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Sample records for evaluating disease progression

  1. Evaluating Alzheimer's Disease Progression by Modeling Crosstalk Network Disruption

    Science.gov (United States)

    Liu, Haochen; Wei, Chunxiang; He, Hua; Liu, Xiaoquan

    2016-01-01

    Aβ, tau, and P-tau have been widely accepted as reliable markers for Alzheimer's disease (AD). The crosstalk between these markers forms a complex network. AD may induce the integral variation and disruption of the network. The aim of this study was to develop a novel mathematic model based on a simplified crosstalk network to evaluate the disease progression of AD. The integral variation of the network is measured by three integral disruption parameters. The robustness of network is evaluated by network disruption probability. Presented results show that network disruption probability has a good linear relationship with Mini Mental State Examination (MMSE). The proposed model combined with Support vector machine (SVM) achieves a relative high 10-fold cross-validated performance in classification of AD vs. normal and mild cognitive impairment (MCI) vs. normal (95% accuracy, 95% sensitivity, 95% specificity for AD vs. normal; 90% accuracy, 94% sensitivity, 83% specificity for MCI vs. normal). This research evaluates the progression of AD and facilitates AD early diagnosis. PMID:26834548

  2. Evaluating Alzheimer's disease progression using rate of regional hippocampal atrophy.

    Directory of Open Access Journals (Sweden)

    Edit Frankó

    Full Text Available Alzheimer's disease (AD is characterized by neurofibrillary tangle and neuropil thread deposition, which ultimately results in neuronal loss. A large number of magnetic resonance imaging studies have reported a smaller hippocampus in AD patients as compared to healthy elderlies. Even though this difference is often interpreted as atrophy, it is only an indirect measurement. A more direct way of measuring the atrophy is to use repeated MRIs within the same individual. Even though several groups have used this appropriate approach, the pattern of hippocampal atrophy still remains unclear and difficult to relate to underlying pathophysiology. Here, in this longitudinal study, we aimed to map hippocampal atrophy rates in patients with AD, mild cognitive impairment (MCI and elderly controls. Data consisted of two MRI scans for each subject. The symmetric deformation field between the first and the second MRI was computed and mapped onto the three-dimensional hippocampal surface. The pattern of atrophy rate was similar in all three groups, but the rate was significantly higher in patients with AD than in control subjects. We also found higher atrophy rates in progressive MCI patients as compared to stable MCI, particularly in the antero-lateral portion of the right hippocampus. Importantly, the regions showing the highest atrophy rate correspond to those that were described to have the highest burden of tau deposition. Our results show that local hippocampal atrophy rate is a reliable biomarker of disease stage and progression and could also be considered as a method to objectively evaluate treatment effects.

  3. Evaluating Alzheimer’s disease progression by modeling crosstalk network disruption

    Directory of Open Access Journals (Sweden)

    Haochen eLiu

    2016-01-01

    Full Text Available Aβ, tau and P-tau have been widely accepted as reliable markers for Alzheimer’s disease (AD. The crosstalk between these markers forms a complex network. AD may induce the integral variation and disruption of the network. The aim of this study was to develop a novel mathematic model based on a simplified crosstalk network to evaluate the disease progression of AD. The integral variation of the network is measured by three integral disruption parameters. The robustness of network is evaluated by network disruption probability. Presented results show that network disruption probability has a good linear relationship with Mini Mental State Examination (MMSE. The proposed model combined with Support vector machine (SVM achieves a relative high 10-fold cross-validated performance in classification of AD vs normal and mild cognitive impairment (MCI vs normal (95% accuracy, 95% sensitivity, 95% specificity for AD vs normal; 90% accuracy, 94% sensitivity, 83% specificity for MCI vs normal. This research evaluates the progression of AD and facilitates AD early diagnosis.

  4. Evaluating Alzheimer’s Disease Progression Using Rate of Regional Hippocampal Atrophy

    Science.gov (United States)

    Frankó, Edit; Joly, Olivier

    2013-01-01

    Alzheimer’s disease (AD) is characterized by neurofibrillary tangle and neuropil thread deposition, which ultimately results in neuronal loss. A large number of magnetic resonance imaging studies have reported a smaller hippocampus in AD patients as compared to healthy elderlies. Even though this difference is often interpreted as atrophy, it is only an indirect measurement. A more direct way of measuring the atrophy is to use repeated MRIs within the same individual. Even though several groups have used this appropriate approach, the pattern of hippocampal atrophy still remains unclear and difficult to relate to underlying pathophysiology. Here, in this longitudinal study, we aimed to map hippocampal atrophy rates in patients with AD, mild cognitive impairment (MCI) and elderly controls. Data consisted of two MRI scans for each subject. The symmetric deformation field between the first and the second MRI was computed and mapped onto the three-dimensional hippocampal surface. The pattern of atrophy rate was similar in all three groups, but the rate was significantly higher in patients with AD than in control subjects. We also found higher atrophy rates in progressive MCI patients as compared to stable MCI, particularly in the antero-lateral portion of the right hippocampus. Importantly, the regions showing the highest atrophy rate correspond to those that were described to have the highest burden of tau deposition. Our results show that local hippocampal atrophy rate is a reliable biomarker of disease stage and progression and could also be considered as a method to objectively evaluate treatment effects. PMID:23951142

  5. A Comparative Study Evaluating the Impact of Physical Exercise on Disease Progression in a Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Maliszewska-Cyna, Ewelina; Xhima, Kristiana; Aubert, Isabelle

    2016-05-06

    Evidence suggests that physical exercise can serve as a preventive strategy against Alzheimer's disease (AD). In contrast, much less is known about the impact of exercise when it is introduced after cognitive deficits are established. Using the TgCRND8 mouse model of amyloidosis, we compared the effects of exercise as an intervention strategy aimed at altering disease progression. Voluntary running for 1 month or 2 months was introduced in 3-month-old TgCRND8 mice, which exhibit amyloid-beta (Aβ) plaque pathology and cognitive deficits at this age. Specifically, we examined Aβ plaque load, spatial memory, and neurogenesis in the dentate gyrus in the hippocampus. After 1 month of running, TgCRND8 mice spent more time in the novel arm of the Y-maze compared to the familiar arms, indicating improved memory. The levels of doublecortin (a marker of immature neurons) were increased in TgCRND8 mice running for 1 month, but with no significant difference in the number of new mature neurons or plaque burden. As the disease progressed, running prevented further deficits in the Y-maze performance and hippocampal neurogenesis and it reduced plaque load pathology in TgCRND8 mice running for 2 months, compared to non-running transgenics. Therefore, the impact of running on memory, neurogenesis, and amyloid pathology was of greater significance when sustained through later stages of the disease.

  6. Progression of Liver Disease

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    ... Legacy Society Make Gifts of Stock Donate Your Car Personal Fundraising Partnership & Support Share Your Story Spread the Word Give While You Shop Contact Us Donate Now The Progression of Liver ...

  7. Progress on diabetic cerebrovascular diseases.

    Science.gov (United States)

    Zhou, Houguang; Zhang, Xiaoming; Lu, Jianfeng

    2014-11-09

    Diabetic cerebrovascular diseases are defined as cerebral vascular diseases induced by diabetes with sugar, fat and a series of nutrient substance metabolic disorders, resulting in intracranial large and small vessel diseases. About 20%-40% patients with type 2 diabetes suffer from cerebral blood vessel diseases. Diabetic cerebrovascular diseases are the main causes of death in patients with diabetes mellitus. The major clinical manifestations are asymptomatic cerebral atherosclerosis, stroke, cerebral small vessel disease and acute cerebral vascular disease. The pathogenesis, clinical characteristics, treatment and prognosis of diabetic cerebrovascular disease are obviously different from non-diabetic cerebral vascular diseases. This paper will focus on the diabetic cerebrovascular disease, including its latest research progress. Diabetic cerebral large vascular disease and diabetic cerebral small vessel disease will be reviewed here.

  8. 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.

  9. Value of serum NGAL and HE4 content change for diagnosing lung cancer and evaluating disease progression

    Directory of Open Access Journals (Sweden)

    Xue Yuan

    2017-10-01

    Full Text Available Objective: To study the value of serum NGAL and HE4 content change for diagnosing non- small cell lung cancer (NSCLC and evaluating disease progression. Methods: Patients who were diagnosed with NSCLC and underwent surgical resection in the First Affiliated Hospital of Chengdu Medical College between February 2015 and March 2017 were selected as the NSCLC group, and healthy volunteers who received physical examination over the same period were selected as control group. The NGAL and HE4 contents in serum of NSCLC group and control group as well as the expression of proliferation, apoptosis and invasion genes in NSCLC lesion of NSCLC group were detected. Results: Serum NGAL and HE4 levels of NSCLC group were significantly higher than those of control group, serum NGAL and HE4 levels of patients with TNM II and TNM III NSCLC were significantly higher than those of patients with TNM I NSCLC, and serum NGAL and HE4 levels of patients with TNM III NSCLC were significantly higher than those of patients with TNM II NSCLC; c-myc, Survivin, CatL, Vimentin, Slug and Snail mRNA expression in NSCLC lesion were significantly higher than those in adjacent lesion and positively correlated with serum NGAL and HE4 levels while PTEN, LATS1 and E-cadherin mRNA expression were significantly lower than those in adjacent lesion and negatively correlated with serum NGAL and HE4 levels. Conclusion: Abnormally elevated NGAL and HE4 in the serum of NSCLC patients can evaluate the proliferation and invasion of cancer cells to a certain extent.

  10. Usefulness of the computed tomography and magnetic resonance in evaluation of progress of treatment of the neoplasmatic diseases in children

    International Nuclear Information System (INIS)

    Myga-Porosiło, Jolanta; Borowiak, Hanna; Sraga, Wojciech; Jackowska, Zuzanna; Serafin, Magdalena; Kluczewska, Ewa

    2012-01-01

    Neoplastmatic diseases constitute about 1% diseases in children in Poland, what makes about 1200 new incidents during one year. Fast diagnosis in those illnesses is crucial in treatment results. The point of this work was to value usefulness of CT and MRI in diagnostics of neoplasmatic diseases in children. The retrospective study involved 121 children examined in CT and MRI because of suspicion or during treatment of neoplasmatic disease. Together 184 CT and 119 MRI examination were performed. Eventually in 106 children neoplasmatic disease was diagnosed. In 16 cases neoplasm was excluded. In the analyzed group of patients acute lymphoblastic and non lymphoblastic leukemia was diagnosed in 68 children (55.7%); among them mycosis was identified after radiological examinations in 7 cases (10.3%). 8 children (6.6%) with non Hodgkin lymphoma and 11 (9%) with Hodgkin lymphoma were examined. Nephroblastoma was found after MRI and CT in 6 cases (4.9%). Presence of tumors, that were classified histopatologically as PNET, was confirmed in 4 children. In 15 cases after MRI and CT neoplasmatic disease was excluded. Depending on the kind of sickness MRI and CT may fulfill basic or subsidiary role in diagnostic and estimating the progress of treatment in neoplasmatic diseases among children

  11. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of white matter lesions on MRI: the evaluation of vascular care in Alzheimer's disease (EVA) study.

    Science.gov (United States)

    Richard, Edo; Gouw, Alida A; Scheltens, Philip; van Gool, Willem A

    2010-03-01

    White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts. A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up. Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3, P=0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease.

  12. Evaluating the predictive power of multivariate tensor-based morphometry in Alzheimer's disease progression via convex fused sparse group Lasso

    Science.gov (United States)

    Tsao, Sinchai; Gajawelli, Niharika; Zhou, Jiayu; Shi, Jie; Ye, Jieping; Wang, Yalin; Lepore, Natasha

    2014-03-01

    Prediction of Alzheimers disease (AD) progression based on baseline measures allows us to understand disease progression and has implications in decisions concerning treatment strategy. To this end we combine a predictive multi-task machine learning method1 with novel MR-based multivariate morphometric surface map of the hippocampus2 to predict future cognitive scores of patients. Previous work by Zhou et al.1 has shown that a multi-task learning framework that performs prediction of all future time points (or tasks) simultaneously can be used to encode both sparsity as well as temporal smoothness. They showed that this can be used in predicting cognitive outcomes of Alzheimers Disease Neuroimaging Initiative (ADNI) subjects based on FreeSurfer-based baseline MRI features, MMSE score demographic information and ApoE status. Whilst volumetric information may hold generalized information on brain status, we hypothesized that hippocampus specific information may be more useful in predictive modeling of AD. To this end, we applied Shi et al.2s recently developed multivariate tensor-based (mTBM) parametric surface analysis method to extract features from the hippocampal surface. We show that by combining the power of the multi-task framework with the sensitivity of mTBM features of the hippocampus surface, we are able to improve significantly improve predictive performance of ADAS cognitive scores 6, 12, 24, 36 and 48 months from baseline.

  13. Evaluating the Predictive Power of Multivariate Tensor-based Morphometry in Alzheimers Disease Progression via Convex Fused Sparse Group Lasso.

    Science.gov (United States)

    Tsao, Sinchai; Gajawelli, Niharika; Zhou, Jiayu; Shi, Jie; Ye, Jieping; Wang, Yalin; Lepore, Natasha

    2014-03-21

    Prediction of Alzheimers disease (AD) progression based on baseline measures allows us to understand disease progression and has implications in decisions concerning treatment strategy. To this end we combine a predictive multi-task machine learning method 1 with novel MR-based multivariate morphometric surface map of the hippocampus 2 to predict future cognitive scores of patients. Previous work by Zhou et al. 1 has shown that a multi-task learning framework that performs prediction of all future time points (or tasks) simultaneously can be used to encode both sparsity as well as temporal smoothness. They showed that this can be used in predicting cognitive outcomes of Alzheimers Disease Neuroimaging Initiative (ADNI) subjects based on FreeSurfer-based baseline MRI features, MMSE score demographic information and ApoE status. Whilst volumetric information may hold generalized information on brain status, we hypothesized that hippocampus specific information may be more useful in predictive modeling of AD. To this end, we applied Shi et al. 2 s recently developed multivariate tensor-based (mTBM) parametric surface analysis method to extract features from the hippocampal surface. We show that by combining the power of the multi-task framework with the sensitivity of mTBM features of the hippocampus surface, we are able to improve significantly improve predictive performance of ADAS cognitive scores 6, 12, 24, 36 and 48 months from baseline.

  14. Allopurinol Against Progression of Chronic Kidney Disease.

    Science.gov (United States)

    Golmohammadi, Sima; Almasi, Afshin; Manouchehri, M; Omrani, Hamid Reza; Zandkarimi, Mohammad Reza

    2017-07-01

    Hyperuricemia is common in approximately 50% of patients with kidney failure due to decreased uric acid excretion, and it has been recently known as an independent factor in the progression of renal insufficiency. Allopurinol inhibits the production of uric acid. The aim of this study was to evaluate the effect of allopurinol on chronic kidney disease progression. In a clinical trial, patients with stages 3 and 4 of chronic kidney disease were divided into two groups to receive allopurinol, 100 mg, daily and placebo for 12 months. Patients' kidney function and serum uric acid levels were assessed at baseline and 3, 6, and 12 months after initial administration. Subgroups of patients with severe and mild glomerular filtration rate (GFR) impairment (GFR, 15 mL/min/1.73 m2 to 30 mL/min/1.73 m2 and 30 mL/min/1.73 m2 to 60 mL/min/1.73 m2, respectively), were compared between the groups. Serum uric acid levels decreased significantly during after 12 months of allopurinol administration (P = .004). In patients with severe GFR impairment, serum creatinine levels did not decrease significantly and there was no significant increase in GFR, but in those with mild GFR impairment, serum creatinine levels decreased and GFR increase significantly (P chronic kidney disease progression and could be administered with other effective medications for controlling the kidney disease.

  15. Progress in genetics of coronary artery disease

    African Journals Online (AJOL)

    Radwa Gamal

    Progress in genetics of coronary artery disease. To the Editor. Coronary Heart Disease (CHD) is the leading cause of mortality and morbidity worldwide [1] and it is a result of coronary artery disease (CAD). Coronary artery disease refers to the build-up of atherosclerotic plaque in the blood vessels that supply oxygen.

  16. 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

  17. Early disease progression of Hurler syndrome.

    Science.gov (United States)

    Kiely, Bridget T; Kohler, Jennifer L; Coletti, Hannah Y; Poe, Michele D; Escolar, Maria L

    2017-02-14

    Newborn screening for mucopolysaccharidosis type I (MPS I) shows promise to improve outcomes by facilitating early diagnosis and treatment. However, diagnostic tests for MPS I are of limited value in predicting whether a child will develop severe central nervous system disease associated with Hurler syndrome, or minimal or no central nervous system involvement associated with the attenuated phenotypes (Hurler-Scheie and Scheie syndromes). Given that the optimal treatment differs between Hurler syndrome and the attenuated MPS I phenotypes, the absence of a reliable prognostic biomarker complicates clinical decision making for infants diagnosed through newborn screening. Information about the natural history of Hurler syndrome may aid in the management of affected infants, contribute to treatment decisions, and facilitate evaluation of treatment effectiveness and prognosis. Thus, the aim of this study was to characterize the progression and timing of symptom onset in infants with Hurler syndrome. Clinical data from 55 patients evaluated at a single center were retrospectively reviewed. Information about each child's medical history was obtained following a standardized protocol including a thorough parent interview and the review of previous medical records. All patients underwent systematic physical and neurodevelopmental evaluations by a multidisciplinary team. Nearly all patients (98%) showed signs of disease during the first 6 months of life. Common early disease manifestations included failed newborn hearing screen, respiratory symptoms, difficulty latching, and otitis media. Other symptoms such as kyphosis, corneal clouding, cardiac disease, joint restrictions, and enlarged head circumference typically appeared slightly later (median age, 8-10 months). During the first 12 months, gross motor development was the most severely affected area of functioning, and a significant number of patients also experienced language delays. Cognition was typically preserved

  18. Amyotrophic lateral sclerosis disease progression model.

    Science.gov (United States)

    Gomeni, Roberto; Fava, Maurizio

    2014-03-01

    Our objective was to develop: 1) a longitudinal model to describe amyotrophic lateral sclerosis (ALS) disease progression using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R); and 2) a probabilistic model to estimate the presence of clusters of trajectories in ALS progression over 12 months of treatment. Three hundred and thirty-eight patients treated with placebo from the PRO-ACT database were included in the analyses. A non-linear Weibull model best described the ALS disease progression, and a stepwise logistic regression approach was used to select the variables predicting a slow or fast disease progression. Results identified two clusters of trajectories: 1) slow disease progressors (46% of patients with a change from baseline of 13%); 2) fast disease progressors (54% of patients with a change from baseline of 49%). ROC curve analysis estimated the optimal cut-off for classifying patients as slow or fast disease progressors given ALSFRS-R measurements at 2-4 weeks. Results showed that the degree of ALS disease progression quantified by the ALSFRS-R symptomatic change on placebo is highly heterogeneous. In conclusion, this finding indicates the potential interest of disease progression models for implementing a population enrichment strategy to control the level of heterogeneity in the patients included in new trials.

  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. Progress on Autosomal Dominant Polycystic Kidney Disease ...

    African Journals Online (AJOL)

    Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most common life threatening hereditary disease of the kidney. It is a systemic disease characterized by multiple, bilateral renal cysts that result in massive renal enlargement and progressive functional impairment. This review discusses the current ...

  1. Alternative end points to evaluate a therapeutic strategy in advanced colorectal cancer: evaluation of progression-free survival, duration of disease control, and time to failure of strategy--an Aide et Recherche en Cancerologie Digestive Group Study.

    Science.gov (United States)

    Chibaudel, Benoist; Bonnetain, Franck; Shi, Qian; Buyse, Marc; Tournigand, Christophe; Sargent, Daniel J; Allegra, Carmen J; Goldberg, Richard M; de Gramont, Aimery

    2011-11-01

    Progression-free survival (PFS) is not an optimal end point to evaluate therapeutic strategies in advanced colorectal cancer (ACRC). Therefore, composite end points have been proposed to evaluate a chemotherapy strategy when sequential treatments are available: duration of disease control (DDC) and time to failure of strategy (TFS). The goal of this study was to evaluate these alternative end points and their potential surrogacy for overall survival (OS). We pooled individual patient data from three randomized trials evaluating chemotherapy strategy, which accrued 1,042 patients with previously untreated ACRC. In these trials, first-line treatment was either oxaliplatin- or irinotecan-based chemotherapy. Compared with TFS, DDC included neither time interval between progression and next sequence of treatment nor time to progression if the best result of the next sequence of treatment was progression. There was good correlation between DDC and OS (correlation of median: r, 0.62; correlation of hazard ratio [HR]: adjusted copula R(2), 0.72) and between TFS and OS (correlation of median: r, 0.59; correlation of HR: adjusted copula R(2), 0.67). There was no correlation between PFS and OS (correlation of median: r, 0.45; correlation of HR: adjusted copula R(2), 0.47). DDC and TFS roughly achieved the same results. Both are acceptable new end points to evaluate a therapeutic strategy in ACRC. Although TFS achieved a pragmatic evaluation of a multiline strategy, DDC captured the effect of a specific sequence in a therapeutic strategy.

  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. Differential distribution of striatal [123I]β-CIT in Parkinson's disease and progressive supranuclear palsy, evaluated with single-photon emission tomography

    International Nuclear Information System (INIS)

    Messa, C.; Volonte, M.A.; Fazio, F.; Zito, F.; Carpinelli, A.; D'Amico, A.; Rizzo, G.; Moresco, R.M.; Paulesu, E.; Franceschi, M.; Lucignani, G.

    1998-01-01

    Functional imaging of the presynaptic dopaminergic activity using single-photon emission tomography (SPET) and iodine-123 labelled 2-β-carboxymethoxy-3-β-(4-iodophenyl)tropane ([ 123 I]β-CIT) is important for the assessment of disease severity and progression in patients with Parkinson's disease (PD). However, its capability to discriminate between different extrapyramidal disorders has not yet been assessed. The aim of this study was to evaluate the possibility of differentiating patients with PD and with progressive supranuclear palsy (PSP) by means of this method. The distribution of [ 123 I]β-CIT in the basal ganglia was assessed in six normal subjects, 13 petients with PD and five patients with PSP in whom the disease was mild. SPET images were obtained 24±2 h after i.v. injection of the tracer using a brain-dedicated system (CERASPECT). MR and SPET images were co-registered in four normal subjects and used to define a standard set of 16 circular regions of interest (ROIs) on the slice showing the highest striatal activity. The basal ganglia ROIs corresponded to (1) the head of caudate, (2) a region of transition between the head of caudate and the anterior putamen, (3) the anterior putamen and (4) the posterior putamen. A ratio of specific to non-displaceable striatal uptake was calculated normalising the activity of the basal ganglia ROIs to that of the occipital cortex (V3''). ANOVA revealed a global reduction of V3'' in all ROIs of PD and PSP patients compared with normal controls (P 123 I]β-CIT distribution in discrete striatal areas provides information on the relative caudate-putamen damage, with different values being obtained in patients clinically diagnosed as having either PD or PSP. (orig.)

  4. 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.

  5. 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...

  6. High affinity radiopharmaceuticals based upon lansoprazole for PET imaging of aggregated tau in Alzheimer's disease and progressive supranuclear palsy: synthesis, preclinical evaluation, and lead selection.

    Science.gov (United States)

    Fawaz, Maria V; Brooks, Allen F; Rodnick, Melissa E; Carpenter, Garrett M; Shao, Xia; Desmond, Timothy J; Sherman, Phillip; Quesada, Carole A; Hockley, Brian G; Kilbourn, Michael R; Albin, Roger L; Frey, Kirk A; Scott, Peter J H

    2014-08-20

    Abnormally aggregated tau is the hallmark pathology of tauopathy neurodegenerative disorders and is a target for development of both diagnostic tools and therapeutic strategies across the tauopathy disease spectrum. Development of carbon-11- or fluorine-18-labeled radiotracers with appropriate affinity and specificity for tau would allow noninvasive quantification of tau burden using positron emission tomography (PET) imaging. We have synthesized [(18)F]lansoprazole, [(11)C]N-methyl lansoprazole, and [(18)F]N-methyl lansoprazole and identified them as high affinity radiotracers for tau with low to subnanomolar binding affinities. Herein, we report radiosyntheses and extensive preclinical evaluation with the aim of selecting a lead radiotracer for translation into human PET imaging trials. We demonstrate that [(18)F]N-methyl lansoprazole, on account of the favorable half-life of fluorine-18 and its rapid brain entry in nonhuman primates, favorable kinetics, low white matter binding, and selectivity for binding to tau over amyloid, is the lead compound for progression into clinical trials.

  7. High Affinity Radiopharmaceuticals Based Upon Lansoprazole for PET Imaging of Aggregated Tau in Alzheimer’s Disease and Progressive Supranuclear Palsy: Synthesis, Preclinical Evaluation, and Lead Selection

    Science.gov (United States)

    2014-01-01

    Abnormally aggregated tau is the hallmark pathology of tauopathy neurodegenerative disorders and is a target for development of both diagnostic tools and therapeutic strategies across the tauopathy disease spectrum. Development of carbon-11- or fluorine-18-labeled radiotracers with appropriate affinity and specificity for tau would allow noninvasive quantification of tau burden using positron emission tomography (PET) imaging. We have synthesized [18F]lansoprazole, [11C]N-methyl lansoprazole, and [18F]N-methyl lansoprazole and identified them as high affinity radiotracers for tau with low to subnanomolar binding affinities. Herein, we report radiosyntheses and extensive preclinical evaluation with the aim of selecting a lead radiotracer for translation into human PET imaging trials. We demonstrate that [18F]N-methyl lansoprazole, on account of the favorable half-life of fluorine-18 and its rapid brain entry in nonhuman primates, favorable kinetics, low white matter binding, and selectivity for binding to tau over amyloid, is the lead compound for progression into clinical trials. PMID:24896980

  8. Evaluating the SERCA2 and VEGF mRNAs as Potential Molecular Biomarkers of the Onset and Progression in Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Federica Cesca

    Full Text Available Abnormalities of intracellular Ca2+ homeostasis and signalling as well as the down-regulation of neurotrophic factors in several areas of the central nervous system and in peripheral tissues are hallmarks of Huntington's disease (HD. As there is no therapy for this hereditary, neurodegenerative fatal disease, further effort should be made to slow the progression of neurodegeneration in patients through the definition of early therapeutic interventions. For this purpose, molecular biomarker(s for monitoring disease onset and/or progression and response to treatment need to be identified. In the attempt to contribute to the research of peripheral candidate biomarkers in HD, we adopted a multiplex real-time PCR approach to analyse the mRNA level of targeted genes involved in the control of cellular calcium homeostasis and in neuroprotection. For this purpose we recruited a total of 110 subjects possessing the HD mutation at different clinical stages of the disease and 54 sex- and age-matched controls. This study provides evidence of reduced transcript levels of sarco-endoplasmic reticulum-associated ATP2A2 calcium pump (SERCA2 and vascular endothelial growth factor (VEGF in peripheral blood mononuclear cells (PBMCs of manifest and pre-manifest HD subjects. Our results provide a potentially new candidate molecular biomarker for monitoring the progression of this disease and contribute to understanding some early events that might have a role in triggering cellular dysfunctions in HD.

  9. The urine albumin-to-creatinine ratio is a reliable indicator for evaluating complications of chronic kidney disease and progression in IgA nephropathy in China

    Directory of Open Access Journals (Sweden)

    Lu Huan

    2016-05-01

    Full Text Available OBJECTIVE: This study investigated the correlation between the albumin-to-creatinine ratio in the urine and 24-hour urine proteinuria and whether the ratio can predict chronic kidney disease progression even more reliably than 24-hour proteinuria can, particularly in primary IgA nephropathy. METHODS: A total of 182 patients with primary IgA nephropathy were evaluated. Their mean urine albumin-to-creatinine ratio and 24-hour proteinuria were determined during hospitalization. Blood samples were also analyzed. Follow-up data were recorded for 44 patients. A cross-sectional study was then conducted to test the correlation between these parameters and their associations with chronic kidney disease complications. Subsequently, a canonical correlation analysis was employed to assess the correlation between baseline proteinuria and parameters of the Oxford classification. Finally, a prospective observational study was performed to evaluate the association between proteinuria and clinical outcomes. Our study is registered in the Chinese Clinical Trial Registry, and the registration number is ChiCTR-OCH-14005137. RESULTS: A strong correlation (r=0.81, p<0.001 was found between the ratio and 24-hour proteinuria except in chronic kidney disease stage 5. First-morning urine albumin-to-creatinine ratios of ≥125.15, 154.44 and 760.31 mg/g reliably predicted equivalent 24-hour proteinuria ‘thresholds’ of ≥0.15, 0.3 and 1.0 g/24 h, respectively. In continuous analyses, the albumin-to-creatinine ratio was significantly associated with anemia, acidosis, hypoalbuminemia, hyperphosphatemia, hyperkalemia, hypercholesterolemia and higher serum cystatin C. However, higher 24-hour proteinuria was only associated with hypoalbuminemia and hypercholesterolemia. Higher tubular atrophy and interstitial fibrosis scores were also associated with a greater albumin-to-creatinine ratio, as observed in the canonical correlation analysis. Finally, the albumin

  10. Vascular Care in Patients With Alzheimer Disease With Cerebrovascular Lesions Slows Progression of White Matter Lesions on MRI The Evaluation of Vascular Care in Alzheimer's Disease (EVA) Study

    NARCIS (Netherlands)

    Richard, Edo; Gouw, Alida A.; Scheltens, Philip; van Gool, Willem A.

    2010-01-01

    Background and Purpose-White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in

  11. Vascular Care in Patients With Alzheimer Disease With Cerebrovascular Lesions Slows Progression of White Matter Lesions on MRI The Evaluation of Vascular Care in Alzheimer's Disease (EVA) Study

    NARCIS (Netherlands)

    Richard, E.; Gouw, A.A.; Scheltens, P.; van Gool, W.A.

    2010-01-01

    Background and Purpose:White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in

  12. 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......, 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....... 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

  13. 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.

  14. Progress of international evaluation cooperation

    Energy Technology Data Exchange (ETDEWEB)

    Shibata, Keiichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1998-03-01

    The international evaluation cooperation started to remove the differences among major nuclear data libraries such as JENDL, ENDF, and JEF. The results obtained from the cooperation have been used to improve the quality of the libraries. This paper describes the status of the ongoing projects and several remarkable results so far obtained from the projects already finished. (author)

  15. The role of CA 125 in the early diagnosis of progressive disease in ovarian cancer

    NARCIS (Netherlands)

    van der Burg, M. E.; Lammes, F. B.; Verweij, J.

    1990-01-01

    The role of CA 125 determination in diagnosing progression of ovarian cancer was evaluated in 98 patients of whom forty-nine had progressive disease. An elevated CA 125 level at the time of progression was found in 36 (73%) patients. In 31 (63%) patients CA 125 increase preceded clinical progression

  16. A Study of Alternate Biomarkers in HIV Disease and Evaluating their Efficacy in Predicting T CD4+ Cell Counts and Disease Progression in Resource Poor Settings in Highly Active Antiretroviral Therapy (HAART) Era.

    Science.gov (United States)

    Ramana, K V; Sabitha, V; Rao, Ratna

    2013-07-01

    Human Immunodeficiency Virus (HIV), the causative agent of AIDS, has been a challenge to medical fraternity since it was first discovered in 1983. About 40 million people are living with HIV infection globally and 99% of the infected people are in south East Asia (SEA). Traditionally, HIV disease and progression, initiation of HAART and response to therapy is monitored by assessing in regular intervals, the T CD4+ cell counts and plasma HIV/RNA viral load. Resource poor, low and low - middle income group countries still have no finances to acquire infrastructure and scientific technology for performing such tests. Since very few studies are available, they have demonstrated the role of alternate biomarkers that can be used to predict CD4 cell counts and thereby, monitor HIV disease progression and HAART. We aimed to measure certain haematological parameters in HIV seropositive patients and to evaluate their efficacy in predicting TCD4+ cell counts. The study group included 250 HIV seropositive patients with an age range of 18-65 years. 140(56%) males and 110(44%) females were included in the study. Absolute TCD4+cell counts and CD8+T cell counts were measured by using a flow cytometer. (MMWR Recommendations and Reports, 1992) TLC; HB%, AEC and ESR were estimated by using conventional haematological methods. CRP was evaluated by latex agglutination test (Immuno CRP Latex Agglutination Test). Among the tested haematological markers, a TLC of counts of counts showed high specificities of 84.09% and 94.32% respectively in predicting CD4 counts which were below 350 cells/mm(3). ESR with 98.98% sensitivity and AEC which had 83.67% sensitivity were able to predict CD4 counts of counts of more than 550 cells/mm(3), Blood Haemoglobin which was less than 10 g%, ESR which measured more than 20 mm, CRP values of >1.2 and TLC of counts of < 350 and <200 cells/mm(3).

  17. Evaluation of Crohn's disease

    International Nuclear Information System (INIS)

    Fishman, E.K.; Jones, B.

    1988-01-01

    The application of CT to the evaluation of inflammatory disease of the small bowel and colon has evolved in parallel with the development of scanners with shorter scan times and higher resolution and with increasing sophistication of the radiologist in the use of this imaging technique. Although high-quality barium studies remain the examination of choice for the demonstration of mucosal disease, CT is now considered the gold standard for evaluating the extraluminal components of the disease process. This chapter reviews the typical CT findings and possible complications of Crohn's disease and discusses the potential impact of CT on the clinical management of the patient with Crohn's disease

  18. Nutritional status is associated with disease progression in very mild Alzheimer disease.

    Science.gov (United States)

    Ousset, Pierre-Jean; Nourhashemi, Fati; Reynish, Emma; Vellas, Bruno

    2008-01-01

    The objective of this study is to identify, in a sample of very mild Alzheimer disease (AD) patients, factors associated with disease progression. The authors followed 160 AD patients from a multicenter cohort with a Clinical Dementia Rating (CDR) of 0.5, corresponding to very mild AD but with impairment insufficient to be classified as dementia. Patients with disease progression were defined as those with CDR> or =1 at 1 year; those with no progression (stable) remained at CDR 0.5. The baseline characteristics of these 2 groups of patients were compared in search of predictors of progression. After a 1-year follow-up, 84 (52.5%) of the patients remained stable, CDR 0.5; 76 (47.5%) progressed to a CDR score > or =1. A baseline lower nutritional status assessed by the Mini Nutritional Assessment [odds ratio 0.80, 95% confidence interval (0.68-0.94), P=0.007] and a lower cognitive performance on the Alzheimer Disease Assessment Scale [odds ratio 1.22, 95% confidence interval (1.07-1.39), P=0.003] were found as predictors of progression. The results suggest that clinical assessment of nutritional status, along with cognitive data, may help detect patients at risk of progression in very early AD. Nutritional assessment should therefore form part of clinical evaluation of patients with AD at an early stage of the disease.

  19. Predictors of autosomal dominant polycystic kidney disease progression.

    Science.gov (United States)

    Schrier, Robert W; Brosnahan, Godela; Cadnapaphornchai, Melissa A; Chonchol, Michel; Friend, Keith; Gitomer, Berenice; Rossetti, Sandro

    2014-11-01

    Autosomal dominant polycystic kidney disease is a genetic disorder associated with substantial variability in its natural course within and between affected families. Understanding predictors for rapid progression of this disease has become increasingly important with the emergence of potential new treatments. This systematic review of the literature since 1988 evaluates factors that may predict and/or effect autosomal dominant polycystic kidney disease progression. Predicting factors associated with early adverse structural and/or functional outcomes are considered. These factors include PKD1 mutation (particularly truncating mutation), men, early onset of hypertension, early and frequent gross hematuria, and among women, three or more pregnancies. Increases in total kidney volume and decreases in GFR and renal blood flow greater than expected for a given age also signify rapid disease progression. Concerning laboratory markers include overt proteinuria, macroalbuminuria, and perhaps, elevated serum copeptin levels in affected adults. These factors and others may help to identify patients with autosomal dominant polycystic kidney disease who are most likely to benefit from early intervention with novel treatments. Copyright © 2014 by the American Society of Nephrology.

  20. 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

  1. Nox-4 and progressive kidney disease.

    Science.gov (United States)

    Thallas-Bonke, Vicki; Jandeleit-Dahm, Karin A M; Cooper, Mark E

    2015-01-01

    Nox-4 is a member of the NADPH oxidase (Nox) family of enzymes implicated in reactive oxygen species generation. Nox-4 is distributed in many tissues; however, its physiological functions remain poorly understood. In contrast to other Nox isoforms, it is unique in that it produces large amounts of hydrogen peroxide constitutively and does not require other cytosolic oxidase components for its activation. This review highlights the recent developments in Nox-4 research and progressive kidney disease as well as the potential of new Nox-4 inhibitors to reduce renal damage. Recently, Nox-4 was shown to be implicated in kidney diseases such as diabetic nephropathy. Nox-4 has been identified as playing a role in damage to the kidney induced by hyperglycaemia and other major pathways of renal damage, including advanced glycation end-products, the renin-angiotensin system, TGF-β and protein kinase C. The role of Nox-4 as a target for renoprotection remains controversial, although recent positive preclinical data have stimulated increased interest in inhibiting the enzyme in clinical trials of renal disease.

  2. Nondestructive Evaluation Program: Progress in 1986

    International Nuclear Information System (INIS)

    1987-07-01

    The increasing cost of equipment for power generating plants and the potential increases in productivity and safety available through rapidly developing Nondestructive Evaluation (NDE) technology led EPRI to initiate a Nondestructive Evaluation Program in 1974. To date, the major focus has been on light water reactor inspection problems; however, increased application to other systems is now under way. This report presents a comprehensive review of the EPRI effort in the NDE area. Most of the report consists of contractor-supplied progress reports on each current project. An organizational plan of the program is presented in overview. In addition, organization from several viewpoints is presented, e.g., in-service inspection operators, R and D personnel, and utility representatives. The report summarizes significant progress made since the previous EPRI Special Report NP-4315-SR was issued in May 1986. Section 1 contains information about the program organization, and the sections that follow contain contractor-supplied progress reports of each current project. The progress reports are grouped by plant components - pipe, pressure vessel, steam generator and boiler tubes, and turbine. In addition, Part 6 is devoted to discussions of technology transfer

  3. 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.

  4. Generalizability of the Disease State Index Prediction Model for Identifying Patients Progressing from Mild Cognitive Impairment to Alzheimer's Disease

    NARCIS (Netherlands)

    Hall, A.; Munoz-Ruiz, M.; Mattila, J.; Koikkalainen, J.; Tsolaki, M.; Mecocci, P.; Kloszewska, I.; Vellas, B.; Lovestone, S.; Visser, P.J.; Lotjonen, J.; Soininen, H.

    2015-01-01

    Background: The Disease State Index (DSI) prediction model measures the similarity of patient data to diagnosed stable and progressive mild cognitive impairment (MCI) cases to identify patients who are progressing to Alzheimer's disease. Objectives: We evaluated how well the DSI generalizes across

  5. 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.

  6. [Research progress on quality evaluation of saffron].

    Science.gov (United States)

    Liu, Jiang-di; Ouyang, Zhen; Yang, Bin

    2017-02-01

    Saffron, a precious spice and a traditional medicinal herb in the international trade market, has attracted much attention about its quality evaluation.Saffron has been successfully cultivated in some areas in China,such as Shanghai, Zhejiang, Jiangsu, but few studies were focused on the quality difference between saffron cultivated in China and in foreign countries, which obstructed the entrance of saffron cultivated in China into international trade market. The paper is to review the current research progress on quality evaluation of saffron from the following respects: the chemical composition, the identification of authenticity and adulterants, the detection of artificial colorants, the indexes and methods of quality evaluation,the quality evaluation of different specifications in the international trade market, and the parameters which affected the quality of saffron. Copyright© by the Chinese Pharmaceutical Association.

  7. Visual Evaluation of Medial Temporal Lobe Atrophy as a Clinical Marker of Conversion from Mild Cognitive Impairment to Dementia and for Predicting Progression in Patients with Mild Cognitive Impairment and Mild Alzheimer's Disease.

    Science.gov (United States)

    Persson, Karin; Barca, Maria Lage; Eldholm, Rannveig Sakshaug; Cavallin, Lena; Šaltytė Benth, Jūratė; Selbæk, Geir; Brækhus, Anne; Saltvedt, Ingvild; Engedal, Knut

    2017-01-01

    To evaluate whether visual assessment of medial temporal lobe atrophy (vaMTA) can predict 2-year conversion from mild cognitive impairment (MCI) to dementia and progression of MCI and Alzheimer's disease dementia as measured by the Clinical Dementia Rating Scale Sum of Boxes score (CDR-SB). vaMTA was performed in 94 patients with MCI according to the Winblad criteria and in 124 patients with AD according to ICD-10 and NINCDS-ADRDA criteria. Demographic data, the Consortium to Establish a Registry for Alzheimer's Disease 10-word delayed recall, APOE ɛ4 status, Cornell Scale for Depression in Dementia, and comorbid hypertension were used as covariates. vaMTA was associated with MCI conversion in an unadjusted model but not in an adjusted model (p = 0.075), where delayed recall and APOE ɛ4 status were significant predictors. With CDR-SB change as the outcome, an interaction between vaMTA and diagnosis was found, but in the adjusted model only delayed recall and age were significant predictors. For vaMTA below 2, the association between vaMTA and CDR-SB change differed between diagnostic groups. Similar results were found based on a trajectory analysis. In adjusted models, memory function, APOE ɛ4 status and age were significant predictors of disease progression, not vaMTA. The association between vaMTA and CDR-SB change was different in patients with MCI and Alzheimer's disease dementia. © 2017 S. Karger AG, Basel.

  8. 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 ...

  9. Progressive myoclonic epilepsy due to Gaucher's disease in an adult.

    Science.gov (United States)

    King, J O

    1975-01-01

    A 39 year old Jewish male with a 22 year history of progressive myoclonic epilepsy was found to have Gaucher cells in his sternal bone marrow. The diagnosis of Gaucher's disease was confirmed by the demonstration of beta-glucosidase deficiency in fibroblasts. Although neurological involvement is extremely rare in adults with Gaucher's disease, this disease is another lipidosis which should be considered in patients with progressive myoclonic epilepsy. Images PMID:1185223

  10. 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

  11. 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 ...

  12. Progress and challenges in RNA interference therapy for Huntington disease.

    Science.gov (United States)

    Harper, Scott Q

    2009-08-01

    Huntington disease is an incurable, dominant neurodegenerative disorder caused by polyglutamine repeat expansion in the huntingtin protein. Reducing mutant huntingtin expression may offer a treatment for Huntington disease. RNA interference has emerged as a powerful method to silence dominant disease genes. As such, it is being developed as a prospective Huntington disease therapy. Here I discuss the current progress and important remaining challenges of RNA interference therapy for Huntington disease.

  13. 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.

  14. Sludge Treatment Evaluation: 1992 Technical progress

    International Nuclear Information System (INIS)

    Silva, L.J.; Felmy, A.R.; Ding, E.R.

    1993-01-01

    This report documents Fiscal Year 1992 technical progress on the Sludge Treatment Evaluation Task, which is being conducted by Pacific Northwest Laboratory. The objective of this task is to develop a capability to predict the performance of pretreatment processes for mixed radioactive and hazardous waste stored at Hanford and other US Department of Energy (DOE) sites. Significant cost savings can be achieved if radionuclides and other undesirable constituents can be effectively separated from the bulk waste prior to final treatment and disposal. This work is initially focused on chemical equilibrium prediction of water washing and acid or base dissolution of Hanford single-shell tank (SST) sludges, but may also be applied to other steps in pretreatment processes or to other wastes. Although SST wastes contain many chemical species, there are relatively few constituents -- Na, Al, NO 3 , NO 2 , PO 4 , SO 4 , and F -- contained in the majority of the waste. These constituents comprise 86% and 74% of samples from B-110 and U-110 SSTS, respectively. The major radionuclides of interest (Cs, Sr, Tc, U) are present in the sludge in small molal quantities. For these constituents, and other important components that are present in small molal quantities, the specific ion-interaction terms used in the Pitzer or NRTL equations may be assumed to be zero for a first approximation. Model development can also be accelerated by considering only the acid or base conditions that apply for the key pretreatment steps. This significantly reduces the number of chemical species and chemical reactions that need to be considered. Therefore, significant progress can be made by developing all the specific ion interactions for a base model and an acid dissolution model

  15. 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.

  16. 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.......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....

  17. Biomarkers for disease progression and AAV therapeutic efficacy in feline Sandhoff disease.

    Science.gov (United States)

    Bradbury, Allison M; Gray-Edwards, Heather L; Shirley, Jamie L; McCurdy, Victoria J; Colaco, Alexandria N; Randle, Ashley N; Christopherson, Pete W; Bird, Allison C; Johnson, Aime K; Wilson, Diane U; Hudson, Judith A; De Pompa, Nicholas L; Sorjonen, Donald C; Brunson, Brandon L; Jeyakumar, Mylvaganam; Platt, Frances M; Baker, Henry J; Cox, Nancy R; Sena-Esteves, Miguel; Martin, Douglas R

    2015-01-01

    The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are progressive neurodegenerative disorders that are caused by a mutation in the enzyme β-N-acetylhexosaminidase (Hex). Due to the recent emergence of novel experimental treatments, biomarker development has become particularly relevant in GM2 gangliosidosis as an objective means to measure therapeutic efficacy. Here we describe blood, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), and electrodiagnostic methods for evaluating disease progression in the feline SD model and application of these approaches to assess AAV-mediated gene therapy. SD cats were treated by intracranial injections of the thalami combined with either the deep cerebellar nuclei or a single lateral ventricle using AAVrh8 vectors encoding feline Hex. Significantly altered in untreated SD cats, blood and CSF based biomarkers were largely normalized after AAV gene therapy. Also reduced after treatment were expansion of the lysosomal compartment in peripheral blood mononuclear cells and elevated activity of secondary lysosomal enzymes. MRI changes characteristic of the gangliosidoses were documented in SD cats and normalized after AAV gene therapy. The minimally invasive biomarkers reported herein should be useful to assess disease progression of untreated SD patients and those in future clinical trials. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. 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

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

    African Journals Online (AJOL)

    of patients, and just over half of these affect only the brain.1,2. Presentation is often late, with mortality rates in excess of 60%.2. PTLD comprises a heterogeneous group of lymphoproliferative diseases, ranging from the early indolent disorders that resemble infectious mononucleosis, through to polymorphic PTLD and onto.

  20. Early disease progression of Hurler syndrome

    OpenAIRE

    Kiely, Bridget T.; Kohler, Jennifer L.; Coletti, Hannah Y.; Poe, Michele D.; Escolar, Maria L.

    2017-01-01

    Background Newborn screening for mucopolysaccharidosis type I (MPS I) shows promise to improve outcomes by facilitating early diagnosis and treatment. However, diagnostic tests for MPS I are of limited value in predicting whether a child will develop severe central nervous system disease associated with Hurler syndrome, or minimal or no central nervous system involvement associated with the attenuated phenotypes (Hurler?Scheie and Scheie syndromes). Given that the optimal treatment differs be...

  1. Recent achievements in restorative neurology: Progressive neuromuscular diseases

    International Nuclear Information System (INIS)

    Dimitrijevic, M.R.; Kakulas, B.A.; Vrbova, G.

    1986-01-01

    This book contains 27 chapters. Some of the chapter titles are: Computed Tomography of Muscles in Neuromuscular Disease; Mapping the Genes for Muscular Dystrophy; Trophic Factors and Motor Neuron Development; Size of Motor Units and Firing Rate in Muscular Dystrophy; Restorative Possibilities in Relation to the Pathology of Progressive Neuromuscular Disease; and An Approach to the Pathogenesis of some Congenital Myopathies

  2. 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.

  3. In vivo evaluation of early disease progression by X-ray phase-contrast imaging in the adjuvant-induced arthritic rat

    International Nuclear Information System (INIS)

    Yu, Yongqiang; Xiong, Zhuang; Lv, Yizhong; Qian, Yinfeng; Jiang, Shiping; Tian, Yulian

    2006-01-01

    To study the early change of bone matrix and soft tissue around articulation in adjuvant-induced arthritic (AIA) rats non-invasively by X-ray phase-contrast imaging (XPCI), a new imaging method. Adjuvant-induced arthritis was established in male Sprague-Dawley (SD) rats (n=6, age 40 days) by subcutaneous injection of Freund's complete adjuvant (FCA) into the left hindpaw. In vivo XPCI evaluation of the early soft tissue and bone changes in AIA rats was consecutively performed and correlated with changes in volumes of right hindpaws and body weights. In comparison, the changes in the AIA rats were also evaluated with absorption-contrast imaging using the same X-ray source as XPCI and conventional radiography at the same time. After the imaging evaluation, AIA rats were subjected to histological examination. There was significant difference between the score of XPCI and the other two methods in demonstrating soft tissue (P<0.01), bone details (P<0.01) and lesions (P<0.001). By day 10 after subcutaneous injection of FCA, bone changes in the right hindpaw were not obvious, but swelling of soft tissue appeared. By day 12, bone erosion in the articular facet and the area around the articular facet, was detected, along with osteoporosis, and swelling of soft tissue was aggravated. By day 14 bone erosions became fused and expanded, especially in the margin area around the articular facet. At day 16 bone erosion still existed. Joint interspaces seemed wider than normal, and swelling of soft tissue was significant. By day 18 periosteal new bone formation was seen definitely, destruction of bone decreased, bone density around the articular was enhanced, and swelling of soft tissue was relieved. XPCI could clearly distinguish all these alterations, which could not be demonstrated by absorption-contrast imaging and conventional radiography. During the test period, the volume of the right hindpaw and the body weight of the AIA rats also changed significantly compared with the

  4. The utility of cerebral blood flow imaging in patients with the unique syndrome of progressive dementia with motor neuron disease

    International Nuclear Information System (INIS)

    Ohnishi, T.; Hoshi, H.; Jinnouchi, S.; Nagamachi, S.; Watanabe, K.; Mituyama, Y.

    1990-01-01

    Two patients presenting with progressive dementia coupled with motor neuron disease underwent brain SPECT using N-isopropyl-p iodine-123-iodoamphetamine [( 123 I]IMP). The characteristic clinical features of progressive dementia and motor neuron disease were noted. IMP SPECT also revealed reduced uptake in the bilateral frontal and temporal regions, with no reduction of uptake in the parietal, parietal-occipital regions. We conclude that IMP SPECT has potential for the evaluation of progressive dementia with motor neuron disease

  5. Analysis of genetic copy number changes in cervical disease progression

    International Nuclear Information System (INIS)

    Policht, Frank A; Song, Minghao; Sitailo, Svetlana; O'Hare, Anna; Ashfaq, Raheela; Muller, Carolyn Y; Morrison, Larry E; King, Walter; Sokolova, Irina A

    2010-01-01

    Cervical dysplasia and tumorigenesis have been linked with numerous chromosomal aberrations. The goal of this study was to evaluate 35 genomic regions associated with cervical disease and to select those which were found to have the highest frequency of aberration for use as probes in fluorescent in-situ hybridization. The frequency of gains and losses using fluorescence in-situ hybridization were assessed in these 35 regions on 30 paraffin-embedded cervical biopsy specimens. Based on this assessment, 6 candidate fluorescently labeled probes (8q24, Xp22, 20q13, 3p14, 3q26, CEP15) were selected for additional testing on a set of 106 cervical biopsy specimens diagnosed as Normal, CIN1, CIN2, CIN3, and SCC. The data were analyzed on the basis of signal mean, % change of signal mean between histological categories, and % positivity. The study revealed that the chromosomal regions with the highest frequency of copy number gains and highest combined sensitivity and specificity in high-grade cervical disease were 8q24 and 3q26. The cytological application of these two probes was then evaluated on 118 ThinPrep™ samples diagnosed as Normal, ASCUS, LSIL, HSIL and Cancer to determine utility as a tool for less invasive screening. Using gains of either 8q24 or 3q26 as a positivity criterion yielded specificity (Normal +LSIL+ASCUS) of 81.0% and sensitivity (HSIL+Cancer) of 92.3% based on a threshold of 4 positive cells. The application of a FISH assay comprised of chromosomal probes 8q24 and 3q26 to cervical cytology specimens confirms the positive correlation between increasing dysplasia and copy gains and shows promise as a marker in cervical disease progression

  6. Development of a Conceptual Model of Disease Progression for Use in Economic Modeling of Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Tabberer, Maggie; Gonzalez-McQuire, Sebastian; Muellerova, Hana; Briggs, Andrew H; Rutten-van Mölken, Maureen P M H; Chambers, Mike; Lomas, David A

    2017-05-01

    To develop and validate a new conceptual model (CM) of chronic obstructive pulmonary disease (COPD) for use in disease progression and economic modeling. The CM identifies and describes qualitative associations between disease attributes, progression and outcomes. A literature review was performed to identify any published CMs or literature reporting the impact and association of COPD disease attributes with outcomes. After critical analysis of the literature, a Steering Group of experts from the disciplines of health economics, epidemiology and clinical medicine was convened to develop a draft CM, which was refined using a Delphi process. The refined CM was validated by testing for associations between attributes using data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). Disease progression attributes included in the final CM were history and occurrence of exacerbations, lung function, exercise capacity, signs and symptoms (cough, sputum, dyspnea), cardiovascular disease comorbidities, 'other' comorbidities (including depression), body composition (body mass index), fibrinogen as a biomarker, smoking and demographic characteristics (age, gender). Mortality and health-related quality of life were determined to be the most relevant final outcome measures for this model, intended to be the foundation of an economic model of COPD. The CM is being used as the foundation for developing a new COPD model of disease progression and to provide a framework for the analysis of patient-level data. The CM is available as a reference for the implementation of further disease progression and economic models.

