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Sample records for system atrophy diagnosed

  1. Multiple system atrophy

    MedlinePlus

    ... nervous system that controls important functions such as heart rate, blood pressure, and sweating. ... A pacemaker that is programmed to stimulate the heart to beat at ... blood pressure for some people. Constipation can be treated with ...

  2. Models of Multiple System Atrophy

    PubMed Central

    Fellner, Lisa; Wenning, Gregor K.; Stefanova, Nadia

    2016-01-01

    Multiple system atrophy (MSA) is a predominantly sporadic, adult-onset, fatal neurodegenerative disease of unknown etiology. MSA is characterized by autonomic failure, levodopa-unresponsive parkinsonism, cerebellar ataxia and pyramidal signs in any combination. MSA belongs to a group of neurodegenerative disorders termed α-synucleinopathies, which also include Parkinson’s disease and dementia with Lewy bodies. Their common pathological feature is the occurrence of abnormal α-synuclein positive inclusions in neurons or glial cells. In MSA, the main cell type presenting aggregates composed of α-synuclein are oligodendroglial cells. This pathological hallmark, also called glial cytoplasmic inclusions (GCIs), is associated with progressive and profound neuronal loss in various regions of the brain. The development of animal models of MSA is justified by the limited understanding of the mechanisms of neurodegeneration and GCIs formation, which is paralleled by a lack of therapeutic strategies. Two main types of rodent models have been generated to replicate different features of MSA neuropathology. On one hand, neurotoxin-based models have been produced to reproduce neuronal loss in substantia nigra pars compacta and striatum. On the other hand, transgenic mouse models with overexpression of α-synuclein in oligodendroglia have been used to reproduce GCIs-related pathology. This chapter gives an overview of the atypical Parkinson’s syndrome MSA and summarizes the currently available MSA animal models and their relevance for pre-clinical testing of disease-modifying therapies. PMID:24338664

  3. Genetics Home Reference: multiple system atrophy

    MedlinePlus

    ... inability to hold the body upright and balanced (postural instability). The other type of multiple system atrophy , known as MSA-C, is characterized by cerebellar ataxia , which causes problems with coordination and balance. This form of the condition can also include ...

  4. [Susceptibility gene in multiple system atrophy (MSA)].

    PubMed

    Tsuji, Shoji

    2014-01-01

    To elucidate molecular bases of multiple system atrophy (MSA), we first focused on recently identified MSA multiplex families. Though linkage analyses followed by whole genome resequencing, we have identified a causative gene, COQ2, for MSA. We then conducted comprehensive nucleotide sequence analysis of COQ2 of sporadic MSA cases and controls, and found that functionally deleterious COQ2 variants confer a strong risk for developing MSA. COQ2 encodes an enzyme in the biosynthetic pathway of coenzyme Q10. Decreased synthesis of coenzyme Q10 is considered to be involved in the pathogenesis of MSA through decreased electron transport in mitochondria and increased vulnerability to oxidative stress.

  5. Diagnosable systems for intermittent faults

    NASA Technical Reports Server (NTRS)

    Mallela, S.; Masson, G. M.

    1978-01-01

    The fault diagnosis capabilities of systems composed of interconnected units capable of testing each other are studied for the case of systems with intermittent faults. A central role is played by the concept of t(i)-fault diagnosability. A system is said to be t(i)-fault diagnosable when it is such that if no more than t(i) units are intermittently faulty then a fault-free unit will never be diagnosed as faulty and the diagnosis at any time is at worst incomplete. Necessary and sufficient conditions for t(i)-fault diagnosability are proved, and bounds for t(i) are established. The conditions are in general more restrictive than those for permanent-fault diagnosability. For intermittent faults there is only one testing strategy (repetitive testing), and consequently only one type of intermittent-fault diagnosable system.

  6. In vitro models of multiple system atrophy.

    PubMed

    Stefanova, Nadia; Reindl, Markus; Poewe, Werner; Wenning, Gregor K

    2005-08-01

    alpha-Synuclein represents the major constituent of oligodendroglial cytoplasmic inclusions, the hallmark lesion of multiple system atrophy (MSA), a progressive disorder that is associated with selective degenerative cell loss in basal ganglia, cerebellum, brainstem, and spinal cord. The role of abnormal alpha-synuclein aggregation in oligodendroglial cells is still obscure, in particular, whether alpha-synuclein might impair oligodendroglial and, secondarily, neuronal integrity of those cells in the diseased brain. In an attempt to answer some of these questions, we have developed an "in vitro model of MSA" by expressing the wild-type or C-terminally truncated form of alpha-synuclein in glial cell cultures. With this simplified system, we have demonstrated that alpha-synuclein significantly affects the survival of glia and its vulnerability to environmental stress, which might represent a major step in the pathogenesis of MSA.

  7. Anhidrosis in multiple system atrophy: a preganglionic sudomotor dysfunction?

    PubMed

    Donadio, Vincenzo; Nolano, Maria; Elam, Mikael; Montagna, Pasquale; Provitera, Vincenzo; Bugiardini, Enrico; Baruzzi, Agostino; Santoro, Lucio; Liguori, Rocco

    2008-04-30

    Anhidrosis occurs in the majority of multiple system atrophy (MSA) patients but the underlying site of lesion is not well established. We describe three patients with long-standing MSA and anhidrosis diagnosed on the basis of a thermoregulatory sweating test. In biopsies of anhidrotic skin, immunofluorescence analysis disclosed a well preserved postganglionic sudomotor innervation in all three patients supporting the hypothesis of a preganglionic nerve fiber lesion underlying their anhidrosis. Postganglionic sudomotor fiber integrity was also confirmed by normal electrodermal responses in one patient, whereas such responses and microneurographically detectable skin sympathetic nerve activity were absent in the other two MSA patients, suggesting a functional inactivity of structurally intact postganglionic sympathetic skin fibers.

  8. Towards translational therapies for multiple system atrophy

    PubMed Central

    Kuzdas-Wood, Daniela; Stefanova, Nadia; Jellinger, Kurt A.; Seppi, Klaus; Schlossmacher, Michael G.; Poewe, Werner; Wenning, Gregor K.

    2014-01-01

    Multiple system atrophy (MSA) is a fatal adult-onset neurodegenerative disorder of uncertain etiopathogenesis manifesting with autonomic failure, parkinsonism, and ataxia in any combination. The underlying neuropathology affects central autonomic, striatonigral and olivopontocerebellar pathways and it is associated with distinctive glial cytoplasmic inclusions (GCIs, Papp-Lantos bodies) that contain aggregates of α-synuclein. Current treatment options are very limited and mainly focused on symptomatic relief, whereas disease modifying options are lacking. Despite extensive testing, no neuroprotective drug treatment has been identified up to now; however, a neurorestorative approach utilizing autologous mesenchymal stem cells has shown remarkable beneficial effects in the cerebellar variant of MSA. Here, we review the progress made over the last decade in defining pathogenic targets in MSA and summarize insights gained from candidate disease-modifying interventions that have utilized a variety of well-established preclinical MSA models. We also discuss the current limitations that our field faces and suggest solutions for possible approaches in cause-directed therapies of MSA. PMID:24598411

  9. Novel Therapeutic Approaches in Multiple System Atrophy

    PubMed Central

    Palma, Jose-Alberto; Kaufmann, Horacio

    2014-01-01

    Multiple system atrophy (MSA) is a sporadic, adult onset, relentlessly, progressive neurodegenerative disease characterized by autonomic abnormalities associated with parkinsonism, cerebellar dysfunction, pyramidal signs, or combinations thereof. Treatments that can halt or reverse the progression of MSA have not yet been identified. MSA is neuropathologically defined by the presence of α-synuclein–containing inclusions, particularly in the cytoplasm of oligodendrocytes (glial cytoplasmic inclusions, GCIs), which are associated with neurodegeneration. The mechanisms by which oligodendrocytic α-synuclein inclusions cause neuronal death in MSA are not completely understood. The MSA neurodegenerative process likely comprise cell-to-cell transmission of α-synuclein in a prion-like manner, α-synuclein aggregation, increased oxidative stress, abnormal expression of tubulin proteins, decreased expression of neurotrophic factors, excitotoxicity and microglial activation, and neuroinflammation. In an attempt to block each of these pathogenic mechanisms, several pharmacologic approaches have been tried and shown to exert neuroprotective effects in transgenic mouse or cellular models of MSA. These include sertraline, paroxetine, and lithium, which hamper arrival of α-synuclein to oligodendroglia; rifampicin, lithium, and non-steroidal anti-inflamatory drugs, which inhibit α-synuclein aggregation in oligodendrocytes; riluzole, rasagiline, fluoxetine and mesenchimal stem cells, which exert neuroprotective actions; and minocycline and intravenous immunoglobulins, which reduce neuroinflammation and microglial activation. These and other potential therapeutic strategies for MSA are summarized in this review. PMID:24928797

  10. System diagnosability using triplet assertion

    SciTech Connect

    Lombardi, F.

    1982-01-01

    A new technique for system diagnosability is presented. It is based on a triplet assertion strategy to overcome the asymmetric invalidation and the requirement of a central test controller. The basic characteristics of the triplet assertion are generalized to higher networks. The application of this technique to parallel processing is outlined. 24 references.

  11. Progressive Retinal Structure Abnormalities in Multiple System Atrophy

    PubMed Central

    Mendoza-Santiesteban, Carlos E.; Palma, Jose-Alberto; Martinez, Jose; Norcliffe-Kaufmann, Lucy; Hedges, Thomas R.; Kaufmann, Horacio

    2015-01-01

    Background Objective measures of disease progression that can be used as end-points in clinical trials of multiple system atrophy are necessary. We studied retinal thickness in patients with multiple system atrophy, and assessed changes over time to determine its usefulness as imaging biomarker of disease progression. Methods Cross sectional study including 24 patients with multiple system atrophy, 20 patients with Parkinson disease (PD) and 35 controls; followed by a longitudinal study of 13 multiple system atrophy (MSA) patients. Patients were evaluated with high definition-optical coherence tomography and the Unified Multiple System Atrophy Rating Scale. Evaluations were performed at baseline and at consecutive follow-up visits for up to 26 months. Results MSA subjects had normal visual acuity and color discrimination. Compared to controls, retinal nerve fiber layer (p=0.008 and p=0.001) and ganglion cell complex (p=0.013 and p=0.001) thicknesses were reduced in multiple system atrophy and in PD. No significant differences between MSA and PD were found. Over time, in patients with MSA, there was a significant reduction of the retinal nerve fiber layer and ganglion cell complex thicknesses, with estimated annual average losses of 3.7 μm and 1.8 μm respectively. Conclusions Visually asymptomatic MSA patients exhibit progressive reductions in the thickness of the retinal nerve fiber layer and, to a lesser extent, in the macular ganglion cell complex, which can be quantified by high-definition optical coherence tomography. Specific patterns of retinal nerve fiber damage could be a useful imaging biomarker of disease progression in future clinical trials. PMID:26359930

  12. Diagnosability issues in multiprocessor systems

    SciTech Connect

    Raghavan, V.

    1989-01-01

    In a seminal paper on fault diagnosis, Preparata, Metze, and Chien introduced a graph-theoretical model. Barsi, Grandoni, and Maestrini relaxed some constraints in this model to create a different model for fault diagnosis. Both these models have become the subject of intense research in the past two decades. A major open problem for these models is the question of sequential t-diagnosability-Given an arbitrary system of units and that there are no more than t faulty units in it, can we always identify at least one faulty unit The author shows that this problem is co-NP complete in both models. Recent research has shown that there are polynomial time algorithms to find the maximum number of faulty units a system can withstand and still identify all of them from a single collection of test results. He presents improved algorithms to solve this problem in both models. Using the letters n,m, and {tau} to denote the number of units, the number of tests, and the maximum number of faulty units respectively, our results can be summarized as follows: in the model of Barsi, Grandoni, and Maestrini, the algorithm has a time complexity of O(n{tau}{sup 2}/log{tau}) improving on the currently known O(n{tau}{sup 2}); in the model of Preparata, Metze, and Chien, the algorithm has a complexity of O(n{tau}{sup 2.5}) improving on the currently known O(mn{sup 1.5}). He also presents related results in the latter model, which suggest the possibility of reducing the complexity even further. Finally, he develops a general scheme for characterizing diagnosable systems. Using this scheme, he solves the open problem of characterizing t/s and sequentially t-diagnosable systems. The characterizations are then used to rederive some known results.

  13. Abnormal right hepatic artery injury resulting in right hepatic atrophy: diagnosed by laparoscopic cholecystectomy

    PubMed Central

    Martino, Valter; Ferrarese, Alessia; Bindi, Marco; Marola, Silvia; Gentile, Valentina; Rivelli, Matteo; Ferrara, Yuri; Enrico, Stefano; Berti, Stefano; Solej, Mario

    2015-01-01

    An intact hepatic artery is the gateway to successful hepato-biliary surgery. Introduction of laproscopic cholecystectomy (LC) has stimulated a renewed interest in the anatomy of hepatic artery. In this case report we have highlighted importance of variations of right hepatic artery in terms of origin and course We present a rare asymptomatic case of liver atrophy due to an intraoperative lesion of right hepatic artery. We also performed a literature review about surgical vascular lesions and tried to confirm the right concept behind “non trivial procedure” of the LC. PMID:28352750

  14. Acoustic Characteristics of Stridor in Multiple System Atrophy

    PubMed Central

    Lee, Jee Young; Joo, Eun Yeon; Nam, Hyunwoo

    2016-01-01

    Nocturnal stridor is a breathing disorder prevalent in patients with multiple system atrophy (MSA). An improved understanding of this breathing disorder is essential since nocturnal stridor carries a poor prognosis (an increased risk of sudden death). In this study, we aimed to classify types of stridor by sound analysis and to reveal their clinical significance. Patients who met the criteria for probable MSA and had undergone polysomnography (PSG) were recruited. Patients were then assessed clinically with sleep questionnaires, including the Pittsburgh Sleep Quality Index, and the Hoehn and Yahr scale. Nocturnal stridor and snoring were analyzed with the Multi-Dimensional Voice Program. Nocturnal stridor was recorded in 22 patients and snoring in 18 patients using the PSG. Waveforms of stridors were classified into rhythmic or semirhythmic after analysis of the oscillogram. Formants and harmonics were observed in both types of stridor, but not in snoring. Of the 22 patients diagnosed with stridor during the present study, fifteen have subsequently died, with the time to death after the PSG study being 1.9 ± 1.4 years (range 0.8 to 5.0 years). The rhythmic waveform group presented higher scores on the Hoehn and Yahr scale and the survival outcome of this group was lower compared to the semirhythmic waveform group (p = 0.030, p = 0.014). In the Kaplan Meier’s survival curve, the outcome of patients with rhythmic waveform was significantly less favorable than the outcome of patients with semirhythmic waveform (log-rank test, p < 0.001). Stridor in MSA can be classified into rhythmic and semirhythmic types and the rhythmic component signifies a poorer outcome. PMID:27093692

  15. A Case of Multiple System Atrophy-Cerebellar Type Preceded by Dementia

    PubMed Central

    Jang, Eun Hye; Lee, Joo Kyung; Jang, Hyun Jung; Kim, Mi-Jung; Chung, Sun Ju

    2012-01-01

    Multiple system atrophy (MSA) is a sporadic, adult-onset disease characterized by progressive degeneration of nervous systems including cerebellar, pyramidal, extrapyramidal, and autonomic system. Although a few recent studies reported that cognitive impairments could occur in patients with MSA, prominent dementia with progressive decline is not a typical clinical manifestation of MSA. In particular, dementia with MSA-cerebellar type is very rare. We have experienced a patient with 2-year history of severe cognitive impairment, who was finally diagnosed as MSA-cerebellar type. PMID:24868414

  16. Expanding the spectrum of neuronal pathology in multiple system atrophy.

    PubMed

    Cykowski, Matthew D; Coon, Elizabeth A; Powell, Suzanne Z; Jenkins, Sarah M; Benarroch, Eduardo E; Low, Phillip A; Schmeichel, Ann M; Parisi, Joseph E

    2015-08-01

    Multiple system atrophy is a sporadic alpha-synucleinopathy that typically affects patients in their sixth decade of life and beyond. The defining clinical features of the disease include progressive autonomic failure, parkinsonism, and cerebellar ataxia leading to significant disability. Pathologically, multiple system atrophy is characterized by glial cytoplasmic inclusions containing filamentous alpha-synuclein. Neuronal inclusions also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 patients with multiple system atrophy (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of patients, not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. Neuronal inclusions also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of patients

  17. Can patients without early, prominent visual deficits still be diagnosed of posterior cortical atrophy?

    PubMed Central

    Suárez-González, A.; Crutch, S.J.; Roldán Lora, F.; Franco-Macías, E.; Gil-Néciga, E.

    2016-01-01

    Background Early and progressive disabling visual impairment is a core feature for the diagnosis of posterior cortical atrophy (PCA). However, some individuals that fulfil criteria over time might initially present with an onset of prominent posterior dysfunction other than visuoperceptual. Methods The clinical profile of five patients with a predominantly ‘non-visual’ posterior presentation (PCA2) was investigated and compared with sixteen individuals with visually predominant PCA (PCA1) and eighteen with typical amnestic Alzheimer disease (tAD). Results PCA2 patients showed significantly better performance than PCA1 in one visuospatial task and were free of Balint's syndrome and visual agnosia. Compared to tAD, PCA2 showed trends towards significantly lower performance in visuoperceptual tasks, more severe apraxia and more symptoms of Gerstmann's syndrome. Conclusions Our sample of PCA2 patients did not present with clinically prominent visual symptoms but did show visual dysfunction on formal neuropsychological assessment (less pronounced than in PCA1 but more than in tAD) in addition to other posterior deficits. Broadening the definition of PCA to encompass individuals presenting with prominent ‘non-visual’ posterior dysfunction should be potentially considered in clinical and research contexts. PMID:27423559

  18. Multiple system atrophy (MSA) with massive macrophage infiltration in the ponto-cerebellar afferent system.

    PubMed

    Yokoyama, Teruo; Hasegawa, Kazuko; Horiuchi, Emiko; Yagishita, Saburou

    2007-08-01

    Multiple system atrophy (MSA) is characterized pathologically by a systemic degeneration of the olivopontocerebellar (OPC), striatonigral (SN) and autonomic systems. Massive glial cytoplasmic inclusions (GCIs) are specific for this disease. Massive lipid-laden macrophage infiltration in the degenerating tracts has not been described up to now. We here report a case of MSA with this rare event in the ponto-cerebellar (cerebellopetal) fibers. The patient, 54-year-old housewife, developed ataxia. At the age of 55 years, she was diagnosed as having MSA by cerebellar ataxia, extrapyramidal signs, autonomic failure and Horner syndrome. She died from asphyxia at the age of 57. The autopsy revealed OPC and SN system atrophy, degeneration and numerous GCIs, compatible with MSA. Numerous lipid-laden macrophages were seen in the pontine nuclei and its transverse fibers including the white matter of the cerebellum, which has not been reported up to now. There was no macrophage infiltration in the other areas. Transient ischemia, infarction and wallerian degeneration do not account for this rare event. The ponto-cerebellar (cerebellopetal) tract pathology, as observed by postmortem neuropathological study, may occur in the context of MSA.

  19. Counteracting Muscle Atrophy using Galvanic Stimulation of the Vestibular System

    NASA Technical Reports Server (NTRS)

    Fox, Robert A.; Polyakov, Igor

    1999-01-01

    The unloading of weight bearing from antigravity muscles during space flight produces significant muscle atrophy and is one of the most serious health problems facing the space program. Various exercise regimens have been developed and used either alone or in combination with pharmacological techniques to ameliorate this atrophy, but no effective countermeasure exists for this problem. The research in this project was conducted to evaluate the potential use of vestibular galvanic stimulation (VGS) to prevent muscle atrophy resulting from unloading of weight bearing from antigravity muscles. This approach was developed based on two concepts related to the process of maintaining the status of the anti-gravity neuromuscular system. These two premises are: (1) The "tone," or bias on spinal motorneurons is affected by vestibular projections that contribute importantly to maintaining muscle health and status. (2) VGS can be used to modify the excitability, or 'tone' of motorneuron of antigravity muscles. Thus, the strategy is to use VGS to modify the gain of vestibular projections to antigravity muscles and thereby change the general status of these muscles.

  20. Involvement of medullary serotonergic groups in multiple system atrophy.

    PubMed

    Benarroch, Eduardo E; Schmeichel, Ann M; Low, Phillip A; Parisi, Joseph E

    2004-03-01

    We sought to determine whether medullary serotonergic neurons were affected in multiple system atrophy (MSA). Immunostaining for tryptophan hydroxylase was performed on serial 50 microm sections of the medulla of brains obtained at autopsy from six control subjects, eight subjects with clinical diagnosis of MSA, and four with Parkinson's disease. There was a severe depletion of serotonergic neurons in the nucleus raphe magnus, raphe obscurus, raphe pallidus, and ventrolateral medulla in MSA. Depletion of serotonergic neurons may contribute to impaired control of sympathetic outflow and other abnormalities in MSA.

  1. Diagnose

    NASA Astrophysics Data System (ADS)

    Schauer, Wolfgang

    Die Zunahme der Elektronik im Kraftfahrzeug, die Nutzung von Software zur Steuerung des Fahrzeugs und die erhöhte Komplexität moderner Einspritzsysteme stellen hohe Anforderungen an das Diagnosekonzept, die Überwachung im Fahrbetrieb (On-Board-Diagnose) und die Werkstattdiagnose (Bild 1). Basis der Werkstattdiagnose ist die geführte Fehlersuche, die verschiedene Möglichkeiten von Onboard- und Offboard-Prüfmethoden und Prüfgeräten verknüpft. Im Zuge der Verschärfung der Abgasgesetzgebung und der Forderung nach laufender Überwachung hat auch der Gesetzgeber die On-Board-Diagnose als Hilfsmittel zur Abgasüberwachung erkannt und eine herstellerunabhängige Standardisierung geschaffen. Dieses zusätzlich installierte System wird OBD-System (On Board Diagnostic System) genannt.

  2. Instrumentation System Diagnoses a Thermocouple

    NASA Technical Reports Server (NTRS)

    Perotti, Jose; Santiago, Josephine; Mata, Carlos; Vokrot, Peter; Zavala, Carlos; Burns, Bradley

    2008-01-01

    An improved self-validating thermocouple (SVT) instrumentation system not only acquires readings from a thermocouple but is also capable of detecting deterioration and a variety of discrete faults in the thermocouple and its lead wires. Prime examples of detectable discrete faults and deterioration include open- and short-circuit conditions and debonding of the thermocouple junction from the object, the temperature of which one seeks to measure. Debonding is the most common cause of errors in thermocouple measurements, but most prior SVT instrumentation systems have not been capable of detecting debonding. The improved SVT instrumentation system includes power circuitry, a cold-junction compensator, signal-conditioning circuitry, pulse-width-modulation (PWM) thermocouple-excitation circuitry, an analog-to-digital converter (ADC), a digital data processor, and a universal serial bus (USB) interface. The system can operate in any of the following three modes: temperature measurement, thermocouple validation, and bonding/debonding detection. The software running in the processor includes components that implement statistical algorithms to evaluate the state of the thermocouple and the instrumentation system. When the power is first turned on, the user can elect to start a diagnosis/ monitoring sequence, in which the PWM is used to estimate the characteristic times corresponding to the correct configuration. The user also has the option of using previous diagnostic values, which are stored in an electrically erasable, programmable read-only memory so that they are available every time the power is turned on.

  3. The nature of the autonomic dysfunction in multiple system atrophy

    NASA Technical Reports Server (NTRS)

    Parikh, Samir M.; Diedrich, Andre; Biaggioni, Italo; Robertson, David

    2002-01-01

    The concept that multiple system atrophy (MSA, Shy-Drager syndrome) is a disorder of the autonomic nervous system is several decades old. While there has been renewed interest in the movement disorder associated with MSA, two recent consensus statements confirm the centrality of the autonomic disorder to the diagnosis. Here, we reexamine the autonomic pathophysiology in MSA. Whereas MSA is often thought of as "autonomic failure", new evidence indicates substantial persistence of functioning sympathetic and parasympathetic nerves even in clinically advanced disease. These findings help explain some of the previously poorly understood features of MSA. Recognition that MSA entails persistent, constitutive autonomic tone requires a significant revision of our concepts of its diagnosis and therapy. We will review recent evidence bearing on autonomic tone in MSA and discuss their therapeutic implications, particularly in terms of the possible development of a bionic baroreflex for better control of blood pressure.

  4. Systems-based discovery of tomatidine as a natural small molecule inhibitor of skeletal muscle atrophy.

    PubMed

    Dyle, Michael C; Ebert, Scott M; Cook, Daniel P; Kunkel, Steven D; Fox, Daniel K; Bongers, Kale S; Bullard, Steven A; Dierdorff, Jason M; Adams, Christopher M

    2014-05-23

    Skeletal muscle atrophy is a common and debilitating condition that lacks an effective therapy. To address this problem, we used a systems-based discovery strategy to search for a small molecule whose mRNA expression signature negatively correlates to mRNA expression signatures of human skeletal muscle atrophy. This strategy identified a natural small molecule from tomato plants, tomatidine. Using cultured skeletal myotubes from both humans and mice, we found that tomatidine stimulated mTORC1 signaling and anabolism, leading to accumulation of protein and mitochondria, and ultimately, cell growth. Furthermore, in mice, tomatidine increased skeletal muscle mTORC1 signaling, reduced skeletal muscle atrophy, enhanced recovery from skeletal muscle atrophy, stimulated skeletal muscle hypertrophy, and increased strength and exercise capacity. Collectively, these results identify tomatidine as a novel small molecule inhibitor of muscle atrophy. Tomatidine may have utility as a therapeutic agent or lead compound for skeletal muscle atrophy.

  5. Systems-based Discovery of Tomatidine as a Natural Small Molecule Inhibitor of Skeletal Muscle Atrophy*

    PubMed Central

    Dyle, Michael C.; Ebert, Scott M.; Cook, Daniel P.; Kunkel, Steven D.; Fox, Daniel K.; Bongers, Kale S.; Bullard, Steven A.; Dierdorff, Jason M.; Adams, Christopher M.

    2014-01-01

    Skeletal muscle atrophy is a common and debilitating condition that lacks an effective therapy. To address this problem, we used a systems-based discovery strategy to search for a small molecule whose mRNA expression signature negatively correlates to mRNA expression signatures of human skeletal muscle atrophy. This strategy identified a natural small molecule from tomato plants, tomatidine. Using cultured skeletal myotubes from both humans and mice, we found that tomatidine stimulated mTORC1 signaling and anabolism, leading to accumulation of protein and mitochondria, and ultimately, cell growth. Furthermore, in mice, tomatidine increased skeletal muscle mTORC1 signaling, reduced skeletal muscle atrophy, enhanced recovery from skeletal muscle atrophy, stimulated skeletal muscle hypertrophy, and increased strength and exercise capacity. Collectively, these results identify tomatidine as a novel small molecule inhibitor of muscle atrophy. Tomatidine may have utility as a therapeutic agent or lead compound for skeletal muscle atrophy. PMID:24719321

  6. Multiple system atrophy--the nature of the beast.

    PubMed Central

    Quinn, N

    1989-01-01

    Multiple system atrophy (MSA) is generally considered a rare disease, but may account for up to 10% of patients with Parkinsonism. The profusion of names for this disease, which may present to general physicians, psychiatrists, cardiologists, autonomic specialists, general neurologists and those with a special interest in Parkinsonism (this author's own perspective) or cerebellar disorders, together with ignorance of its protean manifestations, may account for its underrecognition and misdiagnosis. In this article, the history and nosology of the condition are considered, and provisional diagnostic criteria are advanced. The usefulness (or otherwise) of ancillary investigations is addressed, and the shortcomings of current methods of treatment are stressed. As with idiopathic Parkinson's disease, the ultimate goal of eradicating the disease entails better diagnosis in order to establish the cause, and thence to develop a radical treatment capable of preventing or arresting the disease process. PMID:2666581

  7. Multiple system atrophy: current and future approaches to management

    PubMed Central

    Flabeau, Olivier; Meissner, Wassilios G.; Tison, François

    2010-01-01

    Multiple system atrophy (MSA) is a rare neurodegenerative disorder without any effective treatment in slowing or stopping disease progression. It is characterized by poor levodopa responsive Parkinsonism, cerebellar ataxia, pyramidal signs and autonomic failure in any combination. Current therapeutic strategies are primarily based on dopamine replacement and improvement of autonomic failure. However, symptomatic management remains disappointing and no curative treatment is yet available. Recent experimental evidence has confirmed the key role of alpha-synuclein aggregation in the pathogenesis of MSA. Referring to this hypothesis, transgenic and toxic animal models have been developed to assess candidate drugs for MSA. The standardization of diagnosis criteria and assessment procedures will allow large multicentre clinical trials to be conducted. In this article we review the available symptomatic treatment, recent results of studies investigating potential neuroprotective drugs, and future approaches for the management in MSA. PMID:21179616

  8. Multiple System Atrophy: A Clinical and Neuropathological Perspective

    PubMed Central

    Ubhi, Kiren; Low, Phillip; Masliah, Eliezer

    2011-01-01

    Multiple System Atrophy (MSA) is a neurodegenerative disease presenting with motor abnormalities including akinesia, rigidity and postural instability. Whilst improved diagnostic criteria have aided accurate diagnosis of MSA, understanding of neuropathological aspects underlying MSA was bolstered by the identification of alpha-synuclein (α-syn) as the primary constituent of the abnormal protein aggregations observed in the brains of MSA patients. The generation of transgenic animal models of MSA coupled with an increasing understanding of the biochemical structure and function of α-syn has highlighted a number of key pathological pathways thought to underlie the neurodegeneration observed in MSA. This review will summarize key findings in the field, discuss current areas of debate and describe current experimental approaches towards disease-modifying therapies. PMID:21962754

  9. Clinicopathological study of 35 cases of multiple system atrophy.

    PubMed Central

    Wenning, G K; Ben-Shlomo, Y; Magalhães, M; Daniel, S E; Quinn, N P

    1995-01-01

    The clinical and pathological features of 35 cases with multiple system atrophy collected in the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) between 1985 and 1992 have been analysed. The median age of onset was 55 (range 33.3-75.8) years and median survival was 7.3 (range 2.1-11.5) years. Parkinsonism, usually asymmetric, occurred in all, and autonomic failure in all but one case. Cerebellar signs were noted in 34% and pyramidal features in 54% of the cases. Glial cytoplasmic inclusions were found in all cases with adequate fixation. Lewy bodies were detected in three cases. The substantia nigra was (usually severely) depleted of cells in all cases. With two exceptions the putamen was atrophic; the caudate and pallidum were less commonly and less severely affected. Overall nigrostriatal cell loss correlated with severity of disease at the time of death. The latest, but not the best, recorded levodopa response tended to be inversely related to the degree of putaminal degeneration. The olivopontocerebellar system was involved in 88% of the cases, the cerebellar vermis usually being more severely affected than the hemispheres. The presence of associated cerebellar pathology was, however, unrelated to the presence of cerebellar signs in life. PMID:7876845

  10. Convenient diagnosis of spinal and bulbar muscular atrophy using a microchip electrophoresis system.

    PubMed

    Maruyama, Hirofumi; Morino, Hiroyuki; Izumi, Yuishin; Noda, Kouichi; Kawakami, Hideshi

    2013-01-01

    Spinal and bulbar muscular atrophy (SBMA) is a slowly progressive motor neuron disease. Lower and primary sensory neuronopathy is one of the major neuropathological changes that occurs in SBMA. However, many sings are common to SBMA and amyotrophic lateral sclerosis (ALS), and SBMA patients are sometimes diagnosed with ALS. Leuprorelin may be used to treat SBMA, but an accurate diagnosis is necessary for treatment and care. Genetic diagnosis can be performed to detect the expansion of a CAG repeat in the androgen receptor gene in SBMA patients. To screen for this expansion, we used a microchip electrophoresis system. The discrepancy between the actual repeat length and that found by the microchip electrophoresis system was roughly dependent on the repeat length. The mean difference was -6.8 base pairs (bp) in SBMA patients, -0.30 bp in controls. The microchip electrophoresis results were approximately 2 CAG repeats shorter than the actual repeat length in SBMA patients. Using this method, we screened our ALS samples (31 were familial, 271 were sporadic): 4 subjects were diagnosed with SBMA; 2 had familial ALS, and 2 had sporadic ALS (0.7%). The microchip electrophoresis system is semi-quantitative, convenient and useful for screening a large number of samples.

  11. Skin vasodilator response to local heating in multiple system atrophy.

    PubMed

    Yamanaka, Yoshitaka; Asahina, Masato; Mathias, Christopher J; Akaogi, Yuichi; Koyama, Yu; Hattori, Takamichi

    2007-12-01

    Local heating of nonglabrous skin increases skin blood flow (SkBF) in two phases. The initial peak (P1) is mediated by a sensory-axon reflex and the plateau phase (P2) by local production of substances such as nitric oxide. We evaluated the SkBF response to local heating in 15 multiple system atrophy (MSA) patients with autonomic failure and 12 age-matched healthy controls. The mean ratio of SkBF at P1 to that at baseline (SkBF(P1)/SkBF(base) ratio) in MSA was significantly lower than that in controls (P < 0.01). The mean ratio of SkBF at P2 seemed to be slightly reduced in the MSA patients, compared with controls, although there was no significant difference. The P1 phase is thought to be mediated by a sensory-axon reflex modulated by sympathetic nerve activity. These findings are indicative of the skin sympathetic vasomotor dysfunction in MSA.

  12. Therapeutic advances in multiple system atrophy and progressive supranuclear palsy.

    PubMed

    Poewe, Werner; Mahlknecht, Philipp; Krismer, Florian

    2015-09-15

    Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are relentlessly progressive neurodegenerative diseases leading to severe disability and ultimately death within less than 10 y. Despite increasing efforts in basic and clinical research, effective therapies for these atypical parkinsonian disorders are lacking. Although earlier small clinical studies in MSA and PSP mainly focused on symptomatic treatment, advances in the understanding of the molecular underpinnings of these diseases and in the search for biomarkers have paved the way for the first large and well-designed clinical trials aiming at disease modification. Targets of intervention in these trials have included α-synuclein inclusion pathology in the case of MSA and tau-related mechanisms in PSP. Since 2013, four large randomized, placebo-controlled, double-blind disease-modification trials have been completed and published, using rasagiline (MSA), rifampicin (MSA), tideglusib (PSP), or davunetide (PSP). All of these failed to demonstrate signal efficacy with regard to the primary outcome measures. In addition, two randomized, placebo-controlled, double-blind trials have studied the efficacy of droxidopa in the symptomatic treatment of neurogenic orthostatic hypotension, including patients with MSA, with positive results in one trial. This review summarizes the design and the outcomes of these and other smaller trials published since 2013 and attempts to highlight priority areas of future therapeutic research in MSA and PSP. © 2015 International Parkinson and Movement Disorder Society.

  13. Diffusion tensor imaging in the characterization of multiple system atrophy

    PubMed Central

    Rulseh, Aaron Michael; Keller, Jiri; Rusz, Jan; Syka, Michael; Brozova, Hana; Rusina, Robert; Havrankova, Petra; Zarubova, Katerina; Malikova, Hana; Jech, Robert; Vymazal, Josef

    2016-01-01

    Purpose Multiple system atrophy (MSA) is a rare neurodegenerative disease that remains poorly understood, and the diagnosis of MSA continues to be challenging. We endeavored to improve the diagnostic process and understanding of in vivo characteristics of MSA by diffusion tensor imaging (DTI). Materials and methods Twenty MSA subjects, ten parkinsonian dominant (MSA-P), ten cerebellar dominant (MSA-C), and 20 healthy volunteer subjects were recruited. Fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity maps were processed using tract-based spatial statistics. Diffusion data were additionally evaluated in the basal ganglia. A support vector machine was used to assess diagnostic utility, leave-one-out cross-validation in the evaluation of classification schemes, and receiver operating characteristic analyses to determine cutoff values. Results We detected widespread changes in the brain white matter of MSA subjects; however, no group-wise differences were found between MSA-C and MSA-P subgroups. Altered DTI metrics in the putamen and middle cerebellar peduncles were associated with a positive parkinsonian and cerebellar phenotype, respectively. Concerning clinical applicability, we achieved high classification performance on mean diffusivity data in the combined bilateral putamen and middle cerebellar peduncle (accuracy 90.3%±9%, sensitivity 86.5%±11%, and specificity 99.3%±4%). Conclusion DTI in the middle cerebellar peduncle and putamen may be used in the diagnosis of MSA with a high degree of accuracy. PMID:27616888

  14. Transmission of multiple system atrophy prions to transgenic mice

    PubMed Central

    Watts, Joel C.; Giles, Kurt; Oehler, Abby; Middleton, Lefkos; Dexter, David T.; Gentleman, Steve M.; DeArmond, Stephen J.; Prusiner, Stanley B.

    2013-01-01

    Prions are proteins that adopt alternative conformations, which become self-propagating. Increasing evidence argues that prions feature in the synucleinopathies that include Parkinson’s disease, Lewy body dementia, and multiple system atrophy (MSA). Although TgM83+/+ mice homozygous for a mutant A53T α-synuclein transgene begin developing CNS dysfunction spontaneously at ∼10 mo of age, uninoculated TgM83+/− mice (hemizygous for the transgene) remain healthy. To determine whether MSA brains contain α-synuclein prions, we inoculated the TgM83+/− mice with brain homogenates from two pathologically confirmed MSA cases. Inoculated TgM83+/− mice developed progressive signs of neurologic disease with an incubation period of ∼100 d, whereas the same mice inoculated with brain homogenates from spontaneously ill TgM83+/+ mice developed neurologic dysfunction in ∼210 d. Brains of MSA-inoculated mice exhibited prominent astrocytic gliosis and microglial activation as well as widespread deposits of phosphorylated α-synuclein that were proteinase K sensitive, detergent insoluble, and formic acid extractable. Our results provide compelling evidence that α-synuclein aggregates formed in the brains of MSA patients are transmissible and, as such, are prions. The MSA prion represents a unique human pathogen that is lethal upon transmission to Tg mice and as such, is reminiscent of the prion causing kuru, which was transmitted to chimpanzees nearly 5 decades ago. PMID:24218576

  15. Analysis of the prion protein gene in multiple system atrophy.

    PubMed

    Chelban, Viorica; Manole, Andreea; Pihlstrøm, Lasse; Schottlaender, Lucia; Efthymiou, Stephanie; OConnor, Emer; Meissner, Wassilios G; Holton, Janice L; Houlden, Henry

    2017-01-01

    Neurodegenerative diseases are a very diverse group of disorders but they share some common mechanisms such as abnormally misfolded proteins with prion-like propagation and aggregation. Creutzfeldt-Jakob disease (CJD) is the most prevalent prion disease in humans. In the sporadic form of CJD the only known risk factor is the codon 129 polymorphism. Recent reports suggested that α-synuclein in multiple system atrophy (MSA) has similar pathogenic mechanisms as the prion protein. Here we present 1 Italian family with MSA and prion disease. Also, cases of concurrent MSA and prion pathology in the same individual or family suggest the possibility of molecular interaction between prion protein and α-synuclein in the process of protein accumulation and neurodegeneration, warranting further investigations. We assessed the PRNP gene by whole-exome sequencing in 264 pathologically confirmed MSA cases and 462 healthy controls to determine whether the 2 diseases share similar risk factors. We then analyzed codon 129 polymorphism by Sanger sequencing and compared with previously published results in sporadic CJD. Homozygosity at codon 129 was present in 50% of pathologically confirmed MSA cases and in 58% of normal controls (odds ratio, 0.7 (95% confidence interval of 0.5-0.9)) compared with 88.2% in sporadic CJD. Our data show that the homozygous state of position 129 in the PRNP is not a risk factor for MSA. No other variants in the PRNP gene were associated with increased risk for MSA.

  16. Pathogenesis of laryngeal narrowing in patients with multiple system atrophy

    PubMed Central

    Isono, Shiroh; Shiba, Keisuke; Yamaguchi, Mika; Tanaka, Atsuko; Hattori, Takamichi; Konno, Akiyoshi; Nishino, Takashi

    2001-01-01

    We do not fully understand the pathogenesis of nocturnal laryngeal stridor in patients with multiple system atrophy (MSA). Recent studies suggest that inspiratory thyroarytenoid (TA) muscle activation has a role in the development of the stridor.The breathing pattern and firing timing of TA muscle activation were determined in ten MSA patients, anaesthetized with propofol and breathing through the laryngeal mask airway, while the behaviour of the laryngeal aperture was being observed endoscopically.Two distinct breathing patterns, i.e. no inspiratory flow limitation (no-IFL) and IFL, were identified during the measurements. During IFL, significant laryngeal narrowing was observed leading to an increase in laryngeal resistance and end-tidal carbon dioxide concentration. Development of IFL was significantly associated with the presence of phasic inspiratory activation of TA muscle. Application of continuous positive airway pressure suppressed the TA muscle activation.The results indicate that contraction of laryngeal adductors during inspiration narrows the larynx leading to development of inspiratory flow limitation accompanied by stridor in patients with MSA under general anaesthesia. PMID:11579172

  17. Animal modeling an oligodendrogliopathy--multiple system atrophy.

    PubMed

    Bleasel, Jonathan M; Halliday, Glenda M; Kim, Woojin Scott

    2016-02-09

    Multiple system atrophy (MSA) is a rare, yet rapidly-progressive neurodegenerative disease that presents clinically with autonomic failure in combination with parkinsonism or cerebellar ataxia. The definitive neuropathology differentiating MSA from Lewy body diseases is the presence of α-synuclein aggregates in oligodendrocytes (called glial cytoplasmic inclusion or GCI) rather than the fibrillar aggregates in neurons (called Lewy bodies). This makes the pathological pathway(s) in MSA unique in that oligodendrocytes are involved rather than predominantly neurons, as is most other neurodegenerative disorders. MSA is therefore regarded as an oligodendrogliopathy. The etiology of MSA is unknown. No definitive risk factors have been identified, although α-synuclein and other genes have been variably linked to MSA risk. Utilization of postmortem brain tissues has greatly advanced our understanding of GCI pathology and the subsequent neurodegeneration. However, extrapolating the early pathogenesis of MSA from such resource has been difficult and limiting. In recent years, cell and animal models developed for MSA have been instrumental in delineating unique MSA pathological pathways, as well as aiding in clinical phenotyping. The purpose of this review is to bring together and discuss various animal models that have been developed for MSA and how they have advanced our understanding of MSA pathogenesis, particularly the dynamics of α-synuclein aggregation. This review will also discuss how animal models have been used to explore potential therapeutic avenues for MSA, and future directions of MSA modeling.

  18. A genome-wide association study in multiple system atrophy

    PubMed Central

    Sailer, Anna; Nalls, Michael A.; Schulte, Claudia; Federoff, Monica; Price, T. Ryan; Lees, Andrew; Ross, Owen A.; Dickson, Dennis W.; Mok, Kin; Mencacci, Niccolo E.; Schottlaender, Lucia; Chelban, Viorica; Ling, Helen; O'Sullivan, Sean S.; Wood, Nicholas W.; Traynor, Bryan J.; Ferrucci, Luigi; Federoff, Howard J.; Mhyre, Timothy R.; Morris, Huw R.; Deuschl, Günther; Quinn, Niall; Widner, Hakan; Albanese, Alberto; Infante, Jon; Bhatia, Kailash P.; Poewe, Werner; Oertel, Wolfgang; Höglinger, Günter U.; Wüllner, Ullrich; Goldwurm, Stefano; Pellecchia, Maria Teresa; Ferreira, Joaquim; Tolosa, Eduardo; Bloem, Bastiaan R.; Rascol, Olivier; Meissner, Wassilios G.; Hardy, John A.; Revesz, Tamas; Holton, Janice L.; Gasser, Thomas; Wenning, Gregor K.; Singleton, Andrew B.

    2016-01-01

    Objective: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS). Methods: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed. Results: We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 × 10−6, including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA. Conclusions: We present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps. PMID:27629089

  19. Urinary and erectile dysfunction in multiple system atrophy (MSA).

    PubMed

    Papatsoris, A G; Papapetropoulos, S; Singer, C; Deliveliotis, C

    2008-01-01

    Multiple system atrophy (MSA) is a neurodegenerative disease of undetermined etiology that occurs sporadically and manifests itself as a combination of parkinsonian, autonomic, cerebellar, and pyramidal signs. Despite the lack of effective therapies, some of the symptoms may be, at least temporarily, improved with adequate symptomatic therapies. Urinary and erectile dysfunction (ED) symptoms are prominent early features in male MSA patients. Lower urinary tract infections (UTIs) are a major cause of morbidity and mortality in this disorder. More than 50% of MSA patients suffer from recurrent lower UTIs and a significant number (approximately 25%) die of complications related to them. Urogenital symptoms in MSA are usually due to a complex mixture of central and peripheral nervous abnormalities, sometimes superimposed on previous local pathological conditions such as benign prostatic hyperplasia and perineal laxity. There have been instances were MSA-related urological symptoms were confused with symptoms of benign prostatic hyperplasia, leading to unnecessary urological surgery. In this review, we present the phenotypic range and therapeutic approaches for common storage and voiding urological symptoms and ED, in patients with MSA.

  20. Chronic Traumatic Encephalopathy Pathology in Multiple System Atrophy.

    PubMed

    Koga, Shunsuke; Dickson, Dennis W; Bieniek, Kevin F

    2016-10-01

    Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder associated with repetitive traumatic brain injury. Multiple system atrophy (MSA) is a Parkinsonian disorder that can result in repetitive falls with associated head trauma. We hypothesized that patients with neurodegenerative disorders like MSA could develop CTE pathology. Therefore, we assessed CTE pathology in 139 MSA cases in our brain bank. Sections from convexity cerebral cortices were screened by immunohistochemistry with anti-phospho-tau antibody. For cases with suggestive CTE pathology, further sections of basal forebrain and hippocampus were immunostained. Consensus criteria were used to make the diagnosis of CTE and aging-related tau astrogliopathy (ARTAG) was differentiated from CTE pathology. Pertinent clinical information was derived from the available records and online searches. Of the 139 MSA cases, 8 (6%) had CTE pathology and 10 (8%) had ARTAG pathology. All 8 cases with CTE were male and 4 of them had a documented history of contact sports. The median age at death in MSA with CTE was younger than in MSA without CTE or MSA with ARTAG (60, 67, and 74 years, respectively; p = 0.002). Even without a known history of contact sports or head trauma, a small subset of cases with MSA had CTE pathology.

  1. Microglial activation in multiple system atrophy: a potential role for NF-kappaB/rel proteins.

    PubMed

    Schwarz, S C; Seufferlein, T; Liptay, S; Schmid, R M; Kasischke, K; Foster, O J; Daniel, S; Schwarz, J

    1998-09-14

    Microglial activation is a prominent feature of affected brain areas in multiple system atrophy. Microglia express proinflammatory peptides, which may be a result of activation of nuclear factor-KB. We investigated the nuclear presence of RelA, the 65 kDa subunit of the NF-KB/RelA family in striatum and brain stem of patients with multiple system atrophy. Affected brain areas of patients with multiple system atrophy showed a marked immunoreactivity for nuclear Rel A p65, which was almost exclusively localized in activated microglia. Interestingly nuclear translocation of Rel A was not detected in striatal tissue of controls and Parkinson disease patients. Thus, NF-kappaB/Rel A complexes may play a role in mediating microglial activation in multiple system atrophy.

