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Sample records for rapidly progressive disease

  1. Rapidly progressive post-transplant lymphoproliferative disease ...

    African Journals Online (AJOL)

    Sirolimus, a potent inhibitor of B- and T-cell activation, is a commonly used immunosuppressant after renal transplantation. Withdrawal of sirolimus from the immunosuppression regimen may reduce B-cell surveillance. We present a case of rapidly progressive central nervous system (CNS) polymorphic Epstein-Barr virus ...

  2. B-Cell Depletion Salvage Therapy in Rapidly Progressive Dermatomyositis Related Interstitial Lung Disease.

    Science.gov (United States)

    Eissa, Khaled; Palomino, Jaime

    2016-01-01

    Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with idiopathic inflammatory myopathies (IIM). Glucocorticoids are the initial standard treatment. However, many patients fail to respond and continue to progress despite treatment with high dose glucocorticoids. The efficacy of rituximab has been suggested in case reports and case series of refractory antisynthetase (AS) syndrome, but data on patients without auto-antibodies or with rapidly progressive ILD are scarce. We report a case of rapidly progressive dermatomyositis (DM) associated ILD treated successfully with B-cell depletion therapy.

  3. Research progress on the pathogenesis of rapid eye movement sleep behavior disorder and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Hai-yang JIANG

    2017-10-01

    Full Text Available Rapid eye movement sleep behavior disorder (RBD is a sleep disorder characterized by the disappearance of muscle relaxation and enacting one's dreams during rapid eye movement (REM, with most of the dreams being violent or aggressive. Prevalence of RBD, based on population, is 0.38%-2.01%, but it becomes much higher in patients with neurodegenerative diseases, especially α - synucleinopathies. RBD may herald the emergence of α-synucleinopathies by decades, thus it may be used as an effective early marker of neurodegenerative diseases. In this review, we summarized the progress on the pathogenesis of RBD and its relationship with neurodegenerative diseases. DOI: 10.3969/j.issn.1672-6731.2017.10.003

  4. Activation of Notch3 in Glomeruli Promotes the Development of Rapidly Progressive Renal Disease.

    Science.gov (United States)

    El Machhour, Fala; Keuylian, Zela; Kavvadas, Panagiotis; Dussaule, Jean-Claude; Chatziantoniou, Christos

    2015-07-01

    Notch3 expression is found in the glomerular podocytes of patients with lupus nephritis or focal segmental GN but not in normal kidneys. Here, we show that activation of the Notch3 receptor in the glomeruli is a turning point inducing phenotypic changes in podocytes promoting renal inflammation and fibrosis and leading to disease progression. In a model of rapidly progressive GN, Notch3 expression was induced by several-fold in podocytes concurrently with disease progression. By contrast, mice lacking Notch3 expression were protected because they exhibited less proteinuria, uremia, and inflammatory infiltration. Podocyte outgrowth from glomeruli isolated from wild-type mice during the early phase of the disease was higher than outgrowth from glomeruli of mice lacking Notch3. In vitro studies confirmed that podocytes expressing active Notch3 reorganize their cytoskeleton toward a proliferative/migratory and inflammatory phenotype. We then administered antisense oligodeoxynucleotides targeting Notch3 or scramble control oligodeoxynucleotides in wild-type mice concomitant to disease induction. Both groups developed chronic renal disease, but mice injected with Notch3 antisense had lower values of plasma urea and proteinuria and inflammatory infiltration. The improvement of renal function was accompanied by fewer deposits of fibrin within the glomeruli and by decreased peritubular inflammation. Finally, abnormal Notch3 staining was observed in biopsy samples of patients with crescentic GN. These results demonstrate that abnormal activation of Notch3 may be involved in the progression of renal disease by promoting migratory and proinflammatory pathways. Inhibiting Notch3 activation could be a novel, promising approach to treat GN. Copyright © 2015 by the American Society of Nephrology.

  5. Rapidly Progressive Encephalopathy: Initial Diagnosis of Creutzfeldt Jakob Disease in an Intensive Care Unit

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    Patrícia Afonso Mendes

    2017-01-01

    Full Text Available Creutzfeldt-Jakob disease (CJD is a rare, incurable and fatal condition that can only be confirmed through neuropathological investigation, such as brain biopsy or post-mortem study. However, a probable diagnosis can be made using clinical criteria. CJD manifests as rapidly progressive dementia with myoclonus and to a lesser extent visual impairment and cerebellar and pyramidal/extrapyramidal signs. We report the case of a previously independent adult male that met all the clinical criteria. Taken together, the investigation results suggested probable CJD.

  6. A Case of Sarcoidosis with Interstitial Lung Disease Mimicking Clinically Amyopathic Dermatomyositis and Rapidly Progressive Interstitial Lung Disease

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    Shinji Sato

    2014-01-01

    Full Text Available Here, we report a patient with sarcoidosis who developed edematous erythema and interstitial lung disease. At the initial visit, clinically amyopathic dermatomyositis (CADM with rapidly progressive interstitial lung disease (RP-ILD was suspected because he had progressive dyspnea but no muscle weakness. The presence of anti-CADM-140/MDA5 autoantibodies was immediately assessed to facilitate a precise diagnosis, with negative results. Thereafter, skin and transbronchial lung biopsies revealed noncaseating granuloma with Langhans giant cells in both specimens, leading to a diagnosis of sarcoidosis. In this case, clinical features of skin and lung were unable to distinguish DM (including CADM from sarcoidosis, but the lack of anti-CADM-140/MDA5 antibody was useful for differentiating CADM with RP-ILD mimicking sarcoidosis from bona fide sarcoidosis.

  7. A Case of Sarcoidosis with Interstitial Lung Disease Mimicking Clinically Amyopathic Dermatomyositis and Rapidly Progressive Interstitial Lung Disease

    Science.gov (United States)

    Nogi, Shinichi; Sasaki, Noriko; Chinen, Naofumi; Honda, Kiri; Saito, Eiko; Wakabayashi, Takayuki; Yamada, Chiho; Suzuki, Yasuo

    2014-01-01

    Here, we report a patient with sarcoidosis who developed edematous erythema and interstitial lung disease. At the initial visit, clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP-ILD) was suspected because he had progressive dyspnea but no muscle weakness. The presence of anti-CADM-140/MDA5 autoantibodies was immediately assessed to facilitate a precise diagnosis, with negative results. Thereafter, skin and transbronchial lung biopsies revealed noncaseating granuloma with Langhans giant cells in both specimens, leading to a diagnosis of sarcoidosis. In this case, clinical features of skin and lung were unable to distinguish DM (including CADM) from sarcoidosis, but the lack of anti-CADM-140/MDA5 antibody was useful for differentiating CADM with RP-ILD mimicking sarcoidosis from bona fide sarcoidosis. PMID:25431723

  8. A Case of Immunotactoid Glomerulopathy with Rapid Progression to End-Stage Renal Disease

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    Shikha Jain

    2009-01-01

    Full Text Available Immunotactoid glomerulopathy (IGN is a rare immunoglobulin deposition disease. It is often mistaken for cryoglobulinemia or amyloidosis due to the similarities on biopsy findings. The disease progresses to end-stage renal disease (ESRD within 7 months to 10 years. This is the first case reported of a patient with a diagnosis of IGN who developed acute kidney injury (AKI and ESRD within 1 week of initial presentation.

  9. Injury Markers but not Amyloid Markers are Associated with Rapid Progression from Mild Cognitive Impairment to Dementia in Alzheimer's Disease

    NARCIS (Netherlands)

    van Rossum, I.A.; Visser, P.J.; Knol, D.L.; van der Flier, W.M.; Teunissen, C.E.; Barkhof, F.; Blankenstein, M.A.; Scheltens, P.

    2012-01-01

    Alzheimer's disease (AD) is a common cause of mild cognitive impairment (MCI). However, the time between the diagnosis of MCI and the diagnosis of dementia is highly variable. In this study we investigated which known risk factors and biomarkers of AD pathology were associated with rapid progression

  10. A rapidly progressing, deadly disease ofActias selene (Indian moon ...

    Indian Academy of Sciences (India)

    A mixed baculoviral–bacterial infection observed among Actias selene (Hübner 1807), the Indian moon moth (Insecta: Lepidoptera: Saturniidae), larvae was characterized and followed by a photographic documentation of the disease progression. The etiological agents were determined using mass spectrometry and ...

  11. A Case of Adventitial Cystic Disease of the Popliteal Artery Progressing Rapidly after Percutaneous Ultrasound-guided Aspiration.

    Science.gov (United States)

    Seo, Hiroyuki; Fujii, Hiromichi; Aoyama, Takanobu; Sasako, Yoshikado

    2014-01-01

    Adventitial cystic disease is a rare non-atherosclerotic vascular disease. We report a 36-year-old man with right intermittent claudication by adventitial cystic disease. computed tomography (CT) and magnetic resonance imaging (MRI) revealed an ovoid cystic mass compressing the right popliteal artery and causing severe stenosis of the lumen. Percutaneous aspiration was performed, which improved his symptoms. However, he complained of identical intermittent claudication two weeks later. Radiographic findings revealed that the cystic lesion had progressed rapidly. The cystic lesion was resected and the affected arterial segment was interposed. We consider that conventional surgical intervention remains the favored treatment option in the management of adventitial cystic disease.

  12. Headache attack followed by rapid disease progression in pediatric moyamoya disease--how should we manage it?

    Science.gov (United States)

    Vuignier, Sandra; Akioka, Naoki; Hamada, Hideo; Kashiwazaki, Daina; Kuroda, Satoshi

    2014-10-01

    A 4-year-old female was presented at our hospital with frequent right frontal headache attack. She was diagnosed with moyamoya disease and was conservatively followed up. One year later, the frequency of headache gradually decreased. However, follow-up MR imaging revealed that the disease stage markedly progressed in the right side and cerebral infarction occurred in the temporal lobe with atrophy of the right frontal lobe. She underwent direct and indirect revascularization on the right side. Aware of this case, we would like to emphasize that headache may be one subtype of ischemic attacks and require frequent MR follow-up to see the disease course. If there is any sign of disease progression, immediate surgical intervention should be indicated to avoid irreversible brain damage.

  13. Systemic and rapidly progressive light-chain deposition disease initially presenting as tubulointerstitial nephritis.

    Science.gov (United States)

    Takahashi, Satoko; Soma, Jun; Nakaya, Izaya; Yahata, Mayumi; Sakuma, Tsutomu; Yaegashi, Hiroshi; Sato, Akiyoshi; Wano, Masaharu; Sato, Hiroshi

    2012-11-01

    A 42-year-old woman was admitted to a hospital after first-time detection of proteinuria and hematuria during a routine medical check-up. Because her serum creatinine level had rapidly increased from 0.9 to 3.2 mg/dl since measurement 3 months earlier, she was referred to our hospital. Renal biopsy revealed extensive tubular atrophy and interstitial fibrosis with mild leukocyte infiltration. Glomeruli showed minimal changes, and no immunoglobulin or complement deposition was observed by immunofluorescence. Oral prednisolone was commenced under the diagnosis of chronic tubulointerstitial nephritis, and she discharged once. However, its effects were transient; her renal function deteriorated rapidly and hemodialysis was initiated 5 months after her initial check-up. On readmission, urinary Bence-Jones protein κ-type was detected, and examination of bone marrow led to a diagnosis of Bence-Jones κ-type multiple myeloma. Light-chain staining using a renal biopsy specimen obtained 2 months earlier showed κ-light-chain deposition on tubular basement membranes but not glomeruli. Despite undergoing chemotherapy with vincristine, doxirubicin, and dexamethasone, the patient died suddenly from a cardiac arrhythmia. Autopsy showed κ-light-chain deposition in the heart, thyroid, liver, lungs, spleen, and ovaries. Congo red staining yielded negative results. Typical light-chain deposition disease (LCDD) characterized by nodular glomerulosclerosis was observed in the kidneys. This case demonstrates that tubulointerstitial nephritis can be an early pathological variant of LCDD, which may be followed by accelerated and massive light-chain deposition in glomeruli.

  14. A rapidly progressing, deadly disease ofActias selene(Indian moon ...

    Indian Academy of Sciences (India)

    2015-07-08

    Jul 8, 2015 ... The outbreak of an infectious disease in captive-bred Lepidoptera can cause death of all the caterpillars within days. A mixed baculoviral–bacterial infection observed among Actias selene (Hübner 1807), the Indian moon moth (Insecta: Lepidoptera: Saturniidae), larvae was characterized and followed by a ...

  15. Progression of Liver Disease

    Science.gov (United States)

    ... The Progression of Liver Disease Diagnosing Liver Disease – Liver Biopsy and Liver Function Tests Clinical Trials Liver Transplant ... The Progression of Liver Disease Diagnosing Liver Disease: Liver Biopsy and Liver Function Tests Clinical Trials Liver Transplant ...

  16. Rapidly progressive periodontitis. A distinct clinical condition.

    Science.gov (United States)

    Page, R C; Altman, L C; Ebersole, J L; Vandesteen, G E; Dahlberg, W H; Williams, B L; Osterberg, S K

    1983-04-01

    We report radiographic, clinical, historical, and laboratory observations on seven patients selected to illustrate the features and characteristics of rapidly progressive periodontitis, with the aim of establishing this disease as a distinct clinical entity. This form of periodontitis is seen most commonly in young adults in their twenties, but it can occur in postpubertal individuals up to approximately 35 years of age. During the active phase, the gingival tissues are extremely inflamed and there is hemorrhage, proliferation of the marginal gingiva, and exudation. Destruction is very rapid, with loss of much of the alveolar bone occurring within a few weeks or months. This phase may be accompanied by general malaise, weight loss, and depression, although these symptoms are not seen in all patients. The disease may progress, without remission, to tooth loss, or alternatively, it may subside and become quiescent with or without therapy. The quiescent phase is characterized by the presence of clinically normal gingiva that may be tightly adapted to the roots of teeth with very advanced bone loss and deep periodontal pockets. The quiescent phase may be permanent, it may persist for an indefinite period, or the disease activity may return. Most patients with rapidly progressive periodontitis have serum antibodies specific for various species of Bacteroides, Actinobacillus, or both, and manifest defects in either neutrophil or monocyte chemotaxis. Affected patients generally respond favorably to treatment by scaling and open or closed curettage, especially when accompanied by standard doses of antibiotics for conventional time periods. A small minority of patients do not respond to any treatment, including antibiotics, and the disease progresses inexorably to tooth loss even in the presence of aggressive periodontal therapy and maintenance. At the present time it is not possible to distinguish prior to treatment which individuals will respond to therapy and which will

  17. Rapidly progressive young-onset dementia.

    Science.gov (United States)

    Kelley, Brendan J; Boeve, Bradley F; Josephs, Keith A

    2009-03-01

    To characterize a cohort of individuals who have experienced rapidly progressive dementia with onset before age 45. Very little data regarding the clinical features or clinical spectrum of rapidly progressive young-onset dementia (RP-YOD) is available, primarily consisting of case reports or small series. A search of the Mayo Clinic medical record was employed to identify patients who had onset before age 45 of rapidly progressive dementia. All available medical records, laboratory data, neuroimaging studies, and pathologic data were reviewed. Twenty-two patients met the predefined inclusion and exclusion criteria. Behavioral and affective disorders, cerebellar dysfunction, and visual and/or oculomotor dysfunction were common early clinical features within the cohort, as were clinical features often associated with Creutzfeldt-Jakob disease. Diagnostic testing identified an etiology in most patients. Presentations of RP-YOD result from a variety of etiologies and significant overlap in clinical features is observed. Clinical features often associated with Creutzfeldt-Jakob disease seem to be common within the entire cohort of RP-YOD patients. Diagnostic studies aided in establishing a diagnosis in most patients, however 5 had uncertain diagnoses despite exhaustive evaluation.

  18. An Unusual Case of Rapidly Progressive Hyperbilirubinemia

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    Kimberly M. Thornton

    2013-01-01

    Full Text Available We present an unusual case of hyperbilirubinemia with rapid early progression leading to bilirubin encephalopathy in a term neonate. Despite early recognition and intervention, the total serum bilirubin reached a maximum level of 39 mg/dL at 32 hours of life. Prior to an emergent exchange transfusion, the patient’s diagnostic evaluation was significant for Coombs-negative microangiopathic hemolytic anemia and thrombocytopenia. Further testing revealed a deficiency of ADAMTS13 protein, or von Willebrand factor-cleaving protease, a finding diagnostic of congenital thrombotic thrombocytopenic purpura, or Upshaw-Schulman syndrome. This rare disease is often misdiagnosed, especially in the newborn period.

  19. Emergence of CXCR4-tropic HIV-1 variants followed by rapid disease progression in hemophiliac slow progressors.

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    Tsunefusa Hayashida

    Full Text Available The association between emergence of CXCR4-tropic HIV-1 variants (X4 variants and disease progression of HIV-1 infection has been reported. However, it is not known whether the emergence of X4 variants is the cause or result of HIV-1 disease progression. We tried to answer this question.HIV-1 env sequences around the V3 region were analyzed in serially stocked samples in order to determine whether X4 variants emerged before or after the fall in CD4+ T-cell count.The study subjects were five HIV-1-infected hemophiliac slow progressors. Deep sequencing around the HIV-1 env V3 region was conducted in duplicate. Tropism was predicted by geno2pheno [coreceptor] 2.5 with cutoff value of false positive ratio at <5%. When X4 variant was identified in the latest stocked sample before the introduction of antiretroviral therapy, we checked viral genotype in previously stocked samples to determine the time of emergence of X4 variants.Emergence of X4 variants was noted in two of the five patients when their CD4+ T-cell counts were still high. The rate of decrease of CD4+ T-cell count or of rise of HIV-1 load accelerated significantly after the emergence of X4 variants in these two cases. Phylogenetic analysis showed that these X4 variants emerged from CCR5-tropic HIV-1 viruses with several amino acid changes in the V3 region.The emergence of X4 variants preceded HIV-1 disease progression in two hemophiliac slow progressors.

  20. Rapid progressive visual decline and visual field defects in two patients with the Heidenhain variant of Creutzfeld-Jakob disease.

    Science.gov (United States)

    Lenk, Janine; Engellandt, Kay; Terai, Naim; Bottesi, Antonia; Matthé, Egbert

    2018-02-08

    Heidenhain variant of Creutzfeldt-Jakob (HvCJD) is a rare disease, patients presenting with loss of visual acuity and a decline in visual fields. Two patients with rapid loss of visual acuity and declining visual fields presented with homonymic hemianopsia over several weeks. Cranial MRI showed neither stroke nor other morphological changes explaining the severe visual field defects. Neurological examination revealed no pathologies. However, lumbar puncture showed an increase in total protein in cerebrospinal fluid (CSF). Visual field testing revealed further deterioration during follow-up. Several weeks later, patients' behaviour changed markedly, exhibiting aggression, declining memory function and physical degeneration. The suspected diagnosis was the Heidenhain variant of Creutzfeld-Jakob disease (HvCJD). CSF analysis showed evidence of PrP Sc and 14-3-3 protein. Both patients died within 8 weeks of the CJD diagnosis. Loss of visual acuity and a decline in visual fields without corresponding MRI findings and marked changes in behaviour should lead to a diagnosis of HvCJD. Corresponding diagnostic tests should be performed for confirmation. The prognosis for survival is poor and should be immediately communicated to affected patients and their relatives. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Considering Valproate as a Risk Factor for Rapid Exacerbation of Complex Movement Disorder in Progressed Stages of Late-Infantile CLN2 Disease.

    Science.gov (United States)

    Johannsen, Jessika; Nickel, Miriam; Schulz, Angela; Denecke, Jonas

    2016-06-01

    Neuronal ceroid lipofuscinosis type 2 (CLN2 disease, OMIM 204500) is a rare autosomal-recessive lysosomal storage disorder. It is one of the most common neurodegenerative disorders in childhood. Symptoms include epilepsy, rapid motor and language regression, dementia, visual loss, and a complex movement disorder in later stages of the disease. We report on two children with genetically confirmed late-infantile CLN2 disease who developed a severe exacerbation of their complex movement disorder leading to hyperthermia, hyper-CK-emia and decreased level of consciousness over several weeks despite different therapeutic approaches. Both patients were on long-term antiepileptic treatment with valproate and only after the withdrawal of valproate, the movement disorder disappeared and level of consciousness improved. These observations emphasize that valproate has to be considered as a possible risk factor in patients in later stages of late-infantile CLN2 disease who develop a rapidly progressive complex movement disorder. Georg Thieme Verlag KG Stuttgart · New York.

  2. Rapid disease progression in human immunodeficiency virus type 1-infected individuals with adverse reactions to trimethoprim-sulfamethoxazole prophylaxis

    NARCIS (Netherlands)

    Veenstra, J.; Veugelers, P. J.; Keet, I. P.; van der Ven, A. J. A. M.; Miedema, F.; Lange, J. M.; Coutinho, R. A.

    1997-01-01

    We studied the relation between the occurrence of adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis and the subsequent course of human immunodeficiency virus (HIV) infection in a cohort of homosexual men. Adverse reactions to TMP-SMZ were associated with a more rapid

  3. Predicting progression of Alzheimer's disease.

    Science.gov (United States)

    Doody, Rachelle S; Pavlik, Valory; Massman, Paul; Rountree, Susan; Darby, Eveleen; Chan, Wenyaw

    2010-02-23

    Clinicians need to predict prognosis of Alzheimer's disease (AD), and researchers need models of progression to develop biomarkers and clinical trials designs. We tested a calculated initial progression rate to see whether it predicted performance on cognition, function and behavior over time, and to see whether it predicted survival. We used standardized approaches to assess baseline characteristics and to estimate disease duration, and calculated the initial (pre-progression) rate in 597 AD patients followed for up to 15 years. We designated slow, intermediate and rapidly progressing groups. Using mixed effects regression analysis, we examined the predictive value of a pre-progression group for longitudinal performance on standardized measures. We used Cox survival analysis to compare survival time by progression group. Patients in the slow and intermediate groups maintained better performance on the cognitive (ADAScog and VSAT), global (CDR-SB) and complex activities of daily living measures (IADL) (P values < 0.001 slow versus fast; P values < 0.003 to 0.03 intermediate versus fast). Interaction terms indicated that slopes of ADAScog and PSMS change for the slow group were smaller than for the fast group, and that rates of change on the ADAScog were also slower for the intermediate group, but that CDR-SB rates increased in this group relative to the fast group. Slow progressors survived longer than fast progressors (P = 0.024). A simple, calculated progression rate at the initial visit gives reliable information regarding performance over time on cognition, global performance and activities of daily living. The slowest progression group also survives longer. This baseline measure should be considered in the design of long duration Alzheimer's disease clinical trials.

  4. Rapid tumor progression in a patient with HPV type 16 associated anal squamous cell carcinoma suffering from long-standing Crohn's disease: A case report

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    Fischer AK

    2016-10-01

    Full Text Available Background and aim: Squamous cell carcinoma (SCC is the most common cancer of the anal region, typically associated with high-risk (hr HPV infection. Furthermore, there is evidence that Crohn's disease predisposes to adenocarcinoma in patients with perianal disease. Materials and methods: A 57-year old patient presenting with long history of Crohn's disease since the age of mid-twenties, went through several surgeries including ileocolectomy and anal fistula resection, combined with immunosuppressive therapy additionally periodically since 2008. One year before death (in 2015 a painful fistula was diagnosed with extensive high grade anal intraepithelial neoplasia (AIN-HG and evidence of invasive growth as non-keratinizing SCC. Tissue samples from several previous and current resection specimens were re-evaluated and extensively investigated for Crohn´s type inflammation, dysplasia and HPV both by immunohistochemistry (p16/Ki67 and molecular subtyping of HPV. Results: AIN-HG and invasive anal squamous cell carcinoma turned out to be strongly positive for p16/Ki67 staining and molecular analysis disclosed a HPV-16 subtype. In contrast, HPV-analysis was negative in all available previous tissue samples including one anal fistula resected five years before (in 2009 which was lined by non-keratinized squamous epithelium without any evidence of dysplasia. Thus, the patient was diagnosed as Crohn's disease with hr-HPV infection that rapidly (< 5ys progressed to AIN-HG and anal SCC. Finally, osseous metastases occurred and the patient died shortly after. Conclusions: This case of a patient diagnosed with SCC of the anal canal in combination with Crohn's disease as well as HPV Type 16 infection, points to the pathomechanism leading to dysplasia and finally cancer. We assume that immunosuppressive therapy in Crohn's disease may predispose to both persistent HPV infection and HPV related invasive anal carcinoma. The accelerated progression of HPV

  5. Decreased phasic EMG activity during rapid eye movement sleep in treatment-naïve Parkinson's disease: effects of treatment with levodopa and progression of illness.

    Science.gov (United States)

    Garcia-Borreguero, Diego; Caminero, Ana B; De La Llave, Yolanda; Larrosa, Oscar; Barrio, Soledad; Granizo, Juan J; Pareja, Juan A

    2002-09-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is frequently associated with Parkinson's disease (PD) and may anticipate its diagnosis by several years. We assessed the presence of motor dyscontrol during REM sleep in treatment-naïve PD patients and investigated the putative effect of levodopa (L-dopa) treatment on motor activity. Overnight sleep studies were performed on 15 previously untreated PD patients and 14 controls at baseline, again after a 3- to 9-month treatment period with a low dose of L-dopa, and 2 to 5 days after treatment discontinuation (in 8 patients). No differences in sleep parameters were observed across groups or treatment conditions. None of the patients met criteria for RBD at baseline, whereas 5 patients were symptomatic at the time of the second sleep study. A quantitative analysis of electromyographic (EMG) activity during REM sleep showed a lower phasic twitching activity in untreated PD than in controls. However, an increase in both phasic twitching and tonic activity was found after treatment with L-dopa. Discontinuation of treatment resulted in a return to pretreatment values of phasic but not of tonic EMG activity. Thus, the increase in phasic activity seems to depend on the effects of L-dopa, whereas the increase in tonic EMG activity during REM sleep might be caused by other factors such as the progression of disease. Potential implications for the understanding of the relationship between RBD and PD are discussed. Copyright 2002 Movement Disorder Society

  6. Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred Turkish family due to a novel WFS1 mutation (p.Leu511Pro)

    DEFF Research Database (Denmark)

    Yuca, Sevil Ari; Rendtorff, Nanna Dahl; Boulahbel, Houda

    2012-01-01

    in a large inbred Turkish family. The patients showed early onset of IDDM, diabetes insipidus, optic atrophy, sensorineural hearing impairment and very rapid progression to renal failure before age 12 in three females. Ectopic expression of the wolframin mutant in HEK cells results in greatly reduced levels...

  7. Case of Rapid Progression of Hemiatrophy on the Face: A New Clinical Entity?

    Directory of Open Access Journals (Sweden)

    Hisashi Nomura

    2015-01-01

    Full Text Available A lot of diseases, including lupus profundus, morphea, lipodystrophy, and Parry-Romberg syndrome, may manifest progressive hemifacial atrophy. These diseases usually progress slowly and rapid progression of atrophy is extremely rare. We report a case of elderly-onset rapid progression of hemifacial atrophy only in three weeks. Our case did not meet variable differential diagnoses. We discuss the clinical character of the patient against the past of literature and suppose it may be a new clinical entity.

  8. Rapidly Progressive Atrioventricular Block in a Patient with Sarcoidosis

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    Nagham Saeed Jafar

    2014-01-01

    Full Text Available Cardiac sarcoidosis is a major cause of death in patients with systemic sarcoidosis. Cardiac manifestations are seen in 2.3% of the patients. Atrioventricular (AV block is one of the common manifestations of cardiac sarcoidosis. Other presentations of cardiac involvement include congestive heart failure, ventricular arrhythmias, and sudden cardiac death. The presence of AV block in young patients should raise the suspicion of sarcoidosis. AV block may be the only manifestation and patients may not have clinical evidence of pulmonary involvement. Here we describe a young male presented with exercise induced AV block rapidly progressing to complete heart block with recurrent syncope needing urgent pacemaker implantation. Factors that suggested an infiltrative process included his young age, rapidly progressive conduction abnormalities in the ECG in the absence of coronary disease, and previous history of cutaneous sarcoidosis.

  9. Syndromes of rapidly progressive cognitive decline-our experience

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    Sadanandavalli Retnaswami Chandra

    2017-01-01

    Full Text Available Background: Dementias are fairly slowly progressive degenerative diseases of brain for which treatment options are very less and carry a lot of burden on family and society. A small percentage of them are rapidly progressive and mostly carry a different course outcome. However, there are no definite criteria other than the time line for these patients. Aims: The aim of this was to identify and categorize the causes and course of rapidly progressive dementias seen in our center. Settings and Design: Patients who presented with rapid deterioration of cognitive functions within weeks to 1 year between 2011 and December 2016 were evaluated. Patients and Methods: All patients underwent all mandatory tests for dementia including brain imaging. Complete vasculitis workup, autoimmune encephalitis profile including Voltage Gated Potassium Channel, N-methyl-D-aspartic acid receptor, glutamic acid-decarboxylase, thyroid-peroxidase antibody, cerebrospinal fluid, and other special tests such as duodenal biopsy and paraneoplastic workup were done based on clinical indications. Results and Conclusions: Out of 144 patients 42 had immune-mediated encephalopathy, 18 had Creutzfeldt-Jakob disease, 3 had Vitamin B12 deficiency, 63 had infection with neurocysticercosis, 7 had tuberculosis, 2 had HIV, 1 had herpes simplex encephalitis, 1 had neurosyphilis, 1 Whipples disease, 1 had Subacute Sclerosing Panencephalitis, 1 had Mass lesion, 3 had Frontotemporal dementia, and 3 had small vessel disease. Good majority of these patients have infective and immune-mediated causes and less number belong to degenerative group. Therefore, caution is needed to look for treatable cause as it carries a different treatment options and outcome.

  10. Adult-onset phenylketonuria with rapidly progressive dementia and parkinsonism.

    Science.gov (United States)

    Tufekcioglu, Zeynep; Cakar, Arman; Bilgic, Basar; Hanagasi, Hasmet; Gurvit, Hakan; Emre, Murat

    2016-06-01

    Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Although it is principally a childhood disorder, in rare cases, the first signs of PKU may develop in late adulthood resembling common neurological diseases. Here we report a 59-year-old, previously normal functioning man who was admitted with blurred vision, cognitive problems, and gait difficulty that began 8 months before. He had brisk reflexes and left side dominant parkinsonism. His Mini-Mental State Examination (MMSE) score was 25/30, and neuropsychological evaluation revealed a dysexecutive syndrome with simultanagnosia and constructional apraxia. His Clinical Dementia Rating score (CDR) was 1. Cranial MRI revealed bilateral diffuse hyperintense lesions in parietal and occipital white matter in T2, fluid-attenuated inversion recovery, and diffusion weighted images. Diagnostic workup for rapidly progressive dementias was all normal except PHE level which was found to be highly elevated (1075 μmol/L, normal 39-240 μmol/L) with normal tyrosine level (61.20 μmol/L, normal 35-100 μmol/L). Three months after PHE-restricted diet, his cognitive impairment and signs of parkinsonism significantly improved, with MRI scan unchanged. This case demonstrates that late-onset PKU is a rare, treatable cause of rapidly progressive dementia and parkinsonism with certain constellations such as consanguinity and white matter abnormalities (WMAs) in imaging.

  11. The usefulness and significance of assessing rapidly progressive spermatozoa

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    Björndahl, Lars

    2010-01-01

    It is possible and clinically relevant to distinguish between slow and rapid progressive spermatozoa in basic semen analysis. This is discussed in light of the different purposes of semen analysis for the subfertile couple and the male patient. The two groups of progressive spermatozoa should be distinguished to help ensure that pertinent information available in the semen sample is not neglected. PMID:20111079

  12. Rapidly Progressive and Almost Lethal Pneumonia.

    Science.gov (United States)

    Martínez-González, Juancarlo; Robles-Arias, Carlos; Rodríguez-Cintrón, William

    2017-03-01

    We herein describe the case of a 65-year-old male patient who presented with Osler's triad, which is the combination of endocarditis, pneumonia, and meningitis. This report is even more unusual since the pathogen isolated was the invasive and virulent strain of Streptococcus pneumoniae serotype 3. The clinical entity described is also called Austrian syndrome. Even though rare in this antibiotic era, the syndrome remains one of high morbidity and mortality. This particular case is of paramount importance for the clinician reader. First, it documents the clinical features associated with invasive pneumococcal disease and the Austrian syndrome. Second, and equally important, it highlights why following the Surviving Sepsis Campaign guidelines saves lives. For this case, the following steps were taken: 1. As a surrogate for perfusion, early and aggressive fluid resuscitation therapy (guided by lactic acid levels) was instituted; 2. also early in the treatment, broad spectrum antibiotics were administered; 3. to guide antibiotic therapy, microbiological cultures were obtained. The patient subsequently improved and was transferred to the internal medicine ward to complete 4 weeks of antibiotic therapy.

  13. Exploratory analysis of seven Alzheimer's disease genes: disease progression.

    Science.gov (United States)

    Ruiz, Agustín; Hernández, Isabel; Ronsende-Roca, Maiteé; González-Pérez, Antonio; Rodriguez-Noriega, Emma; Ramírez-Lorca, Reposo; Mauleón, Ana; Moreno-Rey, Concha; Boswell, Lucie; Tune, Larry; Valero, Sergi; Alegret, Montserrat; Gayán, Javier; Becker, James T; Real, Luis Miguel; Tárraga, Lluís; Ballard, Clive; Terrin, Michael; Sherman, Stephanie; Payami, Haydeh; López, Oscar L; Mintzer, Jacobo E; Boada, Mercè

    2013-04-01

    The relationships between genome wide association study-identified and replicated genetic variants associated with Alzheimer's disease (AD) risk and disease progression or therapeutic responses in AD patients are almost unexplored. Seven hundred and one AD patients with at least 3 different cognitive evaluations and genotypic information for APOE and 6 genome wide association study-significant single-nucleotide polymorphisms were selected for this study. Mean differences in Global Deterioration Score and Mini Mental State Examination (MMSE) were evaluated using nonparametric tests, general linear model and mixed models for repeated measurements. Each chart was also reviewed for evidence of treatment with any cholinesterase inhibitor, memantine, or both. Relationships between therapeutic protocols, genetic markers, and progression were explored using stratified analysis looking for specific effects on progression in each therapeutic category separately. Neither calculation rendered a Bonferroni-corrected statistically significant difference in any genetic marker. Mixed model results suggested differences in the average point in MMSE test for patients carrying PICALM GA or AA genotype compared with GG carriers at the end of the follow-up (MMSE mean difference = -0.57; 95% confidence interval, -1.145 to 0.009; p = 0.047). This observation remained unaltered after covariate adjustments although it did not achieve predefined multiple testing significance threshold. The PICALM single-nucleotide polymorphism also displayed a significant effect protecting against rapid progression during pharmacogenetic assays although its observed effect displayed heterogeneity among AD therapeutic protocols (p = 0.039). None of the studied genetic markers were convincingly linked to AD progression or drug response. However, by using different statistical approaches, the PICALM rs3851179 marker displayed consistent but weak effects on disease progression phenotypes. Copyright © 2013

  14. Rapidly progressive post-transplant lymphoproliferative disease ...

    African Journals Online (AJOL)

    He presented with ataxia and acute confusion. In the 3 months preceding presentation he had experienced unexplained, asymptomatic weight loss. Clinical examination was unremarkable. Sirolimus had been stopped. 1 month before the onset of symptoms, owing to an apparent functional iron deficiency in the absence of ...

  15. Progression of motor symptoms in Parkinson's disease

    National Research Council Canada - National Science Library

    Xia, Ruiping; Mao, Zhi-Hong

    2012-01-01

    Parkinson's disease (PD) is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity, bradykinesia and tremor - due to loss of dopaminergic neurons...

  16. Rapidly progressive systemic sclerosis with a fatal outcome in male patients

    Directory of Open Access Journals (Sweden)

    Małgorzata Widuchowska

    2010-02-01

    Full Text Available Objectives: Retrospective analysis of clinical outcomes of malepatients with particularly severe and rapidly progressive diffusesystemic sclerosis (SSc with a fatal outcome with emphasis onorgan involvement and results of diagnostic tests, and tentativedistinction of a subgroup of especially progressive SSc. Material and methods: In the last few years among patients withSSc hospitalized in our centres, five patients with particularlyrapidly progressive disease were distinguished. Despiteaggressive treatment, the disease led to a fatal outcome ina short time. Their clinical history and results of diagnostic testswere evaluated. Results: All of them were smokers and three of them did not stopsmoking after the diagnosis. Laboratory findings revealed hightitres of Scl70 antibodies and enhanced erythrocytesedimentation rate (ESR in all of the patients. Most of them hadincreased serum creatine kinase (CK values. During the diseaserapidly progressive severe organ involvement was observed(pulmonary fibrosis, renal failure, cardiac failure, pulmonaryarterial hypertension. The skin thickening increased rapidly andthey died within 12-24 months after the first signs of skinthickening. Acute cardiac failure was the cause of death. Conclusions: The described cases suggest possible distinction ofa subset of a subgroup of patients with a particularly severe and rapidly progressive disease. It might be a population of patientswith the following characteristics: males over 40 years of agewith high titres of anti-Scl70 antibodies and elevated serum CKlevels. This is consistent with the presently published data onfactors associated with fatal prognosis in patients with SSc.

  17. Rapid progress on the vertebrate tree of life

    Directory of Open Access Journals (Sweden)

    Shaffer H Bradley

    2010-03-01

    Full Text Available Abstract Background Among the greatest challenges for biology in the 21st century is inference of the tree of life. Interest in, and progress toward, this goal has increased dramatically with the growing availability of molecular sequence data. However, we have very little sense, for any major clade, of how much progress has been made in resolving a full tree of life and the scope of work that remains. A series of challenges stand in the way of completing this task but, at the most basic level, progress is limited by data: a limited fraction of the world's biodiversity has been incorporated into a phylogenetic analysis. More troubling is our poor understanding of what fraction of the tree of life is understood and how quickly research is adding to this knowledge. Here we measure the rate of progress on the tree of life for one clade of particular research interest, the vertebrates. Results Using an automated phylogenetic approach, we analyse all available molecular data for a large sample of vertebrate diversity, comprising nearly 12,000 species and 210,000 sequences. Our results indicate that progress has been rapid, increasing polynomially during the age of molecular systematics. It is also skewed, with birds and mammals receiving the most attention and marine organisms accumulating far fewer data and a slower rate of increase in phylogenetic resolution than terrestrial taxa. We analyse the contributors to this phylogenetic progress and make recommendations for future work. Conclusions Our analyses suggest that a large majority of the vertebrate tree of life will: (1 be resolved within the next few decades; (2 identify specific data collection strategies that may help to spur future progress; and (3 identify branches of the vertebrate tree of life in need of increased research effort.

  18. Quantifying Disease Progression in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Simon, Neil G; Turner, Martin R; Vucic, Steve; Al-Chalabi, Ammar; Shefner, Jeremy; Lomen-Hoerth, Catherine; Kiernan, Matthew C

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) exhibits characteristic variability of onset and rate of disease progression, with inherent clinical heterogeneity making disease quantitation difficult. Recent advances in understanding pathogenic mechanisms linked to the development of ALS impose an increasing need to develop strategies to predict and more objectively measure disease progression. This review explores phenotypic and genetic determinants of disease progression in ALS, and examines established and evolving biomarkers that may contribute to robust measurement in longitudinal clinical studies. With targeted neuroprotective strategies on the horizon, developing efficiencies in clinical trial design may facilitate timely entry of novel treatments into the clinic. PMID:25223628

  19. Progress of neuroimaging research on Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Kun-cheng LI

    2014-03-01

    Full Text Available Alzheimer's disease is the most common neurodegenerative disease which gives rise to senile dementia. High morbidity and poor efficacy of Alzheimer's disease have brought about much pressure to the aging society. However, based on early diagnosis, early clinical intervention may slow down the progression of disease and improve its prognosis. In this review, we attempt to introduce the progress of early neuroimaging diagnosis of Alzheimer's disease. doi: 10.3969/j.issn.1672-6731.2014.03.006

  20. Fibrogenesis in progressive renal disease

    NARCIS (Netherlands)

    Baelde, H.

    2005-01-01

    Molecular biology offers new opportunities for experimental and clinical medicine. Promising clinical applications for patient care include identification of mRNA expression patterns (gene profiling) in diseased organs in correlation with diagnosis, prognosis, and responsiveness to different

  1. Progression of Alzheimer Disease in Europe

    DEFF Research Database (Denmark)

    Vellas, B; Hausner, L; Frolich, L

    2012-01-01

    /first year, -2.5 pts/second year; ADAScog: + 3.5 pts/first year, + 4.8 pts/second year), while the progression of behavioral disturbances (NPI scale) was linear. Neither scale showed regional differences, and progression of the disease was similar across Europe despite different health care systems...

  2. Progression of Alzheimer Disease in Europe

    DEFF Research Database (Denmark)

    Vellas, B; Hausner, L; Frolich, L

    2012-01-01

    The clinical progression of Alzheimer disease (AD) was studied in European subjects under treatment with AChE inhibitors (AChE-I) in relation to geographical location over a 2-years period. One thousand three hundred and six subjects from 11 European countries were clustered into 3 regions (North....../first year, -2.5 pts/second year; ADAScog: + 3.5 pts/first year, + 4.8 pts/second year), while the progression of behavioral disturbances (NPI scale) was linear. Neither scale showed regional differences, and progression of the disease was similar across Europe despite different health care systems...

  3. Central Blood Pressure and Chronic Kidney Disease Progression

    Directory of Open Access Journals (Sweden)

    Debbie L. Cohen

    2011-01-01

    Full Text Available Hypertension, diabetes, and proteinuria are well-recognized risk factors for progressive kidney function loss. However, despite excellent antihypertensive and antidiabetic drug therapies, which also often lower urinary protein excretion, there remains a significant reservoir of patients with chronic kidney disease who are at high risk for progression to end-stage kidney disease. This has led to the search for less traditional cardiovascular risk factors that will help stratify patients at risk for more rapid kidney disease progression. Among these are noninvasive estimates of vascular structure and function. Arterial stiffness, manifested by the pulse wave velocity in the aorta, has been established in a number of studies as a significant risk factor for kidney disease progression and cardiovascular endpoints. Much less well studied in chronic kidney disease are measures of central arterial pressures. In this paper we cover the physiology behind the generation of the central pulse wave contour and the studies available using these approaches and conclude with some speculations on the rationale for why measurements of central pressure may be informative for the study of chronic kidney disease progression.

  4. Rapidly progressive atherosclerosis after domino liver transplantation from a teenage donor with homozygous familial hypercholesterolemia.

    Science.gov (United States)

    Golbus, Jessica R; Farhat, Linda; Fontana, Robert J; Rubenfire, Melvyn

    Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by impaired clearance of low-density lipoprotein cholesterol. Given limitations in pharmacologic therapy and the significant morbidity and mortality associated with this disease, liver transplantation may be offered to select homozygous FH patients in childhood in an effort to slow progression of atherosclerotic cardiovascular disease. In rare cases, domino liver transplantation can be performed, transplanting the livers of patients with various metabolic disorders into elderly recipients whose projected survival precludes prolonged waiting on the transplant list. Herein, we report a case of domino liver transplantation using the liver of a 14-year-old boy with homozygous FH into a 65-year-old man with primary sclerosing cholangitis and cirrhosis who developed rapidly progressive atherosclerotic cardiovascular disease involving the arteries of his proximal bilateral lower extremities, carotid arteries and superior mesenteric artery. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  5. Rapidly progressing dual infection with Aspergillus and Rhizopus: when soil inhabitants become deadly invaders.

    Science.gov (United States)

    Bhagat, Milind; Rapose, Alwyn

    2016-12-08

    We present a case report of a 61-year-old patient with acute pulmonary and cerebral infections with Aspergillus and Rhizopus. The only risk factor for invasive fungal disease was high-dose corticosteroids used to treat her chronic obstructive pulmonary disease exacerbation. She had rapid progression and succumbed to her infections within 2 weeks of diagnosis in spite of aggressive antifungal therapy and surgery. To the best of our knowledge, this is the first reported case of rapidly fatal dual infection with Aspergillus and Rhizopus Our case highlights the role of high-dose corticosteroids as a risk factor for invasive fungal disease in patients without traditional risk factors like haematological malignancies, solid organ transplantation or uncontrolled diabetes. 2016 BMJ Publishing Group Ltd.

  6. Rapidly progressive cryptogenic organising pneumonia presenting as a lung mass

    Science.gov (United States)

    Akram, Saeed; Irfan, Muhammad; Aftab, Kanwal

    2009-01-01

    A very rare case of a rapidly progressive variant of cryptogenic organising pneumonia (COP) presenting as a focal mass-like lesion with compression of the large airways leading to respiratory failure is described. A 60-year-old lady presented to the Aga Khan University Hospital Emergency Department in hypoxaemic respiratory failure with a 6-day history of dyspnoea, productive cough and fever. Chest x ray showed a right upper lobe mass-like lesion compressing the large airways and right pleural effusion. She deteriorated in the Emergency Department and was intubated due to worsening hypoxaemic respiratory failure. The pleural fluid and bronchoscopic specimens were negative on microbiological and cytological examination. CT-guided right lung biopsy revealed chronic non-specific inflammation without granuloma and malignancy. COP was diagnosed on video-assisted thoracoscopic (VATS) lung biopsy. She was successfully treated with high dose steroids and discharged in a stable condition; her 3-month follow-up chest x rays showed complete resolution of the lung lesion with some residual fibrosis. PMID:21686529

  7. Caffeine, creatine, GRIN2A and Parkinson's disease progression.

    Science.gov (United States)

    Simon, David K; Wu, Cai; Tilley, Barbara C; Lohmann, Katja; Klein, Christine; Payami, Haydeh; Wills, Anne-Marie; Aminoff, Michael J; Bainbridge, Jacquelyn; Dewey, Richard; Hauser, Robert A; Schaake, Susen; Schneider, Jay S; Sharma, Saloni; Singer, Carlos; Tanner, Caroline M; Truong, Daniel; Wei, Peng; Wong, Pei Shieen; Yang, Tianzhong

    2017-04-15

    Caffeine is neuroprotective in animal models of Parkinson's disease (PD) and caffeine intake is inversely associated with the risk of PD. This association may be influenced by the genotype of GRIN2A, which encodes an NMDA-glutamate-receptor subunit. In two placebo-controlled studies, we detected no association of caffeine intake with the rate of clinical progression of PD, except among subjects taking creatine, for whom higher caffeine intake was associated with more rapid progression. We now have analyzed data from 420 subjects for whom DNA samples and caffeine intake data were available from a placebo-controlled study of creatine in PD. The GRIN2A genotype was not associated with the rate of clinical progression of PD in the placebo group. However, there was a 4-way interaction between GRIN2A genotype, caffeine, creatine and the time since baseline. Among subjects in the creatine group with high levels of caffeine intake, but not among those with low caffeine intake, the GRIN2A T allele was associated with more rapid progression (p=0.03). These data indicate that the deleterious interaction between caffeine and creatine with respect to rate of progression of PD is influenced by GRIN2A genotype. This example of a genetic factor interacting with environmental factors illustrates the complexity of gene-environment interactions in the progression of PD. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Hummingbird sign in progressive supranuclear palsy disease

    Directory of Open Access Journals (Sweden)

    Sanjay Pandey

    2012-01-01

    Full Text Available Progressive supranuclear palsy (PSP is characterized by slowness, rigidity, bradykinesia, repeated falls, downgaze limitation and dementia. Midbrain atrophy on magnetic resonance imaging is highly suggestive of PSP and is described as "hummingbird sign". This sign is very helpful in differentiating PSP patients from those with Parkinson′s disease. We hereby report a 72-year-old female case of PSP primarily diagnosed with Parkinson′s disease.

  9. A perspective on chronic kidney disease progression.

    Science.gov (United States)

    Zhong, Jianyong; Yang, Hai-Chun; Fogo, Agnes B

    2017-03-01

    Chronic kidney disease (CKD) will progress to end stage without treatment, but the decline of renal function may not be linear. Compared with glomerular filtration rate and proteinuria, new surrogate markers, such as kidney injury molecule-1, neutrophil gelatinase-associated protein, apolipoprotein A-IV, and soluble urokinase receptor, may allow potential intervention and treatment in the earlier stages of CKD, which could be useful for clinical trials. New omic-based technologies reveal potential new genomic and epigenomic mechanisms that appear different from those causing the initial disease. Various clinical studies also suggest that acute kidney injury is a major risk for progressive CKD. To ameliorate the progression of CKD, the first step is optimizing renin-angiotensin-aldosterone system blockade. New drugs targeting endothelin, transforming growth factor-β, oxidative stress, and inflammatory- and cell-based regenerative therapy may have add-on benefit. Copyright © 2017 the American Physiological Society.

  10. Progression of Alzheimer Disease in Europe

    DEFF Research Database (Denmark)

    Vellas, B; Hausner, L; Frolich, L

    2012-01-01

    The clinical progression of Alzheimer disease (AD) was studied in European subjects under treatment with AChE inhibitors (AChE-I) in relation to geographical location over a 2-years period. One thousand three hundred and six subjects from 11 European countries were clustered into 3 regions (North...

  11. Recent progress in ERCP for biliary and pancreatic diseases

    Directory of Open Access Journals (Sweden)

    MIAO Lin

    2014-12-01

    Full Text Available In recent years, with the continuous development of endoscopic and interventional techniques, many new devices and methods have been used in clinical practice, and the application of endoscopic retrograde cholangiopancreatography (ERCP in biliary and pancreatic diseases has developed rapidly. This paper reviews and summarizes the recent progress in ERCP among patients with biliary and pancreatic diseases, including those with altered gastrointestinal anatomy, pregnant patients, patients with benign and malignant biliary strictures, and patients with pancreatic pseudocysts, as well as the application of SpyGlass, photodynamic therapy, and radiofrequency ablation, the management of ERCP-related duodenal perforation, and the prevention of post-ERCP pancreatitis. All the progress has made a great contribution to the diagnosis and treatment of biliary and pancreatic diseases.

  12. Diagnosis of Ebola Virus Disease: Progress and Prospects

    Directory of Open Access Journals (Sweden)

    Mingjuan Yang

    2015-12-01

    Full Text Available Ebola virus disease (EVD represents one of the deadliest diseases in the world, with a fatality rate of over 70% and absence of effective vaccine and treatment. Rapid and specific diagnosis of EVD is essential for isolation, treatment of patients, and prevention of outbreak spread. Although many assays for EVD diagnosis have been reported, there is still an urgent requirement for practical assays for use in resource-limited areas, like Africa. Here we summarize the progresses of EVD diagnostic techniques.

  13. Rapidly Progressive Frontotemporal Dementia Associated with MAPT Mutation G389R.

    Science.gov (United States)

    Sun, Lin; Chen, Kathryn; Li, Xia; Xiao, Shifu

    2017-01-01

    Frontotemporal dementia includes a large spectrum of neurodegenerative disorders. Here, we report the case of a young patient with MAPT mutation G389R, who was 27 years old when he progressively developed severe behavioral disturbances. Initially, he presented with slowly progressive personality change. After 1 year, he exhibited moderate dementia with extrapyramidal and pyramidal symptoms. MRI showed frontotemporal atrophy. He rapidly progressed to severe dementia 3 years after onset. Genetic testing revealed a heterozygous guanine to cytosine mutation at the first base of codon 389 (c.1165G>A) of MAPT, the tau gene, resulting in a glycine to arginine substitution in the patient and two unaffected relatives. We predicted the model of mutant tau protein through I-TASSER software, and speculated the structural change of tau protein caused by mutant site. We also detected the MAPT gene transcript and methylation of samples from peripheral blood leucocytes in an attempt to explain the possible mechanisms of incomplete penetrance, although there were not positive findings. This case is remarkable because of the early onset and rapid progression of the disease.

  14. Acute HIV infection with rapid progression to AIDS

    Directory of Open Access Journals (Sweden)

    Marcio de Oliveira Silva

    Full Text Available Acute HIV infection is rarely recognized as the signs and symptoms are normally unspecific and can persist for days or weeks. The normal HIV course is characterized by a progressive loss of CD4+ cells, which normally leads to severe immunodeficiency after a variable time interval. The mean time from initial infection to development of clinical AIDS is approximately 8-10 years, but it is variable among individuals and depends on a complex interaction between virus and host. Here we describe an extraordinary case of a man who developed Pneumocisits jiroveci pneumonia within one month after sexual exposure to HIV-1, and then presented with 3 consecutive CD4 counts bellow 200 cells/mm³ within 3 months, with no other opportunistic disease. Although antiretroviral therapy (AZT+3TC+ATZ/r was started, with full adherence of the patient, and genotyping indicating no primary antiretroviral resistance mutations, he required more than six months to have a CD4 restoration to levels above 200 cells/mm³ and 10 months to HIV-RNA to become undetectable.

  15. Progress and Challenges in Infectious Disease Cartography.

    Science.gov (United States)

    Kraemer, Moritz U G; Hay, Simon I; Pigott, David M; Smith, David L; Wint, G R William; Golding, Nick

    2016-01-01

    Quantitatively mapping the spatial distributions of infectious diseases is key to both investigating their epidemiology and identifying populations at risk of infection. Important advances in data quality and methodologies have allowed for better investigation of disease risk and its association with environmental factors. However, incorporating dynamic human behavioural processes in disease mapping remains challenging. For example, connectivity among human populations, a key driver of pathogen dispersal, has increased sharply over the past century, along with the availability of data derived from mobile phones and other dynamic data sources. Future work must be targeted towards the rapid updating and dissemination of appropriately designed disease maps to guide the public health community in reducing the global burden of infectious disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Multiple Orderings of Events in Disease Progression.

    Science.gov (United States)

    Young, Alexandra L; Oxtoby, Neil P; Huang, Jonathan; Marinescu, Razvan V; Daga, Pankaj; Cash, David M; Fox, Nick C; Ourselin, Sebastien; Schott, Jonathan M; Alexander, Daniel C

    2015-01-01

    The event-based model constructs a discrete picture of disease progression from cross-sectional data sets, with each event corresponding to a new biomarker becoming abnormal. However, it relies on the assumption that all subjects follow a single event sequence. This is a major simplification for sporadic disease data sets, which are highly heterogeneous, include distinct subgroups, and contain significant proportions of outliers. In this work we relax this assumption by considering two extensions to the event-based model: a generalised Mallows model, which allows subjects to deviate from the main event sequence, and a Dirichlet process mixture of generalised Mallows models, which models clusters of subjects that follow different event sequences, each of which has a corresponding variance. We develop a Gibbs sampling technique to infer the parameters of the two models from multi-modal biomarker data sets. We apply our technique to data from the Alzheimer's Disease Neuroimaging Initiative to determine the sequence in which brain regions become abnormal in sporadic Alzheimer's disease, as well as the heterogeneity of that sequence in the cohort. We find that the generalised Mallows model estimates a larger variation in the event sequence across subjects than the original event-based model. Fitting a Dirichlet process model detects three subgroups of the population with different event sequences. The Gibbs sampler additionally provides an estimate of the uncertainty in each of the model parameters, for example an individual's latent disease stage and cluster assignment. The distributions and mixtures of sequences that this new family of models introduces offer better characterisation of disease progression of heterogeneous populations, new insight into disease mechanisms, and have the potential for enhanced disease stratification and differential diagnosis.

  17. Aluminum involvement in the progression of Alzheimer's disease.

    Science.gov (United States)

    Walton, J R

    2013-01-01

    The neuroanatomic specificity with which Alzheimer's disease (AD) progresses could provide clues to AD etiopathology. Magnetic resonance imaging studies of AD clinical progression have confirmed general conclusions from earlier studies of AD neuropathological progression wherein neurofibrillary tangle pathology was observed to spread along a well-defined sequence of corticocortical and corticosubcortical connections, preferentially affecting certain cell types, while sparing others. Identical and non-identical twin studies have consistently shown AD has mixed (environmental and genetic) etiopathogenesis. The decades-long prodromal phase over which AD develops suggests slow but progressive accumulation of a toxic or infective agent over time. Major environmental candidates are reviewed to assess which best fits the profile of an agent that slowly accrues in susceptible cell types of AD-vulnerable brain regions to toxic levels by old age, giving rise to AD neuropathology without rapid neuronal lysis. Chronic aluminum neurotoxicity best matches this profile. Many humans routinely ingest aluminum salts as additives contained in processed foods and alum-treated drinking water. The physical properties of aluminum and ferric iron ions are similar, allowing aluminum to use mechanisms evolved for iron to enter vulnerable neurons involved in AD progression, accumulate in those neurons, and cause neurofibrillary damage. The genetic component of AD etiopathogenesis apparently involves a susceptibility gene, yet to be identified, that increases aluminum absorption because AD and Down syndrome patients have higher than normal plasma, and brain, aluminum levels. This review describes evidence for aluminum involvement in AD neuropathology and the clinical progression of sporadic AD.

  18. Critical Role for Monocytes/Macrophages in Rapid Progression to AIDS in Pediatric Simian Immunodeficiency Virus-Infected Rhesus Macaques.

    Science.gov (United States)

    Sugimoto, Chie; Merino, Kristen M; Hasegawa, Atsuhiko; Wang, Xiaolei; Alvarez, Xavier A; Wakao, Hiroshi; Mori, Kazuyasu; Kim, Woong-Ki; Veazey, Ronald S; Didier, Elizabeth S; Kuroda, Marcelo J

    2017-09-01

    Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4(+) T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection. We reported previously that a high peripheral blood monocyte turnover rate was predictive for the onset of disease progression to AIDS in SIV-infected adult macaques. The purpose of this study was to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. We observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. Early after SIV infection, the monocyte turnover further increased, and it remained high during progression to AIDS. A high percentage of terminal deoxynucleotidyltransferase dUTP nick end label (TUNEL)-positive macrophages in the lymph nodes (LNs) and intestine corresponded with an increasing number of macrophages derived from circulating monocytes (bromodeoxyuridine positive [BrdU(+)] CD163(+)), suggesting that the increased blood monocyte turnover was required to rapidly replenish destroyed tissue macrophages. Immunofluorescence analysis further demonstrated that macrophages were a significant portion of the virus-producing cells found in LNs, intestinal tissues, and lungs. The higher baseline monocyte turnover in infant macaques and subsequent macrophage damage by SIV infection may help explain the basis of more rapid disease progression to AIDS in infants.IMPORTANCE HIV infection progresses much more rapidly in pediatric cases than in adults; however, the mechanism for this difference is unclear. Using the rhesus macaque model

  19. Motor neurone disease: progress and challenges.

    Science.gov (United States)

    Dharmadasa, Thanuja; Henderson, Robert D; Talman, Paul S; Macdonell, Richard Al; Mathers, Susan; Schultz, David W; Needham, Merrillee; Zoing, Margaret; Vucic, Steve; Kiernan, Matthew C

    2017-05-01

    Major progress has been made over the past decade in the understanding of motor neurone disease (MND), changing the landscape of this complex disease. Through identifying positive prognostic factors, new evidence-based standards of care have been established that improve patient survival, reduce burden of disease for patients and their carers, and enhance quality of life. These factors include early management of respiratory dysfunction with non-invasive ventilation, maintenance of weight and nutritional status, as well as instigation of a multidisciplinary team including neurologists, general practitioners and allied health professionals. Advances in technology have enhanced our understanding of the genetic architecture of MND considerably, with implications for patients, their families and clinicians. Recognition of extra-motor involvement, particularly cognitive dysfunction, has identified a spectrum of disease from MND through to frontotemporal dementia. Although riluzole remains the only disease-modifying medication available in clinical practice in Australia, several new therapies are undergoing clinical trials nationally and globally, representing a shift in treatment paradigms. Successful translation of this clinical research through growth in community funding, awareness and national MND research organisations has laid the foundation for closing the research-practice gap on this debilitating disease. In this review, we highlight these recent developments, which have transformed treatment, augmented novel therapeutic platforms, and established a nexus between research and the MND community. This era of change is of significant relevance to both specialists and general practitioners who remain integral to the care of patients with MND.

  20. Clinical reasoning: rapidly progressive quadriparesis in a forgetful patient.

    Science.gov (United States)

    Mantoan Ritter, Laura; Isaacs, Jeremy D; McEntagart, Meriel; O'Dwyer, John P

    2013-11-19

    A 50-year-old right-handed retired family business manager developed progressive left-sided weakness over 5 days after a mechanical fall. She remembered catching her foot on the carpet and falling down a flight of stairs, followed by severe neck pain over C4-C5 and inability to get up for nearly an hour. Over the subsequent month her symptoms progressed and she presented to hospital with an asymmetric spastic paraparesis, loss of pinprick sensation in her arms and legs, loss of vibration sense to both hips, and double incontinence.

  1. Crevicular Fluid Biomarkers and Periodontal Disease Progression

    Science.gov (United States)

    Oh, Min; Braun, Thomas M.; Ramseier, Christoph A.; Sugai, Jim V.; Giannobile, William V.

    2014-01-01

    Aim Assess the ability of a panel of gingival crevicular fluid (GCF) biomarkers as predictors of periodontal disease progression (PDP). Materials and Methods 100 individuals participated in a 12-month longitudinal investigation and categorized into 4 groups according to their periodontal status. GCF, clinical parameters, and saliva were collected bi-monthly. Sub-gingival plaque and serum were collected bi-annually. For 6 months, no periodontal treatment was provided. At 6-months, patients received periodontal therapy and continued participation from 6-12 months. GCF samples were analyzed by ELISA for MMP-8, MMP-9, OPG, CRP and IL-1β. Differences in median levels of GCF biomarkers were compared between stable and progressing participants using Wilcoxon Rank Sum test (p=0.05). Clustering algorithm was used to evaluate the ability of oral biomarkers to classify patients as either stable or progressing. Results Eighty-three individuals completed the 6-month monitoring phase. With the exception of GCF C-reactive protein, all biomarkers were significantly higher in the PDP group compared to stable patients. Clustering analysis showed highest sensitivity levels when biofilm pathogens and GCF biomarkers were combined with clinical measures, 74% (95% CI = 61,86). Conclusions Signature of GCF fluid-derived biomarkers combined with pathogens and clinical measures provides a sensitive measure for discrimination of PDP (ClinicalTrials.gov NCT00277745). PMID:24303954

  2. Primary progressive aphasia: from syndrome to disease.

    Science.gov (United States)

    Matías-Guiu, J A; García-Ramos, R

    2013-01-01

    Primary progressive aphasia (PPA) is a clinical syndrome characterised by a progressive decline in language and speech of neurodegenerative origin. Major breakthroughs made in recent years have lent us a better understanding of this syndrome, which may be the first manifestation of any of a number of neurodegenerative diseases. We reviewed the main aspects of PPA epidemiology, clinical manifestations, diagnosis, aetiology and treatment. Most cases manifest sporadically and the typical age of onset is between 50 and 70 years. Three clinically distinct variants have been described: nonfluent or agrammatic PPA, semantic PPA and logopenic PPA. Each of these variants tends to be associated with specific histopathological findings, but clinical diagnostic methods are imperfect predictors of underlying pathology. Anatomical and functional neuroimaging can provide useful biomarkers. Several treatments have been proposed, and while no clear benefits have been demonstrated, acetylcholinesterase inhibitors may be useful, especially in the logopenic variant. PPA is an emerging syndrome which may be more prevalent than we might expect. It was previously listed as part of the frontotemporal dementia spectrum, and it is also related to Alzheimer disease. Clinical diagnosis, complemented by a biomarker evaluation, may predict the underlying pathology, which in turn will improve treatment possibilities. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  3. Research Progress of Moyamoya Disease in Children

    Science.gov (United States)

    Piao, Jianmin; Wu, Wei; Yang, Zhongxi; Yu, Jinlu

    2015-01-01

    During the onset of Moyamoya disease (MMD), progressive occlusion occurs at the end of the intracranial internal carotid artery, and compensatory net-like abnormal vessels develop in the skull base, generating the corresponding clinical symptoms. MMD can affect both children and adults, but MMD in pediatric patients exhibits distinct clinical features, and the treatment prognoses are different from adult patients. Children are the group at highest risk for MMD. In children, the disease mainly manifests as ischemia, while bleeding is the primary symptom in adults. The pathogenesis of MMD in children is still unknown, and some factors are distinct from those in adults. MMD in children could result in progressive, irreversible nerve functional impairment, and an earlier the onset corresponds to a worse prognosis. Therefore, active treatment at an early stage is highly recommended. The treatment methods for MMD in children mainly include indirect and direct surgeries. Indirect surgeries mainly include multiple burr-hole surgery (MBHS), encephalomyosynangiosis (EMS), and encephaloduroarteriosynangiosis (EDAS); direct surgeries mainly include intra- and extracranial vascular reconstructions that primarily consist of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. Indirect surgery, as a treatment for MMD in children, has shown a certain level of efficacy. However, a standard treatment approach should combine both indirect and direct procedures. Compared to MMD in adults, the treatment and prognosis of MMD in children has higher clinical significance. If the treatment is adequate, a satisfactory outcome is often achieved. PMID:26180513

  4. Renal hemosiderosis and rapidly progressive glomerulonephritis associated with primary hemochromatosis.

    Science.gov (United States)

    Ozkurt, Sultan; Acikalin, Mustafa Fuat; Temiz, Gokhan; Akay, Olga Meltem; Soydan, Mehmet

    2014-06-01

    Hereditary hemochromatosis leads to the accumulation of iron in many organs including the liver, spleen and heart and results in injury and dysfunction of these organs. On the other hand, iron accumulation and functional impairment in kidney is extremely rare. We report a 61-year-old male patient with hereditary hemochromatosis, in whom the renal function was deteriorated rapidly. Renal biopsy revealed crescentic glomeruli and hemosiderin accumulation in tubular epithelial cells.

  5. Treatment of nephrotic syndrome associated with idiopathic rapidly progressive glomerulonephritis and cyclosporin A.

    Science.gov (United States)

    Maduell, F; Sánchez-Alcaraz, A; Sigüenza, F; Caridad, A; Sangrador, G

    1993-02-01

    Recent reports suggest that cyclosporin A is beneficial in inducing remission of idiopathic nephrotic syndrome. Nephrotic syndrome is seen in 10-30% of patients with rapidly progressive glomerulonephritis. We report a case of a 69-year-old man with nephrotic syndrome, associated with idiopathic rapidly progressive glomerulonephritis, who was treated initially with corticosteroid and cyclophosphamide. Three months later he developed thrombophlebitis and leucopenia and cyclophosphamide was suspended. Relapse of nephrotic syndrome associated with rapidly progressive glomerulonephritis developed and therapy with cyclosporin A was used with a good response.

  6. Clinical neurorestorative progress in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Chen L

    2015-06-01

    Full Text Available Lin Chen,1,2 Hongyun Huang,3–5 Wei-Ming Duan,6 Gengsheng Mao3 1Department of Neurosurgery, Yuquan Hospital, Tsinghua University, 2Department of Neurosurgery, Medical Center, Tsinghua University, 3Department of Neurosurgery, General Hospital of Chinese People's Armed Police Forces, 4Center of Cell Research, Beijing Rehabilitation Hospital of Capital Medical University, 5Beijing Hongtianji Neuroscience Academy, 6Department of Anatomy, Capital Medical University, Beijing, People's Republic of China Abstract: Parkinson’s disease (PD is one of the common neurodegenerative diseases. Besides the symptomatic therapies, the increasing numbers of neurorestorative therapies have shown the potential therapeutic value of reversing the neurodegenerative process and improving the patient's quality of life. Currrently available novel clinical neurorestorative strategies include pharmacological managements (glial cell-line derived neurotrophic factor, selegiline, recombinant human erythropoietin, neuromodulation intervention (deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, tissue and cell transplantation (fetal ventral mesencephalic tissue, sympathetic neurons, carotid body cells, bone marrow stromal cells, retinal pigment epithelium cells, gene therapy, and neurorehabilitative therapy. Herein, we briefly review the progress in this field and describe the neurorestorative mechanisms of the above-mentioned therapies for PD. Keywords: Parkinson’s disease, clinical study, neurorestorative treatment, cell transplantation, neuromodulation

  7. Progressive wheeze: atrial myxoma masquerading as chronic obstructive pulmonary disease.

    Science.gov (United States)

    Sinha, Aish; Apps, Andrew; Liong, Wei Chuen; Firoozan, Soroosh

    2015-07-23

    Atrial myxoma, the commonest primary cardiac neoplasm, presents with symptoms of heart failure, embolic phenomena or constitutional upset. We present an atypical case, with wheeze and symptomatic exacerbations typical of chronic obstructive pulmonary disease. With no early clinical evidence of heart failure, the patient was managed with inhaled steroids and bronchodilators, with little relief. Only when the patient was in extremis requiring intubation, due to respiratory failure, did clinical evidence of left heart failure become apparent, with echocardiography demonstrating a massive left atrial myxoma obstructing the mitral valve annulus. Following successful surgical resection, the patient's symptoms fully abated. This case highlights the importance of considering cardiac wheeze in those initially managed as obstructive airway disease not responding in a typical fashion to initial bronchodilator therapy, and particularly in those with rapidly progressive symptoms. Such patients should be referred early for cardiac imaging. The excellent prognosis and quick recovery after timely surgical resection of a myxoma are also highlighted. 2015 BMJ Publishing Group Ltd.

  8. Peranan Terapi Awal dan Terapi Pemeliharaan pada Rapidly Progressive Periodontitis Type 1

    Directory of Open Access Journals (Sweden)

    Anita H. Joedo

    2015-08-01

    Full Text Available Rapidly Progressive Periodontitis (RPP is a severe form of a periodontal disease which starts since a puberty age. The disease if a generalized periodontal destruction without a specific distribution mode: it develops more progressively but does not in accordance to local factors. The first step to the RPP treatment is initial therapy: i.e. DHE, scaling and root planing, and eliminating predisposing local factors and continued with a maintence therapy which will support the success of a surgery later. A study case: a 21-year old RPP woman showed hyperaemia, an abscess, a 10 mm mesial pocket depth, a 5 mm distal pocker depth, a 5 mm buccal pocket depth, a 2nd degree tooth mobility and a 3 mm buccal recession on 25. In the initial therapy she was given an amoxicillin, a metronidazole for killing a supra and subgingival baterial, vitamins B and C, and also a chlorhexidine 0.2% mouth wash for a week. After a week the abscess and the inflammation decreased, but the mobility was still in the same condition and the DHE was still evaluated because of the patient's social factor, the FO was delayed. The next visit was done every 2 monts for a year for maintenance care. The clinical result showed the gingival inflammation and the tooth mobility disappeared. Radiographically, the alveolar bone showed more radiopaque and the lamina dura was seen. In conclusio, the initial and the maintenance therapy was seen to heal the RPP.

  9. Progress on high-performance rapid prototype aluminum mirrors

    Science.gov (United States)

    Woodard, Kenneth S.; Myrick, Bruce H.