  7. Periodontal profile classes predict periodontal disease progression and tooth loss.

    Science.gov (United States)

    Morelli, Thiago; Moss, Kevin L; Preisser, John S; Beck, James D; Divaris, Kimon; Wu, Di; Offenbacher, Steven

    2018-02-01

    Current periodontal disease taxonomies have limited utility for predicting disease progression and tooth loss; in fact, tooth loss itself can undermine precise person-level periodontal disease classifications. To overcome this limitation, the current group recently introduced a novel patient stratification system using latent class analyses of clinical parameters, including patterns of missing teeth. This investigation sought to determine the clinical utility of the Periodontal Profile Classes and Tooth Profile Classes (PPC/TPC) taxonomy for risk assessment, specifically for predicting periodontal disease progression and incident tooth loss. The analytic sample comprised 4,682 adult participants of two prospective cohort studies (Dental Atherosclerosis Risk in Communities Study and Piedmont Dental Study) with information on periodontal disease progression and incident tooth loss. The PPC/TPC taxonomy includes seven distinct PPCs (person-level disease pattern and severity) and seven TPCs (tooth-level disease). Logistic regression modeling was used to estimate relative risks (RR) and 95% confidence intervals (CI) for the association of these latent classes with disease progression and incident tooth loss, adjusting for examination center, race, sex, age, diabetes, and smoking. To obtain personalized outcome propensities, risk estimates associated with each participant's PPC and TPC were combined into person-level composite risk scores (Index of Periodontal Risk [IPR]). Individuals in two PPCs (PPC-G: Severe Disease and PPC-D: Tooth Loss) had the highest tooth loss risk (RR = 3.6; 95% CI = 2.6 to 5.0 and RR = 3.8; 95% CI = 2.9 to 5.1, respectively). PPC-G also had the highest risk for periodontitis progression (RR = 5.7; 95% CI = 2.2 to 14.7). Personalized IPR scores were positively associated with both periodontitis progression and tooth loss. These findings, upon additional validation, suggest that the periodontal/tooth profile classes and the derived

  8. Progressive neuronal degeneration of childhood with liver disease

    International Nuclear Information System (INIS)

    Kendall, B.E.; Boyd, S.G.; Egger, J.; Harding, B.N.

    1987-01-01

    The clinical, electrophysiological and neuroradiological features of thirteen patients suffering from progressive neuronal degeneration of childhood with liver failure are presented. The disease commonly presents very early in life with progressive mental retardation, followed by intractable epilepsy, and should be suspected clinically especially if there is a family history of similar disorder in a sibling. On computed tomography there are low density regions, particularly in the occipital and posterior temporal lobes, involving both cortex and white matter, combined with or followed by progressive atrophy. Typical EEG findings may be confirmatory. (orig.)

  9. High Resolution Discovery Proteomics Reveals Candidate Disease Progression Markers of Alzheimer's Disease in Human Cerebrospinal Fluid.

    Directory of Open Access Journals (Sweden)

    Ronald C Hendrickson

    Full Text Available Disease modifying treatments for Alzheimer's disease (AD constitute a major goal in medicine. Current trends suggest that biomarkers reflective of AD neuropathology and modifiable by treatment would provide supportive evidence for disease modification. Nevertheless, a lack of quantitative tools to assess disease modifying treatment effects remains a major hurdle. Cerebrospinal fluid (CSF biochemical markers such as total tau, p-tau and Ab42 are well established markers of AD; however, global quantitative biochemical changes in CSF in AD disease progression remain largely uncharacterized. Here we applied a high resolution open discovery platform, dMS, to profile a cross-sectional cohort of lumbar CSF from post-mortem diagnosed AD patients versus those from non-AD/non-demented (control patients. Multiple markers were identified to be statistically significant in the cohort tested. We selected two markers SME-1 (p<0.0001 and SME-2 (p = 0.0004 for evaluation in a second independent longitudinal cohort of human CSF from post-mortem diagnosed AD patients and age-matched and case-matched control patients. In cohort-2, SME-1, identified as neuronal secretory protein VGF, and SME-2, identified as neuronal pentraxin receptor-1 (NPTXR, in AD were 21% (p = 0.039 and 17% (p = 0.026 lower, at baseline, respectively, than in controls. Linear mixed model analysis in the longitudinal cohort estimate a decrease in the levels of VGF and NPTXR at the rate of 10.9% and 6.9% per year in the AD patients, whereas both markers increased in controls. Because these markers are detected by mass spectrometry without the need for antibody reagents, targeted MS based assays provide a clear translation path for evaluating selected AD disease-progression markers with high analytical precision in the clinic.

  10. Clinical value of nutritional status in neurodegenerative diseases: What is its impact and how it affects disease progression and management?

    Science.gov (United States)

    Tsagalioti, Eftyhia; Trifonos, Christina; Morari, Aggeliki; Vadikolias, Konstantinos; Giaginis, Constantinos

    2018-04-01

    Neurodegenerative diseases constitute a major problem of public health that is associated with an increased risk of mortality and poor quality of life. Malnutrition is considered as a major problem that worsens the prognosis of patients suffering from neurodegenerative diseases. In this aspect, the present review is aimed to critically collect and summarize all the available existing clinical data regarding the clinical impact of nutritional assessment in neurodegenerative diseases, highlighting on the crucial role of nutritional status in disease progression and management. According to the currently available clinical data, the nutritional status of patients seems to play a very important role in the development and progression of neurodegenerative diseases. A correct nutritional evaluation of neurodegenerative disease patients and a right nutrition intervention is essential in monitoring their disease.

  11. Evaluation of Probabilistic Disease Forecasts.

    Science.gov (United States)

    Hughes, Gareth; Burnett, Fiona J

    2017-10-01

    The statistical evaluation of probabilistic disease forecasts often involves calculation of metrics defined conditionally on disease status, such as sensitivity and specificity. However, for the purpose of disease management decision making, metrics defined conditionally on the result of the forecast-predictive values-are also important, although less frequently reported. In this context, the application of scoring rules in the evaluation of probabilistic disease forecasts is discussed. An index of separation with application in the evaluation of probabilistic disease forecasts, described in the clinical literature, is also considered and its relation to scoring rules illustrated. Scoring rules provide a principled basis for the evaluation of probabilistic forecasts used in plant disease management. In particular, the decomposition of scoring rules into interpretable components is an advantageous feature of their application in the evaluation of disease forecasts.

  12. 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....

  13. Response of patients with Alzheimer disease to rivastigmine treatment is predicted by the rate of disease progression.

    Science.gov (United States)

    Farlow, M R; Hake, A; Messina, J; Hartman, R; Veach, J; Anand, R

    2001-03-01

    Evidence suggests that disease severity predicts the response of patients with Alzheimer disease (AD) to cholinesterase inhibitor treatment, raising the question of whether disease progression also predicts response to this treatment. To evaluate retrospectively whether rate of disease progression during placebo treatment affects response to subsequent rivastigmine tartrate therapy for patients with mild to moderately severe AD. A 26-week, open-label extension study following a 26-week, double-blind, randomized, placebo-controlled trial. Outpatient research centers at 22 sites in the United States. We studied 187 of 235 patients originally randomized to receive placebo treatment in the double-blind phase of the trial who continued with open-label (rivastigmine) extension therapy. Placebo treatment for 26 weeks followed by rivastigmine treatment, 2 to 12 mg/d, for 26 weeks. Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog), Progressive Deterioration Scale, Mini-Mental State Examination, and Global Deterioration Scale scores. Rivastigmine administration during open-label extension therapy benefited patients who had progressed slowly and those who had progressed rapidly during initial double-blind placebo treatment. Slowly progressive patients responded with a mean 1.03-point improvement in the week 26 (ie, start of open-label rivastigmine treatment) ADAS-Cog score at 12 weeks of rivastigmine treatment (week 38 of treatment; P =.02 vs week 26). However, more rapidly progressive patients had a significantly larger mean 4.97-point improvement from the week 26 ADAS-Cog score at 12 weeks (with respect to week 26 of treatment and slowly progressive patient scores, Pmild to moderate AD seems to predict response to rivastigmine treatment. Patients with more rapidly progressive disease might be particularly likely to benefit from rivastigmine therapy.

  14. 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.

  15. 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.

  16. Hypoxia — a Leading Factor of Chronic Kidney Disease Progression

    Directory of Open Access Journals (Sweden)

    O.Yu. Lysianska

    2016-02-01

    Full Text Available Recent data indicate the involvement of hypoxia in the formation of kidney fibrosis and progression of chronic renal disease. One of the main factors in the chain of damage in the tissue oxygen deficiency is a hypoxia-induced factor. Understanding the process of kidney damage during hypoxia can complement the concept of nephroprotection in patients with chronic kidney disease, will provide an opportunity to improve the guidelines on the management of this group of patients.

  17. 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.

  18. Managing Air Quality - Ongoing Evaluation of Progress

    Science.gov (United States)

    Describes the importance of evaluating if air quality programs are achieving the desired results to inform environmental program managers, regulated industry and the public, and provides EPA examples.

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

    Indian Academy of Sciences (India)

    The enormous advances in our understanding of the progression of diseases at the molecular level have been supplemented by the new field of 'molecular imaging', which provides for in vivo visualization of molecular events at the cellular level in living organisms. Molecular imaging is a noninvasive assessment of gene ...

  20. 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 ...

  1. Disease progression in multiple sclerosis: combining physicians' and patients' perspectives?

    NARCIS (Netherlands)

    Kragt, J.J.; Nielsen, J.M.; van der Linden, F.A.H.; Polman, C.H.; Uitdehaag, B.M.J.

    2011-01-01

    Background: To assess disease progression in multiple sclerosis (MS) several outcome measures are available. The interrelation of changes on different scales has not been studied extensively and the concept of combining scales has only recently been introduced in MS. Objective: To explore combining

  2. An event-based model for disease progression and its application in familial Alzheimer's disease and Huntington's disease

    NARCIS (Netherlands)

    Fonteijn, H.M.; Modat, M.; Clarkson, M.J.; Barnes, J.; Lehmann, M.; Hobbs, N.Z.; Scahill, R.I.; Tabrizi, S.J.; Ourselin, S.; Fox, N.C.; Alexander, D.C.

    2012-01-01

    Understanding the progression of neurological diseases is vital for accurate and early diagnosis and treatment planning. We introduce a new characterization of disease progression, which describes the disease as a series of events, each comprising a significant change in patient state. We provide

  3. Excercise 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

    activity) and MS disease progression. A systematic literature search was conducted in the following databases: PubMed, SweMed+, Embase, Cochrane Library, PEDro, SPORTDiscus and ISI Web of Science. Different methodological approaches to the problem have been applied including (1) longitudinal exercise...... (3) and data from the EAE model (4) indicate a possible disease-modifying effect of exercise, but the strength of the evidence limits definite conclusions. It was concluded that some evidence supports the possibility of a disease-modifying potential of exercise (or physical activity) in MS patients...

  4. 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

  5. Evaluating progress | IDRC - International Development Research ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2010-11-03

    Nov 3, 2010 ... Together, these reports and other evaluations form the basis of an Annual Learning Forum where staff push themselves to imagine new and more effective ways of working. In the coming year, we will identify priorities for new strategic evaluations to inform the implementation of the Strategic Framework ...

  6. HIV-1 Transmission, Replication Fitness and Disease Progression

    Directory of Open Access Journals (Sweden)

    Tasha Biesinger

    2008-01-01

    Full Text Available Upon transmission, human immunodeficiency virus type 1 (HIV-1 establishes infection of the lymphatic reservoir, leading to profound depletion of the memory CD4+T cell population despite the induction of the adaptive immune response. The rapid evolution and association of viral variants having distinct characteristics during different stages of infection, the level of viral burden, and rate of disease progression suggest a role for viral variants in this process. Here, we review the literature on HIV-1 variants and disease and discuss the importance of viral fitness for transmission and disease.

  7. 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.

  8. Role of Diet and Nutritional Supplements in Parkinson's Disease Progression.

    Science.gov (United States)

    Mischley, Laurie K; Lau, Richard C; Bennett, Rachel D

    2017-01-01

    The goal of this study is to describe modifiable lifestyle variables associated with reduced rate of Parkinson's disease (PD) progression. 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. 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 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). These are the first data to provide evidence that targeted nutrition is associated with the rate of PD progression.

  9. 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.

  10. 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.

  11. Disease progression and regression in sporadic small vessel disease-insights from neuroimaging.

    Science.gov (United States)

    van Leijsen, Esther M C; de Leeuw, Frank-Erik; Tuladhar, Anil M

    2017-06-01

    Cerebral small vessel disease (SVD) is considered the most important vascular contributor to the development of dementia. Comprehensive characterization of the time course of disease progression will result in better understanding of aetiology and clinical consequences of SVD. SVD progression has been studied extensively over the years, usually describing change in SVD markers over time using neuroimaging at two time points. As a consequence, SVD is usually seen as a rather linear, continuously progressive process. This assumption of continuous progression of SVD markers was recently challenged by several studies that showed regression of SVD markers. Here, we provide a review on disease progression in sporadic SVD, thereby taking into account both progression and regression of SVD markers with emphasis on white matter hyperintensities (WMH), lacunes and microbleeds. We will elaborate on temporal dynamics of SVD progression and discuss the view of SVD progression as a dynamic process, rather than the traditional view of SVD as a continuous progressive process, that might better fit evidence from longitudinal neuroimaging studies. We will discuss possible mechanisms and clinical implications of a dynamic time course of SVD, with both progression and regression of SVD markers. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  12. A composite measure of cognitive and functional progression in Alzheimer's disease: Design of the Capturing Changes in Cognition study

    NARCIS (Netherlands)

    R.J. Jutten (Roos); Harrison, J. (John); F.J. De Jong (Frank J.); A. Aleman (André); Ritchie, C.W. (Craig W.); P. Scheltens (Philip); S.A.M. Sikkes (Sietske A.M.)

    2017-01-01

    markdownabstract__Introduction__ Cognitive testing in Alzheimer's disease (AD) is essential for establishing diagnosis, monitoring progression, and evaluating treatments. Assessments should ideally be brief, reliable, valid, and reflect clinically meaningful changes. There is a lack of instruments

  13. Volumetric MRI for evaluation of regional pattern and progression of neocortical degeneration in Alzheimer's disease; MR-Volumetrie zur Darstellung von Verteilung und zeitlicher Abfolge neokortikaler Degeneration bei Morbus Alzheimer

    Energy Technology Data Exchange (ETDEWEB)

    Leinsinger, G. [Institut fuer Klinische Radiologie, Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Muenchen (Germany); Institut fuer Klinische Radiologie, LMU Muenchen, Ziemssenstrasse 1, 80336, Muenchen (Germany); Teipel, S.; Pruessner, J.; Hampel, H. [Klinik fuer Psychiatrie, Ludwig-Maximilians-Universitaet Muenchen, Muenchen (Germany); Wismueller, A.; Born, C.; Meindl, T.; Flatz, W.; Schoenberg, S.; Reiser, M. [Institut fuer Klinische Radiologie, Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Muenchen (Germany)

    2003-07-01

    Volumetric analysis of the corpus callosum and hippocampus using MRI in Alzheimer's disease (AD) to evaluate the regional pattern and progression of neocortical neurodegeneration. In subsequent studies we investigated patients with AD and healthy controls. Volumetry was based on MRI-data from a sagittal 3D T1w-gradient echo sequence. The corpus callosum (CC) was measured in a midsagittal slice, and subdivided into 5 subregions. Volumetry of the hippocampus/amygdala-formation (HAF) was performed by segmentation in coronary reoriented slices. In AD patients we found a significant atrophy in the rostrum und splenium of CC. The atrophy was correlated with the severity of dementia, but no correlation was found with the load of white matter lesions. In comparison with {sup 18}FDG-PET, we found a significant correlation of regional CC-atrophy with the regional decline of cortical glucose metabolism. A ROC-analysis demonstrated no significant differences in the diagostic accuracy of HAF volumetry and regional CC volumetry of the splenium (region C5) even in mild stages of dementia. Regional atrophy of CC can be used as a marker of neocortical degeneration even in early stages of dementia in AD. (orig.) [German] Volumetrische Analyse des Corpus callosum und Hippokampus mittels MRT bei der Alzheimer-Erkrankung (AD), mit dem Ziel die regionale Verteilung und Progression der neokortikalen relativ zur allokortikalen Neurodegeneration zu erfassen. In mehreren Studienabschnitten wurden Patienten mit AD und gesunde Kontrollen untersucht. Als Grundlage fuer die Volumetrie diente eine sagittale 3D-T1w-Gradientenechosequenz. Die Vermessung des Corpus callosum (CC) erfolgte in der mittsagittalen Schicht, wobei 5 Subregionen definiert wurden. Die Volumetrie des Hippokampus-Amygdala-Komplexes (HAK) wurde durch Segmentierung an koronar reorientierten Schichten durchgefuehrt. Bei Patienten mit AD fand sich eine signifikante Atrophie in Rostrum und Splenium des CC. Dabei zeigte sich

  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. 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

  16. 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

  17. Pregnancy and HIV Disease Progression in an Early Infection Cohort from Five African Countries.

    Science.gov (United States)

    Wall, Kristin M; 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

    2017-03-01

    Understanding associations between pregnancy and HIV disease progression is critical to provide appropriate counseling and care to HIV-positive women. 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 <200 cells/μl, percent CD4 <14%, or category C event, with censoring at antiretroviral (ART) initiation for reasons other than prevention of mother-to-child transmission (PMTCT). Immunologic progression was defined as two consecutive CD4s ≤350 cells/μl or a single CD4 ≤350 cells/μl followed by non-PMTCT ART initiation. Generalized estimating equations assessed changes in CD4 before and after pregnancy. 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. 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.

  18. HIV infection in Haiti: natural history and disease progression.

    Science.gov (United States)

    Deschamps, M M; Fitzgerald, D W; Pape, J W; Johnson, W D

    2000-11-10

    A study was conducted to define the natural history and disease progression of HIV infection in a developing country. A prospective longitudinal cohort study. Forty-two patients with documented dates of HIV seroconversion were followed in Port-au-Prince, Haiti. Patients were seen at 3 month intervals or when ill. Patients were treated for bacterial, mycobacterial, parasitic, and fungal infections, but antiretroviral therapy was not available. Patients were followed until death or until 1 January 2000; median follow-up was 66 months. By Kaplan-Meier analyses, the median time to symptomatic HIV disease (CDC category B or C) was 3.0 years [95% confidence interval (CI) 2.3-5.0 years]. The median time to AIDS (CDC category C) was 5.2 years (95% CI 4.7-6.5 years), and the median time to death was 7.4 years (95% CI 6.2-10.2 years). Community-acquired infections, including respiratory tract infections, acute diarrhea, and skin infections were common in the pre-AIDS period. AIDS-defining illnesses included tuberculosis, wasting syndrome, cryptosporidiosis, cyclosporiasis, candida esophagitis, toxoplasmosis, and cryptococcal meningitis. Rapid progression to death was associated with anemia at the time of seroconversion hazards ratio (HR) 4.1 (95% CI 1.1-15.0), age greater than 35 years at seroconversion HR 4.4 (95% CI 1.1-16.6), and lymphopenia at seroconversion HR 11.0 (95% CI 2.3-53.0). This report documents rapid disease progression from HIV seroconversion until death among patients living in a developing country. Interventions, including nutritional support and prophylaxis of common community-acquired infections during the pre-AIDS period may slow disease progression and prolong life for HIV-infected individuals in less-developed countries.

  19. Flammable gas data evaluation. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Whitney, P.D.; Meyer, P.A.; Miller, N.E. [and others

    1996-10-01

    The Hanford Site is home to 177 large, underground nuclear waste storage tanks. Numerous safety and environmental concerns surround these tanks and their contents. One such concern is the propensity for the waste in these tanks to generate, retain, and periodically release flammable gases. This report documents some of the activities of the Flammable Gas Project Data Evaluation Task conducted for Westinghouse Hanford Company during fiscal year 1996. Described in this report are: (1) the results of examining the in-tank temperature measurements for insights into gas release behavior; (2) the preliminary results of examining the tank waste level measurements for insights into gas release behavior; and (3) an explanation for the observed hysteresis in the level/pressure measurements, a phenomenon observed earlier this year when high-frequency tank waste level measurements came on-line.

  20. Review of progress in quantitative nondestructive evaluation

    CERN Document Server

    Chimenti, Dale

    1999-01-01

    This series provides a comprehensive review of the latest research results in quantitative nondestructive evaluation (NDE). Leading investigators working in government agencies, major industries, and universities present a broad spectrum of work extending from basic research to early engineering applications. An international assembly of noted authorities in NDE thoroughly cover such topics as: elastic waves, guided waves, and eddy-current detection, inversion, and modeling; radiography and computed tomography, thermal techniques, and acoustic emission; laser ultrasonics, optical methods, and microwaves; signal processing and image analysis and reconstruction, with an emphasis on interpretation for defect detection; and NDE sensors and fields, both ultrasonic and electromagnetic; engineered materials and composites, bonded joints, pipes, tubing, and biomedical materials; linear and nonlinear properties, ultrasonic backscatter and microstructure, coatings and layers, residual stress and texture, and constructi...

  1. 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.

  2. Progressive atlanto-axial subluxation in Behcet's disease

    International Nuclear Information System (INIS)

    Kim, Sang-hyuk; Eoh, Whan

    2010-01-01

    Behcet's disease is a chronic inflammatory condition involving several organs, such as the skin, mucous membranes, eyes, joints, intestines, lungs and central nervous system. It rarely affects the spinal column. We describe a case of progressive atlanto-axial subluxation in a 44-year-old woman with Behcet's disease. The patient started complaining of posterior neck pain 10 years after the diagnosis of her Behcet's disease. Initial radiographs showed no abnormal finding, but follow-up radiographs 6 month later demonstrated atlanto-axial subluxation. To the best of our knowledge, this is the second reported case in the worldwide literature of an atlanto-axial instability in a patient with Behcet's disease. (orig.)

  3. How to detect disease progression in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    J-L. Vachiéry

    2012-03-01

    Full Text Available Pulmonary arterial hypertension (PAH is a rapidly progressive disease, ultimately leading to right heart failure and death. Accumulating evidence indicates that intervention early in disease progression results in better outcomes than delaying treatment. In this review we will discuss the assessments and strategies that can be used to monitor disease progression and guide clinical management. Many tools, such as symptoms, functional classification, exercise capacity, haemodynamic measures, findings on cardiac imaging and levels of biomarkers, have shown to be prognostic for survival both at diagnosis and during treatment. However, attempts to define goal thresholds have produced a variety of results. Several groups have developed risk calculators to estimate individual patients' mortality risk, but the accuracy of these tools across different patient populations remains unknown. What is clear is the importance of regularly assessing a range of parameters and then tailoring treatment goals to each patient. In addition, the use of a multidisciplinary team approach is crucial in order to support patients through all aspects of managing their condition. There is still an urgent need for prospective collaborative initiatives to assess novel goals and improve treatment strategies that would allow physicians to personalise and optimise clinical management for their patients with PAH.

  4. 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 gag IMPORTANCE 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

  5. 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

  6. 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...... 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...... 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...

  7. 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.

  8. 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.

  9. 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.

  10. Celiac disease: progress towards diagnosis and definition of pathogenic mechanisms.

    Science.gov (United States)

    Rossi, Mauro; Bot, Adrian

    2011-08-01

    The current issue of the International Reviews of Immunology is dedicated entirely to Celiac Disease (CD). Recent development of additional biomarkers and diagnostics resulted in a sharp revision of the prevalence of this condition, with a previously unrecognized subclinical occurrence in the adult population. This was paralleled by groundbreaking progress in understanding its molecular pathogenesis: while gluten-derived peptides activate the innate immunity, post-translationally modified gluten elicits an adaptive immunity. These arms amplify each other, resulting in a self- perpetuating autoimmune condition, influenced by disturbances of the gut flora and mucus chemistry. The process evolves dramatically in a subset of patients with vulnerable immune homeostasis (eg. Treg cells) explaining the progressive, aggravating syndrome in the clinically overt version of CD. In depth understanding of the pathogenesis of CD thus creates the premises of developing novel, more accurate animal models that should support a rationale development of new prophylactic and therapeutic interventions.

  11. Progressive disease in glioblastoma: Benefits and limitations of semi-automated volumetry.

    Directory of Open Access Journals (Sweden)

    Thomas Huber

    Full Text Available Unambiguous evaluation of glioblastoma (GB progression is crucial, both for clinical trials as well as day by day routine management of GB patients. 3D-volumetry in the follow-up of GB provides quantitative data on tumor extent and growth, and therefore has the potential to facilitate objective disease assessment. The present study investigated the utility of absolute changes in volume (delta or regional, segmentation-based subtractions for detecting disease progression in longitudinal MRI follow-ups.165 high resolution 3-Tesla MRIs of 30 GB patients (23m, mean age 60.2y were retrospectively included in this single center study. Contrast enhancement (CV and tumor-related signal alterations in FLAIR images (FV were semi-automatically segmented. Delta volume (dCV, dFV and regional subtractions (sCV, sFV were calculated. Disease progression was classified for every follow-up according to histopathologic results, decisions of the local multidisciplinary CNS tumor board and a consensus rating of the neuro-radiologic report.A generalized logistic mixed model for disease progression (yes / no with dCV, dFV, sCV and sFV as input variables revealed that only dCV was significantly associated with prediction of disease progression (P = .005. Delta volume had a better accuracy than regional, segmentation-based subtractions (79% versus 72% and a higher area under the curve by trend in ROC curves (.83 versus .75.Absolute volume changes of the contrast enhancing tumor part were the most accurate volumetric determinant to detect progressive disease in assessment of GB and outweighed FLAIR changes as well as regional, segmentation-based image subtractions. This parameter might be useful in upcoming objective response criteria for glioblastoma.

  12. Orphan drugs in development for Huntington's disease: challenges and progress

    Directory of Open Access Journals (Sweden)

    Burgunder JM

    2015-02-01

    Full Text Available Jean-Marc Burgunder1–4 1Swiss Huntington’s Disease Centre, Department of Neurology, University of Bern, Bern, Switzerland; 2Department of Neurology, West China Hospital, Sichuan University, Chengdu, 3Department of Neurology, Xiangya Hospital, Central South University, Changsha, 4Department of Neurology, Sun Yat-sen University, Guangzhou, People’s Republic of China Abstract: Huntington’s disease is a monogenic disorder encompassing a variable phenotype with progressive cognitive, psychiatric, and movement disorders. Knowledge of the mechanisms involved in this disorder has made substantial advances since the discovery of the gene mutation. The dynamic mutation is the expansion of a CAG (cytosine-adenine-guanine repeat in the huntingtin (HTT gene, which is transcribed into an abnormal protein with an elongated polyglutamine tract. Polyglutamine HTT accumulates and is changed in its function in multifaceted ways related to the numerous roles of the normal protein. The protein is expressed in numerous areas of the brain and also in other organs. The major brain region involved in the disease process is the striatum, but it is clear that other systems are involved as well. This accumulated knowledge has now led to the development of treatment strategies based on specific molecular pathways for symptomatic and disease course-modifying treatment. The most proximal way to handle the disturbed protein is to hinder the gene transcription, translation, and/or to increase protein clearance. Other mechanisms now being approached include modulation of energy and intracellular signaling, induction of factors potentially leading to neuroprotection, as well as modulation of glial function. Several clinical trials based on these approaches are now under way, and it is becoming clear that a future disease-modifying therapy will be a combination of several approaches harmonized with symptomatic treatments. In this review, some of the most promising and

  13. Immune Evasion Mechanisms of Entamoeba histolytica: Progression to Disease.

    Science.gov (United States)

    Begum, Sharmin; Quach, Jeanie; Chadee, Kris

    2015-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Parkinsonian syndroms: Clinical phenotype, differential diagnosis and disease progression

    International Nuclear Information System (INIS)

    Storch, A.

    2002-01-01

    Parkinsonian syndromes include idiopathic Parkinson's disease (IPD), other neurodegenerative diseases with parkinsonism, the so-called atypical parkinsonian syndromes, and symptomatic parkinsonian syndromes, such as Wilson's disease. IPD is the most frequent disease with parkinsonism as the main clinical feature and is responsible for approx. 80% of all parkinsonian syndromes. Atypical parkinsonian syndromes are the most important differential diagnoses of IPD. The two most frequent types are multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). For clinical diagnosis it is essential to take a careful medical history and to examine the patients physically in regular intervals. However, various clinico-pathological studies have shown that approx. 25% of patients with clinical diagnosis of IPD may have other causes of parkinsonism. Selected technical investigations, in particular functional imaging of the central dopaminergic system using PET or SPECT, may help to make clinical diagnosis more secure. This paper reviews the clinical features and diagnostic findings in diseases with parkinsonism and summarises the difficulties in establishing early and differential diagnoses. (orig.) [de

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Research Progress of Intestinal Microbiota in Inflammatory Bowel Diseases

    Directory of Open Access Journals (Sweden)

    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.

  1. 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

  2. Cellular Transplantation Alters the Disease Progression in Becker's Muscular Dystrophy.

    Science.gov (United States)

    Sharma, Alok; Paranjape, Amruta; Sane, Hemangi; Bhagawanani, Khushboo; Gokulchandran, Nandini; Badhe, Prerna

    2013-01-01

    Becker's Muscular Dystrophy (BMD) is a dystrophinopathy manifested as progressive muscle degeneration. Autologous Bone Marrow Mononuclear Cells (BMMNCs) have shown some myogenic potential. The paracrine effects of the BMMNCs reduce the inflammation and are thought to reduce muscle degeneration. We treated a 39 year old dental surgeon suffering from BMD. Muscle strength was reduced when measured using modified Medical Research Council's Manual Muscle Testing (mMRC-MMT). Static sitting balance was poor. He was wheelchair dependent for ambulation and moderately independent in Activities of Daily Living (ADL). Functional Independence Measure (FIM) score was 93. Musculoskeletal Magnetic Resonance Imaging (MRI-MSK) showed moderate fatty infiltration in the muscles. Three cellular transplantations were carried out. Clinical assessment and the investigations were repeated. Progressive increase in the muscle strength was noted. Ambulation was independent using push-knee splints and minimal assistance when weary. Static and dynamic balance in sitting and standing improved. FIM score increased from 93 to 105. There was no increase in the degree of fatty infiltration, as seen on the MRI-MSK. The case study provides evidence for the putative benefits of cellular therapy in altering the disease progression in BMD. It also suggests augmented clinical benefits of combination of cellular therapy and rehabilitation.

  3. 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.

  4. The role of acquired immunity and periodontal disease progression.

    Science.gov (United States)

    Teng, Yen-Tung A

    2003-01-01

    Our understanding of the pathogenesis in human periodontal diseases is limited by the lack of specific and sensitive tools or models to study the complex microbial challenges and their interactions with the host's immune system. Recent advances in cellular and molecular biology research have demonstrated the importance of the acquired immune system not only in fighting the virulent periodontal pathogens but also in protecting the host from developing further devastating conditions in periodontal infections. The use of genetic knockout and immunodeficient mouse strains has shown that the acquired immune response-in particular, CD4+ T-cells-plays a pivotal role in controlling the ongoing infection, the immune/inflammatory responses, and the subsequent host's tissue destruction. In particular, studies of the pathogen-specific CD4+ T-cell-mediated immunity have clarified the roles of: (i) the relative diverse immune repertoire involved in periodontal pathogenesis, (ii) the contribution of pathogen-associated Th1-Th2 cytokine expressions in periodontal disease progression, and (iii) micro-organism-triggered periodontal CD4+ T-cell-mediated osteoclastogenic factor, 'RANK-L', which is linked to the induction of alveolar bone destruction in situ. The present review will focus on some recent advances in the acquired immune responses involving B-cells, CD8+ T-cells, and CD4+ T-cells in the context of periodontal disease progression. New approaches will further facilitate our understanding of their underlying molecular mechanisms that may lead to the development of new treatment modalities for periodontal diseases and their associated complications.

  5. 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.

  6. Natural Progression of Canine Glycogen Storage Disease Type IIIa.

    Science.gov (United States)

    Brooks, Elizabeth D; Yi, Haiqing; Austin, Stephanie L; Thurberg, Beth L; Young, Sarah P; Fyfe, John C; Kishnani, Priya S; Sun, Baodong

    2016-02-01

    Glycogen storage disease type IIIa (GSD IIIa) is caused by a deficiency of glycogen debranching enzyme activity. Hepatomegaly, muscle degeneration, and hypoglycemia occur in human patients at an early age. Long-term complications include liver cirrhosis, hepatic adenomas, and generalized myopathy. A naturally occurring canine model of GSD IIIa that mimics the human disease has been described, with progressive liver disease and skeletal muscle damage likely due to excess glycogen deposition. In the current study, long-term follow-up of previously described GSD IIIa dogs until 32 mo of age (n = 4) and of family-owned GSD IIIa dogs until 11 to 12 y of age (n = 2) revealed that elevated concentrations of liver and muscle enzyme (AST, ALT, ALP, and creatine phosphokinase) decreased over time, consistent with hepatic cirrhosis and muscle fibrosis. Glycogen deposition in many skeletal muscles; the tongue, diaphragm, and heart; and the phrenic and sciatic nerves occurred also. Furthermore, the urinary biomarker Glc4, which has been described in many types of GSD, was first elevated and then decreased later in life. This urinary biomarker demonstrated a similar trend as AST and ALT in GSD IIIa dogs, indicating that Glc4 might be a less invasive biomarker of hepatocellular disease. Finally, the current study further demonstrates that the canine GSD IIIa model adheres to the clinical course in human patients with this disorder and is an appropriate model for developing novel therapies.

  7. Naturalism about health and disease: adding nuance for progress.

    Science.gov (United States)

    Kingma, Elselijn

    2014-12-01

    The literature on health and diseases is usually presented as an opposition between naturalism and normativism. This article argues that such a picture is too simplistic: there is not one opposition between naturalism and normativism, but many. I distinguish four different domains where naturalist and normativist claims can be contrasted: (1) ordinary usage, (2) conceptually clean versions of "health" and "disease," (3) the operationalization of dysfunction, and (4) the justification for that operationalization. In the process I present new arguments in response to Schwartz (2007) and Hausman (2012) and expose a link between the arguments made by Schwartz (2007) and Kingma (2010). Distinguishing naturalist claims at these four domains will allow us to make progress by (1) providing more nuanced, intermediate positions about a possible role for values in health and disease; and (2) assisting in the addressing of relativistic worries about the value-ladenness of health and disease. © The Author 2014. 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.

  8. New progress and clinical application of PET-CT in coronary artery disease

    International Nuclear Information System (INIS)

    Zhang Guojian; Wang Xuemei; Liu Yanyang

    2010-01-01

    PET-CT is a useful noninvasive method for the diagnosis of coronary artery disease (CAD), and can assessment the nature of the atherosclerosis plaque. It plays an important role in the diagnosis of CAD and is useful for selection of surgical approaches, and for the evaluation of prognosis. The clinical application of PET-CT and its new progress are introduced in this paper. (authors)

  9. Progress on Chinese evaluated nuclear parameters library (CENPL). Pt. 3

    International Nuclear Information System (INIS)

    Su Zongdi; Ge Zhigang; Zhou Chunmei

    1994-01-01

    The progress on Chinese evaluated nuclear parameters library (CENPL) is introduced. The setting up work of each sub-library of CENPL has got some new progresses at the past period. These sub-libraries are atomic mass and characteristic constant for nuclear ground state sub-library, discrete level scheme and batch ratio of γ decay sub-library, level density parameter sub-library, giant dipole resonance parameter for γ-ray strength function sub-library and optical model parameter sub-library

  10. 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

  11. 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.

  12. Dipeptidyl peptidase-4 inhibitors in progressive kidney disease.

    Science.gov (United States)

    Makino, Yuichi; Fujita, Yukihiro; Haneda, Masakazu

    2015-01-01

    Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs approved for the treatment of type 2 diabetes. The main action of DPP-4 inhibitors is to increase the level of incretin hormones such as glucagon-like peptide-1 (GLP-1), thereby stimulating insulin secretion from pancreatic β cells. Recently emerging evidence suggests the pleiotropic extrapancreatic function of GLP-1 or DPP-4 inhibitors, including kidney and cardiovascular protection. Here, we review the effects of DPP-4 inhibitors on progressive kidney disease such as diabetic nephropathy from a therapeutic point of view. A growing number of studies in animal models and human diseases have shown that DPP-4 inhibition ameliorates kidney disease by a process independent of glucose lowering. Possible mechanisms underlying such protective properties include the facilitation of natriuresis and reduction of blood pressure, and also local effects of the reduction of oxidative stress, inflammation and improvement of endothelial function in the kidney. DPP-4 inhibitors may also restore other DPP-4 substrates which have proven renal effects. Treatment of diabetes with DPP-4 inhibitors is likely to involve a variety of extrapancreatic effects including renal protection. Such pleiotropic action of DPP-4 inhibitors might occur by both incretin-dependent and incretin-independent mechanisms. Conclusive evidence is needed to translate the favorable results from animal models to humans.

  13. Biomarkers for disease progression and AAV therapeutic efficacy in feline Sandhoff disease

    OpenAIRE

    Bradbury, Allison M; Gray-Edwards, Heather L; Shirley, Jamie L; McCurdy, Victoria J; Colaco, Alexandria N; Randle, Ashley N; Christopherson, Pete W; Bird, Allison C; Johnson, Aime K; Wilson, Diane U; Hudson, Judith A; De Pompa, Nicholas L; Sorjonen, Donald C; Brunson, Brandon L; Jeyakumar, Mylvaganam

    2014-01-01

    The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are progressive neurodegenerative disorders that are caused by a mutation in the enzyme β-N-acetylhexosaminidase (Hex). Due to the recent emergence of novel experimental treatments, biomarker development has become particularly relevant in GM2 gangliosidosis as an objective means to measure therapeutic efficacy. Here we describe blood, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), and electrodiagnostic m...

  14. Progressive nodular histiocytosis associated with eale′s disease

    Directory of Open Access Journals (Sweden)

    Abhilasha Williams

    2015-01-01

    Full Text Available Progressive nodular histiocytosis (PNH is a rare normolipemic macrophage disorder and belongs to a subgroup of non-Langerhans cell histiocytosis (LCHs which is characterized by a progressive course with no sign of spontaneous resolution but without systemic involvement. We report a 30-year-old gentleman who presented with skin lesions all over the body associated with gradual bilateral painless loss of vision. On examination, approximately 30 to 40, skin-colored, firm, non-tender papules and nodules were noted over the body especially on the face and trunk. A skin biopsy revealed a cellular tumor in the dermis composed of oval to spindle-shaped cells, positive for CD68 but negative for S-100, CD34, CD21, CD35 and HMB45, supporting a diagnosis of spindle cell histiocytic tumor. Ophthalmic examination revealed a generalized arteriolar attenuation in both eyes. He received Tab Imatinib 400 mg OD for 5 months followed by Tab Pazopanib 800 mg OD for 4 months and both the drugs were stopped due to lack of any response in the skin lesions. We report this case due to its rarity, characteristic clinical presentation, and its association with Eale′s disease. Primary treatment remains surgical excision of bothersome lesions and optimal systemic treatment is still unknown.

  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....... 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-traumatic......, 64% had been in contact with the hospital or outpatient clinics within the last 3 years, and 29% received a prescription of opioids 3 years prior to the amputation. CONCLUSION: Among patients with non-traumatic lower extremity amputation, one-third live with undiagnosed and untreated atherosclerosis...

  16. Estimating Alzheimer's disease progression rates from normal cognition through mild cognitive impairment and stages of dementia.

    Science.gov (United States)

    Davis, Matthew; O Connell, Thomas; Johnson, Scott; Cline, Stephanie; Merikle, Elizabeth; Martenyi, Ferenc; Simpson, Kit N

    2018-01-18

    Background Alzheimer's disease (AD) can be conceptualized as a continuum: patients progress from normal cognition to mild cognitive impairment (MCI) due to AD, followed by increasing severity of AD dementia. Prior research has measured transition probabilities among later stages of AD, but not for the complete spectrum. Objective To estimate annual progression rates across the AD continuum and evaluate the impact of a delay in MCI due to AD on the trajectory of AD dementia and clinical outcomes. Methods Patient-level longitudinal data from the National Alzheimer's Coordinating Center for n=18,103 patients with multiple visits over the age of 65 were used to estimate annual, age-specific transitional probabilities between normal cognition, MCI due to AD, and AD severity states (defined by Clinical Dementia Rating score). Multivariate models predicted the likelihood of death and institutionalization for each health state, conditional on age and time from the previous evaluation. These probabilities were used to populate a transition matrix describing the likelihood of progressing to a particular disease state or death for any given current state and age. Finally, a health state model was developed to estimate the expected effect of a reduction in the risk of transitioning from normal cognition to MCI due to AD on disease progression rates for a cohort of 65-year-old patients over a 35-year time horizon. Results Annual transition probabilities to more severe states were 8%, 22%, 25%, 36%, and 16% for normal cognition, MCI due to AD, and mild/moderate/severe AD, respectively, at age 65, and increased as a function of age. Progression rates from normal cognition to MCI due to AD ranged from 4% to 10% annually. Severity of cognitive impairment and age both increased the likelihood of institutionalization and death. For a cohort of 100 patients with normal cognition at age 65, a 20% reduction in the annual progression rate to MCI due to AD avoided 5.7 and 5.6 cases of MCI

  17. Effect of early-life gut mucosal compromise on disease progression in NOD mice

    DEFF Research Database (Denmark)

    Bendtsen, Katja M.; Hansen, Camilla HF; Krych, Lukasz

    2017-01-01

    Disease expression in spontaneous nonobese diabetic (NOD) mice depends on environmental stimuli such as stress, diet, and gut microbiota composition. We evaluated a brief, early-life gut intervention in which pups were weaned to low-dose dextran sulfate sodium (DSS). We hypothesized that the mucus...... of the microbiota during weeks 4 through 6 led to increased cecal length and weight and, in week 13, a tendency toward decreased colon length, with increased leakage of LPS to the blood. We conclude that mucus reduction and subsequent increased host–bacterial contact did not affect overall disease progression...

  18. Supercritical Wing Technology: A Progress Report on Flight Evaluations

    Science.gov (United States)

    1972-01-01

    The papers in this compilation were presented at the NASA Symposium on "Supercritical Wing Technology: A Progress Report on Flight Evaluation" held at the NASA Flight Research Center, Edwards, Calif., on February 29, 1972. The purpose of the symposium was to present timely information on flight results obtained with the F-8 and T-2C supercritical wing configurations, discuss comparisons with wind-tunnel predictions, and project [ ] flight programs planned for the F-8 and F-III (TACT) airplanes.

  19. 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.

  20. Progressive multifocal leukoencephalopathy and other forms of JC virus disease.

    Science.gov (United States)

    Brew, Bruce J; Davies, Nicholas W S; Cinque, Paola; Clifford, David B; Nath, Avindra

    2010-12-01

    Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the brain caused by the JC virus (JCV). PML usually occurs via reactivation of JCV when an immune system becomes compromised. A diagnosis of PML is normally made on the basis of distinguishing neurological features at presentation, characteristic brain MRI changes and the presence of JCV DNA in cerebrospinal fluid. PML has a 3 month mortality rate of 20-50%, so prompt intervention is essential. Currently, reconstitution of the immune system affords the best prognosis for this condition. When PML is first suspected, and where possible, immunosuppressant or immunomodulatory therapy should be suspended or reduced. If PML is associated with a protein therapy that has a long half-life the use of plasma exchange to accelerate the removal of the drug from the circulation may aid the restoration of immune system function. Rapid improvements in immune function, however, might lead to transient worsening of the disease. In this Review, we critically appraise the controversies surrounding JCV infection, and provide practical management guidelines for PML.

  1. 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

  2. CA-125 in Disease Progression and Treatment of Lymphangioleiomyomatosis.

    Science.gov (United States)

    Glasgow, Connie G; Pacheco-Rodriguez, Gustavo; Steagall, Wendy K; Haughey, Mary E; Julien-Williams, Patricia A; Stylianou, Mario P; Gochuico, Bernadette R; Moss, Joel

    2018-02-01

    Lymphangioleiomyomatosis (LAM) is a destructive lung disease of women caused by proliferation of neoplastic-like LAM cells, with mutations in the TSC1/2 tumor suppressor genes. Based on case reports, levels of cancer antigen 125 (CA-125), an ovarian cancer biomarker, can be elevated in patients with LAM. We hypothesized that elevated serum CA-125 levels seen in some patients with LAM were due to LAM, not other malignancies, and might respond to sirolimus treatment. Serum CA-125 levels were measured for 241 patients at each visit. Medical records were reviewed for co-morbidities, disease progression, and response to sirolimus treatment. CA-125 expression in LAM cells was determined by using immunohistochemical analysis. Almost 25% of patients with LAM had at least one elevated serum CA-125 measurement. Higher serum CA-125 levels correlated with lower FEV 1 , premenopausal status, and pleural effusion in a multivariate model (each P CA-125 levels decreased following sirolimus treatment (P = .002). CA-125 and α-smooth muscle actin were co-expressed in LAM lung nodules. Higher serum CA-125 levels were associated with pleural effusions and reduced pulmonary function and were decreased with sirolimus therapy. LAM cells express CA-125. Some elevated serum CA-125 levels may reflect serosal membrane involvement. Copyright © 2017. Published by Elsevier Inc.

  3. New Mexico Supercomputing Challenge 1993 evaluation report. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Trainor, M.; Eker, P.; Kratzer, D.; Foster, M.; Anderson, M.

    1993-11-01

    This report provides the evaluation of the third year (1993) of the New Mexico High School Supercomputing Challenge. It includes data to determine whether we met the program objectives, measures participation, and compares progress from the first to the third years. This year`s report is a more complete assessment than last year`s, providing both formative and summative evaluation data. Data indicates that the 1993 Challenge significantly changed many students` career plans and attitudes toward science, provided professional development for teachers, and caused some changes in computer offerings in several participating schools.

  4. Oral health information systems--towards measuring progress in oral health promotion and disease prevention

    DEFF Research Database (Denmark)

    Petersen, Poul Erik; Bourgeois, Denis; Bratthall, Douglas

    2005-01-01

    programmes oriented towards disease prevention and health promotion. The WHO Oral Health Country/Area Profile Programme (CAPP) provides data on oral health from countries, as well as programme experiences and ideas targeted to oral health professionals, policy-makers, health planners, researchers...... systems are being developed within the framework of the WHO STEPwise approach to surveillance of noncommunicable, chronic disease, and data stored in the WHO Global InfoBase may allow advanced health systems research. Sound knowledge about progress made in prevention of oral and chronic disease......This article describes the essential components of oral health information systems for the analysis of trends in oral disease and the evaluation of oral health programmes at the country, regional and global levels. Standard methodology for the collection of epidemiological data on oral health has...

  5. Natural Besnoitia besnoiti infections in cattle: chronology of disease progression.

    Science.gov (United States)

    Gollnick, Nicole S; Scharr, Julia C; Schares, Gereon; Langenmayer, Martin C

    2015-02-14

    Bovine besnoitiosis is an emerging protozoan disease in cattle. Neither vaccines nor chemotherapeutic drugs are currently available for prevention and treatment of Besnoitia besnoiti infections. Therefore the implementation of appropriate disease management strategies is of utmost importance. The aim of this longitudinal study was to complement current knowledge on the chronology of disease progression. This was realized by correlating clinical findings in early stages of naturally acquired bovine besnoitiosis with results of real-time PCR of skin biopsies and of two western immunoblots and an immunofluorescent antibody test (IFAT). Animals for this study were obtained by i) closely monitoring a cow-calf operation with a high prevalence of bovine besnoitiosis for cases of acute disease, and by ii) conducting a 12-week cohabitation experiment on pasture with five healthy heifers, a healthy bull and five B. besnoiti infected cows. A control group of six healthy heifers was kept at a minimal distance of 20 m. Further, the spectrum of potential insect vectors was determined. Infected cattle were followed up to a maximum of 221 days after first detection of B. besnoiti antibodies. Two severely affected cows developed visible and palpable alterations of skin, a decrease in body condition despite good feed intake, and chronic bovine besnoitiosis-associated laminitis leading to non-healing sole ulcers. The cows also had high reciprocal IFAT titers and high loads of parasite DNA in skin samples. Two heifers developed a mild clinical course characterized by few parasitic cysts visible in the scleral conjunctivae and vestibula vaginae. Both heifers became infected during the time of high insect activity of the species Musca domestica, Musca autumnalis, Haematobia irritans, and Stomoxys calcitrans. When a third heifer became subclinically infected, low insect activity was recorded. None of the six control heifers contracted a B. besnoiti infection. In chronic besnoitiosis

  6. Evaluation of argyrophilic nucleolar organizer regions in oral tumor progression.

    Science.gov (United States)

    Spolidorio, L C; Neves, K A; Soares, C P; Spolidorio, D M P; Basso, M F M; Malavazzi, I; Almeida, O P

    2002-01-01

    The aim of this study was to compare the presence of nucleolar organizer regions (NORs) in normal oral mucosa, dysplasia and microinvasive carcinoma. All histological specimens were reviewed according to the modified classification and staging system for oral leukoplakia described by van-der-Waal et al. [Oral Oncol. 36 (2000) 264]. NOR quantification was performed with an image analyzer after staining by the argyrophilic nucleolar region technique. The morphometric results were statistically different for normal mucosa, dysplasia and microinvasive carcinoma. It was concluded that an increase of NOR activity follows the disease progression and may reflect the degree of cellular proliferation and malignancy.

  7. Progressive diaphyseal dysplasia (Engelmann's disease) - Report of a case -

    International Nuclear Information System (INIS)

    Soh, M. H.; Rhee, S. J.; Won, J. J.