  2. Diagnosing Parkinson's Diseases Using Fuzzy Neural System

    PubMed Central

    Abiyev, Rahib H.; Abizade, Sanan

    2016-01-01

    This study presents the design of the recognition system that will discriminate between healthy people and people with Parkinson's disease. A diagnosing of Parkinson's diseases is performed using fusion of the fuzzy system and neural networks. The structure and learning algorithms of the proposed fuzzy neural system (FNS) are presented. The approach described in this paper allows enhancing the capability of the designed system and efficiently distinguishing healthy individuals. It was proved through simulation of the system that has been performed using data obtained from UCI machine learning repository. A comparative study was carried out and the simulation results demonstrated that the proposed fuzzy neural system improves the recognition rate of the designed system. PMID:26881009

  3. Differential involvement of hypothalamic vasopressin neurons in multiple system atrophy.

    PubMed

    Benarroch, Eduardo E; Schmeichel, Ann M; Sandroni, Paola; Low, Phillip A; Parisi, Joseph E

    2006-10-01

    We sought to determine whether there is differential involvement of different groups of hypothalamic arginine-vasopressin (AVP) synthesizing neurons in multiple system atrophy (MSA). Hypothalamus was obtained from five subjects with clinical diagnosis of MSA confirmed neuropathologically and five age-matched controls. Sections were immunostained for AVP, and cells with visible nuclei were counted in the posterior portion of the paraventricular nucleus (PVNp), supraoptic nucleus (SON), magnocellular PVN and suprachiasmatic nucleus (SCN). Sections of the hypothalamus and medulla were also immunostained for tyrosine hydroxylase (TH). There was a significant loss of AVP neurons in the PVNp in MSA compared with controls (17 +/- 3 versus 59 +/- 10 cells/section, P < 0.01). There was preservation of AVP- and TH-immunoreactive neurons in the SON and magnocellular PVN in all MSA cases. In contrast, there was marked depletion of TH-immunoreactive fibres innervating these magnocellular AVP neurons, coincident with a loss of neurons in the A1 area (6 +/- 1 versus 13 +/- 1 cells/section, P < 0.01). There was loss of AVP neurons in the SCN in MSA compared with control cases (14 +/- 3 versus 71 +/- 16 cells/section, P < 0.02). Our results indicate that, in MSA, loss of AVP neurons in the PVNp may contribute to sympathetic failure, whereas loss of catecholaminergic input from the brainstem to the magnocellular AVP neurons may contribute to impaired AVP secretion in response to orthostatic stress. Loss of AVP neurons in the SCN may contribute to impaired circadian regulation of endocrine and autonomic functions.

  4. Comparison of Different Symptom Assessment Scales for Multiple System Atrophy.

    PubMed

    Matsushima, Masaaki; Yabe, Ichiro; Oba, Koji; Sakushima, Ken; Mito, Yasunori; Takei, Asako; Houzen, Hideki; Tsuzaka, Kazufumi; Yoshida, Kazuto; Maruo, Yasunori; Sasaki, Hidenao

    2016-04-01

    To identify the most sensitive scale for use in clinical trials on multiple system atrophy (MSA), a short and sensitive scale is needed for MSA clinical trials. Potential candidates are the Unified MSA Rating Scale (UMSARS), Scale for the Assessment and Rating of Ataxia (SARA), Berg Balance Scale (BBS), MSA Health-Related Quality of Life scale (MSA-QoL), and Scales for Outcomes in Parkinson's Disease-Autonomic questionnaire (SCOPA-AUT). We enrolled patients with MSA from eight hospitals in Hokkaido, Japan. Board-certified neurologists assessed each patient at 6-month intervals and scored them on the UMSARS, SARA, BBS, MSA-QoL, and SCOPA-AUT. Score changes were evaluated using the standardized response mean (SRM). The correlation between disease duration and each score was examined. The first evaluation was conducted on 85 patients (60 patients with MSA cerebellar ataxia dominant subtype [MSA-C] and 25 patients with MSA Parkinsonism-dominant subtype [MSA-P]). Sixty-nine patients were examined after 6 months and 63 patients after 12 months. The UMSARS Part 4 had the largest SRM after 6 months and the SARA after 12 months. SRMs for MSA-P, the shorter duration group, and the early-onset group were larger than were those for MSA-C, the longer duration group, and the late-onset group. SRMs for items regarding skilled hand activities, walking, and standing were relatively large. Our study indicates that the UMSARS (parts 2 and 4), SARA, and BBS are sensitive scales for evaluating MSA progression over 12 months. Items with large SRMs effectively evaluated short-term changes.

  5. Health-related quality of life in multiple system atrophy.

    PubMed

    Schrag, Anette; Geser, Felix; Stampfer-Kountchev, Michaela; Seppi, Klaus; Sawires, Martin; Köllensperger, Martin; Scherfler, Christoph; Quinn, Niall; Pellecchia, Maria T; Barone, Paolo; Del Sorbo, Francesca; Albanese, Alberto; Ostergaard, Karen; Dupont, Erik; Cardozo, Adriana; Tolosa, Eduardo; Nilsson, Christer F; Widner, Håkan; Lindvall, Olle; Giladi, Nir; Gurevich, Tanya; Daniels, Christine; Deuschl, Günther; Coelho, Miguel; Sampaio, Cristina; Abele, Michael; Klockgether, Thomas; Schimke, Nicole; Eggert, Karla M; Oertel, Wolfgang; Djaldetti, Ruth; Colosimo, Carlo; Meco, Giuseppe; Poewe, Werner; Wenning, Gregor K

    2006-06-01

    Although multiple system atrophy (MSA) is a neurodegenerative disorder leading to progressive disability and decreased life expectancy, little is known about patients' own evaluation of their illness and factors associated with poor health-related quality of life (Hr-QoL). We, therefore, assessed Hr-QoL and its determinants in MSA. The following scales were applied to 115 patients in the European MSA-Study Group (EMSA-SG) Natural History Study: Medical Outcome Study Short Form (SF-36), EQ-5D, Beck Depression Inventory (BDI), Mini-Mental state examination (MMSE), Unified MSA Rating Scale (UMSARS), Hoehn & Yahr (H&Y) Parkinson's disease staging scale, Composite Autonomic Symptom Scale (COMPASS), and Parkinson's Disease Sleep Scale (PDSS). Forty-six percent of patients had moderate to severe depression (BDI > or = 17); Hr-QoL scores on the SF-36 and EQ-5D were significantly impaired. Pain, the only domain with similar scores in MSA and published PD patients, was reported more frequently in patients with MSA-P (predominantly parkinsonian motor subtype) than MSA-C (predominantly cerebellar motor subtype; 76% vs. 50%; P = 0.005). Hr-QoL scores correlated most strongly with UMSARS motor, COMPASS, and BDI scores but not with MMSE scores, age at onset, or disease duration. The COMPASS and UMSARS activities of daily living scores were moderate-to-strong predictors for the SF-36 physical summary score and the BDI and UMSARS motor scores for the SF-36 mental summary score. This report is the first study to show that Hr-QoL is significantly impaired in MSA. Although not all possible factors related to impaired Hr-QoL in MSA could be assessed, autonomic dysfunction, motor impairment, and depression were most closely associated with poor Hr-QoL, and therapeutic management, therefore, should concentrate upon these aspects of the disease.

  6. Fuzzy expert system for diagnosing diabetic neuropathy

    PubMed Central

    Rahmani Katigari, Meysam; Ayatollahi, Haleh; Malek, Mojtaba; Kamkar Haghighi, Mehran

    2017-01-01

    AIM To design a fuzzy expert system to help detect and diagnose the severity of diabetic neuropathy. METHODS The research was completed in 2014 and consisted of two main phases. In the first phase, the diagnostic parameters were determined based on the literature review and by investigating specialists’ perspectives (n = 8). In the second phase, 244 medical records related to the patients who were visited in an endocrinology and metabolism research centre during the first six months of 2014 and were primarily diagnosed with diabetic neuropathy, were used to test the sensitivity, specificity, and accuracy of the fuzzy expert system. RESULTS The final diagnostic parameters included the duration of diabetes, the score of a symptom examination based on the Michigan questionnaire, the score of a sign examination based on the Michigan questionnaire, the glycolysis haemoglobin level, fasting blood sugar, blood creatinine, and albuminuria. The output variable was the severity of diabetic neuropathy which was shown as a number between zero and 10, had been divided into four categories: absence of the disease, (the degree of severity) mild, moderate, and severe. The interface of the system was designed by ASP.Net (Active Server Pages Network Enabled Technology) and the system function was tested in terms of sensitivity (true positive rate) (89%), specificity (true negative rate) (98%), and accuracy (a proportion of true results, both positive and negative) (93%). CONCLUSION The system designed in this study can help specialists and general practitioners to diagnose the disease more quickly to improve the quality of care for patients. PMID:28265346

  7. [A Patient with Early-Stage Multiple System Atrophy Showing Augmented Nystagmus in Light].

    PubMed

    Oguri, Masayoshi; Nakamura, Yousuke; Hara, Ayako; Kitano, Hiroya; Motokura, Toru

    2015-04-01

    The ability to fix the eyes on a target, visual fixation, is important for the maintenance of equilibrium. The visual suppression (VS) test is one method of measuring the function of visual fixation. The test records caloric nystagmus by electrooculography, and the maximum slow phase velocity of caloric nystagmus in darkness is compared with the slow phase velocity in light with eyes fixed. Lesions of the cerebellum, brain stem, and cerebrum cause abnormalities of VS. We report a patient whose VS became a clue in the diagnosis of a disorder of the central nervous system. A 54-year-old man complained of dizziness, which gradually increased in frequency over 5 months. He visited several clinics, where vestibular neutritis and cervical spondylosis were suspected and treated without improvement. Although a pure-tone auditory test revealed bilateral normal hearing, a caloric test showed a weak response and VS was lost with augmentation of caloric nystagmus in light on both sides. Both eye tracking and optokinetic nystagmus tests were abnormal. Although magnetic resonance imaging showed no abnormalities, single photon emission computed tomography revealed decreased blood flow in the parietal area. VS of caloric nystagmus towards the side of a lesion is reduced or abolished after unilateral flocculus damage, and is abolished bilaterally after bilateral flocculus damage. In the case of a parietal lobe or pontine lesion, VS is strongly abolished, and even augmentation of caloric nystagmus may be observed. In the present case, the patient was diagnosed with multiple-system atrophy after onset of dizziness.

  8. Vaginal Atrophy

    MedlinePlus

    Vaginal atrophy Overview By Mayo Clinic Staff Vaginal atrophy (atrophic vaginitis) is thinning, drying and inflammation of the vaginal walls due to your body having less estrogen. Vaginal atrophy occurs most ...

  9. Atrophy, hypertrophy, and hypoxemia induce transcriptional regulators of the ubiquitin proteasome system in the rat heart

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In skeletal muscle, transcript levels of proteins regulating the ubiquitin proteasome system (UPS) increase with atrophy and decrease with hypertrophy. Whether the same is true for heart muscle is not known. We set out to characterize the transcriptional profile of regulators of the UPS during atrop...

  10. Cognitive impairment in patients with multiple system atrophy and progressive supranuclear palsy.

    PubMed

    Brown, Richard G; Lacomblez, Lucette; Landwehrmeyer, Bernard G; Bak, Thomas; Uttner, Ingo; Dubois, Bruno; Agid, Yves; Ludolph, Albert; Bensimon, Gilbert; Payan, Christine; Leigh, Nigel P

    2010-08-01

    This article reports the severity and profile of neuropsychological impairment on a prevalent cohort of patients with a clinical diagnosis of either multiple system atrophy (n=372) or progressive supranuclear palsy (n=311) from the Neuroprotection and Natural History in Parkinson Plus Syndromes cohort. The Dementia Rating Scale and Frontal Assessment Battery were used to assess global cognition and executive dysfunction. For the Dementia Rating Scale impairment was observed in approximately 57% of the progressive supranuclear palsy group and 20% of the multiple system atrophy group. In the former, impairment in a single cognitive domain was observed in 40%, with the same number showing impairment in multiple domains, while in the latter the figures were 28.6 and 13.5%, respectively. On the Frontal Assessment Battery, impairment was observed in 62.0% of patients with progressive supranuclear palsy and 31.8% of those with multiple system atrophy. Although the progressive supranuclear palsy group performed worse overall, the cognitive profiles of the two groups on the Dementia Rating Scale subscales were identical, with the main impairment of the Initiation and Perseveration subscale. The impaired patients in the two groups were largely indistinguishable, qualitatively and quantitatively. Impairment was associated with greater age and clinical disability in both groups and was evident even in the early stages (22% in multiple system atrophy and 50% in progressive supranuclear palsy). Where a pathological diagnosis was available, the original clinical diagnosis was confirmed in the majority of cases, including those with significant cognitive impairment. The rate of impairment in those with a confirmed pathological diagnosis was comparable to that of the sample as a whole. These results demonstrate, in the largest prospectively recruited cohort of patients with progressive supranuclear palsy and multiple system atrophy studied to date, the existence of a cognitive

  11. Multiple System Atrophy with Orthostatic Hypotension (Shy-Drager Syndrome)

    MedlinePlus

    ... the onset of symptoms. A problem with the respiratory system is the most common cause of death. × Prognosis ... the onset of symptoms. A problem with the respiratory system is the most common cause of death. View ...

  12. Erythropoietin is Neuroprotective in a Transgenic Mouse Model of Multiple System Atrophy

    PubMed Central

    Pallua, Anton; Stefanova, Nadia; Poewe, Werner; Wenning, Gregor K.

    2016-01-01

    Multiple system atrophy is a rapidly progressive neurodegenerative disorder with a markedly reduced life expectancy. Failure of symptomatic treatment raises an urgent need for disease-modifying strategies. We have investigated the neuroprotective potential of erythropoietin in (proteolipid protein)-α-synuclein transgenic mice exposed to 3-nitropropionic acid featuring multiple system atrophy-like pathology including oligodendroglial α-synuclein inclusions and selective neuronal degeneration. Mice were treated with erythropoietin starting before (early erythropoietin) and after (late erythropoietin) intoxication with 3-nitropropionic acid. Nonintoxicated animals receiving erythropoietin and intoxicated animals treated with saline served as control groups. Behavioral tests included pole test, open field activity, and motor behavior scale. Immunohistochemistry for tyrosine hydroxylase and dopamine and cyclic adenosine monophosphate-regulated phosphoprotein (DARPP-32) was analyzed stereologically. Animals receiving erythropoietin before and after 3-nitropropionic acid intoxication scored significantly lower on the motor behavior scale and they performed better in the pole test than controls with no significant difference between early and late erythropoietin administration. Similarly, rearing scores were worse in 3-nitropropionic acid-treated animals with no difference between the erythropoietin subgroups. Immunohistochemistry revealed significant attenuation of 3-nitropropionic acid-induced loss of tyrosine hydroxylase and DARPP-32 positive neurons in substantia nigra pars compacta and striatum, respectively, in both erythropoietin-treated groups without significant group difference in the substantia nigra. However, at striatal level, a significant difference between early and late erythropoietin administration was observed. In the combined (proteolipid protein)-α-synuclein 3-nitropropionic acid multiple system atrophy mouse model, erythropoietin appears to rescue

  13. Quantifying cerebellar atrophy in multiple system atrophy of the cerebellar type (MSA-C) using three-dimensional gyrification index analysis.

    PubMed

    Wu, Yu-Te; Shyu, Kuo-Kai; Jao, Chii-Wen; Liao, Yuan-Lin; Wang, Tzu-Yun; Wu, Hsiu-Mei; Wang, Po-Shan; Soong, Bing-Wen

    2012-05-15

    Multiple system atrophy of the cerebellar type (MSA-C) is a degenerative neurological disease of the central nervous system. This study employed a method named, "surface-based three-dimensional gyrification index" (3D-GI) to quantify morphological changes in normal cerebellum (including brainstem) and atrophied cerebellum, in patients with MSA-C. We assessed whether 3D-GI can exclude gender and age differences to quantify cerebellum and brainstem atrophy more accurately. Sixteen healthy subjects and 16 MSA-C patients participated in this study. We compared 3D-GI values and volumes in the cerebellum, based on T1-weighted MR images. We also compared the images of reconstructed 3D cerebellum gray matter (3D-CBGM) and cerebellum white matter (3D-CBWM) to detect the atrophied cerebellar region in MSA-C patients. The 3D-GI values were in a stable range with small variances, exhibiting no gender effect and no age-related shrinkage. Significantly lower 3D-GI values were exhibited in both CBGM and CBWM of the MSA-C patients compared with healthy subjects, even in the early phases of the disease. Decreases in 3D-GI values indicated the degeneration of the cerebellar folding structure, exactly reflecting the morphological changes in cerebellum. The 3D-GI method based on CBGM resulted in superior discriminative accuracy compared with the CBGM volumetric method. Using the two-dimensional 3D-GI values, the K-means classifier can evidently discriminate the MSA-C patients from healthy subjects.

  14. Laryngeal stridor in multiple system atrophy: Clinicopathological features and causal hypotheses.

    PubMed

    Ozawa, Tetsutaro; Sekiya, Kanako; Aizawa, Naotaka; Terajima, Kenshi; Nishizawa, Masatoyo

    2016-02-15

    Laryngeal stridor is recognized as a characteristic clinical manifestation in patients with multiple system atrophy (MSA). However, the pathogenic mechanisms underlying this symptom are controversial. Neurogenic atrophy of the posterior cricoarytenoid muscle has been identified in cases of MSA, suggesting that laryngeal abductor weakness contributes to laryngeal stridor. However, dystonia in the laryngeal adductor muscles has also been reported to cause laryngeal stridor. Depletion of serotonergic neurons in the medullary raphe nuclei, which exert tonic drive to activate the posterior cricoarytenoid muscle, has recently been identified in MSA cases. This adds weight to the possibility that laryngeal abductor weakness underlies laryngeal stridor in MSA. Continuous positive airway pressure therapy is currently used in the treatment of laryngeal stridor, but should be used with caution in patients showing contraindications. Current knowledge of the clinical and neuropathological features of laryngeal stridor is summarized in this paper, and the hypothesized causes and possible therapeutic options for this symptom are discussed.

  15. Survival of patients with pathologically proven multiple system atrophy: a meta-analysis.

    PubMed

    Ben-Shlomo, Y; Wenning, G K; Tison, F; Quinn, N P

    1997-02-01

    A systematic review of the neurologic literature identified 433 cases of pathologically proven multiple system atrophy over a 100-year period. Earlier case reports included patients younger in age with more frequent cerebellar involvement. Mean age of onset was 54.2 years (range 31 to 78) and survival was 6.2 years (range 0.5 to 24). Survival analysis showed a secular trend from a median duration of 4.9 years for publications between 1887 and 1970 to 6.8 years between 1991 and 1994. Older age of onset was associated with shorter survival; the hazard ratio for patients with onset after 60 years was 1.8 (95% CI 1.4 to 2.3) compared with patients between 31 and 49 years. Cerebellar features were associated with marginally increased survival (6.1 years versus 5.4 years; p = 0.04). There were no difference in survival according to gender, parkinsonian, or pyramidal features or whether the patient was classified as striatonigral degeneration or olivopontocerebellar atrophy type. These results demonstrate the poor prognosis for patients with multiple system atrophy but may be biased toward the worst cases. Future research needs to recruit more representative samples.

  16. Complementary PET studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson's disease.

    PubMed

    Antonini, A; Leenders, K L; Vontobel, P; Maguire, R P; Missimer, J; Psylla, M; Günther, I

    1997-12-01

    We used PET with the tracers [18F]fluorodeoxyglucose (FDG), [18F]fluorodopa (FDOPA) and [11C]raclopride (RACLO) to study striatal glucose and dopa metabolism, and dopamine D2 receptor binding, respectively, in nine patients with multiple system atrophy. Ten patients with classical Parkinson's disease were investigated with the same three PET tracers' and three separate groups, each of 10 healthy subjects, served as control populations. We found that striatal FDOPA values separated all healthy subjects from patients with parkinsonism but they were not useful in distinguishing multiple system atrophy from Parkinson's disease. Conversely, striatal RACLO as well as FDG values discriminated all multiple system atrophy from Parkinson's disease patients as well as from healthy control subjects. Metabolic and receptor binding decrements in the putamen of multiple system atrophy patients were significantly correlated. Stepwise regression analysis revealed that a linear combination of putamen RACLO and FDOPA values accurately predicted clinical measures of disease severity in the multiple system atrophy group. Our findings suggest that striatal FDG and particularly RACLO are sensitive and effective measures of striatal function and may help characterizing patients with multiple system atrophy. In contrast, FDOPA measurements are accurate in detecting abnormalities of the nigrostriatal dopaminergic system but may not distinguish among different forms of parkinsonism.

  17. Diagnosing the PEP-II Injection System

    SciTech Connect

    Decker, F.-J.; Donald, M.H.; Iverson, R.H.; Kulikov, A.; Pappas, G.C.; Weaver, M.; /SLAC

    2005-05-09

    The injection of beam into the PEP-II B-Factory, especially into the High Energy Ring (HER) has some challenges. A high background level in the BaBar detector has for a while inhibited us from trickling charge into the HER similar to the Low Energy Ring (LER). Analyzing the injection system has revealed many issues which could be improved. The injection bump between two kickers was not closed, mainly because the phase advance wasn't exactly 180{sup o} and the two kicker strengths were not balanced. Additionally we found reflections which kick the stored beam after the main kick and cause the average luminosity to drop about 3% for a 10 Hz injection rate. The strength of the overall kick is nearly twice as high as the design, indicating a much bigger effective septum thickness. Compared with single beam the background is worse when the HER beam is colliding with the LER beam. This hints that the beam-beam force and the observed vertical blow-up in the HER pushes the beam and especially the injected beam further out to the edge of the dynamic aperture or beyond.

  18. Subclinical nigrostriatal dopaminergic denervation in the cerebellar subtype of multiple system atrophy (MSA-C).

    PubMed

    Muñoz, Esteban; Iranzo, Alex; Rauek, Sebastian; Lomeña, Francisco; Gallego, Judith; Ros, Doménec; Santamaría, Joan; Tolosa, Eduardo

    2011-12-01

    Nigrostriatal involvement is considered an additional feature in the new consensus criteria for the diagnosis of the cerebellar variant of multiple system atrophy (MSA-C). However, so far, only a few studies, which include a relative small number of patients, give support to this criterion. Our objective was to assess nigrostriatal dopaminergic innervation in patients with MSA-C without parkinsonism by use of dopamine transporter single photon emission computed tomography (DAT SPECT). Thirteen patients that fulfilled criteria for possible or probable MSA-C and presented no parkinsonian signs, and 12 age-matched healthy controls underwent ((123)I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ([(123)I]FP-CIT) SPECT. Patients were also evaluated through the Unified Multiple System Atrophy Rating Scale (UMSARS) and brain magnetic resonance imaging (MRI). The mean duration of the cerebellar syndrome was 3.8 ± 1.7 years. DAT SPECT showed a significant decrease of striatal [(123)I]FP-CIT uptake ratios in patients (p < 0.001). Radiotracer uptake reduction was 21% in the entire striatum, 19% in putamen, and 24% in caudate nuclei. Striatal binding ratios were within the normal range in 3 patients. We did not find correlation between striatal uptake and disease duration, age of patients, UMSARS-II score, and pontine diameter. [(123)I]FP-CIT SPECT shows that most but not all MSA-C patients without parkinsonism have subclinical nigrostriatal dopaminergic denervation which is not related to disease duration, cerebellar dysfunction, or pontine atrophy.

  19. A Testing System for Diagnosing Misconceptions in DC Electric Circuits.

    ERIC Educational Resources Information Center

    Chang, Kuo-En; Liu, Sei-Hua; Chen, Sei-Wang

    1998-01-01

    Outlines a test-based diagnosis system for misconceptions in DC electric circuits and its three parts: problem library, problem selector and diagnoser. Discusses misconception discrimination and diagnosis theories, and reports the system supports satisfactory diagnosis. Includes an analysis of nine student misconceptions about electrical circuits…

  20. The improvement of movement and speech during rapid eye movement sleep behaviour disorder in multiple system atrophy.

    PubMed

    De Cock, Valérie Cochen; Debs, Rachel; Oudiette, Delphine; Leu, Smaranda; Radji, Fatai; Tiberge, Michel; Yu, Huan; Bayard, Sophie; Roze, Emmanuel; Vidailhet, Marie; Dauvilliers, Yves; Rascol, Olivier; Arnulf, Isabelle

    2011-03-01

    Multiple system atrophy is an atypical parkinsonism characterized by severe motor disabilities that are poorly levodopa responsive. Most patients develop rapid eye movement sleep behaviour disorder. Because parkinsonism is absent during rapid eye movement sleep behaviour disorder in patients with Parkinson's disease, we studied the movements of patients with multiple system atrophy during rapid eye movement sleep. Forty-nine non-demented patients with multiple system atrophy and 49 patients with idiopathic Parkinson's disease were interviewed along with their 98 bed partners using a structured questionnaire. They rated the quality of movements, vocal and facial expressions during rapid eye movement sleep behaviour disorder as better than, equal to or worse than the same activities in an awake state. Sleep and movements were monitored using video-polysomnography in 22/49 patients with multiple system atrophy and in 19/49 patients with Parkinson's disease. These recordings were analysed for the presence of parkinsonism and cerebellar syndrome during rapid eye movement sleep movements. Clinical rapid eye movement sleep behaviour disorder was observed in 43/49 (88%) patients with multiple system atrophy. Reports from the 31/43 bed partners who were able to evaluate movements during sleep indicate that 81% of the patients showed some form of improvement during rapid eye movement sleep behaviour disorder. These included improved movement (73% of patients: faster, 67%; stronger, 52%; and smoother, 26%), improved speech (59% of patients: louder, 55%; more intelligible, 17%; and better articulated, 36%) and normalized facial expression (50% of patients). The rate of improvement was higher in Parkinson's disease than in multiple system atrophy, but no further difference was observed between the two forms of multiple system atrophy (predominant parkinsonism versus cerebellar syndrome). Video-monitored movements during rapid eye movement sleep in patients with multiple system

  1. Clinical outcomes of two main variants of progressive supranuclear palsy and multiple system atrophy: a prospective natural history study.

    PubMed

    Jecmenica-Lukic, Milica; Petrovic, Igor N; Pekmezovic, Tatjana; Kostic, Vladimir S

    2014-08-01

    Progressive supranuclear palsy (PSP) and parkinsonian subtype of multiple system atrophy (MSA-P) are, after Parkinson's disease (PD), the most common forms of neurodegenerative parkinsonism. Clinical heterogeneity of PSP includes two main variants, Richardson syndrome (PSP-RS) and PSP-parkinsonism (PSP-P). Clinical differentiation between them may be impossible at least during the first 2 years of the disease. Little is known about the differences in natural course of PSP-RS and PSP-P and, therefore, in this study we prospectively followed the clinical outcomes of consecutive, pathologically unconfirmed patients with the clinical diagnoses of PSP-RS (51 patients), PSP-P (21 patients) and MSA-P (49 patients). Estimated mean survival time was 11.2 years for PSP-P, 6.8 years for PSP-RS, and 7.9 years for MSA-P, where a 5-year survival probabilities were 90, 66 and 78 %, respectively. More disabling course of PSP-RS compared to PSP-P was also highlighted through the higher number of milestones reached in the first 3 years of the disease, as well as in the trend to reach all clinical milestones earlier. We found that PSP-P variant had a more favorable course with longer survival, not only when compared to PSP-RS, but also when compared to another form of atypical parkinsonism, MSA-P.

  2. Autonomic nervous system testing may not distinguish multiple system atrophy from Parkinson's disease

    PubMed Central

    Riley, D; Chelimsky, T

    2003-01-01

    Background: Formal laboratory testing of autonomic function is reported to distinguish between patients with Parkinson's disease and those with multiple system atrophy (MSA), but such studies segregate patients according to clinical criteria that select those with autonomic dysfunction for the MSA category. Objective: To characterise the profiles of autonomic disturbances in patients in whom the diagnosis of Parkinson's disease or MSA used criteria other than autonomic dysfunction. Methods: 47 patients with parkinsonism and autonomic symptoms who had undergone autonomic laboratory testing were identified and their case records reviewed for non-autonomic features. They were classified clinically into three diagnostic groups: Parkinson's disease (19), MSA (14), and uncertain (14). The performance of the patients with Parkinson's disease was compared with that of the MSA patients on five autonomic tests: RR variation on deep breathing, heart rate changes with the Valsalva manoeuvre, tilt table testing, the sudomotor axon reflex test, and thermoregulatory sweat testing. Results: None of the tests distinguished one group from the other with any statistical significance, alone or in combination. Parkinson's disease and MSA patients showed similar patterns of autonomic dysfunction on formal testing of cardiac sympathetic and parasympathetic, vasomotor, and central and peripheral sudomotor functions. Conclusions: This study supports the clinical observation that Parkinson's disease is often indistinguishable from MSA when it involves the autonomic nervous system. The clinical combination of parkinsonism and dysautonomia is as likely to be caused by Parkinson's disease as by MSA. Current clinical criteria for Parkinson's disease and MSA that direct patients with dysautonomia into the MSA group may be inappropriate. PMID:12486267

  3. Multiple system atrophy as emerging template for accelerated drug discovery in α-synucleinopathies

    PubMed Central

    Krismer, Florian; Jellinger, Kurt A.; Scholz, Sonja W.; Seppi, Klaus; Stefanova, Nadia; Antonini, Angelo; Poewe, Werner; Wenning, Gregor K.

    2014-01-01

    There is evidence that the α-synucleinopathies Parkinson's disease (PD) and the Parkinson variant of multiple system atrophy (MSA-P) overlap at multiple levels. Both disorders are characterized by deposition of abnormally phosphorylated fibrillar α-synuclein within the central nervous system suggesting shared pathophysiological mechanisms. Despite the considerable clinical overlap in the early disease stages, MSA-P, in contrast to PD, is fatal and rapidly progressive. Moreover recent clinical studies have shown that surrogate markers of disease progression can be quantified easily and may reliably depict the rapid course of MSA. We therefore posit that, MSA-P may be exploited as a filter barrier in the development of disease-modifying therapeutic strategies targeting common pathophysiological mechanisms of α-synucleinopathies. This approach might reduce the number of negative phase III clinical trials, and, in turn, shift the available resources to earlier development stages, thereby increasing the number of candidate compounds validated. PMID:24894118

  4. Brain stem auditory evoked potentials in patients with multiple system atrophy with progressive autonomic failure (Shy-Drager syndrome).

    PubMed Central

    Prasher, D; Bannister, R

    1986-01-01

    Brain stem potentials from three groups of patients, namely those with pure progressive autonomic failure, Parkinson's disease and multisystem atrophy with progressive autonomic failure (Shy-Drager syndrome) were compared with each other and a group of normal subjects. In virtually all the patients with multisystem atrophy with progressive autonomic failure the brain stem potentials were abnormal in contrast to normal findings with Parkinson's disease. The closely associated group of patients with progressive autonomic failure alone also revealed no abnormalities of the BAEP. This separation of the two groups, Parkinson's disease and progressive autonomic failure from multisystem atrophy with progressive autonomic failure is important clinically as multiple system atrophy of the Shy-Drager type has extra-pyramidal features closely resembling Parkinsonism or a late onset cerebellar degeneration. From the abnormalities of the brain stem response in multisystem atrophy with progressive autonomic failure, it is clear that some disruption of the auditory pathway occurs in the ponto-medullary region as in nearly all patients there is a significant delay or reduction in the amplitude of components of the response generated beyond this region. The most likely area involved is the superior olivary complex. Images PMID:3958741

  5. Psychotic-affective symptoms and multiple system atrophy expand phenotypes of spinocerebellar ataxia type 2.

    PubMed

    Chen, Kai-Hsiang; Lin, Chin-Hsien; Wu, Ruey-Meei

    2012-03-20

    Spinocerebellar ataxia type 2 (SCA2) is a progressive neurodegenerative disorder, characterised by ataxic gait, slow saccades and peripheral neuropathy. Levodopa-responsive parkinsonism could be a clinical phenotype of SCA2, especially those of Chinese origin. In addition to these motor symptoms, SCA2 has been associated with depression and cognitive dysfunction, with only rare reports of psychosis. The authors report the presence of severe psychosis, major depression and multiple system atrophy in affected subjects of a Taiwanese family with intermediate CAG repeats within the ATXN2 gene. The identification of this rare and distinctive SCA2 phenotype expands the current knowledge of the phenotypic variability of SCA2 and suggests that modifier genes could influence the clinical phenotype of SCA2.

  6. Parkinson’s disease with Onuf’s nucleus involvement mimicking multiple system atrophy

    PubMed Central

    O’Sullivan, Sean Stephen; Massey, Luke A; Williams, David R; Revesz, Tamas; Lees, Andrew; Holton, Janice

    2009-01-01

    Urinary frequency, urgency and nocturia are common complaints in Parkinson’s disease (PD). The hypothesis most widely proposed to explain neurogenic bladder symptoms in PD is that cell loss in the substantia nigra may cause detrusor hyperactivity due to a loss in the D1 receptor-mediated tonic inhibition of the micturition reflex, although other causes including anti-parkinsonian medication cortical effects have been considered.1 We present the clinical and pathological findings of a patient with parkinsonism who presented with prominent dysautonomia and a poor response to dopaminergic medications and was considered to have possible multiple system atrophy parkinsonism (MSA-P). Pathological examination revealed that the patient had PD with α-synuclein pathology in the Onuf’s nucleus (ON). PMID:21686637

  7. Unusual compulsive behaviors primarily related to dopamine agonist therapy in Parkinson's disease and multiple system atrophy.

    PubMed

    McKeon, Andrew; Josephs, Keith A; Klos, Kevin J; Hecksel, Kathleen; Bower, James H; Michael Bostwick, J; Eric Ahlskog, J

    2007-12-01

    Unusual compulsive behaviors (weighing, card and video game playing, fishing, gardening, intense interest in established hobbies, locking and unlocking doors, repetitive dressing and undressing) occurred in relation to dopamine agonist therapy (six patients) and levodopa therapy (one patient) in seven patients with parkinsonism (seven Parkinson's disease, one multiple system atrophy). These behaviors occurred in tandem with pathological gambling, hypersexuality, compulsive eating, compulsive shopping or punding in six of the seven cases. Obsessive thoughts were present in one patient, with no prior history of obsessive-compulsive disorder. The simultaneous occurrence of these phenomenologically distinct behaviors in this group of patients suggests that a broad spectrum of psychopathology may occur in this context and should be monitored for in routine neurological practice.

  8. Mutational analysis of parkin and PINK1 in multiple system atrophy

    PubMed Central

    Brooks, Janet A.; Houlden, Henry; Melchers, Anna; Islam, Ansha J.; Ding, Jinhui; Li, Abi; Paudel, Reema; Revesz, Tamas; Holton, Janice L.; Wood, Nick; Lees, Andrew; Singleton, Andrew B.; Scholz, Sonja W.

    2009-01-01

    Multiple system atrophy (MSA) and Parkinson’s disease (PD) are progressive neurodegenerative disorders with overlapping clinical, biochemical and genetic features. To test the hypothesis that the Parkinson’s disease genes parkin and PINK1 also play a role in the pathogenesis of MSA, we performed a mutational screening study involving 87 pathology-proven MSA cases. In parkin we identified eight sequence variants and four heterozygous deletions, and in PINK1 we identified nine variants of which two silent mutations have not been previously reported (p.Gly189Gly and p.Arg337Arg). The frequencies of the observed variants were not significantly different from previously published control data and none of the possibly pathogenic variants were found in a homozygous state. Our results indicate that genetic variants at the parkin and PINK1 loci do not play a critical role in the pathogenesis of MSA. PMID:20034704

  9. Complexity of system-level fault diagnosis and diagnosability

    SciTech Connect

    Sullivan, G.F.

    1986-01-01

    It is now possible to design and build systems that incorporate a large number of processing elements. For this reason, fault-diagnosis at the system level, a research area pioneered by the work of Preparata, Metze, and Chien, is of increasing importance. The formalization of their model utilizes directed graphs together with labelings on edges and vertices. The two central problems introduced by the model are called the diagnosis and diagnosability problems. In the diagnosis problem, an algorithm must identify the faulty units of a system based on test results. In the diagnosability problem, an algorithm must determine the maximum number of faulty units a system can contain and still be guaranteed capable of successfully testing itself. One of the main open questions is resolved for this model by presenting the first polynomial time algorithm for the diagnosability problem. The solution uses network-flow techniques and runs in O(absolute value E absolute value V/sup 3/2/) time. Also presented is a new time-complexity bound of O(min(t absolute value E, t/sup 3/ + absolute value E)) for the diagnosis problem, where t is the maximum number of faulty units.

  10. MOORE: A prototype expert system for diagnosing spacecraft problems

    NASA Technical Reports Server (NTRS)

    Howlin, Katherine; Weissert, Jerry; Krantz, Kerry

    1988-01-01

    MOORE is a rule-based, prototype expert system that assists in diagnosing operational Tracking and Data Relay Satellite (TDRS) problems. It is intended to assist spacecraft engineers at the TDRS ground terminal in trouble shooting problems that are not readily solved with routine procedures, and without expert counsel. An additional goal of the prototype system is to develop in-house expert system and knowledge engineering skills. The prototype system diagnoses antenna pointing and earth pointing problems that may occur within the TDRS Attitude Control System (ACS). Plans include expansion to fault isolation of problems in the most critical subsystems of the TDRS spacecraft. Long term benefits are anticipated with use of an expert system during future TDRS programs with increased mission support time, reduced problem solving time, and retained expert knowledge and experience. Phase 2 of the project is intended to provide NASA the necessary expertise and capability to define requirements, evaluate proposals, and monitor the development progress of a highly competent expert system for NASA's Tracking Data Relay Satellite. Phase 2 also envisions addressing two unexplored applications for expert systems, spacecraft integration and tests (I and T) and support to launch activities. The concept, goals, domain, tools, knowledge acquisition, developmental approach, and design of the expert system. It will explain how NASA obtained the knowledge and capability to develop the system in-house without assistance from outside consultants. Future plans will also be presented.

  11. [Towards more efficient clinical trials for multiple system atrophy in Japan].

    PubMed

    Ichikawa, Yaeko

    2012-10-01

    Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder characterized by various combinations of autonomic dysfunction, cerebellar symptoms, parkinsonism, and pyramidal signs. Although MSA is known as a sporadic disease, multiplex families with MSA suggest a genetic predisposition to MSA. The advanced genome research using high-throughput sequencing technology will enable identification of MSA-related genes. Disease-modifying therapy for MSA is expected to be available in the near future. In 2003, the Japan MSA research consortium (JAMSAC) was established to understand the natural history of MSA, which could be the basis for designing clinical trials, and to elucidate the molecular pathogenetic mechanisms of MSA. In Japan, MSA with predominant cerebellar ataxia (MSA-C) is more frequent than that MSA with predominant parkinsonism (MSA-P); this is in contrast to the previous reports from Europe and North America. JAMSAC has conducted a prospective study on the natural history of MSA by using the established consensus criteria for MSA and the unified multiple system atrophy rating scale (UMSARS). Determining the optimum endpoint, sample size, and duration of trial is essential for designing efficient clinical trials. In addition, more sensitive diagnostic criteria are needed to recruit MSA patients in the earlier phase of the condition. Sample size estimation from a longitudinal study suggested the need for sensitive outcome measures, other than UMSARS. Although the knowledge on MSA has increased in the past several decades, biomarkers for this disease are not yet available. The establishment of more sensitive diagnostic criteria and the development of biomarkers are required to conduct more efficient clinical trials for MSA.

  12. Diagnosing battery behavior with an expert system in PROLOG

    NASA Technical Reports Server (NTRS)

    Kirkwood, N.; Weeks, D. J.

    1986-01-01

    Power for the Hubble Space Telescope comes from a system of 20 solar panel assemblies (SPAs) and six nickel-cadmium batteries. The HST battery system is simulated by the HST Electrical Power System (EPS) testbed at Marshall Space Flight Center. The Nickel Cadmium Battery Expert System (NICBES) is being used to diagnose faults of the testbed system, evaluate battery status and provide decision support for the engineer. Extensive telemetry of system operating conditions is relayed through a DEC LSI-11. A BASIC program running on a PC monitors the flow of data, figures cell divergence and recharge ratio, and stores these values, along with other selected data, for use by the expert system.

  13. "Atypical" atypical parkinsonism: new genetic conditions presenting with features of progressive supranuclear palsy, corticobasal degeneration, or multiple system atrophy-a diagnostic guide.

    PubMed

    Stamelou, Maria; Quinn, Niall P; Bhatia, Kailash P

    2013-08-01

    Recently, a number of genetic parkinsonian conditions have been recognized that share some features with the clinical syndromes of progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA), the classic phenotypic templates of atypical parkinsonism. For example, patients with progranulin, dynactin, or ATP13A gene mutations may have vertical supranuclear gaze palsy. This has made differential diagnosis difficult for practitioners. In this review, our goal is to make clinicians aware of these genetic disorders and provide clinical clues and syndromic associations, as well as investigative features, that may help in diagnosing these disorders. The correct identification of these patients has important clinical, therapeutic, and research implications. © 2013 Movement Disorder Society.

  14. Pharmacodynamics of a low subacute levodopa dose helps distinguish between multiple system atrophy with predominant Parkinsonism and Parkinson's disease.

    PubMed

    Calandra-Buonaura, Giovanna; Doria, Andrea; Lopane, Giovanna; Guaraldi, Pietro; Capellari, Sabina; Martinelli, Paolo; Cortelli, Pietro; Contin, Manuela

    2016-02-01

    The differential diagnosis between multiple system atrophy with predominant parkinsonism (MSA-P) and Parkinson's disease (PD) may be challenging at disease onset. Levodopa responsiveness helps distinguish the two groups, but studies evaluating this issue using objective standardized tests are scanty. We retrospectively examined the extent of levodopa response by an objective kinetic-dynamic test in a series of patients prospectively followed up for a parkinsonian syndrome and eventually diagnosed as MSA-P or PD. Sixteen MSA-P and 31 PD patients under chronic levodopa therapy received a first morning fasting dose of levodopa/benserazide (100/25 mg) or levodopa/carbidopa (125/12.5 or 100/25 mg) and underwent simultaneous serial assessments of plasma levodopa concentration and alternate finger tapping frequency up to 3 h post dosing. The main levodopa pharmacodynamic variables were the maximum percentage increase in tapping frequency over baseline values (ΔTapmax %) and the area under the tapping effect-time curve (AUCTap). Levodopa pharmacokinetics did not show significant differences between MSA-P and PD, whereas both the magnitude and overall extent of levodopa tapping effect were markedly reduced in the MSA-P group (p < 0.001). The combined use of specific cut-off values for both the main pharmacodynamic variables, ΔTapmax % <20% and AUCTap <1900 [(tapping/min)·min], correctly discriminated 15 out of 16 MSA-P patients from PD patients. A combined estimation of these pharmacodynamic variables after a subacute low levodopa dose may be a simple and practical clinical tool to aid the differential diagnosis between MSA-P and PD.

  15. The TWEAK-Fn14 system is a critical regulator of denervation-induced skeletal muscle atrophy in mice.

    PubMed

    Mittal, Ashwani; Bhatnagar, Shephali; Kumar, Akhilesh; Lach-Trifilieff, Estelle; Wauters, Sandrine; Li, Hong; Makonchuk, Denys Y; Glass, David J; Kumar, Ashok

    2010-03-22

    Skeletal muscle atrophy occurs in a variety of clinical settings, including cachexia, disuse, and denervation. Inflammatory cytokines have been shown to be mediators of cancer cachexia; however, the role of cytokines in denervation- and immobilization-induced skeletal muscle loss remains unknown. In this study, we demonstrate that a single cytokine, TNF-like weak inducer of apoptosis (TWEAK), mediates skeletal muscle atrophy that occurs under denervation conditions. Transgenic expression of TWEAK induces atrophy, fibrosis, fiber-type switching, and the degradation of muscle proteins. Importantly, genetic ablation of TWEAK decreases the loss of muscle proteins and spared fiber cross-sectional area, muscle mass, and strength after denervation. Expression of the TWEAK receptor Fn14 (fibroblast growth factor-inducible receptor 14) and not the cytokine is significantly increased in muscle upon denervation, demonstrating an unexpected inside-out signaling pathway; the receptor up-regulation allows for TWEAK activation of nuclear factor kappaB, causing an increase in the expression of the E3 ubiquitin ligase MuRF1. This study reveals a novel mediator of skeletal muscle atrophy and indicates that the TWEAK-Fn14 system is an important target for preventing skeletal muscle wasting.

  16. Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy

    PubMed Central

    Powis, Rachael A.; Karyka, Evangelia; Boyd, Penelope; Côme, Julien; Jones, Ross A.; Zheng, Yinan; Szunyogova, Eva; Groen, Ewout J.N.; Hunter, Gillian; Thomson, Derek; Wishart, Thomas M.; Becker, Catherina G.; Parson, Simon H.; Martinat, Cécile; Azzouz, Mimoun; Gillingwater, Thomas H.

    2016-01-01

    The autosomal recessive neuromuscular disease spinal muscular atrophy (SMA) is caused by loss of survival motor neuron (SMN) protein. Molecular pathways that are disrupted downstream of SMN therefore represent potentially attractive therapeutic targets for SMA. Here, we demonstrate that therapeutic targeting of ubiquitin pathways disrupted as a consequence of SMN depletion, by increasing levels of one key ubiquitination enzyme (ubiquitin-like modifier activating enzyme 1 [UBA1]), represents a viable approach for treating SMA. Loss of UBA1 was a conserved response across mouse and zebrafish models of SMA as well as in patient induced pluripotent stem cell–derive motor neurons. Restoration of UBA1 was sufficient to rescue motor axon pathology and restore motor performance in SMA zebrafish. Adeno-associated virus serotype 9–UBA1 (AAV9-UBA1) gene therapy delivered systemic increases in UBA1 protein levels that were well tolerated over a prolonged period in healthy control mice. Systemic restoration of UBA1 in SMA mice ameliorated weight loss, increased survival and motor performance, and improved neuromuscular and organ pathology. AAV9-UBA1 therapy was also sufficient to reverse the widespread molecular perturbations in ubiquitin homeostasis that occur during SMA. We conclude that UBA1 represents a safe and effective therapeutic target for the treatment of both neuromuscular and systemic aspects of SMA. PMID:27699224

  17. Dominant optic atrophy

    PubMed Central

    2012-01-01

    Definition of the disease Dominant Optic Atrophy (DOA) is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC) and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. Epidemiology The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. Clinical description DOA patients usually suffer of moderate visual loss, associated with central or paracentral visual field deficits and color vision defects. The severity of the disease is highly variable, the visual acuity ranging from normal to legal blindness. The ophthalmic examination discloses on fundoscopy isolated optic disc pallor or atrophy, related to the RGC death. About 20% of DOA patients harbour extraocular multi-systemic features, including neurosensory hearing loss, or less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. Aetiology Two genes (OPA1, OPA3) encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8) are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7) are responsible for X-linked or recessive optic atrophy. All OPA genes yet identified encode mitochondrial proteins embedded in the inner membrane and ubiquitously expressed, as are the proteins mutated in the Leber Hereditary Optic Neuropathy. OPA1 mutations affect mitochondrial fusion, energy metabolism, control of apoptosis, calcium clearance and maintenance of mitochondrial genome integrity. OPA3 mutations only affect the energy metabolism and the control of apoptosis. Diagnosis Patients are usually diagnosed during their early childhood, because of bilateral, mild

  18. Chemotherapy in newly diagnosed primary central nervous system lymphoma

    PubMed Central

    Hashemi-Sadraei, Nooshin; Peereboom, David M.

    2010-01-01

    Primary central nervous system lymphoma (PCNSL) accounts for only 3% of brain tumors. It can involve the brain parenchyma, leptomeninges, eyes and the spinal cord. Unlike systemic lymphoma, durable remissions remain uncommon. Although phase III trials in this rare disease are difficult to perform, many phase II trials have attempted to define standards of care. Treatment modalities for patients with newly diagnosed PCNSL include radiation and/or chemotherapy. While the role of radiation therapy for initial management of PCNSL is controversial, clinical trials will attempt to improve the therapeutic index of this modality. Routes of chemotherapy administration include intravenous, intraocular, intraventricular or intra-arterial. Multiple trials have outlined different methotrexate-based chemotherapy regimens and have used local techniques to improve drug delivery. A major challenge in the management of patients with PCNSL remains the delivery of aggressive treatment with preservation of neurocognitive function. Because PCNSL is rare, it is important to perform multicenter clinical trials and to incorporate detailed measurements of long-term toxicities. In this review we focus on different chemotherapeutic approaches for immunocompetent patients with newly diagnosed PCNSL and discuss the role of local drug delivery in addition to systemic therapy. We also address the neurocognitive toxicity of treatment. PMID:21789140

  19. [Posterior cortical atrophy (Benson-syndrome)].

    PubMed

    Rózsa, Anikó; Szilvássy, Ildikó; Kovács, Krisztina; Boór, Krisztina; Gács, Gyula

    2010-01-30

    We present the characteristics of posterior cortical atrophy--a very rare cortical dementia--in a 69 year old woman's case. Our patient's symptoms began with a visual problem which was initially explained by ophthalmological disorder. After neurological exam visual agnosia was diagnosed apart from other cognitive disorder (alexia without agraphia, acalculia, prosopagnosia, constructional disorder, clock-time recognition disorder, dressing apraxia, visuospatial disorientation). The brain MRI showed bilateral asymmetric parieto-occipital atrophy which is characteristic of posterior cortical atrophy.

