequency standards.

  7. Rheumatoid Arthritis and Incidence of Twelve Initial Presentations of Cardiovascular Disease: A Population Record-Linkage Cohort Study in England.

    Directory of Open Access Journals (Sweden)

    Mar Pujades-Rodriguez

    Full Text Available While rheumatoid arthritis is an established risk factor for cardiovascular disease (CVD, our knowledge of how the pattern of risk varies for different cardiovascular phenotypes is incomplete. The association between rheumatoid arthritis and the initial presentation of 12 types of CVDs were examined in a contemporary population of men and women of a wide age range.CALIBER data, which links primary care, hospital and mortality data in England, was analysed. A cohort of people aged ≥18 years and without history of CVD was assembled and included all patients with prospectively recorded rheumatoid arthritis from January 1997, until March 2010, matched with up to ten people without rheumatoid arthritis by age, sex and general practice. The associations between rheumatoid arthritis and the initial presentation of 12 types of CVDs were estimated using multivariable random effects Poisson regression models.The analysis included 12,120 individuals with rheumatoid arthritis and 121,191 comparators. Of these, 2,525 patients with and 18,146 without rheumatoid arthritis developed CVDs during a median of 4.2 years of follow-up. Patients with rheumatoid arthritis had higher rates of myocardial infarction (adjusted incidence ratio [IRR] = 1.43, 95%CI 1.21-1.70, unheralded coronary death (IRR = 1.60, 95%CI 1.18-2.18, heart failure (IRR = 1.61, 95%CI 1.43-1.83, cardiac arrest (HR = 2.26, 95%CI 1.69-3.02 and peripheral arterial disease (HR = 1.36, 95%CI 1.14-1.62; and lower rates of stable angina (HR = 0.83, 95%CI 0.73-0.95. There was no evidence of association with cerebrovascular diseases, abdominal aortic aneurysm or unstable angina, or of interactions with sex or age.The observed associations with some but not all types of CVDs inform both clinical practice and the selection of cardiovascular endpoints for trials and for the development of prognostic models for patients with rheumatoid arthritis.

  8. Economic evaluation of participation in a voluntary Johne's disease prevention and control program from a farmer's perspective--The Alberta Johne's Disease Initiative.

    Science.gov (United States)

    Wolf, R; Clement, F; Barkema, H W; Orsel, K

    2014-05-01

    The Alberta Johne's Disease Initiative (AJDI) is a Johne's disease (JD) control program with the goal of reducing the spread of Mycobacterium avium ssp. paratuberculosis (MAP) through implementation of best management practices. The objective was to estimate the economic benefit of participation in the AJDI. A decision tree was constructed in which disease prevalence, test characteristics, and probabilities for implementation of best management practices suggested by herd veterinarians were implemented. Analysis was performed using a Markov analysis, and input data were assigned using estimates from the AJDI and published data. A cost-effectiveness analysis was performed and the net benefit of participation (from the perspective of a dairy farmer) in the AJDI compared with no participation was calculated. A series of 1-way sensitivity analyses were used to control for uncertainty. Farms participating in the AJDI were estimated to have a net benefit of Can$74 per cow over the course of 10 yr. If project costs were covered by the participating farm, the net benefit was Can$27. In addition to the effects on MAP infection, a reduction in calf diarrhea was modeled for farms that improved their calf management through the use of pasteurizers. In that case, the additional costs outweighed additional revenues compared with the baseline analysis, resulting in a reduced net benefit of Can$19. Participation would not be cost effective if cows in early stages of MAP infection did not have decreased production and if prevalence of MAP infection did not increase on farms with poor management. A limitation of the study, despite high uncertainty in some input parameters, was the lack of knowledge regarding changes in prevalence on farms with various management strategies. In conclusion, participation in the AJDI was cost effective for the average Alberta dairy farm.

  9. National Studies as a Component of the World Health Organization Initiative to Estimate the Global and Regional Burden of Foodborne Disease.

    Directory of Open Access Journals (Sweden)

    Robin J Lake

    Full Text Available The World Health Organization (WHO initiative to estimate the global burden of foodborne diseases established the Foodborne Diseases Burden Epidemiology Reference Group (FERG in 2007. In addition to global and regional estimates, the initiative sought to promote actions at a national level. This involved capacity building through national foodborne disease burden studies, and encouragement of the use of burden information in setting evidence-informed policies. To address these objectives a FERG Country Studies Task Force was established and has developed a suite of tools and resources to facilitate national burden of foodborne disease studies. This paper describes the process and lessons learned during the conduct of pilot country studies under the WHO FERG initiative.Pilot country studies were initiated in Albania, Japan and Thailand in 2011 and in Uganda in 2012. A brief description of each study is provided. The major scientific issue is a lack of data, particularly in relation to disease etiology, and attribution of disease burden to foodborne transmission. Situation analysis, knowledge translation, and risk communication to achieve evidence-informed policies require specialist expertise and resources.The FERG global and regional burden estimates will greatly enhance the ability of individual countries to fill data gaps and generate national estimates to support efforts to reduce the burden of foodborne disease.