    1981-01-01

    Progressive diaphyseal dysplasia is a rare condition and radiographic finding provides conclusive proof. We have experienced a sporadic case of progressive disphyseal dysplasia (Engelmann's disease) of 8 year-old-Korean girl, confirmed by radiographic skeletal survey and biopsy. This patient was admitted to the Jeonbug National University Hospital because of painful swelling of the distal part of the right femur after trauma and intermittent pain in her lower legs with a peculiar wadding gait for 2 years. On a physical examination, the patient appeared thin and slender. The skeletal musculature was poorly developed and the upper and lower extremities were weak. She walked with a peculiar wadding gait. The height was normal. No joint abnormality was noted and the mental state was alert. The child was the product of a normal gestation and delivery. Radiographic studies of the skeleton showed a generalized and symmetrical distribution of the bone characterized by cortical thickening, fusiform enlargement, and a narrowed medullary cavity in the diaphyseal of long bones while the epiphyses and metaphyses was not involved. Abrupt demarcation of the lesion with loss of normal trabecular pattern was note. Elongation of the extremities relative to the size of the child was present. The above radiographic findings showed involvement of all the long tubular bones such as the ulna, radius, tibia, fibula, femur and humerus. A sight sclerosis of the base of her skull was present, but the calvarium was not involved. The hands, feet, pelvis, spine, clavicle, rib, scapula and mandible were not affected. There was no specific laboratory finding except for the slightly elevated ESR. Histological examination of the bone biopsies from the femur revealed thickening of periosteum and proliferation of the walls of the small arterioles with reduction in the size of the lumen. The bony cortex showed essentially normal bone with the increased osteoblastic and osteoclastic activity

  8. Decreased RECQL5 correlated with disease progression of osteosarcoma

    International Nuclear Information System (INIS)

    Wu, Junlong; Zhi, Liqiang; Dai, Xin; Cai, Qingchun; Ma, Wei

    2015-01-01

    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.

  9. 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.

  10. An advanced case of indium lung disease with progressive emphysema.

    Science.gov (United States)

    Nakano, Makiko; Tanaka, Akiyo; Hirata, Miyuki; Kumazoe, Hiroyuki; Wakamatsu, Kentaro; Kamada, Dan; Omae, Kazuyuki

    2016-09-30

    To report the occurrence of an advanced case of indium lung disease with severely progressive emphysema in an indium-exposed worker. A healthy 42-year-old male smoker was employed to primarily grind indium-tin oxide (ITO) target plates, exposing him to indium for 9 years (1998-2008). In 2004, an epidemiological study was conducted on indium-exposed workers at the factory in which he worked. The subject's serum indium concentration (In-S) was 99.7 μg/l, while his serum Krebs von den Lungen-6 level was 2,350 U/ml. Pulmonary function tests showed forced vital capacity (FVC) of 4.17 l (91.5% of the JRS predicted value), forced expiratory volume in 1 s (FEV 1 ) of 3.19 l (80.8% of predicted), and an FEV 1 -to-FVC ratio of 76.5%. A high-resolution chest computed tomography (HRCT) scan showed mild interlobular septal thickening and mild emphysematous changes. In 2008, he was transferred from the ITO grinding workplace to an inspection work section, where indium concentrations in total dusts had a range of 0.001-0.002 mg/m 3 . In 2009, the subject's In-S had increased to 132.1 μg/l, and pulmonary function tests revealed obstructive changes. In addition, HRCT scan showed clear evidence of progressive lung destruction with accompanying severe centrilobular emphysema and interlobular septal thickening in both lung fields. The subject's condition gradually worsened, and in 2015, he was registered with the Japan Organ Transplant Network for lung transplantation (LTx). Heavy indium exposure is a risk factor for emphysema, which can lead to a severity level that requires LTx as the final therapeutic option.

  11. In silico regulatory analysis for exploring human disease progression

    Directory of Open Access Journals (Sweden)

    DeLisi Charles

    2008-06-01

    Full Text Available Abstract Background An important goal in bioinformatics is to unravel the network of transcription factors (TFs and their targets. This is important in the human genome, where many TFs are involved in disease progression. Here, classification methods are applied to identify new targets for 152 transcriptional regulators using publicly-available targets as training examples. Three types of sequence information are used: composition, conservation, and overrepresentation. Results Starting with 8817 TF-target interactions we predict an additional 9333 targets for 152 TFs. Randomized classifiers make few predictions (~2/18660 indicating that our predictions for many TFs are significantly enriched for true targets. An enrichment score is calculated and used to filter new predictions. Two case-studies for the TFs OCT4 and WT1 illustrate the usefulness of our predictions: • Many predicted OCT4 targets fall into the Wnt-pathway. This is consistent with known biology as OCT4 is developmentally related and Wnt pathway plays a role in early development. • Beginning with 15 known targets, 354 predictions are made for WT1. WT1 has a role in formation of Wilms' tumor. Chromosomal regions previously implicated in Wilms' tumor by cytological evidence are statistically enriched in predicted WT1 targets. These findings may shed light on Wilms' tumor progression, suggesting that the tumor progresses either by loss of WT1 or by loss of regions harbouring its targets. • Targets of WT1 are statistically enriched for cancer related functions including metastasis and apoptosis. Among new targets are BAX and PDE4B, which may help mediate the established anti-apoptotic effects of WT1. • Of the thirteen TFs found which co-regulate genes with WT1 (p ≤ 0.02, 8 have been previously implicated in cancer. The regulatory-network for WT1 targets in genomic regions relevant to Wilms' tumor is provided. Conclusion We have assembled a set of features for the targets of

  12. 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.

  13. 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.

  14. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes.

    Science.gov (United States)

    Wanner, Christoph; Inzucchi, Silvio E; Lachin, John M; Fitchett, David; von Eynatten, Maximilian; Mattheus, Michaela; Johansen, Odd Erik; Woerle, Hans J; Broedl, Uli C; Zinman, Bernard

    2016-07-28

    Diabetes confers an increased risk of adverse cardiovascular and renal events. In the EMPA-REG OUTCOME trial, empagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes at high risk for cardiovascular events. We wanted to determine the long-term renal effects of empagliflozin, an analysis that was a prespecified component of the secondary microvascular outcome of that trial. We randomly assigned patients with type 2 diabetes and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m(2) of body-surface area to receive either empagliflozin (at a dose of 10 mg or 25 mg) or placebo once daily. Prespecified renal outcomes included incident or worsening nephropathy (progression to macroalbuminuria, doubling of the serum creatinine level, initiation of renal-replacement therapy, or death from renal disease) and incident albuminuria. Incident or worsening nephropathy occurred in 525 of 4124 patients (12.7%) in the empagliflozin group and in 388 of 2061 (18.8%) in the placebo group (hazard ratio in the empagliflozin group, 0.61; 95% confidence interval, 0.53 to 0.70; Pempagliflozin group and in 60 of 2323 (2.6%) in the placebo group, a significant relative risk reduction of 44%. Renal-replacement therapy was initiated in 13 of 4687 patients (0.3%) in the empagliflozin group and in 14 of 2333 patients (0.6%) in the placebo group, representing a 55% lower relative risk in the empagliflozin group. There was no significant between-group difference in the rate of incident albuminuria. The adverse-event profile of empagliflozin in patients with impaired kidney function at baseline was similar to that reported in the overall trial population. In patients with type 2 diabetes at high cardiovascular risk, empagliflozin was associated with slower progression of kidney disease and lower rates of clinically relevant renal events than was placebo when added to standard care

  15. Association between time to disease progression end points and overall survival in patients with neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Singh S

    2014-08-01

    Full Text Available Simron Singh,1 Xufang Wang,2 Calvin HL Law1 1Sunnybrook Odette Cancer Center, University of Toronto, Toronto, ON, Canada; 2Novartis Oncology, Florham Park, NJ, USA Abstract: Overall survival can be difficult to determine for slowly progressing malignancies, such as neuroendocrine tumors. We investigated whether time to disease progression is positively associated with overall survival in patients with such tumors. A literature review identified 22 clinical trials in patients with neuroendocrine tumors that reported survival probabilities for both time to disease progression (progression-free survival and time to progression and overall survival. Associations between median time to disease progression and median overall survival and between treatment effects on time to disease progression and treatment effects on overall survival were analyzed using weighted least-squares regression. Median time to disease progression was significantly associated with median overall survival (coefficient 0.595; P=0.022. In the seven randomized studies identified, the risk reduction for time to disease progression was positively associated with the risk reduction for overall survival (coefficient on −ln[HR] 0.151; 95% confidence interval −0.843, 1.145; P=0.713. The significant association between median time to disease progression and median overall survival supports the assertion that time to disease progression is an alternative end point to overall survival in patients with neuroendocrine tumors. An apparent albeit not significant trend correlates treatment effects on time to disease progression and treatment effects on overall survival. Informal surveys of physicians’ perceptions are consistent with these concepts, although additional randomized trials are needed. Keywords: neuroendocrine tumors, progression-free survival, disease progression, mortality

  16. Research progress in association between nonalcoholic fatty liver disease and gallstone disease

    Directory of Open Access Journals (Sweden)

    HUANG Ying

    2014-11-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD and gallstone disease (GD are considered the manifestations of metabolic syndrome in the liver and gallbladder. NAFLD and GD are closely related to insulin resistance (IR, obesity, dyslipidemia, abnormal glucose metabolism, and so on. Worldwide studies, which have been reviewed, show that both NAFLD and GD have the common risk factors, such as IR, obesity, dyslipidemia, abnormal glucose metabolism, and middle-aged and elderly women. NAFLD is the risk factor for GD. GD, closely related to nonalcoholic steatohepatitis and liver fibrosis, accelerates the progression of NAFLD. Thus, it is considered that the prevention and treatment of NAFLD can reduce the incidence of GD, and the progression of NAFLD can be delayed by the prevention and treatment of GD.

  17. Optical Coherence Tomography as a Biomarker for Diagnosis, Progression, and Prognosis of Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Maria Satue

    2016-01-01

    Full Text Available Neurodegenerative diseases present a current challenge for accurate diagnosis and for providing precise prognostic information. Developing imaging biomarkers for multiple sclerosis (MS, Parkinson disease (PD, and Alzheimer’s disease (AD will improve the clinical management of these patients and may be useful for monitoring treatment effectiveness. Recent research using optical coherence tomography (OCT has demonstrated that parameters provided by this technology may be used as potential biomarkers for MS, PD, and AD. Retinal thinning has been observed in these patients and new segmentation software for the analysis of the different retinal layers may provide accurate information on disease progression and prognosis. In this review we analyze the application of retinal evaluation using OCT technology to provide better understanding of the possible role of the retinal layers thickness as biomarker for the detection of these neurodegenerative pathologies. Current OCT analysis of the retinal nerve fiber layer and, specially, the ganglion cell layer thickness may be considered as a good biomarker for disease diagnosis, severity, and progression.

  18. Inferring biomarkers for Mycobacterium avium subsp. paratuberculosis infection and disease progression in cattle using experimental data

    Science.gov (United States)

    Magombedze, Gesham; Shiri, Tinevimbo; Eda, Shigetoshi; Stabel, Judy R.

    2017-03-01

    Available diagnostic assays for Mycobacterium avium subsp. paratuberculosis (MAP) have poor sensitivities and cannot detect early stages of infection, therefore, there is need to find new diagnostic markers for early infection detection and disease stages. We analyzed longitudinal IFN-γ, ELISA-antibody and fecal shedding experimental sensitivity scores for MAP infection detection and disease progression. We used both statistical methods and dynamic mathematical models to (i) evaluate the empirical assays (ii) infer and explain biological mechanisms that affect the time evolution of the biomarkers, and (iii) predict disease stages of 57 animals that were naturally infected with MAP. This analysis confirms that the fecal test is the best marker for disease progression and illustrates that Th1/Th2 (IFN-γ/ELISA antibodies) assays are important for infection detection, but cannot reliably predict persistent infections. Our results show that the theoretical simulated macrophage-based assay is a potential good diagnostic marker for MAP persistent infections and predictor of disease specific stages. We therefore recommend specifically designed experiments to test the use of a based assay in the diagnosis of MAP infections.

  19. Brain correlates of progressive olfactory loss in Parkinson's disease.

    Science.gov (United States)

    Campabadal, Anna; Uribe, Carme; Segura, Barbara; Baggio, Hugo C; Abos, Alexandra; Garcia-Diaz, Anna Isabel; Marti, Maria Jose; Valldeoriola, Francesc; Compta, Yaroslau; Bargallo, Nuria; Junque, Carme

    2017-08-01

    Olfactory dysfunction is present in a large proportion of patients with Parkinson's disease (PD) upon diagnosis. However, its progression over time has been poorly investigated. The few available longitudinal studies lack control groups or MRI data. To investigate the olfactory changes and their structural correlates in non-demented PD over a four-year follow-up. We assessed olfactory function in a sample of 25 PD patients and 24 normal controls of similar age using the University of Pennsylvania Smell Identification test (UPSIT). Structural magnetic resonance imaging data, obtained with a 3-T Siemens Trio scanner, were analyzed using FreeSurfer software. Analysis of variance showed significant group (F = 53.882; P effects, but the group-by-time interaction was not statistically significant. UPSIT performance declined ≥1.5 standard deviations in 5 controls and 7 patients. Change in UPSIT scores of patients correlated positively with volume change in the left putamen, right thalamus, and right caudate nucleus. Olfactory loss over time in PD and controls is similar, but we have observed significant correlation between this loss and basal ganglia volumes only in patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Protease-activated receptors in kidney disease progression.

    Science.gov (United States)

    Palygin, Oleg; Ilatovskaya, Daria V; Staruschenko, Alexander

    2016-12-01

    Protease-activated receptors (PARs) are members of a well-known family of transmembrane G protein-coupled receptors (GPCRs). Four PARs have been identified to date, of which PAR1 and PAR2 are the most abundant receptors, and have been shown to be expressed in the kidney vascular and tubular cells. PAR signaling is mediated by an N-terminus tethered ligand that can be unmasked by serine protease cleavage. The receptors are activated by endogenous serine proteases, such as thrombin (acts on PARs 1, 3, and 4) and trypsin (PAR2). PARs can be involved in glomerular, microvascular, and inflammatory regulation of renal function in both normal and pathological conditions. As an example, it was shown that human glomerular epithelial and mesangial cells express PARs, and these receptors are involved in the pathogenesis of crescentic glomerulonephritis, glomerular fibrin deposition, and macrophage infiltration. Activation of these receptors in the kidney also modulates renal hemodynamics and glomerular filtration rate. Clinical studies further demonstrated that the concentration of urinary thrombin is associated with glomerulonephritis and type 2 diabetic nephropathy; thus, molecular and functional mechanisms of PARs activation can be directly involved in renal disease progression. We briefly discuss here the recent literature related to activation of PAR signaling in glomeruli and the kidney in general and provide some examples of PAR1 signaling in glomeruli podocytes. Copyright © 2016 the American Physiological Society.

  1. Bicarbonate therapy for prevention of chronic kidney disease progression.

    Science.gov (United States)

    Łoniewski, Igor; Wesson, Donald E

    2014-03-01

    Kidney injury in chronic kidney disease (CKD) is likely multifactorial, but recent data support that a component is mediated by mechanisms used by the kidney to increase acidification in response to an acid challenge to systemic acid-base status. If so, systemic alkalization might attenuate this acid-induced component of kidney injury. An acid challenge to systemic acid-base status increases nephron acidification through increased production of endothelin, aldosterone, and angiotensin II, each of which can contribute to kidney inflammation and fibrosis that characterizes CKD. Systemic alkalization that ameliorates an acid challenge might attenuate the contributions of angiotensin II, endothelin, and aldosterone to kidney injury. Some small clinical studies support the efficacy of alkalization in attenuating kidney injury and slowing glomerular filtration rate decline in CKD. This review focuses on the potential that orally administered NaHCO₃ prevents CKD progression and additionally addresses its mechanism of action, side effects, possible complications, dosage, interaction, galenic form description, and contraindications. Current National Kidney Foundation guidelines recommend oral alkali, including NaHCO₃(-), in CKD patients with serum HCO₃(-) <22 mmol/l. Although oral alkali can be provided by other medications and by base-inducing dietary constituents, oral NaHCO₃ will be the focus of this review because of its relative safety and apparent efficacy, and its comparatively low cost.

  2. 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 ...

  3. Triple pelvic osteotomy: effect on limb function and progression of degenerative joint disease

    International Nuclear Information System (INIS)

    Johnson, A.L.; Smith, C.W.; Pijanowski, G.J.; Hungerford, L.L.

    1998-01-01

    The objective of this study was to evaluate prospectively the outcome of 21 clinical patients treated with triple pelvic osteotomies during the year following surgery. Specific aims included documenting the time of and extent of improved limb function as measured by force plate analysis, evaluating the progression of degenerative joint disease (DJD) in the treated and untreated coxofemoral joints, and determining whether or not triple pelvic osteotomy resulted in degenerative joint changes in the ipsilateral stifle and hock. Twelve dogs were treated unilaterally and nine dogs were treated bilaterally with triple pelvic osteotomies. There were no differences in mean anteversion angles, angles of inclination, or preoperative DJD between treated hips and untreated hips. Degenerative joint disease progressed significantly in all hips regardless of treatment. Two cases developed hyperextension of their hocks after the triple pelvic osteotomies. However, no radiographic evidence of DJD was observed for any of the stifles or hocks at any observation time. A significant increase in vertical peak force (VPF) scores was noted for treated legs by two-to-three months after surgery, which continued over time. Untreated legs did not show a significant change in VPF scores over time. No differences were found in progression to higher scores when unilaterally treated legs, first-side treated legs, and second-side treated legs were compared

  4. Vitamin D deficiency aggravates chronic kidney disease progression after ischemic acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Janaína Garcia Gonçalves

    Full Text Available Despite a significant improvement in the management of chronic kidney disease (CKD, its incidence and prevalence has been increasing over the years. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including Transforming growth factor-β1 (TGF-β1. Besides cardiovascular diseases and infections, several studies show that Vitamin D status has been considered as a non-traditional risk factor for the progression of CKD. Given the importance of vitamin D in the maintenance of essential physiological functions, we studied the events involved in the chronic kidney disease progression in rats submitted to ischemia/reperfusion injury under vitamin D deficiency (VDD.Rats were randomized into four groups: Control; VDD; ischemia/reperfusion injury (IRI; and VDD+IRI. At the 62 day after sham or IRI surgery, we measured inulin clearance, biochemical variables and hemodynamic parameters. In kidney tissue, we performed immunoblotting to quantify expression of Klotho, TGF-β, and vitamin D receptor (VDR; gene expression to evaluate renin, angiotensinogen, and angiotensin-converting enzyme; and immunohistochemical staining for ED1 (macrophages, type IV collagen, fibronectin, vimentin, and α-smooth mucle actin. Histomorphometric studies were performed to evaluate fractional interstitial area.IRI animals presented renal hypertrophy, increased levels of mean blood pressure and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of ED1 cells, increased expression of collagen IV, fibronectin, vimentin and α-actin, and reduced expression of Klotho protein were observed. VDD deficiency contributed to increased levels of plasma PTH as well as for important chronic tubulointerstitial changes (fibrosis, inflammatory infiltration, tubular dilation and atrophy, increased expression of TGF-β1 and decreased expression of VDR and Klotho protein observed in VDD+IRI animals.Through inflammatory

  5. High Resolution Discovery Proteomics Reveals Candidate Disease Progression Markers of Alzheimer’s Disease in Human Cerebrospinal Fluid

    Science.gov (United States)

    Lee, Anita Y. H.; Song, Qinghua; Liaw, Andy; Wiener, Matt; Paweletz, Cloud P.; Seeburger, Jeffrey L.; Li, Jenny; Meng, Fanyu; Deyanova, Ekaterina G.; Mazur, Matthew T.; Settlage, Robert E.; Zhao, Xuemei; Southwick, Katie; Du, Yi; Holder, Dan; Sachs, Jeffrey R.; Laterza, Omar F.; Dallob, Aimee; Chappell, Derek L.; Snyder, Karen; Modur, Vijay; King, Elizabeth; Joachim, Catharine; Bondarenko, Andrey Y.; Shearman, Mark; Soper, Keith A.; Smith, A. David; Potter, William Z.; Koblan, Ken S.; Sachs, Alan B.

    2015-01-01

    Disease modifying treatments for Alzheimer’s disease (AD) constitute a major goal in medicine. Current trends suggest that biomarkers reflective of AD neuropathology and modifiable by treatment would provide supportive evidence for disease modification. Nevertheless, a lack of quantitative tools to assess disease modifying treatment effects remains a major hurdle. Cerebrospinal fluid (CSF) biochemical markers such as total tau, p-tau and Ab42 are well established markers of AD; however, global quantitative biochemical changes in CSF in AD disease progression remain largely uncharacterized. Here we applied a high resolution open discovery platform, dMS, to profile a cross-sectional cohort of lumbar CSF from post-mortem diagnosed AD patients versus those from non-AD/non-demented (control) patients. Multiple markers were identified to be statistically significant in the cohort tested. We selected two markers SME-1 (p<0.0001) and SME-2 (p = 0.0004) for evaluation in a second independent longitudinal cohort of human CSF from post-mortem diagnosed AD patients and age-matched and case-matched control patients. In cohort-2, SME-1, identified as neuronal secretory protein VGF, and SME-2, identified as neuronal pentraxin receptor-1 (NPTXR), in AD were 21% (p = 0.039) and 17% (p = 0.026) lower, at baseline, respectively, than in controls. Linear mixed model analysis in the longitudinal cohort estimate a decrease in the levels of VGF and NPTXR at the rate of 10.9% and 6.9% per year in the AD patients, whereas both markers increased in controls. Because these markers are detected by mass spectrometry without the need for antibody reagents, targeted MS based assays provide a clear translation path for evaluating selected AD disease-progression markers with high analytical precision in the clinic. PMID:26270474

  6. 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.

  7. 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.

  8. A novel biomarker of laminin turnover is associated with mortality and disease progression in chronic kidney disease

    DEFF Research Database (Denmark)

    Nielsen, Signe Holm; Guldager Kring Rasmussen, Daniel; Fenton, Anthony

    2017-01-01

    INTRODUCTION AND AIMS: Patients with chronic kidney disease (CKD) have increased risk of progressing to end-stage renal disease (ESRD) and a high mortality rate. One of the major underlying causes of progression of renal failure is renal fibrosis, which is caused by dysregulated extracellular...

  9. A new semiquantitative method for evaluation of metastasis progression.

    Science.gov (United States)

    Volarevic, A; Ljujic, B; Volarevic, V; Milovanovic, M; Kanjevac, T; Lukic, A; Arsenijevic, N

    2012-01-01

    Although recent technical advancements are directed toward developing novel assays and methods for detection of micro and macro metastasis, there are still no reports of reliable, simple to use imaging software that could be used for the detection and quantification of metastasis in tissue sections. We herein report a new semiquantitative method for evaluation of metastasis progression in a well established 4T1 orthotopic mouse model of breast cancer metastasis. The new semiquantitative method presented here was implemented by using the Autodesk AutoCAD 2012 program, a computer-aided design program used primarily for preparing technical drawings in 2 dimensions. By using the Autodesk AutoCAD 2012 software- aided graphical evaluation we managed to detect each metastatic lesion and we precisely calculated the average percentage of lung and liver tissue parenchyma with metastasis in 4T1 tumor-bearing mice. The data were highly specific and relevant to descriptive histological analysis, confirming reliability and accuracy of the AutoCAD 2012 software as new method for quantification of metastatic lesions. The new semiquantitative method using AutoCAD 2012 software provides a novel approach for the estimation of metastatic progression in histological tissue sections.

  10. Mechanisms of copper ion mediated Huntington's disease progression.

    Directory of Open Access Journals (Sweden)

    Jonathan H Fox

    2007-03-01

    Full Text Available Huntington's disease (HD is caused by a dominant polyglutamine expansion within the N-terminus of huntingtin protein and results in oxidative stress, energetic insufficiency and striatal degeneration. Copper and iron are increased in the striata of HD patients, but the role of these metals in HD pathogenesis is unknown. We found, using inductively-coupled-plasma mass spectroscopy, that elevations of copper and iron found in human HD brain are reiterated in the brains of affected HD transgenic mice. Increased brain copper correlated with decreased levels of the copper export protein, amyloid precursor protein. We hypothesized that increased amounts of copper bound to low affinity sites could contribute to pro-oxidant activities and neurodegeneration. We focused on two proteins: huntingtin, because of its centrality to HD, and lactate dehydrogenase (LDH, because of its documented sensitivity to copper, necessity for normoxic brain energy metabolism and evidence for altered lactate metabolism in HD brain. The first 171 amino acids of wild-type huntingtin, and its glutamine expanded mutant form, interacted with copper, but not iron. N171 reduced Cu(2+in vitro in a 1:1 copper:protein stoichiometry indicating that this fragment is very redox active. Further, copper promoted and metal chelation inhibited aggregation of cell-free huntingtin. We found decreased LDH activity, but not protein, and increased lactate levels in HD transgenic mouse brain. The LDH inhibitor oxamate resulted in neurodegeneration when delivered intra-striatially to healthy mice, indicating that LDH inhibition is relevant to neurodegeneration in HD. Our findings support a role of pro-oxidant copper-protein interactions in HD progression and offer a novel target for pharmacotherapeutics.

  11. 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

  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. Low-level laser therapy ameliorates disease progression in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Farfara, Dorit; Tuby, Hana; Trudler, Dorit; Doron-Mandel, Ella; Maltz, Lidya; Vassar, Robert J; Frenkel, Dan; Oron, Uri

    2015-02-01

    Low-level laser therapy (LLLT) has been used to treat inflammation, tissue healing, and repair processes. We recently reported that LLLT to the bone marrow (BM) led to proliferation of mesenchymal stem cells (MSCs) and their homing in the ischemic heart suggesting its role in regenerative medicine. The aim of the present study was to investigate the ability of LLLT to stimulate MSCs of autologous BM in order to affect neurological behavior and β-amyloid burden in progressive stages of Alzheimer's disease (AD) mouse model. MSCs from wild-type mice stimulated with LLLT showed to increase their ability to maturate towards a monocyte lineage and to increase phagocytosis activity towards soluble amyloid beta (Aβ). Furthermore, weekly LLLT to BM of AD mice for 2 months, starting at 4 months of age (progressive stage of AD), improved cognitive capacity and spatial learning, as compared to sham-treated AD mice. Histology revealed a significant reduction in Aβ brain burden. Our results suggest the use of LLLT as a therapeutic application in progressive stages of AD and imply its role in mediating MSC therapy in brain amyloidogenic diseases.

  14. Recent progress in gene therapy for Parkinson's disease.

    Science.gov (United States)

    Nakata, Y; Yasuda, T; Mochizuki, H

    2012-12-01

    Parkinson's disease (PD) is an age-related and the second most common neurodegenerative disorder beyond Alzheimer's disease. A neuropathological hallmark of PD is a prominent loss of dopaminergic neurons in the substantia nigra projecting into the caudate and putamen. Oral administration of L-dopa and/or dopamine agonists ameliorates cardinal motor symptoms of PD. However, an intermittent and long-term treatment with L-dopa frequently induces adverse side effects such as motor fluctuations and dyskinesia. As alternative therapeutic strategies, the following four approaches are currently under evaluation for clinical gene therapy trials in PD; 1) recombinant adeno-associated virus 2 system encoding aromatic L-amino acid decarboxylase (AADC), 2) glutamic acid decarboxylase (GAD) and 3) Neurturin, and 4) equine infectious anemia virus-based lentiviral system encoding AADC, tyrosine hydroxylase (TH) and GTP cyclohydrolase I (GCH) in a single transcriptional unit. GAD and Neurturin have been assessed in double blind placebocontrolled phase II studies; GAD showed a significant improvement in motor function, and Neurturin, although it failed to show significant effects at 12 months post-treatment, exhibited promising outcomes in additional examinations at 18 months. The other two approaches also represented significant effects in phase I or I/II studies. Adverse side effects due to surgery have not been observed. Here, we review preclinical and clinical trials encouraging further investigations of curative treatment for the patients suffering from PD.

  15. 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.

  16. Association of plasma adipokines with chronic obstructive pulmonary disease severity and progression.

    Science.gov (United States)

    Oh, Yeon-Mok; Jeong, Byeong-Ho; Woo, Sook-Young; Kim, Su-Young; Kim, Hojoong; Lee, Ji-Hyun; Lim, Seong Yong; Rhee, Chin Kook; Yoo, Kwang Ha; Lee, Jin Hwa; Yoon, Hyoung Kyu; Sin, Don D; Lee, Sang-Do; Kim, Eun Kyung; Park, Hye Yun

    2015-07-01

    Two adipokines, leptin and adiponectin, regulate metabolic and inflammatory systems reciprocally. The role of adiponectin in chronic obstructive pulmonary disease (COPD) has been studied. However, there are few data evaluating the relationship of plasma leptin with COPD severity or progression. The objective of this study was to evaluate the relationship of leptin, adiponectin, and the leptin/adiponectin ratio with COPD severity and progression according to COPD phenotypes. Plasma leptin and adiponectin levels were measured in 196 subjects with COPD selected from the Korean Obstructive Lung Disease cohort. Using a linear regression model and mixed linear regression, we determined the relationship of plasma leptin and adiponectin levels and the leptin/adiponectin ratio to COPD severity and progression over 3 years. The concentration of adiponectin in plasma positively correlated with percent emphysema on initial computed tomography (CT) (adjusted P = 0.022), whereas plasma leptin concentrations and the leptin/adiponectin ratio exhibited a significant inverse correlation with initial FEV1 (adjusted P = 0.013 for leptin and adjusted P = 0.041 for leptin/adiponectin ratio). Increased plasma leptin and leptin/adiponectin ratio were significantly associated with change in percent emphysema over 3 years (adjusted P = 0.037 for leptin and adjusted P = 0.029 for leptin/adiponectin ratio), whereas none of the adipokines demonstrated an association with FEV1 decline over the 3-year period. Plasma adiponectin and leptin vary according to COPD phenotypes. Plasma leptin and the leptin/adiponectin ratio, but not adiponectin, were significantly associated with changes in CT-assessed emphysema, suggesting a potential role as a biomarker in emphysema progression in patients with COPD.

  17. Plasma levels of nucleosomes and nucleosome-autoantibody complexes in murine lupus: effects of disease progression and lipopolyssacharide administration.

    NARCIS (Netherlands)

    Licht, R.; Bruggen, M.C.J. van; Oppers-Walgreen, B.; Rijke, T.P.M.; Berden, J.H.M.

    2001-01-01

    OBJECTIVE: To evaluate the effect of disease progression and lipopolysaccharide (LPS) administration on the presence of nucleosomes, antinucleosome reactivity, and nucleosome-Ig complexes in the circulation of MRL and control mice. METHODS: Plasma samples from lupus-prone (MRL/lpr and MRL/+) and

  18. [Research progress on identification and quality evaluation of glues medicines].

    Science.gov (United States)

    Li, Hui-Hu; Ren, Gang; Chen, Li-Min; Zhong, Guo-Yue

    2018-01-01

    Glues medicines is a special kind of traditional Chinese medicine.As the market demand is large, the raw materials are in short supply and lacks proper quality evaluation technology, which causes inconsistent quality of products on the market. Its authentic identification and evaluation stay a problem to be solved. In this paper, the research progress of the methods and techniques of the evaluation of the identification and quality of glues medicines were reviewed. The researches of medicinal glue type identification and quality evaluation mainly concentrated in four aspects of medicinal materials of physical and chemical properties, trace elements, organic chemicals and biological genetic methods and techniques. The methods of physicochemical properties include thermal analysis, gel electrophoresis, isoelectric focusing electrophoresis, infrared spectroscopy, gel exclusion chromatography, and circular dichroism. The methods including atomic absorption spectrometry, X-ray fluorescence spectrometry, plasma emission spectrometry and visible spectrophotometry were used for the study of the trace elements of glues medicines. The organic chemical composition was studied by methods of composition of amino acids, content detection, odor detection, lipid soluble component, organic acid detection. Methods based on the characteristics of biogenetics include DNA, polypeptide and amino acid sequence difference analysis. Overall, because of relative components similarity of the glues medicines (such as amino acids, proteins and peptides), its authenticity and quality evaluation index is difficult to judge objectively, all sorts of identification evaluation methods have different characteristics, but also their limitations. It indicates that further study should focus on identification of evaluation index and various technology integrated application combining with the characteristics of the production process. Copyright© by the Chinese Pharmaceutical Association.

  19. 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...

  20. Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease

    NARCIS (Netherlands)

    Jafar, TH; Stark, PC; Schmid, CH; Landa, M; Maschio, G; Marcantoni, C; de Jong, PE; de Zeeuw, D; Shahinfar, S; Ruggenenti, P; Remuzzi, G; Levey, AS

    Background. Angiotensin-converting enzyme (ACE) inhibitors reduce urine protein excretion and slow the progression of renal disease. The beneficial effect in slowing the progression of renal disease is greater in patients with higher urine protein excretion at the onset of treatment. We hypothesized

  1. 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.

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

    Indian Academy of Sciences (India)

    2011-08-07

    based positron emission tomography (PET) and single photon emitted ... Such approaches have immense potential to track progression of metastasis, immune cell trafficking, stem cell therapy, transgenic animals and even ...

  3. Progressive development of renal cysts in glycogen storage disease type I.

    Science.gov (United States)

    Gjorgjieva, Monika; Raffin, Margaux; Duchampt, Adeline; Perry, Ariane; Stefanutti, Anne; Brevet, Marie; Tortereau, Antonin; Dubourg, Laurence; Hubert-Buron, Aurélie; Mabille, Mylène; Pelissou, Coralie; Lassalle, Louis; Labrune, Philippe; Mithieux, Gilles; Rajas, Fabienne

    2016-09-01

    Glycogen storage disease type I (GSDI) is a rare metabolic disease due to glucose-6 phosphatase deficiency, characterized by fasting hypoglycemia. Patients also develop chronic kidney disease whose mechanisms are poorly understood. To decipher the process, we generated mice with a kidney-specific knockout of glucose-6 phosphatase (K.G6pc -/- mice) that exhibited the first signs of GSDI nephropathy after 6 months of G6pc deletion. We studied the natural course of renal deterioration in K.G6pc -/- mice for 18 months and observed the progressive deterioration of renal functions characterized by early tubular dysfunction and a later destruction of the glomerular filtration barrier. After 15 months, K.G6pc -/- mice developed tubular-glomerular fibrosis and podocyte injury, leading to the development of cysts and renal failure. On the basis of these findings, we were able to detect the development of cysts in 7 out of 32 GSDI patients, who developed advanced renal impairment. Of these 7 patients, 3 developed renal failure. In addition, no renal cysts were detected in six patients who showed early renal impairment. In conclusion, renal pathology in GSDI is characterized by progressive tubular dysfunction and the development of polycystic kidneys that probably leads to the development of irreversible renal failure in the late stages. Systematic observations of cyst development by kidney imaging should improve the evaluation of the disease's progression, independently of biochemical markers. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. [Retrospective analysis of influence of differential protein intake on renal prognosis for progressive chronic kidney disease].

    Science.gov (United States)

    Dai, Wendi; Yin, Daoxin; Cui, Wenying; Liu, Wenhu

    2014-01-28

    To explore retrospectively the influence of differential protein intake on renal prognosis for progressive chronic kidney disease (CKD). A total of 159 chronic kidney disease patients at stages 2, 3 and 4 were enrolled and a questionnaire survey was conducted from January 2009 to July 2012. They were followed monthly and their clinical data collected, including primary disease, blood pressure, body mass index and adverse events. Laboratory tests were performed every 3 months, including biochemical parameters, protein-energy malnutrition (PEM), diet reviews and daily protein intake (DPI). A simplified MDRD formula was employed to evaluate the level of estimated glomerular filtration rate (eGFR). According to the level of DPI, they were divided into 3 groups of very low protein diet (VLPD): DPI ≤ 0.6 g · kg(-1) · d(-1), low-protein diet (LPD): DPI >0.6-protein diet (NPD): DPI ≥ 0.8 · g · kg(-1) · d(-1). Among them, 4 cases (2.50%) progressed to uremia stage and received renal replacement therapy, 2(1.25%) experienced rapid decline in renal function, 9(5.66%) were hospitalized from cardio-cerebral diseases and the 2-year kidney survival rate was 97.5%. At the end of study, among 9 patients of PEM, 2 subjects had a serum level of albumin under 32 g/L and another 7 with a BMI 0.05). Within a certain range, differential protein intake may not significantly affect the prognosis of kidney for progressive CKD patients.

  5. Evaluating innovation. Part 1: The concept of progressive scholarly acceptance.

    Science.gov (United States)

    Schnurman, Zane; Kondziolka, Douglas

    2016-01-01

    Understanding how the relevant medical community accepts new therapies is vital to patients, physicians, and society. Increasingly, focus is placed on how medical innovations are evaluated. But recognizing when a treatment has become accepted practice-essentially, acceptance by the scientific community-remains a challenge and a barrierto investigating treatment development. This report aims to demonstrate the theory, method, and limitations of a model for measuring a new metric that the authors term "progressive scholarly acceptance." A model was developed to identify when the scientific community has accepted an innovation, by observing when researchers have moved beyond the initial study of efficacy. This model could enable further investigations into the methods and influences of treatment development.

  6. Embryonic Stem Cells-loaded Gelatin Microcryogels Slow Progression of Chronic Kidney Disease

    Science.gov (United States)

    Geng, Xiao-Dong; Zheng, Wei; Wu, Cong-Mei; Wang, Shu-Qiang; Hong, Quan; Cai, Guang-Yan; Chen, Xiang-Mei; Wu, Di

    2016-01-01

    Background: Chronic kidney disease (CKD) has become a public health problem. New interventions to slow or prevent disease progression are urgently needed. In this setting, cell therapies associated with regenerative effects are attracting increasing interest. We evaluated the effect of embryonic stem cells (ESCs) on the progression of CKD. Methods: Adult male Sprague–Dawley rats were subjected to 5/6 nephrectomy. We used pedicled greater omentum flaps packing ESC-loaded gelatin microcryogels (GMs) on the 5/6 nephrectomized kidney. The viability of ESCs within the GMs was detected using in vitro two-photon fluorescence confocal imaging. Rats were sacrificed after 12 weeks. Renal injury was evaluated using serum creatinine, urea nitrogen, 24 h protein, renal pathology, and tubular injury score results. Structural damage was evaluated by periodic acid-Schiff and Masson trichrome staining. Results: In vitro, ESCs could be automatically loaded into the GMs. Uniform cell distribution, good cell attachment, and viability were achieved from day 1 to 7 in vitro. After 12 weeks, in the pedicled greater omentum flaps packing ESC-loaded GMs on 5/6 nephrectomized rats group, the plasma urea nitrogen levels were 26% lower than in the right nephrectomy group, glomerulosclerosis index was 62% lower and tubular injury index was 40% lower than in the 5/6 nephrectomized rats group without GMs. Conclusions: In a rat model of established CKD, we demonstrated that the pedicled greater omentum flaps packing ESC-loaded GMs on the 5/6 nephrectomized kidney have a long-lasting therapeutic rescue function, as shown by the decreased progression of CKD and reduced glomerular injury. PMID:26879011

  7. Technology development, evaluation, and application (TDEA) FY 1997 progress report

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, L.G.

    1998-05-01

    The public expects that the Los Alamos National Laboratory (LANL) will operate in a manner that prevents negative impacts to the environment and protects the safety and health of its employees and the public. To achieve this goal within budget, the Department of Energy (DOE) and LANL must develop new and improved environment, safety, and health (ES and H) technologies and implement innovative, more cost-effective ES and H approaches to operations. In FY95, the Environment, Safety, and Health (ESH) Division initiated a Technology Development, Evaluation, and Application (TDEA) program. The purpose of this unique program is to test and develop technologies that solve LANL ES and H problems and improve the safety of LANL operations. This progress report presents the results of 10 projects funded in FY97 by the TDEA Committee of the Environment, Safety, and Health Division. Products generated from the projects funded in FY97 included implementation of radiation worker dosimetric monitoring systems (two); evaluation and validation of cost-effective animal-tracking systems for environmental studies (two); evaluation of personal protective equipment (two); and development of a method for optimal placement of continuous air monitors in the workplace.

  8. Technology development, evaluation, and application (TDEA) FY 1997 progress report

    International Nuclear Information System (INIS)

    Hoffman, L.G.

    1998-05-01

    The public expects that the Los Alamos National Laboratory (LANL) will operate in a manner that prevents negative impacts to the environment and protects the safety and health of its employees and the public. To achieve this goal within budget, the Department of Energy (DOE) and LANL must develop new and improved environment, safety, and health (ES and H) technologies and implement innovative, more cost-effective ES and H approaches to operations. In FY95, the Environment, Safety, and Health (ESH) Division initiated a Technology Development, Evaluation, and Application (TDEA) program. The purpose of this unique program is to test and develop technologies that solve LANL ES and H problems and improve the safety of LANL operations. This progress report presents the results of 10 projects funded in FY97 by the TDEA Committee of the Environment, Safety, and Health Division. Products generated from the projects funded in FY97 included implementation of radiation worker dosimetric monitoring systems (two); evaluation and validation of cost-effective animal-tracking systems for environmental studies (two); evaluation of personal protective equipment (two); and development of a method for optimal placement of continuous air monitors in the workplace

  9. 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

  10. IL-17 Axis Driven Inflammation in Non-Alcoholic Fatty Liver Disease Progression

    Science.gov (United States)

    Giles, Daniel A.; Moreno-Fernandez, Maria E; Divanovic, Senad

    2016-01-01

    Obesity is a primary risk factor for the development of non-alcoholic fatty liver disease (NAFLD). NAFLD, the most common chronic liver disease in the world, represents a spectrum of disorders that range from steatosis (NAFL) to steatohepatitis (NASH) to cirrhosis. It is anticipated that NAFLD will soon surpass chronic hepatitis C infection as the leading cause for needing liver transplantation. Despite its clinical and public health significance no specific therapies are available. Although the etiology of NAFLD is multifactorial and remains largely enigmatic, it is well accepted that inflammation is a central component of NAFLD pathogenesis. Despite the significance, critical immune mediators, loci of immune activation, the immune signaling pathways and the mechanism(s) underlying disease progression remain incompletely understood. Recent findings have focused on the role of Interleukin 17 (IL-17) family of proinflammatory cytokines in obesity and pathogenesis of obesity-associated sequelae. Notably, obesity favors a Th17 bias and is associated with increased IL-17A expression in both humans and mice. Further, in mice, IL-17 axis has been implicated in regulation of both obesity and NAFLD pathogenesis. However, despite these recent advances several important questions require further evaluation including: the relevant cellular source of IL-17A production; the critical IL-17RA-expressing cell type; the critical liver infiltrating immune cells; and the underlying cellular effector mechanisms. Addressing these questions may aid in the identification and development of novel therapeutic targets for prevention of inflammation-driven NAFLD progression. PMID:26028039

  11. Predictors of the Progression of Dementia Severity in Brazilian Patients with Alzheimer's Disease and Vascular Dementia

    Directory of Open Access Journals (Sweden)

    Márcia L. Chaves

    2010-01-01

    Full Text Available Introduction. This study evaluates the progression of dementia and identifies prognostic risk factors for dementia. Methods. A group of 80 Brazilian community residents with dementia (34 with Alzheimer's disease and 46 with vascular dementia was assessed over the course of 2 years. Data were analyzed with Cox regression survival analysis. Results. The data showed that education predicted cognitive decline (HR=1.2; P<.05 when analyzed without controlling for vascular risk factors. After the inclusion of vascular risk factors, education (HR=1.32; P<.05 and hypertension were predictive for cognitive decline (HR=38; P<.05, and Alzheimer's disease diagnosis was borderline predictive (P=.055. Conclusion. Vascular risk factors interacted with the diagnosis of vascular dementia. Education was a strong predictor of decline.

  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 (pspecific to progressive supranuclear palsy and may also be observed in Parkinson'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. 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.

  14. Molecular sampling of prostate cancer: a dilemma for predicting disease progression

    Directory of Open Access Journals (Sweden)

    Mucci Lorelei A

    2010-03-01

    Full Text Available Abstract Background Current prostate cancer prognostic models are based on pre-treatment prostate specific antigen (PSA levels, biopsy Gleason score, and clinical staging but in practice are inadequate to accurately predict disease progression. Hence, we sought to develop a molecular panel for prostate cancer progression by reasoning that molecular profiles might further improve current clinical models. Methods We analyzed a Swedish Watchful Waiting cohort with up to 30 years of clinical follow up using a novel method for gene expression profiling. This cDNA-mediated annealing, selection, ligation, and extension (DASL method enabled the use of formalin-fixed paraffin-embedded transurethral resection of prostate (TURP samples taken at the time of the initial diagnosis. We determined the expression profiles of 6100 genes for 281 men divided in two extreme groups: men who died of prostate cancer and men who survived more than 10 years without metastases (lethals and indolents, respectively. Several statistical and machine learning models using clinical and molecular features were evaluated for their ability to distinguish lethal from indolent cases. Results Surprisingly, none of the predictive models using molecular profiles significantly improved over models using clinical variables only. Additional computational analysis confirmed that molecular heterogeneity within both the lethal and indolent classes is widespread in prostate cancer as compared to other types of tumors. Conclusions The determination of the molecularly dominant tumor nodule may be limited by sampling at time of initial diagnosis, may not be present at time of initial diagnosis, or may occur as the disease progresses making the development of molecular biomarkers for prostate cancer progression challenging.

  15. 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), Pde Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  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. Retrospective study of the effect of disease progression on patient reported outcomes in HER-2 negative metastatic breast cancer patients

    Directory of Open Access Journals (Sweden)

    Yu Elaine

    2011-06-01

    Full Text Available Abstract Background This retrospective study evaluated the impact of disease progression and of specific sites of metastasis on patient reported outcomes (PROs that assess symptom burden and health related quality of life (HRQoL in women with metastatic breast cancer (mBC. Methods HER-2 negative mBC patients (n = 102 were enrolled from 7 U.S. community oncology practices. Demographic, disease and treatment characteristics were abstracted from electronic medical records and linked to archived Patient Care Monitor (PCM assessments. The PCM is a self-report measure of symptom burden and HRQoL administered as part of routine care in participating practices. Linear mixed models were used to examine change in PCM scores over time. Results Mean age was 57 years, with 72% of patients Caucasian, and 25% African American. Median time from mBC diagnosis to first disease progression was 8.8 months. Metastasis to bone (60%, lung (28% and liver (26% predominated at initial metastatic diagnosis. Results showed that PCM items assessing fatigue, physical pain and trouble sleeping were sensitive to either general effects of disease progression or to effects associated with specific sites of metastasis. Progression of disease was also associated with modest but significant worsening of General Physical Symptoms, Treatment Side Effects, Acute Distress and Impaired Performance index scores. In addition, there were marked detrimental effects of liver metastasis on Treatment Side Effects, and of brain metastasis on Acute Distress. Conclusions Disease progression has a detrimental impact on cancer-related symptoms. Delaying disease progression may have a positive impact on patients' HRQoL.

  18. Occupational therapy for patients with chronic diseases: CVA, rheumatoid arthritis and progressive diseases of the central nervous system.

    NARCIS (Netherlands)

    Driessen, M.J.; Dekker, J.; Lankhorst, G.; Zee, J. van der

    1997-01-01

    A substantial proportion of the patients treated by occupational therapists have a chronic disease. The aim of this study was to describe the outlines of occupational therapy treatment for three specific groups of chronic diseases: progressive neurological diseases, cerebrovascular accident and

  19. Evaluation of medication treatment for Alzheimer's disease on clinical evidence

    Directory of Open Access Journals (Sweden)

    Meng-qiu LI

    2014-03-01

    Full Text Available Objective To formulate the best treatment plan for Alzheimer's disease patients by evaluating the therapeutic efficacy and side effect of various evidence-based programs. Methods Alzheimer's disease, donepezil, rivastigmine, galantamine, memantine, rosiglitazone, etc. were defined as retrieval words. PubMed, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure (CNKI databases were used with applying of manual searching. Systematic reviews, randomized controlled trials (RCT, controlled clinical trials and case-observation studies were collected and evaluated by Jadad Scale. Results After screening, 33 selected resources included 14 systematic reviews, 14 randomized controlled trials, 4 controlled clinical trials and 1 case-observation study. According to Jadad Scale, total 28 articles were evaluated to be high quality (12 with score 4, 10 score 5, 6 score 7, and 5 were low quality with score 3. It was summarized as follows: 1 Alzheimer's disease is a progressive neurodegenerative disease for which no cure exists. To date, only symptomatic treatments with cholinesterase inhibitors (donepezil, rivastigmine, galantamine and an N-methyl-D-aspartate (NMDA receptor noncompetitive antagonist (memantine, are effective and well tolerated to counterbalance the neurotransmitter disturbance, but cannot limit or impact on disease progression. 2 Disease modifying drug is an potential agent, with persistent effect on slowing the progression of structural damage, and can be detected even after withdrawing the treatment. Many types of disease modifying drugs are undergoing clinical trials. Conclusions Using evidence-based medicine methods can provide best clinical evidence on Alzheimer's disease treatment. doi: 10.3969/j.issn.1672-6731.2014.03.009

  20. Etiology and pediatric chronic kidney disease progression: Taiwan Pediatric Renal Collaborative Study.

    Science.gov (United States)

    Chiou, Yuan-Yow; Lin, Ching-Yuang; Chen, Mei-Ju; Chiou, Yee-Hsuan; Wang, Yi-Fan; Wang, Hsin-Hui; Tain, You-Lin; Chou, Hsin-Hsu

    2016-09-01

    This study aims to examine the characteristics of Taiwanese children with chronic kidney disease (CKD) and delineate the factors that lead to disease progression in this population. We reviewed the records of the Taiwan Pediatric Renal Collaborative Study, a multicenter database of Taiwanese children with CKD. Multivariate regression analysis was used to identify the main factors associated with disease progression. A total of 382 children aged 1-18 years were included in the study (median age was 10.6 years; interquartile range: 6.4-13.8). There were 197 males (51.6%) and 185 females. CKD Stage 1 was diagnosed in 159 children (41.6%), Stage 2 in 160 (41.9%), Stage 3 in 51 (13.4%), and Stage 4 in 12 (3.1%). Fifty-six children (14.7%) experienced CKD progression. A multivariate analysis for all patients indicated that the risk for disease progression was increased in children with CKD secondary to a structural abnormality, genetic disease, anemia, elevated diastolic blood pressure, or elevated blood urea nitrogen. Compared with children with Stage 1 CKD, those with Stage 2 and Stage 4 CKD had decreased risk for CKD progression in this short-term cohort follow-up. CKD etiology affects disease progression. Careful monitoring and treatment of anemia and elevated blood pressure in children with CKD may slow disease progression. Copyright © 2015. Published by Elsevier B.V.

  1. Hepatitis C virus: risk factors and disease progression

    NARCIS (Netherlands)

    Grady, B.P.X.