  20. Multiple system atrophy presenting as parkinsonism: clinical features and diagnostic criteria.

    PubMed Central

    Albanese, A; Colosimo, C; Bentivoglio, A R; Fenici, R; Melillo, G; Colosimo, C; Tonali, P

    1995-01-01

    To evaluate the possibility that parkinsonian signs may be the only presenting feature of multiple system atrophy (MSA), parkinsonian patients were studied who had no atypical clinical signs and had no symptoms of autonomic dysfunction, but who reported that they had not experienced the anticipated good response to dopaminergic treatment. These stringent criteria identified 20 patients from a series of 298 consecutive parkinsonian outpatients. The following clinical pointers were analysed: (a) rate of disease progression; (b) symmetry of parkinsonian symptoms and signs; (c) occurrence of resting tremor during the first three years from onset. In addition, all patients underwent (d) acute and chronic challenge with dopaminergic drugs; (e) cardiovascular reflex autonomic function tests; (f) high field MRI. Rapid progression of disease was seen in 45% of patients, onset was symmetric in 25%, tremor was absent at onset in 70%, response to dopaminergic drug challenges was inadequate in 40%, abnormal cardiovascular reflexes occurred in 50%, and some abnormal MRI finding occurred in 35% of cases. Each of these features was equally weighted by giving to each patient a 0 to 6 point score corresponding to the number of abnormal findings. Fifteen patients scoring higher than 1 were considered at risk for having MSA: five of them were classified as clinically possible (score 2), six as clinically probable (score 3-4), and four patients were classified as clinically definite multiple system atrophy (score 5). The six pointers considered were variably combined in each patient, none of them being universally abnormal in patients with high scores. The patients were followed up for a mean 2.1 (SEM 0.65) years. All but one of the 10 patients prospectively classified as probable or definite MSA developed unequivocal clinical signs of fully symptomatic MSA. A receiver operator characteristic cure was plotted for the prospective score based on follow up diagnosis. The best compromise

  1. Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy

    PubMed Central

    Hazell, Gareth; Shabanpoor, Fazel; Saleh, Amer F.; Bowerman, Melissa; Meijboom, Katharina E.; Zhou, Haiyan; Muntoni, Francesco; Talbot, Kevin; Gait, Michael J.; Wood, Matthew J. A.

    2016-01-01

    The development of antisense oligonucleotide therapy is an important advance in the identification of corrective therapy for neuromuscular diseases, such as spinal muscular atrophy (SMA). Because of difficulties of delivering single-stranded oligonucleotides to the CNS, current approaches have been restricted to using invasive intrathecal single-stranded oligonucleotide delivery. Here, we report an advanced peptide-oligonucleotide, Pip6a-morpholino phosphorodiamidate oligomer (PMO), which demonstrates potent efficacy in both the CNS and peripheral tissues in severe SMA mice following systemic administration. SMA results from reduced levels of the ubiquitously expressed survival motor neuron (SMN) protein because of loss-of-function mutations in the SMN1 gene. Therapeutic splice-switching oligonucleotides (SSOs) modulate exon 7 splicing of the nearly identical SMN2 gene to generate functional SMN protein. Pip6a-PMO yields SMN expression at high efficiency in peripheral and CNS tissues, resulting in profound phenotypic correction at doses an order-of-magnitude lower than required by standard naked SSOs. Survival is dramatically extended from 12 d to a mean of 456 d, with improvement in neuromuscular junction morphology, down-regulation of transcripts related to programmed cell death in the spinal cord, and normalization of circulating insulin-like growth factor 1. The potent systemic efficacy of Pip6a-PMO, targeting both peripheral as well as CNS tissues, demonstrates the high clinical potential of peptide-PMO therapy for SMA. PMID:27621445

  2. Overexpression of the alpha1B-adrenergic receptor causes apoptotic neurodegeneration: multiple system atrophy.

    PubMed

    Zuscik, M J; Sands, S; Ross, S A; Waugh, D J; Gaivin, R J; Morilak, D; Perez, D M

    2000-12-01

    Progress toward elucidating the function of alpha1B-adrenergic receptors (alpha1BARs) in the central nervous system has been constrained by a lack of agonists and antagonists with adequate alpha1B-specificity. We have obviated this constraint by generating transgenic mice engineered to overexpress either wild-type or constitutively active alpha1BARs in tissues that normally express the receptor, including the brain. All transgenic lines showed granulovacular neurodegeneration, beginning in alpha1B-expressing domains of the brain and progressing with age to encompass all areas. The degeneration was apoptotic and did not occur in non-transgenic mice. Correspondingly, transgenic mice showed an age-progressive hindlimb disorder that was parkinsonian-like, as demonstrated by rescue of the dysfunction by 3, 4-dihydroxyphenylalanine and considerable dopaminergic-neuronal degeneration in the substantia nigra. Transgenic mice also had a grand mal seizure disorder accompanied by a corresponding dysplasia and neurodegeneration of the cerebral cortex. Both behavioral phenotypes (locomotor impairment and seizure) could be partially rescued with the alpha1AR antagonist terazosin, indicating that alpha1AR signaling participated directly in the pathology. Our results indicate that overstimulation of alpha1BAR leads to apoptotic neurodegeneration with a corresponding multiple system atrophy indicative of Shy-Drager syndrome, a disease whose etiology is unknown.

  3. An autopsy case of preclinical multiple system atrophy (MSA-C).

    PubMed

    Kon, Tomoya; Mori, Fumiaki; Tanji, Kunikazu; Miki, Yasuo; Wakabayashi, Koichi

    2013-12-01

    Multiple system atrophy (MSA) is divided into two clinical subtypes: MSA with predominant parkinsonian features (MSA-P) and MSA with predominant cerebellar dysfunction (MSA-C). We report a 71-year-old Japanese man without clinical signs of MSA, in whom post mortem examination revealed only slight gliosis in the pontine base and widespread occurrence of glial cytoplasmic inclusions in the central nervous system, with the greatest abundance in the pontine base and cerebellar white matter. Neuronal cytoplasmic inclusions (NCIs) and neuronal nuclear inclusions (NNIs) were almost restricted to the pontine and inferior olivary nuclei. It was noteworthy that most NCIs were located in the perinuclear area, and the majority of NNIs were observed adjacent to the inner surface of the nuclear membrane. To our knowledge, only four autopsy cases of preclinical MSA have been reported previously, in which neuronal loss was almost entirely restricted to the substantia nigra and/or putamen. Therefore, the present autopsy case of preclinical MSA-C is considered to be the first of its kind to have been reported. The histopathological features observed in preclinical MSA may represent the early pattern of MSA pathology.

  4. Diagnosing delivery problems in the White House Information Distribution System

    SciTech Connect

    Nahabedian, M.; Shrobe, H.

    1996-12-31

    As part of a collaboration with the White House Office of Media Affairs, members of the MIT Artificial Intelligence Laboratory designed a system, called COMLINK, which distributes a daily stream of documents released by the Office of Media Affairs. Approximately 4000 direct subscribers receive information from this service but more than 100,000 people receive the information through redistribution channels. The information is distributed via Email and the World Wide Web. In such a large scale distribution scheme, there is a constant problem of subscriptions becoming invalid because the user`s Email account has terminated. This causes a backwash of hundreds of {open_quotes}bounced mail{close_quotes} messages per day which must be processed by the operators of the COMLINK system. To manage this annoying but necessary task, an expert system named BMES was developed to diagnose the failures of information delivery.

  5. Distinct Functional and Macrostructural Brain Changes in Parkinson’s Disease and Multiple System Atrophy

    PubMed Central

    Planetta, Peggy J.; Kurani, Ajay S.; Shukla, Priyank; Prodoehl, Janey; Corcos, Daniel M.; Comella, Cynthia L.; McFarland, Nikolaus R.; Okun, Michael S.; Vaillancourt, David E.

    2016-01-01

    Parkinson’s disease (PD) and the parkinsonian variant of multiple system atrophy (MSAp) are neurodegenerative disorders that can be difficult to differentiate clinically. This study provides the first characterization of the patterns of task-related functional magnetic resonance imaging (fMRI) changes across the whole brain in MSAp. We used fMRI during a precision grip force task and also performed voxel-based morphometry (VBM) on T1-weighted images in MSAp patients, PD patients, and healthy controls. All groups were matched on age, and the patient groups had comparable motor symptom durations and severities. There were three main findings. First, MSAp and PD had reduced fMRI activation in motor control areas, including the basal ganglia, thalamus, insula, primary sensorimotor and prefrontal cortices, and cerebellum compared with controls. Second, there were no activation differences among the disease groups in the basal ganglia, thalamus, insula, or primary sensorimotor cortices, but PD had more extensive activation deficits throughout the cerebrum compared with MSAp and controls. Third, VBM revealed reduced volume in the basal ganglia, middle and inferior cerebellar peduncles, pons, and throughout the cerebrum in MSAp compared with controls and PD, and additionally throughout the cerebellar cortex and vermis in MSAp compared with controls. Collectively, these results provide the first evidence that fMRI activation is abnormal in the basal ganglia, cerebellum, and cerebrum in MSAp, and that a key distinguishing feature between MSAp and PD is the extensive and widespread volume loss throughout the brain in MSAp. PMID:25413603

  6. Distinctive Features of NREM Parasomnia Behaviors in Parkinson’s Disease and Multiple System Atrophy

    PubMed Central

    Ratti, Pietro-Luca; Sierra-Peña, Maria; Manni, Raffaele; Simonetta-Moreau, Marion; Bastin, Julien; Mace, Harrison; Rascol, Olivier; David, Olivier

    2015-01-01

    Objective To characterize parasomnia behaviors on arousal from NREM sleep in Parkinson’s Disease (PD) and Multiple System Atrophy (MSA). Methods From 30 patients with PD, Dementia with Lewy Bodies/Dementia associated with PD, or MSA undergoing nocturnal video-polysomnography for presumed dream enactment behavior, we were able to select 2 PD and 2 MSA patients featuring NREM Parasomnia Behviors (NPBs). We identified episodes during which the subjects seemed to enact dreams or presumed dream-like mentation (NPB arousals) versus episodes with physiological movements (no-NPB arousals). A time-frequency analysis (Morlet Wavelet Transform) of the scalp EEG signals around each NPB and no- NPB arousal onset was performed, and the amplitudes of the spectral frequencies were compared between NPB and no-NPB arousals. Results 19 NPBs were identified, 12 of which consisting of ‘elementary’ NPBs while 7 resembling confusional arousals. With quantitative EEG analysis, we found an amplitude reduction in the 5-6 Hz band 40 seconds before NPBs arousal as compared to no-NPB arousals at F4 and C4 derivations (p<0.01). Conclusions Many PD and MSA patients feature various NREM sleep-related behaviors, with clinical and electrophysiological differences and similarities with arousal parasomnias in the general population. Significance This study help bring to attention an overlooked phenomenon in neurodegenerative diseases. PMID:25756280

  7. Differences in Dopaminergic Modulation to Motor Cortical Plasticity between Parkinson's Disease and Multiple System Atrophy

    PubMed Central

    Kawashima, Shoji; Ueki, Yoshino; Mima, Tatsuya; Fukuyama, Hidenao; Ojika, Kosei; Matsukawa, Noriyuki

    2013-01-01

    Dopamine modulates the synaptic plasticity in the primary motor cortex (M1). To evaluate whether the functioning of the cortico-striatal circuit is necessary for this modulation, we applied a paired associative stimulation (PAS) protocol that comprised an electric stimulus to the right median nerve at the wrist and subsequent transcranial magnetic stimulation of the left M1, to 10 patients with Parkinson's disease (PD) and 10 with multiple system atrophy of the parkinsonian type (MSA-P) with and without dopamine replacement therapy (-on/off). To investigate the M1 function, motor-evoked potentials (MEPs) were measured before and after the PAS. In both patient groups without medication, the PAS protocol failed to increase the averaged amplitude of MEPs. The dopamine replacement therapy in PD, but not in MSA-P effectively restored the PAS-induced MEP increase. This suggests that not the existence of dopamine itself but the activation of cortico-striatal circuit might play an important role for cortical plasticity in the human M1. PMID:23658735

  8. Differences in dopaminergic modulation to motor cortical plasticity between Parkinson's disease and multiple system atrophy.

    PubMed

    Kawashima, Shoji; Ueki, Yoshino; Mima, Tatsuya; Fukuyama, Hidenao; Ojika, Kosei; Matsukawa, Noriyuki

    2013-01-01

    Dopamine modulates the synaptic plasticity in the primary motor cortex (M1). To evaluate whether the functioning of the cortico-striatal circuit is necessary for this modulation, we applied a paired associative stimulation (PAS) protocol that comprised an electric stimulus to the right median nerve at the wrist and subsequent transcranial magnetic stimulation of the left M1, to 10 patients with Parkinson's disease (PD) and 10 with multiple system atrophy of the parkinsonian type (MSA-P) with and without dopamine replacement therapy (-on/off). To investigate the M1 function, motor-evoked potentials (MEPs) were measured before and after the PAS. In both patient groups without medication, the PAS protocol failed to increase the averaged amplitude of MEPs. The dopamine replacement therapy in PD, but not in MSA-P effectively restored the PAS-induced MEP increase. This suggests that not the existence of dopamine itself but the activation of cortico-striatal circuit might play an important role for cortical plasticity in the human M1.

  9. Novel treatment strategies targeting alpha-synuclein in multiple system atrophy as a model of synucleinopathy

    PubMed Central

    Valera, Elvira; Compagnoni, Giacomo Monzio; Masliah, Eliezer

    2016-01-01

    Neurodegenerative disorders with alpha-synuclein (α-syn) accumulation (synucleinopathies) include Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies and multiple system atrophy (MSA). Due to the involvement of toxic α-syn aggregates in the molecular origin of these disorders, developing effective therapies targeting α-syn is a priority as a disease-modifying alternative to current symptomatic treatments. Importantly, the clinical and pathological attributes of MSA make this disorder an excellent candidate as a synucleinopathy model for accelerated drug development. Recent therapeutic strategies targeting α-syn in in vivo and in vitro models of MSA, as well as in clinical trials, have been focused on the pathological mechanisms of α-syn synthesis, aggregation, clearance, and/or cell-to-cell propagation of its neurotoxic conformers. Here we summarize the most relevant approaches in this direction, with emphasis on their potential as general synucleinopathy modifiers, and enumerate research areas for potential improvement in MSA drug discovery. PMID:26924723

  10. Brain structural profile of multiple system atrophy patients with cognitive impairment.

    PubMed

    Fiorenzato, Eleonora; Weis, Luca; Seppi, Klaus; Onofrj, Marco; Cortelli, Pietro; Zanigni, Stefano; Tonon, Caterina; Kaufmann, Horacio; Shepherd, Timothy Michael; Poewe, Werner; Krismer, Florian; Wenning, Gregor; Antonini, Angelo; Biundo, Roberta

    2017-03-01

    Current consensus diagnostic criteria for multiple system atrophy (MSA) consider dementia a non-supporting feature, although cognitive impairment and even frank dementia are reported in clinical practice. Mini-Mental State Examination (MMSE) is a commonly used global cognitive scale, and in a previous study, we established an MSA-specific screening cut-off score <27 to identify cognitive impairment. Finally, MSA neuroimaging findings suggest the presence of structural alterations in patients with cognitive deficits, although the extent of the anatomical changes is unclear. The aim of our multicenter study is to better characterize anatomical changes associated with cognitive impairment in MSA and to further investigate cortical and subcortical structural differences versus healthy controls (HC). We examined retrospectively 72 probable MSA patients [50 with normal cognition (MSA-NC) and 22 cognitively impaired (MSA-CI) based on MMSE <27] and compared them to 36 HC using gray- and white-matter voxel-based morphometry and fully automated subcortical segmentation. Compared to HC, MSA patients showed widespread cortical (bilateral frontal, occipito-temporal, and parietal areas), subcortical, and white-matter alterations. However, MSA-CI showed only focal volume reduction in the left dorsolateral prefrontal cortex compared with MSA-NC. These results suggest only a marginal contribution of cortical pathology to cognitive deficits. We believe that cognitive dysfunction is driven by focal fronto-striatal degeneration in line with the concept of "subcortical cognitive impairment".

  11. FBXO7 immunoreactivity in α-synuclein-containing inclusions in Parkinson disease and multiple system atrophy.

    PubMed

    Zhao, Tianna; Severijnen, Lies-Anne; van der Weiden, Marcel; Zheng, Ping Pin; Oostra, Ben A; Hukema, Renate K; Willemsen, Rob; Kros, Johan M; Bonifati, Vincenzo

    2013-06-01

    Mutations in the gene encoding the F-box only protein 7 (FBXO7) cause PARK15, an autosomal recessive form of juvenile parkinsonism. Although the brain pathology in PARK15 patients remains unexplored, in vivo imaging displays severe loss of nigrostriatal dopaminergic terminals. Understanding the pathogenesis of PARK15 might therefore illuminate the mechanisms of the selective dopaminergic neuronal degeneration, which could also be important for understanding idiopathic Parkinson disease (PD). The expression of FBXO7 in the human brain remains poorly characterized, and its expression in idiopathic PD and different neurodegenerative diseases has not been investigated. Here, we studied FBXO7 protein expression in brain samples of normal controls (n = 9) and from patients with PD (n = 13), multiple system atrophy (MSA) (n = 5), Alzheimer disease (AD) (n = 5), and progressive supranuclear palsy (PSP) (n = 5) using immunohistochemistry with 2 anti-FBXO7 antibodies. We detected widespread brain FBXO7 immunoreactivity, with the highest levels in neurons of the cerebral cortex, putamen, and cerebellum. There were no major differences between normal and PD brains overall, but FBXO7 immunoreactivity was detected in large proportions of α-synuclein-positive inclusions (Lewy bodies, Lewy neurites, glial cytoplasmic inclusions), where it colocalized with α-synuclein in PD and MSA cases. By contrast, weak FBXO7 immunoreactivity was occasionally detected in tau-positive inclusions in AD and PSP. These findings suggest a role for FBXO7 in the pathogenesis of the synucleinopathies.

  12. Fluid biomarkers in multiple system atrophy: A review of the MSA Biomarker Initiative.

    PubMed

    Laurens, Brice; Constantinescu, Radu; Freeman, Roy; Gerhard, Alexander; Jellinger, Kurt; Jeromin, Andreas; Krismer, Florian; Mollenhauer, Brit; Schlossmacher, Michael G; Shaw, Leslie M; Verbeek, Marcel M; Wenning, Gregor K; Winge, Kristian; Zhang, Jing; Meissner, Wassilios G

    2015-08-01

    Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results suggest that combining several CSF fluid biomarkers may be more successful than using single markers, at least for the diagnosis. Currently, the clinically most useful markers may comprise a combination of the light chain of neurofilament (which is consistently elevated in MSA compared to controls and Parkinson's disease), metabolites of the catecholamine pathway and proteins such as α-synuclein, DJ-1 and total-tau. Beyond future efforts in biomarker discovery, the harmonization of standard operating procedures will be crucial for future success.

  13. Prediction of orthostatic hypotension in multiple system atrophy and Parkinson disease

    PubMed Central

    Sun, Zhanfang; Jia, Dandan; Shi, Yuting; Hou, Xuan; Yang, Xiaosu; Guo, Jifeng; Li, Nan; Wang, Junling; Sun, Qiying; Zhang, Hainan; Lei, Lifang; Shen, Lu; Yan, Xinxiang; Xia, Kun; Jiang, Hong; Tang, Beisha

    2016-01-01

    Orthostatic hypotension (OH) is common in multiple system atrophy (MSA) and Parkinson disease (PD), generally assessed through a lying-to-standing orthostatic test. However, standing blood pressure may not be available due to orthostatic intolerance or immobilization for such patients. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were successively measured in supine, sitting, and standing positions in patients with MSA and PD. Receiver operating characteristic analysis was used to evaluate diagnostic performance of the drops of sitting SBP or DBP. OH and severe OH were respectively regarded as “gold standard”. The drops of SBP in standing position were associated with increased disease severity for MSA and correlated with age for PD. In MSA group, drops in sitting SBP ≥ 14 mmHg or DBP ≥ 6 mmHg had highest validity for prediction of OH, and drops in sitting SBP ≥ 18 mmHg or DBP ≥ 8 mmHg for severe OH. In PD group, drops in sitting SBP ≥ 10 mmHg or DBP ≥ 6 mmHg had highest validity for prediction of OH. The lying-to-sitting orthostatic test is an alternative method for detection of OH in MSA and PD, especially when standing BP could not be validly measured due to various reasons. PMID:26867507

  14. Depletion of catecholaminergic neurons of the rostral ventrolateral medulla in multiple systems atrophy with autonomic failure

    NASA Technical Reports Server (NTRS)

    Benarroch, E. E.; Smithson, I. L.; Low, P. A.; Parisi, J. E.

    1998-01-01

    The ventrolateral portion of the intermediate reticular formation of the medulla (ventrolateral medulla, VLM), including the C1/A1 groups of catecholaminergic neurons, is thought to be involved in control of sympathetic cardiovascular outflow, cardiorespiratory interactions, and reflex control of vasopressin release. As all these functions are affected in patients with multiple systems atrophy (MSA) with autonomic failure, we sought to test the hypothesis that catecholaminergic (tyrosine hydroxylase [TH]-positive) neurons of the VLM are depleted in these patients. Medullas were obtained at autopsy from 4 patients with MSA with prominent autonomic failure and 5 patients with no neurological disease. Patients with MSA had laboratory evidence of severe adrenergic sudomotor and cardiovagal failure. Tissue was immersion fixed in 2% paraformaldehyde at 4 degrees C for 24 hours and cut into 1-cm blocks in the coronal plane from throughout the medulla. Serial 50-microm sections were collected and one section every 300 microm was stained for TH. There was a pronounced depletion of TH neurons in the rostral VLM in all cases of MSA. There was also significant reduction of TH neurons in the caudal VLM in 3 MSA patients compared with 3 control subjects. In 2 MSA cases and in 2 control subjects, the thoracic spinal cord was available for study. There was also depletion of TH fibers and sympathetic preganglionic neurons (SPNs) in the 2 MSA cases examined. Thus, depletion of catecholaminergic neurons in the VLM may provide a substrate for some of the autonomic and endocrine manifestations of MSA.

  15. Abnormal ghrelin secretion contributes to gastrointestinal symptoms in multiple system atrophy patients.

    PubMed

    Ozawa, Tetsutaro; Tokunaga, Jun; Arakawa, Musashi; Ishikawa, Atsushi; Takeuchi, Ryoko; Mezaki, Naomi; Miura, Takeshi; Sakai, Naoko; Hokari, Mariko; Takeshima, Akari; Utsumi, Kota; Kondo, Takashi; Yokoseki, Akio; Nishizawa, Masatoyo

    2013-08-01

    Patients with multiple system atrophy (MSA) often have evidence of compromised gastrointestinal motility. Ghrelin is a gut hormone that influences gastrointestinal motility in humans. The aim of this study was to determine whether ghrelin secretion is affected in MSA patients, and to investigate the relation between ghrelin secretion and gastrointestinal symptoms. Plasma levels of active ghrelin and unacylated ghrelin were measured in patients with MSA (n = 30), other atypical parkinsonian disorders including progressive supranuclear palsy-Richardson syndrome and corticobasal syndrome (n = 24), and control subjects (n = 24) using enzyme-linked immunosorbent assays. Gastrointestinal symptoms were quantified in all subjects using a self-report questionnaire. The ratio of active ghrelin to total ghrelin in the plasma (active ghrelin ratio) was lower in patients with MSA (mean: 8.0 %) than in patients with other atypical parkinsonian disorders (mean: 13.7 %, P = 0.001) and control subjects (mean: 13.9 %, P = 0.001). The active ghrelin ratio was correlated with the severity of gastrointestinal symptoms in MSA (r = -0.5, P = 0.004). Our observations indicate that ghrelin secretion is affected in patients with MSA. The low active ghrelin ratio may contribute to gastrointestinal symptoms in MSA.

  16. A novel approach to modeling and diagnosing the cardiovascular system

    SciTech Connect

    Keller, P.E.; Kangas, L.J.; Hashem, S.; Kouzes, R.T.; Allen, P.A.

    1995-07-01

    A novel approach to modeling and diagnosing the cardiovascular system is introduced. A model exhibits a subset of the dynamics of the cardiovascular behavior of an individual by using a recurrent artificial neural network. Potentially, a model will be incorporated into a cardiovascular diagnostic system. This approach is unique in that each cardiovascular model is developed from physiological measurements of an individual. Any differences between the modeled variables and the variables of an individual at a given time are used for diagnosis. This approach also exploits sensor fusion to optimize the utilization of biomedical sensors. The advantage of sensor fusion has been demonstrated in applications including control and diagnostics of mechanical and chemical processes.

  17. Diagnosing Hybrid Systems: a Bayesian Model Selection Approach

    NASA Technical Reports Server (NTRS)

    McIlraith, Sheila A.

    2005-01-01

    In this paper we examine the problem of monitoring and diagnosing noisy complex dynamical systems that are modeled as hybrid systems-models of continuous behavior, interleaved by discrete transitions. In particular, we examine continuous systems with embedded supervisory controllers that experience abrupt, partial or full failure of component devices. Building on our previous work in this area (MBCG99;MBCG00), our specific focus in this paper ins on the mathematical formulation of the hybrid monitoring and diagnosis task as a Bayesian model tracking algorithm. The nonlinear dynamics of many hybrid systems present challenges to probabilistic tracking. Further, probabilistic tracking of a system for the purposes of diagnosis is problematic because the models of the system corresponding to failure modes are numerous and generally very unlikely. To focus tracking on these unlikely models and to reduce the number of potential models under consideration, we exploit logic-based techniques for qualitative model-based diagnosis to conjecture a limited initial set of consistent candidate models. In this paper we discuss alternative tracking techniques that are relevant to different classes of hybrid systems, focusing specifically on a method for tracking multiple models of nonlinear behavior simultaneously using factored sampling and conditional density propagation. To illustrate and motivate the approach described in this paper we examine the problem of monitoring and diganosing NASA's Sprint AERCam, a small spherical robotic camera unit with 12 thrusters that enable both linear and rotational motion.

  18. Skeletal muscle atrophy in bioengineered skeletal muscle: a new model system.

    PubMed

    Lee, Peter H U; Vandenburgh, Herman H

    2013-10-01

    Skeletal muscle atrophy has been well characterized in various animal models, and while certain pathways that lead to disuse atrophy and its associated functional deficits have been well studied, available drugs to counteract these deficiencies are limited. An ex vivo tissue-engineered skeletal muscle offers a unique opportunity to study skeletal muscle physiology in a controlled in vitro setting. Primary mouse myoblasts isolated from adult muscle were tissue engineered into bioartificial muscles (BAMs) containing hundreds of aligned postmitotic muscle fibers expressing sarcomeric proteins. When electrically stimulated, BAMs generated measureable active forces within 2-3 days of formation. The maximum isometric tetanic force (Po) increased for ∼3 weeks to 2587±502 μN/BAM and was maintained at this level for greater than 80 days. When BAMs were reduced in length by 25% to 50%, muscle atrophy occurred in as little as 6 days. Length reduction resulted in significant decreases in Po (50.4%), mean myofiber cross-sectional area (21.7%), total protein synthesis rate (22.0%), and noncollagenous protein content (6.9%). No significant changes occurred in either the total metabolic activity or protein degradation rates. This study is the first in vitro demonstration that length reduction alone can induce skeletal muscle atrophy, and establishes a novel in vitro model for the study of skeletal muscle atrophy.

  19. Differing patterns of striatal sup 18 F-dopa uptake in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy

    SciTech Connect

    Brooks, D.J.; Ibanez, V.; Sawle, G.V.; Quinn, N.; Lees, A.J.; Mathias, C.J.; Bannister, R.; Marsden, C.D.; Frackowiak, R.S. )

    1990-10-01

    Using positron emission tomography (PET), we studied regional striatal 18F-dopa uptake in 16 patients with L-dopa-responsive Parkinson's disease (PD), 18 patients with multiple system atrophy, and 10 patients with progressive supranuclear palsy. Results were compared with those of 30 age-matched normal volunteers. The patients with PD showed significantly reduced mean uptake of 18F-dopa in the caudate and putamen compared to controls, but while function in the posterior part of the putamen was severely impaired (45% of normal), function in the anterior part of the putamen and in the caudate was relatively spared (62% and 84% of normal). Mean 18F-dopa uptake in the posterior putamen was depressed to similar levels in all patients. Unlike patients with PD, the patients with progressive supranuclear palsy showed equally severe impairment of mean 18F-dopa uptake in the anterior and posterior putamen. Caudate 18F-dopa uptake was also significantly lower in patients with progressive supranuclear palsy than in patients with PD, being depressed to the same level as that in the putamen. Mean 18F-dopa uptake values in the anterior putamen and caudate in patients with multiple system atrophy lay between PD and progressive supranuclear palsy levels. Locomotor disability of individual patients with PD or multiple system atrophy correlated with decline in striatal 18F-dopa uptake, but this was not the case for the patients with progressive supranuclear palsy. We conclude that patients with PD have selective nigral pathological features with relative preservation of the dopaminergic function in the anterior putamen and caudate, whereas there is progressively more extensive nigral involvement in multiple system atrophy and progressive supranuclear palsy.

  20. An expert system for diagnosing environmentally induced spacecraft anomalies

    NASA Technical Reports Server (NTRS)

    Rolincik, Mark; Lauriente, Michael; Koons, Harry C.; Gorney, David

    1992-01-01

    A new rule-based, machine independent analytical tool was designed for diagnosing spacecraft anomalies using an expert system. Expert systems provide an effective method for saving knowledge, allow computers to sift through large amounts of data pinpointing significant parts, and most importantly, use heuristics in addition to algorithms, which allow approximate reasoning and inference and the ability to attack problems not rigidly defined. The knowledge base consists of over two-hundred (200) rules and provides links to historical and environmental databases. The environmental causes considered are bulk charging, single event upsets (SEU), surface charging, and total radiation dose. The system's driver translates forward chaining rules into a backward chaining sequence, prompting the user for information pertinent to the causes considered. The use of heuristics frees the user from searching through large amounts of irrelevant information and allows the user to input partial information (varying degrees of confidence in an answer) or 'unknown' to any question. The modularity of the expert system allows for easy updates and modifications. It not only provides scientists with needed risk analysis and confidence not found in algorithmic programs, but is also an effective learning tool, and the window implementation makes it very easy to use. The system currently runs on a Micro VAX II at Goddard Space Flight Center (GSFC). The inference engine used is NASA's C Language Integrated Production System (CLIPS).

  1. System and method for diagnosing EGR performance using NOx sensor

    DOEpatents

    Mazur, Christopher John

    2003-12-23

    A method and system for diagnosing a condition of an EGR valve used in an engine system. The EGR valve controls the portion exhaust gases produced by such engine system and fed back to an intake of such engine system. The engine system includes a NOx sensor for measuring NOx in such exhaust. The method includes: determining a time rate of change in NOx measured by the NOx sensor; comparing the determined time rate of change in the measured NOx with a predetermined expected time rate of change in measured NOx; and determining the condition of the EGR valve as a function of such comparison. The method also includes: determining from NOx measured by the NOx sensor and engine operating conditions indications of instances when samples of such measured NOx are greater than an expected maximum NOx level for such engine condition and less than an expected minimum NOx level for such engine condition; and determining the condition of the EGR valve as a function of a statistical analysis of such indications. The method includes determining whether the NOx sensor is faulty and wherein the EGR condition determining includes determining whether the NOx sensor is faulty.

  2. Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism

    PubMed Central

    Prusiner, Stanley B.; Woerman, Amanda L.; Mordes, Daniel A.; Watts, Joel C.; Rampersaud, Ryan; Berry, David B.; Patel, Smita; Oehler, Abby; Lowe, Jennifer K.; Kravitz, Stephanie N.; Geschwind, Daniel H.; Glidden, David V.; Halliday, Glenda M.; Middleton, Lefkos T.; Gentleman, Steve M.; Grinberg, Lea T.; Giles, Kurt

    2015-01-01

    Prions are proteins that adopt alternative conformations that become self-propagating; the PrPSc prion causes the rare human disorder Creutzfeldt–Jakob disease (CJD). We report here that multiple system atrophy (MSA) is caused by a different human prion composed of the α-synuclein protein. MSA is a slowly evolving disorder characterized by progressive loss of autonomic nervous system function and often signs of parkinsonism; the neuropathological hallmark of MSA is glial cytoplasmic inclusions consisting of filaments of α-synuclein. To determine whether human α-synuclein forms prions, we examined 14 human brain homogenates for transmission to cultured human embryonic kidney (HEK) cells expressing full-length, mutant human α-synuclein fused to yellow fluorescent protein (α-syn140*A53T–YFP) and TgM83+/− mice expressing α-synuclein (A53T). The TgM83+/− mice that were hemizygous for the mutant transgene did not develop spontaneous illness; in contrast, the TgM83+/+ mice that were homozygous developed neurological dysfunction. Brain extracts from 14 MSA cases all transmitted neurodegeneration to TgM83+/− mice after incubation periods of ∼120 d, which was accompanied by deposition of α-synuclein within neuronal cell bodies and axons. All of the MSA extracts also induced aggregation of α-syn*A53T–YFP in cultured cells, whereas none of six Parkinson’s disease (PD) extracts or a control sample did so. Our findings argue that MSA is caused by a unique strain of α-synuclein prions, which is different from the putative prions causing PD and from those causing spontaneous neurodegeneration in TgM83+/+ mice. Remarkably, α-synuclein is the first new human prion to be identified, to our knowledge, since the discovery a half century ago that CJD was transmissible. PMID:26324905

  3. A flash x-ray system for diagnosing liner implosions

    SciTech Connect

    Anderson, B. G.; Oro, D. M.; Olson, R. T.; Studebaker, J. K.; Platts, D.

    2003-01-01

    This paper describes a low energy flash X-ray system that is ideal for radiographing a wide variety of experimental phenomenon on both capacitor-bank pulsed power facilities and explosively driven magnetic-flux compression experiments. The versatility of this system has allowed us to obtain both single X-radiographs of imploding liners and multiple, temporally resolved radiographic sequences of target evolution. The dynamic liner radiographs are acquired with radially oriented X-ray heads that are instrumental for observing and diagnosing liner shape and symmetry, Rayleigh-Taylor instability growth, and liner-glide plane interaction (see Fig. 1). Multiframe radiographs acquired along the axis of a cylindrical target are used to provide physical data on phenomena such as shock-driven target hydrodynamics, Richtmyer-Meshkov instability growth, spall, fiction, and equations of state. The flexibility of this X-ray system has also allowed it to be successfully fielded both at various gas and powder gun facilities and explosively driven shock physics experiments.

  4. Computer-aided intelligent system for diagnosing pediatric asthma.

    PubMed

    Zolnoori, Maryam; Fazel Zarandi, Mohammad Hossein; Moin, Mostafa; Heidarnezhad, Hassan; Kazemnejad, Anoshirvan

    2012-04-01

    Asthma is a lung chronic inflammatory disorder estimated between 1.4% and 27.1% in different area of the world. Result of various studies show that asthma is usually underdiagnosed especially in developing countries, because of limitations on access to medical specialists and laboratory facilities. In this paper, we report on the development and evaluation of a novel patient-based fuzzy system that promotes the diagnosis method of asthma. The design of this application addresses five critical issues included: 1) modular representation of asthma diagnostic variables regard to patients' perception of the disease, 2) algorithmic approaches conducting inference of diagnosing based on patient's response to questions, 4) front-end mechanism for capturing data from patient, 5) output for both patient and physician regard to asthma possibility. for the system output score (0-10) the efficacy of this system calculated in the study sample included 139 asthmatic patients and 139 non-asthmatic patients (age range 6-18) reinforce the sensitivity of 88% and specificity of 100% for cut off value 0.7.

  5. Resistance Training with Instability in Multiple System Atrophy: A Case Report

    PubMed Central

    Silva-Batista, Carla; Kanegusuku, Hélcio; Roschel, Hamilton; Souza, Eduardo O.; Cunha, Telma F.; Laurentino, Gilberto C.; Manoel, N.; De Mello, Marco T.; Piemonte, Maria E.P.; Brum, Patrícia C.; Forjaz, Claudia L.; Tricoli, Valmor; Ugrinowitsch, Carlos

    2014-01-01

    This case report assessed quality of life, activities of daily living, motor symptoms, functional ability, neuromuscular parameters and mRNA expression of selected genes related to muscle protein synthesis and degradation in a patient with Multiple System Atrophy (MSA). The patient underwent resistance training with instability devices (i.e., bosu, dyna disk, balance disk, Swiss ball) for six months twice a week. After the six months training, the patient’s left and right quadriceps muscle cross-sectional area and leg press one-repetition maximum increased 6.4%, 6.8%, and 40%, respectively; the patient’s timed up and go, sit to stand, dynamic balance, and activities of daily living improved 33.3%, 28.6%, 42.3%, and 40.1%, respectively; the patient’s severity of motor symptoms and risk of falls decreased 32% and 128.1%, respectively. Most of the subscales of quality of life demonstrated improvements as well, varying from 13.0% to 100.0%. mRNA expression of mechanogrowth factor and mammalian target of rapamycin increased 12.7-fold and 1.5-fold, respectively. This case report describes likely the first nonpharmacological therapeutic tool that might be able to decrease the severity of motor symptoms and risk of falls, and to improve functional ability, neuromuscular parameters, and quality of the life in a patient with MSA. Key points Six months of resistance training with instability alleviate the MSA-related effects and improve the quality of life in a patient with MSA. High complexity exercise intervention (i.e., resistance training with instability) may be very beneficial to individuals with impaired motor control and function as MSA patients. Caution should be exercised when interpreting our findings as they cannot be generalized to the entire MSA population and they do not allow establishing causal conclusions on the effects of this mode of exercise on MSA. PMID:25177187

  6. Decreased Vesicular Storage and Aldehyde Dehydrogenase Activity in Multiple System Atrophy

    PubMed Central

    Goldstein, David S.; Sullivan, Patricia; Holmes, Courtney; Kopin, Irwin J.; Sharabi, Yehonatan; Mash, Deborah C.

    2015-01-01

    Background Parkinson disease (PD) and multiple system atrophy (MSA) share some neuropathologic findings (nigrostriatal dopaminergic lesion, alpha-synuclein deposition) but not others (Lewy bodies in PD, glial cytoplasmic inclusions in MSA). In PD evidence has accrued for a vesicular storage defect and aldehyde dehydrogenase (ALDH) inhibition in residual dopaminergic terminals, resulting in accumulation of the toxic dopamine (DA) metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). In this study we asked whether MSA entails a similar abnormal neurochemical pattern. Methods DA and its main neuronal metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), norepinephrine (NE) and its main neuronal metabolite 3,4-dihydroxyphenylglycol (DHPG), the catecholamine precursor DOPA, and DOPAL were measured in striatal and frontal cortical tissue from patients with pathologically proven end-stage MSA (N=15), sporadic PD (N=17), and control subjects (N=18). Results Compared to the control group, the MSA and PD groups had similarly decreased putamen DA (by 96% and 93%, p<0.0001), DOPAC (97% and 95%, p<0.0001), NE (91% and 74%, p<0.0001), and DHPG (81% and 74%, p<0.0001). In the MSA and PD groups, ratios of DOPAL:DA were 2.3 and 3.5 times control and DHPG:NE 3.1 and 2.6 times control, while DOPAC:DOPAL ratios were decreased by 61% and 74%. In both diseases cortical NE and DHPG were decreased, while DA and DOPAC were not. Conclusions MSA and PD entail a catecholamine metabolic profile indicating impaired vesicular storage, decreased ALDH activity, and DOPAL buildup, which may be part of a common pathway in catecholamine neuronal death. Targeting this pathway by interfering with catecholaldehyde production or effects constitutes a novel treatment approach. PMID:25829070

  7. Resistance training with instability in multiple system atrophy: a case report.

    PubMed

    Silva-Batista, Carla; Kanegusuku, Hélcio; Roschel, Hamilton; Souza, Eduardo O; Cunha, Telma F; Laurentino, Gilberto C; Manoel, N; De Mello, Marco T; Piemonte, Maria E P; Brum, Patrícia C; Forjaz, Claudia L; Tricoli, Valmor; Ugrinowitsch, Carlos

    2014-09-01

    This case report assessed quality of life, activities of daily living, motor symptoms, functional ability, neuromuscular parameters and mRNA expression of selected genes related to muscle protein synthesis and degradation in a patient with Multiple System Atrophy (MSA). The patient underwent resistance training with instability devices (i.e., bosu, dyna disk, balance disk, Swiss ball) for six months twice a week. After the six months training, the patient's left and right quadriceps muscle cross-sectional area and leg press one-repetition maximum increased 6.4%, 6.8%, and 40%, respectively; the patient's timed up and go, sit to stand, dynamic balance, and activities of daily living improved 33.3%, 28.6%, 42.3%, and 40.1%, respectively; the patient's severity of motor symptoms and risk of falls decreased 32% and 128.1%, respectively. Most of the subscales of quality of life demonstrated improvements as well, varying from 13.0% to 100.0%. mRNA expression of mechanogrowth factor and mammalian target of rapamycin increased 12.7-fold and 1.5-fold, respectively. This case report describes likely the first nonpharmacological therapeutic tool that might be able to decrease the severity of motor symptoms and risk of falls, and to improve functional ability, neuromuscular parameters, and quality of the life in a patient with MSA. Key pointsSix months of resistance training with instability alleviate the MSA-related effects and improve the quality of life in a patient with MSA.High complexity exercise intervention (i.e., resistance training with instability) may be very beneficial to individuals with impaired motor control and function as MSA patients.Caution should be exercised when interpreting our findings as they cannot be generalized to the entire MSA population and they do not allow establishing causal conclusions on the effects of this mode of exercise on MSA.

  8. Daytime sleepiness in Japanese patients with multiple system atrophy: prevalence and determinants

    PubMed Central

    2012-01-01

    Background The recent SLEEMSA study that evaluated excessive daytime sleepiness (EDS) in Caucasian patients with multiple system atrophy (MSA) demonstrated that EDS was more frequent in patients (28%) than in healthy subjects (2%). However, the prevalence and determinants of EDS in other ethnic populations have not been reported to date. Methods We performed a single-hospital prospective study on patients with probable MSA. To ascertain the prevalence and determinants of EDS in Japanese MSA patients, we assessed the patients’ degree of daytime sleepiness by using the Japanese version of the Epworth Sleepiness Scale (ESS). In addition, we investigated the effects of sleep-disordered breathing (SDB) and abnormal periodic leg movements in sleep (PLMS), which were measured by polysomnography, on the patients’ ESS scores. Results A total of 25 patients with probable MSA (21 patients with cerebellar MSA and 4 patients with parkinsonian MSA) were included in this study. All patients underwent standard polysomnography. The mean ESS score was 6.2 ± 0.9, and EDS was identified in 24% of the patients. SDB and abnormal PLMS were identified in 24 (96%) and 11 (44%) patients, respectively. The prevalences of EDS in patients with SDB and abnormal PLMS were 25% and 18%, respectively. No correlations were observed between ESS scores and the parameters of SDB or abnormal PLMS. Conclusions The frequency of EDS in Japanese patients with MSA was similar to that in Caucasian MSA patients. SDB and abnormal PLMS were frequently observed in MSA patients, although the severities of these factors were not correlated with EDS. Further investigations using objective sleep tests need to be performed. PMID:23116490

  9. Degeneration of cardiac sympathetic nerve can occur in multiple system atrophy.

    PubMed

    Orimo, Satoshi; Kanazawa, Toshiro; Nakamura, Ayako; Uchihara, Toshiki; Mori, Fumiaki; Kakita, Akiyoshi; Wakabayashi, Koichi; Takahashi, Hitoshi

    2007-01-01

    Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [(123)I] MIBG myocardial scintigraphy, a sensitive biological marker for Parkinson's disease (PD), is related to cardiac sympathetic denervation in patients with PD. A slight decrease in cardiac uptake of MIBG has also been reported in some patients with multiple system atrophy (MSA). However, the pathophysiological mechanism accounting for the slight decrease in MIBG uptake in MSA remains to be elucidated. For confirmation, we examined cardiac tissue and sympathetic ganglia from patients with MSA. We immunohistochemically examined each specimen of 15 patients with MSA together with 10 control subjects using antibodies against tyrosine hydroxylase (TH) and neurofilament (NF). The number of TH-immunoreactive nerve fibers in the epicardium was preserved in 8 of 15 patients with MSA as well as in 10 control subjects. The number of TH-immunoreactive, but not of NF-immunoreactive nerve fibers in the epicardium was mildly or moderately decreased in six patients with MSA, of whom four showed a decrease of TH immunoreactivity in the neuronal somata in the sympathetic ganglia. Moreover, TH- and NF-immunoreactive nerve fibers almost entirely disappeared in the heart of one patient with MSA, in whom Lewy body pathology was present in the sympathetic ganglia. These findings suggest that mild degeneration of the cardiac sympathetic nerve can occur in MSA which is closely related to the pathological change of neurons in the sympathetic ganglia, accounting for the slight decrease in cardiac uptake of MIBG. Moreover, concurrent Lewy body pathology in the sympathetic ganglia might accelerate cardiac sympathetic denervation even in MSA.

  10. Clinical features and disability milestones in multiple system atrophy and progressive supranuclear palsy.

    PubMed

    Lee, Sang-Wook; Koh, Seong-Beom

    2012-10-01

    Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are an adult-onset progressive neurodegenerative disorder that are known to display diverse clinical features and disease progression. We aim to characterize the clinical features and disease progression in patients with MSA and PSP by using a number of relevant disability milestones in Koreans. Forty-one patients with MSA and 14 patients with PSP had been enrolled. The mean age at onset of MSA-C, MSA-P and PSP was 56.7 ± 7.8, 62.5 ± 8.0, 68.9 ± 6.1 years respectively. The most commonly reported symptom at disease onset is disequilibrium/dizziness in MSA-C, tremor in MSA-P and frequent falling in PSP. The mean duration of reaching milestones after disease onset in MSA-C were as followings: 20.8 (urinary incontinence), 22.9 (frequent falling), 27.8 (wheelchair bound), 31.8 (dysarthria) and 35.8 months (diagnosis). The mean duration of reaching milestones after disease onset were 22.0 (urinary incontinence), 32.6 (frequent falling and diagnosis), 41.2 (dysarthria), 61.4 months (wheelchair bound) in MSA-P and 16.8 (dysarthria), 21.6 (diagnosis), 21.7 (frequent falling), 24.0 months (wheel chair bound) in PSP. In the case of MSA, dizziness may occur for the first time. Thus, when the patient complains of non-specific dizziness, a follow-up examination to distinguish it from MSA can be helpful. There was a trend for patients with MSA-C to reach more disability milestones than in MSA-P and PSP before diagnosis. It may explain why patients with MSA-C are required more detail history taking and neurologic examination at an earlier stage.

  11. MicroRNAs in Cerebrospinal Fluid as Potential Biomarkers for Parkinson's Disease and Multiple System Atrophy.

    PubMed

    Marques, Tainá M; Kuiperij, H Bea; Bruinsma, Ilona B; van Rumund, Anouke; Aerts, Marjolein B; Esselink, Rianne A J; Bloem, Bas R; Verbeek, Marcel M

    2016-11-14

    Parkinson's disease (PD) and multiple system atrophy (MSA) are both part of the spectrum of neurodegenerative movement disorders and α-synucleinopathies with overlap of symptoms especially at early stages of the disease but with distinct disease progression and responses to dopaminergic treatment. Therefore, having biomarkers that specifically classify patients, which could discriminate PD from MSA, would be very useful. MicroRNAs (miRNAs) regulate protein translation and are observed in biological fluids, including cerebrospinal fluid (CSF), and may therefore have potential as biomarkers of disease. The aim of our study was to determine if miRNAs in CSF could be used as biomarkers for either PD or MSA. Using quantitative PCR (qPCR), we evaluated expression levels of 10 miRNAs in CSF patient samples from PD (n = 28), MSA (n = 17), and non-neurological controls (n = 28). We identified two miRNAs (miR-24 and miR-205) that distinguished PD from controls and four miRNAs that differentiated MSA from controls (miR-19a, miR-19b, miR-24, and miR-34c). Combinations of miRNAs accurately discriminated either PD (area under the curve (AUC) = 0.96) or MSA (AUC = 0.86) from controls. In MSA, we also observed that miR-24 and miR-148b correlated with cerebellar ataxia symptoms, suggesting that these miRNAs are involved in cerebellar degeneration in MSA. Our findings support the potential of miRNA panels as biomarkers for movement disorders and may provide more insights into the pathological mechanisms related to these disorders.