    2017-05-01

    Near net shape parts can be produced using some very old processes (investment casting) and the relatively new direct metal laser sintering (DMLS) process. These processes have significant advantages for complex blank lightweighting and costs but are not inherently suited for producing high performance mirrors. The DMLS process can provide extremely complex lightweight structures but the high residual stresses left in the material results in unstable mirror figure retention. Although not to the extreme intricacy of DMLS, investment casting can also provide complex lightweight structures at considerably lower costs than DMLS and even conventional wrought mirror blanks but the less than 100% density for casting (and also DMLS) limits finishing quality. This paper will cover the progress that has been made to make both the DMLS and investment casting processes into viable near net shape blank options for high performance aluminum mirrors. Finish and figure results will be presented to show performance commensurate with existing conventional processes.

  10. Non-inflammatory cerebral amyloid angiopathy as a cause of rapidly progressive dementia: A case study

    Directory of Open Access Journals (Sweden)

    Leonel Tadao Takada

    Full Text Available Abstract A 77 year-old men developed a subacute-onset, rapidly progressive cognitive decline. After 6 months of evolution, he scored 6 on the Mini-Mental State Examination and had left hemiparesis and hemineglect. The patient died 11 months after the onset of cognitive symptoms. Brain MRI showed microhemorrhages on gradient-echo sequence and confluent areas of white matter hyperintensities on T2-weighted images. Brain biopsy revealed amyloid-b peptide deposition in vessel walls, some of them surrounded by micro-bleeds. In this case report, we discuss the role of cerebral amyloid angiopathy (CAA in cognitive decline, due to structural lesions associated with hemorrhages and infarcts, white matter lesions and co-morbidity of Alzheimer's disease, as well as the most recently described amyloid angiopathy-related inflammation.

  11. Patterns of progression, treatment of progressive disease and post-progression survival in the New EPOC study.

    Science.gov (United States)

    Pugh, Siân A; Bowers, Megan; Ball, Alexandre; Falk, Stephen; Finch-Jones, Meg; Valle, Juan W; O'Reilly, Derek A; Siriwardena, Ajith K; Hornbuckle, Joanne; Rees, Myrddin; Rees, Charlotte; Iveson, Tim; Hickish, Tamas; Maishman, Tom; Stanton, Louise; Dixon, Elizabeth; Corkhill, Andrea; Radford, Mike; Garden, O James; Cunningham, David; Maughan, Tim S; Bridgewater, John A; Primrose, John N

    2016-08-09

    The addition of cetuximab (CTX) to perioperative chemotherapy (CT) for operable colorectal liver metastases resulted in a shorter progression-free survival. Details of disease progression are described to further inform the primary study outcome. A total of 257 KRAS wild-type patients were randomised to CT alone or CT with CTX. Data regarding sites and treatment of progressive disease were obtained for the 109 (CT n=48, CT and CTX n=61) patients with progressive disease at the cut-off date for analysis of November 2012. The liver was the most frequent site of progression (CT 67% (32/48); CT and CTX 66% (40/61)). A higher proportion of patients in the CT and group had multiple sites of progressive disease (CT 8%, 4/48; CT and CTX 23%, 14/61 P=0.04). Further treatment for progressive disease is known for 84 patients of whom 69 received further CT, most frequently irinotecan based. Twenty-two patients, 11 in each arm, received CTX as a further line agent. Both the distribution of progressive disease and further treatment are as expected for such a cohort. The pattern of disease progression seen is consistent with failure of systemic micrometastatic disease control rather than failure of local disease control following liver surgery.

  12. Clinical criteria for subtyping Parkinson's disease: biomarkers and longitudinal progression.

    Science.gov (United States)

    Fereshtehnejad, Seyed-Mohammad; Zeighami, Yashar; Dagher, Alain; Postuma, Ronald B

    2017-07-01

    Parkinson's disease varies widely in clinical manifestations, course of progression and biomarker profiles from person to person. Identification of distinct Parkinson's disease subtypes is of great priority to illuminate underlying pathophysiology, predict progression and develop more efficient personalized care approaches. There is currently no clear way to define and divide subtypes in Parkinson's disease. Using data from the Parkinson's Progression Markers Initiative, we aimed to identify distinct subgroups via cluster analysis of a comprehensive dataset at baseline (i.e. cross-sectionally) consisting of clinical characteristics, neuroimaging, biospecimen and genetic information, then to develop criteria to assign patients to a Parkinson's disease subtype. Four hundred and twenty-one individuals with de novo early Parkinson's disease were included from this prospective longitudinal multicentre cohort. Hierarchical cluster analysis was performed using data on demographic and genetic information, motor symptoms and signs, neuropsychological testing and other non-motor manifestations. The key classifiers in cluster analysis were a motor summary score and three non-motor features (cognitive impairment, rapid eye movement sleep behaviour disorder and dysautonomia). We then defined three distinct subtypes of Parkinson's disease patients: 223 patients were classified as 'mild motor-predominant' (defined as composite motor and all three non-motor scores below the 75th percentile), 52 as 'diffuse malignant' (composite motor score plus either ≥1/3 non-motor score >75th percentile, or all three non-motor scores >75th percentile) and 146 as 'intermediate'. On biomarkers, people with diffuse malignant Parkinson's disease had the lowest level of cerebrospinal fluid amyloid-β (329.0 ± 96.7 pg/ml, P = 0.006) and amyloid-β/total-tau ratio (8.2 ± 3.0, P = 0.032). Data from deformation-based magnetic resonance imaging morphometry demonstrated a Parkinson's disease

  13. Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons

    DEFF Research Database (Denmark)

    Kamara, David A; Nielsen, Lene Ryom; Ross, Michael

    2014-01-01

    No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90ml/min/1.73m2 (using Cockcroft Gault) in the Data Collec...

  14. Lingual Kinematics during Rapid Syllable Repetition in Parkinson's Disease

    Science.gov (United States)

    Wong, Min Ney; Murdoch, Bruce E.; Whelan, Brooke-Mai

    2012-01-01

    Background: Rapid syllable repetition tasks are commonly used in the assessment of motor speech disorders. However, little is known about the articulatory kinematics during rapid syllable repetition in individuals with Parkinson's disease (PD). Aims: To investigate and compare lingual kinematics during rapid syllable repetition in dysarthric…

  15. DISTURBANCES OF THE VASCULAR THROMBOCYTE MECHANISM OF HEMOSTASIS IN PATHOGENESIS OF THE MICROCIRCULATORY DISORDERS IN RAPIDLY PROGRESSIVE PERIODONTITIS

    Directory of Open Access Journals (Sweden)

    I.N. Karpenko

    2008-03-01

    Full Text Available In modern stomatology the problem ofatypicalforms ofinflammatoryperiodontaldiseases origination, namely of rapidly progressive periodontitis (RPP, has got special importance due to its widespread. The article presents one of the impotant parts of the pathogenesis- the disturbance of microcirculation processes caused by the decrease of blood clot resistencyofa vascularwall in pathogenesis ofmicrocirculatori disorders in patients with RPP. These disturbances are predetermined by endothelial dysfunction with the subsequent degradation of the clinical presentation of disease, the stomatologic status and quality of patients life.

  16. Stratification by Genetic and Demographic Characteristics Improves Diagnostic Accuracy of Cerebrospinal Fluid Biomarkers in Rapidly Progressive Dementia.

    Science.gov (United States)

    Karch, André; Llorens, Franc; Schmitz, Matthias; Arora, Amandeep Singh; Zafar, Saima; Lange, Peter; Schmidt, Christian; Zerr, Inga

    2016-10-18

    Cerebrospinal fluid (CSF) biomarkers are routinely used for the differential diagnosis of rapidly progressive dementia, but are also affected by patients' characteristics. To assess if stratification by age, sex, and genetic risk factors improves the accuracy of cerebrospinal fluid (CSF) biomarkers in patients with rapidly progressive dementia. 1,538 individuals with sporadic Creutzfeldt-Jakob disease (CJD), 173 with classic Alzheimer's disease (cAD), 37 with rapidly progressive Alzheimer's disease (rpAD), and 589 without signs of dementia were included in this retrospective diagnostic study. The effect of age, sex, PRNP codon 129, and APOE genotype on CSF levels of tau, p-tau, Aβ1-42, and Aβ1-40 values measured at time of diagnostic work-up was assessed. Tau was a better marker for the differentiation of CJD and rpAD in older (AUC:0.97; 95% CI:0.96-1.00) than in younger (AUC:0.91; 95% CI:0.87-0.94) patients as tau levels increased with age in CJD patients, but not in rpAD patients. PRNP codon 129 and APOE genotype had complex effects on biomarkers in all diseases, making stratification by genotype a powerful tool. In females (AUC:0.78; 95% CI:0.65-0.91) and patients older than 70 (AUC:0.78; 95% CI:0.62-0.93), tau was able to differentiate with moderate accuracy between cAD and rpAD patients. Implementation of stratum-specific reference ranges improves the diagnostic accuracy of CSF biomarkers for the differential diagnosis of rapidly progressive dementia. Diagnostic criteria developed for this setting have to take this into account.

  17. Alcohol, coffee, fish, smoking and disease progression in multiple sclerosis

    NARCIS (Netherlands)

    D'hooghe, M. B.; Haentjens, P.; Nagels, G.; De Keyser, J.

    Background: Certain lifestyle factors might influence disease activity in multiple sclerosis (MS). Objectives: To investigate the consumption of alcoholic beverages, caffeinated drinks, fish and cigarette smoking in relation to disability progression in relapsing onset and progressive onset MS.

  18. Rapid progression of gliomatosis cerebri to secondary glioblastoma, factors that affects the progression rate: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee Kyung; Yu, In Kyu; Kim, Seung Min; Kim, Joo Heon; Lee, Seung Hoon; Lee, Seung Yeon [Eulji University Hospital, Daejeon (Korea, Republic of)

    2017-03-15

    Glioblastomas may develop de novo or through progression from low-grade or anaplastic astrocytomas. The term 'primary glioblastoma' refers to a glioblastoma that lacks a precursor lesion and has a clinical history of less than three months. On the other hand, the term 'secondary glioblastoma' indicates that the glioblastoma has progressed from a low-grade tumor after a long latency period and often manifests in younger patients. These subtypes of glioblastoma develop via different genetic pathways, and they differ in prognosis and response to therapy. Thus, differential diagnosis of these subtypes and prediction of the factors that affect the progression from low-grade diffuse astrocytoma to secondary glioblastoma would be clinically very important. We present a rare case of secondary glioblastoma, which developed only three months after the follow up imaging evaluations, with a history of low grade glioma, and present the factors that cause rapid progression.

  19. Patient with rapidly evolving neurological disease with neuropathological lesions of Creutzfeldt-Jakob disease, Lewy body dementia, chronic subcortical vascular encephalopathy and meningothelial meningioma.

    Science.gov (United States)

    Vita, Maria Gabriella; Tiple, Dorina; Bizzarro, Alessandra; Ladogana, Anna; Colaizzo, Elisa; Capellari, Sabina; Rossi, Marcello; Parchi, Piero; Masullo, Carlo; Pocchiari, Maurizio

    2017-04-01

    We report a case of rapidly evolving neurological disease in a patient with neuropathological lesions of Creutzfeldt-Jakob disease (CJD), Lewy body dementia (LBD), chronic subcortical vascular encephalopathy and meningothelial meningioma. The coexistence of severe multiple pathologies in a single patient strengthens the need to perform accurate clinical differential diagnoses in rapidly progressive dementias. © 2016 Japanese Society of Neuropathology.

  20. Genetic architecture of human fibrotic diseases: disease risk and disease progression

    Directory of Open Access Journals (Sweden)

    Agnès eGardet

    2013-12-01

    Full Text Available Genetic studies of human diseases have identified multiple genetic risk loci for various fibrotic diseases. This has provided insights into the myriad of biological pathways potentially involved in disease pathogenesis. These discoveries suggest that alterations in immune responses, barrier function, metabolism and telomerase activity may be implicated in the genetic risks for fibrotic diseases. In addition to genetic disease-risks, the identification of genetic disease-modifiers associated with disease complications, severity or prognosis provides crucial insights into the biological processes implicated in disease progression. Understanding the biological processes driving disease progression may be critical to delineate more effective strategies for therapeutic interventions. This review provides an overview of current knowledge and gaps regarding genetic disease-risks and genetic disease-modifiers in human fibrotic diseases.

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

    Science.gov (United States)

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

    2015-10-01

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

  2. Primary Cutaneous Peripheral T-Cell Lymphoma Not Otherwise Specified: A Rapidly Progressive Variant of Cutaneous T-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Kimberly Aderhold

    2015-01-01

    Full Text Available Primary Cutaneous Peripheral T-Cell Lymphoma NOS (PTL-NOS is a rare, progressive, fatal dermatologic disease that presents with features similar to many common benign plaque-like skin conditions, making recognition of its distinguishing features critical for early diagnosis and treatment (Bolognia et al., 2008. A 78-year-old woman presented to ambulatory care with a single 5 cm nodule on her shoulder that had developed rapidly over 1-2 weeks. Examination was suspicious for malignancy and a biopsy was performed. Biopsy results demonstrated CD4 positivity, consistent with Mycosis Fungoides with coexpression of CD5, CD47, and CD7. Within three months her cancer had progressed into diffuse lesions spanning her entire body. As rapid progression is usually uncharacteristic of Mycosis Fungoides, her diagnosis was amended to PTL-NOS. Cutaneous T-Cell Lymphoma (CTCL should be suspected in patients with patches, plaques, erythroderma, or papules that persist or multiply despite conservative treatment. Singular biopsies are often nondiagnostic, requiring a high degree of suspicion if there is deviation from the anticipated clinical course. Multiple biopsies are often necessary to make the diagnosis. Physicians caring for patients with rapidly progressive, nonspecific dermatoses with features described above should keep more uncommon forms of CTCL in mind and refer for early biopsy.

  3. Accuracy Improvement for Predicting Parkinson’s Disease Progression

    OpenAIRE

    Mehrbakhsh Nilashi; Othman Ibrahim; Ali Ahani

    2016-01-01

    Parkinson?s disease (PD) is a member of a larger group of neuromotor diseases marked by the progressive death of dopamineproducing cells in the brain. Providing computational tools for Parkinson disease using a set of data that contains medical information is very desirable for alleviating the symptoms that can help the amount of people who want to discover the risk of disease at an early stage. This paper proposes a new hybrid intelligent system for the prediction of PD progression using noi...

  4. Subacute sclerosing panencephalitis presenting as rapidly progressive young-onset dementia.

    Science.gov (United States)

    Chakor, Rahul Tryambak; Santosh, Nandanavana Subbareddy

    2013-07-01

    Onset of dementia before 65 years of age is termed as young-onset dementia (YOD). Very little literature exists regarding the clinical features and diagnoses of dementia in younger individuals. We present a case series of four patients of age 10 to 23 years with severe dementia within 18 months of clinical onset (rapidly progressive dementia). Three patients had generalised periodic complexes typical of subacute sclerosing panencephalitis (SSPE) on electroencephalogram (EEG). All patients had elevated cerebrospinal fluid (CSF) IgG measles antibodies. Our case series highlights that SSPE is an important cause of rapidly progressive YOD in developing countries like India.

  5. Biomarkers for disease progression of primary sclerosing cholangitis

    NARCIS (Netherlands)

    de Vries, Elisabeth M. G.; Beuers, Ulrich; Ponsioen, Cyriel Y.

    2015-01-01

    Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown origin. There is no medical treatment of proven benefit on survival; once patients have progressed to end-stage liver disease, the only treatment option is liver transplantation. Over the last years, some progress

  6. Natural History of Progression of Chronic Kidney Disease in Stages ...

    African Journals Online (AJOL)

    Introduction: Patients with chronic kidney disease (CKD) often continue to progress spontaneously towards end stage renal disease (ESRD). In this report we studied the natural history of progression of CKD in a cohort of patients with stage 4 and 5 CKD. Methods: We retrospectively studied a cohort of patients in stage 4 ...

  7. Obesity induced rapid melanoma progression is reversed by orlistat treatment and dietary intervention: Role of adipokines‡

    OpenAIRE

    Malvi, Parmanand; Chaube, Balkrishna; Pandey, Vimal; Vijayakumar, Maleppillil Vavachan; Boreddy, Purushotham Reddy; Mohammad, Naoshad; Singh, Shivendra Vikram; Bhat, Manoj Kumar

    2014-01-01

    Obesity, owing to adiposity, is associated with increased risk and development of various cancers, and linked to their rapid growth as well as progression. Although a few studies have attempted to understand the relationship between obesity and melanoma, the consequences of controlling body weight by reducing adiposity on cancer progression is not well understood. By employing animal models of obesity, we report that controlling obesity either by orlistat treatment or by restricting caloric i...

  8. Rapidly progressing and resistant warts in an immuno-competent male

    Directory of Open Access Journals (Sweden)

    Md. Shahidullah Sikder

    2016-08-01

    Full Text Available Cutaneous warts are common skin conditions caused by different specific strains of the human papilloma virus (HPV, mostly affect children as localized lesion on the hands and feet. They are slowly progressing and disseminated lesions are found in immuno-compromised situations. Usually majority of warts disappear by few months to two years. This is a case of extensive, giant, rapidly progressing and resistant warts in an immuno-competent adult male. 

  9. Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Katsuhisa Masaki

    Full Text Available BACKGROUND: Multiple sclerosis (MS and neuromyelitis optica (NMO occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx pathology and disease aggressiveness in Asian patients with MS and NMO. METHODS/PRINCIPAL FINDINGS: Samples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD, six with MS, and 20 with other neurological diseases (OND. Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59, chronic active (n=58 and chronic inactive (n=23. Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090. Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296. Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients. CONCLUSIONS

  10. Tracking and predicting disease progression in progressive supranuclear palsy: CSF and blood biomarkers.

    Science.gov (United States)

    Jabbari, Edwin; Zetterberg, Henrik; Morris, Huw R

    2017-10-01

    Progressive supranuclear palsy (PSP) is a rare and progressive neurodegenerative condition characterised pathologically by neuronal cell loss due to abnormal tau deposits. Clinically, the condition manifests as parkinsonism with the addition of progressive balance, speech, swallowing, eye movement and cognitive impairment, ultimately leading to death. Measuring change over time in neurodegenerative conditions is central to defining the effects of therapeutic intervention and disease biology. The current gold standard for measuring clinical disease progression in PSP is the PSP Rating Scale score. However, such scales may be affected by intrarater and inter-rater variability. In addition, their use in clinical trials may be hindered by differences in the time interval between pathological disease progression/response to therapeutics and change in clinical state. Therefore, the need for reliable disease progression biomarkers to complement clinical rating scales is clear. Here we discuss the benefits of using biomarkers to predict and track disease progression in both clinical and research settings. Through reviewing the literature to date on the role of cerebrospinal fluid (CSF) and blood biomarkers, we highlight data that reveals the ability of CSF and plasma neurofilament light chain (NF-L) to predict and track clinical disease progression in PSP. We also discuss the need for large-scale longitudinal studies to identify novel biomarkers. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. LYS12 LysM receptor decelerates Phytophthora palmivora disease progression in Lotus japonicus

    DEFF Research Database (Denmark)

    Füchtbauer, Winnie; Yunusov, Temur; Bozsóki, Zoltán

    2018-01-01

    and rapidly induced during P. palmivora infection. Mutants of Lys12 displayed an accelerated disease progression, earlier plant death, and lower level of defense gene expression, while the defense program after chitin, laminarin, oligogalacturonide or flg22 treatment, or the root symbioses with nitrogen...

  12. Research progress in association between interleukin-23 and liver diseases

    Directory of Open Access Journals (Sweden)

    BAO Suxia

    2016-02-01

    Full Text Available Interleukin 23 (IL-23 is a recently discovered cytokine, and growing evidence suggests that IL-23 plays an important role in the development and progression of autoimmune diseases and inflammatory diseases. In recent years, certain research advances in association between IL-23 and liver diseases have been achieved at home and abroad. General features and biological characteristics of IL-23 are described, and its role in the development and progression of diseases such as hepatitis B, hepatitis C, and hepatocellular carcinoma is reviewed here, so that clinicians will have a deeper understanding of the effect of IL-23 in liver diseases and provide optimized therapies for patients with liver diseases.

  13. Metabolic acidosis and the progression of chronic kidney disease

    Science.gov (United States)

    2014-01-01

    Metabolic acidosis is a common complication of chronic kidney disease. Accumulating evidence identifies acidosis not only as a consequence of, but as a contributor to, kidney disease progression. Several mechanistic pathways have been identified in this regard. The dietary acid load, even in the absence of overt acidosis, may have deleterious effects. Several small trials now suggest that the treatment of acidosis with oral alkali can slow the progression of kidney disease. PMID:24708763

  14. [Rapidly progressive puberty in a patient with mosaic Turner syndrome: a case report and literature review].

    Science.gov (United States)

    Liang, Y; Wei, H; Yu, X; Huang, W; Luo, X P

    2017-02-02

    Objective: To explore the clinical characteristics of diagnosis and treatment in patients with Turner syndrome and rapidly progressive puberty. Method: A rare case of rapidly progressive puberty in Turner syndrome with a mosaic karyotype of 45, X/46, X, del(X)(p21)(80%/20%)was diagnosed at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in January. 2015. Clinical characteristics and the related literature were reviewed. Original papers on precocious puberty or rapidly progressive puberty in Turner syndrome, published until Apr. 2016 were retrieved at PubMed and CNKI databases by the use of the key words "Turner syndrome" , "precocious puberty" and "rapidly progressive puberty" . Result: The patient was born at term with birth weight of 2 450 g and was diagnosed with SGA at 3 years of age for the first evaluating of growth and development. Then recombined human growth hormone (rhGH )was given at 4 years of age due to short stature (heightpuberty in a 45, X/46, X, del(X)(p21) mosaic Turner syndrome is reported. Although short stature and ovarian dysgenesis are common in TS, precocious puberty may occur in TS, which is liable to cause delayed diagnosis and misdiagnosis. Careful examination is recommended for patients with unusual growth pattern, even though girls have normal height in accord with standard growth curve or spontaneous puberty. Evaluation for TS and subsequent investigation should be prompted.

  15. Proteinuria and progression in glomerular diseases

    NARCIS (Netherlands)

    Branten, Amanda Johanna Wilhelmina

    2005-01-01

    Proteinuria is a strong predictor of progressive renal insufficiency. The precise mechanisms to explain this relationship are still unknown, although many experimental studies have shown that proteinuria may induce tubulo-interstitial injury. Many investigators have observed that tubulo-interstitial

  16. Progression of autosomal dominant kidney disease: measurement of the stage transitions of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Christopher M Blanchette

    2015-04-01

    Full Text Available Background: Autosomal dominant polycystic kidney disease (ADPKD is a progressive genetic disorder characterized by the development of numerous kidney cysts that result in kidney failure. Little is known regarding the key patient characteristics and utilization of healthcare resources for ADPKD patients along the continuum of disease progression. This observational study was designed to describe the characteristics of ADPKD patients and compare them with those of patients with other chronic kidney diseases. Methods: This retrospective cohort study involved patients with a claim for ADPKD or PKD unspecified from 1/1/2000–2/28/2013 and ≥6 months of previous continuous enrollment (baseline within a large database of administrative claims in the USA. A random sample of chronic kidney disease (CKD patients served as comparators. For a subset of ADPKD patients who had only a diagnosis code of unspecified PKD, abstraction of medical records was undertaken to estimate the proportion of patients who had medical chart-confirmed ADPKD. In patients with linked electronic laboratory data, the estimated glomerular filtration rate was calculated via serum creatinine values to determine CKD stage at baseline and during follow-up. Proportions of patients transitioning to another stage and the mean age at transition were calculated. Results: ADPKD patients were, in general, younger and had fewer physician visits, but had more specific comorbidities at observation start compared with CKD patients. ADPKD patients had a longer time in the milder stages and longer duration before recorded transition to a more severe stage compared with CKD patients. Patients with ADPKD at risk of rapid progression had a shorter time-to-end-stage renal disease than patients with CKD and ADPKD patients not at risk, but stage duration was similar between ADPKD patients at risk and those not at risk. Conclusions: These results suggest that distribution of patients by age at transition

  17. Frontal deficits differentiate progressive supranuclear palsy from Parkinson's disease.

    Science.gov (United States)

    Lee, Young-Eun C; Williams, David R; Anderson, Jacqueline F I

    2016-03-01

    The clinical differentiation of progressive supranuclear palsy from Parkinson's disease can be challenging, due to overlapping clinical features and a lack of diagnostic markers. Abnormalities in cognitive function form part of the clinical spectrums of these diseases and distinctive cognitive profiles may be helpful in differentiating these diseases in the diagnostic period. A comprehensive neuropsychological test battery was administered to 12 patients with clinically diagnosed progressive supranuclear palsy and 12 patients with Parkinson's disease matched for age and disease duration. Effect size (Cohen's d) was calculated for cognitive tests that were significantly different between groups. Patients with progressive supranuclear palsy performed significantly worse than those with Parkinson's disease on measures of processing speed, verbal fluency, planning, verbal abstract reasoning, verbal memory, and made more perseverative responses on a set shifting task. Measures of executive function, manual dexterity and processing speed were most diagnostically useful (Cohen's d > 2.0) in differentiating between progressive supranuclear palsy and Parkinson's disease. These findings suggest that more severe and prominent 'frontal' cognitive deficits in patients with progressive parkinsonism would be helpful in predicting progressive supranuclear palsy rather than Parkinson's disease and these findings may contribute to the development of diagnostic criteria. © 2014 The British Psychological Society.

  18. Rapid progression of mediastinal tumor within a few days: A case report of T cell lymphoblastic lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Tae Ran; Lee, Young Kyung; Jun, Hyun Jung; Jung, Eun Ah; Son, Jin Sung [Seoul Medical Center, Seoul (Korea, Republic of)

    2016-05-15

    T-cell lymphoblastic lymphoma is a highly aggressive tumor derived from lymphocyte of the thymus, which accounts for 2% of non-Hodgkin's lymphoma. The disease occurs most commonly in adolescent and young adult males. It often results in respiratory emergency because of high proliferation rate. In this case, we confirmed the rapid progression of T-cell lymphoblastic lymphoma through the chest CT scan with one week interval. Three days of empirical chemotherapy resulted in substantial reduction of mediastinal mass, pleural thickening and pleural effusion.

  19. Metabolic network as a progression biomarker of premanifest Huntington's disease

    NARCIS (Netherlands)

    Tang, Chris C.; Feigin, Andrew; Ma, Yilong; Habeck, Christian; Paulsen, Jane S.; Leenders, Klaus L.; Teune, Laura K.; van Oostrom, Joost C. H.; Guttman, Mark; Dhawan, Vijay; Eidelberg, David

    Background. The evaluation of effective disease-modifying therapies for neurodegenerative disorders relies on objective and accurate measures of progression in at-risk individuals. Here we used a computational approach to identify a functional brain network associated with the progression of

  20. Proteinuria and progression of renal disease : Therapeutic implications

    NARCIS (Netherlands)

    Gansevoort, RT; Navis, GJ; Wapstra, JH; de Jong, PE; de Zeeuw, D

    The relationship between proteinuria and progression of renal disease has long been an issue of debate. The present review deals with some of the recent publications on this topic. New concepts are emphasized: the possible causal role of proteinuria in the pathophysiology of progressive renal

  1. Haptocorrin as marker of disease progression in fibrolamellar hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Lildballe, Dorte Launholt; Nguyen, Khoa Tran; Poulsen, Steen Seier

    2011-01-01

    No valid markers are routinely available to follow disease progression in patients with fibrolamellar hepatocellular carcinoma (FLHCC). We report data suggesting that the vitamin B12 binding protein haptocorrin (HC) may prove a suitable marker....

  2. Rapidly progressive periodontal disease associated with human immunodeficiency virus.

    Science.gov (United States)

    Al-Hezaimi, Khalid; Javed, Fawad; Ali, Tazeen Saeed; Al-Askar, Mansour; Al-Rasheed, Abdulaziz

    2012-03-01

    Severe periodontal inflammation with generalized dental plaque accumulation, spontaneous and severe gingival bleeding, fungal infection, and interdental papillae necrosis are presented in a patient infected with human immunodeficiency virus (HIV). Bite-wing radiographs revealed a generalized horizontal alveolar bone loss of 7-8 millimetres in both arches. Erythematous patches were noted on the gingival mucosa in both jaws. DNA testing was performed to indentify the periodontopathogens. The patient had no signs or symptoms of acquired immunodeficiency syndrome. This case-report presents the massive periodontal destruction that occurred in a patient infected with HIV. Therefore, it is highly recommended that patients infected with HIV should be regularly monitored to aid in early detection and to provide proper management of periodontal inflammatory conditions to minimize its destruction.

  3. Progression of Late-Onset Stargardt Disease

    NARCIS (Netherlands)

    Lambertus, S.; Lindner, M.; Bax, N.M.; Mauschitz, M.M.; Nadal, J.; Schmid, M.; Schmitz-Valckenberg, S.; Hollander, A.I. den; Weber, B.H.; Holz, F.G.; Wilt, G.J. van der; Fleckenstein, M.; Hoyng, C.B.

    2016-01-01

    Purpose: Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy

  4. [A young man with rapidly progressing dyspnoea and a mediastinal mass].

    Science.gov (United States)

    van Spronsen, D J; van den Berkmortel, F W P J; Bootsma, G P; de Mulder, P H M

    2004-11-13

    An 18-year-old male presented with a 2-week history of rapid progressive dyspnoea and dry cough due to a large mediastinal mass with compression of the trachea. Based on the raised serum values of the tumour markers chorionogonadotrophin and alphafoetoprotein the diagnosis of germ-cell tumour was made. Because of the severity of his symptoms chemotherapy with bleomycin, etoposide and cisplatin was begun on the same day and before the results of the histology investigations were known. The next day the symptoms were diminished and after completing four courses of chemotherapy there was complete remission. The differential diagnosis of a rapid progressive mediastinal mass is limited and mainly relates to malignant lymphoma and germ-cell tumours. In emergency situations if tumour markers are raised then anti-tumour therapy may be begun before any histological confirmation is available.

  5. Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer's disease

    OpenAIRE

    Gross Hyman; Tobinick Edward L

    2008-01-01

    Abstract Background Recent clinical studies point to rapid and sustained clinical, cognitive, and behavioral improvement in both Alzheimer's disease and primary progressive aphasia following weekly perispinal administration of etanercept, a TNF-alpha inhibitor that acts by blocking the binding of this cytokine to its receptors. This outcome is concordant with recent basic science studies suggesting that TNF-alpha functions in vivo as a gliotransmitter that regulates synaptic function in the b...

  6. Case report of rapidly progressive proliferative verrucous leukoplakia and a proposal for aetiology in mainland China

    Directory of Open Access Journals (Sweden)

    Zeng Xin

    2011-02-01

    Full Text Available Abstract Proliferative verrucous leukoplakia (PVL is a rare oral leukoplakia and has four features such as chronic proliferation, multiple occurrences, refractoriness to treatment and high rate of malignant transformation. As mentioned above, most PVL cases processed to malignancy over many years, sometimes 20 years. However, this report described a case of rapid progress, which had malignant transformation in a short period. Additionally, the aetiology of PVL was discussed and immunity was proposed as the possible cause.

  7. Inflammatory Bowel Disease: Progress Towards a Gene

    Directory of Open Access Journals (Sweden)

    David A van Heel

    2000-01-01

    Full Text Available The pathogenesis of ulcerative colitis (UC and Crohn’s disease (CD is still unknown, but the importance of genetic susceptibility has been clearly shown by epidemiological data from family and twin studies. Linkage studies have identified two susceptibility loci for inflammatory bowel disease (IBD on chromosomes 12 and 16. Importantly, these linkages have been replicated by independent investigators, and studies of positional candidates within these regions continue, together with fine mapping strategies. Regions of ’suggestive’ linkage on chromosomes 1, 3, 4, 6, 7, 10, 22 and X have also been reported in individual studies. Other important candidate genes investigated include the interleukin-1 receptor antagonist, MUC3 and genes of the human leukocyte antigen (HLA system. The apparently conflicting data in different studies from around the world may be explained by ethnic differences, case mix and genetic heterogeneity. Replicated class II HLA associations include HLA DRB1*0103 and DR2 (DRB1*1502, involved in UC susceptibility, and HLA DRB1*03 and DR4 as resistance alleles for CD and UC respectively. Animal studies have provided insights from targeted mutations and quantitative trait locus analysis. The goals of continuing research include narrowing the regions of linkages and analysis of candidate genes, and possibly the application of newly developed methods using single nucleotide polymorphisms. Advances in IBD genetics hold the potential to provide knowledge about the disease pathogenesis at the molecular level, with ensuing benefits for clinical practice.

  8. Neurocognitive features distinguishing primary central nervous system lymphoma from other possible causes of rapidly progressive dementia.

    Science.gov (United States)

    Deutsch, Mariel B; Mendez, Mario F

    2015-03-01

    Define the neurocognitive features of primary central nervous system lymphoma (PCNSL) presenting with dementia, and compare with other causes of rapidly progressive dementia (RPD). PCNSL can present as an RPD. Differentiating PCNSL from other RPDs is critical because lymphomatous dementia may be reversible, and untreated PCNSL is fatal. We performed a meta-analysis of case reports of dementia from PCNSL (between 1950 and 2013); 20 patients (14 with lymphomatosis cerebri) met our criteria. We compared these patients to a case series of patients with RPD from Creutzfeldt-Jakob disease and other non-PCNSL etiologies (Sala et al, 2012. Alzheimer Dis Assoc Disord. 26:267-271). Median age was 66 years (range 41 to 81); 70% were men. Time from symptom onset to evaluation was <6 months in 65%. No patients had seizures; 5% had headaches; 45% had non-aphasic speech difficulty. There was significantly more memory impairment in patients with PCNSL than other RPDs and significantly less myoclonus and parkinsonism. Behavioral changes and cerebellar signs were not significantly different. Significantly more patients with PCNSL than other RPDs had white matter changes; significantly fewer had atrophy. Elevated CSF protein and pleocytosis were more frequent in PCNSL; patients with other RPDs tended to have normal CSF±14-3-3 protein. Unlike patients with RPD from other causes, those with PCNSL commonly present with impaired memory, apathy, and abnormal speech and gait, without headache, seizure, or myoclonus. White matter changes and CSF abnormalities predominate. Improved clinical awareness of PCNSL can prompt earlier diagnosis and treatment.

  9. Glutathione dysregulation and the etiology and progression of human diseases.

    NARCIS (Netherlands)

    Ballatori, N.; Krance, S.M.; Notenboom, S.; Shi, S.; Tieu, K.; Hammond, C.L.

    2009-01-01

    Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and as a result, disturbances in GSH homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases

  10. Asymmetric Inter-Eye Progression in Stargardt Disease

    NARCIS (Netherlands)

    Lambertus, S.; Bax, N.M.; Groenewoud, J.M.M.; Cremers, F.P.M.; Wilt, G.J. van der; Klevering, B.J.; Theelen, T.; Hoyng, C.B.

    2016-01-01

    Purpose: Asymmetry in disease progression between left and right eyes can occur in Stargardt disease (STGD1), and this needs to be considered in novel therapeutic trials with a fellow-eye paired controlled design. This study investigated the inter-eye discordance of best-corrected visual acuity

  11. Predictors of disease progression in pediatric dilated cardiomyopathy.

    Science.gov (United States)

    Molina, Kimberly M; Shrader, Peter; Colan, Steven D; Mital, Seema; Margossian, Renee; Sleeper, Lynn A; Shirali, Girish; Barker, Piers; Canter, Charles E; Altmann, Karen; Radojewski, Elizabeth; Tierney, Elif Seda Selamet; Rychik, Jack; Tani, Lloyd Y

    2013-11-01

    Despite medical advances, children with dilated cardiomyopathy (DCM) remain at high risk of death or need for cardiac transplantation. We sought to identify predictors of disease progression in pediatric DCM. The Pediatric Heart Network evaluated chronic DCM patients with prospective echocardiographic and clinical data collection during an 18-month follow-up. Inclusion criteria were age DCM disease duration >2 months. Patients requiring intravenous inotropic/mechanical support or listed status 1A/1B for transplant were excluded. Disease progression was defined as an increase in transplant listing status, hospitalization for heart failure, intravenous inotropes, mechanical support, or death. Predictors of disease progression were identified using Cox proportional hazards modeling and classification and regression tree analysis. Of the 127 patients, 28 (22%) had disease progression during the 18-month follow-up. Multivariable analysis identified older age at diagnosis (hazard ratio=1.14 per year; Pmode dimension z-score (hazard ratio=1.49; Pmode dimension z-score ≥7.7, LV ejection fraction mode) z-score DCM, a combination of diagnosis after late infancy and echocardiographic parameters of larger LV size and systolic and diastolic function predicted disease progression. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00123071.

  12. Partial status epilepticus - rapid genetic diagnosis of Alpers' disease.

    LENUS (Irish Health Repository)

    McCoy, Bláthnaid

    2011-11-01

    We describe four children with a devastating encephalopathy characterised by refractory focal seizures and variable liver dysfunction. We describe their electroencephalographic, radiologic, genetic and pathologic findings. The correct diagnosis was established by rapid gene sequencing. POLG1 based Alpers\\' disease should be considered in any child presenting with partial status epilepticus.

  13. [Progression factors for chronic kidney disease. Secondary prevention].

    Science.gov (United States)

    García de Vinuesa, S

    2008-01-01

    The natural history of most chronic kidney diseases (CKD) indicates that glomerular filtration gradually declines over time, progressing to more advanced stages of kidney failure. Since the publication of the first studies by the Modification of Diet in Renal Disease (MDRD) Study Group, numerous factors have been identified that can accelerate this progression. Some are dependent on the etiology, but other are common to all and may accelerate progression of kidney disease: Non-modifiable progression factors for CKD: - Etiology of kidney disease - Degree of initial kidney function - Gender - Age - Ethnicity/Other genetic factors - Birth weight Modifiable progression factors for CKD: - Proteinuria - High blood pressure - Poor glycemic control in diabetes - Smoking - Obesity - Metabolic syndrome/Insulin resistance - Dyslipidemia - Anemia - Metabolic factors (Ca/P, uric acid) - Use of nephrotoxic drugs. Therapeutic intervention on these factors has shown that it reduce the rate of progression of CKD (Strength of Recommendation A).There is no clear evidence that correction of these factors slows CKD (Strength of Recommendation C), although it has been shown to have a beneficial effect on cardiovascular risk at other levels.

  14. [Hepatitis B virus and chronic progressive kidney disease].

    Science.gov (United States)

    Kes, Petar; Slavicek, Jasna

    2009-12-01

    associated with HBV, testing for HBV DNA is recommended to confirm active viral replication and kidney biopsy to confirm the presence of an underlying glomerular process, or biopsy at another tissue site to confirm polyarteritis nodosa. It is recommended to treat these patients with an antiviral agent using appropriate dose adjustment for the level of kidney function. In patients with associated vasculitis or rapidly progressive glomerulonephritis, a short course of glucocorticoids may be considered.

  15. Periodontal disease's contribution to Alzheimer's disease progression in Down syndrome.

    Science.gov (United States)

    Kamer, Angela R; Fortea, Juan O; Videla, Sebastià; Mayoral, Angela; Janal, Malvin; Carmona-Iragui, Maria; Benejam, Bessy; Craig, Ronald G; Saxena, Deepak; Corby, Patricia; Glodzik, Lidia; Annam, Kumar Raghava Chowdary; Robbins, Miriam; de Leon, Mony J

    2016-01-01

    People with Down syndrome (DS) are at an increased risk for Alzheimer's disease (AD). After 60 years of age, >50% of DS subjects acquire dementia. Nevertheless, the age of onset is highly variable possibly because of both genetic and environmental factors. Genetics cannot be modified, but environmental risk factors present a potentially relevant intervention for DS persons at risk for AD. Among them, inflammation, important in AD of DS type, is potential target. Consistent with this hypothesis, chronic peripheral inflammation and infections may contribute to AD pathogenesis in DS. People with DS have an aggressive form of periodontitis characterized by rapid progression, significant bacterial and inflammatory burden, and an onset as early as 6 years of age. This review offers a hypothetical mechanistic link between periodontitis and AD in the DS population. Because periodontitis is a treatable condition, it may be a readily modifiable risk factor for AD.

  16. Obesity induced rapid melanoma progression is reversed by orlistat treatment and dietary intervention: role of adipokines.

    Science.gov (United States)

    Malvi, Parmanand; Chaube, Balkrishna; Pandey, Vimal; Vijayakumar, Maleppillil Vavachan; Boreddy, Purushotham Reddy; Mohammad, Naoshad; Singh, Shivendra Vikram; Bhat, Manoj Kumar

    2015-03-01

    Obesity, owing to adiposity, is associated with increased risk and development of various cancers, and linked to their rapid growth as well as progression. Although a few studies have attempted to understand the relationship between obesity and melanoma, the consequences of controlling body weight by reducing adiposity on cancer progression is not well understood. By employing animal models of obesity, we report that controlling obesity either by orlistat treatment or by restricting caloric intake significantly slows down melanoma progression. The diminished tumor progression was correlated with decreased fat mass (adiposity) in obese mice. Obesity associated factors contributing to tumor progression were decreased in the experimental groups compared to respective controls. In tumors, protein levels of fatty acid synthase (FASN), caveolin (Cav)-1 and pAkt, which are tumor promoting molecules implicated in melanoma growth under obese state, were decreased. In addition, increased necrosis and reduction in angiogenesis as well as proliferative markers PCNA and cyclin D1 were observed in tumors of the orlistat treated and/or calorically restricted obese mice. We observed that growth of melanoma cells cultured in conditioned medium (CM) from orlistat-treated adipocytes was reduced. Adipokines (leptin and resistin), via activating Akt and modulation of FASN as well as Cav-1 respectively, enhanced melanoma cell growth and proliferation. Together, we demonstrate that controlling body weight reduces adipose mass thereby diminishing melanoma progression. Therefore, strategic means of controlling obesity by reduced caloric diet or with antiobesity drugs treatment may render obesity-promoted tumor progression in check and prolong survival of patients. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  17. CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba.

    Science.gov (United States)

    Kouri, Vivian; Khouri, Ricardo; Alemán, Yoan; Abrahantes, Yeissel; Vercauteren, Jurgen; Pineda-Peña, Andrea-Clemencia; Theys, Kristof; Megens, Sarah; Moutschen, Michel; Pfeifer, Nico; Van Weyenbergh, Johan; Pérez, Ana B; Pérez, Jorge; Pérez, Lissette; Van Laethem, Kristel; Vandamme, Anne-Mieke

    2015-03-01

    Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba. Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as > 3 years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis. CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba.

  18. Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Disease.

    Science.gov (United States)

    Howell, Michael Joseph; Schenck, Carlos Hugh

    2015-06-01

    The dream enactment of rapid eye movement sleep behavior disorder (RBD) is often the first indication of an impending α-synuclein disorder, such as Parkinson disease, multiple-system atrophy, or dementia with Lewy bodies. To provide an overview of RBD from the onset of dream enactment through the emergence of a parkinsonian disorder. Peer-reviewed articles, including case reports, case series, retrospective reviews, prospective randomized trials, and basic science investigations, were identified in a PubMed search of articles on RBD from January 1, 1986, through July 31, 2014. Under normal conditions, vivid dream mentation combined with skeletal muscle paralysis characterizes rapid eye movement sleep. In RBD, α-synuclein abnormalities in the brainstem disinhibit rapid eye movement sleep motor activity, leading to dream enactment. The behaviors of RBD are often theatrical, with complexity, aggression, and violence; fighting and fleeing actions can be injurious to patients as well as bed partners. Rapid eye movement sleep behavior disorder is distinguished from other parasomnias by clinical features and the demonstration of rapid eye movement sleep without atonia on polysomnography. Consistent with early neurodegeneration, patients with RBD demonstrate subtle motor, cognitive, and autonomic impairments. Approximately 50% of patients with spontaneous RBD will convert to a parkinsonian disorder within a decade. Ultimately, nearly all (81%-90%) patients with RBD develop a neurodegenerative disorder. Among patients with Parkinson disease, RBD predicts a non-tremor-predominant subtype, gait freezing, and an aggressive clinical course. The most commonly cited RBD treatments include low-dose clonazepam or high-dose melatonin taken orally at bedtime. Treatment of RBD can prevent injury to patients and bed partners. Because RBD is a prodromal syndrome of Parkinson disease (or related disorder), it represents a unique opportunity for developing and testing disease

  19. ALS patients’ regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity

    Science.gov (United States)

    Beers, David R.; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R.; Alsuliman, Abdullah S.; Shpall, Elizabeth J.; Rezvani, Katy

    2017-01-01

    Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression. PMID:28289705

  20. ALS patients' regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity.

    Science.gov (United States)

    Beers, David R; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R; Alsuliman, Abdullah S; Shpall, Elizabeth J; Rezvani, Katy; Appel, Stanley H

    2017-03-09

    Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression.

  1. Immunological Basis for Rapid Progression of Diabetes in Older NOD Mouse Recipients Post BM-HSC Transplantation.

    Directory of Open Access Journals (Sweden)

    Nan Wang

    Full Text Available Type I diabetes (T1D, mediated by autoreactive T cell destruction of insulin-producing islet beta cells, has been treated with bone marrow-derived hematopoietic stem cell (BM-HSC transplantation. Older non-obese diabetic (NOD mice recipients (3m, at disease-onset stage receiving syngeneic BM-HSC progressed more rapidly to end-stage diabetes post-transplantation than younger recipients (4-6w, at disease-initiation stage. FACS analyses showed a higher percentage and absolute number of regulatory T cells (Treg and lower proportion of proliferating T conventional cells (Tcon in pancreatic lymph nodes from the resistant mice among the younger recipients compared to the rapid progressors among the older recipients. Treg distribution in spleen, mesenteric lymph nodes (MLN, blood and thymus between the two groups was similar. However, the percentage of thymic Tcon and the proliferation of Tcon in MLN and blood were lower in the young resistants. These results suggest recipient age and associated disease stage as a variable to consider in BM-HSC transplantation for treating T1D.

  2. Progress towards Rapid Detection of Measles Vaccine Strains: a Tool To Inform Public Health Interventions.

    Science.gov (United States)

    Hacker, Jill K

    2017-03-01

    Rapid differentiation of vaccine from wild-type strains in suspect measles cases is a valuable epidemiological tool that informs the public health response to this highly infectious disease. Few public health laboratories sequence measles virus-positive specimens to determine genotype, and the vaccine-specific real-time reverse transcriptase PCR (rRT-PCR) assay described by F. Roy et al. (J. Clin. Microbiol. 55:735-743, 2017, https://doi.org/10.1128/JCM.01879-16) offers a rapid, easily adoptable method to identify measles vaccine strains in suspect cases. Copyright © 2017 American Society for Microbiology.

  3. Ubiquitin: a potential cerebrospinal fluid progression marker in Huntington's disease.

    Science.gov (United States)

    Vinther-Jensen, T; Simonsen, A H; Budtz-Jørgensen, E; Hjermind, L E; Nielsen, J E

    2015-10-01

    Finding early and dynamic biomarkers in Huntington's disease is a key to understanding the early pathology of Huntington's disease and potentially to tracking disease progression. This would benefit the future evaluation of potential neuroprotective and disease-modifying therapies, as well as aid in identifying an optimal time point for initiating a potential therapeutic intervention. This explorative proteomics study evaluated cerebrospinal fluid from 94 Huntington's disease gene-expansion carriers (39 premanifest and 55 manifest) and 27 Huntington's disease gene-expansion negative individuals using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry. Differences in peak intensity from SELDI-TOF spectra were evaluated. Levels of 10 peaks were statistically significantly different between manifest gene-expansion carriers and controls. One of them identified as ubiquitin was shown to be dependent on the Unified Huntington Disease Rating Scale Total Functional Capacity, a pseudo-measure of disease severity (P = 0.001), and the Symbol Digit Modalities Test (0.04) in manifest and CAG-age product score (P = 0.019) in all gene-expansion carriers. Multiple studies have shown that the ubiquitin-proteasome system is involved in Huntington's disease pathogenesis and understanding of this involvement may have therapeutic potential in humans. This is the first study on cerebrospinal fluid to confirm the involvement of the ubiquitin-proteasome system in Huntington's disease. Furthermore it is shown that ubiquitin increases with disease progression and CAG-age product score and therefore may have the potential as a Huntington's disease progression marker, also prior to motor onset. © 2015 EAN.

  4. State of progress in treating cystic fibrosis respiratory disease

    Directory of Open Access Journals (Sweden)

    Flume Patrick A

    2012-08-01

    Full Text Available Abstract Since the discovery of the gene associated with cystic fibrosis (CF, there has been tremendous progress in the care of patients with this disease. New therapies have entered the market and are part of the standard treatment of patients with CF, and have been associated with marked improvement in survival. Now there are even more promising therapies directed at different components of the pathophysiology of this disease. In this review, our current knowledge of the pathophysiology of lung disease in patients with CF is described, along with the current treatment of CF lung disease, and the therapies in development that offer great promise to our patients.

  5. Rapidly progressive subacute sclerosing panencephalitis presenting with acute loss of vision.

    Science.gov (United States)

    Ekici, Bariş; Calişkan, Mine; Tatli, Burak; Aydinli, Nur; Ozmen, Meral

    2011-12-01

    A 10-year-old male presented with vision loss and behavioral changes. He had midpoint pupils with no reaction to light and normal funduscopic examination. Cranial magnetic resonance imaging revealed bilateral cortical lesions at parieto-occipital lobes. Elevated measles antibody titers in the cerebrospinal fluid confirmed the diagnosis of subacute sclerosing panencephalitis. Despite oral inosiplex and supportive care, patient developed generalized seizures with frequent myoclonic jerks and rapidly progressed into coma. Cortical blindness in subacute sclerosing panencephalitis can be an early indicator for fulminant course.

  6. Silent disease progression in clinically stable heart failure.

    Science.gov (United States)

    Sabbah, Hani N

    2017-04-01

    Heart failure with reduced ejection fraction (HFrEF) is a progressive disorder whereby cardiac structure and function continue to deteriorate, often despite the absence of clinically apparent signs and symptoms of a worsening disease state. This silent yet progressive nature of HFrEF can contribute to the increased risk of death-even in patients who are 'clinically stable', or who are asymptomatic or only mildly symptomatic-because it often goes undetected and/or undertreated. Current therapies are aimed at improving clinical symptoms, and several agents more directly target the underlying causes of disease; however, new therapies are needed that can more fully address factors responsible for underlying progressive cardiac dysfunction. In this review, mechanisms that drive HFrEF, including ongoing cardiomyocyte loss, mitochondrial abnormalities, impaired calcium cycling, elevated LV wall stress, reactive interstitial fibrosis, and cardiomyocyte hypertrophy, are discussed. Additionally, limitations of current HF therapies are reviewed, with a focus on how these therapies are designed to counteract the deleterious effects of compensatory neurohumoral activation but do not fully prevent disease progression. Finally, new investigational therapies that may improve the underlying molecular, cellular, and structural abnormalities associated with HF progression are reviewed. © 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

  7. COMT Val158Met Polymorphism Modulates Huntington's Disease Progression

    Science.gov (United States)

    Rebeix, Isabelle; Dupoux, Emmanuel; Durr, Alexandra; Brice, Alexis; Charles, Perrine; Cleret de Langavant, Laurent; Youssov, Katia; Verny, Christophe; Damotte, Vincent; Azulay, Jean-Philippe; Goizet, Cyril; Simonin, Clémence; Tranchant, Christine; Maison, Patrick; Rialland, Amandine; Schmitz, David; Jacquemot, Charlotte; Fontaine, Bertrand; Bachoud-Lévi, Anne-Catherine

    2016-01-01

    Little is known about the genetic factors modulating the progression of Huntington’s disease (HD). Dopamine levels are affected in HD and modulate executive functions, the main cognitive disorder of HD. We investigated whether the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, which influences dopamine (DA) degradation, affects clinical progression in HD. We carried out a prospective longitudinal multicenter study from 1994 to 2011, on 438 HD gene carriers at different stages of the disease (34 pre-manifest; 172 stage 1; 130 stage 2; 80 stage 3; 17 stage 4; and 5 stage 5), according to Total Functional Capacity (TFC) score. We used the Unified Huntington’s Disease Rating Scale to evaluate motor, cognitive, behavioral and functional decline. We genotyped participants for COMT polymorphism (107 Met-homozygous, 114 Val-homozygous and 217 heterozygous). 367 controls of similar ancestry were also genotyped. We compared clinical progression, on each domain, between groups of COMT polymorphisms, using latent-class mixed models accounting for disease duration and number of CAG (cytosine adenine guanine) repeats. We show that HD gene carriers with fewer CAG repeats and with the Val allele in COMT polymorphism displayed slower cognitive decline. The rate of cognitive decline was greater for Met/Met homozygotes, which displayed a better maintenance of cognitive capacity in earlier stages of the disease, but had a worse performance than Val allele carriers later on. COMT polymorphism did not significantly impact functional and behavioral performance. Since COMT polymorphism influences progression in HD, it could be used for stratification in future clinical trials. Moreover, DA treatments based on the specific COMT polymorphism and adapted according to disease duration could potentially slow HD progression. PMID:27657697

  8. Disruption of gut homeostasis by opioids accelerates HIV disease progression

    Directory of Open Access Journals (Sweden)

    Jingjing eMeng

    2015-06-01

    Full Text Available Cumulative studies during the past 30 years have established the correlation between opioid abuse and human immunodeficiency virus (HIV infection. Further studies also demonstrate that opioid addiction is associated with faster progression to AIDS in patients. Recently, it was revealed that disruption of gut homeostasis and subsequent microbial translocation play important roles in pathological activation of the immune system during HIV infection and contributes to accelerated disease progression. Similarly, opioids have been shown to modulate gut immunity and induce gut bacterial translocation. This review will explore the mechanisms by which opioids accelerate HIV disease progression by disrupting gut homeostasis. Better understanding of these mechanisms will facilitate the search for new therapeutic interventions to treat HIV infection especially in opioid abusing population.

  9. Association of AIDS and Bipolar Mania with Rapid Progression to Dementia and Death

    Directory of Open Access Journals (Sweden)

    Chin-Yi Yang

    2005-02-01

    Full Text Available Neuropsychiatric complications of human immunodeficiency virus (HIV infection or acquired immune deficiency syndrome (AIDS may present clinically as acute or chronic organic brain syndrome, or mimic functional psychiatric diseases. Among such psychiatric diseases, mania tends to occur with increased frequency after the onset of AIDS. We report a case in which manic manifestations were noted before the diagnosis of AIDS. The patient had no past or family history of mood disorders, but had risk factors for HIV infection. He had a rapid downhill course from initial manic symptoms to depression, dementia and then death within 10 months. Such rapid cognitive deterioration into AIDS dementia after mania is consistent with previous reports. Cases like this will become more common with spread of the AIDS pandemic in Asian regions, including Taiwan. Clinicians should be mindful of HIV infection/AIDS as a differential diagnosis in patients with manic episodes and risk factors for HIV infection.

  10. Slow progression of paediatric HIV disease: Selective adaptation or ...

    African Journals Online (AJOL)

    In the European Caucasian populations, the chemokine-cell receptor variant CCR5 \\"Delta 32\\" is a the genetic determinant of HIV disease progression that is believed to have been selected for in the general population by exposure to antigens closely interlinked to HIV like Yersinia pestis or small pox virus. Among African ...

  11. Sodium intake, RAAS-blockade and progressive renal disease

    NARCIS (Netherlands)

    de Borst, Martin H; Navis, Gerjan

    Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors or angiotensin receptor blockers is the current standard treatment to prevent progressive renal function loss in patients with chronic kidney disease. Yet in many patients the

  12. Acetaminophen, aspirin and progression of advanced chronic kidney disease

    NARCIS (Netherlands)

    Evans, Marie; Fored, Carl Michael; Bellocco, Rino; Fitzmaurice, Garrett; Fryzek, Jon P.; McLaughlin, Joseph K.; Nyren, Olof; Elinder, Carl-Gustaf

    Background. Although many studies have investigated the possible association between analgesic use (acetaminophen and aspirin) and the development of chronic kidney disease (CKD), the effect of analgesics on the progression of established CKD of any cause has not yet been investigated. Methods. In

  13. Natural History of Progression of Chronic Kidney Disease in Stages ...

    African Journals Online (AJOL)

    In this report we studied the natural history of progression of CKD in a cohort of ... was estimated using the Modification of Diet in Renal Disease (MDRD) formula. ... low baseline serum bicarbonate level and high urinary protein excretion as ...

  14. Predictors of disease progression in HIV infection: a review

    Directory of Open Access Journals (Sweden)

    Ananworanich Jintanat

    2007-05-01

    Full Text Available Abstract During the extended clinically latent period associated with Human Immunodeficiency Virus (HIV infection the virus itself is far from latent. This phase of infection generally comes to an end with the development of symptomatic illness. Understanding the factors affecting disease progression can aid treatment commencement and therapeutic monitoring decisions. An example of this is the clear utility of CD4+ T-cell count and HIV-RNA for disease stage and progression assessment. Elements of the immune response such as the diversity of HIV-specific cytotoxic lymphocyte responses and cell-surface CD38 expression correlate significantly with the control of viral replication. However, the relationship between soluble markers of immune activation and disease progression remains inconclusive. In patients on treatment, sustained virological rebound to >10 000 copies/mL is associated with poor clinical outcome. However, the same is not true of transient elevations of HIV RNA (blips. Another virological factor, drug resistance, is becoming a growing problem around the globe and monitoring must play a part in the surveillance and control of the epidemic worldwide. The links between chemokine receptor tropism and rate of disease progression remain uncertain and the clinical utility of monitoring viral strain is yet to be determined. The large number of confounding factors has made investigation of the roles of race and viral subtype difficult, and further research is needed to elucidate their significance. Host factors such as age, HLA and CYP polymorphisms and psychosocial factors remain important, though often unalterable, predictors of disease progression. Although gender and mode of transmission have a lesser role in disease progression, they may impact other markers such as viral load. Finally, readily measurable markers of disease such as total lymphocyte count, haemoglobin, body mass index and delayed type hypersensitivity may come into favour

  15. Sustaining global agriculture through rapid detection and deployment of genetic resistance to deadly crop diseases.

    Science.gov (United States)

    Periyannan, Sambasivam

    2017-12-04

    Contents I. II. III. IV. V. VI. VII. VIII. References SUMMARY: Genetically encoded resistance is a major component of crop disease management. Historically, gene loci conferring resistance to pathogens have been identified through classical genetic methods. In recent years, accelerated gene cloning strategies have become available through advances in sequencing, gene capture and strategies for reducing genome complexity. Here, I describe these approaches with key emphasis on the isolation of resistance genes to the cereal crop diseases that are an ongoing threat to global food security. Rapid gene isolation enables their efficient deployment through marker-assisted selection and transgenic technology. Together with innovations in genome editing and progress in pathogen virulence studies, this creates further opportunities to engineer long-lasting resistance. These approaches will speed progress towards a future of farming using fewer pesticides. © 2017 Commonwealth of Australia. New Phytologist © 2017 New Phytologist Trust.

  16. Imiquimod 5% cream treatment for rapidly progressive genital condyloma in a 3-year-old girl.

    Science.gov (United States)

    Leclair, Emily; Black, Amanda; Fleming, Nathalie

    2012-12-01

    The incidence of genital warts in children has increased in the last 50 years. Although pediatric genital warts may resolve spontaneously, the treatment of extensive perianal genital warts in children can be challenging. Imiquimod, although not approved in the pediatric population, may avoid the pain or extensive scarring associated with other treatment modalities. A 3-year-old female was scheduled for surgical resection of genital warts. At surgery, she had extensive condylomas that had progressed rapidly from initial presentation. They were not amenable to surgical treatment due to concerns of incomplete resection, post-operative pain, and genital scarring. After 6 weeks of imiquimod treatment, the condylomatous lesions had completely resolved with minimal side effects. Imiquimod 5% cream is an effective treatment option for children with extensive and rapidly progressive perianal warts and is associated with minimal side effects. Its use should be considered in children with extensive condyloma in order to avoid the pain and possible scarring associated with other approved treatment modalities. Copyright © 2012 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  17. Rapidly progressive osteoarthritis after arthroscopic labral repair in patients with hip dysplasia.

    Science.gov (United States)

    Matsuda, Dean K; Khatod, Monti

    2012-11-01

    Recent reports of poor clinical outcomes after arthroscopic surgery in hips with marked dysplasia have emerged. Arthroscopic resection of the hypertrophic labrum in cases of dysplasia, especially in the absence of periacetabular osteotomy (PAO), has been implicated. Some patients will refuse PAO because it is a major open procedure, opting for a less invasive arthroscopic procedure. We present the cases of 2 young adults with marked dysplasia who had rapidly progressive osteoarthrosis despite arthroscopic labral repair. Though perhaps beneficial as an isolated procedure in borderline or mild dysplasia cases, arthroscopic hip surgery, even labral repair, may best be performed with PAO in cases with more severe dysplasia. Albeit attractive as a less invasive labral-preserving surgery, arthroscopic labral repair not only may fail to provide symptomatic improvement but may compromise or preclude a later PAO if rapidly progressive osteoarthrosis ensues. Hip arthroscopy may best be performed concurrently with or after PAO but not proceeding PAO in patients requiring both procedures. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  18. Rapidly progressive antineutrophil cytoplasm antibodies associated with pulmonary-renal syndrome in a 10-year-old girl

    Directory of Open Access Journals (Sweden)

    Fermin Blanco Filho

    2001-01-01

    Full Text Available CONTEXT: The term pulmonary-renal syndrome has been used frequently to describe the clinical manifestations of a great number of diseases in which pulmonary hemorrhage and glomerulonephritis coexist. The classic example of this type of vasculitis is Goodpasture´s syndrome, a term used to describe the association of pulmonary hemorrhage, glomerulonephritis and the presence of circulating antiglomerular basement membrane antibodies (anti-GBM. Among the several types of systemic vasculitides that can present clinical manifestations of the pulmonary-renal syndrome, we focus the discussion on two types more frequently associated with antineutrophil cytoplasm antibodies (ANCA, microscopic polyangiitis and Wegener´s granulomatosis, concerning a 10 year old girl with clinical signs and symptoms of pulmonary-renal syndrome, with positive ANCA and rapidly progressive evolution. CASE REPORT: We describe the case of a 10-year-old girl referred to our hospital for evaluation of profound anemia detected in a primary health center. Five days before entry she had experienced malaise, pallor and began to cough up blood-tinged sputum that was at first attributed to dental bleeding. She was admitted to the infirmary with hemoglobin = 4 mg/dL, hematocrit = 14%, platelets = 260,000, white blood cells = 8300, 74% segmented, 4% eosinophils, 19% lymphocytes and 3% monocytes. Radiographs of the chest revealed bilateral diffuse interstitial alveolar infiltrates. There was progressive worsening of cough and respiratory distress during the admission day, when she began to cough up large quantities of blood and hematuria was noted. There was rapid and progressive loss of renal function and massive lung hemorrhage. The antineutrophil cytoplasm antibody (ANCA test with antigen specificity for myeloperoxidase (anti-MPO was positive and the circulating anti-GBM showed an indeterminate result.

  19. Identification of genetic variants associated with Huntington's disease progression

    DEFF Research Database (Denmark)

    Hensman Moss, Davina J; Pardiñas, Antonio F; Langbehn, Douglas

    2017-01-01

    BACKGROUND: Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate...... indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008-11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers...... at this SNP was associated with a 0·4 units per year (95% CI 0·16-0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06-0·18) in the rate of change of UHDRS Total Functional Capacity score...

  20. Rapid non-invasive tests for diagnostics of infectious diseases

    Science.gov (United States)

    Malamud, Daniel

    2014-06-01

    A rapid test for an infectious disease that can be used at point-of-care at a physician's office, a pharmacy, or in the field is critical for the prompt and appropriate therapeutic intervention. Ultimately by treating infections early on will decrease transmission of the pathogen. In contrast to metabolic diseases or cancer where multiple biomarkers are required, infectious disease targets (e.g. antigen, antibody, nucleic acid) are simple and specific for the pathogen causing the disease. Our laboratory has focused on three major infectious disease; HIV, Tuberculosis, and Malaria. These diseases are pandemic in much of the world thus putting natives, tourists and military personnel at risk for becoming infected, and upon returning to the U.S., transmitting these diseases to their contacts. Our devices are designed to detect antigens, antibodies or nucleic acids in blood or saliva samples in less than 30 minutes. An overview describing the current status of each of the three diagnostic platforms is presented. These microfluidic point-of-care devices will be relatively inexpensive, disposable, and user friendly.

  1. Rapid progressing allele HLA-B35 Px restricted anti-HIV-1 CD8+ T cells recognize vestigial CTL epitopes.

    Directory of Open Access Journals (Sweden)

    Christian B Willberg

    Full Text Available The HLA-B*35-Px allele has been associated with rapid disease progression in HIV-1 infection, in contrast to the HLA-B*35-Py allele.Immune responses to two HLA-B*35 restricted HIV-1 specific CTL epitopes and their variants were followed longitudinally during early HIV-1 infection in 16 HLA-B*35+ individuals. Subjects expressing HLA-B*35-Px alleles showed no difference in response to the consensus epitopes compared to individuals with HLA-B*35-Py alleles. Surprisingly, all the HLA-B*35-Px+ individuals responded to epitope-variants even in the absence of a consensus response. Sequencing of the viral population revealed no evidence of variant virus in any of the individuals.This demonstrates a novel phenomenon that distinguishes individuals with the HLA-B*35-Px rapid progressing allele and those with the HLA-B*35-Py slower progressing allele.

  2. Progression of Lung Disease in Preschool Patients with Cystic Fibrosis.

    Science.gov (United States)

    Stanojevic, Sanja; Davis, Stephanie D; Retsch-Bogart, George; Webster, Hailey; Davis, Miriam; Johnson, Robin C; Jensen, Renee; Pizarro, Maria Ester; Kane, Mica; Clem, Charles C; Schornick, Leah; Subbarao, Padmaja; Ratjen, Felix A

    2017-05-01

    Implementation of intervention strategies to prevent lung damage in early cystic fibrosis (CF) requires objective outcome measures that capture and track lung disease. To define the utility of the Lung Clearance Index (LCI), measured by multiple breath washout, as a means to track disease progression in preschool children with CF. Children with CF between the ages of 2.5 and 6 years with a confirmed diagnosis of CF and age-matched healthy control subjects were enrolled at three North American CF centers. Multiple breath washout tests were performed at baseline, 1, 3, 6, and 12 months to mimic time points chosen in clinical care and interventional trials; spirometry was also conducted. A generalized linear mixed-effects model was used to distinguish LCI changes associated with normal growth and development (i.e., healthy children) from the progression of CF lung disease. Data were collected on 156 participants with 800 LCI measurements. Although both LCI and spirometry discriminated health from disease, only the LCI identified significant deterioration of lung function in CF over time. The LCI worsened during cough episodes and pulmonary exacerbations, whereas similar symptoms in healthy children were not associated with increased LCI values. LCI is a useful marker to track early disease progression and may serve as a tool to guide therapies in young patients with CF.

  3. A rapidly progressive defective spermatogenesis in a Mexican family affected by spino-bulbar muscular atrophy.

    Science.gov (United States)

    Piña-Aguilar, Raul Eduardo; Regalado-Hernández, Miguel Ángel; Moreno-García, Jesús Daniel; Buentello-Volante, Beatriz; Chacón-Camacho, Oscar Francisco; Gallegos-Rivas, Mayra Celina; Kazakova, Ekaterina; Santillán-Hernández, Yuritzi; Zenteno, Juan Carlos

    2016-01-01

    Spino-bulbar muscular atrophy (SBMA) is an X-linked recessive adult progressive disorder affecting motor neurons. It is caused by a poly-glutamine tract expansion in the androgen receptor (AR) which generates protein aggregates that cannot be processed by proteasomes. A secondary mild androgen resistance is developed by AR dysfunction and patients present endocrine abnormalities including gynecomastia and poor function of testosterone in tissues; however, normally they are fertile. In this report we describe a Mexican family with three affected brothers with primary infertility caused by a progressive impairment of spermatogenesis leading to azoospermia before 40 years of age. They presented common features associated to patients affected by SMBA, such as gynecomastia, high level of CPK, muscle cramps, fasciculations, muscle wastage, and impaired swallowing. Two intracytoplasmic sperm injection (ICSI) cycles were performed in one of the patients resulting in fertilization failure. Molecular analysis of AR gene exon 1 revealed 54 CAG repeats in DNA extracted from leukocytes in affected patients and 22 repeats in the fertile non-affected brother. Severe impaired spermatogenesis of rapid progression has not been associated before to SBMA. This is the first report of assisted reproduction techniques indicated by male infertility in patients with this rare disorder. Further studies are required to confirm the unusual result of intracytoplasmic sperm injection cycles. We discuss the implications and possible pathogenesis of these unique features of SBMA in this family.

  4. Relationship between enzyme properties and disease progression in Canavan disease.

    Science.gov (United States)

    Zano, Stephen; Wijayasinghe, Yasanandana S; Malik, Radhika; Smith, Joshua; Viola, Ronald E

    2013-01-01

    Canavan disease (CD) is a fatal neurological disorder caused by defects in the gene that encodes for a critical metabolic enzyme. The enzyme aspartoacylase catalyzes the deacetylation of N-acetylaspartate to produce acetate required for fatty acid biosynthesis in the brain. The loss of aspartoacylase activity leads to the demyelination and disrupted brain development that is found in CD patients. Sixteen different clinical mutants of aspartoacylase have been cloned, expressed and purified to examine their properties and the relationship between enzyme properties and disease phenotype. In contrast to numerous cell culture studies that reported virtually complete loss of function, each of these purified mutant enzymes was found to have measureable catalytic activity. However, the activities of these mutants are diminished, by as little as three-fold to greater than 100-fold when compared to the native enzyme. Many of these mutated enzyme forms show decreased thermal stability and an increased propensity for denaturation upon exposure to urea, but only four of the 16 mutants examined showed both diminished thermal and diminished conformational stability. Significantly, each of these lower stability mutants are responsible for the more severe phenotypes of CD, while patients with milder forms of CD have aspartoacylase mutants with generally high catalytic activity and with either good thermal or good conformational stability. These results suggest that the loss of catalytic function and the accumulation of N-acetylaspartate in Canavan disease is at least partially a consequence of the decreased protein stability caused by these mutations.

  5. Bronchoalveolar lavage fluid and progression of scleroderma interstitial lung disease.

    Science.gov (United States)

    De Santis, Maria; Bosello, Silvia Laura; Peluso, Giusy; Pinnelli, Michela; Alivernini, Stefano; Zizzo, Gaetano; Bocci, Mario; Capacci, Annunziata; La Torre, Giuseppe; Mannocci, Alice; Pagliari, Gabriella; Varone, Francesco; Pistelli, Roberto; Danza, Francesco Maria; Ferraccioli, Gianfranco

    2012-01-01

    So far no clinical or experimental evidences clearly explain how and which systemic sclerosis (SSc) patients will experience a functional and radiological progression of interstitial lung disease (ILD). The aim of the study was to investigate whether any bronchoalveolar lavage fluid (BALF) characteristic, compared with clinical, functional and radiological parameters, is associated with the risk of progression of ILD and worse survival in SSc patients. Lung involvement was evaluated in 110 consecutively examined SSc patients with pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT); 73 patients with evidence of ILD on HRCT underwent BAL. The progression of ILD was evaluated with PFTs and HRCT after 1-year follow-up. A 36-month survival analysis was assessed. ILD patients with alveolitis had a higher risk to have restrictive lung disease and honeycombing, to experience a worsening in honeycombing score or to develop honeycombing. ILD progression was associated with the evidence of honeycombing on HRCT, with the presence of eosinophils, with an inverted CD4/CD8 ratio and with a higher CD19 percentage count in the BALF or with a positive BALF microbiological culture. The patients with ILD had a worse overall survival. The diffuse disease was the only independent risk factor of overall mortality, and the extent of honeycombing on HRCT was the only independent risk factor of lung disease-related mortality. Our study suggests the importance of evaluating ILD with HRCT and BAL in order to characterize the risk factors of SSc lung involvement progression. © 2010 Blackwell Publishing Ltd.