    2015-01-01

    Hepatitis C virus (HCV) is a single-stranded RNA virus and was first identified in 1989 as a cause for transfusion-associated non-A, non-B hepatitis. Transmission of HCV occurs predominantly via blood-to-blood contact. After acute infection about 75% of those infected progress to a persistent

  2. Apathy in Alzheimer’s disease: Contribution to a clinical view on progression of dementia

    Science.gov (United States)

    Stella, Florindo; de Andrade, Larissa Pires; Vital, Thays Martins; Coelho, Flávia Gomes de Melo; Nascimento, Carla Manuela Crispim; Hernández, Salma Stephany Soleman

    2010-01-01

    In addition to cognitive impairment, apathy is increasingly recognized as an important neuropsychiatric syndrome in Alzheimer’s disease (AD). Aims To identify the relationship between dementia severity and apathy levels, and to discuss the association of this condition with other psychopathological manifestations in AD patients. Methods This study involved 15 AD patients (mean age: 77 years; schooling: 4.9 years), with mild, moderate and severe dementia, living in Rio Claro SP, Brazil. Procedures included evaluation of cognitive status by the Mini-Mental State Examination, Clinical Dementia Rating, and Global Deterioration Scale. Apathy syndrome was assessed by the Apathy Evaluation Scale and Neuropsychiatric Inventory (NPI-apathy domain). Other psychopathological manifestations such as depression were also considered. Results Patients with more severe dementia presented higher levels of apathy, reinforcing the hypothesis that apathy severity aggravates as the disease progresses. Using the Spearman coefficient correlation an association was identified between the MMSE and Apathy Evaluation Scale (r=0.63; p=0.01), and also between the MMSE and NPI-apathy domain (r=0.81; p=0.01). Associations were also found between the Global Deterioration Scale and Apathy Evaluation Scale (r=0.58; p=0.02), and between the Global Deterioration Scale and NPI-apathy domain (r=0.81; p=0.01). Conclusions Apathy is a distinct syndrome among patients with AD and increases with global deterioration. PMID:29213685

  3. Apathy in Alzheimer's disease: Contribution to a clinical view on progression of dementia

    Directory of Open Access Journals (Sweden)

    Florindo Stella

    Full Text Available Abstract In addition to cognitive impairment, apathy is increasingly recognized as an important neuropsychiatric syndrome in Alzheimer's disease (AD. Aims: To identify the relationship between dementia severity and apathy levels, and to discuss the association of this condition with other psychopathological manifestations in AD patients. Methods: This study involved 15 AD patients (mean age: 77 years; schooling: 4.9 years, with mild, moderate and severe dementia, living in Rio Claro SP, Brazil. Procedures included evaluation of cognitive status by the Mini-Mental State Examination, Clinical Dementia Rating, and Global Deterioration Scale. Apathy syndrome was assessed by the Apathy Evaluation Scale and Neuropsychiatric Inventory (NPI-apathy domain. Other psychopathological manifestations such as depression were also considered. Results: Patients with more severe dementia presented higher levels of apathy, reinforcing the hypothesis that apathy severity aggravates as the disease progresses. Using the Spearman coefficient correlation an association was identified between the MMSE and Apathy Evaluation Scale (r=0.63; p=0.01, and also between the MMSE and NPI-apathy domain (r=0.81; p=0.01. Associations were also found between the Global Deterioration Scale and Apathy Evaluation Scale (r=0.58; p=0.02, and between the Global Deterioration Scale and NPI-apathy domain (r=0.81; p=0.01. Conclusions: Apathy is a distinct syndrome among patients with AD and increases with global deterioration.

  4. Progression and prognostic indicators of bronchial disease in children with sickle cell disease.

    Science.gov (United States)

    Williams, Sophia N; Nussbaum, Eliezer; Yoonessi, Leila; Morphew, Tricia; Randhawa, Inderpal

    2014-06-01

    The pulmonary complications of sickle cell disease (SCD) are a leading cause of morbidity and mortality (MacLean et al. Am J Respir Crit Care Med 178:1055-1059, 2008; Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; National Heart, Lung, and Blood Institute, 2009). Despite this recognition, predictive markers of lung dysfunction progression remain elusive (Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; Platt et al. N Engl J Med 330:1639-1644, 1994; Caboot et al. Curr Opin Pediatr 20:279-287, 2008; Field et al. Am J Hematol 83:574-576, 2008; Shirlo et al. Peadiatr Respir Review 12:78-82, 2011). This study was designed describe the longitudinal progression and identify specific markers that influence bronchial disease in SCD. A retrospective, chart review of 89 patients with SCD was conducted. All patients underwent spirometry in conjunction with body plethysmography as part of routine care. Eleven lung function variables were assessed, five of which were selected to establish patterns of normal, obstructive, restrictive, or mixed obstructive-restrictive physiology (Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; Field et al. Am J Hematol 83:574-576, 2008). In the unadjusted model, forced expiratory volume in one second (FEV1)% of predicted trended downward with age, while total lung capacity (TLC)% of predicted showed a bimodal distribution and carbon monoxide diffusion capacity corrected for hemoglobin (DLCOcor)% of predicted remained stable. Adjusting for acute chest syndrome (ACS) episodes, medication status, and growth velocity (GV), the final model demonstrated that the downward trend between FEV1% of predicted with age was further influenced by the latter two factors. Initial decline in FEV1% of predicted is associated with worsening pulmonary dysfunction over time. Independent of ACS episodes, the factors most influential on the progression of FEV1% predicted include the introduction of medications as well as the

  5. Demyelination load as predictor for disease progression in juvenile metachromatic leukodystrophy.

    Science.gov (United States)

    Strölin, Manuel; Krägeloh-Mann, Ingeborg; Kehrer, Christiane; Wilke, Marko; Groeschel, Samuel

    2017-06-01

    The aim of this study was to investigate whether the extent and topography of cerebral demyelination correlates with and predicts disease progression in patients with juvenile metachromatic leukodystrophy (MLD). A total of 137 MRIs of 46 patients with juvenile MLD were analyzed. Demyelination load and brain volume were quantified using the previously developed Software "clusterize." Clinical data were collected within the German Leukodystrophy Network and included full scale intelligence quotient (FSIQ) and gross motor function data. Voxel-based lesion-symptom mapping (VLSM) across the whole brain was performed to investigate the spatial relationship of cerebral demyelination with motor or cognitive function. The prognostic value of the demyelination load at disease onset was assessed to determine the severity of disease progression. The demyelination load (corrected by the individual brain volume) correlated significantly with gross motor function ( r = +0.55) and FSIQ ( r = -0.55). Demyelination load at disease onset was associated with the severity of disease progression later on ( P loss in FSIQ and more central region demyelination with decline of motor function. Especially progression of demyelination within the motor area was associated with severe disease progression. We were able to show for the first time in a large cohort of patients with juvenile MLD that the demyelination load correlates with motor and cognitive symptoms. Moreover, demyelination load at disease onset, especially the involvement of the central region, predicts severity of disease progression. Thus, demyelination load seems a functionally relevant MRI parameter.

  6. Inhibition of 5-Lipoxygenase inhibitor zileuton in high-fat diet-induced nonalcoholic fatty liver disease progression model

    Directory of Open Access Journals (Sweden)

    Kuifen Ma

    2017-11-01

    Full Text Available Objective(s: Arachidonic Acid/5-lipoxygenase (AA/5-LOX pathway connects lipid metabolism and proinflammatory cytokine, which are both related to the development and progression of nonalcoholic fatty liver disease (NAFLD. Therefore, the present study was designed to investigate the role of AA/5-LOX pathway in progression of NAFLD, and the effect of zileuton, an inhibitor of 5-LOX, in this model. Materials and Methods: Animal model for progression of NAFLD was established via feeding high saturated fat diet (HFD. Liver function, HE staining, NAFLD activity score (NAS were used to evaluate NAFLD progression. We detected the lipid metabolism substrates: free fatty acids (FFA and AA, products: cysteinyl-leukotrienes (CysLTs, and changes in gene and protein level of key enzyme in AA/5-LOX pathway including PLA2 and 5-LOX. Furthermore, we determined whether NAFLD progression pathway was delayed or reversed when zileuton (1-[1-(1-benzothiophen-2-ylethyl]-1-hydroxyurea was administrated. Results: Rat model for progression of NAFLD was well established as analyzed by liver transaminase activities, hematoxylin-eosin (HE staining and NAS. The concentrations of substrates and products in AA/5-LOX pathway were increased with the progression of NAFLD. mRNA and protein expression of PLA2 and 5-LOX were all enhanced. Moreover, administration of zileuton inhibited AA/5-LOX pathway and reversed the increased transamine activities and NAS. Conclusion: AA/5-LOX pathway promotes the progression of NAFLD, which can be reversed by zileuton.

  7. Characterization of LEDGF/p75 genetic variants and association with HIV-1 disease progression.

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    Peter Messiaen

    Full Text Available BACKGROUND: As Lens epithelium-derived growth factor (LEDGF/p75 is an important co-factor involved in HIV-1 integration, the LEDGF/p75-IN interaction is a promising target for the new class of allosteric HIV integrase inhibitors (LEDGINs. Few data are available on the genetic variability of LEDGF/p75 and the influence on HIV disease in vivo. This study evaluated the relation between LEDGF/p75 genetic variation, mRNA expression and HIV-1 disease progression in order to guide future clinical use of LEDGINs. METHODS: Samples were derived from a therapy-naïve cohort at Ghent University Hospital and a Spanish long-term-non-progressor cohort. High-resolution melting curve analysis and Sanger sequencing were used to identify all single nucleotide polymorphisms (SNPs in the coding region, flanking intronic regions and full 3'UTR of LEDGF/p75. In addition, two intronic tagSNPs were screened based on previous indication of influencing HIV disease. LEDGF/p75 mRNA was quantified in patient peripheral blood mononuclear cells (PBMC using RT-qPCR. RESULTS: 325 samples were investigated from patients of Caucasian (n = 291 and African (n = 34 origin, including Elite (n = 49 and Viremic controllers (n = 62. 21 SNPs were identified, comprising five in the coding region and 16 in the non-coding regions and 3'UTR. The variants in the coding region were infrequent and had no major impact on protein structure according to SIFT and PolyPhen score. One intronic SNP (rs2737828 was significantly under-represented in Caucasian patients (P<0.0001 compared to healthy controls (HapMap. Two SNPs showed a non-significant trend towards association with slower disease progression but not with LEDGF/p75 expression. The observed variation in LEDGF/p75 expression was not correlated with disease progression. CONCLUSIONS: LEDGF/p75 is a highly conserved protein. Two non-coding polymorphisms were identified indicating a correlation with disease outcome, but further

  8. Primary progressive aphasia patients evaluated using diffusion tensor imaging and voxel based volumetry-preliminary results

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    Fábio Pascotto de Oliveira

    2011-06-01

    Full Text Available There are individuals who have a progressive language deficit without presenting cognitive deficits in other areas. One of the diseases related to this presentation is primary progressive aphasia (PPA. OBJECTIVE: Identify by means of diffusion tensor imaging (DTI and measurements of cortical volume, brain areas that lead to dysphasia when presenting signs of impaired connectivity or reduced volume. METHOD: Four patients with PPA were evaluated using DTI, and measurements of cortical volumes in temporal areas. These patients were compared with two normal volunteers. RESULTS: There is a trend to a difference in the number and volume of related fibers between control group and patients with PPA. Comparing cortical volumes in temporal areas between groups yielded a trend to a smaller volume in PPA patients. CONCLUSION: Patients with PPA have a trend to impairment in cortical and subcortical levels regarding relevant areas.

  9. Switch of predicted HIV-1 tropism in treated subjects and its association with disease progression

    Science.gov (United States)

    Castagna, Antonella; Monno, Laura; Carta, Stefania; Galli, Laura; Carrara, Stefania; Fedele, Valentina; Punzi, Grazia; Fanti, Iuri; Caramello, Pietro; Lepri, Alessandro Cozzi; De Luca, Andrea; Ceccherini-Silberstein, Francesca; Monforte, Antonella d’Arminio

    2016-01-01

    Abstract Dynamics of human immunodeficiency virus type 1 (HIV-1) tropism after antiretroviral therapy (ART) initiation and their association with disease progression are poorly investigated. This was a cohort study on subjects from the ICONA cohort receiving ART with persistently detectable (PD) or persistently undetectable (PU) viral load (VL) and with stored plasma or peripheral blood mononuclear cell (PBMC) samples at 2 time-points (T1, T2) after ART initiation. HIV-1 co-receptor tropism was determined by V3-loop sequencing and the geno2pheno algorithm. A switch in viral tropism was defined if the tropism classification at T2 differed from that observed at T1. Time to disease progression, defined as the occurrence of a new acquired immune deficiency syndrome (AIDS)-defining event/death from T2, was also evaluated. One hundred ninety-five patients were analyzed (124 PD, 71 PU). Over a median follow-up of 22.6 (19.8–28.1) months, PD and PU patients showed similar rates (95% confidence interval) of switch to a non-R5 virus [PD: 6.9 (3.7–11.2)/100-person-years of follow-up (PYFU); PU: 8.0 (3.4–14.5)/100-PYFU; P = 0.63] and of switch to a R5 virus [PD: 15.4 (7.3–26.4)/100-PYFU; PU: 8.1 (2.5–16.7)/100-PYFU; P = 0.38]. Switch to non-R5 virus was predicted by nadir CD4+ before T1. Twenty-two (18%) PD and 4 (6%) PU subjects experienced disease progression (P = 0.02). The risk of disease progression was independently associated with a switch in co-receptor tropism (adjusted hazard ratio = 4.06, 95% CI: 1.20–13.80, P = 0.03) as well as age, AIDS diagnosis, nadir CD4+ before T2, current CD4+, and VL. Switch of HIV-1 tropism under ART occurs in both directions, with similar rates in subjects with PD or PU VL and it might be predictive of future unfavorable clinical outcome. PMID:27858869

  10. Clinical course of nonalcoholic fatty liver disease: an assessment of severity, progression, and outcomes

    Directory of Open Access Journals (Sweden)

    Simeone JC

    2017-12-01

    Full Text Available Jason C Simeone,1 Jay P Bae,2 Byron J Hoogwerf,3 Qian Li,1 Axel Haupt,3 Ayad K Ali,4 Marilyn K Boardman,3 Beth L Nordstrom1 1Real-world Evidence, Evidera, Waltham, MA, USA; 2Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 3Lily Diabetes, Eli Lilly and Company, Indianapolis, IN, USA; 4Global Patient Safety, Eli Lilly and Company, Indianapolis, IN, USA Purpose: To identify the characteristics and initial disease severity of patients with nonalcoholic fatty liver disease (NAFLD and assess incidence and risk factors for disease progression in a retrospective study.Methods: Patients ≥18 years of age without alcoholism or other liver diseases (eg, hepatitis B/C were selected from Geisinger Health System electronic medical record data from 2004 to 2015. Initial disease stage was stratified into uncomplicated NAFLD, advanced fibrosis, cirrhosis, hepatocellular carcinoma (HCC, and liver transplant using clinical biomarkers, diagnosis, and procedure codes. Disease progression was defined as stage progression or death and analyzed via Kaplan–Meier plots and multistate models.Results: In the NAFLD cohort (N=18,754, 61.5% were women, 39.0% had type 2 diabetes mellitus (T2DM, and the mean body mass index was 38.2±10.2 kg/m2. At index, 69.9% had uncomplicated NAFLD, 11.7% had advanced fibrosis, and 17.8% had cirrhosis. Of 18,718 patients assessed for progression, 17.3% progressed (11.0% had stage progression, 6.3% died without evidence of stage progression during follow-up (median=842 days. Among subgroups, 12.3% of those without diabetes mellitus progressed vs 24.7% of those with T2DM. One-year mortality increased from 0.5% in uncomplicated NAFLD to 22.7% in HCC. After liver transplant, mortality decreased to 5.6% per year.Conclusions: In 2.3 years of follow-up, approximately 17% of patients progressed or died without evidence of stage progression. T2DM was associated with approximately twice the risk of

  11. Impairment of vowel articulation as a possible marker of disease progression in Parkinson's disease.

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    Sabine Skodda

    Full Text Available PURPOSE: The aim of the current study was to survey if vowel articulation in speakers with Parkinson's disease (PD shows specific changes in the course of the disease. METHOD: 67 patients with PD (42 male and 40 healthy speakers (20 male were tested and retested after an average time interval of 34 months. Participants had to read a given text as source for subsequent calculation of the triangular vowel space area (tVSA and vowel articulation index (VAI. Measurement of tVSA and VAI were based upon analysis of the first and second formant of the vowels /α/, /i/and /u/ extracted from defined words within the text. RESULTS: At first visit, VAI values were reduced in male and female PD patients as compared to the control group, and showed a further decrease at the second visit. Only in female Parkinsonian speakers, VAI was correlated to overall speech impairment based upon perceptual impression. VAI and tVSA were correlated to gait impairment, but no correlations were seen between VAI and global motor impairment or overall disease duration. tVSA showed a similar reduction in the PD as compared to the control group and was also found to further decline between first and second examination in female, but not in male speakers with PD. CONCLUSIONS: Measurement of VAI seems to be superior to tVSA in the description of impaired vowel articulation and its further decline in the course of the disease in PD. Since impairment of vowel articulation was found to be independent from global motor function but correlated to gait dysfunction, measurement of vowel articulation might have a potential to serve as a marker of axial disease progression.

  12. Cellular Transplantation Alters the Disease Progression in Becker's Muscular Dystrophy

    OpenAIRE

    Sharma, Alok; Paranjape, Amruta; Sane, Hemangi; Bhagawanani, Khushboo; Gokulchandran, Nandini; Badhe, Prerna

    2013-01-01

    Becker’s Muscular Dystrophy (BMD) is a dystrophinopathy manifested as progressive muscle degeneration. Autologous Bone Marrow Mononuclear Cells (BMMNCs) have shown some myogenic potential. The paracrine effects of the BMMNCs reduce the inflammation and are thought to reduce muscle degeneration. We treated a 39 year old dental surgeon suffering from BMD. Muscle strength was reduced when measured using modified Medical Research Council’s Manual Muscle Testing (mMRC-MMT). Static sitting balance ...

  13. [Musical long-term memory throughout the progression of Alzheimer disease].

    Science.gov (United States)

    Groussard, Mathilde; Mauger, Caroline; Platel, Hervé

    2013-03-01

    In Alzheimer patients with a solid musical background, isolated case-reports have reported the maintenance of remarkable musical abilities despite clear difficulties in their verbal memory and linguistic functions. These reports have encouraged a number of scientists to undertake more systematic studies which would allow a rigorous approach to the analysis of musical memory in Alzheimer patients with no formal musical background. Although restricted in number, the latest data are controversial regarding preserved musical capacities in Alzheimer patients. Our current review of the literature addresses this topic and advances the hypothesis that the processes of musical memory are function of illness progression. In the earlier stages, the majority of evaluations concerned musical episodic memory and suggested a dysfunction of this memory whereas in the moderate and severe stages, musical semantic memory and implicit learning are the majority of investigations and seemed more resistant to Alzheimer disease. In summary, our current review bring to understand the memory circuits involved and highlight the necessity to adapted the investigational tools employed to conform with the severity of the signs and symptoms of progressive Alzheimer disease in order to demonstrate the preserved musical capacities.

  14. Host and viral genetic correlates of clinical definitions of HIV-1 disease progression.

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    Concepción Casado

    Full Text Available BACKGROUND: Various patterns of HIV-1 disease progression are described in clinical practice and in research. There is a need to assess the specificity of commonly used definitions of long term non-progressor (LTNP elite controllers (LTNP-EC, viremic controllers (LTNP-VC, and viremic non controllers (LTNP-NC, as well as of chronic progressors (P and rapid progressors (RP. METHODOLOGY AND PRINCIPAL FINDINGS: We re-evaluated the HIV-1 clinical definitions, summarized in Table 1, using the information provided by a selected number of host genetic markers and viral factors. There is a continuous decrease of protective factors and an accumulation of risk factors from LTNP-EC to RP. Statistical differences in frequency of protective HLA-B alleles (p-0.01, HLA-C rs9264942 (p-0.06, and protective CCR5/CCR2 haplotypes (p-0.02 across groups, and the presence of viruses with an ancestral genotype in the "viral dating" (i.e., nucleotide sequences with low viral divergence from the most recent common ancestor support the differences among principal clinical groups of HIV-1 infected individuals. CONCLUSIONS: A combination of host genetic and viral factors supports current clinical definitions that discriminate among patterns of HIV-1 progression. The study also emphasizes the need to apply a standardized and accepted set of clinical definitions for the purpose of disease stratification and research.

  15. Injectable and oral contraception and the incidence and progression of cervical disease in HIV-infected women in South Africa

    Science.gov (United States)

    Westreich, Daniel; Jamal, Naiomi; Smith, Jennifer S.; Schulze, Doreen; Williams, Sophie; Michelow, Pam; Levin, Simon; Firnhaber, Cynthia

    2014-01-01

    Background Few data exist regarding the effect of hormonal contraception (HC) on incidence and progression of cervical disease (e.g., cervical dysplasia, squamous intraepithelial lesions, cervical intraepithelial neoplasia) in HIV-infected African women. Study Design We conducted an observational study of HIV-seropositive women in Johannesburg, South Africa. The effect of individual HC types on the incidence and progression of cervical disease was determined using Poisson regression to obtain adjusted incidence rate ratios (IRR). Results We evaluated 594 HIV-infected women, with median follow-up time of 445 days; 75 of these women were receiving some form of hormonal contraception (largely DMPA, NET-EN, or COCs) at baseline. Risks of incidence and progression of cervical disease were similar comparing women not receiving HCs to women receiving DMPA, NET-EN, or COCs both individually by HC-type and considering all HC together. Conclusions There was no statistically significant effect of particular HC methods or of HC use in general on rates of incidence or progression of cervical disease in this study. These results should reassure us that use of HC is unlikely to substantially increase risks of cervical disease among HIV-positive women. PMID:24485095

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

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    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.

  17. Progress of radionuclide diagnostic methods in central nervous system diseases

    International Nuclear Information System (INIS)

    Badmaev, K.N.; Zen'kovich, S.G.

    1982-01-01

    A summarry on modern radionuclide diagnosis achivements of central nervous system diseases is presented. Most optimal tumorotropic preparations and compounds in the view of decreasing irradiation does and optimazing image are given

  18. Progress in Early Diagnosis of Sickle Cell Disease

    Science.gov (United States)

    Pearson, Howard A.

    1971-01-01

    Discusses the basis of sickle cell Anemia, including: a description of the diseased blood, genetic implications, recognition of symptoms in infancy, the need for implementation of wide screening procedures, and the future prospects of a cure. (AJ)

  19. Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: A systematic review and meta-analysis

    NARCIS (Netherlands)

    Currie, G. (Gemma); Taylor, A.H.M. (Alison H. M.); Fujita, T. (Toshiro); Ohtsu, H. (Hiroshi); Lindhardt, M. (Morten); K. Rossing; Boesby, L. (Lene); Edwards, N.C. (Nicola C.); Ferro, C.J. (Charles J.); J. Townend (Jonathan); A.H. van den Meiracker (Anton); Saklayen, M.G. (Mohammad G.); Oveisi, S. (Sonia); Jardine, A.G. (Alan G.); C. Delles (Christian); Preiss, D.J. (David J.); Mark, P.B. (Patrick B.)

    2016-01-01

    textabstractBackground: 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.

  20. Anthesis, the infectious process and disease progress curves for fusarium head blight in wheat

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    Erlei Melo Reis

    2016-06-01

    Full Text Available ABSTRACT Fusarium head blight of wheat (Triticum aestivum, caused by the fungus Gibberella zeae, is a floral infecting disease that causes quantitative and qualitative losses to winter cereals. In Brazil, the sanitary situation of wheat has led to research in order to develop strategies for sustainable production, even under adverse weather conditions. To increase the knowledge of the relationship among the presence of anthesis, the infectious process, the disease progress and the saprophytic fungi present in wheat anthers, studies were conducted in the experimental field of University of Passo Fundo (UPF, using the cultivar Marfim, in the 2011 growing season. The disease incidence in spikes and spikelets was evaluated. The presence of exserted anthers increased the spike exposure time to the inoculum. The final incidence of fusarium head blight, in the field, was dependent on the presence of exserted anthers. The disease followed an aggregation pattern and its evolution increased with time, apparently showing growth according to secondary cycles. The fungi isolated from exserted anthers (Alternaria sp., Fusarium sp., Drechslera spp. and Epicoccum sp. did not compete for the infection site of fusarium head blight in wheat, not interfering with the incidence of F. graminearum.

  1. Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis

    Science.gov (United States)

    Li, Ting; Guo, Li; Chen, Zhiwei; Gu, Liyang; Sun, Fangfang; Tan, Xiaoming; Chen, Sheng; Wang, Xiaodong; Ye, Shuang

    2016-09-01

    To evaluate the efficacy of pirfenidone in patients with rapidly progressive interstitial lung disease (RPILD) related to clinically amyopathic dermatomyositis (CADM), we conducted an open-label, prospective study with matched retrospective controls. Thirty patients diagnosed with CADM-RPILD with a disease duration <6 months at Renji Hospital South Campus from June 2014 to November 2015 were prospectively enrolled and treated with pirfenidone at a target dose of 1800 mg/d in addition to conventional treatment, such as a glucocorticoid and/or other immunosuppressants. Matched patients without pirfenidone treatment (n = 27) were retrospectively selected as controls between October 2012 and September 2015. We found that the pirfenidone add-on group displayed a trend of lower mortality compared with the control group (36.7% vs 51.9%, p = 0.2226). Furthermore, the subgroup analysis indicated that the pirfenidone add-on had no impact on the survival of acute ILD patients (disease duration <3 months) (50% vs 50%, p = 0.3862) while for subacute ILD patients (disease duration 3-6 months), the pirfenidone add-on (n = 10) had a significantly higher survival rate compared with the control subgroup (n = 9) (90% vs 44.4%, p = 0.0450). Our data indicated that the pirfenidone add-on may improve the prognosis of patients with subacute ILD related to CADM.

  2. Oxidative stress: Lipid peroxidation products as predictors in disease progression

    OpenAIRE

    Suranjana Ray Halder; Maitree Bhattacharyya

    2014-01-01

    Oxidative stress is implicated in the pathogenesis of numerous disease processes, including diabetes mellitus, atherosclerosis, ischemia reperfusion injury, rheumatoid arthritis, neurodegenerative diseases as well as in the aging process. Chemical modification of amino acids in protein during lipid peroxidation (LPO) results in the formation of lipoxidation products, which may serve as indicators of oxidative stress in vivo. The various types of aldehydes such as 4-hydroxynonenal, malondialde...

  3. Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease.

    Science.gov (United States)

    Lambertus, Stanley; Bax, Nathalie M; Fakin, Ana; Groenewoud, Joannes M M; Klevering, B Jeroen; Moore, Anthony T; Michaelides, Michel; Webster, Andrew R; van der Wilt, Gert Jan; Hoyng, Carel B

    2017-01-01

    Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options-including gene therapy-are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date) and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including variable rates of functional and structural progression, thereby potentially limiting the ability of phase I/II clinical trials to assess efficacy of novel therapies with few patients. To accommodate this problem, we developed and validated a sensitive and reliable composite clinical trial endpoint for disease progression based on structural measurements of retinal degeneration. We used longitudinal data from early-onset Stargardt patients from the Netherlands (development cohort, n = 14) and the United Kingdom (external validation cohort, n = 18). The composite endpoint was derived from best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography. Weighting optimization techniques excluded visual acuity from the composite endpoint. After optimization, the endpoint outperformed each univariable outcome, and showed an average progression of 0.41° retinal eccentricity per year (95% confidence interval, 0.30-0.52). Comparing with actual longitudinal values, the model accurately predicted progression (R2, 0.904). These properties were largely preserved in the validation cohort (0.43°/year [0.33-0.53]; prediction: R2, 0.872). We subsequently ran a two-year trial simulation with the composite endpoint, which detected a 25% decrease in disease progression with 80% statistical power using only 14 patients. These results suggest that a multimodal endpoint, reflecting structural macular changes, provides a sensitive measurement of disease progression in

  4. Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease.

    Directory of Open Access Journals (Sweden)

    Stanley Lambertus

    progression in Stargardt disease. It can be very useful in the evaluation of novel therapeutic modalities in rare disorders.

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

    Science.gov (United States)

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

    2016-06-01

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

  6. Infection with concurrent multiple hepatitis C virus genotypes is associated with faster HIV disease progression

    NARCIS (Netherlands)

    van Asten, Liselotte; Prins, Maria

    2004-01-01

    OBJECTIVE: To elucidate the importance of hepatitis C Virus (HCV) genotype in HIV disease progression. DESIGN: This study was conducted among 126 HIV/HCV co-infected drug users with a known interval of HIV seroconversion whose HCV genotype was known early in HIV infection. Both clinical progression

  7. 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

  8. Weight preserving image registration for monitoring disease progression in lung CT.

    Science.gov (United States)

    Gorbunova, Vladlena; Lol, Pechin; Ashraf, Haseem; Dirksen, Asger; Nielsen, Mads; de Bruijne, Marleen

    2008-01-01

    We present a new image registration based method for monitoring regional disease progression in longitudinal image studies of lung disease. A free-form image registration technique is used to match a baseline 3D CT lung scan onto a following scan. Areas with lower intensity in the following scan compared with intensities in the deformed baseline image indicate local loss of lung tissue that is associated with progression of emphysema. To account for differences in lung intensity owing to differences in the inspiration level in the two scans rather than disease progression, we propose to adjust the density of lung tissue with respect to local expansion or compression such that the total weight of the lungs is preserved during deformation. Our method provides a good estimation of regional destruction of lung tissue for subjects with a significant difference in inspiration level between CT scans and may result in a more sensitive measure of disease progression than standard quantitative CT measures.

  9. Postmortem Pittsburgh Compound B (PiB) binding increases with Alzheimer's disease progression.

    Science.gov (United States)

    Beckett, Tina L; Webb, Robin L; Niedowicz, Dana M; Holler, Christopher J; Matveev, Sergey; Baig, Irfan; LeVine, Harry; Keller, Jeffrey N; Murphy, M Paul

    2012-01-01

    The development of imaging reagents is of considerable interest in the Alzheimer's disease (AD) field. Some of these, such as Pittsburgh Compound B (PiB), were designed to bind to the amyloid-β peptide (Aβ), the major component of amyloid deposits in the AD brain. Although these agents were designed for imaging amyloid deposits in vivo, a major avenue of evaluation relies on postmortem cross validation with established indices of AD pathology. In this study, we evaluated changes in the postmortem binding of PiB and its relationship to other aspects of Aβ-related pathology in a series of AD cases and age-matched controls. We also examined cases of preclinical AD (PCAD) and amnestic mild cognitive impairment (MCI), both considered early points in the AD continuum. PiB binding was found to increase with the progression of the disease and paralleled increases in the less soluble forms of Aβ, including SDS-stable Aβ oligomers. Increased PiB binding and its relationship to Aβ was only significant in a brain region vulnerable to the development of AD pathology (the superior and middle temporal gyri) but not in an unaffected region (cerebellum). This implies that the amyloid deposited in disease-affected regions may possess fundamental, brain region specific characteristics that may not as yet be fully appreciated. These data support the idea that PiB is a useful diagnostic tool for AD, particularly in the early stage of the disease, and also show that PiB could be a useful agent for the discovery of novel disease-related properties of amyloid.

  10. 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...

  11. Current and future disease progression of the chronic HCV population in the United States.

    Directory of Open Access Journals (Sweden)

    Martin Zalesak

    Full Text Available Chronic hepatitis C virus (HCV infection can lead to advanced liver disease (AdvLD, including cirrhosis, decompensated cirrhosis, and liver cancer. The aim of this study was to determine recent historical rates of HCV patient progression to AdvLD and to project AdvLD prevalence through 2015. We first determined total 2008 US chronic HCV prevalence from the National Health and Nutrition Evaluation Surveys. Next, we examined disease progression and associated non-pharmacological costs of diagnosed chronic HCV-infected patients between 2007-2009 in the IMS LifeLink and CMS Medicare claims databases. A projection model was developed to estimate AdvLD population growth through 2015 in patients diagnosed and undiagnosed as of 2008, using the 2007-2009 progression rates to generate a "worst case" projection of the HCV-related AdvLD population (i.e., scenario where HCV treatment is the same in the forecasted period as it was before 2009. We found that the total diagnosed chronic HCV population grew from 983,000 to 1.19 million in 2007-2009, with patients born from 1945-1964 accounting for 75.0% of all patients, 83.7% of AdvLD patients, and 79.2% of costs in 2009, indicating that HCV is primarily a disease of the "baby boomer" population. Non-pharmacological costs grew from $7.22 billion to $8.63 billion, with the majority of growth derived from the 60,000 new patients that developed AdvLD in 2007-2009, 91.5% of whom were born between 1945 and 1964. The projection model estimated the total AdvLD population would grow from 195,000 in 2008 to 601,000 in 2015, with 73.5% of new AdvLD cases from patients undiagnosed as of 2008. AdvLD prevalence in patients diagnosed as of 2008 was projected to grow 6.5% annually to 303,000 patients in 2015. These findings suggest that strategies to diagnose and treat HCV-infected patients are urgently needed to increase the likelihood that progression is interrupted, particularly for patients born from 1945-1964.

  12. An evaluability assessment of a West Africa based Non-Governmental Organization's (NGO) progressive evaluation strategy.

    Science.gov (United States)

    D'Ostie-Racine, Léna; Dagenais, Christian; Ridde, Valéry

    2013-02-01

    While program evaluations are increasingly valued by international organizations to inform practices and public policies, actual evaluation use (EU) in such contexts is inconsistent. Moreover, empirical literature on EU in the context of humanitarian Non-Governmental Organizations (NGOs) is very limited. The current article focuses on the evaluability assessment (EA) of a West-Africa based humanitarian NGO's progressive evaluation strategy. Since 2007, the NGO has established an evaluation strategy to inform its maternal and child health care user-fee exemption intervention. Using Wholey's (2004) framework, the current EA enabled us to clarify with the NGO's evaluation partners the intent of their evaluation strategy and to design its program logic model. The EA ascertained the plausibility of the evaluation strategy's objectives, the accessibility of relevant data, and the utility for intended users of evaluating both the evaluation strategy and the conditions that foster EU. Hence, key evaluability conditions for an EU study were assured. This article provides an example of EA procedures when such guidance is scant in the literature. It also offers an opportunity to analyze critically the use of EAs in the context of a humanitarian NGO's collaboration with evaluators and political actors. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Petra Steinacker

    Full Text Available BACKGROUND: Biomarkers of disease progression in amyotrophic lateral sclerosis (ALS could support the identification of beneficial drugs in clinical trials. We aimed to test whether soluble fragments of beta-amyloid precursor protein (sAPPα and sAPPß correlated with clinical subtypes of ALS and were of prognostic value. METHODOLOGY/PRINCIPAL FINDINGS: In a cross-sectional study including patients with ALS (N = 68 with clinical follow-up data over 6 months, Parkinson's disease (PD, N = 20, and age-matched controls (N = 40, cerebrospinal fluid (CSF levels of sAPPα a, sAPPß and neurofilaments (NfH(SMI35 were measured by multiplex assay, Progranulin by ELISA. CSF sAPPα and sAPPß levels were lower in ALS with a rapidly-progressive disease course (p = 0.03, and p = 0.02 and with longer disease duration (p = 0.01 and p = 0.01, respectively. CSF NfH(SMI35 was elevated in ALS compared to PD and controls, with highest concentrations found in patients with rapid disease progression (p<0.01. High CSF NfH(SMI3 was linked to low CSF sAPPα and sAPPß (p = 0.001, and p = 0.007, respectively. The ratios CSF NfH(SMI35/CSF sAPPα,-ß were elevated in patients with fast progression of disease (p = 0.002 each. CSF Progranulin decreased with ongoing disease (p = 0.04. CONCLUSIONS: This study provides new CSF candidate markers associated with progression of disease in ALS. The data suggest that a deficiency of cellular neuroprotective mechanisms (decrease of sAPP is linked to progressive neuro-axonal damage (increase of NfH(SMI35 and to progression of disease.

  14. HOTAIR role in melanoma progression and its identification in the blood of patients with advanced disease.

    Science.gov (United States)

    Cantile, Monica; Scognamiglio, Giosuè; Marra, Laura; Aquino, Gabriella; Botti, Chiara; Falcone, Maria Rosaria; Malzone, Maria Gabriella; Liguori, Giuseppina; Di Bonito, Maurizio; Franco, Renato; Ascierto, Paolo Antonio; Botti, Gerardo

    2017-12-01

    The molecular mechanisms responsible for the metastatic progression of melanoma have not been fully defined yet. We have recently shown that an important role in this process is certainly played by HOX genes, whose regulation is under control of particular non-coding RNAs, some of which are present within the HOX locus. HOTAIR is the most studied among them, whose aberrant expression is associated with the metastatic progression of many malignancies. The aim of this study was to verify the role played by HOTAIR in metastatic progression of melanoma and to evaluate the circulating levels of HOTAIR in the blood of patients with metastatic melanoma. A series of melanocytic lesions were selected to evaluate the potential changes in the expression of HOTAIR during the evolution of the disease through in situ and molecular approaches. None of the benign melanocytic lesions showed the presence of HOTAIR. The staining of HOTAIR resulted very weak in the primary pT1 lesions, while it was very strong in all pairs of primary tissues and corresponding metastases. Surprisingly, we found the presence of HOTAIR in some intratumoral lymphocytes, while this positivity decreased in lymphocyte component further away from the tumor. HOTAIR was also detected in the serum of selected metastatic patients. These data allowed us to speculate on the fundamental role played by HOTAIR in tumor evolution of melanoma. Its presence in intratumoral lymphocytes might suggest that its involvement in the modulation of tumor microenvironment and the detection in the serum could be used in the management of melanoma patients. © 2017 Wiley Periodicals, Inc.

  15. Bile microbiota in primary sclerosing cholangitis: Impact on disease progression and development of biliary dysplasia.

    Directory of Open Access Journals (Sweden)

    Pedro Pereira

    Full Text Available The etiopathogenesis and risk for development of biliary neoplasia in primary sclerosing cholangitis (PSC are largely unknown. Microbes or their metabolites have been suggested to play a role. To explore this potential microbial involvement, we evaluated the differences in biliary microbiota in PSC patients at an early disease stage without previous endoscopic retrograde cholangiography (ERC examinations, advanced disease stage, and with biliary dysplasia or cholangiocarcinoma.Bile samples from the common bile duct were collected from 46 controls and 80 patients with PSC during ERC (37 with early disease, 32 with advanced disease, and 11 with biliary dysplasia. DNA isolation, amplification, and Illumina MiSeq sequencing were performed for the V1-V3 regions of the bacterial 16S rRNA gene.The most common phyla found were Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria, and Actinobacteria. The most common families were Prevotellaceae, Streptococcaceae, Veillonellaceae, Fusobacteriaceae, and Pasteurellaceae, and the most common genera were Prevotella, Streptococcus, Veillonella, Fusobacterium, and Haemophilus. The bacterial communities of non-PSC subjects and early stage PSC patients were similar. Alpha diversity was lower in patients with biliary dysplasia/cholangiocarcinoma than in other groups. An increase in Streptococcus abundance was positively correlated with the number of ERC examinations. Streptococcus abundance was also positively correlated with an increase in disease severity, even after controlling for the number of ERC examinations.Our findings suggest that the aetiology of PSC is not associated with changes in bile microbial communities, but the genus Streptococcus may play a pathogenic role in the progression of the disease.

  16. Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease.

    Science.gov (United States)

    Harambat, Jérôme; Kunzmann, Kevin; Azukaitis, Karolis; Bayazit, Aysun K; Canpolat, Nur; Doyon, Anke; Duzova, Ali; Niemirska, Anna; Sözeri, Betul; Thurn-Valsassina, Daniela; Anarat, Ali; Bessenay, Lucie; Candan, Cengiz; Peco-Antic, Amira; Yilmaz, Alev; Tschumi, Sibylle; Testa, Sara; Jankauskiene, Augustina; Erdogan, Hakan; Rosales, Alejandra; Alpay, Harika; Lugani, Francesca; Arbeiter, Klaus; Mencarelli, Francesca; Kiyak, Aysel; Dönmez, Osman; Drozdz, Dorota; Melk, Anette; Querfeld, Uwe; Schaefer, Franz

    2017-12-01

    Recent studies in adult chronic kidney disease (CKD) suggest that metabolic acidosis is associated with faster decline in estimated glomerular filtration rate (eGFR). Alkali therapies improve the course of kidney disease. Here we investigated the prevalence and determinants of abnormal serum bicarbonate values and whether metabolic acidosis may be deleterious to children with CKD. Associations between follow-up serum bicarbonate levels categorized as under 18, 18 to under 22, and 22 or more mmol/l and CKD outcomes in 704 children in the Cardiovascular Comorbidity in Children with CKD Study, a prospective cohort of pediatric patients with CKD stages 3-5, were studied. The eGFR and serum bicarbonate were measured every six months. At baseline, the median eGFR was 27 ml/min/1.73m 2 and median serum bicarbonate level 21 mmol/l. During a median follow-up of 3.3 years, the prevalence of metabolic acidosis (serum bicarbonate under 22 mmol/l) was 43%, 60%, and 45% in CKD stages 3, 4, and 5, respectively. In multivariable analysis, the presence of metabolic acidosis as a time-varying covariate was significantly associated with log serum parathyroid hormone through the entire follow-up, but no association with longitudinal growth was found. A total of 211 patients reached the composite endpoint (ESRD or 50% decline in eGFR). In a multivariable Cox model, children with time-varying serum bicarbonate under 18 mmol/l had a significantly higher risk of CKD progression compared to those with a serum bicarbonate of 22 or more mmol/l (adjusted hazard ratio 2.44; 95% confidence interval 1.43-4.15). Thus, metabolic acidosis is a common complication in pediatric patients with CKD and may be a risk factor for secondary hyperparathyroidism and kidney disease progression. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  17. 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 ...

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

    Indian Academy of Sciences (India)

    endogenous Raman signatures from tissues, photo acoustic imaging, a hybrid biomedical imaging modality ... The definition of molecular imaging, as provided by the. Society of Nuclear Medicine, is 'the visualization, ... ties targeted to endogenous molecules of diseased tissue. On the other hand, indirect imaging utilizes ...

  19. Modulation of endogenous antioxidant defense and the progression of kidney disease in multi-heritage groups of patients with type 2 diabetes: PRospective EValuation of Early Nephropathy and its Treatment (PREVENT)

    OpenAIRE

    Earle, Kenneth A.; Zitouni, Karima; Pepe, John; Karaflou, Maria; Godbold, James

    2016-01-01

    BACKGROUND: Diabetes is the western world's leading cause of end-stage renal disease. Glucose-dependent, oxidative stress is linked to the development of renal inflammation and sclerosis, which, in animal models of diabetes, can be prevented by anti-oxidative treatment. Patients of non-Caucasian heritage have low activity of the selenoprotein, antioxidant enzyme, glutathione peroxidase (GPx) and its co-factor vitamin E, which may be linked to their increased propensity to developing end-stage...

  20. One-Dimensional-Ratio Measures of Atrophy Progression in Multiple Sclerosis as Evaluated by Longitudinal Magnetic Resonance Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Martola, J.; Wiberg Kristoffersen, M.; Aspelin, P. (Div. of Radiology, Dept. of Clinical Science, Intervention and Technology, Karolinska Inst., Stockholm (Sweden)); Stawiarz, L.; Fredrikson, S.; Hillert, J. (Div. of Neurology, Dept. of Clinical Neuroscience, Karolinska Inst., Stockholm (Sweden)); Bergstroem, J. (Medical Statistics Unit, Dept. of Learning, Informatics, Management, and Ethics (LIME), Karolinska Inst., Stockholm (Sweden)); Flodmark, O. (Dept. of Neuroradiology, Karolinska Univ. Hospital, Stockholm (Sweden))

    2009-10-15

    Background: For decades, normalized one-dimensional (1D) measures have been used in the evaluation of brain atrophy. In multiple sclerosis (MS), the use of normalized linear measures over longitudinal follow-up remains insufficiently documented. Purpose: To evaluate the association between different regional atrophy measures and disability in MS patients over four decades in a longitudinal cross-sectional study. Material and Methods: 37 consecutively selected MS patients were included. At baseline, patients had a range of disease duration (1-33 years) and age (24-65 years). Each patient was followed by magnetic resonance imaging (MRI) for a mean of 9.25 years (range 7.3-10 years). Four 1D measures were applied at three time points on axial 5-mm T1-weighted images. Three clinical MS subgroups were represented: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS). Results: There were significant changes in all 1D ratios during follow-up. The Evans ratio (ER) and the bifrontal ratio (BFR) were associated with the development of disability. Changes of ER and BFR reflected more aggressive disease progression, as expressed by MS severity score (MSSS). Conclusion: All four normalized ratios showed uniform atrophy progression, suggesting a consistent rate of atrophy over long-term disease duration independent of MS course. Disability status correlated with 1D measures, suggesting that serial evaluation of Evans and bifrontal ratios might contribute to the radiological evaluation of MS patients.

  1. One-Dimensional-Ratio Measures of Atrophy Progression in Multiple Sclerosis as Evaluated by Longitudinal Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Martola, J.; Wiberg Kristoffersen, M.; Aspelin, P.; Stawiarz, L.; Fredrikson, S.; Hillert, J.; Bergstroem, J.; Flodmark, O.

    2009-01-01

    Background: For decades, normalized one-dimensional (1D) measures have been used in the evaluation of brain atrophy. In multiple sclerosis (MS), the use of normalized linear measures over longitudinal follow-up remains insufficiently documented. Purpose: To evaluate the association between different regional atrophy measures and disability in MS patients over four decades in a longitudinal cross-sectional study. Material and Methods: 37 consecutively selected MS patients were included. At baseline, patients had a range of disease duration (1-33 years) and age (24-65 years). Each patient was followed by magnetic resonance imaging (MRI) for a mean of 9.25 years (range 7.3-10 years). Four 1D measures were applied at three time points on axial 5-mm T1-weighted images. Three clinical MS subgroups were represented: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS). Results: There were significant changes in all 1D ratios during follow-up. The Evans ratio (ER) and the bifrontal ratio (BFR) were associated with the development of disability. Changes of ER and BFR reflected more aggressive disease progression, as expressed by MS severity score (MSSS). Conclusion: All four normalized ratios showed uniform atrophy progression, suggesting a consistent rate of atrophy over long-term disease duration independent of MS course. Disability status correlated with 1D measures, suggesting that serial evaluation of Evans and bifrontal ratios might contribute to the radiological evaluation of MS patients

  2. Prognostic indicators of renal disease progression in adults with Fabry disease: natural history data from the Fabry Registry

    NARCIS (Netherlands)

    Wanner, Christoph; Oliveira, João P.; Ortiz, Alberto; Mauer, Michael; Germain, Dominique P.; Linthorst, Gabor E.; Serra, Andreas L.; Maródi, László; Mignani, Renzo; Cianciaruso, Bruno; Vujkovac, Bojan; Lemay, Roberta; Beitner-Johnson, Dana; Waldek, Stephen; Warnock, David G.

    2010-01-01

    These analyses were designed to characterize renal disease progression in untreated adults with Fabry disease. Data from the Fabry Registry for 462 untreated adults (121 men and 341 women) who had at least two estimated GFR (eGFR) values over a span of ≥12 months before starting enzyme replacement

  3. Neutrophil gelatinase-associated lipocalin as a biomarker of disease progression in patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    M L Patel

    2016-01-01

    Full Text Available Chronic kidney disease (CKD is associated with early mortality, decreased quality of life and increased health care expenditures. The aim of this study was to determine whether or not urinary NGAL (uNGAL level is associated with renal damage and kidney disease progression in patients with CKD and to evaluate the predictive value of uNGAL in progression of CKD. Totally, 91 cases of CKD stage II, III, IV, and 50 age-matched healthy controls were enrolled. The follow-up end-point was 18 months; end-point of the study was progression to an estimated glomerular filtration rate (eGFR of <15 ml/min and/or CKD stage V. Forty-five cases (49.4% were progressors and 46 were nonprogressors. uNGAL levels were significantly higher in CKD subjects as compared to healthy controls (log 1.09 ± 0.22 μg/ml in controls versus log 1.22 ± 2.08 μg/ml in stage II, log 3.34 ± 2.74 μg/ml in stage III and log 3.70 ± 0.18 μg/ml in stage IV. Univariate Cox proportional hazards model showed that only eGFR (hazard ratio [HR]: 0.95; 95% confidence interval [CI]: 0.93-0.96; P < 0.001 and uNGAL (HR: 1.11; 95% CI: 1.01-1.20; P < 0.001 were significantly associated with end-point of CKD stage V, but multiple Cox proportional regression model showed significant association of uNGAL (HR: 1.11; 95% CI: 1.01-1.20; P < 0.001 and eGFR (HR: 0.962, 95% CI: 0.95-0.98; P < 0.001 with end-point of CKD stage V. This suggests that uNGAL would not be a simple surrogate index of baseline eGFR, but a marker of CKD progression beyond the information provided by eGFR estimation.

  4. Albuminuria, Proteinuria, and Renal Disease Progression in Children with CKD.

    Science.gov (United States)

    Fuhrman, Dana Y; Schneider, Michael F; Dell, Katherine M; Blydt-Hansen, Tom D; Mak, Robert; Saland, Jeffrey M; Furth, Susan L; Warady, Bradley A; Moxey-Mims, Marva M; Schwartz, George J

    2017-06-07

    The role of albuminuria as an indicator of progression has not been investigated in children with CKD in the absence of diabetes. Children were enrolled from 49 centers of the CKD in Children study between January of 2005 and March of 2014. Cross-sectional multivariable linear regression ( n =647) was used to examine the relationship between urine protein-to-creatinine (UP/C [milligrams per milligram]) and albumin-to-creatinine (ACR [milligrams per gram]) with eGFR (milliliters per minute per 1.73 m 2 ). Parametric time-to-event analysis ( n =751) was used to assess the association of UP/C, ACR, and urine nonalbumin-to-creatinine (Unon-alb/cr [milligrams per gram]) on the time to the composite endpoint of initiation of RRT or 50% decline in eGFR. The median follow-up time was 3.4 years and 202 individuals experienced the event. Participants with a UP/C≥0.2 mg/mg and ACR≥30 mg/g had a mean eGFR that was 16 ml/min per 1.73 m 2 lower than those with a UP/C2.0 mg/mg], RT=0.09 for ACR [>1333 mg/g], RT=0.07 for Unon-alb/cr [>715 mg/g]) levels to the lowest levels. A similar trend was seen when categories were created on the basis of clinically meaningful cutoff values of ACR (300 mg/g). In children with CKD without diabetes, the utility of an initial UP/C, ACR, and Unon-alb/cr for characterizing progression is similar. Copyright © 2017 by the American Society of Nephrology.

  5. [Recent progress in multiple sclerosis research: astrocytopathy in demyelinating diseases].

    Science.gov (United States)

    Kira, Jun-Ichi

    2010-11-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) while neuromyelitis optica (NMO) is an inflammatory disease of the CNS that selectively affects the optic nerves and spinal cord. Recently, a specific IgG against NMO, designated NMO-IgG, was discovered, and the relevant antigen was found to be aquaporin 4 (AQP4), one of the major water channel proteins in the CNS. The sensitivity of NMO-IgG/anti-AQP4 antibodies for NMO varies from 30% to 80%, while specificity is 90-100%. Pathological studies on NMO patients have revealed perivascular immune complex (IgM, IgG and C9neo) deposition and extensive loss of AQP4 in active lesions, while myelin basic protein (MBP) staining was relatively preserved. IgG from NMO-IgG-seropositive NMO patients induces astrocyte death in culture in the presence of complement, and reproduces astrocyte loss in vivo when MBP-specific T cells are co-transferred to cause experimental autoimmune encephalomyelitis. Therefore, it is postulated that the complement-activating anti-AQP4 antibodies have a pivotal role in the development of NMO lesions through astrocyte necrosis, and that demyelination is a secondary event. Baló's disease is characterized by alternating rings of demyelination and preserved myelin. As additional MS-like lesions often coexist in Baló's cases, Baló's disease is regarded as a variant of MS. However, Baló's concentric rings are also observed in NMO cases and in Asian opticospinal MS patients in the cerebral white matter, spinal cord and optic chiasm. In demyelinated areas, many hypertrophic astrocytes are present, in close contact with oligodendrocytes that often show apoptotic features. In the outermost layer of preserved myelin, stress proteins involved in tissue preconditioning are abundant in oligodendrocytes. The peri-plaque white matter is thus assumed resistant to subsequent attack, thereby leaving a layer of preserved myelin. In some patients, Baló's concentric rings develop

  6. Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis

    Directory of Open Access Journals (Sweden)

    Izumi Masashi

    2012-08-01

    Full Text Available Abstract Background Recent data have suggested a relationship between acute arthritic pain and acid sensing ion channel 3 (ASIC3 on primary afferent fibers innervating joints. The purpose of this study was to clarify the role of ASIC3 in a rat model of osteoarthritis (OA which is considered a degenerative rather than an inflammatory disease. Methods We induced OA via intra-articular mono-iodoacetate (MIA injection, and evaluated pain-related behaviors including weight bearing measured with an incapacitance tester and paw withdrawal threshold in a von Frey hair test, histology of affected knee joint, and immunohistochemistry of knee joint afferents. We also assessed the effect of ASIC3 selective peptide blocker (APETx2 on pain behavior, disease progression, and ASIC3 expression in knee joint afferents. Results OA rats showed not only weight-bearing pain but also mechanical hyperalgesia outside the knee joint (secondary hyperalgesia. ASIC3 expression in knee joint afferents was significantly upregulated approximately twofold at Day 14. Continuous intra-articular injections of APETx2 inhibited weight distribution asymmetry and secondary hyperalgesia by attenuating ASIC3 upregulation in knee joint afferents. Histology of ipsilateral knee joint showed APETx2 worked chondroprotectively if administered in the early, but not late phase. Conclusions Local ASIC3 immunoreactive nerve is strongly associated with weight-bearing pain and secondary hyperalgesia in MIA-induced OA model. APETx2 inhibited ASIC3 upregulation in knee joint afferents regardless of the time-point of administration. Furthermore, early administration of APETx2 prevented cartilage damage. APETx2 is a novel, promising drug for OA by relieving pain and inhibiting disease progression.