  12. Spinal Cord Lesion by Minor Trauma as an Early Sign of Multiple System Atrophy

    PubMed Central

    Brum, Marisa; Reimão, Sofia; Sousa, Djalma; de Carvalho, Rui; Ferreira, Joaquim J.

    2016-01-01

    Multiple system atrophy (MSA) is characterized clinically by parkinsonism, cerebellar, autonomic, and corticospinal features of variable severity. When the presentation is only parkinsonism, the disease might be difficult to differentiate from Parkinson’s disease (PD). We present a case of an 80-year-old man with previous diagnosis of PD. One year after the diagnosis, he had a whiplash cervical trauma due to a tricycle accident caused by a hole in the road. This low-energy trauma caused an unstable C4–C5 cervical fracture with spinal cord injury, which required surgical decompression and stabilization. Neurological examination showed marked postural instability, no rest and postural tremor, finger tapping slowed on the right, spastic tetraparesis (ASIA D) – predominantly on the left side, brisk deep tendon reflexes in the upper and lower extremities, and bilateral extensor plantar response. He also presented with vertical gaze restriction, mild hypometria in horizontal saccades, moderate dysphagia, and dysphonia. As atypical parkinsonism was suspected, he underwent an MRI that revealed conjunction of findings suggestive of parkinsonian-type MSA. In our case, we hypothesize that the loss of postural reflexes, as an early manifestation of MSA, did not allow the patient to have an effective reaction response to a low-energy trauma, resulting in a more severe injury. With this case report, we speculate that the severe spinal lesions caused by minor accidents can be an early sign of postural instability, which may lead to clinical suspicion of neurodegenerative disorder manifested by postural reflexes impairment. PMID:27014185

  13. The involvement of supratentorial white matter in multiple system atrophy: a diffusion tensor imaging tractography study.

    PubMed

    Wang, Po-Shan; Yeh, Chien-Li; Lu, Chia-Feng; Wu, Hsiu-Mei; Soong, Bing-Wen; Wu, Yu-Te

    2017-03-01

    It has been assumed that cognitive disorder and visual-spatial disturbance in multiple system atrophy of the predominantly cerebellar type (MSA-C) are attributable to degradation of cerebellar function. The purpose of this study was to use diffusion tensor imaging (DTI) tractography to determine if patients with MSA-C characterized in part by visual-spatial disorders and cognitive disorders have changes of the structural connectivity network of nerve fibers, and to further describe the structural connectivity network. The study included 20 patients with MSA-C and 30 age- and sex-matched healthy controls. A 1.5T magnetic resonance imaging (MRI) scanner was used to obtain images for DTI tractography. Image preprocessing was done by large deformation diffeomorphic metric mapping. Whole-brain connectivity analysis was carried out. The patients had decreased numbers of long association fibers connecting the right parietal lobe to the frontal lobe. The commissural fibers and short association fibers connecting the bilateral frontal and occipital lobes and the number of short association fibers at the bilateral frontal and occipital region were also decreased significantly. The patients had a significant decrease in fiber density in the cerebellum compared to the healthy subjects. Our results provide DTI evidence suggesting that frontal and occipital white matter is involved in patients with MSA-C. This finding may correlate with their clinical symptoms such as cognitive disturbance as well as visual-spatial impairment. Therefore, cognitive disturbance and visual-spatial deficits in MSA-C might not be due to cerebellar lesions only as is widely believed but also involve cerebral lesions.

  14. Adult-onset cerebello-brainstem dominant form of X-linked adrenoleukodystrophy presenting as multiple system atrophy: Case report and literature review

    PubMed Central

    Ogaki, Kotaro; Koga, Shunsuke; Aoki, Naoya; Lin, Wenlang; Suzuki, Kinuko; Ross, Owen A.; Dickson, Dennis W.

    2015-01-01

    X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder and is caused by ABCD1 mutations. A cerebello-brainstem dominant form that mainly involves the cerebellum and brainstem is summarized in a review of the literature, with autopsy confirmed cases exceedingly rare. We report a 69-year-old white man who was diagnosed with this rare disorder and describe neuropathologic, ultrastructural and genetic analyses. He did not have adrenal insufficiency or a family history of X-ALD or Addison’s disease. His initial symptom was temporary loss of eyesight at age 34 years. His major symptoms were chronic and progressive gait disorder, weakness in his lower extremities, and spasticity, as well as autonomic failure and cerebellar ataxia suggesting possible multiple system atrophy (MSA). He also had seizures, hearing loss, and sensory disturbances. His brain MRI showed no obvious atrophy or significant white matter pathology in cerebrum, brainstem or cerebellum. He died at age 69 years with a diagnosis of multiple system atrophy. Microscopic analysis showed mild, patchy myelin rarefaction with perivascular clusters of PAS-positive, CD68-positive macrophages in the white matter most prominent in the cerebellum and occipital lobe, but also affecting optic tract and internal capsule. Electron microscopy of cerebellar white matter showed cleft-like trilamellar cytoplasmic inclusions in macrophages typical of X-ALD, which prompted genetic analysis that revealed a novel ABCD1 mutation, p.R163G. Given the relatively mild pathological findings and long disease duration, it is likely that the observed pathology was the result of a slow and indolent disease process. We described a patient who had sporadic cerebello-brainstem dominant form of X-ALD with long clinical course, mild pathological findings, and an ABCD1 p.R163G substitution. We also review a total of 34 cases of adult-onset cerebello-brainstem dominant form of X-ALD. Although rare, X-ALD should be

  15. Prodegenerative IκBα expression in oligodendroglial α-synuclein models of multiple system atrophy

    PubMed Central

    Kragh, Christine L.; Gysbers, Amanda M.; Rockenstein, Edward; Murphy, Karen; Halliday, Glenda M.; Masliah, Eliezer; Jensen, Poul Henning

    2016-01-01

    Multiple system atrophy is a progressive, neurodegenerative disease characterized by parkinsonism, ataxia, autonomic dysfunction, and accumulation of α-synuclein in oligodendrocytes. To understand how α-synuclein aggregates impact oligodendroglial homeostasis, we investigated an oligodendroglial cell model of α-synuclein dependent degeneration and identified responses linked to the NF-κB transcription factor stress system. Coexpression of human α-synuclein and the oligodendroglial protein p25α increased the expression of IκBα mRNA and protein early during the degenerative process and this was dependent on both aggregation and Ser129 phosphorylation of α-synuclein. This response was prodegenerative because blocking IκBα expression by siRNA rescued the cells. IκBα is an inhibitor of NF-κB and acts by binding and retaining NF-κB p65 in the cytoplasm. The protection obtained by silencing IκBα was accompanied by a strong increase in nuclear p65 translocation indicating that NF-κB activation protects against α-synuclein aggregate stress. In the cellular model, two different phenotypes were observed; degenerating cells retracting their microtubules and resilient cells tolerating the coexpression of α-synuclein and p25α. The resilient cells displayed a significant higher nuclear translocation of p65 and activation of the NF-κB system relied on stress elicited by aggregated and Ser129 phosphorylated α-synuclein. To validate the relationship between oligodendroglial α-synuclein expression and IκBα, we analyzed two different lines of transgenic mice expressing human α-synuclein under the control of the oligodendrocytic MBP promotor (intermediate-expresser line 1 and high-expresser line 29). IκBα mRNA expression was increased in both lines and immunofluorescence microscopy and in situ hybridization revealed that IκBα mRNA and protein is expressed in oligodendrocytes. IκBα mRNA expression was demonstrated prior to activation of microglia and

  16. Systemic Complement Inhibition with Eculizumab for Geographic Atrophy in Age-Related Macular Degeneration

    PubMed Central

    Yehoshua, Zohar; Filho, Carlos Alexandre de Amorim Garcia; Nunes, Renata Portella; Gregori, Giovanni; Penha, Fernando M.; Moshfeghi, Andrew A.; Zhang, Kang; Sadda, SriniVas; Feuer, William; Rosenfeld, Philip J.

    2014-01-01

    Purpose To evaluate the effect of eculizumab, a systemic inhibitor of complement component (C5), on the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). Design Prospective, double-masked, randomized clinical trial. Participants Patients with GA measuring from 1.25 to 18 mm2 based on spectral-domain optical coherence tomography imaging. Methods Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 6 months. In the eculizumab treatment arm, the first 10 patients received a low-dose regimen of 600 mg weekly for 4 weeks followed by 900 mg every 2 weeks until week 24, and the next 10 patients received a high-dose regimen of 900 mg weekly for 4 weeks followed by 1200 mg every 2 weeks until week 24. The placebo group was infused with saline. Patients were observed off treatment for an additional 26 weeks. Both normal-luminance and lowluminance visual acuities were measured throughout the study, and the low-luminance deficits were calculated as the difference between the letter scores. Main Outcome Measures Change in area of GA at 26 weeks. Results Thirty eyes of 30 patients were enrolled. Eighteen fellow eyes also met inclusion criteria and were analyzed as a secondary endpoint. For the 30 study eyes, mean square root of GA area measurements ± standard deviation at baseline were 2.55±0.94 and 2.02±0.74 mm in the eculizumab and placebo groups,respectively (P = 0.13). At 26 weeks, GA enlarged by a mean of 0.19±0.12 and 0.18±0.15 mm in the eculizumab and placebo groups, respectively (P = 0.96). At 52 weeks of follow-up, GA enlarged by a mean of 0.37±0.22 mm in the eculizumab-treated eyes and by a mean of 0.37±0.21 mm in the placebo group (P = 0.93, 2 sample t test). None of the eyes converted to wet AMD. No drug-related adverse events were identified. Conclusions Systemic complement inhibition with eculizumab was well tolerated through 6 months but did not decrease the growth rate of GA significantly

  17. [Laryngeal paralysis and olivopontocerebellar atrophy. Apropos of a case].

    PubMed

    Sánchez Segura, A; Ramos Pérez, P L; Rodríguez Sánchez, A; Aguirre Sánchez, J J; Gutiérrez Díez, J A; Alvarez Domínguez, J

    1990-01-01

    We display the study performed to a female patient affected of laryngeal paralysis to become, based in clinical and radiologic criteria, to diagnose her cerebellar atrophy. We justify our work because of how infrequently this illness heredodegenerative of the central nervous system begins with cranial pairs paralysis. We emphasize the importance that the new methods of explorations specially TAC and IRM, have to guess the possible etiologies of central originated paralysis.

  18. Familial olivopontocerebellar atrophy with neonatal onset: a recessively inherited syndrome with systemic and biochemical abnormalities.

    PubMed Central

    Harding, B N; Dunger, D B; Grant, D B; Erdohazi, M

    1988-01-01

    Clinical and pathological findings are reported in two siblings who presented in the neonatal period with failure to thrive, hypotonia, pericardial effusions, limitation of joint movement, retinal dystrophy and loss of visual function. Additional features were biochemical evidence of purine overproduction and liver dysfunction. Post mortem, the neuropathological findings in both children were typical of olivopontocerebellar atrophy. It is suggested that the cases represent a recessively inherited inborn error of metabolism. Images PMID:3162953

  19. Videourodynamic and sphincter motor unit potential analyses in Parkinson's disease and multiple system atrophy

    PubMed Central

    Sakakibara, R; Hattori, T; Uchiyama, T; Yamanishi, T

    2001-01-01

    OBJECTIVES—Urinary dysfunction is a prominent autonomic feature in Parkinson's disease (PD) and multiple system atrophy (MSA), which is not only troublesome but also a cause of morbidity in these disorders. Recent advances in investigative uroneurology offer a better insight into the underlying pathophysiology and appropriate management for urinary dysfunction.
METHODS—twenty one patients with PD (15 men, six women, mean age 64 (49-76), mean disease duration 4 years (1-8 years), median Hoehn and Yahr grade 3 (1-4), all taking 300 mg/day of levodopa (100-500 mg)) and 15 with MSA (eight men, seven women, mean age 59 (48-72), mean disease duration 3 years (0.5-6 years)) were recruited. Videourodynamic and sphincter motor unit potential analyses in the patients with PD and MSA were carried out, looking for distinguishing hallmarks that might be useful in the differential diagnosis of these two diseases.
RESULTS—Urinary symptoms were found in 72% of patients with PD and in 100% with MSA. Filling phase abnormalities in the videourodynamic study included detrusor hyperreflexia in 81% of patients with PD and 56% with MSA, and uninhibited external sphincter relaxation in 33% of patients with PD and 33% of those with MSA. However, open bladder neck at the start of filling was not seen in patients with PD but was present in 53% of those with MSA, suggestive of internal sphincter denervation. Sphincter motor unit potential analysis showed neurogenic motor unit potentials in 5% of patients with PD and in 93% of those with MSA, suggestive of external sphincter denervation. On voiding, detrusor-external sphincter dyssynergia was not seen in patients with PD but was present in 47% of those with MSA. Pressure-flow analysis showed that the Abrams-Griffiths number, a grading of urethral obstruction (outflow obstruction >40), in PD (40 in women and 43 in men) was larger than that in MSA (12 in women and 28 in men). Weak detrusor in PD (66% of women and 40% of men) was less

  20. Natural History of Multiple System Atrophy in North America: A Prospective Cohort Study

    PubMed Central

    Low, Phillip A.; Reich, Stephen G.; Jankovic, Joseph; Shults, Clifford W.; Stern, Matthew B.; Novak, Peter; Tanner, Caroline M.; Gilman, Sid; Marshall, Frederick J.; Wooten, Frederick; Racette, Brad; Chelimsky, Thomas; Singer, Wolfgang; Sletten, David M.; Sandroni, Paola; Mandrekar, Jay

    2015-01-01

    Background Multiple system atrophy (MSA) is a rare, fatal neurodegenerative disorder exhibiting a combination of parkinsonism and/or cerebellar ataxia with autonomic failure. We report the first North American prospective natural history study of MSA, and the effects of phenotype and autonomic failure on prognosis. Methods 175 subjects with probable MSA, both MSA-P and MSA-C, were recruited and prospectively followed for 5 years with evaluations every 6 months in 12 centers. Natural history was evaluated by Kaplan-Meier survival analysis. We compared MSA-P with MSA-C and evaluated predictors of outcome. These subjects were evaluated with UMSARS I (a functional score of symptoms and ability to undertake activities of daily living), UMSARS II (neurological motor evaluation), and the Composite Autonomic Symptoms Scale (COMPASS)-select (a measure of autonomic symptoms and autonomic functional status. Findings Mean age of symptom onset was 63.4 (SD 8.57) years. Median survival from symptom onset by Kaplan-Meier analysis was 9.8 years (95% CI 8.8-10.7). Subjects with severe symptomatic autonomic failure (symptomatic orthostatic hypotension, urinary incontinence) at diagnosis had a worse prognosis, surviving 8.0 years (95% CI, 6.5-9.5, n=62) while remaining subjects survived a median of 10.3 years (95% CI, 9.3-11.4, n=113). At baseline MSA-P (n=126) and MSA-C (n=49) were not different in symptoms and function, UMSARS I, 25.2 (8.08) vs 24.6 (8.34), p=0.835; UMSARS II, 26.4 (8.77) vs 25.4 (10.51), p=0.7635; COMPASS_select), 43.5 (18.66) vs 42.8 (19.56), p=0.835. Progression, evaluated by change in UMSARS I, UMSARS II, COMPASS_select over the next 5 years, was not significantly different between MSA-P and MSA-C. Median time to death from enrollment baseline was 1.8 (95% CI, 0.9-2.7) years. Interpretation Probable MSA represents late-stage disease with short survival. Natural history of MSA-P and MSA-C are similar. Severe symptomatic autonomic failure at diagnosis is

  1. Tonic Electromyogram Density in Multiple System Atrophy with Predominant Parkinsonism and Parkinson's Disease

    PubMed Central

    Wang, Yi; Shen, Yun; Xiong, Kang-Ping; He, Pei-Cheng; Mao, Cheng-Jie; Li, Jie; Wang, Fu-Yu; Wang, Ya-Li; Huang, Jun-Ying; Liu, Chun-Feng

    2017-01-01

    Background: Both Parkinson's disease (PD) and multiple system atrophy (MSA) have associated sleep disorders related to the underlying neurodegenerative pathology. Clinically, MSA with predominant parkinsonism (MSA-P) resembles PD in the manifestation of prominent parkinsonism. Whether the amount of rapid eye movement (REM) sleep without atonia could be a potential marker for differentiating MSA-P from PD has not been thoroughly investigated. This study aimed to examine whether sleep parameters could provide a method for differentiating MSA-P from PD. Methods: This study comprised 24 MSA-P patients and 30 PD patients, and they were of similar age, gender, and REM sleep behavior disorder (RBD) prevalence. All patients underwent clinical evaluation and one night of video-polysomnography recording. The tonic and phasic chin electromyogram (EMG) activity was manually quantified during REM sleep of each patient. We divided both groups in terms of whether they had RBD to make subgroup analysis. Results: No significant difference between MSA-P group and PD group had been found in clinical characteristics and sleep architecture. However, MSA-P patients had higher apnea-hypopnea index (AHI; 1.15 [0.00, 8.73]/h vs. 0.00 [0.00, 0.55]/h, P = 0.024) and higher tonic chin EMG density (34.02 [18.48, 57.18]% vs. 8.40 [3.11, 13.06]%, P < 0.001) as compared to PD patients. Subgroup analysis found that tonic EMG density in MSA + RBD subgroup was higher than that in PD + RBD subgroup (55.04 [26.81, 69.62]% vs. 11.40 [8.51, 20.41]%, P < 0.001). Furthermore, no evidence of any difference in tonic EMG density emerged between PD + RBD and MSA - RBD subgroups (P > 0.05). Both disease duration (P = 0.056) and AHI (P = 0.051) showed no significant differences during subgroup analysis although there was a trend toward longer disease duration in PD + RBD subgroup and higher AHI in MSA - RBD subgroup. Stepwise multiple linear regression analysis identified the presence of MSA-P (β = 0.552, P

  2. Research on Key Technology in Remote Education System of Spirit Diagnosing by Eye in TCM

    ERIC Educational Resources Information Center

    Guo, Feng; Li, Shaozi; Dai, Ying; Zhou, Changle; Lin, Ying

    2011-01-01

    Spirit diagnosing is an important theory in TCM (Traditional Chinese Medicine), by which a TCM doctor can diagnose a patient's body state. But this theory is complicated and difficult to master simply learned from books. To further the theory and skill of spirit diagnosing, in this paper, the authors propose a remote education system that can…

  3. Validation of Autism Spectrum Disorder Diagnoses in Large Healthcare Systems with Electronic Medical Records

    ERIC Educational Resources Information Center

    Coleman, Karen J.; Lutsky, Marta A.; Yau, Vincent; Qian, Yinge; Pomichowski, Magdalena E.; Crawford, Phillip M.; Lynch, Frances L.; Madden, Jeanne M.; Owen-Smith, Ashli; Pearson, John A.; Pearson, Kathryn A.; Rusinak, Donna; Quinn, Virginia P.; Croen, Lisa A.

    2015-01-01

    To identify factors associated with valid Autism Spectrum Disorder (ASD) diagnoses from electronic sources in large healthcare systems. We examined 1,272 charts from ASD diagnosed youth <18 years old. Expert reviewers classified diagnoses as confirmed, probable, possible, ruled out, or not enough information. A total of 845 were classified with…

  4. [Multiple system atrophy and Alzheimer's disease: a case report of a rare association of two neuro-degenerative disorders].

    PubMed

    Rusina, R; Bourdain, F; Matej, R

    2007-12-01

    Multiple system atrophy (MSA) is a neurodegenerative disorder typically characterised by cerebellar dysfunction, parkinsonism, pyramidal signs and dysautonomy. Cognitive impairement is usually limited to a moderate subcortical dysexecutive syndrom. We report the case of a 62-year-old woman suffering from MSA who progressively developed severe dementia. Neuropathological examination confirmed the diagnosis of definite MSA and also showed histopathological hallmarks of Alzheimer's disease. This association is extremely rare in the literature. Our observation confirmes that franc dementia in MSA should prompt a search for another associated cause and underlines the usefulness of neuropathological verifications in atypical clinical pictures.

  5. Probable hereditary multiple system atrophy-autonomic (MSA-A) in a family in the United States.

    PubMed

    Hohler, A D; Singh, V J

    2012-03-01

    Multiple system atrophy-autonomic (MSA-A) is a typically spontaneous neurological disorder. The disease, distinguished by a "hot cross bun" sign on MRI, causes a series of autonomic dysfunctions including orthostatic hypotension and genitourinary and gastrointestinal problems. We present an 84 year-old woman with MSA-A symptoms who was positive for a "hot cross bun" sign. Genetic testing was used to rule out other possible ataxias. Importantly, the patient's two sisters also presented with similar symptoms indicating a possible autosomal dominant linkage. To our knowledge, this is the first report of hereditary MSA-A in the USA.

  6. Depletion of medullary serotonergic neurons in patients with multiple system atrophy who succumbed to sudden death.

    PubMed

    Tada, Mari; Kakita, Akiyoshi; Toyoshima, Yasuko; Onodera, Osamu; Ozawa, Tetsutaro; Morita, Takashi; Nishizawa, Masatoyo; Takahashi, Hitoshi

    2009-07-01

    Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by prominent autonomic failure with ataxia and/or parkinsonism. The leading cause of death in MSA is sudden death. We have shown that the early development of autonomic failure is an independent risk factor for sudden death. The depletion of sympathetic preganglionic neurons in the spinal intermediolateral cell column (IML) and its afferent medullary catecholaminergic and serotonergic neurons has been proposed to be partly responsible for autonomic failure in MSA. In this study, we investigated whether the depletion of neurons in any of these autonomic neuron groups contributes to sudden death in MSA. Out of 52 autopsy-proven patients with MSA, we selected 12 individuals who had died within 3.5 years after disease onset to define the accurate levels of slices and identify early neuropathological changes of autonomic nuclei in MSA. Four patients succumbed to sudden death and eight patients died through established causes. Serial 10 mum sections were obtained from the 8th segment of the thoracic cord and the rostral medulla oblongata. Sections from the medulla oblongata were immunostained for thyrosine hydroxylase and tryptophan hydroxylase. The total cell number in the five sections was computed for comparison. Compared with the control, the MSA group showed a marked depletion of neurons in the IML (38.0 +/- 7.1 versus 75.2 +/- 7.6 cells, P < 0.001), thyrosine hydroxylase-immunoreactive neurons in the ventrolateral medulla (VLM) (17.4 +/- 5.1 versus 72.8 +/- 13.6 cells, P < 0.01) and tryptophan hydroxylase-immunoreactive neurons in the VLM (15.6 +/- 9.2 versus 60.8 +/- 17.0 cells, P < 0.01), nucleus raphe obscurus (19.3 +/- 4.4 versus 75.3 +/- 8.6 cells, P < 0.001), nucleus raphe pallidus (2.1 +/- 2.7 versus 9.0 +/- 3.4 cells, P < 0.03), and arcuate nucleus (0.4 +/- 0.8 versus 2.3 +/- 1.5 cells, P < 0.05). Moreover, in patients who succumbed to sudden death, when compared with patients who

  7. Regulatory circuitry of TWEAK-Fn14 system and PGC-1α in skeletal muscle atrophy program.

    PubMed

    Hindi, Sajedah M; Mishra, Vivek; Bhatnagar, Shephali; Tajrishi, Marjan M; Ogura, Yuji; Yan, Zhen; Burkly, Linda C; Zheng, Timothy S; Kumar, Ashok

    2014-03-01

    Skeletal muscle wasting attributed to inactivity has significant adverse functional consequences. Accumulating evidence suggests that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and TNF-like weak inducer of apoptosis (TWEAK)-Fn14 system are key regulators of skeletal muscle mass in various catabolic states. While the activation of TWEAK-Fn14 signaling causes muscle wasting, PGC-1α preserves muscle mass in several conditions, including functional denervation and aging. However, it remains unknown whether there is any regulatory interaction between PGC-1α and TWEAK-Fn14 system during muscle atrophy. Here we demonstrate that TWEAK significantly reduces the levels of PGC-1α and mitochondrial content (∼50%) in skeletal muscle. Levels of PGC-1α are significantly increased in skeletal muscle of TWEAK-knockout (KO) and Fn14-KO mice compared to wild-type mice on denervation. Transgenic (Tg) overexpression of PGC-1α inhibited progressive muscle wasting in TWEAK-Tg mice. PGC-1α inhibited the TWEAK-induced activation of NF-κB (∼50%) and dramatically reduced (∼90%) the expression of atrogenes such as MAFbx and MuRF1. Intriguingly, muscle-specific overexpression of PGC-1α also prevented the inducible expression of Fn14 in denervated skeletal muscle. Collectively, our study demonstrates that TWEAK induces muscle atrophy through repressing the levels of PGC-1α. Overexpression of PGC-1α not only blocks the TWEAK-induced atrophy program but also diminishes the expression of Fn14 in denervated skeletal muscle.

  8. Cognitive deficits in progressive supranuclear palsy, Parkinson's disease, and multiple system atrophy in tests sensitive to frontal lobe dysfunction.

    PubMed Central

    Robbins, T W; James, M; Owen, A M; Lange, K W; Lees, A J; Leigh, P N; Marsden, C D; Quinn, N P; Summers, B A

    1994-01-01

    Groups of patients with idiopathic Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy or Steele-Richardson-Olszewski syndrome, matched for overall clinical disability, were compared using three computerised cognitive tests previously shown to be sensitive to frontal lobe dysfunction. On a test of planning based on the Tower of London task, all three groups were impaired, but in different ways. The groups with palsy and Parkinson's disease were slower in the measure of initial thinking time, whereas the group with multiple system atrophy was only slower in a measure of thinking time subsequent to the first move, resembling patients with frontal lobe damage. On a test of spatial working memory, each group showed deficits relative to their matched control groups, but the three groups differed in their strategy for dealing with this task. On a test of attentional set shifting, each group was again impaired, mainly at the extradimensional shifting stage, but the group with Steele-Richardson-Olszewski syndrome exhibited the greatest deficit. The results are compared with previous findings in patients with Alzheimer's disease or frontal lobe damage. It is concluded that these basal ganglia disorders share a distinctive pattern of cognitive deficits on tests of frontal lobe dysfunction, but there are differences in the exact nature of the impairments, in comparison not only with frontal lobe damage but also with one another. PMID:8301310

  9. Fault Diagnosis in Discrete-Event Systems with Incomplete Models: Learnability and Diagnosability.

    PubMed

    Kwong, Raymond H; Yonge-Mallo, David L

    2015-07-01

    Most model-based approaches to fault diagnosis of discrete-event systems require a complete and accurate model of the system to be diagnosed. However, the discrete-event model may have arisen from abstraction and simplification of a continuous time system, or through model building from input-output data. As such, it may not capture the dynamic behavior of the system completely. In a previous paper, we addressed the problem of diagnosing faults given an incomplete model of the discrete-event system. We presented the learning diagnoser which not only diagnoses faults, but also attempts to learn missing model information through parsimonious hypothesis generation. In this paper, we study the properties of learnability and diagnosability. Learnability deals with the issue of whether the missing model information can be learned, while diagnosability corresponds to the ability to detect and isolate a fault after it has occurred. We provide conditions under which the learning diagnoser can learn missing model information. We define the notions of weak and strong diagnosability and also give conditions under which they hold.

  10. Morphological substrate of autonomic failure and neurohormonal dysfunction in multiple system atrophy: impact on determining phenotype spectrum.

    PubMed

    Ozawa, Tetsutaro

    2007-09-01

    Autonomic failure is a prominent clinical feature of patients with multiple system atrophy (MSA). Neurohormonal dysfunction is also a frequent accompaniment in patients with MSA. The determination of the pathological involvement of the autonomic neurons, which are responsible for circadian rhythms and responses to stress, provides new insight into autonomic failure and neurohormonal dysfunction in MSA. The disruptions of circadian rhythms and responses to stress may underlie the impairment of homeostatic integration responsible for cardiovascular and respiratory failures. These notions lead to the hypothesis that a pathological involvement of autonomic neurons is a significant factor of the poor prognosis of MSA. Beyond this perspective, endeavors to find the morphological phenotype that represents a predominant loss of autonomic neurons may elucidate the full spectrum of pathological involvements in MSA.

  11. [Obese woman presenting as vocal cord abductor paralysis and floppy arytenoid associated with early signs of multiple system atrophy].

    PubMed

    Sakuta, Hideki; Miyamoto, Masayuki; Suzuki, Keisuke; Miyamoto, Tomoyuki; Nakajima, Itsuo; Nakamura, Toshiki; Hirata, Koichi

    2012-01-01

    In multiple system atrophy (MSA), sleep-related breathing disorders are commonly observed, including vocal cord abductor paralysis (VCAP), which can cause sudden death. In its early stage, VCAP occurs only during sleep, but as the disease progresses, it appears when both awake and asleep. We encountered a 59-year-old obese woman who had been under continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea syndrome (OSAS) for approximately one year but later developed acute respiratory failure because of VCAP. VCAP was the predominant finding that led to the diagnosis of MSA in our patient. On laryngoscopic examination, the movement of the patient's larynx was normal during wakefulness, but VCAP, paradoxical movements of the vocal cord and a floppy arytenoid were observed during drug-induced sleep. We suggest that detection of VCAP and laryngopharyngeal abnormalities such as floppy arytenoid in the early stage of MSA is important for determining treatment options.

  12. Increased cerebellar activation after repetitive transcranial magnetic stimulation over the primary motor cortex in patients with multiple system atrophy

    PubMed Central

    Li, Linling; Wu, Tianxia; Hou, Bo; Wu, Shuang; Feng, Feng; Cui, Liying

    2016-01-01

    Background Previous review reported that the high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor area (M1) of Parkinson’s disease (PD) patients could alleviate their symptoms. This study aimed to investigate the effect of rTMS over the left M1 of patients with multiple system atrophy (MSA). Methods Fifteen MSA patients were randomly assigned to receive a 10-session real (EP: group of experimental patients; n=7) or sham (CP: group of control patients; n=8) rTMS stimulation over two weeks. The overall experimental procedure consisted of two functional magnetic resonance imaging (fMRI) sessions, before and after a 10-session rTMS treatment. A complex self-paced sequential tapping task was performed during fMRI scanning. In addition, 18 age and gender matched healthy controls (HC) were enrolled. Subjects from the HC group did not receive any rTMS treatment and they underwent fMRI examination only once. The primary end point was the motor score change of the Unified Multiple System Atrophy Rating Scale (UMSARS-II) measured before and after the 5th and 10th session. Task-related activation was also compared among groups. Results After active rTMS treatment, only patients of EP group significant improvement in UMSARS-II score. Compared to HC, MSA patients showed significant activation over similar brain areas except for the cerebellum. Increased activation was obtained in the bilateral cerebellum after rTMS treatment in the EP group. On the contrary, no increased activation was identified in the CP group. Conclusions Our results highlight rTMS over M1 induced motor improvement in MSA patients that may be associated with increased activation in the cerebellum. PMID:27127756

  13. Differential diagnostic relevance of high resolution magnetic resonance in patients with possible multiple system atrophy (MSA) - A case report.

    PubMed

    Baronica, Koraljka Bacić; Ivkić, Goran; Ozretić, David; Milicević, Goran

    2011-01-01

    Multiple system atrophy (MSA) is sporadic, progressive neurodegenerative disorder characterized clinically by autonomic dysfunction, Parkinsonism (MSA-P), and cerebellar ataxia (MSA-C) in any combination. Parkinsonism is present in the majority of patients (80%). Early in the course of the disease autonomic dysfunctions are present in approximately 40% of patients, while the domination of cerebellar symptoms is present in 20% of all patients. According to second consensus statement on diagnosis of MSA, to make the diagnosis of possible MSA, except Parkinsonism or a cerebellar syndrome, there must be one feature involving autonomic dysfunction plus one other additional that can include findings on history, clinical examination or changes in structural or functional imaging. We present a case of 60-year old male with Parkinsonism and cerebellar symptoms accompanied with signs of autonomic nervous system involvement. Level of autonomic dysfunction was not the level required for the diagnosis of probable MSA. On initially performed 1.5T MRI, the most prominent neurodegenerative feature of brain stem, cerebellum and basal ganglia was atrophy, however features like "hot-cross bun" sign, "slit-like" putaminal rim and middle cerebellar peduncle hyperintensities were detected only after MR imaging on higher resolution (3T) device. Our case points to the possibility that some typical structural changes that can help in diagnostic process may not be clearly visible on 1.5 T MRI devices. In such cases we suggest using 3T MRI device, if feasible, in order to demonstrate findings that may help in establishing the diagnosis of possible MSA.

  14. Progression of multiple system atrophy (MSA): a prospective natural history study by the European MSA Study Group (EMSA SG).

    PubMed

    Geser, Felix; Wenning, Gregor K; Seppi, Klaus; Stampfer-Kountchev, Michaela; Scherfler, Christoph; Sawires, Martin; Frick, Carolin; Ndayisaba, Jean-Pierre; Ulmer, Hanno; Pellecchia, Maria T; Barone, Paolo; Kim, Hee T; Hooker, Juzar; Quinn, Niall P; Cardozo, Adriana; Tolosa, Eduardo; Abele, Michael; Klockgether, Thomas; Østergaard, Karen; Dupont, Erik; Schimke, Nicole; Eggert, Karla M; Oertel, Wolfgang; Djaldetti, Ruth; Poewe, Werner

    2006-02-01

    The disease-specific Unified Multiple System Atrophy Rating Scale (UMSARS) has been developed recently and validated for assessing disease severity in multiple system atrophy (MSA). Here, we aimed at (1) assessing rates of disease progression in MSA and (2) validating UMSARS for sensitivity to change over time. Impairment was assessed at two time points 12 months apart using UMSARS Part I (historical review), UMSARS Part II (motor examination), as well as measures of global disease severity, including UMSARS Part IV, Hoehn and Yahr (HY) Parkinson's disease staging, Schwab England Activities of Daily Living (SE ADL), and a three-point global Severity Scale (SS3). Fifty patients (male:female ratio, 1:0.9; possible MSA, 16%; probable MSA, 84%; MSA-parkinsonian, 58%; MSA-cerebellar, 42%) were assessed twice with an interval of 12.3 months. UMSARS II scores progressed by 57.3% (P<0.0001) and UMSARS I scores by 35.6% (P<0.0001) in relation to the respective baseline scores with no differences between motor subtypes, diagnostic categories and gender. Significant inverse correlations between (1) UMSARS I or UMSARS II progression and (2) baseline disability measures (i.e., the respective UMSARS or SS3 scores) and disease duration were found. Furthermore, the increases in HY staging, SE ADL and SS3 correlated significantly with UMSARS I, UMSARS II, and UMSARS IV progression. This report is the first prospective study showing rapid annual UMSARS rates of decline in MSA. Our data contribute to the ongoing validation process of UMSARS, and they facilitate the planning and implementation of future neuroprotective intervention trials.

  15. Optic nerve atrophy

    MedlinePlus

    Optic atrophy; Optic neuropathy ... There are many causes of optic atrophy. The most common is poor blood flow. This is called ischemic optic neuropathy. The problem most often affects older adults. ...

  16. Temporal Causal Diagrams for Diagnosing Failures in Cyber Physical Systems

    DTIC Science & Technology

    2014-10-02

    Guo, W., Wen, F., Ledwich, G., Liao, Z., He, X., & Liang, J. (2010). An Analytic Model for Fault Diagnosis in Power Systems Considering Malfunctions...IEEE Transactions on, 19(2), 524–532. Lin, X., Ke, S., Li, Z., Weng, H., & Han, X. (2010). A Fault Diagnosis Method of Power Systems Based on...On Control System Technology, 4(2), 105–124. Sekine, Y., Akimoto, Y., Kunugi, M., Fukui, C., & Fukui, S. (2002). Fault diagnosis of power systems

  17. Vaginal Atrophy

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... Clinical Trials Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ...

  18. Postural and action myoclonus in patients with parkinsonian type multiple system atrophy.

    PubMed

    Salazar, G; Valls-Solé, J; Martí, M J; Chang, H; Tolosa, E S

    2000-01-01

    Patients with a parkinsonian syndrome and features of multisystem atrophy (pMSA) may exhibit abnormal movements of the hands and fingers, which are reported in the literature either as "jerky" tremor or myoclonus. We studied clinically and electrophysiologically these movements in 11 consecutive patients with pMSA. No abnormal movements were observed when the patients were at complete rest, except for a characteristic parkinsonian "pill-rolling" tremor in one patient. Abnormal small-amplitude, nonrhythmic movements involving just one or a few fingers, or more rarely the whole hand, were observed in nine patients when holding a posture or at the beginning of an action. Accelerometric recordings showed small-amplitude irregular oscillations which, contrary to those of patients with tremor, had no predominant peak in the Fast Fourier frequency spectrum analysis. Electromyographic recordings in the forearm and hand muscles showed brief jerks of less than 100 ms duration which were synchronous in antagonist muscles of the forearm and alternated with brief periods of silence. Electrical stimulation of the digital nerves evoked consistent reflex responses in the wrist flexor and extensor muscles at a latency of 55.3+/-4.1 ms (range, 50-63 ms). Routine electroencephalographic (EEG) and somatosensory evoked potentials to median nerve stimulation were normal. Back-averaging of the EEG activity time-locked to the jerks was performed in two patients with no evidence of abnormal cortical activity. Two patients had episodes of transient respiratory failure related to pneumonia. This caused a long-lasting enhancement of the abnormal hand and finger movements, which became larger and more widespread, with features of posthypoxic myoclonus. We conclude that the abnormal hand and finger movements of patients with pMSA are a form of postural and action myoclonus, and can be described as mini-polymyoclonus.

  19. Using a Client Team to Diagnose Work Systems.

    ERIC Educational Resources Information Center

    Ombrello, Leon

    1979-01-01

    Explains the use of a trained team selected from an organization to supply knowledge of the work system and help gather and process the data within a reasonable time. Role relationships, diagnostic team activities, team knowledge and skill requirements, team member selection, and costs are discussed. (JD)

  20. Mobile In Vivo Infrared Data Collection and Diagnoses Comparison System

    NASA Technical Reports Server (NTRS)

    Mintz, Frederick W. (Inventor); Moynihan, Philip I. (Inventor); Gunapala, Sarath D. (Inventor)

    2013-01-01

    Described is a mobile in vivo infrared brain scan and analysis system. The system includes a data collection subsystem and a data analysis subsystem. The data collection subsystem is a helmet with a plurality of infrared (IR) thermometer probes. Each of the IR thermometer probes includes an IR photodetector capable of detecting IR radiation generated by evoked potentials within a user's skull. The helmet is formed to collect brain data that is reflective of firing neurons in a mobile subject and transmit the brain data to the data analysis subsystem. The data analysis subsystem is configured to generate and display a three-dimensional image that depicts a location of the firing neurons. The data analysis subsystem is also configured to compare the brain data against a library of brain data to detect an anomaly in the brain data, and notify a user of any detected anomaly in the brain data.

  1. Sequential Window Diagnoser for Discrete-Event Systems Under Unreliable Observations

    SciTech Connect

    Wen-Chiao Lin; Humberto E. Garcia; David Thorsley; Tae-Sic Yoo

    2009-09-01

    This paper addresses the issue of counting the occurrence of special events in the framework of partiallyobserved discrete-event dynamical systems (DEDS). Developed diagnosers referred to as sequential window diagnosers (SWDs) utilize the stochastic diagnoser probability transition matrices developed in [9] along with a resetting mechanism that allows on-line monitoring of special event occurrences. To illustrate their performance, the SWDs are applied to detect and count the occurrence of special events in a particular DEDS. Results show that SWDs are able to accurately track the number of times special events occur.

  2. Newly Diagnosed

    MedlinePlus

    ... of transmitting HIV to others. Do I Have AIDS? Being HIV-positive does NOT necessarily mean you ... Children Newly Diagnosed: Older Adults Related Topics on AIDS.gov Stages of HIV Infection Immune System 101 ...

  3. Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy.

    PubMed

    Milan, Giulia; Romanello, Vanina; Pescatore, Francesca; Armani, Andrea; Paik, Ji-Hye; Frasson, Laura; Seydel, Anke; Zhao, Jinghui; Abraham, Reimar; Goldberg, Alfred L; Blaauw, Bert; DePinho, Ronald A; Sandri, Marco

    2015-04-10

    Stresses like low nutrients, systemic inflammation, cancer or infections provoke a catabolic state characterized by enhanced muscle proteolysis and amino acid release to sustain liver gluconeogenesis and tissue protein synthesis. These conditions activate the family of Forkhead Box (Fox) O transcription factors. Here we report that muscle-specific deletion of FoxO members protects from muscle loss as a result of the role of FoxOs in the induction of autophagy-lysosome and ubiquitin-proteasome systems. Notably, in the setting of low nutrient signalling, we demonstrate that FoxOs are required for Akt activity but not for mTOR signalling. FoxOs control several stress-response pathways such as the unfolded protein response, ROS detoxification, DNA repair and translation. Finally, we identify FoxO-dependent ubiquitin ligases including MUSA1 and a previously uncharacterised ligase termed SMART (Specific of Muscle Atrophy and Regulated by Transcription). Our findings underscore the central function of FoxOs in coordinating a variety of stress-response genes during catabolic conditions.

  4. Systems biology investigation of cAMP modulation to increase SMN levels for the treatment of spinal muscular atrophy.

    PubMed

    Mack, Sean G; Cook, Daniel J; Dhurjati, Prasad; Butchbach, Matthew E R

    2014-01-01

    Spinal muscular atrophy (SMA), a leading genetic cause of infant death worldwide, is an autosomal recessive disorder caused by the loss of SMN1 (survival motor neuron 1), which encodes the protein SMN. The loss of SMN1 causes a deficiency in SMN protein levels leading to motor neuron cell death in the anterior horn of the spinal cord. SMN2, however, can also produce some functional SMN to partially compensate for loss of SMN1 in SMA suggesting increasing transcription of SMN2 as a potential therapy to treat patients with SMA. A cAMP response element was identified on the SMN2 promoter, implicating cAMP activation as a step in the transcription of SMN2. Therefore, we investigated the effects of modulating the cAMP signaling cascade on SMN production in vitro and in silico. SMA patient fibroblasts were treated with the cAMP signaling modulators rolipram, salbutamol, dbcAMP, epinephrine and forskolin. All of the modulators tested were able to increase gem formation, a marker for SMN protein in the nucleus, in a dose-dependent manner. We then derived two possible mathematical models simulating the regulation of SMN2 expression by cAMP signaling. Both models fit well with our experimental data. In silico treatment of SMA fibroblasts simultaneously with two different cAMP modulators resulted in an additive increase in gem formation. This study shows how a systems biology approach can be used to develop potential therapeutic targets for treating SMA.

  5. Distinct Parameters in the EEG of the PLP α-SYN Mouse Model for Multiple System Atrophy Reinforce Face Validity

    PubMed Central

    Härtner, Lorenz; Keil, Tobias W. M.; Kreuzer, Matthias; Fritz, Eva Maria; Wenning, Gregor K.; Stefanova, Nadia; Fenzl, Thomas

    2017-01-01

    Multiple system atrophy (MSA) is a neurodegenerative movement disorder characterized by parkinsonian symptoms and cerebellar symptoms. Sleep disturbances also play a crucial role in MSA. One of the most convincing animal models in MSA research is the PLP α-SYN model, but to date no studies on sleep disturbances in this mouse model, frequently found in MSA patients are available. We identified spectral shifts within the EEG of the model, strikingly resembling results of clinical studies. We also characterized muscle activity during REM sleep, which is one of the key symptoms in REM sleep behavioral disorder. Spectral shifts and REM sleep-linked muscle activity were age dependent, supporting Face Validity of the PLP α-SYN model. We also strongly suggest our findings to be critically evaluated for Predictive Validity in future studies. Currently, research on MSA lacks potential compounds attenuating or curing MSA. Future drugs must prove its potential in animal models, for this our study provides potential biomarkers. PMID:28119583

  6. Muscle expression of mutant androgen receptor accounts for systemic and motor neuron disease phenotypes in spinal and bulbar muscular atrophy.

    PubMed

    Cortes, Constanza J; Ling, Shuo-Chien; Guo, Ling T; Hung, Gene; Tsunemi, Taiji; Ly, Linda; Tokunaga, Seiya; Lopez, Edith; Sopher, Bryce L; Bennett, C Frank; Shelton, G Diane; Cleveland, Don W; La Spada, Albert R

    2014-04-16

    X-linked spinal and bulbar muscular atrophy (SBMA) is characterized by adult-onset muscle weakness and lower motor neuron degeneration. SBMA is caused by CAG-polyglutamine (polyQ) repeat expansions in the androgen receptor (AR) gene. Pathological findings include motor neuron loss, with polyQ-AR accumulation in intranuclear inclusions. SBMA patients exhibit myopathic features, suggesting a role for muscle in disease pathogenesis. To determine the contribution of muscle, we developed a BAC mouse model featuring a floxed first exon to permit cell-type-specific excision of human AR121Q. BAC fxAR121 mice develop systemic and neuromuscular phenotypes, including shortened survival. After validating termination of AR121 expression and full rescue with ubiquitous Cre, we crossed BAC fxAR121 mice with Human Skeletal Actin-Cre mice. Muscle-specific excision prevented weight loss, motor phenotypes, muscle pathology, and motor neuronopathy and dramatically extended survival. Our results reveal a crucial role for muscle expression of polyQ-AR in SBMA and suggest muscle-directed therapies as effective treatments.

  7. The Economic Costs of Progressive Supranuclear Palsy and Multiple System Atrophy in France, Germany and the United Kingdom

    PubMed Central

    McCrone, Paul; Payan, Christine Anne Mary; Knapp, Martin; Ludolph, Albert; Agid, Yves; Leigh, P. Nigel; Bensimon, Gilbert

    2011-01-01

    Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are progressive disabling neurological conditions usually fatal within 10 years of onset. Little is known about the economic costs of these conditions. This paper reports service use and costs from France, Germany and the UK and identifies patient characteristics that are associated with cost. 767 patients were recruited, and 760 included in the study, from 44 centres as part of the NNIPPS trial. Service use during the previous six months was measured at entry to the study and costs calculated. Mean six-month costs were calculated for 742 patients. Data on patient sociodemographic and clinical characteristics were recorded and used in regression models to identify predictors of service costs and unpaid care costs (i.e., care from family and friends). The mean six-month service costs of PSP were €24,491 in France, €30,643 in Germany and €25,655 in the UK. The costs for MSA were €28,924, €25,645 and €19,103 respectively. Unpaid care accounted for 68–76%. Formal and unpaid costs were significantly higher the more severe the illness, as indicated by the Parkinson's Plus Symptom scale. There was a significant inverse relationship between service and unpaid care costs. PMID:21931694

  8. Effect of Repetitive Transcranial Magnetic Stimulation on fMRI Resting-State Connectivity in Multiple System Atrophy

    PubMed Central

    Chou, Ying-hui; Zhao, Yan-Ping; Hou, Bo; Feng, Feng

    2015-01-01

    Abstract Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that has been used to treat neurological and psychiatric conditions. Although results of rTMS intervention are promising, so far, little is known about the rTMS effect on brain functional networks in clinical populations. In this study, we used a whole-brain connectivity analysis of resting-state functional magnetic resonance imaging data to uncover changes in functional connectivity following rTMS intervention and their association with motor symptoms in patients with multiple system atrophy (MSA). Patients were randomized to active rTMS or sham rTMS groups and completed a 10-session 5-Hz rTMS treatment over the left primary motor area. The results showed significant rTMS-related changes in motor symptoms and functional connectivity. Specifically, (1) significant improvement of motor symptoms was observed in the active rTMS group, but not in the sham rTMS group; and (2) several functional links involving the default mode, cerebellar, and limbic networks exhibited positive changes in functional connectivity in the active rTMS group. Moreover, the positive changes in functional connectivity were associated with improvement in motor symptoms for the active rTMS group. The present findings suggest that rTMS may improve motor symptoms by modulating functional links connecting to the default mode, cerebellar, and limbic networks, inferring a future therapeutic candidate for patients with MSA. PMID:25786196

  9. Multiple system atrophy of the cerebellar type (MSA-C) with concomitant beta-amyloid and tau pathology.

    PubMed

    Bujan, Bartosz; Hofer, Markus J; Oertel, Wolfgang H; Pagenstecher, Axel; Bürk, Katrin

    2013-01-01

    Multiple system atrophy (MSA) is a rapidly progressive sporadic α-synucleinopathy with adult onset characterized by progressive cerebellar ataxia, basal ganglia symptoms, autonomic dysfunction and pyramidal tract signs. While full-blown dementia is considered an exclusion criterion according to Consensus Guidelines, mild cognitive deficits such as fronto-executive dysfunction have been reported in some MSA individuals. However, the underlying anatomic correlate still has to be elucidated. We here report a 74-year-old patient with a clinical diagnosis of "probable MSA of the cerebellar type (MSA-C)" who developed pronounced clinical symptoms of fronto-executive dysfunction. Neuropathologic investigations revealed (1) numerous glial cytoplasmic inclusions (GCI) in the putamen, mesencephalon and cerebellum, (2) pronounced betaamyloid pathology in the frontal lobe and (3) mild hippocampal τ-pathology. In this patient, fronto-executive dysfunction can easily be explained by frontal degeneration typical for AD. These findings challenge the concept of cognitive dysfunction as a core feature of MSA as long as concomitant pathology other than MSA has not been reliably excluded by post mortem analysis.