  6. Role of Diet and Nutritional Supplements in Parkinson’s Disease Progression

    Directory of Open Access Journals (Sweden)

    Laurie K. Mischley

    2017-01-01

    Full Text Available Objectives. The goal of this study is to describe modifiable lifestyle variables associated with reduced rate of Parkinson’s disease (PD progression. Methods. The patient-reported outcomes in PD (PRO-PD were used as the primary outcome measure, and a food frequency questionnaire (FFQ was used to assess dietary intake. In this cross-sectional analysis, regression analysis was performed on baseline data to identify the nutritional and pharmacological interventions associated with the rate of PD progression. All analyses were adjusted for age, gender, and years since diagnosis. Results. 1053 individuals with self-reported idiopathic PD were available for analysis. Foods associated with the reduced rate of PD progression included fresh vegetables, fresh fruit, nuts and seeds, nonfried fish, olive oil, wine, coconut oil, fresh herbs, and spices (P<0.05. Foods associated with more rapid PD progression include canned fruits and vegetables, diet and nondiet soda, fried foods, beef, ice cream, yogurt, and cheese (P<0.05. Nutritional supplements coenzyme Q10 and fish oil were associated with reduced PD progression (P=0.026 and P=0.019, resp., and iron supplementation was associated with faster progression (P=0.022. Discussion. These are the first data to provide evidence that targeted nutrition is associated with the rate of PD progression.

  7. The beneficial role of intensive exercise on Parkinson disease progression.

    Science.gov (United States)

    Frazzitta, Giuseppe; Balbi, Pietro; Maestri, Roberto; Bertotti, Gabriella; Boveri, Natalia; Pezzoli, Gianni

    2013-06-01

    In the last decade, a considerable number of articles has shown that exercise is effective in improving motor performance in Parkinson disease. In particular, recent studies have focused on the efficacy of intensive exercise in achieving optimal results in the rehabilitation of patients with Parkinson disease. The effects of intensive exercise in promoting cell proliferation and neuronal differentiation in animal models are reported in a large cohort of studies, and these neuroplastic effects are probably related to increased expression of a variety of neurotrophic factors. The authors outline the relation between intensive exercises and neuroplastic activity on animal models of Parkinson disease and discuss the clinical results of different intensive strategies on motor performance and disease progression in patients with Parkinson disease.

  8. Amyotrophic Lateral Sclerosis: A Focus on Disease Progression

    Science.gov (United States)

    Calvo, Ana C.; Manzano, Raquel; Mendonça, Deise M. F.; Muñoz, María J.; Zaragoza, Pilar

    2014-01-01

    Since amyotrophic lateral sclerosis (ALS) was discovered and described in 1869 as a neurodegenerative disease in which motor neuron death is induced, a wide range of biomarkers have been selected to identify therapeutic targets. ALS shares altered molecular pathways with other neurodegenerative diseases, such as Alzheimer's, Huntington's, and Parkinson's diseases. However, the molecular targets that directly influence its aggressive nature remain unknown. What is the first link in the neurodegenerative chain of ALS that makes this disease so peculiar? In this review, we will discuss the progression of the disease from the viewpoint of the potential biomarkers described to date in human and animal model samples. Finally, we will consider potential therapeutic strategies for ALS treatment and future, innovative perspectives. PMID:25157374

  9. Imaging and CFD in the analysis of vascular disease progression

    Science.gov (United States)

    Saloner, David; Acevedo-Bolton, Gabriel; Rayz, Vitaliy; Wintermark, Max; Martin, Alastair; Dispensa, Brad; Young, William; Lawton, Michael; Rapp, Joseph; Jou, Liang-Der

    2006-03-01

    Conventional evaluation of the significance of vascular disease has focused on estimates of geometric factors. There is now substantial interest in investigating whether the onset and progression of vascular pathology can be related to hemodynamic factors. Current imaging modalities have excellent capabilities in delineating the geometric boundaries of the vascular lumen. Advanced non-invasive imaging modalities such as Multi Detector CT and MRI are also able to define the extent of disease within the vessel wall and to provide information on the composition of thrombotic and atherosclerotic components. Finally, it is also possible to use imaging techniques to measure flow velocities across the lumen of vessels of interest, and to determine the pulsatile variation of these velocities through the cardiac cycle. Despite these advanced capabilities, imaging alone is unable to determine important features of the vascular hemodynamics such as wall shear stress or pressure distributions. However, the information on lumenal geometry and the inlet and outlet flow conditions can be used as input into numerical simulation models that are able to predict those quantities. These Computational Fluid Dynamics models can be used to predict hemodynamic parameters on a patient-specific basis. It is therefore possible to use non-invasive imaging methods to follow the progression of vascular disease over time, and to relate changes in lumenal and wall structure to calculated hemodynamic descriptors. This approach can be used not only to understand the natural progression of vascular disease, but as a tool to predict the likely outcome of a surgical intervention.

  10. An unusual case of rapidly progressive contractures: Case report and brief review

    Directory of Open Access Journals (Sweden)

    Subasree R

    2008-01-01

    Full Text Available An 8-year-old boy, diagnosed as cervical dystonia, was referred to our tertiary center. After a trivial trauma he had developed painful lumps in the axial region, which was followed by restricted movements of neck, shoulder, and abdominal muscles over 4 months. He had kyphoscoliosis, torticollis, rigid abdomen, and multiple muscle contractures. He also had short great toes. A detailed skeletal survey showed calcification in the soft tissues surrounding the shoulder anterior chest wall, thorax, and paraspinal muscles; there was also beaking of vertebrae, which was confirmed by CT thorax. This report showcases the diagnostic challenge posed by myositis ossificans progressiva, which can rarely cause rapidly progressing muscle contractures. A brief review of literature is also presented.

  11. Lung Transplantation for FLNA-Associated Progressive Lung Disease.

    Science.gov (United States)

    Burrage, Lindsay C; Guillerman, R Paul; Das, Shailendra; Singh, Shipra; Schady, Deborah A; Morris, Shaine A; Walkiewicz, Magdalena; Schecter, Marc G; Heinle, Jeffrey S; Lotze, Timothy E; Lalani, Seema R; Mallory, George B

    2017-07-01

    To describe a series of patients with pathogenic variants in FLNA and progressive lung disease necessitating lung transplantation. We conducted a retrospective chart review of 6 female infants with heterozygous presumed loss-of-function pathogenic variants in FLNA whose initial presentation was early and progressive respiratory failure. Each patient received lung transplantation at an average age of 11 months (range, 5-15 months). All patients had pulmonary arterial hypertension and chronic respiratory failure requiring tracheostomy and escalating levels of ventilator support before transplantation. All 6 patients survived initial lung transplantation; however, 1 patient died after a subsequent heart-lung transplant. The remaining 5 patients are living unrestricted lives on chronic immunosuppression at most recent follow-up (range, 19 months to 11.3 years post-transplantation). However, in all patients, severe ascending aortic dilation has been observed with aortic regurgitation. Respiratory failure secondary to progressive obstructive lung disease during infancy may be the presenting phenotype of FLNA-associated periventricular nodular heterotopia. We describe a cohort of patients with progressive respiratory failure related to a pathogenic variant in FLNA and present lung transplantation as a viable therapeutic option for this group of patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Advanced and rapidly progressing head and neck cancer: good palliation following intralesional bleomycin.

    LENUS (Irish Health Repository)

    Quintyne, Keith Ian

    2011-09-01

    The authors herein report the case of a 61-year-old man undergoing adjuvant therapy for locally advanced laryngeal cancer, who developed parastomal recurrence in his radiation field around his tracheotomy site, while he was undergoing radiation therapy, and compromised the secure placement of his tracheotomy tube and maintenance of his upper airway. MRI restaging and biopsy confirmed recurrence and progressive disease in his mediastinum. He underwent local therapy with intralesional bleomycin with good palliation, and ability to maintain the patency of his upper airway.

  13. Progress in treatment of Charcot-Marie-Tooth disease

    Directory of Open Access Journals (Sweden)

    Ru-xu ZHANG

    2017-09-01

    Full Text Available Charcot-Marie-Tooth disease (CMT comprises a group of monogenic inherited peripheral neuropathies with highly clinical and genetic heterogeneity, more than 80 causative genes have been cloned at present. Usually starts in childhood or juvinile period, the main clinical manifestations include progressive length.dependent muscle weakness and atrophy, sensory loss, areflexia and pes cavus. Although there is no specific treatment to reverse the natural disease course of CMT, symptomatic treatments such as rehabilitation, orthopedic surgery and medication can improve the overall fitness and life quality of CMT patients. Targeted treatments based on pathogenesis study is expected to provide precise therapy for CMT patients. This paper aims to make a review of the clinical application of symptomatic treatments and progress of target therapy researches in different CMT subtypes. DOI: 10.3969/j.issn.1672-6731.2017.08.003

  14. Effects of Lowering LDL Cholesterol on Progression of Kidney Disease

    DEFF Research Database (Denmark)

    Haynes, Richard; Lewis, David; Emberson, Jonathan

    2014-01-01

    Lowering LDL cholesterol reduces the risk of developing atherosclerotic events in CKD, but the effects of such treatment on progression of kidney disease remain uncertain. Here, 6245 participants with CKD (not on dialysis) were randomly assigned to simvastatin (20 mg) plus ezetimibe (10 mg) daily...... or matching placebo. The main prespecified renal outcome was ESRD (defined as the initiation of maintenance dialysis or kidney transplantation). During 4.8 years of follow-up, allocation to simvastatin plus ezetimibe resulted in an average LDL cholesterol difference (SEM) of 0.96 (0.02) mmol/L compared...... with placebo; rate ratio, 0.93; 95% CI, 0.86 to 1.01; P=0.09). Exploratory analyses also showed no significant effect on the rate of change in eGFR. Lowering LDL cholesterol by 1 mmol/L did not slow kidney disease progression within 5 years in a wide range of patients with CKD....

  15. Progression of disease preceding lower extremity amputation in Denmark

    DEFF Research Database (Denmark)

    Jensen, Pia Søe; Petersen, Janne; Kirketerp-Møller, Klaus

    2017-01-01

    OBJECTIVES: Patients with non-traumatic lower extremity amputation are characterised by high age, multi-morbidity and polypharmacy and long-term complications of atherosclerosis and diabetes. To ensure early identification of patients at risk of amputation, we need to gain knowledge about...... the progression of diseases related to lower extremity amputations during the years preceding the amputation. DESIGN: A retrospective population-based national registry study. SETTING: The study includes data on demographics, diagnoses, surgery, medications and healthcare services from five national registries....... Data were retrieved from 14 years before until 1 year after the amputation. Descriptive statistics were used to describe the progression of diseases and use of medication and healthcare services. PARTICIPANTS: An unselected cohort of patients (≥50 years; n=2883) subjected to a primary non...

  16. Male patients presenting with rapidly progressive puberty associated with malignant tumors

    Directory of Open Access Journals (Sweden)

    Soo Jung Kim

    2016-03-01

    Full Text Available In males, precocious puberty (PP is defined as the development of secondary sexual characteristics before age 9 years. PP is usually idiopathic; though, organic abnormalities including tumors are more frequently found in male patients with PP. However, advanced puberty in male also can be an important clinical manifestation in tumors. We report 2 cases of rapidly progressive puberty in males, each associated with a germ-cell tumor. First, an 11-year-old boy presented with mild fever and weight loss for 1 month. Physical examination revealed a pubertal stage of G3P3 with 10-mL testes. Investigations revealed advanced bone age (16 years with elevated basal luteinizing hormone and testosterone levels. An anterior mediastinal tumor was identified by chest radiography and computed tomography, and elevated α-fetoprotein (AFP and β-human chorionic gonadotropin (β-hCG levels were noted. Histopathologic analysis confirmed a yolk-sac tumor. Second, a 12-year-old boy presented with diplopia, polydipsia, and polyuria for 4 months. Physical examination revealed a pubertal stage of G3P3 with 8-mL testes. Bone age was advanced (16 years and laboratory tests indicated panhypopituitarism with elevated testosterone level. A mixed germ-cell tumor was diagnosed with elevated AFP and β-hCG levels. Of course, these patients also have other symptoms of suspecting tumors, however, rapidly progressive puberty can be the more earlier screening sign of tumors. Therefore, in male patients with accelerated or advanced puberty, malignancy should be considered, with evaluation of tumor markers. In addition, advanced puberty in male should be recognized more widely as a unique sign of neoplasm.

  17. Progressive focal degenerative disease of the posterior associative cortex.

    Science.gov (United States)

    Attig, E; Jacquy, J; Uytdenhoef, P; Roland, H

    1993-05-01

    A 72-year-old man developed a very progressive neuropsychologic deficit 6 years ago, beginning with isolated visual topographic memory disturbances and visuo-constructive apraxia without additional manifestations of dementia. The syndrome worsened thereafter with the emergence of visual agnosia, simultagnosia, psychic paralysis of gaze, auditivo-verbal agnosia, and recently an amnestic syndrome with confabulation and confusion (at the end of 1989). CT scans, which remained unchanged over the years, showed mild, focal atrophic changes revealed by dilatation of the right occipital horn. His angiograms were normal. Two SPECT studies (with HMPAO measurements), performed 6 years from the onset, detected marked hypoperfusion in both parieto-occipital regions, mainly on the right side. Progressive focal degenerative disease without dementia is a relatively new syndrome, especially in cases with progressive aphasia. As noted in our patient, progressive disturbances initially localized in the right parieto-occipital region followed by posterior bilobar degeneration (pronounced on the right side) without dementia until late in the course may represent another exceptionally reported characteristic of this new syndrome. It is suggested that this variant of the Mesulam syndrome is more likely explained by progressive atrophy of the Alzheimer type.

  18. Disease Severity and Progression in Progressive Supranuclear Palsy and Multiple System Atrophy: Validation of the NNIPPS – PARKINSON PLUS SCALE

    Science.gov (United States)

    Payan, Christine A. M.; Viallet, François; Landwehrmeyer, Bernhard G.; Bonnet, Anne-Marie; Borg, Michel; Durif, Franck; Lacomblez, Lucette; Bloch, Frédéric; Verny, Marc; Fermanian, Jacques; Agid, Yves; Ludolph, Albert C.

    2011-01-01

    Background The Natural History and Neuroprotection in Parkinson Plus Syndromes (NNIPPS) study was a large phase III randomized placebo-controlled trial of riluzole in Progressive Supranuclear Palsy (PSP, n = 362) and Multiple System Atrophy (MSA, n = 398). To assess disease severity and progression, we constructed and validated a new clinical rating scale as an ancillary study. Methods and Findings Patients were assessed at entry and 6-montly for up to 3 years. Evaluation of the scale's psychometric properties included reliability (n = 116), validity (n = 760), and responsiveness (n = 642). Among the 85 items of the initial scale, factor analysis revealed 83 items contributing to 15 clinically relevant dimensions, including Activity of daily Living/Mobility, Axial bradykinesia, Limb bradykinesia, Rigidity, Oculomotor, Cerebellar, Bulbar/Pseudo-bulbar, Mental, Orthostatic, Urinary, Limb dystonia, Axial dystonia, Pyramidal, Myoclonus and Tremor. All but the Pyramidal dimension demonstrated good internal consistency (Cronbach α≥0.70). Inter-rater reliability was high for the total score (Intra-class coefficient = 0.94) and 9 dimensions (Intra-class coefficient = 0.80–0.93), and moderate (Intra-class coefficient = 0.54–0.77) for 6. Correlations of the total score with other clinical measures of severity were good (rho≥0.70). The total score was significantly and linearly related to survival (p<0.0001). Responsiveness expressed as the Standardized Response Mean was high for the total score slope of change (SRM = 1.10), though higher in PSP (SRM = 1.25) than in MSA (SRM = 1.0), indicating a more rapid progression of PSP. The slope of change was constant with increasing disease severity demonstrating good linearity of the scale throughout disease stages. Although MSA and PSP differed quantitatively on the total score at entry and on rate of progression, the relative contribution of clinical dimensions to overall

  19. Disease severity and progression in progressive supranuclear palsy and multiple system atrophy: validation of the NNIPPS--Parkinson Plus Scale.

    Directory of Open Access Journals (Sweden)

    Christine A M Payan

    Full Text Available The Natural History and Neuroprotection in Parkinson Plus Syndromes (NNIPPS study was a large phase III randomized placebo-controlled trial of riluzole in Progressive Supranuclear Palsy (PSP, n = 362 and Multiple System Atrophy (MSA, n = 398. To assess disease severity and progression, we constructed and validated a new clinical rating scale as an ancillary study.Patients were assessed at entry and 6-montly for up to 3 years. Evaluation of the scale's psychometric properties included reliability (n = 116, validity (n = 760, and responsiveness (n = 642. Among the 85 items of the initial scale, factor analysis revealed 83 items contributing to 15 clinically relevant dimensions, including Activity of daily Living/Mobility, Axial bradykinesia, Limb bradykinesia, Rigidity, Oculomotor, Cerebellar, Bulbar/Pseudo-bulbar, Mental, Orthostatic, Urinary, Limb dystonia, Axial dystonia, Pyramidal, Myoclonus and Tremor. All but the Pyramidal dimension demonstrated good internal consistency (Cronbach α ≥ 0.70. Inter-rater reliability was high for the total score (Intra-class coefficient = 0.94 and 9 dimensions (Intra-class coefficient = 0.80-0.93, and moderate (Intra-class coefficient = 0.54-0.77 for 6. Correlations of the total score with other clinical measures of severity were good (rho ≥ 0.70. The total score was significantly and linearly related to survival (p<0.0001. Responsiveness expressed as the Standardized Response Mean was high for the total score slope of change (SRM = 1.10, though higher in PSP (SRM = 1.25 than in MSA (SRM = 1.0, indicating a more rapid progression of PSP. The slope of change was constant with increasing disease severity demonstrating good linearity of the scale throughout disease stages. Although MSA and PSP differed quantitatively on the total score at entry and on rate of progression, the relative contribution of clinical dimensions to overall severity and progression was similar.The NNIPPS-PPS has suitable validity, is

  20. [Parkinson Disease With Rapid Eye Movement Sleep Behavior Disorder].

    Science.gov (United States)

    Hu, Yang; Zhang, Wei

    2015-06-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by lack of muscle atonia during REM sleep and enactment of dream content. RBD is associated with Parkinson disease (PD) and has high incidence in PD patients. PD patient with RBD mainly presents rigid type, has longer disease duration, more severe motor and non-motor symptoms and poorer activity of daily living and life quality. The pathophysiological mechanisms of RBD may be related to dysfunctions of pontine tegmentum, locus coeruleus/sub-locus coeruleus complex and related projections. The diagnosis of RBD depends on clinical histories and video-polysomnography (v-PSG). Besides treatment for PD, protective measures have to be taken for patients and their sleep partners. If abnormal behaviors during sleep cause distress and danger,patients should be given drug therapy.

  1. Progression of Alzheimer disease in Europe: data from the European ICTUS study.

    Science.gov (United States)

    Vellas, B; Hausner, L; Frölich, L; Cantet, C; Gardette, V; Reynish, E; Gillette, S; Agüera-Morales, E; Auriacombe, S; Boada, M; Bullock, R; Byrne, J; Camus, V; Cherubini, A; Eriksdotter-Jönhagen, M; Frisoni, G B; Hasselbalch, S; Jones, R W; Martinez-Lage, P; Rikkert, M O; Tsolaki, M; Ousset, P-J; Pasquier, F; Ribera-Casado, J M; Rigaud, A S; Robert, P; Rodriguez, G; Salmon, E; Salva, A; Scheltens, P; Schneider, A; Sinclair, A; Spiru, L; Touchon, J; Zekry, D; Winblad, B; Andrieu, S

    2012-10-01

    The clinical progression of Alzheimer disease (AD) was studied in European subjects under treatment with AChE inhibitors (AChE-I) in relation to geographical location over a 2-years period. One thousand three hundred and six subjects from 11 European countries were clustered into 3 regions (North, South, West) and investigated with biannual follow-up over 2 years. Primary outcomes were cognitive, functional and behavioral measures. Caregiver burden, hospital admission and admission to nursing home were also recorded. Participant cognitive function declined non-linearly over time (MMSE: -1.5 pts/first year, -2.5 pts/second year; ADAScog: + 3.5 pts/first year, + 4.8 pts/second year), while the progression of behavioral disturbances (NPI scale) was linear. Neither scale showed regional differences, and progression of the disease was similar across Europe despite different health care systems. Functional decline (ADL, IADL) tended to progress more rapidly in Southern Europe (p=0.09), while progression of caregiver burden (Zarit Burden Interview) was most rapid in Northern Europe (5.6 pts/y, p=0.04). Incidences of hospital admission (10.44, 95%CI: 8.13-12.75, p < 0.001) and admission to nursing home (2.97, 95%CI: 1.83-4.11, p < 0.001) were lowest in Southern Europe. In general cognitive and functional decline was slower than in former cohorts. European geographical location reflecting differences in culture and in health care system does not impact on the progression of AD but does influence the management of AD subjects and caregiver burden.

  2. Clinical features and predictors for disease natural progression in adults with Pompe disease: a nationwide prospective observational study

    Directory of Open Access Journals (Sweden)

    van der Beek Nadine AME

    2012-11-01

    Full Text Available Abstract Background Due partly to physicians’ unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression. Methods We conducted a single-center, prospective, observational study. Muscle strength (manual muscle testing, and hand-held dynamometry, muscle function (quick motor function test, and pulmonary function (forced vital capacity in sitting and supine positions were assessed every 3–6 months and analyzed using repeated-measures ANOVA. Results Between October 2004 and August 2009, 94 patients aged between 25 and 75 years were included in the study. Although skeletal muscle weakness was typically distributed in a limb-girdle pattern, many patients had unfamiliar features such as ptosis (23%, bulbar weakness (28%, and scapular winging (33%. During follow-up (average 1.6 years, range 0.5-4.2 years, skeletal muscle strength deteriorated significantly (mean declines of −1.3% point/year for manual muscle testing and of −2.6% points/year for hand-held dynamometry; both p15 years and pulmonary involvement (forced vital capacity in sitting position Conclusions Recognizing patterns of common and less familiar characteristics in adults with Pompe disease facilitates timely diagnosis. Longer disease duration and reduced pulmonary function stand out as predictors of rapid disease progression, and aid in deciding whether to initiate enzyme replacement therapy, or when.

  3. A cumulative genetic risk score predicts progression in Parkinson's disease.

    Science.gov (United States)

    Pihlstrøm, Lasse; Morset, Kristina Rebekka; Grimstad, Espen; Vitelli, Valeria; Toft, Mathias

    2016-04-01

    The contribution of genetic variability to clinical heterogeneity in Parkinson's disease is insufficiently understood. We aimed to investigate the effect of cumulative genetic risk on clinical outcomes. In a single-center study of 336 patients we genotyped 19 independent susceptibility variants identified in genome-wide association studies of Parkinson's disease. We tested for association between a cumulative genetic risk score and 3 outcome measures: survival, time until progression to Hoehn and Yahr stage 3, and Unified Parkinson's Disease Rating Scale motor score severity. Genetic risk score was significantly associated with time from diagnosis to Hoehn and Yahr stage 3 in a Cox regression model (P = 0.010). We observed no clear association for the other outcomes. We present results linking cumulative genetic risk to a motor outcome in Parkinson's disease. Our findings provide a valuable starting point for future large-scale efforts to map the genetic determinants of phenotypic variability. © 2016 International Parkinson and Movement Disorder Society.

  4. Alzheimer's disease: a mathematical model for onset and progression

    CERN Document Server

    Bertsch, Michiel; Marcello, Norina; Tesi, Maria Carla; Tosin, Andrea

    2015-01-01

    In this paper we propose a mathematical model for the onset and progression of Alzheimer's disease based on transport and diffusion equations. We regard brain neurons as a continuous medium, and structure them by their degree of malfunctioning. Two different mechanisms are assumed to be relevant for the temporal evolution of the disease: i) diffusion and agglomeration of soluble polymers of amyloid, produced by damaged neurons; ii) neuron-to-neuron prion-like transmission. We model these two processes by a system of Smoluchowski equations for the amyloid concentration, coupled to a kinetic-type transport equation for the distribution function of the degree of malfunctioning of neurons. The second equation contains an integral term describing the random onset of the disease as a jump process localized in particularly sensitive areas of the brain. Even though we deliberately neglect many aspects of the complexity of the brain and the disease, numerical simulations are in good qualitative agreement with clinical...

  5. Wegener's granulomatosis: report of a case with rapidly progressive glomerulonephritis and diabetes mellitus.

    Science.gov (United States)

    Kakoi, H; Hiraide, F; Nishizawa, S; Inouye, T; Yoshizawa, N

    1986-01-01

    A patient with the classic form of Wegener's granulomatosis with severe dabetes mellitus and rapidly progressive glomerulonephritis is described. This 61-year-old male presented with epistaxis and nasal pain and obstruction. The nasal cavities were filled with crusts covering eroded mucosa. The diagnosis was made by biopsy of nasal and bronchial mucosa, and laboratory data. The epistaxis was stopped by 10 Gy irradiation over the nasal cavities. The patient had severe diabetes mellitus. His blood sugar was not controlled by diet and insulin injection. His general condition worsened rapidly as the growth of granuloma in the nose and lung. Accordingly, prednisolone therapy reinitiated to suppress the granuloma although it has a reverse effect on diabetes mellitus. Approximately one month after admission, he died of acute renal failure. Autopsy was carried out. Granulomatous lesions were noted in the nasal cavities, lungs and spleen. Many petechiae were found macroscopically over the cortex of the kidney. Hyalinization or sclerosis with crescent formation was found microscopically in estimated 85% of the glomeruli. Immunohistologic analysis of the renal tissue demonstrated an irregular linear pattern deposition of IgG, IgA and C3 and a granular pattern deposition of IgM and C1q.

  6. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis.

    Science.gov (United States)

    Anstee, Quentin M; Targher, Giovanni; Day, Christopher P

    2013-06-01

    NAFLD is a spectrum of progressive liver disease that encompasses simple steatosis, NASH, fibrosis and, ultimately, cirrhosis. NAFLD is recognized as the hepatic component of the metabolic syndrome, as these conditions have insulin resistance as a common pathophysiological mechanism. Therefore, NAFLD is strongly associated with type 2 diabetes mellitus and abdominal obesity. As lifestyles have become increasingly sedentary and dietary patterns have changed, the worldwide prevalence of NAFLD has increased dramatically and is projected to be the principal aetiology for liver transplantation within the next decade. Importantly, a growing body of clinical and epidemiological evidence suggests that NAFLD is associated not only with liver-related morbidity and mortality, but also with an increased risk of developing both cardiovascular disease and type 2 diabetes mellitus. This article reviews the evidence that suggests NAFLD is a multisystem disease and the factors that might determine interindividual variation in the development and progression of its major hepatic and extrahepatic manifestations (principally type 2 diabetes mellitus and cardiovascular disease).

  7. Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss

    Science.gov (United States)

    Bonafede, Lucas; Ficicioglu, Can H.; Serrano, Leona; Han, Grace; Morgan, Jessica I. W.; Mills, Monte D.; Forbes, Brian J.; Davidson, Stefanie L.; Binenbaum, Gil; Kaplan, Paige B.; Nichols, Charles W.; Verloo, Patrick; Leroy, Bart P.; Maguire, Albert M.; Aleman, Tomas S.

    2015-01-01

    Purpose To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Methods Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Results Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Conclusions Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC. PMID:26658511

  8. Does correction of metabolic acidosis slow chronic kidney disease progression?

    Science.gov (United States)

    Goraya, Nimrit; Wesson, Donald E

    2013-03-01

    Most patients with chronic kidney disease (CKD) have progressive decline in glomerular filtration rate (GFR), despite current treatment practices. Recent studies support that dietary acid reduction with oral sodium based alkali or base-inducing food types add kidney protection to that provided by current kidney-protective interventions. Related studies also support that correction of metabolic acidosis with dietary acid reduction slows CKD progression. We reviewed these recent studies that show improvement in CKD parameters and slower CKD progression in response to improvement of CKD-associated metabolic acidosis with these interventions. Animal as well as human models of CKD show that alkali treatment ameliorates indices of kidney injury and also might slow GFR decline in patients with or without metabolic acidosis. These benefits have been similar with oral sodium-based alkali and base-inducing fruits and vegetables, supporting dietary acid reduction as an effective adjunct to conventional kidney-protective interventions. Recent studies suggest that metabolic acidosis mediates nephropathy progression, and its treatment with the comparatively inexpensive and well tolerated intervention of dietary acid reduction holds promise to be an additional kidney-protective strategy in CKD management.

  9. Biomarkers of Renal Disease and Progression in Patients with Diabetes

    Directory of Open Access Journals (Sweden)

    Radovan Hojs

    2015-05-01

    Full Text Available Diabetes prevalence is increasing worldwide, mainly due to the increase in type 2 diabetes. Diabetic nephropathy occurs in up to 40% of people with type 1 or type 2 diabetes. It is important to identify patients at risk of diabetic nephropathy and those who will progress to end stage renal disease. In clinical practice, most commonly used markers of renal disease and progression are serum creatinine, estimated glomerular filtration rate and proteinuria or albuminuria. Unfortunately, they are all insensitive. This review summarizes the evidence regarding the prognostic value and benefits of targeting some novel risk markers for development of diabetic nephropathy and its progression. It is focused mainly on tubular biomarkers (neutrophil-gelatinase associated lipocalin, kidney injury molecule 1, liver-fatty acid-binding protein, N-acetyl-beta-d-glucosaminidase, markers of inflammation (pro-inflammatory cytokines, tumour necrosis factor-α and tumour necrosis factor-α receptors, adhesion molecules, chemokines and markers of oxidative stress. Despite the promise of some of these new biomarkers, further large, multicenter prospective studies are still needed before they can be used in everyday clinical practice.

  10. Progression of kidney disease in elderly stage 3 and 4 chronic kidney disease patients.

    Science.gov (United States)

    Arora, Pradeep; Jalal, Kabir; Gupta, Anu; Carter, Randolph L; Lohr, James W

    2017-06-01

    The prevalence of chronic kidney disease (CKD) has been rising steadily in the elderly population. We studied the rate of progression of CKD in this population and the factors associated with progression of CKD to better identify patients who are likely to progress to ESRD. This was an observational study including 4562 patients older than 65 years with two outpatient estimated glomerular filtration rates (eGFRs) of 60 ml/min/1.73 m(2) (March 1, 2001, and March 31, 2008) at VA healthcare facilities. Patients with eGFR 4 ml/min/1.73 m(2). Mean age of the study participants was 77.2 years. 24.3% were diabetics. 4.3% had proteinuria. In univariate comparison of different rates of progression, 54.2% patients had an annual rate of progression of disease, diabetes mellitus, and proteinuria were associated with significantly increased rate of progression of CKD. Serum albumin and hemoglobin level were inversely associated with progression of CKD. CKD progresses at a slower rate in the elderly population. We have identified risk factors associated with an increased risk of progression of CKD in the elderly. This may help to improve health care planning and resource utilization.

  11. Kinetics of disease progression and host response in a rat model of bubonic plague.

    Science.gov (United States)

    Sebbane, Florent; Gardner, Donald; Long, Daniel; Gowen, Brian B; Hinnebusch, B Joseph

    2005-05-01

    Plague, caused by the gram-negative bacterium Yersinia pestis, primarily affects rodents but is also an important zoonotic disease of humans. Bubonic plague in humans follows transmission by infected fleas and is characterized by an acute, necrotizing lymphadenitis in the regional lymph nodes that drain the intradermal flea bite site. Septicemia rapidly follows with spread to spleen, liver, and other organs. We developed a model of bubonic plague using the inbred Brown Norway strain of Rattus norvegicus to characterize the progression and kinetics of infection and the host immune response after intradermal inoculation of Y. pestis. The clinical signs and pathology in the rat closely resembled descriptions of human bubonic plague. The bacteriology; histopathology; host cellular response in infected lymph nodes, blood, and spleen; and serum cytokine levels were analyzed at various times after infection to determine the kinetics and route of disease progression and to evaluate hypothesized Y. pestis pathogenic mechanisms. Understanding disease progression in this rat infection model should facilitate further investigations into the molecular pathogenesis of bubonic plague and the immune response to Y. pestis at different stages of the disease.

  12. Effect of Urate Lowering Therapy on Renal Disease Progression in Hyperuricemic Patients with Chronic Kidney Disease.

    Science.gov (United States)

    Kim, Yoonjin; Shin, Sungjoon; Kim, Kyungsoo; Choi, Sangtae; Lee, Kwanghoon

    2015-11-01

    To determine whether urate lowering therapy (ULT) could delay renal disease progression in hyperuricemic patients with chronic kidney disease (CKD). We performed a retrospective review of hyperuricemic patients with stage 3 CKD followed from September 2005 to July 2014 in Dongguk University Ilsan Hospital, Goyang, Korea. A total of 158 eligible patients were identified and 65 of them were treated with ULT in addition to the usual CKD management. We divided the patients according to the use of ULT and compared the estimated glomerular filtration rate (eGFR) change from baseline value and the proportion of renal disease progression (decline of eGFR > 30% of the baseline value, initiation of dialysis or eGFR renal disease progression were identified by logistic regression analysis. After a median followup of 118.5 weeks (minimum 25, maximum 465), the ULT group showed better outcomes compared to the non-ULT group in terms of eGFR change from baseline (-1.19 ± 12.07 vs -7.37 ± 11.17 ml/min/1.73 m(2), p = 0.001) and the proportion of renal disease progression (12.3% vs 27.9%, p = 0.01). Goal-directed ULT showed better clinical outcomes compared to maintaining the initial ULT dose. Actual (area under the SUA-time curve adjusted by total observation time period) serum uric acid was significantly associated with the risk of renal disease progression (p for trend = 0.04) and actual serum uric acid level renal disease progression by 69.4%. ULT significantly delayed renal disease progression in hyperuricemic patients with CKD. Goal-directed ULT seems to be better than continuing the initial ULT prescription.

  13. Urinary endotrophin predicts disease progression in patients with chronic kidney disease

    DEFF Research Database (Denmark)

    Rasmussen, Daniel Guldager Kring; Fenton, Anthony; Jesky, Mark

    2017-01-01

    Renal fibrosis is the central pathogenic process in progression of chronic kidney disease (CKD). Collagen type VI (COL VI) is upregulated in renal fibrosis. Endotrophin is released from COL VI and promotes pleiotropic pro-fibrotic effects. Kidney disease severity varies considerably and accurate...... of 499 CKD patients. Endotrophin localised to areas of increased COL VI deposition in fibrotic kidneys but was not present in histologically normal kidneys. The third and fourth quartiles of urinary endotrophin:creatinine ratio (ECR) were independently associated with one-year disease progression after...... information regarding CKD progression may improve clinical decisions. We tested the hypothesis that urinary endotrophin derived during COL VI deposition in fibrotic human kidneys is a marker for progression of CKD in the Renal Impairment in Secondary Care (RIISC) cohort, a prospective observational study...

  14. The MPTP/probenecid model of progressive Parkinson's disease.

    Science.gov (United States)

    Carta, Anna R; Carboni, Ezio; Spiga, Saturnino

    2013-01-01

    Parkinson's disease (PD) is characterized by a progressive degeneration of dopamine (DA) neurons and a chronic loss of motor functions. The investigation of progressive degenerative mechanisms and possible neuroprotective approaches for PD depends upon the development of an experimental animal model that reproduces the neuropathology observed in humans. This chapter describes the generation of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTPp) chronic mouse model of PD. This model displays key features of PD, including impairment of motor and olfactory functions associated with partial loss of tyrosine hydroxylase-positive neurons and DA levels in the brain. The MPTPp mouse model provides an important tool for the study of mechanisms contributing to the pathological dysfunction of PD at the cellular and whole animal level.

  15. Measles viral load may reflect SSPE disease progression

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    Jin L

    2006-06-01

    Full Text Available Abstract Subacute sclerosing panencephalitis (SSPE is a rare, slowly progressive neurological disorder caused by the persistent infection with measles virus (MV. Despite much research into SSPE, its pathology remains obscure. We examined autopsy tissues of eight SSPE patients by real time quantitative PCR, immunohistochemistry and immunoblotting to determine viral load. MV N, M and H gene RNA could be detected in the central nervous system (CNS of all patients and in two non-CNS tissues of one patient. The viral burden between patients differed up to four-fold by quantitative PCR and corresponded with detection of MV protein. The level of both viral RNA and antigen in the brain may correlate with disease progression.

  16. Rapidly progressive polyneuropathy due to dry beriberi in a man: a case report

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    Lekwuwa Godwin

    2010-12-01

    Full Text Available Abstract Introduction We describe a case of rapidly progressive and severely debilitating polyneuropathy in a patient with confirmed hypovitaminosis B1, consistent with dry beriberi. Crucially, this is a treatable condition, although sometimes with incomplete recovery, but it is probably under-recognized yet increasingly common given increasing levels of alcohol abuse in the western world. Case presentation A 49-year-old Caucasian British man presented with progressive weakness of both lower limbs of approximately seven months' duration. He noted difficulty climbing stairs. He also complained of lethargy, and loss of muscle bulk, including his thighs. He had a history of type 2 diabetes mellitus and admitted prior alcohol abuse but denied excessive alcohol intake in the five years prior to presentation. Initial clinical and neurophysiological examinations were consistent with a mild peripheral neuropathy and probable proximal myopathy. However, over the subsequent four months he evolved a marked tetraparesis, with profound sensory disturbance of all limbs. Repeat neurophysiology revealed a widespread polyneuropathy with extensive acute and sub-acute denervation changes in all four limbs, and reduced or absent sensory nerve action potentials. Hypovitaminosis B1 was confirmed (45 nmol/L, reference range 66-200 nmol/L. His rapid clinical deterioration was in keeping with dry beriberi. He was treated with thiamine. Subsequent follow-up revealed slow but significant improvement, such that by 15-16 months from the initial onset of symptoms, and approximately six months after the onset of his marked tetraparesis, he was able to stand independently and was gradually gaining confidence in walking pending a period of in-patient neurorehabilitation. Conclusion A potentially wide differential diagnosis exists for this type of presentation. Confirming hypovitaminosis B1 by requesting the assay prior to vitamin replacement ensures accurate diagnosis and

  17. Homeostasis of metals in the progression of Alzheimer's disease.

    Science.gov (United States)

    González-Domínguez, Raúl; García-Barrera, Tamara; Gómez-Ariza, José Luis

    2014-06-01

    In order to study the involvement of metals in the progression of Alzheimer's disease, serum samples from patients with Alzheimer and mild cognitive impairment were investigated. For this purpose, metal content was analyzed after size-fractionation of species and then, inter-element and inter-fraction ratios were computed. In this way, the analysis allowed discovering changes that could be used as markers of disease, but also provided a new insight into the interactions in the homeostasis of elements in neurodegeneration and its progression. Aluminum and labile forms of iron and copper were increased in demented patients, while manganese, zinc and selenium were reduced. Interestingly, levels of different elements, principally iron, aluminum and manganese, were closely inter-related, which could evidence a complex interdependency between the homeostasis of the different metals in this disorder. On the other hand, imbalances in metabolism of copper, zinc and selenium could be associated to abnormal redox status. Therefore, this study may contribute to our understanding of the pathological mechanisms related to metals in Alzheimer's disease.

  18. Quantifying Parkinson's disease progression by simulating gait patterns

    Science.gov (United States)

    Cárdenas, Luisa; Martínez, Fabio; Atehortúa, Angélica; Romero, Eduardo

    2015-12-01

    Modern rehabilitation protocols of most neurodegenerative diseases, in particular the Parkinson Disease, rely on a clinical analysis of gait patterns. Currently, such analysis is highly dependent on both the examiner expertise and the type of evaluation. Development of evaluation methods with objective measures is then crucial. Physical models arise as a powerful alternative to quantify movement patterns and to emulate the progression and performance of specific treatments. This work introduces a novel quantification of the Parkinson disease progression using a physical model that accurately represents the main gait biomarker, the body Center of Gravity (CoG). The model tracks the whole gait cycle by a coupled double inverted pendulum that emulates the leg swinging for the single support phase and by a damper-spring System (SDP) that recreates both legs in contact with the ground for the double phase. The patterns generated by the proposed model are compared with actual ones learned from 24 subjects in stages 2,3, and 4. The evaluation performed demonstrates a better performance of the proposed model when compared with a baseline model(SP) composed of a coupled double pendulum and a mass-spring system. The Frechet distance measured differences between model estimations and real trajectories, showing for stages 2, 3 and 4 distances of 0.137, 0.155, 0.38 for the baseline and 0.07, 0.09, 0.29 for the proposed method.

  19. Tracking motor impairments in the progression of Huntington's disease.

    Science.gov (United States)

    Long, Jeffery D; Paulsen, Jane S; Marder, Karen; Zhang, Ying; Kim, Ji-In; Mills, James A

    2014-03-01

    The Unified Huntington's Disease Rating Scale is used to characterize motor impairments and establish motor diagnosis. Little is known about the timing of diagnostic confidence level categories and the trajectory of motor impairments during the prodromal phase. Goals of this study were to estimate the timing of categories, model the prodromal trajectory of motor impairments, estimate the rate of motor impairment change by category, and provide required sample size estimates for a test of efficacy in clinical trials. In total, 1010 gene-expanded participants from the Neurobiological Predictors of Huntington's Disease (PREDICT-HD) trial were analyzed. Accelerated failure time models were used to predict the timing of categories. Linear mixed effects regression was used to model the longitudinal motor trajectories. Age and length of gene expansion were incorporated into all models. The timing of categories varied significantly by gene expansion, with faster progression associated with greater expansion. For the median expansion, the third diagnostic confidence level category was estimated to have a first occurrence 1.5 years before diagnosis, and the second and first categories were estimated to occur 6.75 years and 19.75 years before diagnosis, respectively. Motor impairments displayed a nonlinear prodromal course. The motor impairment rate of change increased as the diagnostic confidence level increased, with added acceleration for higher progression scores. Motor items can detect changes in motor impairments before diagnosis. Given a sufficiently high progression score, there is evidence that the diagnostic confidence level can be used for prodromal staging. Implications for Huntington's disease research and the planning of clinical trials of efficacy are discussed. © 2013 International Parkinson and Movement Disorder Society.

  20. Semantic Memory in the Clinical Progression of Alzheimer Disease.

    Science.gov (United States)

    Tchakoute, Christophe T; Sainani, Kristin L; Henderson, Victor W

    2017-09-01

    Semantic memory measures may be useful in tracking and predicting progression of Alzheimer disease. We investigated relationships among semantic memory tasks and their 1-year predictive value in women with Alzheimer disease. We conducted secondary analyses of a randomized clinical trial of raloxifene in 42 women with late-onset mild-to-moderate Alzheimer disease. We assessed semantic memory with tests of oral confrontation naming, category fluency, semantic recognition and semantic naming, and semantic density in written narrative discourse. We measured global cognition (Alzheimer Disease Assessment Scale, cognitive subscale), dementia severity (Clinical Dementia Rating sum of boxes), and daily function (Activities of Daily Living Inventory) at baseline and 1 year. At baseline and 1 year, most semantic memory scores correlated highly or moderately with each other and with global cognition, dementia severity, and daily function. Semantic memory task performance at 1 year had worsened one-third to one-half standard deviation. Factor analysis of baseline test scores distinguished processes in semantic and lexical retrieval (semantic recognition, semantic naming, confrontation naming) from processes in lexical search (semantic density, category fluency). The semantic-lexical retrieval factor predicted global cognition at 1 year. Considered separately, baseline confrontation naming and category fluency predicted dementia severity, while semantic recognition and a composite of semantic recognition and semantic naming predicted global cognition. No individual semantic memory test predicted daily function. Semantic-lexical retrieval and lexical search may represent distinct aspects of semantic memory. Semantic memory processes are sensitive to cognitive decline and dementia severity in Alzheimer disease.

  1. Immune evasion mechanisms of Entamoeba histolytica: progression to disease

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    Sharmin eBegum

    2015-12-01

    Full Text Available Entamoeba histolytica (Eh is a protozoan parasite that infects 10% of the world’s population and results in 100,000 deaths/year from amebic dysentery and/or liver abscess. In most cases, this extracellular parasite colonizes the colon by high affinity binding to MUC2 mucin without disease symptoms, whereas in some cases, Eh triggers an aggressive inflammatory response upon invasion of the colonic mucosa. The specific host-parasite factors critical for disease pathogenesis are still not well characterized. From the parasite, the signature events that lead to disease progression are cysteine protease cleavage of the C-terminus of MUC2 that dissolves the mucus layer followed by Eh binding and cytotoxicity of the mucosal epithelium. The host mounts an ineffective excessive host pro-inflammatory response following contact with host cells that causes tissue damage and participates in disease pathogenesis as Eh escapes host immune clearance by mechanisms that are not completely understood. Ameba can modulate or destroy effector immune cells by inducing neutrophil apoptosis and suppressing respiratory burst or nitric oxide (NO production from macrophages. Eh adherence to the host cells also induce multiple cytotoxic effects that can promote cell death through phagocytosis, apoptosis or by trogocytosis (ingestion of living cells that might play critical roles in immune evasion. This review focuses on the immune evasion mechanisms that Eh uses to survive and induce disease manifestation in the host.

  2. HPLC method for rapidly following biodiesel fuel transesterification reaction progress using a core-shell column

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Samuel J.; Ott, Lisa S. [California State University, Chico, CA (United States)

    2012-07-15

    There are a wide and growing variety of feedstocks for biodiesel fuel. Most commonly, these feedstocks contain triglycerides which are transesterified into the fatty acid alkyl esters (FAAEs) which comprise biodiesel fuel. While the tranesterification reaction itself is simple, monitoring the reaction progress and reaction products is not. Gas chromatography-mass spectrometry is useful for assessing the FAAE products, but does not directly address either the tri-, di-, or monoglycerides present from incomplete transesterification or the free fatty acids which may also be present. Analysis of the biodiesel reaction mixture is complicated by the solubility and physical property differences among the components of the tranesterification reaction mixture. In this contribution, we present a simple, rapid HPLC method which allows for monitoring all of the main components in a biodiesel fuel transesterification reaction, with specific emphasis on the ability to monitor the reaction as a function of time. The utilization of a relatively new, core-shell stationary phase for the HPLC column allows for efficient separation of peaks with short elution times, saving both time and solvent. (orig.)

  3. A rapidly progressing Pancoast syndrome due to pulmonary mucormycosis: a case report

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    Hiatt Kim M

    2011-08-01

    Full Text Available Abstract Introduction Pancoast syndrome is characterized by Horner syndrome, shoulder pain radiating down the arm, compression of the brachial blood vessels, and, in long-standing cases, atrophy of the arm and hand muscles. It is most commonly associated with lung carcinoma but rarely is seen with certain infections. Case presentation We present the case of a 51-year-old Caucasian man who had acute myeloid leukemia and who developed a rapidly fulminating pneumonia along with signs and symptoms of acute brachial plexopathy and left Horner syndrome. Also, a purpuric plaque developed over his left chest wall and progressed to skin necrosis. The skin biopsy and bronchoalveolar lavage showed a Rhizopus species, leading to a diagnosis of mucormycosis. This is a rare case of pneumonia due to mucormycosis associated with acute Pancoast syndrome. Conclusions According to our review of the literature, only a few infectious agents have been reported to be associated with Pancoast syndrome. We found only three case reports of mucormycosis associated with acute Pancoast syndrome. Clinicians should consider mucormycosis in their differential diagnosis in a patient with pulmonary lesions and chest wall invasion with or without neurological symptoms, especially in the setting of neutropenia or other immunosuppressed conditions. It is important to recognize this condition early in order to target therapy and interventions.

  4. Research Progress of Intestinal Microbiota in Inflammatory Bowel Diseases

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    Shao-shun YE

    2017-06-01

    Full Text Available Inflammatory bowel disseases (IBD are chronic recurrent diseases occurring in the gastrointestinal tract, mainly including ulcerative colitis (UC and Crohn’s disease (CD. At present, the etiological factors and mechanism of IBD are still unclear yet. However, it is widely believed that IBD is caused by immune dysfunction, genetic factors, gut barrier dysfuction and dysbacteriosis, change of dietary structure, use of antibiotics, smoking, and environment. Studies suggest that breaking the accurate balance between host and intestinal microbiota in patients with IBD can trigger immuno-inflammatory responses in genetically susceptible individuals. Therefore, regulating intestinal microbiota disturbance and recovery of intestinal homeostasis between host and intestinal microbiota become a new treatment direction for IBD. This article mainly reviewed research progress of intestinal microbiota in pathogenetic mechanism and treatment of IBD.

  5. Acidosis: progression of chronic kidney disease and quality of life.

    Science.gov (United States)

    de-Brito Ashurst, Ione; O'Lone, Emma; Kaushik, Tarun; McCafferty, Kieran; Yaqoob, Muhammad M

    2015-06-01

    Metabolic acidosis (MA) is relatively common in patients with chronic kidney disease (CKD) particularly in stages 4 and 5. It is assumed to play a contributory role in the development of several complications including bone disease, skeletal muscle wasting, altered protein synthesis, and degradation. Recent evidence also suggests that even mild acidosis might play a role in progressive glomerular filtration rate loss. Experimental and clinical studies suggest that correction of acidosis by alkali therapy attenuates these complications and improves quality of life. Despite several recent small and single-center studies supporting this notion, more robust evidence is required with regard to the long-term benefits of alkali therapy, type of alkali supplements, and the optimal level of serum bicarbonate.

  6. Cytokines: Roles in atherosclerosis disease progression and potential therapeutic targets

    Science.gov (United States)

    Moss, Joe W. E.; Ramji, Dipak P.

    2017-01-01

    Atherosclerosis, the primary cause of cardiovascular disease (CVD), is a chronic inflammatory disorder in the walls of medium and large arteries. CVD is currently responsible for about one in three global deaths and this is expected to rise in the future due to an increase in the prevalence of obesity and diabetes. Current therapies for atherosclerosis mainly modulate lipid homeostasis and whilst successful at reducing the risk of a CVD-related death, they are associated with considerable residual risk and various side effects. There is therefore a need for alternative therapies aimed at regulating inflammation in order to reduce atherogenesis. This review will highlight the key role cytokines play during disease progression as well as potential therapeutic strategies to target them. PMID:27357616

  7. Progress in treatment of nonalcoholic fatty liver disease

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    SHI Junping

    2014-08-01

    Full Text Available The incidence of nonalcoholic fatty liver disease (NAFLD increases with the prevalence of obesity, but specific treatment for this disease is lacking. First, the possible clinical benefits from different strategies of lifestyle modification, as well as the methods for improving intervention effect and existing problems, are reviewed. Second, the indications for bariatric surgery and the main research directions are briefly presented. Finally, several promising drugs including vitamin E, farnesoid X receptor agonist, intestinal probiotics, polyunsaturated fatty acids, glucagon-like peptide-1 receptor agonist, and pentoxifylline are elaborated on. The currently acquired clinical evidence and progress in basic research suggest that lifestyle modification is the basis for treatment in all patients with NAFLD, but better schemes are needed to improve the intervention effect; bariatric surgery is one of the effective therapies for NAFLD patients with morbid obesity who have no relevant contraindications; drug treatment should be selectively applied to the population with a confirmed diagnosis of NAFLD.

  8. Directed progression brain networks in Alzheimer's disease: properties and classification.

    Science.gov (United States)

    Friedman, Eric J; Young, Karl; Asif, Danial; Jutla, Inderjit; Liang, Michael; Wilson, Scott; Landsberg, Adam S; Schuff, Norbert

    2014-06-01

    This article introduces a new approach in brain connectomics aimed at characterizing the temporal spread in the brain of pathologies like Alzheimer's disease (AD). The main instrument is the development of "directed progression networks" (DPNets), wherein one constructs directed edges between nodes based on (weakly) inferred directions of the temporal spreading of the pathology. This stands in contrast to many previously studied brain networks where edges represent correlations, physical connections, or functional progressions. In addition, this is one of a few studies showing the value of using directed networks in the study of AD. This article focuses on the construction of DPNets for AD using longitudinal cortical thickness measurements from magnetic resonance imaging data. The network properties are then characterized, providing new insights into AD progression, as well as novel markers for differentiating normal cognition (NC) and AD at the group level. It also demonstrates the important role of nodal variations for network classification (i.e., the significance of standard deviations, not just mean values of nodal properties). Finally, the DPNets are utilized to classify subjects based on their global network measures using a variety of data-mining methodologies. In contrast to most brain networks, these DPNets do not show high clustering and small-world properties.

  9. Pharmacotherapy of Parkinson’s disease:Progress or regress?

    Directory of Open Access Journals (Sweden)

    Karolina Pytka

    2013-07-01

    Full Text Available Parkinson’s disease (PD is a chronic, progressive disease of the central nervous system (CNS,characterized by a slow loss of dopaminergic neurons in the substantia nigra, leading to significantdecrease in dopamine (DA levels in the striatum. Currently used drugs, such as levodopa(L-DOPA, amantadine, dopamine agonists (D or anticholinergic drugs, are not effective enough,and do not eliminate the causes of disease. Many research centers are conducting researchon new forms of currently used drugs (e.g. Duodopa, XP21279, IPX066, new drugs of alreadyknown groups (e.g. safinamide, medicines that suppress side effects of L-DOPA (e.g. AFQ056,fipamezole, and, finally, compounds with a novel mechanism of action (e.g. PMY50028, A2Areceptor antagonists. A lot of scientific reports indicate an important role of A2A receptorsin the regulation of the central movement system, so a new group of compounds – selectiveantagonists of A2A receptors (e.g. istradefylline, preladenant, SYN115 – has been developed and their potential use in PD has been examined. Clinical studies of A2A receptor antagonistshave shown that this group of compounds can shorten off periods and at the same time theydo not worsen dyskinesias in patients with PD. Moreover, there is ongoing research on newforms of treatment, such as gene therapy. Attempts to apply the viral vector AAV-2, whichwill be able to infect neurons with a variety of genes, including the gene of glutamate decarboxylase(GAD, neurturin (NTN, or aromatic L-amino acid decarboxylase, are currently beingcarried out. The results of phase I and II clinical studies showed some efficacy of this form oftreatment, but the method requires further studies. An analysis of potential future therapiesof Parkinson’s disease suggests that some progress in this field has been made.

  10. Characteristics and Progression of Preclinical Inflammatory Bowel Disease.

    Science.gov (United States)

    Rodríguez-Lago, Iago; Merino, Olga; Azagra, Irene; Maiz, Ainara; Zapata, Eva; Higuera, Rebeca; Montalvo, Isabel; Fernández-Calderón, María; Arreba, Paz; Carrascosa, Juan; Iriarte, Ainara; Portillo, Isabel; Aguirre, Urko; Barreiro-de Acosta, Manuel; Muñoz-Navas, Miguel; Cabriada, José Luis

    2017-11-11

    Inflammatory bowel disease (IBD) is a chronic disease usually diagnosed after the appearance of gastrointestinal symptoms. Little is known about IBD progression during its early and even preclinical phases. We aimed to determine the number of new incidental diagnoses of IBD in an older population, and evaluate disease progression from its early stages. We performed a retrospective analysis of 31,005 colonoscopies performed during colorectal cancer screening of patients with positive results from fecal immunochemical tests, at 11 centers in the Basque Country (Spain) from 2009 through 2014. We collected clinical and laboratory data from all asymptomatic individuals suspected to have IBD during screening colonoscopies, with histologic confirmation. Colonoscopy screening led to 79 new diagnoses of ulcerative colitis, 24 of Crohn's disease, and 7 of unclassified colitis (average patient age, 57 y; interquartile range, 52-62 y; 57% male). Eleven patients had symptoms before colonoscopy and were excluded from the analysis. Among those patients who were asymptomatic at diagnosis, 36% developed symptoms after a follow-up period of 25 months (interquartile range, 10.5-42 mo), mostly rectal bleeding and diarrhea. Treatment was prescribed for 81 patients (88%), and 2 cases required surgery. We analyzed data from a large cohort of patients with IBD diagnosed at early or even preclinical stages, from an older population. New incidental diagnoses of IBD were made in 0.35% of individuals undergoing a population-based screening colonoscopy-most were classified as ulcerative colitis. Approximately one third of patients developed symptoms during the follow-up period. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Plasma Leucine-Rich α-2-Glycoprotein 1 Predicts Rapid eGFR Decline and Albuminuria Progression in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Liu, Jian-Jun; Pek, Sharon Li Ting; Ang, Kevin; Tavintharan, Subramaniam; Lim, Su Chi

    2017-10-01

    Abnormal angiogenesis plays an important role in pathogenesis of diabetic kidney disease (DKD). Leucine-rich α-2 glycoprotein 1 (LRG1) is a newly identified angiogenic factor. To study whether plasma LRG1 may independently predict progression of DKD in individuals with type 2 diabetes mellitus (T2DM). Prospective cohort study in a regional hospital. In total, 1226 T2DM participants were followed for a mean ± standard deviation (SD) of 3.1 ± 0.4 years. Albuminuria progression was defined as elevation in albuminuria level to a higher category. Chronic kidney disease (CKD) progression [rapid estimated glomerular filtration rate (eGFR) decline] was defined as a 40% or greater deterioration in eGFR in 3 years. Both participants with albuminuria progression and those with CKD progression had higher plasma LRG1 levels at baseline. LRG1 independently predicted albuminuria progression above traditional risk factors, including baseline eGFR and urine albumin to creatinine ratio. A 1-SD increment in LRG1 was associated with a 1.26-fold [95% confidence interval (CI), 1.04 to 1.53, P = 0.018] higher adjusted risk for albuminuria progression. The association of LRG1 with microalbuminuria to macroalbuminuria progression was stronger than its association with normoalbuminuria to microalbuminuria progression [odds ratio (OR), 1.51; 95% CI, 1.04 to 2.18, P = 0.029 vs OR, 1.09; 95% CI, 0.86 to 1.37, P = 0.486, per 1-SD LRG1 increment]. Also, LRG1 independently predicted CKD progression above traditional risk factors. A 1-SD increment in LRG1 was associated with a 1.48-fold (95% CI, 1.04 to 2.11, P = 0.032) higher adjusted risk for CKD progression. Plasma LRG1 predicts both albuminuria and CKD progression beyond traditional risk factors. It may play a role in the pathologic pathway leading to progression of DKD in T2DM.

  12. Progressive Coronary Dilatation Predicts Worse Outcome in Kawasaki Disease.

    Science.gov (United States)

    Chih, Wan-Ling; Wu, Pei-Yuan; Sun, Li-Chuang; Lin, Ming-Tai; Wang, Jou-Kou; Wu, Mei-Hwan

    2016-04-01

    To explore the implication of serial coronary changes on the late coronary outcomes in patients with Kawasaki disease (KD) with coronary aneurysms ≧ 4 mm. We performed a retrospective review of 78 patients with KD with large coronary aneurysms (1980-2013, male: 76.9%; 792 patient-years). Progressive coronary dilatation was defined for those with progressive enlargement of coronary arteries in 3 consecutive echocardiograms. We studied 27 patients with KD with giant aneurysms (≧ 8 mm) and 51 patients with KD with medium aneurysms (4-8 mm). All the giant and 43.1% of medium aneurysms persisted during the study period. For the patients with giant aneurysms, their 10-year freedom from acute myocardial infarction/cardiovascular death and all ischemia was 66% and 52%, respectively. The median intervals for the aneurysm diameters reaching their peak were 3.3 months (giant) and 0.25 months (medium), respectively. In patients with giant aneurysms, the 10-year freedom from ischemia was much lower in those with progressive coronary dilatation (28% vs 59%, P = .021). In patients with medium aneurysms, the probability of 5-year persistence of aneurysm was much greater (67.2% vs 14.8%, P outcomes in the patients with KD who had aneurysms larger than 4 mm. In addition to coronary diameters 1 month after the onset of KD, progressive coronary dilatation at 2 or more months after diagnosis may be an indicator of duration, and the severity of vasculitis and adverse dilative remodeling were associated with worse late coronary outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Modeling Disease Progression via Multisource Multitask Learners: A Case Study With Alzheimer's Disease.

    Science.gov (United States)

    Nie, Liqiang; Zhang, Luming; Meng, Lei; Song, Xuemeng; Chang, Xiaojun; Li, Xuelong

    2017-07-01

    Understanding the progression of chronic diseases can empower the sufferers in taking proactive care. To predict the disease status in the future time points, various machine learning approaches have been proposed. However, a few of them jointly consider the dual heterogeneities of chronic disease progression. In particular, the predicting task at each time point has features from multiple sources, and multiple tasks are related to each other in chronological order. To tackle this problem, we propose a novel and unified scheme to coregularize the prior knowledge of source consistency and temporal smoothness. We theoretically prove that our proposed model is a linear model. Before training our model, we adopt the matrix factorization approach to address the data missing problem. Extensive evaluations on real-world Alzheimer's disease data set have demonstrated the effectiveness and efficiency of our model. It is worth mentioning that our model is generally applicable to a rich range of chronic diseases.

  14. Alzheimer's disease: a mathematical model for onset and progression.

    Science.gov (United States)

    Bertsch, Michiel; Franchi, Bruno; Marcello, Norina; Tesi, Maria Carla; Tosin, Andrea

    2017-06-01

    In this article we propose a mathematical model for the onset and progression of Alzheimer's disease based on transport and diffusion equations. We regard brain neurons as a continuous medium and structure them by their degree of malfunctioning. Two different mechanisms are assumed to be relevant for the temporal evolution of the disease: i) diffusion and agglomeration of soluble polymers of amyloid, produced by damaged neurons and ii) neuron-to-neuron prion-like transmission. We model these two processes by a system of Smoluchowski equations for the amyloid concentration, coupled to a kinetic-type transport equation for the distribution function of the degree of malfunctioning of neurons. The second equation contains an integral term describing the random onset of the disease as a jump process localized in particularly sensitive areas of the brain. Our numerical simulations are in good qualitative agreement with clinical images of the disease distribution in the brain which vary from early to advanced stages. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  15. Rapid Progression of Metastatic Pulmonary Calcification and Alveolar Hemorrhage in a Patient with Chronic Renal Failure and Primary Hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Eun Joo; Kim, Dong Hun; Yoon, Seong Ho [Chosun University College of Medicine, Gwangju (Korea, Republic of); Suk, Eun Ha [Dept. of Anaesthesiology and Pain Medicine, Seonam University College of Medicine, Namwon (Korea, Republic of)

    2013-06-15

    Metastatic pulmonary calcification (MPC) is common in patients with chronic renal failure. The authors experienced a patient with chronic renal failure and primary hyperparathyroidism by parathyroid adenoma accompanied with rapid progressions of MPC and alveolar hemorrhage. Recent chest radiographs, compared with previous chest radiographs, showed rapid accumulation of calcification in both upper lungs. Following up on the high-resolution CT scan after five years demonstrates more increased nodules in size and ground glass opacity. The patient was diagnosed with MPC and alveolar hemorrhage by transbronchial lung biopsy. We assumed rapid progression of MPC and alveolar hemorrhage in underlying chronic renal failures could be a primary hyperparathyroidism which may be caused by parathyroid adenoma detected incidentally. Therefore parathyroid adenoma was treated with ethanol injections. Herein, we have reported on CT findings of MPC with alveolar hemorrhage and reviewed our case along with other articles.

  16. EYS Mutations Causing Autosomal Recessive Retinitis Pigmentosa: Changes of Retinal Structure and Function with Disease Progression

    Directory of Open Access Journals (Sweden)

    David B. McGuigan

    2017-07-01

    Full Text Available Mutations in the EYS (eyes shut homolog gene are a common cause of autosomal recessive (ar retinitis pigmentosa (RP. Without a mammalian model of human EYS disease, there is limited understanding of details of disease expression and rates of progression of the retinal degeneration. We studied clinically and with chromatic static perimetry, spectral-domain optical coherence tomography (OCT, and en face autofluoresence imaging, a cohort of 15 patients (ages 12–51 at first visit, some of whom had longitudinal data of function and structure. Rod sensitivity was able to be measured by chromatic perimetry in most patients at their earliest visits and some patients retained patchy rod function into the fifth decade of life. As expected from RP, cone sensitivity persisted after rod function was no longer measurable. The photoreceptor nuclear layer of the central retina was abnormal except at the fovea in most patients at first visit. Perifoveal disease measured over a period of years indicated that photoreceptor structural loss was followed by dysmorphology of the inner retina and loss of retinal pigment epithelial integrity. Although there could be variability in severity, preliminary analyses of the rates of vision loss suggested that EYS is a more rapidly progressive disease than other ciliopathies causing arRP, such as USH2A and MAK.

  17. Drosophila provides rapid modeling of renal development, function, and disease

    Science.gov (United States)

    Romero, Michael F.

    2010-01-01

    The evolution of specialized excretory cells is a cornerstone of the metazoan radiation, and the basic tasks performed by Drosophila and human renal systems are similar. The development of the Drosophila renal (Malpighian) tubule is a classic example of branched tubular morphogenesis, allowing study of mesenchymal-to-epithelial transitions, stem cell-mediated regeneration, and the evolution of a glomerular kidney. Tubule function employs conserved transport proteins, such as the Na+, K+-ATPase and V-ATPase, aquaporins, inward rectifier K+ channels, and organic solute transporters, regulated by cAMP, cGMP, nitric oxide, and calcium. In addition to generation and selective reabsorption of primary urine, the tubule plays roles in metabolism and excretion of xenobiotics, and in innate immunity. The gene expression resource FlyAtlas.org shows that the tubule is an ideal tissue for the modeling of renal diseases, such as nephrolithiasis and Bartter syndrome, or for inborn errors of metabolism. Studies are assisted by uniquely powerful genetic and transgenic resources, the widespread availability of mutant stocks, and low-cost, rapid deployment of new transgenics to allow manipulation of renal function in an organotypic context. PMID:20926630

  18. Albumin contributes to kidney disease progression in Alport syndrome.

    Science.gov (United States)

    Jarad, George; Knutsen, Russell H; Mecham, Robert P; Miner, Jeffrey H

    2016-07-01

    Alport syndrome is a familial kidney disease caused by defects in the collagen type IV network of the glomerular basement membrane. Lack of collagen-α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. To directly investigate the role that albumin plays in the progression of disease in Alport syndrome, we generated albumin knockout (Alb(-/-)) mice to use as a tool for removing albuminuria as a component of kidney disease. Mice lacking albumin were healthy and indistinguishable from control littermates, although they developed hypertriglyceridemia. Dyslipidemia was observed in Alb(+/-) mice, which displayed half the normal plasma albumin concentration. Alb mutant mice were bred to collagen-α3(IV) knockout (Col4a3(-/-)) mice, which are a model for human Alport syndrome. Lack of circulating and filtered albumin in Col4a3(-/-);Alb(-/-) mice resulted in dramatically improved kidney disease outcomes, as these mice lived 64% longer than did Col4a3(-/-);Alb(+/+) and Col4a3(-/-);Alb(+/-) mice, despite similar blood pressures and serum triglyceride levels. Further investigations showed that the absence of albumin correlated with reduced transforming growth factor-β1 signaling as well as reduced tubulointerstitial, glomerular, and podocyte pathology. We conclude that filtered albumin is injurious to kidney cells in Alport syndrome and perhaps in other proteinuric kidney diseases, including diabetic nephropathy. Copyright © 2016 the American Physiological Society.

  19. Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer's disease

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    Gross Hyman

    2008-07-01

    Full Text Available Abstract Background Recent clinical studies point to rapid and sustained clinical, cognitive, and behavioral improvement in both Alzheimer's disease and primary progressive aphasia following weekly perispinal administration of etanercept, a TNF-alpha inhibitor that acts by blocking the binding of this cytokine to its receptors. This outcome is concordant with recent basic science studies suggesting that TNF-alpha functions in vivo as a gliotransmitter that regulates synaptic function in the brain. We hypothesized that perispinal etanercept had the potential to improve verbal function in Alzheimer's disease, so we included several standarized measures of verbal ability to evaluate language skills in a clinical trial of perispinal etanercept for Alzheimer's disease. Methods This was a prospective, single-center, open-label, pilot study, in which 12 patients with mild-to-severe Alzheimer's disease were administered etanercept, 25–50 mg, weekly by perispinal administration for six months. Two additional case studies are presented. Results Two-tailed, paired t-tests were conducted comparing baseline performance to 6-month performance on all neuropsychological measures. Test batteries included the California Verbal Learning Test-Second Edition, Adult Version; Logical Memory I and II(WMS-LM-II from the Wechsler Memory Scale-Abbreviated; the Comprehensive Trail Making Test (TMT; Boston Naming Test; and letter(FAS and category verbal fluency. All measures revealed a significant effect except for the Boston Naming Test and the TMT-4, with WMS-LM-II being marginally significant at p = .05. The FAS test for letter fluency was most highly significant with a p Conclusion In combination with the previously reported results of perispinal etanercept in Alzheimer's disease and primary progressive aphasia, these results further argue that larger scale studies of this therapeutic intervention, including Phase 3 trials, are warranted in dementias. In addition

  20. Blood platelets in the progression of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Nina S Gowert

    Full Text Available Alzheimer's disease (AD is characterized by neurotoxic amyloid-ß plaque formation in brain parenchyma and cerebral blood vessels known as cerebral amyloid angiopathy (CAA. Besides CAA, AD is strongly related to vascular diseases such as stroke and atherosclerosis. Cerebrovascular dysfunction occurs in AD patients leading to alterations in blood flow that might play an important role in AD pathology with neuronal loss and memory deficits. Platelets are the major players in hemostasis and thrombosis, but are also involved in neuroinflammatory diseases like AD. For many years, platelets were accepted as peripheral model to study the pathophysiology of AD because platelets display the enzymatic activities to generate amyloid-ß (Aß peptides. In addition, platelets are considered to be a biomarker for early diagnosis of AD. Effects of Aß peptides on platelets and the impact of platelets in the progression of AD remained, however, ill-defined. The present study explored the cellular mechanisms triggered by Aß in platelets. Treatment of platelets with Aß led to platelet activation and enhanced generation of reactive oxygen species (ROS and membrane scrambling, suggesting enhanced platelet apoptosis. More important, platelets modulate soluble Aß into fibrillar structures that were absorbed by apoptotic but not vital platelets. This together with enhanced platelet adhesion under flow ex vivo and in vivo and platelet accumulation at amyloid deposits of cerebral vessels of AD transgenic mice suggested that platelets are major contributors of CAA inducing platelet thrombus formation at vascular amyloid plaques leading to vessel occlusion critical for cerebrovascular events like stroke.