  10. Real-world characterization and differentiation of the Global Initiative for Chronic Obstructive Lung Disease strategy classification

    Directory of Open Access Journals (Sweden)

    Price DB

    2014-05-01

    Full Text Available David B Price,1 Christine L Baker,2 Kelly H Zou,3 Victoria S Higgins,4 James T Bailey,4 James S Pike4 1University of Aberdeen, Division of Applied Health Sciences, Aberdeen, UK; 2Pfizer Inc, Outcomes and Evidence, Global Health and Value, New York, USA; 3Pfizer Inc, Statistical Center for Outcomes, Real-World and Aggregate Data, Global Innovative Pharma Business, New York, USA; 4Adelphi Real World, Macclesfield, UK Background: This study aimed to characterize and differentiate the Global Initiative for Chronic Obstructive Lung Disease (GOLD strategy 2011 cut points through the modified Medical Research Council dyspnea scale (mMRC and chronic obstructive pulmonary disease (COPD assessment test (CAT. Methods: Analysis of COPD patient data from the 2012 Adelphi Respiratory Disease Specific Program was conducted in Europe and US. Matched data from physicians and patients included CAT and mMRC scores. Receiver operating characteristic curves and kappa analysis determined a cut point for CAT and mMRC alignment and thus defined patient movement (“movers” within GOLD groups A–D, depending on the tool used. Logistic regression analysis, with a number of physician- and patient-reported covariates, characterized those movers. Results: Comparing GOLD-defined high-symptom patients using mMRC and CAT cut points (≥2 and ≥10, respectively, there were 890 (53.65% movers; 887 of them (99.66% moved from less symptomatic GOLD groups A and C (using mMRC to more symptomatic groups B and D (using CAT. For receiver operating characteristic (area under the curve: 0.82, P<0.001 and kappa (maximized: 0.45 recommended CAT cut points of ≥24 and ≥26, movers reduced to 429 and 403 patients, respectively. Logistic regression analysis showed variables significantly associated with movers were related to impact on normal life, age, cough, and sleep (all P<0.05. Within movers, direction of movement was significantly associated with the same variables (all P<0

  11. Study on Fabry-Perot interference optic fiber temperature sensor%Fabry-Perot干涉式光纤温度传感器的研究

    Institute of Scientific and Technical Information of China (English)

    曹满婷

    2001-01-01

    分析了温度对相位的调制作用以及Fabry-Perot干涉结构检测相位变化的原理,提出了一种具有高灵敏度和高分辨率的相位调制型全光纤结构,并进行了系统的噪声分析

  12. Optic Fiber Fabry-Perot Interferometer Applied to Measuring Temperature and Displacement%测量温度和位移的光纤Fabry-Perot干涉仪

    Institute of Scientific and Technical Information of China (English)

    陈国霖; 戴福隆; 周辛庚

    2002-01-01

    本文描述了两种光纤Fabry-Peort干涉仪的原理、结构和制造方法.采用光频调制方法用以辨别干涉时域条纹的移动方向,实现了对温度和位移的测量.另外还介绍了条纹计数检测的电路原理.

  13. Salvage of relapse of patients with Hodgkin's disease in clinical stages I or II who were staged with laparotomy and initially treated with radiotherapy alone. A report from the international database on Hodgkin's disease

    DEFF Research Database (Denmark)

    Specht, L; Horwich, A; Ashley, S

    1994-01-01

    To analyze presentation variables that might indicate a high or low likelihood of success of the treatment of patients relapsing after initial radiotherapy of Hodgkin's disease in clinical Stages I or II who were staged with laparotomy....

  14. Beneficial effects of atorvastatin on myocardial regions with initially low vasodilatory capacity at various stages of coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Wielepp, Peter [Ruhr-University Bochum, Institute of Molecular Biophysics, Radiopharmacy and Nuclear Medicinea, Bad Oeynhausen (Germany); Heart and Diabetes Center North Rhine-Westphalia, Bad Oeynhausen (Germany); Baller, Detlev [Ruhr-University Bochum, Department of Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Bad Oeynhausen (Germany); Heart and Diabetes Center North Rhine-Westphalia, Bad Oeynhausen (Germany); Gleichmann, Ulrich; Pulawski, Ewa; Horstkotte, Dieter [Ruhr-University Bochum, Department of Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Bad Oeynhausen (Germany); Burchert, Wolfgang [Ruhr-University Bochum, Institute of Molecular Biophysics, Radiopharmacy and Nuclear Medicinea, Bad Oeynhausen (Germany)