  10. The evolution of shortcomings in Incident Command System: Revisions have allowed critical management functions to atrophy.

    PubMed

    Stambler, Kimberly S; Barbera, Joseph A

    2015-01-01

    The original Incident Command System (ICS) was created through the federally funded Firefighting Resources of Southern California Organized for Potential Emergencies (FIRESCOPE) program. Initially developed as one element of multiagency coordination for managing severe wildfires, the FIRESCOPE ICS guidance was adopted and evolved through increasingly routine wildl and firefighting. It then was modified for all hazards for the fire service. Only later, through the National Incident Management System (NIMS), was ICS officially adopted for all hazards and all responders. Over this multidecade evolution, the current NIMS ICS version became simplified in several key areas compared to the original, robust FIRESCOPE ICS. NIMS ICS is now promulgated as guidance for managing today's novel, complex, and lengthy disasters involving multidisciplinary response but experiences recurrent problems in key functions. This article examines the history of the subtle, yet critical differences in current ICS compared to the original system design, and focuses on information dissemination and intermediate, long-range and contingency planning. ICS transitions resulted in simplification and consolidation of positions and functions, without recognizing and maintaining critical position tasks necessary for managing complex, extended incidents.

  11. Reducing C-terminal truncation mitigates synucleinopathy and neurodegeneration in a transgenic model of multiple system atrophy

    PubMed Central

    Bassil, Fares; Fernagut, Pierre-Olivier; Bezard, Erwan; Pruvost, Alain; Leste-Lasserre, Thierry; Hoang, Quyen Q.; Ringe, Dagmar; Petsko, Gregory A.; Meissner, Wassilios G.

    2016-01-01

    Multiple system atrophy (MSA) is a sporadic orphan neurodegenerative disorder. No treatment is currently available to slow down the aggressive neurodegenerative process, and patients die within a few years after disease onset. The cytopathological hallmark of MSA is the accumulation of alpha-synuclein (α-syn) aggregates in affected oligodendrocytes. Several studies point to α-syn oligomerization and aggregation as a mediator of neurotoxicity in synucleinopathies including MSA. C-terminal truncation by the inflammatory protease caspase-1 has recently been implicated in the mechanisms that promote aggregation of α-syn in vitro and in neuronal cell models of α-syn toxicity. We present here an in vivo proof of concept of the ability of the caspase-1 inhibitor prodrug VX-765 to mitigate α-syn pathology and to mediate neuroprotection in proteolipid protein α-syn (PLP-SYN) mice, a transgenic mouse model of MSA. PLP-SYN and age-matched wild-type mice were treated for a period of 11 wk with VX-765 or placebo. VX-765 prevented motor deficits in PLP-SYN mice compared with placebo controls. More importantly, VX-765 was able to limit the progressive toxicity of α-syn aggregation by reducing its load in the striatum of PLP-SYN mice. Not only did VX-765 reduce truncated α-syn, but it also decreased its monomeric and oligomeric forms. Finally, VX-765 showed neuroprotective effects by preserving tyrosine hydroxylase-positive neurons in the substantia nigra of PLP-SYN mice. In conclusion, our results suggest that VX-765, a drug that was well tolerated in a 6 wk-long phase II trial in patients with epilepsy, is a promising candidate to achieve disease modification in synucleinopathies by limiting α-syn accumulation. PMID:27482103

  12. Reducing C-terminal truncation mitigates synucleinopathy and neurodegeneration in a transgenic model of multiple system atrophy.

    PubMed

    Bassil, Fares; Fernagut, Pierre-Olivier; Bezard, Erwan; Pruvost, Alain; Leste-Lasserre, Thierry; Hoang, Quyen Q; Ringe, Dagmar; Petsko, Gregory A; Meissner, Wassilios G

    2016-08-23

    Multiple system atrophy (MSA) is a sporadic orphan neurodegenerative disorder. No treatment is currently available to slow down the aggressive neurodegenerative process, and patients die within a few years after disease onset. The cytopathological hallmark of MSA is the accumulation of alpha-synuclein (α-syn) aggregates in affected oligodendrocytes. Several studies point to α-syn oligomerization and aggregation as a mediator of neurotoxicity in synucleinopathies including MSA. C-terminal truncation by the inflammatory protease caspase-1 has recently been implicated in the mechanisms that promote aggregation of α-syn in vitro and in neuronal cell models of α-syn toxicity. We present here an in vivo proof of concept of the ability of the caspase-1 inhibitor prodrug VX-765 to mitigate α-syn pathology and to mediate neuroprotection in proteolipid protein α-syn (PLP-SYN) mice, a transgenic mouse model of MSA. PLP-SYN and age-matched wild-type mice were treated for a period of 11 wk with VX-765 or placebo. VX-765 prevented motor deficits in PLP-SYN mice compared with placebo controls. More importantly, VX-765 was able to limit the progressive toxicity of α-syn aggregation by reducing its load in the striatum of PLP-SYN mice. Not only did VX-765 reduce truncated α-syn, but it also decreased its monomeric and oligomeric forms. Finally, VX-765 showed neuroprotective effects by preserving tyrosine hydroxylase-positive neurons in the substantia nigra of PLP-SYN mice. In conclusion, our results suggest that VX-765, a drug that was well tolerated in a 6 wk-long phase II trial in patients with epilepsy, is a promising candidate to achieve disease modification in synucleinopathies by limiting α-syn accumulation.

  13. A Ground-Based Comparison of the Muscle Atrophy Research and Exercise System (MARES) and a Standard Isokinetic Dynamometer

    NASA Technical Reports Server (NTRS)

    Hackney, K. J.; English, K. L.; Redd, E.; DeWitt, J. K.; Ploutz-Snyder, R.; Ploutz-Snyder, L. L.

    2010-01-01

    PURPOSE: 1) To compare the test-to-test reliability of Muscle Atrophy Research and Exercise System (MARES) with a standard laboratory isokinetic dynamometer (ISOK DYN) and; 2) to determine if measures of peak torque and total work differ between devices. METHODS: Ten subjects (6M, 4F) completed two trials on both MARES and an ISOK DYN in a counterbalanced order. Peak torque values at 60 deg & 180 deg / s were obtained from five maximal repetitions of knee extension (KE) and knee flexion (KF). Total work at 180 deg / s was determined from the area under the torque vs. displacement curve during twenty maximal repetitions of KE and KF. Reliability of measures within devices was interpreted from the intraclass correlation coefficient (ICC) and compared between devices using the ratio of the within-device standard deviations. Indicators of agreement for the two devices were evaluated from: 1) a calculation of concordance (rho) and; 2) the correlation between the mean of measures versus the delta difference between measures (m u vs delta). RESULTS: For all outcome measures ICCs were high for both the ISOK DYN (0.95-0.99) and MARES (0.90-0.99). However, ratios of the within-device standard deviation were 1.3 to 4.3 times higher on MARES. On average, a wide range (3.3 to 1054 Nm) of differences existed between the values obtained. Only KE peak torque measured at 60 deg & 180 deg / s showed similarities between devices (rho = 0.91 & 0.87; Pearson's r for m u vs delta = -0.22 & -0.37, respectively). CONCLUSION: Although MARES was designed for use in microgravity it was quite reliable during ground-based testing. However, MARES was consistently more variable than an ISOK DYN. Future longitudinal studies evaluating a change in isokinetic peak torque or total work should be limited within one device.

  14. Involvement of Peripheral Nerves in the Transgenic PLP-α-Syn Model of Multiple System Atrophy: Extending the Phenotype

    PubMed Central

    Kuzdas-Wood, Daniela; Irschick, Regina; Theurl, Markus; Malsch, Philipp; Mair, Norbert; Mantinger, Christine; Wanschitz, Julia; Klimaschewski, Lars; Poewe, Werner; Stefanova, Nadia; Wenning, Gregor K.

    2015-01-01

    Multiple system atrophy (MSA) is a fatal, rapidly progressive neurodegenerative disease with (oligodendro-)glial cytoplasmic α-synuclein (α-syn) inclusions (GCIs). Peripheral neuropathies have been reported in up to 40% of MSA patients, the cause remaining unclear. In a transgenic MSA mouse model featuring GCI-like inclusion pathology based on PLP-promoter driven overexpression of human α-syn in oligodendroglia motor and non-motor deficits are associated with MSA-like neurodegeneration. Since α-syn is also expressed in Schwann cells we aimed to investigate whether peripheral nerves are anatomically and functionally affected in the PLP-α-syn MSA mouse model. Results To this end, heat/cold as well as mechanical sensitivity tests were performed. Furthermore, in vivo and ex vivo nerve conduction and the G-ratios of the sciatic nerve were analyzed, and thermosensitive ion channel mRNA expression in dorsal root ganglia (DRG) was assessed. The presence of human α-syn in Schwann cells was associated with subtle behavioral impairments. The G-ratio of the sciatic nerve, the conduction velocity of myelinated and unmyelinated primary afferents and the expression of thermosensitive ion channels in the sensory neurons, however, were similar to wildtype mice. Conclusion Our results suggest that the PNS appears to be affected by Schwann cell α-syn deposits in the PLP-α-syn MSA mouse model. However, there was no consistent evidence for functional PNS perturbations resulting from such α-syn aggregates suggesting a more central cause of the observed behavioral abnormalities. Nonetheless, our results do not exclude a causal role of α-syn in the pathogenesis of MSA associated peripheral neuropathy. PMID:26496712

  15. A ground-based comparison of the Muscle Atrophy Research and Exercise System (MARES) and a commercially available isokinetic dynamometer

    NASA Astrophysics Data System (ADS)

    English, Kirk L.; Hackney, Kyle J.; De Witt, John K.; Ploutz-Snyder, Robert J.; Goetchius, Elizabeth L.; Ploutz-Snyder, Lori L.

    2013-11-01

    IntroductionInternational Space Station (ISS) crewmembers perform muscle strength and endurance testing pre- and postflight to assess the physiologic adaptations associated with long-duration exposure to microgravity. However, a reliable and standardized method to document strength changes in-flight has not been established. To address this issue, a proprietary dynamometer, the Muscle Atrophy Research and Exercise System (MARES) has been developed and flown aboard the ISS. The aims of this ground-based investigation were to: (1) evaluate the test-retest reliability of MARES and (2) determine its agreement with a commercially available isokinetic dynamometer previously used for pre- and postflight medical testing. MethodsSix males (179.5±4.7 cm; 82.0±8.7 kg; 31.3±4.0 yr) and four females (163.2±7.3 cm; 63.2±1.9 kg; 32.3±6.8 yr) completed two testing sessions on a HUMAC NORM isokinetic dynamometer (NORM) and two sessions on MARES using a randomized, counterbalanced, cross-over design. Peak torque values at 60° and 180° s-1 were calculated from five maximal repetitions of knee extension (KE) and knee flexion (KF) for each session. Total work at 180° s-1 was determined from the area under the torque versus displacement curve during 20 maximal repetitions of KE and KF. ResultsIntraclass correlation coefficients were relatively high for both devices (0.90-0.99). Only one dependent measure, KE peak torque at 60° s-1 exhibited good concordance between devices (ρ=0.92) and a small average difference (0.9±17.3 N m). ConclusionMARES demonstrated acceptable test-retest reliability and thus should serve as a good tool to monitor in-flight strength changes. However, due to poor agreement with NORM, it is not advisable to compare absolute values obtained on these devices.

  16. Cisplatin triggers atrophy of skeletal C2C12 myotubes via impairment of Akt signalling pathway and subsequent increment activity of proteasome and autophagy systems

    SciTech Connect

    Fanzani, Alessandro Zanola, Alessandra; Rovetta, Francesca; Rossi, Stefania; Aleo, Maria Francesca

    2011-02-01

    Cisplatin (cisPt) is an antineoplastic drug which causes an array of adverse effects on different organs and tissues, including skeletal muscle. In this work we show that cisPt behaves as a potent trigger to activate protein hypercatabolism in skeletal C2C12 myotubes. Within 24 h of 50 {mu}M cisPt administration, C2C12 myotubes displayed unchanged cell viability but showed a subset of hallmark signs typically recognized during atrophy, including severe reduction in body size, repression of Akt phosphorylation, transcriptional up-regulation of atrophy-related genes, such as atrogin-1, gabarap, beclin-1 and bnip-3, and loss of myogenic markers. As a consequence, proteasomal activity and formation of autophagosomes were remarkably increased in cisPt-treated myotubes, but forced stimulation of Akt pathway, as obtained through insulin administration or delivery of a constitutively activated Akt form, was sufficient to counter the cisPt-induced protein breakdown, leading to rescue of atrophic size. Overall, these results indicate that cisPt induces atrophy of C2C12 myotubes via activation of proteasome and autophagy systems, suggesting that the Akt pathway represents one sensitive target of cisPt molecular action in skeletal muscle.

  17. Diagnoses and Presenting Symptoms in an Infant Psychiatry Clinic: Comparison of Two Diagnostic Systems.

    ERIC Educational Resources Information Center

    Frankel, Karen A.; Boyum, Lisa A.; Harmon, Robert J.

    2004-01-01

    Objective: To present data from a general infant psychiatry clinic, including range and frequency of presenting symptoms, relationship between symptoms and diagnoses, and comparison of two diagnostic systems, DSM-IV and Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC: 0-3). Method: A…

  18. On the diagnosability of multicomputer systems with homogeneous and incomplete tests

    SciTech Connect

    Krawczyk, H.; Kozlowski, W.E. )

    1988-11-01

    A generalized PMC model, where only a subset of possible unit faults (the same for each unit) can be detected by unit tests, is considered. A category of visible faults is introduced and the necessary and sufficient condition for the new class of tupsilon-diagnosable system is determined. Moreover, an O(absolute value T ) diagnosis algorithm is presented.

  19. A second generation expert system for checking and diagnosing AXAF's electric power system

    NASA Astrophysics Data System (ADS)

    Bykat, Alex

    1992-12-01

    AXAF - Advanced X-ray Astrophysics Facility - is a third NASA's great space observatory. Each of these observatories is intended to cover different parts of the electromagnetic spectrum (x-ray for AXAF) and to provide high resolution images of celestial sources in our universe. While the spacecraft is in orbit, the electric power system (EPS) performance is monitored via sensors measuring voltages, currents, pressures, and temperatures. The sensor data are sent from the spacecraft to the ground station as telemetry and analyzed on arrival. Monitoring, diagnosis and maintenance of such EPS is an arduous task which requires expertise and constant attention of the ground personnel. To help the ground crew in this task, much of it should be automated and delegated to expert systems, which draw engineer's attention to possible malfunctions and allows him to review the telemetry to determine the source of the trouble, diagnose the suspected fault and to propose a corrective action. Those systems are built on assumptions such as: (1) domain knowledge is available and can be represented as a set of rules; (2) domain knowledge is circumscribed, static, and monotonic; and (3) expert decision making can be emulated by a logical inference mechanism.

  20. A second generation expert system for checking and diagnosing AXAF's electric power system

    NASA Technical Reports Server (NTRS)

    Bykat, Alex

    1992-01-01

    AXAF - Advanced X-ray Astrophysics Facility - is a third NASA's great space observatory. Each of these observatories is intended to cover different parts of the electromagnetic spectrum (x-ray for AXAF) and to provide high resolution images of celestial sources in our universe. While the spacecraft is in orbit, the electric power system (EPS) performance is monitored via sensors measuring voltages, currents, pressures, and temperatures. The sensor data are sent from the spacecraft to the ground station as telemetry and analyzed on arrival. Monitoring, diagnosis and maintenance of such EPS is an arduous task which requires expertise and constant attention of the ground personnel. To help the ground crew in this task, much of it should be automated and delegated to expert systems, which draw engineer's attention to possible malfunctions and allows him to review the telemetry to determine the source of the trouble, diagnose the suspected fault and to propose a corrective action. Those systems are built on assumptions such as: (1) domain knowledge is available and can be represented as a set of rules; (2) domain knowledge is circumscribed, static, and monotonic; and (3) expert decision making can be emulated by a logical inference mechanism.

  1. Multiple System Atrophy (MSA)

    MedlinePlus

    ... Constipation Loss of bladder or bowel control (incontinence) Sweating abnormalities A reduction in the production of perspiration, ... as well as heat intolerance due to impaired sweating Sleep disorders Agitated sleep due to "acting out" ...

  2. Multiple System Atrophy

    MedlinePlus

    ... Strategy Current Research Research Funded by NINDS Basic Neuroscience Clinical Research Translational Research Research at NINDS Focus ... Information Current Research Research Funded by NINDS Basic Neuroscience Clinical Research Translational Research Research at NINDS Focus ...

  3. Progressive hemifacial atrophy

    PubMed Central

    Sande, Abhijeet; Risbud, Mukund; Kshar, Avinash; Paranjpe, Arati Oka

    2013-01-01

    Progressive hemifacial atrophy, also known as Parry-Romberg Syndrome, is an uncommon degenerative and poorly understood condition. It is characterized by a slow and progressive but self-limited atrophy affecting one side of the face. The incidence and the cause of this alteration are unknown. A cerebral disturbance of fat metabolism has been proposed as a primary cause. Possible factors that are involved in the pathogenesis include trauma, viral infections, heredity, endocrine disturbances and auto-immunity. The most common complications that appear in association to this disorder are: trigeminal neuralgia, facial paresthesia, severe headache and epilepsy. Characteristically, the atrophy progresses slowly for several years and, it becomes stable. The objective of this work is, through the presentation of a clinical case, to accomplish a literature review concerning general characteristics, etiology, physiopathology and treatment of progressive hemifacial atrophy. PMID:23878573

  4. Parkinsonism in multiple system atrophy: natural history, severity (UPDRS-III), and disability assessment compared with Parkinson's disease.

    PubMed

    Tison, François; Yekhlef, Farid; Chrysostome, Virginie; Balestre, Eric; Quinn, Niall P; Poewe, Werner; Wenning, Gregor K

    2002-07-01

    We analyzed parkinsonian features in multiple system atrophy (MSA) compared with age- and disease duration-matched Parkinson's disease (PD) patients, and assessed the applicability of the Unified Parkinson's Disease Rating Scale (UPDRS) -III motor scale as a means of rating their severity. Cross-sectional analysis of parkinsonism was done using UPDRS-III, International Cerebellar Atatia Rating Scale, and disability scales (Hoehn and Yahr [H&A], Schwab and England, Katz and Lawton) in 50 unselected MSA patients and in 50 matched PD patients. At symptom onset, falls occurred 10 times more frequently in MSA, whereas limb tremor was 10 times more common in PD. At first visit (10.2 months), hemiparkinsonism and pill-rolling rest tremor were less common in MSA. Hypomimia, atypical rest, postural or action tremor, as well as postural instability were more frequent in MSA. At study examination (62.4 months), parkinsonian signs in MSA patients were more frequently symmetrical and associated with axial rigidity, antecollis and postural instability. A levodopa response of >50% was seen in <10% of MSA patients. Modified H&Y stages (3.2 +/- 1.3 vs. 2.2 +/- 0.78) and UPDRS-III scores (48.14 +/- 19.5 vs. 31.74 +/- 12.9) were significantly (P = 0.0001) higher in MSA. The internal consistency of the UPDRS-III was fair in MSA patients (Cronbach's alpha >0.90), and correlated well with marked dependency on the Schwab and England and Katz and Lawton scales. Factor structure analysis of UPDRS-III in MSA showed five clinically distinct subscores accounting for 74% of the variance, differing from PD by the dependency of the face-speech and limb bradykinesia items and independence of the postural-action tremor from the rest tremor items. There was a significant correlation (R(2) = 0.70, P = 0.001) between ICARS ataxia and UPDRS-III scores in MSA patients. Results confirm a distinct profile of parkinsonism in MSA and greater severity and disability compared with PD. It also indicates that

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

    PubMed Central

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

    2011-01-01

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

  6. Wolfram Syndrome presenting with optic atrophy and diabetes mellitus: two case reports.

    PubMed

    Manaviat, Masoud Reza; Rashidi, Maryam; Mohammadi, Seyed Mohammad

    2009-12-19

    Wolfram syndrome is the constellation of juvenile onset diabetes mellitus and optic atrophy, known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness).Patients demonstrate diabetes mellitus followed by optic atrophy in the first decade, diabetes insipidus and sensorineural deafness in the second decade, dilated renal outflow tracts early in the third decade, and multiple neurological abnormalities early in the fourth decade.This study reports two siblings with late diagnosed wolfram syndrome with diabetes insipidus, diabetes mellitus, optic atrophy, deafness and severe urological abnormalities.In conclusion, cases having early onset insulin-dependent diabetes mellitus and optic atrophy together need to be evaluated with respect to Wolfram.

  7. [Creating diagnoses and interventions under the auspices of different nursing classification systems].

    PubMed

    da Mata, Luciana Regina Ferreira; de Souza, Cristiane Chaves; Chianca, Tânia Couto Machado; de Carvalho, Emília Campos

    2012-12-01

    This study analyzes the use of different nursing classification systems to meet the standards established by the norm ISO 18.104:2003, based on a fictitious clinical situation. Nursing diagnoses and interventions were created using NANDA-I, NIC and ICNP® and an analysis was performed of the terminology agreement of these classification systems with the model proposed by the norm ISO 18.104:2003. For the creation of nursing diagnoses, NANDA-I and ICNP® comply with norm ISO 18.104:2003. As for the creation of nursing interventions, ICNP® meets the terminology reference model proposed by ISO 18104:2003. NIC, on the other hand, does not propose a combinatory terminology reference model. The unification of nursing terminology depends on reviewing, standardizing and testing these classifications in order to establish a common and sound language for the profession.

  8. A machine independent expert system for diagnosing environmentally induced spacecraft anomalies

    NASA Technical Reports Server (NTRS)

    Rolincik, Mark J.

    1991-01-01

    A new rule-based, machine independent analytical tool for diagnosing spacecraft anomalies, the EnviroNET expert system, was developed. Expert systems provide an effective method for storing knowledge, allow computers to sift through large amounts of data pinpointing significant parts, and most importantly, use heuristics in addition to algorithms which allow approximate reasoning and inference, and the ability to attack problems not rigidly defines. The EviroNET expert system knowledge base currently contains over two hundred rules, and links to databases which include past environmental data, satellite data, and previous known anomalies. The environmental causes considered are bulk charging, single event upsets (SEU), surface charging, and total radiation dose.

  9. Utilization of computer-aided detection system in diagnosing unilateral maxillary sinusitis on panoramic radiographs

    PubMed Central

    Ohashi, Yasufumi; Katsumata, Akitoshi; Fujita, Hiroshi; Nakayama, Miwa; Fukuda, Motoki; Nozawa, Michihito; Ariji, Eiichiro

    2016-01-01

    Objectives: It is unclear whether computer-aided detection (CAD) systems for panoramic radiography can help inexperienced dentists to diagnose maxillary sinusitis. The aim of this study was to clarify whether a CAD system for panoramic radiography can contribute to improved diagnostic performance for maxillary sinusitis by inexperienced dentists. Methods: The panoramic radiographs of 49 patients with maxillary sinusitis and 49 patients with healthy sinuses were evaluated in this study. The diagnostic performance of the CAD system was determined. 12 inexperienced dentists and 4 expert oral and maxillofacial radiologists observed the total of 98 panoramic radiographs and judged the presence or absence of maxillary sinusitis, under conditions with and without the support of the CAD system. The receiver operating characteristic curves of the two groups were compared. Results: The CAD system provided sensitivity of 77.6%, specificity of 69.4% and accuracy of 73.5%. The diagnostic performance of the inexperienced dentists increased with the support of the CAD system. When the inexperienced dentists diagnosed maxillary sinusitis with CAD support, the area under the curve (AUC) was significantly higher than that without CAD support. When the focus was only on panoramic radiographs in which CAD support led to a correct diagnosis, the AUC of the inexperienced dentists increased to an equivalent level to that of the experienced radiologists. Conclusions: The CAD system supported the inexperienced dentists in diagnosing maxillary sinusitis on the panoramic radiographs. If the accuracy of the CAD system can be increased, the benefits of CAD support will be further enhanced. PMID:26837670

  10. Bed Rest Muscular Atrophy

    NASA Technical Reports Server (NTRS)

    Greenleaf, John E.

    2000-01-01

    A major debilitating response from prolonged bed rest (BR) is muscle atrophy, defined as a "decrease in size of a part of tissue after full development has been attained: a wasting away of tissue as from disuse, old age, injury or disease". Part of the complicated mechanism for the dizziness, increased body instability, and exaggerated gait in patients who arise immediately after BR may be a result of not only foot pain, but also of muscular atrophy and associated reduction in lower limb strength. Also, there seems to be a close association between muscle atrophy and bone atrophy. A discussion of many facets of the total BR homeostatic syndrome has been published. The old adage that use determines form which promotes function of bone (Wolff's law) also applies to those people exposed to prolonged BR (without exercise training) in whom muscle atrophy is a consistent finding. An extreme case involved a 16-year-old boy who was ordered to bed by his mother in 1932: after 50 years in bed he had "a lily-white frame with limbs as thin as the legs of a ladder-back chair". These findings emphasize the close relationship between muscle atrophy and bone atrophy. In addition to loss of muscle mass during deconditioning, there is a significant loss of muscle strength and a decrease in protein synthesis. Because the decreases in force (strength) are proportionately greater than those in fiber size or muscle cross-sectional area, other contributory factors must be involved; muscle fiber dehydration may be important.

  11. Molecular evidence for central nervous system involvement in children with newly diagnosed acute lymphoblastic leukemia.

    PubMed

    Januszkiewicz, D A; Nowak, J S

    1995-01-01

    Central nervous system (CNS) involvement in children with newly diagnosed acute lymphoblastic leukemia (ALL) would have profound implication for the prognosis and accurate stratification of CNS prophylactic therapy. Using PCR technique with specific primers for V, D and J segments of TCRD gene, the pattern of TCRD gene rearrangements in bone marrow lymphoblasts and in cells from cerebrospinal fluid (CSF) have been investigated. The study involved 21 children at the time of diagnosis with B-lineage ALL. In nine of 21 patients incomplete TCRDVD gene rearrangement has been found in CSF cells, which was identical to that observed in bone marrow of the same children. It can be concluded that at least in 43 per cent of all analysed cases, there were signs of CNS involvement in newly diagnosed ALL patients.

  12. [A clinical report of five cases of central nervous system miliary tuberculomas first diagnosed by neurologists].

    PubMed

    Huang, X; Wang, X Y; Zhu, Z H; Qi, X K; Yu, Y X

    2017-03-01

    To explore the clinical characteristics and imaging features of miliary tuberculomas in central nervous system(CNS). A total of 5 cases diagnosed with tuberculosis in CNS first diagnosed by neurologists in Navy General Hospital of PLA were enrolled in the study. All clinical and imaging data were collected and analyzed retrospectively. The main initial symptoms were fever and headache (4/5). Multiple diffused miliary lesions were shown by brain MRI, with maximum diameter ranged from 1-4 mm and ring-shape or nodular enhancement after gadolinium injection. As mycobacterium tuberculosis could seldomly be found in serum and cerebrospinal fluid, contrast MRI remains the effective method for detecting miliary tuberculomas in CNS.

  13. [Correlations between serum 25-hydroxyvitamin D and cytokines in patients newly diagnosed with systemic lupus erythematosus].

    PubMed

    Su, Jiang; Zhu, Jing; Dong, Wei; Long, Li; Long, Wubin; Chen, Xixi

    2016-12-01

    Objective To investigate the correlations between serum 25-hydroxyvitamin D (25-OH-VitD) and serum cytokines of interferon (IFN)-α2, interleukin(IL)-6, IL-10, and IL-17A in Chinese Han patients newly diagnosed with systemic lupus erythematosus (SLE). Methods This study recruited 86 Chinese patients newly diagnosed with SLE and 73 healthy volunteers. The serum 25-OH-VitD was detected using ELISA. The serum levels of IFN-α2, IL-6, IL-10 and IL-17A were detected using Luminex liquichip. The associations between serum 25-OH-VitD and serum cytokines, clinical manifestations and laboratory findings were analyzed using Spearman linear correlation analysis. Results The serum 25-OH-VitD was significantly lower in SLE patients than in healthy controls. The serum 25-OH-VitD was positively correlated with serum C3, negatively correlated with serum IL-17A and 24 hour urine protein excretion, but not obviously correlated with serum IFN-α2, IL-6 and IL-10. Conclusion The serum 25-OH-VitD decreases in Chinese patients newly diagnosed with SLE and it is negatively correlated with serum IL-17A.

  14. Hypoactivation of reward motivational system in patients with newly diagnosed hypertension grade I-II.

    PubMed

    Aftanas, L I; Brak, I V; Gilinskaya, O M; Korenek, V V; Pavlov, S V; Reva, N V

    2014-08-01

    In patients with newly diagnosed untreated grade I-II hypertension, EEG oscillations were recorded under conditions activation of the two basic motivational systems, defensive motivational system and positive reinforcement system, evoked by recall of personally meaningful emotional events. The 64-channel EEG and cardiovascular reactivity (beat-by-beat technology) were simultaneously recorded. At rest, hypertensive patients had significantly reduced platelet serotonin concentrations in comparison with healthy individuals. The patients experiencing emotional activation were characterized by significantly lower intensity of positive emotions associated with more pronounced suppression of EEG activity in the delta (2-4 Hz) and theta (ranges of frequency 4-6 and 6-8 Hz) oscillators in the parieto-occipital cortex (zones P and PO) in both hemispheres of the brain. The findings attest to insufficient function of the brain serotonin system and hypoactivation of the reward/reinforcement system in patients with primary hypertension.

  15. Wireless telemedicine systems for diagnosing sleep disorders with Zigbee star network topology

    NASA Astrophysics Data System (ADS)

    Oh, Sechang; Kwon, Hyeokjun; Varadan, Vijay K.

    2012-10-01

    Good sleep is critical for one's overall physical and mental health but more than 50 million Americans have experienced or are suffering from sleep disorders. Nevertheless, 85% of them remain undiagnosed or untreated. They can lead to chronic diseases. Sleep disorders are diagnosed through polysomnography, also known as sleep study, performed in a sleep laboratory overnight. This perturbs his/her daily sleep routine, and consequently, an accurate diagnosis cannot be made. Many companies have been developing home sleep test systems to reduce the cost of sleep studies and provide a more convenience solution to patients. The category of the system varies as type II, type III and type IV according to the type of sleep study. Current systems cannot be easily extended from one type to include a higher type. A patient who has a type III system to diagnose sleep apnea should additionally purchase a type II system which has functions that overlap with a type III system, to evaluate sleep stages. In this paper, we propose a wireless telemedicine system for easy extension of channels using the start network topology of the Zigbee protocol. The HST system consists of two wireless HST devices with a Zigbee module, a wireless HST receiver with both a Zigbee and a Wi-Fi module, and a sever which monitors/saves the physiological signals. One transmitter provides 5 channels for 2x EOG, 2x EEG and EMG to evaluate sleep stages. The other transmitter provides 5 additional channels for ECG, nasal air flow, body position, abdominal/chest efforts and oxygen saturation to diagnose sleep apnea. These two transmitters, acting as routers, and the receiver as a coordinator form a Zigbee star network. The data from each transmitter in the receiver are retransmitted to the monitoring unit through Wi-Fi. By building a star network with Zigbee, channels can be easily extended so that low level systems can be upgraded to higher level systems by simply adding the necessary channels. In addition

  16. Spinal Muscular Atrophy (SMA)

    MedlinePlus

    ... Lessons? Visit KidsHealth in the Classroom What Other Parents Are Reading Your Child's Development (Birth to 3 Years) Feeding Your 1- to 3-Month-Old Feeding Your 4- to 7-Month-Old Feeding Your 8- to 12-Month-Old Feeding Your 1- to 2-Year-Old Spinal ... > For Parents > Spinal Muscular Atrophy (SMA) Print A A A ...

  17. Research opportunities in muscle atrophy

    NASA Technical Reports Server (NTRS)

    Herbison, G. J. (Editor); Talbot, J. M. (Editor)

    1984-01-01

    Muscle atrophy in a weightless environment is studied. Topics of investigation include physiological factors of muscle atrophy in space flight, biochemistry, countermeasures, modelling of atrophied muscle tissue, and various methods of measurement of muscle strength and endurance. A review of the current literature and suggestions for future research are included.

  18. Improvements of vaginal atrophy without systemic side effects after topical application of Pueraria mirifica, a phytoestrogen-rich herb, in postmenopausal cynomolgus macaques.

    PubMed

    Jaroenporn, Sukanya; Urasopon, Nontakorn; Watanabe, Gen; Malaivijitnond, Suchinda

    2014-01-01

    The estrogenic efficacy of topical vaginal application of Pueraria mirifica extract (PM) on the restoration of vaginal atrophy, and the presence of any systemic side effects, were investigated in postmenopausal cynomolgus macaques. Twelve postmenopausal cynomolgus macaques, with complete cessation of menstruation for at least 5 years before start of this experiment, were divided into three groups. They received a topical vaginal application daily of 0.1 or 1% (w/w) PM cream or a conjugated equine estrogen (CEE) cream (a mixture of estrone, equilin, 17β-dihydroequilin, 17α-estradiol and 17α-dihydroequilin at 0.625 mg total estrogen/g cream) for 28 days. Estrogenic efficacy was assessed weekly by vaginal cytology assay and vaginal pH measurement, whilst the plasma luteinizing hormone (LH) and sex skin coloration levels were determined at the end of each treatment period to evaluate the systemic side effects. PM significantly increased the proportion of superficial cells in a dose-dependent manner, with a similar efficacy between 1% (w/w) PM and CEE. Together with increased vaginal maturation, PM decreased the vaginal pH to acidic levels, as observed in the CEE group. PM induced no detected systemic side effects, whilst CEE decreased the plasma LH level and increased the reddish color of the sex skin during the posttreatment period. Topical vaginal treatment with PM stimulated the maturation of the vaginal epithelium without causing systemic side effects in postmenopausal monkeys. The implication is that PM could be a safer alternative to treat vaginal atrophy in postmenopausal women.

  19. Siblings’ Perceptions of Their ADHD-Diagnosed Sibling’s Impact on the Family System

    PubMed Central

    King, Kerry; Alexander, Daleen; Seabi, Joseph

    2016-01-01

    This qualitative study explored siblings’ perceptions of the impact a sibling diagnosed with ADHD has within the family system. Specific focus was placed on the different ways these different sibling cohorts were parented. Participants constituted eight adult females with a mean age of 20 years from different cultural and socio-economic backgrounds in the province of Gauteng, South Africa. Data was collected using semi-structured interviews and was analysed thematically. The four themes that emerged from the interviews include differential parental treatment, rejection, discrepancy with discipline, and the parentified child. Specifically, the results of this study revealed feelings of differential parental treatment and discipline that took place in the home and rejection experienced by the non-ADHD sibling. There was also a common theme of a parentified child, who had to carry a burden of caring for their sibling with ADHD. The non-diagnosed siblings perceive themselves to be particularly negatively impacted. The results are discussed in light of the previous empirical studies, and recommendations are made. PMID:27649212

  20. Frequent globular neuronal cytoplasmic inclusions in the medial temporal region as a possible characteristic feature in multiple system atrophy with dementia.

    PubMed

    Homma, Taku; Mochizuki, Yoko; Komori, Takashi; Isozaki, Eiji

    2016-10-01

    Multiple system atrophy (MSA) is an adult-onset neurodegenerative disease, which is characterized clinically by parkinsonism, cerebellar ataxia and/or autonomic dysfunction, and pathologically by alpha-synuclein-related multisystem neurodegeneration, so-called alpha-synucleinopathy, which particularly involves the striatonigral and olivopontocerebellar systems, with glial cytoplasmic inclusions and neuronal cytoplasmic/nuclear inclusions (NCIs/NNIs). In the recent consensus criteria for the diagnosis of MSA, dementia is described as one of the features not supporting a diagnosis of MSA. However, MSA with dementia has been reported, although the location of the lesion responsible for the dementia remains unclear. In the present study, we aimed to investigate where this lesion may be found, by analyzing 12 autopsy-proven MSA cases, with a particular focus on the medial temporal region. Three of 12 cases with MSA had dementia (MSA-D). Compared with MSA cases without dementia, MSA-D cases had frequent globular NCIs (G-NCIs) in the medial temporal region, especially in their subiculum. In addition, MSA-D cases could be divided into two types; MSA-D with distinct fronto-temporal lobar degeneration (FTLD type) and without distinct fronto-temporal lobar degeneration (non-FTLD type). There was no association between dementia and Alzheimer pathologies, such as neurofibrillary tangles and senile plaques. We suggest that frequent G-NCIs in the medial temporal region, and particularly the subiculum, is one of the important pathological findings of MSA-D, even when a case with MSA-D reveals no significant cerebral atrophy.

  1. An on-line expert system for diagnosing environmentally induced spacecraft anomalies using CLIPS

    NASA Technical Reports Server (NTRS)

    Lauriente, Michael; Rolincik, Mark; Koons, Harry C; Gorney, David

    1993-01-01

    A new rule-based, expert system for diagnosing spacecraft anomalies is under development. The knowledge base consists of over two-hundred rules and provide links to historical and environmental databases. Environmental causes considered are bulk charging, single event upsets (SEU), surface charging, and total radiation dose. The system's driver translates forward chaining rules into a backward chaining sequence, prompting the user for information pertinent to the causes considered. The use of heuristics frees the user from searching through large amounts of irrelevant information (varying degrees of confidence in an answer) or 'unknown' to any question. The expert system not only provides scientists with needed risk analysis and confidence estimates not available in standard numerical models or databases, but it is also an effective learning tool. In addition, the architecture of the expert system allows easy additions to the knowledge base and the database. For example, new frames concerning orbital debris and ionospheric scintillation are being considered. The system currently runs on a MicroVAX and uses the C Language Integrated Production System (CLIPS).

  2. Quasi-optical design for systems to diagnose the electron temperature and density fluctuations on EAST.

    PubMed

    Cao, Qifo; Liu, Yong; Zhao, Hailin; Zhou, Tianfu; Ti, Ang; Hu, Liqun

    2016-11-01

    A system to simultaneously diagnose the electron temperature and density fluctuations is proposed for Experimental Advanced Superconducting Tokamak device. This system includes a common quasi-optical antenna, a correlation electron cyclotron emission (CECE) system that is used to measure the electron temperature fluctuations and a Doppler backscattering (DBS) system that is used to measure the electron density fluctuations. The frequency range of the proposed CECE system is 108-120 GHz, and this corresponds to a radial coverage of normalized radius ((R - R0)/a, R0 = 1850 mm, a = 450 mm) from 0.2 to 0.67 for the plasma operation with a toroidal magnetic field of 2.26 T. This paper focuses on the design of the quasi-optical antenna and aims at optimizing the poloidal resolution for different frequency bands. An optimum result gives the beam radius for the CECE system of 13-15 mm and this corresponds to a wave number range of kθ < 2.4 cm(-1). The beam radius is 20-30 mm for V band (50-75 GHz) and 15-20 mm for W band (75-110 GHz).

  3. Quasi-optical design for systems to diagnose the electron temperature and density fluctuations on EAST

    NASA Astrophysics Data System (ADS)

    Cao, Qifo; Liu, Yong; Zhao, Hailin; Zhou, Tianfu; Ti, Ang; Hu, Liqun

    2016-11-01

    A system to simultaneously diagnose the electron temperature and density fluctuations is proposed for Experimental Advanced Superconducting Tokamak device. This system includes a common quasi-optical antenna, a correlation electron cyclotron emission (CECE) system that is used to measure the electron temperature fluctuations and a Doppler backscattering (DBS) system that is used to measure the electron density fluctuations. The frequency range of the proposed CECE system is 108-120 GHz, and this corresponds to a radial coverage of normalized radius ((R - R0)/a, R0 = 1850 mm, a = 450 mm) from 0.2 to 0.67 for the plasma operation with a toroidal magnetic field of 2.26 T. This paper focuses on the design of the quasi-optical antenna and aims at optimizing the poloidal resolution for different frequency bands. An optimum result gives the beam radius for the CECE system of 13-15 mm and this corresponds to a wave number range of kθ < 2.4 cm-1. The beam radius is 20-30 mm for V band (50-75 GHz) and 15-20 mm for W band (75-110 GHz).

  4. Diagnosing Disaster Resilience of Communities as Multi-scale Complex Socio-ecological Systems

    NASA Astrophysics Data System (ADS)

    Liu, Wei; Mochizuki, Junko; Keating, Adriana; Mechler, Reinhard; Williges, Keith; Hochrainer, Stefan

    2014-05-01

    Global environmental change, growing anthropogenic influence, and increasing globalisation of society have made it clear that disaster vulnerability and resilience of communities cannot be understood without knowledge on the broader social-ecological system in which they are embedded. We propose a framework for diagnosing community resilience to disasters, as a form of disturbance to social-ecological systems, with feedbacks from the local to the global scale. Inspired by iterative multi-scale analysis employed by Resilience Alliance, the related socio-ecological systems framework of Ostrom, and the sustainable livelihood framework, we developed a multi-tier framework for thinking of communities as multi-scale social-ecological systems and analyzing communities' disaster resilience and also general resilience. We highlight the cross-scale influences and feedbacks on communities that exist from lower (e.g., household) to higher (e.g., regional, national) scales. The conceptual framework is then applied to a real-world resilience assessment situation, to illustrate how key components of socio-ecological systems, including natural hazards, natural and man-made environment, and community capacities can be delineated and analyzed.

  5. An Intelligent computer-aided tutoring system for diagnosing anomalies of spacecraft in operation

    NASA Technical Reports Server (NTRS)

    Rolincik, Mark; Lauriente, Michael; Koons, Harry C.; Gorney, David

    1993-01-01

    A new rule-based, expert system for diagnosing spacecraft anomalies is under development. The knowledge base consists of over two-hundred (200) rules and provides links to historical and environmental databases. Environmental causes considered are bulk charging, single event upsets (SEU), surface charging, and total radiation dose. The system's driver translates forward chaining rules into a backward chaining sequence, prompting the user for information pertinent to the causes considered. When the user selects the novice mode, the system automatically gives detailed explanations and descriptions of terms and reasoning as the session progresses, in a sense teaching the user. As such it is an effective tutoring tool. The use of heuristics frees the user from searching through large amounts of irrelevant information and allows the user to input partial information (varying degrees of confidence in an answer) or 'unknown' to any question. The system is available on-line and uses C Language Integrated Production System (CLIPS), an expert shell developed by the NASA Johnson Space Center AI Laboratory in Houston.

  6. Getting Diagnosed

    MedlinePlus

    ... also for those with related disorders. How is Marfan syndrome diagnosed? getting_diagnosed.jpg A Marfan diagnosis ... spinal column). Is there a genetic test for Marfan syndrome? Genetic testing can provide helpful information in ...

  7. Neuroblastoma in a Patient With Spinal Muscular Atrophy Type I: Is It Just a Coincidence?

    PubMed

    Sag, Erdal; Sen, Hilal Susam; Haliloglu, Goknur; Yalcin, Bilgehan; Kutluk, Tezer

    2015-07-01

    Spinal muscular atrophy is an autosomal recessive disorder characterized by progressive degeneration of anterior horn cells of the spinal cord resulting in hypotonia, skeletal muscle atrophy, and weakness. Herein, we report a 4-month-old male infant who presented to our hospital with an abdominal mass that was diagnosed as neuroblastoma and spinal muscular atrophy type I. We would like to discuss the course and differential diagnosis with an algorithm leading to the diagnosis in this peculiar patient. To our knowledge, coexistence of spinal muscular atrophy type I and neuroblastoma is defined for the first time in the literature.

  8. Comparative assessment of rule-based and Bayes' theorem as inference engines in diagnosing symptoms for Islamic medication expert system

    NASA Astrophysics Data System (ADS)

    Daud, H.; Razali, R.; Low, T. J.; Sabdin, M.; Zafrul, S. Z. Mohd

    2014-06-01

    An expert system for diagnosing sickness and suggesting treatment based on Islamic Medication (IM) was constructed using Rule Based (RB) and Bayes' theorem (BT) algorithms independently as its inference engine. Comparative assessment on the quality of diagnosing based on symptoms provided by users for certain type of sickness using RB and BT reasoning that lead to the suggested treatment (based on IM) are discussed. Both approaches are found to be useful, each has its own advantages and disadvantages. Major difference of the two algorithms is the selection of symptoms during the diagnosing process. For BT, likely combinations of symptoms need to be classified for each sickness before the diagnosing process. This eliminates any irrelevant sickness based on the combination of symptoms provided by user and combination of symptoms that is unlikely. This is not the case for RB, it will diagnose the sickness as long as one the symptoms is related to the sickness regardless of unlikely combination. Few tests have been carried out using combinations of symptoms for same sickness to investigate their diagnosing accuracy in percentage. BT gives more promising diagnosing results compared to RB for each sickness that comes with common symptoms.

  9. Method and system for the diagnosis of disease using retinal image content and an archive of diagnosed human patient data

    DOEpatents

    Tobin, Kenneth W; Karnowski, Thomas P; Chaum, Edward

    2013-08-06

    A method for diagnosing diseases having retinal manifestations including retinal pathologies includes the steps of providing a CBIR system including an archive of stored digital retinal photography images and diagnosed patient data corresponding to the retinal photography images, the stored images each indexed in a CBIR database using a plurality of feature vectors, the feature vectors corresponding to distinct descriptive characteristics of the stored images. A query image of the retina of a patient is obtained. Using image processing, regions or structures in the query image are identified. The regions or structures are then described using the plurality of feature vectors. At least one relevant stored image from the archive based on similarity to the regions or structures is retrieved, and an eye disease or a disease having retinal manifestations in the patient is diagnosed based on the diagnosed patient data associated with the relevant stored image(s).

  10. Treatment of vaginal atrophy.

    PubMed

    Domoney, Claudine

    2014-03-01

    Vaginal or vulvovaginal atrophy is a widespread but poorly recognized condition of peri- and post-menopausal women. It causes urogenital symptoms of dryness, reduced lubrication, itching, burning, irritable bladder symptoms and painful intercourse. This impacts quality of life and sexual health, but increases with time rather than reduces, as with most other menopausal symptoms. With early identification, treatments can improve these symptoms and reverse the physical changes. However, when embedded, bladder and sexual changes have occurred and these may be more difficult to remedy. Therefore, it is important to educate both healthcare professionals and women about these symptoms and advise on the range of interventions available.

  11. Unyvero i60 implant and tissue infection (ITI) multiplex PCR system in diagnosing periprosthetic joint infection.

    PubMed

    Hischebeth, Gunnar T R; Randau, Thomas M; Buhr, Johanna K; Wimmer, Matthias D; Hoerauf, Achim; Molitor, Ernst; Bekeredjian-Ding, Isabelle; Gravius, Sascha

    2016-02-01

    Periprosthetic joint infection (PJI) is one of the most challenging complications in orthopedic surgery. In cases of suspected periprosthetic joint infection several diagnostic methods are available. In this study we investigated the performance of the newly available Unyvero i60 implant and tissue infection (ITI) multiplex PCR System. 62 specimens from 31 patients with suspected PJI or aseptic loosening of a painful joint arthoplasty were included in this study. Besides the established diagnostic procedures we included a commercial multiplex PCR detection system for diagnosis of PJI. The PCR results obtained from analysis of sonication and synovial fluids (62 specimens) showed a sensitivity of 66.7%, a specificity of 100%, a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 68.4% when compared to cultural methods. Notably, cultures from sonication fluid displayed a sensitivity of 88.9%, a specificity of 61.5%, a PPV of 76.2% and a NPV of 80.0% when compared to tissue cultures. In conclusion, multiplex PCR is an additional - rapid - method for diagnosing PJI. Positive results with the PCR assay used in this study were always confirmed by subsequent matching culture positivity. However, apart from the time saved the nucleic acid amplification technique did not yield additional information than that obtained from microbiological cultures.