  1. Diagnosis of Parkinson’s disease: progress and future prospects

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    Patel RA

    2015-07-01

    Full Text Available Roshni A Patel,1 Jennifer G Goldman2 1Rush Medical College, Rush University, Chicago, IL, USA; 2Section of Parkinson’s Disease and Movement Disorders, Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA Abstract: This review focuses on methods for diagnosing Parkinson’s disease (PD, highlighting clinical, pathological, and biomarker-driven approaches. For each of these diagnostic approaches, the past, present, and future prospects of diagnosing PD will be explored. Our understanding of PD – its pathogenesis and clinical spectrum – is ever changing. PD is now recognized as a complex multisystem disorder with motor and nonmotor features, including those preceding the onset of classic motor features as well as different phenotypes, often associated with different genetic mutations. Theories regarding the pathophysiology of PD and the role of α-synuclein, its deposition outside of the central nervous system, and possible progression or propagation are discussed. It has been almost 200 years since James Parkinson first described this disorder, and since then, our understanding of the disease process has evolved and become more sophisticated. However, the clinical diagnostic criteria used have remained fairly static for decades. Proposals for redefining PD’s diagnostic criteria incorporate clinical, pathological, and biomarker-driven elements, individually and/or collectively, and may need to consider whether individualized risk and personalized profiles could be ascertained. Keywords: α-synuclein, biomarker, cerebrospinal fluid, imaging, neuropathology

  2. Rapidly Progressive Pancreatic Lipomatosis in a Young Adult Patient with Transfusion-dependent Myelodysplastic Syndrome

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    Wei-Ching Lin

    2007-08-01

    Full Text Available Pancreatic lipomatosis is defined as deposition of fat cells in pancreatic parenchyma. Although the etiology of this condition is still unclear, it is not uncommon in the elderly obese individuals, and a variety of transfusion-dependent hematologic diseases such as β-thalassemia major. Pancreatic lipomatosis associated with transfusion-dependent myelodysplastic syndrome (MDS has never been reported. We present a 17-year-old male patient with transfusion-dependent MDS. He received transfusion of a total of 345 units of blood in a period of 18 months but without iron chelating agent. Progressive fatty replacement of the pancreas parenchyma was found by a series of computed tomography images over seven hospital admissions due to repeated infections. Bone marrow biopsy revealed hemosiderin deposition. Because of his poor response to induction chemotherapy, stem cell transplantation was suggested, but the patient died of sepsis before the therapeutic procedure could take place. Although most patients with pancreatic lipomatosis have neither clinical symptoms nor abnormal laboratory data, it may cause endocrine and exocrine pancreas dysfunction. In this reported case, mild exocrine dysfunction was noted on the last admission. Clinicians should be cautious of hemosiderin deposition after large amount of blood transfusion and chelating therapy should be given to avoid iron overload.

  3. Progress in the molecular diagnosis of Lyme disease.

    Science.gov (United States)

    Ružić-Sabljić, Eva; Cerar, Tjaša

    2017-01-01

    Current laboratory testing of Lyme borreliosis mostly relies on serological methods with known limitations. Diagnostic modalities enabling direct detection of pathogen at the onset of the clinical signs could overcome some of the limitations. Molecular methods detecting borrelial DNA seem to be the ideal solution, although there are some aspects that need to be considered. Areas covered: This review represent summary and discussion of the published data obtained from literature searches from PubMed and The National Library of Medicine (USA) together with our own experience on molecular diagnosis of Lyme disease. Expert commentary: Molecular methods are promising and currently serve as supporting diagnostic testing in Lyme borreliosis. Since the field of molecular diagnostics is under rapid development, molecular testing could become an important diagnostic modality.

  4. Assessing Risk of Disease Progression and Pharmacological Management of Autosomal Dominant Polycystic Kidney Disease

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    Steven Soroka

    2017-03-01

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is the most common inherited renal disorder worldwide. The disease is characterized by renal cysts and progressive renal failure due to progressive enlargement of cysts and renal fibrosis. An estimated 45% to 70% of patients with ADPKD progress to end-stage renal disease by age 65 years. Although both targeted and nontargeted therapies have been tested in patients with ADPKD, tolvaptan is currently the only pharmacological therapy approved in Canada for the treatment of ADPKD. The purpose of this consensus recommendation is to develop an evidence-informed recommendation for the optimal management of adult patients with ADPKD. This document focuses on the role of genetic testing, the role of renal imaging, predicting the risk of disease progression, and pharmacological treatment options for ADPKD. These areas of focus were derived from 2 national surveys that were disseminated to nephrologists and patients with ADPKD with the aim of identifying unmet needs in the management of ADPKD in Canada. Specific recommendations are provided for the treatment of ADPKD with tolvaptan.

  5. Assessing Risk of Disease Progression and Pharmacological Management of Autosomal Dominant Polycystic Kidney Disease

    Science.gov (United States)

    Soroka, Steven; Alam, Ahsan; Bevilacqua, Micheli; Girard, Louis-Philippe; Komenda, Paul; Loertscher, Rolf; McFarlane, Philip; Pandeya, Sanjaya; Tam, Paul; Bichet, Daniel G.

    2017-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder worldwide. The disease is characterized by renal cysts and progressive renal failure due to progressive enlargement of cysts and renal fibrosis. An estimated 45% to 70% of patients with ADPKD progress to end-stage renal disease by age 65 years. Although both targeted and nontargeted therapies have been tested in patients with ADPKD, tolvaptan is currently the only pharmacological therapy approved in Canada for the treatment of ADPKD. The purpose of this consensus recommendation is to develop an evidence-informed recommendation for the optimal management of adult patients with ADPKD. This document focuses on the role of genetic testing, the role of renal imaging, predicting the risk of disease progression, and pharmacological treatment options for ADPKD. These areas of focus were derived from 2 national surveys that were disseminated to nephrologists and patients with ADPKD with the aim of identifying unmet needs in the management of ADPKD in Canada. Specific recommendations are provided for the treatment of ADPKD with tolvaptan. PMID:28321325

  6. Syndrome of rapid onset end stage renal disease in incident Mayo Clinic chronic hemodialysis patient

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    M. A. C. Onuigbo

    2014-01-01

    Full Text Available Despite decades of research, a full understanding of chronic kidney disease (CKD-end stage renal disease (ESRD progression remains elusive. The common consensus is a predictable, linear, progressive and time-dependent decline of CKD to ESRD. Acute kidney injury (AKI on CKD is usually assumed to be transient, with recovery as the expected outcome. AKI-ESRD association in current nephrology literature is blamed on the so-called "residual confounding." We had previously described a relationship between AKI events and rapid onset yet irreversible ESRD happening in a continuum in a high-risk CKD cohort. However, the contribution of the syndrome of rapid onset-ESRD (SORO-ESRD to incident United States ESRD population remained conjectural. In this retrospective analysis, we analyzed serum creatinine trajectories of the last 100 consecutive ESRD patients in 4 Mayo Clinic chronic hemodialysis units to determine the incidence of SORO-ESRD. Excluding 9 patients, 31 (34% patients, including two renal transplant recipients, had SORO-ESRD: 18 males and 13 females age 72 (range 50-92 years. Precipitating AKI followed pneumonia (8, acutely decompensated heart failure (7, pyelonephritis (4, post-operative (5, sepsis (3, contrast-induced nephropathy (2, and others (2. Time to dialysis was shortest following surgical procedures. Concurrent renin angiotensin aldosterone system blockade was higher with SORO-ESRD - 23% versus 5%, P = 0.0113. In conclusion, SORO-ESRD is not uncommon among the incident general US ESRD population. The implications for ESRD care planning, AV-fistula-first programs, general CKD care and any associations with renal ageing/senescence warrant further study.

  7. Plasma viscosity increase with progression of peripheral arterial atherosclerotic disease.

    Science.gov (United States)

    Poredos, P; Zizek, B

    1996-03-01

    -macroglobulin (r=0.78, P < 0.01). These results indicate that in patients with peripheral arterial disease plasma viscosity increases with the progression of the atherosclerotic process and is correlated with the clinical stages of the disease.

  8. Progressive changes in a recognition memory network in Parkinson's disease.

    Science.gov (United States)

    Segura, Bàrbara; Ibarretxe-Bilbao, Naroa; Sala-Llonch, Roser; Baggio, Hugo Cesar; Martí, María Jose; Valldeoriola, Francesc; Vendrell, Pere; Bargalló, Nuria; Tolosa, Eduard; Junqué, Carme

    2013-04-01

    In a previous functional MRI (fMRI) study, we found that patients with Parkinson's disease (PD) presented with dysfunctions in the recruitment of recognition memory networks. We aimed to investigate the changes in these networks over time. We studied 17 PD patients and 13 age and sex matched healthy subjects. In both groups fMRI (recognition memory paradigm) and neuropsychological assessments were obtained at baseline and at follow-up. To analyse changes over time in functional networks, model free (independent component analysis) analyses of the fMRI data were carried out. Then, a cross correlation approach was used to assess the changes in the strength of functional connectivity. At follow-up, patients showed reduced recruitment of one network, including decreased activation in the orbitofrontal cortices, middle frontal gyri, frontal poles, anterior paracingulate cortex, superior parietal lobes and left middle temporal gyrus, as well as decreased deactivation in the anterior paracingulate gyrus and precuneus. Cross correlation analyses over time showed a decrease in the strength of functional connectivity between the middle frontal gyrus and the superior parietal lobe in PD patients. Model free fMRI and cross correlation connectivity analyses were able to detect progressive changes in functional networks involved in recognition memory in PD patients at early disease stages and without overt clinical deterioration. Functional connectivity analyses could be useful to monitor changes in brain networks underlying neuropsychological deficits in PD.

  9. The Dynamics of Disease Progression in Cystic Fibrosis.

    Science.gov (United States)

    Adler, Frederick R; Liou, Theodore G

    2016-01-01

    In cystic fibrosis, statistical models have been more successful in predicting mortality than the time course of clinical status. We develop a system of partial differential equations that simultaneously track mortality and patient status, with all model parameters estimated from the extensive and carefully maintained database from the Cystic Fibrosis Foundation. Cystic fibrosis is an autosomal recessive disease that leads to loss of lung function, most commonly assessed using the Forced Expiratory Volume in 1 second (FEV1%). This loss results from inflammation secondary to chronic bacterial infections, particularly Pseudomonas aeruginosa, methicillin-sensitive Staphylococcus aureus (MSSA) and members of the virulent Burkholderia complex. The model tracks FEV1% and carriage of these three bacteria over the course of a patient's life. Analysis of patient state changes from year to year reveals four feedback loops: a damaging positive feedback loop between P. aeruginosa carriage and lower FEV1%, negative feedback loops between P. aeruginosa and MSSA and between P. aeruginosa and Burkholderia, and a protective positive feedback loop between MSSA carriage and higher FEV1%. The partial differential equations built from this data analysis accurately capture the life-long progression of the disease, quantify the key role of high annual FEV1% variability in reducing survivorship, the relative unimportance of short-term bacterial interactions for long-term survival, and the potential benefits of eradicating the most harmful bacteria.

  10. Hypoxemia in patients with COPD: cause, effects, and disease progression.

    LENUS (Irish Health Repository)

    Kent, Brian D

    2012-02-01

    Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability internationally. Alveolar hypoxia and consequent hypoxemia increase in prevalence as disease severity increases. Ventilation\\/perfusion mismatch resulting from progressive airflow limitation and emphysema is the key driver of this hypoxia, which may be exacerbated by sleep and exercise. Uncorrected chronic hypoxemia is associated with the development of adverse sequelae of COPD, including pulmonary hypertension, secondary polycythemia, systemic inflammation, and skeletal muscle dysfunction. A combination of these factors leads to diminished quality of life, reduced exercise tolerance, increased risk of cardiovascular morbidity, and greater risk of death. Concomitant sleep-disordered breathing may place a small but significant subset of COPD patients at increased risk of these complications. Long-term oxygen therapy has been shown to improve pulmonary hemodynamics, reduce erythrocytosis, and improve survival in selected patients with severe hypoxemic respiratory failure. However, the optimal treatment for patients with exertional oxyhemoglobin desaturation, isolated nocturnal hypoxemia, or mild-to-moderate resting daytime hypoxemia remains uncertain.

  11. The Dynamics of Disease Progression in Cystic Fibrosis.

    Directory of Open Access Journals (Sweden)

    Frederick R Adler

    Full Text Available In cystic fibrosis, statistical models have been more successful in predicting mortality than the time course of clinical status. We develop a system of partial differential equations that simultaneously track mortality and patient status, with all model parameters estimated from the extensive and carefully maintained database from the Cystic Fibrosis Foundation. Cystic fibrosis is an autosomal recessive disease that leads to loss of lung function, most commonly assessed using the Forced Expiratory Volume in 1 second (FEV1%. This loss results from inflammation secondary to chronic bacterial infections, particularly Pseudomonas aeruginosa, methicillin-sensitive Staphylococcus aureus (MSSA and members of the virulent Burkholderia complex. The model tracks FEV1% and carriage of these three bacteria over the course of a patient's life. Analysis of patient state changes from year to year reveals four feedback loops: a damaging positive feedback loop between P. aeruginosa carriage and lower FEV1%, negative feedback loops between P. aeruginosa and MSSA and between P. aeruginosa and Burkholderia, and a protective positive feedback loop between MSSA carriage and higher FEV1%. The partial differential equations built from this data analysis accurately capture the life-long progression of the disease, quantify the key role of high annual FEV1% variability in reducing survivorship, the relative unimportance of short-term bacterial interactions for long-term survival, and the potential benefits of eradicating the most harmful bacteria.

  12. Hypoxemia in patients with COPD: cause, effects, and disease progression

    Directory of Open Access Journals (Sweden)

    Brian D Kent

    2011-03-01

    Full Text Available Brian D Kent1,2, Patrick D Mitchell1, Walter T McNicholas1,21Pulmonary and Sleep Disorders Unit, St. Vincent’s University Hospital, Dublin; 2Conway Institute of Biomolecular and Biomedical Research, University College Dublin, IrelandAbstract: Chronic obstructive pulmonary disease (COPD is a leading cause of death and disability internationally. Alveolar hypoxia and consequent hypoxemia increase in prevalence as disease severity increases. Ventilation/perfusion mismatch resulting from progressive airflow limitation and emphysema is the key driver of this hypoxia, which may be exacerbated by sleep and exercise. Uncorrected chronic hypoxemia is associated with the development of adverse sequelae of COPD, including pulmonary hypertension, secondary polycythemia, systemic inflammation, and skeletal muscle dysfunction. A combination of these factors leads to diminished quality of life, reduced exercise tolerance, increased risk of cardiovascular morbidity, and greater risk of death. Concomitant sleep-disordered breathing may place a small but significant subset of COPD patients at increased risk of these complications. Long-term oxygen therapy has been shown to improve pulmonary hemodynamics, reduce erythrocytosis, and improve survival in selected patients with severe hypoxemic respiratory failure. However, the optimal treatment for patients with exertional oxyhemoglobin desaturation, isolated nocturnal hypoxemia, or mild-to-moderate resting daytime hypoxemia remains uncertain.Keywords: COPD, hypoxia, sleep, inflammation, pulmonary hypertension

  13. Hypoxemia in patients with COPD: cause, effects, and disease progression

    Science.gov (United States)

    Kent, Brian D; Mitchell, Patrick D; McNicholas, Walter T

    2011-01-01

    Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability internationally. Alveolar hypoxia and consequent hypoxemia increase in prevalence as disease severity increases. Ventilation/perfusion mismatch resulting from progressive airflow limitation and emphysema is the key driver of this hypoxia, which may be exacerbated by sleep and exercise. Uncorrected chronic hypoxemia is associated with the development of adverse sequelae of COPD, including pulmonary hypertension, secondary polycythemia, systemic inflammation, and skeletal muscle dysfunction. A combination of these factors leads to diminished quality of life, reduced exercise tolerance, increased risk of cardiovascular morbidity, and greater risk of death. Concomitant sleep-disordered breathing may place a small but significant subset of COPD patients at increased risk of these complications. Long-term oxygen therapy has been shown to improve pulmonary hemodynamics, reduce erythrocytosis, and improve survival in selected patients with severe hypoxemic respiratory failure. However, the optimal treatment for patients with exertional oxyhemoglobin desaturation, isolated nocturnal hypoxemia, or mild-to-moderate resting daytime hypoxemia remains uncertain. PMID:21660297

  14. Chronic Kidney Disease Progression in Elderly Iranian Patients: A Cohort Study

    Science.gov (United States)

    Shojamoradi, Mohammad Hossein; Saberi Isfeedvajani, Mohsen; Mahdavi-Mazdeh, Mitra; Ahmadi, Farrokhlagha; Gatmiri, Seyed Mansour; Abbasi Larki, Rozina

    2014-01-01

    Background: In the past few decades, Chronic Kidney Disease (CKD) - a disease with progressive decline in renal function - has become an important problem of global public health, not only in developed countries, but also in developing countries with less economic power. Objectives: In this study, CKD progression to death or End Stage Renal Disease (ESRD) in elderly Iranian patients was compared with younger counterparts. Patients and Methods: This retrospective cohort study was conducted on CKD patients with estimated Glomerular Filtration Rate (eGFR) < 60 mL/min, in a nephrology clinic in Tehran from December of 2006 until December of 2012. eGFR trend, death and need to renal replacement therapy (RRT) were evaluated as outcomes and compared between patients younger and older than 60 years. Data were analyzed using SPSS version 13. Results: Five-hundred and two patients were enrolled and followed up for an average of 37.6 months. Two thirds of the patients were older than 60 years. The incidence density of ESRD in patients younger and older than 60 years were 6.3 and 3.6 for 100 persons per year, respectively. Younger ones showed more rapid decline in their eGFR, while older patients had more stable renal function. Conclusions: It seems necessary to conduct more researches in order to redefine CKD and identify its prognostic markers in elderly population. PMID:25695035

  15. Decreased RECQL5 correlated with disease progression of osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Junlong; Zhi, Liqiang; Dai, Xin; Cai, Qingchun; Ma, Wei, E-mail: doctormawei@163.com

    2015-11-27

    Human RecQ helicase family, consisting of RECQL, RECQL4, RECQL5, BLM and WRN, has critical roles in genetic stability and tumorigenesis. Although RECQL5 has been reported to correlate with the susceptibility to malignances including osteosarcoma, the specific effect on tumor genesis and progression is not yet clarified. Here we focused on the relationship between RECQL5 expression and osteosarcoma disease progression, and further investigated the function of RECQL5 on MG-63 cell proliferation and apoptosis. By immunohistochemical analysis, qRT-PCR and western blot, we found that RECQL5 expression was downregulated in osteosarcoma tissues and cells. Patients with advanced tumor stage and low grade expressed lower RECQL5. To construct a stable RECQL5 overexpression osteosarcoma cell line (MG-63-RECQL5), RECQL5 gene was inserted into the human AAVS1 safe harbor by CRISPR/Cas9 system. The overexpression of RECQL5 was verified by qRT-PCR and western blot. Cell proliferation, cell cycle and apoptosis assay revealed that RECQL5 overexpression inhibited proliferation, induced G1-phase arrest and promoted apoptosis in MG-63 cells. Collectively, our results suggested RECQL5 as a tumor suppressor in osteosarcoma and may be a potential therapeutic target for osteosarcoma treatment. - Highlights: • The expression of RECQL5 was downregulated in osteosarcoma tissues and cells. • Decreased RECQL5 correlated with osteosarcoma Enneking surgical classification. • We constructed a stable RECQL5 overexpression cell line by CRISPR/Cas9 system. • RECQL5 overexpression inhibited proliferation of MG-63 cells. • RECQL5 overexpression promoted apoptosis of MG-63 cells.

  16. Brain Dopamine Transporter Binding and Glucose Metabolism in Progressive Supranuclear Palsy-Like Creutzfeldt-Jakob Disease

    Directory of Open Access Journals (Sweden)

    Eero Rissanen

    2014-01-01

    Full Text Available Here, we present a patient with Creutzfeldt-Jakob disease (CJD who developed initial symptoms mimicking progressive supranuclear palsy (PSP. Before the development of typical CJD symptoms, functional imaging supported a diagnosis of PSP when [123I]-FP-CIT-SPECT showed a defect in striatal dopamine transporter binding, while [18F]-fluorodeoxyglucose PET showed cortical hypometabolism suggestive of Lewy body dementia. However, the postmortem neuropathological examination was indicative of CJD only, without tau protein or Lewy body findings. This case demonstrates that CJD should be taken into account in rapidly progressing atypical cases of parkinsonism, even when functional imaging supports a diagnosis of a movement disorder.

  17. Managing marine disease emergencies in an era of rapid change.

    Science.gov (United States)

    Groner, Maya L; Maynard, Jeffrey; Breyta, Rachel; Carnegie, Ryan B; Dobson, Andy; Friedman, Carolyn S; Froelich, Brett; Garren, Melissa; Gulland, Frances M D; Heron, Scott F; Noble, Rachel T; Revie, Crawford W; Shields, Jeffrey D; Vanderstichel, Raphaël; Weil, Ernesto; Wyllie-Echeverria, Sandy; Harvell, C Drew

    2016-03-05

    Infectious marine diseases can decimate populations and are increasing among some taxa due to global change and our increasing reliance on marine environments. Marine diseases become emergencies when significant ecological, economic or social impacts occur. We can prepare for and manage these emergencies through improved surveillance, and the development and iterative refinement of approaches to mitigate disease and its impacts. Improving surveillance requires fast, accurate diagnoses, forecasting disease risk and real-time monitoring of disease-promoting environmental conditions. Diversifying impact mitigation involves increasing host resilience to disease, reducing pathogen abundance and managing environmental factors that facilitate disease. Disease surveillance and mitigation can be adaptive if informed by research advances and catalysed by communication among observers, researchers and decision-makers using information-sharing platforms. Recent increases in the awareness of the threats posed by marine diseases may lead to policy frameworks that facilitate the responses and management that marine disease emergencies require. © 2016 The Author(s).

  18. Perspective Insights into Disease Progression, Diagnostics, and Therapeutic Approaches in Alzheimer's Disease: A Judicious Update

    Directory of Open Access Journals (Sweden)

    Arif Tasleem Jan

    2017-11-01

    Full Text Available Alzheimer's disease (AD is a neurodegenerative disorder characterized by the progressive accumulation of β-amyloid fibrils and abnormal tau proteins in and outside of neurons. Representing a common form of dementia, aggravation of AD with age increases the morbidity rate among the elderly. Although, mutations in the ApoE4 act as potent risk factors for sporadic AD, familial AD arises through malfunctioning of APP, PSEN-1, and−2 genes. AD progresses through accumulation of amyloid plaques (Aβ and neurofibrillary tangles (NFTs in brain, which interfere with neuronal communication. Cellular stress that arises through mitochondrial dysfunction, endoplasmic reticulum malfunction, and autophagy contributes significantly to the pathogenesis of AD. With high accuracy in disease diagnostics, Aβ deposition and phosphorylated tau (p-tau are useful core biomarkers in the cerebrospinal fluid (CSF of AD patients. Although five drugs are approved for treatment in AD, their failures in achieving complete disease cure has shifted studies toward a series of molecules capable of acting against Aβ and p-tau. Failure of biologics or compounds to cross the blood-brain barrier (BBB in most cases advocates development of an efficient drug delivery system. Though liposomes and polymeric nanoparticles are widely adopted for drug delivery modules, their use in delivering drugs across the BBB has been overtaken by exosomes, owing to their promising results in reducing disease progression.

  19. Metabolic Syndrome and Periodontal Disease Progression in Men

    Science.gov (United States)

    Kaye, E.K.; Chen, N.; Cabral, H.J.; Vokonas, P.; Garcia, R.I.

    2016-01-01

    Metabolic syndrome, a cluster of 3 or more risk factors for cardiovascular disease, is associated with periodontal disease, but few studies have been prospective in design. This study’s aim was to determine whether metabolic syndrome predicts tooth loss and worsening of periodontal disease in a cohort of 760 men in the Department of Veterans Affairs Dental Longitudinal Study and Normative Aging Study who were followed up to 33 y from 1981 to 2013. Systolic and diastolic blood pressures were measured with a standard mercury sphygmomanometer. Waist circumference was measured in units of 0.1 cm following a normal expiration. Fasting blood samples were measured in duplicate for glucose, triglyceride, and high-density lipoprotein. Calibrated periodontists served as dental examiners. Periodontal outcome events on each tooth were defined as progression to predefined threshold levels of probing pocket depth (≥5 mm), clinical attachment loss (≥5 mm), mobility (≥0.5 mm), and alveolar bone loss (≥40% of the distance from the cementoenamel junction to the root apex, on radiographs). Hazards ratios (95% confidence intervals) of tooth loss or a periodontitis event were estimated from tooth-level extended Cox proportional hazards regression models that accounted for clustering of teeth within individuals and used time-dependent status of metabolic syndrome. Covariates included age, education, smoking status, plaque level, and initial level of the appropriate periodontal disease measure. Metabolic syndrome as defined by the International Diabetes Federation increased the hazards of tooth loss (1.39; 1.08 to 1.79), pocket depth ≥5 mm (1.37; 1.14 to 1.65), clinical attachment loss ≥5 mm (1.19; 1.00 to 1.41), alveolar bone loss ≥40% (1.25; 1.00 to 1.56), and tooth mobility ≥0.5 mm (1.43; 1.07 to 1.89). The number of positive metabolic syndrome conditions was also associated with each of these outcomes. These findings suggest that the metabolic disturbances that

  20. Early myeloid dendritic cell dysregulation is predictive of disease progression in simian immunodeficiency virus infection.

    Directory of Open Access Journals (Sweden)

    Viskam Wijewardana

    2010-12-01

    Full Text Available Myeloid dendritic cells (mDC are lost from blood in individuals with human immunodeficiency virus (HIV infection but the mechanism for this loss and its relationship to disease progression are not known. We studied the mDC response in blood and lymph nodes of simian immunodeficiency virus (SIV-infected rhesus macaques with different disease outcomes. Early changes in blood mDC number were inversely correlated with virus load and reflective of eventual disease outcome, as animals with stable infection that remained disease-free for more than one year had average increases in blood mDC of 200% over preinfection levels at virus set-point, whereas animals that progressed rapidly to AIDS had significant loss of mDC at this time. Short term antiretroviral therapy (ART transiently reversed mDC loss in progressor animals, whereas discontinuation of ART resulted in a 3.5-fold increase in mDC over preinfection levels only in stable animals, approaching 10-fold in some cases. Progressive SIV infection was associated with increased CCR7 expression on blood mDC and an 8-fold increase in expression of CCL19 mRNA in lymph nodes, consistent with increased mDC recruitment. Paradoxically, lymph node mDC did not accumulate in progressive infection but rather died from caspase-8-dependent apoptosis that was reduced by ART, indicating that increased recruitment is offset by increased death. Lymph node mDC from both stable and progressor animals remained responsive to exogenous stimulation with a TLR7/8 agonist. These data suggest that mDC are mobilized in SIV infection but that an increase in the CCR7-CCL19 chemokine axis associated with high virus burden in progressive infection promotes exodus of activated mDC from blood into lymph nodes where they die from apoptosis. We suggest that inflamed lymph nodes serve as a sink for mDC through recruitment, activation and death that contributes to AIDS pathogenesis.

  1. The area under the disease progress stairs: calculation, advantage, and application.

    Science.gov (United States)

    Simko, Ivan; Piepho, Hans-Peter

    2012-04-01

    The area under the disease progress curve (AUDPC) is frequently used to combine multiple observations of disease progress into a single value. However, our analysis shows that this approach severely underestimates the effect of the first and last observation. To get a better estimate of disease progress, we have developed a new formula termed the area under the disease progress stairs (AUDPS). The AUDPS approach improves the estimation of disease progress by giving a weight closer to optimal to the first and last observations. Analysis of real data indicates that AUDPS outperforms AUDPC in most of the tested trials and may be less precise than AUDPC only when assessments in the first or last observations have a comparatively large variance. We propose using AUDPS and its standardized (sAUDPS) and relative (rAUDPS) forms when combining multiple observations from disease progress experiments into a single value.

  2. Vitamin D and clinical disease progression in HIV infection

    DEFF Research Database (Denmark)

    Viard, Jean-Paul; Souberbielle, Jean-Claude; Kirk, Ole

    2011-01-01

    BACKGROUND:: We examined the association between vitamin D [25(OH)D] level and disease progression in HIV infection. METHODS:: Within the EuroSIDA study, 2000 persons were randomly selected for 25(OH)D measurement in stored plasma samples closest to study entry. 25(OH)D results were stratified...... into tertiles. Factors associated with 25(OH)D levels and associations of 25(OH) levels with subsequent risk of all-cause mortality, AIDS and non-AIDS events were analyzed. RESULTS:: Of 1985 persons with 25(OH)D levels available, 23.7% had 25(OH)D 30 ng/ml. At the time of 25(OH)D measurement, older persons......, persons of black ethnic origin, living outside Southern Europe/Argentina, sampled during winter, and infected with HIV through non-homosexual exposure were at higher odds of having low 25(OH)D levels, while persons receiving protease inhibitors were at lower odds. Compared to those in the lowest 25(OH)D...

  3. Glucose targets for preventing diabetic kidney disease and its progression.

    Science.gov (United States)

    Ruospo, Marinella; Saglimbene, Valeria M; Palmer, Suetonia C; De Cosmo, Salvatore; Pacilli, Antonio; Lamacchia, Olga; Cignarelli, Mauro; Fioretto, Paola; Vecchio, Mariacristina; Craig, Jonathan C; Strippoli, Giovanni Fm

    2017-06-08

    Diabetes is the leading cause of end-stage kidney disease (ESKD) around the world. Blood pressure lowering and glucose control are used to reduce diabetes-associated disability including kidney failure. However there is a lack of an overall evidence summary of the optimal target range for blood glucose control to prevent kidney failure. To evaluate the benefits and harms of intensive (HbA1c fasting glucose levels fasting glucose levels ≥ 120 mg/dL for preventing the onset and progression of kidney disease among adults with diabetes. We searched the Cochrane Kidney and Transplant Specialised Register up to 31 March 2017 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Randomised controlled trials evaluating glucose-lowering interventions in which people (aged 14 year or older) with type 1 or 2 diabetes with and without kidney disease were randomly allocated to tight glucose control or less stringent blood glucose targets. Two authors independently assessed studies for eligibility and risks of bias, extracted data and checked the processes for accuracy. Outcomes were mortality, cardiovascular complications, doubling of serum creatinine (SCr), ESKD and proteinuria. Confidence in the evidence was assessing using GRADE. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Fourteen studies involving 29,319 people with diabetes were included and 11 studies involving 29,141 people were included in our meta-analyses. Treatment duration was 56.7 months on average

  4. Progress on Complications of Direct Bypass for Moyamoya Disease.

    Science.gov (United States)

    Yu, Jinlu; Shi, Lei; Guo, Yunbao; Xu, Baofeng; Xu, Kan

    2016-01-01

    Moyamoya disease (MMD) involves progressive occlusion of the intracranial internal carotid artery resulting in formation of moyamoya-like vessels at the base of the brain. It can be characterized by hemorrhage or ischemia. Direct vascular bypass is the main and most effective treatment of MMD. However, patients with MMD differ from those with normal cerebral vessels. MMD patients have unstable intracranial artery hemodynamics and a poor blood flow reserve; therefore, during the direct bypass of superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis, perioperative risk factors and anesthesia can affect the hemodynamics of these patients. When brain tissue cannot tolerate a high blood flow rate, it becomes prone to hyperperfusion syndrome, which leads to neurological function defects and can even cause intracranial hemorrhage in severe cases. The brain tissue is prone to infarction when hemodynamic equilibrium is affected. In addition, bypass vessels become susceptible to occlusion or atrophy when blood resistance increases. Even compression of the temporalis affects bypass vessels. Because the STA is used in MMD surgery, the scalp becomes ischemic and is likely to develop necrosis and infection. These complications of MMD surgery are difficult to manage and are not well understood. To date, no systematic studies of the complications that occur after direct bypass in MMD have been performed, and reported complications are hidden among various case studies; therefore, this paper presents a review and summary of the literature in PubMed on the complications of direct bypass in MMD.

  5. Isolated Acute Terminal Ileitis Without Preexisting Inflammatory Bowel Disease Rarely Progresses to Crohn's Disease.

    Science.gov (United States)

    Tse, Chung Sang; Deepak, Parakkal; Smyrk, Thomas C; Raffals, Laura E

    2017-10-24

    Isolated acute terminal ileitis without chronic features of inflammation poses a diagnostic challenge. Few studies have investigated the clinical significance of this entity in patients without history of inflammatory bowel disease. We sought to elucidate the long-term prognosis of patients with isolated acute terminal ileitis, its rate of progression to Crohn's disease, and the factors associated with terminal ileitis development to Crohn's disease. Retrospective review of clinical, endoscopic, and radiographic records was performed on 108 patients with histologic evidence of isolated acute terminal ileitis on terminal ileal biopsies obtained by diagnostic ileocolonoscopy performed between January 1, 2002, and December 31, 2014, at the Mayo Clinic. Statistical analysis was performed with Student's t test and Fisher's exact test to identify the factors associated with the progression of isolated acute terminal ileitis to Crohn's disease. The median follow-up time across 108 patients was 54.7 months (interquartile range 32.0-89.0 months). Five patients (4.6%) developed Crohn's disease after a median of 32.3 months (7.5-43.2 months). The presence of narrowing/stricturing (p = 0.03) on abdominal cross-sectional imaging at the time of terminal ileitis diagnosis was correlated with eventual Crohn's disease development. No significant correlation was found with clinical symptoms, endoscopic features, laboratory testing, NSAID use, smoking history, or family history of inflammatory bowel disease. Isolated acute terminal ileitis discovered on diagnostic ileocolonoscopy rarely develops to Crohn's disease. Presence of stricturing/narrowing on cross-sectional imaging may predict eventual Crohn's disease development.

  6. Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

    OpenAIRE

    Hensman Moss, Davina J; Pardinas, Antonio; Langbehn, Douglas; Lo, Kitty; Leavitt, Blair R; Roos, Raymund; Durr, Alexandra; Mead, Simon; Holmans, Peter; Jones, Lesley; Tabrizi, Sarah J; Coleman, A; Santos, R Dar; Decolongon, J; Sturrock, A

    2017-01-01

    Background\\ud \\ud Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure.\\ud \\ud Methods\\ud \\ud We generated a progression score on the basis of principal ...

  7. Timely Referral to Outpatient Nephrology Care Slows Progression and Reduces Treatment Costs of Chronic Kidney Diseases

    Directory of Open Access Journals (Sweden)

    Gerhard Lonnemann

    2017-03-01

    Discussion: Timely referral to outpatient nephrology care is associated with slowed disease progression, less hospital admissions, reduced total treatment costs, and improved survival in patients with CKD.

  8. Progressive Stroke-Like Symptoms in a Patient with Sporadic Creutzfeldt-Jakob Disease

    Directory of Open Access Journals (Sweden)

    Jukka Lyytinen

    2010-03-01

    Full Text Available Sporadic Creutzfeldt-Jakob disease (sCJD is a rare neurodegenerative disorder in which accumulation of a pathogenic isoform of prion protein (PrPSc induces neuronal damage with distinct pathologic features. The prognosis of sCJD is devastating: rapid clinical decline is followed by death generally within months after onset of symptoms. The classic clinical manifestations of sCJD are rapidly progressing dementia, myoclonus, and ataxia. However, the spectrum of clinical features can vary considerably. We describe a definite, neuropathologically verified sCJD in a 67-year-old woman who initially presented with progressive stroke-like symptoms: left-sided hemiparesis and ataxia within a few days. The initial brain magnetic resonance imaging (MRI showed bilateral cortical hyperintensity on diffusion-weighted sequences (DWI resembling multiple ischemic lesions. Despite anticoagulation with low-molecular-weight heparin, the patient deteriorated rapidly, became dysphagic and bedridden with myoclonic jerks on her left side extremities correlating with intermittent high-amplitude epileptiform discharges on electroencephalography (EEG. Basal ganglia hyperintense signal changes in addition to cortical ribboning were seen in DWI images of a follow-up MRI. Repeated EEG recordings showed an evolution to periodic sharp wave complexes. Protein 14-3-3 was positive in her cerebrospinal fluid specimen, in addition to an abnormally high total tau level. In the terminal stage the patient was in an akinetic, mutistic state with deteriorating consciousness. She died 19 days after admission to the hospital. Neuropathologic investigation corroborated the clinical diagnosis of sCJD with spongiform degeneration and immunohistochemical demonstration of the deposition of pathologic PrPSc.

  9. Smell identification function as a severity and progression marker in Alzheimer's disease.

    Science.gov (United States)

    Velayudhan, Latha; Pritchard, Megan; Powell, John F; Proitsi, Petroula; Lovestone, Simon

    2013-07-01

    Olfactory dysfunction, impaired smell identification in particular, is known as a diagnostic and a marker of conversion in Alzheimer's disease (AD). We aimed to evaluate the associations of olfactory identification impairments with cognition, illness severity, and progression in AD patients. Fifty-seven outpatients with late onset mild to moderate AD and 24 elderly non-demented controls (NDC) were assessed, at baseline and after three months, for Mini-Mental State Examination (MMSE), University of Pennsylvania Smell Identification Test (UPSIT), and Bristol Activities of Daily Living and Neuropsychiatry Inventory. AD participants were classified as Rapid Cognitive Decliners (RCD) defined on a priori with a loss of ≥2 points in MMSE within the previous six months. AD participants had lower olfactory scores than NDC. RCD had lower olfaction scores compared with Non-Rapid Cognitive Decliners (NRCD). Although the baseline UPSIT scores were associated with baseline MMSE scores, it did not interact significantly with change in MMSE over the follow-up period. Using a median split for olfactory scores, the AD participants were classified as Rapid Olfactory Progressors (ROP) (UPSIT ≤ 15) and Slow Olfactory Progressors correlating significantly with RCD/NRCD groups. The ROP group with higher olfactory impairment indicated more symptomatic illness or severity, i.e. lower cognition, higher functional dependence, and presence of behavioral symptoms. Our study supports association of smell identification function with cognition and its utility as an adjunct clinical measure to assess severity in AD. Further work, including larger longitudinal studies, is needed to explore its value in predicting AD progression.

  10. Lower corneal hysteresis is associated with more rapid glaucomatous visual field progression.

    Science.gov (United States)

    De Moraes, Carlos V Gustavo; Hill, Victoria; Tello, Celso; Liebmann, Jeffrey M; Ritch, Robert

    2012-01-01

    We investigated the correlation between central corneal thickness (CCT) and corneal hysteresis (CH) and their relationship with the rate of visual field (VF) change. Glaucoma patients who underwent complete ophthalmic examination and tonometry using both the Goldmann applanation tonometer and the Ocular Response Analyzer were prospectively enrolled. Only eyes with ≥5 SITA Standard 24-2 VF tests were included. Automated pointwise linear regression analysis was used to determine VF progression. One hundred fifty-three eyes (153 patients; mean age, 61.3 ± 14.0 y; mean number of VF, 8.5 ± 3.4; mean follow-up time, 5.3 ± 2.0 y) met the enrollment criteria. The mean global rate of VF change was -0.34 ± 0.7 dB/y. Twenty-five eyes (16%) reached a progression endpoint. Progressing eyes had lower CCT (525.0 ± 34.2 vs 542.3 ± 3 8.5 μm, P=0.04) and lower CH (7.5 ± 1.4 vs 9.0 ± 1.8 mm Hg, PCorneal biomechanical and physical properties, such as CH and CCT, are highly correlated and associated with VF progression. As CH may describe corneal properties more completely than thickness alone, it may be a parameter that is better associated with progression.

  11. Haematuria as a risk factor for chronic kidney disease progression in glomerular diseases: A review.

    Science.gov (United States)

    Moreno, Juan Antonio; Yuste, Claudia; Gutiérrez, Eduardo; Sevillano, Ángel M; Rubio-Navarro, Alfonso; Amaro-Villalobos, Juan Manuel; Praga, Manuel; Egido, Jesús

    2016-04-01

    Haematuria has long been considered to be a benign condition associated with glomerular diseases. However, new evidences suggest that haematuria has a pathogenic role in promoting kidney disease progression. An increased risk for end-stage renal disease has been reported in adolescents and young adults with persistent microscopic haematuria. A persistent impairment of renal function has been also reported following macroscopic haematuria-associated acute kidney injury in immunoglobulin A nephropathy. Haematuria-induced renal damage has been related to oxidant, cytotoxic and inflammatory effects induced by haemoglobin or haem released from red blood cells. The pathophysiological origin of haematuria may be due to a more fragile and easily ruptured glomerular filtration barrier, as reported in several glomerular diseases. In this review we describe a number of the key issues associated with the epidemiology and pathogenesis of haematuria-associated diseases, provide an update of recent knowledge on the role of haematuria on renal function outcome and discuss specific therapeutic approaches in this setting. KEY SUMMARY POINTS: 1. Glomerular haematuria is a common observation in a number of renal diseases that may lead to persistent renal injury. 2. Haematuria in children differs from that in adults in specific aspects, particularly in the frequency of glomerular diseases and renal disease outcome. 3. Regular follow-up of renal function in children with isolated microhaematuria may be recommended.

  12. Identification of unstable network modules reveals disease modules associated with the progression of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Masataka Kikuchi

    Full Text Available Alzheimer's disease (AD, the most common cause of dementia, is associated with aging, and it leads to neuron death. Deposits of amyloid β and aberrantly phosphorylated tau protein are known as pathological hallmarks of AD, but the underlying mechanisms have not yet been revealed. A high-throughput gene expression analysis previously showed that differentially expressed genes accompanying the progression of AD were more down-regulated than up-regulated in the later stages of AD. This suggested that the molecular networks and their constituent modules collapsed along with AD progression. In this study, by using gene expression profiles and protein interaction networks (PINs, we identified the PINs expressed in three brain regions: the entorhinal cortex (EC, hippocampus (HIP and superior frontal gyrus (SFG. Dividing the expressed PINs into modules, we examined the stability of the modules with AD progression and with normal aging. We found that in the AD modules, the constituent proteins, interactions and cellular functions were not maintained between consecutive stages through all brain regions. Interestingly, the modules were collapsed with AD progression, specifically in the EC region. By identifying the modules that were affected by AD pathology, we found the transcriptional regulation-associated modules that interact with the proteasome-associated module via UCHL5 hub protein, which is a deubiquitinating enzyme. Considering PINs as a system made of network modules, we found that the modules relevant to the transcriptional regulation are disrupted in the EC region, which affects the ubiquitin-proteasome system.

  13. Clinical features and predictors for disease natural progression in adults with Pompe disease : a nationwide prospective observational study

    NARCIS (Netherlands)

    van der Beek, Nadine A. M. E.; de Vries, Juna M.; Hagemans, Marloes L. C.; Hop, Wim C. J.; Kroos, Marian A.; Wokke, John H. J.; de Visser, Marianne; van Engelen, Baziel G. M.; Kuks, Jan B. M.; van der Kooi, Anneke J.; Notermans, Nicolette C.; Faber, Karin G.; Verschuuren, Jan J. G. M.; Reuser, Arnold J. J.; van der Ploeg, Ans T.; van Doorn, Pieter A.

    2012-01-01

    Background: Due partly to physicians' unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults,

  14. Early energy deficit in Huntington disease: identification of a plasma biomarker traceable during disease progression.

    Directory of Open Access Journals (Sweden)

    Fanny Mochel

    Full Text Available Huntington disease (HD is a fatal neurodegenerative disorder, with no effective treatment. The pathogenic mechanisms underlying HD has not been elucidated, but weight loss, associated with chorea and cognitive decline, is a characteristic feature of the disease that is accessible to investigation. We, therefore, performed a multiparametric study exploring body weight and the mechanisms of its loss in 32 presymptomatic carriers and HD patients in the early stages of the disease, compared to 21 controls. We combined this study with a multivariate statistical analysis of plasma components quantified by proton nuclear magnetic resonance ((1H NMR spectroscopy. We report evidence of an early hypermetabolic state in HD. Weight loss was observed in the HD group even in presymptomatic carriers, although their caloric intake was higher than that of controls. Inflammatory processes and primary hormonal dysfunction were excluded. (1H NMR spectroscopy on plasma did, however, distinguish HD patients at different stages of the disease and presymptomatic carriers from controls. This distinction was attributable to low levels of the branched chain amino acids (BCAA, valine, leucine and isoleucine. BCAA levels were correlated with weight loss and, importantly, with disease progression and abnormal triplet repeat expansion size in the HD1 gene. Levels of IGF1, which is regulated by BCAA, were also significantly lower in the HD group. Therefore, early weight loss in HD is associated with a systemic metabolic defect, and BCAA levels may be used as a biomarker, indicative of disease onset and early progression. The decreased plasma levels of BCAA may correspond to a critical need for Krebs cycle energy substrates in the brain that increased metabolism in the periphery is trying to provide.

  15. Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration

    National Research Council Canada - National Science Library

    Tobinick, Edward L; Gross, Hyman

    2008-01-01

    ...) is centrally involved in the pathogenesis of Alzheimer's disease. In addition to its pro-inflammatory functions, TNF-alpha has recently been recognized to be a gliotransmitter that regulates synaptic function in neural networks...

  16. Papillary tumor of the pineal region: report of a rapidly progressive tumor with possible multicentric origin

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Takashi S. [University of Iowa, Carver College of Medicine, Iowa City, IA (United States); Kirby, Patricia A. [University of Iowa, Department of Pathology, Iowa City, IA (United States); Buatti, John M. [University of Iowa, Department of Radiation Oncology, Iowa City, IA (United States); Moritani, Toshio [University of Iowa Hospitals and Clinics, Department of Radiology, Iowa City, IA (United States)

    2009-02-15

    Papillary tumor of the pineal region (PTPR) is an uncommon tumor recently added to the WHO classification of CNS tumors. We report a case of PTPR in a young boy that was noteworthy for early CSF dissemination and relentless progression. In spite of intensive chemotherapy and comprehensive radiotherapy, the boy died. The neuroimaging appearance is unique with possible multicentric origin of the tumor and intense uptake of {sup 111}In-DTPA-pentetreotide. (orig.)

  17. Measuring disease progression in early Parkinson disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) experience.

    Science.gov (United States)

    Parashos, Sotirios A; Luo, Sheng; Biglan, Kevin M; Bodis-Wollner, Ivan; He, Bo; Liang, Grace S; Ross, G Webster; Tilley, Barbara C; Shulman, Lisa M

    2014-06-01

    Optimizing assessments of rate of progression in Parkinson disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents. To examine the value of measures of impairment, disability, and quality of life in assessing progression in early PD. Inception cohort analysis of data from 413 patients with early, untreated PD who were enrolled in 2 multicenter, randomized, double-blind clinical trials. Participants were randomly assigned to 1 of 5 treatments (67 received creatine, 66 received minocycline, 71 received coenzyme Q10, 71 received GPI-1485, and 138 received placebo). We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment. Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression. After adjusting for baseline confounding variables with regard to the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score, the UPDRS Part III score, the modified Rankin Scale score, level of education, and treatment group, we assessed the rate of change for the following measurements: the UPDRS Part II score; the UPDRS Part III score; the Schwab and England Independence Scale score (which measures activities of daily living); the Total Functional Capacity scale; the 39-item Parkinson's Disease Questionnaire, summary index, and activities of daily living subscale; and version 2 of the 12-item Short Form Health Survey Physical Summary and Mental Summary. Variables reaching the statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid change (ie, worsening) in the UPDRS Part II score (hazard ratio, 1.15 [95% CI, 1.08-1.22] for 1 scale unit change per 6 months), the UPDRS Part III score (hazard ratio, 1.09 [95

  18. Gender differences in HIV progression to AIDS and death in industrialized countries: slower disease progression following HIV seroconversion in women

    NARCIS (Netherlands)

    Jarrin, Inmaculada; Geskus, Ronald; Bhaskaran, Krishnan; Prins, Maria; Perez-Hoyos, Santiago; Muga, Roberto; Hernández-Aguado, Ildefonso; Meyer, Laurence; Porter, Kholoud; del Amo, Julia; Bucher, Heiner; Chêne, Geneviève; Pillay, Deenan; Rosinska, Magda; Sabin, Caroline; Touloumi, Giota; Walker, Sarah; Babiker, Abdel; Darbyshire, Janet; de Luca, Andrea; Fisher, Martin; Goujard, Cécile; Kaldor, John; Kelleher, Tony; Gelgor, Linda; Ramacciotti, Tim; Cooper, David; Smith, Don; Gill, John; Jørgensen, Louise Bruun; Nielsen, Claus; Pedersen, Court; Lutsar, Irja; Dabis, Francois; Thiebaut, Rodolphe; Masquelier, Bernard; Costagliola, Dominique; Vanhems, Philippe; Boufassa, Faroudy; Hamouda, Osamah; Kucherer, Claudia; Pantazis, Nikos; Hatzakis, Angelos; Paraskevis, Dimitrios; Karafoulidou, Anastasia; Rezza, Giovanni; Dorrucci, Maria; Longo, Benedetta; Balotta, Claudia; van Asten, Liselotte; van der Bij, Akke; Coutinho, Roel; Sannes, Mette; Brubakk, Oddbjorn; Eskild, Anne; Bruun, Johan N.; Rosinska, Magdalena; Camacho, Ricardo; Smolskaya, Tatyana; Tor, Jordi; de Olalla, Patricia Garcia; Caylà, Joan; del Romero, Jorge; Pérez-Hoyos, Santiago; Aguado, Ildefonso Hernandez; Belda, Josefina; Rickenbach, Martin; Francioli, Patrick; Malyuta, Ruslan; Brettle, Ray; Delpech, Valerie; Lattimore, Sam; Murphy, Gary; Parry, John; Gill, Noel; Lee, Christine; Johnson, Anne; Phillips, Andrew; Jaffe, Harold

    2008-01-01

    To evaluate sex differences in human immunodeficiency virus (HIV) disease progression before (pre-1997) and after (1997-2006) introduction of highly active antiretroviral therapy, the authors used data from a collaboration of 23 HIV seroconverter cohort studies from Europe, Australia, and Canada

  19. Chronic kidney disease in pregnancy: Maternal and fetal outcomes and progression of kidney disease.

    Science.gov (United States)

    Davidson, Natalie L; Wolski, Penny; Callaway, Leonie K; Barrett, Helen L; Fagermo, Narelle; Lust, Karin; Shakhovskoy, Rebekah E

    2015-06-01

    There is a paucity of Australian data regarding renal disease in pregnancy. We undertook a retrospective cohort study at a tertiary institution to examine the impact of renal disease on pregnancy outcomes and the effect of pregnancy on disease progression. A total of 55 pregnancies of patients with renal disease admitted from 2003 to 2010 to the Royal Brisbane and Women's Hospital were analysed. Pre-conception variables, fetal/delivery and maternal outcomes were analysed in this group and in a control group of women with normal kidney function pre-pregnancy. Of the 55 pregnancies, 71% experienced pre-term delivery, 38% had intra-uterine growth restriction and 62% required caesarean section. Of all, 60% of neonates required neonatal intensive care unit (NICU) admission and six perinatal deaths occurred. Of all, 67% of women suffered preeclampsia, 47% anaemia and 3 patients required dialysis in pregnancy. Postpartum deterioration of renal function occurred in patients with pre-conception chronic kidney disease stage 3-5. Chronic kidney disease of all stages is a risk factor for adverse pregnancy outcomes. In a tertiary institution however, there is a high rate of successful pregnancy (84%).

  20. Monitoring disease progression in mild cognitive impairment: Associations between atrophy patterns, cognition, APOE and amyloid

    Directory of Open Access Journals (Sweden)

    Farshad Falahati

    2017-01-01

    Conclusions: Longitudinal changes in the SI reflect structural brain changes and can identify MCI patients at risk of progression to AD. Disease-related brain structural changes are influenced independently by APOE genotype and amyloid pathology. The SI has the potential to be used as a sensitive tool to predict future dementia, monitor disease progression as well as an outcome measure for clinical trials.

  1. Do HIV disease progression and HAART response vary among injecting drug users in Europe?

    NARCIS (Netherlands)

    van Asten, Liselotte; Zangerle, Robert; Hernández Aguado, Ildefonso; Boufassa, Faroudy; Broers, Barbara; Brettle, Raymond P.; Roy Robertson, J.; McMenamin, Jim; Coutinho, Roel A.; Prins, Maria

    2005-01-01

    Prior to HAART availability, there was no evidence of a geographical variation in HIV disease progression among injecting drug users (IDU) from different European regions. Nowadays, factors of importance regarding HIV disease progression in the face of HAART availability, such as HAART access,

  2. Quantitative muscle MRI as an assessment tool for monitoring disease progression in LGMD2I

    DEFF Research Database (Denmark)

    Willis, Tracey A; Hollingsworth, Kieren G; Coombs, Anna

    2013-01-01

    Outcome measures for clinical trials in neuromuscular diseases are typically based on physical assessments which are dependent on patient effort, combine the effort of different muscle groups, and may not be sensitive to progression over short trial periods in slow-progressing diseases. We hypoth...... hypothesised that quantitative fat imaging by MRI (Dixon technique) could provide more discriminating quantitative, patient-independent measurements of the progress of muscle fat replacement within individual muscle groups....

  3. Disease Progression in HIV Late Presenters: the Role of HIV Clinical Indicator Diseases Prior to HIV Diagnosis.

    Science.gov (United States)

    Guardigni, Viola; Morieri, Mario Luca; Segala, Daniela; Sighinolfi, Laura

    2016-01-01

    Late diagnosis represents a major challenge in the control of HIV epidemics. The rate of disease progression is higher among late presenters. In Europe, HIV Clinical Indicator Diseases (CIDs) have been proposed to improve early diagnosis. Our observational study evaluated the presence of these HIV CIDs prior to HIV diagnosis among a population of late presenters and assessed its correlation to disease progression. A retrospective cohort study was conducted in HIV late presenters diagnosed from 2007 to 2013 at University Hospital of Ferrara (Italy). Hazard Ratios (H.R.s) for disease progression (new AIDS-events and death) were estimated by Cox proportional hazard model. We analysed 77 patients and we found that those with CIDs prior to HIV diagnosis (22%) had a 2.8 fold higher rate of disease progression compared to those without HIV CIDs (H.R. 2.82; 95% CI 1.21-6.53; P 0.02). Other factors associated with disease progression were AIDS presentation, HCV coinfection and Haemoglobin levels, with H.R.s of 3.14 (95%CI 1.23-7.99), 2.95 (95% CI 1.14-7.61) and 0.74 (95% CI 0.60-0.91), respectively. HIV CIDs confer a higher risk for disease progression even after adjustment for these confounding factors. Evaluation of previous HIV CIDs at HIV diagnosis could be an additional tool to identify and better manage HIV late presenters with higher risks of disease progression.

  4. Rapid eye movement sleep disturbances in Huntington disease

    DEFF Research Database (Denmark)

    Arnulf, I.; Nielsen, J.; Lohmann, E.

    2008-01-01

    Background: Sleep disorders including insomnia, movements during sleep, and daytime sleepiness are common but poorly studied in Huntington disease (HD). Objective: To evaluate the HD sleep-wake phenotype (including abnormal motor activity during sleep) in patients with various HD stages and the l......Background: Sleep disorders including insomnia, movements during sleep, and daytime sleepiness are common but poorly studied in Huntington disease (HD). Objective: To evaluate the HD sleep-wake phenotype (including abnormal motor activity during sleep) in patients with various HD stages...

  5. Progression of chronic kidney disease in a multi-ethnic community cohort of patients with diabetes mellitus.

    Science.gov (United States)

    Dreyer, G; Hull, S; Mathur, R; Chesser, A; Yaqoob, M M

    2013-08-01

    Ethnicity is a risk factor for the prevalence of severe chronic kidney disease among patients with diabetes. We studied the effect of ethnicity on progression of chronic kidney disease in people with diabetes managed in community settings. A 5-year retrospective, community-based cohort study of 3855 people with diabetes mellitus of white, black or South Asian ethnicity with an estimated glomerular filtration rate of chronic kidney disease progression was significantly greater in South Asian groups (-1.01 ml min⁻¹ 1.73 m⁻²) compared with white groups (-0.70 ml min⁻¹ 1.73 m⁻²) (P = 0.001). For those with proteinuria at baseline, the annual decline was greater at 2.05 ml min⁻¹ 1.73 m⁻², with both South Asian and black groups having a significantly faster rate of decline than white groups. For patients with diabetes and chronic kidney disease managed in primary care, the annual decline of renal function is less than previously thought and approximates the age-related annual decline of 1 ml min⁻¹ 1.73 m⁻². Patients with proteinuria and those of South Asian and Black ethnicity need additional monitoring as they are at greater risk of rapid chronic kidney disease progression. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  6. Hepatitis C virus molecular evolution: Transmission, disease progression and antiviral therapy

    Science.gov (United States)

    Preciado, Maria Victoria; Valva, Pamela; Escobar-Gutierrez, Alejandro; Rahal, Paula; Ruiz-Tovar, Karina; Yamasaki, Lilian; Vazquez-Chacon, Carlos; Martinez-Guarneros, Armando; Carpio-Pedroza, Juan Carlos; Fonseca-Coronado, Salvador; Cruz-Rivera, Mayra

    2014-01-01

    Hepatitis C virus (HCV) infection represents an important public health problem worldwide. Reduction of HCV morbidity and mortality is a current challenge owned to several viral and host factors. Virus molecular evolution plays an important role in HCV transmission, disease progression and therapy outcome. The high degree of genetic heterogeneity characteristic of HCV is a key element for the rapid adaptation of the intrahost viral population to different selection pressures (e.g., host immune responses and antiviral therapy). HCV molecular evolution is shaped by different mechanisms including a high mutation rate, genetic bottlenecks, genetic drift, recombination, temporal variations and compartmentalization. These evolutionary processes constantly rearrange the composition of the HCV intrahost population in a staging manner. Remarkable advances in the understanding of the molecular mechanism controlling HCV replication have facilitated the development of a plethora of direct-acting antiviral agents against HCV. As a result, superior sustained viral responses have been attained. The rapidly evolving field of anti-HCV therapy is expected to broad its landscape even further with newer, more potent antivirals, bringing us one step closer to the interferon-free era. PMID:25473152

  7. Role of rasagiline in treating Parkinson’s disease: effect on disease progression

    Directory of Open Access Journals (Sweden)

    Irene A Malaty

    2009-05-01

    Full Text Available Irene A Malaty, Hubert H FernandezUniversity of Florida Movement Disorders Center, Gainesville, FL, USAAbstract: Rasagiline is a second generation, selective, irreversible monoamine oxidase type B (MAO-B inhibitor. It has demonstrated efficacy in monotherapy for early Parkinson’s disease (PD patients in one large randomized, placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson’s Disease Outpatients, and has shown ability to reduce off time in more advanced PD patients with motor fluctuations in two large placebo-controlled trials (Parkinson’s Rasagiline: Efficacy and Safety in the Treatment of “Off”, and Lasting Effect in Adjunct Therapy With Rasagiline Given Once Daily. Preclinical data abound to suggest potential for neuroprotection by this compound against a variety of neurotoxic insults in cell cultures and in animals. The lack of amphetamine metabolites provides an advantage over the first generation MAO-B inhibitor selegiline. One large trial has investigated the potential for disease modification in PD patients (Attenuation of Disease progression with Azilect Given Once-daily and preliminary results maintain some possible advantage to earlier initiation of the 1 mg/day dose. The clinical significance of the difference detected remains a consideration.Keywords: rasagiline, Parkinson’s disease, neuroprotection, selegiline

  8. 3D Printing of Tissue Engineered Constructs for In Vitro Modeling of Disease Progression and Drug Screening.

    Science.gov (United States)

    Vanderburgh, Joseph; Sterling, Julie A; Guelcher, Scott A

    2017-01-01

    2D cell culture and preclinical animal models have traditionally been implemented for investigating the underlying cellular mechanisms of human disease progression. However, the increasing significance of 3D vs. 2D cell culture has initiated a new era in cell culture research in which 3D in vitro models are emerging as a bridge between traditional 2D cell culture and in vivo animal models. Additive manufacturing (AM, also known as 3D printing), defined as the layer-by-layer fabrication of parts directed by digital information from a 3D computer-aided design file, offers the advantages of simultaneous rapid prototyping and biofunctionalization as well as the precise placement of cells and extracellular matrix with high resolution. In this review, we highlight recent advances in 3D printing of tissue engineered constructs that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs.

  9. 3D Printing of Tissue Engineered Constructs for in vitro Modeling of Disease Progression and Drug Screening

    Science.gov (United States)

    Vanderburgh, Joseph; Sterling, Julie A.

    2016-01-01

    2D cell culture and preclinical animal models have traditionally been implemented for investigating the underlying cellular mechanisms of human disease progression. However, the increasing significance of 3D versus 2D cell culture has initiated a new era in cell culture research in which 3D in vitro models are emerging as a bridge between traditional 2D cell culture and in vivo animal models. Additive manufacturing (AM, also known as 3D printing), defined as the layer-by-layer fabrication of parts directed by digital information from a 3D computer-aided design (CAD) file, offers the advantages of simultaneous rapid prototyping and biofunctionalization as well as the precise placement of cells and extracellular matrix with high resolution. In this review, we highlight recent advances in 3D printing of tissue engineered constructs (TECs) that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs. PMID:27169894

  10. New progress in brain aging and its related neurological diseases

    Directory of Open Access Journals (Sweden)

    Ming-wei ZHU

    2014-03-01

    Full Text Available Brain aging-related neurological diseases including Alzheimer's disease (AD, Parkinson's disease (PD and cerebral amyloid angiopathy (CAA have become one of the major diseases endangering the health of old people in China. Although the mechanism of brain aging and pathogenesis of its related neurodegenerative diseases remain unclear, protein pathological studies such as tau, α-synuclein (α-Syn, TDP-43 and amyloid-β protein (Aβ based on brain tissue bank and case registration database are opening the door to solve the mystery in the brain aging process and unlock pathogenesis of aging-related neurodegenerative diseases. Research on functional neuroimaging including 11C-PIB PET and 18F-FDDNP PET in Alzheimer's disease and 18F-FDG PET in Parkinson's disease, and biomarkers such as total-tau, phosphorylated-tau, and the 42 amino acid fragment of β-amyloid in cerebrospinal fluid (CSF in the preclinical stages of Alzheimer's disease now become hot topics in the field of elderly dementia and movement disorders. Clinicopathological correlation research of Alzheimer's disease, Parkinson's disease and cerebral amyloid angiopathy is also one of focuses in the geriatric neurological diseases. doi: 10.3969/j.issn.1672-6731.2014.03.004

  11. Acute Q Fever Presenting as Fever of Unknown Origin with Rapidly Progressive Hepatic Failure in a Patient with Alcoholism

    Directory of Open Access Journals (Sweden)

    Po-Han Lin

    2008-11-01

    Full Text Available We report a case of fulminant acute Q fever presenting as fever of unknown origin with rapidly progressive hepatic failure in a patient with alcoholism. A 51-year-old electrician, who was a habitual drinker, presented with a 2-week history of intermittent high fever, acute hepatomegaly and rapidly progressive jaundice after being accidentally exposed to dust from bird nests when he was repairing electrical equipment and circuitry at an abandoned factory in Taipei County. Ascites and prolonged prothrombin time were noted at admission. Transjugular liver biopsy and bone marrow biopsy found multiple small fibrinoid-ring granulomas in liver parenchyma and bone marrow. Doxycycline therapy was empirically started. The fever gradually subsided over a 2-week period, along with the recovery of liver function. The diagnosis of acute Q fever was confirmed by high titers of antibodies against Coxiella burnetii (phase I IgM 1:160 and IgG 1:2560, phase II IgM > 1:320 and IgG 1:5120 and a four-fold elevation of phase II IgG titer in the paired serum. The experience of this case shows that the possibility of Q fever should not be overlooked in patients who have an unexplained febrile illness and severe liver function impairment following exposure to a contaminated environment in Taiwan.

  12. Rapid Detection and Characterization of Emerging Foreign Animal Disease Pathogens

    Energy Technology Data Exchange (ETDEWEB)

    Jaing, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-11-18

    To best safeguard human and animal health requires early detection and characterization of disease events. This must include effective surveillance for emerging infectious diseases. Both deliberate and natural outbreaks have enormous economic and public health impacts, and can present serious threats to national security. In this project, we developed novel next generation detection technologies to protect the agricultural economy and biosecurity. The first technology is a multiplexed assay to simultaneously detection 10 swine viral and bacterial pathogens. The second one is the Lawrence Livermore Microbial Detection Array (LLMDA) which can detect more than 10,000 microbial species including 4219 viruses, 5367 bacteria, 265 fungi, 117 protozoa and 293 archaea. We analyzed a series of swine clinical samples from past disease events to demonstrate the utility of the assays for faster and cheaper detection of emerging and foreign animal disease pathogens, and their utility as s routine diagnosis and surveillance tool. A second goal of the study is to better understand mechanisms of African swine fever virus (ASFV) infection in pigs to aid the development of countermeasures and diagnostics. There is no vaccine available for ASF. ASF outbreak is on the rise on several European countries. Though ASF is not currently in the U.S., a potential outbreak in the U.S. would be detrimental to the swine industry and the US agricultural economy. We pursued a genome-wide approach to characterize the pig immune responses after ASFV infection. We used RNA sequencing and bioinformatics methods to identify genes and pathways that are affected during ASF infection. We have identified a list of most differentially expressed genes that are in the immune response pathways.

  13. Plasma Exchange for Renal Vasculitis and Idiopathic Rapidly Progressive Glomerulonephritis: A Meta-analysis

    DEFF Research Database (Denmark)

    Walsh, Michael; Catapano, Fausta; Szpirt, Wladimir

    2010-01-01

    .9). LIMITATIONS:: Although the primary result was statistically significant, there is insufficient statistical information to reliably determine whether plasma exchange decreases the composite of end-stage renal disease or death. CONCLUSIONS:: Plasma exchange may decrease the composite end point of end...

  14. Homocysteine concentrations in the cognitive progression of Alzheimer’s disease

    OpenAIRE

    Farina, Nicolas; Jernerén, Fredrik; Turner, Cheryl; Hart, Kathryn; Tabet, Naji

    2017-01-01

    Objectives: Hyperhomocysteinemia in Alzheimer’s disease (AD) is widely reported and appears to worsen as the disease progresses. While active dietary intervention with vitamins B12 and folate decreases homocysteine blood levels, with promising clinical outcomes in Mild Cognitive Impairment (MCI), this so far has not been replicated in established AD populations. The aim of the study is to explore the relationship between hyperhomocystenemia and relevant vitamins as the disease progresses.\\ud ...

  15. Difficult preoperative diagnosis in a case of rapidly progressive carcinomatous pericarditis.

    Science.gov (United States)

    Wada, Tomoyuki; Anai, Hirofumi; Shuto, Takashi; Okamoto, Keitaro; Kawano, Madoka; Kozaki, Satoshi; Hirota, Jun; Miyamoto, Shinji

    2016-04-01

    A 54-year-old woman initially diagnosed with stage IIIb squamous cell carcinoma of the uterine cervix was treated with chemotherapy and radiation therapy. After 8 months, she developed dyspnea, leg edema, pleural effusion, pericardial effusion, and liver congestion. Her cardiac ejection fraction was normal and cardiomegaly was not evident. Metastatic carcinomatous pericarditis or pleurisy was suspected, but laboratory findings, including tumor markers, were normal. She was transferred to our hospital for the repair a cardiac injury caused by a pericardial drainage procedure. Emergency surgery was performed for the misplaced drainage catheter in the right atrium and for an abnormal mass in her right and left atria. The clinical diagnosis of carcinomatous pericarditis was made; however, her condition rapidly deteriorated, and she died 6 days postoperatively. At autopsy, metastasis was identified in a large area of the pericardium and myocardium.

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

    LENUS (Irish Health Repository)

    Lonergan, Roisin

    2012-02-01

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

  17. The BSSG rat model of Parkinson's disease: progressing towards a valid, predictive model of disease.

    Science.gov (United States)

    Van Kampen, Jackalina M; Robertson, Harold A

    2017-09-01

    Parkinson's disease (PD) is a neurodegenerative disorder, classically considered a movement disorder. A great deal is known about the anatomical connections and neuropathology and pharmacological changes of PD, as they relate to the loss of dopaminergic function and the appearance of cardinal motor symptoms. Our understanding of the role of dopamine in PD has led to the development of effective pharmacological treatments of the motor symptoms in the form of dopamine replacement therapy using levodopa and dopaminergic agonists. Much of the information concerning these drug treatments has been obtained using classical neurotoxic models that mimic dopamine depletion (e.g., 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or MPTP, 6-hydroxydopamine, reserpine). However, PD is more than a disorder of the nigrostriatal dopamine pathway. Our understanding of the neuropathology of PD has undergone massive changes, with the discovery that mutations in α-synuclein cause a familial form of PD and that PD pathology may spread, affecting multiple neurotransmitter systems and brain regions. These new developments in our understanding of PD demand that we reconsider our animal models. While classic neurotoxin models have been useful for the development of effective symptomatic treatments for motor manifestations, the paucity of a valid animal model exhibiting the progressive development of multiple key features of PD pathophysiology and phenotype has impeded the search for neuroprotective therapies, capable of slowing or halting disease progression. What characteristics would a good animal model of human PD have? In so much as is possible, a good model would exhibit as many behavioral, anatomical, biochemical, immunological, and pathological changes as are observed in the human condition, developing progressively, with clear, identifiable biomarkers along the way. Here, we review the BSSG rat model of PD, a novel environmental model of PD, with strong construct, face, and predictive

  18. Rapid progression to glioblastoma in a subset of IDH-mutated astrocytomas: a genome-wide analysis.

    Science.gov (United States)

    Richardson, Timothy E; Snuderl, Matija; Serrano, Jonathan; Karajannis, Matthias A; Heguy, Adriana; Oliver, Dwight; Raisanen, Jack M; Maher, Elizabeth A; Pan, Edward; Barnett, Samuel; Cai, Chunyu; Habib, Amyn A; Bachoo, Robert M; Hatanpaa, Kimmo J

    2017-05-01

    According to the recently updated World Health Organization (WHO) classification (2016), grade II-III astrocytomas are divided into IDH-wildtype and IDH-mutant groups, the latter being significantly less aggressive in terms of both progression-free and total survival. We identified a small cohort of WHO grade II-III astrocytomas that harbored the IDH1 R132H mutation, as confirmed by both immunohistochemistry and molecular sequence analysis, which nonetheless had unexpectedly rapid recurrence and subsequent progression to glioblastoma. Among these four cases, the mean time to recurrence as glioblastoma was only 16 months and the mean total survival among the three patients who have died during the follow-up was only 31 months. We hypothesized that these tumors had other, unfavorable genetic or epigenetic alterations that negated the favorable effect of the IDH mutation. We applied genome-wide profiling with a methylation array (Illumina Infinium Human Methylation 450k) to screen for genetic and epigenetic alterations in these tumors. As expected, the methylation profiles of all four tumors were found to match most closely with IDH-mutant astrocytomas. Compared with a control group of four indolent, age-similar WHO grade II-III astrocytomas, the tumors showed markedly increased levels of overall copy number changes, but no consistent specific genetic alterations were seen across all of the tumors. While most IDH-mutant WHO grade II-III astrocytomas are relatively indolent, a subset may rapidly recur and progress to glioblastoma. The precise underlying cause of the increased aggressiveness in these gliomas remains unknown, although it may be associated with increased genomic instability.