  7. Renal outcome and risk factors for end-stage renal disease in pediatric rapidly progressive glomerulonephritis.

    Science.gov (United States)

    Piyaphanee, Nuntawan; Ananboontarick, Chompoonut; Supavekin, Suroj; Sumboonnanonda, Achra

    2017-03-01

    Rapidly progressive glomerulonephritis (RPGN), defined as acute nephritic syndrome with dramatic loss of renal function within a few months, is associated with crescentic glomerulonephritis (CresGN), which requires ≥50% crescents on pathology. The disease characteristics and renal outcome in children with RPGN, however, will differ according to the percentage of crescents. To evaluate the renal outcomes and factors associated with end-stage renal disease (ESRD), this retrospective cohort study assessed children aged ≤15 years with RPGN at a tertiary medical center. Of 67 patients with RPGN, 32 (47.8%) were male; mean age was 10.6 ± 3.0 years; median follow up was 1.1 years (range, 0.02-9.17 years) and 24 (35.8%) progressed to ESRD. Post-infectious glomerulonephritis was the most frequent cause of RPGN (50.7%). The incidence of ESRD was significantly higher in patients with ≥50% than disease etiology, serum creatinine >3 mg/dL, need for acute dialysis, ≥80% crescents and ≥20% tubular atrophy and interstitial fibrosis (TA/IF) were associated with ESRD. On multivariate analysis, need for acute dialysis (HR, 2.8; 95% CI: 1.1-7.3, P = 0.041) and ≥20% TA/IF (HR, 4.8; 95% CI: 1.4-16.1, P = 0.011) were independent risk factors for the development of ESRD. Approximately one-third of children with RPGN developed ESRD; and need for acute dialysis and TA/IF ≥20% were independent risk factors for ESRD. © 2016 Japan Pediatric Society.

  8. 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.

  9. 20 YEARS OF PROGRESS IN DIARRHEAL DISEASE RESEARCH

    Directory of Open Access Journals (Sweden)

    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.

  10. Mechanisms of Copper Ion Mediated Huntington's Disease Progression

    OpenAIRE

    Fox, Jonathan H.; Kama, Jibrin A.; Lieberman, Gregory; Chopra, Raman; Dorsey, Kate; Chopra, Vanita; Volitakis, Irene; Cherny, Robert A.; Bush, Ashley I.; Hersch, Steven

    2007-01-01

    Huntington's disease (HD) is caused by a dominant polyglutamine expansion within the N-terminus of huntingtin protein and results in oxidative stress, energetic insufficiency and striatal degeneration. Copper and iron are increased in the striata of HD patients, but the role of these metals in HD pathogenesis is unknown. We found, using inductively-coupled-plasma mass spectroscopy, that elevations of copper and iron found in human HD brain are reiterated in the brains of affected HD transgeni...

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

    OpenAIRE

    Long, JD; Paulsen, JS; Marder, K; Zhang, Y; Kim, JI; Mills, JA; Cross, S; Ryan, P; Epping, EA; Vik, S; Chiu, E; Preston, J; Goh, A; Antonopoulos, S; Loi, S

    2014-01-01

    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 effi...

  12. Smoking and Progression of Alzheimers Disease: Connecting Edges

    Directory of Open Access Journals (Sweden)

    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. 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

    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...

  14. Mutant TDP-43 within motor neurons drives disease onset but not progression in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Ditsworth, Dara; Maldonado, Marcus; McAlonis-Downes, Melissa; Sun, Shuying; Seelman, Amanda; Drenner, Kevin; Arnold, Eveline; Ling, Shuo-Chien; Pizzo, Donald; Ravits, John; Cleveland, Don W; Da Cruz, Sandrine

    2017-06-01

    Mutations in TDP-43 cause amyotrophic lateral sclerosis (ALS), a fatal paralytic disease characterized by degeneration and premature death of motor neurons. The contribution of mutant TDP-43-mediated damage within motor neurons was evaluated using mice expressing a conditional allele of an ALS-causing TDP-43 mutant (Q331K) whose broad expression throughout the central nervous system mimics endogenous TDP-43. TDP-43 Q331K mice develop age- and mutant-dependent motor deficits from degeneration and death of motor neurons. Cre-recombinase-mediated excision of the TDP-43 Q331K gene from motor neurons is shown to delay onset of motor symptoms and appearance of TDP-43-mediated aberrant nuclear morphology, and abrogate subsequent death of motor neurons. However, reduction of mutant TDP-43 selectively in motor neurons did not prevent age-dependent degeneration of axons and neuromuscular junction loss, nor did it attenuate astrogliosis or microgliosis. Thus, disease mechanism is non-cell autonomous with mutant TDP-43 expressed in motor neurons determining disease onset but progression defined by mutant acting within other cell types.

  15. Lack of genetic association among coat colors, progressive retinal atrophy and polycystic kidney disease in Persian cats.

    Science.gov (United States)

    Rah, HyungChul; Maggs, David J; Lyons, Leslie A

    2006-10-01

    An inherited form of progressive retinal atrophy (PRA) is recognized in Persian cats; however, the prevalence of PRA in the breed has not been determined. Breeders suggest that cats from only brown ('chocolate') or Himalayan ('pointed') lines are at risk for PRA, suggesting the disease is not widespread. This study was designed to evaluate whether PRA in Persian cats is associated with three coat colors, including chocolate, or with a highly prevalent inherited disease in this breed--polycystic kidney disease (PKD). Sixty related cats were evaluated for PRA by ophthalmic examination and genetically typed for PKD and the mutations that cause coat color variants in agouti, brown and color (producing the pointed coloration in Himalayan). No associations were identified among any of the traits, including between PRA and chocolate. These data suggest that PRA is not limited to cats with chocolate coat coloration and breeders and veterinarians should be aware that the prevalence of the disease may be higher than currently claimed.

  16. Predictors of Rapid Progression of Glomerular and Nonglomerular Kidney Disease in Children and Adolescents: The Chronic Kidney Disease in Children (CKiD) Cohort.

    Science.gov (United States)

    Warady, Bradley A; Abraham, Alison G; Schwartz, George J; Wong, Craig S; Muñoz, Alvaro; Betoko, Aisha; Mitsnefes, Mark; Kaskel, Frederick; Greenbaum, Larry A; Mak, Robert H; Flynn, Joseph; Moxey-Mims, Marva M; Furth, Susan

    2015-06-01

    Few studies have prospectively evaluated the progression of chronic kidney disease (CKD) in children and adolescents, as well as factors associated with progression. Prospective multicenter observational cohort study. 496 children and adolescents with CKD enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Proteinuria, hypoalbuminemia, blood pressure, dyslipidemia, and anemia. Parametric failure-time models were used to characterize adjusted associations between baseline levels and changes in predictors and time to a composite event of renal replacement therapy or 50% decline in glomerular filtration rate (GFR). 398 patients had nonglomerular disease and 98 had glomerular disease; of these, 29% and 41%, respectively, progressed to the composite event after median follow-ups of 5.2 and 3.7 years, respectively. Demographic and clinical characteristics and outcomes differed substantially according to the underlying diagnosis; hence, risk factors for progression were assessed in stratified analyses, and formal interactions by diagnosis were performed. Among patients with nonglomerular disease and after adjusting for baseline GFR, times to the composite event were significantly shorter with urinary protein-creatinine ratio > 2mg/mg, hypoalbuminemia, elevated blood pressure, dyslipidemia, male sex, and anemia, by 79%, 69%, 38%, 40%, 38%, and 45%, respectively. Among patients with glomerular disease, urinary protein-creatinine ratio >2mg/mg, hypoalbuminemia, and elevated blood pressure were associated with significantly reduced times to the composite event by 94%, 71%, and 67%, respectively. Variables expressing change in patient clinical status over the initial year of the study contributed significantly to the model, which was cross-validated internally. Small number of events in glomerular patients and use of internal cross-validation. Characterization and modeling of risk factors for CKD progression can be used to predict the extent to which these factors

  17. Caregiver–Recipient Closeness and Symptom Progression in Alzheimer Disease. The Cache County Dementia Progression Study

    Science.gov (United States)

    Piercy, Kathleen W.; Rabins, Peter V.; Green, Robert C.; Breitner, John C. S.; Østbye, Truls; Corcoran, Christopher; Welsh-Bohmer, Kathleen A.; Lyketsos, Constantine G.; Tschanz, JoAnn T.

    2009-01-01

    Applying Rusbult's investment model of dyadic relationships, we examined the effect of caregiver–care recipient relationship closeness (RC) on cognitive and functional decline in Alzheimer's disease. After diagnosis, 167 participants completed up to six visits, observed over an average of 20 months. Participants were 64% women, had a mean age of 86 years, and mean dementia duration of 4 years. Caregiver-rated closeness was measured using a six-item scale. In mixed models adjusted for dementia severity, dyads with higher levels of closeness (p caregivers (p = .01) had slower cognitive decline. Effect of higher RC on functional decline was greater with spouse caregivers (p = .007). These findings of attenuated Alzheimer's dementia (AD) decline with closer relationships, particularly with spouse caregivers, are consistent with investment theory. Future interventions designed to enhance the caregiving dyadic relationship may help slow decline in AD. PMID:19564210

  18. Podoplanin Expression Correlates with Disease Progression in Mycosis Fungoides.

    Science.gov (United States)

    Jankowska-Konsur, Alina; Kobierzycki, Christopher; Grzegrzółka, Jędrzej; Piotrowska, Aleksandra; Gomulkiewicz, Agnieszka; Glatzel-Plucinska, Natalia; Reich, Adam; Podhorska-Okołów, Marzenna; Dzięgiel, Piotr; Szepietowski, Jacek C

    2017-02-08

    The aim of this study was to investigate the role of lymphangiogenesis in the clinical progression and outcome of mycosis fungoides. Immunohistochemistry and Western blot techniques were used to assess the expression of podoplanin and vascular endothelial growth factor C in mycosis fungoides. Expression of vascular endothelial growth factor C measured by immunohistochemistry was significantly higher in mycosis fungoides samples in comparison with control cases (chronic benign dermatoses) (p = 0.0012). Increased expression of podoplanin was found in advanced vs. early mycosis fungoides (p < 0.0001), and was positively correlated with cutaneous and nodal involvement (p < 0.001, p < 0.0001; respectively). Higher podoplanin expression was also significantly associated with shorter survival (p < 0.001). Strong positive correlation was observed between expression of podoplanin analysed by immunohistochemistry and Western blot (r = 0.75, p < 0.0001). A similar association was shown regarding expression of vascular endothelial growth factor C (r = 0.68, p = 0.0007). In conclusion, these results suggest that increased expression of podoplanin is associated with poor clinical course, as well as shorter survival, of patients with mycosis fungoides.

  19. Disease progression in patients with single, large-scale mitochondrial DNA deletions

    Science.gov (United States)

    Grady, John P.; Campbell, Georgia; Ratnaike, Thiloka; Blakely, Emma L.; Falkous, Gavin; Nesbitt, Victoria; Schaefer, Andrew M.; McNally, Richard J.; Gorman, Grainne S.; Taylor, Robert W.

    2014-01-01

    Single, large-scale deletions of mitochondrial DNA are a common cause of mitochondrial disease and cause a broad phenotypic spectrum ranging from mild myopathy to devastating multi-system syndromes such as Kearns-Sayre syndrome. Studies to date have been inconsistent on the value of putative predictors of clinical phenotype and disease progression such as mutation load and the size or location of the deletion. Using a cohort of 87 patients with single, large-scale mitochondrial DNA deletions we demonstrate that a variety of outcome measures such as COX-deficient fibre density, age-at-onset of symptoms and progression of disease burden, as measured by the Newcastle Mitochondrial Disease Adult Scale, are significantly (P < 0.05) correlated with the size of the deletion, the deletion heteroplasmy level in skeletal muscle, and the location of the deletion within the genome. We validate these findings with re-analysis of 256 cases from published data and clarify the previously conflicting information of the value of these predictors, identifying that multiple regression analysis is necessary to understand the effect of these interrelated predictors. Furthermore, we have used mixed modelling techniques to model the progression of disease according to these predictors, allowing a better understanding of the progression over time of this strikingly variable disease. In this way we have developed a new paradigm in clinical mitochondrial disease assessment and management that sidesteps the perennial difficulty of ascribing a discrete clinical phenotype to a broad multi-dimensional and progressive spectrum of disease, establishing a framework to allow better understanding of disease progression. PMID:24277717

  20. Progress on different ocular surgeries and dry eye disease

    Directory of Open Access Journals (Sweden)

    Ling Li

    2013-11-01

    Full Text Available The health of ocular surface is maintained by the ocular surface(cornea and conjunctiva, accessory lacrimal gland and meibomian gland, the main lacrimal gland and the lachrymal function units between them, any damage in which can lead to the failure of integrity and normal function of tear film. With the development of medical science, more and more eye surgeries are operated to treat eye diseases. However, preoperative anesthetic applications, operation process, preservatives in the eye drops may lead to tear film instability and/or abnormal manifestation on eye surface which may cause dry eyes.

  1. Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood

    NARCIS (Netherlands)

    Mastrokolias, A.; Ariyurek, Y.; Goeman, J.J.; Duijn, E. van; Roos, R.A.; Mast, R.C. van der; Ommen, G.B. van; Dunnen, J.T. den; Hoen, P.A.C. 't; Roon-Mom, W.M. van

    2015-01-01

    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

  2. Prion protein polymorphisms affect chronic wasting disease progression.

    Directory of Open Access Journals (Sweden)

    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.

  3. The progression of coeliac disease: its neurological and psychiatric implications.

    Science.gov (United States)

    Campagna, Giovanna; Pesce, Mirko; Tatangelo, Raffaella; Rizzuto, Alessia; La Fratta, Irene; Grilli, Alfredo

    2017-06-01

    The aim of the paper is to show the various neurological and psychiatric symptoms in coeliac disease (CD). CD is a T cell-mediated, tissue-specific autoimmune disease which affects genetically susceptible individuals after dietary exposure to proline- and glutamine-rich proteins contained in certain cereal grains. Genetics, environmental factors and different immune systems, together with the presence of auto-antigens, are taken into account when identifying the pathogenesis of CD. CD pathogenesis is related to immune dysregulation, which involves the gastrointestinal system, and the extra-intestinal systems such as the nervous system, whose neurological symptoms are evidenced in CD patients. A gluten-free diet (GFD) could avoid cerebellar ataxia, epilepsy, neuropathies, migraine and mild cognitive impairment. Furthermore, untreated CD patients have more symptoms and psychiatric co-morbidities than those treated with a GFD. Common psychiatric symptoms in untreated CD adult patients include depression, apathy, anxiety, and irritability and schizophrenia is also common in untreated CD. Several studies show improvement in psychiatric symptoms after the start of a GFD. The present review discusses the state of the art regarding neurological and psychiatric complications in CD and highlights the evidence supporting a role for GFD in reducing neurological and psychiatric complications.

  4. Pulmonary Hypertension Due to Left Ventricular Cardiomyopathy: Is it the Result or Cause of Disease Progression?

    Science.gov (United States)

    Adusumalli, Srinath; Mazurek, Jeremy A

    2017-12-01

    The purpose of this review is to define pulmonary hypertension in the setting of left heart disease (PH-LHD), discuss its epidemiology and pathophysiology, and highlight the cause and effect relationship it has with disease progression in the setting of cardiomyopathy. Both pulmonary hypertension (PH) and heart failure are becoming increasingly common. As such, PH-LHD is now the most common form of PH. The pathophysiology of the condition relates to backward transmission of elevated left ventricular filling pressures into the pulmonary circulation and, ultimately, right ventricular (RV) strain/dysfunction. It is evident that these pathophysiologic processes are both the effect and cause of left heart disease progression. In this review, we describe the complex relationship between disease progression in left ventricular cardiomyopathy and PH-LHD. Clinicians and researchers should take note of the importance of PH-LHD and RV dysfunction to appropriately risk stratify patients and develop therapies for the condition.

  5. Embodiment of activity progress: The temporalities of service evaluation

    DEFF Research Database (Denmark)

    Oshima, Sae

    2017-01-01

    their satisfaction. Yet, an efficient progress of this activity is crucial, as there are often subsequent customers waiting. My analysis shows that this dilemma of taking enough time without taking too much time is managed by the participants’ embodiment of valid activity progress, which is realized through...... their (sometimes asynchronous) mobilization of multimodal resources. I argue that such activity organization helps participants not only to embody the meaningful (versus wasted) consumption of time, but also to secure the customer’s enhanced appreciation of the service outcome....

  6. Roentgenologic assessment of spondylolisthesis. Pt. 2. An evaluation of progression

    Energy Technology Data Exchange (ETDEWEB)

    Danielson, B.; Frennered, K.; Selvik, G.; Irstam, L.

    Different degrees of artificial L5-S1 spondylolisthesis were created using a lumbar specimen. Lateral radiographs were obtained of each, with the specimen tilted and/or rotated. The true spondylolisthesis was determined stereophotogrammetrically. The slip, measured on the radiographs, was calculated according to two methods modified from BOXALL et coll. (2). No significant difference in accuracy was found between these two methods. The difference in calculated slip between examinations needs to be at least 20 per cent of the sagittal length of L5 to be regarded as a true progression. A true progress of slip of less than 20 per cent is difficult to detect with statistical certainty.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Prospective cohort analyzing risk factors for chronic kidney disease progression in children.

    Science.gov (United States)

    Belangero, Vera M S; Prates, Liliane C; Watanabe, Andreia; Schvartsman, Benita S G; Nussenzveig, Paula; Cruz, Natalia A; Abreu, Ana L S; Paz, Isabel P; Facincani, Inalda; Morgantetti, Fernanda E C; Silva, Andreia O; Andrade, Olberes V B; Camargo, Maria F C; Nogueira, Paulo C Koch

    2017-10-02

    To identify risk factors for chronic kidney disease progression in Brazilian children and to evaluate the interactions between factors. This was a multicenter prospective cohort in São Paulo, involving 209 children with CKD stages 3-4. The study outcome included: (a) death, (b) start of kidney replacement therapy, (c) eGFR decrease >50% during the followup. Thirteen risk factors were tested using univariate regression models, followed by multivariable Cox regression models. The terms of interaction between the variables showing significant association with the outcome were then introduced to the model. After a median follow-up of 2.5 years (IQR=1.4-3.0), the outcome occurred in 44 cases (21%): 22 started dialysis, 12 had >50% eGFR decrease, seven underwent transplantation, and three died. Advanced CKD stage at onset (HR=2.16, CI=1.14-4.09), nephrotic proteinuria (HR=2.89, CI=1.49-5.62), age (HR=1.10, CI=1.01-1.17), systolic blood pressure Z score (HR=1.36, CI=1.08-1.70), and anemia (HR=2.60, CI=1.41-4.77) were associated with the outcome. An interaction between anemia and nephrotic proteinuria at V1 (HR=0.25, CI=0.06-1.00) was detected. As the first CKD cohort in the southern hemisphere, this study supports the main factors reported in developed countries with regards to CKD progression, affirming the potential role of treatments to slow CKD evolution. The detected interaction suggests that anemia may be more deleterious for CKD progression in patients without proteinuria and should be further studied. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  9. Mild cognitive impairment and progression to dementia of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Ana Beatriz Quintes Steiner

    Full Text Available Summary The increase in life expectancy in the Brazilian population raises questions about the preparation of the public health system in identifying elderly patients with signs of cognitive impairment. Currently, as a consequence of the long duration of preclinical phase of Alzheimer's disease, efforts of early detection have been emphasized. Clinical dementia presents an important impact on the individual's caregivers, family, society and economy. Identifying individuals who already have some cognitive impairment, despite remaining functional, as well as analyzing associated comorbidities, constitutes an opportunity to analyze possibilities for future interventions. Dementias are clinical conditions that impose a burden on the health system with its high costs, whereas the identification of individuals with cognitive impairment without dementia can aid patients and their families to plan the future and mitigate costs. This narrative revision can provide general practitioners with more information on the subject.

  10. 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.

  11. Addressing voice recording replications for tracking Parkinson's disease progression.

    Science.gov (United States)

    Naranjo, Lizbeth; Pérez, Carlos J; Martín, Jacinto

    2017-03-01

    Tracking Parkinson's disease symptom severity by using characteristics automatically extracted from voice recordings is a very interesting and challenging problem. In this context, voice features are automatically extracted from multiple voice recordings from the same subjects. In principle, for each subject, the features should be identical at a concrete time, but the imperfections in technology and the own biological variability result in nonidentical replicated features. The involved within-subject variability must be addressed since replicated measurements from voice recordings can not be directly used in independence-based pattern recognition methods as they have been routinely used through the scientific literature. Besides, the time plays a key role in the experimental design. In this paper, for the first time, a Bayesian linear regression approach suitable to handle replicated measurements and time is proposed. Moreover, a version favoring the best predictors and penalizing the worst ones is also presented. Computational difficulties have been avoided by developing Gibbs sampling-based approaches.

  12. A Blood Test for Alzheimer's Disease: Progress, Challenges, and Recommendations.

    Science.gov (United States)

    Kiddle, Steven J; Voyle, Nicola; Dobson, Richard J B

    2018-03-29

    Ever since the discovery of APOEɛ4 around 25 years ago, researchers have been excited about the potential of a blood test for Alzheimer's disease (AD). Since then researchers have looked for genetic, protein, metabolite, and/or gene expression markers of AD and related phenotypes. However, no blood test for AD is yet being used in the clinical setting. We first review the trends and challenges in AD blood biomarker research, before giving our personal recommendations to help researchers overcome these challenges. While some degree of consistency and replication has been seen across independent studies, several high-profile studies have seemingly failed to replicate. Partly due to academic incentives, there is a reluctance in the field to report predictive ability, to publish negative findings, and to independently replicate the work of others. If this can be addressed, then we will know sooner whether a blood test for AD or related phenotypes with clinical utility can be developed.

  13. Functional progression of patients with neurological diseases in a tertiary paediatric intensive care unit: Our experience.

    Science.gov (United States)

    Madurga Revilla, P; López Pisón, J; Samper Villagrasa, P; García Íñiguez, J P; Garcés Gómez, R; Domínguez Cajal, M; Gil Hernández, I

    2017-11-23

    Neurological diseases explain a considerable proportion of admissions to paediatric intensive care units (PICU), and are a significant cause of morbidity and mortality. This study aims to analyse the functional progression of children with critical neurological conditions. Retrospective descriptive study of children admitted to PICU with neurological diseases over a period of 3 years (2012-2014), assessing vital and functional prognosis at PICU discharge and at one year according to the Pediatric Cerebral and Overall Performance Category scales (PCPC-POPC) and the Functional Status Scale (FSS). The results are compared with our previous data (1990-1999), and those of the international multicentre PANGEA study. A total of 266 children were studied. The mortality rate was 3%; the PRISM-III and PIM2 models did not show predictive ability. Clinically significant worsening was observed in functional health at discharge in 30% of the sample, according to POPC, 15% according to PCPC, and 5% according to FSS. After one year, functional performance improved according to PCPC-POPC, but not according to FSS. Children with no underlying neurological disease had a higher degree of functional impairment; this was prolonged over time. We observed a decrease in overall and neurocritical mortality compared with our previous data (5.60 vs. 2.1%, P=.0003, and 8.44 vs. 2.63%, P=.0014, respectively). Compared with the PANGEA study, both mortality and cerebral functional impairment in neurocritical children were lower in our study (1.05 vs. 13.32%, P<.0001, and 10.47% vs. 23.79%, P<.0001, respectively). Nearly one-third of critically ill children have neurological diseases. A significant percentage, mainly children without underlying neurological diseases, had a clinically significant functional impact at PICU discharge and after a year. Neuromonitoring and neuroprotection measures and the evaluation of functional progression are necessary to improve critical child care. Copyright

  14. Half the story: Thermal effects on within-host infectious disease progression in a warming climate.

    Science.gov (United States)

    Stewart, Alexander; Hablützel, Pascal I; Brown, Martha; Watson, Hayley V; Parker-Norman, Sophie; Tober, Anya V; Thomason, Anna G; Friberg, Ida M; Cable, Joanne; Jackson, Joseph A

    2018-01-01

    Immune defense is temperature dependent in cold-blooded vertebrates (CBVs) and thus directly impacted by global warming. We examined whether immunity and within-host infectious disease progression are altered in CBVs under realistic climate warming in a seasonal mid-latitude setting. Going further, we also examined how large thermal effects are in relation to the effects of other environmental variation in such a setting (critical to our ability to project infectious disease dynamics from thermal relationships alone). We employed the three-spined stickleback and three ecologically relevant parasite infections as a "wild" model. To generate a realistic climatic warming scenario we used naturalistic outdoors mesocosms with precise temperature control. We also conducted laboratory experiments to estimate thermal effects on immunity and within-host infectious disease progression under controlled conditions. As experimental readouts we measured disease progression for the parasites and expression in 14 immune-associated genes (providing insight into immunophenotypic responses). Our mesocosm experiment demonstrated significant perturbation due to modest warming (+2°C), altering the magnitude and phenology of disease. Our laboratory experiments demonstrated substantial thermal effects. Prevailing thermal effects were more important than lagged thermal effects and disease progression increased or decreased in severity with increasing temperature in an infection-specific way. Combining laboratory-determined thermal effects with our mesocosm data, we used inverse modeling to partition seasonal variation in Saprolegnia disease progression into a thermal effect and a latent immunocompetence effect (driven by nonthermal environmental variation and correlating with immune gene expression). The immunocompetence effect was large, accounting for at least as much variation in Saprolegnia disease as the thermal effect. This suggests that managers of CBV populations in variable

  15. Nanoparticle-based sorting of circulating tumor cells by epithelial antigen expression during disease progression in an animal model.

    Science.gov (United States)

    Muhanna, Nidal; Mepham, Adam; Mohamadi, Reza M; Chan, Harley; Khan, Tahsin; Akens, Margarete; Besant, Justin D; Irish, Jonathan; Kelley, Shana O

    2015-10-01

    Circulating tumor cells (CTCs) can be used as markers for the detection, characterization, and targeted therapeutic management of cancer. We recently developed a nanoparticle-mediated approach for capture and sorting of CTCs based on their specific epithelial phenotype. In the current study, we investigate the phenotypic transition of tumor cells in an animal model and show the correlation of this transition with tumor progression. VX2 tumor cells were injected into rabbits, and CTCs were evaluated during tumor progression and correlated with computerized tomography (CT) measurements of tumor volume. The results showed a dramatic increase of CTCs during the four weeks of tumor growth. Following resection, CTC levels dropped but then rebounded, likely due to lymph node metastases. Additionally, CTCs showed a marked loss of the epithelial cell adhesion molecule (EpCAM) relative to precursor cells. In conclusion, the device accurately traces disease progression and CTC phenotypic shift in an animal model. The detection of circulating tumor cells (CTCs) has been used to predict disease prognosis. In this study, the authors developed a nanoparticle-mediated platform based on microfluidics to analyze the differential expressions of epithelial cell adhesion molecule (EpCAM) on CTCs in an animal model. It was found that the loss of EpCAM correlated with disease progression. Hence, the use of this platform may be further applied in other cancer models in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. MONITORING DISEASE PROGRESSION USING HIGH-DENSITY MOTOR UNIT NUMBER ESTIMATION IN AMYOTROPHIC LATERAL SCLEROSIS

    NARCIS (Netherlands)

    van Dijk, Johannes P.; Schelhaas, Helenius J.; van Schaik, Ivo N.; Janssen, Henny M. H. A.; Stegeman, Dick F.; Zwarts, Machiel J.

    2010-01-01

    In amyotrophic lateral sclerosis (ALS), progressive motor neuron loss causes severe weakness. Functional measurements tend to underestimate the underlying pathology because of collateral reinnervation. A more direct marker of lower motor neuron loss is of significant importance. We evaluated

  19. Estudo comparativo das avaliações clínica e ecocardiográfica Doppler na evolução das lesões valvares em crianças e adolescentes portadores de febre reumática Comparative study of clinical and Doppler echocardiographic evaluations of the progression of valve diseases in children and adolescents with rheumatic fever

    Directory of Open Access Journals (Sweden)

    Zilda Maria Alves Meira

    2006-01-01

    Full Text Available OBJETIVO: Comparar os exames clínico e ecocardiográfico Doppler na avaliação das lesões valvares em crianças e adolescentes com febre reumática, bem como investigar a evolução da doença segundo essas avaliações. MÉTODOS: Trata-se de estudo observacional longitudinal que englobou 258 crianças e adolescentes com diagnóstico de febre reumática, baseado nos critérios de Jones. Os pacientes foram acompanhados durante o período de 2 a 15 anos. A presença e a quantificação das lesões valvares nas fases aguda e crônica foram determinadas pelas avaliações clínica e ecocardiográfica Doppler. Utilizou-se a estatística de Kappa para estimar a concordância entre as avaliações, e as evoluções clínica e ecocardiográfica Doppler da cardite e valvite, respectivamente, foram comparadas pelo teste do qui-quadrado ou de Fisher, p OBJECTIVE: Compare clinical and Doppler echocardiographic evaluations in assessing valvular diseases in children and adolescents with rheumatic fever, as well as assess the progression of the disease in light of these assessments. METHODS: This is a longitudinal study of 258 children and adolescents diagnosed with rheumatic fever according to Jones’ criteria. The follow-up period ranged from 2-15 years. The presence and quantification of valve diseases were determined by means of clinical and Doppler echocardiographic evaluations performed during the acute and chronic phases. The Kappa statististics method was used to estimate the degree of agreement between clinical and Doppler echocardiographic evaluations. Comparisons between clinical and Doppler echocardiographic findings on the progress of carditis and valvulitis, respectively, were made using chi-square test or Fisher’s exact test, p< 0.05. RESULTS: Of the 109 patients who underwent Doppler echocardiographic evaluation during the acute phase, 31 did not present clinical evidence of carditis, but the Doppler echocardiograms of 17 (54.8% of them

  20. Mast cells are associated with the onset and progression of celiac disease.

    Science.gov (United States)

    Frossi, Barbara; Tripodo, Claudio; Guarnotta, Carla; Carroccio, Antonio; De Carli, Marco; De Carli, Stefano; Marino, Marco; Calabrò, Antonino; Pucillo, Carlo E

    2017-04-01

    Celiac disease (CD) is an immune-mediated disorder characterized by an accumulation of immune cells in the duodenal mucosa as a consequence of both adaptive and innate immune responses to undigested gliadin peptides. Mast cells (MCs) are innate immune cells that are a major source of costimulatory signals and inflammatory mediators in the intestinal mucosa. Although MCs have previously been associated with CD, functional studies have never been performed. We aimed at evaluating the role of MCs in the pathogenesis of CD. Intestinal biopsy specimens of patients with CD were scored according to the Marsh classification and characterized for leukocyte infiltration and MC distribution. Moreover, MC reactivity to gliadin and its peptides was characterized by using in vitro assays. Infiltrating MCs were associated with the severity of mucosal damage, and their numbers were increased in patients with higher Marsh scores. MCs were found to directly respond to nonimmunodominant gliadin fragments by releasing proinflammatory mediators. Immunohistochemical characterization of infiltrating MCs and the effects of gliadin peptides on intestinal MCs indicated an increase in proinflammatory MC function in advanced stages of the disease. This was also associated with increased neutrophil accumulation, the prevalence of M1 macrophages, and the severity of tissue damage. We provide a description of the progressive stages of CD, in which MCs are the hallmark of the inflammatory process. Thus the view of CD should be revised, and the contribution of MCs in the onset and progression of CD should be reconsidered in developing new therapeutic approaches. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease

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    Kanoto, Masafumi, E-mail: mkanoto@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Hosoya, Takaaki, E-mail: thosoya@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Toyoguchi, Yuuki, E-mail: c-elegans_0201g@mail.goo.ne.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Oda, Atsuko, E-mail: a.oda@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan)

    2013-01-15

    Purpose: Chronic progressive neuro-Behçet's disease (CPNBD) resembles multiple sclerosis (MS) on patient background and image findings, and therefore is difficult to diagnose. The purpose is to identify the characteristic magnetic resonance imaging (MRI) findings of CPNBD and to clarify the differences between the MRI findings of CPNBD and those of MS. Materials and methods: The subjects consist of a CPNBD group (n = 4; 1 male and 3 females; mean age, 51 y.o.), a MS group (n = 19; 3 males and 16 females; mean age, 45 y.o.) and a normal control group (n = 23; 10 males and 13 females; mean age, 45 y.o.). Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were retrospectively evaluated in each subjects. In middle sagittal brain MR images, the prepontine distance was measured as an indirect index of brain stem and cerebellar atrophy and the pontine and mesencephalic distance was measured as a direct index of brain stem atrophy. These indexes were statistically analyzed. Results: Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were seen in all CPNBD cases. Prepontine distance was significantly different between the CPNBD group and the MS group (p < 0.05), and between the CPNBD group and the normal control group (p < 0.001). Pontine and mesencephalic distance were significantly different between the CPNBD group and the MS group (p < 0.001, p < 0.01 respectively), and between the CPNBD group and the normal control group (p < 0.001). Conclusions: Chronic progressive neuro-Behçet's disease should be considered in patients with brain stem and cerebellar atrophy in addition to leukoencephalopathy similar to that seen in multiple sclerosis.

  2. Hepcidin-25 in diabetic chronic kidney disease is predictive for mortality and progression to end stage renal disease.

    Directory of Open Access Journals (Sweden)

    Martin Wagner

    Full Text Available Anemia is common and is associated with impaired clinical outcomes in diabetic chronic kidney disease (CKD. It may be explained by reduced erythropoietin (EPO synthesis, but recent data suggest that EPO-resistance and diminished iron availability due to inflammation contribute significantly. In this cohort study, we evaluated the impact of hepcidin-25--the key hormone of iron-metabolism--on clinical outcomes in diabetic patients with CKD along with endogenous EPO levels.249 diabetic patients with CKD of any stage, excluding end-stage renal disease (ESRD, were enrolled (2003-2005, if they were not on EPO-stimulating agent and iron therapy. Hepcidin-25 levels were measured by radioimmunoassay. The association of hepcidin-25 at baseline with clinical variables was investigated using linear regression models. All-cause mortality and a composite endpoint of CKD progression (ESRD or doubling of serum creatinine were analyzed by Cox proportional hazards models.Patients (age 67 yrs, 53% male, GFR 51 ml/min, hemoglobin 131 g/L, EPO 13.5 U/L, hepcidin-25 62.0 ng/ml were followed for a median time of 4.2 yrs. Forty-nine patients died (19.7% and forty (16.1% patients reached the composite endpoint. Elevated hepcidin levels were independently associated with higher ferritin-levels, lower EPO-levels and impaired kidney function (all p<0.05. Hepcidin was related to mortality, along with its interaction with EPO, older age, greater proteinuria and elevated CRP (all p<0.05. Hepcidin was also predictive for progression of CKD, aside from baseline GFR, proteinuria, low albumin- and hemoglobin-levels and a history of CVD (all p<0.05.We found hepcidin-25 to be associated with EPO and impaired kidney function in diabetic CKD. Elevated hepcidin-25 and EPO-levels were independent predictors of mortality, while hepcidin-25 was also predictive for progression of CKD. Both hepcidin-25 and EPO may represent important prognostic factors of clinical outcome and have the

  3. Hdac6 knock-out increases tubulin acetylation but does not modify disease progression in the R6/2 mouse model of Huntington's disease.

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    Anna Bobrowska

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder for which there is no effective disease modifying treatment. Following-on from studies in HD animal models, histone deacetylase (HDAC inhibition has emerged as an attractive therapeutic option. In parallel, several reports have demonstrated a role for histone deacetylase 6 (HDAC6 in the modulation of the toxicity caused by the accumulation of misfolded proteins, including that of expanded polyglutamine in an N-terminal huntingtin fragment. An important role for HDAC6 in kinesin-1 dependent transport of brain-derived neurotrophic factor (BDNF from the cortex to the striatum has also been demonstrated. To elucidate the role that HDAC6 plays in HD progression, we evaluated the effects of the genetic depletion of HDAC6 in the R6/2 mouse model of HD. Loss of HDAC6 resulted in a marked increase in tubulin acetylation throughout the brain. Despite this, there was no effect on the onset and progression of a wide range of behavioural, physiological, molecular and pathological HD-related phenotypes. We observed no change in the aggregate load or in the levels of soluble mutant exon 1 transprotein. HDAC6 genetic depletion did not affect the efficiency of BDNF transport from the cortex to the striatum. Therefore, we conclude that HDAC6 inhibition does not modify disease progression in R6/2 mice and HDAC6 should not be prioritized as a therapeutic target for HD.

  4. Haemodynamic evaluation of carotid artery disease

    DEFF Research Database (Denmark)

    Sillesen, H; Schroeder, T

    1989-01-01

    evaluating therapeutic modalities or natural history of carotid artery disease should therefore include a test capable of assessing cerebral haemodynamics. However, most studies, invasive as well as non-invasive, have focused on the ability of the test to diagnose the ICA lesions itself, rather than...... the haemodynamic changes induced by the stenosis. This paper reviews non-invasive methods for haemodynamic evaluation of carotid artery disease. Haemodynamic evaluation of ICA stenoses may be performed accurately by different techniques. Analysis of Doppler waveforms obtained distal to the ICA lesion and CBF...

  5. 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.

  6. Measuring the progression of idiopathic Parkinson's disease with [123I] β-CIT SPECT

    International Nuclear Information System (INIS)

    Staffen, W.; Mair, A.; Unterrainer, J.; Trinka, E.; Ladurner, G.

    2000-01-01

    Idiopathic Parkinson's disease (PD) is the most common neuro degenerative disorder. An important step in diagnosing the disease has been achieved with the development of the cocaine derivative [ 123 I] β-CIT for single photon emission computed tomography (SPECT). The aim of this study was to demonstrate the disease progression by repeated measuring presynaptic dopamine transporter density and relating it to clinical data. The presynaptic dopamine, transporter density of 15 PD patients was measured two times with a mean interval of 15 months. All patients were clinically assessed at the time of the experiments according to the classification scheme of Hoehn and Yahr. 11 healthy volunteers were used as a control group. [ 123 I] β-CIT was injected intravenously and measured with a triple-headed camera twenty hours later. The pictures were evaluated semi quantitatively by using the ratio of specific to non-displaceable binding. Presynaptic dopamine transporter density differed significantly between controls and PD patients. A significant correlation between imaging data and clinical stages (H/Y I 27 %, H/Y II -40 %, H/Y III 58 %) was observed for the patient group in the initial experiment. The subsequent decrease of dopamine transporter binding depended on the initial clinical stage (H/Y I -6.81 %; H/Y II -6.05 %; H/Y III -1.25 %) of the patients, and regression analysis revealed that. 91.4 % of the variance of the second measurement were predicted by the initial measurement. No correlations were found for age, gender and disease progression. All patients were treated with L-DOPA and those given a higher dose showed a more rapid decrease of dopamine transporter density. This result could be interpreted as an indication for in vivo neurotoxicity of high concentrations of L-DOPA. We conclude that combining [ 123 I] β-CIT with SPECT imaging is not only a powerful tool for diagnosing PD patients, but may also be used to demonstrate neuro degeneration in vivo. (author)

  7. 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

  8. RAPID progression: tool for screening aggressive course of disease (ACD) in Alzheimer dementia.

    Science.gov (United States)

    Thavichachart, Nuntika; Worakul, Puangsoy; Farlow, Martin R

    2011-04-01

    There is a need for a tool in clinical practice to assess the rate of progression of Alzheimer's disease (AD) patients. The present study purpose was to develop a tool for screening and progression assessing of AD patients with Aggressive Course of Disease (ACD). The Thai Realtime Assessment of Progression In Dementia (RAPID) was developed for screening AD patients with ACD through a caregiver questionnaire. At baseline and at a 6-month follow up visit, patients were tested by the Alzheimer's Disease Assessment Scale cognitive component (ADAS-Cog), while their caregivers completed the Thai RAPID. The tests were run by a team of psychiatrists in the Department of Psychiatry, Chulalongkorn Memorial Hospital. Fifty patients with cognitive impairment were recruited. As a screening tool, the Thai RAPID cut-off point of 9-points yielded a fair sensitivity and specificity (0.625 and 0.643, respectively) for rapid progression as defined by 4 point or greater deterioration in ADAS-Cog. As a progression assessment tool, a cutoff point of 3-points yielded a good sensitivity and specificity (0.875 and 0.810, respectively). The present pilot study suggests that the Thai RAPID can be a valuable tool for the ACD screening and for progression assessment in AD patients.

  9. PNPLA3, a genetic marker of progressive liver disease, still hiding its metabolic function?

    Science.gov (United States)

    Dubuquoy, Céline; Burnol, Anne-Françoise; Moldes, Marthe

    2013-02-01

    Non-alcoholic fatty liver disease (NAFLD) is an emerging epidemic disease. It represents a large spectrum of liver diseases, and affects both adults and children. The etiology of NAFLD is multifactorial. Indeed, several events such as caloric imbalance including sedentary lifestyle, obesity and/or a predisposing genetic background are key players in the increasing risk for NAFLD development and its progression. Recently, a sequence variation within the gene encoding for patatin-like phospholipase containing 3 (PNPLA3, rs738409) was found to modulate steatosis, inflammation and fibrosis in NAFLD. It was also demonstrated as a novel genetic marker associated with progressive ALD (alcoholic liver disease). In this mini-review, we summarize the current knowledge on (i) PNPLA3 variant(s) in the pathogenesis of liver diseases, and (ii) PNPLA3 gene regulation and potential function in liver. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  10. Serum cysteine proteases and their inhibitors in rheumatoid arthritis: relation to disease activity and radiographic progression

    DEFF Research Database (Denmark)

    Jørgensen, Iben; Kos, Janko; Krašovec, Marta

    2011-01-01

    This study aims to investigate the serum levels of cysteine proteases cathepsins B and H and their inhibitors stefin A, stefin B, and cystatin C, as well as traditional inflammatory markers such as C-reactive protein in patients with rheumatoid arthritis and to correlate these markers with scores...... of disease activity and radiographic progression. Seventy-two patients with rheumatoid arthritis were included from two previously described cohorts of patients with chronic polyarthritis. At inclusion, disease activity was assessed by a 28-joint count, patient global assessment, and serum C-reactive protein...... associated with disease activity, presence or progression of erosive disease. Number of swollen joints correlated with serum levels of stefin A and B and correlated negatively with cystatin C serum levels. Erosive disease was associated with high serum levels of C-reactive protein and stefin A and low serum...

  11. Weight preserving image registration for monitoring disease progression in lung CT

    DEFF Research Database (Denmark)

    Gorbunova, Vladlena; Lo, Pechin Chien Pau; Haseem, Ashraf

    2008-01-01

    compared with intensities in the deformed baseline image indicate local loss of lung tissue that is associated with progression of emphysema. To account for differences in lung intensity owing to differences in the inspiration level in the two scans rather than disease progression, we propose to adjust......We present a new image registration based method for monitoring regional disease progression in longitudinal image studies of lung disease. A free-form image registration technique is used to match a baseline 3D CT lung scan onto a following scan. Areas with lower intensity in the following scan...... the density of lung tissue with respect to local expansion or compression such that the total weight of the lungs is preserved during deformation. Our method provides a good estimation of regional destruction of lung tissue for subjects with a significant difference in inspiration level between CT scans...

  12. Wall Shear Stress Characteristics for the Progression of the Disease, Atherosclerosis

    Science.gov (United States)

    Goswami, P.; Mandal, D. K.; Manna, N. K.; Chakrabarti, S.

    2014-12-01

    Wall shear stress (WSS) characteristics of a stenosed artery which are the important physiological parameters for the progression of the arterial diseases atherosclerosis, are studied and compared for different Reynolds numbers and different Womersley numbers. Numerical simulations of physiological pulsatile flow through a model stenotic artery are performed by finite volume method. From this study, it is revealed that the chance of formation of atherosclerosis increases with increase in Reynolds number and decreases with increase in Womersley number. The phenomenon of mass transportation across arterial wall is more in case of increase in Womersley number rather than Reynolds number. The chance of formation of atheromatous plaque will be high with higher Reynolds number and Womersley number. In the low WSS region, high magnitude of Womersley number indicates high chance of progression of the disease atherosclerosis. High magnitude of Womersley number with low Reynolds number is more dangerous for the progression of the disease in the low WSS region.

  13. Evaluation and Management of Pulmonary Disease in Ataxia-Telangiectasia

    Science.gov (United States)

    McGrath-Morrow, Sharon A.; Gower, W. Adam; Rothblum-Oviatt, Cynthia; Brody, Alan S.; Langston, Claire; Fan, Leland L.; Lefton-Greif, Maureen A.; Crawford, Thomas O.; Troche, Michelle; Sandlund, John T; Auwaerter, Paul G.; Easley, Blaine; Loughlin, Gerald M.; Carroll, John L.; Lederman, Howard M.

    2014-01-01

    Summary Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the ATM gene, resulting in faulty repair of breakages in double-stranded DNA. The clinical phenotype is complex, and is characterized by neurologic abnormalities, immunodeficiencies, susceptibility to malignancies, recurrent sinopulmonary infections, and cutaneous abnormalities. Lung disease is common in patients with A-T and often progresses with age and neurological decline. Diseases of the respiratory system cause significant morbidity and are a frequent cause of death in the A-T population. Lung disease in this population is thought to exhibit features of one or more of the following phenotypes: recurrent sinopulmonary infections with bronchiectasis, interstitial lung disease, and lung disease associated with neurological abnormalities. Here, we review available evidence and present expert opinion on the diagnosis, evaluation, and management of lung disease in A-T, as discussed in a recent multidisciplinary workshop. Although more data are emerging on this unique population, many recommendations are made based on similarities to other more well-studied diseases. Gaps in current knowledge and areas for future research in the field of pulmonary disease in A-T are also outlined. PMID:20583220

  14. Economic value evaluation in disease management programs.

    Science.gov (United States)

    Magnezi, Racheli; Reicher, Sima; Shani, Mordechai

    2008-05-01

    Chronic disease management has been a rapidly growing entity in the 21st century as a strategy for managing chronic illnesses in large populations. However, experience has shown that disease management programs have not been able to demonstrate their financial value. The objectives of disease management programs are to create quality benchmarks, such as principles and guidelines, and to establish a uniform set of metrics and a standardized methodology for evaluating them. In order to illuminate the essence of disease management and its components, as well as the complexity and the problematic nature of performing economic calculations of their profitability and value, we collected data from several reports that dealt with the economic intervention of disease management programs. The disease management economic evaluation is composed of a series of steps, including the following major categories: data/information technology, information generation, assessment/recommendations, actionable customer plans, and program assessment/reassessment. We demonstrate the elements necessary for economic analysis. Disease management is one of the most innovative tools in the managed care environment and is still in the process of being defined. Therefore, objectives should include the creation of quality measures, such as principles and guidelines, and the establishment of a uniform set of metrics and a standardized methodology for evaluating them.

  15. 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.

  16. 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

  17. 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).

  18. A clinical index to predict progression from mild cognitive impairment to dementia due to Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Sei J Lee

    Full Text Available 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.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.382 participants diagnosed with amnestic mild cognitive impairment enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI, a multi-site, longitudinal, observational study.Demographics, comorbid conditions, caregiver report of participant symptoms and function, and participant performance on individual items from basic neuropsychological scales.Progression to probable Alzheimer's disease.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.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 differentiate between mild cognitive impairment patients at low vs. high risk of progression.

  19. 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.

  20. 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.

    2015-01-01

    Objective To examine the associations between hormonal contraceptive use and measures of HIV disease progression and antiretroviral treatment (ART) effectiveness. Study design 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. Results During a total of 5233 months follow-up among participants not using ART with enrollment CD4 ≥ 350 cells/mm3 (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. Conclusion Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. Implications Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. PMID:26197261

  1. Regression of Nonalcoholic Fatty Liver Disease with Zinc and Selenium Co-supplementation after Disease Progression in Rats

    Directory of Open Access Journals (Sweden)

    Farzad Shidfar

    2018-01-01

    Full Text Available Background: Studies have shown that zinc and selenium deficiency is common in nonalcoholic fatty liver disease (NAFLD. However, the effects of zinc and selenium co-supplementation before and/or after disease progression on NAFLD are not clear enough. The aim of this study was to compare the effects of zinc and selenium co-supplementation before and/or after disease progression on NAFLD prognosis. Methods: Forty male Sprague–Dawley rats (197±4 g were randomly assigned to 4 dietary groups: normal-fat diet (NFD; receiving 9% of calories as fat, high-fat diet (HFD; receiving 82% of calories as fat, supplementation before disease progression (S+HFD, and supplementation after disease progression (HFD+S. The diets were implemented over a 20-week period in all the groups. Biochemical and histologic parameters were compared between the 4 groups, and between-group comparisons were also carried out. Results: There were significant differences in the average food dietary intake (P<0.001, weight (P<0.001, fasting blood sugar (P=0.005, triglyceride (P<0.001, total cholesterol (P<0.001, low-density lipoprotein cholesterol (P=0.002, high-density lipoprotein cholesterol (P=0.001, alanine aminotransferase (P<0.001, and aspartate aminotransferase (P<0.001 between the 4 dietary groups. Serum triglyceride and total cholesterol were significantly lower in the HFD+S Group than in the S+HFD Group (P<0.001 and P=0.003, respectively. Fat accumulation was significantly reduced in the HFD+S Group (P<0.001. Conclusion: Zinc and selenium co-supplementation after disease progression improved biochemical and histologic parameters in an experimental model of NAFLD.