    2005-12-01

    The aim of this study was to analyse non-invasively the regional effect of therapy with an HMG-CoA reductase inhibitor on myocardial blood flow in patients with coronary artery disease (CAD) with special reference to segments with initially substantially impaired vasodilation. The study included 26 patients with untreated hypercholesterolaemia. Coronary angiography revealed CAD in nine patients with stenosis >50% and wall irregularities or minimal stenosis <30% in 17 patients. Before and 4.6{+-}1.8 months after atorvastatin therapy,{sup 13}N-ammonia positron emission tomography (PET) studies were performed at rest and under pharmacological stress. Minimum coronary vascular resistance (MCR) and coronary flow reserve (CFR) were determined. Segments were divided into those with normal or near-normal (MBF during adenosine {>=}2.0 ml/min/g) and those with abnormal (MBF<2.0 ml/min/g) vasodilator flow response. In CAD patients, 156 segments were analysed, 85 of which had abnormal MBF; in the non-obstructive group, 59 of 297 segments had abnormal MBF. LDL cholesterol decreased after atorvastatin therapy from 186{+-}43 mg/dl to 101{+-}26 mg/dl (p<0.001). In normal segments no significant changes in MBF, CFR and MCR were found. However, initially abnormal segments showed significant improvements in MCR (15%, p<0.0001) and MBF during adenosine (30%, p<0.0001) after therapy. The improvement in regional coronary vasodilator function after atorvastatin in patients with coronary atherosclerosis may be caused, at least in part, by increased flow-mediated (endothelium-dependent) dilation of the total arteriolar and arterial vascular system. These data further support the concept of non-invasive management of stable CAD by statin therapy and life-style modification guided by PET. (orig.)

  15. A New Method of processing the Fabry-Perot Interference Fringes%一种新的Fabry-Perot干涉条纹处理方法

    Institute of Scientific and Technical Information of China (English)

    鄂非; 高秋艳; 艾勇

    2009-01-01

    介绍了一种提取Fabry-Perot(法布里-帕罗)干涉条纹圆心点坐标和条纹半径的新方法.首先对干涉图像依次进行二值化处理,对所得到的条纹强度曲线进行均平滤波和自适应滤波,根据条纹灰度值强度余弦函数分布的特点,对条纹灰度值数据进行最小二乘法拟合,获得条纹强度峰值坐标,通过精确的迭代算法,进而获得Fabry-Perot干涉条纹圆心点的坐标;然后再对干涉条纹进行圆周积分,从而可以确定每级Fabry-Perot干涉条纹的半径长度.该方法可提高计算精度,减小计算误差.

  16. A national Vascular Quality Initiative database comparison of hybrid and open repair for aortoiliac-femoral occlusive disease.

    Science.gov (United States)

    Zavatta, Marco; Mell, Matthew W

    2017-08-16

    We sought to analyze the outcomes of revascularization for aortoiliac-femoral occlusive disease by comparing hybrid repair by endovascular revascularization and open common femoral endarterectomy (ER-CFE) with open aortoiliac reconstruction and CFE (OR-CFE). Using the national Society for Vascular Surgery Vascular Quality Initiative database from 2009 to 2015, we identified all patients receiving open or endovascular revascularization of the aortoiliac system and who additionally underwent CFE. Patients with concomitant infrainguinal procedures were excluded, as were procedures performed at centers with CFE group and 1472 in the ER-CFE group with follow-up of at least 9 months. Patients with ER-CFE were older (68 ± 9 years vs 63 ± 9 years; P CFE were more likely to have received a previous inflow procedure (27% vs 21%; P CFE (5.2 ± 1.6 vs 2.9 ± 1.0; P CFE was associated with lower 30-day mortality (1.8% vs 3.4%; P = .01), shorter length of stay (median 3 vs 7 days; P CFE had greater ABI improvement at long-term follow-up (0.39 ± 0.37 vs 0.26 ± 0.23; P CFE appeared to have improved short-term outcomes and equivalent freedom from major amputation compared with open surgical repair with CFE. Conversely, open repair with CFE was associated with better long-term improvement in ABI and ambulatory status. Open repair should therefore be considered for patients with aortoiliac-femoral occlusive disease and reasonable surgical risk. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  17. Determinants of initial utilization of community healthcare services among patients with major non-communicable chronic diseases in South China.