  19. Independent and combined effect of bilirubin and smoking on the progression of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Wang J

    2018-01-01

    Full Text Available Jiancheng Wang,1,* Binyan Wang,1,2,* Min Liang,1 Guobao Wang,1 Jianping Li,3 Yan Zhang,3 Yong Huo,3 Yimin Cui,4 Xiping Xu,1,5 Xianhui Qin1 1National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, 2Institute for Biomedicine, Anhui Medical University, Hefei, 3Department of Cardiology, 4Department of Pharmacy, Peking University First Hospital, Beijing, 5Beijing Advanced Innovation Center for Food Nutrition and Human Health, Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China *These authors contributed equally to this work Objective: Whether serum bilirubin and cigarette smoking affect the risk of renal function decline remains inconclusive. We aimed to test the independent and combined effects of bilirubin and cigarette smoking on the progression of chronic kidney disease (CKD in hypertensive adults. Methods: The study population consisted of 12,633 patients in the renal sub-study of the China Stroke Primary Prevention Trial. The primary outcome was progression of CKD, defined as a decrease in estimated glomerular filtration rate (eGFR of ≥30% and to a level of <60 mL/min/1.73 m2 if baseline eGFR was ≥60 mL/min/1.73 m2, or a decrease in eGFR of ≥50% if baseline eGFR was <60 mL/min/1.73 m2, or end-stage renal disease. The secondary outcomes included 1 rapid decline in renal function and 2 annual rate of eGFR decline. Results: The median follow-up duration was 4.4 years. Cigarette smoking had no significant effect on the progression of CKD (odds ratio [OR]: 1.11, 95% confidence interval [95% CI]: 0.78–1.57. However, a significantly lower risk of the primary event (OR: 0.72, 95% CI: 0.55–0.95 was found in participants in tertile 3 compared to those in tertiles 1–2 for total bilirubin (TBiL levels. More importantly, there was an interaction

  20. Multimodality molecular imaging of disease progression in living ...

    Indian Academy of Sciences (India)

    2011-08-07

    Aug 7, 2011 ... ... events from single live cells to whole animals with high sensitivity and accurate quantification are discussed. Such approaches have immense potential to track progression of metastasis, immune cell trafficking, stem cell therapy, transgenic animals and even molecular interactions in living subjects.

  1. Rapid In Vivo Validation of Tumor Suppressor Gene Function in Prostate Cancer Progression

    Science.gov (United States)

    2016-07-01

    cancer is critical to distinguish lethal forms of the disease to those that are indolent. Our goal was to establish CRISPR / Cas9 -based methods to...platform to systematically interrogate genes that are significantly mutated in human prostate cancer. Keywords CRISPR / Cas9 , Genetically engineered...goal with the following specific aims: Aim1: Develop in vitro methods to identify effective guide RNAs to quantify CRISPR / Cas9 efficiency We have

  2. Uterine cervical melanoma presenting with rapid progression detected by PET/CT

    Directory of Open Access Journals (Sweden)

    Ya-Ju Tsai

    2012-05-01

    Full Text Available Malignant melanoma of the uterine cervix is a rare extracutaneous melanoma which develops aggressively and is associated with a bleak prognosis. To our knowledge, no prior published reports have discussed the role of 18F-FDG positron emission tomography/computed tomography (PET/CT in managing this disease. Our case study involved a 66-year-old woman with a malignant melanoma of the uterine cervix. The patient received PET/CT that identified metastases and lesions which had not been detected from her MRI. Serial PET/CT elucidated that the disease was initially limited to the pelvis, but then metastasized to the abdominal para-aortic lymph nodes, followed by extensive metastases to the brain, lungs, breast, supraclavicular, neck, and other abdominal lymph nodes, as observed at 6-month follow-up. PET/CT was used to complement conventional anatomic imaging modalities, and provided a novel modality for whole body screening. Visualization of the metabolic activity of indeterminate lesions may help in staging, re-staging, treatment planning, and prognostic prediction for patients with this rare disease.

  3. Acute gouty arthritis and rapidly progressive renal failure as manifestation of multiple myeloma: clinical case description

    Directory of Open Access Journals (Sweden)

    O.V. Gudym

    2017-08-01

    Full Text Available The article describes a clinical case of multiple myeloma in 78-year-old man, its clinical onset was as an acute attack of gout. The patient was admitted to hospital due to the development of the first acute attack of gout. The attack was characterized by polyarthricular joint lesion of the upper and lower extremities, pronounced inflammatory reaction, insufficient response to the use of non-steroidal anti-inflammatory drugs, and a high level of hyperuricemia. The serum uric acid concentration ranged from 636 to 712 μmol/l. The study of the synovial fluid of the inflamed knee joint made it possible to reveal uric acid crystals and to confirm the diagnosis of acute gouty arthritis. Simultaneously, the patient had significant renal impairment: creatinine was 574 μmol/l, urea — 39.9 mmol/l, glomerular filtration rate according to CKD-EPI — 8 ml/min. The daily proteinuria was 1.8 g. A retrospective assessment of laboratory parameters allowed to reveal completely normal indicators of renal function 6 months ago. Considering the development of acute gouty arthritis, its polyarticular nature, persistent course, rapid involvement of new joints, high uric acid levels during an acute attack exceeding 600 μmol/l (10 mg/dL, rapid development of renal failure within 6 months until the terminal stage, it was suggested the secondary nature of gout on the background of kidney damage by another pathological process. Further clinical, laboratory and instrumental studies allowed verifying multiple myeloma with renal damage. Bence Jones protein in the urine was not detected, there was also no evidence of hyperproteinemia. However, pain in the spine, ribs and chest was the basis for carrying out an X-ray study of the bones of the skeleton. Changes in the skeleton typical for multiple myeloma have been identified. Myelogram showed a high content of plasma cells (21.1 %, electrophoresis of blood proteins showed a high M-gradient (30.42 %, and a cytochemical

  4. Model-based economic evaluation in Alzheimer's disease: a review of the methods available to model Alzheimer's disease progression.

    Science.gov (United States)

    Green, Colin; Shearer, James; Ritchie, Craig W; Zajicek, John P

    2011-01-01

    To consider the methods available to model Alzheimer's disease (AD) progression over time to inform on the structure and development of model-based evaluations, and the future direction of modelling methods in AD. A systematic search of the health care literature was undertaken to identify methods to model disease progression in AD. Modelling methods are presented in a descriptive review. The literature search identified 42 studies presenting methods or applications of methods to model AD progression over time. The review identified 10 general modelling frameworks available to empirically model the progression of AD as part of a model-based evaluation. Seven of these general models are statistical models predicting progression of AD using a measure of cognitive function. The main concerns with models are on model structure, around the limited characterization of disease progression, and on the use of a limited number of health states to capture events related to disease progression over time. None of the available models have been able to present a comprehensive model of the natural history of AD. Although helpful, there are serious limitations in the methods available to model progression of AD over time. Advances are needed to better model the progression of AD and the effects of the disease on peoples' lives. Recent evidence supports the need for a multivariable approach to the modelling of AD progression, and indicates that a latent variable analytic approach to characterising AD progression is a promising avenue for advances in the statistical development of modelling methods. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  5. Large cross-sectional study of presbycusis reveals rapid progressive decline in auditory temporal acuity.

    Science.gov (United States)

    Ozmeral, Erol J; Eddins, Ann C; Frisina, D Robert; Eddins, David A

    2016-07-01

    The auditory system relies on extraordinarily precise timing cues for the accurate perception of speech, music, and object identification. Epidemiological research has documented the age-related progressive decline in hearing sensitivity that is known to be a major health concern for the elderly. Although smaller investigations indicate that auditory temporal processing also declines with age, such measures have not been included in larger studies. Temporal gap detection thresholds (TGDTs; an index of auditory temporal resolution) measured in 1071 listeners (aged 18-98 years) were shown to decline at a minimum rate of 1.05 ms (15%) per decade. Age was a significant predictor of TGDT when controlling for audibility (partial correlation) and when restricting analyses to persons with normal-hearing sensitivity (n = 434). The TGDTs were significantly better for males (3.5 ms; 51%) than females when averaged across the life span. These results highlight the need for indices of temporal processing in diagnostics, as treatment targets, and as factors in models of aging. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Stopping rules employing response rates, time to progression, and early progressive disease for phase II oncology trials

    Directory of Open Access Journals (Sweden)

    Goffin John R

    2011-12-01

    Full Text Available Abstract Background Response rate (RR, the most common early means of assessing oncology drugs, is not suitable as the sole endpoint for phase II trials of drugs which induce disease stability but not regression. Time to progression (TTP may be more sensitive to such agents, but induces recruitment delays in multistage studies. Early progressive disease (EPD is the earliest signal of time to progression, but is less intuitive to investigators, To study drugs with unknown anti-tumour effect, we designed the Combination Stopping Rule (CSR, which allows investigators to establish a hypothesis using RR and TTP, while the program also employs early progressive disease (EPD to assess for drug inactivity during the first stage of study accrual. Methods A computer program was created to generate stopping rules based on specified error rates, trial size, and RR and median TTP of interest and disinterest for a two-stage phase II trial. Rules were generated for stage II such that the null hypothesis (Hnul was rejected if either RR or TTP met desired thresholds, and accepted if both did not. Assuming an exponential distribution for progression, EPD thresholds were determined based on specified TTP values. Stopping rules were generated for stage I such that Hnul was accepted and the study stopped if both RR and EPD were unacceptable. Results Patient thresholds were generated for RR, median TTP, and EPD which achieved specified error rates and which allowed early stopping based on RR and EPD. For smaller proportional differences between interesting and disinteresting values of RR or TTP, larger trials are required to maintain alpha error, and early stopping is more common with a larger first stage. Conclusion Stopping rules are provided for phase II trials for drugs which have either a desirable RR or TTP. In addition, early stopping can be achieved using RR and EPD.

  7. Primary pleural leiomyosarcoma with rapid progression and fatal outcome: a case report

    Directory of Open Access Journals (Sweden)

    Rais Ghizlane

    2012-04-01

    Full Text Available Abstract Introduction Leiomyosarcomas are neoplasms of smooth muscles that most commonly arise from the uterus, gastrointestinal tract, or soft tissue. Primary pleural leiomyosarcoma is extremely rare. To the best of our knowledge, only nine cases have been published to date. Because of the rarity of pleural leiomyosarcoma and its similarity (clinical and histological to other pleural neoplasms, particularly sarcomatous mesothelioma, diagnosis is often difficult. Case presentation A 58-year-old North African man was admitted with complaints of dyspnea and chest pain to our hospital. Chest computed tomography revealed right pleural effusion and pleural thickening. A transthoracic needle biopsy yielded a diagnosis of leiomyosarcoma, and tumor cells were strongly and uniformly positive for vimentin, a smooth muscle actin at immunohistochemical analysis. A general examination did not show any metastatic lesions in other areas. One month after diagnosis, the tumor grew rapidly, with pulmonary invasion, and therefore he was treated only by palliative care. He died from respiratory failure one month later. Because no organ of origin of the leiomyosarcoma, other than the pleura, was detected, this case was diagnosed as a primary pleural leiomyosarcoma. Conclusions Although leiomyosarcoma originating from the pleura is rare, this entity is increasingly described. The purpose of presenting this case report is to raise awareness among clinicians to consider this clinical entity as a differential diagnosis when a pleural mass is identified.

  8. Characterization of annual disease progression of multiple sclerosis patients: A population-based study

    DEFF Research Database (Denmark)

    Freilich, Jonatan; Manouchehrinia, Ali; Trusheim, Mark

    2017-01-01

    Previous research characterizing factors influencing multiple sclerosis (MS) disease progression has typically been based on time to disease milestones (Kaplan-Meier, Cox hazard regression, etc.). A limitation of these methods is the handling of the often large groups of patients not reaching...... the milestone. To characterize clinical factors influencing MS disease progression as annual transitions from each Expanded Disability Status Scale (EDSS). The annual progression of 11,964 patients from the Swedish MS Registry was analysed with 10 multinomial logistic regressions, that is, one for transition...

  9. Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study

    NARCIS (Netherlands)

    Kamara, David A.; Ryom, Lene; Ross, Michael; Kirk, Ole; Reiss, Peter; Morlat, Philippe; Moranne, Olivier; Fux, Christoph A.; Mocroft, Amanda; Sabin, Caroline; Lundgren, Jens D.; Smith, Colette J.; Powderly, B.; Shortman, N.; Moecklinghoff, C.; Reilly, G.; Franquet, X.; Ryom, L.; Sabin, C. A.; Kamara, D.; Smith, C.; Phillips, A.; Mocroft, A.; Tverland, J.; Mansfeld, M.; Nielsen, J.; Raben, D.; Lundgren, J. D.; Brandt, R. Salbøl; Rickenbach, M.; Fanti, I.; Krum, E.; Hillebregt, M.; Geffard, S.; Sundström, A.; Delforge, M.; Fontas, E.; Torres, F.; McManus, H.; Wright, S.; Kjær, J.; Sjøl, A.; Meidahl, P.; Helweg-Larsen, J.; Iversen, J. Schmidt; Kirk, O.; Ross, M.; Fux, C. A.; Morlat, P.; Moranne, O.; Kesselring, A. M.; Kamara, D. A.; Weber, R.; Pradier, C.; Friis-Møller, N.; Kowalska, J.; Sabin, C.; Law, M.; d'Arminio Monforte, A.; Dabis, F.; Bruyand, M.; Bower, M.; Fätkenheuer, G.; Donald, A.; Grulich, A.; Zaheri, S.; Gras, L.; Prins, J. M.; Kuijpers, T. W.; Scherpbier, H. J.; van der Meer, J. T. M.; Wit, F. W. M. N.; Godfried, M. H.; van der Poll, dr T.; Nellen, F. J. B.; Lange, J. M. A.; Geerlings, S. E.; van Vugt, M.; Pajkrt, D.; Bos, Drs J. C.; van der Valk, Drs M.; Grijsen, M. L.; Wiersinga, W. J.; Goorhuis, A.; Hovius, J. W. R.; Lowe, S.; Oude Lashof, A.; Posthouwer, D.; Ammerlaan, H. S. M.; Pronk, M. J. H.; van der Ende, M. E.; de Vries-Sluijs, T. E. M. S.; Schurink, C. A. M.; Nouwen, J. L.; Verbon, A.; Rijnders, B. J. A.; van Gorp, E. C. M.; van der Feltz, M.; Driessen, G. J. A.; van Rossum, A. M. C.; Branger, J.; Schippers, F.; van Nieuwkoop, C.; van Elzakker, E. P.; Groeneveld, P. H. P.; Bouwhuis, J. W.; Soetekouw, R.; ten Kate, R. W.; Kroon, F. P.; van Dissel, J. T.; Arend, S. M.; de Boer, M. G. J.; Jolink, H.; ter Vollaard, H. J. M.; Bauer, M. P.; den Hollander, J. G.; Pogany, K.; van Twillert, Drs G.; Kortmann, W.; Stuart, J. W. T. Cohen; Diederen, B. M. W.; Leyten, M. S.; Gelinck, L. B. S.; Kootstra, G. J.; Delsing, C. E.; Brinkman, K.; Blok, W. L.; Frissen, P. H. J.; Schouten, W. E. M.; van den Berk, G. E. L.; van Kasteren, M. E. E.; Brouwer, A. E.; Veenstra, J.; Lettinga, K. D.; Mulder, J. W.; Vrouenraets, S. M. E.; Lauw, F. N.; van Eeden, A.; Verhagen, D. W. M.; Sprenger, H. G.; Doedens, R.; Scholvinck, E. H.; van Assen, S.; Bierman, W. F. W.; Koopmans, P. P.; Keuter, M.; van der Ven, A. J. A. M.; ter Hofstede, H. J. M.; Dofferhoff, A. S. M.; Warris, A.; van Crevel, R.; Hoepelman, A. I. M.; Mudrikova, T.; Schneider, M. M. E.; Ellerbroek, P. M.; Oosterheert, J. J.; Arends, J. E.; Wassenberg, M. W. M.; Barth, R. E.; van Agtmael, M. A.; Perenboom, R. M.; Claessen, F. A. P.; Bomers, M.; Peters, E. J. G.; Geelen, S. P. M.; Wolfs, T. F. W.; Bont, L. J.; Richter, C.; van der Berg, J. P.; Gisolf, E. H.; van den Berge, M.; Stegeman, A.; van Vonderen, M. G. A.; van Houte, D. P. F.; Weijer, S.; el Moussaoui, R.; Winkel, C.; Muskiet, F.; Durand, N. N.; Voigt, R.; Chêne, G.; Lawson-Ayayi, S.; Thiébaut, R.; Bonnal, F.; Bonnet, F.; Bernard, N.; Caunègre, L.; Cazanave, C.; Ceccaldi, J.; Chambon, D.; Chossat, I.; Dauchy, F. A.; de Witte, S.; Dupon, M.; Duffau, P.; Dutronc, H.; Farbos, S.; Gaborieau, V.; Gemain, M. C.; Gerard, Y.; Greib, C.; Hessamfar, M.; Lacoste, D.; Lataste, P.; Lafarie, S.; Lazaro, E.; Malvy, D.; Meraud, J. P.; Mercié, P.; Monlun, E.; Neau, D.; Ochoa, A.; Pellegrin, J. L.; Pistone, T.; Ragnaud, J. M.; Receveur, M. C.; Tchamgoué, S.; Vandenhende, M. A.; Viallard, J. F.; Moreau, J. F.; Pellegrin, I.; Fleury, H.; Lafon, M. E.; Masquelier, B.; Trimoulet, P.; Breilh, D.; Haramburu, F.; Miremont-Salamé, G.; Blaizeau, M. J.; Decoin, M.; Delaune, J.; Delveaux, S.; D'Ivernois, C.; Hanapier, C.; Leleux, O.; Uwamaliya-Nziyumvira, B.; Sicard, X.; Palmer, G.; Touchard, D.; Petoumenos, K.; Bendall, C.; Moore, R.; Edwards, S.; Hoy, J.; Watson, K.; Roth, N.; Nicholson, J.; Bloch, M.; Franic, T.; Baker, D.; Vale, R.; Carr, A.; Cooper, D.; Chuah, J.; Ngieng, M.; Nolan, D.; Skett, J.; Calvo, G.; Mateu, S.; Domingo, P.; Sambeat, M. A.; Gatell, J.; del Cacho, E.; Cadafalch, J.; Fuster, M.; Codina, C.; Sirera, G.; Vaqué, A.; de Wit, S.; Clumeck, N.; Necsoi, C.; Gennotte, A. F.; Gerard, M.; Kabeya, K.; Konopnicki, D.; Libois, A.; Martin, C.; Payen, M. C.; Semaille, P.; van Laethem, Y.; Neaton, J.; Bartsch, G.; El-Sadr, W. M.; Thompson, G.; Wentworth, D.; Luskin-Hawk, R.; Telzak, E.; Abrams, D. I.; Cohn, D.; Markowitz, N.; Arduino, R.; Mushatt, D.; Friedland, G.; Perez, G.; Tedaldi, E.; Fisher, E.; Gordin, F.; Crane, L. R.; Sampson, J.; Baxter, J.; Lundgren, J.; Cozzi-Lepri, A.; Grint, D.; Podlekareva, D.; Peters, L.; Reekie, J.; Fischer, A. H.; Losso, M.; Elias, C.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Suetnov, O.; Colebunders, R.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Machala, L.; Begovac, J.; Jilich, D.; Sedlacek, D.; Kronborg, G.; Gerstoft, J.; Benfield, T.; Larsen, M.; Katzenstein, T.; Hansen, A.-B. E.; Skinhøj, P.; Pedersen, C.; Ostergaard, L.; Zilmer, K.; Smidt, Jelena; Ristola, M.; Katlama, C.; Viard, J.- P.; Girard, P.- M.; Livrozet, J. M.; Vanhems, P.; Rockstroh, J.; Schmidt, R.; van Lunzen, J.; Degen, O.; Stellbrink, H. J.; Staszewski, S.; Bickel, M.; Kosmidis, J.; Gargalianos, P.; Xylomenos, G.; Perdios, J.; Panos, G.; Filandras, A.; Karabatsaki, E.; Sambatakou, H.; Banhegyi, D.; Mulcahy, F.; Yust, I.; Turner, D.; Burke, M.; Pollack, S.; Hassoun, G.; Maayan, S.; Vella, S.; Esposito, R.; Mazeu, I.; Mussini, C.; Arici, C.; Pristera, R.; Mazzotta, F.; Gabbuti, A.; Vullo, V.; Lichtner, M.; Chirianni, A.; Montesarchio, E.; Gargiulo, M.; Antonucci, G.; Testa, A.; Narciso, P.; Vlassi, C.; Zaccarelli, M.; Lazzarin, A.; Castagna, A.; Gianotti, N.; Galli, M.; Ridolfo, A.; Rozentale, B.; Zeltina, I.; Chaplinskas, S.; Hemmer, R.; Staub, T.; Ormaasen, V.; Maeland, A.; Bruun, J.; Knysz, B.; Gasiorowski, J.; Horban, A.; Bakowska, E.; Grzeszczuk, A.; Flisiak, R.; Boron-Kaczmarska, A.; Pynka, M.; Parczewski, M.; Beniowski, M.; Mularska, E.; Trocha, H.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Antunes, F.; Doroana, M.; Caldeira, L.; Mansinho, K.; Maltez, F.; Duiculescu, D.; Rakhmanova, A.; Babes, Victor; Zakharova, N.; Jevtovic, D.; Mokráš, M.; Staneková, D.; Tomazic, J.; González-Lahoz, J.; Soriano, V.; Labarga, P.; Medrano, J.; Moreno, S.; Rodriguez, J. M.; Clotet, B.; Jou, A.; Paredes, R.; Tural, C.; Puig, J.; Bravo, I.; Gatell, J. M.; Miró, J. M.; Gutierrez, M.; Karlsson, A.; Mateo, G.; Flamholc, L.; Ledergerber, B.; Francioli, P.; Cavassini, M.; Hirschel, B.; Boffi, E.; Kravchenko, E.; Furrer, H.; Battegay, M.; Elzi, L.; Chentsova, N.; Frolov, V.; Kutsyna, G.; Servitskiy, S.; Krasnov, M.; Barton, S.; Johnson, A. M.; Mercey, D.; Johnson, M. A.; Murphy, M.; Weber, J.; Scullard, G.; Fisher, M.; Leen, C.; Morfeldt, L.; Thulin, G.; Åkerlund, B.; Koppel, K.; Håkangård, C.; Moroni, M.; Angarano, G.; Antinori, A.; Armignacco, O.; Castelli, F.; Cauda, R.; Di Perri, G.; Iardino, R.; Ippolito, G.; Perno, C. F.; von Schloesser, F.; Viale, P.; Ceccherini-Silberstein, F.; Girardi, E.; Lo Caputo, S.; Puoti, M.; Andreoni, Massimo; Ammassari, Adriana; Antinori, Andrea; Balotta, Claudia; Bonfanti, Paolo; Bonora, Stefano; Borderi, Marco; Capobianchi, M. Rosaria; Castagna, Antonella; Ceccherini-Silberstein, Francesca; Cingolani, Antonella; Cinque, Paola; Cozzi-Lepri, Alessandro; de Luca, Andrea; Di Biagio, Antonio; Girardi, Enrico; Gianotti, Nicola; Gori, Andrea; Guaraldi, Giovanni; Lapadula, Giuseppe; Lichtner, Miriam; Madeddu, Giordano; Maggiolo, Franco; Marchetti, Giulia; Marcotullio, Simone; Monno, Laura; Mussini, Cristina; Puoti, Massimo; Quiros, Eugenia; Rusconi, Stefano; Cicconi, P.; Formenti, T.; Galli, L.; Lorenzini, P.; Giacometti, A.; Costantini, A.; Monno, L.; Santoro, C.; Maggiolo, F.; Suardi, C.; Vanino, E.; Verucchi, G.; Quiros Roldan, E.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Cassola, G.; Viscoli, G.; Alessandrini, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Bonfanti, P.; Caramma, I.; Castelli, A. P.; Rizzardini, G.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Marchetti, G.; Puzzolante, C.; Gori, A.; Onofrio, M.; Lapadula, G.; Abrescia, N.; Guida, M. G.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Andreoni, M.; Cingolani, A.; d' Avino, A.; Ammassari, A.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Tebano, G.; Cattelan, A.; Mura, M. S.; Madeddu, G.; Caramello, P.; Orofino, G. C.; Bonora, S.; Sciandra, M.; Pellizzer, G.; Manfrin, V.; Caissotti, C.; Dellamonica, P.; Bernard, E.; Cua, E.; de Salvador- Guillouet, F.; Durant, J.; Ferrando, S.; Mondain-Miton, V.; Naqvi, A.; Perbost, I.; Prouvost-Keller, B.; Pillet, S.; Pugliese, P.; Rahelinirina, V.; Roger, P. M.; Dollet, K.; Aubert, V.; Barth, J.; Bernasconi, E.; Böni, J.; Bucher, H. C.; Burton- Jeangros, C.; Calmy, A.; Egger, M.; Fehr, J.; Fellay, J.; Gorgievski, M.; Günthard, H.; Haerry, D.; Hasse, B.; Hirsch, H. H.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Klimkait, T.; Kovari, H.; Martinetti, G.; de Tejada, B. Martinez; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, A.; Rudin, C.; Schmid, P.; Schultze, D.; Schöni-Affolter, F.; Schüpbach, J.; Speck, R.; Taffé, P.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Yerly, S.

    2014-01-01

    No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data

  10. Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons : the D:A:D study

    NARCIS (Netherlands)

    Kamara, David A; Ryom, Lene; Ross, Michael; Kirk, Ole; Reiss, Peter; Morlat, Philippe; Moranne, Olivier; Fux, Christoph A; Mocroft, Amanda; Sabin, Caroline; Lundgren, Jens D; Smith, Colette J; Schölvinck, Elisabeth H.

    2014-01-01

    BACKGROUND: No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the

  11. Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study

    NARCIS (Netherlands)

    Kamara, D.A.; Ryom, L.; Ross, M.; Kirk, O.; Reiss, P.; Morlat, P.; Moranne, O.; Fux, C.A.; Mocroft, A.; Sabin, C.; Lundgren, J.D.; Smith, C.J.; Koopmans, P.P.; Keuter, M.; Ven, A.J.A.M. van der; Hofstede, H.J.M. ter; Dofferhoff, A.S.M.; Warris, A.; Crevel, R. van

    2014-01-01

    BACKGROUND: No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in

  12. The applause sign and neuropsychological profile in progressive supranuclear palsy and Parkinson's disease.

    Science.gov (United States)

    Somme, Johanne; Gómez-Esteban, Juan Carlos; Tijero, Beatriz; Berganzo, Koldo; Lezcano, Elena; Zarranz, Juan Jose

    2013-08-01

    The applause sign has been associated with various neurodegenerative diseases. We investigate its validity in the differential diagnosis of progressive supranuclear palsy and Parkinson's disease, and its relationship with neuropsychological tests. 23 patients with progressive supranuclear palsy and 106 patients with Parkinson's disease were included and administered the following scales: progressive supranuclear palsy rating scale, unified Parkinson's disease rating scale (UPDRS), mini-mental state examination (MMSE), frontal assessment battery (FAB), neuropsychiatric inventory and three-clap test. 73.9% with progressive supranuclear palsy and 21.7% with Parkinson's disease showed a positive applause sign. Only a positive applause sign, UPDRS II score and disease duration were found to be predictors of progressive supranuclear palsy. Both patient-groups showed statistically significant correlations between the applause sign and neuropsychological tests: in progressive supranuclear palsy patients MMSE correlation coefficient: 0.62 (p: 0.002) and FAB correlation coefficient: 0.48 (p: 0.02), and in Parkinson's disease patients MMSE correlation coefficient: 0.47 (pParkinson's disease patients with altered cognition, and it's related to cortical frontal abnormalities such as language disorders and inhibitory control. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Anosognosia in Alzheimer disease: Prevalence, associated factors, and influence on disease progression.

    Science.gov (United States)

    Castrillo Sanz, A; Andrés Calvo, M; Repiso Gento, I; Izquierdo Delgado, E; Gutierrez Ríos, R; Rodríguez Herrero, R; Rodríguez Sanz, F; Tola-Arribas, M A

    2016-06-01

    Anosognosia is a frequent symptom in Alzheimer disease (AD). The objective of this article is to describe prevalence of this condition at time of diagnosis and analyse any predisposing factors and their influence on disease progression. Observational, prospective, and analytical multi-centre study in an outpatient setting. Patients recently diagnosed with AD (NINCDS-ADRDA criteria) were included. Each patient underwent two cognitive, functional, and neuropsychiatric assessments separated by an interval of 18 months. The Clinical Insight Rating Scale was employed as a measure of anosognosia (CIR, scored 0-8). Progression was defined as an increase in the Clinical Dementia Rating Scale-sum of boxes of more than 2.5 points. The predictor variables were analysed using binary logistic regression. The study included 127 patients, and 94 completed both assessments. Of the total, 31.5% displayed severe anosognosia (CIR 7-8); 39.4%, altered level of consciousness (CIR 3-6); and 29.1%, normal awareness (CIR 0-2). The median baseline CIR in this cohort was 4 (Q1-Q3: 1-7), and at 18 months, 6 (Q1-Q3: 3-8), P<.001. Advanced age (odds ratio (OR) 2.43; CI 95%:1.14-5.19), lower educational level (OR 2.15; CI 95%:1.01-4.58), and more marked neuropsychiatric symptoms (OR 2.66; CI 95%:1.23-5.74) were predictor variables of anosognosia. Baseline CIR was similar in the groups with and without significant clinical progression. The large majority of patients with AD at the time of diagnosis showed significant anosognosia, and this condition was associated with advanced age, lower educational level, and more marked behavioural symptoms. Our results did not show that anosognosia had an effect on the initial clinical progression of AD after diagnosis. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Clinical follow-up data and the rate of development of precocious and rapidly progressive puberty in patients with premature thelarche.

    Science.gov (United States)

    Çiçek, Dilek; Savas-Erdeve, Senay; Cetinkaya, Semra; Aycan, Zehra

    2018-01-26

    We aimed to evaluate the clinical follow-up data of patients with premature thelarche and determine the rate of development of precocious and early puberty in these patients. The charts of 158 girls with premature thelarche who were followed-up in our pediatric endocrinology polyclinic were reviewed. The patients were divided into three groups according to the age at onset: group 1 (0-1 month) (n=12), group 2 (1-24 months) (n=40) and group 3 (2-8 years) (n=106). At admission, the mean height standard deviation score (SDS), body weight (BW)-SDS, body mass index (BMI) and BMI-SDS were significantly higher in group 3 than in group 1 and group 2. At admission, 8.8% of the patients were obese and 24% of the patients were overweight. The majority of patients who were obese and overweight were in group 3. At the end of the follow-up, thelarche regressed in 24.7%, persisted in 32.9%, progressed in 25.9% and had a cyclic pattern in 16.5% of the patients. Precocious or rapidly progressive puberty developed in 47 of the 158 patients (29.7%). The mean age at progression to early or rapidly progressive puberty was 98.1±17.6 months. A total of 89.3% of the patients who progressed to early or rapidly progressive puberty were in group 3. Precocious or rapidly progressive puberty developed in 29.7% of subjects with premature thelarche. As patients who developed rapidly progressive puberty had a higher BW-SDS and BMI-SDS than those who did not, it is suggested that the increase in weight could stimulate rapidly progressive puberty in cases with premature thelarche.

  15. Serial Noninvasive Assessment of Apoptosis During Right Ventricular Disease Progression in Rats

    NARCIS (Netherlands)

    Campian, Maria E.; Verberne, Hein J.; Hardziyenka, Maxim; de Bruin, Kora; Selwaness, Mariana; van den Hoff, Maurice J. B.; Ruijter, Jan M.; van Eck-Smit, Berthe L. F.; de Bakker, Jacques M. T.; Tan, Hanno L.

    2009-01-01

    Right ventricular (RV) function is the major determinant of survival in patients with pulmonary hypertension. Yet, the pathophysiologic basis of RV disease is unresolved. We aimed to study the role of apoptosis in RV disease by monitoring it serially during disease progression using in vivo

  16. Brain Region Specific Degeneration with Disease Progression in Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2 Disease)

    Science.gov (United States)

    Dyke, JP; Sondhi, D; Voss, HU; Yohay, K; Hollmann, C; Mancenido, D; Kaminsky, SM; Heier, LA; Rudser, KD; Kosofsky, B; Casey, BJ; Crystal, RG; Ballon, D

    2015-01-01

    Background and Purpose Late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is a uniformly fatal lysosomal storage disease resulting from mutations in the CLN2 gene. Our hypothesis was that regional analysis of cortical brain degeneration may identify brain regions that are affected earliest as well as most severely by the disease. Materials and Methods Fifty-two high resolution 3.0 Tesla MRI data sets were prospectively acquired on thirty-eight subjects with CLN2. A retrospective cohort of fifty-two disease free children served as a control population. The FreeSurfer software suite was used for calculation of cortical thickness. Results An increased rate of global cortical thinning in CLN2 versus control subjects was the primary finding in this study. Three distinct patterns were observed across brain regions. In the first, CLN2 subjects exhibited differing rates of cortical thinning versus age. This was true in 22 and 26 of 34 regions in the left and right hemisphere respectively, and was also clearly discernable when considering brain lobes as a whole and Brodmann’s regions. The second pattern exhibited a difference in thickness from normal controls but with no discernable change with age (9 left hemisphere; 5 right hemisphere). In the third pattern there was no difference in either the rate of cortical thinning or the mean cortical thickness between groups (3 left hemisphere; 3 right hemisphere). Conclusions This study demonstrates that CLN2 causes differential rates of degeneration across the brain. Anatomical and functional regions that degenerate sooner and more severely than others compared to normal controls may offer targets for directed therapies. The information gained may also provide neurobiological insights regarding the mechanisms underlying disease progression. PMID:26822727

  17. Radiation cataracts: mechanisms involved in their long delayed occurrence but then rapid progression.

    Science.gov (United States)

    Wolf, Norman; Pendergrass, William; Singh, Narendra; Swisshelm, Karen; Schwartz, Jeffrey

    2008-02-05

    This study was directed to assess the DNA damage and DNA repair response to X-ray inflicted lens oxidative damage and to investigate the subsequent changes in lens epithelial cell (LEC) behavior in vivo that led to long delayed but then rapidly developing cataracts. Two-month-old C57Bl/6 female mice received 11 Grays (Gy) of soft x-irradiation to the head only. The animals' eyes were examined for cataract status in 30 day intervals by slit lamp over an 11 month period post-irradiation. LEC migration, DNA fragment, free DNA retention, and reactive oxygen species (ROS) presence were established in the living lenses with fluorescent dyes using laser scanning confocal microscopy (LSCM). The extent and removal of initial LEC DNA damage were determined by comet assay. Immunohistochemistry was used to determine the presence of oxidized DNA and the response of a DNA repair protein in the lenses. This treatment resulted in advanced cortical cataracts that developed 5-11 months post-irradiation but then appeared suddenly within a 30 day period. The initially incurred DNA strand breaks were repaired within 30 min, but DNA damage remained as shown 72 h post-irradiation by the presence of the DNA adduct, 8-hydroxyguanosine (8-OHG), and a DNA repair protein, XRCC1. This was followed months later by abnormal behavior by LEC descendant cells with abnormal differentiation and migration patterns as seen with LSCM and fluorescent dyes. The sudden development of cortical cataracts several months post-irradiation coupled with the above findings suggests an accumulation of damaged descendants from the initially x-irradiated LECs. As these cells migrate abnormally and leave acellular lens surface sites, eventually a crisis point may arrive for lens entry of environmental O(2) with resultant ROS formation that overwhelms protection by resident antioxidant enzymes and results in the coagulation of lens proteins. The events seen in this study indicate the retention and transmission of

  18. Inhibition of Aerobic Glycolysis Attenuates Disease Progression in Polycystic Kidney Disease.

    Directory of Open Access Journals (Sweden)

    Meliana Riwanto

    Full Text Available Dysregulated signaling cascades alter energy metabolism and promote cell proliferation and cyst expansion in polycystic kidney disease (PKD. Here we tested whether metabolic reprogramming towards aerobic glycolysis ("Warburg effect" plays a pathogenic role in male heterozygous Han:SPRD rats (Cy/+, a chronic progressive model of PKD. Using microarray analysis and qPCR, we found an upregulation of genes involved in glycolysis (Hk1, Hk2, Ldha and a downregulation of genes involved in gluconeogenesis (G6pc, Lbp1 in cystic kidneys of Cy/+ rats compared with wild-type (+/+ rats. We then tested the effect of inhibiting glycolysis with 2-deoxyglucose (2DG on renal functional loss and cyst progression in 5-week-old male Cy/+ rats. Treatment with 2DG (500 mg/kg/day for 5 weeks resulted in significantly lower kidney weights (-27% and 2-kidney/total-body-weight ratios (-20% and decreased renal cyst index (-48% compared with vehicle treatment. Cy/+ rats treated with 2DG also showed higher clearances of creatinine (1.98±0.67 vs 1.41±0.37 ml/min, BUN (0.69±0.26 vs 0.40±0.10 ml/min and uric acid (0.38±0.20 vs 0.21±0.10 ml/min, and reduced albuminuria. Immunoblotting analysis of kidney tissues harvested from 2DG-treated Cy/+ rats showed increased phosphorylation of AMPK-α, a negative regulator of mTOR, and restoration of ERK signaling. Assessment of Ki-67 staining indicated that 2DG limits cyst progression through inhibition of epithelial cell proliferation. Taken together, our results show that targeting the glycolytic pathway may represent a promising therapeutic strategy to control cyst growth in PKD.

  19. Rapid cortical bone loss in patients with chronic kidney disease.

    Science.gov (United States)

    Nickolas, Thomas L; Stein, Emily M; Dworakowski, Elzbieta; Nishiyama, Kyle K; Komandah-Kosseh, Mafo; Zhang, Chiyuan A; McMahon, Donald J; Liu, Xiaowei S; Boutroy, Stephanie; Cremers, Serge; Shane, Elizabeth

    2013-08-01

    Chronic kidney disease (CKD) patients may have high rates of bone loss and fractures, but microarchitectural and biochemical mechanisms of bone loss in CKD patients have not been fully described. In this longitudinal study of 53 patients with CKD Stages 2 to 5D, we used dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT), and biochemical markers of bone metabolism to elucidate effects of CKD on the skeleton. Median follow-up was 1.5 years (range 0.9 to 4.3 years); bone changes were annualized and compared with baseline. By DXA, there were significant declines in areal bone mineral density (BMD) of the total hip and ultradistal radius: -1.3% (95% confidence interval [CI] -2.1 to -0.6) and -2.4% (95% CI -4.0 to -0.9), respectively. By HRpQCT at the distal radius, there were significant declines in cortical area, density, and thickness and increases in porosity: -2.9% (95% CI -3.7 to -2.2), -1.3% (95% CI -1.6 to -0.6), -2.8% (95% CI -3.6 to -1.9), and +4.2% (95% CI 2.0 to 6.4), respectively. Radius trabecular area increased significantly: +0.4% (95% CI 0.2 to 0.6), without significant changes in trabecular density or microarchitecture. Elevated time-averaged levels of parathyroid hormone (PTH) and bone turnover markers predicted cortical deterioration. Higher levels of serum 25-hydroxyvitamin D predicted decreases in trabecular network heterogeneity. These data suggest that significant cortical loss occurs with CKD, which is mediated by hyperparathyroidism and elevated turnover. Future investigations are required to determine whether these cortical losses can be attenuated by treatments that reduce PTH levels and remodeling rates. Copyright © 2013 American Society for Bone and Mineral Research.

  20. Progressive age-related changes in sleep and EEG profiles in the PLB1Triple mouse model of Alzheimer's disease.

    Science.gov (United States)

    Jyoti, Amar; Plano, Andrea; Riedel, Gernot; Platt, Bettina

    2015-10-01

    Sleep disturbances are common in Alzheimer's disease (AD) and now assumed to contribute to disease onset and progression. Here, we investigated whether activity, sleep/wake pattern, and electroencephalogram (EEG) profiles are altered in the knock-in PLB1Triple mouse model from 5 to 21 months of age. PLB1Triple mice displayed a progressive increase in wakefulness and non-rapid eye movement sleep fragmentation from 9 months onward, whereas PLB1WT wild type controls showed such deterioration only at 21 months. Impaired habituation to spatial novelty was also detected in PLB1Triple mice. Hippocampal power spectra of transgenic mice revealed progressive, vigilance stage-, brain region-, and age-specific changes. Age had an impact on EEG spectra in both cohorts but led to accelerated genotype-dependent differences, ultimately affecting all bands at 21 months. Overall, although PLB1Triple animals display only subtle amyloid and tau pathologies, robust sleep-wake and EEG abnormalities emerged. We hypothesize that such endophenotypes are sensitive, noninvasive, and reliable biomarker to identify onset and progression of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Clinical Aspects of Melatonin Intervention in Alzheimers Disease Progression

    National Research Council Canada - National Science Library

    Daniel P. Cardinali; Analia M. Furio; Luis I. Brusco

    2010-01-01

    Melatonin secretion decreases in Alzheimers disease (AD) and this decrease has been postulated as responsible for the circadian disorganization, decrease in sleep efficiency and impaired cognitive function seen in those patients...

  2. Research progress on animal models of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Wen DONG

    2015-08-01

    Full Text Available Alzheimer's disease (AD is a degenerative disease of the central nervous system, and its pathogenesis is complex. Animal models play an important role in study on pathogenesis and treatment of AD. This paper summarized methods of building models, observation on animal models and evaluation index in recent years, so as to provide related evidence for basic and clinical research in future. DOI: 10.3969/j.issn.1672-6731.2015.08.003

  3. Rapid eye movement sleep behavior disorder in Parkinson's disease: magnetic resonance imaging study.

    Science.gov (United States)

    Ford, Andrew H; Duncan, Gordon W; Firbank, Michael J; Yarnall, Alison J; Khoo, Tien K; Burn, David J; O'Brien, John T

    2013-06-01

    Rapid eye movement sleep behavior disorder has poor prognostic implications for Parkinson's disease. The authors recruited 124 patients with early Parkinson's disease to compare clinical and neuroimaging findings based on the presence of this sleep disorder. The presence of rapid eye movement sleep behavior disorder was assessed with the Mayo Sleep Questionnaire. Magnetic resonance imaging sequences were obtained for voxel-based morphometry and diffusion tensor imaging. Patients with sleep disorder had more advanced disease, but groups had similar clinical characteristics and cognitive performance. Those with sleep disorder had areas of reduced cortical grey matter volume and white matter changes compared with those who did not have sleep disorder. However, differences were slight and were not significant when the analyses were adjusted for multiple comparisons. Rapid eye movement sleep behavior disorder was associated with subtle changes in white matter integrity and grey matter volume in patients with early Parkinson's disease. Copyright © 2013 Movement Disorder Society.

  4. Delineating genetic pathways of disease progression in head and neck squamous cell carcinoma

    NARCIS (Netherlands)

    Worsham, MJ; Pals, G; Schouten, JP; van Spaendonk, RML; Concus, A; Carey, TE; Benninger, MS

    Objective: To identify altered gene targets that characterize disease progression in squamous cell carcinoma (SCC) of the head and neck (HNSCC). Genetic alterations in HNSCC cell lines reflect the tumor in vivo and can serve as valuable tools to study the development and progression of HNSCC.

  5. [Rapidly progressive ANCA positive glomerulonephritis as the presenting feature of infectious endocarditis].

    Science.gov (United States)

    Hanf, W; Serre, J-E; Salmon, J-H; Fabien, N; Ginon, I; Dijoud, F; Trolliet, P

    2011-12-01

    The association of positive cytoplasmic antineutrophil antibody (ANCA) necrotizing crescentic glomerulonephritis with endocarditis raises diagnostic issues. Indeed, it is often difficult to determine if the kidney injury is either secondary to an infectious disease or caused by an ANCA-associated small vessel vasculitis. We report a 59-year-old man admitted in nephrology for acute glomerular syndrome in whom the renal biopsy showed a crescentic necrotizing glomerulonephritis. A diagnosis of vasculitis was initially considered in the presence of high titer of ANCA (anti-proteinase 3). Because of associated Staphyloccocus aureus endocarditis the patient received both corticosteroids and antibiotics that allowed remission of both kidney injury and endocarditis. The renal presentation and the disappearance of ANCA support the infectious etiology of this glomerulonephritis rather than an ANCA-associated small vessel vasculitis. It is important to be cautious in the presence of ANCA positive extracapillary glomerulonephritis and endocarditis should be ruled out before initiation of corticosteroids that may be nevertheless necessary in severe acute glomerulonephritis. Copyright © 2011 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  6. Association between IgG4-related disease and progressively transformed germinal centers of lymph nodes.

    Science.gov (United States)

    Sato, Yasuharu; Inoue, Dai; Asano, Naoko; Takata, Katsuyoshi; Asaoku, Hideki; Maeda, Yoshinobu; Morito, Toshiaki; Okumura, Hirokazu; Ishizawa, Shin; Matsui, Shoko; Miyazono, Takayoshi; Takeuchi, Tamotsu; Kuroda, Naoto; Orita, Yorihisa; Takagawa, Kiyoshi; Kojima, Masaru; Yoshino, Tadashi

    2012-07-01

    Progressively transformed germinal centers is a benign condition of unknown pathogenesis characterized by a distinctive variant form of reactive follicular hyperplasia in lymph nodes. We recently reported Ig G4-related disease in progressively transformed germinal centers. However, no large case series has been reported and clinicopathologic findings remain unclear. Here, we report 40 Japanese patients (28 men, 12 women; median age, 56 years) with progressively transformed germinal centers of the lymph nodes who fulfilled the histological diagnostic criteria for IgG4-related disease (IgG4(+) progressively transformed germinal centers), with asymptomatic localized lymphadenopathy involving the submandibular nodes in 24, submandibular and cervical nodes in 14, cervical nodes only in 1, and cervical and supraclavicular nodes in 1. In all, 16 (52%) of 31 examined patients had allergic disease. Histologically, the lymph nodes demonstrated uniform histological findings, namely marked follicular hyperplasia with progressively transformed germinal centers, and localization of the majority of IgG4(+) plasma cells in the germinal centers. Serum IgG4, serum IgE and peripheral blood eosinophils were elevated in 87%, 92% and 53% of examined patients, respectively. Eighteen patients subsequently developed extranodal lesions (including five who developed systemic disease), which on histological examination were consistent with IgG4-related disease. IgG4(+) progressively transformed germinal centers presents with uniform clinicopathological features of asymptomatic localized submandibular lymphadenopathy, which persists and/or relapses, and sometimes progresses to extranodal lesions or systemic disease. Nine patients were administered steroid therapy when the lesions progressed, to which all responded well. We suggest that IgG4(+) progressively transformed germinal centers should be included in the IgG4-related disease spectrum.

  7. Progress and potential of nanomedicine to address infectious diseases of poverty

    CSIR Research Space (South Africa)

    Hayeshi, R

    2013-11-01

    Full Text Available Nanomedical Device and Systems Design: Challenges, Possibilities, Visions Chapter 13, pp 483-508 Progress and Potential of Nanomedicine to Address Infectious Diseases of Poverty Rose Hayeshi, Boitumelo Semete, Lonji Kalombo, Yolandy Lemmer, Lebogang...

  8. Mitochondrial respiratory chain disease presenting as progressive bulbar paralysis of childhood

    NARCIS (Netherlands)

    Roeleveld-Versteegh, ABC; Braun, KPJ; Smeitink, JAM; Dorland, L; de Koning, TJ

    2004-01-01

    We report two siblings with a mitochondrial respiratory chain defect who presented with progressive bulbar paralysis of childhood ( Fazio-Londe disease). Mitochondrial respiratory chain defects should be considered in the differential diagnosis of this rare clinical entity.

  9. Mitochondrial respiratory chain disease presenting as progressive bulbar paralysis of childhood.

    NARCIS (Netherlands)

    Roeleveld-Versteegh, A.B.; Braun, K.P.; Smeitink, J.A.M.; Dorland, L.; Koning, T.J.

    2004-01-01

    We report two siblings with a mitochondrial respiratory chain defect who presented with progressive bulbar paralysis of childhood (Fazio-Londe disease). Mitochondrial respiratory chain defects should be considered in differential diagnosis of this rare clinical entity.

  10. Effect of hormonal contraceptive methods on HIV disease progression: a systematic review

    National Research Council Canada - National Science Library

    Phillips, Sharon J; Curtis, Kathryn M; Polis, Chelsea B

    .... We searched PUBMED and EMBASE for articles published in peer-reviewed journals through December 15, 2011 for evidence relevant to all hormonal contraceptive methods and HIV-disease progression...

  11. Dietary manipulation and social isolation alter disease progression in a murine model of coronary heart disease.

    Directory of Open Access Journals (Sweden)

    Yumiko Nakagawa-Toyama

    Full Text Available BACKGROUND: Mice with a deficiency in the HDL receptor SR-BI and low expression of a modified apolipoprotein E gene (SR-BI KO/ApoeR61(h/h called 'HypoE' when fed an atherogenic, 'Paigen' diet develop occlusive, atherosclerotic coronary arterial disease (CHD, myocardial infarctions (MI, and heart dysfunction and die prematurely (50% mortality ~40 days after initiation of this diet. Because few murine models share with HypoE mice these cardinal, human-like, features of CHD, HypoE mice represent a novel, small animal, diet-inducible and genetically tractable model for CHD. To better describe the properties of this model, we have explored the effects of varying the composition and timing of administration of atherogenic diets, as well as social isolation vs. group housing, on these animals. METHODOLOGY/PRINCIPAL FINDINGS: HypoE mice were maintained on a standard lab chow diet (control until two months of age. Subsequently they received one of three atherogenic diets (Paigen, Paigen without cholate, Western or control diet for varying times and were housed in groups or singly, and we determined the plasma cholesterol levels, extent of cardiomegaly and/or survival. The rate of disease progression could be reduced by lowering the severity of the atherogenic diet and accelerated by social isolation. Disease could be induced by Paigen diets either containing or free of cholate. We also established conditions under which CHD could be initiated by an atherogenic diet and then subsequently, by replacing this diet with standard lab chow, hypercholesterolemia could be reduced and progression to early death prevented. CONCLUSIONS/SIGNIFICANCE: HypoE mice provide a powerful, surgery-free, diet-'titratable' small animal model that can be used to study the onset of recovery from occlusive, atherosclerotic CHD and heart failure due to MI. HypoE mice can be used for the analysis of the effects of environment (diet, social isolation on a variety of features of

  12. Assessment of Definitions of Sustained Disease Progression in Relapsing-Remitting Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Brian C. Healy

    2013-01-01

    Full Text Available Sustained progression on the expanded disability status scale (EDSS is a common outcome measure of disease progression in clinical studies of MS. Unfortunately, this outcome may not accurately measure long-term and irreversible disease progression. To assess the performance of definitions of sustained progression, patients with relapsing-remitting MS (RRMS or a clinically isolated syndrome with evidence of lesions on a brain MRI were included in our study. Fifteen definitions of sustained progression using both the EDSS and the functional system (FS scales were investigated. The impact of both relapses and changes in provider on the probability of maintaining progression was also evaluated. Although the provider scoring the EDSS sometimes changed during followup, the provider had access to previous EDSS scores. Between 15.8% and 42.2% of patients experienced sustained progression based on the definitions using EDSS as the outcome, but nearly 50% of these patients failed to maintain sustained progression for the duration of followup. When FS scales were used, progression was most common on the pyramidal and sensory scales. Unfortunately, progression on specific FS scales failed to be more sensitive to irreversible disability. Relapses or changes in provider did not explain the poor performance of the measures. Short-term changes in the EDSS or FS scores may not be an accurate marker of irreversible change in RRMS.

  13. Contribution of vascular risk factors to disease progression in Alzheimer’s Disease

    Science.gov (United States)

    Helzner, Elizabeth P.; Luchsinger, José A.; Scarmeas, Nikolaos; Cosentino, Stephanie; Brickman, Adam M.; Glymour, M. Maria; Stern, Yaakov

    2010-01-01

    Objective To determine whether pre-diagnosis vascular risk factors are associated with Alzheimer’s disease progression. Design Inception cohort followed longitudinally for a mean of 3.5 (up to 10.2) years. Setting Washington Heights Inwood Columbia Aging Project, New York City Participants 156 incident AD patients (mean age 83 years at diagnosis) Predictor variables Vascular factors including medical history (heart disease, stroke, diabetes, hypertension), smoking, and pre-diagnosis blood lipid measurements (total cholesterol, High density lipoproteins (HDL-C), Low density lipoproteins (LDL-C) and triglycerides). Main Outcome Measure Change in a composite score of cognitive ability from diagnosis on. Results In Generalized Estimating Equation (GEE) models (adjusted for age, race/ethnicity and education), higher cholesterol (total and LDL-C), and diabetes history were associated with faster cognitive decline. Each 10-unit increase in cholesterol and LDL-C was associated with a 10% of a standard deviation decrease in cognitive score per year of follow-up (p<0.001 for total cholesterol, p=0.001 for LDL-C). HDL and triglycerides were not associated with rate of decline. Diabetes history was associated with an additional 50% of a standard deviation decrease in cognitive score per year (p=0.05). History of heart disease and stroke were associated with cognitive decline among APOE-ε4 carriers only. In a final GEE model that included HDL-C, LDL-C and diabetes, only higher LDL-C was independently associated with faster cognitive decline. Conclusions Higher pre-diagnosis total cholesterol, LDL-C, and diabetes were associated with faster cognitive decline among incident AD patients, providing further evidence for the role of vascular risk factors in Alzheimer’s disease course. PMID:19273753

  14. Corticosterone dysregulation exacerbates disease progression in the R6/2 transgenic mouse model of Huntington's disease.

    Science.gov (United States)

    Dufour, Brett D; McBride, Jodi L

    2016-09-01

    Huntington's disease (HD) is a genetic neurological disorder that causes severe and progressive motor, cognitive, psychiatric, and metabolic symptoms. There is a robust, significant elevation in circulating levels of the stress hormone, cortisol, in HD patients; however, the causes and consequences of this elevation are largely uncharacterized. Here, we evaluated whether elevated levels of corticosterone, the rodent homolog of cortisol, contributed to the development of symptomology in transgenic HD mice. Wild-type (WT) and transgenic R6/2 mice were given either 1) adrenalectomy with WT-level corticosterone replacement (10ng/ml), 2) adrenalectomy with high HD-level corticosterone replacement (60ng/ml), or 3) sham surgery without replacement. R6/2 mice on HD-level replacement showed severe and rapid weight loss (ptransgenic HD mice display a spontaneous elevation in circulating corticosterone levels that became significant at 10weeks of age. Furthermore, we identified significant dysregulation of circadian rhythmicity of corticosterone release measured over a 24h period compared to wild-type controls. Unexpectedly, we found that R6/2 transgenic mice show a blunted corticosterone response to restraint stress, compared to wild-type mice. Together, these data provide further evidence that HPA-axis activity is abnormal in R6/2 mice, and highlight the important role that cortisol plays in HD symptom development. Our findings suggest that cortisol-reducing therapeutics may be of value in improving HD patient quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Leveraging rapid community-based hiv testing campaigns for non-communicable diseases in rural uganda

    OpenAIRE

    Gabriel Chamie; Dalsone Kwarisiima; Clark, Tamara D; Jane Kabami; Vivek Jain; Elvin Geng; Petersen, Maya L; Harsha Thirumurthy; Moses R Kamya; Havlir, Diane V.; Charlebois, Edwin D.

    2012-01-01

    Background The high burden of undiagnosed HIV in sub-Saharan Africa limits treatment and prevention efforts. Community-based HIV testing campaigns can address this challenge and provide an untapped opportunity to identify non-communicable diseases (NCDs). We tested the feasibility and diagnostic yield of integrating NCD and communicable diseases into a rapid HIV testing and referral campaign for all residents of a rural Ugandan parish. Methods A five-day, multi-disease campaign, offering diag...

  16. Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease

    DEFF Research Database (Denmark)

    Aziz, N A; Jurgens, C K; Landwehrmeyer, G B

    2009-01-01

    OBJECTIVE: Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HD gene (HTT). We aimed to assess whether interaction between CAG repeat sizes in the mutant and normal allele could affect disease severity and progression. METHODS: Using...... with less severe symptoms and pathology. CONCLUSIONS: Increasing CAG repeat size in normal HTT diminishes the association between mutant CAG repeat size and disease severity and progression in Huntington disease. The underlying mechanism may involve interaction of the polyglutamine domains of normal...

  17. Extranodal NK/T-cell lymphoma, nasal type, manifesting as rapidly progressive dementia without any mass or enhancing brain lesion.

    Science.gov (United States)

    Shimatani, Yoshimitsu; Nakano, Yuta; Tsuyama, Naoko; Murayama, Shigeo; Oki, Ryosuke; Miyamoto, Ryosuke; Murakami, Nagahisa; Fujita, Koji; Watanabe, Syunsuke; Uehara, Hisanori; Abe, Takashi; Nodera, Hiroyuki; Kawarai, Toshitaka; Izumi, Yuishin; Kaji, Ryuji

    2016-10-01

    Among the many potential etiologies for rapidly progressive dementia (RPD), primary central nervous system extranodal NK/T-cell lymphoma, nasal-type (ENKL) is a rare entity. We present the first reported case of autopsy-proven RPD due to ENKL without any mass or enhancing lesion of the brain. A 54-year-old immunocompetent man presented with RPD, myoclonus and ataxia. The mini-mental state examination (MMSE) score was 22/30. His brain MRI revealed progressive brain atrophy without gadolinium enhancement or mass lesion. Five months after the initial evaluation, cognitive impairment further worsened with an MMSE score of 3/30. At the advanced stage, lumbar MRI showed swollen cauda equina with gadolinium enhancement. The number of Epstein-Barr virus (EBV) DNA in cerebrospinal fluid had gradually increased. Twelve months after onset, the patient died of respiratory failure. Pathological findings revealed that lymphoma cells had diffusely invaded the meninges, parenchyma of the brain, spinal cord and cauda equina. Cells were positive for CD3, CD56 and EBV-encoded small RNAs and negative for CD20. No evidence of malignancy was identified in the visceral organs. This report indicates that ENKL should be recognized as one of the rare causes of RPD. Early testing for EBV-DNA in cerebrospinal fluid and imaging of cauda equina would be useful diagnostic tools. © 2016 Japanese Society of Neuropathology.

  18. Rapidly progressive psychotic symptoms triggered by infection in a patient with methylenetetrahydrofolate reductase deficiency: a case report.

    Science.gov (United States)

    Iida, Shin; Nakamura, Masataka; Asayama, Shinya; Kunieda, Takenobu; Kaneko, Satoshi; Osaka, Hitoshi; Kusaka, Hirofumi

    2017-02-28

    Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare inborn error of metabolism inherited in autosomal recessive pattern and is associated with a wide spectrum of neurological abnormalities. We herein describe a 15-year-old boy with MTHFR deficiency who presented with a slowly progressive decline of school performance and a spastic gait. Rapidly deteriorating psychosis and repetitive seizures triggered by a febrile infection prompted neurological investigation. He had significantly elevated total plasma homocysteine and urinary homocystine levels, as well as a decreased plasma methionine level. Brain magnetic resonance imaging (MRI) revealed leukoencephalopathy. DNA gene sequencing showed c.446_447 del GC ins TT and c.137G > A, and c.665C > T heterozygous mutations in the MTHFR gene of the patient. Oral administration of betaine drastically improved his clinical symptoms within a few months. After 8 months of treatment, his total plasma homocysteine level moderately decreased; and the plasma methionine concentration became normalized. Furthermore, the white matter lesions on MRI had disappeared. This patient demonstrates the possibility that MTHFR deficiency should be considered in mentally retarded adolescents who display an abnormally elevated plasma level of homocysteine in association with progressive neurological dysfunction and leukoencephalopathy. Febrile infections may be an aggravating factor in patients with MTHFR deficiency.

  19. The Chronic Kidney Disease Model: A General Purpose Model of Disease Progression and Treatment

    Directory of Open Access Journals (Sweden)

    Patel Uptal D

    2011-06-01

    Full Text Available Abstract Background Chronic kidney disease (CKD is the focus of recent national policy efforts; however, decision makers must account for multiple therapeutic options, comorbidities and complications. The objective of the Chronic Kidney Disease model is to provide guidance to decision makers. We describe this model and give an example of how it can inform clinical and policy decisions. Methods Monte Carlo simulation of CKD natural history and treatment. Health states include myocardial infarction, stroke with and without disability, congestive heart failure, CKD stages 1-5, bone disease, dialysis, transplant and death. Each cycle is 1 month. Projections account for race, age, gender, diabetes, proteinuria, hypertension, cardiac disease, and CKD stage. Treatment strategies include hypertension control, diabetes control, use of HMG-CoA reductase inhibitors, use of angiotensin converting enzyme inhibitors, nephrology specialty care, CKD screening, and a combination of these. The model architecture is flexible permitting updates as new data become available. The primary outcome is quality adjusted life years (QALYs. Secondary outcomes include health state events and CKD progression rate. Results The model was validated for GFR change/year -3.0 ± 1.9 vs. -1.7 ± 3.4 (in the AASK trial, and annual myocardial infarction and mortality rates 3.6 ± 0.9% and 1.6 ± 0.5% vs. 4.4% and 1.6% in the Go study. To illustrate the model's utility we estimated lifetime impact of a hypothetical treatment for primary prevention of vascular disease. As vascular risk declined, QALY improved but risk of dialysis increased. At baseline, 20% and 60% reduction: QALYs = 17.6, 18.2, and 19.0 and dialysis = 7.7%, 8.1%, and 10.4%, respectively. Conclusions The CKD Model is a valid, general purpose model intended as a resource to inform clinical and policy decisions improving CKD care. Its value as a tool is illustrated in our example which projects a relationship between

  20. Progression of experimental chronic Aleutian mink disease virus infection

    DEFF Research Database (Denmark)

    Jensen, Trine Hammer; Chriél, Mariann; Hansen, Mette Sif

    2016-01-01

    Aleutian mink disease virus (AMDV) is found world-wide and has a major impact on mink health and welfare by decreasing reproduction and fur quality. In the majority of mink, the infection is subclinical and the diagnosis must be confirmed by serology or polymerase chain reaction (PCR). Increased...

  1. Calprotectin as a biomarker for melioidosis disease progression and management

    Science.gov (United States)

    2017-04-03

    Sanmarti R. 2015. Serum Calprotectin More 239 Accurately Discriminates the Inflammatory Disease Activity of Rheumatoid Arthritis Patients 240...Group Melioidosis (acute) Non-melioidosis sepsis Healthy controls Age in years, median (range) 50 (32-74) 40 (18-74) 39 (22-66) Gender

  2. Research Progresses in Understanding the Pathophysiology of Moyamoya Disease

    NARCIS (Netherlands)

    Bersano, A.; Guey, S.; Bedini, G.; Nava, S.; Herve, D.; Vajkoczy, P.; Tatlisumak, T.; Sareela, M.; Zwan, A. van der; Klijn, C.J.; Braun, K.P.; Kronenburg, A.; Acerbi, F.; Brown, M.M.; Calviere, L.; Cordonnier, C.; Henon, H.; Thines, L.; Khan, N.; Czabanka, M.; Kraemer, M.; Simister, R.; Prontera, P.; Tournier-Lasserve, E.; Parati, E.

    2016-01-01

    BACKGROUND: The pathogenesis of moyamoya disease (MMD) is still unknown. The detection of inflammatory molecules such as cytokines, chemokines and growth factors in MMD patients' biological fluids supports the hypothesis that an abnormal angiogenesis is implicated in MMD pathogenesis. However, it is

  3. Research Progresses in Understanding the Pathophysiology of Moyamoya Disease

    NARCIS (Netherlands)

    Bersano, Anna; Guey, Stephanie; Bedini, Gloria; Nava, Sara; Hervé, Dominique; Vajkoczy, Peter; Tatlisumak, Turgut; Sareela, Marika; van der Zwan, Albert; Klijn, Catharina J. M.; Braun, Kees P J; Kronenburg, Annick; Acerbi, Francesco; Brown, Martin M.; Calviere, Lionel; Cordonnier, Charlotte; Henon, Hilde; Thines, Laurent; Khan, Nadia; Czabanka, M.; Kraemer, Markus; Simister, Robert; Prontera, Paolo; Tournier-Lasserve, E.; Parati, Eugenio

    Background: The pathogenesis of moyamoya disease (MMD) is still unknown. The detection of inflammatory molecules such as cytokines, chemokines and growth factors in MMD patients' biological fluids supports the hypothesis that an abnormal angiogenesis is implicated in MMD pathogenesis. However, it is

  4. Progress in Defining Disease: Improved Approaches and Increased Impact.

    Science.gov (United States)

    Schwartz, Peter H

    2017-08-01

    In a series of recent papers, I have made three arguments about how to define "disease" and evaluate and apply possible definitions. First, I have argued that definitions should not be seen as traditional conceptual analyses, but instead as proposals about how to define and use the term "disease" in the future. Second, I have pointed out and attempted to address a challenge for dysfunction-requiring accounts of disease that I call the "line-drawing" problem: distinguishing between low-normal functioning and dysfunctioning. Finally, I have used a dysfunction-requiring approach to argue that some extremely prevalent conditions, such as high blood pressure, high cholesterol, and ductal carcinoma in situ, are not diseases, but instead are risk factors. Four of the papers in this issue directly engage my previous work. In this commentary, I applaud the advances these authors make, address points of disagreement, and make suggestions about where the discussion should go next. © The Author 2017. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. GNE myopathy: a prospective natural history study of disease progression.

    Science.gov (United States)

    Mori-Yoshimura, Madoka; Oya, Yasushi; Yajima, Hiroyuki; Yonemoto, Naohiro; Kobayashi, Yoko; Hayashi, Yukiko K; Noguchi, Satoru; Nishino, Ichizo; Murata, Miho

    2014-05-01

    Mutations in the glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase gene cause GNE myopathy, a mildly progressive autosomal recessive myopathy. We performed a prospective natural history study in 24 patients with GNE myopathy to select evaluation tools for use in upcoming clinical trials. Patient clinical conditions were evaluated at study entry and one-year follow-up. Of the 24 patients, eight (33.3%) completed a standard 6-min walk test without assistance. No cardiac events were observed. Summed manual muscle testing of 17 muscles, grip power, and percent force vital capacity (%FVC) were significantly reduced (pmanual muscle testing, grip power, and %FVC reflect annual changes and are thus considered good evaluation tools for clinical trials. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

    Dalgas, Ulrik; Stenager, Egon

    2012-01-01

    It has been suggested that exercise (or physical activity) might have the potential to have an impact on multiple sclerosis (MS) pathology and thereby slow down the disease process in MS patients. The objective of this literature review was to identify the literature linking physical exercise (or...... studies evaluating the effects on clinical outcome measures, (2) cross-sectional studies evaluating the relationship between fitness status and MRI findings, (3) cross-sectional and longitudinal studies evaluating the relationship between exercise/physical activity and disability/relapse rate and, finally...

  7. Unresolved Subclinical Hypothyroidism is Independently Associated with Progression of Chronic Kidney Disease

    Science.gov (United States)

    Kim, Eun Oh; Lee, Ihn Suk; Choi, Yoo A; Lee, Sang Ju; Chang, Yoon Kyung; Yoon, Hye Eun; Jang, Yi Sun; Lee, Jong Min; Kim, Hye Soo; Yang, Chul Woo; Kim, Suk Young; Hwang, Hyeon Seok

    2014-01-01

    Background and Aim: Patients with chronic kidney disease (CKD) often have subclinical hypothyroidism. However, few reports have investigated changes in the status of subclinical hypothyroidism in CKD patients and its clinical significance in CKD progression. Methods: We included 168 patients with nondialysis-dependent CKD stages 2-4. The normalization of subclinical hypothyroidism during follow-up was assessed, and the association between transitions in subclinical hypothyroid status and the rate of decline of the estimated glomerular filtration rate (eGFR) was investigated. Results: At baseline, 127 patients were euthyroid and 41 (24.4%) patients were diagnosed with subclinical hypothyroidism. Of these 41 patients, 21 (51.2%) spontaneously resolved to euthyroid during follow-up. The rate of eGFR decline of patients with resolved subclinical hypothyroidism was similar to that of euthyroid patients. The patients with unresolved subclinical hypothyroidism showed a steeper renal function decline than patients with euthyroidism or resolved subclinical hypothyroidism (all p hypothyroidism than in those who were euthyroid (p = 0.006). In multivariate linear regression for rate of eGFR decrease, unresolved subclinical hypothyroidism (β = -5.77, p = 0.001), baseline renal function (β = -0.12, p hypothyroidism did not resolve to euthyroidism, and this lack of resolution was independently associated with rapid renal function decline. PMID:24396286

  8. 20 YEARS OF PROGRESS IN DIARRHEAL DISEASE RESEARCH

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    Narain H. Punjabi

    2012-09-01

    Full Text Available When NAMRU started its collaboration work with the National Institute of Health, Research and Development (NIHRD, it became apparent that diarrheal disease was one of the most important causes of morbidity and mortality in Indonesia, especially in children. Many of the most important etiologic agents of diarrhea were not known and the percentage of diarrheas with an identifiable etiologic agent was very low. Since these early times NAMRU and NIHRD have worked together in all aspects of diarrheal disease research. Increased capabilities for the identification of bac­tériologie, parasitic and viral enteropathogens, new vaccines, and better treatment via oral rehydration solutions are some of the results of this collaboration.

  9. Periodontal Pocket Depth, Hyperglycemia, and Progression of Chronic Kidney Disease: A Population-Based Longitudinal Study.