  2. Geoscientific evaluation factors and criteria for siting and site evaluation. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Stroem, A.; Ericsson, Lars O.; Svemar, C. [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Almen, K.E. [KEA GEO-konsult AB (Sweden); Andersson, Johan [Golder Grundteknik KB (Sweden)

    1999-03-01

    The purposes of the present report are to: present the work that has been done to identify the parameters that need to be determined in a geoscientific site investigation and that serve as the basis for the work with geoscientific evaluation factors; give a progress report from the project that was initiated in 1997 named Siting Factors and Criteria for Site Evaluation, with an emphasis on definitions, outline and structure for the execution of the work; present geoscientific requirements on function both general and in detail in the form of an example for the discipline rock mechanics; present geoscientific evaluation factors associated with different stages in the siting work in the form of an example for the discipline hydrogeochemical composition; present plans for further work as regards criteria for site evaluation in different siting stages. The project is under way, and this is to be regarded as a progress report since e.g. criteria for site evaluation will be presented at a later date. The long-term performance and safety of the deep repository must always be evaluated by means of an integrated safety assessment. The work with factors and criteria can never take the place of such an assessment, but can provide guidance regarding its outcome. Requirements and preferences regarding the function of the rock in the deep repository have been clarified in this progress report. What is new here is the structuring that has been carried out, with a classification into different geoscientific disciplines, and the formalism that has been given to the terms requirement, preference and function. Based on fundamental safety and construction functions, requirements on function have been specified for the disciplines geology, thermal properties, hydro-geology, rock mechanics, chemistry and transport properties. Furthermore, function analyses have been identified by means of which it is possible to concretize requirements on function and which geoscientific parameters are

  3. White matter disease correlates with lexical retrieval deficits in primary progressive aphasia

    Directory of Open Access Journals (Sweden)

    John P. Powers

    2013-12-01

    Full Text Available Objective: To relate fractional anisotropy changes associated with the semantic and logopenic variants of primary progressive aphasia to measures of lexical retrieval.Methods: We collected neuropsychological testing, volumetric MRI, and diffusion-weighted imaging on semantic variant primary progressive aphasia (n=11 and logopenic variant primary progressive aphasia (n=13 patients diagnosed using published criteria. We also acquired neuroimaging data on a group of demographically comparable healthy seniors (n=34. Fractional anisotropy was calculated and analyzed using a white matter tract-specific analysis approach. This approach utilizes anatomically guided data reduction to increase sensitivity and localizes results within canonically defined tracts. We used non-parametric, cluster-based statistical analysis to relate language performance to fractional anisotropy and determine regions of reduced fractional anisotropy in patients. Results: We found widespread fractional anisotropy reductions in white matter for both variants of primary progressive aphasia. Fractional anisotropy was related to both confrontation naming and category naming fluency performance in left uncinate fasciculus and corpus callosum in semantic variant primary progressive aphasia and left superior and inferior longitudinal fasciculi in logopenic variant primary progressive aphasia. Conclusions: Semantic variant primary progressive aphasia and logopenic variant primary progressive aphasia are associated with distinct disruptions of a large-scale network implicated in lexical retrieval, and the white matter disease in each phenotype may contribute to language impairments including lexical retrieval.

  4. JAK2V617F mutation in chronic myeloid leukemia predicts early disease progression

    International Nuclear Information System (INIS)

    Pahore, Z.A.A.; Shamsi, T.S.; Taj, M.; Farzana, T.; Ansari, S.H.; Nadeem, M.; Ahmad, M.; Naz, A.

    2011-01-01

    Objective: To determine the association of JAK2V617F mutation along with BCR-ABL translocation or Philadelphia chromosome in chronic myeloid leukemia with early disease progression to advanced stages (accelerated phase or blast crisis) and poor outcome. Study Design: Case series. Place and Duration of Study: National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, from February 2008 to August 2009. Methodology: All the newly diagnosed cases of BCR-ABL or Philadelphia positive CML were tested for JAK2V617F mutation by Nested PCR. Demographic data, spleen size, hemoglobin levels, white blood cell and platelet counts were recorded. Independent sample t-test was used for age, haemoglobin level and spleen size. Fisher's exact test was applied to compare disease progression in JAK2V617F mutation positive and negative cases. Results: Out of 45 newly diagnosed cases of CML, 40 were in chronic phase, 01 in accelerated phase and 04 in blast crisis. JAK2V617F mutation was detected in 12 (26.7%) patients; 09 (22.5%) in chronic phase, none in accelerated phase and 03 (75%) in blast crisis. During a mean follow-up of 8 months, 03 patients in chronic phase transformed in blast crisis and 02 into accelerated phase. Overall 08 out of 11 (73%) JAK2V617F positive patients either had advanced disease or showed disease progression. Only 2 of 20 (10%) available patients, negative for the mutation, showed disease progression by transforming into blast crisis (p < 0.001). No statistically significant difference was seen in the age, spleen size, haemoglobin levels, white blood cells and platelets counts in JAK2V617F positive patients. Conclusion: JAK2V617F mutation was detected in 26.7% cases of chronic myeloid leukemia. A significant proportion of them showed early disease progression. (author)

  5. 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.

  6. 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.

  7. Factors associated with coronary artery disease progression assessed by serial coronary computed tomography angiography

    Energy Technology Data Exchange (ETDEWEB)

    Camargo, Gabriel Cordeiro; Gottlieb, Ilan, E-mail: ilangottlieb@gmail.com [Casa de Saúde São José, Rio de Janeiro, RJ (Brazil); Rothstein, Tamara; Derenne, Maria Eduarda; Sabioni, Leticia; Lima, Ronaldo de Souza Leão [Centro de Diagnóstico por Imagem CDPI, Rio de Janeiro, RJ (Brazil); Lima, João A. C. [Johns Hopkins University, Baltimore (United States)

    2017-05-15

    Background: Coronary computed tomography angiography (CCTA) allows for noninvasive coronary artery disease (CAD) phenotyping. Factors related to CAD progression are epidemiologically valuable. Objective: To identify factors associated with CAD progression in patients undergoing sequential CCTA testing. Methods: We retrospectively analyzed 384 consecutive patients who had at least two CCTA studies between December 2005 and March 2013. Due to limitations in the quantification of CAD progression, we excluded patients who had undergone surgical revascularization previously or percutaneous coronary intervention (PCI) between studies. CAD progression was defined as any increase in the adapted segment stenosis score (calculated using the number of diseased segments and stenosis severity) in all coronary segments without stent (in-stent restenosis was excluded from the analysis). Stepwise logistic regression was used to assess variables associated with CAD progression. Results: From a final population of 234 patients, a total of 117 (50%) had CAD progression. In a model accounting for major CAD risk factors and other baseline characteristics, only age (odds ratio [OR] 1.04, 95% confidence interval [95%CI] 1.01–1.07), interstudy interval (OR 1.03, 95%CI 1.01–1.04), and past PCI (OR 3.66, 95%CI 1.77–7.55) showed an independent relationship with CAD progression. Conclusions: A history of PCI with stent placement was independently associated with a 3.7-fold increase in the odds of CAD progression, excluding in-stent restenosis. Age and interstudy interval were also independent predictors of progression. (author)

  8. Review of progress in quantitative nondestructive evaluation. Volume 7

    International Nuclear Information System (INIS)

    Thompson, D.O.; Chimenti, D.E.

    1988-01-01

    Research in nondestructive evaluation theory, techniques, and equipment for materials ranging from metals to composites is described in the 218 papers contained in these conference proceedings. The topics covered include the fundamentals of ultrasonic, eddy current, and thermal wave testing; imaging, tomography, and inversion; sensors and probes; image enhancement and signal processing; adhesive bond and composite testing; electronic materials and device evaluation; materials characterization for aspects such as microstructure, bonds and interfaces, acoustoelasticity, stress, and texture; ferromagnetic materials and weldment testing; crack and deformation evaluation; nondestructive applications in process control; and nondestructive evaluation systems and reliability assessment

  9. Primate amygdala neurons evaluate the progress of self-defined economic choice sequences.

    Science.gov (United States)

    Grabenhorst, Fabian; Hernadi, Istvan; Schultz, Wolfram

    2016-10-12

    The amygdala is a prime valuation structure yet its functions in advanced behaviors are poorly understood. We tested whether individual amygdala neurons encode a critical requirement for goal-directed behavior: the evaluation of progress during sequential choices. As monkeys progressed through choice sequences toward rewards, amygdala neurons showed phasic, gradually increasing responses over successive choice steps. These responses occurred in the absence of external progress cues or motor preplanning. They were often specific to self-defined sequences, typically disappearing during instructed control sequences with similar reward expectation. Their build-up rate reflected prospectively the forthcoming choice sequence, suggesting adaptation to an internal plan. Population decoding demonstrated a high-accuracy progress code. These findings indicate that amygdala neurons evaluate the progress of planned, self-defined behavioral sequences. Such progress signals seem essential for aligning stepwise choices with internal plans. Their presence in amygdala neurons may inform understanding of human conditions with amygdala dysfunction and deregulated reward pursuit.

  10. Reduced retinal nerve fiber layer (RNFL) thickness in ALS patients: a window to disease progression.

    Science.gov (United States)

    Rohani, Mohammad; Meysamie, Alipasha; Zamani, Babak; Sowlat, Mohammad Mahdi; Akhoundi, Fahimeh Haji

    2018-04-30

    To assess RNFL thickness in ALS patients and compare it to healthy controls, and to detect possible correlations between RNFL thickness in ALS patients and disease severity and duration. Study population consisted of ALS patients and age- and sex-matched controls. We used the revised ALS functional rating scale (ALSFRS-R) as a measure of disease severity. RNFL thickness in the four quadrants were measured with a spectral domain OCT (Topcon 3D, 2015). We evaluated 20 ALS patients (40 eyes) and 25 healthy matched controls. Average RNFL thickness in ALS patients was significantly reduced compared to controls (102.57 ± 13.46 compared to 97.11 ± 10.76, p 0.04). There was a significant positive correlation between the functional abilities of the patients based on the ALSFRS-R and average RNFL thickness and also RNFL thickness in most quadrants. A linear regression analysis proved that this correlation was independent of age. In ALS patients, RNFL thickness in the nasal quadrant of the left eyes was significantly reduced compared to the corresponding quadrant in the right eyes even after adjustment for multiplicity (85.80 ± 23.20 compared to 96.80 ± 16.96, p = 0.008). RNFL thickness in ALS patients is reduced compared to healthy controls. OCT probably could serve as a marker of neurodegeneration and progression of the disease in ALS patients. RNFL thickness is different among the right and left eyes of ALS patients pointing to the fact that asymmetric CNS involvement in ALS is not confined to the motor system.

  11. 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...... of the 11 candidate genes have overlapping biological functions and interact in a common network. Our results may help predict disease progression in newly diagnosed children with T1D which can be exploited for optimizing treatment....

  12. 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...

  13. 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.

  14. 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].

  15. EVALUATION OF STEROID HORMONES AND THEIR RECEPTORS IN DEVELOPMENT AND PROGRESSION OF RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Nigel Bennett

    2014-06-01

    Full Text Available Steroid hormones and their receptors have important roles in normal kidney biology, and alterations in their expression and function help explain the differences in development of kidney diseases, such as nephrotic syndrome and chronic kidney disease. The distinct gender difference in incidence of renal cell carcinoma (RCC, with males having almost twice the incidence as females globally, also suggests a role for sex hormones or their receptors in RCC development and progression. There was a peak in interest in evaluating the roles of androgen and estrogen receptors in RCC pathogenesis in the late 20th century, with some positive outcomes for RCC therapy that targeted estrogen receptors, especially for metastatic disease. Since that time, however, there have been few studies that look at use of steroid hormone modulators for RCC, especially in the light of new therapies such as the tyrosine kinase inhibitors and new immune therapies, which are having some success for treatment of metastatic RCC. This review summarises past and current literature and attempts to stimulate renewed interest in research into the steroid hormones and their receptors, which might be used to effect, for example, in combination with the other newer targeted therapies for RCC.

  16. 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 w...... 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.......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...... here the first study on the putative role of MBL deficiency on HIV progression and survival in an African adult population. We hypothesized that MBL deficiency has a role to play in HIV infection by increasing HIV disease progression and decreasing survival. We assessed the role of MBL deficiency...

  17. 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.

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

    Science.gov (United States)

    Hensman Moss, Davina J; 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

  19. 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.

  20. Does significant renal ablation truly and invariably lead to hyperfiltration and progressive chronic kidney disease?

    Science.gov (United States)

    Wang, Andrew; Sam, Ramin

    2017-06-01

    It is generally believed that significant renal ablation leads to hyperfiltration and eventually progressively worsening chronic kidney disease. The data behind this belief have not been scrutinized intensively. More importantly, the above belief leads many physicians to manage patients differently than they otherwise would manage. Here, we examine the data behind whether hyperfiltration occurs when patients lose kidney mass (by excision or by disease) and whether the hyperfiltration is uniformly injurious.

  1. 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.

  2. Progress on neutron data evaluation activities in Lanzhou University

    International Nuclear Information System (INIS)

    Yao Lishan

    1991-01-01

    Lanzhou University is one of the earliest units which joined the Chinese Nuclear Data coordination Network. The evaluation of neutron nuclear data, the theoretical calculation for neutron data and the systematics of neutron reaction cross section in Lanzhou University is introduced. The evaluations of Ti, Sn, Sb, 181 Ta have been completed respectively. The systematic study for (n, 2n), (n, 3n) and (n, x) (x = p, t, 3 He, d, α) reaction cross sections have been performed. The evaluations and theoretical calculations of neutron resonance parameters, γ production data and the double differential neutron emitted cross sections are performed

  3. Evaluation of progress under the EU National Emission Ceilings Directive. Progress towards EU air quality objectives

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-10-15

    The objective of this report was to assess to what extent the NEC Directive's environmental and health objectives concerning acidification, eutrophication and ground-level ozone exposure for the year 2010 have been achieved. The main basis for the assessment is the emission inventory data officially reported by Member States. The analysis was conducted by using the same scientific methods of 2001 (original knowledge) and 2010 (present knowledge) that support European air pollution abatement policies. The original knowledge consisted of modelling concentrations and exposure using the older Lagrangian EMEP model (utilising a 150 x 150 km{sup 2} grid for the computation of grid-average S and N depositions and ground-level ozone concentrations, together with the 1998 European critical load database for assessing the risk of acidification and eutrophication). The assessment performed on the basis of present knowledge used the current Eulerian EMEP model on a 50 x 50 km{sup 2} grid for the computation of ecosystem-specific depositions and ground-level ozone concentrations, in combination with the 2008 European critical loads database. When assessing progress using original knowledge, the NEC Directive's interim environmental acidification objective has been met in almost all grid cells, while the eutrophication objective - provided in a footnote within the NEC Directive and which was formulated on the European Union area as a whole - has been met both for the EU-15 and the EU-27 regions as a whole. If, in contrast, the eutrophication objective had been required to be met in individual grid cells (as for acidification) or in individual Member States, it would be exceeded in many grid cells and in 11 Member States. While acidification has been markedly reduced, eutrophication is now recognised as a major environmental problem in Europe, especially in the context of its potential adverse impacts on biodiversity. An assessment using present knowledge indicates that

  4. Structural Disease Progression in Axial Spondyloarthritis: Still a Cause for Concern?

    Science.gov (United States)

    Neerinckx, Barbara; Lories, Rik J

    2017-03-01

    Progressive ankylosis is a feared consequence of long-standing axial spondyloarthritis. We aim to critically review current insights into the effect of therapy, the molecular pathways involved in this process, and to present a model explaining the sequence of events. Long-term follow-up data suggest that successful control of inflammation may slow down radiographic progression of disease in axial spondyloarthritis. Structural effects of new therapies such as interleukin-17 targeting need to be further studied. Bone loss and architectural changes could act as driver for the tissue remodeling process trying to maintain spinal stability in the presence of inflammation. Despite some progress, the nature and mechanisms of new bone formation in axial spondyloarthritis still remain incompletely understood. However, long-term control of inflammation appears critical to avoid progressive disability due to structural damage.

  5. 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.......27-2.79; P complications (HR, 1.66; 95% CI, 1.22-2.27; 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...... 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...

  6. Impact of HIV Type 1 DNA Levels on Spontaneous Disease Progression: A Meta-Analysis

    DEFF Research Database (Denmark)

    Tsiara, Chrissa G; Nikolopoulos, Georgios K; Bagos, Pantelis G

    2012-01-01

    Abstract Several studies have reported the prognostic strength of HIV-1 DNA with variable results however. The aims of the current study were to estimate more accurately the ability of HIV-1 DNA to predict progression of HIV-1 disease toward acquired immunodeficiency syndrome (AIDS) or death...... of primary studies indicated that HIV-1 DNA was a significantly better predictor than HIV-1 RNA of either AIDS alone (ratio of RRs=1.47, 95% CI: 1.05-2.07) or of combined (AIDS or death) progression outcomes (ratio of RRs=1.51, 95% CI: 1.11-2.05). HIV-1 DNA is a strong predictor of HIV-1 disease progression...

  7. 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.

  8. Rapid Disease Progression With Delay in Treatment of Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Mohammed, Nasiruddin; Kestin, Larry Llyn; Grills, Inga Siiner; Battu, Madhu; Fitch, Dwight Lamar; Wong, Ching-yee Oliver; Margolis, Jeffrey Harold; Chmielewski, Gary William; Welsh, Robert James

    2011-01-01

    Purpose: To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change. Results: Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6-8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7-38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05. Conclusions: With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4-8 weeks of delay, complete restaging should be strongly considered.

  9. 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.; Guera-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.M.; 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,

  10. Accelerating regional atrophy rates in the progression from normal aging to Alzheimer's disease

    NARCIS (Netherlands)

    Sluimer, J.D.; van der Flier, W.M.; Karas, G.B.; van Schijndel, R.; Barnes, J.; Boyes, R.G.; Cover, K.S.; Olabarriaga, S.D.; Fox, N.C.; Scheltens, P.; Vrenken, H.; Barkhof, F.

    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

  11. 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%),

  12. Correction to: Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event.

    Science.gov (United States)

    Berger, Joseph R; Malik, Vineeta; Lacey, Stuart; Brunetta, Paul; Lehane, Patricia B

    2018-04-10

    The article "Progressive multifocal leukoencephalopathy in rituximab-treated rheumatic diseases: a rare event," written by Joseph R. Berger, Vineeta Malik, Stuart Lacey, Paul Brunetta, and Patricia B. Lehane 3 , was originally published electronically on the publisher's internet portal (currently SpringerLink).

  13. Cognitive dysfunction in lower motor neuron disease: executive and memory deficits in progressive muscular atrophy

    NARCIS (Netherlands)

    Raaphorst, J.; de Visser, M.; van Tol, M.-J.; Linssen, W.H.J.P.; van der Kooi, A.J.; de Haan, R.J.; van den Berg, L.H.; Schmand, B.

    2011-01-01

    Aim In contrast with findings in amyotrophic lateral sclerosis (ALS), cognitive impairments have as yet not been shown in the lower motor neuron variant of motor neuron disease, progressive spinal muscular atrophy (PMA). The objective of this study was to investigate cognitive function in PMA and to

  14. 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...

  15. 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.

  16. Untreated periodontal disease in Indonesian adolescents : Subgingival microbiota in relation to experienced progression of periodontitis

    NARCIS (Netherlands)

    Timmerman, MF; Van der Weijden, GA; Arief, EM; Armand, S; Abbas, F; Winkel, EG; Van Winkelhoff, AJ; Van der Velden, U

    Background/aims: In an Indonesian population deprived of regular dental care, the experienced progression of disease between baseline (1987) and follow-up (1994) was investigated in relation to the composition of the subgingival microbiota at follow-up. At baseline the age ranged from 15 to 25

  17. Effect of Sex Hormones on Progression of Diabetic Renal Disease in ...

    African Journals Online (AJOL)

    Effect of Sex Hormones on Progression of Diabetic Renal Disease in Experimental Model of Streptozotocin Induced Diabetic Rats. ... into five groups 8 rats each, normal control, diabetic, gonadectomized diabetic, 17 beta estradiol is given to female and testosterone propionate to male diabetic and gonadectomized diabetic.

  18. 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

  19. 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.

  20. 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)…

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

    Science.gov (United States)

    Perifano, A; Scelles, R

    2015-09-01

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

  2. Cushing's disease: diagnostic evaluation, therapeutics and prognostic

    International Nuclear Information System (INIS)

    Pereira, M.A.A.; Jugue, S.M.; Moura, O.M.D.; Gross, K.; Halpern, A.; Nicolau, W.; Liberman, B.; Bloise, W.; Mendonca, B.; Cabral, N.D.; Marino Junior, R.; Wajchenberg, B.L.

    1992-01-01

    Aspects as clinical, diagnosis, laboratory tests and radiological evaluations concerning Cushing's disease are analysed in 56 patients. Several options of non medicamental therapy are presented. The relationship between preoperative data (hormonal and radiological information), postoperative findings and hypophyseal adenomectomy is discussed. (M.A.C.)

  3. Evaluation of two group therapies to reduce fear of progression in cancer patients.

    Science.gov (United States)

    Herschbach, Peter; Book, Katrin; Dinkel, Andreas; Berg, Petra; Waadt, Sabine; Duran, Gabriele; Engst-Hastreiter, Ursula; Henrich, Gerhard

    2010-04-01

    This paper aims to evaluate the effects of two psychotherapeutic interventions on dysfunctional fear of progression (FoP) in cancer patients and to investigate illness-specific influences. One hundred seventy-four cancer patients were recruited from two rehabilitation clinics and randomly assigned to either a four-session cognitive-behavioral group therapy or a supportive-experiential group therapy. The main outcome criterion was FoP that was assessed with the Fear of Progression Questionnaire (FoP-Q) directly before (T1) and after (T2) the intervention, as well as 3 (T3) and 12 months (T4) after discharge. Secondary outcomes were anxiety, depression, and quality of life that were assessed with the following questionnaires: Questions on Life Satisfaction, Questionnaire for General Health Status, and the Hospital Anxiety and Depression Scale. Patients from the control group (n = 91) who received treatment as usual were recruited 1 year later with the same inclusion criteria and assessed with the FoP-Q at T1, T2, and T4. Analyses showed a significant main effect for time and a significant interaction for group x time for the main outcome variable. FoP decreased significantly over time in both intervention groups in contrast to the control group that showed only short-term improvements. The interventions were also effective in improving secondary outcomes except general life satisfaction. Analyses of cancer specific influences on FoP indicated a significant influence of disease status, i.e., patients with metastases and recurrence of cancer gained most from the interventions. Fear of progression, one of the main sources of distress for cancer patients, can be reduced with short psychotherapeutic interventions.

  4. Comprehensive noninvasive evaluation of extracranial cerebrovascular disease

    International Nuclear Information System (INIS)

    Roederer, G.O.; Langlois, Y.; Strandness, D.E. Jr.

    1984-01-01

    Noninvasive tests for the detection of carotid occlusive disease have focused primarily on the indirect assessment of the internal carotid artery by the analysis of arterial pressure and flow. These tests can only detect the presence of flow-reducing lesions and occlusions; they cannot differentiate between these two entities. Also, the assessment of bilateral disease is difficult using these techniques. Direct noninvasive tests are ideal to evaluate atherosclerotic disease at the carotid bifurcation. The methods based on the auditory analysis of bruits are limited by the poor predictive value of the finding for the presence of internal carotid disease. Although the quantitative analysis of a bruit overcomes the inadequacy of auditory interpretation, the test is most suitable in combination with other techniques and most valuable in the follow-up of symptomatic patients with a bruit

  5. 20 CFR 638.522 - Evaluation of student progress.

    Science.gov (United States)

    2010-04-01

    ... Section 638.522 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.522 Evaluation of... issued by the Job Corps Director. ...

  6. A Progress Evaluation of Four Bilingual Children's Television Shows.

    Science.gov (United States)

    Klein, Stephen P.; And Others

    An evaluation of a bilingual education TV series was conducted involving 6-year-old English speaking, Spanish speaking, and bilingual children at four sites. Children were assigned to control and experimental groups with the latter group seeing four 30 minute shows. A pretest-posttest design was employed with the pretest serving as the covariate…

  7. Evaluating the development of life and progress of heavy vehicles ...

    African Journals Online (AJOL)

    The development of automotive products considering product lifecycle is considered as one of the automotive strategic key issues. In this article, Analytical Hierarchy Process (AHP) is used to evaluate the lifetime of heavy vehicles. To do this research, subsystems of weighted Titan heavy vehicle and the position of desired ...

  8. Progression of MRI markers in cerebral small vessel disease: Sample size considerations for clinical trials

    Science.gov (United States)

    Zeestraten, Eva; Lambert, Christian; Chis Ster, Irina; Williams, Owen A; Lawrence, Andrew J; Patel, Bhavini; MacKinnon, Andrew D; Barrick, Thomas R; Markus, Hugh S

    2016-01-01

    Detecting treatment efficacy using cognitive change in trials of cerebral small vessel disease (SVD) has been challenging, making the use of surrogate markers such as magnetic resonance imaging (MRI) attractive. We determined the sensitivity of MRI to change in SVD and used this information to calculate sample size estimates for a clinical trial. Data from the prospective SCANS (St George’s Cognition and Neuroimaging in Stroke) study of patients with symptomatic lacunar stroke and confluent leukoaraiosis was used (n = 121). Ninety-nine subjects returned at one or more time points. Multimodal MRI and neuropsychologic testing was performed annually over 3 years. We evaluated the change in brain volume, T2 white matter hyperintensity (WMH) volume, lacunes, and white matter damage on diffusion tensor imaging (DTI). Over 3 years, change was detectable in all MRI markers but not in cognitive measures. WMH volume and DTI parameters were most sensitive to change and therefore had the smallest sample size estimates. MRI markers, particularly WMH volume and DTI parameters, are more sensitive to SVD progression over short time periods than cognition. These markers could significantly reduce the size of trials to screen treatments for efficacy in SVD, although further validation from longitudinal and intervention studies is required. PMID:26036939

  9. An alpha-synuclein MRM assay with diagnostic potential for Parkinson's disease and monitoring disease progression

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. 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

  11. The effect of cigarette smoking, tea, and coffee consumption on the progression of Parkinson's disease.

    Science.gov (United States)

    Kandinov, Boris; Giladi, Nir; Korczyn, Amos D

    2007-05-01

    Previous epidemiological studies found a negative association between cigarette smoking, tea or coffee drinking with the occurrence of Parkinson's disease (PD). However, it is unknown how these factors affect the rate of progression of the disease. A retrospective study was conducted among 278 consecutive PD patients. Data on smoking and coffee or tea consumption were obtained through direct or proxy interviews, and the time from onset of motor symptoms until reaching Hoehn & Yahr (H&Y) stage 3 was retrieved from the case records. Cox proportional hazards model and Kaplan-Meyer model were used to estimate whether the dependent variables (smoking, drinking coffee or tea) affect the rate of progression of the disease, which was measured by the time it took patients to reach H&Y stage 3. We found that disease progression was not affected by cigarette smoking, tea or coffee consumption. The present study suggests that these variables do not have a disease modifying effect in already diagnosed PD patients.

  12. Assembly and interrogation of Alzheimer's disease genetic networks reveal novel regulators of progression.

    Directory of Open Access Journals (Sweden)

    Soline Aubry

    Full Text Available Alzheimer's disease (AD is a complex multifactorial disorder with poorly characterized pathogenesis. Our understanding of this disease would thus benefit from an approach that addresses this complexity by elucidating the regulatory networks that are dysregulated in the neural compartment of AD patients, across distinct brain regions. Here, we use a Systems Biology (SB approach, which has been highly successful in the dissection of cancer related phenotypes, to reverse engineer the transcriptional regulation layer of human neuronal cells and interrogate it to infer candidate Master Regulators (MRs responsible for disease progression. Analysis of gene expression profiles from laser-captured neurons from AD and controls subjects, using the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe, yielded an interactome consisting of 488,353 transcription-factor/target interactions. Interrogation of this interactome, using the Master Regulator INference algorithm (MARINa, identified an unbiased set of candidate MRs causally responsible for regulating the transcriptional signature of AD progression. Experimental assays in autopsy-derived human brain tissue showed that three of the top candidate MRs (YY1, p300 and ZMYM3 are indeed biochemically and histopathologically dysregulated in AD brains compared to controls. Our results additionally implicate p53 and loss of acetylation homeostasis in the neurodegenerative process. This study suggests that an integrative, SB approach can be applied to AD and other neurodegenerative diseases, and provide significant novel insight on the disease progression.

  13. Co-expression of GPR30 and ERβ and their association with disease progression in uterine carcinosarcoma

    Science.gov (United States)

    Huang, Gloria S.; Gunter, Marc J.; Arend, Rebecca C.; Li, Maomi; Arias-Pulido, Hugo; Prossnitz, Eric R.; Goldberg, Gary L.; Smith, Harriet O.

    2010-01-01

    Objective To evaluate the expression of G-coupled protein receptor 30 (GPR30) and estrogen receptor beta (ERβ) in uterine carcinosarcoma. Study Design Immunohistochemistry was performed using antibodies to GPR30, ERβ, estrogen receptor alpha (ERα), and progesterone receptor (PR). The staining intensity and percentage of positive cells were scored for each tissue section. Expression levels were compared using the Wilcoxon rank-sum test. Correlation was evaluated by Spearman’s rho and logistic regression. Results Compared with normal endometrium, carcinosarcoma had lower ERα and PR expression (both pcarcinosarcoma had higher GPR30 (pcarcinosarcoma. Expression of GPR30 and ERβ correlated with each other (pcarcinosarcoma, GPR30 and ERβ are coordinately overexpressed and expression levels increase in advanced stage disease, supporting the involvement of alternative estrogen receptors in disease progression. PMID:20605134

  14. Cloning of the canine ABCA4 gene and evaluation in canine cone-rod dystrophies and progressive retinal atrophies.

    Science.gov (United States)

    Kijas, James W; Zangerl, Barbara; Miller, Brian; Nelson, Jacque; Kirkness, Ewen F; Aguirre, Gustavo D; Acland, Gregory M

    2004-03-29

    To characterize a novel early onset canine retinal disease, and evaluate the ATP-binding cassette transporter gene ABCA4 as a potential candidate gene in this and other canine retinal degenerations. Retinal disease was characterized ophthalmoscopically and electroretinographically in two pit bull terrier dogs and their purpose-bred descendants. All 50 exons of the canine ABCA4 gene were amplified, cloned and sequenced from retinal mRNA of a normal, a carrier and an affected animal, and polymorphisms identified. The latter were used to search for association between ABCA4 and retinal disease both within the study pedigrees and in additional canine breeds segregating retinal degenerations. The disease derived from either founder is distinguished by early, severe, and rapidly progressive loss of cone function accompanied by progressive rod loss that is only relatively slower. Cloning and comparative sequencing of ABCA4 identified six point mutations, none of which were obviously pathogenic. Crossbreeding studies revealed that the diseases in the two founders, although similar, are nonallelic. Pedigree analysis of segregating polymorphisms revealed dissociation between ABCA4 and both retinal phenotypes. The early, severe cone dysfunction in these diseases distinguish them from other forms of canine Progressive Retinal Atrophy. The development of a research population segregating these diseases presents two large animal models for the heterogenous human diseases termed cone-rod dystrophies. Analysis of the canine ABCA4 homolog gene documented its sequence and identified a set of point mutations that were used to exclude this gene as causal to these canine cone-rod dystrophies.

  15. Cysteine 138 mutation in HIV-1 Nef from patients with delayed disease progression

    DEFF Research Database (Denmark)

    Tolstrup, Martin; Laursen, Alex Lund; Gerstoft, J.

    2006-01-01

    .0139). The phylogeny of isolates was investigated and the variants harbouring the cysteine 138 mutation clustered independently. CONCLUSION: The present study describes a viral genetic polymorphism related to AIDS disease progression. The polymorphism (cysteine 138) has previously been reported to confer decreased......-1 isolates from patients in a long-term non-progressor (LTNP) cohort and a slow-progressor (SP) cohort (n = 11) was analysed and compared with isolates from a control patient group of progressors (n = 18). Most of the patients with delayed disease progression had extensive medical records, providing...... an insight into the LTNP disease profile and allowing for the stratification of patients based on their CD4 cell decline. RESULTS: In sequences from nine patients, most of the functional domains of HIV-1 Nef appeared intact, and no major deletions were observed to possibly account for an effect...

  16. High resolution molecular and histological analysis of renal disease progression in ZSF1 fa/faCP rats, a model of type 2 diabetic nephropathy.

    Science.gov (United States)

    Dower, Ken; Zhao, Shanrong; Schlerman, Franklin J; Savary, Leigh; Campanholle, Gabriela; Johnson, Bryce G; Xi, Li; Nguyen, Vuong; Zhan, Yutian; Lech, Matthew P; Wang, Ju; Nie, Qing; Karsdal, Morten A; Genovese, Federica; Boucher, Germaine; Brown, Thomas P; Zhang, Baohong; Homer, Bruce L; Martinez, Robert V

    2017-01-01

    ZSF1 rats exhibit spontaneous nephropathy secondary to obesity, hypertension, and diabetes, and have gained interest as a model system with potentially high translational value to progressive human disease. To thoroughly characterize this model, and to better understand how closely it recapitulates human disease, we performed a high resolution longitudinal analysis of renal disease progression in ZSF1 rats spanning from early disease to end stage renal disease. Analyses included metabolic endpoints, renal histology and ultrastructure, evaluation of a urinary biomarker of fibrosis, and transcriptome analysis of glomerular-enriched tissue over the course of disease. Our findings support the translational value of the ZSF1 rat model, and are provided here to assist researchers in the determination of the model's suitability for testing a particular mechanism of interest, the design of therapeutic intervention studies, and the identification of new targets and biomarkers for type 2 diabetic nephropathy.

  17. Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases.

    Science.gov (United States)

    Bacioglu, Mehtap; Maia, Luis F; Preische, Oliver; Schelle, Juliane; Apel, Anja; Kaeser, Stephan A; Schweighauser, Manuel; Eninger, Timo; Lambert, Marius; Pilotto, Andrea; Shimshek, Derya R; Neumann, Ulf; Kahle, Philipp J; Staufenbiel, Matthias; Neumann, Manuela; Maetzler, Walter; Kuhle, Jens; Jucker, Mathias

    2016-07-06

    A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (α-synuclein, Tau, Aβ). To monitor such treatments, fluid biomarkers reflecting the underlying disease process are crucial. We found robust increases of neurofilament light chain (NfL) in CSF and blood in murine models of α-synucleinopathies, tauopathy, and β-amyloidosis. Blood and CSF NfL levels were strongly correlated, and NfL increases coincided with the onset and progression of the corresponding proteopathic lesions in brain. Experimental induction of α-synuclein lesions increased CSF and blood NfL levels, while blocking Aβ lesions attenuated the NfL increase. Consistently, we also found NfL increases in CSF and blood of human α-synucleinopathies, tauopathies, and Alzheimer's disease. Our results suggest that CSF and particularly blood NfL can serve as a reliable and easily accessible biomarker to monitor disease progression and treatment response in mouse models and potentially in human proteopathic neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Instrumentation and quantitative methods of evaluation. Progress report, January 15-September 14, 1986

    International Nuclear Information System (INIS)

    Beck, R.N.

    1986-09-01

    This document reports progress under grant entitled ''Instrumentation and Quantitative Methods of Evaluation.'' Individual reports are presented on projects entitled the physical aspects of radionuclide imaging, image reconstruction and quantitative evaluation, PET-related instrumentation for improved quantitation, improvements in the FMI cyclotron for increased utilization, and methodology for quantitative evaluation of diagnostic performance

  19. Assessment and evaluation of technologies for environmental restoration. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Uzochukwu, G. A. [North Carolina A and T State Univ., Greensboro, NC (United States)

    2000-06-30

    Nuclear and commercial non-nuclear technologies that have the potential of meeting the environmental restoration objectives of the Department of Energy are being evaluated. A detailed comparison of innovative technologies available will be performed to determine the safest and most economical technology for meeting these objectives. Information derived from this effort will be matched with the multi-objective of the environmental restoration effort to ensure that the best, most economical, and the safest technologies are used in decision making at USDOE-SRS. Technology-related variables will be developed and the resulting data formatted and computerized for multimedia systems. The multimedia system will be made available to technology developers and evaluators to ensure that the safest and most economical technologies are developed for use at SRS and other DOE sites.

  20. Assessment and evaluation of technologies for environmental restoration. Progress report

    International Nuclear Information System (INIS)

    Uzochukwu, G. A.

    2000-01-01

    Nuclear and commercial non-nuclear technologies that have the potential of meeting the environmental restoration objectives of the Department of Energy are being evaluated. A detailed comparison of innovative technologies available will be performed to determine the safest and most economical technology for meeting these objectives. Information derived from this effort will be matched with the multi-objective of the environmental restoration effort to ensure that the best, most economical, and the safest technologies are used in decision making at USDOE-SRS. Technology-related variables will be developed and the resulting data formatted and computerized for multimedia systems. The multimedia system will be made available to technology developers and evaluators to ensure that the safest and most economical technologies are developed for use at SRS and other DOE sites.

  1. Assessment and evaluation of technologies for environmental restoration. Progress report

    International Nuclear Information System (INIS)

    Uzochukwu, G.A.

    1999-01-01

    Nuclear and commercial non-nuclear technologies that have the potential of meeting the environmental restoration objectives of the Department of Energy are being evaluated. A detailed comparison of innovative technologies available will be performed to determine the safest and most economical technology for meeting these objectives. Information derived from this effort will be matched with the multi-objective of the environmental restoration effort to ensure that the best, most economical, and the safest technologies are used in decision making at USDOE-SRS. Technology-related variables will be developed and the resulting data formatted and computerized for multimedia systems. The multimedia system will be made available to technology developers and evaluators to ensure that the safest and most economical technologies are developed for use at SRS and other DOE sites

  2. Assessment and evaluation of technologies for environmental restoration. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Uzochukwu, G.A.

    1999-01-15

    Nuclear and commercial non-nuclear technologies that have the potential of meeting the environmental restoration objectives of the Department of Energy are being evaluated. A detailed comparison of innovative technologies available will be performed to determine the safest and most economical technology for meeting these objectives. Information derived from this effort will be matched with the multi-objective of the environmental restoration effort to ensure that the best, most economical, and the safest technologies are used in decision making at USDOE-SRS. Technology-related variables will be developed and the resulting data formatted and computerized for multimedia systems. The multimedia system will be made available to technology developers and evaluators to ensure that the safest and most economical technologies are developed for use at SRS and other DOE sites.

  3. Subjective cognitive concerns and neuropsychiatric predictors of progression to the early clinical stages of Alzheimer disease.

    Science.gov (United States)

    Donovan, Nancy J; Amariglio, Rebecca E; Zoller, Amy S; Rudel, Rebecca K; Gomez-Isla, Teresa; Blacker, Deborah; Hyman, Bradley T; Locascio, Joseph J; Johnson, Keith A; Sperling, Reisa A; Marshall, Gad A; Rentz, Dorene M

    2014-12-01

    To examine neuropsychiatric and neuropsychological predictors of progression from normal to early clinical stages of Alzheimer disease (AD). From a total sample of 559 older adults from the Massachusetts Alzheimer's Disease Research Center longitudinal cohort, 454 were included in the primary analysis: 283 with clinically normal cognition (CN), 115 with mild cognitive impairment (MCI), and 56 with subjective cognitive concerns (SCC) but no objective impairment, a proposed transitional group between CN and MCI. Two latent cognitive factors (memory-semantic, attention-executive) and two neuropsychiatric factors (affective, psychotic) were derived from the Alzheimer's Disease Centers' Uniform Data Set neuropsychological battery and Neuropsychiatric Inventory brief questionnaire. Factors were analyzed as predictors of time to progression to a worse diagnosis using a Cox proportional hazards regression model with backward elimination. Covariates included baseline diagnosis, gender, age, education, prior depression, antidepressant medication, symptom duration, and interaction terms. Higher/better memory-semantic factor score predicted lower hazard of progression (hazard ratio [HR] = 0.4 for 1 standard deviation [SD] increase, p diagnosis as a sole predictor of transition to MCI, the SCC diagnosis carried a fourfold risk of progression compared with CN (HR = 4.1, p <0.0001). These results identify affective and memory-semantic factors as significant predictors of more rapid progression from normal to early stages of cognitive decline and highlight the subgroup of cognitively normal elderly with SCC as those with elevated risk of progression to MCI. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  4. Progress in fusion reactors blanket analysis and evaluation at CEA

    International Nuclear Information System (INIS)

    Proust, E.; Gervaise, F.; Carre, F.; Chevereau, G.; Doutriaux, D.

    1986-09-01

    In the frame of the recent CEA studies aiming at the development, evaluation and comparison of solid breeder blanket concepts in view of their adaptation to NET, the evaluation of specific questions related to the first wall design, the present paper examines first the performances of a helium cooled toroidal blanket design for NET, based on innovative Beryllium/Ceramics breeder rod elements. Neutronic and thermo-mechanical optimisation converges on a concept featured by a breeding capability in excess of 1.2, a reasonnable pumping power of 1% and a narrow breeder temperature range (470+-30 deg C of the breeder), the latter being largely independent of the power level. This design proves naturally adapted to ceramic breeder assigned to very strict working conditions, and provides for any change in the thermal and heat transfer characteristics over the blanket lifetime. The final section of the paper is devoted to the evaluation of the heat load poloidal distribution and to the irradiation effects on first wall structural materials

  5. Organophosphate pesticides and PON1 L55M in Parkinson's disease progression.

    Science.gov (United States)

    Paul, Kimberly C; Sinsheimer, Janet S; Cockburn, Myles; Bronstein, Jeff M; Bordelon, Yvette; Ritz, Beate

    2017-10-01

    Parkinson's disease (PD) has motor and non-motor features that contribute to its phenotype and functional decline. Organophosphate (OP) pesticides and PON1 L55M, which influences OP metabolism, have been implicated in multiple mechanisms related to neuronal cell death and may influence PD symptom progression. To investigate whether ambient agricultural OP exposure and PON1 L55M influence the rate of motor, cognitive, and mood-related symptom progression in PD. We followed a longitudinal cohort of 246 incident PD patients on average over 5years (7.5years after diagnosis), repeatedly measuring symptom progression with the Mini-Mental State Exam (MMSE), Unified Parkinson's Disease Rating Scale (UPDRS), and Geriatric Depressive Scale (GDS). OP exposures were generated with a geographic information system (GIS) based exposure assessment tool. We employed repeated-measures regression to assess associations between OP exposure and/or PON1 L55M genotype and progression. High OP exposures were associated with faster progression of motor (UPDRS β=0.24, 95% CI=-0.01, 0.49) and cognitive scores (MMSE β=-0.06, 95% CI=-0.11, -0.01). PON1 55MM was associated with faster progression of motor (UPDRS β=0.28, 95% CI=0.08, 0.48) and depressive symptoms (GDS β=0.07; 95% CI=0.01, 0.13). We also found the PON1 L55M variant to interact with OP exposures in influencing MMSE cognitive scores (β=-1.26, 95% CI=-2.43, -0.09). Our study provides preliminary support for the involvement of OP pesticides and PON1 in PD-related motor, cognitive, or depressive symptom progression. Future studies are needed to replicate findings and examine whether elderly populations generally are similarly impacted by pesticides or PON1 55M genotypes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. 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.

  7. Prevention of disease progression in Leishmania infantum-infected dogs with dietary nucleotides and active hexose correlated compound.

    Science.gov (United States)

    Segarra, Sergi; Miró, Guadalupe; Montoya, Ana; Pardo-Marín, Luis; Teichenné, Joan; Ferrer, Lluís; Cerón, José Joaquín

    2018-02-21

    The prevalence of Leishmania infantum infection in clinically healthy dogs can be several times higher than that of clinical disease in endemic areas. Although treatment is not recommended in dogs with subclinical infection, these animals should be managed to prevent disease progression and parasite transmission to human beings or to other dogs. Dietary nucleotides and active hexose correlated compound (AHCC) have been shown to modulate the immune response. A recent study in dogs with clinical leishmaniosis receiving an initial 28-day course of methylglucamine antimoniate showed that six-month administration of a dietary supplement containing nucleotides plus AHCC achieves similar efficacy to allopurinol. Since the type of immune response plays a key role in the evolution of patients with leishmaniosis, the present study was aimed at evaluating the preventive effect of this supplement in avoiding or delaying disease progression in clinically healthy Leishmania-infected dogs. Forty-six dogs were included in this multicenter, randomized, double-blind, placebo-controlled trial. Dogs received once-daily oral administration of a placebo or a dietary supplement containing nucleotides plus AHCC. Disease progression was monitored throughout the study in both groups. At 0, 60, 180 and 365 days of treatment, clinical signs were evaluated using a validated clinical scoring system, and several analytes were measured from blood, urine, and bone marrow samples. During the study, a significantly lower (P = 0.047) proportion of dogs changed their clinical status and became sick in the supplement group (3/20; 15%), compared to the placebo group (10/22; 45.5%). ELISA-determined antibody titers were significantly reduced compared to baseline at all time points with the supplement (P < 0.01), but not with the placebo. The mean clinical score of disease severity was significantly lower in the supplement group after 180 days (P = 0.014). No significant differences were

  8. Progress in genetic diagnosis and management of glycogen storage disease typeⅡ

    Directory of Open Access Journals (Sweden)

    Cheng ZHANG

    2014-05-01

    Full Text Available Glycogen storage disease type Ⅱ (GSD Ⅱ is a rare autosomal recessive hereditary metabolic disorder characterized by progressive atrophy and weakness of skeletal muscle. It can be confirmed by clinical history, acid α-glucosidase (GAA testing and GAA mutations. Early targeting treatment and nursing can improve the prognosis and quality of life of patients with GSDⅡ. Progress in genetic diagnosis and management of GSDⅡ will be reviewed in this paper. doi: 10.3969/j.issn.1672-6731.2014.05.005

  9. Disease progression despite protective HLA expression in an HIV-infected transmission pair

    OpenAIRE

    Brener, Jacqui; Gall, Astrid; Batorsky, Rebecca; Riddell, Lynn; Buus, Soren; Leitman, Ellen; Kellam, Paul; Allen, Todd; Goulder, Philip; Matthews, Philippa C

    2015-01-01

    Background The precise immune responses mediated by HLA class I molecules such as HLA-B*27:05 and HLA-B*57:01 that protect against HIV disease progression remain unclear. We studied a CRF01_AE clade HIV infected donor-recipient transmission pair in which the recipient expressed both HLA-B*27:05 and HLA-B*57:01. Results Within 4.5?years of diagnosis, the recipient had progressed to meet criteria for antiretroviral therapy initiation. We employed ultra-deep sequencing of the full-length virus g...

  10. 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

  11. Validating a proxy for disease progression in metastatic cancer patients using prescribing and dispensing data.

    Science.gov (United States)

    Joshi, Vikram; Adelstein, Barbara-Ann; Schaffer, Andrea; Srasuebkul, Preeyaporn; Dobbins, Timothy; Pearson, Sallie-Anne

    2017-10-01

    Routine data collections are used increasingly to examine outcomes of real-world cancer drug use. These datasets lack clinical details about important endpoints such as disease progression. To validate a proxy for disease progression in metastatic cancer patients using prescribing and dispensing claims. We used data from a cohort study of patients undergoing chemotherapy who provided informed consent to the collection of cancer-treatment data from medical records and linkage to pharmaceutical claims. We derived proxy decision rules based on changes to drug treatment in prescription histories (n = 36 patients) and validated the proxy in prescribing data (n = 62 patients). We adapted the decision rules and validated the proxy in dispensing data (n = 109). Our gold standard was disease progression ascertained in patient medical records. Individual progression episodes were the unit of analysis for sensitivity and Positive Predictive Value (PPV) calculations and specificity and Negative Predictive Value (NPV) were calculated at the patient level. The sensitivity of our proxy in prescribing data was 74.3% (95% Confidence Interval (CI), 55.6-86.6%) and PPV 61.2% (95% CI, 45.0-75.3%); specificity and NPV were 87.8% (95% CI, 73.8-95.9%) and 100% (95% CI, 90.3-100%), respectively. In dispensing data, the sensitivity of our proxy was 64% (95% CI, 55.0-77.0%) and PPV 56.0% (95% CI, 43.0-69.0%); specificity and NPV were 81% (95% CI, 70.05-89.0%) and 91.0% (95% CI, 82.0-97.0%), respectively. Our proxy overestimated episodes of disease progression. The proxy's performance is likely to improve if the date of prescribing is used instead of date of dispensing in claims data and by incorporating medical service claims (such as imaging prior to drug changes) in the algorithm. Our proxy is not sufficiently robust for use in real world comparative effectiveness research for cancer medicines. © 2016 John Wiley & Sons Australia, Ltd.

  12. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

    2013-01-01

    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

  13. 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.

  14. Transcranial magnetic stimulation follow-up study in early Parkinson's disease: A decline in compensation with disease progression?

    Science.gov (United States)

    Kojovic, Maja; Kassavetis, Panagiotis; Bologna, Matteo; Pareés, Isabel; Rubio-Agusti, Ignacio; Berardelli, Alfredo; Beraredelli, Alfredo; Edwards, Mark J; Rothwell, John C; Bhatia, Kailash P

    2015-07-01

    A number of neurophysiological abnormalities have been described in patients with Parkinson's disease, but very few longitudinal studies of how these change with disease progression have been reported. We describe measures of motor cortex inhibition and plasticity at 6 and 12 mo in 12 patients that we previously reported at initial diagnosis. Given the well-known interindividual variation in these measures, we were particularly concerned with the within-subject changes over time. Patients were assessed clinically, and transcranial magnetic stimulation (TMS) was used to measure motor cortical excitability, inhibition (short interval intracortical inhibition, cortical silent period), and plasticity (response to excitatory paired associative stimulation protocol) in both hemispheres. All measurements were performed 6 mo and 12 mo after the baseline experiments. Asymmetry in clinical motor symptoms was reflected in asymmetry of plasticity and inhibition. In the group as a whole, little change was seen in any of the parameters over 12 mo. However, analysis of within-individual data showed clear correlations between changes in clinical asymmetry and asymmetry of response to paired associative stimulation protocol and cortical silent period. Longitudinal changes in cortical silent period and response to paired associative stimulation protocol in Parkinson's disease reflect dynamic effects on motor cortex that are related to progression of motor signs. They are useful objective markers of early disease progression that could be used to detect effects of disease-modifying therapies. The decline in heightened plasticity that was present at disease onset may reflect failure of compensatory mechanisms that maintained function in the preclinical state. © 2015 International Parkinson and Movement Disorder Society.

  15. Progression of chronic kidney disease in children with vesicoureteral reflux: the North American Pediatric Renal Trials Collaborative Studies Database.

    Science.gov (United States)

    Novak, Thomas E; Mathews, Ranjiv; Martz, Karen; Neu, Alicia

    2009-10-01

    We describe a cohort of children with chronic kidney disease due to vesicoureteral reflux. We compared the rate of progression to end stage renal disease in those patients to the rate in children with another cause of chronic kidney disease and identified potential risk factors for progression. We performed a retrospective cohort study using data from the North American Pediatric Renal Trials and Collaborative Studies Registry. Patients with vesicoureteral reflux as a cause of chronic kidney disease were compared to 2 other diagnostic cohorts. The 3 groups were compared with respect to baseline characteristics and progression to end stage renal disease based on diagnostic category. Multivariate analysis was performed to identify risk factors for progression to end stage renal disease using Cox proportional hazards regression model. Data on 6,981 patients were available for analysis. Patients with vesicoureteral reflux as a cause of chronic kidney disease had a significantly slower rate of progression to end stage renal disease than patients with renal aplasia, hypoplasia or dysplasia and all other causes (log rank p renal disease in patients with vesicoureteral reflux as the cause of chronic kidney disease we found that, in addition to older age and more advanced chronic kidney disease stage, a history of urinary tract infection at registration was significantly associated with an increased risk of progression. Children with vesicoureteral reflux had a slower rate of progression to end stage renal disease than children with another cause of chronic kidney disease even after controlling for multiple possible confounders. In children with vesicoureteral reflux as the cause of chronic kidney disease older age, higher chronic kidney disease stage and history of urinary tract infection are significantly associated with the risk of progression to end stage renal disease.

  16. Qualitative and quantitative analysis of diffusion-weighted imaging of gestational trophoblastic disease: Can it predict progression of molar pregnancy to persistent form of disease?