    Directory of Open Access Journals (Sweden)

    Huajie Yang

    Full Text Available BACKGROUND: Although expected to act as gate-keeping primary care providers, as community health service (CHS facilities are severely under-utilized; Chinese people in both rural and urban areas used predominantly higher-tier facilities for primary care purpose, with significant financial and outcome consequences. This study intends to explore the determinants of initial utilization of CHS among patients with major non-communicable chronic diseases (NCDs in order to understand the care-seeking behavior among urban and rural residents in South China. METHODS: A multi-stage cluster random sampling methodology was adopted to create a sample of 19,466 adults with NCDs from 7,970 urban households and 32,035 adults with NCDs from 3,860 rural households in Guangdong, China. Interviews and physical examinations were conducted in 2010 to collect data on patient characteristics, medical conditions, and awareness and utilization of healthcare. Descriptive analysis and logistic regression analysis were performed to study utilization patterns and the factors associated with the patterns. RESULTS: Prevalence of major NCDs in urban areas was significantly higher than that in rural areas (12.55% vs. 8.70%; p<0.001. Second-tier district hospitals were most preferred for initial consultation (46.05% in rural areas vs. 45.32% in urban areas; p<0.001, followed by tertiary general or specialized hospitals (28.39% in rural areas vs. 33.89% in urban areas; p<0.001. The proportion of patients who had initial use of CHS was relatively low (25.56% in rural areas vs. 20.79% in urban areas; p<0.001. Awareness of self-care and the presence of medical insurance were leading factors associated with first contact of CHS facilities in both urban and rural areas. CONCLUSION: The study suggests that CHS facilities are not often used as the first contact for patients in both rural and urban areas in south China. Much effect must be made to enhance the gatekeeper system and improve

  18. Podocitúria na doença de Fabry

    Directory of Open Access Journals (Sweden)

    Ester Miranda Pereira

    2016-03-01

    Full Text Available Resumo Introdução: A doença de Fabry (DF é uma desordem lisossômica ligada ao cromossomo X ocasionada por mutações no gene que codifica a enzima lisossômica α-galactosidase A (α-GAL. A redução ou ausência da atividade dessa enzima leva ao acúmulo progressivo de gb3. A doença renal é uma importante consequência clínica da acumulação de Gb3. Podócito é o tipo celular mais afetado na doença renal, que mostra apenas uma resposta parcial à Terapia de Reposição Enzimática. Além disso, a disfunção podocitária é a principal contribuinte para a perda progressiva da função renal e pode ser encontrada alterada mesmo antes do início da microalbuminúria. Assim, a podocitúria na DF pode ser uma ferramenta importante para prever a doença renal. Objetivo: O objetivo deste estudo foi quantificar a excreção urinária de podócitos em pacientes com DF (V269M, n = 14 e controles saudáveis (n = 40, e relacioná-las com as variáveis sexo, idade, tempo de terapia e a razão albumina: creatinina (AUC. Métodos: Podócitos urinários foram identificados utilizando imunofluorescência para podocalixina e DAPI. O número de células podocalixina positivo foi contado e o número médio foi utilizado (faixa normal 0-0.6 podócitos/mL. Resultados: O número médio de podócitos na urina de pacientes com DF foi significativamente maior do que os controles saudáveis (p < 0.0001. Observou-se uma correlação positiva entre podocitúria e AUC (p = 0.004; r2 = 0.6417. Conclusão: A podocitúria pode ser uma ferramenta adicional para avaliar a progressão da doença renal em pacientes que se espera que tenha um fenótipo mais agressivo.

  19. Effects of disturbance on regeneration of Abies fabri forests at the upper reaches of the Yangtze River

    Institute of Scientific and Technical Information of China (English)

    Gao Jia-rong; Gao Yang

    2007-01-01

    Mudflow is the principal disturbance in Abies fabri forests. In the Gongga Mountain areas of the upper reaches of the Yangtze River, the intensities and periodicity of different scale mudflows vary. Small-scale mudflows are more frequent, occurring every one or two years while large-scale mudflows may occur once in more than one hundred years. Through a field study of A. fabri forests during different stages of growth, we analyzed their structural characteristics and discovered that after different sizes of mudflow, poplar and birch often occupy the dominant canopy at the expense of the slow growing A. fabri, for only a small number of saplings are A. fabri that occurs in the first regeneration stage. However, a large number of seed resources can be found in mature A.fabri forests and as a unique regeneration species, A. fabri will gradually replace all the other species and form a stable community of strong shade-tolerant trees. Because of the intimate relationship between growing conditions and soil and water conservation at the upper reaches of the Yangtze River, we should carry out some artificial measurements to control and promote the slow regeneration process of A. fabri.

  20. Simultaneous wavelength and orbital angular momentum demultiplexing using tunable MEMS-based Fabry-Perot filter

    DEFF Research Database (Denmark)

    Lyubopytov, Vladimir; Porfirev, Alexey P.; Gurbatov, Stanislav O.

    2017-01-01

    In this paper, we experimentally demonstrate simultaneous wavelength and orbital angular momentum (OAM) multiplexing/demultiplexing of 10 Gbit/s data streams using a new on-chip micro-component-tunable MEMS-based Fabry-Perot filter integrated with a spiral phase plate. In the experiment, two...