  12. Posterior Cortical Atrophy

    PubMed Central

    Crutch, Sebastian J; Lehmann, Manja; Schott, Jonathan M; Rabinovici, Gil D; Rossor, Martin N; Fox, Nick C

    2013-01-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome that is characterized by a progressive decline in visuospatial, visuoperceptual, literacy and praxic skills. The progressive neurodegeneration affecting parietal, occipital and occipito-temporal cortices which underlies PCA is attributable to Alzheimer's disease (AD) in the majority of patients. However, alternative underlying aetiologies including Dementia with Lewy Bodies (DLB), corticobasal degeneration (CBD) and prion disease have also been identified, and not all PCA patients have atrophy on clinical imaging. This heterogeneity has led to diagnostic and terminological inconsistencies, caused difficulty comparing studies from different centres, and limited the generalizability of clinical trials and investigations of factors driving phenotypic variability. Significant challenges remain in identifying the factors associated with both the selective vulnerability of posterior cortical regions and the young age of onset seen in PCA. Greater awareness of the syndrome and agreement over the correspondence between syndrome-and disease-level classifications are required in order to improve diagnostic accuracy, research study design and clinical management. PMID:22265212

  13. Nanocarriers as pulmonary drug delivery systems to treat and to diagnose respiratory and non respiratory diseases

    PubMed Central

    Smola, Malgorzata; Vandamme, Thierry; Sokolowski, Adam

    2008-01-01

    The purpose of this review is to discuss the impact of nanocarriers administered by pulmonary route to treat and to diagnose respiratory and non respiratory diseases. Indeed, during the past 10 years, the removal of chlorofluorocarbon propellants from industrial and household products intended for the pulmonary route has lead to the developments of new alternative products. Amongst these ones, on one hand, a lot of attention has been focused to improve the bioavailability of marketed drugs intended for respiratory diseases and to develop new concepts for pulmonary administration of drugs and, on the other hand, to use the pulmonary route to administer drugs for systemic diseases. This has led to some marketed products through the last decade. Although the introduction of nanotechnology permitted to step over numerous problems and to improve the bioavailability of drugs, there are, however, unresolved delivery problems to be still addressed. These scientific and industrial innovations and challenges are discussed along this review together with an analysis of the current situation concerning the industrial developments. PMID:18488412

  14. [Nursing diagnoses and outcomes related to the circulatory-system terms (ICNP®) represented in an ontology].

    PubMed

    Cubas, Marcia Regina; Brondani, Arianny Macedo; Malucelli, Andreia

    2013-10-01

    The aim of the present study was to develop titles of Nursing Diagnoses and Outcomes (ND/NO) through the relationship between the terms of the Focus axis, limited to the Circulatory System Process, and the terms of other ICNP® axes and to integrate these terms into an ontology. Titles were developed linking 17 terms of the focus axis, which were evaluated by expert nurses in five Brazilian cities. Titles whose use concordance was above 0.80 were included in the ontology. In total, 89 titles for ND/NO were supported in the literature, and 19 were not supported; 37 were assessed as eligible for use in healthcare practice and were included in the ontology. The construction of ND/NO titles based on the ICNP® and using a formal representation of knowledge is a task that requires deepening concepts used for nursing and adequate classification revisions. The elaborated titles will facilitate the composition of diagnostics that are more consistent with practice.

  15. Inflammation, atrophy, and gastric cancer

    PubMed Central

    Fox, James G.; Wang, Timothy C.

    2006-01-01

    The association between chronic inflammation and cancer is now well established. This association has recently received renewed interest with the recognition that microbial pathogens can be responsible for the chronic inflammation observed in many cancers, particularly those originating in the gastrointestinal system. A prime example is Helicobacter pylori, which infects 50% of the world’s population and is now known to be responsible for inducing chronic gastric inflammation that progresses to atrophy, metaplasia, dysplasia, and gastric cancer. This Review provides an overview of recent progress in elucidating the bacterial properties responsible for colonization of the stomach, persistence in the stomach, and triggering of inflammation, as well as the host factors that have a role in determining whether gastritis progresses to gastric cancer. We also discuss how the increased understanding of the relationship between inflammation and gastric cancer still leaves many questions unanswered regarding recommendations for prevention and treatment. PMID:17200707

  16. Using MERRA Gridded Innovation for Quantifying Uncertainties in Analysis Fields and Diagnosing Observing System Inhomogeneities

    NASA Astrophysics Data System (ADS)

    da Silva, A.; Redder, C. R.

    2010-12-01

    -likelihood estimates of background and observation errors, as well as global bias estimates. Starting with the joint PDF of innovations and analysis increments at observation locations we propose a technique for diagnosing bias among the observing systems, and document how these contextual biases have evolved during the satellite era covered by MERRA.

  17. Using MERRA Gridded Innovations for Quantifying Uncertainties in Analysis Fields and Diagnosing Observing System Inhomogeneities

    NASA Technical Reports Server (NTRS)

    da Silva, Arlindo; Redder, Christopher

    2010-01-01

    -likelihood estimates of background and observation errors, as well as global bias estimates. Starting with the joint PDF of innovations and analysis increments at observation locations we propose a technique for diagnosing bias among the observing systems, and document how these contextual biases have evolved during the satellite era covered by MERRA.

  18. Diagnosing ALS

    MedlinePlus

    ... that a person diagnosed with ALS seek a second opinion from an ALS "expert" - someone who diagnoses and treats many ALS patients and has training in this medical specialty. The ALS Association maintains a list of recognized experts in the field of ALS. See ALS Association Certified Centers of ...

  19. Diagnosing Snow and Sea Ice Radiative Forcing in the Community Earth System Model

    NASA Astrophysics Data System (ADS)

    Perket, J.; Flanner, M. G.

    2012-12-01

    Earth's albedo is evolving from changes in seasonal snow and sea-ice. Albedo feedback in climate models has been evaluated previously using the radiative kernel technique, where top-of-atmosphere (TOA) radiative fluxes associated with albedo change are calculated "offline" using pre-defined atmospheric states. This approach facilitates model intercomparisons, but can lead to inaccuracies associated with inconsistent surface and cloud states. We have incorporated a new diagnostic feature in the NCAR Community Earth System Model (CESM) that provides the instantaneous effect of land snow and sea ice on the TOA radiation budget at each time step. This diagnostic provides a precise measure of the radiative influence of model snow and sea ice, enables direct model comparison with observation-derived cryosphere radiative forcing (CrRF) estimates, and provides a means to evaluate the accuracy of the radiative kernel technique for diagnosing albedo feedback. Compared with observed northern hemisphere CrRF, we find that CESM produces a larger radiative effect for both land snow and sea ice. Preliminary analysis shows the snow radiative effect in the Northern Hemisphere to be higher in coupled ocean-land-atmosphere simulations compared to standalone land simulations forced with atmospheric reanalysis data. The same is true for ice when comparing the coupled system to offline ice simulations in the Southern Hemisphere. Differences are not as appreciable for sea ice in the North or snow in the South. Studies are planned to assess the accuracy of different radiative kernels, evaluate reasons for model-observation discrepancy in cryosphere radiative forcing, and quantify model changes in CrRF under different climate forcing scenarios.

  20. The effects of Capn1 gene inactivation on skeletal muscle growth, development, and atrophy, and the compensatory role of other proteolytic systems.

    PubMed

    Kemp, C M; Oliver, W T; Wheeler, T L; Chishti, A H; Koohmaraie, M

    2013-07-01

    Myofibrillar protein turnover is a key component of muscle growth and degeneration, requiring proteolytic enzymes to degrade the skeletal muscle proteins. The objective of this study was to investigate the role of the calpain proteolytic system in muscle growth development using μ-calpain knockout (KO) mice in comparison with control wild-type (WT) mice, and evaluate the subsequent effects of silencing this gene on other proteolytic systems. No differences in muscle development between genotypes were observed during the early stages of growth due to the up regulation of other proteolytic systems. The KO mice showed significantly greater m-calpain protein abundance (P < 0.01) and activity (P < 0.001), and greater caspase 3/7 activity (P < 0.05). At 30 wk of age, KO mice showed increased protein:DNA (P < 0.05) and RNA:DNA ratios (P < 0.01), greater protein content (P < 0.01) at the expense of lipid deposition (P < 0.05), and an increase in size and number of fast-twitch glycolytic muscle fibers (P < 0.05), suggesting that KO mice exhibit an increased capacity to accumulate and maintain protein in their skeletal muscle. Also, expression of proteins associated with muscle regeneration (neural cell adhesion molecule and myoD) were both reduced in the mature KO mice (P < 0.05 and P < 0.01, respectively), indicating less muscle regeneration and, therefore, less muscle damage. These findings indicate the concerted action of proteolytic systems to ensure muscle protein homeostasis in vivo. Furthermore, these data contribute to the existing evidence of the importance of the calpain system's involvement in muscle growth, development, and atrophy. Collectively, these data suggest that there are opportunities to target the calpain system to promote the growth and/or restoration of skeletal muscle mass.

  1. Comparison of brain MRI and 18F-FDG PET in the differential diagnosis of multiple system atrophy from Parkinson's disease.

    PubMed

    Kwon, Kyum-Yil; Choi, Choong G; Kim, Jae S; Lee, Myoung C; Chung, Sun J

    2007-12-01

    To investigate the diagnostic value of brain magnetic resonance image (MRI) and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in the differentiation of multiple system atrophy (MSA) from Parkinson's disease (PD). Thirty-five patients with MSA (23 MSA-P and 12 MSA-C) and 17 patients with PD were included in this study. Overall correct diagnosis rates between clinical and imaging diagnosis among MSA-P, MSA-C, and PD patients were 80% for visual MRI analysis, 88.5% for visual (18)F-FDG PET analysis, and 84.3% for SPM-supported analysis of (18)F-FDG PET. The sensitivity of brain MRI, and visual and SPM analysis of (18)F-FDG PET in differentiating MSA from PD was 72.7%, 90.9%, and 95.5%, respectively, the specificity was 100% for each imaging analysis, the positive predictive value was 100% for each imaging analysis, and the negative predictive value was 60%, 81.8%, and 90%, respectively. Our results suggest that brain MRI and (18)F-FDG PET are diagnostically useful in differentiating MSA (MSA-P and MSA-C) from PD, and indicate that (18)F-FDG PET has a tendency toward higher sensitivity compared to brain MRI, but a larger longitudinal study including pathological data will be required to confirm our findings.

  2. The Utility of Post-Void Residual Volume versus Sphincter Electromyography to Distinguish between Multiple System Atrophy and Parkinson’s Disease

    PubMed Central

    Yamamoto, Tatsuya; Asahina, Masato; Yamanaka, Yoshitaka; Uchiyama, Tomoyuki; Hirano, Shigeki; Fuse, Miki; Koga, Yasuko; Sakakibara, Ryuji; Kuwabara, Satoshi

    2017-01-01

    Objective To determine the ability of sphincter electromyography (EMG) and post-void residual urine volume (PVR) during a free-flow study and a pressure-flow study (PFS) for distinguishing multiple system atrophy (MSA) from Parkinson’s disease (PD). Methods We retrospectively reviewed 241 case records; both urodynamic study and sphincter EMG were performed in patients with MSA (n = 147) and PD (n = 94). Results There was a statistically significant difference (p < 0.01) in the mean PVR during the free-flow study (113.1 ± 7.5 mL in MSA and 40.4 ± 3.8 mL in PD), mean PVR during PFS (230.1 ± 12.6 mL in MSA and 71.7 ± 6.6 mL in PD), and mean duration of MUP for sphincter EMG (9.3 ± 0.1 ms in MSA and 7.7 ± 0.1 ms in PD). The area under the curve used for differentiating MSA from PD was 0.79 and 0.73 for PVR during PFS and the free-flow study, respectively. There was a mean duration of 0.69 ms for the sphincter EMG. Conclusions The present results suggested that PVR was more appropriate than sphincter EMG for differentiating MSA from PD. PMID:28060892

  3. [A case of an anti-Ma2 antibody-positive patient presenting with variable CNS symptoms mimicking multiple system atrophy with a partial response to immunotherapy].

    PubMed

    Shiraishi, Wataru; Iwanaga, Yasutaka; Yamamoto, Akifumi

    2015-01-01

    A 70-year-old man with a 5-month history of progressive bradykinesia of the bilateral lower extremities was admitted to our hospital. At the age of 64, he underwent proximal gastrectomy for gastric cancer. He also had a history of subacute combined degeneration of the spinal cord since the age of 67, which was successfully treated with vitamin B12 therapy. Four weeks before admission to our hospital, he admitted himself to his former hospital complaining of walking difficulty. Two weeks later, however, his symptoms progressed rapidly; he was immobilized for two weeks and did not respond to the vitamin therapy. On admission to our hospital, he showed moderate paralysis of the lower extremities, cog-wheel rigidity of the four extremities, and dystonic posture of his left hand. He also showed orthostatic hypotension and vesicorectal disorders. Blood examination and cerebrospinal fluid analysis revealed no remarkable abnormalities. Electroencephalography showed frontal dominant, high voltage, sharp waves. His brain and spinal MRI revealed no notable abnormalities. We suspected autoimmune disease and commenced one course of intravenous methylprednisolone therapy, resulting in improvement of the parkinsonism and orthostatic hypotension. Based on these results, we investigated possible neural antigens and detected anti-Ma2 antibody. In addition to limbic encephalitis, anti-Ma2 antibody-positive neural disorders are characterized by rapid eye movement sleep behavior disorders or parkinsonism. Here, we report an anti-Ma2 antibody positive patient presenting variable CNS symptoms mimicking multiple system atrophy, who responded to immunotherapy.

  4. Hypocupremia: A Possible Association with Late Cortical Cerebellar Atrophy

    PubMed Central

    Mittal, Shivam Om; Machado, Duarte G.

    2014-01-01

    Background We report a patient, diagnosed with late cortical cerebellar atrophy, who had persistent low serum copper levels. Case report A 48-year-old male developed progressive difficulty with balance, frequent falls, and dysarthric speech, which worsened over a short time span. He had an extensive ataxia work-up, which was unremarkable except for persistent low serum copper levels despite adequate supplementation. Magnetic resonance imaging of the brain showed marked cerebellar atrophy. The patient experienced progressive worsening of symptoms, which did not improve with either oral or parenteral copper supplementation. Discussion To our knowledge, ours is the first case report of late cortical cerebellar atrophy in the setting of low serum copper levels. The current report should trigger further research in mechanisms leading to copper deficiency and its possible role in cerebellar disease. PMID:25247109

  5. Developing Expert System for Tuberculosis Diagnose to Support Knowledge Sharing in the Era of National Health Insurance System

    NASA Astrophysics Data System (ADS)

    Lidya, L.

    2017-03-01

    National Health Insurance has been implemented since 1st January 2014. A number of new policies have been established including multilevel referral system. The multilevel referral system classified health care center into three levels, it determined that the flow of patient treatment should be started from first level health care center. There are 144 kind of diseases that must be treat in the first level which mainly consists of general physicians. Unfortunately, competence of the physician in the first level may not fulfil the standard competence yet. To improved the physisians knowledge, government has created many events to accelerate knowledge sharing. However, it still needs times and many resources to give significan results. Expert system is kind of software that provide consulting services to non-expert users in accordance with the area of its expertise. It can improved effectivity and efficiency of knowledge sharing and learning. This research was developed a model of TB diagnose expert system which comply with the standard procedure of TB diagnosis and regulation. The proposed expert system has characteristics as follows provide facility to manage multimedia clinical data, supporting the complexity of TB diagnosis (combine rule-based and case-based expert system), interactive interface, good usability, multi-platform, evolutionary.

  6. Rates of cerebral atrophy differ in different degenerative pathologies

    PubMed Central

    Whitwell, Jennifer L; Jack, Clifford R.; Parisi, Joseph E.; Knopman, David S.; Boeve, Bradley F.; Petersen, Ronald C.; Ferman, Tanis J.; Dickson, Dennis W.; Josephs, Keith A.

    2009-01-01

    SUMMARY Neurodegenerative disorders are pathologically characterized by the deposition of abnormal proteins in the brain. It is likely that future treatment trials will target the underlying protein biochemistry and it is therefore increasingly important to be able to distinguish between different pathologies during life. The aim of this study was to determine whether rates of brain atrophy differ in neurodegenerative dementias that vary by pathological diagnoses and characteristic protein biochemistry. Fifty-six autopsied subjects were identified with a clinical diagnosis of dementia and two serial head MRI. Subjects were subdivided based on pathological diagnoses into Alzheimer's disease (AD), dementia with Lewy bodies (DLB), mixed AD/DLB, frontotemporal lobar degeneration with ubiquitin-only-immunoreactive changes (FTLD-U), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). Twenty-five controls were matched by age, gender, and scan interval, to the study cohort. The boundary-shift integral was used to calculate change over time in whole brain (BBSI) and ventricular volume (VBSI). All BSI results were annualized by adjusting for scan interval. The rates of whole brain atrophy and ventricular expansion were significantly increased compared to controls in the AD, mixed AD/DLB, FTLD-U, CBD and PSP groups. However, atrophy rates in the DLB group were not significantly different from control rates of atrophy. The largest rates of atrophy were observed in the CBD group which had a BBSI of 2.3% and VBSI of 16.2%. The CBD group had significantly greater rates of BBSI and VBSI than the DLB, mixed AD/DLB, AD and PSP groups, with a similar trend observed when compared to the FTLD-U group. The FTLD-U group showed the next largest rates with a BBSI of 1.7% and VBSI of 9.6% which were both significantly greater than the DLB group. There was no significant difference in the rates of atrophy between the AD, mixed AD/DLB and PSP groups, which all showed

  7. Brain atrophy in frontotemporal dementia.

    PubMed Central

    Frisoni, G B; Beltramello, A; Geroldi, C; Weiss, C; Bianchetti, A; Trabucchi, M

    1996-01-01

    OBJECTIVES--To evaluate the pattern of regional brain atrophy in patients with frontotemporal dementia by comparing it with that in patients with Alzheimer's disease and normal controls. METHODS--Fourteen patients with frontotemporal dementia, 13 with moderate, and 33 with mild Alzheimer's disease, and 31 controls were studied. Atrophy was evaluated with linear measures in the anterior brain, medial temporal lobe, and hippocampal formation regions using MRI. RESULTS--Patients with frontotemporal dementia had greater atrophy in the anterior brain regions than patients with Alzheimer's disease or controls. Atrophy of the hippocampal formation, which best discriminates Alzheimer's disease from controls, was present also in patients with frontotemporal dementia. By contrast, atrophy of the medial temporal lobe, which is also present in Alzheimer's disease, was absent in frontotemporal dementia. CONCLUSION--A pattern of atrophy in the frontal lobes and hippocampal formation with sparing of the medial temporal lobe might be distinctive of frontotemporal dementia. Hippocampal involvement might not be specific for Alzheimer's disease and specific patterns of atrophy might be distinctive of some forms of degenerative dementia. Images PMID:8708683

  8. Transcriptional profile of a myotube starvation model of atrophy

    NASA Technical Reports Server (NTRS)

    Stevenson, Eric J.; Koncarevic, Alan; Giresi, Paul G.; Jackman, Robert W.; Kandarian, Susan C.

    2005-01-01

    Skeletal muscle wasting is a pervasive phenomenon that can result from a wide range of pathological conditions as well as from habitual muscular inactivity. The present work describes a cell-culture condition that induces significant atrophy in skeletal muscle C2C12 myotubes. The failure to replenish differentiation media in mature myotubes leads to rapid atrophy (53% in diameter), which is referred to here as starvation. Affymetrix microarrays were used to develop a transcriptional profile of control (fed) vs. atrophied (nonfed) myotubes. Myotube starvation was characterized by an upregulation of genes involved in translational inhibition, amino acid biosynthesis and transport, and cell cycle arrest/apoptosis, among others. Downregulated genes included several structural and regulatory elements of the extracellular matrix as well as several elements of Wnt/frizzled and TGF-beta signaling pathways. Interestingly, the characteristic transcriptional upregulation of the ubiquitin-proteasome system, calpains, and cathepsins known to occur in multiple in vivo models of atrophy were not seen during myotube starvation. With the exception of the downregulation of extracellular matrix genes, serine protease inhibitor genes, and the upregulation of the translation initiation factor PHAS-I, this model of atrophy in cell culture has a transcriptional profile quite distinct from any study published to date with atrophy in whole muscle. These data show that, although the gross morphology of atrophied muscle fibers may be similar in whole muscle vs. myotube culture, the processes by which this phenotype is achieved differ markedly.

  9. Newly Diagnosed?

    MedlinePlus

    ... Suggestions Examine Your Skin Newly Diagnosed? Understanding Your Pathology Biopsy: The First Step Sentinel Node Biopsy Melanoma ... start this journey: Get a copy of your pathology report. We can help you understand the report ...

  10. The Significance of Bronchial Atrophy

    PubMed Central

    Maisel, John C.; Silvers, G. Wayne; George, Marlyce S.; Dart, Gladys A.; Petty, Thomas L.; Mitchell, Roger S.

    1972-01-01

    In a 4-year period, 196 lungs from patients with and without chronic obstructive pulmonary disease were examined postmortem for the presence of atrophy in segmental and subsegmental bronchi. As a result of simultaneous postmortem spirometry, cinefluorobronchography and partitioning of airways resistance, plus later assessment of anatomic emphysema, bronchial atrophy emerges as only one of at least three factors usually cooperating in production of abnormal expiratory airway collapse. In selected cases, bronchial atrophy appears to be an important contributor to expiratory airways obstruction. ImagesFig 1 PMID:5021107

  11. Spinal muscular atrophy

    PubMed Central

    2011-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. Estimated incidence is 1 in 6,000 to 1 in 10,000 live births and carrier frequency of 1/40-1/60. This disease is characterized by generalized muscle weakness and atrophy predominating in proximal limb muscles, and phenotype is classified into four grades of severity (SMA I, SMAII, SMAIII, SMA IV) based on age of onset and motor function achieved. This disease is caused by homozygous mutations of the survival motor neuron 1 (SMN1) gene, and the diagnostic test demonstrates in most patients the homozygous deletion of the SMN1 gene, generally showing the absence of SMN1 exon 7. The test achieves up to 95% sensitivity and nearly 100% specificity. Differential diagnosis should be considered with other neuromuscular disorders which are not associated with increased CK manifesting as infantile hypotonia or as limb girdle weakness starting later in life. Considering the high carrier frequency, carrier testing is requested by siblings of patients or of parents of SMA children and are aimed at gaining information that may help with reproductive planning. Individuals at risk should be tested first and, in case of testing positive, the partner should be then analyzed. It is recommended that in case of a request on carrier testing on siblings of an affected SMA infant, a detailed neurological examination should be done and consideration given doing the direct test to exclude SMA. Prenatal diagnosis should be offered to couples who have previously had a child affected with SMA (recurrence risk 25%). The role of follow-up coordination has to be managed by an expert in neuromuscular disorders and in SMA who is able to plan a multidisciplinary intervention that includes pulmonary, gastroenterology/nutrition, and orthopedic care. Prognosis depends on the phenotypic

  12. Systemic, postsymptomatic antisense oligonucleotide rescues motor unit maturation delay in a new mouse model for type II/III spinal muscular atrophy

    PubMed Central

    Bogdanik, Laurent P.; Osborne, Melissa A.; Davis, Crystal; Martin, Whitney P.; Austin, Andrew; Rigo, Frank; Bennett, C. Frank; Lutz, Cathleen M.

    2015-01-01

    Clinical presentation of spinal muscular atrophy (SMA) ranges from a neonatal-onset, very severe disease to an adult-onset, milder form. SMA is caused by the mutation of the Survival Motor Neuron 1 (SMN1) gene, and prognosis inversely correlates with the number of copies of the SMN2 gene, a human-specific homolog of SMN1. Despite progress in identifying potential therapies for the treatment of SMA, many questions remain including how late after onset treatments can still be effective and what the target tissues should be. These questions can be addressed in part with preclinical animal models; however, modeling the array of SMA severities in the mouse, which lacks SMN2, has proven challenging. We created a new mouse model for the intermediate forms of SMA presenting with a delay in neuromuscular junction maturation and a decrease in the number of functional motor units, all relevant to the clinical presentation of the disease. Using this new model, in combination with clinical electrophysiology methods, we found that administering systemically SMN-restoring antisense oligonucleotides (ASOs) at the age of onset can extend survival and rescue the neurological phenotypes. Furthermore, these effects were also achieved by administration of the ASOs late after onset, independent of the restoration of SMN in the spinal cord. Thus, by adding to the limited repertoire of existing mouse models for type II/III SMA, we demonstrate that ASO therapy can be effective even when administered after onset of the neurological symptoms, in young adult mice, and without being delivered into the central nervous system. PMID:26460027

  13. Research opportunities in muscle atrophy

    NASA Technical Reports Server (NTRS)

    Herbison, G. J.; Talbot, J. M.

    1984-01-01

    A trophy of skeletal muscle; muscle a trophy associated with manned space flight; the nature, causes, and mechanisms of muscle atrophy associated with space flight, selected physiological factors, biochemical aspects, and countermeasures are addressed.

  14. Diagnostic Approach to Childhood-onset Cerebellar Atrophy: A 10-Year Retrospective Study of 300 Patients

    PubMed Central

    Al-Maawali, Almundher; Blaser, Susan; Yoon, Grace

    2013-01-01

    Hereditary ataxias associated with cerebellar atrophy are a heterogeneous group of disorders. Selection of appropriate clinical and genetic tests for patients with cerebellar atrophy poses a diagnostic challenge. Neuroimaging is a crucial initial investigation in the diagnostic evaluation of ataxia in childhood, and the presence of cerebellar atrophy helps guide further investigations. We performed a detailed review of 300 patients with confirmed cerebellar atrophy on magnetic resonance imaging over a 10-year period. A diagnosis was established in 47% of patients: Mitochondrial disorders were most common, followed by the neuronal ceroid lipofuscinoses, ataxia telangectasia, and late GM2-gangliosidosis. We review the common causes of cerebellar atrophy in childhood and propose a diagnostic approach based on correlating specific neuroimaging patterns with clinical and genetic diagnoses. PMID:22764178

  15. Validation of a novel sleep-monitoring system for diagnosing obstructive sleep apnea: A comparison with polysomnography

    PubMed Central

    Meng, Lili; Xu, Huajun; Guan, Jian; Yi, Hongliang; Wu, Hongmin; Yin, Shankai

    2016-01-01

    Overnight polysomnography (PSG) is currently the gold standard for diagnosing obstructive sleep apnea (OSA); however, it is time-consuming, expensive and uncomfortable for the patient. A micromovement sensitive mattress (MSM) sleep-monitoring system was developed as an alternative to PSG, however, there has yet to be a study verifying the accuracy of diagnosing OSA with this device. Therefore, the present study assessed the validity of the MSM sleep-monitoring system. Chinese Han participants who were suspected of having OSA were recruited between June 2013 and June 2014. The MSM sleep-monitoring system and PSG were utilized simultaneously overnight on each subject. The apnea-hypopnea index (AHI) was measured by the MSM sleep-monitoring system (AHIMSM) and compared with that determined by PSG (AHIPSG), revealing a significant correlation between the two values (r=0.97, P<0.001). Bland-Altman plots also indicated good agreement (97%) between MSM and PSG. Using an AHIPSG cut-off of ≥5, ≥15 and ≥30 events/h, the sensitivity (specificity) of detecting an AHIMSM of ≥5, ≥15, and ≥30 events/h were 94.9 (100%), 89.9 (96.9%) and 90.3% (94.9%), respectively. The areas under the receiver operating characteristic curve, which were used to differentiate an AHIPSG of ≥5, ≥15 and ≥30 events/h in clinically diagnosed OSA, were 0.984, 0.982 and 0.980, respectively. Thus, the MSM sleeping system may accurately diagnose OSA in the Chinese Han population. Further community-based studies with larger sample sizes are warranted to confirm the validity of this MSM sleeping system. PMID:27882098

  16. Validation of a novel sleep-monitoring system for diagnosing obstructive sleep apnea: A comparison with polysomnography.

    PubMed

    Meng, Lili; Xu, Huajun; Guan, Jian; Yi, Hongliang; Wu, Hongmin; Yin, Shankai

    2016-11-01

    Overnight polysomnography (PSG) is currently the gold standard for diagnosing obstructive sleep apnea (OSA); however, it is time-consuming, expensive and uncomfortable for the patient. A micromovement sensitive mattress (MSM) sleep-monitoring system was developed as an alternative to PSG, however, there has yet to be a study verifying the accuracy of diagnosing OSA with this device. Therefore, the present study assessed the validity of the MSM sleep-monitoring system. Chinese Han participants who were suspected of having OSA were recruited between June 2013 and June 2014. The MSM sleep-monitoring system and PSG were utilized simultaneously overnight on each subject. The apnea-hypopnea index (AHI) was measured by the MSM sleep-monitoring system (AHIMSM) and compared with that determined by PSG (AHIPSG), revealing a significant correlation between the two values (r=0.97, P<0.001). Bland-Altman plots also indicated good agreement (97%) between MSM and PSG. Using an AHIPSG cut-off of ≥5, ≥15 and ≥30 events/h, the sensitivity (specificity) of detecting an AHIMSM of ≥5, ≥15, and ≥30 events/h were 94.9 (100%), 89.9 (96.9%) and 90.3% (94.9%), respectively. The areas under the receiver operating characteristic curve, which were used to differentiate an AHIPSG of ≥5, ≥15 and ≥30 events/h in clinically diagnosed OSA, were 0.984, 0.982 and 0.980, respectively. Thus, the MSM sleeping system may accurately diagnose OSA in the Chinese Han population. Further community-based studies with larger sample sizes are warranted to confirm the validity of this MSM sleeping system.

  17. MRI derived brain atrophy in PSP and MSA-P. Determining sample size to detect treatment effects.

    PubMed

    Paviour, Dominic C; Price, Shona L; Lees, Andrew J; Fox, Nick C

    2007-04-01

    Progressive supranuclear palsy (PSP) and multiple system (MSA) atrophy are associated with progressive brain atrophy. Serial MRI can be applied in order to measure this change in brain volume and to calculate atrophy rates. We evaluated MRI derived whole brain and regional atrophy rates as potential markers of progression in PSP and the Parkinsonian variant of multiple system atrophy (MSA-P). 17 patients with PSP, 9 with MSA-P and 18 healthy controls underwent two MRI brain scans. MRI scans were registered, and brain and regional atrophy rates (midbrain, pons, cerebellum, third and lateral ventricles) measured. Sample sizes required to detect the effect of a proposed disease-modifying treatment were estimated. The effect of scan interval on the variance of the atrophy rates and sample size was assessed. Based on the calculated yearly rates of atrophy, for a drug effect equivalent to a 30% reduction in atrophy, fewer PSP subjects are required in each treatment arm when using midbrain rather than whole brain atrophy rates (183 cf. 499). Fewer MSA-P subjects are required, using pontine/cerebellar, rather than whole brain atrophy rates (164/129 cf. 794). A reduction in the variance of measured atrophy rates was observed with a longer scan interval. Regional rather than whole brain atrophy rates calculated from volumetric serial MRI brain scans in PSP and MSA-P provide a more practical and powerful means of monitoring disease progression in clinical trials.

  18. The utility of susceptibility-weighted imaging for differentiating Parkinsonism-predominant multiple system atrophy from Parkinson's disease: correlation with 18F-flurodeoxyglucose positron-emission tomography.

    PubMed

    Yoon, Ra Gyoung; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Kim, Jae Seung; Oh, Jungsu; Chung, Sun J; Lee, Chong Sik

    2015-01-01

    Our study was intended to demonstrate the different signal intensity (SI) pattern of the putamen seen on susceptibility-weighted imaging (SWI) between that of Parkinson's disease (PD) and Parkinsonism-predominant multiple system atrophy (MSA-P), and to correlate it with (18)F-flurodeoxyglucose positron-emission tomography ((18)F-FDG PET). Thirty patients with PD and 17 with MSA-P underwent SWI, and (18)F-FDG PET were included. The SI was measured on SWI in the anterior and posterior halves of the putamen using a region-of-interest (ROI) on both sides. The normalized regional glucose metabolism (standardized uptake value ratio, SUVR) was measured on co-registered (18)F-FDG PET images using the ROI obtained with SWI. Analysis included a group-level comparison of the SI values obtained on SWI, and these results were correlated with the SUVR on (18)F-FDG PET. The SIs of the bilateral posterior, dominant-side of the posterior, mean values of the bilateral anterior and posterior halves of the putamen on SWI, differed significantly between the two groups (P < 0.001, respectively). The SUVR of the all locations also differed significantly between PD and MSA-P (P < 0.001, respectively). There was a moderate degree of positive correlation between the SI and the SUVR of the left posterior half, and mean value of the bilateral posterior putamen in MSA-P (r = 0.634, P = 0.006, r = 0.492, P = 0.045). In conclusion, the low SI seen on the posterior putamen may differentiate MSA-P from PD. Furthermore, low SI in the putamen correlated with hypometabolism on (18)F-FDG PET. Therefore, SWI could be a potential complementary diagnostic tool to (18)F-FDG PET for differentiating these conditions.

  19. Analysis and meta-analysis of five polymorphisms of the LINGO1 and LINGO2 genes in Parkinson's disease and multiple system atrophy in a Chinese population.

    PubMed

    Chen, YongPing; Cao, Bei; Yang, Jing; Wei, QianQian; Ou, Ru Wei; Zhao, Bi; Song, Wei; Guo, XiaoYan; Shang, HuiFang

    2015-11-01

    Whether polymorphisms rs11856808 and rs9652490 of the Leucine-rich repeat and Ig domain containing, Nogo receptor-interacting protein-1 (LINGO1) gene, as well as rs10968280, rs13362909 and rs7033345 of the LINGO2 gene, increase the risk for Parkinson's disease (PD) is controversial. Considering the overlap of the clinical and pathological characteristics among PD and multiple system atrophy (MSA), we explored the associations between these five polymorphisms and PD and MSA in a Chinese population. A total of 1055 PD patients, 320 MSA patients, and 810 healthy controls (HCs) were genotyped for these five polymorphisms in LINGO1 and LINGO 2 using Sequenom iPLEX Assay technology. Moreover, after combining our results with available published data, a meta-analysis was conducted to investigate the associations between LINGO 1 rs11856808 and rs9652490 and the risk of PD. The frequency of the minor alleles "T" of LINGO1 rs11856808 was significantly lower in PD than that in HCs (p = 0.011, OR 0.89, 95 % CI 0.81-0.97), but not in MSA. Moreover, there were no significant differences in the minor allele frequency distributions of the other four polymorphisms between PD and HCs, and between MSA and HCs. The meta-analysis showed a lack of association of rs9652490 and PD, regardless of the genetic model or ethnic origin. However, the rs11856808 allele decreased the risk of PD in patients of Asian origin in a dominant genetic model. Our findings suggest that rs11856808 plays a protective role by decreasing the risk for PD, but not for MSA, in Asian population, the other four polymorphisms do not contribute to the risk for PD and MSA.

  20. Genetic Variants of SNCA Are Associated with Susceptibility to Parkinson’s Disease but Not Amyotrophic Lateral Sclerosis or Multiple System Atrophy in a Chinese Population

    PubMed Central

    Ou, RuWei; Cao, Bei; Chen, XuePing; Zhao, Bi; Guo, XiaoYan; Yang, Yuan; Chen, Ke; Wu, Ying; Song, Wei; Shang, Hui-Fang

    2015-01-01

    Background The polymorphisms of α-synuclein (SNCA), rs3775444, rs3822086 and rs11931074 that are strongly associated with Parkinson’s disease (PD) in Caucasian populations, were examined in this study to elucidate the role of polymorphisms in different ethnic backgrounds. The possible associations of these three polymorphisms were also investigated in PD, amyotrophic lateral sclerosis (ALS), and multiple system atrophy (MSA) in a Chinese population based on the overlapping of clinical manifestations and pathological characteristics of these three neurodegenerative diseases. Methods A total of 1276 PD, 885 sporadic ALS (SALS), 364 MSA patients, and 846 healthy controls (HCs) were included. All subjects were genotyped for the three polymorphisms using Sequenom iPLEX Assay technology. Results Significant differences in the genotype distributions (p = 5.99E-06 and p = 4.98E-06, respectively) and the minor allele frequency (MAF) (p = 2.16E-06 and p = 2.15E-06, respectively) of SNCA rs3822086 (C) and rs11931074 (G) were observed between PD and HCs. However, no differences were found in the genotype distributions and MAF of SNCA rs3775444 (T) between PD and HCs. Haplotype that incorporated the three SNPs further strengthened the association with PD (best haplotype, p = 9.62E-005). No significant differences in the genotype distributions and MAF of the SNPs were found between SALS and HCs, MSA and HCs, and subgroups of PD and SALS. However, the MAF of SNCA rs3775444 (T) was significantly higher in MSA patients with frontal lobe dysfunction than MSA patients without dysfunction (p = 0.0002, OR 2.53, 95%CI: 1.55-4.15). Conclusion Our results suggest that the rs3822086 (C) allele and rs11931074 (G) allele in SNCA decrease the risk for PD, and SNCA rs11931074 may affect frontal lobe dysfunction of MSA in the Chinese population. However, these SNCA polymorphisms are not likely a common cause of SALS or MSA. PMID:26208350

  1. Smart cloud system with image processing server in diagnosing brain diseases dedicated for hospitals with limited resources.

    PubMed

    Fahmi, Fahmi; Nasution, Tigor H

    2017-01-19

    The use of medical imaging in diagnosing brain disease is growing. The challenges are related to the big size of data and complexity of the image processing. High standard of hardware and software are demanded, which can only be provided in big hospitals. Our purpose was to provide a smart cloud system to help diagnosing brain diseases for hospital with limited infrastructure. The expertise of neurologists was first implanted in cloud server to conduct an automatic diagnosis in real time using image processing technique developed based on ITK library and web service. Users upload images through website and the result, in this case the size of tumor was sent back immediately. A specific image compression technique was developed for this purpose. The smart cloud system was able to measure the area and location of tumors, with average size of 19.91 ± 2.38 cm2 and an average response time 7.0 ± 0.3 s. The capability of the server decreased when multiple clients accessed the system simultaneously: 14 ± 0 s (5 parallel clients) and 27 ± 0.2 s (10 parallel clients). The cloud system was successfully developed to process and analyze medical images for diagnosing brain diseases in this case for tumor.

  2. Diagnosing Flu

    MedlinePlus

    ... your symptoms and their clinical judgment. Will my health care provider test me for flu if I have flu-like ... flu symptoms do not require testing because the test results usually do not change how you are treated. Your health care provider may diagnose you with flu based on ...

  3. The Bethesda system for reporting thyroid cytopathology in Colombia: Correlation with histopathological diagnoses in oncology and non-oncology institutions

    PubMed Central

    Melo-Uribe, Mario Alexander; Sanabria, Álvaro; Romero-Rojas, Alfredo; Pérez, Gabriel; Vargas, Elga Johanna; Abaúnza, María Claudia; Gutiérrez, Víctor

    2015-01-01

    Aim: To determine the correlation between the results of thyroid fine-needle aspirations interpreted using the Bethesda system and final histopathological reports for patients at an oncology hospital (OH) and non-oncology hospitals (NOHs). Materials and Methods: A retrospective, cross-sectional, descriptive study was performed to compare the cytology and histopathology results for patients with thyroid nodules in three Colombian hospitals. The final correlation of diagnoses between the two methods is reported. In Colombia, the health system provides the existence of general care hospitals and hospitals specializing in care of patients with cancer. Results: A total of 196 reports were reviewed, of which 53% were from OH and 47% were from NOHs. A greater proportion of category V (37.5%) was diagnosed at the OH, whereas NOHs diagnosed a greater proportion of category II (42.3%). The global correlation between diagnoses made using cytology and histopathology was 93.3% for categories V and VI (based on the final malignant diagnosis) and 86.9% for benign category II. Significant differences between institution types were observed when category IV and V and malignant histopathology were compared (56.3% OH vs. 23.5% NOH; P = 0.05 for category IV, 97.4% OH vs. 82.3% NOH; P = 0.03 for category V), while no significant difference between institution types was observed when category II and final benign diagnosis were compared (P = 0.6). Conclusions: The Bethesda system for thyroid cytology correlates adequately with final histopathological diagnosis in Colombia. Significant differences were identified in the diagnostic correlation for malignant lesions between the OH and NOHs in categories IV and V caused by selection bias of the population. PMID:25948937

  4. Space travel directly induces skeletal muscle atrophy.

    PubMed

    Vandenburgh, H; Chromiak, J; Shansky, J; Del Tatto, M; Lemaire, J

    1999-06-01

    Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

  5. Space travel directly induces skeletal muscle atrophy

    NASA Technical Reports Server (NTRS)

    Vandenburgh, H.; Chromiak, J.; Shansky, J.; Del Tatto, M.; Lemaire, J.

    1999-01-01

    Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

  6. Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy.

    PubMed

    Shakespeare, Timothy J; Kaski, Diego; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Ryan, Natalie S; Schott, Jonathan M; Crutch, Sebastian J

    2015-07-01

    The clinico-neuroradiological syndrome posterior cortical atrophy is the cardinal 'visual dementia' and most common atypical Alzheimer's disease phenotype, offering insights into mechanisms underlying clinical heterogeneity, pathological propagation and basic visual phenomena (e.g. visual crowding). Given the extensive attention paid to patients' (higher order) perceptual function, it is surprising that there have been no systematic analyses of basic oculomotor function in this population. Here 20 patients with posterior cortical atrophy, 17 patients with typical Alzheimer's disease and 22 healthy controls completed tests of fixation, saccade (including fixation/target gap and overlap conditions) and smooth pursuit eye movements using an infrared pupil-tracking system. Participants underwent detailed neuropsychological and neurological examinations, with a proportion also undertaking brain imaging and analysis of molecular pathology. In contrast to informal clinical evaluations of oculomotor dysfunction frequency (previous studies: 38%, current clinical examination: 33%), detailed eyetracking investigations revealed eye movement abnormalities in 80% of patients with posterior cortical atrophy (compared to 17% typical Alzheimer's disease, 5% controls). The greatest differences between posterior cortical atrophy and typical Alzheimer's disease were seen in saccadic performance. Patients with posterior cortical atrophy made significantly shorter saccades especially for distant targets. They also exhibited a significant exacerbation of the normal gap/overlap effect, consistent with 'sticky fixation'. Time to reach saccadic targets was significantly associated with parietal and occipital cortical thickness measures. On fixation stability tasks, patients with typical Alzheimer's disease showed more square wave jerks whose frequency was associated with lower cerebellar grey matter volume, while patients with posterior cortical atrophy showed large saccadic intrusions

  7. Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy

    PubMed Central

    Kaski, Diego; Yong, Keir X. X.; Paterson, Ross W.; Slattery, Catherine F.; Ryan, Natalie S.; Schott, Jonathan M.; Crutch, Sebastian J.

    2015-01-01

    The clinico-neuroradiological syndrome posterior cortical atrophy is the cardinal ‘visual dementia’ and most common atypical Alzheimer’s disease phenotype, offering insights into mechanisms underlying clinical heterogeneity, pathological propagation and basic visual phenomena (e.g. visual crowding). Given the extensive attention paid to patients’ (higher order) perceptual function, it is surprising that there have been no systematic analyses of basic oculomotor function in this population. Here 20 patients with posterior cortical atrophy, 17 patients with typical Alzheimer’s disease and 22 healthy controls completed tests of fixation, saccade (including fixation/target gap and overlap conditions) and smooth pursuit eye movements using an infrared pupil-tracking system. Participants underwent detailed neuropsychological and neurological examinations, with a proportion also undertaking brain imaging and analysis of molecular pathology. In contrast to informal clinical evaluations of oculomotor dysfunction frequency (previous studies: 38%, current clinical examination: 33%), detailed eyetracking investigations revealed eye movement abnormalities in 80% of patients with posterior cortical atrophy (compared to 17% typical Alzheimer’s disease, 5% controls). The greatest differences between posterior cortical atrophy and typical Alzheimer’s disease were seen in saccadic performance. Patients with posterior cortical atrophy made significantly shorter saccades especially for distant targets. They also exhibited a significant exacerbation of the normal gap/overlap effect, consistent with ‘sticky fixation’. Time to reach saccadic targets was significantly associated with parietal and occipital cortical thickness measures. On fixation stability tasks, patients with typical Alzheimer’s disease showed more square wave jerks whose frequency was associated with lower cerebellar grey matter volume, while patients with posterior cortical atrophy showed large

  8. Idiopathic atrophie blanche.

    PubMed

    Amato, Lauretta; Chiarini, Caterina; Berti, Samantha; Massi, Daniela; Fabbri, Paolo

    2006-01-01

    clinical, serologic, histopathologic, and immunopathologic findings, a diagnosis of idiopathic atrophie blanche was made. The patient was treated with dapsone (50 mg p.o. q.d.) and pentoxifylline (400 mg p.o. t.i.d.) with pain relief and complete resolution of the ulcerations after 6 weeks of therapy.

  9. Changes in the miRNA-mRNA Regulatory Network Precede Motor Symptoms in a Mouse Model of Multiple System Atrophy: Clinical Implications

    PubMed Central

    Refolo, Violetta; Venezia, Serena; Sturm, Edith; Piatti, Paolo; Hechenberger, Clara; Hackl, Hubert; Kessler, Roman; Willi, Michaela; Gstir, Ronald; Krogsdam, Anne; Lusser, Alexandra; Poewe, Werner; Wenning, Gregor K.; Hüttenhofer, Alexander; Stefanova, Nadia

    2016-01-01

    Multiple system atrophy (MSA) is a fatal rapidly progressive α-synucleinopathy, characterized by α-synuclein accumulation in oligodendrocytes. It is accepted that the pathological α-synuclein accumulation in the brain of MSA patients plays a leading role in the disease process, but little is known about the events in the early stages of the disease. In this study we aimed to define potential roles of the miRNA-mRNA regulatory network in the early pre-motor stages of the disease, i.e., downstream of α-synuclein accumulation in oligodendroglia, as assessed in a transgenic mouse model of MSA. We investigated the expression patterns of miRNAs and their mRNA targets in substantia nigra (SN) and striatum, two brain regions that undergo neurodegeneration at a later stage in the MSA model, by microarray and RNA-seq analysis, respectively. Analysis was performed at a time point when α-synuclein accumulation was already present in oligodendrocytes at neuropathological examination, but no neuronal loss nor deficits of motor function had yet occurred. Our data provide a first evidence for the leading role of gene dysregulation associated with deficits in immune and inflammatory responses in the very early, non-symptomatic disease stages of MSA. While dysfunctional homeostasis and oxidative stress were prominent in SN in the early stages of MSA, in striatum differential gene expression in the non-symptomatic phase was linked to oligodendroglial dysfunction, disturbed protein handling, lipid metabolism, transmembrane transport and altered cell death control, respectively. A large number of putative miRNA-mRNAs interaction partners were identified in relation to the control of these processes in the MSA model. Our results support the role of early changes in the miRNA-mRNA regulatory network in the pathogenesis of MSA preceding the clinical onset of the disease. The findings thus contribute to understanding the disease process and are likely to pave the way towards

  10. Comparison Study of Polysomnographic Features in Multiple System Atrophy-cerebellar Types Combined with and without Rapid Eye Movement Sleep Behavior Disorder

    PubMed Central

    Ding, Yan; Hu, Yue-Qing; Zhan, Shu-Qin; Li, Cun-Jiang; Wang, Hong-Xing; Wang, Yu-Ping

    2016-01-01

    Background: The brain stem is found to be impaired in multiple system atrophy-cerebellar types (MSA-C). Rapid eye movement (REM) sleep behavior disorder (RBD) is reported as a marker of progressive brain stem dysfunction. Few systematic studies about the sleep disturbances in MSA-C patients combined with or without RBD were reported. This study aimed to explore the polysomnographic (PSG) features of sleep disturbances between MSA-C patients with and without RBD. Methods: Totally, 46 MSA-C patients (23 with RBD, and 23 without RBD) were enrolled in this study. All patients underwent a structured interview for their demographic data, history of sleep pattern, and movement disorders; and then, overnight video-PSG was performed in each patient. All the records were evaluated by specialists at the Sleep Medicine Clinic for RBD and the Movement Disorder Clinic for MSA-C. The Student's t-test, Mann-Whitney U-test for continuous variables, and the Chi-square test for categorical variables were used in this study. Results: MSA-C patients with RBD had younger visiting age (52.6 ± 7.4 vs. 56.7 ± 6.0 years, P = 0.046) and shorter duration of the disease (12.0 [12.0, 24.0] vs. 24.0 [14.0, 36.0] months, P = 0.009) than MSA-C patients without RBD. MSA-C with RBD had shorter REM sleep latency (111.7 ± 48.2 vs. 157.0 ± 68.8 min, P = 0.042), higher percentage of REM sleep (14.9% ±4.0% vs. 10.0% ± 3.2%, P = 0.019), and lower Stage I (9.5% ±7.2% vs. 15.9% ±8.0%, P = 0.027) than MSA-C without RBD. Moreover, MSA-C patients with RBD had more decreased sleep efficiency (52.4% ±12.6% vs. 65.8% ±15.9%, P = 0.029) than that without RBD. Conclusions: In addition to the RBD, MSA-C patients with RBD had other more severe sleep disturbances than those without RBD. The sleep disorders of MSA patients might be associated with the progress of the disease. PMID:27625088

  11. Optic atrophy and glaucomatous cupping.

    PubMed

    Radius, R L; Maumenee, A E

    1978-02-01

    We reviewed 170 eyes of 112 patients with optic atrophy from various causes. Special attention was directed towards measured cup:disk ratios as well as presence of glaucomatous-like cupping of the optic nerve head. We observed a small but significant increase in nerve head cupping in eyes with optic atrophy when compared to contralateral eyes, as well as to eyes of 50 diabetic patients. No characteristic glaucomatous disk changes were documented. We evaluated these findings with respect to possible causes of glaucomatous disk and field changes.