    Energy Technology Data Exchange (ETDEWEB)

    Sefidbakht, Sepideh [Medical imaging research center, Department of Radiology and Imaging, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of); Hosseini, Fatemeh, E-mail: f.hoseini88@gmail.com [Medical imaging research center, Department of Radiology and Imaging, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of); Bijan, Bijan [Abdominal Imaging/MR and Nonvascular Interventional Division, University of California, Davis, CA (United States); Hamedi, Bahareh; Azizi, Tayyebeh [Obstetrics& Gynecology Department, Medical School, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)

    2017-03-15

    Highlights: • The incidence of GTD in Iran is significantly higher than America and Europe. • ADC value of GTD is (1.96 ± 0.32 × 10{sup −3} mm{sup 2}/s). • GTD in T1 and T2-weighted images shows heterogeneous “snow-storm” appearance. • Focal intratumoral hemorrhage is bright in DWI and low signal in the ADC map. • ADC value and DWI are not helpful to predict progression of HM to persistent disease. - Abstract: Purpose: To describe the diffusion-weighted imaging (DWI) appearance of gestational trophoblastic disease (GTD) and to determine its apparent diffusion coefficient (ADC) values. To evaluate the feasibility of DWI to predict progression of hydatidiform mole (HM) to persistent disease. Methods: During a period of 6 months, women with preliminary diagnosis of GTD, based on ultrasound and ßhCG levels, underwent 1.5T MRI (T2 high-resolution and DWI; b values 50, 400, 800; sagittal and perpendicular to the endometrium; and T1, T2 Turbo Spin Echo [TSE] axial images). Patients were followed for 6–12 months to monitor progression to persistent form of the disease. ADC values and image characteristics were compared between HM and persistent neoplasia and between GTD and non-molar pregnancy using Mann–Whitney U and Fisher’s exact tests, respectively. Results: Among the 23 studied patients, 19 (83%) were classified as molar and 4 (17%) as non-molar, based on pathology reports. After 6–12 months of follow-up, 5 (26%) cases progressed to persistent disease and 14 (74%) cases were benign HM. There was no significant difference between ADC values for HM (1.93 ± 0.33 × 10{sup −3} mm{sup 2}/s) and persistent neoplasia (2.03 ± 0.28 × 10{sup −3} mm{sup 2}/s) (P = 0.69). The ADC of non-molar pregnancies was (0.96 ± 0.46 × 10{sup −3} mm{sup 2}/s), which was significantly different from GTD (1.96 ± 0.32 × 10{sup −3} mm{sup 2}/s) (P = 0.001). Heterogeneous snowstorm appearance, focal intratumoral hemorrhage, myometrial contraction, and

  17. HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP): A comparative study to identify factors that influence disease progression.

    Science.gov (United States)

    Matsuura, Eiji; Nozuma, Satoshi; Tashiro, Yuichi; Kubota, Ryuji; Izumo, Shuji; Takashima, Hiroshi

    2016-12-15

    HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) can progress slowly or rapidly even though a set of symptoms such as spastic paraparesis with pathological reflexes and sweating loss of the lower extremities are commonly observed in patients. Although most of the patients are thought to be infected to HTLV-1 from their mothers by breast feeding, symptoms of HAM/TSP typically manifest in patients later in life (50-60years old in age) and also with a higher prevalence of women to men at a ratio of approximately 3:1. Probability of developing HAM/TSP and how fast an individual's disease may progress from the time of diagnosis could be multifactorial. We reviewed the records of 150 patients with HAM/TSP admitted to Kagoshima University Hospital between 2002 and 2014. Laboratory data of cerebrospinal fluid and serum and the clinical measurements including age, age of disease onset, progression rate, duration of illness, initial symptoms, Osame's Motor Disability Score were evaluated. Rapid disease progression of the disease was defined by deterioration of motor disability by >3 grades within 2years. Of 150 HAM/TSP patients in our cohort, 114 cases (76%) were females. Patients presenting with rapid disease progression are approximately 15years older at the age of onset than those with a protracted disease course, and have increased number of cell, and elevated levels of protein as well as anti-HTLV-1 antibody titer in the CSF, suggesting a more active inflammatory process. There is no significant difference in the average values of clinical and laboratory parameters between the sexes. Furthermore, there is no apparent correlation between rate of disease progression and gender. Our results suggest that age and virus mediated inflammation are correlated with disease phenotypes while additional factors such as host or HTLV-1 genetics and gender may influence disease susceptibility. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights

  18. 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.

  19. Phenotypic Progression of Stargardt Disease in a Large Consanguineous Tunisian Family Harboring New ABCA4 Mutations

    Directory of Open Access Journals (Sweden)

    Yousra Falfoul

    2018-01-01

    Full Text Available To assess the progression of Stargardt (STGD disease over nine years in two branches of a large consanguineous Tunisian family. Initially, different phenotypes were observed with clinical intra- and interfamilial variations. At presentation, four different retinal phenotypes were observed. In phenotype 1, bull’s eye maculopathy and slight alteration of photopic responses in full-field electroretinography were observed in the youngest child. In phenotype 2, macular atrophy and yellow white were observed in two brothers. In phenotype 3, diffuse macular, peripapillary, and peripheral RPE atrophy and hyperfluorescent dots were observed in two sisters. In phenotype 4, Stargardt disease-fundus flavimaculatus phenotype was observed in two cousins with later age of onset. After a progression of 9 years, all seven patients displayed the same phenotype 3 with advanced stage STGD and diffuse atrophy. WES and MLPA identified two ABCA4 mutations M1: c.[(?_4635_(5714+?dup; (?_6148_(6479_+? del] and M2: c.[2041C>T], p.[R681∗]. In one branch, the three affected patients had M1/M1 causal mutations and in the other branch the two affected patients had M1/M2 causal mutations. After 9-year follow-up, all patients showed the same phenotypic evolution, confirming the progressive nature of the disease. Genetic variations in the two branches made no difference to similar end-stage disease.

  20. Markers of inflammation and endothelial dysfunction are associated with incident cardiovascular disease, all-cause mortality, and progression of coronary calcification in type 2 diabetic patients with microalbuminuria

    DEFF Research Database (Denmark)

    von Scholten, Bernt Johan; Reinhard, Henrik; Hansen, Tine Willum

    2016-01-01

    BACKGROUND: We evaluated markers of inflammation and endothelial dysfunction and their associations with incident cardiovascular disease (CVD), all-cause mortality and progression of coronary artery calcium (CAC) in patients with type 2 diabetes (T2D) and microalbuminuria but without known corona...

  1. Salvage therapy of progressive and recurrent Hodgkin's disease: results from a multicenter study of the pediatric DAL/GPOH-HD study group.

    NARCIS (Netherlands)

    Schellong, G.; Dorffel, W.; Claviez, A.; Korholz, D.; Mann, G.; Scheel-Walter, H.G.; Bökkerink, J.P.M.; Riepenhausen, M.; Luders, H.; Potter, R.; Ruhl, U.

    2005-01-01

    PURPOSE: To evaluate a salvage therapy (ST-HD-86) for patients with progressive and relapsed Hodgkin's disease after primary treatment in the pediatric DAL/GPOH studies. The essential chemotherapeutic regimens were ifosfamide, etoposide, and prednisone (IEP) and doxorubicin, bleomycin, vinblastine,

  2. C-Reactive Protein Predicts Progression of Peripheral Arterial Disease in Patients with Type 2 Diabetes: A 5-Year Follow-Up Study

    Directory of Open Access Journals (Sweden)

    Popović Ljiljana

    2014-09-01

    Full Text Available Background: Previous studies have indicated that high sensitivity C-reactive protein (hs-CRP is a risk factor for the peripheral arterial disease (PAD in diabetes. This study aimed to evaluate the possible predictive significance of hs-CRP for the development and progression of PAD in patients with type 2 diabetes (T2D.

  3. Idaho Steelhead Monitoring and Evaluation Studies : Annual Progress Report 2007.

    Energy Technology Data Exchange (ETDEWEB)

    Copeland, Timothy; Putnam, Scott

    2008-12-01

    The goal of Idaho Steelhead Monitoring and Evaluation Studies is to collect monitoring data to evaluate wild and natural steelhead populations in the Clearwater and Salmon river drainages. During 2007, intensive population data were collected in Fish Creek (Lochsa River tributary) and Rapid River (Little Salmon River tributary); extensive data were collected in other selected spawning tributaries. Weirs were operated in Fish Creek and Rapid River to estimate adult escapement and to collect samples for age determination and genetic analysis. Snorkel surveys were conducted in Fish Creek, Rapid River, and Boulder Creek (Little Salmon River tributary) to estimate parr density. Screw traps were operated in Fish Creek, Rapid River, Secesh River, and Big Creek to estimate juvenile emigrant abundance, to tag fish for survival estimation, and to collect samples for age determination and genetic analysis. The estimated wild adult steelhead escapement in Fish Creek was 81 fish and in Rapid River was 32 fish. We estimate that juvenile emigration was 24,127 fish from Fish Creek; 5,632 fish from Rapid River; and 43,674 fish from Big Creek. The Secesh trap was pulled for an extended period due to wildfires, so we did not estimate emigrant abundance for that location. In cooperation with Idaho Supplementation Studies, trap tenders PIT tagged 25,618 steelhead juveniles at 18 screw trap sites in the Clearwater and Salmon river drainages. To estimate age composition, 143 adult steelhead and 5,082 juvenile steelhead scale samples were collected. At the time of this report, 114 adult and 1,642 juvenile samples have been aged. Project personnel collected genetic samples from 122 adults and 839 juveniles. We sent 678 genetic samples to the IDFG Eagle Fish Genetics Laboratory for analysis. Water temperature was recorded at 37 locations in the Clearwater and Salmon river drainages.

  4. A Low Geriatric Nutrition Risk Index Is Associated with Progression to Dialysis in Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    I-Ching Kuo

    2017-11-01

    Full Text Available Evaluating nutritional status is crucial to detecting malnutrition in patients with chronic kidney disease (CKD. The Geriatric Nutritional Risk Index (GNRI has been associated with overall and cardiovascular mortality in the dialysis population. The aim of this study was to evaluate whether the GNRI is associated with progression to dialysis in patients with moderate to advanced CKD. We enrolled 496 patients with stage 3–5 CKD who had received echocardiographic examinations, and categorized them according to baseline GNRI values calculated using the serum albumin level and body weight. The renal end-point was defined as the commencement of dialysis. During follow-up (mean, 25.2 ± 12.5 months; range, 3.3–50.1 months, 106 (21.4% of the patients progressed to dialysis. The GNRI was positively correlated with the left ventricular ejection fraction (LVEF (r = 0.111, p = 0.014, and negatively correlated with the left ventricular mass index (r = −0.116, p = 0.001, left ventricular hypertrophy (r = −0.095, p = 0.035, and LVEF < 50% (r = −0.138, p = 0.002. In multivariable Cox analysis, a low GNRI, female sex, high systolic blood pressure, high fasting glucose, and low estimated glomerular filtration rate were independently associated with progression to dialysis. A low GNRI was independently associated with progression to dialysis in our study cohort. The GNRI may be useful in predicting the risk of adverse renal outcomes in patients with CKD stages 3–5. Additional studies are needed to explore whether an improvement in GNRI delays CKD progression.

  5. 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.

  6. Urate as a Marker of Risk and Progression of Neurodegenerative Disease.

    Science.gov (United States)

    Paganoni, Sabrina; Schwarzschild, Michael A

    2017-01-01

    Urate is a naturally occurring antioxidant whose levels are associated with reduced risk of developing Parkinson's disease (PD) and Alzheimer's disease. Urate levels are also associated with favorable progression in PD, amyotrophic lateral sclerosis, Huntington's disease, and multisystem atrophy. These epidemiological data are consistent with laboratory studies showing that urate exhibits neuroprotective effects by virtue of its antioxidant properties in several preclinical models. This body of evidence supports the hypothesis that urate may represent a shared pathophysiologic mechanism across neurodegenerative diseases. Most importantly, beyond its role as a molecular predictor of disease risk and progression, urate may constitute a novel therapeutic target. Indeed, clinical trials of urate elevation in PD and amyotrophic lateral sclerosis are testing the impact of raising peripheral urate levels on disease outcomes. These studies will contribute to unraveling the neuroprotective potential of urate in human pathology. In parallel, preclinical experiments are deepening our understanding of the molecular pathways that underpin urate's activities. Altogether, these efforts will bring about new insights into the translational potential of urate, its determinants, and its targets and their relevance to neurodegeneration.

  7. Conduction system disease in fetuses evaluated for irregular cardiac rhythm.

    Science.gov (United States)

    Cuneo, Bettina F; Strasburger, Janette F; Wakai, Ronald T; Ovadia, Marc

    2006-01-01

    To determine the prevalence of 1st and 2nd degree AV block in fetuses with an irregular cardiac rhythm, and to summarize outcome of these pregnancies. The diagnosis of irregular cardiac rhythm or 'skipped beats' includes isolated ectopy that resolves spontaneously. Recently, Doppler measurements of the 'mechanical' PR interval have been shown to identify AV conduction disease prenatally. Prenatal therapy of these conduction abnormalities may limit the progression to more advanced disease either in utero or after birth. A retrospective review was performed of fetuses evaluated between 1996 and 2004 with the findings of irregular cardiac rhythm. 1st or 2nd degree AV block was diagnosed on Doppler and M-mode recordings, and confirmed using either fetal magnetocardiography (fMCG) or postnatal 12-lead ECG. Dexamethasone was administered to 4 mothers with abnormal fetal AV conduction in the setting of anti-Ro/anti-La antibodies. Of 702 fetuses initially referred for arrhythmia, 306 had an irregular rhythm. Eight (2.6%) had intermittent 1st or 2nd degree AV block confirmed by fMCG and/or postnatal 12-lead ECG. AV block was presumed idiopathic in 2, associated with congenital long QT syndrome in 2 or with clinically unsuspected maternal anti-Ro or anti-La antibodies in 4. During the intrauterine period there was no progression to complete AV block and all were born alive at 34-40 weeks of gestation. A small but clinically significant population of fetuses with irregular rhythm will have 1st or 2nd degree AV block. Transplacental therapy may limit the intrauterine progression to more advanced disease. Copyright 2006 S. Karger AG, Basel.

  8. Analysis of the value of post-radiation prostate biopsy in predicting subsequent disease progression

    International Nuclear Information System (INIS)

    Benda, R.; Shamsa, F.; Meetze, K.; Bolton, S.; Littrup, P.; Grignon, D.; Washington, T.; Forman, J.D.

    1997-01-01

    -RT PSA ( 1.5ng/ml at the time of biopsy had a 53% failure rate vs. 21% for patients with a PSA ≤1.5 (p<0.05, κ=.3). Patients with a positive biopsy had a 53% failure rate compared to 17% if biopsy was negative (p<0.05, κ=0.378). There was no significant difference between patients with a negative biopsy or a biopsy with a marked therapeutic effect (p=0.13). Conclusions: Post RT, TRUS and CFD are inaccurate in reliably identifying residual disease. The serum PSA at this time of biopsy was twice as good at predicting a positive biopsy. Since the serum PSA is as accurate in predicting subsequent disease progression, the use of post RT biopsies should be limited to protocol situations evaluating local control or for patients being considered for a salvage local treatment

  9. TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity

    DEFF Research Database (Denmark)

    Molnar, Christoph; Scherer, Almut; Baraliakos, Xenofon

    2018-01-01

    OBJECTIVES: To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS). METHODS: Patients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years...... were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial...... generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis. RESULTS: A total...

  10. 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

  11. 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.

  12. 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.

  13. Quantitative Evaluation of Heavy Duty Machine Tools Remanufacturing Based on Modified Catastrophe Progression Method

    Science.gov (United States)

    shunhe, Li; jianhua, Rao; lin, Gui; weimin, Zhang; degang, Liu

    2017-11-01

    The result of remanufacturing evaluation is the basis for judging whether the heavy duty machine tool can remanufacture in the EOL stage of the machine tool lifecycle management.The objectivity and accuracy of evaluation is the key to the evaluation method.In this paper, the catastrophe progression method is introduced into the quantitative evaluation of heavy duty machine tools’ remanufacturing,and the results are modified by the comprehensive adjustment method,which makes the evaluation results accord with the standard of human conventional thinking.Using the catastrophe progression method to establish the heavy duty machine tools’ quantitative evaluation model,to evaluate the retired TK6916 type CNC floor milling-boring machine’s remanufacturing.The evaluation process is simple,high quantification,the result is objective.

  14. A systematic review of the effect of moderate intensity exercise on function and disease progression in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Lui, Andrew J; Byl, Nancy N

    2009-06-01

    Amyotrophic lateral sclerosis (ALS) is an idiopathic disease of adults affecting upper and lower motor neurons. In one to four years, progressive weakness, spasticity, and respiratory insufficiency compromise independence and survival. Current medical treatment is limited to medication and supportive care. The benefit and harm of moderate physical exercise are controversial. This review examined current research related to moderate exercise for maintaining independence without accelerating disease progression in persons with ALS. An evidence-based search was conducted using keywords alone and in combination (ALS, exercise, Lou Gehrig's disease, physical therapy) to search PubMed, PEDro, Hooked on Evidence, Ovid, and Cochrane databases. Human and animal models were included and graded on level of evidence and strength of recommendations for developing guidelines to practice. A secondary reviewer evaluated all selected studies, and statistics were calculated. The search yielded the following nine studies: four small clinical studies, one clinical systematic review, and four randomized, controlled trials based on animal models. In human studies, there were small to moderate effect sizes supporting the benefit of moderate exercise in persons with early-stage ALS, with no adverse affects on disease progression or survival time. In transgenic mice with superoxide dismutase-1 ALS, moderate exercise most often had a moderate effect size for increasing life span. Large randomized clinical trials are needed to develop specific exercise guidelines. However, evidence suggests that moderate exercise is not associated with adverse outcomes in persons with early-stage ALS. Moderate exercise programs can be safely adapted to abilities, interests, specific response to exercise, accessibility, and family support.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease

    DEFF Research Database (Denmark)

    Jafar, Tazeen H; Stark, Paul C; Schmid, Christopher H

    2005-01-01

    BACKGROUND: It is not known whether angiotensin-converting-enzyme (ACE) inhibitors slow the progression of polycystic kidney disease (PKD). We performed a patient-level meta-analysis to compare the effect of antihypertensive regimens, including ACE inhibitors, to those without ACE inhibitors...... of doubling of baseline serum creatinine or onset of kidney failure). We also performed multivariable linear regression and Cox proportional hazards analyses. Based on previous findings, we searched for interactions between the treatment effect (effect of ACE inhibitors vs. controls) and baseline urine......%) in the ACE inhibitor group and 30 patients (41%) in the control group (P= 0.17). ACE inhibitors had a greater effect on lowering urine protein excretion and slowing kidney disease progression in patients with higher levels of baseline urine protein excretion (interaction P

  20. 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

    from each full EDSS with explanatory variables age, sex, age at onset, time in current EDSS, highest prior EDSS, MS course and treatment. All factors (except sex) investigated had statistically significant impacts on transitions from at least one EDSS. However, significance and size of the effect...... are dependent on the EDSS state of the patient. Greater age, longer time in a state, highest prior EDSS, having progressive MS and treatment had significant impacts, whereas age at onset had minor impact. Our study confirms that established factors associated with MS disease worsening in time to disease...... milestones also have impacts on annual progression. This approach adds granularity to what EDSS these factors have an influence....

  1. 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.

  2. CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP.

    Science.gov (United States)

    Rojas, Julio C; Bang, Jee; Lobach, Iryna V; Tsai, Richard M; Rabinovici, Gil D; Miller, Bruce L; Boxer, Adam L

    2018-01-23

    To determine the ability of CSF biomarkers to predict disease progression in progressive supranuclear palsy (PSP). We compared the ability of baseline CSF β-amyloid 1-42 , tau, phosphorylated tau 181 (p-tau), and neurofilament light chain (NfL) concentrations, measured by INNO-BIA AlzBio3 or ELISA, to predict 52-week changes in clinical (PSP Rating Scale [PSPRS] and Schwab and England Activities of Daily Living [SEADL]), neuropsychological, and regional brain volumes on MRI using linear mixed effects models controlled for age, sex, and baseline disease severity, and Fisher F density curves to compare effect sizes in 50 patients with PSP. Similar analyses were done using plasma NfL measured by single molecule arrays in 141 patients. Higher CSF NfL concentration predicted more rapid decline (biomarker × time interaction) over 52 weeks in PSPRS ( p = 0.004, false discovery rate-corrected) and SEADL ( p = 0.008), whereas lower baseline CSF p-tau predicted faster decline on PSPRS ( p = 0.004). Higher CSF tau concentrations predicted faster decline by SEADL ( p = 0.004). The CSF NfL/p-tau ratio was superior for predicting change in PSPRS, compared to p-tau ( p = 0.003) or NfL ( p = 0.001) alone. Higher NfL concentrations in CSF or blood were associated with greater superior cerebellar peduncle atrophy (fixed effect, p ≤ 0.029 and 0.008, respectively). Both CSF p-tau and NfL correlate with disease severity and rate of disease progression in PSP. The inverse correlation of p-tau with disease severity suggests a potentially different mechanism of tau pathology in PSP as compared to Alzheimer disease. Copyright © 2017 American Academy of Neurology.

  3. Plasma concentrations of transforming growth factor beta 1 in non-progressive HIV-1 infection correlates with markers of disease progression.

    Science.gov (United States)

    Maina, Edward K; Abana, C Z; Bukusi, E A; Sedegah, M; Lartey, M; Ampofo, W K

    2016-05-01

    The human immunodeficiency virus (HIV) infection shows variable rate of disease progression. The underlying biological and molecular mechanisms involved in determining progression of HIV infection are not fully understood. The aims of this study were to determine plasma concentrations of active TGF β 1, Th1 and Th2 cytokines in patients with non-progressive and those with progressive HIV-1 infection, as well as to determine if there is an association of these cytokines to disease progression. In a cross-sectional study of 61 HIV-1 infected individuals categorized according to disease progression as having non-progressive HIV-1 infection (n=14) and progressive infection (n=47), plasma levels of active TGF β 1, INF-γ, TNF-α, IL-10, IL-1β, IL-12p70 and IL-13 were compared with HIV uninfected healthy controls (n=12). Plasma concentration of these cytokines was measured using a highly sensitive luminex200 XMAP assay. Pearson correlation test was used to assess the correlation of cytokines with CD4+ and CD8+ T cells, CD4:CD8 ratio and plasma HIV-1 RNA in the different study groups. Plasma concentrations of TGF β 1 and IL-10 were significantly decreased while IL-1β, IL-12p70 and TNF-α were increased in patients with non-progressive HIV-1 infection compared to patients with progressive infection. Plasma levels of TGF β 1 and IL-10 showed an inverse correlation with CD8+ T cell counts and CD4:CD8 ratios in patients with non-progressive HIV-1 infection, while plasma HIV-1 RNA positively correlated with CD4+ T cell counts. Plasma levels of TNF-α, IL-1β, IL-12p70 and IL-13 positively correlated with CD4+ T cell counts and inversely correlated with plasma HIV-1 RNA, CD8+ T cell count and CD4:CD8 ratio in patients with non-progressive infection. The correlation of cytokines to the state of T-lymphocyte and plasma HIV-1 RNA found in this study may provide insight into the role of cytokines in both progressive and non-progressive HIV-1 infection. Additionally, these

  4. Failed Tubule Recovery, AKI-CKD Transition, and Kidney Disease Progression

    Science.gov (United States)

    Weinberg, Joel M.; Kriz, Wilhelm; Bidani, Anil K.

    2015-01-01

    The transition of AKI to CKD has major clinical significance. As reviewed here, recent studies show that a subpopulation of dedifferentiated, proliferating tubules recovering from AKI undergo pathologic growth arrest, fail to redifferentiate, and become atrophic. These abnormal tubules exhibit persistent, unregulated, and progressively increasing profibrotic signaling along multiple pathways. Paracrine products derived therefrom perturb normal interactions between peritubular capillary endothelium and pericyte-like fibroblasts, leading to myofibroblast transformation, proliferation, and fibrosis as well as capillary disintegration and rarefaction. Although signals from injured endothelium and inflammatory/immune cells also contribute, tubule injury alone is sufficient to produce the interstitial pathology required for fibrosis. Localized hypoxia produced by microvascular pathology may also prevent tubule recovery. However, fibrosis is not intrinsically progressive, and microvascular pathology develops strictly around damaged tubules; thus, additional deterioration of kidney structure after the transition of AKI to CKD requires new acute injury or other mechanisms of progression. Indeed, experiments using an acute-on-chronic injury model suggest that additional loss of parenchyma caused by failed repair of AKI in kidneys with prior renal mass reduction triggers hemodynamically mediated processes that damage glomeruli to cause progression. Continued investigation of these pathologic mechanisms should reveal options for preventing renal disease progression after AKI. PMID:25810494

  5. Variants in GBA, SNCA, and MAPT Influence Parkinson Disease Risk, Age at Onset, and Progression

    Science.gov (United States)

    Davis, Albert A.; Andruska, Kristin M.; Benitez, Bruno A.; Racette, Brad A.; Perlmutter, Joel S.; Cruchaga, Carlos

    2015-01-01

    Multiple genetic variants have been linked to risk of Parkinson disease (PD), but known mutations do not explain a large proportion of the total PD cases. Similarly, multiple loci have been associated with PD risk by Genome-Wide Association Studies (GWAS). The influence that genetic factors confer upon phenotypic diversity remains unclear. Few studies have been performed to determine whether the GWAS loci are also associated with age at onset (AAO) or motor progression. We used two PD case-control datasets (Washington University and the Parkinson’s Progression Markers Initiative) to determine whether polymorphisms located at the GWAS top hits (GBA, ACMSD/TMEM163, STK39, MCCC1/LAMP3, GAK/TMEM175, SNCA, and MAPT) show association with AAO or motor progression. We found associations between SNPs at the GBA and MAPT loci and PD AAO and progression. These findings reinforce the complex genetic basis of PD and suggest that distinct genes and variants explain the genetic architecture of PD risk, onset, and progression. PMID:26601739

  6. Klinefelter′s syndrome associated with progressive muscular atrophy simulating Kennedy′s disease

    OpenAIRE

    Pedro Enrique Jiménez Caballero

    2012-01-01

    Kennedy′s disease, an X-linked spinal and bulbar muscular atrophy, is characterized by loss of lower motor neurons. Mild sensory deficits, gynecomastia and infertility may be observed. Klinefelter′s syndrome is a variation of sex chromosome disorder characterized by hypogonadism, gynecomastia and azoospermia, and the most frequent karyotype is XXY. A 55-year-old man who presented with slowly progressive and diffuse neurogenic muscle atrophy without bulbar or sensory symptoms. He also had Klin...

  7. HIV disease progression by hormonal contraceptive method: secondary analysis of a randomized trial.

    Science.gov (United States)

    Stringer, Elizabeth M; Levy, Jens; Sinkala, Moses; Chi, Benjamin H; Matongo, Inutu; Chintu, Namwinga; Stringer, Jeffrey S A

    2009-07-17

    HIV-infected women need access to safe contraception. We hypothesized that women using depomedroxyprogesterone acetate (DMPA) contraception would have faster HIV disease progression than women using oral contraceptive pills (OCPs) and nonhormonal methods. In a previously reported trial, we randomized 599 HIV-infected women to the intrauterine device (IUD) or hormonal contraception. Women randomized to hormonal contraception chose between OCPs and DMPA. This analysis investigates the relationship between exposure to hormonal contraception and HIV disease progression [defined as death, becoming eligible for antiretroviral therapy (ART), or both]. Of the 595 women not on ART at the time of randomization, 302 were allocated to hormonal contraception, of whom 190 (63%) initiated DMPA and 112 (37%) initiated OCPs. Women starting IUD, OCPs, or DMPA were similar at baseline. Compared with women using the IUD, the adjusted hazard of death was not significantly increased among women using OCPs [1.24; 95% confidence interval (CI) 0.42-3.63] or DMPA (1.83; 95% CI 0.82-4.08). However, women using OCPs (adjusted hazard ratio (AHR) 1.69; 95% CI 1.09-2.64) or DMPA (AHR 1.56; 95% CI 1.08-2.26) trended toward an increased likelihood of becoming eligible for ART. Women exposed to OCPs (AHR 1.67; 95% CI 1.10-2.51) and DMPA (AHR 1.62; 95% CI 1.16-2.28) also had an increased hazard of meeting our composite disease progression outcome (death or becoming ART eligible) than women using the IUD. In this secondary analysis, exposure to OCPs or DMPA was associated with HIV disease progression among women not yet on ART. This finding, if confirmed elsewhere, would have global implications and requires urgent further investigation.

  8. Retarding chronic kidney disease (CKD) progression : a practical nutritional approach for non-dialysis CKD

    OpenAIRE

    Bellizzi, V.; Carrero, J..J.; Chauveau, P.; Cozzolino, M.; Cupisti, A.; D'Alessandro, C.; De Nicola, L.; Fiaccadori, E.; Johansson, L.; Minutolo, R.; Molina, P.; Sezer, S.; Ter Wee, P.; Teta, D.; Wanner, C.

    2016-01-01

    This is a case report on a patient with non-dialysis chronic kidney disease (CKD) in whom several nutritional issues are briefly discussed from a practical point of view. The article is accompanied by an editorial published in this Journal in relation to the 2nd International Conference of the European Renal Nutrition working group at ERA-EDTA—“Retarding CKD progression: readily available through comprehensive nutritional management?”—and focuses on several practical topics associated with th...

  9. Minimal Residual Disease in Acute Myeloid Leukemia: Still a Work in Progress?

    Directory of Open Access Journals (Sweden)

    Federico Mosna

    2017-06-01

    Full Text Available Minimal residual disease evaluation refers to a series of molecular and immunophenotypical techniques aimed at detecting submicroscopic disease after therapy. As such, its application in acute myeloid leukemia has greatly increased our ability to quantify treatment response, and to determine the chemosensitivity of the disease, as the final product of the drug schedule, dose intensity, biodistribution, and the pharmakogenetic profile of the patient. There is now consistent evidence for the prognostic power of minimal residual disease evaluation in acute myeloid leukemia, which is complementary to the baseline prognostic assessment of the disease. The focus for its use is therefore shifting to individualize treatment based on a deeper evaluation of chemosensitivity and residual tumor burden. In this review, we will summarize the results of the major clinical studies evaluating minimal residual disease in acute myeloid leukemia in adults in recent years and address the technical and practical issues still hampering the spread of these techniques outside controlled clinical trials. We will also briefly speculate on future developments and offer our point of view, and a word of caution, on the present use of minimal residual disease measurements in “real-life” practice. Still, as final standardization and diffusion of the methods are sorted out, we believe that minimal residual disease will soon become the new standard for evaluating response in the treatment of acute myeloid leukemia.

  10. Research progress of rehabilitation therapy in Parkinson's disease and its mechanism

    Directory of Open Access Journals (Sweden)

    Jin LIU

    2017-07-01

    Full Text Available Parkinson's disease (PD is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta. Rehabilitation therapy can delay the development of disease, improve motor symptoms and non - motor symptoms (NMS, and consequently improve the activities of daily living (ADL in patients with PD. The mechanism of rehabilitation improving the symptoms of PD is very complex, involving a variety of molecular mechanisms. Thus, this review will focus on the effect of rehabilitation therapy on PD and the underlying molecular mechanism including neurotransmitters, trophic factors, synaptic plasticity and immune system. DOI: 10.3969/j.issn.1672-6731.2017.06.003

  11. Markers, Cofactors and Staging Systems in the Study of HIV Disease Progression: A Review

    Directory of Open Access Journals (Sweden)

    MC Portela

    1997-07-01

    Full Text Available This paper is aimed at providing a comprehensive review of markers, cofactors and staging systems used for HIV disease, focusing on some aspects that nowadays could even be considered historical, and advancing in current issues such as the prognostic value of viral load measurements, viral genotypic and phenotypic characterization, and new HIV disease treatment protocols. CD4+ cell values, combined with the new viral markers mentioned are promising as a parsimonious predictor set for defining both severity and progression. An adequate predictor of patient resource use for planning purposes still needs to be defined

  12. [Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].

    Science.gov (United States)

    Zhu, Ling; Cao, Cong; Sun, Jiji; Gao, Tao; Liang, Xiaoyang; Nie, Zhipeng; Ji, Yanchun; Jiang, Pingping; Guan, Minxin

    2017-02-10

    Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.

  13. Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia

    Science.gov (United States)

    Jabbour, Elias J.; Hughes, Timothy P.; Cortés, Jorge E.; Kantarjian, Hagop M.; Hochhaus, Andreas

    2014-01-01

    Despite vast improvements in treatment of Philadelphia chromosome–positive chronic myeloid leukemia (CML) in chronic phase (CP), advanced stages of CML, accelerated phase or blast crisis, remain notoriously difficult to treat. Treatments that are highly effective against CML-CP produce disappointing results against advanced disease. Therefore, a primary goal of therapy should be to maintain patients in CP for as long as possible, by (1) striving for deep, early molecular response to treatment; (2) using tyrosine kinase inhibitors that lower risk of disease progression; and (3) more closely observing patients who demonstrate cytogenetic risk factors at diagnosis or during treatment. PMID:24050507

  14. 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.

  15. PLOS Neglected Tropical Diseases: Ten years of progress in neglected tropical disease control and elimination … More or less.

    Directory of Open Access Journals (Sweden)

    Peter Hotez

    2017-04-01

    Full Text Available This year PLOS Neglected Tropical Diseases (PLOS NTDs celebrates its tenth anniversary following the publication of the first issue in 2007 [1]. When PLOS NTDs was founded, the framework of the neglected tropical diseases (NTDs as an alternative to "other diseases" (as they were then referred to in the Millennium Development Goals was just getting started-especially for Africa [2, 3]. In the decade since, PLOS NTDs has overseen enormous successes in NTD control and elimination. Here, we want to briefly review the ten year progress made towards the control or elimination of the diseases now identified by the WHO as NTDs. Many of the details are highlighted in PLOS NTDs papers cited here, but the summary information is based on the recently released Global Burden of Disease (GBD Study 2015 (also launched with Gates Foundation support that summarized past-decade changes in disease prevalence, mortality, or disability rates (from the years 2005 to 2015 [4-6], as well as the GBD Study 2013 that summarizes disease prevalence changes over a longer time horizon from 1990 to 2013 [7].

  16. Progressive atlanto-axial subluxation in Behcet's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang-hyuk [Chonbuk National University Hospital, Department of Neurosurgery, Jeonju City, Jeonbuk (Korea); Eoh, Whan [Sungkyunkwan University School of Medicine, Samsung Medical Center, Department of Neurosurgery, Seoul (Korea)

    2010-03-15

    Behcet's disease is a chronic inflammatory condition involving several organs, such as the skin, mucous membranes, eyes, joints, intestines, lungs and central nervous system. It rarely affects the spinal column. We describe a case of progressive atlanto-axial subluxation in a 44-year-old woman with Behcet's disease. The patient started complaining of posterior neck pain 10 years after the diagnosis of her Behcet's disease. Initial radiographs showed no abnormal finding, but follow-up radiographs 6 month later demonstrated atlanto-axial subluxation. To the best of our knowledge, this is the second reported case in the worldwide literature of an atlanto-axial instability in a patient with Behcet's disease. (orig.)

  17. Lipidomic analysis of epidermal lipids: a tool to predict progression of inflammatory skin disease in humans.

    Science.gov (United States)

    Li, Shan; Ganguli-Indra, Gitali; Indra, Arup K

    2016-05-01

    Lipidomics is the large-scale profiling and characterization of lipid species in a biological system using mass spectrometry. The skin barrier is mainly comprised of corneocytes and a lipid-enriched extracellular matrix. The major skin lipids are ceramides, cholesterol and free fatty acids (FFA). Lipid compositions are altered in inflammatory skin disorders with disrupted skin barrier such as atopic dermatitis (AD). Here we discuss some of the recent applications of lipidomics in human skin biology and in inflammatory skin diseases such as AD, psoriasis and Netherton syndrome. We also review applications of lipidomics in human skin equivalent and in pre-clinical animal models of skin diseases to gain insight into the pathogenesis of the skin disease. Expert commentary: Skin lipidomics analysis could be a fast, reliable and noninvasive tool to characterize the skin lipid profile and to monitor the progression of inflammatory skin diseases such as AD.

  18. Cognitive decline tracks motor progression and not disease duration in Parkinson patients

    Directory of Open Access Journals (Sweden)

    BD Riggeal

    2007-01-01

    Full Text Available BD Riggeal1, GP Crucian1, P Seignourel2, CE Jacobson IV1, MS Okun1, RL Rodriguez1, Hubert H Fernandez11Department of Neurology; 2Department of Community Health and Psychology, University of Florida, Gainesville, FL, USAAbstract: We performed an analysis of prospectively-acquired cross sectional data on 106 Parkinson disease (PD patients who underwent comprehensive neuropsychological testing and the Unified Parkinson Disease Rating Scale (UPDRS motor scale. A significant correlation between the UPDRS motor and neuropsychological tests in all cognitive domains except for general intelligence and visuo-spatial function was seen. In this study, cognitive decline within this PD cohort correlated with motor impairment but not disease duration. Our findings suggest that overall cognitive impairment (except visuospatial dysfunction may track motor progression in PD more than duration of disease. Longitudinal studies are needed to confirm our results.Keywords: Parkinson, dementia, cognition, visual-spatial dysfunction

  19. Real-time progressive hyperspectral remote sensing detection methods for crop pest and diseases

    Science.gov (United States)

    Wu, Taixia; Zhang, Lifu; Peng, Bo; Zhang, Hongming; Chen, Zhengfu; Gao, Min

    2016-05-01

    Crop pests and diseases is one of major agricultural disasters, which have caused heavy losses in agricultural production each year. Hyperspectral remote sensing technology is one of the most advanced and effective method for monitoring crop pests and diseases. However, Hyperspectral facing serial problems such as low degree of automation of data processing and poor timeliness of information extraction. It resulting we cannot respond quickly to crop pests and diseases in a critical period, and missed the best time for quantitative spraying control on a fixed point. In this study, we take the crop pests and diseases as research point and breakthrough, using a self-development line scanning VNIR field imaging spectrometer. Take the advantage of the progressive obtain image characteristics of the push-broom hyperspectral remote sensor, a synchronous real-time progressive hyperspectral algorithms and models will development. Namely, the object's information will get row by row just after the data obtained. It will greatly improve operating time and efficiency under the same detection accuracy. This may solve the poor timeliness problem when we using hyperspectral remote sensing for crop pests and diseases detection. Furthermore, this method will provide a common way for time-sensitive industrial applications, such as environment, disaster. It may providing methods and technical reserves for the development of real-time detection satellite technology.

  20. The effects of electroshock on immune function and disease progression in juvenile spring chinook salmon

    Science.gov (United States)

    VanderKooi, S.P.; Maule, A.G.; Schreck, C.B.

    2001-01-01

    Although much is known about the effects of electroshock on fish physiology, consequences to the immune system and disease progression have not received attention. Our objectives were to determine the effects of electroshock on selected immune function in juvenile spring chinook salmon Oncorhynchus tshawytscha, the mechanism of any observed alteration, and the effects of electroshock on disease progression. We found that the ability of anterior kidney leukocytes to generate antibody-producing cells (APC) was suppressed 3 h after a pulsed-DC electroshock (300 V, 50 Hz, 8 ms pulse width) but recovered within 24 h. This response was similar in timing and magnitude to that of fish subjected to an acute handling stress. The mechanism of suppression is hypothesized to be via an elevation of plasma cortisol concentrations in response to stress. Other monitored immune functions, skin mucous lysozyme levels, and respiratory burst activity were not affected by exposure to electroshock. The progression of a Renibacterium salmoninarum (RS) infection may have been altered after exposure to an electroshock. The electroshock did not affect infection severity or the number of mortalities, but may have accelerated the time to death. The limited duration of APC suppression and lack of effects on lysozyme and respiratory burst, as well as infection severity and mortality levels in RS-infected fish, led us to conclude that electrofishing under the conditions we tested is a safe procedure in regards to immunity and disease.

  1. Metabolomics insights into activated redox signaling and lipid metabolism dysfunction in chronic kidney disease progression

    Directory of Open Access Journals (Sweden)

    Hua Chen

    2016-12-01

    Full Text Available Early detection is critical in prevention and treatment of kidney disease. However currently clinical laboratory and histopathological tests do not provide region-specific and accurate biomarkers for early detection of kidney disease. The present study was conducted to identify sensitive biomarkers for early detection and progression of tubulo-interstitial nephropathy in aristolochic acid I-induced rats at weeks 4, 8 and 12. Biomarkers were validated using aristolochic acid nephropathy (AAN rats at week 24, adenine-induced chronic kidney disease (CKD rats and CKD patients. Compared with control rats, AAN rats showed anemia, increased serum urea and creatinine, progressive renal interstitial fibrosis, activation of nuclear factor-kappa B, and up-regulation of pro-inflammatory, pro-oxidant, and pro-fibrotic proteins at weeks 8 and 12. However, no significant difference was found at week 4. Metabolomics identified 12-ketodeoxycholic acid, taurochenodesoxycholic acid, LPC(15:0 and docosahexaenoic acid as biomarkers for early detection of tubulo-interstitial nephropathy. With prolonging aristolochic acid I exposure, LPE(20:2, cholic acid, chenodeoxycholic acid and LPC(17:0 were identified as biomarkers for progression from early to advanced AAN and lysoPE(22:5, indoxyl sulfate, uric acid and creatinine as biomarkers of advanced AAN. These biomarkers were reversed by treatment of irbesartan and ergone in AAN rats at week 24 and adenine-induced CKD rats. In addition, these biomarkers were also reversed by irbesartan treatment in CKD patients.

  2. Tempol, a Superoxide Dismutase-Mimetic Drug, Ameliorates Progression of Renal Disease in CKD Mice

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    Wei Ding

    2015-07-01

    Full Text Available Background: Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD and antioxidants may ameliorate disease progression. We investigate the beneficial effect of Tempol, a superoxide dismutase-mimetic drug, on progression of disease in a mouse model of CKD. Methods: CKD was surgically induced in c57BL/6 mice by 5/6 nephrectomy. Mice were randomly divided into 3 groups: sham group, 5/6 nephrectomized group (Nx and Nx+Tempol (2 mmol/l in drinking water. Mice were sacrificed at the end of 12 weeks. Renal function, structure as well as expression of key molecules involved in the pathogenesis of inflammation, fibrosis and progression in mice were measured. Results: Reduced body weight and impaired renal function (elevation on serum creatinine, blood urea nitrogen, urine albumin, segmental sclerosis and tubulointerstitial damage was demonstrated in Nx mice but was significantly improved by Tempol administration. Nx animals exhibited significantly elevated proinflammatory and profibrotic factors, activation of NF-κB, increased expression of NADPH oxidase related subunits (p47phox, p67phox, gp91phox, and elevated activation of TGF-ß/Smad3, EGFR, MAPK signaling pathway. Tempol inhibited NF-κB mediated inflammation, TGF-ß/Smad3-induced renal fibrosis as well as EGFR and MAPK signaling pathway activation. Conclusions: Tempol administration attenuated renal injury in CKD mice through NF-κB, TGF-ß/Smad3, redox-senstive EGFR activation and c-Raf/MEK/ERK pathways.

  3. Tempol, a Superoxide Dismutase-Mimetic Drug, Ameliorates Progression of Renal Disease in CKD Mice.

    Science.gov (United States)

    Ding, Wei; Wang, Bin; Zhang, Minmin; Gu, Yong

    2015-01-01

    Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD) and antioxidants may ameliorate disease progression. We investigate the beneficial effect of Tempol, a superoxide dismutase-mimetic drug, on progression of disease in a mouse model of CKD. CKD was surgically induced in c57BL/6 mice by 5/6 nephrectomy. Mice were randomly divided into 3 groups: sham group, 5/6 nephrectomized group (Nx) and Nx+Tempol (2 mmol/l in drinking water). Mice were sacrificed at the end of 12 weeks. Renal function, structure as well as expression of key molecules involved in the pathogenesis of inflammation, fibrosis and progression in mice were measured. Reduced body weight and impaired renal function (elevation on serum creatinine, blood urea nitrogen, urine albumin, segmental sclerosis and tubulointerstitial damage) was demonstrated in Nx mice but was significantly improved by Tempol administration. Nx animals exhibited significantly elevated proinflammatory and profibrotic factors, activation of NF-κB, increased expression of NADPH oxidase related subunits (p47phox, p67phox, gp91phox), and elevated activation of TGF-β/Smad3, EGFR, MAPK signaling pathway. Tempol inhibited NF-κB mediated inflammation, TGF-β/Smad3-induced renal fibrosis as well as EGFR and MAPK signaling pathway activation. Tempol administration attenuated renal injury in CKD mice through NF-κB, TGF-β/Smad3, redox-senstive EGFR activation and c-Raf/MEK/ERK pathways. © 2015 S. Karger AG, Basel.

  4. Evaluation of Absolute and Relative Reinforcer Value Using Progressive-Ratio Schedules

    Science.gov (United States)

    Francisco, Monica T.; Borrero, John C.; Sy, Jolene R.

    2008-01-01

    We evaluated behavior exhibited by individuals with developmental disabilities using progressive-ratio (PR) schedules. High- and low-preference stimuli were determined based on the results of a paired-stimulus preference assessment and were evaluated in subsequent reinforcer and PR assessments using concurrent and single schedules of presentation.…

  5. 18F-AV-1451 positron emission tomography in Alzheimer's disease and progressive supranuclear palsy.

    Science.gov (United States)

    Passamonti, Luca; Vázquez Rodríguez, Patricia; Hong, Young T; Allinson, Kieren S J; Williamson, David; Borchert, Robin J; Sami, Saber; Cope, Thomas E; Bevan-Jones, W Richard; Jones, P Simon; Arnold, Robert; Surendranathan, Ajenthan; Mak, Elijah; Su, Li; Fryer, Tim D; Aigbirhio, Franklin I; O'Brien, John T; Rowe, James B

    2017-03-01

    The ability to assess the distribution and extent of tau pathology in Alzheimer's disease and progressive supranuclear palsy in vivo would help to develop biomarkers for these tauopathies and clinical trials of disease-modifying therapies. New radioligands for positron emission tomography have generated considerable interest, and controversy, in their potential as tau biomarkers. We assessed the radiotracer 18F-AV-1451 with positron emission tomography imaging to compare the distribution and intensity of tau pathology in 15 patients with Alzheimer's pathology (including amyloid-positive mild cognitive impairment), 19 patients with progressive supranuclear palsy, and 13 age- and sex-matched controls. Regional analysis of variance and a support vector machine were used to compare and discriminate the clinical groups, respectively. We also examined the 18F-AV-1451 autoradiographic binding in post-mortem tissue from patients with Alzheimer's disease, progressive supranuclear palsy, and a control case to assess the 18F-AV-1451 binding specificity to Alzheimer's and non-Alzheimer's tau pathology. There was increased 18F-AV-1451 binding in multiple regions in living patients with Alzheimer's disease and progressive supranuclear palsy relative to controls [main effect of group, F(2,41) = 17.5, P AV-1451 binding was significantly increased in patients with Alzheimer's disease, relative to patients with progressive supranuclear palsy and with control subjects, in the hippocampus and in occipital, parietal, temporal, and frontal cortices (t's > 2.2, P's AV-1451 binding was elevated in the midbrain (t = 2.1, P AV-1451 uptake in the putamen, pallidum, thalamus, midbrain, and in the dentate nucleus of the cerebellum (t's > 2.7, P's AV-1451 strongly bound to Alzheimer-related tau pathology, but less specifically in progressive supranuclear palsy. 18F-AV-1451 binding to the basal ganglia was strong in all groups in vivo. Postmortem histochemical staining showed absence of

  6. Progress towards the elimination of transmission of Chagas disease in Latin America.

    Science.gov (United States)

    Moncayo, A

    1997-01-01

    From a global perspective, Chagas disease represents the third largest tropical disease burden after malaria and schistosomiasis. The estimated average annual per-capita gross domestic product in Latin America is US$2,966. The economic loss for the continent due to early mortality and disability by this disease in economically most productive young adults currently amounts to US$8,156 million which is equivalent to 2.5% of the external debt of the whole continent in 1995. In 1991, the Ministers of Health of Argentina, Bolivia, Brazil, Chile, Paraguay and Uruguay, launched the Southern Cone Initiative for elimination of transmission of Chagas disease. The progress towards elimination of vectorial and transfusional transmission of Chagas disease in Uruguay, Chile, Argentina and Brazil has been documented by reports from the national control programmes of the above countries. Current data on disinfestation of houses, coverage of screening in blood banks and serology in children and young adults indicate that the interruption of the vectorial and transfusional transmission of Chagas disease will be achieved in these countries as follows: Uruguay and Chile in 1999, Brazil and Argentina in 2003. By eliminating the transmission of Chagas disease in the above countries, the incidence of the disease in the whole of Latin America will be reduced by more than 70%.

  7. Successful human epidermal growth receptor 2-targeted therapy beyond disease progression for extramammary Paget's disease.

    Science.gov (United States)

    Watanabe, Satomi; Takeda, Masayuki; Takahama, Takayuki; Iwasa, Tsutomu; Tsurutani, Junji; Tanizaki, Junko; Shimizu, Toshio; Sakai, Kazuko; Wada, Yoshitaka; Isogai, Noritaka; Nishio, Kazuto; Nakagawa, Kazuhiko

    2016-06-01

    Extramammary Paget's disease is a malignant intraepithelial carcinoma, which constitutes less than 1 % of all vulvar malignancies. Surgical resection is the first treatment of choice and standard chemotherapy has not been established for advanced or recurrent disease. Experimental and clinical studies have identified human epidermal growth receptor 2 as a potential therapeutic target. A 63-year-old male was referred for recurrent extramammary Paget's disease after surgery. Human epidermal growth receptor 2 was shown to be overexpressed and amplified by immunohistochemical analysis and fluorescence in situ hybridization analysis, respectively. After two cycles of trastuzumab monotherapy, all lymph node metastases decreased in size. However, he experienced recurrence in the lymph nodes during the seven courses of trastuzumab. As a subsequent treatment, trastuzumab was administered in combination with docetaxel and pertuzumab; clinical response was sustained for 12 months without significant adverse events.

  8. Retinal thickness as a marker of disease progression in longitudinal observation of patients with Wolfram syndrome.

    Science.gov (United States)

    Zmyslowska, Agnieszka; Fendler, Wojciech; Waszczykowska, Arleta; Niwald, Anna; Borowiec, Maciej; Jurowski, Piotr; Mlynarski, Wojciech

    2017-11-01

    Wolfram syndrome (WFS) is a recessively inherited monogenic form of diabetes coexisting with optic atrophy and neurodegenerative disorders with no currently recognized markers of disease progression. The aim of the study was to evaluate retinal parameters by using optical coherence tomography (OCT) in WFS patients after 2 years of follow-up and analysis of the parameters in relation to visual acuity. OCT parameters and visual acuity were measured in 12 WFS patients and 31 individuals with type 1 diabetes. Total thickness of the retinal nerve fiber layer (RNFL), average retinal thickness and total retinal volume decreased in comparison with previous OCT examination. Significant decreases were noted for RNFL (average difference -17.92 µm 95% CI -30.74 to -0.10; p = 0.0157), macular average thickness (average difference -5.38 µm 95% CI -10.63 to -2.36; p = 0.0067) and total retinal volume (average difference -0.15 mm 3 95% CI -0.30 to -0.07; p = 0.0070). Central thickness remained unchanged (average difference 1.5 µm 95% CI -7.61 to 10.61; p = 0.71). Visual acuity of WFS patients showed a strong negative correlation with diabetes duration (R = -0.82; p = 0.0010). After division of WFS patients into two groups (with low-vision and blind patients), all OCT parameters except for the RNFL value were lower in blind WFS patients. OCT measures structural parameters and can precede visual acuity loss. The OCT study in WFS patients should be performed longitudinally, and serial retinal examinations may be helpful as a potential end point for future clinical trials.

  9. Hyperuricemia and Progression of CKD in Children and Adolescents: The Chronic Kidney Disease in Children (CKiD) Cohort Study.