    Science.gov (United States)

    Chang, Jia-Feng; Yeh, Jih-Chen; Chiu, Ya-Lin; Liou, Jian-Chiun; Hsiung, Jing-Ru; Tung, Tao-Hsin

    2017-01-01

    No large epidemiological study has been conducted to investigate the interaction and joint effects of periodontal pocket depth and hyperglycemia on progression of chronic kidney disease in patients with periodontal diseases. Periodontal pocket depth was utilized for the grading severity of periodontal disease in 2831 patients from January 2002 to June 2013. Progression of chronic kidney disease was defined as progression of color intensity in glomerular filtration rate and albuminuria grid of updated Kidney Disease-Improving Global Outcomes guidelines. Multivariable-adjusted hazard ratios (aHR) in various models were presented across different levels of periodontal pocket depth and hemoglobin A1c (HbA1c) in forest plots and 3-dimensional histograms. During 7621 person-years of follow-up, periodontal pocket depth and HbA1C levels were robustly associated with incremental risks for progression of chronic kidney disease (aHR 3.1; 95% confidence interval [CI], 2.0-4.6 for periodontal pocket depth >4.5 mm, and 2.5; 95% CI, 1.1-5.4 for HbA1C >6.5%, respectively). The interaction between periodontal pocket depth and HbA1C on progression of chronic kidney disease was strong (P periodontal pocket depth (>4.5 mm) and higher HbA1C (>6.5%) had the greatest risk (aHR 4.2; 95% CI, 1.7-6.8) compared with the lowest aHR group (periodontal pocket depth ≤3.8 mm and HbA1C ≤6%). Our study identified combined periodontal pocket depth and HbA1C as a valuable predictor of progression of chronic kidney disease in patients with periodontal diseases. While considering the interaction between periodontal diseases and hyperglycemia, periodontal survey and optimizing glycemic control are warranted to minimize the risk of worsening renal function. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Progress in gene therapy of dystrophic heart disease

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    Lai, Y.; Duan, D.

    2012-01-01

    The heart is frequently afflicted in muscular dystrophy. In severe cases, cardiac lesion may directly result in death. Over the years, pharmacological and/or surgical interventions have been the mainstay to alleviate cardiac symptoms in muscular dystrophy patients. Although these traditional modalities remain useful, the emerging field of gene therapy has now provided an unprecedented opportunity to transform our thinking/approach in the treatment of dystrophic heart disease. In fact, the pre...

  11. Progress in Understanding Postnatal Immune Dysregulation in Allergic Disease

    OpenAIRE

    Prescott, Susan L.; Martino, David; Hodder, Megan; Richman, Tara; Tulic, Meri K.

    2010-01-01

    Abstract: It is increasingly unlikely that allergic disease is the result of isolated immune defects, but rather the result of altered gene activation patterns in intricate immune networks. This appears to be driven by complex environmental changes, including microbial exposure, diet, and pollutants, which are known to modify immune development in early life, beginning in pregnancy. The first models showing possible epigenetic mechanisms for these effects are beginning to emerge. This review ...

  12. Smoking and Progression of Alzheimers Disease: Connecting Edges

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    Vivek Sharma

    2014-06-01

    Full Text Available Smoking is a practice to burn and inhale the smoke and is primarily a route of administration for recreational drugs. The combustion releases the active substances in drugs such as nicotine and make them available for absorption through the lungs.The most common form of smoking is ciggarate smoking and is associated with life threatening complications like heart diseases, lung cancer, atherosclerosis, rheumatoid arthritis, osteoporosios, immune system dysfunction, hypertension, chronic obstructive pulmonary diseases, miscarriage, premature birth and dysfunctions of reproductive system as well. Smoking affet almost every organ of the body however, compared to the volume of research on the cardiovascular, pulmonary and cancer related health consequences of chronic smoking, lesser attention has been devoted to investigation of its effects on human neurocognition and brain neurobiology. In central nervous system, it leads to deficiencies in auditory verbal learning and/or memory, general intellectual abilities, visual search speeds, processing speed, cognitive flexibility, working memory and executive functions across a wide age range. The present work makes an effort to compile the evidence to challenge the notion/myth that smoking may be neuroprotective in cases of Alzheimers disease. The neuroprotective effects of smoking may be accredited only to nicotinic content of cigarrate smoke that too in part, but smoke is a deadly mixture of thousands of chemicals that must have disastrous effect on central nervous system. The various effets of cigarrate smoke and its ingredients on pathological markers of Alzheimers disease as oxidative stress, senile plaques, tau hyperphosphorylation, neuroinflammation, synapse loss and effects on blood brain barrier are disussed. [Archives Medical Review Journal 2014; 23(3.000: 534-561

  13. Progress in gene therapy of dystrophic heart disease.

    Science.gov (United States)

    Lai, Y; Duan, D

    2012-06-01

    The heart is frequently afflicted in muscular dystrophy. In severe cases, cardiac lesion may directly result in death. Over the years, pharmacological and/or surgical interventions have been the mainstay to alleviate cardiac symptoms in muscular dystrophy patients. Although these traditional modalities remain useful, the emerging field of gene therapy has now provided an unprecedented opportunity to transform our thinking/approach in the treatment of dystrophic heart disease. In fact, the premise is already in place for genetic correction. Gene mutations have been identified and animal models are available for several types of muscular dystrophy. Most importantly, innovative strategies have been developed to effectively deliver therapeutic genes to the heart. Dystrophin-deficient Duchenne cardiomyopathy is associated with Duchenne muscular dystrophy (DMD), the most common lethal muscular dystrophy. Considering its high incidence, there has been a considerable interest and significant input in the development of Duchenne cardiomyopathy gene therapy. Using Duchenne cardiomyopathy as an example, here we illustrate the struggles and successes experienced in the burgeoning field of dystrophic heart disease gene therapy. In light of abundant and highly promising data with the adeno-associated virus (AAV) vector, we have specially emphasized on AAV-mediated gene therapy. Besides DMD, we have also discussed gene therapy for treating cardiac diseases in other muscular dystrophies such as limb-girdle muscular dystrophy.

  14. Progress in the Diagnosis and Control of Ebola Disease.

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    Woźniak-Kosek, Agnieszka; Kosek, Jarosław; Mierzejewski, Jerzy; Rapiejko, Piotr

    2015-01-01

    Ebola hemorrhagic fever is one of numerous viral hemorrhagic fevers. It is a severe, often fatal disease in humans and nonhuman primates (gorillas and chimpanzees). This article discusses the history of Ebola disease, already known routes of infection together with defining prevention methods and treatment trials. The importance of increasing awareness of the risk of disease among people who do not inhabit endemic regions is emphasized. This risk is associated especially with the increasing popularity of tourism to African countries, even to those where the virus is endemic. The research conducted over the years shows that three species of frugivorous bats are subjected to contamination by Ebola, but the infection is asymptomatic in them. It is believed that the saliva of these mammals and other body fluids may be a potential source of infection for primates and humans. In the laboratory, infection through small-particle aerosols has been demonstrated in primates, and airborne spread among humans is strongly suspected, although it has not yet been conclusively demonstrated. The importance of this route of transmission remains unclear. Poor hygienic conditions can aid the spread of the virus. These observations suggest approaches to the study of routes of transmission to and among humans.

  15. Lack of association between anemia and renal disease progression in Chinese patients with type 2 diabetes.

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    Gu, Liubao; Lou, Qinglin; Wu, Haidi; Ouyang, Xiaojun; Bian, Rongwen

    2016-01-01

    Anemia has a close interaction with renal dysfunction in diabetes patients. More proof is still awaited on the relationship between anemia and the progression of renal disease in this population. In the present longitudinal study, 1,645 Chinese type 2 diabetes patients without end-stage renal disease were included in the analysis in Nanjing, China, during January 2006 and December 2012. All patients were managed by staged diabetes management protocol, and clinical parameters were collected at each visit. The end-point of progression of renal disease was evaluated during the follow up. Cox regression analysis was used to estimate the risk of anemia on renal disease progression. On recruitment, 350 (21.3%) patients had anemia, which was more common among those with older ages, longer diabetes duration, lower estimated glomerular filtration rate or more albuminura. On median follow up of 49 months (range 28-62 months), 37 patients (2.2%) developed the defined renal end-point. Compared with those without anemia, patients with anemia had a higher risk of renal disease progression. However, multivariate analysis showed that anemia lost its statistical significance once estimated glomerular filtration rate was added into the model. Although the incidence of renal disease progression markedly increased by anemia status in patients of estimated glomerular filtration rate renal disease progression in this subgroup. Anemia was a common finding in Chinese type 2 diabetes patients. Anemia was a risk factor for renal disease progression, but lost its significance once baseline renal function was adjusted.

  16. Electrostimulation to reduce synaptic scaling driven progression of Alzheimer's disease

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    Mark eRowan

    2014-04-01

    Full Text Available Cell death and synapse dysfunction are two likely causes of cognitive decline in AD. As cells die and synapses lose their drive, remaining cells suffer an initial decrease in activity. Neuronal homeostatic synaptic scaling then provides a feedback mechanism to restore activity. This homeostatic mechanism is believed to sense levels of activity-dependent cytosolic calcium within the cell and to adjust neuronal firing activity by increasing the density of AMPA synapses at remaining synapses to achieve balance. The scaling mechanism increases the firing rates of remaining cells in the network to compensate for decreases in network activity. However, this effect can itself become a pathology, as it produces increased imbalance between excitatory and inhibitory circuits, leading to greater susceptibility to further cell loss via calcium-mediated excitotoxicity.Here, we present a mechanistic explanation of how directed brain stimulation might be expected to slow AD progression based on computational simulations in a 470-neuron biomimetic model of a neocortical column. The simulations demonstrate that the addition of low-intensity electrostimulation (neuroprosthesis to a network undergoing AD-like cell death can raise global activity and break this homeostatic-excitotoxic cascade. The increase in activity within the remaining cells in the column results in lower scaling-driven AMPAR upregulation, reduced imbalances in excitatory and inhibitory circuits, and lower susceptibility to ongoing damage.

  17. Serum tryptase concentration and progression to end-stage renal disease.

    Science.gov (United States)

    Jesky, Mark D; Stringer, Stephanie J; Fenton, Anthony; Ng, Khai Ping; Yadav, Punit; Ndumbo, Miguel; McCann, Katerina; Plant, Tim; Dasgupta, Indranil; Harding, Stephen J; Drayson, Mark T; Redegeld, Frank; Ferro, Charles J; Cockwell, Paul

    2016-05-01

    Mast cell activation can lead to nonclassical activation of the Renin-Angiotensin-Aldosterone System. However, the relevance of this to human chronic kidney disease is unknown. We assessed the association between serum tryptase, a product of mast cell activation, and progression to end-stage renal disease or mortality in patients with advanced chronic kidney disease. We stratified patients by use of angiotensin-converting enzyme inhibitors/angiotensin receptor II blockers (ACEi/ARB). This was a prospective cohort study of 446 participants recruited into the Renal Impairment in Secondary Care study. Serum tryptase was measured at recruitment by sandwich immunoassay. Cox regression analysis was undertaken to determine variables associated with progression to end-stage renal disease or death. Serum tryptase concentration was independently associated with progression to end-stage renal disease but not with death. In patients treated with ACEi or ARB, there was a strong independent association between higher tryptase concentrations and progression to end-stage renal disease; when compared to the lowest tertile, tryptase concentrations in the middle and highest tertiles had hazard ratios [HR] of 5·78 (95% confidence interval [CI] 1·19-28·03, P = 0·029) and 6·19 (95% CI 1·49-25·69, P = 0·012), respectively. The other independent risk factors for progression to end-stage renal disease were lower age, male gender, lower estimated glomerular filtration rate and higher urinary albumin creatinine ratio. Elevated serum tryptase concentration is an independent prognostic factor for progression to end-stage renal disease in patients with chronic kidney disease who are receiving treatment with an ACEi or ARB. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

  18. Case of streptococcal toxic shock syndrome caused by rapidly progressive group A hemolytic streptococcal infection during postoperative chemotherapy for cervical cancer.

    Science.gov (United States)

    Nogami, Yuya; Tsuji, Kousuke; Banno, Kouji; Umene, Kiyoko; Katakura, Satomi; Kisu, Iori; Tominaga, Eiichiro; Aoki, Daisuke

    2014-01-01

    Streptococcal toxic shock syndrome (STSS) is a severe infectious disease caused by group A hemolytic streptococcus (Streptococcus pyogenes). This condition is a serious disease that involves rapidly progressive septic shock. We experienced a case of STSS caused by primary peritonitis during treatment with paclitaxel and cisplatin (TP therapy) as postoperative chemotherapy for cervical cancer. STSS mostly develops after extremity pain, but initial influenza-like symptoms of fever, chill, myalgia and gastrointestinal symptoms may also occur. TP therapy is used to treat many cancers, including gynecological cancer, but may cause adverse reactions of neuropathy and nephrotoxicity and sometimes fever, arthralgia, myalgia, abdominal pain and general malaise. The case reported here indicates that development of STSS can be delayed after chemotherapy and that primary STSS symptoms may be overlooked because they may be viewed as adverse reactions to chemotherapy. To our knowledge, this is the first report of a case of STSS during chemotherapy. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  19. Prevalence of obesity in paediatric psoriasis and its impact on disease severity and progression.

    Science.gov (United States)

    Ergun, Tulin; Seckin Gencosmanoglu, Dilek; Karakoc-Aydiner, Elif; Salman, Andac; Tekin, Burak; Bulbul-Baskan, Emel; Alpsoy, Erkan; Cakıroglu, Aylin; Onsun, Nahide

    2017-11-01

    The current literature suggests there is a possible connection between paediatric psoriasis and obesity. However, there is a paucity of research on the influence of increased adiposity on the severity of paediatric psoriasis and disease progression. We aimed to compare the prevalence of being overweight or obese in paediatric psoriasis patients and controls and assess the potential impact of being overweight/obese on disease severity and progression of disease. This multicentre prospective case-control study included 289 psoriasis patients (aged < 18 years) treated and followed up by one of the four university hospitals in Turkey. The control group consisted of 151 consecutive age-matched and sex-matched children who lacked a personal or family history of psoriasis. The participants' characteristics, psoriasis-related parametres (e.g., initial subtype, psoriasis area and severity index, presence of psoriatic arthritis) and body mass index were determined. The difference between the prevalence of being overweight/obese among psoriatics (28%) and the control group (19%) was significant (P = 0.024). Being overweight/obese had no significant impact on disease severity and unresponsiveness to topical treatment. Within a median follow-up time of 12 months, 23% of our patients with localised disease at disease onset progressed to generalised disease. The impact of being overweight/obese on disease progression was found to be non-significant; however, disease duration was found to have a significant impact on disease progression (P = 0.026). Although it is not associated with disease severity and course, increased bodyweight may be a health problem for psoriatic children. © 2016 The Australasian College of Dermatologists.

  20. RandomForest4Life: a Random Forest for predicting ALS disease progression.

    Science.gov (United States)

    Hothorn, Torsten; Jung, Hans H

    2014-09-01

    We describe a method for predicting disease progression in amyotrophic lateral sclerosis (ALS) patients. The method was developed as a submission to the DREAM Phil Bowen ALS Prediction Prize4Life Challenge of summer 2012. Based on repeated patient examinations over a three- month period, we used a random forest algorithm to predict future disease progression. The procedure was set up and internally evaluated using data from 1197 ALS patients. External validation by an expert jury was based on undisclosed information of an additional 625 patients; all patient data were obtained from the PRO-ACT database. In terms of prediction accuracy, the approach described here ranked third best. Our interpretation of the prediction model confirmed previous reports suggesting that past disease progression is a strong predictor of future disease progression measured on the ALS functional rating scale (ALSFRS). We also found that larger variability in initial ALSFRS scores is linked to faster future disease progression. The results reported here furthermore suggested that approaches taking the multidimensionality of the ALSFRS into account promise some potential for improved ALS disease prediction.

  1. Prion protein polymorphisms affect chronic wasting disease progression.

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    Chad J Johnson

    Full Text Available Analysis of the PRNP gene in cervids naturally infected with chronic wasting disease (CWD suggested that PRNP polymorphisms affect the susceptibility of deer to infection. To test this effect, we orally inoculated 12 white-tailed deer with CWD agent. Three different PRNP alleles, wild-type (wt; glutamine at amino acid 95 and glycine at 96, Q95H (glutamine to histidine at amino acid position 95 and G96S (glycine to serine at position 96 were represented in the study cohort with 5 wt/wt, 3 wt/G96S, and 1 each wt/Q95H and Q95H/G96S. Two animals were lost to follow-up due to intercurrent disease. The inoculum was prepared from Wisconsin hunter-harvested homozygous wt/wt animals. All infected deer presented with clinical signs of CWD; the orally infected wt/wt had an average survival period of 693 days post inoculation (dpi and G96S/wt deer had an average survival period of 956 dpi. The Q95H/wt and Q95H/G96S deer succumbed to CWD at 1,508 and 1,596 dpi respectively. These data show that polymorphisms in the PRNP gene affect CWD incubation period. Deer heterozygous for the PRNP alleles had extended incubation periods with the Q95H allele having the greatest effect.

  2. [Hepatitis C virus and chronic progressive kidney disease].

    Science.gov (United States)

    Kes, Petar; Slavicek, Jasna

    2009-12-01

    Soon upon its discovery, hepatitis C virus (HCV) was recognized as an important cause and consequence of chronic kidney disease (CKD). HCV is a significant cause of some forms of glomerulonephritis (GN), especially membranoproliferative GN (MPGN). Subsequent population-based studies found an association between HCV positivity and CKD markers such as albuminuria or proteinuria. HCV infection is a frequent sequel of CKD. Blood transfusions (before effective screening of blood donors for HCV was instituted), nosocomial transmission in dialysis units, and transmission by kidney grafts all have contributed to the much higher prevalence of HCV infection in end-stage renal disease (ESRD) and transplant patients as compared to the general population. The current prevalence of HCV in dialysis centers is between 5% and 10% in European Union, and around 8.4% in Croatia. Strict adherence to 'universal precautions', careful attention to hygiene and strict sterilization of dialysis machines is recommended. The prevalence of HCV infection in CKD transplant patients is also high. Consistent risk factors include total time spent on dialysis and a history and/or number of blood transfusions, yet paralleling the prevalence in the general population of the same country or region. Patients with CKD who are considered for treatment should have virologic evidence of chronic HCV infection (i.e. HCV RNA detectable in serum). Treating chronic HCV infection in CKD patients is associated with a number of challenges. As the glomerular filtration rate (GFR) decreases, the half-life of both interferons (IFNs) (standard and pegylated) and ribavirin increases, resulting in a potentially poorer tolerance and the need for dosage adaptations in severe CKD. In kidney graft recipients, the use of IFNs and immunostimulants further entails a substantial risk of rejection. IFN therapy in hemodialysis patients results in good biochemical and virologic response and appears to exert a beneficial effect on

  3. Five-year follow-up of angiographic disease progression after medicine, angioplasty, or surgery

    Directory of Open Access Journals (Sweden)

    Oliveira Sergio A

    2010-10-01

    Full Text Available Abstract Background Progression of atherosclerosis in coronary artery disease is observed through consecutive angiograms. Prognosis of this progression in patients randomized to different treatments has not been established. This study compared progression of coronary artery disease in native coronary arteries in patients undergoing surgery, angioplasty, or medical treatment. Methods Patients (611 with stable multivessel coronary artery disease and preserved ventricular function were randomly assigned to CABG, PCI, or medical treatment alone (MT. After 5-year follow-up, 392 patients (64% underwent new angiography. Progression was considered a new stenosis of ≥ 50% in an arterial segment previously considered normal or an increased grade of previous stenosis > 20% in nontreated vessels. Results Of the 392 patients, 136 underwent CABG, 146 PCI, and 110 MT. Baseline characteristics were similar among treatment groups, except for more smokers and statin users in the MT group, more hypertensives and lower LDL-cholesterol levels in the CABG group, and more angina in the PCI group at study entry. Analysis showed greater progression in at least one native vessel in PCI patients (84% compared with CABG (57% and MT (74% patients (p Conclusion The angioplasty treatment conferred greater progression in native coronary arteries, especially in the left anterior descending territories and treated vessels. The progression was independently associated with hypertension, male sex, and previous myocardial infarction.

  4. Respiratory syncytial virus in hematopoietic cell transplant recipients: factors determining progression to lower respiratory tract disease.

    Science.gov (United States)

    Kim, Yae-Jean; Guthrie, Katherine A; Waghmare, Alpana; Walsh, Edward E; Falsey, Ann R; Kuypers, Jane; Cent, Anne; Englund, Janet A; Boeckh, Michael

    2014-04-15

    Respiratory syncytial virus (RSV) lower respiratory tract disease (LRD) is a life-threatening complication in hematopoietic cell transplant (HCT) recipients. Lymphopenia has been associated with an increased risk of progression from upper respiratory tract infection (URI) to LRD. This study retrospectively analyzed the significance of lymphocyte engraftment dynamics, lung function, smoking history, corticosteroids, antiviral treatment, viral subtypes, and RSV-specific neutralizing antibodies for the progression to LRD in 181 HCT recipients with RSV URI. In multivariable models, smoking history, conditioning with high-dose total body irradiation, and an absolute lymphocyte count (ALC) ≤100/mm(3) at the time of URI onset were significantly associated with disease progression. No progression occurred in patients with ALCs of >1000/mm(3) at URI onset. Lymphocyte engraftment dynamics were similar in progressors and nonprogressors. Pre- and posttransplant donor and posttransplant recipient RSV subtype-specific neutralizing antibody levels, RSV viral subtypes, and corticosteroids also were not significantly associated with LRD progression. Host and transplant related factors appear to determine the risk of progression to LRD more than viral factors. Dysfunctional cell-mediated immunity appears to be important in the pathogenesis of progressive RSV disease after HCT. A characterization of RSV-specific T-cell immunity is warranted.

  5. Caffeine and Progression of Parkinson Disease: A Deleterious Interaction With Creatine.

    Science.gov (United States)

    Simon, David K; Wu, Cai; Tilley, Barbara C; Wills, Anne-Marie; Aminoff, Michael J; Bainbridge, Jacquelyn; Hauser, Robert A; Schneider, Jay S; Sharma, Saloni; Singer, Carlos; Tanner, Caroline M; Truong, Daniel; Wong, Pei Shieen

    2015-01-01

    Increased caffeine intake is associated with a lower risk of Parkinson disease (PD) and is neuroprotective in mouse models of PD. However, in a previous study, an exploratory analysis suggested that, in patients taking creatine, caffeine intake was associated with a faster rate of progression. In the current study, we investigated the association of caffeine with the rate of progression of PD and the interaction of this association with creatine intake. Data were analyzed from a large phase 3 placebo-controlled clinical study of creatine as a potentially disease-modifying agent in PD. Subjects were recruited for this study from 45 movement disorders centers across the United States and Canada. A total of 1741 subjects with PD participated in the primary clinical study, and caffeine intake data were available for 1549 of these subjects. The association of caffeine intake with rate of progression of PD as measured by the change in the total Unified Parkinson Disease Rating Scale score and the interaction of this association with creatine intake were assessed. Caffeine intake was not associated with the rate of progression of PD in the main analysis, but higher caffeine intake was associated with significantly faster progression among subjects taking creatine. This is the largest and longest study conducted to date that addresses the association of caffeine with the rate of progression of PD. These data indicate a potentially deleterious interaction between caffeine and creatine with respect to the rate of progression of PD.

  6. Effect of HIV-1 subtypes on disease progression in rural Uganda: a prospective clinical cohort study.

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    Deogratius Ssemwanga

    Full Text Available We examined the association of HIV-1 subtypes with disease progression based on three viral gene regions.A prospective HIV-1 clinical cohort study in rural Uganda.Partial gag, env and pol genes were sequenced. Cox proportional hazard regression modelling was used to estimate adjusted hazard ratios (aHRs of progression to: CD4≤250, AIDS onset and death, adjusted for sex, age and CD4 count at enrolment.Between 1990 and 2010, 292 incident cases were subtyped: 25% had subtype A, 45% had D, 26% had A/D recombinants, 1% had C and 4% were other recombinant forms. Of the 278 incident cases included in the disease progression analysis, 62% progressed to CD4≤250, 32% to AIDS, and 34% died with a higher proportion being among subtype D cases. The proportions of individuals progressing to the three endpoints were significantly higher among individuals infected with subtype D. Throughout the study period, individuals infected with subtype D progressed faster to CD4≤250, adjusted HR (aHR, (95% CI = 1.72 (1.16-2.54, but this was mainly due to events in the period before antiretroviral therapy (ART introduction, when individuals infected with subtype D significantly progressed faster to CD4≤250 than subtype A cases; aHR (95% CI = 1.78 (1.01-3.14.In this population, HIV-1 subtype D was the most prevalent and was associated with faster HIV-1 disease progression than subtype A. Further studies are needed to examine the effect of HIV-1 subtypes on disease progression in the ART period and their effect on the virological and immunological ART outcomes.

  7. The Alzheimer's Disease Mitochondrial Cascade Hypothesis: Progress and Perspectives

    Science.gov (United States)

    Swerdlow, Russell H.; Burns, Jeffrey M.; Khan, Shaharyar M.

    2013-01-01

    Ten years ago we first proposed the Alzheimer's disease (AD) mitochondrial cascade hypothesis. This hypothesis maintains gene inheritance defines an individual's baseline mitochondrial function; inherited and environmental factors determine rates at which mitochondrial function changes over time; and baseline mitochondrial function and mitochondrial change rates influence AD chronology. Our hypothesis unequivocally states in sporadic, late-onset AD, mitochondrial function affects amyloid precursor protein (APP) expression, APP processing, or beta amyloid (Aβ) accumulation and argues if an amyloid cascade truly exists, mitochondrial function triggers it. We now review the state of the mitochondrial cascade hypothesis, and discuss it in the context of recent AD biomarker studies, diagnostic criteria, and clinical trials. Our hypothesis predicts biomarker changes reflect brain aging, new AD definitions clinically stage brain aging, and removing brain Aβ at any point will marginally impact cognitive trajectories. Our hypothesis, therefore, offers unique perspective into what sporadic, late-onset AD is and how to best treat it. PMID:24071439

  8. Progress and controversy surrounding vaccines against Lyme disease.

    Science.gov (United States)

    Hanson, Mark S; Edelman, Robert

    2003-10-01

    Less than 20 years elapsed between the 1982 report of the identification and isolation of Borrelia burgdorferi and the licensure and marketing in the USA of a prophylactic vaccine against this pathogen. However, the manufacturer removed the vaccine from the market under 4 years after its release. The low demand undoubtedly was the result of limited efficacy, need for frequent boosters, the high price of the vaccine, exclusion of children, fear of vaccine-induced musculoskeletal symptoms and litigation surrounding the vaccine. Second-generation polyvalent outer surface protein (Osp)C vaccines may overcome some of these concerns but the precise antigenic components required for efficacy are uncertain. The development of the next generation of Lyme disease vaccines is in its infancy.

  9. The Alzheimer's disease mitochondrial cascade hypothesis: progress and perspectives.

    Science.gov (United States)

    Swerdlow, Russell H; Burns, Jeffrey M; Khan, Shaharyar M

    2014-08-01

    Ten years ago we first proposed the Alzheimer's disease (AD) mitochondrial cascade hypothesis. This hypothesis maintains that gene inheritance defines an individual's baseline mitochondrial function; inherited and environmental factors determine rates at which mitochondrial function changes over time; and baseline mitochondrial function and mitochondrial change rates influence AD chronology. Our hypothesis unequivocally states in sporadic, late-onset AD, mitochondrial function affects amyloid precursor protein (APP) expression, APP processing, or beta amyloid (Aβ) accumulation and argues if an amyloid cascade truly exists, mitochondrial function triggers it. We now review the state of the mitochondrial cascade hypothesis, and discuss it in the context of recent AD biomarker studies, diagnostic criteria, and clinical trials. Our hypothesis predicts that biomarker changes reflect brain aging, new AD definitions clinically stage brain aging, and removing brain Aβ at any point will marginally impact cognitive trajectories. Our hypothesis, therefore, offers unique perspective into what sporadic, late-onset AD is and how to best treat it. © 2013.

  10. Research progress of antagonistic interactions among root canal irrigations disease

    Directory of Open Access Journals (Sweden)

    Chen QU

    2013-07-01

    Full Text Available Root canal therapy is the most effective way to treat various pulposis and periapical disease. Simple mechanical apparatus can not clean root canal thoroughly, but may affect tight filling instead. It can achieve a satisfactory cleansing effect only when it is combined with a chemical solution. Irrigation fluid for root canal should possess the properties of tissue dissolution, antimicrobial, lubrication, and removal of smear layer. So far, no solution is able to fulfill all these functions. Therefore, a combined use of multiple irrigation solutions is suggested. It can not only achieve good effect in cleaning and disinfection, also it can lower the concentration of different solutions, thus reducing the side effects. Nevertheless, some experiments proved that antagonism existed among the chemicals used for irrigations. The purpose of present article is to review the antagonistic effect among the chemicals used for irrigation when they are used together for root canal treatment.

  11. Can Better Management of Periodontal Disease Delay the Onset and Progression of Alzheimer's Disease?

    Science.gov (United States)

    Harding, Alice; Robinson, Sarita; Crean, StJohn; Singhrao, Sim K

    2017-01-01

    A risk factor relationship exists between periodontal disease and Alzheimer's disease (AD) via tooth loss, and improved memory following dental intervention. This links the microbial contribution from indigenous oral periodontal pathogens to the manifestation of chronic conditions, such as AD. Here, we use Porphyromonas gingivalis infection to illustrate its effect on mental health. P. gingivalis infection, in its primary sub-gingival niche, can cause polymicrobial synergy and dysbiosis. Dysbiosis describes the residency of select commensals from the oral cavity following co-aggregation around the dominant keystone pathogen, such as P. gingivalis, to gain greater virulence. The initial process involves P. gingivalis disturbing neutrophil mediated innate immune responses in the healthy gingivae and then downregulating adaptive immune cell differentiation and development to invade, and subsequently, establish new dysbiotic bacterial communities. Immune responses affect the host in general and functionally via dietary adjustments caused by tooth loss. Studies from animals orally infected with P. gingivalis confirm this bacterium can transmigrate to distant organ sites (the brain) and contribute toward peripheral and intracerebral inflammation, and compromise vascular and microvascular integrity. In another study, P. gingivalis infection caused sleep pattern disturbances by altering glial cell light/dark molecular clock activity, and this, in turn, can affect the clearance of danger associated molecular patterns, such as amyloid-β, via the glymphatic system. Since P. gingivalis can transmigrate to the brain and modulate organ-specific inflammatory innate and adaptive immune responses, this paper explores whether better management of indigenous periodontal bacteria could delay/prevent the onset and/or progression of dementia.

  12. Circadian Intraocular Pressure Fluctuation and Disease Progression in Primary Angle Closure Glaucoma.

    Science.gov (United States)

    Tan, Shaoying; Yu, Marco; Baig, Nafees; Chan, Poemen Pui-man; Tang, Fang Yao; Tham, Clement C

    2015-07-01

    To document the continuous circadian intraocular pressure (IOP) fluctuation using a contact lens sensor during normal daily activities, and to study the relationship between IOP fluctuation and disease progression in primary angle closure glaucoma (PACG) eyes. Circadian IOP fluctuations were recorded by Sensimed Triggerfish sensors in 25 PACG eyes. The sensor output signals were smoothed using B-spline smoothing transform and described by functional data analysis. Glaucoma progression was documented with serial changes in mean deviation (MD) and visual field index (VFI) in Humphrey automated perimetry and retinal nerve fiber layer (RNFL) thickness. The signals were compared between the progressive and stable groups by permutation tests on functional t-statistic. Statistically significant differences were found from 2200 to 2300 and from 0700 to 0800 in gradients of the IOP fluctuation curve, as well as from 2300 to 2400 and 0800 to 0900 in curvatures of the IOP fluctuation curves, between the progressive MD and stable MD groups (P < 0.05). Significant gradient differences were also found from 1500 to 1600 and 0600 to 0800 between the progressive VFI and stable VFI groups, and from 2400 to 0100 and 0200 to 0300 between the progressive RNFL and stable RNFL groups (P < 0.05). Significant differences in circadian IOP fluctuation between progressive and stable PACG eyes were identified. Large IOP fluctuations may be associated with disease progression in PACG eyes.

  13. Phosphorylated human tau associates with mouse prion protein amyloid in scrapie-infected mice but does not increase progression of clinical disease.

    Science.gov (United States)

    Race, Brent; Phillips, Katie; Kraus, Allison; Chesebro, Bruce

    2016-07-03

    Tauopathies are a family of neurodegenerative diseases in which fibrils of human hyperphosphorylated tau (P-tau) are believed to cause neuropathology. In Alzheimer disease, P-tau associates with A-beta amyloid and contributes to disease pathogenesis. In familial human prion diseases and variant CJD, P-tau often co-associates with prion protein amyloid, and might also accelerate disease progression. To test this latter possibility, here we compared progression of amyloid prion disease in vivo after scrapie infection of mice with and without expression of human tau. The mice used expressed both anchorless prion protein (PrP) and membrane-anchored PrP, that generate disease associated amyloid and non-amyloid PrP (PrPSc) after scrapie infection. Human P-tau induced by scrapie infection was only rarely associated with non-amyloid PrPSc, but abundant human P-tau was detected at extracellular, perivascular and axonal deposits associated with amyloid PrPSc. This pathology was quite similar to that seen in familial prion diseases. However, association of human and mouse P-tau with amyloid PrPSc did not diminish survival time following prion infection in these mice. By analogy, human P-tau may not affect prion disease progression in humans. Alternatively, these results might be due to other factors, including rapidity of disease, blocking effects by mouse tau, or low toxicity of human P-tau in this model.

  14. The performance of matrices in daily clinical practice to predict rapid radiologic progression in patients with early RA.

    Science.gov (United States)

    De Cock, D; Vanderschueren, G; Meyfroidt, S; Joly, J; Van der Elst, K; Westhovens, R; Verschueren, P

    2014-04-01

    To compare in daily clinical practice the reliability of matrices that forecast rapid radiologic progression (RRP) at year one, at year two, and over 2 years in patients with early rheumatoid arthritis (RA). Overall, 74 early RA patients with X-rays of hands and feet at baseline, year one, and year two were included. Initial DMARD combination therapy with steroids (ICTS) or DMARD monotherapy (IMT) was initiated according to patients' RA severity, based on rheumatologist opinion. The images were scored via the modified Sharp/van der Heijde (SvH) method. A total Sharp score progression of equal or higher than five per year was considered RRP. Six matrices were tested: ASPIRE CRP/ESR matrices, the BEST matrix, two SWEFOT matrices, and the ESPOIR matrix. Patients were placed in each of them yielding a RRP probability. The performance was tested by Area Under the Curve analysis reflecting the predictive value. Four patients developed RRP in year one, five in year two, and four over 2 years. With regard to face validity, the predicted probability did not correspond to the risk in reality: the one ICTS patient who developed RRP over 2 years was always found in the lowest RRP categories of all matrices. The ASPIRE CRP matrix yielded at least a moderate predicting value for the three time points. The other matrices showed moderate to no predicting value. The performance of all matrices was disappointing and it is impossible to fully rely on the existing matrices in daily clinical practice. © 2013 Published by Elsevier Inc.

  15. Plasma indoxyl sulfate concentration predicts progression of chronic kidney disease in dogs and cats.

    Science.gov (United States)

    Chen, C N; Chou, C C; Tsai, P S J; Lee, Y J

    2018-02-01

    Indoxyl sulfate is a protein-bound uremic toxin that increases as the severity of impaired renal function increases in humans, laboratory animals, dogs and cats. An elevation of indoxyl sulfate is related to prognosis among people with chronic kidney disease. However, whether indoxyl sulfate is able to predict the progression of chronic kidney disease in dogs and cats has not been previously studied. In the present study, 58 cats and 36 dogs with chronic kidney disease were enrolled. Plasma indoxyl sulfate was measured by high performance liquid chromatography. Renal progression was defined as an increase by one International Renal Interest Society (IRIS) stage and/or a rise in serum creatinine concentration of 0.5mg/dL during the same stage within a 3-month period. Compared with the non-progression groups, across different stages of renal failure, the baseline plasma indoxyl sulfate concentration was increased in the renal progression group (P<0.05), especially for IRIS stages 2 and 3 animals. The area under the receiver operator characteristic curves of indoxyl sulfate, when predicting renal progression, was above 0.75 for both dogs and cats. Indoxyl sulfate concentrations were also correlated with the increase of blood urea nitrogen, serum creatinine, and phosphate and the decrease of hematocrit among cats; while in dogs, concentrations were only correlated with the increase of phosphate concentrations. Indoxyl sulfate served as a biomarker of progression risk in dogs and cats with chronic kidney disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Risk factors for the progression of cystic fibrosis lung disease throughout childhood.

    Science.gov (United States)

    Sanders, Don B; Li, Zhanhai; Laxova, Anita; Rock, Michael J; Levy, Hara; Collins, Jannette; Ferec, Claude; Farrell, Philip M

    2014-01-01

    Previous studies of risk factors for progression of lung disease in cystic fibrosis (CF) have suffered from limitations that preclude a comprehensive understanding of the determinants of CF lung disease throughout childhood. The epidemiologic component of the 27-year Wisconsin Randomized Clinical Trial of CF Neonatal Screening Project (WI RCT) afforded us a unique opportunity to evaluate the significance of potential intrinsic and extrinsic risk factors for lung disease in children with CF. Describe the most important intrinsic and extrinsic risk factors for progression of lung disease in children with CF. Variables hypothesized at the onset of the WI RCT study to be determinants of the progression of lung disease and potential risk factors previously identified in the WI RCT study were assessed with multivariable generalized estimating equation models for repeated measures of chest radiograph scores and pulmonary function tests in the WI RCT cohort. Combining all patients in the WI RCT, 132 subjects were observed for a mean of 16 years and contributed 1,579 chest radiographs, and 1,792 pulmonary function tests. The significant determinants of lung disease include genotype, poor growth, hospitalizations, meconium ileus, and infection with mucoid Pseudomonas aeruginosa. The previously described negative effect of female sex was not seen. Modifiable extrinsic risk factors are the major determinants of progression of lung disease in children with CF. Better interventions to prevent or treat these risk factors may lead to improvements in lung health for children with CF.

  17. Uraemia progression in chronic kidney disease stages 3-5 is not constant

    DEFF Research Database (Denmark)

    Heaf, James Goya; Mortensen, Leif Spange

    2011-01-01

    Chronic kidney disease (CKD) is a progressive disease leading to loss of glomerular filtration rate (ΔGFR, measured in ml/min/1.73 m(2)/year). ΔGFR is usually assumed to be constant, but the hyperfiltration theory suggests that it accelerates in severe uraemia. A retrospective analysis of estimated...... GFR (eGFR) calculated from the Modification of Diet in Renal Disease equation was performed to evaluate whether ΔGFR is constant or accelerating....

  18. Progressive Hemifacial Atrophy and Linear Scleroderma En Coup de Sabre: A Spectrum of the Same Disease?

    Directory of Open Access Journals (Sweden)

    Irina Khamaganova

    2018-01-01

    Full Text Available Similar clinical and histhopathological features in progressive hemifacial atrophy and linear scleroderma en coup de sabre are well known. Trauma may predispose to the development of both diseases. The lack of association with anti-Borrelia antibodies was shown in both cases as well. The otolaryngological and endocrine disorders may be associated findings in both diseases. However, there are certain differences in neurological and ophthalmological changes in the diseases.

  19. Uremic Solutes in Chronic Kidney Disease and Their Role in Progression.

    Directory of Open Access Journals (Sweden)

    Jan A J G van den Brand

    Full Text Available To date, over 150 possible uremic solutes have been listed, but their role in the progression of CKD is largely unknown. Here, the association between a selected panel of uremic solutes and progression in CKD patients was investigated.Patients from the MASTERPLAN study, a randomized controlled trial in CKD patients with a creatinine clearance between 20 and 70 ml/min per 1.73m2, were selected based on their rate of eGFR decline during the first five years of follow-up. They were categorized as rapid (decline >5 ml/min per year or slow progressors. Concentrations of eleven uremic solutes were obtained at baseline and after one year of follow-up. Logistic regression was used to compare the odds for rapid to slow progression by uremic solute concentrations at baseline. Variability in uremic solute levels was assessed using scatter plots, and limits of variability were calculated.In total, 40 rapidly and 40 slowly progressing patients were included. Uremic solutes were elevated in all patients compared to reference values for healthy persons. The serum levels of uremic solutes were not associated with rapid progression. Moreover, we observed substantial variability in solute levels over time.Elevated concentrations of uremic solutes measured in this study did not explain differences in rate of eGFR decline in CKD patients, possibly due to lack of power as a result of the small sample size, substantial between patient variability, and variability in solute concentrations over time. The etiology of intra-individual variation in uremic solute levels remains to be elucidated.

  20. Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease.

    Science.gov (United States)

    Wu, Xiao-Xin; Yao, Hang-Ping; Wu, Nan-Ping; Gao, Hai-Nv; Wu, Hai-Bo; Jin, Chang-Zhong; Lu, Xiang-Yun; Xie, Tian-Shen; Li, Lan-Juan

    2015-01-01

    Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD) in humans and non-human primates (NHPs). Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs), vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV)-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirusx2206;VP30, recombinant cytomegalovirus (CMV)-based vaccines, recombinant rabies virus (RABV)-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV)-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD. © 2015 The Author(s) Published by S. Karger AG, Basel.

  1. Rapid Molecular detection of citrus brown spot disease using ACT gene in Alternaria alternata

    Directory of Open Access Journals (Sweden)

    Hamid Moghimi

    2017-06-01

    Full Text Available Introduction:Using rapid detection methods is important for detection of plant pathogens and also prevention through spreading pests in agriculture. Citrus brown spot disease caused by pathogenic isolates of Alternaria alternata is a common disease in Iran. Materials and methods: In this study, for the first time a PCR based molecular method was used for rapid diagnosis of brown spot disease. Nine isolates of A. Alternata were isolated in PDA medium from different citrus gardens. The plant pathogenic activity was examined in tangerine leaves for isolates. Results showed that these isolates are the agents of brown spot disease. PCR amplification of specific ACT-toxin gene was performed for DNA extracted from A. alternata isolates, with 11 different fungal isolates as negative controls and 5 DNA samples extracted from soil. Results: Results showed that A. alternata, the causal agent of brown spot disease, can be carefully distinguished from other pathogenic agents by performing PCR amplification with specific primers for ACT toxin gene. Also, the results from Nested-PCR method confirmed the primary reaction and the specificity of A. alternata for brown spot disease. PCR results to control samples of the other standard fungal isolates, showed no amplification band. In addition, PCR with the DNA extracted from contaminated soils confirmed the presence of ACT toxin gene. Discussion and conclusion: Molecular procedure presented here can be used in rapid identification and prevention of brown spot infection in citrus gardens all over the country.

  2. Impact of exacerbations on emphysema progression in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Tanabe, Naoya; Muro, Shigeo; Hirai, Toyohiro; Oguma, Tsuyoshi; Terada, Kunihiko; Marumo, Satoshi; Kinose, Daisuke; Ogawa, Emiko; Hoshino, Yuma; Mishima, Michiaki

    2011-06-15

    Low-attenuation areas assessed by computed tomography reflect the extent of pathological emphysema and correlate with airflow limitation and mortality in patients with chronic obstructive pulmonary disease. The cumulative size distribution of low-attenuation area clusters follows a power law characterized by an exponent, D. The values of D reflect the complexity of the terminal airspace geometry and sensitively detect alveolar structural changes. Exacerbations of chronic obstructive pulmonary disease have a negative impact on lung function and prognosis. However, the impact on emphysema progression remains unclear. We investigated the relationship between exacerbation and emphysema progression assessed by computed tomography in patients with chronic obstructive pulmonary disease. Exacerbations were prospectively recorded for 2 years. Annual changes in computed tomography parameters of emphysema were compared between patients with and without a history of exacerbations. In patients with exacerbations, increases in the percentage of low-attenuation areas and decreases in D were greater than in patients without exacerbations. To interpret these results, we established a novel simulation model and found that not only enlargement of preexisting low-attenuation areas but also coalescence of adjoining low-attenuation areas due to alveolar wall destruction caused emphysema progression in patients with exacerbations. This is the first longitudinal study to demonstrate that exacerbations are involved in emphysema progression in patients with chronic obstructive pulmonary disease. Emphysema progression should be evaluated as part of the outcomes of exacerbations in the management of chronic obstructive pulmonary disease.

  3. Defective folding and rapid degradation of mutant proteins is a common disease mechanism in genetic disorders

    DEFF Research Database (Denmark)

    Gregersen, N; Bross, P; Jørgensen, M M

    2000-01-01

    Many disease-causing point mutations do not seriously compromise synthesis of the affected polypeptide but rather exert their effects by impairing subsequent protein folding or stability of the folded protein. This often results in rapid degradation of the affected protein. The concepts...

  4. Defective folding and rapid degradation of mutant proteins is a common disease mechanism in genetic disorders

    DEFF Research Database (Denmark)

    Gregersen, Niels; Bross, Peter; Jørgensen, Malene Munk

    2000-01-01

    Many disease-causing point mutations do not seriously compromise synthesis of the affected polypeptides but rather exert their effects by impairing subsequent protein folding or stability of the folded protein. This often results in rapid degradation of the affected protein. The concepts...

  5. Rapid test for fecal calprotectin levels in children with crohn disease

    DEFF Research Database (Denmark)

    Kolho, K L; Turner, D; Veereman-Wauters, G

    2012-01-01

    Assessment of fecal calprotectin, a surrogate marker of mucosal inflammation, is a promising means to monitor therapeutic response in pediatric inflammatory bowel disease, especially if the result is readily available. We tested the performance of a novel calprotectin rapid test, Quantum Blue...

  6. Rapid Newcastle Disease Virus Detection Based on Loop-Mediated Isothermal Amplification and Optomagnetic Readout

    DEFF Research Database (Denmark)

    Tian, Bo; Ma, Jing; Zardán Gómez de la Torre, Teresa

    2016-01-01

    efficiency of loop-mediated isothermal amplification (LAMP) with an optomagnetic nanoparticle-based readout system, we demonstrate ultrasensitive and rapid detection of Newcastle disease virus RNA. Biotinylated amplicons of LAMP and reverse transcription LAMP (RT-LAMP) bind to streptavidin-coated magnetic...

  7. Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function.

    Science.gov (United States)

    Ontaneda, Daniel; Thompson, Alan J; Fox, Robert J; Cohen, Jeffrey A

    2017-04-01

    Multiple sclerosis is a major cause of neurological disability, which accrues predominantly during progressive forms of the disease. Although development of multifocal inflammatory lesions is the underlying pathological process in relapsing-remitting multiple sclerosis, the gradual accumulation of disability that characterises progressive multiple sclerosis seems to result more from diffuse immune mechanisms and neurodegeneration. As a result, the 14 anti-inflammatory drugs that have regulatory approval for treatment of relapsing-remitting multiple sclerosis have little or no efficacy in progressive multiple sclerosis without inflammatory lesion activity. Effective therapies for progressive multiple sclerosis that prevent worsening, reverse damage, and restore function are a major unmet need. In this Series paper we summarise the current status of therapy for progressive multiple sclerosis and outline prospects for the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Progression to symptomatic disease in people infected with HIV-1 in rural Uganda: prospective cohort study

    OpenAIRE

    Morgan, D.; Mahe, C.; Mayanja, B; Whitworth, JA

    2002-01-01

    OBJECTIVES: To estimate the rate of progression from seroconversion to symptomatic disease in adults infected with HIV-1, and to establish whether the background level of signs and symptoms commonly associated with HIV-1 in uninfected controls are likely to affect progression rates. DESIGN: Longitudinal, prospective cohort study of people infected with HIV-1 and randomly selected subjects negative for HIV-1 antibodies identified during population studies. SETTING: Study clinic with basic medi...

  9. Relationship between decrease of erythrocyte count and progression of periodontal disease in a rural Japanese population.

    Science.gov (United States)

    Yamamoto, Tatsuo; Tsuneishi, Midori; Furuta, Michiko; Ekuni, Daisuke; Morita, Manabu; Hirata, Yukio

    2011-01-01

    Limited research has been reported on the relationship between periodontal status and erythrocyte parameters. In the present study, longitudinal data from health checkups are used to clarify the relationship between periodontal disease progression and changes in parameters of erythrocytes. In this prospective study, a total of 120 subjects (35 men and 85 women; age range: 30 to 63 years) participated in a comprehensive health screening and dental checkup in 2006 and 2007. Medical examinations, including anthropometric and manometric measurements, blood-chemistry tests, and oral examinations, were performed. Subjects with periodontal disease progression (i.e., the progression group) were defined based on the presence of ≥1 tooth demonstrating a longitudinal loss of periodontal attachment ≥3 mm or tooth loss during the study period. The Wilcoxon signed-rank, χ(2), Fisher exact, and Mann-Whitney U tests and stepwise logistic regression analysis were used for statistical analyses. The progression group comprised 30 subjects. A significant difference between the progression and non-progression groups was observed in changes of erythrocyte counts but not those of the body mass index, systolic and diastolic blood pressure, creatinine, fasting blood glucose, hemoglobin, hematocrit, triglycerides, high- and low-density lipoprotein cholesterol, total cholesterol, aspartate and alanine aminotransferase, and γ-glutamyl transpeptidase. Stepwise logistic regression analysis showed that the progression of periodontal disease was associated with a change (year 2007 minus year 2006) of erythrocyte counts (adjusted odds ratio = 0.970; P = 0.009) after adjusting for age at baseline. Within the limitations of this study, the progression of periodontal disease is associated with a decrease in erythrocyte counts in a rural Japanese population.

  10. Induction of systemic CTL responses in melanoma patients by dendritic cell vaccination: Cessation of CTL responses is associated with disease progression

    DEFF Research Database (Denmark)

    Andersen, M.H.; Keikavoussi, P.; Brocker, E.B.

    2001-01-01

    Two HLA-A2-positive patients with advanced stage IV melanoma were treated with monocyte-derived dendritic cells (DC) pulsed with either tumor peptide antigens from gp100, MART-1 and MAGE- 3 alone or in combination with autologous oncolysates. Clinically, the rapid progression of disease was subst......Two HLA-A2-positive patients with advanced stage IV melanoma were treated with monocyte-derived dendritic cells (DC) pulsed with either tumor peptide antigens from gp100, MART-1 and MAGE- 3 alone or in combination with autologous oncolysates. Clinically, the rapid progression of disease...... by Western blotting was decreased in PBL at this time. In summary, our data confirm that DC-based vaccinations induce peptide-specific T cells in the peripheral blood of advanced-stage melanoma patients. Although successful induction of systemic tumor antigen-specific CTL may not lead to objective clinical...... tumor regression, their presence are indicative of a prolonged survival....

  11. Gender differences in HIV progression to AIDS and death in industrialized countries: slower disease progression following HIV seroconversion in women.

    Science.gov (United States)

    Jarrin, Inmaculada; Geskus, Ronald; Bhaskaran, Krishnan; Prins, Maria; Perez-Hoyos, Santiago; Muga, Roberto; Hernández-Aguado, Ildefonso; Meyer, Laurence; Porter, Kholoud; del Amo, Julia

    2008-09-01

    To evaluate sex differences in human immunodeficiency virus (HIV) disease progression before (pre-1997) and after (1997-2006) introduction of highly active antiretroviral therapy, the authors used data from a collaboration of 23 HIV seroconverter cohort studies from Europe, Australia, and Canada restricted to the 6,923 seroconverters infected through injecting drug use and sex between men and women. Within a competing risk framework, they used Cox proportional hazards models allowing for late entry to evaluate sex differences in time from HIV seroconversion to death, to acquired immunodeficiency syndrome (AIDS), and to each first AIDS-defining disease and death without AIDS. While no significant sex differences were found before 1997, from 1997 onward, women had a lower risk of AIDS (adjusted cumulative relative risk (aCRR) = 0.76, 95% confidence interval (CI): 0.63, 0.90) and death (adjusted hazard ratio = 0.68, 95% CI: 0.56, 0.82) than men did. Compared with men, women also had lower risks of AIDS dementia complex (aCRR = 0.23, 95% CI: 0.07, 0.74), tuberculosis (aCRR = 0.60, 95% CI: 0.39, 0.92), Kaposi's sarcoma (aCRR = 0.27, 95% CI: 0.07, 0.99), lymphomas (aCRR = 0.47, 95% CI: 0.23, 0.96), and death without AIDS (aCRR = 0.74, 95% CI: 0.56, 0.98). Sex differences in HIV disease progression have become larger and statistically significant in the era of highly active antiretroviral therapy, supporting a stronger impact of health interventions among women.

  12. Effects of temperature on disease progression and swimming stamina in Ichthyophonus-infected rainbow trout, Oncorhynchus mykiss (Walbaum)

    Science.gov (United States)

    Kocan, R.; Hershberger, P.; Sanders, G.; Winton, J.

    2009-01-01

    Rainbow trout, Oncorhynchus mykiss, were infected with Ichthyophonus sp. and held at 10 ??C, 15 ??C and 20 ??C for 28 days to monitor mortality and disease progression. Infected fish demonstrated more rapid onset of disease, higher parasite load, more severe host tissue reaction and reduced mean-day-to-death at higher temperature. In a second experiment, Ichthyophonus-infected fish were reared at 15 ??C for 16 weeks then subjected to forced swimming at 10 ??C, 15 ??C and 20 ??C. Stamina improved significantly with increased temperature in uninfected fish; however, this was not observed for infected fish. The difference in performance between infected and uninfected fish became significant at 15 ??C (P = 0.02) and highly significant at 20 ??C (P = 0.005). These results have implications for changes in the ecology of fish diseases in the face of global warming and demonstrate the effects of higher temperature on the progression and severity of ichthyophoniasis as well as on swimming stamina, a critical fitness trait of salmonids. This study helps explain field observations showing the recent emergence of clinical ichthyophoniasis in Yukon River Chinook salmon later in their spawning migration when water temperatures were high, as well as the apparent failure of a substantial percentage of infected fish to successfully reach their natal spawning areas. ?? 2009 Blackwell Publishing Ltd.

  13. MMP-7 is a predictive biomarker of disease progression in patients with idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Yasmina Bauer

    2017-03-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a progressive interstitial lung disease with poor prognosis, which is characterised by destruction of normal lung architecture and excessive deposition of lung extracellular matrix. The heterogeneity of disease progression in patients with IPF poses significant obstacles to patient care and prevents efficient development of novel therapeutic interventions. Blood biomarkers, reflecting pathobiological processes in the lung, could provide objective evidence of the underlying disease. Longitudinally collected serum samples from the Bosentan Use in Interstitial Lung Disease (BUILD-3 trial were used to measure four biomarkers (metalloproteinase-7 (MMP-7, Fas death receptor ligand, osteopontin and procollagen type I C-peptide, to assess their potential prognostic capabilities and to follow changes during disease progression in patients with IPF. In baseline BUILD-3 samples, only MMP-7 showed clearly elevated protein levels compared with samples from healthy controls, and further investigations demonstrated that MMP-7 levels also increased over time. Baseline levels of MMP-7 were able to predict patients who had higher risk of worsening and, notably, baseline levels of MMP-7 could predict changes in FVC as early as month 4. MMP-7 shows potential to be a reliable predictor of lung function decline and disease progression.

  14. Parkinson's disease progression at 30 years: a study of subthalamic deep brain-stimulated patients.

    Science.gov (United States)

    Merola, Aristide; Zibetti, Maurizio; Angrisano, Serena; Rizzi, Laura; Ricchi, Valeria; Artusi, Carlo A; Lanotte, Michele; Rizzone, Mario G; Lopiano, Leonardo

    2011-07-01

    Clinical findings in Parkinson's disease suggest that most patients progressively develop disabling non-levodopa-responsive symptoms during the course of the disease. Nevertheless, several heterogeneous factors, such as clinical phenotype, age at onset and genetic aspects may influence the long-term clinical picture. In order to investigate the main features of long-term Parkinson's disease progression, we studied a cohort of 19 subjects treated with subthalamic nucleus deep brain stimulation after >20 years of disease, reporting clinical and neuropsychological data up to a mean of 30 years from disease onset. This group of patients was characterized by an early onset of disease, with a mean age of 38.63 years at Parkinson's disease onset, which was significantly lower than in the other long-term subthalamic nucleus deep brain stimulation follow-up cohorts reported in the literature. All subjects were regularly evaluated by a complete Unified Parkinson's Disease Rating Scale, a battery of neuropsychological tests and a clinical interview, intended to assess the rate of non-levodopa-responsive symptom progression. Clinical data were available for all patients at presurgical baseline and at 1, 3 and 5 years from the subthalamic nucleus deep brain stimulation surgical procedure, while follow-up data after >7 years were additionally reported in a subgroup of 14 patients. The clinical and neuropsychological performance progressively worsened during the course of follow-up; 64% of patients gradually developed falls, 86% dysphagia, 57% urinary incontinence and 43% dementia. A progressive worsening of motor symptoms was observed both in 'medication-ON' condition and in 'stimulation-ON' condition, with a parallel reduction in the synergistic effect of 'medication-ON/stimulation-ON' condition. Neuropsychological data also showed a gradual decline in the performances of all main cognitive domains, with an initial involvement of executive functions, followed by the impairment

  15. Ketogenic Diet Prevents Epileptogenesis and Disease Progression in Adult Mice and Rats

    Science.gov (United States)

    Lusardi, Theresa A.; Akula, Kiran K.; Coffman, Shayla Q.; Ruskin, David; Masino, Susan A.; Boison, Detlev

    2015-01-01

    Epilepsy is a highly prevalent seizure disorder which tends to progress in severity and become refractory to treatment. Yet no therapy is proven to halt disease progression or to prevent the development of epilepsy. Because a high fat low carbohydrate ketogenic diet (KD) augments adenosine signaling in the brain and because adenosine not only suppresses seizures but also affects epileptogenesis, we hypothesized that a ketogenic diet might prevent epileptogenesis through similar mechanisms. Here, we tested this hypothesis in two independent rodent models of epileptogenesis. Using a pentylenetetrazole kindling paradigm in mice, we first show that a KD, but not a conventional antiepileptic drug (valproic acid), suppressed kindling-epileptogenesis. Importantly, after treatment reversal, increased seizure thresholds were maintained in those animals kindled in the presence of a KD, but not in those kindled in the presence of valproic acid. Next, we tested whether a KD can halt disease progression in a clinically relevant model of progressive epilepsy. Epileptic rats that developed spontaneous recurrent seizures after a pilocarpine-induced status epilepticus were treated with a KD or control diet (CD). Whereas seizures progressed in severity and frequency in the CD-fed animals, KD-fed animals showed a prolonged reduction of seizures, which persisted after diet reversal. KD-treatment was associated with increased adenosine and decreased DNA methylation, the latter being maintained after diet discontinuation. Our findings demonstrate that a KD prevented disease progression in two mechanistically different models of epilepsy, and suggest an epigenetic mechanism underlying the therapeutic effects. PMID:26256422

  16. Novel GFAP Variant in Adult-onset Alexander Disease With Progressive Ataxia and Palatal Tremor.

    Science.gov (United States)

    Gass, Jennifer M; Cheema, Anvir; Jackson, Jessica; Blackburn, Patrick R; Van Gerpen, Jay; Atwal, Paldeep S

    2017-11-01

    Alexander disease is a rare neurodegenerative disease caused by variants in the glial fibrillary acidic protein gene (GFAP). This disorder can develop as an infantile, juvenile or adult-onset form and is characterized by several clinical features, including macrocephaly, seizures, ataxia, and bulbar/pseudobulbar signs. While the majority of these patients have the more progressive infantile form which causes severe leukodystrophy and early death; the less common adult form is more variable (ie, onset age, symptoms), with bulbar dysfunction as the primary feature. In our investigation, we describe a patient with progressive neuromuscular issues including dyspnea, dysphagia, dysarthria and progressive ataxia with palatal tremor. Through genetic testing, we determined that our patient has a novel variant in GFAP typical of Alexander disease.

  17. EFFECT OF ALTITUDE AND WOUNDING ON BLOOD DISEASE PROGRESS OF PLANTAIN

    Directory of Open Access Journals (Sweden)

    Hadiwiyono, S. Subandiyah, C. Sumardiyono, J. Widada, and M. Fegan.

    2012-02-01

    Full Text Available Effect of Altitude and Wounding on Blood Disease Progress of Plantain. In the latest decade, the blood disease of banana has spread in almost all provinces in Indonesia and caused wilting of millions banana clusters in several provinces.  It is very difficult to control the disease due  to the base data about ecology and epidemiology of the pathogen are still poorly understood. This research aimed to evaluate the effect of  wounding of inoculation site on blood disease progress of plantain. The experiment was arranged using randomized completely block design It was conducted at three locations with altitude of 100, 1000, and 1600 m above sea levels as replication block. The treatments were wounding, unwounding inoculation site, inoculation, and uninoculation of plantain cv. Kepok Kuning Wounding was applied by stabbing with an injection pin around the corm of 15 stabs/seedling. The seedlings were planted singly in one liter of non sterile soil in plastic bag.  Each treatment consisted of 5 seedlings which was replicated 3 times. Inoculation was done  by soil drenching of 20 ml bacterial suspension at  concentration of 108 cfu/ml two week after planting.  The pathogen used for inoculation originated from low land area (about 100 m above sea level.  Observation was done weekly for 5 weeks. The variables observed were wilt intensity and area under disease progress (AUDPC. The results showed that blood disease was able to establish at altitude of 1600 m above sea level. The disease progress however was slower that those at 100 and 1000 m above sea level. On wounded seedling, the disease progress was more aggressive than those on unwounded one.

  18. Surface plasmon resonance based biosensor: A new platform for rapid diagnosis of livestock diseases

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    Pravas Ranjan Sahoo

    2016-12-01

    Full Text Available Surface plasmon resonance (SPR based biosensors are the most advanced and developed optical label-free biosensor technique used for powerful detection with vast applications in environmental protection, biotechnology, medical diagnostics, drug screening, food safety, and security as well in livestock sector. The livestock sector which contributes the largest economy of India, harbors many bacterial, viral, and fungal diseases impacting a great loss to the production and productive potential which is a major concern in both small and large ruminants. Hence, an accurate, sensitive, and rapid diagnosis is required for prevention of these above-mentioned diseases. SPR based biosensor assay may fulfill the above characteristics which lead to a greater platform for rapid diagnosis of different livestock diseases. Hence, this review may give a detail idea about the principle, recent development of SPR based biosensor techniques and its application in livestock sector.

  19. Multivariate clustering of progression profiles reveals different depression patterns in prodromal Huntington disease.

    Science.gov (United States)

    Kim, Ji-in; Long, Jeffrey D; Mills, James A; McCusker, Elizabeth; Paulsen, Jane S

    2015-11-01

    Although Huntington disease (HD) is caused by an autosomal dominant mutation, its phenotypic presentation differs widely. Variability in clinical phenotypes of HD may reflect the existence of disease subtypes. This hypothesis was tested in prodromal participants from the longitudinal Neurobiological Predictors of Huntington Disease (PREDICT-HD) study. We performed clustering using longitudinal data assessing motor, cognitive, and depression symptoms. Using data from 521 participants with 2,716 data points, we fit growth mixture models (GMM) that identify groups based on multivariate trajectories. In various GMM, different phases of disease progression were partitioned by progression trajectories of motor and cognitive signs, and by overall level of depression symptoms. More progressed motor signs were accompanied by more progressed cognitive signs, but not always by higher levels of depressive symptoms. In several models, there were at least 2 groups with similar trajectories for motor and cognitive signs that showed different levels for depression symptoms-one with a very low level of depression and the other with a higher level of depression. Findings indicate that at least intermediate HD progression might be associated with different levels of depression. Depression is one of the few symptoms that is treatable in HD and has implications for clinical care. Identification of potential depression subtypes may also help to select appropriate patients for clinical trials. (c) 2015 APA, all rights reserved).

  20. DiME: a scalable disease module identification algorithm with application to glioma progression.

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    Yunpeng Liu

    Full Text Available Disease module is a group of molecular components that interact intensively in the disease specific biological network. Since the connectivity and activity of disease modules may shed light on the molecular mechanisms of pathogenesis and disease progression, their identification becomes one of the most important challenges in network medicine, an emerging paradigm to study complex human disease. This paper proposes a novel algorithm, DiME (Disease Module Extraction, to identify putative disease modules from biological networks. We have developed novel heuristics to optimise Community Extraction, a module criterion originally proposed for social network analysis, to extract topological core modules from biological networks as putative disease modules. In addition, we have incorporated a statistical significance measure, B-score, to evaluate the quality of extracted modules. As an application to complex diseases, we have employed DiME to investigate the molecular mechanisms that underpin the progression of glioma, the most common type of brain tumour. We have built low (grade II--and high (GBM--grade glioma co-expression networks from three independent datasets and then applied DiME to extract potential disease modules from both networks for comparison. Examination of the interconnectivity of the identified modules have revealed changes in topology and module activity (expression between low- and high- grade tumours, which are characteristic of the major shifts in the constitution and physiology of tumour cells during glioma progression. Our results suggest that transcription factors E2F4, AR and ETS1 are potential key regulators in tumour progression. Our DiME compiled software, R/C++ source code, sample data and a tutorial are available at http://www.cs.bham.ac.uk/~szh/DiME.

  1. Progression of Common Variable Immunodeficiency Interstitial Lung Disease Accompanies Distinct Pulmonary and Laboratory Findings.

    Science.gov (United States)

    Maglione, Paul J; Overbey, Jessica R; Cunningham-Rundles, Charlotte

    2015-01-01

    Common variable immunodeficiency may be complicated by interstitial lung disease, which leads to worsened morbidity and mortality in some. Although immunomodulatory treatment has efficacy, choice of patient, duration of treatment, and long-term follow-up are not available. Interstitial lung disease appears stable in certain instances, so it is not known whether all patients will develop progressive disease or require immunomodulatory therapy. This study aims to determine if all common variable immunodeficiency patients with interstitial lung disease have physiological worsening, and if clinical and/or laboratory parameters may correlate with disease progression. A retrospective review of medical records at Mount Sinai Medical Center in New York was conducted for referred patients with common variable immunodeficiency, CT scan-confirmed interstitial lung disease, and periodic pulmonary function testing covering 20 or more months before immunomodulatory therapy. Fifteen patients were identified from the retrospective review and included in this study. Of the 15 patients with common variable immunodeficiency, 9 had physiological worsening of interstitial lung disease adapted from consensus guidelines, associated with significant reductions in forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of the lung for carbon monoxide. Those with progressive lung disease also had significantly lower mean immunoglobulin G levels, greater increases and highest levels of serum immunoglobulin M (IgM), and more significant thrombocytopenia. Interstitial lung disease resulted in physiological worsening in many, but not all subjects, and was associated with suboptimal immunoglobulin G replacement. Those with worsening pulmonary function tests, elevated IgM, and severe thrombocytopenic episodes appear to be at highest risk for progressive disease. Such patients may benefit from immunomodulatory treatment. Copyright © 2015 American Academy of Allergy

  2. A clinical index to predict progression from mild cognitive impairment to dementia due to Alzheimer's disease.

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    Sei J Lee

    Full Text Available BACKGROUND: Mild cognitive impairment is often a precursor to dementia due to Alzheimer's disease, but many patients with mild cognitive impairment never develop dementia. New diagnostic criteria may lead to more patients receiving a diagnosis of mild cognitive impairment. OBJECTIVE: To develop a prediction index for the 3-year risk of progression from mild cognitive impairment to dementia relying only on information that can be readily obtained in most clinical settings. DESIGN AND PARTICIPANTS: 382 participants diagnosed with amnestic mild cognitive impairment enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI, a multi-site, longitudinal, observational study. MAIN PREDICTORS MEASURES: Demographics, comorbid conditions, caregiver report of participant symptoms and function, and participant performance on individual items from basic neuropsychological scales. MAIN OUTCOME MEASURE: Progression to probable Alzheimer's disease. KEY RESULTS: Subjects had a mean (SD age of 75 (7 years and 43% progressed to probable Alzheimer's disease within 3 years. Important independent predictors of progression included being female, resisting help, becoming upset when separated from caregiver, difficulty shopping alone, forgetting appointments, number of words recalled from a 10-word list, orientation and difficulty drawing a clock. The final point score could range from 0 to 16 (mean [SD]: 4.2 [2.9]. The optimism-corrected Harrell's c-statistic was 0.71(95% CI: 0.68-0.75. Fourteen percent of subjects with low risk scores (0-2 points, n = 124 converted to probable Alzheimer's disease over 3 years, compared to 51% of those with moderate risk scores (3-8 points, n = 223 and 91% of those with high risk scores (9-16 points, n = 35. CONCLUSIONS: An index using factors that can be obtained in most clinical settings can predict progression from amnestic mild cognitive impairment to probable Alzheimer's disease and may help clinicians

  3. Associations of hormonal contraceptive use with measures of HIV disease progression and antiretroviral therapy effectiveness.

    Science.gov (United States)

    Whiteman, Maura K; Jeng, Gary; Samarina, Anna; Akatova, Natalia; Martirosyan, Margarita; Kissin, Dmitry M; Curtis, Kathryn M; Marchbanks, Polly A; Hillis, Susan D; Mandel, Michele G; Jamieson, Denise J

    2016-01-01

    To examine the associations between hormonal contraceptive use and measures of HIV disease progression and antiretroviral treatment (ART) effectiveness. A prospective cohort study of women with prevalent HIV infection in St. Petersburg, Russia, was conducted. After contraceptive counseling, participants chose to use combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), a copper intrauterine device (IUD) or male condoms for pregnancy prevention. Among participants not using ART at enrollment, we used multivariate Cox regression to assess the association between current (time-varying) contraceptive use and disease progression, measured by the primary composite outcome of CD4 decline to contraceptive method. During a total of 5233 months follow-up among participants not using ART with enrollment CD4 ≥350 cells/mm(3) (n=315), 97 experienced disease progression. Neither current use of COCs [adjusted hazard ratio (aHR) 0.91, 95% confidence interval (CI) 0.56-1.48] nor DMPA (aHR 1.28, 95% CI 0.71-2.31) was associated with a statistically significant increased risk for disease progression compared with use of nonhormonal methods (IUD or condoms). Among participants using ART at enrollment (n=77), we found no statistically significant differences in the predicted mean changes in CD4 cell count comparing current use of COCs (p=.1) or DMPA (p=.3) with nonhormonal methods. Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. Published by Elsevier Inc.

  4. Effects of melatonin on cardiovascular diseases: progress in the past year.

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    Sun, Hang; Gusdon, Aaron M; Qu, Shen

    2016-08-01

    Melatonin is a neuroendocrine hormone synthesized primarily by the pineal gland. Numerous studies have suggested that melatonin plays an important role in various cardiovascular diseases. In this article, recent progress regarding melatonin's effects on cardiovascular diseases is reviewed. In the past year, studies have focused on the mechanism of protection of melatonin on cardiovascular diseases, including myocardial ischemia-reperfusion injury, myocardial hypoxia-reoxygenation injury, pulmonary hypertension, hypertension, atherosclerosis, valvular heart diseases, and other cardiovascular diseases. Studies have demonstrated that melatonin has significant effects on ischemia-reperfusion injury, myocardial chronic intermittent hypoxia injury, pulmonary hypertension, hypertension, valvular heart diseases, vascular diseases, and lipid metabolism. As an inexpensive and well tolerated drug, melatonin may be a new therapeutic option for cardiovascular disease.