  12. Usefulness of the MrWALLETS Scoring System to Predict First Diagnosed Atrial Fibrillation in Patients With Ischemic Stroke.

    PubMed

    Muscari, Antonio; Bonfiglioli, Andrea; Faccioli, Luca; Ghinelli, Marco; Magalotti, Donatella; Manzetto, Francesco; Pontarin, Anna; Puddu, Giovanni M; Spinardi, Luca; Tubertini, Eleonora; Zoli, Marco

    2017-04-01

    Some cryptogenic strokes are caused by undetected paroxysmal atrial fibrillation (AF) and could benefit from oral anticoagulation. In this study, we searched for echocardiographic parameters associated with first diagnosed AF, to form a scoring system for the identification of patients with AF. We examined 571 patients with ischemic stroke (72.7 ± 13.5 years, 50.6% women), subdivided into 4 groups: documented cause without AF, first diagnosed AF, known paroxysmal AF, and permanent AF. All patients underwent transthoracic echocardiography, brain computed tomography scan, carotid/vertebral ultrasound, and continuous electrocardiographic monitoring. Eight factors independently characterized first diagnosed AF and formed the "MrWALLETS" score: mitral regurgitation, mild-to-moderate (+1), white matter lesions (-1), age ≥75 years (+1), left atrium ≥4 cm (+1), cerebral lesion diameter ≥4 cm (+1), left ventricular end-diastolic volume <65 ml (+1), tricuspid regurgitation ≥moderate (+1), carotid stenosis ≥50% (-1). In the patients with ≥3 points, positive predictive value was 80%, specificity 97.5%, and sensitivity 57.1%. In the patients with ≥2 points sensitivity rose to 85.7%, but positive predictive value was 47.1%. The area under the receiver-operating characteristic curve was 0.89 (95% CI 0.83 to 0.95). There were important differences among AF groups, which therefore could not be merged. In conclusion, 4 echocardiographic parameters, 3 additional instrumental parameters, and age allow the identification of stroke patients with first diagnosed AF with high positive predictive value.

  13. Storage and retrieval of SNOP-coded pathologic diagnoses using offsite computing and optical character recognizing systems.

    PubMed

    Cechner, R L; Carter, J R

    1976-05-01

    A computerized cross-reference system for retrieving autopsy and surgical pathology cases on the basis of case number or diagnosis has been implemented. The system achieves economy and flexibility by using offsite computer service bureaus for job production, eliminating the need for expensive onsite equipment. Coded diagnoses may be typed using the OCR (Optical Character Recognition) font simultaneously with or separately from the clinical documentation. The flexibility of new OCR equipment permits production of machine-readable code sheets with an ordinary pencil and completely eliminates the need for typing. The system produces year-to-date books that list all diagnoses, on an accumulating basis, in alphabetic order by SNOP* topology, morphology, etiology and function, and will be compatible with SNOMed. Because all data are stored on magnetic tape, they may be manipulated and retrieved as desired through user programming. The initial setup cost was dollar 1,000 for programming and testing, and production runs and all report printing cost about dollar 1,000 per year (autopsies and surgical pathology cases), which is about 1.1 cents per diagnosis.

  14. Learning about Spinal Muscular Atrophy

    MedlinePlus

    ... causes the disorder. Top of page NHGRI Clinical Research on Spinal Muscular Atrophy Currently, NHGRI is not conducting studies on SMA. The National Institutes of Health is conducting clinical trials identified as enrolling individuals with SMA: Quantitative Analysis of SMN1 and SMN2 Gene Based on ...

  15. A case of extensive left-sided facial atrophy of Romberg

    PubMed Central

    Verma, Rajesh; Ram, Hari; Gupta, Mani; Vidhate, Mukund R

    2013-01-01

    Progressive facial atrophy or Parry-Romberg syndrome is characterized by slowly progressive facial atrophy involving skin, subcutaneous tissue, cartilage and bony structures. Apart from facial atrophy, it can be associated with diverse clinical manifestations including headache, partial seizures, trigeminal neuralgia, cerebral hemiatrophy and ocular abnormalities. The exact etiology is unknown although sympathetic system dysfunction, autoimmune disorders, focal scleroderma, trauma and genetic factors have been postulated. We hereby report a patient having marked left-sided facial atrophy and wasting of the tongue. Such an extensive wasting is not previously reported in the literature. PMID:24163557

  16. Artificial intelligence techniques applied to the development of a decision–support system for diagnosing celiac disease

    PubMed Central

    Tenório, Josceli Maria; Hummel, Anderson Diniz; Cohrs, Frederico Molina; Sdepanian, Vera Lucia; Pisa, Ivan Torres; de Fátima Marin, Heimar

    2013-01-01

    Background Celiac disease (CD) is a difficult-to-diagnose condition because of its multiple clinical presentations and symptoms shared with other diseases. Gold-standard diagnostic confirmation of suspected CD is achieved by biopsying the small intestine. Objective To develop a clinical decision–support system (CDSS) integrated with an automated classifier to recognize CD cases, by selecting from experimental models developed using intelligence artificial techniques. Methods A web-based system was designed for constructing a retrospective database that included 178 clinical cases for training. Tests were run on 270 automated classifiers available in Weka 3.6.1 using five artificial intelligence techniques, namely decision trees, Bayesian inference, k-nearest neighbor algorithm, support vector machines and artificial neural networks. The parameters evaluated were accuracy, sensitivity, specificity and area under the ROC curve (AUC). AUC was used as a criterion for selecting the CDSS algorithm. A testing database was constructed including 38 clinical CD cases for CDSS evaluation. The diagnoses suggested by CDSS were compared with those made by physicians during patient consultations. Results The most accurate method during the training phase was the averaged one-dependence estimator (AODE) algorithm (a Bayesian classifier), which showed accuracy 80.0%, sensitivity 0.78, specificity 0.80 and AUC 0.84. This classifier was integrated into the web-based decision–support system. The gold-standard validation of CDSS achieved accuracy of 84.2% and k = 0.68 (p < 0.0001) with good agreement. The same accuracy was achieved in the comparison between the physician’s diagnostic impression and the gold standard k = 0. 64 (p < 0.0001). There was moderate agreement between the physician’s diagnostic impression and CDSS k = 0.46 (p = 0.0008). Conclusions The study results suggest that CDSS could be used to help in diagnosing CD, since the algorithm tested achieved excellent

  17. Lessons Learned from using a Livingstone Model to Diagnose a Main Propulsion System

    NASA Technical Reports Server (NTRS)

    Sweet, Adam; Bajwa, Anupa

    2003-01-01

    NASA researchers have demonstrated that qualitative, model-based reasoning can be used for fault detection in a Main Propulsion System (MPS), a complex, continuous system. At the heart of this diagnostic system is Livingstone, a discrete, propositional logic-based inference engine. Livingstone comprises a language for specifying a discrete model of the system and a set of algorithms that use the model to track the system's state. Livingstone uses the model to test assumptions about the state of a component - observations from the system are compared with values predicted by the model. The intent of this paper is to summarize some advantages of Livingstone seen through our modeling experience: for instance, flexibility in modeling, speed and maturity. We also describe some shortcomings we perceived in the implementation of Livingstone, such as modeling continuous dynamics and handling of transients. We list some upcoming enhancements to the next version of Livingstone that may resolve some of the current limitations.

  18. Cardiac transplant in young female patient diagnosed with diffuse systemic sclerosis.

    PubMed

    Bennasar, Guillermo; Carlevaris, Leandro; Secco, Anastasia; Romanini, Felix; Mamani, Marta

    2016-01-01

    Systemic sclerosis (SS) in a multifactorial and systemic, chronic, autoimmune disease that affects the connective tissue. We present this clinical case given the low prevalence of diffuse SS with early and progressive cardiac compromise in a young patient, and treatment with cardiac transplantation.

  19. An integrated decision support system for diagnosing and managing patients with community-acquired pneumonia.

    PubMed Central

    Aronsky, D.; Haug, P. J.

    1999-01-01

    Decision support systems that integrate guidelines have become popular applications to reduce variation and deliver cost-effective care. However, adverse characteristics of decision support systems, such as additional and time-consuming data entry or manually identifying eligible patients, result in a "behavioral bottleneck" that prevents decision support systems to become part of the clinical routine. This paper describes the design and the implementation of an integrated decision support system that explores a novel approach for bypassing the behavioral bottleneck. The real-time decision support system does not require health care providers to enter additional data and consists of a diagnostic and a management component. Images Fig. 1 Fig. 2 Fig. 3 PMID:10566348

  20. Spinal Muscular Atrophy Type I: Is It Ethical to Standardize Supportive Care Intervention in Clinical Trials?

    PubMed Central

    Finkel, Richard S.; Bishop, Kathie M.; Nelson, Robert M.

    2016-01-01

    The natural history of spinal muscular atrophy type I (SMA-I) has changed as improved medical support has become available. With investigational drugs for spinal muscular atrophy now in clinical trials, efficient trial design focuses on enrolling recently diagnosed infants, providing best available supportive care, and minimizing subject variation. The quandary has arisen whether it is ethically appropriate to specify a predefined level of nutritional and/or ventilation support for spinal muscular atrophy type I subjects while participating in these studies. We conducted a survey at 2 spinal muscular atrophy investigator meetings involving physician investigators, clinical evaluators, and study coordinators from North America, Europe, and Asia-Pacific. Each group endorsed the concept that having a predefined degree of nutritional and ventilation support was warranted in this context. We discuss how autonomy, beneficence/non-maleficence, noncoercion, social benefit, and equipoise can be maintained when a predefined level of supportive care is proposed, for participation in a clinical trial. PMID:27760875

  1. Simulation modelling as a tool to diagnose the complex networks of security systems

    NASA Astrophysics Data System (ADS)

    Iskhakov, S. Y.; Shelupanov, A. A.; Meshcheryakov, R. V.

    2017-01-01

    In the article, the questions of modelling of complex security system networks are considered. The simulation model of operation of similar complexes and approbation of the offered approach to identification of the incidents are presented. The approach is based on detection of uncharacteristic alterations of the network operation mode. The results of the experiment allow one to draw a conclusion on possibility of the offered model application to analyse the current status of heterogeneous security systems. Also, it is confirmed that the application of short-term forecasting methods for the analysis of monitoring system data allows one to automate the process of formation the criteria to reveal the incidents.

  2. [The logic of diagnoses used in expert systems. II. Applications in virology].

    PubMed

    Cristea, A; Zaharia, C N

    1988-01-01

    Inference capacity of different clinical or paraclinical examinations are analyzed, whose results allow to establish the definitive diagnosis through gradual integrations. The knowledge of the inference capacity is very useful for the expert systems applied in virology.

  3. A method for diagnosing time dependent faults using model-based reasoning systems

    NASA Technical Reports Server (NTRS)

    Goodrich, Charles H.

    1995-01-01

    This paper explores techniques to apply model-based reasoning to equipment and systems which exhibit dynamic behavior (that which changes as a function of time). The model-based system of interest is KATE-C (Knowledge based Autonomous Test Engineer) which is a C++ based system designed to perform monitoring and diagnosis of Space Shuttle electro-mechanical systems. Methods of model-based monitoring and diagnosis are well known and have been thoroughly explored by others. A short example is given which illustrates the principle of model-based reasoning and reveals some limitations of static, non-time-dependent simulation. This example is then extended to demonstrate representation of time-dependent behavior and testing of fault hypotheses in that environment.

  4. Sensor configuration and test for fault diagnoses of subway braking system based on signed digraph method

    NASA Astrophysics Data System (ADS)

    Zuo, Jianyong; Chen, Zhongkai

    2014-05-01

    Fault diagnosis of various systems on rolling stock has drawn the attention of many researchers. However, obtaining an optimized sensor set of these systems, which is a prerequisite for fault diagnosis, remains a major challenge. Available literature suggests that the configuration of sensors in these systems is presently dependent on the knowledge and engineering experiences of designers, which may lead to insufficient or redundant development of various sensors. In this paper, the optimization of sensor sets is addressed by using the signed digraph (SDG) method. The method is modified for use in braking systems by the introduction of an effect-function method to replace the traditional quantitative methods. Two criteria are adopted to evaluate the capability of the sensor sets, namely, observability and resolution. The sensors configuration method of braking system is proposed. It consists of generating bipartite graphs from SDG models and then solving the set cover problem using a greedy algorithm. To demonstrate the improvement, the sensor configuration of the HP2008 braking system is investigated and fault diagnosis on a test bench is performed. The test results show that SDG algorithm can improve single-fault resolution from 6 faults to 10 faults, and with additional four brake cylinder pressure (BCP) sensors it can cover up to 67 double faults which were not considered by traditional fault diagnosis system. SDG methods are suitable for reducing redundant sensors and that the sensor sets thereby obtained are capable of detecting typical faults, such as the failure of a release valve. This study investigates the formal extension of the SDG method to the sensor configuration of braking system, as well as the adaptation supported by the effect-function method.

  5. Image Analysis of Chlorophyll Fluorescence Transients for Diagnosing the Photosynthetic System of Attached Leaves

    PubMed Central

    Omasa, Kenji; Shimazaki, Ken-Ichiro; Aiga, Ichiro; Larcher, Walter; Onoe, Morio

    1987-01-01

    A new image instrumentation system for quantitative analysis of the rapid change in intensity of chlorophyll fluorescence during dark-light transition (CFI, chlorophyll fluorescence induction), which is a sensitive indicator of the various reactions of photosynthesis, was developed and its performance was evaluated. This system made it possible to resolve CFI at any small leaf area (about 1 square millimeter) of a whole leaf when the plant was illuminated by blue-green light at more than 50 micromoles photons per square meter per second. In order to test the usefulness of this system, we applied it to analyze the effect of SO2 on photosynthetic apparatus in attached sunflower leaves. Dynamic CFI imaging over the whole single leaf, where there was no visible injury, indicated not only the local changes in photosynthetic activity but also the site of inhibition in photosynthetic electron transport system in chloroplasts. The new instrumentation system will be useful for the analytical diagnosis of various stress-actions on plants in situ. Images Fig. 1 Fig. 5 Fig. 6 PMID:16665515

  6. A Respiratory Movement Monitoring System Using Fiber-Grating Vision Sensor for Diagnosing Sleep Apnea Syndrome

    NASA Astrophysics Data System (ADS)

    Takemura, Yasuhiro; Sato, Jun-Ya; Nakajima, Masato

    2005-01-01

    A non-restrictive and non-contact respiratory movement monitoring system that finds the boundary between chest and abdomen automatically and detects the vertical movement of each part of the body separately is proposed. The system uses a fiber-grating vision sensor technique and the boundary position detection is carried out by calculating the centers of gravity of upward moving and downward moving sampling points, respectively. In the experiment to evaluate the ability to detect the respiratory movement signals of each part and to discriminate between obstructive and central apneas, detected signals of the two parts and their total clearly showed the peculiarities of obstructive and central apnea. The cross talk between the two categories classified automatically according to several rules that reflect the peculiarities was ≤ 15%. This result is sufficient for discriminating central sleep apnea syndrome from obstructive sleep apnea syndrome and indicates that the system is promising as screening equipment. Society of Japan

  7. Spinal Muscular Atrophy (SMA)

    MedlinePlus

    ... children with SMA develop spinal deformities, such as scoliosis (sideways curvature of the spine) and kyphosis (front- ... Magnetic Resonance Imaging (MRI) Brain and Nervous System Scoliosis Contact Us Print Resources Send to a friend ...

  8. Using an Educational Electronic Documentation System to Help Nursing Students Accurately Identify Nursing Diagnoses

    ERIC Educational Resources Information Center

    Pobocik, Tamara J.

    2013-01-01

    The use of technology and electronic medical records in healthcare has exponentially increased. This quantitative research project used a pretest/posttest design, and reviewed how an educational electronic documentation system helped nursing students to identify the accurate related to statement of the nursing diagnosis for the patient in the case…

  9. The Accuracy of Expert-System Diagnoses of Mathematical Problem Solutions.

    ERIC Educational Resources Information Center

    Bennett, Randy Elliot; Sebrechts, Marc M.

    1996-01-01

    Four human judges agreed highly among themselves about the presence of errors committed by 60 adults solving algebra word problems, but were in less agreement about categorizing faults. An expert system agreed with judges about correctness of answers, but was in even less agreement about categorizing the faults. (SLD)

  10. Strategies to diagnose and control microbial souring in natural gas storage reservoirs and produced water systems

    SciTech Connect

    Morris, E.A.; Derr, R.M.; Pope, D.H.

    1995-12-31

    Hydrogen sulfide production (souring) in natural gas storage reservoirs and produced water systems is a safety and environmental problem that can lead to operational shutdown when local hydrogen sulfide standards are exceeded. Systems affected by microbial souring have historically been treated using biocides that target the general microbial community. However, requirements for more environmentally friendly solutions have led to treatment strategies in which sulfide production can be controlled with minimal impact to the system and environment. Some of these strategies are based on microbial and/or nutritional augmentation of the sour environment. Through research sponsored by the Gas Research Institute (GRI) in Chicago, Illinois, methods have been developed for early detection of microbial souring in natural gas storage reservoirs, and a variety of mitigation strategies have been evaluated. The effectiveness of traditional biocide treatment in gas storage reservoirs was shown to depend heavily on the methods by which the chemical is applied. An innovative strategy using nitrate was tested and proved ideal for produced water and wastewater systems. Another strategy using elemental iodine was effective for sulfide control in evaporation ponds and is currently being tested in microbially sour natural gas storage wells.

  11. Sensor placement for diagnosability in space-borne systems - A model-based reasoning approach

    NASA Technical Reports Server (NTRS)

    Chien, Steve; Doyle, Richard; Rouquette, Nicolas

    1992-01-01

    This paper presents an approach to evaluating sensor placements on the basis of how well they are able to discriminate between a given fault and normal operating modes and/or other fault modes. In this approach, a model of the system in both normal operations and fault modes is used to evaluate possible sensor placements upon the basis of three criteria. Discriminability measures how much of a divergence in expected sensor readings the two system modes can be expected to produce. Accuracy measures confidence in the particular model predictions. Timeliness measures how long after the fault occurrence the expected divergence will take place. These three metrics then can be used to form a recommendation for a sensor placement. This paper describes how these measures can be computed and illustrated these methods with a brief example.

  12. Diagnosing unknown aberrations in an adaptive optics system by use of phase diversity.

    PubMed

    Lee, D J; Welsh, B M; Roggemann, M C; Ellerbroek, B L

    1997-07-01

    We outline a novel method for estimating a fixed aberration that is in the image path but not in the wave-front-sensor (WFS) path of an adaptive optics (AO) imaging system. We accomplish this through a nontraditional application of the Gonsalves [Proc. SPIE 207, 32 (1997)] least-squares phase-diversity technique, using an ensemble of images and WFS data. The diversity phases required for this technique are provided by the temporal differences in WFS residual phase measurements for different members of the ensemble. We demonstrate the technique by using actual observations from an operational AO system exhibiting such an aberration. An estimate of this aberration was obtained by the proposed algorithm that agrees reasonably well with the observed point-spread function.

  13. Progressive Hemifacial Atrophy With Contralateral Uveitis: A Case Report

    PubMed Central

    Ayyildiz, Onder; Ayyildiz, Simel; Durukan, Ali Hakan; Sobaci, Gungor

    2015-01-01

    Introduction: Progressive hemifacial atrophy, known as Parry-Romberg syndrome (PRS), was first described by Parry in 1825. There is a progressive atrophy of facial tissues including skin, bones and muscles. Ophthalmic disorders are common and include keratitis, uveitis, cataract, ipsilateral enophthalmos, optic neuritis, retinal vasculitis and scleral melting. Case Presentation: We describe a patient with progressive hemifacial atrophy at right facial side who developed granulomatous uveitis and periferic retinal vasculitis in his left eye. We started topical and systemic steroid therapy. Uveitic reaction had regressed almost entirely after a 3-month steroid treatment. Conclusions: The individuals should have multidisciplinary approach for the variety of disorders to maintain the appropriate treatment for a better appearance of the patients. PMID:26473067

  14. The adult literacy evaluator: An intelligent computer-aided training system for diagnosing adult illiterates

    NASA Technical Reports Server (NTRS)

    Yaden, David B., Jr.

    1992-01-01

    An important part of NASA's mission involves the secondary application of its technologies in the public and private sectors. One current application being developed is The Adult Literacy Evaluator, a simulation-based diagnostic tool designed to assess the operant literacy abilities of adults having difficulties in learning to read and write. Using ICAT system technology in addition to speech recognition, closed-captioned television (CCTV), live video and other state-of-the art graphics and storage capabilities, this project attempts to overcome the negative effects of adult literacy assessment by allowing the client to interact with an intelligent computer system which simulates real-life literacy activities and materials and which measures literacy performance in the actual context of its use. The specific objectives of the project are as follows: (1) To develop a simulation-based diagnostic tool to assess adults' prior knowledge about reading and writing processes in actual contexts of application; (2) to provide a profile of readers' strengths and weaknesses; and (3) to suggest instructional strategies and materials which can be used as a beginning point for remediation. In the first and developmental phase of the project, descriptions of literacy events and environments are being written and functional literacy documents analyzed for their components. Examples of literacy events and situations being considered included interactions with environmental print (e.g., billboards, street signs, commercial marquees, storefront logos, etc.), functional literacy materials (e.g., newspapers, magazines, telephone books, bills, receipts, etc.) and employment related communication (i.e., job descriptions, application forms, technical manuals, memorandums, newsletters, etc.). Each of these situations and materials is being analyzed for its literacy requirements in terms of written display (i.e., knowledge of printed forms and conventions), meaning demands (i

  15. Validity of COPD diagnoses reported through nationwide health insurance systems in the People’s Republic of China

    PubMed Central

    Kurmi, Om P; Vaucher, Julien; Xiao, Dan; Holmes, Michael V; Guo, Yu; Davis, Kourtney J; Wang, Chen; Qin, Haiyan; Turnbull, Iain; Peng, Peng; Bian, Zheng; Clarke, Robert; Li, Liming; Chen, Yiping; Chen, Zhengming

    2016-01-01

    Background COPD is the fourth leading cause of death worldwide, with particularly high rates in the People’s Republic of China, even among never smokers. Large population-based cohort studies should allow for reliable assessment of the determinants of diseases, which is dependent on the quality of disease diagnoses. We assessed the validity of COPD diagnoses collected through electronic health records in the People’s Republic of China. Methods The CKB study recruited 0.5 million adults aged 30–79 years from ten diverse regions in the People’s Republic of China during the period 2004–2008. During 7 years of follow-up, 11,800 COPD cases were identified by linkage with mortality registries and the national health insurance system. We randomly selected ~10% of the reported COPD cases and then undertook an independent adjudication of retrieved hospital medical records in 1,069 cases. Results Overall, these 1,069 cases were accrued over a 9-year period (2004–2013) involving 153 hospitals across ten regions. A diagnosis of COPD was confirmed in 911 (85%) cases, corresponding to a positive predictive value of 85% (95% confidence interval [CI]: 83%–87%), even though spirometry testing was not widely used (14%) in routine hospital care. The positive predictive value for COPD did not vary significantly by hospital ranking or calendar period, but was higher in men than women (89% vs 79%), at age ≥70 years than in younger people (88%, 95% CI: 85%–91%), and when the cases were reported from both death registry and health insurance systems (97%, 95% CI: 94%–100%). Among the remaining cases, 87 (8.1%) had other respiratory diseases (chiefly pneumonia and asthma; n=85) and 71 (6.6%) cases showed no evidence of any respiratory disease on their clinical records. Conclusion In the People’s Republic of China, COPD diagnoses obtained from electronic health records are of good quality and suitable for large population-based studies and do not warrant systematic

  16. How to Diagnose and Classify Tattoo Complications in the Clinic: A System of Distinctive Patterns.

    PubMed

    Serup, Jørgen

    2017-01-01

    Tattoo complications represent a broad spectrum of clinical entities and disease mechanisms. Infections are known, but chronic inflammatory reactions have hitherto been inconsistently reported and given many interpretations and terms. A clinical classification system of distinct patterns with emphasis on inflammatory tattoo reactions is introduced. Allergic reactions prevalent in red tattoos and often associated with azo pigments are manifested as the 'plaque elevation', 'excessive hyperkeratosis', and 'ulceronecrotic' patterns. The allergen is a hapten. Nonallergic reactions prevalent in black tattoos and associated with carbon black are manifested as the 'papulonodular' pattern. Carbon black nanoparticles agglomerate in the dermis over time forming foreign bodies that elicit reactions. Many black tattoos even develop sarcoid granuloma, and the 'papulonodular' pattern is strongly associated with sarcoidosis affecting other organs. Tattoo complications include a large group of less frequent but nevertheless specific entities, i.e. irritant and toxic local events, photosensitivity, urticaria, eczematous rash due to soluble allergen, neurosensitivity and pain syndrome, lymphopathies, pigment diffusion or fan, scars, and other sequels of tattooing or tattoo removal. Keratoacanthoma occurs in tattoos. Carcinoma and melanoma are rare and occur by coincidence only. Different tattoo complications require different therapeutic approaches, and precise diagnosis is thus important as a key to therapy. The proposed new classification with characteristic patterns relies on simple tools, namely patient history, objective findings, and supplementary punch biopsy. By virtue of simplicity and broad access, these methods make the proposed classification widely applicable in clinics and hospitals. The system is reported to the 11th revision of the WHO diagnosis classification used as international standard.

  17. A Boolean Consistent Fuzzy Inference System for Diagnosing Diseases and Its Application for Determining Peritonitis Likelihood

    PubMed Central

    Dragović, Ivana; Turajlić, Nina; Pilčević, Dejan; Petrović, Bratislav; Radojević, Dragan

    2015-01-01

    Fuzzy inference systems (FIS) enable automated assessment and reasoning in a logically consistent manner akin to the way in which humans reason. However, since no conventional fuzzy set theory is in the Boolean frame, it is proposed that Boolean consistent fuzzy logic should be used in the evaluation of rules. The main distinction of this approach is that it requires the execution of a set of structural transformations before the actual values can be introduced, which can, in certain cases, lead to different results. While a Boolean consistent FIS could be used for establishing the diagnostic criteria for any given disease, in this paper it is applied for determining the likelihood of peritonitis, as the leading complication of peritoneal dialysis (PD). Given that patients could be located far away from healthcare institutions (as peritoneal dialysis is a form of home dialysis) the proposed Boolean consistent FIS would enable patients to easily estimate the likelihood of them having peritonitis (where a high likelihood would suggest that prompt treatment is indicated), when medical experts are not close at hand. PMID:27069500

  18. Muscle atrophy and metal-on-metal hip implants

    PubMed Central

    Berber, Reshid; Khoo, Michael; Cook, Erica; Guppy, Andrew; Hua, Jia; Miles, Jonathan; Carrington, Richard; Skinner, John; Hart, Alister

    2015-01-01

    Background and purpose Muscle atrophy is seen in patients with metal-on-metal (MOM) hip implants, probably because of inflammatory destruction of the musculo-tendon junction. However, like pseudotumors, it is unclear when atrophy occurs and whether it progresses with time. Our objective was to determine whether muscle atrophy associated with MOM hip implants progresses with time. Patients and methods We retrospectively reviewed 74 hips in 56 patients (32 of them women) using serial MRI. Median age was 59 (23–83) years. The median time post-implantation was 83 (35–142) months, and the median interval between scans was 11 months. Hip muscles were scored using the Pfirrmann system. The mean scores for muscle atrophy were compared between the first and second MRI scans. Blood cobalt and chromium concentrations were determined. Results The median blood cobalt was 6.84 (0.24–90) ppb and median chromium level was 4.42 (0.20–45) ppb. The median Oxford hip score was 34 (5–48). The change in the gluteus minimus mean atrophy score between first and second MRI was 0.12 (p = 0.002). Mean change in the gluteus medius posterior portion (unaffected by surgical approach) was 0.08 (p = 0.01) and mean change in the inferior portion was 0.10 (p = 0.05). Mean pseudotumor grade increased by 0.18 (p = 0.02). Interpretation Worsening muscle atrophy and worsening pseudotumor grade occur over a 1-year period in a substantial proportion of patients with MOM hip implants. Serial MRI helps to identify those patients who are at risk of developing worsening soft-tissue pathology. These patients should be considered for revision surgery before irreversible muscle destruction occurs. PMID:25588091

  19. Iris atrophy in sickle cell disease.

    PubMed Central

    Acheson, R W; Ford, S M; Maude, G H; Lyness, R W; Serjeant, G R

    1986-01-01

    Iris atrophy, of unknown origin and believed to be secondary to the vaso-occlusive process of sickle cell disease, has been observed in 25 eyes of 22 patients (two SS disease, 20 SC disease). The crude prevalence was highest in males with SC disease, in whom 14.7% of patients were affected. Iris atrophy was closely associated with proliferative sickle retinopathy in the same eye. Analysis of haematological indices failed to reveal any significant differences between patients with and without iris atrophy. The characteristics and distribution of iris atrophy are described as well as the histopathology in one 68-year-old male patient with SS disease. Images PMID:3718915

  20. Mobile telecare system for intensive insulin treatment and patient education. First applications for newly diagnosed type 1 diabetic patients.

    PubMed

    Ładyzyński, P; Wójcicki, J M; Krzymień, J; Foltyński, P; Migalska-Musiał, K; Tracz, M; Karnafel, W

    2006-11-01

    The aim of the work was to develop and to evaluate the clinical efficiency of a mobile telecare system implementing teleconsultations based on the continuous transmission of patient-collected data directly to the physician and to the clinic. The developed TeleMed system consists of the patients' and the diabetologist's mobile units, the diabetologist's clinic and home workstations and the clinical server. The evaluation of the system was performed on a group of 13 newly diagnosed type 1 diabetic patients, during a single-arm study with 3-days run-in period, including a one-day intensive educational program, and 3-week study period, when the intensive insulin treatment was conducted without visits of patients to the clinic. The MBG dropped from 7.2 +/- 1.7 mmol/L before the study to 6.1 +/- 1.0 mmol/L in the third week of the study (P = 0.02) and the J-index from 30.2+/-19.2 to 19.7+/-7.7 (P = 0.04). Hemoglobin A1c decreased from 11.8 +/- 3.3% to 8.6 +/- 1.2% (P = 0.0002) in one month. The total daily insulin dose declined from 39.9 +/- 8.5 U to 20.0 +/- 9.6 U (P = 0.000006). The number of hypoglycemia episodes per patient per day decreased by 66% (P = 0.08) and the number of hyperglycemia episodes was reduced by 47% (P < 0.0001). The TeleMed facilitates not only efficient realization of the intensive insulin treatment but also successful remote patient training and education. No formal patient satisfaction study was done. However, some of the findings indicate that the application of the developed system increases patient self-confidence and quality of life.

  1. Characterization of disuse skeletal muscle atrophy and the efficacy of a novel muscle atrophy countermeasure during spaceflight and simulated microgravity

    NASA Astrophysics Data System (ADS)

    Hanson, Andrea Marie

    Humans are an integral part of the engineered systems that will enable return to the Moon and eventually travel to Mars. Major advancements in countermeasure development addressing deleterious effects of microgravity and reduced gravity on the musculoskeletal system need to be made to ensure mission safety and success. The primary objectives of this dissertation are to advance the knowledge and understanding of skeletal muscle atrophy, and support development of novel countermeasures for disuse atrophy to enable healthy long-duration human spaceflight. Models simulating microgravity and actual spaceflight were used to examine the musculoskeletal adaptations during periods of unloading. Myostatin inhibition, a novel anti-atrophy drug therapy, and exercise were examined as a means of preventing and recovering from disuse atrophy. A combination of assays was used to quantify adaptation responses to unloading and examine efficacy of the countermeasures. Body and muscle masses were collected to analyze systemic changes due to treatments. Hindlimb strength and individual muscle forces were measured to demonstrate functional adaptations to treatments. Muscle fiber morphology and myosin heavy chain (MHC) expression was examined to identify adaptations at the cellular level. Protein synthesis signals insulin-like growth factor-1 (IGF-1), Akt, and p70s6 kinase; and the degradation signals Atrogin-1 and MuRF-1 were examined to identify adaptations at the molecular level that ultimately lead to muscle hypertrophy and atrophy. A time course study provided a thorough characterization of the adaptation of skeletal muscle during unloading in C57BL/6 mice, and baseline data for comparison to and evaluation of subsequent studies. Time points defining the on-set and endpoints of disuse muscle atrophy were identified to enable characterization of rapid vs. long-term responses of skeletal muscle to hindlimb suspension. Unloading-induced atrophy primarily resulted from increased protein

  2. Bone and Spinal Muscular Atrophy.

    PubMed

    Vai, Silvia; Bianchi, Maria Luisa; Moroni, Isabella; Mastella, Chiara; Broggi, Francesca; Morandi, Lucia; Arnoldi, Maria Teresa; Bussolino, Chiara; Baranello, Giovanni

    2015-10-01

    Spinal Muscular Atrophy (SMA) is an autosomal recessive neuromuscular disease, leading to progressive denervation atrophy in the involved skeletal muscles. Bone status has been poorly studied. We assessed bone metabolism, bone mineral density (BMD) and fractures in 30 children (age range 15-171 months) affected by SMA types 2 and 3. Eighteen children (60%) had higher than normal levels of CTx (bone resorption marker); 25-OH vitamin D was in the lower range of normal (below 20 ng/ml in 9 children and below 12 ng/ml in 2). Lumbar spine BMAD (bone mineral apparent density) Z-score was below -1.5 in 50% of children. According to clinical records, four children had sustained four peripheral fractures; on spine X-rays, we observed 9 previously undiagnosed vertebral fractures in 7 children. There was a significant inverse regression between PTH and 25-OH D levels, and a significant regression between BMC and BMAD values and the scores of motor-functional tests. Even if this study could not establish the pathogenesis of bone derangements in SMA, its main findings - reduced bone density, low 25OH vitamin D levels, increased bone resorption markers and asymptomatic vertebral fractures also in very young patients - strongly suggest that even young subjects affected by SMA should be considered at risk of osteopenia and even osteoporosis and fractures.

  3. Neuronal involvement in muscular atrophy.

    PubMed

    Cisterna, Bruno A; Cardozo, Christopher; Sáez, Juan C

    2014-01-01

    The innervation of skeletal myofibers exerts a crucial influence on the maintenance of muscle tone and normal operation. Consequently, denervated myofibers manifest atrophy, which is preceded by an increase in sarcolemma permeability. Recently, de novo expression of hemichannels (HCs) formed by connexins (Cxs) and other none selective channels, including P2X7 receptors (P2X7Rs), and transient receptor potential, sub-family V, member 2 (TRPV2) channels was demonstrated in denervated fast skeletal muscles. The denervation-induced atrophy was drastically reduced in denervated muscles deficient in Cxs 43 and 45. Nonetheless, the transduction mechanism by which the nerve represses the expression of the above mentioned non-selective channels remains unknown. The paracrine action of extracellular signaling molecules including ATP, neurotrophic factors (i.e., brain-derived neurotrophic factor (BDNF)), agrin/LDL receptor-related protein 4 (Lrp4)/muscle-specific receptor kinase (MuSK) and acetylcholine (Ach) are among the possible signals for repression for connexin expression. This review discusses the possible role of relevant factors in maintaining the normal functioning of fast skeletal muscles and suppression of connexin hemichannel expression.

  4. [Visual impairment in juvenile diabetes mellitus due to optic atrophy: Wolfram's syndrome].

    PubMed

    Immink, Annelies; Reeser, H Maarten; Brus, Frank

    2010-01-01

    Wolfram's syndrome is a rare neurodegenerative disorder, which usually first manifests itself around the age of 6 years. The diagnosis can be made based on the characteristics incorporated in the 'DIDMOAD' acronym: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. We present 2 boys, diagnosed with diabetes mellitus at the age of 5 and 4 years respectively. Both children developed optic atrophy over the years. These 2 cases illustrate that alongside diabetic retinopathy, possible syndromes, such as Wolfram's syndrome, should also be considered in children with diabetes mellitus and visual impairment.

  5. Assessment of bone mineral density and bone metabolism in young male adults recently diagnosed with systemic lupus erythematosus in China.

    PubMed

    Guo, Qinyue; Fan, Ping; Luo, Jing; Wu, Shufang; Sun, Hongzhi; He, Lan; Zhou, Bo

    2017-03-01

    Objective Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease. However, the exact mechanism underlying SLE-related osteopenia and osteoporosis in patients newly diagnosed with SLE remains unknown. Methods 60 male subjects with SLE aged 20-30 years were enrolled. Serum osteocalcin was examined as a marker of bone formation and type I collagen degradation products (β-crosslaps) as markers of bone resorption. Lumbar spine (L1-L4) and total hip bone mineral density (BMD) were determined by dual energy X-ray absorption (DXA). Results Among the 60 subjects with SLE at the time of diagnosis, the cohort showed a significant reduction of osteocalcin (12.62 ± 2.16 ng/mL), and serum β-crosslaps level (992.6 ± 162.6 pg/mL) was markedly elevated. Univariate correlation analyses revealed negative correlations between osteocalcin and SLEDAI, dsDNA antibody and β-crosslaps. A positive correlation was also observed between osteocalcin and C3, C4, 25-OH vitamin D, BMD L1-L4 and BMD total hip (see Table 3). Osteocalcin and β-crosslaps were strongly associated with SLE disease activity by multiple stepwise logistic regression analysis. Conclusion Osteocalcin was negatively associated with SLE disease activity, and β-crosslaps was positively associated with SLE disease activity, suggesting SLE disease activity itself directly contributed to the development of SLE-associated osteopenia and osteoporosis.

  6. RAIRS2 a new expert system for diagnosing tuberculosis with real-world tournament selection mechanism inside artificial immune recognition system.

    PubMed

    Saybani, Mahmoud Reza; Shamshirband, Shahaboddin; Golzari, Shahram; Wah, Teh Ying; Saeed, Aghabozorgi; Mat Kiah, Miss Laiha; Balas, Valentina Emilia

    2016-03-01

    Tuberculosis is a major global health problem that has been ranked as the second leading cause of death from an infectious disease worldwide, after the human immunodeficiency virus. Diagnosis based on cultured specimens is the reference standard; however, results take weeks to obtain. Slow and insensitive diagnostic methods hampered the global control of tuberculosis, and scientists are looking for early detection strategies, which remain the foundation of tuberculosis control. Consequently, there is a need to develop an expert system that helps medical professionals to accurately diagnose the disease. The objective of this study is to diagnose tuberculosis using a machine learning method. Artificial immune recognition system (AIRS) has been used successfully for diagnosing various diseases. However, little effort has been undertaken to improve its classification accuracy. In order to increase the classification accuracy, this study introduces a new hybrid system that incorporates real tournament selection mechanism into the AIRS. This mechanism is used to control the population size of the model and to overcome the existing selection pressure. Patient epacris reports obtained from the Pasteur laboratory in northern Iran were used as the benchmark data set. The sample consisted of 175 records, from which 114 (65 %) were positive for TB, and the remaining 61 (35 %) were negative. The classification performance was measured through tenfold cross-validation, root-mean-square error, sensitivity, and specificity. With an accuracy of 100 %, RMSE of 0, sensitivity of 100 %, and specificity of 100 %, the proposed method was able to successfully classify tuberculosis cases. In addition, the proposed method is comparable with top classifiers used in this research.

  7. Crustacean muscles: atrophy and regeneration during molting

    SciTech Connect

    Mykles, D.L.; Skinner, D.M.

    1981-01-01

    The ultrastructural basis of atrophy of claw closer muscle of the land crab and the organization of myofibrils and sacroplasmic reticulum during the hydrolysis of protein that occurs during proecdysis was examined. The changes that occur in contractile proteins during claw muscle atrophy and the involvement of Ca/sup 2 +/-dependent proteinases (CDP) in myofilament degradation were investigated. (ACR)

  8. Seronegative Intestinal Villous Atrophy: A Diagnostic Challenge

    PubMed Central

    Teixeira, Cristina; Ribeiro, Suzane; Trabulo, Daniel; Cardoso, Cláudia; Mangualde, João; Freire, Ricardo; Alves, Ana Luísa; Gamito, Élia; Cremers, Isabelle; Oliveira, Ana Paula

    2016-01-01

    Celiac disease is the most important cause of intestinal villous atrophy. Seronegative intestinal villous atrophy, including those that are nonresponsive to a gluten-free diet, is a diagnostic challenge. In these cases, before establishing the diagnosis of seronegative celiac disease, alternative etiologies of atrophic enteropathy should be considered. Recently, a new clinical entity responsible for seronegative villous atrophy was described—olmesartan-induced sprue-like enteropathy. Herein, we report two uncommon cases of atrophic enteropathy in patients with arterial hypertension under olmesartan, who presented with severe chronic diarrhea and significant involuntary weight loss. Further investigation revealed intestinal villous atrophy and intraepithelial lymphocytosis. Celiac disease and other causes of villous atrophy were ruled out. Drug-induced enteropathy was suspected and clinical improvement and histologic recovery were verified after olmesartan withdrawal. These cases highlight the importance for clinicians to maintain a high index of suspicion for olmesartan as a precipitant of sprue-like enteropathy. PMID:27803820

  9. Quantitative Raman characterization of cross-linked collagen thin films as a model system for diagnosing early osteoarthritis

    NASA Astrophysics Data System (ADS)

    Wang, Chao; Durney, Krista M.; Fomovsky, Gregory; Ateshian, Gerard A.; Vukelic, Sinisa

    2016-03-01

    The onset of osteoarthritis (OA)in articular cartilage is characterized by degradation of extracellular matrix (ECM). Specifically, breakage of cross-links between collagen fibrils in the articular cartilage leads to loss of structural integrity of the bulk tissue. Since there are no broadly accepted, non-invasive, label-free tools for diagnosing OA at its early stage, Raman spectroscopyis therefore proposed in this work as a novel, non-destructive diagnostic tool. In this study, collagen thin films were employed to act as a simplified model system of the cartilage collagen extracellular matrix. Cross-link formation was controlled via exposure to glutaraldehyde (GA), by varying exposure time and concentration levels, and Raman spectral information was collected to quantitatively characterize the cross-link assignments imparted to the collagen thin films during treatment. A novel, quantitative method was developed to analyze the Raman signal obtained from collagen thin films. Segments of Raman signal were decomposed and modeled as the sum of individual bands, providing an optimization function for subsequent curve fitting against experimental findings. Relative changes in the concentration of the GA-induced pyridinium cross-links were extracted from the model, as a function of the exposure to GA. Spatially resolved characterization enabled construction of spectral maps of the collagen thin films, which provided detailed information about the variation of cross-link formation at various locations on the specimen. Results showed that Raman spectral data correlate with glutaraldehyde treatment and therefore may be used as a proxy by which to measure loss of collagen cross-links in vivo. This study proposes a promising system of identifying onset of OA and may enable early intervention treatments that may serve to slow or prevent osteoarthritis progression.

  10. How Are Arrhythmias Diagnosed?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Are Arrhythmias Diagnosed? Arrhythmias can be hard to diagnose, especially the types ... symptoms every once in a while. Doctors diagnose arrhythmias based on medical and family histories, a physical ...

  11. Is hippocampal atrophy a future drug target?

    PubMed

    Dhikav, Vikas; Anand, Kuljeet Singh

    2007-01-01

    Hippocampus is the brain structure, vital for episodic and declarative memory. Atrophy of the human hippocampus is seen in a variety of psychiatric and neurological disorders e.g. recurrent depression, schizophrenia, bipolar disorder, post-traumatic stress disorder, epilepsy, head injury, and Alzheimer's disease (AD). Importantly, aging hippocampus also undergoes atrophy. In many instances, for example, AD, the atrophy precedes the development of symptoms while in others, there is a temporal relationship between atrophy and symptomatology. The presence of atrophied hippocampus is one of the most consistent features of many common psychiatric disorders. Several factors contribute to this atrophy. Stress is one of the most profound factors implicated and the mechanisms involve glucocorticoids, serotonin, excitatory amino acids etc. Hippocampal formation as a whole can undergo atrophy or its individual structural components e.g. apical dendrities can exhibit atrophy. Several drugs of unrelated classes have been shown to prevent atrophy indicating heterogenous manner in which hippocampal atrophy is produced. These include, tianeptine (affects structural plasticity in hippocampus and is an effective antidepressant); phenytoin (antiseizure and neuroprotective); fluoxetine (downregulates neurodegenerative enzyme and increases neuroprotective hippocampal S100 beta); lithium (neuroprotective and antiapoptotic); tricyclic antidepressants (increase hippocampal neurogenesis); antipsychotics (reduce hippocampal neuronal suppression); sodium valproate (increases neurogenesis) and mifepristone (antioxidant, neuroprotective and anti-glucocorticoid). Now the most important question is: to what extent does the hippocampal atrophy play a role in the genesis of symptoms of diseases or their progression? And if it does, can we achieve the same degree of prevention or reversal seen in experimental animals, in humans also. An even more important question is: whether the prevention of

  12. Early Warning Implementation Guide: "Using the Massachusetts Early Warning Indicator System (EWIS) and Local Data to Identify, Diagnose, Support, and Monitor Students in Grades 1-12"

    ERIC Educational Resources Information Center

    Massachusetts Department of Elementary and Secondary Education, 2014

    2014-01-01

    The purpose of this guide is to provide information on how to use early warning data, including the Massachusetts Early Warning Indicator System (EWIS), to identify, diagnose, support and monitor students in grades 1-12. It offers educators an overview of EWIS and how to effectively use these data in conjunction with local data by following a…

  13. CHOD/BVAM Chemotherapy and Whole-Brain Radiotherapy for Newly Diagnosed Primary Central Nervous System Lymphoma

    SciTech Connect

    Laack, Nadia N.; O'Neill, Brian Patrick; Ballman, Karla V.; O'Fallon, Judith Rich; Carrero, Xiomara W.; Kurtin, Paul J.; Scheithauer, Bernd W.; Brown, Paul D.; Habermann, Thomas M.; Colgan, Joseph P.; Gilbert, Mark R.; Hawkins, Roland B.; Morton, Roscoe F.; Windschitl, Harry E.; Fitch, Tom R.; Pajon, Eduardo R.