    Science.gov (United States)

    Rodenbach, Kyle E; Schneider, Michael F; Furth, Susan L; Moxey-Mims, Marva M; Mitsnefes, Mark M; Weaver, Donald J; Warady, Bradley A; Schwartz, George J

    2015-12-01

    Hyperuricemia is associated with essential hypertension in children. No previous studies have evaluated the effect of hyperuricemia on progression of chronic kidney disease (CKD) in children. Prospective observational cohort study. Children and adolescents (n=678 cross-sectional; n=627 longitudinal) with a median age of 12.3 (IQR, 8.6-15.6) years enrolled at 52 North American sites of the CKiD (CKD in Children) Study. Serum uric acid level (7.5mg/dL). Composite end point of either >30% decline in glomerular filtration rate (GFR) or initiation of renal replacement therapy. Age, sex, race, blood pressure status, GFR, CKD cause, urine protein-creatinine ratio ( 95th percentile, use of diuretics, and serum uric acid level. Older age, male sex, lower GFR, and body mass index > 95th percentile were associated with higher uric acid levels. 162, 294, and 171 participants had initial uric acid levels 7.5 mg/dL, respectively. We observed 225 instances of the composite end point over 5 years. In a multivariable parametric time-to-event analysis, compared with participants with initial uric acid levels 7.5mg/dL had 17% shorter (relative time, 0.83; 95% CI, 0.62-1.11) or 38% shorter (relative time, 0.62; 95% CI, 0.45-0.85) times to event, respectively. Hypertension, lower GFR, glomerular CKD cause, and elevated urine protein-creatinine ratio were also associated with faster times to the composite end point. The study lacked sufficient data to examine how use of specific medications might influence serum uric acid levels and CKD progression. Hyperuricemia is a previously undescribed independent risk factor for faster progression of CKD in children and adolescents. It is possible that treatment of children and adolescents with CKD with urate-lowering therapy could slow disease progression. Copyright © 2015 National Kidney Foundation, Inc. All rights reserved.

  10. Impairment of Vowel Articulation as a Possible Marker of Disease Progression in Parkinson's Disease

    OpenAIRE

    Skodda, Sabine; Grönheit, Wenke; Schlegel, Uwe

    2012-01-01

    PURPOSE: The aim of the current study was to survey if vowel articulation in speakers with Parkinson's disease (PD) shows specific changes in the course of the disease. METHOD: 67 patients with PD (42 male) and 40 healthy speakers (20 male) were tested and retested after an average time interval of 34 months. Participants had to read a given text as source for subsequent calculation of the triangular vowel space area (tVSA) and vowel articulation index (VAI). Measurement of tVSA and VAI were ...

  11. Progress of PET imaging in the study of neural stem cell transplantation treating Parkinson's disease

    International Nuclear Information System (INIS)

    Tan Haibo; Liu Xingdang

    2004-01-01

    PET imaging has important value in the study of neural stem cell transplantation treating Parkinson's disease, especial in the evaluation of the effect, the study of treating mechanisms and the comparation of effect in different transplantation places. PET imaging as a non-invasive method plays a more and more important role in the study of neural stem cell transplantation treating Parkinson's disease. (authors)

  12. The fundamental role of mechanical properties in the progression of cancer disease and inflammation

    Science.gov (United States)

    Mierke, Claudia Tanja

    2014-07-01

    The role of mechanical properties in cancer disease and inflammation is still underinvestigated and even ignored in many oncological and immunological reviews. In particular, eight classical hallmarks of cancer have been proposed, but they still ignore the mechanics behind the processes that facilitate cancer progression. To define the malignant transformation of neoplasms and finally reveal the functional pathway that enables cancer cells to promote cancer progression, these classical hallmarks of cancer require the inclusion of specific mechanical properties of cancer cells and their microenvironment such as the extracellular matrix as well as embedded cells such as fibroblasts, macrophages or endothelial cells. Thus, this review will present current cancer research from a biophysical point of view and will therefore focus on novel physical aspects and biophysical methods to investigate the aggressiveness of cancer cells and the process of inflammation. As cancer or immune cells are embedded in a certain microenvironment such as the extracellular matrix, the mechanical properties of this microenvironment cannot be neglected, and alterations of the microenvironment may have an impact on the mechanical properties of the cancer or immune cells. Here, it is highlighted how biophysical approaches, both experimental and theoretical, have an impact on the classical hallmarks of cancer and inflammation. It is even pointed out how these biophysical approaches contribute to the understanding of the regulation of cancer disease and inflammatory responses after tissue injury through physical microenvironmental property sensing mechanisms. The recognized physical signals are transduced into biochemical signaling events that guide cellular responses, such as malignant tumor progression, after the transition of cancer cells from an epithelial to a mesenchymal phenotype or an inflammatory response due to tissue injury. Moreover, cell adaptation to mechanical alterations, in

  13. 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.

  14. Osteoarthritis in the XXIst Century: Risk Factors and Behaviours that Influence Disease Onset and Progression

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    Giuseppe Musumeci

    2015-03-01

    Full Text Available 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.

  15. Real-time monitoring of disease progression in rhesus macaques infected with Borrelia turicatae by tick bite.

    Science.gov (United States)

    Lopez, Job E; Vinet-Oliphant, Heather; Wilder, Hannah K; Brooks, Christopher P; Grasperge, Britton J; Morgan, Timothy W; Stuckey, Kerstan J; Embers, Monica E

    2014-11-15

    The hallmark of disease caused by tick- and louse-borne relapsing fever due to Borrelia infection is cyclic febrile episodes, which in humans results in severe malaise and may lead to death. To evaluate the pathogenesis of relapsing fever due to spirochetes in an animal model closely related to humans, disease caused by Borrelia turicatae after tick bite was compared in 2 rhesus macaques in which radiotelemetry devices that recorded body temperatures in 24-hour increments were implanted. The radiotelemetry devices enabled real-time acquisition of core body temperatures and changes in heart rates and electrocardiogram intervals for 28 consecutive days without the need to constantly manipulate the animals. Blood specimens were also collected from all animals for 14 days after tick bite, and spirochete densities were assessed by quantitative polymerase chain reaction. The complexity of disease caused by relapsing-fever spirochetes was demonstrated in the nonhuman primates monitored in real time. The animals experienced prolonged episodes of hyperthermia and hypothermia; disruptions in their diurnal patterns and repolarization of the heart were also observed. This is the first report of the characterizing disease progression with continuous monitoring in an animal model of relapsing fever due to Borrelia infection. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Evaluation of bioluminescent imaging for noninvasive monitoring of colorectal cancer progression in the liver and its response to immunogene therapy

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    Gonzalez-Aparicio Manuela

    2009-01-01

    Full Text Available Abstract Background Bioluminescent imaging (BLI is based on the detection of light emitted by living cells expressing a luciferase gene. Stable transfection of luciferase in cancer cells and their inoculation into permissive animals allows the noninvasive monitorization of tumor progression inside internal organs. We have applied this technology for the development of a murine model of colorectal cancer involving the liver, with the aim of improving the pre-clinical evaluation of new anticancer therapies. Results A murine colon cancer cell line stably transfected with the luciferase gene (MC38Luc1 retains tumorigenicity in immunocompetent C57BL/6 animals. Intrahepatic inoculation of MC38Luc1 causes progressive liver infiltration that can be monitored by BLI. Compared with ultrasonography (US, BLI is more sensitive, but accurate estimation of tumor mass is impaired in advanced stages. We applied BLI to evaluate the efficacy of an immunogene therapy approach based on the liver-specific expression of the proinflammatory cytokine interleukin-12 (IL-12. Individualized quantification of light emission was able to determine the extent and duration of antitumor responses and to predict long-term disease-free survival. Conclusion We show that BLI is a rapid, convenient and safe technique for the individual monitorization of tumor progression in the liver. Evaluation of experimental treatments with complex mechanisms of action such as immunotherapy is possible using this technology.

  17. The effect of progressive resistance training on aerobic fitness and strength in adults with coronary heart disease: A systematic review and meta-analysis of randomised controlled trials.

    Science.gov (United States)

    Hollings, Matthew; Mavros, Yorgi; Freeston, Jonathan; Fiatarone Singh, Maria

    2017-08-01

    Design We aimed to evaluate the effect of progressive resistance training on cardiorespiratory fitness and muscular strength in coronary heart disease, when compared to control or aerobic training, and when combined with aerobic training. Secondary aims were to evaluate the safety and efficacy of progressive resistance training on other physiological and clinical outcomes. Methods and results Electronic databases were searched from inception until July 2016. Designs included progressive resistance training vs control, progressive resistance training vs aerobic training, and combined training vs aerobic training. From 268,778 titles, 34 studies were included (1940 participants; 71.9% male; age 60 ± 7 years). Progressive resistance training was more effective than control for lower (standardized mean difference 0.57, 95% confidence interval (0.17-0.96)) and upper (1.43 (0.73-2.13)) body strength. Aerobic fitness improved similarly after progressive resistance training (16.9%) or aerobic training (21.0%); (standardized mean difference -0.13, 95% confidence interval (-0.35-0.08)). Combined training was more effective than aerobic training for aerobic fitness (0.21 (0.09-0.34), lower (0.62 (0.32-0.92)) and upper (0.51 (0.27-0.74)) body strength. Twenty studies reported adverse event information, with five reporting 64 cardiovascular complications, 63 during aerobic training. Conclusion Isolated progressive resistance training resulted in an increase in lower and upper body strength, and improved aerobic fitness to a similar degree as aerobic training in coronary heart disease cohorts. Importantly, when progressive resistance training was added to aerobic training, effects on both fitness and strength were enhanced compared to aerobic training alone. Reporting of adverse events was poor, and clinical gaps were identified for women, older adults, high intensity progressive resistance training and long-term outcomes, warranting future trials to confirm safety and

  18. The Progressive BSSG Rat Model of Parkinson's: Recapitulating Multiple Key Features of the Human Disease.

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    Jackalina M Van Kampen

    Full Text Available The development of effective neuroprotective therapies for Parkinson's disease (PD has been severely hindered by the notable lack of an appropriate animal model for preclinical screening. Indeed, most models currently available are either acute in nature or fail to recapitulate all characteristic features of the disease. Here, we present a novel progressive model of PD, with behavioural and cellular features that closely approximate those observed in patients. Chronic exposure to dietary phytosterol glucosides has been found to be neurotoxic. When fed to rats, β-sitosterol β-d-glucoside (BSSG triggers the progressive development of parkinsonism, with clinical signs and histopathology beginning to appear following cessation of exposure to the neurotoxic insult and continuing to develop over several months. Here, we characterize the progressive nature of this model, its non-motor features, the anatomical spread of synucleinopathy, and response to levodopa administration. In Sprague Dawley rats, chronic BSSG feeding for 4 months triggered the progressive development of a parkinsonian phenotype and pathological events that evolved slowly over time, with neuronal loss beginning only after toxin exposure was terminated. At approximately 3 months following initiation of BSSG exposure, animals displayed the early emergence of an olfactory deficit, in the absence of significant dopaminergic nigral cell loss or locomotor deficits. Locomotor deficits developed gradually over time, initially appearing as locomotor asymmetry and developing into akinesia/bradykinesia, which was reversed by levodopa treatment. Late-stage cognitive impairment was observed in the form of spatial working memory deficits, as assessed by the radial arm maze. In addition to the progressive loss of TH+ cells in the substantia nigra, the appearance of proteinase K-resistant intracellular α-synuclein aggregates was also observed to develop progressively, appearing first in the

  19. Physical Equilibrium Evaluation in Parkinson Disease

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    Schmidt, Paula da Silva

    2011-04-01

    Full Text Available Introduction: The Parkinson disease can be among the multiple causes of alterations in the physical equilibrium. Accordingly, this study has the objective to evaluate Parkinson patients' physical equilibrium. Method: Potential study in which 12 Parkinson individuals were evaluated by way of tests of static and dynamic equilibrium, dynamic posturography and vectoelectronystagmograph. To compare the dynamic posturography results a group of gauged control was used. Results: Alterations in Romberg-Barré, Unterberger and Walk tests were found. The vestibular exam revealed 06 normal cases, 04 central vestibular syndrome and 02 cases of peripheral vestibular syndrome. In the dynamic posturography, an equilibrium alteration has been verified, when compared to the control group in all Sensorial Organization Tests, in average and in the utilization of vestibular system. Conclusion: Parkinson patients present a physical equilibrium alteration. The dynamic posturography was more sensitive to detect the equilibrium alterations than vectoelectronystagmograph.

  20. The roles of microglia/macrophages in tumor progression of brain cancer and metastatic disease.

    Science.gov (United States)

    Wu, Shih-Ying; Watabe, Kounosuke

    2017-06-01

    Malignant brain tumors and brain metastases are highly aggressive diseases that are often resistant to treatment. Consequently, the current prognosis of patients with brain tumors and metastases is dismal. Activated microglia and macrophages are often observed in close proximity to or within the malignant tumor masses, suggesting that microglia/macrophages play an important role in brain tumor progression. Microglia, being resident macrophages of the central nervous system, form a major component of the brain immune system. They exhibit anti-tumor functions by phagocytosis and the release of cytotoxic factors. However, these microglia/macrophages can be polarized into becoming tumor-supportive and immunosuppressive cells by certain tumor-derived soluble factors, thereby promoting tumor maintenance and progression. The activated microglia/macrophages also participate in the process of tumor angiogenesis, metastasis, dormancy, and relapse. In this review, we discuss the recent literature on the dual roles of microglia/macrophages in brain tumor progression. We have also reviewed the effect of several well-known microglia/macrophages-derived molecules and signals on brain tumor progression and further discussed the potential therapeutic strategies for targeting the pro-tumor and metastatic functions of microglia/macrophages.

  1. Radiologic evaluation of nonalcoholic fatty liver disease

    Science.gov (United States)

    Lee, Seung Soo; Park, Seong Ho

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a frequent cause of chronic liver diseases, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH)-related liver cirrhosis. Although liver biopsy is still the gold standard for the diagnosis of NAFLD, especially for the diagnosis of NASH, imaging methods have been increasingly accepted as noninvasive alternatives to liver biopsy. Ultrasonography is a well-established and cost-effective imaging technique for the diagnosis of hepatic steatosis, especially for screening a large population at risk of NAFLD. Ultrasonography has a reasonable accuracy in detecting moderate-to-severe hepatic steatosis although it is less accurate for detecting mild hepatic steatosis, operator-dependent, and rather qualitative. Computed tomography is not appropriate for general population assessment of hepatic steatosis given its inaccuracy in detecting mild hepatic steatosis and potential radiation hazard. However, computed tomography may be effective in specific clinical situations, such as evaluation of donor candidates for hepatic transplantation. Magnetic resonance spectroscopy and magnetic resonance imaging are now regarded as the most accurate practical methods of measuring liver fat in clinical practice, especially for longitudinal follow-up of patients with NAFLD. Ultrasound elastography and magnetic resonance elastography are increasingly used to evaluate the degree of liver fibrosis in patients with NAFLD and to differentiate NASH from simple steatosis. This article will review current imaging methods used to evaluate hepatic steatosis, including the diagnostic accuracy, limitations, and practical applicability of each method. It will also briefly describe the potential role of elastography techniques in the evaluation of patients with NAFLD. PMID:24966609

  2. Parkinson’s disease progression: implicit acquisition, cognitive and motor impairments, and medication effects

    Directory of Open Access Journals (Sweden)

    Rodrigo ePavão

    2012-08-01

    Full Text Available Parkinson’s disease (PD symptoms have been collectively ascribed to malfunctioning of dopamine-related nigro-striatal and cortico-striatal loops. However, some doubts about this proposition are raised by controversies about the temporal progression of the impairments, and whether they are concomitant or not. The present study consists of a systematic revision of literature data on both functional PD impairments and dopaminergic medication effects in order to draw a coherent picture about the disease progression. It was done in terms of an explanatory model for the disruption of implicit knowledge acquisition, motor and cognitive impairments, and the effects of dopaminergic medication on these functions. Cognitive impairments arise at early stages of PD and stabilizes while disruption of acquisition of implicit knowledge and motor impairments are still in progression; additionally, dopaminergic medication reduces motor impairments and increases disruption of acquisition of implicit knowledge. Since this model revealed consistency and plausibility when confronted with data of others studies not included in model's formulation, it may turn out to be a useful tool for understanding the multifaceted characteristics of PD.

  3. PROGRESSIVE MUSCLE RELAXATION INCREASE PEAK EXPIRATORY FLOW RATE ON CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS

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    Tintin Sukartini

    2017-07-01

    Full Text Available Introduction: Limited progressive air flow in Chronic Obstructive Pulmonary Disease (COPD can caused by small airway disease (bronchiolitis obstructive and loss of elasticity of the lung (emphysema. Further it can be decreasing the quality of life in COPD patients because dyspnea and uncomfortable in activity. Progressive muscle relaxation (PMR is one of the relaxation technique that can repair pulmonary ventilation by decreasing chronic constriction of the respiratory muscles. The objective of this study was to analyze the effect of progressive muscle relaxation on raised peak expiratory flow rate (PEFR. Method: A pre-experimental one group pre-post test design was used in this study. Population was all of the COPD patients at Pulmonary Specialist Polyclinic Dr Mohamad Soewandhie Surabaya. There were 8 respondents taken by using purposive sampling. PEFR was counted by using peak flow meter every six day. Data were analyzed by using Paired t-Test with significance level  p≤0.05. Result: The result showed that PMR had significance level on increasing of PEFR (p=0.012. Discussion: It can be concluded that PMR has an effect on raise PEFR. Further studies are recommended to measure the effect of PMR on respiratory rate (RR, heart rate (HR subjective dyspnoe symptoms, forced expiration volume on the first minute (FEV1 and mid maximum flow rate (MMFR in COPD patients.

  4. The Role of Dendritic Cells in Fibrosis Progression in Nonalcoholic Fatty Liver Disease

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    Paloma Almeda-Valdes

    2015-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most frequent cause of chronic liver disease. NAFLD encompasses a wide range of pathologies, from simple steatosis to steatosis with inflammation to fibrosis. The pathogenesis of NAFLD progression has not been completely elucidated, and different liver cells could be implicated. This review focuses on the current evidence of the role of liver dendritic cells (DCs in the progression from NAFLD to fibrosis. Liver DCs are a heterogeneous population of hepatic antigen-presenting cells; their main function is to induce T-cell mediated immunity by antigen processing and presentation to T cells. During the steady state liver DCs are immature and tolerogenic. However, in an environment of chronic inflammation, DCs are transformed to potent inducers of immune responses. There is evidence about the role of DC in liver fibrosis, but it is not clearly understood. Interestingly, there might be a link between lipid metabolism and DC function, suggesting that immunogenic DCs are associated with liver lipid storage, representing a possible pathophysiological mechanism in NAFLD development. A better understanding of the interaction between inflammatory pathways and the different cell types and the effect on the progression of NAFLD is of great relevance.

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

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    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.

  6. Effect of oral alkali supplementation on progression of chronic kidney disease.

    Science.gov (United States)

    Gaggl, Martina; Sliber, Christopher; Sunder-Plassmann, Gere

    2014-01-01

    Metabolic acidosis is a frequent but asymptomatic complication in chronic kidney disease (CKD). In early stages of CKD acidosis is limited to the renal tissue and progresses to reduced serum bicarbonate levels. Reduced renal tissue pH and increased ammoniagenesis are the key mechanisms of the kidney to enhance acid excretion to the urine. The expressed protein patterns in the proximal tubular epithelial cells change remarkably, the proximal convoluted tubule develops hypertrophy, and an intra-renal enhanced renin-angiotensin-system leads to interstitial fibrosis. Since nephrons are numerically reduced in CKD each remaining functional unit has to progressively increase these mechanisms to keep up the equilibrium. The adverse effects of chronic metabolic acidosis include aside from acceleration of progression of kidney disease, the development or exacerbation of bone disease, increased degradation of muscle with muscle wasting, enhanced protein degradation and inflammation. Genome wide association studies demonstrated that tubular acid-base transporters are involved in the development of arterial hypertension. Several retrospective analyses have indicated that low serum bicarbonate predicts death in cohorts with CKD and cardiovascular disease. All studies confirmed a U-shaped association of mortality and serum bicarbonate, indicating that both, acidosis and alkalosis are associated with increased mortality. Randomized controlled trials showed that base substitution, either by modification of the diet or by simply adding alkalizing agents, might halt the decline of kidney function in subjects with CKD. In 2012 a meta-analysis concluded that alkali therapy might provide a long-term favorable effect on renal function in patients with CKD.

  7. Klinefelter′s syndrome associated with progressive muscular atrophy simulating Kennedy′s disease

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    Pedro Enrique Jiménez Caballero

    2012-01-01

    Full Text Available Kennedy′s disease, an X-linked spinal and bulbar muscular atrophy, is characterized by loss of lower motor neurons. Mild sensory deficits, gynecomastia and infertility may be observed. Klinefelter′s syndrome is a variation of sex chromosome disorder characterized by hypogonadism, gynecomastia and azoospermia, and the most frequent karyotype is XXY. A 55-year-old man who presented with slowly progressive and diffuse neurogenic muscle atrophy without bulbar or sensory symptoms. He also had Klinefelter′s syndrome. Genetic study of Kennedy′s disease was normal. Our patient differs from those with Kennedy′s disease in the absence of bulbar and sensory symptoms. It is suggested that the X chromosome plays an important role in the biology of motor neurons.

  8. Latest progress of BIGH3 gene in corneal diseases and diabetic retinopathy

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    Fan-Qian Song

    2017-03-01

    Full Text Available BIGH3 gene plays an important role in ocular diseases. On the one hand, it is closely related to the occurrence of corneal diseases. BIGH3 gene can inhibit corneal neovascularization, lead to corneal dystrophy, participate in keratoconus formation. On the other hand, it can lead to the formation of neovascularization in diabetic retinopathy. The latest experiments show that TGF beta secreted by macrophages can promote the expression of BIGH3 mRNA and BIGH3 protein, and promote apoptosis of retinal endothelial cells and pericytes, which leads to the formation of neovascularization in diabetic retinopathy. This article will describe the new progress of BIGH3 gene in ocular diseases from several aspects as mentioned above.

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

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    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

  10. Evaluation of Progressive Failure Analysis and Modeling of Impact Damage in Composite Pressure Vessels

    Science.gov (United States)

    Sanchez, Christopher M.

    2011-01-01

    NASA White Sands Test Facility (WSTF) is leading an evaluation effort in advanced destructive and nondestructive testing of composite pressure vessels and structures. WSTF is using progressive finite element analysis methods for test design and for confirmation of composite pressure vessel performance. Using composite finite element analysis models and failure theories tested in the World-Wide Failure Exercise, WSTF is able to estimate the static strength of composite pressure vessels. Additionally, test and evaluation on composites that have been impact damaged is in progress so that models can be developed to estimate damage tolerance and the degradation in static strength.

  11. Changes in mitochondrial stability during the progression of the Barrett’s esophagus disease sequence

    International Nuclear Information System (INIS)

    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.

    2016-01-01

    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 < 0.005) and increased levels of random mitochondrial mutations (p < 0.05) compared with all other stages of the Barrett’s 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 < 0.05), a gene linked to oxidative stress, compared with all other points across the 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 <0.05) were secreted from Barrett’s metaplastic tissue compared with matched normal squamous epithelium. We have demonstrated that increased mitochondrial instability and markers of cellular and mitochondrial stress are early events in the Barrett’s disease sequence

  12. Chronic kidney disease progression: a retrospective analysis of 3-year adherence to a low protein diet.

    Science.gov (United States)

    Rizzetto, Felipe; Leal, Viviane de Oliveira; Bastos, Leonardo Soares; Fouque, Denis; Mafra, Denise

    2017-11-01

    The potential benefits and dangers of dietary protein restriction in chronic kidney disease (CKD) are still controversial. Thus, the aim of this study is to evaluate the effect of low protein diet (LPD) on the renal function in nondialysis CKD patients. A retrospective study was conducted from 321 nondialysis CKD patient's medical files (65.1 ± 12.7 yrs, 58.2% men). These patients received individualized dietary protein prescription (0.6-0.8 g protein/kg/day). Protein intake was evaluated by food diary and 24 h-food recall. Adherence to the LPD was considered when patients intake from 90 to 110% of the prescribed amount of protein. The patients were divided into 4 groups: (G1) adherent diabetes mellitus (DM) patients (n = 83); (G2) non-adherent DM patients (n = 106); (G3) adherent non-DM patients (n = 75); (G4) non-adherent non-DM patients (n = 57). Renal function was assessed by estimated glomerular filtration rate (eGFR). Both groups of patients (DM and non-DM) that adhered to the LPD showed significant improvement in eGFR (G1: 38.7 ± 13.2 mL/min to 51.1 ± 17.0 mL/min (p patients, no differences in albumin and BMI were observed at the end of follow up. In non-adherent patients, eGFR significantly decreased in DM group (G2: 44.2 ± 18.5 mL/min to 38.2 ± 15.8 mL/min (p = 0.003)). According to multivariate analysis, annual changes in eGFR were not independent associated with age, gender, BMI, lipid profile, bicarbonate or smoking status. In summary, adherence to low protein diet could be able to improve serum creatinine and eGFR, well-known markers of renal function. However, prospective studies are needed to control confounders which affect renal function and CKD progression.

  13. MRI evaluation of soft tissue hydatid disease

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    Garcia-Diez, A.I.; Ros Mendoza, L.H.; Villacampa, V.M.; Cozar, M.; Fuertes, M.I. [Dept. of Radiology, Hospital Miguel Servet, Zaragoza (Spain)

    2000-03-01

    Infestation in soft tissue by Echinococcus granulosus is not a common disease, and its diagnosis is based on clinical, laboratory data and radiological findings. The aim of our retrospective study is to give an overview of the different signs and patterns shown by MRI that can be useful in characterizing soft tissue hydatid disease. The MRI images obtained in seven patients with soft tissue and subcutaneous hydatidosis were reviewed. Typical signs of hydatidosis were multivesicular lesions with or without hypointense peripheral ring (''rim sign''). Related to the presence and absence, respectively, of viable scolices in the microscopic exam, daughter cysts were presented either as high signal intensity or low signal intensity on T2-weighted images. Low-intensity detached layers within the cyst and peripheral enhancement with gadolinium-DTPA were also presented. Atypical signs were presented in an infected muscular cyst, a subcutaneous unilocular cyst and several unilocular cysts. Knowledge of the different patterns in MRI of soft tissue hydatid disease can be useful in diagnosing this entity. We observed that the ''rim sign'' is not as common as in other locations, and in addition, MRI seems to be of assistance when evaluating the vitality of the cysts. (orig.)

  14. Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

    Science.gov (United States)

    Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D

    2018-01-01

    The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

  15. Performance Evaluation of Moment Connections of Moment Resisting Frames Against Progressive Collapse

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    M. Mahmoudi

    2017-02-01

    Full Text Available When a primary structural element fails due to sudden load such as explosion, the building undergoes progressive collapse. The method for design of moment connections during progressive collapse is different to seismic design of moment connections. Because in this case, the axial force on the connections makes it behave differently. The purpose of this paper is to evaluate the performance of a variety of moment connections in preventing progressive collapse in steel moment frames. To achieve this goal, three prequalified moment connections (BSEEP, BFP and WUP-W were designed according seismic codes. These moment connections were analyzed numerically using ABAQUS software for progressive collapse. The results show that the BFP connection (bolted flange plate has capacity much more than other connections because of the use of plates at the junction of beam-column.

  16. Identification of Major Signaling Pathways in Prion Disease Progression Using Network Analysis.

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    Khalique Newaz

    Full Text Available Prion diseases are transmissible neurodegenerative diseases that arise due to conformational change of normal, cellular prion protein (PrPC to protease-resistant isofrom (rPrPSc. Deposition of misfolded PrpSc proteins leads to an alteration of many signaling pathways that includes immunological and apoptotic pathways. As a result, this culminates in the dysfunction and death of neuronal cells. Earlier works on transcriptomic studies have revealed some affected pathways, but it is not clear which is (are the prime network pathway(s that change during the disease progression and how these pathways are involved in crosstalks with each other from the time of incubation to clinical death. We perform network analysis on large-scale transcriptomic data of differentially expressed genes obtained from whole brain in six different mouse strain-prion strain combination models to determine the pathways involved in prion diseases, and to understand the role of crosstalks in disease propagation. We employ a notion of differential network centrality measures on protein interaction networks to identify the potential biological pathways involved. We also propose a crosstalk ranking method based on dynamic protein interaction networks to identify the core network elements involved in crosstalk with different pathways. We identify 148 DEGs (differentially expressed genes potentially related to the prion disease progression. Functional association of the identified genes implicates a strong involvement of immunological pathways. We extract a bow-tie structure that is potentially dysregulated in prion disease. We also propose an ODE model for the bow-tie network. Predictions related to diseased condition suggests the downregulation of the core signaling elements (PI3Ks and AKTs of the bow-tie network. In this work, we show using transcriptomic data that the neuronal dysfunction in prion disease is strongly related to the immunological pathways. We conclude that

  17. 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

    patient characteristics, and changes from baseline to follow-up systolic blood pressure (SBP) and urine protein (UP) excretion. RESULTS: The total number of patients was 1860: 645 (35%) females and 1215 (65%) males. Mean duration of follow-up was 2.2 years. The proportions randomized to ACEI (51%), mean...... ACEIs and baseline UP, and 1.36 (1.06-1.75) after adjusting for baseline variables and changes in SBP and UP during follow-up. Similar results were found for the outcome of ESRD. CONCLUSIONS: Our findings suggest that the rate of renal disease progression may not be slower, and may even be faster...... in women compared with men, after adjusting for other factors associated with a faster rate of progression. We caution that most women in our database were of post-menopausal age, and thus our findings may not extend to younger women....

  18. Re-evaluation of the diagnostic criteria for Wilson disease in children with mild liver disease.

    Science.gov (United States)

    Nicastro, Emanuele; Ranucci, Giusy; Vajro, Pietro; Vegnente, Angela; Iorio, Raffaele

    2010-12-01

    The diagnosis of Wilson disease (WD) is challenging, especially in children. Early detection is desirable in order to avoid dramatic disease progression. The aim of our study was to re-evaluate in WD children with mild liver disease the conventional diagnostic criteria and the WD scoring system proposed by an international consensus in 2001. Forty children with WD (26 boys and 14 girls, age range = 1.1-20.9 years) and 58 age-matched and sex-matched patients with a liver disease other than WD were evaluated. Both groups were symptom-free and had elevated aminotransferases as predominant signs of liver disease. In all WD patients, the diagnosis was supported by molecular analysis, the liver copper content, or both. A receiver operating characteristic (ROC) analysis of ceruloplasmin at the cutoff value of 20 mg/dL showed a sensitivity of 95% [95% confidence interval (CI) = 83%-99.4%] and a specificity of 84.5% (95% CI = 72.6%-92.6%). The optimal basal urinary copper diagnostic cutoff value was found to be 40 μg/24 hours (sensitivity = 78.9%, 95% CI = 62.7%-90.4%; specificity = 87.9%, 95% CI = 76.7%-95%). Urinary copper values after penicillamine challenge did not significantly differ between WD patients and control subjects, and the ROC analysis showed a sensitivity of only 12%. The WD scoring system was proved to have positive and negative predictive values of 93% and 91.6%, respectively. Urinary copper excretion greater than 40 μg/24 hours is suggestive of WD in asymptomatic children, whereas the penicillamine challenge test does not have a diagnostic role in this subset of patients. The WD scoring system provides good diagnostic accuracy. Copyright © 2010 American Association for the Study of Liver Diseases.

  19. International vision requirements for driver licensing and disability pensions: using a milestone approach in characterization of progressive eye disease

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    Alain M Bron

    2010-11-01

    Full Text Available Alain M Bron1, Ananth C Viswanathan2, Ulrich Thelen3, Renato de Natale4, Antonio Ferreras5, Jens Gundgaard6, Gail Schwartz7, Patricia Buchholz81Department of Ophthalmology, University Hospital, Dijon, France; 2Glaucoma Research Unit, Moorfields Eye Hospital NHS Foundation Trust and Department of Genetics, University College of London Institute of Ophthalmology, London, UK; 3Private Practice, Munster, Germany; 4Ospedale Civile di Monselice, Monselice, Italy; 5Ophthalmology, Miguel Servet University Hospital, Zaragoza, Spain; 6COWI, Kolding, Denmark; 7Wilmer Eye Institute, Johns Hopkins University, Glaucoma Consultants, Baltimore, MD, USA; 8Patricia Buchholz Consulting, Karlsruhe, GermanyObjective: Low vision that causes forfeiture of driver’s licenses and collection of disability pension benefits can lead to negative psychosocial and economic consequences. The purpose of this study was to review the requirements for holding a driver’s license and rules for obtaining a disability pension due to low vision. Results highlight the possibility of using a milestone approach to describe progressive eye disease.Methods: Government and research reports, websites, and journal articles were evaluated to review rules and requirements in Germany, Spain, Italy, France, the UK, and the US.Results: Visual acuity limits are present in all driver’s license regulations. In most countries, the visual acuity limit is 0.5. Visual field limits are included in some driver’s license regulations. In Europe, binocular visual field requirements typically follow the European Union standard of ≥120°. In the US, the visual field requirements are typically between 110° and 140°. Some countries distinguish between being partially sighted and blind in the definition of legal blindness, and in others there is only one limit.Conclusions: Loss of driving privileges could be used as a milestone to monitor progressive eye disease. Forfeiture could be standardized as a

  20. Objectively measured physical activity and inflammatory markers among US adults with diabetes: implications for attenuating disease progression.

    Science.gov (United States)

    Loprinzi, Paul D; Ramulu, Pradeep Y

    2013-09-01

    To examine the association between objectively measured physical activity and markers of inflammation (ie, white blood cell count, neutrophil count, and C-reactive protein level) among a national sample of adults with diabetes. Data from the 2003-2006 National Health and Nutrition Examination Survey cycles were used. The data were evaluated from November 25, 2012, to May 3, 2013. Participants wore an accelerometer for 4 days or longer to assess physical activity, with blood samples obtained to assess the aforementioned inflammatory markers. Accelerometer-derived light physical activity and moderate to vigorous physical activity were inversely associated with white blood cell and neutrophil counts, whereas time spent in moderate to vigorous physical activity was inversely associated with C-reactive protein levels. Adults with diabetes engaging in more physical activity have lower degrees of inflammation, suggesting that physical activity may reduce disease progression through mitigating inflammation, which is an important finding because increased inflammation among those with diabetes can worsen disease progression, including diabetic end-organ damage. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  1. Diallel analyze of yield and progress of the severity of leaf diseases in maize hybrids in two population density

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    Marcos Ventura Faria

    2015-02-01

    Full Text Available Seven commercial maize hybrids (AS1575, 2B688, Penta, GNZ2004, AG8021, Sprint e P30F53 were intercrossed in a complete diallel, excluded reciprocal, obtaining 21 crosses. The 28 treatments were evaluated in two environments characterized by different densities (62,500 and 90,000 plants ha-1, with the aim of selecting the most promising parents for generating base population to obtain lines. Two experiments were carried out in Guarapuava-PR, at randomized block design with three replications. We estimated the general (GCA and specific (SCA combining abilities for yield and disease severity assessed by the area under the common rust (Puccinia sorghi progress curve (AURPC and the area under the leaf spot (Cercospora zeae-maydis progress curve (AULPC. The effects of GCA and SCA were significant for grain yield and diseases severity in both densities, revealing the importance of both additive and non-additive effects. There GCA x densities interaction was significant only for grain yield. Crossings P30F53 x AG8021 and P30F53 x Penta had negative estimates of SCA for AURPC and AULPC on the environments average. Hybrids GNZ 2004 and P30F53 stood out showing positive GCA for grain yield and negative for AURPC and AULPC in both densities and therefore are recommended for generating base populations for obtaining lines adapted for both densities, conventional and denser plantings, given the current trends in management of maize.

  2. Serum creatinine is associated with the prevalence but not disease progression of multiple system atrophy in Chinese population.

    Science.gov (United States)

    Cao, Bei; Guo, XiaoYan; Chen, Ke; Song, Wei; Huang, Rui; Wei, QianQian; Zhao, Bi; Shang, Hui-Fang

    2016-03-01

    Oxidative stress is involved in the pathogenesis of multiple system atrophy (MSA). Creatine, which is converted to creatinine, has an anti-oxidative effect. Our aim is to clarify the correlations between creatinine and the occurrence as well as the progression of MSA. A total of 115 patients with probable MSA and 115 age- and gender-matched healthy controls were included in the study. The serum creatinine level of all patients and controls were evaluated and compared. The mean age of MSA patients was 58.18 ± 8.67 years and the mean disease duration was 2.85 ± 1.71 years. The creatinine level of MSA patients was significantly lower than that of healthy controls (P creatinine quartiles compared with the lowest creatinine quartiles. In a gender-specific analysis, patients with the highest quartiles and second quartiles of creatinine level had decreased occurrence than patients with the lowest quartile in females, but not in males. The serum level of creatinine was not found correlated with the mean rate of annualised changes, neither with other independent factors, such as age, body mass index (BMI), sex, Unified MSA Rating Scale (UMSARS) scores and disease duration at the initial visit in patients with MSA. High level of serum creatinine may be associated with a low occurrence of MSA in Chinese population, especially in female. However, serum creatinine does not deteriorate or ameliorate the progression of MSA.

  3. Medical history and progress in infectious diseases, especially systemic fungal infections in Japan.

    Science.gov (United States)

    Mori, Takeshi

    2008-01-01

    This paper reports on medical history from the end of the Edo period to the present and development of studies on infectious diseases, especially medical mycology including systemic fungal diseases. With the inflow of Dutch studies at the end of the Edo period and the adoption of European, mainly German, medicine in the Meiji Restoration, Japanese medical studies gradually developed. However, evolution in the medical field as well as other scientific fields was prevented during the 2nd World War. After the War, there was marked progress in scientific fields and medical research made strong advances. In the past 20 years, basic fungal studies and clinical fungal diseases, especially clinical analysis, clinical diagnosis and treatment of systemic fungal infections have progressed. The level in this field is now equivalent to or higher than that in European countries. Further development is necessary, however, to relieve patients suffering from systemic fungal infections. Members of the Japanese Association of Medical Mycology must be leaders among international medical mycologists.

  4. Risk factors for the progression of periodontal disease in a Greek adult population.

    Science.gov (United States)

    Chrysanthakopoulos, Nikolaos A

    2017-05-01

    The purpose of the present study was to investigate the progression risk factors of periodontal disease by individual characteristics at baseline in a Greek adult population. The study sample consisted of 854 individuals. All participants were clinically examined and answered questions regarding sex, smoking status, socioeconomic status, low educational level, frequency of dental follow up, and oral hygiene habits. Serum levels of disease markers were investigated, and attachment levels were clinically recorded. For the assessment of periodontal disease progression, additional clinical attachment loss (CAL) was used if one or more sites showed a 3 mm or more increase in probing attachment level over a 2-year period. Statistical analysis was performed by using a modified multiple Poisson's analysis model. A total of 74% of the participants exhibited additional CAL over a 2-year period. Significant associations were observed between additional CAL and smoking (relative risk [RR] = 0.78, 95% confidence level [CI] = 0.65-0.92), attachment level of 5 mm or more at baseline (RR = 0.89, 95% CI = 0.75-1.05), educational level (RR = 0.90, 95% CI = 0.76-1.07), socioeconomic status (RR = 0.86, 95% CI = 0.59-1.14), and irregular dental follow up (RR = 1.23, 95% CI = 1.04-1.45). Smoking, baseline attachment level of 5 mm or more, low educational level, low socioeconomic status, and irregular dental follow up could be considered risk factors for further CAL. © 2015 Wiley Publishing Asia Pty Ltd.

  5. [Progress in induced pluripotent stem cell research for age-related neurodegenerative diseases].

    Science.gov (United States)

    Ito, Daisuke; Yagi, Takuya; Suzuki, Norihiro

    2013-03-01

    In 2006, Takahashi et al. established a method for reprogramming somatic cells by introducing definite transcription factors, which enabled the generation of induced pluripotent stem cells (iPSCs) with pluripotency comparable to that of embryonic stem cells. In turn, it has become possible to use these iPSCs for producing various tissues needed for the treatment of neurodegenerative disorders, which have been difficult to obtain from living bodies. This advancement is expected to bring forth rapid progress in the clarification of mechanisms underlying the diseases and discovery of new innovative drugs and lead to rapid progress in regenerative medicine. In recent years, recapitulation and analysis of disease conditions using iPSCs derived from the patients themselves have been reported, and remarkable advances have been made, even for late-onset neurodegenerative disorders. These findings show that the phenotypes of late-onset neurodegenerative disorders can be recapitulated in iPSC-derived neuronal cells, which are reflected the early developmental stages, indicating cellular abnormalities exist from the prenatal period, despite the late onset diseases. In this review, we summarize the state of iPSCs research in the context of neurodegenerative disorders, discuss the possible ways for understanding the mechanisms underlying neurodegenerative disorders and discovering new drugs, and describe some other aspects of regenerative medicine.

  6. Is COPD a Progressive Disease? A Long Term Bode Cohort Observation.

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    Juan P de-Torres

    Full Text Available The Global Initiative for Obstructive Lung Diseases (GOLD defines COPD as a disease that is usually progressive. GOLD also provides a spirometric classification of airflow limitation. However, little is known about the long-term changes of patients in different GOLD grades.Explore the proportion and characteristics of COPD patients that change their spirometric GOLD grade over long-term follow-up.Patients alive for at least 8 years since recruitment and those who died with at least 4 years of repeated spirometric measurements were selected from the BODE cohort database. We purposely included the group of non survivors to avoid a "survival selection" bias. The proportion of patients that had a change (improvement or worsening in their spirometric GOLD grading was calculated and their characteristics compared with those that remained in the same grade.A total of 318 patients were included in the survivor and 217 in the non-survivor groups. Nine percent of survivors and 11% of non survivors had an improvement of at least one GOLD grade. Seventy one percent of survivors and non-survivors remained in the same GOLD grade. Those that improved had a greater degree of airway obstruction at baseline.In this selected population of COPD patients, a high proportion of patients remained in the same spirometric GOLD grade or improved in a long-term follow-up. These findings suggest that once diagnosed, COPD is usually a non-progressive disease.

  7. Exercise Does Not Attenuate Early Coronary Artery Disease Progression in a Pig Model

    Science.gov (United States)

    Arce-Esquivel, Arturo A.; Kreutzer, Kurt V.; Rush, James W. E.; Turk, James R.; Laughlin, M. Harold

    2012-01-01

    Purpose This study was designed to examine the effects of high fat (HF) diet and subsequent exercise training (Ex) on coronary arteries of an animal model of early stage coronary artery disease (CAD). We hypothesized that HF diet would induce early stage disease and promote a pro-atherogenic coronary phenotype, while Ex would blunt disease progression and induce a healthier anti-inflammatory environment reflected by increased expression of antioxidant capacity and decreased expression of inflammatory markers in both the macro and microvasculature of the coronary circulation. Methods Immunohistochemistry in left anterior descending (LAD) and right coronary arteries (RCA), and immunoblots in LAD and left ventricular (LV) arterioles were used to characterize effects of HF diet and Ex on the progression of coronary atherosclerosis. Results Our results revealed that HF diet promoted a pro-atherogenic coronary endothelial cell phenotype as evidenced by the endothelial expression of inflammatory and oxidative stress markers. Ex did not significantly alter any of these immunohistochemical markers in conduit arteries; however, Ex did increase antioxidant protein content in LV arterioles. Conclusions We conclude that, at this early stage of CAD, Ex did not seem to modify vascular cell phenotypes of conduit coronary arteries from pro- to a more favorable anti-atherogenic status; however, Ex increased antioxidant protein content in coronary arterioles. These findings also support the idea that endothelial phenotype expression follows different patterns in the macro and microvasculature of the coronary circulation. PMID:21685817

  8. Progressively Disrupted Intrinsic Functional Connectivity of Basolateral Amygdala in Very Early Alzheimer’s Disease

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    Marion Ortner

    2016-09-01

    Full Text Available Abstract:Very early Alzheimer’s disease (AD - i.e., AD at stages of mild cognitive impairment (MCI and mild dementia - is characterized by progressive structural and neuropathologic changes such as atrophy or tangle deposition in medial temporal lobes, including hippocampus and entorhinal cortex but also adjacent amygdala. While progressively disrupted intrinsic connectivity of hippocampus with other brain areas has been demonstrated by many studies, amygdala connectivity was rarely investigated in AD, notwithstanding its known relevance for emotion processing and mood disturbances, which are both important in early AD. Intrinsic functional connectivity (iFC patterns of hippocampus and amygdala overlap in healthy persons. Thus, we hypothesized that increased alteration of iFC patterns along AD is not limited to the hippocampus but also concerns the amygdala, independent from atrophy. To address this hypothesis, we applied structural and functional resting-state MRI in healthy controls (CON, n=33 and patients with AD in the stages of MCI (AD-MCI, n=38 and mild dementia (AD-D, n=36. Outcome measures were voxel-based morphometry (VBM values and region of interest-based intrinsic functional connectivity maps (iFC of basolateral amygdala, which has extended cortical connectivity. Amygdala VBM values were progressively reduced in patients (CON > AD-MCI and AD-D. Amygdala iFC was progressively reduced along impairment severity (CON > AD-MCI > AD-D, particularly for hippocampus, temporal lobes, and fronto-parietal areas. Notably, decreased iFC was independent of amygdala atrophy. Results demonstrate progressively impaired amygdala intrinsic connectivity in temporal and fronto-parietal lobes independent from increasing amygdala atrophy in very early AD. Data suggest that early AD disrupts intrinsic connectivity of medial temporal lobe key regions including that of amygdala.

  9. Timing of progression from Chlamydia trachomatis infection to pelvic inflammatory disease: a mathematical modelling study

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    Herzog Sereina A

    2012-08-01

    Full Text Available Abstract Background Pelvic inflammatory disease (PID results from the ascending spread of microorganisms from the vagina and endocervix to the upper genital tract. PID can lead to infertility, ectopic pregnancy and chronic pelvic pain. The timing of development of PID after the sexually transmitted bacterial infection Chlamydia trachomatis (chlamydia might affect the impact of screening interventions, but is currently unknown. This study investigates three hypothetical processes for the timing of progression: at the start, at the end, or throughout the duration of chlamydia infection. Methods We develop a compartmental model that describes the trial structure of a published randomised controlled trial (RCT and allows each of the three processes to be examined using the same model structure. The RCT estimated the effect of a single chlamydia screening test on the cumulative incidence of PID up to one year later. The fraction of chlamydia infected women who progress to PID is obtained for each hypothetical process by the maximum likelihood method using the results of the RCT. Results The predicted cumulative incidence of PID cases from all causes after one year depends on the fraction of chlamydia infected women that progresses to PID and on the type of progression. Progression at a constant rate from a chlamydia infection to PID or at the end of the infection was compatible with the findings of the RCT. The corresponding estimated fraction of chlamydia infected women that develops PID is 10% (95% confidence interval 7-13% in both processes. Conclusions The findings of this study suggest that clinical PID can occur throughout the course of a chlamydia infection, which will leave a window of opportunity for screening to prevent PID.

  10. Validating predictors of disease progression in a large cohort of primary-progressive multiple sclerosis based on a systematic literature review.

    Directory of Open Access Journals (Sweden)

    Jan-Patrick Stellmann

    Full Text Available New agents with neuroprotective or neuroregenerative potential might be explored in primary-progressive Multiple Sclerosis (PPMS--the MS disease course with leading neurodegenerative pathology. Identification of patients with a high short-term risk for progression may minimize study duration and sample size. Cohort studies reported several variables as predictors of EDSS disability progression but findings were partially contradictory.To analyse the impact of published predictors on EDSS disease progression in a large cohort of PPMS patients.A systematic literature research was performed to identify predictors for disease progression in PPMS. Individual case data from the Sylvia Lawry Centre (SLC and the Hamburg MS patient database (HAPIMS was pooled for a retrospective validation of these predictors on the annualized EDSS change.The systematic literature analysis revealed heterogeneous data from 3 prospective and 5 retrospective natural history cohort studies. Age at onset, gender, type of first symptoms and early EDSS changes were available for validation. Our pooled cohort of 597 PPMS patients (54% female had a mean follow-up of 4.4 years and mean change of EDSS of 0.35 per year based on 2503 EDSS assessments. There was no significant association between the investigated variables and the EDSS-change.None of the analysed variables were predictive for the disease progression measured by the annualized EDSS change. Whether PPMS is still unpredictable or our results may be due to limitations of cohort assessments or selection of predictors cannot be answered. Large systematic prospective studies with new endpoints are needed.

  11. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression.

    Science.gov (United States)

    Jädersten, Martin; Saft, Leonie; Smith, Alexander; Kulasekararaj, Austin; Pomplun, Sabine; Göhring, Gudrun; Hedlund, Anette; Hast, Robert; Schlegelberger, Brigitte; Porwit, Anna; Hellström-Lindberg, Eva; Mufti, Ghulam J

    2011-05-20

    To determine the frequency of TP53 mutations and the level of p53 protein expression by immunohistochemistry (IHC) in low-risk myelodysplastic syndromes (MDS) with del(5q) and to assess their impact on disease progression. Pre- and postprogression bone marrow (BM) samples from 55 consecutive patients with International Prognostic Scoring System low risk (n = 32) or intermediate-1 risk (n = 23) were studied by next-generation sequencing of TP53. IHC for p53 was performed on 148 sequential BM samples. TP53 mutations with a median clone size of 11% (range, 1% to 54%) were detected in 10 patients (18%) already at an early phase of the disease. Mutations were equally common in low-risk and intermediate-1-risk patients and were associated with evolution to acute myeloid leukemia (5 of 10 v 7 of 45; P = .045). Nine of 10 patients carrying mutations showed more than 2% BM progenitors with strong p53 staining. The probability of a complete cytogenetic response to lenalidomide was lower in mutated patients (0 of 7 v 12 of 24; P = .024). By using sensitive deep-sequencing technology, we demonstrated that TP53 mutated populations may occur at an early disease stage in almost a fifth of low-risk MDS patients with del(5q). Importantly, mutations were present years before disease progression and were associated with an increased risk of leukemic evolution. TP53 mutations could not be predicted by common clinical features but were associated with p53 overexpression. Our findings indicate a previously unrecognized heterogeneity of the disease which may significantly affect clinical decision making.

  12. Involvement of CCR6/CCL20/IL-17 Axis in NSCLC Disease Progression

    Science.gov (United States)

    Amir, Gail; Demma, Jonathan; Vernea, Fiona; Beider, Katia; Shlomai, Zippora; Wald, Hanna; Zamir, Gideon; Shapira, Oz M.; Peled, Amnon; Wald, Ori

    2011-01-01

    Objectives Autocrine and paracrine chemokine/chemokine receptor-based interactions promote non-small-cell-lung-cancer (NSCLC) carcinogenesis. CCL20/CCR6 interactions are involved in prostatic and colonic malignancy pathogenesis. The expression and function of CCL20/CCR6 and its related Th-17 type immune response in NSCLC is not yet defined. We sought to characterize the role of the CCL20/CCR6/IL-17 axis in NSCLC tumor growth. Methods A specialized histopathologist blindly assessed CCL20/CCR6 expression levels in 49 tissue samples of NSCLC patients operated in our department. Results were correlated to disease progression. Colony assays, ERK signaling and chemokine production were measured to assess cancer cell responsiveness to CCL20 and IL-17 stimulation. Results CCL20 was highly expressed in the majority (38/49, 77.5%) of tumor samples. Only a minority of samples (8/49, 16.5%) showed high CCR6 expression. High CCR6 expression was associated with a shorter disease-free survival (P = 0.008) and conferred a disease stage-independent 4.87-fold increased risk for disease recurrence (P = 0.0076, CI 95% 1.52–15.563). Cancerous cell colony-forming capacity was increased by CCL20 stimulation; this effect was dependent in part on ERK phosphorylation and signaling. IL-17 expression was detected in NSCLC; IL-17 potentiated the production of CCL20 by cancerous cells. Conclusion Our findings suggest that the CCL20/CCR6 axis promotes NSCLC disease progression. CCR6 is identified as a potential new prognostic marker and the CCL20/CCR6/IL-17 axis as a potential new therapeutic target. Larger scale studies are required to consolidate these observations. PMID:21949768

  13. Biomarkers of evasive resistance predict disease progression in cancer patients treated with antiangiogenic therapies

    Science.gov (United States)

    Pircher, Andreas; Jöhrer, Karin; Kocher, Florian; Steiner, Normann; Graziadei, Ivo; Heidegger, Isabel; Pichler, Renate; Leonhartsberger, Nicolai; Kre