  5. A critical role for interleukin-1β in the progression of autoimmune diseases.

    Science.gov (United States)

    Zhao, Ruijuan; Zhou, Hongyan; Su, Shao Bo

    2013-11-01

    Interleukin-1β (IL-1β) belongs to IL-1 family and is a potent pro-inflammatory cytokine. It is known to be also involved in a variety of cellular activities, including cell proliferation, differentiation and apoptosis. In addition to its pathophysiologic role in host protection, IL-1β promotes the progression of a number of autoimmune diseases. Most of such diseases can be controlled by anti-IL-1β treatment. This review discusses the contribution of IL-1β to the course of autoimmune diseases, such as rheumatic diseases, uveitis, autoimmune thyroid diseases (AITD), insulin-dependent diabetes mellitus (IDDM), autoimmune inner ear disease (AIED), multiple sclerosis (MS), myocarditis, hepatitis and kidney diseases. The critical involvement of IL-1β in the pathogenesis of autoimmune diseases provides targets for developing therapeutic treatment. © 2013. Published by Elsevier B.V. All rights reserved.

  6. Investigating rapid eye movement sleep without atonia in Parkinson's disease using the rapid eye movement sleep behavior disorder screening questionnaire.

    Science.gov (United States)

    Bolitho, Samuel J; Naismith, Sharon L; Terpening, Zoe; Grunstein, Ron R; Melehan, Kerri; Yee, Brendon J; Coeytaux, Alessandra; Gilat, Moran; Lewis, Simon J G

    2014-05-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is frequently observed in patients with Parkinson's disease (PD). Accurate diagnosis is essential for managing this condition. Furthermore, the emergence of idiopathic RBD in later life can represent a premotor feature, heralding the development of PD. Reliable, accurate methods for identifying RBD may offer a window for early intervention. This study sought to identify whether the RBD screening questionnaire (RBDSQ) and three questionnaires focused on dream enactment were able to correctly identify patients with REM without atonia (RWA), the neurophysiological hallmark of RBD. Forty-six patients with PD underwent neurological and sleep assessment in addition to completing the RBDSQ, the RBD single question (RBD1Q), and the Mayo Sleep Questionnaire (MSQ). The REM atonia index was derived for all participants as an objective measure of RWA. Patients identified to be RBD positive on the RBDSQ did not show increased RWA on polysomnography (80% sensitivity and 55% specificity). However, patients positive for RBD on questionnaires specific to dream enactment correctly identified higher degrees of RWA and improved the diagnostic accuracy of these questionnaires. This study suggests that the RBDSQ does not accurately identify RWA, essential for diagnosing RBD in PD. Furthermore, the results suggest that self-report measures of RBD need to focus questions on dream enactment behavior to better identify RWA and RBD. Further studies are needed to develop accurate determination and quantification of RWA in RBD to improve management of patients with PD in the future. © 2014 International Parkinson and Movement Disorder Society.

  7. Role of liver immunological inflammation in development and progression of nonalcoholic fatty liver disease

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    ZHU Juanjuan

    2016-03-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a common liver disease in clinical practice and has a complex pathogenesis. At present, the "two- or three-hit" theory is still widely acknowledged as the major pathogenesis of NAFLD. However, in recent years, the role of liver immunological inflammation in the development and progression of NAFLD has been taken more and more seriously. This article elaborates on the mechanism of liver immunological inflammation in the development and progression of NAFLD from the perspective of liver immunological inflammation.

  8. Replication Capacity of Viruses from Acute Infection Drives HIV-1 Disease Progression.

    Science.gov (United States)

    Selhorst, Philippe; Combrinck, Carina; Ndabambi, Nonkululeko; Ismail, Sherazaan D; Abrahams, Melissa-Rose; Lacerda, Miguel; Samsunder, Natasha; Garrett, Nigel; Abdool Karim, Quarraisha; Abdool Karim, Salim S; Williamson, Carolyn

    2017-04-15

    The viral genotype has been shown to play an important role in HIV pathogenesis following transmission. However, the viral phenotypic properties that contribute to disease progression remain unclear. Most studies have been limited to the evaluation of Gag function in the context of a recombinant virus backbone. Using this approach, important biological information may be lost, making the evaluation of viruses obtained during acute infection, representing the transmitted virus, a more biologically relevant model. Here, we evaluate the roles of viral infectivity and the replication capacity of viruses from acute infection in disease progression in women who seroconverted in the CAPRISA 004 tenofovir microbicide trial. We show that viral replication capacity, but not viral infectivity, correlates with the set point viral load (Spearman r = 0.346; P = 0.045) and that replication capacity (hazard ratio [HR] = 4.52; P = 0.01) can predict CD4 decline independently of the viral load (HR = 2.9; P = 0.004) or protective HLA alleles (HR = 0.61; P = 0.36). We further demonstrate that Gag-Pro is not the main driver of this association, suggesting that additional properties of the transmitted virus play a role in disease progression. Finally, we find that although viruses from the tenofovir arm were 2-fold less infectious, they replicated at rates similar to those of viruses from the placebo arm. This indicates that the use of tenofovir gel did not select for viral variants with higher replication capacity. Overall, this study supports a strong influence of the replication capacity in acute infection on disease progression, potentially driven by interaction of multiple genes rather than a dominant role of the major structural gene gagIMPORTANCE HIV disease progression is known to differ between individuals, and defining which fraction of this variation can be attributed to the virus is important both clinically and epidemiologically. In this study, we show that the replication

  9. Rapid, progressive neuropathic arthropathy of the hip in a patient co-infected with human immunodeficiency virus, hepatitis C virus and tertiary syphilis: case report

    Science.gov (United States)

    2011-01-01

    Background Syphilis is a chronic infection that is classified into three stages. In its tertiary stage, syphilis spreads to the brain, heart and other organs; the lesions may involve the skin, mucous membranes and bones. Neuropathic arthropathy associated with tertiary syphilis has rarely been described in Europe and its association with HIV-HCV co-infection has not been reported so far. This article reports the case of a man with tertiary syphilis presenting with rapidly evolving neuropathic arthropathy of the hip and extensive bone destruction. Case presentation On initial presentation, the patient complained of progressively worsening left-sided coxalgia without localized or generalized inflammation. The patient reported to have no history of previous infections, trauma or cancer. Plain x-ray films of the left coxofemoral joint showed marked degeneration with necrosis of the proximal epiphysis of femur and morphological alterations of the acetabulum without protrusion. Primary coxarthrosis was diagnosed and hip arthroplasty was offered, but the patient declined treatment. Three months later, the patient presented a marked deterioration of his general condition. He disclosed that he was seropositive for HCV and HIV, as confirmed by serology. Syphilis serology testing was also positive. A Girdlestone's procedure was performed and samples were collected for routine cultures for bacteria and acid fast bacilli, all resulting negative. Although histological findings were inconclusive, confirmed positive serology for syphilis associated with progressive arthropathy was strongly suggestive of tertiary syphilis, probably exacerbated by HIV-HCV co-infection. The patient partially recovered the ability to walk. Conclusions Due to the resurgence of syphilis, this disease should be considered as a possible cause of neuropathic arthropathy when other infectious causes have been ruled out, particularly in patients with HIV and/or HCV co-infection. PMID:21645338

  10. Rapid, progressive neuropathic arthropathy of the hip in a patient co-infected with human immunodeficiency virus, hepatitis C virus and tertiary syphilis: case report

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    Pasqualini Marco

    2011-06-01

    Full Text Available Abstract Background Syphilis is a chronic infection that is classified into three stages. In its tertiary stage, syphilis spreads to the brain, heart and other organs; the lesions may involve the skin, mucous membranes and bones. Neuropathic arthropathy associated with tertiary syphilis has rarely been described in Europe and its association with HIV-HCV co-infection has not been reported so far. This article reports the case of a man with tertiary syphilis presenting with rapidly evolving neuropathic arthropathy of the hip and extensive bone destruction. Case presentation On initial presentation, the patient complained of progressively worsening left-sided coxalgia without localized or generalized inflammation. The patient reported to have no history of previous infections, trauma or cancer. Plain x-ray films of the left coxofemoral joint showed marked degeneration with necrosis of the proximal epiphysis of femur and morphological alterations of the acetabulum without protrusion. Primary coxarthrosis was diagnosed and hip arthroplasty was offered, but the patient declined treatment. Three months later, the patient presented a marked deterioration of his general condition. He disclosed that he was seropositive for HCV and HIV, as confirmed by serology. Syphilis serology testing was also positive. A Girdlestone's procedure was performed and samples were collected for routine cultures for bacteria and acid fast bacilli, all resulting negative. Although histological findings were inconclusive, confirmed positive serology for syphilis associated with progressive arthropathy was strongly suggestive of tertiary syphilis, probably exacerbated by HIV-HCV co-infection. The patient partially recovered the ability to walk. Conclusions Due to the resurgence of syphilis, this disease should be considered as a possible cause of neuropathic arthropathy when other infectious causes have been ruled out, particularly in patients with HIV and/or HCV co-infection.

  11. Fundus Autofluorescence and SD-OCT Document Rapid Progression in Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC) Associated with a c.256G > A Mutation in BEST1.

    Science.gov (United States)

    Kellner, Simone; Stöhr, Heidi; Fiebig, Britta; Weinitz, Silke; Farmand, Ghazaleh; Kellner, Ulrich; Weber, Bernhard H F

    2016-06-01

    To report the variability of clinical findings, rapid concentric progression, and successful treatment of macular edema in autosomal dominant vitreoretinochoroidopathy (ADVIRC) associated with a heterozygous c.256G > A missense mutation in the bestrophin-1 (BEST1) gene. Three affected members of a four-generation ADVIRC family were examined with fundus autofluorescence (FAF), near-infrared autofluorescence (NIA) and spectral domain optical coherence tomography (SD-OCT). Direct sequence analysis of coding and flanking intronic regions of the BEST1 gene was performed. Disease manifestations presented with high variability with visual problems manifesting between 10 and 40 years of age. Two probands showed marked signs of peripheral degeneration, while this retinal area was not noticeably affected in the third. Cystoid macular edema was present in one proband, which responded to long-term treatment with topic dorzolamide with improved visual acuity. FAF and NIA revealed mid-peripheral retinal degeneration in areas that appeared normal on ophthalmoscopy. The full-field ERG was markedly reduced in two probands. Within a 5-year period a marked increase in concentric progression of degeneration including the posterior pole was documented with FAF, NIA and SD-OCT in one proband after the age of 63 years. Direct sequence analysis of the BEST1 gene revealed a heterozygous c.256G > A missense mutation in the three affected probands. The findings in this family emphasize the previously noted variability of clinical manifestations in BEST1-associated ADVIRC and the relevance of FAF and NIA imaging. Cystoid macular edema and vascular leakage can be successfully treated using dorzolamide.

  12. Tc-99m-bicisate (ECD)-brain-SPECT in rapidly progressive dementia; Hirn-SPECT mit Tc-99m-Bicisat (ECD) bei rasch progredientem dementiellen Syndrom

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    Marienhagen, J.; Eilles, C. [Regensburg Univ. (Germany). Abt. fuer Nuklearmedizin; Weingaertner, U.; Blaha, L. [Bezirkskrankenhaus Mainkofen (Germany). Psychiatrische Klinik; Zerr, I.; Poser, S. [Goettingen Univ. (Germany). Klinik und Poliklinik fuer Neurologie

    1999-07-01

    We present a 61-year-old male patient with progressive dementia. A brain SPECT with Tc-99m-bicisate was performed for confirmation of clinically suspected Alzheimer-dementia. At the time of the SPECT-investigation marked apraxia and aphasia besides severe dementia were present. Electrophysiological as well as anatomical neuroimaging findings showed non-diagnostic alterations. SPECT revealed distinct perfusion defects, which made Alzheimer Dementia unlikely. The further course of the patient was determined by rapidly progressive deterioration with development of akinetic mutism. Thereafter, increased levels of neuron-specific enolase as well as 14-3-3 proteins were found in the cerebro-spinal fluid (CSF). The patient finally died with signs of cerebral decortication. Due to the clinical course and the CSF-findings the patient's final diagnosis was Creutzfeld-Jakob-disease, nevertheless no autopsy was performed. The presented case report underscores the clinical utility of perfusion brain SPECT in the differential diagnosis of dementias. (orig.) [German] Wir berichten ueber einen 61jaehrigen Patienten mit progredientem dementiellen Syndrom, der unter der Verdachtsdiagnose einer Demenz vom Alzheimer-Typ (DAT) zur Hirn-SPECT-Untersuchung mit TC-99m-Bicisat (ECD) vorgestellt wurde. Zum Untersuchungszeitpunkt bestanden neben dem Vollbild einer Demenz eine ausgepraegte Apraxie und Aphasie bei unspezifischen Veraenderungen im EEG sowie der neuroradiologischen Bildgebung. In der Hirn-SPECT-Untersuchung fanden sich fuer eine DAT untypische ausgedehnte, vorwiegend rechtshemisphaerische Perfusionsstoerungen. Im weiteren Verlauf rasche Progredienz des Krankheitsbildes mit Entwicklung eines akinetischen Mutismus sowie Nachweis erhoehter Werte der neuronspezifischen Enolase und des 14-3-3-Proteins im Liquor. Der Patient verstarb schliesslich unter dem Bild einer Decortication. Aufgrund des klinischen Verlaufs sowie der Liquorbefunde wurde, da eine autoptische Befundsicherung

  13. Identification of expression patterns in the progression of disease stages by integration of transcriptomic data

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    Sara Aibar

    2016-11-01

    Full Text Available Abstract Background In the study of complex diseases using genome-wide expression data from clinical samples, a difficult case is the identification and mapping of the gene signatures associated to the stages that occur in the progression of a disease. The stages usually correspond to different subtypes or classes of the disease, and the difficulty to identify them often comes from patient heterogeneity and sample variability that can hide the biomedical relevant changes that characterize each stage, making standard differential analysis inadequate or inefficient. Results We propose a methodology to study diseases or disease stages ordered in a sequential manner (e.g. from early stages with good prognosis to more acute or serious stages associated to poor prognosis. The methodology is applied to diseases that have been studied obtaining genome-wide expression profiling of cohorts of patients at different stages. The approach allows searching for consistent expression patterns along the progression of the disease through two major steps: (i identifying genes with increasing or decreasing trends in the progression of the disease; (ii clustering the increasing/decreasing gene expression patterns using an unsupervised approach to reveal whether there are consistent patterns and find genes altered at specific disease stages. The first step is carried out using Gamma rank correlation to identify genes whose expression correlates with a categorical variable that represents the stages of the disease. The second step is done using a Self Organizing Map (SOM to cluster the genes according to their progressive profiles and identify specific patterns. Both steps are done after normalization of the genomic data to allow the integration of multiple independent datasets. In order to validate the results and evaluate their consistency and biological relevance, the methodology is applied to datasets of three different diseases: myelodysplastic syndrome

  14. Progression of Parkinson's disease as evaluated by Hoehn and Yahr stage transition times.

    Science.gov (United States)

    Zhao, Ying Jiao; Wee, Hwee Lin; Chan, Yiong-Huak; Seah, Soo Hoon; Au, Wing Lok; Lau, Puay Ngoh; Pica, Emmanuel Camara; Li, Shu Chuen; Luo, Nan; Tan, Louis C S

    2010-04-30

    This study was carried out to evaluate progression in Parkinson's disease (PD) by analyzing time taken to transit from one Hoehn and Yahr (H&Y) stage to the next stage and to investigate the variables that would be associated with H&Y transition times using a large PD database that contained prospectively collected information. Data were obtained from the movement disorder database of the National Neuroscience Institute in Singapore. Kaplan-Meier (KM) survival analysis was adopted to investigate the time taken to progress through various H&Y stages. Cox regression analysis was used to examine the association between the baseline variables at the entry point of each H&Y stage and the progression to the next stage. A total of 695 patients (mean age: 65.2, male: 57.3%) were studied. Using KM analysis, the median time taken to transit from H&Y stage 1 to 2, 2 to 2.5, 2.5 to 3 were 20, 62, and 25 months, respectively; whereas the median time taken to progress from stage 3 to 4 and 4 to 5 were 24 and 26 months, respectively. Cox regression analysis revealed that older age-at-diagnosis, longer PD duration, and higher Unified Parkinson's Disease Rating Scale (UPDRS) motor scores at baseline were associated with a significantly faster progression through various H&Y stages. Gender and ethnicity were not associated with disease progression. In conclusion, H&Y transition time is a useful measure of disease progression in PD and may be utilized in clinical studies evaluating therapeutic interventions and prognostic factors in PD. 2010 Movement Disorder Society

  15. Urinary uromodulin excretion predicts progression of chronic kidney disease resulting from IgA nephropathy.

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    Jingjing Zhou

    Full Text Available BACKGROUND: Uromodulin, or Tamm-Horsfall protein, is the most abundant urinary protein in healthy individuals. Recent studies have suggested that uromodulin may play a role in chronic kidney diseases. We examined an IgA nephropathy cohort to determine whether uromodulin plays a role in the progression of IgA nephropathy. METHODS: A total of 344 IgA nephropathy patients were involved in this study. Morphological changes were evaluated with the Oxford classification of IgA nephropathy. Enzyme Linked Immunosorbent Assay (ELISA measured the urinary uromodulin level on the renal biopsy day. Follow up was done regularly on 185 patients. Time-average blood pressure, time-average proteinuria, estimated glomerular filtration rate (eGFR and eGFR decline rate were caculated. Association between the urinary uromodulin level and the eGFR decline rate was analyzed with SPSS 13.0. RESULTS: We found that lower baseline urinary uromodulin levels (P = 0.03 and higher time-average proteinuria (P = 0.04 were risk factors for rapid eGFR decline in a follow-up subgroup of the IgA nephropathy cohort. Urinary uromodulin level was correlated with tubulointerstitial lesions (P = 0.016. Patients that had more tubular atrophy/interstitial fibrosis on the surface had lower urinary uromodulin levels (P = 0.02. CONCLUSIONS: Urinary uromodulin level is associated with interstitial fibrosis/tubular atrophy and contributes to eGFR decline in IgA nephropathy.

  16. Force control deficits in individuals with Parkinson's disease, multiple systems atrophy, and progressive supranuclear palsy.

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    Kristina A Neely

    Full Text Available This study examined grip force and cognition in Parkinson's disease (PD, Parkinsonian variant of multiple system atrophy (MSAp, progressive supranuclear palsy (PSP, and healthy controls. PD is characterized by a slower rate of force increase and decrease and the production of abnormally large grip forces. Early-stage PD has difficulty with the rapid contraction and relaxation of hand muscles required for precision gripping. The first goal was to determine which features of grip force are abnormal in MSAp and PSP. The second goal was to determine whether a single variable or a combination of motor and cognitive measures would distinguish patient groups. Since PSP is more cognitively impaired relative to PD and MSAp, we expected that combining motor and cognitive measures would further distinguish PSP from PD and MSAp.We studied 44 participants: 12 PD, 12 MSAp, 8 PSP, and 12 controls. Patients were diagnosed by a movement disorders neurologist and were tested off anti-Parkinsonian medication. Participants completed a visually guided grip force task wherein force pulses were produced for 2 s, followed by 1 s of rest. We also conducted four cognitive tests.PD, MSAp, and PSP were slower at contracting and relaxing force and produced longer pulse durations compared to controls. PSP produced additional force pulses during the task and were more cognitively impaired relative to other groups. A receiver operator characteristic analysis revealed that the combination of number of pulses and Brief Test of Attention (BTA discriminated PSP from PD, MSAp, and controls with a high degree of sensitivity and specificity.Slowness in contracting and relaxing force represent general features of PD, MSAp, and PSP, whereas producing additional force pulses was specific to PSP. Combining motor and cognitive measures provides a robust method for characterizing behavioral features of PSP compared to MSAp and PD.

  17. The performance of the progressive resolution optimizer (PRO) for RapidArc planning in targets with low-density media.

    Science.gov (United States)

    Kan, Monica W K; Leung, Lucullus H T; Yu, Peter K N

    2013-11-04

    A new version of progressive resolution optimizer (PRO) with an option of air cavity correction has been implemented for RapidArc volumetric-modulated arc therapy (RA). The purpose of this study was to compare the performance of this new PRO with the use of air cavity correction option (PRO10_air) against the one without the use of the air cavity correction option (PRO10_no-air) for RapidArc planning in targets with low-density media of different sizes and complexities. The performance of PRO10_no-air and PRO10_air was initially compared using single-arc plans created for four different simple heterogeneous phantoms with virtual targets and organs at risk. Multiple-arc planning of 12 real patients having nasopharyngeal carcinomas (NPC) and ten patients having non-small cell lung cancer (NSCLC) were then performed using the above two options for further comparison. Dose calculations were performed using both the Acuros XB (AXB) algorithm with the dose to medium option and the analytical anisotropic algorithm (AAA). The effect of using intermediate dose option after the first optimization cycle in PRO10_air and PRO10_no-air was also investigated and compared. Plans were evaluated and compared using target dose coverage, critical organ sparing, conformity index, and dose homogeneity index. For NSCLC cases or cases for which large volumes of low-density media were present in or adjacent to the target volume, the use of the air cavity correction option in PRO10 was shown to be beneficial. For NPC cases or cases for which small volumes of both low- and high-density media existed in the target volume, the use of air cavity correction in PRO10 did not improve the plan quality. Based on the AXB dose calculation results, the use of PRO10_air could produce up to 18% less coverage to the bony structures of the planning target volumes for NPC cases. When the intermediate dose option in PRO10 was used, there was negligible difference observed in plan quality between

  18. Assessing Risk of Disease Progression and Pharmacological Management of Autosomal Dominant Polycystic Kidney Disease: A Canadian Expert Consensus.

    Science.gov (United States)

    Soroka, Steven; Alam, Ahsan; Bevilacqua, Micheli; Girard, Louis-Philippe; Komenda, Paul; Loertscher, Rolf; McFarlane, Philip; Pandeya, Sanjaya; Tam, Paul; Bichet, Daniel G

    2017-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder worldwide. The disease is characterized by renal cysts and progressive renal failure due to progressive enlargement of cysts and renal fibrosis. An estimated 45% to 70% of patients with ADPKD progress to end-stage renal disease by age 65 years. Although both targeted and nontargeted therapies have been tested in patients with ADPKD, tolvaptan is currently the only pharmacological therapy approved in Canada for the treatment of ADPKD. The purpose of this consensus recommendation is to develop an evidence-informed recommendation for the optimal management of adult patients with ADPKD. This document focuses on the role of genetic testing, the role of renal imaging, predicting the risk of disease progression, and pharmacological treatment options for ADPKD. These areas of focus were derived from 2 national surveys that were disseminated to nephrologists and patients with ADPKD with the aim of identifying unmet needs in the management of ADPKD in Canada. Specific recommendations are provided for the treatment of ADPKD with tolvaptan.

  19. Pregnancy and HIV Disease Progression in an Early Infection Cohort from Five African Countries

    Science.gov (United States)

    Rida, Wasima; Haddad, Lisa B.; Kamali, Anatoli; Karita, Etienne; Lakhi, Shabir; Kilembe, William; Allen, Susan; Inambao, Mubiana; Yang, Annie H.; Latka, Mary H.; Anzala, Omu; Sanders, Eduard J.; Bekker, Linda-Gail; Edward, Vinodh A.; Price, Matt A.

    2017-01-01

    Background: Understanding associations between pregnancy and HIV disease progression is critical to provide appropriate counseling and care to HIV-positive women. Methods: From 2006 to 2011, women less than age 40 with incident HIV infection were enrolled in an early HIV infection cohort in Kenya, Rwanda, South Africa, Uganda, and Zambia. Time-dependent Cox models evaluated associations between pregnancy and HIV disease progression. Clinical progression was defined as a single CD4 measurement pregnancy. Results: Among 222 women, 63 experienced clinical progression during 783.5 person-years at risk (8.0/100). Among 205 women, 87 experienced immunologic progression during 680.1 person-years at risk (12.8/100). The association between pregnancy and clinical progression was adjusted hazard ratio [aHR] = 0.7; 95% confidence interval (CI): 0.2, 1.8. The association between pregnancy and immunologic progression was aHR = 1.7; 95% CI: 0.9, 3.3. Models controlled for age; human leukocyte antigen alleles A*03:01, B*45, B*57; CD4 set point; and HIV-1 subtype. CD4 measurements before versus after pregnancies were not different. Conclusions: In this cohort, pregnancy was not associated with increased clinical or immunologic HIV progression. Similarly, we did not observe meaningful deleterious associations of pregnancy with CD4s. Our findings suggest that HIV-positive women may become pregnant without harmful health effects occurring during the pregnancy. Evaluation of longer-term impact of pregnancy on progression is warranted. PMID:27893488

  20. Intestinal microbial dysbiosis aggravates the progression of Alzheimer's disease in Drosophila.

    Science.gov (United States)

    Wu, Shih-Cheng; Cao, Zih-Syuan; Chang, Kuo-Ming; Juang, Jyh-Lyh

    2017-06-20

    Neuroinflammation caused by local deposits of Aβ42 in the brain is key for the pathogenesis and progression of Alzheimer's disease. However, inflammation in the brain is not always a response to local primary insults. Gut microbiota dysbiosis, which is recently emerging as a risk factor for psychiatric disorders, can also initiate a brain inflammatory response. It still remains unclear however, whether enteric dysbiosis also contributes to Alzheimer's disease. Here we show that in a Drosophila Alzheimer's disease model, enterobacteria infection exacerbated progression of Alzheimer's disease by promoting immune hemocyte recruitment to the brain, thereby provoking TNF-JNK mediated neurodegeneration. Genetic depletion of hemocytes attenuates neuroinflammation and alleviated neurodegeneration. We further found that enteric infection increases the motility of the hemocytes, making them more readily attracted to the brain with an elevated oxidative stress status. This work highlights the importance of gut-brain crosstalk as a fundamental regulatory system in modulating Alzheimer's disease neurodegeneration.Emerging evidence suggests that gut microbiota influences immune function in the brain and may play a role in neurological diseases. Here, the authors offer in vivo evidence from a Drosophila model that supports a role for gut microbiota in modulating the progression of Alzheimer's disease.

  1. Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.

    Directory of Open Access Journals (Sweden)

    Thomas J Scriba

    2017-11-01

    Full Text Available Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors” were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis.Clincialtrials.gov, NCT01119521.

  2. Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.

    Science.gov (United States)

    Scriba, Thomas J; Penn-Nicholson, Adam; Shankar, Smitha; Hraha, Tom; Thompson, Ethan G; Sterling, David; Nemes, Elisa; Darboe, Fatoumatta; Suliman, Sara; Amon, Lynn M; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Johnson, John L; Boom, W Henry; Hatherill, Mark; Valvo, Joe; De Groote, Mary Ann; Ochsner, Urs A; Aderem, Alan; Hanekom, Willem A; Zak, Daniel E

    2017-11-01

    Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors”) were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis. Clincialtrials.gov, NCT01119521.

  3. Apomorphine: a rapid rescue agent for the management of motor fluctuations in advanced Parkinson disease.

    Science.gov (United States)

    Kolls, Brad J; Stacy, Mark

    2006-01-01

    Parkinson disease is one of the most common neurodegenerative diseases in the United States, and the number of late stage patients is rising. In advance-stage disease, fluctuations in motor function, variability in response to dopaminergic therapy, and dyskinesias related to increasing doses of dopamine agonists and levodopa, present a variety of challenges to a managing physician. Traditional methods of treatment have concentrated on therapies to anticipate or prevent states of poor motor function. With the approval of apomorphine as a rapid-acting, subcutaneous injectable anti-Parkinson disease therapy, these off periods may now be treated with apomorphine as a "rescue" medication when they occur. This article reviews the pharmacology of apomorphine, the clinical data that support its use and suggest dosing and methods for initiating therapy in this challenging population of patients with Parkinson disease.

  4. The association of progressive, atrophying, chronic, granulomatous dermohypodermitis with Hodgkin's disease.

    Science.gov (United States)

    Benisovich, V; Papadopoulos, E; Amorosi, E L; Zucker-Franklin, D; Silber, R

    1988-12-01

    The case of a patient with an unusual skin disorder--progressive, atrophying, chronic, granulomatous dermohypodermitis (PACGD)--who developed Hodgkin's disease is reported. A review of the literature revealed only two other cases of PACGD, one of which affected a patient who also was found to have Hodgkin's disease. In an additional report, the diagnosis of Hodgkin's disease was made in a patient who may have had the same dermatologic disorder. The case is reported because the association of these two rare diseases is believed to be more than a chance event.

  5. Cerebrospinal fluid B cells and disease progression in multiple sclerosis - A longitudinal prospective study.

    Directory of Open Access Journals (Sweden)

    Sebastian Wurth

    Full Text Available There is evidence that B cells play an important role in disease pathology of multiple sclerosis (MS. The aim of this prospective observational study was to determine the predictive value of cerebrospinal fluid (CSF B cell subtypes in disease evolution of patients with MS.128 patients were included between 2004 and 2012. Median follow up time was 7.9 years (range 3.3-10.8 years. 10 patients were lost to follow-up. 32 clinically isolated syndrome- (CIS, 25 relapsing remitting MS- (RRMS, 2 secondary progressive MS- (SPMS and 9 primary progressive MS- (PPMS patients were included. The control group consisted of 40 patients with other neurological diseases (OND. CSF samples were analyzed for routine diagnostic parameters. B cell phenotypes were characterized by flow cytometry using CD19 and CD138 specific antibodies. Standardized baseline brain MRI was conducted at the time of diagnostic lumbar puncture. Main outcome variables were likelihood of progressive disease course, EDSS progression, conversion to clinical definite MS (CDMS and relapse rate.CSF mature B cells (CD19+CD138- were increased in bout-onset MS compared to PPMS (p<0.05 and OND (p<0.001, whereas plasma blasts (CD19+CD138+ were increased in bout-onset MS (p<0.001 and PPMS (p<0.05 compared to OND. CSF B cells did not predict a progressive disease course, EDSS progression, an increased relapse rate or the conversion to CDMS. Likelihood of progressive disease course (p<0.05 and EDSS (p<0.01 was predicted by higher age at baseline, whereas conversion to CDMS was predicted by a lower age at onset (p<0.01 and the presence of ≥9 MRI T2 lesions (p<0.05.We detected significant differences in the CSF B cell subsets between different clinical MS subtypes and OND patients. CSF B cells were neither predictive for disease and EDSS progression nor conversion to CDMS after a CIS.

  6. Disease progression in pre-dialysis patients : renal function, symptoms, and health-related quality of life

    NARCIS (Netherlands)

    Goeij, Moniek Cornelia Maria de

    2013-01-01

    This thesis investigated the effect of several risk factors on objectively assessed disease progression (renal function decline and time until the start of renal replacement therapy) and subjectively assessed disease progression (disease-related symptoms and health-related quality of life) in

  7. Racial differences in chronic kidney disease incidence and progression among individuals with HIV

    Science.gov (United States)

    Crews, Deidra C; Jaar, Bernard G

    2009-01-01

    SUMMARY This Practice Point commentary discusses the findings of Lucas et al.’s longitudinal cohort study of chronic kidney disease (CKD) in African American and white individuals with HIV. The study found that—compared with whites—African Americans had a slightly increased risk of incident CKD, but markedly increased rates of estimated glomerular filtration rate decline and progression to end-stage renal disease. This commentary details the clinical implications and limitations of these findings in the context of known racial differences in CKD prevalence and progression to end-stage renal disease in the general population and highlights the importance of screening high-risk HIV patients for kidney disease. CKD is common among HIV patients, and—as in the general population—has a more-aggressive course among African Americans than whites. PMID:18813233

  8. Osteoarthritis in the XXIst Century: Risk Factors and Behaviours that Influence Disease Onset and Progression

    Science.gov (United States)

    Musumeci, Giuseppe; Aiello, Flavia Concetta; Szychlinska, Marta Anna; Di Rosa, Michelino; Castrogiovanni, Paola; Mobasheri, Ali

    2015-01-01

    Osteoarthritis (OA) is a growing public health problem across the globe, affecting more than half of the over 65 population. In the past, OA was considered a wear and tear disease, leading to the loss of articular cartilage and joint disability. Nowadays, thanks to advancements in molecular biology, OA is believed to be a very complex multifactorial disease. OA is a degenerative disease characterized by “low-grade inflammation” in cartilage and synovium, resulting in the loss of joint structure and progressive deterioration of cartilage. Although the disease can be dependent on genetic and epigenetic factors, sex, ethnicity, and age (cellular senescence, apoptosis and lubricin), it is also associated with obesity and overweight, dietary factors, sedentary lifestyle and sport injuries. The aim of this review is to highlight how certain behaviors, habits and lifestyles may be involved in the onset and progression of OA and to summarize the principal risk factors involved in the development of this complicated joint disorder. PMID:25785564

  9. Osteoarthritis in the XXIst century: risk factors and behaviours that influence disease onset and progression.

    Science.gov (United States)

    Musumeci, Giuseppe; Aiello, Flavia Concetta; Szychlinska, Marta Anna; Di Rosa, Michelino; Castrogiovanni, Paola; Mobasheri, Ali

    2015-03-16

    Osteoarthritis (OA) is a growing public health problem across the globe, affecting more than half of the over 65 population. In the past, OA was considered a wear and tear disease, leading to the loss of articular cartilage and joint disability. Nowadays, thanks to advancements in molecular biology, OA is believed to be a very complex multifactorial disease. OA is a degenerative disease characterized by "low-grade inflammation" in cartilage and synovium, resulting in the loss of joint structure and progressive deterioration of cartilage. Although the disease can be dependent on genetic and epigenetic factors, sex, ethnicity, and age (cellular senescence, apoptosis and lubricin), it is also associated with obesity and overweight, dietary factors, sedentary lifestyle and sport injuries. The aim of this review is to highlight how certain behaviors, habits and lifestyles may be involved in the onset and progression of OA and to summarize the principal risk factors involved in the development of this complicated joint disorder.

  10. Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease

    DEFF Research Database (Denmark)

    Currie, Gemma; Taylor, Alison H M; Fujita, Toshiro

    2016-01-01

    BACKGROUND: Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease. Hyperkalaemia...... is a concern with the use of mineralocorticoid receptor antagonists. We aimed to determine whether the renal protective benefits of mineralocorticoid antagonists outweigh the risk of hyperkalaemia associated with this treatment in patients with chronic kidney disease. METHODS: We conducted a meta......-analysis investigating renoprotective effects and risk of hyperkalaemia in trials of mineralocorticoid receptor antagonists in chronic kidney disease. Trials were identified from MEDLINE (1966-2014), EMBASE (1947-2014) and the Cochrane Clinical Trials Database. Unpublished summary data were obtained from investigators...

  11. Progression of lung disease in primary ciliary dyskinesia: is spirometry less accurate than CT?

    Science.gov (United States)

    Maglione, Marco; Bush, Andrew; Montella, Silvia; Mollica, Carmine; Manna, Angelo; Esposito, Antonietta; Santamaria, Francesca

    2012-05-01

    Despite its extensive use, there is no evidence that spirometry is useful in the assessment of progression of lung disease in primary ciliary dyskinesia (PCD). We hypothesize that high-resolution computed tomography (HRCT) is a better indicator of PCD lung disease progression than spirometry. We retrospectively evaluated two paired spirometry and HRCT examinations from 20 PCD patients (age, 11.6 years; range, 6.5-27.5 years). The evaluations were performed in stable state and during unstable lung disease. HRCT scans were scored blind by two raters. Compared to the first assessment, at the second evaluation spirometry did not change while HRCT scores significantly worsened (P spirometry. In PCD, structural lung disease may worsen despite spirometry being stable. Copyright © 2011 Wiley Periodicals, Inc.

  12. The progress of cerebrospinal fluid biomarkers in patients with neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    WANG Wei-zhi

    2013-02-01

    Full Text Available Neurodegenerative diseases include a heterogeneous group of diseases with complicated and overlapped clinical phenotypes. It is difficult to diagnose or identify this kind of disease due to insidious onset and chronic and progressive development. Since processes in the brain can be monitored by analysis of cerebrospinal fluid (CSF, abundant research efforts focus on the efficacy of biomarkers in CSF to indicate specific neurodegenerative lesions and to assist the diagnosis process, assessing whether one biomarker or several biomarkers together could be the reliable tools for diagnosis of specific neurodegenerative diseases. This article mainly reviews the research status and supplementary value in diagnosis and differentiation of CSF biomarkers in common degenerative diseases [e.g. multiple sclerosis (MS, Alzheimer's disease (AD, Parkinson's disease (PD, amyotrophic lateral sclerosis (ALS].

  13. Progress of foliar diseases in wheat crops at Passo Fundo, RS, Brazil

    Directory of Open Access Journals (Sweden)

    Felipe Rafael Garcés Fiallos

    2011-12-01

    Full Text Available The aim was to study the progress of the yellow spot, brown spot and leaf rust in wheat cultivar FUNDACEP 50 in Passo Fundo. Was evaluated the incidence of yellow spot [Drechslera tritici-repentis (Died Drechs.] brown spot [Bipolaris sorokiniana (Sacc.] and leaf rust [Puccinia triticina (Eriks]. Values obtained were integralized as Area Under the Disease Incidence Progress Curve (AUDIPC and to analyze the progress of the disease was considered the disease progress rate (r, which was obtained with the Logistic and Gompertz. Determination coefficients were high (0.93 to 0.98, as well as the mean square error (4.0706 to 7.6831. The r were 0.02 to 0.22 units, while the accumulated AUDIPC 787.5, 1216.3 and 1338.8 units for yellow spot, brown spot and leaf rust, respectively. The two models used satisfactorily explain the progress of yellow spot and brown spot, while the Gompertz explains better leaf rust.

  14. Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study.

    Science.gov (United States)

    Moss, Davina J Hensman; Pardiñas, Antonio F; Langbehn, Douglas; Lo, Kitty; Leavitt, Blair R; Roos, Raymund; Durr, Alexandra; Mead, Simon; Holmans, Peter; Jones, Lesley; Tabrizi, Sarah J

    2017-09-01

    Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008-11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003-13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10(-10)) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10(-8)DHFR p=8·37 × 10(-7) MTRNR2L2 p=2·15 × 10(-9)) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10(-4)DHFR p=8·45 × 10(-4)MTRNR2L2 p=1·20 × 10(-3)). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome

  15. Serial noninvasive assessment of apoptosis during right ventricular disease progression in rats.

    Science.gov (United States)

    Campian, Maria E; Verberne, Hein J; Hardziyenka, Maxim; de Bruin, Kora; Selwaness, Mariana; van den Hoff, Maurice J B; Ruijter, Jan M; van Eck-Smit, Berthe L F; de Bakker, Jacques M T; Tan, Hanno L

    2009-08-01

    Right ventricular (RV) function is the major determinant of survival in patients with pulmonary hypertension. Yet, the pathophysiologic basis of RV disease is unresolved. We aimed to study the role of apoptosis in RV disease by monitoring it serially during disease progression using in vivo (99m)Tc-annexin-V ((99m)Tc-annexin) scintigraphy and study whether the reduction in apoptosis resulting from chronic treatment with valsartan can be detected by (99m)Tc-annexin scintigraphy. RV disease after pulmonary hypertension was induced by monocrotaline injection in rats. The following 3 groups were studied: rats treated with monocrotaline (monocrotaline rats), rats treated with monocrotaline plus valsartan (valsartan rats), and age-matched controls (control rats). Serial echocardiography and in vivo (99m)Tc-annexin scintigraphy were performed. Apoptosis was confirmed by (99m)Tc-annexin autoradiography and terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling. Fibrosis was assessed by picrosirius red staining. In monocrotaline rats, in vivo (99m)Tc-annexin uptake peaked early and declined thereafter but remained elevated, compared with baseline. These stage-dependent changes of in vivo (99m)Tc-annexin uptake were paralleled by changes in autoradiography and terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling. Valsartan rats had longer RV failure-free survival than did monocrotaline rats and had reduced apoptosis. These changes were accompanied by commensurate delays in RV hypertrophy and RV dilation. Valsartan rats also had less fibrosis than monocrotaline rats at all disease stages. RV disease progression is associated with an early increase in RV apoptosis, as monitored using serial in vivo (99m)Tc-annexin scintigraphy. Delay in RV disease progression by valsartan is accompanied by reduction in RV apoptosis. Apoptosis plays a role in RV disease progression and may be assessed by serial in vivo (99m)Tc-annexin scintigraphy.

  16. Progression of relapsing-remitting demyelinating disease does not require increased TCR affinity or epitope spread.

    Science.gov (United States)

    Kersh, Anna E; Edwards, Lindsay J; Evavold, Brian D

    2014-11-01

    In this study, we investigate the basis of T cell recognition of myelin that governs the progression from acute symptoms into disease remission, relapse, and chronic progression in a secondary progressive model of demyelinating disease. Until now, the frequency and affinity of myelin-reactive CD4 T cells that elicit relapsing-remitting disease have not been quantified. The micropipette adhesion frequency assay was used to obtain a sensitive and physiologically relevant two-dimensional measurement of frequency and TCR affinity for myelin, as the inherent low affinity does not allow the use of specific peptide:MHC-II tetramers for this purpose. We found the highest affinity and frequency of polyclonal myelin oligodendrocyte glycoprotein-reactive cells infiltrate the CNS during acute disease, whereas affinities during remission, relapse, and chronic disease are not significantly different from each other. Frequency analysis revealed that the vast majority of CNS-infiltrating CD4 T cells are myelin oligodendrocyte glycoprotein reactive at all time points, demonstrating epitope spread is not a predominant factor for disease progression. Furthermore, time points at which mice were symptomatic were characterized by an infiltration of Th17 cells in the CNS, whereas symptom remission showed an enrichment of cells producing IFN-γ. Also, the ratio of regulatory T cells to Foxp3(-) CD4 T cells was significantly higher in the CNS at remission than during acute disease. The results of this study indicate that a high frequency of T cells specific for a single myelin Ag, rather than increased TCR affinity or epitope spread, governs the transition from acute symptoms through remission, relapse, and chronic disease states. Copyright © 2014 by The American Association of Immunologists, Inc.

  17. Prospects for the use of celecoxib in patients with ankylosing spondylitis: impact on retarding disease progression

    Directory of Open Access Journals (Sweden)

    Yulia Leonidovna Korsakova

    2012-01-01

    Full Text Available Ankylosing spondylitis (AS is one of the major inflammatory diseases that affect the vertebral column and joints. The first-line drugs for the treatment of this disease are now nonsteroidal anti-inflammatory drugs (NSAIDs that not only reduce painful sensations and rigidity, but also retard the radiological progression of AS. Celecoxib is one of the effective and safe NDAIDs that are promising for the treatment of AS.

  18. Risk factors of accelerated progression of peripheral artery disease in hemodialysis.

    Science.gov (United States)

    Hsu, Shang-Reu; Su, Ho-Ming; Hsieh, Ming-Chia; Su, Shin-Li; Chen, Szu-Chia; Chen, Hung-Chun

    2013-02-01

    Ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are markers for peripheral artery occlusive disease (PAOD) and arterial stiffness, respectively. The aims of this study were to assess whether PAOD and arterial stiffness progressed and to determine the risk factors for ABI and baPWV progression in patients on hemodialysis. This study enrolled 173 routine patients on hemodialysis. Both ABI and baPWV were measured by an ABI-form device at baseline and at 1 year of follow-up. Progression in ABI was defined as reduction in ABI exceeding 0.3, while baPWV measured at 1 year of follow-up exceeding that at baseline indicated baPWV progression. Comparison with baseline data showed increase in both prevalence of ABI hemodialysis. Copyright © 2012. Published by Elsevier B.V.

  19. Adverse effect of the CCR5 promoter -2459A allele on HIV-1 disease progression

    DEFF Research Database (Denmark)

    Knudsen, T B; Kristiansen, T B; Katzenstein, T L

    2001-01-01

    HIV positive individuals heterozygous for a 32 basepair deletion in the CCR5 encoding gene (CCR5 Delta32) have a reduced number of CCR5 receptors on the cell surface and a slower progression towards AIDS and death. Other human polymorphisms, such as the CCR2 64I and the CCR5 promoter -2459 A....../G transition that has been discovered recently, have also been shown to influence HIV progression. Since genetic linkages make these polymorphisms interdependent variables, the aim of the present study was to isolate and evaluate the effect on HIV disease progression for each of these mutations independently....... Genotypes were determined in 119 individuals enrolled in the Copenhagen AIDS Cohort. When including the concurrent effects of the CCR5 Delta32 and CCR2 64I mutations, homozygous carriers of the CCR5 promoter -2459A allele had a significantly faster progression towards death than heterozygous A/G individuals...

  20. Factors That Affect Disease Progression After First Attack of Acute Pancreatitis

    DEFF Research Database (Denmark)

    Bertilsson, Sara; Swärd, Per; Kalaitzakis, Evangelos

    2015-01-01

    BACKGROUND & AIMS: Little is known about recurrence of pancreatitis after an initial episode, and little is known about how the disease progresses or what factors affect progression. We performed a population-based study of patients with acute pancreatitis (AP) to determine their outcomes...... pancreatitis, and mortality. Patients were followed up for a median time of 4.6 years, until death or the end of 2013. RESULTS: We identified 1457 patients with first-time AP (48% biliary disease, 17% alcohol-associated, 9.9% severe); 23% of patients had 1 or more recurrences. Risk for recurrence.......27-2.79; P pancreatitis, although alcohol-associated AP progressed most frequently (2.8/100 patient-years). Patients with recurrent AP were at the highest risk for chronic pancreatitis (HR, 6...

  1. Coping with amyotrophic lateral sclerosis; from diagnosis and during disease progression.

    Science.gov (United States)

    Jakobsson Larsson, Birgitta; Nordin, Karin; Nygren, Ingela

    2016-02-15

    To evaluate coping strategies among patients with Amyotrophic lateral sclerosis starting with diagnosis and during the disease progression, as well as investigate changes and correlations between coping strategies, emotional well-being and physical function. A total of 36 patients participated in the study. The patients filled out the Hospital Anxiety and Depression Scale and the Motor Neuron Disease Coping Scale. Physical function was measured using the revised ALS functional rating scale. Data were collected regularly from diagnosis and over a two years period. As a way to cope with the disease patients relied on both problem focused and emotional focused strategies. The use of coping strategies remained stable. Both physical disabilities and emotional well-being was related to some coping strategies, with some variation during the disease progression. Moreover, some coping strategies were related to symptoms of anxiety and depression. Irrespective of whether the coping strategies affect the emotional well-being or vice versa, the results show the importance of early and continuous evaluation of coping and emotional well-being to ease the emotional distress and provide support to the patient so that he/she can cope with the disease during the disease progression. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Endothelial progenitor cell dysfunction in patients with progressive chronic kidney disease

    NARCIS (Netherlands)

    Krenning, Guido; Dankers, Patricia Y. W.; Drouven, Johannes W.; Waanders, Femke; Franssen, Casper F. M.; van Luyn, Marja J. A.; Harmsen, Martin C.; Popa, Eliane R.

    Krenning G, Dankers PY, Drouven JW, Waanders F, Franssen CF, van Luyn MJ, Harmsen MC, Popa ER. Endothelial progenitor cell dysfunction in patients with progressive chronic kidney disease. Am J Physiol Renal Physiol 296: F1314-F1322, 2009. First published April 1, 2009; doi:

  3. Accuracy of MR markers for differentiating Progressive Supranuclear Palsy from Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Stefano Zanigni

    2016-01-01

    Conclusion: Although several quantitative brain MR markers provided high diagnostic accuracy in differentiating Progressive Supranuclear Palsy-Richardson's Syndrome from Parkinson's disease, the morphometric assessment of midbrain area is the best single diagnostic marker and should be routinely included in the neuroradiological work-up of parkinsonian patients.

  4. Integrative EEG biomarkers predict progression to Alzheimer's disease at the MCI stage

    NARCIS (Netherlands)

    Poil, S.S.; de Haan, W.; van der Flier, W.M.; Mansvelder, H.D.; Scheltens, P.; Linkenkaer-Hansen, K.

    2013-01-01

    Alzheimer's disease (AD) is a devastating disorder of increasing prevalence in modern society. Mild cognitive impairment (MCI) is considered a transitional stage between normal aging and AD; however, not all subjects with MCI progress to AD. Prediction of conversion to AD at an early stage would

  5. Urine liver fatty acid binding protein and chronic kidney disease progression

    DEFF Research Database (Denmark)

    Khatir, Dinah S; Bendtsen, Mette D; Birn, Henrik

    2017-01-01

    , regarding progression of chronic kidney disease (CKD). In a prospective study design a cohort of 74 stage 3-4 CKD patients (age 61 ± 13 years) were included. Glomerular filtration ratio (GFR, 51Cr-EDTA-clearance), 24-hour ambulatory BP, 24-hour urinary albumin/creatinine ratio (UAC) and urinary L...

  6. Disease impact in chronic progressive external ophthalmoplegia: more than meets the eye

    NARCIS (Netherlands)

    Smits, B.W.; Fermont, J.; Delnooz, C.C.S.; Kalkman, J.S.; Bleijenberg, G.; Engelen, B.G.M. van

    2011-01-01

    We determined the extent of disease impact in 28 patients with genetically confirmed chronic progressive external ophthalmoplegia (CPEO) and compared the outcomes to those of matched myotonic dystrophy type I patients. CPEO patients reported a high frequency of severe fatigue (67.9%), pain (96.2%),

  7. Patterns of disease progression in the rheumatoid wrist : A longterm followup

    NARCIS (Netherlands)

    van Vugt, RM; van Jaarsveld, CHM; Hofman, DM; Helders, PJM; Bijlsma, JWJ

    Objective, To identify different patterns of disease manifestation and changes in the rate of progression of rheumatoid arthritis (RA) in the wrist.Methods. Forty wrists, with normal baseline radiographs, of 20 patients with RA were evaluated by means of a retrospective radiographic review for a

  8. White matter lesions are associated with progression of medial temporal lobe atrophy in Alzheimer disease.

    NARCIS (Netherlands)

    Leeuw, F.E. de; Korf, E.; Barkhof, F.; Scheltens, P.

    2006-01-01

    BACKGROUND AND PURPOSE: Medial temporal lobe atrophy (MTA) is a hallmark of Alzheimer disease (AD). Its progression is often seen during the course of AD, but its frequency and risk factors remain unclear. METHODS: We investigated MTA in 35 patients with AD from whom sequential magnetic resonance

  9. Accelerating regional atrophy rates in the progression from normal aging to Alzheimer's disease

    NARCIS (Netherlands)

    Sluimer, Jasper D.; van der Flier, Wiesje M.; Karas, Giorgos B.; van Schijndel, Ronald; Barnes, Josephine; Boyes, Richard G.; Cover, Keith S.; Olabarriaga, Sílvia D.; Fox, Nick C.; Scheltens, Philip; Vrenken, Hugo; Barkhof, Frederik

    2009-01-01

    We investigated progression of atrophy in vivo, in Alzheimer's disease (AD), and mild cognitive impairment (MCI). We included 64 patients with AD, 44 with MCI and 34 controls with serial MRI examinations (interval 1.8 +/- 0.7 years). A nonlinear registration algorithm (fluid) was used to calculate

  10. Progression of carotid-artery disease in type 2 diabetic patients: a cohort prospective study

    Directory of Open Access Journals (Sweden)

    Bosevski M

    2015-10-01

    Full Text Available Marijan Bosevski,1 Lily Stojanovska2 1Faculty of Medicine, University Cardiology Clinic, Skopje, Macedonia; 2Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, VIC, Australia Abstract: In order to assess the progression of carotid-artery disease in type 2 diabetic cohort (n=207 patients, the dynamic change in carotid intima-media thickness (CIMT and the occurrence of plaques were followed for a period of 31.35±10.59 months. The mean CIMT at the beginning of the study was 0.9178±0.1447 mm, with a maximal value of 1.1210±0.2366 mm. The maximal value of CIMT changed by 0.07 mm/year. Progression of CIMT was noted in 86.8% and its regression in 7.8% of patients. The occurrence of carotid plaques was detected in 41.8% of patients. Multiple regression analysis revealed the maximal value of CIMT to be associated with diastolic blood pressure, despite mean CIMT being predicted by body mass index. The presence of peripheral arterial disease and hypo-high-density lipoproteinemia were found to be predictors for the occurrence of carotid plaques. Our data have clinical implications in predicting risk factors for the progression of carotid-artery disease in type 2 diabetic patients for their appropriate management. Keywords: carotid IMT, type 2 diabetes, progression of atherosclerosis, risk factors 

  11. Prediction of progression to severe disease in women with late preterm hypertensive disorders of pregnancy

    NARCIS (Netherlands)

    Zwertbroek, E.F.; Broekhuijsen, K.; Langenveld, J.; Baaren, G.J. van; Berg, P.P. van den; Bremer, H.A.; Ganzevoort, W.; Loon, A.J. van; Mol, B.W.; Pampus, M.G. van; Perquin, D.A.; Rijnders, R.J.; Scheepers, H.C.; Sikkema, M.J.; Woiski, M.D.; Groen, H.; Franssen, M.T.

    2017-01-01

    INTRODUCTION: If hypertensive disorders of pregnancy are diagnosed before term, the benefits of immediate delivery need to be weighed against the neonatal consequences of preterm delivery. If we are able to predict which women are at high risk of progression to severe disease, they could be targeted

  12. Brain Substrates of Learning and Retention in Mild Cognitive Impairment Diagnosis and Progression to Alzheimer's Disease

    Science.gov (United States)

    Chang, Yu-Ling; Bondi, Mark W.; Fennema-Notestine, Christine; McEvoy, Linda K.; Hagler, Donald J., Jr.; Jacobson, Mark W.; Dale, Anders M.

    2010-01-01

    Understanding the underlying qualitative features of memory deficits in mild cognitive impairment (MCI) can provide critical information for early detection of Alzheimer's disease (AD). This study sought to investigate the utility of both learning and retention measures in (a) the diagnosis of MCI, (b) predicting progression to AD, and (c)…

  13. Herpes zoster, immunological deterioration and disease progression in HIV-1 infection

    NARCIS (Netherlands)

    Veenstra, J.; Krol, A.; van Praag, R. M.; Frissen, P. H.; Schellekens, P. T.; Lange, J. M.; Coutinho, R. A.; van der Meer, J. T.

    1995-01-01

    OBJECTIVE: To study the incidence of herpes zoster, the relationship between herpes zoster and immunological markers, and the prognostic value of herpes zoster for progression of HIV disease. DESIGN AND METHODS: A total of 966 homosexual participants in The Amsterdam Cohort Study were studied.

  14. Correlates for disease progression and prognosis during concurrent HIV/TB infection

    DEFF Research Database (Denmark)

    Djoba Siawaya, Joel Fleury; Ruhwald, Morten; Eugen-Olsen, Jesper

    2007-01-01

    between HIV and Mtb and discusses the relevance of sputum smear examination, CD4+ counts, viral load at baseline and after initiation of anti-retroviral therapy, as well as additional existing and new potential immune correlates of disease progression and prognosis. These markers include beta2...

  15. Progression of Alzheimer Disease in Europe: Data from the European ICTUS Study

    NARCIS (Netherlands)

    Vellas, B.; Hausner, L.; Frolich, L.; Cantet, C.; Gardette, V.; Reynish, E.; Gillette, S.; Aguera-Morales, E.; Auriacombe, S.; Boada, M.; Bullock, R.; Byrne, J.; Camus, V.; Cherubini, A.; Eriksdotter-Jonhagen, M.; Frisoni, G.B.; Hasselbalch, S.; Jones, R.W.; Martinez-Lage, P.; Olde Rikkert, M.G.; Tsolaki, M.; Ousset, P.J.; Pasquier, F.; Ribera-Casado, J.M.; Rigaud, A.S.; Robert, P.; Rodriguez, G.; Salmon, E.; Salva, A.; Scheltens, P.; Schneider, A.; Sinclair, A.; Spiru, L.; Touchon, J.; Zekry, D.; Winblad, B.; Andrieu, S.

    2012-01-01

    The clinical progression of Alzheimer disease (AD) was studied in European subjects under treatment with AChE inhibitors (AChE-I) in relation to geographical location over a 2-years period. One thousand three hundred and six subjects from 11 European countries were clustered into 3 regions (North,

  16. Site-level progression of periodontal disease during a follow-up period

    Science.gov (United States)

    Morozumi, Toshiya; Nakagawa, Taneaki; Sugaya, Tsutomu; Kawanami, Masamitsu; Suzuki, Fumihiko; Takahashi, Keiso; Abe, Yuzo; Sato, Soh; Makino-Oi, Asako; Saito, Atsushi; Takano, Satomi; Minabe, Masato; Nakayama, Yohei; Ogata, Yorimasa; Kobayashi, Hiroaki; Izumi, Yuichi; Sugano, Naoyuki; Ito, Koichi; Sekino, Satoshi; Numabe, Yukihiro; Fukaya, Chie; Yoshinari, Nobuo; Fukuda, Mitsuo; Noguchi, Toshihide; Kono, Tomoo; Umeda, Makoto; Fujise, Osamu; Nishimura, Fusanori; Yoshimura, Atsutoshi; Hara, Yoshitaka; Nakamura, Toshiaki; Noguchi, Kazuyuki; Kakuta, Erika; Hanada, Nobuhiro; Takashiba, Shogo; Amitani, Yasuharu; Yoshie, Hiromasa

    2017-01-01

    Periodontal disease is assessed and its progression is determined via observations on a site-by-site basis. Periodontal data are complex and structured in multiple levels; thus, applying a summary statistical approach (i.e., the mean) for site-level evaluations results in loss of information. Previous studies have shown the availability of mixed effects modeling. However, clinically beneficial information on the progression of periodontal disease during the follow-up period is not available. We conducted a multicenter prospective cohort study. Using mixed effects modeling, we analyzed 18,834 sites distributed on 3,139 teeth in 124 patients, and data were collected 5 times over a 24-month follow-up period. The change in the clinical attachment level (CAL) was used as the outcome variable. The CAL at baseline was an important determinant of the CAL changes, which varied widely according to the tooth surface. The salivary levels of periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were affected by CAL progression. “Linear”- and “burst”-type patterns of CAL progression occurred simultaneously within the same patient. More than half of the teeth that presented burst-type progression sites also presented linear-type progression sites, and most of the progressions were of the linear type. Maxillary premolars and anterior teeth tended to show burst-type progression. The parameters identified in this study may guide practitioners in determining the type and extent of treatment needed at the site and patient levels. In addition, these results show that prior hypotheses concerning "burst" and "linear" theories are not valid. PMID:29206238

  17. Portable microfluidic raman system for rapid, label-free early disease signature detection

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Meiye [Sandia National Laboratories (SNL-CA), Livermore, CA (United States); Davis, Ryan Wesley [Sandia National Laboratories (SNL-CA), Livermore, CA (United States); Hatch, Anson [Sandia National Laboratories (SNL-CA), Livermore, CA (United States)

    2015-09-01

    In the early stages of infection, patients develop non-specific or no symptoms at all. While waiting for identification of the infectious agent, precious window of opportunity for early intervention is lost. The standard diagnostics require affinity reagents and sufficient pathogen titers to reach the limit of detection. In the event of a disease outbreak, triaging the at-risk population rapidly and reliably for quarantine and countermeasure is more important than the identification of the pathogen by name. To expand Sandia's portfolio of Biological threat management capabilities, we will utilize Raman spectrometry to analyze immune subsets in whole blood to rapidly distinguish infected from non-infected, and bacterial from viral infection, for the purpose of triage during an emergency outbreak. The goal of this one year LDRD is to determine whether Raman spectroscopy can provide label-free detection of early disease signatures, and define a miniaturized Raman detection system meeting requirements for low- resource settings.

  18. Rapidly progressive disease in a castration-resistant prostate cancer patient after cabazitaxel discontinuation.

    Science.gov (United States)

    Di Lorenzo, Giuseppe; Buonerba, Carlo; de Placido, Sabino

    2015-02-01

    We report the case of a 51-year-old patient with metastatic prostate cancer at diagnosis and primary refractoriness to both androgen ablation therapy and docetaxel. At the time of cabazitaxel initiation, the patient had only osseous metastases and was constrained to a wheelchair because of bone pain. Ten cycles of cabazitaxel were administered, and a remarkable response was achieved, with improvement in biochemical markers, performance status, and bone scan findings. Two months after suspension of treatment by choice, the patient developed jaundice because of massive hepatic metastases and died after a few days because of hepatic failure.

  19. Atypical rapid progression of osteoarticular amyloidosis involving the hip in a patient on hemodialysis using polyacrylonitrile membranes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kenneth S. [University of Wisconsin School of Medicine and Public Health, Department of Radiology, University of Wisconsin Hospital and Clinics, Madison, WI (United States); Holsbeeck, Marnix T. van [Wayne State School of Medicine, Department of Radiology, Henry Ford Hospital, Detroit, MI (United States); Abbud, Alexander [Wayne State School of Medicine, Department of Pathology, Henry Ford Hospital, Detroit, MI (United States)

    2010-01-15

    Amyloidosis related to dialysis is a well-known complication affecting many organ systems, in particular the musculoskeletal system. In 1985 Shirahama et al. (Biochem Biophys Res Commun 53:705-709, 1985) identified beta-2 microglobulin (MG) as the offending constituent by using protein purification techniques. Amyloidosis has been increasing in prevalence because of longer life spans and increased chronic medical conditions such as end-stage renal disease. When dialysis-related amyloidosis involves the musculoskeletal system, it affects the shoulder girdle, the so called shoulder pad sign, the wrist, hip, knee, and spine (Resnick, Diagnosis of bone and joint disorders, 4th edn., pp. 2054-2058 and 2176-2183, 2002). Other osteoarticular manifestations of amyloidosis include osteoporosis, lytic lesions, and pathologic fractures. It has been well documented that the prevalence of amyloid is dependent on duration of dialysis - over 90% in patients on dialysis for over 7 years (Jadoul, Nephrol Dial Transplant 13:61-64, 1998). However, a recent changeover to high-flux membranes used in hemofiltration has been reported to delay its onset (Campistol et al., Contrib Nephrol 125:76-85, 1999). We report on the radiographic, nuclear medicine, and computed tomography (CT) findings of osteoarticular amyloidosis involving the hip, and sequence its atypical rapid onset. The imaging, histopathological findings, and differential diagnosis are discussed. (orig.)

  20. Phosphodiesterase 5 inhibition at disease onset prevents experimental autoimmune encephalomyelitis progression through immunoregulatory and neuroprotective actions.

    Science.gov (United States)

    Pifarré, Paula; Gutierrez-Mecinas, María; Prado, Judith; Usero, Lorena; Roura-Mir, Carme; Giralt, Mercedes; Hidalgo, Juan; García, Agustina

    2014-01-01

    In addition to detrimental inflammation, widespread axon degeneration is an important feature of multiple sclerosis (MS) pathology and a major correlate for permanent clinical deficits. Thus, treatments that combine immunomodulatory and neuroprotective effects are beneficial for MS. Using myelin oligodendrocyte glycoprotein peptide 35-55 (MOG)-induced experimental autoimmune encephalomyelitis (EAE) as a model of MS, we recently showed that daily treatment with the phosphodiesterase 5 (PDE5) inhibitor sildenafil at peak disease rapidly ameliorates clinical symptoms and neuropathology (Pifarre et al., 2011). We have now investigated the immunomodulatory and neuroprotective actions of sildenafil treatment from the onset of EAE when the immune response prevails and show that early administration of the drug prevents disease progression. Ultrastructural analysis of spinal cord evidenced that sildenafil treatment preserves axons and myelin and increases the number of remyelinating axons. Immunostaining of oligodendrocytes at different stages of differentiation showed that sildenafil protects immature and mature myelinating oligodendrocytes. Brain-derived neurotrophic factor (BDNF), a recognized neuroprotectant in EAE, was up-regulated by sildenafil in immune and neural cells suggesting its implication in the beneficial effects of the drug. RNA microarray analysis of spinal cord revealed that sildenafil up-regulates YM-1, a marker of the alternative macrophage/microglial M2 phenotype that has neuroprotective and regenerative properties. Immunostaining confirmed up-regulation of YM-1 while the classical macrophage/microglial activation marker Iba-1 was down-regulated. Microarray analysis also showed a notable up-regulation of several members of the granzyme B cluster (GrBs). Immunostaining revealed expression of GrBs in Foxp3+-T regulatory cells (Tregs) suggesting a role for these proteases in sildenafil-induced suppression of T effector cells (Teffs). In vitro analysis of

  1. PNA FISH: an intelligent stain for rapid diagnosis of infectious diseases.

    Science.gov (United States)

    Stender, Henrik

    2003-09-01

    Fluorescence in situ hybridization using peptide nucleic acid probes (PNA FISH) is a novel diagnostic technique combining the simplicity of traditional staining procedures with the unique performance of PNA probes to provide rapid and accurate diagnosis of infectious diseases; a feature that makes PNA FISH well suited for routine application and enables clinical microbiology laboratories to report important information for patient therapy within a time frame not possible using classic biochemical methods. Having transitioned from an academic curiosity into an advanced diagnostic tool, PNA probes are now debuting on the infectious disease stage, representing the new generation of therapy-directing diagnostics.

  2. Rapid infusion with rituximab: short term safety in systemic autoimmune diseases

    DEFF Research Database (Denmark)

    Larsen, Janni Lisander; Jacobsen, Soren

    2013-01-01

    To describe the incidence, types and severity of adverse events, related to an accelerated regime of rituximab infusion in patients with various autoimmune diseases. Fifty-four patients with systemic autoimmune disease, to be treated with 1,000 mg of rituximab twice 2 weeks apart, participated. Pre...... (1.8%) had grade 2 events on both infusions and two patients (3.6%) had a grade 3 event on both infusions. RA patients more often had an infusion-related reaction (IRR) (9.2%) than the rest. The types of IRR were mostly of allergic or angio-oedematic nature. In practise, the rapid infusion...

  3. Rapid eye movement sleep behavioral events: a new marker for neurodegeneration in early Parkinson disease?

    Science.gov (United States)

    Sixel-Döring, Friederike; Trautmann, Ellen; Mollenhauer, Brit; Trenkwalder, Claudia

    2014-03-01

    To analyze potential markers in sleep for early recognition of neurodegenerative disease in newly diagnosed, unmedicated patients with Parkinson disease (PD) compared to controls. Videopolysomnography (vPSG) was available in 158 newly diagnosed, unmedicated patients with PD and 110 age-, sex-, and education-matched healthy controls (HC). Rapid eye movement (REM) sleep was analyzed for REM without atonia (RWA) and studied by review of time-synchronized video. Motor behaviors and/or vocalizations in REM sleep with a purposeful component other than comfort moves were identified as REM sleep behavioral events (RBE). Two or more events had to be present to be classified as "RBE positive." RBE subjects included rapid eye movement sleep behavior disorder (RBD) and non-RBD subjects based on the presence or absence of RWA > 18.2%. RBE were detected in 81 of 158 patients with de novo PD (51%) and 17 of 110 HC (15%) (P sleep (P = 0.002) and a higher periodic leg movements in sleep index (P = 0.022) compared to subjects without RBE. This first description of REM sleep behavioral events (RBE) shows it occurs more frequently in patients with de novo Parkinson disease (PD) than in healthy controls and may be an early sign of neurodegeneration and precede rapid eye movement sleep behavior disorder (RBD). There is no specific phenotype of PD associated with newly defined RBE or RBD at this early stage.

  4. Association of serum carotenoid, retinol, and tocopherol concentrations with the progression of Parkinson's Disease.

    Science.gov (United States)

    Kim, Ji Hyun; Hwang, Jinah; Shim, Eugene; Chung, Eun-Jung; Jang, Sung Hee; Koh, Seong-Beom

    2017-04-01

    A pivotal role of oxidative stress has been emphasized in the pathogenesis as well as in the disease progression of Parkinson's disease (PD). We aimed at investigating serum levels of antioxidant vitamins and elucidating whether they could be associated with the pathogenesis and progression of PD. Serum levels of retinol, α- and γ-tocopherols, α- and β-carotenes, lutein, lycopene, zeaxanthin and β-cryptoxanthin were measured and compared between 104 patients with idiopathic PD and 52 healthy controls matched for age and gender. In order to examine the relationship between antioxidant vitamins and the disease progression, multiple group comparisons were performed among the early PD (Hoehn and Yahr stage I and II, N = 47), advanced PD (stage III and IV, N = 57) and control groups. Separate correlation analyses were performed between the measured antioxidant vitamins and clinical variables, such as Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Compared to controls, PD patients had lower levels of α- and β-carotenes and lycopene. α-carotene, β-carotene and lycopene levels were significantly reduced in advanced PD patients relative to early PD patients and were negatively correlated with Hoehn and Yahr stage and UPDRS motor score in PD patients. No significant differences were found in serum levels of retinol, α- and γ-tocopherols, and other carotenoids between PD patients and controls. No significant correlations were found between these vitamin levels and clinical variables in PD patients. We found that serum levels of some carotenoids, α-carotene, β-carotene and lycopene, were lower in PD patients, and that these carotenoids inversely correlated with clinical variables representing disease progression. Our findings suggest that decreases in serum α-carotene, β-carotene and lycopene may be associated with the pathogenesis as well as progression of PD.

  5. Hyperuricemia is associated with progression of chronic kidney disease in patients with reduced functioning kidney mass.

    Science.gov (United States)

    Galán, Isabel; Goicoechea, Marian; Quiroga, Borja; Macías, Nicolás; Santos, Alba; García de Vinuesa, Maria Soledad; Verdalles, Úrsula; Cedeño, Santiago; Verde, Eduardo; Pérez de José, Ana; García, Ana; Luño, José

    2017-08-30

    Hyperuricemia plays a major role in the development and progression of chronic kidney disease (CKD). Many large observational studies have indicated that increased serum uric acid level predicts the development and progression of CKD in some population, however this hypothesis has not been yet studied in patients with reduced renal mass. Retrospective study with a cohort of 324 patients with reduced renal mass from an outpatient basis, followed during 60 (36-98) months. Demographics variables, cardiovascular factors, concomitant medications, albuminuria and uric acid levels were recorded yearly. The primary endpoint was the annual fall of estimated glomerular filtration rate (eGFR) by MDRD-4. The sample was divided into three successive groups (A1: patients with fall of eGFR lower than median, A2: greater than median, B: without fall of eGFR). Factors associated and predictors of kidney function decline were analyzed. One hundred and seventy out of 324 patients suffered a fall of eGFR (group A), (median of fall -1.6ml/min/1.73m2/year (-3.0, -0.7)). Male gender, albuminuria>100mg/day and higher pulse pressure were associated to progression in our cohort (group A). Hyperuricemia was more frequent among patients with higher kidney disease progression (group A2) (33% vs 49%, p=0.04) when comparing to lower progression (group A1). Adjusted Cox regression models showed that hyperuricemia, pulse pressure and albuminuria were independent predictors of kidney disease progression (HR 1.67 (1.06-2.63), p=0.023; 1.02 (1.01-1.03), p=0.001 and HR: 2.14 (1.26-3.64), p=0.005, respectively). Kidney disease progression was higher in patients with unilateral renal atrophy or agenesis than nephrectomy (log rank: 7.433, p=0.006). Hyperuricemia is independently associated with kidney disease progression in patients with reduce functioning renal mass. Copyright © 2017. Published by Elsevier España, S.L.U.

  6. Rapid tests for the diagnosis of visceral leishmaniasis in patients with suspected disease

    Science.gov (United States)

    Boelaert, Marleen; Verdonck, Kristien; Menten, Joris; Sunyoto, Temmy; van Griensven, Johan; Chappuis, Francois; Rijal, Suman

    2014-01-01

    Background The diagnosis of visceral leishmaniasis (VL) in patients with fever and a large spleen relies on showing Leishmania parasites in tissue samples and on serological tests. Parasitological techniques are invasive, require sophisticated laboratories, consume time, or lack accuracy. Recently, rapid diagnostic tests that are easy to perform have become available. Objectives To determine the diagnostic accuracy of rapid tests for diagnosing VL in patients with suspected disease presenting at health services in endemic areas. Search methods We searched MEDLINE, EMBASE, LILACS, CIDG SR, CENTRAL, SCI-expanded, Medion, Arif, CCT, and the WHO trials register on 3 December 2013, without applying language or date limits. Selection criteria This review includes original, phase III, diagnostic accuracy studies of rapid tests in patients clinically suspected to have VL. As reference standards, we accepted: (1) direct smear or culture of spleen aspirate; (2) composite reference standard based on one or more of the following: parasitology, serology, or response to treatment; and (3) latent class analysis. Data collection and analysis Two review authors independently extracted data and assessed quality of included studies using the QUADAS-2 tool. Discrepancies were resolved by a third author. We carried out a meta-analysis to estimate sensitivity and specificity of rapid tests, using a bivariate normal model with a complementary log-log link function. We analysed each index test separately. As possible sources of heterogeneity, we explored: geographical area, commercial brand of index test, type of reference standard, disease prevalence, study size, and risk of bias (QUADAS-2). We also undertook a sensitivity analysis to assess the influence of imperfect reference standards. Main results Twenty-four studies containing information about five index tests (rK39 immunochromatographic test (ICT), KAtex latex agglutination test in urine, FAST agglutination test, rK26 ICT, and r

  7. Utility of quantitative ultrasound for tracking the progression of polycystic kidney disease

    Science.gov (United States)

    Hall, Timothy J.; Khant, Htet A.; Insana, Michael F.; Wood, John G.; Zhu, Yanning; Preston, David; Cowley, Benjamin D.

    2000-04-01

    We are combining techniques of quantitative ultrasonic imaging to study polycystic kidney disease (PKD) as the disease progresses to renal failure. Our goal is to use ultrasound noninvasively to detect morphological changes early in the disease process when interventions are most likely to be successful and prior to a significant loss in renal function. We are examining the kidneys of normal rats and those with PKD at various ages with several techniques to obtain comprehensive knowledge of the disease progression. The Han:SPRD rat inherits PKD as an autosomal dominant trait (ADPKD) that closely mimics ADPKD in humans. Changes in renal function are assessed using tracer kinetics (DTPA) and IOH clearance). Ultrasonic techniques, based on measurements of acoustic backscatter coefficients and parameters derived from these measurements, are sensitive to microscopic changes in the tissue morphology. Elasticity imaging is used to study the changes in the tissue macrostructure. All acoustic measurements are made using a state-of-the-art clinical imaging system (Siemens Elegra). Our results show that ultrasonic techniques are very sensitive to early changes in renal microstructure and macrostructure. Ultrasound can be used to detect changes in the renal cortex long before there is a measurable loss of renal function. These techniques are also useful for monitoring the progression of the disease. Most importantly, these techniques are noninvasive and directly applicable to humans.

  8. The importance of total kidney volume in evaluating progression of polycystic kidney disease

    Science.gov (United States)

    Grantham, Jared J.; Torres, Vicente E.

    2017-01-01

    The rate at which autosomal dominant polycystic kidney disease (ADPKD) progresses to end-stage renal disease varies widely and is determined by genetic and non-genetic factors. The ability to determine the prognosis of children and young adults with ADPKD is important for the effective life-long management of the disease and to enable the efficacy of emerging therapies to be determined. Total kidney volume (TKV) reflects the sum volume of hundreds of individual cysts with potentially devastating effects on renal function. The sequential measurement of TKV has been advanced as a dynamic biomarker of disease progression, yet doubt remains among nephrologists and regulatory agencies as to its usefulness. Here, we review the mechanisms that lead to an increase in TKV in ADPKD, and examine the evidence supporting the conclusion that TKV provides a metric of disease progression that can be used to assess the efficacy of potential therapeutic regimens in children and adults with ADPKD. Moreover, we propose that TKV can be used to monitor treatment efficacy in patients with normal levels of renal function, before the pathologic processes of ADPKD cause extensive fibrosis and irreversible loss of functioning renal tissue. PMID:27694979

  9. Modifying progression of aging and reducing the risk of neurodegenerative diseases by probiotics and synbiotics.

    Science.gov (United States)

    Lye, Huey Shi; Lee, Yee Teng; Ooi, Shao Yin; Teh, Lai Kuan; Lim, Lay Ngor; Wei, Loo Keat

    2018-03-01

    Aging, which affects most of the multi-cellular organisms, is due to a potentially complex set of mechanisms that collectively cause a time-dependent decline of physiological functions. Aging restrains longevity and leads to neurodegenerative diseases including dementia, Alzheimer's disease and lacunar stroke. Human microbiota is now considered to have a strong impact on the progression of aging. The impact of aging and the risk of neurodegenerative diseases can be reduced by using probiotics, or preferably by combining probiotics and prebiotics, also known as synbiotics, that can drastically modify the composition of gut microbiome.

  10. Current Understanding of the Pathogenesis of Progressive Chronic Kidney Disease in Cats.

    Science.gov (United States)

    Jepson, Rosanne E

    2016-11-01

    In cats with chronic kidney disease (CKD), the most common histopathologic finding is tubulointerstitial inflammation and fibrosis. However, these changes reflect a nonspecific response of the kidney to any inciting injury. The risk of developing CKD is likely to reflect the composite effects of genetic predisposition, aging, and environmental and individual factors that affect renal function over the course of a cat's life. However, there is still little information available to determine exactly which individual risk factors predispose a cat to develop CKD. Although many cats diagnosed with CKD have stable disease for years, some cats show overtly progressive disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Genetic Deficiency of Complement Component 3 Does Not Alter Disease Progression in a Mouse Model of Huntington's Disease

    Science.gov (United States)

    Larkin, Paul B.; Muchowski, Paul J.

    2012-01-01

    Several genes and proteins of the complement cascade are present at elevated levels in brains of patients with Huntington's disease (HD). The complement cascade is well characterized as an effector arm of the immune system, and in the brain it is important for developmental synapse elimination. We hypothesized that increased levels of complement in HD brains contributes to disease progression, perhaps by contributing to synapse elimination or inflammatory signaling. We tested this hypothesis in the R6/2 mouse model of HD by crossing mice deficient in complement component 3 (C3), a crucial complement protein found at increased levels in HD brains, to R6/2 mice and monitoring behavioral and neuropathological disease progression. We found no alterations in multiple behavioral assays, weight or survival in R6/2 mice lacking C3. We also quantified the expression of several complement cascade genes in R6/2 brains and found that the large scale upregulation of complement genes observed in HD brains is not mirrored in R6/2 brains. These data show that C3 deficiency does not alter disease progression in the R6/2 mouse model of HD. PMID:23097680

  12. An alpha-synuclein MRM assay with diagnostic potential for Parkinson's disease and monitoring disease progression

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    Yang, Li [Department of Pathology, University of Washington, Seattle WA USA; Stewart, Tessandra [Department of Pathology, University of Washington, Seattle WA USA; Shi, Min [Department of Pathology, University of Washington, Seattle WA USA; Pottiez, Gwenael [Department of Pathology, University of Washington, Seattle WA USA; Dator, Romel [Department of Pathology, University of Washington, Seattle WA USA; Wu, Rui [Department of Pathology, University of Washington, Seattle WA USA; Department of Pathology, No. 3 Hospital of Beijing University, Beijing China; Aro, Patrick [Department of Pathology, University of Washington, Seattle WA USA; Schuster, Robert J. [Department of Pathology, University of Washington, Seattle WA USA; Ginghina, Carmen [Department of Pathology, University of Washington, Seattle WA USA; Pan, Catherine [Department of Pathology, University of Washington, Seattle WA USA; Gao, Yuqian [Pacific Northwest National Laboratory, Richland WA USA; Qian, Weijun [Pacific Northwest National Laboratory, Richland WA USA; Zabetian, Cyrus P. [Parkinson' s Disease Research and Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle WA USA; Department of Neurology, University of Washington School of Medicine, Seattle WA USA; Hu, Shu-Ching [Department of Neurology, University of Washington School of Medicine, Seattle WA USA; Quinn, Joseph F. [Department of Neurology, Oregon Health and Science University, Portland OR USA; Zhang, Jing [Department of Pathology, University of Washington, Seattle WA USA; Department of Pathology, Peking University Health Science Centre and Third Hospital, Beijing 100083 China

    2017-04-19

    Aim: The alpha-synuclein (α-syn) level in human cerebrospinal fluid (CSF), as measured by immunoassays, is promising as a Parkinson’s disease (PD) biomarker. However, the levels of total α-syn are inconsistent among studies with large cohorts and different measurement platforms. Total α-syn level also does not correlate with disease severity or progression. Here, we developed a highly sensitive Multiple Reaction Monitoring (MRM) method to measure absolute CSF α-syn peptide concentrations without prior enrichment or fractionation, aiming to discover new candidate biomarkers. Results: Six peptides covering 73% of protein sequence were reliably identified, and two were consistently quantified in cross-sectional and longitudinal cohorts. Absolute concentration of α-syn in human CSF was determined to be 2.1ng/mL. A unique α-syn peptide, TVEGAGSIAAATGFVK (81-96), displayed excellent correlation with previous immunoassay results in two independent PD cohorts (p < 0.001), correlated with disease severity, and its changes significantly tracked the disease progression longitudinally. Conclusions: An MRM assay to quantify human CSF α-syn was developed and optimized. Sixty clinical samples from cross-sectional and longitudinal PD cohorts were analyzed with this approach. Although further larger-scale validation is needed, the results suggest that α-syn peptide could serve as a promising biomarker in PD diagnosis and progression.

  13. IL-33-ST2 Axis in Liver Disease: Progression and Challenge

    Directory of Open Access Journals (Sweden)

    Zijian Sun

    2017-01-01

    Full Text Available The new member of the IL-1 family, interleukin-33 (IL-33, participates in the progression of a variety of diseases through binding with its receptor ST2. Recently, much clinical evidence and experimental data have indicated that IL-33 is associated with various liver diseases. This review primarily addresses the relationship between IL-33 and several hepatic diseases. IL-33 can alleviate high-fat diet- (HFD- induced hepatic steatosis and insulin resistance, and IL-33 acts as an alarmin, which quickly triggers the immune system to respond to virus invasion and toxic damage to the liver. However, when liver injury is chronic, IL-33 promotes Th2 reactions and hepatic stellate cell (HSC activity, facilitating progression to liver fibrosis. The complicated functions of IL-33 should be considered before its clinical application.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Genome-wide association studies (GWAS) have identified over 40 type 1 diabetes risk loci. The clinical impact of these loci on β-cell function during disease progression is unknown. We aimed at testing whether a genetic risk score could predict glycemic control and residual β-cell function in type...... 1 diabetes (T1D). As gene expression may represent an intermediate phenotype between genetic variation and disease, we hypothesized that genes within T1D loci which are expressed in islets and transcriptionally regulated by proinflammatory cytokines would be the best predictors of disease...... progression. Two-thirds of 46 GWAS candidate genes examined were expressed in human islets, and 11 of these significantly changed expression levels following exposure to proinflammatory cytokines (IL-1β + IFNγ + TNFα) for 48 h. Using the GWAS single nucleotide polymorphisms (SNPs) from each locus, we...

  15. The rate of progression of renal disease may not be slower in women compared with men

    DEFF Research Database (Denmark)

    Jafar, Tazeen H; Schmid, Christopher H; Stark, Paul C

    2003-01-01

    BACKGROUND: Some studies suggest that progression of renal disease is slower in women than in men. However, other factors that are also associated with progression of renal disease have not always been taken into account. Therefore, we undertook this analysis to explore the independent association...... was the combined outcome of doubling of baseline serum creatinine or onset of end-stage renal disease (ESRD). The secondary end point was the onset of ESRD alone. We performed multivariable Cox proportional hazards analysis to study the independent effect of gender on these end points after adjusting for baseline...... baseline serum creatinine (2.2 mg/dl) and mean age (52 years) were similar for both genders. Mean baseline SBP was greater in women than in men: 151 vs 147 mmHg (P women compared with men: 1.3 vs 2.1 g/day (P

  16. Risk factors of accelerated progression of peripheral artery disease in hemodialysis

    Directory of Open Access Journals (Sweden)

    Shang-Reu Hsu

    2013-02-01

    Full Text Available Ankle-brachial index (ABI and brachial-ankle pulse wave velocity (baPWV are markers for peripheral artery occlusive disease (PAOD and arterial stiffness, respectively. The aims of this study were to assess whether PAOD and arterial stiffness progressed and to determine the risk factors for ABI and baPWV progression in patients on hemodialysis. This study enrolled 173 routine patients on hemodialysis. Both ABI and baPWV were measured by an ABI-form device at baseline and at 1 year of follow-up. Progression in ABI was defined as reduction in ABI exceeding 0.3, while baPWV measured at 1 year of follow-up exceeding that at baseline indicated baPWV progression. Comparison with baseline data showed increase in both prevalence of ABI < 0.9 (p = 0.045 and baPWV (p = 0.028 at 1 year of follow-up. Multiple linear regression analyses identified high fasting glucose and old age as independent factors of annual change in ABI and baPWV, respectively. Good control of blood sugar may contribute to delay the progression of peripheral artery disease in patients on hemodialysis.

  17. Retrospective Analysis of Structural Disease Progression in Retinitis Pigmentosa Utilizing Multimodal Imaging.

    Science.gov (United States)

    Cabral, Thiago; Sengillo, Jesse D; Duong, Jimmy K; Justus, Sally; Boudreault, Katherine; Schuerch, Kaspar; Belfort, Rubens; Mahajan, Vinit B; Sparrow, Janet R; Tsang, Stephen H

    2017-09-04

    In this report, we assess the natural progression rate of retinitis pigmentosa (RP) over an average of three years using spectral-domain optical coherence tomography (SD-OCT) and short wavelength fundus autofluorescence (SW-AF). Measurement of the ellipsoid zone (EZ) line width and hyperautofluorescent ring diameters was performed in 81 patients with RP in a retrospective, longitudinal fashion. Rate of structural disease progression, symmetry between eyes, and test-retest variability were quantified. We observed on average, EZ-line widths decreased by 140 µm (5.2%, p < 0.001) per year, and average horizontal and vertical hyperautofluorescent ring diameters decreased by 149 µm (3.6%, p < 0.001) and 120 µm (3.9%, p < 0.001) per year, respectively. The 95th percentile of this cohort had differences in progression slopes between eyes that were less than 154 µm, 118 µm, and 132 µm for EZ-line width and horizontal and vertical ring diameters, respectively. For all measures except horizontal ring diameter, progression rates were significantly slower at end-stage disease. From our data, we observed a statistically significant progression rate in EZ line width and SW-AF ring diameters over time, verifying the utility of these measurements for disease monitoring purposes. Additionally, calculated differences in progression slopes between eyes may prove useful for investigators evaluating the efficacy of unilateral treatments for RP in clinical trials.

  18. An Unrecognized Rash Progressing to Lyme Carditis: Important Features and Recommendations Regarding Lyme Disease.

    Science.gov (United States)

    Lee, Shawn; Singla, Montish

    2016-01-01

    We present a case report of 46-year-old man with no medical history, who complained of extreme fatigue, near-syncope, and palpitations. He initially presented in complete heart block. A transvenous pacemaker was placed in the emergency department, and he was started empirically on Ceftriaxone for Lyme disease. He was admitted and over the course of the next few days, his rhythm regressed to Mobitz type I first-degree atrioventricular block and then to normal sinus rhythm. This case report highlights some important features regarding Lyme carditis, a rare presentation of early disseminated Lyme disease (seen in a few weeks to months after the initial tick bite). In 25%-30% of patients, the characteristic targetoid rash may not be seen, a likely culprit of the disease not being detected early and progressing to disseminated disease. The most common cardiac complaint of Lyme disease is palpitations, occurring in 6.6% of patients, which may not accurately reflect progression into disseminated Lyme disease because it is a nonspecific finding. Conduction abnormality, occurring in 1.8% of patients, is a more specific finding of Borrelia invading cardiac tissue. Finally, this case report highlights a recommendation that patients with confirmed Lyme disease or those presenting with cardiac abnormalities or symptoms who have an atypical profile for a cardiac event should be screened with a 12-lead electrocardiogram, Lyme serology, and be considered for antibiotic therapy with the possibility of temporary pacing.

  19. Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood.

    Science.gov (United States)

    Mastrokolias, Anastasios; Ariyurek, Yavuz; Goeman, Jelle J; van Duijn, Erik; Roos, Raymund A C; van der Mast, Roos C; van Ommen, GertJan B; den Dunnen, Johan T; 't Hoen, Peter A C; van Roon-Mom, Willeke M C

    2015-10-01

    With several therapeutic approaches in development for Huntington's disease, there is a need for easily accessible biomarkers to monitor disease progression and therapy response. We performed next-generation sequencing-based transcriptome analysis of total RNA from peripheral blood of 91 mutation carriers (27 presymptomatic and, 64 symptomatic) and 33 controls. Transcriptome analysis by DeepSAGE identified 167 genes significantly associated with clinical total motor score in Huntington's disease patients. Relative to previous studies, this yielded novel genes and confirmed previously identified genes, such as H2AFY, an overlap in results that has proven difficult in the past. Pathway analysis showed enrichment of genes of the immune system and target genes of miRNAs, which are downregulated in Huntington's disease models. Using a highly parallelized microfluidics array chip (Fluidigm), we validated 12 of the top 20 significant genes in our discovery cohort and 7 in a second independent cohort. The five genes (PROK2, ZNF238, AQP9, CYSTM1 and ANXA3) that were validated independently in both cohorts present a candidate biomarker panel for stage determination and therapeutic readout in Huntington's disease. Finally we suggest a first empiric formula predicting total motor score from the expression levels of our biomarker panel. Our data support the view that peripheral blood is a useful source to identify biomarkers for Huntington's disease and monitor disease progression in future clinical trials.

  20. Risk factors for the progression of chronic kidney disease after acute kidney injury

    Directory of Open Access Journals (Sweden)

    Benedito Jorge Pereira

    2017-08-01

    Full Text Available Abstract Introduction: The incidence of chronic kidney disease (CKD is increasing with the increasing age of the population and the increasing number of elderly survivors of acute kidney injury (AKI. The risk factors for the progression of CKD after AKI are unclear. Objective: To investigate the association between AKI and its progression to CKD and the risk factors involved. Methods: An observational, retrospective study of AKI patients followed from 2009 to 2012 was carried out. We evaluated the etiology of AKI, the use of vasoactive drugs and mechanical ventilation, the need for dialysis, the presence of comorbidities, the glomerular filtration rate (GFR, the length of stay and the progression of CKD. Statistical analyses, including the Chi-square test and Pearson's correlation, were performed using SPSS. Results: The 207 patients analyzed had a mean age of 70.1 ± 13.1, and 84.6% of the male patients exhibited decreased renal function and CKD (vs. 60.4% of the female patients. The progression of AKI to CKD was more frequent in patients admitted to wards (63.8%, cancer patients (74.19%, patients with sepsis (67.18% and patients with obstruction (91.66%. Dialyses were performed in 16.4% of the patients, but this was not correlated with the progression of CKD. Conclusions: Being an elderly male patient with AKI due to sepsis and obstruction was correlated with progression to CKD following discharge.

  1. Retarding progression of chronic kidney disease: use of modalities that counter acid retention.

    Science.gov (United States)

    Kraut, Jeffrey A; Madias, Nicolaos E

    2018-03-01

    Acid retention because of chronic kidney disease (CKD) increases tissue acidity and accelerates progression of CKD, whereas reduction in acid retention slows progression of CKD. Herein, we describe the mechanisms through which increased tissue acidity worsens CKD, modalities for countering acid retention and their impact on progression of CKD, and current recommendations for therapy. Studies in animals and humans show that increased tissue acidity raises the renal levels of endothelin, angiotensin II, aldosterone, and ammoniagenesis, thereby worsening renal fibrosis and causing progression of CKD. Measures that counter acid retention, such as providing alkali or modifying the quantity or type of dietary protein, reduce the levels of endothelin, angiotensin II, aldosterone, and ammoniagenesis, slowing progression of CKD. Alkali can be provided as NaHCO3, sodium citrate, or base in fruits and vegetables. A serum [HCO3] of 24-26 mEq/l is targeted, because higher values can be associated with adverse consequences. Insights into the mechanisms through which increased tissue acidity mediates progression of CKD and the beneficial impact of ameliorating positive acid balance underlie our recommendation for modalities that counter acid retention in CKD.

  2. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: cherrington@pharmacy.arizona.edu [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  3. FBN1 gene mutation characteristics and clinical features for the prediction of mitral valve disease progression.

    Science.gov (United States)

    Kühne, Kristin; Keyser, Britta; Groene, Eike F; Sheikhzadeh, Sara; Detter, Christian; Lorenzen, Viktoria; Hillebrand, Mathias; Bernhardt, Alexander M J; Hoffmann, Boris; Mir, Thomas S; Robinson, Peter N; Berger, Jürgen; Reichenspurner, Hermann; von Kodolitsch, Yskert; Rybczynski, Meike

    2013-09-30

    Until today, FBN1 gene mutation characteristics were not compared with clinical features for the prediction of mitral valve disease progression. Therefore, we conducted a study of 116 patients (53 men, 63 women aged 33 ± 15 years) with a causative FBN1 gene mutation and ≤ moderate mitral valve regurgitation at baseline. During 7.4 ± 6.8 years 30 patients developed progression of mitral valve regurgitation ≥ 1 grade (primary endpoint), and 26 patients required mitral valve surgery (secondary endpoint). Cox regression analysis identified an association of atrial fibrillation (hazard ratio (HR)=2.703; 95% confidence interval (CI) 1.013-7.211; P=.047), left ventricular ejection fraction (HR=.970; 95%CI .944-.997; P=.032), indexed end-diastolic left ventricular diameter (HR=15.165; 95%CI 4.498-51.128; Pvalve prolapse (HR=2.599; 95%CI 1.243-5.437; P=.011), posterior leaflet prolapse (HR=1.075; 95%CI 1.023-1.130; P=.009), and posterior leaflet thickening (HR=3.368; 95%CI 1.265-8.968; P=.015) with progression of mitral valve disease, whereas none of the FBN1 gene mutation characteristics were associated with progression of mitral valve disease. However, Cox regression analysis identified a marginal relationship of FBN1 gene mutations located both in a transforming-growth-factor beta-binding protein-like (TGFb-BP) domain (HR=3.453; 95%CI .982-12.143; P=.053), and in the calcium-binding epidermal growth factor-like (cbEGF) domain (HR=2.909; 95%CI .957-8.848; P=.060) with mitral valve surgery, a finding that was corroborated by Kaplan-Meier analysis (P=.014; and P=.041, respectively). Clinical features were better predictors of mitral valve disease progression than FBN1 gene mutation characteristics. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder.

    Science.gov (United States)

    Heintz-Buschart, Anna; Pandey, Urvashi; Wicke, Tamara; Sixel-Döring, Friederike; Janzen, Annette; Sittig-Wiegand, Elisabeth; Trenkwalder, Claudia; Oertel, Wolfgang H; Mollenhauer, Brit; Wilmes, Paul

    2017-08-26

    Increasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson's disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD patients. It is, however, unknown whether these differences can be observed in individuals at high risk, for example, with idiopathic rapid eye movement sleep behavior disorder, a prodromal condition of α-synuclein aggregation disorders including PD. To compare microbiota in carefully preserved nasal wash and stool samples of subjects with idiopathic rapid eye movement sleep behavior disorder, manifest PD, and healthy individuals. Microbiota of flash-frozen stool and nasal wash samples from 76 PD patients, 21 idiopathic rapid eye movement sleep behavior disorder patients, and 78 healthy controls were assessed by 16S and 18S ribosomal RNA amplicon sequencing. Seventy variables, related to demographics, clinical parameters including nonmotor symptoms, and sample processing, were analyzed in relation to microbiome variability and controlled differential analyses were performed. Differentially abundant gut microbes, such as Akkermansia, were observed in PD, but no strong differences in nasal microbiota. Eighty percent of the differential gut microbes in PD versus healthy controls showed similar trends in idiopathic rapid eye movement sleep behavior disorder, for example, Anaerotruncus and several Bacteroides spp., and correlated with nonmotor symptoms. Metagenomic sequencing of select samples enabled the reconstruction of genomes of so far uncharacterized differentially abundant organisms. Our study reveals differential abundances of gut microbial taxa in PD and its prodrome idiopathic rapid eye movement sleep behavior disorder in comparison to the healthy controls, and highlights the potential of metagenomics to identify and characterize microbial taxa, which are enriched or depleted in PD and/or idiopathic rapid eye movement sleep behavior disorder. © 2017 The Authors. Movement

  5. Impact of vascular diseases on the progression of mild cognitive impairment to Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Marta Nesteruk

    2015-04-01

    Full Text Available Introduction: Mild cognitive impairment does not meet the criteria for the diagnosis of dementia, but reaching this diagnosis raises concern about the future state of a patient due to the possibility of the conversion to Alzheimer’s disease. Although the aetiology of Alzheimer’s disease is neurodegenerative, the impact of vascular diseases is also taken into consideration. The aim of this study was to assess the impact of vascular diseases in patients diagnosed with mild cognitive impairment on the conversion to Alzheimer’s disease. Material and methods: In each of 101 patients with a diagnosis of mild cognitive impairment, a detailed medical history was taken, taking into account: hypertension, ischaemic heart disease, arrhythmias, myocardial infarction, stroke, diabetes as well as thyroid diseases, head injuries, alcohol abuse, smoking, exposure to toxic substances, surgery under general anaesthesia and the family character of dementia. Clinical follow-ups were scheduled after 6, 12 and 24 months. Results: Amongst 101 patients with mild cognitive impairment, 17 (16.8% converted to Alzheimer’s disease within two years of observation. The analysis of the distribution of independence tests showed that the conversion is significant for two variables: ischaemic heart disease and myocardial infarction.

  6. Quantitative Electroencephalographic Analysis Provides an Early-Stage Indicator of Disease Onset and Progression in the zQ175 Knock-In Mouse Model of Huntington's Disease

    Science.gov (United States)

    Fisher, Simon P.; Schwartz, Michael D.; Wurts-Black, Sarah; Thomas, Alexia M.; Chen, Tsui-Ming; Miller, Michael A.; Palmerston, Jeremiah B.; Kilduff, Thomas S.; Morairty, Stephen R.

    2016-01-01

    Study Objectives: Patients with Huntington's disease (HD) show a high prevalence of sleep disorders that typically occur prior to the onset of motoric symptoms and neurodegeneration. Our understanding of the pathophysiological alterations in premanifest HD is limited, hindering the ability to measure disease modification in response to treatment. We used a full-length knock-in HD model to determine early changes in the electroencephalogram (EEG) and sleep that may predict the onset and progression of the disease. Methods: A 10-month longitudinal study was designed to determine the effect of the HD mutation on the EEG and sleep/wake changes in heterozygous (HET) and homozygous (HOM) zQ175 mice and wild-type (WT) littermates from 8 to 48 w of age. Mice were instrumented with tethered headmounts to record EEG/electromyography signals. Telemeters were implanted to continuously measure locomotor activity (LMA) and body temperature (Tb). Sleep deprivation (SDep) was performed at 8, 12, 16, 24, 32, and 48 w of age. Results: The HD mutation disrupted the EEG field potential from 8–12 w in an age- and mutant huntington dose-dependent manner, prior to changes in sleep/wake states, LMA, and Tb. Prominent effects of the HD mutation on the EEG included a progressive reduction in low frequency power, a slowing of rapid eye movement peak theta frequency, and the emergence of state-dependent beta/gamma oscillations. There was no effect of genotype on the relative increase in nonrapid eye movement delta power or sleep time in response to SDep. Conclusions: The expression of the Huntington's disease (HD) mutation results in complex EEG alterations that occur prior to deficits in behavioral measures and are one of the earliest phenotypes uncovered in this mouse model. Despite these EEG changes, homeostatic responses to sleep loss were preserved in HET and HOM zQ175 mice. Greater insight into the localization and response of these EEG alterations to novel therapies may enable early

  7. Rapid diagnostic tests duo as alternative to conventional serological assays for conclusive Chagas disease diagnosis.

    Science.gov (United States)

    Egüez, Karina E; Alonso-Padilla, Julio; Terán, Carolina; Chipana, Zenobia; García, Wilson; Torrico, Faustino; Gascon, Joaquim; Lozano-Beltran, Daniel-Franz; Pinazo, María-Jesús

    2017-04-01

    Chagas disease is caused by the parasite Trypanosoma cruzi. It affects several million people, mainly in Latin America, and severe cardiac and/or digestive complications occur in ~30% of the chronically infected patients. Disease acute stage is mostly asymptomatic and infection goes undiagnosed. In the chronic phase direct parasite detection is hampered due to its concealed presence and diagnosis is achieved by serological methods, like ELISA or indirect hemagglutination assays. Agreement in at least two tests must be obtained due to parasite wide antigenic variability. These techniques require equipped labs and trained personnel and are not available in distant regions. As a result, many infected people often remain undiagnosed until it is too late, as the two available chemotherapies show diminished efficacy in the advanced chronic stage. Easy-to-use rapid diagnostic tests have been developed to be implemented in remote areas as an alternative to conventional tests. They do not need electricity, nor cold chain, they can return results within an hour and some even work with whole blood as sample, like Chagas Stat-Pak (ChemBio Inc.) and Chagas Detect Plus (InBIOS Inc.). Nonetheless, in order to qualify a rapidly diagnosed positive patient for treatment, conventional serological confirmation is obligatory, which might risk its start. In this study two rapid tests based on distinct antigen sets were used in parallel as a way to obtain a fast and conclusive Chagas disease diagnosis using whole blood samples. Chagas Stat-Pak and Chagas Detect Plus were validated by comparison with three conventional tests yielding 100% sensitivity and 99.3% specificity over 342 patients seeking Chagas disease diagnosis in a reference centre in Sucre (Bolivia). Combined used of RDTs in distant regions could substitute laborious conventional serology, allowing immediate treatment and favouring better adhesion to it.

  8. Tracking disease progression by searching paths in a temporal network of biological processes.

    Science.gov (United States)

    Anand, Rajat; Chatterjee, Samrat

    2017-01-01

    Metabolic disorders such as obesity and diabetes are diseases which develop gradually over time through the perturbations of biological processes. These perturbed biological processes usually work in an interdependent way. Systematic experiments tracking disease progression at gene level are usually conducted through a temporal microarray data. There is a need for developing methods to analyze such highly complex data to capture disease progression at the molecular level. In the present study, we have considered temporal microarray data from an experiment conducted to study development of obesity and diabetes in mice. We first constructed a network between biological processes through common genes. We analyzed the data to obtain perturbed biological processes at each time point. Finally, we used the biological process network to find links between these perturbed biological processes. This enabled us to identify paths linking initial perturbed processes with final perturbed processes which capture disease progression. Using different datasets and statistical tests, we established that these paths are highly precise to the dataset from which these are obtained. We also established that the connecting genes present in these paths might contain some biological information and thus can be used for further mechanistic studies. The methods developed in our study are also applicable to a broad array of temporal data.

  9. View of God as benevolent and forgiving or punishing and judgmental predicts HIV disease progression.

    Science.gov (United States)

    Ironson, Gail; Stuetzle, Rick; Ironson, Dale; Balbin, Elizabeth; Kremer, Heidemarie; George, Annie; Schneiderman, Neil; Fletcher, Mary Ann

    2011-12-01

    This study assessed the predictive relationship between View of God beliefs and change in CD4-cell and Viral Load (VL) in HIV positive people over an extended period. A diverse sample of HIVseropositive participants (N = 101) undergoing comprehensive psychological assessment and blood draws over the course of 4 years completed the View of God Inventory with subscales measuring Positive View (benevolent/forgiving) and Negative View of God (harsh/judgmental/punishing). Adjusting for initial disease status, age, gender, ethnicity, education, and antiretroviral medication (at every 6-month visit), a Positive View of God predicted significantly slower disease-progression (better preservation of CD4-cells, better control of VL), whereas a Negative View of God predicted faster disease-progression over 4 years. Effect sizes were greater than those previously demonstrated for psychosocial variables known to predict HIV-disease-progression, such as depression and coping. Results remained significant even after adjusting for church attendance and psychosocial variables (health behaviors, mood, and coping). These results provide good initial evidence that spiritual beliefs may predict health outcomes.

  10. Cerebrospinal fluid cortisol and clinical disease progression in MCI and dementia of Alzheimer's type.

    Science.gov (United States)

    Popp, Julius; Wolfsgruber, Steffen; Heuser, Isabella; Peters, Oliver; Hüll, Michael; Schröder, Johannes; Möller, Hans-Jürgen; Lewczuk, Piotr; Schneider, Anja; Jahn, Holger; Luckhaus, Christian; Perneczky, Robert; Frölich, Lutz; Wagner, Michael; Maier, Wolfgang; Wiltfang, Jens; Kornhuber, Johannes; Jessen, Frank

    2015-02-01

    Increased peripheral and central nervous system cortisol levels have been reported in Alzheimer's disease (AD) and may reflect dysfunction of cerebral components of the hypothalamic-pituitary-adrenal (HPA) axis. However, brain exposure to high cortisol concentrations may also accelerate disease progression and cognitive decline. The objectives of this study were to investigate whether HPA-axis dysregulation occurs at early clinical stages of AD and whether plasma and CSF cortisol levels are associated with clinical disease progression. Morning plasma and CSF cortisol concentrations were obtained from the subjects with AD dementia, mild cognitive impairment of AD type (MCI-AD), MCI of other type (MCI-O), and controls with normal cognition included in a multicenter study from the German Dementia Competence Network. A clinical and neuropsychological follow-up was performed in a subgroup of participants with MCI-AD, MCI-O, and AD dementia. CSF cortisol concentrations were increased in the subjects with AD dementia or MCI-AD compared with subjects with MCI-O or normal cognition. After controlling for possible confounders including CSF measures of amyloid beta1-42 and total tau, higher baseline CSF cortisol levels were associated with faster clinical worsening and cognitive decline in MCI-AD. The findings suggest that HPA-axis dysregulation occurs at the MCI stage of AD and may accelerate disease progression and cognitive decline. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Chronic Progressive Neurodegeneration in a transgenic mouse model of Prion disease

    Directory of Open Access Journals (Sweden)

    Nina Fainstein

    2016-11-01

    Full Text Available Neurodegenerative diseases present pathologically with progressive structural destruction of neurons and accumulation of mis-folded proteins specific for each condition leading to brain atrophy and functional disability. Many animal models exert deposition of pathogenic protein without accompanying neurodegeneration pattern. The lack of a comprehensive model hinders the efforts to develop treatment. We performed longitudinal quantification of cellular, neuronal and synaptic density, as well as of neurogenesis in brains of mice, mimicking for genetic Creutzfeldt-Jacob disease as compared to age matched wild type mice. Mice exhibited a neurodegenerative process indicated by progressive reduction in cortical neurons and synapses, starting at age of 4-6 months, in accordance with neurologic disability. This was accompanied by significant decrease in subventricular/subependymal zone neurogenesis. Although increased hippocampal neurogenesis was detected in mice, a neurodegenerative process of CA1 and CA3 regions associated with impaired hippocampal-dependent memory function was observed. In conclusion, mice exhibit pathological neurodegeneration concomitant with progressive neurological disease, indicating these mice can serve as a model for neurodegenerative diseases.

  12. Effect of fluoxetine on disease progression in a mouse model of ALS

    Science.gov (United States)

    Koschnitzky, J. E.; Quinlan, K. A.; Lukas, T. J.; Kajtaz, E.; Kocevar, E. J.; Mayers, W. F.; Siddique, T.

    2014-01-01

    Selective serotonin reuptake inhibitors (SSRIs) and other antidepressants are often prescribed to amyotrophic lateral sclerosis (ALS) patients; however, the impact of these prescriptions on ALS disease progression has not been systematically tested. To determine whether SSRIs impact disease progression, fluoxetine (Prozac, 5 or 10 mg/kg) was administered to mutant superoxide dismutase 1 (SOD1) mice during one of three age ranges: neonatal [postnatal day (P)5–11], adult presymptomatic (P30 to end stage), and adult symptomatic (P70 to end stage). Long-term adult fluoxetine treatment (started at either P30 or P70 and continuing until end stage) had no significant effect on disease progression. In contrast, neonatal fluoxetine treatment (P5-11) had two effects. First, all animals (mutant SOD1G93A and control: nontransgenic and SOD1WT) receiving the highest dose (10 mg/kg) had a sustained decrease in weight from P30 onward. Second, the high-dose SOD1G93A mice reached end stage ∼8 days (∼6% decrease in life span) sooner than vehicle and low-dose animals because of an increased rate of motor impairment. Fluoxetine increases synaptic serotonin (5-HT) levels, which is known to increase spinal motoneuron excitability. We confirmed that 5-HT increases spinal motoneuron excitability during this neonatal time period and therefore hypothesized that antagonizing 5-HT receptors during the same time period would improve disease outcome. However, cyproheptadine (1 or 5 mg/kg), a 5-HT receptor antagonist, had no effect on disease progression. These results show that a brief period of antidepressant treatment during a critical time window (the transition from neonatal to juvenile states) can be detrimental in ALS mouse models. PMID:24598527

  13. The Enhanced liver fibrosis score is associated with clinical outcomes and disease progression in patients with chronic liver disease.

    Science.gov (United States)

    Irvine, Katharine M; Wockner, Leesa F; Shanker, Mihir; Fagan, Kevin J; Horsfall, Leigh U; Fletcher, Linda M; Ungerer, Jacobus P J; Pretorius, Carel J; Miller, Gregory C; Clouston, Andrew D; Lampe, Guy; Powell, Elizabeth E

    2016-03-01

    Current tools for risk stratification of chronic liver disease subjects are limited. We aimed to determine whether the serum-based ELF (Enhanced Liver Fibrosis) test predicted liver-related clinical outcomes, or progression to advanced liver disease, and to compare the performance of ELF to liver biopsy and non-invasive algorithms. Three hundred patients with ELF scores assayed at the time of liver biopsy were followed up (median 6.1 years) for liver-related clinical outcomes (n = 16) and clear evidence of progression to advanced fibrosis (n = 18), by review of medical records and clinical data. Fourteen of 73 (19.2%) patients with ELF score indicative of advanced fibrosis (≥9.8, the manufacturer's cut-off) had a liver-related clinical outcome, compared to only two of 227 (liver-related event (adjusted for age and stage of fibrosis). In patients without advanced fibrosis on biopsy at recruitment, 55% (10/18) with an ELF score ≥9.8 showed clear evidence of progression to advanced fibrosis (after an average 6 years), whereas only 3.5% of those with an ELF score liver disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Role of TGF-alpha in the progression of diabetic kidney disease.

    Science.gov (United States)

    Heuer, Josef G; Harlan, Shannon M; Yang, Derek D; Jaqua, Dianna L; Boyles, Jeffrey S; Wilson, Jonathan M; Heinz-Taheny, Kathleen M; Sullivan, John M; Wei, Tao; Qian, Hui-Rong; Witcher, Derrick R; Breyer, Matthew D

    2017-06-01

    Transforming growth factor-alpha (TGFA) has been shown to play a role in experimental chronic kidney disease associated with nephron reduction, while its role in diabetic kidney disease (DKD) is unknown. We show here that intrarenal TGFA mRNA expression, as well as urine and serum TGFA, are increased in human DKD. We used a TGFA neutralizing antibody to determine the role of TGFA in two models of renal disease, the remnant surgical reduction model and the uninephrectomized (uniNx) db/db DKD model. In addition, the contribution of TGFA to DKD progression was examined using an adeno-associated virus approach to increase circulating TGFA in experimental DKD. In vivo blockade of TGFA attenuated kidney disease progression in both nondiabetic 129S6 nephron reduction and Type 2 diabetic uniNx db/db models, whereas overexpression of TGFA in uniNx db/db model accelerated renal disease. Therapeutic activity of the TGFA antibody was enhanced with renin angiotensin system inhibition with further improvement in renal parameters. These findings suggest a pathologic contribution of TGFA in DKD and support the possibility that therapeutic administration of neutralizing antibodies could provide a novel treatment for the disease. Copyright © 2017 the American Physiological Society.

  15. Changes in mitochondrial stability during the progression of the Barrett's esophagus disease sequence.

    Science.gov (United States)

    O'Farrell, N J; Feighery, R; Picardo, S L; Lynam-Lennon, N; Biniecka, M; McGarrigle, S A; Phelan, J J; MacCarthy, F; O'Toole, D; Fox, E J; Ravi, N; Reynolds, J V; O'Sullivan, J

    2016-07-19

    Barrett's esophagus follows the classic step-wise progression of metaplasia-dysplasia-adenocarcinoma. While Barrett's esophagus is a leading known risk factor for esophageal adenocarcinoma, the pathogenesis of this disease sequence is poorly understood. Mitochondria are highly susceptible to mutations due to high levels of reactive oxygen species (ROS) coupled with low levels of DNA repair. The timing and levels of mitochondria instability and dysfunction across the Barrett's disease progression is under studied. Using an in-vitro model representing the Barrett's esophagus disease sequence of normal squamous epithelium (HET1A), metaplasia (QH), dysplasia (Go), and esophageal adenocarcinoma (OE33), random mitochondrial mutations, deletions and surrogate markers of mitochondrial function were assessed. In-vivo and ex-vivo tissues were also assessed for instability profiles. Barrett's metaplastic cells demonstrated increased levels of ROS (p disease sequence in-vitro. Using patient in-vivo samples, Barrett's metaplasia tissue demonstrated significantly increased levels of random mitochondrial deletions (p = 0.043) compared with esophageal adenocarcinoma tissue, along with increased expression of cytoglobin (CYGB) (p disease sequence. Using ex-vivo Barrett's metaplastic and matched normal patient tissue explants, higher levels of cytochrome c (p = 0.003), SMAC/Diablo (p = 0.008) and four inflammatory cytokines (all p values disease sequence.

  16. Differential Disease Progression in Atrophic Age-Related Macular Degeneration and Late-Onset Stargardt Disease

    NARCIS (Netherlands)

    Lindner, M.; Lambertus, S.; Mauschitz, M.M.; Bax, N.M.; Kersten, E; Luning, A.; Nadal, J.; Schmitz-Valckenberg, S.; Schmid, M.; Holz, F.G.; Hoyng, C.B.; Fleckenstein, M.

    2017-01-01

    Purpose: To compare the disease course of retinal pigment epithelium (RPE) atrophy secondary to age-related macula degeneratio (AMD) and late-onset Stargardt disease (STGD1). Methods: Patients were examined longitudinally by fundus autofluorescence, near-infrared reflectance imaging, and

  17. HIV-1 Disease Progression and Survival in an Adult Population in Zimbabwe

    DEFF Research Database (Denmark)

    Zinyama-Gutsire, Rutendo B L; Chasela, Charles; Kallestrup, Per

    2015-01-01

    HIV infection remains a major global health burden since its discovery in 1983. Sub-Saharan Africa is the region hardest hit by the HIV/AIDS pandemic where 63% of the 33 million infected people live. While there is marked person-to-person variability in susceptibility, progression, and survival...... to HIV progression and mortality. We therefore cannot recommend at this time the use of plasma MBL levels or MBL2 genetic variants as a prognostic marker in HIV infection, disease progression, and survival in this adult population in Africa....... with HIV infection, there is a paucity of predictive diagnostics associated with these clinical endpoints. In this regard, the deficiency in plasma Mannose Binding Lectin (MBL) is a common opsonic defect reported to increase susceptibility infections, including HIV. To the best of our knowledge, we report...

  18. Do intraindividual variation in disease progression and the ensuing tight window of opportunity affect estimation of screening benefits?

    NARCIS (Netherlands)

    Koffijberg, Hendrik; Rinkel, Gabriel; Buskens, Erik

    Background. The effects of variation in disease progression between individuals on the effectiveness of screening have been assessed extensively in the literature. For several diseases, progression may also vary within individuals over time. The authors study the effects of intraindividual variation

  19. Do Intraindividual Variation in Disease Progression and the Ensuing Tight Window of Opportunity Affect Estimation of Screening Benefits?

    NARCIS (Netherlands)

    Koffijberg, Hendrik; Rinkel, Gabriel; Buskens, Erik

    2009-01-01

    Background. The effects of variation in disease progression between individuals on the effectiveness of screening have been assessed extensively in the literature. For several diseases, progression may also vary within individuals over time. The authors study the effects of intraindividual variation

  20. Disease Progression/Clinical Outcome Model for Castration-Resistant Prostate Cancer in Patients Treated with Eribulin

    NARCIS (Netherlands)

    Van Hasselt, J. G C; Gupta, A.; Hussein, Z.; Beijnen, J. H.; Schellens, J. H M; Huitema, A. D R

    2015-01-01

    Frameworks that associate cancer dynamic disease progression models with parametric survival models for clinical outcome have recently been proposed to support decision making in early clinical development. Here we developed such a disease progression clinical outcome model for castration-resistant

  1. Progression marker of Parkinson's disease: a 4-year multi-site imaging study.

    Science.gov (United States)

    Burciu, Roxana G; Ofori, Edward; Archer, Derek B; Wu, Samuel S; Pasternak, Ofer; McFarland, Nikolaus R; Okun, Michael S; Vaillancourt, David E

    2017-08-01

    Progression markers of Parkinson's disease are crucial for successful therapeutic development. Recently, a diffusion magnetic resonance imaging analysis technique using a bitensor model was introduced allowing the estimation of the fractional volume of free water within a voxel, which is expected to increase in neurodegenerative disorders such as Parkinson's disease. Prior work demonstrated that free water in the posterior substantia nigra was elevated in Parkinson's disease compared to controls across single- and multi-site cohorts, and increased over 1 year in Parkinson's disease but not in controls at a single site. Here, the goal was to validate free water in the posterior substantia nigra as a progression marker in Parkinson's disease, and describe the pattern of progression of free water in patients with a 4-year follow-up tested in a multicentre international longitudinal study of de novo Parkinson's disease (http://www.ppmi-info.org/). The analyses examined: (i) 1-year changes in free water in 103 de novo patients with Parkinson's disease and 49 controls; (ii) 2- and 4-year changes in free water in a subset of 46 patients with Parkinson's disease imaged at baseline, 12, 24, and 48 months; (iii) whether 1- and 2-year changes in free water predict 4-year changes in the Hoehn and Yahr scale; and (iv) the relationship between 4-year changes in free water and striatal binding ratio in a subgroup of Parkinson's disease who had undergone both diffusion and dopamine transporter imaging. Results demonstrated that: (i) free water level in the posterior substantia nigra increased over 1 year in de novo Parkinson's disease but not in controls; (ii) free water kept increasing over 4 years in Parkinson's disease; (iii) sex and baseline free water predicted 4-year changes in free water; (iv) free water increases over 1 and 2 years were related to worsening on the Hoehn and Yahr scale over 4 years; and (v) the 4-year increase in free water was associated with the 4-year

  2. Pregnancy and HIV disease progression: a systematic review and meta-analysis.

    Science.gov (United States)

    Calvert, Clara; Ronsmans, Carine

    2015-02-01

    To assess whether pregnancy accelerates HIV disease progression. Studies comparing progression to HIV-related illness, low CD4 count, AIDS-defining illness, HIV-related death, or any death in HIV-infected pregnant and non-pregnant women were included. Relative risks (RR) for each outcome were combined using random effects meta-analysis and were stratified by antiretroviral therapy (ART) availability. 15 studies met the inclusion criteria. Pregnancy was not associated with progression to HIV-related illness [summary RR: 1.32, 95% confidence interval (CI): 0.66-2.61], AIDS-defining illness (summary RR: 0.97, 95% CI: 0.74-1.25) or mortality (summary RR: 0.97, 95% CI: 0.62-1.53), but there was an association with low CD4 counts (summary RR: 1.41, 95% CI: 0.99-2.02) and HIV-related death (summary RR: 1.65, 95% CI: 1.06-2.57). In settings where ART was available, there was no evidence that pregnancy accelerated progress to HIV/AIDS-defining illnesses, death and drop in CD4 count. In settings without ART availability, effect estimates were consistent with pregnancy increasing the risk of progression to HIV/AIDS-defining illnesses and HIV-related or all-cause mortality, but there were too few studies to draw meaningful conclusions. In the absence of ART, pregnancy is associated with small but appreciable increases in the risk of several negative HIV outcomes, but the evidence is too weak to draw firm conclusions. When ART is available, the effects of pregnancy on HIV disease progression are attenuated and there is little reason to discourage healthy HIV-infected women who desire to become pregnant from doing so. © 2014 John Wiley & Sons Ltd.

  3. Enzyme replacement therapy attenuates disease progression in a canine model of late-infantile neuronal ceroid lipofuscinosis (CLN2 disease).

    Science.gov (United States)

    Katz, Martin L; Coates, Joan R; Sibigtroth, Christine M; Taylor, Jacob D; Carpentier, Melissa; Young, Whitney M; Wininger, Fred A; Kennedy, Derek; Vuillemenot, Brian R; O'Neill, Charles A

    2014-11-01

    Using a canine model of classical late-infantile neuronal ceroid lipofuscinosis (CLN2 disease), a study was conducted to evaluate the potential pharmacological activity of recombinant human tripeptidyl peptidase-1 (rhTPP1) enzyme replacement therapy administered directly to the cerebrospinal fluid (CSF). CLN2 disease is a hereditary neurodegenerative disorder resulting from mutations in CLN2, which encodes the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Infants with mutations in both CLN2 alleles develop normally but in the late-infantile/early-childhood period undergo progressive neurological decline accompanied by pronounced brain atrophy. The disorder, a form of Batten disease, is uniformly fatal, with clinical signs starting between 2 and 4 years of age and death usually occurring by the early teenage years. Dachshunds homozygous for a null mutation in the canine ortholog of CLN2 (TPP1) exhibit a similar disorder that progresses to end stage at 10.5-11 months of age. Administration of rhTPP1 via infusion into the CSF every other week, starting at approximately 2.5 months of age, resulted in dose-dependent significant delays in disease progression, as measured by delayed onset of neurologic deficits, improved performance on a cognitive function test, reduced brain atrophy, and increased life span. Based on these findings, a clinical study evaluating the potential therapeutic value of rhTPP1 administration into the CSF of children with CLN2 disease has been initiated. Copyright © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

  4. Recent progress in the etiopathogenesis of pediatric biliary disease, particularly Caroli's disease with congenital hepatic fibrosis and biliary atresia.

    Science.gov (United States)

    Nakanuma, Yasuni; Harada, Kenichi; Sato, Yasunori; Ikeda, Hiroko

    2010-02-01

    Recent progress in elucidating the etiopathogenesis of pediatric biliary diseases, particularly Caroli's disease with congenital hepatic fibrosis (CHF) and biliary atresia (BA), is reviewed. The former is characterized by multiple saccular dilatations of the intrahepatic bile ducts. An animal model of this disease, the PCK rat, is being extensively studied. PCK rats and Calori's disease with CHF belong to autosomal recessive polycystic kidney disease (ARPKD) with ductal plate malformation. Mutations of PKHD1 have been identified in ARPKD, and fibrocystin, a product of PKHD1 located in the cilia of bile ducts is lacking in the pathologic intrahepatic bile ducts of ARPKD. Disordered cell kinetics, including apoptosis of biliary epithelial cells (BECs), may be significantly related to ductal plate malformation, and laminin and type IV collagen were immunohistochemically reduced in the basement membrane of intrahepatic bile ducts of ARPKD, and such a reduction is an additional factor for the dilatation of bile ducts. Abundant connective tissue growth factor retained diffusely in heparan sulfate proteoglycan in the fibrous portal tracts are responsible for non-resolving hepatic fibrosis. In addition, pathologic BECs of ARPKD may acquire mesenchymal features and participate in progressive hepatic fibrosis by producing extracellular matrix molecules. In an animal model of BA, an initial virus-induced, T-cell mediated autoimmune-mediated cholangiopathy has been reported. In human BA, virus-induced apoptosis of BECs by a TNF-related apoptosis-inducing ligand followed by the progressive obliteration of bile ducts is also suggested, and epithelial mesenchymal transition of BECs induced by viral infection may be involved in the fibrotic process in sclerosing cholangitis. However, the role of viral infections in the affected tissues is controversial. Comprehensive and analytical studies of ARPKD and BA using human materials and animal models may lead to the clarification of

  5. Have we made progress in the management of chronic graft-vs-host disease?

    Science.gov (United States)

    Lee, Stephanie J

    2010-12-01

    Chronic graft-vs-host disease (GVHD) is a common long-term complication of allogeneic hematopoietic cell transplant that is associated with very high morbidity and mortality. In order to understand whether we have made progress in the management of chronic GVHD, it is helpful to first propose a definition of meaningful "progress". The following can be considered to be indicators of improved management of chronic GVHD: a decrease in the incidence or severity of chronic GVHD, better efficacy or decreased toxicity of therapies, better quality of life despite chronic GVHD, and improved overall and disease-free survival rates. However, to date, real progress has not been made in these areas, though there are promising new preventive strategies and treatments. Furthermore, a consensus has been reached in the research community about many different issues surrounding chronic GVHD definitions, management, and the conduct of clinical trials. These consensus documents will help to standardize efforts and data collection so that true comparisons can be made in the future and real clinical progress achieved. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Induced Pluripotent Stem Cells Reduce Progression of Experimental Chronic Kidney Disease but Develop Wilms’ Tumors

    Directory of Open Access Journals (Sweden)

    Heloisa Cristina Caldas

    2017-01-01

    Full Text Available The therapeutic effect of induced pluripotent stem cells (iPSs on the progression of chronic kidney disease (CKD has not yet been demonstrated. In this study, we sought to assess whether treatment with iPSs retards progression of CKD when compared with bone marrow mesenchymal stem cells (BMSCs. Untreated 5/6 nephrectomized rats were compared with CKD animals receiving BMSCs or iPSs. Renal function, histology, immunohistochemistry, and gene expression were studied. Implanted iPSs were tracked by the SRY gene expression analysis. Both treatments minimized elevation in serum creatinine, significantly improved clearance, and slowed down progression of disease. The proteinuria was reduced only in the iPS group. Both treatments reduced glomerulosclerosis, iPSs decreased macrophage infiltration, and TGF-β was reduced in kidneys from the BMSC group. Both types of treatments increased VEGF gene expression, TGF-β was upregulated only in the iPS group, and IL-10 had low expression in both groups. The SRY gene was found in 5/8 rats treated with iPSs. These 5 animals presented tumors with histology and cells highly staining positive for PCNA and Wilms’ tumor protein antibody characteristics of Wilms’ tumor. These results suggest that iPSs may be efficient to retard progression of CKD but carry the risk of Wilms’ tumor development.

  7. Review of psychotherapeutic interventions on depression in cancer patients and their impact on disease progression.

    Science.gov (United States)

    Barrera, Ingrid; Spiegel, David

    2014-02-01

    Depression, ranging from mild to severe, is the most frequently found psychological symptom among individuals with cancer. Depression in cancer patients has been known to mitigate emotional distress, quality of life, adherence to medical treatment, and overall health outcomes. Specifically, depression has been associated with impaired immune response and with poorer survival in patients with cancer. Various studies have found that psychotherapeutic interventions are effective in reducing symptoms of depression, which in turn could affect disease progression and mortality. This paper provides updated information on psychotherapeutic interventions geared towards cancer patients suffering from depressive disorders, and its impact on disease progression. PubMed, Cochrane Library database, PsycINFO and PsycARTICLES databases were searched from January 1980 through August 2013 using key words: psychotherapy, treatment, oncology, cancer, psycho-oncology, psychosocial issues, psychosocial stress, depression, mood disorder, and psychoneuroimmunology.

  8. Iron and copper in progressive demyelination--New lessons from Skogholt's disease.

    Science.gov (United States)

    Aspli, Klaus Thanke; Flaten, Trond Peder; Roos, Per M; Holmøy, Trygve; Skogholt, Jon H; Aaseth, Jan

    2015-01-01

    The pathophysiological mechanisms of progressive demyelinating disorders including multiple sclerosis are incompletely understood. Increasing evidence indicates a role for trace metals in the progression of several neurodegenerative disorders. The study of Skogholt disease, a recently discovered demyelinating disease affecting both the central and peripheral nervous system, might shed some light on the mechanisms underlying demyelination. Cerebrospinal fluid iron and copper concentrations are about four times higher in Skogholt patients than in controls. The transit into cerebrospinal fluid of these elements from blood probably occurs in protein bound form. We hypothesize that exchangeable fractions of iron and copper are further transferred from cerebrospinal fluid into myelin, thereby contributing to the pathogenesis of demyelination. Free or weakly bound iron and copper ions may exert their toxic action on myelin by catalyzing production of oxygen radicals. Similarities to demyelinating processes in multiple sclerosis and other myelinopathies are discussed. Copyright © 2014 Elsevier GmbH. All rights reserved.

  9. Body weight is a robust predictor of clinical progression in Huntington disease.

    Science.gov (United States)

    van der Burg, Jorien M M; Gardiner, Sarah L; Ludolph, Albert C; Landwehrmeyer, G Bernhard; Roos, Raymund A C; Aziz, N Ahmad

    2017-09-01

    Unintended weight loss is a hallmark of Huntington disease (HD), but it is unknown to what extent weight loss impacts the rate of disease progression. Therefore, using longitudinal data from the Enroll-HD study, we assessed the association between baseline body mass index (BMI) and the rate of clinical progression in 5,821 HD mutation carriers. We found that high baseline BMI was associated with a significantly slower rate of functional, motor, and cognitive deterioration (all p < 0.001), independent of mutant HTT CAG repeat size. Our findings provide strong rationale for exploration of systemic metabolism as a therapeutic target in HD. Ann Neurol 2017;82:479-483. © 2017 American Neurological Association.

  10. NMR-based lipidomic analysis of blood lipoproteins differentiates the progression of coronary heart disease.

    Science.gov (United States)

    Kostara, Christina E; Papathanasiou, Athanasios; Psychogios, Nikolaos; Cung, Manh Thong; Elisaf, Moses S; Goudevenos, John; Bairaktari, Eleni T

    2014-05-02

    Abnormal lipid composition and metabolism of plasma lipoproteins play a crucial role in the pathogenesis of coronary heart disease (CHD). A (1)H NMR-based lipidomic approach was used to investigate the correlation of coronary artery stenosis with the atherogenic (non-HDL) and atheroprotective (HDL) lipid profiles in 99 patients with CHD of various stages of disease and compared with 60 patients with normal coronary arteries (NCA), all documented in coronary angiography. The pattern recognition models created from lipid profiles predicted the presence of CHD with a sensitivity of 87% and a specificity of 88% in the HDL model and with 90% and 89% in the non-HDL model, respectively. Patients with mild, moderate, and severe coronary artery stenosis were progressively differentiated from those with NCA in the non-HDL model with a statistically significant separation of severe stage from both mild and moderate. In the HDL model, the progressive differentiation of the disease stages was statistically significant only between patients with mild and severe coronary artery stenosis. The lipid constituents of lipoproteins that mainly characterized the initial stages and then the progression of the disease were the high levels of saturated fatty acids in lipids in both HDL and non-HDL particles, the low levels of HDL-phosphatidylcholine, HDL-sphingomyelin, and omega-3 fatty acids and linoleic acid in lipids in non-HDL particles. The conventional lipid marker, total cholesterol, found in low levels in HDL and in high levels in non-HDL, also contributed to the onset of the disease but with a much lower coefficient of significance. (1)H NMR-based lipidomic analysis of atherogenic and atheroprotective lipoproteins could contribute to the early evaluation of the onset of coronary artery disease and possibly to the establishment of an appropriate therapeutic option.

  11. Connected speech as a marker of disease progression in autopsy-proven Alzheimer's disease

    National Research Council Canada - National Science Library

    Ahmed, Samrah; Haigh, Anne-Marie F; de Jager, Celeste A; Garrard, Peter

    2013-01-01

    ... cognitive domains, including language. Previous studies from our group have shown that language changes may be reflected in connected speech production in the earliest stages of typical Alzheimer's disease...

  12. Prognostic models based on patient snapshots and time windows: Predicting disease progression to assisted ventilation in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Carreiro, André V; Amaral, Pedro M T; Pinto, Susana; Tomás, Pedro; de Carvalho, Mamede; Madeira, Sara C

    2015-12-01

    Amyotrophic Lateral Sclerosis (ALS) is a devastating disease and the most common neurodegenerative disorder of young adults. ALS patients present a rapidly progressive motor weakness. This usually leads to death in a few years by respiratory failure. The correct prediction of respiratory insufficiency is thus key for patient management. In this context, we propose an innovative approach for prognostic prediction based on patient snapshots and time windows. We first cluster temporally-related tests to obtain snapshots of the patient's condition at a given time (patient snapshots). Then we use the snapshots to predict the probability of an ALS patient to require assisted ventilation after k days from the time of clinical evaluation (time window). This probability is based on the patient's current condition, evaluated using clinical features, including functional impairment assessments and a complete set of respiratory tests. The prognostic models include three temporal windows allowing to perform short, medium and long term prognosis regarding progression to assisted ventilation. Experimental results show an area under the receiver operating characteristics curve (AUC) in the test set of approximately 79% for time windows of 90, 180 and 365 days. Creating patient snapshots using hierarchical clustering with constraints outperforms the state of the art, and the proposed prognostic model becomes the first non population-based approach for prognostic prediction in ALS. The results are promising and should enhance the current clinical practice, largely supported by non-standardized tests and clinicians' experience. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. What can be learnt about disease progression in breast cancer dormancy from relapse data?

    Science.gov (United States)

    Willis, Lisa; Graham, Trevor A; Alarcón, Tomás; Alison, Malcolm R; Tomlinson, Ian P M; Page, Karen M

    2013-01-01

    Breast cancer patients have an anomalously high rate of relapse many years--up to 25 years--after apparently curative surgery removed the primary tumour. Disease progression during the intervening years between resection and relapse is poorly understood. There is evidence that the disease persists as dangerous, tiny metastases that remain at a growth restricted, clinically undetectable size until a transforming event restarts growth. This is the starting point for our study, where patients who have metastases that are all tiny and growth-restricted are said to have cancer dormancy. Can long-term follow-up relapse data from breast cancer patients be used to extract knowledge about the progression of the undetected disease? Here, we evaluate whether this is the case by introducing and analysing four simple mathematical models of cancer dormancy. These models extend the common assumption that a random transforming event, such as a mutation, can restart growth of a tiny, growth-restricted metastasis; thereafter, cancer dormancy progresses to detectable metastasis. We find that physiopathological details, such as the number of random transforming events that metastases must undergo to escape from growth restriction, cannot be extracted from relapse data. This result is unsurprising. However, the same analysis suggested a natural question that does have a surprising answer: why are interesting trends in long-term relapse data not more commonly observed? Further, our models indicate that (a) therapies which induce growth restriction among metastases but do not prevent increases in metastases' tumourigenicity may introduce a time post-surgery when more patients are prone to relapse; and (b), if a number of facts about disease progression are first established, how relapse data might be used to estimate clinically relevant variables, such as the likely numbers of undetected growth-restricted metastases. This work is a necessary, early step in building a quantitative

  14. What can be learnt about disease progression in breast cancer dormancy from relapse data?

    Directory of Open Access Journals (Sweden)

    Lisa Willis

    Full Text Available Breast cancer patients have an anomalously high rate of relapse many years--up to 25 years--after apparently curative surgery removed the primary tumour. Disease progression during the intervening years between resection and relapse is poorly understood. There is evidence that the disease persists as dangerous, tiny metastases that remain at a growth restricted, clinically undetectable size until a transforming event restarts growth. This is the starting point for our study, where patients who have metastases that are all tiny and growth-restricted are said to have cancer dormancy. Can long-term follow-up relapse data from breast cancer patients be used to extract knowledge about the progression of the undetected disease? Here, we evaluate whether this is the case by introducing and analysing four simple mathematical models of cancer dormancy. These models extend the common assumption that a random transforming event, such as a mutation, can restart growth of a tiny, growth-restricted metastasis; thereafter, cancer dormancy progresses to detectable metastasis. We find that physiopathological details, such as the number of random transforming events that metastases must undergo to escape from growth restriction, cannot be extracted from relapse data. This result is unsurprising. However, the same analysis suggested a natural question that does have a surprising answer: why are interesting trends in long-term relapse data not more commonly observed? Further, our models indicate that (a therapies which induce growth restriction among metastases but do not prevent increases in metastases' tumourigenicity may introduce a time post-surgery when more patients are prone to relapse; and (b, if a number of facts about disease progression are first established, how relapse data might be used to estimate clinically relevant variables, such as the likely numbers of undetected growth-restricted metastases. This work is a necessary, early step in building a

  15. Duchenne Regulatory Science Consortium Meeting on Disease Progression Modeling for Duchenne Muscular Dystrophy

    OpenAIRE

    Larkindale, Jane; Abresch, Richard; Aviles, Enrique; Bronson, Abby; Chin, Janice; Furlong, Pat; Gordish-Dressman, Heather; Habeeb-Louks, Elizabeth; Henricson, Erik; Kroger, Hans; Lynn, Charles; Lynn, Stephen; Martin, Dana; Nuckolls, Glen; Rooney, William

    2017-01-01

    Introduction: The Duchenne Regulatory Science Consortium (D-RSC) was established to develop tools to accelerate drug development for DMD.? The resulting tools are anticipated to meet validity requirements outlined by qualification/endorsement pathways at both the U.S. Food and Drug Administration (FDA) and European Medicines Administration (EMA), and will be made available to the drug development community. The initial goals of the consortium include the development of a disease progression m...

  16. A Case of Cerebral Erdheim-Chester Disease With Progressive Cerebellar Syndrome

    OpenAIRE

    Na, Sang-Jun; Lee, Kee Ook; Kim, Jung Eun; Kim, Yong-Duk

    2008-01-01

    Erdheim-Chester disease (ECD) is a rare non-Langerhans form of histiocytosis. Cerebellar involvement is rare in this syndrome. We report a 37-year-old woman with slowly progressive cerebellar ataxia, dysmetria of limbs, nystagmus, and dysarthria, bilateral painful axillary masses, and generalized arthralgia. Brain MRI revealed cerebellar atrophy with focal lesions in the pons, middle cerebellar peduncle, and the cerebellum. She underwent incisional biopsy of her axillary masses which showed f...

  17. Brain plasticity in the motor network is correlated with disease progression in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Poujois, Aurélia; Schneider, Fabien C; Faillenot, Isabelle; Camdessanché, Jean-Philippe; Vandenberghe, Nadia; Thomas-Antérion, Catherine; Antoine, Jean-Christophe

    2013-10-01

    To test the influence of functional cerebral reorganization in amyotrophic lateral sclerosis (ALS) on disease progression. Nineteen predominantly right-handed ALS patients and 21 controls underwent clinical evaluation, functional Magnetic Resonance Imaging (fMRI), and diffusion tensor imaging. Patients were clinically re-evaluated 1 year later and followed until death. For fMRI, subjects executed and imagined a simple hand-motor task. Between-group comparisons were performed, and correlations were searched with motor deficit arm Medical Research Council (MRC) score, disease progression ALS Functional Rating Scale (ALSFRS), and survival time. By the MRC score, the hand strength was lowered by 12% in the ALS group predominating on the right side in accordance with an abnormal fractional anisotropy (FA) limited to the left corticospinal tract (37.3% reduction vs. controls P < 0.01). Compared to controls, patients displayed overactivations in the controlateral parietal (P < 0.004) and somatosensory (P < 0.004) cortex and in the ipsilateral parietal (P < 0.01) and somatosensory (P < 0.01) cortex to right-hand movement. Movement imagination gave similar results while no difference occurred with left-hand tasks. Stepwise regression analysis corrected for multiple comparisons showed that controlateral parietal activity was inversely correlated with disease progression (R(2) = 0.43, P = 0.001) and ipsilateral somatosensory activations with the severity of the right-arm deficit (R(2) = 0.48, P = 0.001). Cortical Blood Oxygen Level Dependent (BOLD) signal changes occur in the brain of ALS patients during a simple hand-motor task when the motor deficit is still moderate. It is correlated with the rate of disease progression suggesting that brain functional rearrangement in ALS may have prognostic implications. Copyright © 2012 Wiley Periodicals, Inc.

  18. Distinctive Pattern of Serum Elements During the Progression of Alzheimer?s Disease

    OpenAIRE

    Giuseppe Paglia; Oto Miedico; Adriana Cristofano; Michela Vitale; Antonella Angiolillo; Antonio Eugenio Chiaravalle; Gaetano Corso; Alfonso Di Costanzo

    2016-01-01

    Element profiling is an interesting approach for understanding neurodegenerative processes, considering that compelling evidences show that element toxicity might play a crucial role in the onset and progression of Alzheimer?s disease (AD). Aim of this study was to profile 22 serum elements in subjects with or at risk of AD. Thirtyfour patients with probable AD, 20 with mild cognitive impairment (MCI), 24 with subjective memory complaint (SMC) and 40 healthy subjects (HS) were included in the...

  19. Progressive white-matter disease with primary cerebellar involvement: a separate entity?

    Energy Technology Data Exchange (ETDEWEB)

    Yalcinkaya, C. [Division of Child Neurology, Department of Neurology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul (Turkey); Arslanoglu, I. [Division of Endocrinology, Department of Paediatrics, Goeztepe Hospital, Istanbul (Turkey); Islak, C. [Division of Neuroradiology, Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul (Turkey); Aydin, A. [Division of Metabolic Disease, Department of Paediatrics, Cerrahpasa Medical Faculty, Istanbul University, Istanbul (Turkey); Boltshauser, E. [Division of Paediatric Neurology, University Children' s Hospital, Steinwiesstrasse 75, 8032 Zuerich (Switzerland)

    2002-09-01

    Although its metabolic basis has not yet been clarified, we report a progressive white-matter disease in a Turkish girl, starting in the cerebellum and spreading to supratentorial white matter. The onset was at the age of 2.5 years with diabetes insipidus, followed by ataxia and pyramidal signs resulting in loss of walking. Aqueduct stenosis was first recognised at the age of 8 years. To our knowledge, this MRI and clinical pattern does not correspond to a recognised, well-defined white-matter disease and may indicate a separate entity. (orig.)

  20. Progress and prospects: gene therapy for genetic diseases with helper-dependent adenoviral vectors.

    Science.gov (United States)

    Brunetti-Pierri, N; Ng, P

    2008-04-01

    Preclinical studies in small and large animal models using helper-dependent adenoviral vectors (HDAds) have generated promising results for the treatment of genetic diseases. However, clinical translation is complicated by the dose-dependent, capsid-mediated acute toxic response following systemic vector injection. With the advancements in vectorology, a better understanding of vector-mediated toxicity, and improved delivery methods, HDAds may emerge as an important vector for gene therapy of genetic diseases and this report highlights recent progress and prospects in this field.