    2011-10-01

    Purpose: To assess the efficacy and toxicity of chemotherapy consisting of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and dexamethasone (CHOD) plus bis-chloronitrosourea (BCNU), cytosine arabinoside, and methotrexate (BVAM) followed by whole-brain irradiation (WBRT) for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients 70 years old and younger with newly diagnosed, biopsy-proven PCNSL received one cycle of CHOD followed by two cycles of BVAM. Patients then received WBRT, 30.6 Gy, if a complete response was evoked, or 50.4 Gy if the response was less than complete; both doses were given in 1.8-Gy daily fractions. The primary efficacy endpoint was 1-year survival. Results: Thirty-six patients (19 men, 17 women) enrolled between 1995 and 2000. Median age was 60.5 years (range, 34 to 69 years). Thirty (83%) patients had baseline Eastern Cooperative Oncology Group performance scores of 0 to 1. All 36 patients were eligible for survival and response evaluations. Median time to progression was 12.3 months, and median survival was 18.5 months. The percentages of patients alive at 1, 2, and 3 years were 64%, 36%, and 33%, respectively. The best response was complete response in 10 patients and immediate progression in 7 patients. Ten (28%) patients had at least one grade 3 or higher neurologic toxicity. Conclusions: This regimen did improve the survival of PCNSL patients but also caused substantial toxicity. The improvement in survival is less than that reported with high-dose methotrexate-based therapies.

  14. Recessive optic atrophy, sensorimotor neuropathy and cataract associated with novel compound heterozygous mutations in OPA1

    PubMed Central

    LEE, JINHO; JUNG, SUNG-CHUL; HONG, YOUNG BIN; YOO, JEONG HYUN; KOO, HEASOO; LEE, JA HYUN; HONG, HYUN DAE; KIM, SANG-BEOM; CHUNG, KI WHA; CHOI, BYUNG-OK

    2016-01-01

    Mutations in the optic atrophy 1 gene (OPA1) are associated with autosomal dominant optic atrophy and 20% of patients demonstrate extra-ocular manifestations. In addition to these autosomal dominant cases, only a few syndromic cases have been reported thus far with compound heterozygous OPA1 mutations, suggestive of either recessive or semi-dominant patterns of inheritance. The majority of these patients were diagnosed with Behr syndrome, characterized by optic atrophy, ataxia and peripheral neuropathy. The present study describes a 10-year-old boy with Behr syndrome presenting with early-onset severe optic atrophy, sensorimotor neuropathy, ataxia and congenital cataracts. He had optic atrophy and was declared legally blind at six years old. Electrophysiological, radiological, and histopathological findings were compatible with axonal sensorimotor polyneuropathy. At birth, he presented with a congenital cataract, which has not been previously described in patients with OPA1 mutations. Whole exome sequencing indicated a pair of novel compound heterozygous mutations: p.L620fs*13 (c.1857–1858delinsT) and p.R905Q (c.G2714A). Neither mutation was observed in controls (n=300), and thus, they were predicted to be pathogenic by multiple in silico analyses. The mutation sites were highly conserved throughout different vertebrate species. The patients parents did not have any ophthalmic or neurologic symptoms and the results of electrophysiological studies were normal, suggestive of an autosomal recessive pattern of inheritance. The present study identified novel compound heterozygous OPA1 mutations in a patient with recessive optic atrophy, sensorimotor neuropathy and congenital cataracts, indicating an expansion of the clinical spectrum of pathologies associated with OPA1 mutations. Thus, OPA1 gene screening is advisable in the workup of patients with recessive optic atrophy, particularly with Behr syndrome and cataracts. PMID:27150940

  15. Chronic spinal muscular atrophy of facioscapulohumeral type.

    PubMed Central

    Furukawa, T; Toyokura, Y

    1976-01-01

    Chronic spinal muscular atrophy of FSH type affecting a mother and her son and daughter is reported. The relevant literature is reviewed and the relation between this conditon and Kugelberg-Welander (K-W) disease is discussed. Chronic spinal muscular atrophy of FSH type is considered to be a different entity from the eponymous K-W disease. Each type of muscular dystrophy, e.g. limb-girdle, FSH, distal, ocular, or oculopharyngeal type, has its counterpart of nuclear origin. A classification of the chronic spinal muscular atrophies is suggested following the classification of muscular dystrophy. Images PMID:957378

  16. Cobalt triggers necrotic cell death and atrophy in skeletal C2C12 myotubes

    SciTech Connect

    Rovetta, Francesca; Stacchiotti, Alessandra; Faggi, Fiorella; Catalani, Simona; Apostoli, Pietro; Fanzani, Alessandro; Aleo, Maria Francesca

    2013-09-01

    Severe poisoning has recently been diagnosed in humans having hip implants composed of cobalt–chrome alloys due to the release of particulate wear debris on polyethylene and ceramic implants which stimulates macrophagic infiltration and destroys bone and soft tissue, leading to neurological, sensorial and muscular impairments. Consistent with this premise, in this study, we focused on the mechanisms underlying the toxicity of Co(II) ions on skeletal muscle using mouse skeletal C2C12 myotubes as an in vitro model. As detected using propidium iodide incorporation, increasing CoCl{sub 2} doses (from 5 to 200 μM) affected the viability of C2C12 myotubes, mainly by cell necrosis, which was attenuated by necrostatin-1, an inhibitor of the necroptotic branch of the death domain receptor signaling pathway. On the other hand, apoptosis was hardly detectable as supported by the lack of caspase-3 and -8 activation, the latter resulting in only faint activation after exposure to higher CoCl{sub 2} doses for prolonged time points. Furthermore, CoCl{sub 2} treatment resulted in atrophy of the C2C12 myotubes which was characterized by the increased expression of HSP25 and GRP94 stress proteins and other typical 'pro-atrophic molecular hallmarks, such as early activation of the NF-kB pathway and down-regulation of AKT phosphorylation, followed by the activation of the proteasome and autophagy systems. Overall, these results suggested that cobalt may impact skeletal muscle homeostasis as an inducer of cell necrosis and myofiber atrophy. - Highlights: • The effects of cobalt on muscle myofibers in vitro were investigated. • Cobalt treatment mainly causes cell necrosis in skeletal C2C12 myotubes. • Cobalt impacts the PI3K/AKT and NFkB pathways and induces cell stress markers. • Cobalt induces atrophy of C2C12 myotubes through the activation of proteasome and autophagy systems. • Co treatment triggers NF-kB and PI3K/AKT pathways in C2C12 myotubes.

  17. Pharmacological Inhibitors of the Proteosome in Atrophying Muscles

    NASA Technical Reports Server (NTRS)

    Goldberg, Alfred

    1999-01-01

    It is now clear that the marked loss of muscle mass that occurs with disuse, denervation or in many systemic diseases (cancer cachexia, sepsis, acidosis, various endocrine disorders) is due primarily to accelerated degradation of muscle proteins, especially myofibrillar components. Recent work primarily in Dr. Goldberg's laboratory had suggested that in these diverse conditions, the enhancement of muscle proteolysis results mainly from activation of the Ub-proteasome degradative pathway. In various experimental models of atrophy, rat muscles show a common series of changes indicative of activation of this pathway, including increases in MRNA for Ub and proteasome subunits, content of ubiquitinated proteins, and sensitivity to inhibitors of the proteasome. In order to understand the muscle atrophy seen in weightlessness, Dr. Goldberg's laboratory is collaborating with Dr. Baldwin in studies to define the changes in these parameters upon hind-limb suspension. Related experiments will explore the effects on this degradative system of exercise regimens and also of glucocorticoids, which are known to rise in space personnel and to promote muscle, especially in inactive muscles. The main goals will be: (A) to define the enzymatic changes leading to enhanced activity of the Ub-proteasome pathway in inactive muscles upon hind-limb suspension, and the effects on this system of exposure to glucocorticoids or exercise; and (B) to learn whether inhibitors of the Ub-proteasome pathway may be useful in retarding the excessive proteolysis in atrophying muscles. Using muscle extracts, Dr. Goldberg's group hopes to define the rate-limiting, enzymatic changes that lead to the accelerated Ub-conjugation and protein degradation. They have recently developed cell-free preparations from atrophying rat muscles, in which Ub-conjugation to muscle proteins is increased above control levels. Because these new preparations seem to reproduce the changes occurring in vivo, they will analyze in

  18. Acute onset of brain atrophy and dementia in a patient with small cell lung cancer: a case report.

    PubMed

    Asano, Michiko; Fujimoto, Nobukazu; Gemba, Kenichi; Wada, Sae; Ono, Katsuichiro; Ozaki, Shinji; Adachi, Yoshiaki; Yamamoto, Hiromichi; Kishimoto, Takumi

    2011-03-01

    A 59-year-old man who was diagnosed with small cell lung cancer (SCLC), achieved a complete response to the induction chemoradiotherapy and received prophylactic cranial irradiation (PCI) (25 Gy at 250 cGy per fraction) in October 2008. Three months later, he complained of anorexia, weight loss, fatigue, and short-term memory loss and developed dementia and systemic muscle weakness. Magnetic resonance imaging in April and July 2009 revealed the progression of the diffuse brain atrophy without evidence of the metastasis of SCLC. Paraneoplastic neurological syndrome was suspected because anti-Hu antibody was detected in his serum and cerebrospinal fluid, but the adverse effects of chemotherapy and/or radiotherapy were also suspected as the cause of his neurological disorder.

  19. Genetics Home Reference: dentatorubral-pallidoluysian atrophy

    MedlinePlus

    ... trinucleotide repeat often increases in size. Larger repeat expansions are usually associated with an earlier onset of ... pallidoluysian atrophy (DRPLA): close correlation of CAG repeat expansions with the wide spectrum of clinical presentations and ...

  20. Infraspinatus muscle atrophy from suprascapular nerve compression.

    PubMed

    Cordova, Christopher B; Owens, Brett D

    2014-02-01

    Muscle weakness without pain may signal a nerve compression injury. Because these injuries should be identified and treated early to prevent permanent muscle weakness and atrophy, providers should consider suprascapular nerve compression in patients with shoulder muscle weakness.

  1. Genetics Home Reference: spinal muscular atrophy

    MedlinePlus

    ... by a loss of specialized nerve cells, called motor neurons , in the spinal cord and the part ... the spinal cord ( the brainstem ). The loss of motor neurons leads to weakness and wasting ( atrophy ) of ...

  2. Hippocampal atrophy rates in Alzheimer disease

    PubMed Central

    Henneman, W J.P.; Sluimer, J D.; Barnes, J; van der Flier, W M.; Sluimer, I C.; Fox, N C.; Scheltens, P; Vrenken, H; Barkhof, F

    2009-01-01

    Objective: To investigate the added value of hippocampal atrophy rates over whole brain volume measurements on MRI in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and controls. Methods: We included 64 patients with AD (67 ± 9 years; F/M 38/26), 44 patients with MCI (71 ± 6 years; 21/23), and 34 controls (67 ± 9 years; 16/18). Two MR scans were performed (scan interval: 1.8 ± 0.7 years; 1.0 T), using a coronal three-dimensional T1-weighted gradient echo sequence. At follow-up, 3 controls and 23 patients with MCI had progressed to AD. Hippocampi were manually delineated at baseline. Hippocampal atrophy rates were calculated using regional, nonlinear fluid registration. Whole brain baseline volumes and atrophy rates were determined using automated segmentation and registration tools. Results: All MRI measures differed between groups (p < 0.005). For the distinction of MCI from controls, larger effect sizes of hippocampal measures were found compared to whole brain measures. Between MCI and AD, only whole brain atrophy rate differed significantly. Cox proportional hazards models (variables dichotomized by median) showed that within all patients without dementia, hippocampal baseline volume (hazard ratio [HR]: 5.7 [95% confidence interval: 1.5–22.2]), hippocampal atrophy rate (5.2 [1.9–14.3]), and whole brain atrophy rate (2.8 [1.1–7.2]) independently predicted progression to AD; the combination of low hippocampal volume and high atrophy rate yielded a HR of 61.1 (6.1–606.8). Within patients with MCI, only hippocampal baseline volume and atrophy rate predicted progression. Conclusion: Hippocampal measures, especially hippocampal atrophy rate, best discriminate mild cognitive impairment (MCI) from controls. Whole brain atrophy rate discriminates Alzheimer disease (AD) from MCI. Regional measures of hippocampal atrophy are the strongest predictors of progression to AD. GLOSSARY AD = Alzheimer disease; BET = brain

  3. Zika virus causes testicular atrophy

    PubMed Central

    Uraki, Ryuta; Hwang, Jesse; Jurado, Kellie Ann; Householder, Sarah; Yockey, Laura J.; Hastings, Andrew K.; Homer, Robert J.; Iwasaki, Akiko; Fikrig, Erol

    2017-01-01

    Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has recently been found to cause fetal infection and neonatal abnormalities, including microcephaly and neurological dysfunction. ZIKV persists in the semen months after the acute viremic phase in humans. To further understand the consequences of ZIKV persistence in males, we infected Ifnar1−/− mice via subcutaneous injection of a pathogenic but nonlethal ZIKV strain. ZIKV replication persists within the testes even after clearance from the blood, with interstitial, testosterone-producing Leydig cells supporting virus replication. We found high levels of viral RNA and antigen within the epididymal lumen, where sperm is stored, and within surrounding epithelial cells. Unexpectedly, at 21 days post-infection, the testes of the ZIKV-infected mice were significantly smaller compared to those of mock-infected mice, indicating progressive testicular atrophy. ZIKV infection caused a reduction in serum testosterone, suggesting that male fertility can be affected. Our findings have important implications for nonvector-borne vertical transmission, as well as long-term potential reproductive deficiencies, in ZIKV-infected males. PMID:28261663

  4. Zika virus causes testicular atrophy.

    PubMed

    Uraki, Ryuta; Hwang, Jesse; Jurado, Kellie Ann; Householder, Sarah; Yockey, Laura J; Hastings, Andrew K; Homer, Robert J; Iwasaki, Akiko; Fikrig, Erol

    2017-02-01

    Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has recently been found to cause fetal infection and neonatal abnormalities, including microcephaly and neurological dysfunction. ZIKV persists in the semen months after the acute viremic phase in humans. To further understand the consequences of ZIKV persistence in males, we infected Ifnar1(-/-) mice via subcutaneous injection of a pathogenic but nonlethal ZIKV strain. ZIKV replication persists within the testes even after clearance from the blood, with interstitial, testosterone-producing Leydig cells supporting virus replication. We found high levels of viral RNA and antigen within the epididymal lumen, where sperm is stored, and within surrounding epithelial cells. Unexpectedly, at 21 days post-infection, the testes of the ZIKV-infected mice were significantly smaller compared to those of mock-infected mice, indicating progressive testicular atrophy. ZIKV infection caused a reduction in serum testosterone, suggesting that male fertility can be affected. Our findings have important implications for nonvector-borne vertical transmission, as well as long-term potential reproductive deficiencies, in ZIKV-infected males.

  5. [Effectiveness of magnetotherapy in optic nerve atrophy. A preliminary study].

    PubMed

    Zobina, L V; Orlovskaia, L S; Sokov, S L; Sabaeva, G F; Kondé, L A; Iakovlev, A A

    1990-01-01

    Magnetotherapy effects on visual functions (vision acuity and field), on retinal bioelectric activity, on conductive vision system, and on intraocular circulation were studied in 88 patients (160 eyes) with optic nerve atrophy. A Soviet Polyus-1 low-frequency magnetotherapy apparatus was employed with magnetic induction of about 10 mT, exposure 7-10 min, 10-15 sessions per course. Vision acuity of patients with its low (below 0.04 diopters) values improved in 50 percent of cases. The number of patients with vision acuity of 0.2 diopters has increased from 46 before treatment to 75. Magnetotherapy improved ocular hemodynamics in patients with optic nerve atrophy, it reduced the time of stimulation conduction along the vision routes and stimulated the retinal ganglia cells. The maximal effect was achieved after 10 magnetotherapy sessions. A repeated course carried out in 6-8 months promoted a stabilization of the process.

  6. Proteomic and bioinformatic analyses of spinal cord injury-induced skeletal muscle atrophy in rats

    PubMed Central

    WEI, ZHI-JIAN; ZHOU, XIAN-HU; FAN, BAO-YOU; LIN, WEI; REN, YI-MING; FENG, SHI-QING

    2016-01-01

    Spinal cord injury (SCI) may result in skeletal muscle atrophy. Identifying diagnostic biomarkers and effective targets for treatment is an important challenge in clinical work. The aim of the present study is to elucidate potential biomarkers and therapeutic targets for SCI-induced muscle atrophy (SIMA) using proteomic and bioinformatic analyses. The protein samples from rat soleus muscle were collected at different time points following SCI injury and separated by two-dimensional gel electrophoresis and compared with the sham group. The identities of these protein spots were analyzed by mass spectrometry (MS). MS demonstrated that 20 proteins associated with muscle atrophy were differentially expressed. Bioinformatic analyses indicated that SIMA changed the expression of proteins associated with cellular, developmental, immune system and metabolic processes, biological adhesion and localization. The results of the present study may be beneficial in understanding the molecular mechanisms of SIMA and elucidating potential biomarkers and targets for the treatment of muscle atrophy. PMID:27177391

  7. Descriptive epidemiology of spinal muscular atrophy type I in Estonia.

    PubMed

    Vaidla, Eve; Talvik, Inga; Kulla, Andres; Kahre, Tiina; Hamarik, Malle; Napa, Aita; Metsvaht, Tuuli; Piirsoo, Andres; Talvik, Tiina

    2006-01-01

    Spinal muscular atrophy is the second most frequent autosomal-recessive disorder in Europeans. There are no published epidemiological data on SMA in Estonia and other Baltic countries. The aim of this study was to estimate the incidence of SMA I in Estonia. All patients with SMA I diagnosed between January 1994 and December 2003 were included in the study. The diagnosis was established on the basis of neurological evaluation, ENMG findings, molecular studies and muscle biopsy. PCR and restriction enzyme analysis was used to detect the homozygous deletion of the SMN1 gene. A total of 9 cases of SMA I were identified during this 10-year period. The incidence of SMA I in Estonia is 1 in 14,400 live births, which is similar to the result from Hungary but lower than average incidence in the world. Only one of the patients was female. Typical SMN1 gene deletion was found in all cases.

  8. How Is Sarcoidosis Diagnosed?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Is Sarcoidosis Diagnosed? Your doctor will diagnose sarcoidosis based on ... Content: NEXT >> Featured Video Living With and Managing Sarcoidosis 05/18/2011 This video—presented by the ...

  9. How Is Atherosclerosis Diagnosed?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Is Atherosclerosis Diagnosed? Your doctor will diagnose atherosclerosis based on ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  10. Regulation of muscle atrophy in aging and disease.

    PubMed

    Vinciguerra, Manlio; Musaro, Antonio; Rosenthal, Nadia

    2010-01-01

    Muscle aging is characterized by a decline in functional performance and restriction of adaptability, due to progressive loss of muscle tissue coupled with a decrease in strength and force output. Together with selective activation ofapoptotic pathways, a hallmark of age-related muscle loss or sarcopenia is the progressive incapacity of regeneration machinery to replace damaged muscle. These characteristics are shared by pathologies involving muscle wasting, such as muscular dystrophies or amyotrophic lateral sclerosis, cancer and AIDS, all characterized by alterations in metabolic and physiological parameters, progressive weakness in specific muscle groups. Modulation ofextracellular agonists, receptors, protein kinases, intermediate molecules, transcription factors and tissue-specific gene expression collectively compromise the functionality of skeletal muscle tissue, leading to muscle degeneration and persistent protein degradation through activation ofproteolytic systems, such as calpain, ubiquitin-proteasome and caspase. Additional decrements in muscle growth factors compromise skeletal muscle growth, differentiation, survival and regeneration. A better understanding of the mechanisms underlying the pathogenesis of muscle atrophy and wasting associated with different diseases has been the objective of numerous studies and represents an important first step for the development of therapeutic approaches. Among these, insulin-like growth factor-1 (IGF-1) has emerged as a growth factor with a remarkably wide range of actions and a tremendous potential as a therapeutic in attenuating the atrophy and frailty associated with muscle aging and diseases. In this chapter we provide an overview of current concepts in muscle atrophy, focusing specifically on the molecular basis of IGF-1 action and survey current gene and cell therapeutic approaches to rescue muscle atrophy in aging and disease.

  11. Masticatory muscles of mouse do not undergo atrophy in space

    PubMed Central

    Philippou, Anastassios; Minozzo, Fabio C.; Spinazzola, Janelle M.; Smith, Lucas R.; Lei, Hanqin; Rassier, Dilson E.; Barton, Elisabeth R.

    2015-01-01

    Muscle loading is important for maintaining muscle mass; when load is removed, atrophy is inevitable. However, in clinical situations such as critical care myopathy, masticatory muscles do not lose mass. Thus, their properties may be harnessed to preserve mass. We compared masticatory and appendicular muscles responses to microgravity, using mice aboard the space shuttle Space Transportation System-135. Age- and sex-matched controls remained on the ground. After 13 days of space flight, 1 masseter (MA) and tibialis anterior (TA) were frozen rapidly for biochemical and functional measurements, and the contralateral MA was processed for morphologic measurements. Flight TA muscles exhibited 20 ± 3% decreased muscle mass, 2-fold decreased phosphorylated (P)-Akt, and 4- to 12-fold increased atrogene expression. In contrast, MAs had no significant change in mass but a 3-fold increase in P-focal adhesion kinase, 1.5-fold increase in P-Akt, and 50–90% lower atrogene expression compared with limb muscles, which were unaltered in microgravity. Myofibril force measurements revealed that microgravity caused a 3-fold decrease in specific force and maximal shortening velocity in TA muscles. It is surprising that myofibril-specific force from both control and flight MAs were similar to flight TA muscles, yet power was compromised by 40% following flight. Continued loading in microgravity prevents atrophy, but masticatory muscles have a different set point that mimics disuse atrophy in the appendicular muscle.—Philippou, A., Minozzo, F. C., Spinazzola, J. M., Smith, L. R., Lei, H., Rassier, D. E., Barton, E. R. Masticatory muscles of mouse do not undergo atrophy in space. PMID:25795455

  12. Masticatory muscles of mouse do not undergo atrophy in space.

    PubMed

    Philippou, Anastassios; Minozzo, Fabio C; Spinazzola, Janelle M; Smith, Lucas R; Lei, Hanqin; Rassier, Dilson E; Barton, Elisabeth R

    2015-07-01

    Muscle loading is important for maintaining muscle mass; when load is removed, atrophy is inevitable. However, in clinical situations such as critical care myopathy, masticatory muscles do not lose mass. Thus, their properties may be harnessed to preserve mass. We compared masticatory and appendicular muscles responses to microgravity, using mice aboard the space shuttle Space Transportation System-135. Age- and sex-matched controls remained on the ground. After 13 days of space flight, 1 masseter (MA) and tibialis anterior (TA) were frozen rapidly for biochemical and functional measurements, and the contralateral MA was processed for morphologic measurements. Flight TA muscles exhibited 20 ± 3% decreased muscle mass, 2-fold decreased phosphorylated (P)-Akt, and 4- to 12-fold increased atrogene expression. In contrast, MAs had no significant change in mass but a 3-fold increase in P-focal adhesion kinase, 1.5-fold increase in P-Akt, and 50-90% lower atrogene expression compared with limb muscles, which were unaltered in microgravity. Myofibril force measurements revealed that microgravity caused a 3-fold decrease in specific force and maximal shortening velocity in TA muscles. It is surprising that myofibril-specific force from both control and flight MAs were similar to flight TA muscles, yet power was compromised by 40% following flight. Continued loading in microgravity prevents atrophy, but masticatory muscles have a different set point that mimics disuse atrophy in the appendicular muscle.

  13. Patterns of Brain Atrophy in Clinical Variants of Frontotemporal Lobar Degeneration

    PubMed Central

    Lu, Po H.; Mendez, Mario F.; Lee, Grace J.; Leow, Alex D.; Lee, Hyun-Woo; Shapira, Jill; Jimenez, Elvira; Boeve, Bradley B.; Caselli, Richard J.; Graff-Radford, Neill R.; Jack, Clifford R.; Kramer, Joel H.; Miller, Bruce L.; Bartzokis, George; Thompson, Paul M.; Knopman, David S.

    2013-01-01

    Background/Aims The clinical syndromes of frontotemporal lobar degeneration include behavioral variant frontotemporal dementia (bvFTD) and semantic (SV-PPA) and nonfluent variants (NF-PPA) of primary progressive aphasia. Using magnetic resonance imaging (MRI), tensor-based morphometry (TBM) was used to determine distinct patterns of atrophy between these three clinical groups. Methods Twenty-seven participants diagnosed with bvFTD, 16 with SV-PPA, and 19 with NF-PPA received baseline and follow-up MRI scans approximately 1 year apart. TBM was used to create three-dimensional Jacobian maps of local brain atrophy rates for individual subjects. Results Regional analyses were performed on the three-dimensional maps and direct comparisons between groups (corrected for multiple comparisons using permutation tests) revealed significantly greater frontal lobe and frontal white matter atrophy in the bvFTD relative to the SV-PPA group (p < 0.005). The SV-PPA subjects exhibited significantly greater atrophy than the bvFTD in the fusiform gyrus (p = 0.007). The NF-PPA group showed significantly more atrophy in the parietal lobes relative to both bvFTD and SV-PPA groups (p < 0.05). Percent volume change in ventromedial prefrontal cortex was significantly associated with baseline behavioral symptomatology. Conclusion The bvFTD, SV-PPA, and NF-PPA groups displayed distinct patterns of progressive atrophy over a 1-year period that correspond well to the behavioral disturbances characteristic of the clinical syndromes. More specifically, the bvFTD group showed significant white matter contraction and presence of behavioral symptoms at baseline predicted significant volume loss of the ventromedial prefrontal cortex. PMID:23306166

  14. The effects of Capn1 gene inactivation on skeletal muscle growth, development, and atrophy, and the compensatory role of other proteolytic systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Myofibrillar protein turnover is a key component of muscle growth and degeneration, requiring proteolytic enzymes to degrade the skeletal muscle proteins. The objective of this study was to investigate the role of the calpain proteolytic system in muscle growth development using µ-calpain knockout (...

  15. Testicular atrophy as a risk inguinal hernioplasty.

    PubMed

    Wantz, G E

    1982-04-01

    In my experience, the complication of testicular atrophy after primary hernioplasty occurred only in patients in whom a complete indirect inguinal hernia sac was dissected from the spermatic cord. Avoiding this dissection by leaving the distal part of the sac in place reduces the incidence of the complication. All patients with scrotal inguinal hernias and all patients with recurrent inguinal hernias should have the complications of ischemic orchitis and testicular atrophy explained to them in depth because of the litigious nature of some of the men in whom this condition occurs. Patients who had undergone two or more operations for inguinal hernia should give prior written permission for orchiectomy even though this procedure is rarely necessary. In these patients, the performance of preperitoneal inguinal hernioplasty will permit the surgeon to avoid dissecting previously mobilized spermatic cords and should reduce the incidence of testicular atrophy in men fearful of this complication.

  16. [Iridoschisis, a special form of iris atrophy].

    PubMed

    Agard, E; Malcles, A; El Chehab, H; Ract-Madoux, G; Swalduz, B; Aptel, F; Denis, P; Dot, C

    2013-04-01

    Iridoschisis is a rare degenerative disease characterized by the separation of the anterior iris stroma from the posterior layer. The anterior layer splits into strands, and the free ends float freely in the anterior chamber. We report the case of a 57-year-old man, in whom we incidentally discovered isolated unilateral iris atrophy. The patient had no history of the common causes of atrophy (herpes, pigment dispersion, ocular trauma, etc.). During follow-up, the atrophy gradually worsened, with an increase in the number and bilaterality of the lesions. Ultrasound biomicroscopy (UBM) and optical coherence tomography (OCT) of anterior chamber showed thinning of the anterior iris and cleavage of the iris into two layers, an imaging result which, to our knowledge, has not yet been reported in the literature. Familiarity with iridoschisis is important, due to its frequent association with glaucoma, so that appropriate screening can be carried out at the time of diagnosis and on follow-up.

  17. Differential induction of muscle atrophy pathways in two mouse models of spinal muscular atrophy

    PubMed Central

    Deguise, Marc-Olivier; Boyer, Justin G.; McFall, Emily R.; Yazdani, Armin; De Repentigny, Yves; Kothary, Rashmi

    2016-01-01

    Motor neuron loss and neurogenic atrophy are hallmarks of spinal muscular atrophy (SMA), a leading genetic cause of infant deaths. Previous studies have focused on deciphering disease pathogenesis in motor neurons. However, a systematic evaluation of atrophy pathways in muscles is lacking. Here, we show that these pathways are differentially activated depending on severity of disease in two different SMA model mice. Although proteasomal degradation is induced in skeletal muscle of both models, autophagosomal degradation is present only in Smn2B/− mice but not in the more severe Smn−/−; SMN2 mice. Expression of FoxO transcription factors, which regulate both proteasomal and autophagosomal degradation, is elevated in Smn2B/− muscle. Remarkably, administration of trichostatin A reversed all molecular changes associated with atrophy. Cardiac muscle also exhibits differential induction of atrophy between Smn2B/− and Smn−/−; SMN2 mice, albeit in the opposite direction to that of skeletal muscle. Altogether, our work highlights the importance of cautious analysis of different mouse models of SMA as distinct patterns of atrophy induction are at play depending on disease severity. We also revealed that one of the beneficial impacts of trichostatin A on SMA model mice is via attenuation of muscle atrophy through reduction of FoxO expression to normal levels. PMID:27349908

  18. Yersinia pseudotuberculosis infections in goats and other animals diagnosed at the California Animal Health and Food Safety Laboratory System: 1990-2012.

    PubMed

    Giannitti, Federico; Barr, Bradd C; Brito, Bárbara P; Uzal, Francisco A; Villanueva, Michelle; Anderson, Mark

    2014-01-01

    Yersinia pseudotuberculosis is a recognized zoonotic food-borne pathogen; however, little is known about the ecology and epidemiology of diseases caused by the bacterium in California. The objective of the current study was to contribute to the knowledge of the diseases caused by Y. pseudotuberculosis in goats, the animal species most frequently reported with clinical yersiniosis to the California Animal Health and Food Safety Laboratory System, to better understand the epidemiology of this disease. A 23-year retrospective study was conducted to characterize the syndromes caused by the bacterium in goats and their temporospatial distribution, and to determine the number of cases in other animal species. Yersinia pseudotuberculosis-associated disease was diagnosed in 42 goats from 21 counties, with a strong seasonality in winter and spring. Most cases (88%) were observed within particular years (1999, 2004-2006, 2010-2011). The most frequently diagnosed syndrome was enteritis and/or typhlocolitis (64.3%), followed by abscessation (14.3%), abortion (11.9%), conjunctivitis (4.75%), and hepatitis (4.75%). Among other animal species, 59 cases were diagnosed in non-poultry avian species and 33 in mammals other than goats.

  19. Progressive cerebral atrophy in neuromyelitis optica.

    PubMed

    Warabi, Yoko; Takahashi, Toshiyuki; Isozaki, Eiji

    2015-12-01

    We report two cases of neuromyelitis optica patients with progressive cerebral atrophy. The patients exhibited characteristic clinical features, including elderly onset, secondary progressive tetraparesis and cognitive impairment, abnormally elevated CSF protein and myelin basic protein levels, and extremely highly elevated serum anti-AQP-4 antibody titer. Because neuromyelitis optica pathology cannot switch from an inflammatory phase to the degenerative phase until the terminal phase, neuromyelitis optica rarely appears as a secondary progressive clinical course caused by axonal degeneration. However, severe intrathecal inflammation and massive destruction of neuroglia could cause a secondary progressive clinical course associated with cerebral atrophy in neuromyelitis optica patients.

  20. Posterior cortical atrophy: a brief review.

    PubMed

    Kirshner, Howard S; Lavin, Patrick J M

    2006-11-01

    Posterior cortical atrophy is a striking clinical syndrome in which a dementing illness begins with visual symptoms. Initially, the problem may seem to be loss of elementary vision, but over time the patient develops features of visual agnosia, topographical difficulty, optic ataxia, simultanagnosia, ocular apraxia (Balint's syndrome), alexia, acalculia, right-left confusion, and agraphia (Gerstmann's syndrome), and later a more generalized dementia. Occasional patients have visual hallucinations and signs of Parkinson's disease or Lewy body dementia. A number of different neuropathologic disorders are associated with posterior cortical atrophy.

  1. [Geographic atrophy imaging using fundus autofluorescence method].

    PubMed

    Dolar-Szczasny, Joanna; Święch-Zubilewicz, Anna; Mackiewicz, Jerzy

    2015-01-01

    Geographic atrophy is a manifestation of the advanced age-related macular degeneration and form of irreversible atrophy of retinal pigment epithelium and photoreceptor layer. Early detection of changes and the ability to evaluate disease progression accurately constitute a key problem in diagnosis and treatment planning. Fundus autofluorescence is a relatively new imaging method considered nowadays to be the best in diagnosis and observing the natural or treatment-altered course of disease. High resolution images showing the 3D distribution of retinal pigment epithelium autofluorescence as lipofuscin index can be obtained owing to the launch of the confocal scanning laser ophthalmoscope.

  2. Fasciculations masquerading as minipolymyoclonus in bulbospinal muscular atrophy

    PubMed Central

    Bhat, Sushanth; Ma, Wei; Kozochonok, Elena; Chokroverty, Sudhansu

    2015-01-01

    Minipolymyoclonus has been described in both anterior horn cell disorders and central nervous system degenerative conditions. While its etiology remains unclear and speculative, a central generator has been previously proposed. We describe a case of bulbospinal muscular atrophy (Kennedy's disease), where minipolymyoclonus-like movements corresponded to fasciculations in neurophysiological studies. Our novel finding suggests that the etiologies of minipolymyoclonus in central and peripheral nervous system disorders are distinct, despite outward clinical similarity. The term “minipolyfasciculations” may be more reflective of the underlying process causing minipolymyoclonus-like movements in lower motor neuron disorders. PMID:26019432

  3. Bilingualism as a contributor to cognitive reserve: evidence from brain atrophy in Alzheimer's disease.

    PubMed

    Schweizer, Tom A; Ware, Jenna; Fischer, Corinne E; Craik, Fergus I M; Bialystok, Ellen

    2012-09-01

    Much of the research on delaying the onset of symptoms of Alzheimer's disease (AD) has focused on pharmacotherapy, but environmental factors have also been acknowledged to play a significant role. Bilingualism may be one factor contributing to 'cognitive reserve' (CR) and therefore to a delay in symptom onset. If bilingualism is protective, then the brains of bilinguals should show greater atrophy in relevant areas, since their enhanced CR enables them to function at a higher level than would be predicted from their level of disease. We analyzed a number of linear measurements of brain atrophy from the computed tomography (CT) scans of monolingual and bilingual patients diagnosed with probable AD who were matched on level of cognitive performance and years of education. Bilingual patients with AD exhibited substantially greater amounts of brain atrophy than monolingual patients in areas traditionally used to distinguish AD patients from healthy controls, specifically, the radial width of the temporal horn and the temporal horn ratio. Other measures of brain atrophy were comparable for the two groups. Bilingualism appears to contribute to increased CR, thereby delaying the onset of AD and requiring the presence of greater amounts of neuropathology before the disease is manifest.

  4. Grey matter atrophy in patients suffering from multiple sclerosis.

    PubMed

    Kincses, Zsigmond Tamás; Tóth, Eszter; Bankó, Nóra; Veréb, Dániel; Szabó, Nikoletta; Csete, Gergő; Faragó, Péter; Király, András; Bencsik, Krisztina; Vécsei, László

    2014-09-30

    White matter lesions are defining characteristics of multiple sclerosis (MS), whereas grey matter involvement is a less recognised attribute. Recent investigations using dedicated imaging approaches have made it possible to depict cortical lesions. Additionally, grey matter atrophy may be estimated using various methods. Several studies have suggested that grey matter atrophy closely correlates to clinical disability. In this review we have collected information on grey matter atrophy in MS and the effect of disease modifying therapies upon brain atrophy.

  5. Anabolic Steroid Reversal of Denervation Atrophy

    DTIC Science & Technology

    2012-03-01

    10-1-0932 TITLE: Anabolic Steroid Reversal of Denervation Atrophy PRINCIPAL INVESTIGATOR: Dr. Jonathan E. Isaacs...certainly “denervation atrophy” plays a significant role. Anabolic steroids , which have been shown to cause hypertrophy of muscle fibers, increase net...of satellite cells to muscle fibers. In conclusion, there did not seem to be a functional benefit for anabolic steroid treatment following

  6. Inhibition of UCH-L1 in oligodendroglial cells results in microtubule stabilization and prevents α-synuclein aggregate formation by activating the autophagic pathway: implications for multiple system atrophy

    PubMed Central

    Pukaß, Katharina; Richter-Landsberg, Christiane

    2015-01-01

    α-Synuclein (α-syn) positive glial cytoplasmic inclusions (GCI) originating in oligodendrocytes (ODC) are a characteristic hallmark in multiple system atrophy (MSA). Their occurrence may be linked to a failure of the ubiquitin proteasome system (UPS) or the autophagic pathway. For proteasomal degradation, proteins need to be covalently modified by ubiquitin, and deubiquitinated by deubiquitinating enzymes (DUBs) before proteolytic degradation is performed. The DUB ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a component of the UPS, it is abundantly expressed in neuronal brain cells and has been connected to Parkinson’s disease (PD). It interacts with α-syn and tubulin. The present study was undertaken to investigate whether UCH-L1 is a constituent of ODC, the myelin forming cells of the CNS, and is associated with GCIs in MSA. Furthermore, LDN-57444 (LDN), a specific UCH-L1 inhibitor, was used to analyze its effects on cell morphology, microtubule (MT) organization and the proteolytic degradation system. Towards this an oligodendroglial cell line (OLN cells), stably transfected with α-syn or with α-syn and GFP-LC3, to monitor the autophagic flux, was used. The data show that UCH-L1 is expressed in ODC derived from the brains of newborn rats and colocalizes with α-syn in GCIs of MSA brain sections. LDN treatment had a direct impact on the MT network by affecting tubulin posttranslational modifications, i.e., acetylation and tyrosination. An increase in α-tubulin detyrosination was observed and detyrosinated MT were abundantly recruited to the cellular extensions. Furthermore, small α-syn aggregates, which are constitutively expressed in OLN cells overexpressing α-syn, were abolished, and LDN caused the upregulation of the autophagic pathway. Our data add to the knowledge that the UPS and the autophagy-lysosomal pathway are tightly balanced, and that UCH-L1 and its regulation may play a role in neurodegenerative diseases with oligodendroglia

  7. Progressive hemifacial atrophy. A natural history study.

    PubMed Central

    Miller, M T; Spencer, M A

    1995-01-01

    PURPOSE: To describe two very different natural history courses in 2 patients with hemifacial atrophy. Progressive hemifacial atrophy (Parry-Romberg syndrome, Romberg syndrome, PHA) is characterized by slowly progressive atrophy, frequently involving only one side of the face, primarily affecting the subcutaneous tissue and fat. The onset usually occurs during the first 2 decades of life. The cause and pathophysiology are unknown. Ophthalmic involvement is common, with progressive enophthalmos a frequent finding. Pupillary disturbances, heterochromia, uveitis, pigmentary disturbances of the ocular fundus, and restrictive strabismus have also been reported. Neurologic findings may be present, but the natural history and progression of ocular findings are often not described in the literature. METHODS: We studied the records and present findings of 2 patients with progressive hemifacial atrophy who were observed in our institution over a 10-year period. RESULTS: Both patients showed progression of ophthalmic findings, primarily on the affected side. One patient has had chronic uveitis with secondary cataract and glaucoma, in addition to retinal pigmentary changes. She also had a third-nerve paresis of the contralateral eye and mild seizure activity. The other patient had mild uveitis, some progression of unilateral retinal pigmentary changes, and a significant increase in hyperopia in the affected eye, in addition to hypotony at age 19 without a clear cause, but with secondary retinal and refractive changes. CONCLUSION: Ocular manifestations of progressive hemifacial atrophy are varied, but can progress from mild visual impairment to blindness. Images FIGURE 1 FIGURE 2 FIGURE 3A FIGURE 3B FIGURE 4 FIGURE 5 FIGURE 6 PMID:8719679

  8. Development of an e-learning system for teaching endoscopists how to diagnose early gastric cancer: basic principles for improving early detection.

    PubMed

    Yao, Kenshi; Uedo, Noriya; Muto, Manabu; Ishikawa, Hideki

    2017-03-01

    We developed an internet e-learning system in order to improve the ability of endoscopists to diagnose gastric cancer at an early stage. The efficacy of this system at expanding knowledge and providing invaluable experience regarding the endoscopic detection of early gastric cancer was demonstrated through an international multicenter randomized controlled trial. However, the contents of the system have not yet been fully described in the literature. Accordingly, we herein introduce the contents and their principles, which comprise three main subjects: technique, knowledge, and experience. Since all the e-learning contents and principles are based on conventional white-light endoscopy alone, which is commonly available throughout the world, they should provide a good reference point for any endoscopist who wishes to devise learning materials and guidelines for improving their own clinical practice.

  9. Characteristic Retinal Atrophy with Secondary “Inverse” Optic Atrophy Identifies Vigabatrin Toxicity in Children

    PubMed Central

    Buncic, J. Raymond; Westall, Carol A.; Panton, Carole M.; Munn, J. Robert; MacKeen, Leslie D.; Logan, William J.

    2013-01-01

    Objective To describe the clinical pattern of retinal atrophy in children caused by the anticonvulsant vigabatrin. Design An interventional case series report. Participants One hundred thirty-eight patients, mainly infants, were evaluated regularly for evidence of possible vigabatrin toxicity in the Eye and Neurology clinics at the Hospital for Sick Children, Toronto. Method Sequential clinical and electroretinographic (International Society for Clinical Electrophysiology of Vision standards) evaluations every 6 months. Main Outcome Measures Presence of recognizable retinal and optic atrophy in the presence of abnormal electroretinogram (ERG) and other clinical findings. Results Three children being treated for seizures with vigabatrin showed definite clinical findings of peripheral retinal nerve fiber layer atrophy, with relative sparing of the central or macular portion of the retina and relative nasal optic nerve atrophic changes. Some macular wrinkling was evident in 1 case. Progressive ERG changes showing decreased responses, especially the 30-Hz flicker response, supported the presence of decreased retinal function. Conclusions A recognizable and characteristic form of peripheral retinal atrophy and nasal or “inverse” optic disc atrophy can occur in a small number of children being treated with vigabatrin. The changes in superficial light reflexes of the retina in children facilitate the clinical recognition of nerve fiber layer atrophy. The macula is relatively spared, although superficial retinal light reflexes indicating wrinkling of the innermost retina suggest early macular toxicity as well. Because these changes are accompanied by electrophysiologic evidence of retinal dysfunction, discontinuation of vigabatrin should be strongly considered. PMID:15465561

  10. How Is Raynaud's Diagnosed?

    MedlinePlus

    ... diagnose primary Raynaud's (Raynaud's disease) or secondary Raynaud's (Raynaud's phenomenon) based on your medical history, a physical exam, and test results. Specialists Involved Primary care doctors and internists often diagnose and treat Raynaud's. If you have the disorder, you also may ...

  11. Challenges in diagnosing hepatic encephalopathy.

    PubMed

    Weissenborn, K

    2015-02-01

    The term "hepatic encephalopathy" (HE) covers the neuropsychiatric syndrome associated with acute, chronic and acute-on-chronic liver disease (CLD). This paper deals with clinical features and diagnosis of HE in patients with liver cirrhosis and portal hypertension or porto-systemic shunts. The possible impact of concomitant disorders and the cirrhosis underlying liver disease upon brain function is described emphasizing the need of a detailed diagnostic work up of every individual case before diagnosing HE. Currently used methods for diagnosing minimal or covert hepatic encephalopathy are compared with regard to their sensitivity and specificity for diagnosing HE against the background of a multitude of concomitant disorders and diseases that could contribute to brain dysfunction.

  12. Establishing a standardized therapeutic testing protocol for spinal muscular atrophy.

    PubMed

    Tsai, Li-Kai; Tsai, Ming-Shung; Lin, Tzer-Bin; Hwu, Wuh-Liang; Li, Hung

    2006-11-01

    Several mice models have been created for spinal muscular atrophy (SMA); however, there is still no standard preclinical testing system for the disease. We previously generated type III-specific SMA model mice, which might be suitable for use as a preclinical therapeutic testing system for SMA. To establish such a system and test its applicability, we first created a testing protocol and then applied it as a means to investigate the use of valproic acid (VPA) as a possible treatment for SMA. These SMA mice revealed tail/ear/foot deformity, muscle atrophy, poorer motor performances, smaller compound muscle action potential and lower spinal motoneuron density at the age of 9 to 12 months in comparison with age-matched wild-type littermate mice. In addition, VPA attenuates motoneuron death, increases spinal SMN protein level and partially normalizes motor function in SMA mice. These results suggest that the testing protocol developed here is well suited for use as a standardized preclinical therapeutic testing system for SMA.

  13. Sporadic Ataxia and Multiple System Atrophy (MSA)

    MedlinePlus

    ... cells in these particular brain sites: the inferior olive, the pons, and the cerebellum. This group of ... look for degenerative changes in the brainstem (inferior olive and pons) and cerebellum, often an EMG to ...

  14. Endoscopic atrophic classification before and after H. pylori eradication is closely associated with histological atrophy and intestinal metaplasia

    PubMed Central

    Kodama, Masaaki; Okimoto, Tadayoshi; Ogawa, Ryo; Mizukami, Kazuhiro; Murakami, Kazunari

    2015-01-01

    Background and study aims: The relationship between endoscopic atrophy classification (EAC) and histological gastric atrophy and intestinal metaplasia (IM) was examined before and after Helicobacter pylori (H. pylori) eradication in order to evaluate the usefulness of EAC for detecting the risk of gastric cancer following eradication. Patients and methods: A total of 230 patients (137 males, 93 females; mean age: 58.0 ± 11.8 y) with successful eradication were enrolled. EAC score was defined as follows: C0(none): 0, C1: 1, C2: 2, C3: 3, O1: 4, O2: 5, and O3(severe): 6. Histological atrophy and IM score (0 to 3) from the antrum and the corpus were evaluated with updated Sydney system for histological atrophy and IM. Results: The mean EAC scores were 3.46 before eradication and 3.20 after eradication (P = 0.026). The mean atrophy scores before and after eradication were 1.45 and 0.92 at the antrum (P < 0.001) and 0.50 and 0.07 at the corpus (P < 0.001), respectively. The mean IM scores before and after eradication were 0.55 and 0.47 at the antrum (P = 0.154), and 0.09 and 0.05 at the corpus (P = 0.096), respectively. The histological atrophy scores showed significant improvement after eradication, while IM showed no significant change. The Mantel-Haenszel test for trend indicated there was a significant correlation between EAC and histological atrophy and IM, except antral atrophy after eradication. Conclusions: EAC exhibited a significant correlation between histological atrophy and IM, and represents a noninvasive classification method. EAC may be beneficial in evaluating the risk of gastric cancer after H. pylori eradication. PMID:26357676

  15. Cervical Spinal Cord Atrophy Profile in Adult SMN1-Linked SMA

    PubMed Central

    El Mendili, Mohamed-Mounir; Lenglet, Timothée; Stojkovic, Tanya; Behin, Anthony; Guimarães-Costa, Raquel; Salachas, François; Meininger, Vincent; Bruneteau, Gaelle; Le Forestier, Nadine; Laforêt, Pascal; Lehéricy, Stéphane; Benali, Habib; Pradat, Pierre-François

    2016-01-01

    Purpose The mechanisms underlying the topography of motor deficits in spinal muscular atrophy (SMA) remain unknown. We investigated the profile of spinal cord atrophy (SCA) in SMN1-linked SMA, and its correlation with the topography of muscle weakness. Materials and Methods Eighteen SMN1-linked SMA patients type III/V and 18 age/gender-matched healthy volunteers were included. Patients were scored on manual muscle testing and functional scales. Spinal cord was imaged using 3T MRI system. Radial distance (RD) and cord cross-sectional area (CSA) measurements in SMA patients were compared to those in controls and correlated with strength and disability scores. Results CSA measurements revealed a significant cord atrophy gradient mainly located between C3 and C6 vertebral levels with a SCA rate ranging from 5.4% to 23% in SMA patients compared to controls. RD was significantly lower in SMA patients compared to controls in the anterior-posterior direction with a maximum along C4 and C5 vertebral levels (p-values < 10−5). There were no correlations between atrophy measurements, strength and disability scores. Conclusions Spinal cord atrophy in adult SMN1-linked SMA predominates in the segments innervating the proximal muscles. Additional factors such as neuromuscular junction or intrinsic skeletal muscle defects may play a role in more complex mechanisms underlying weakness in these patients. PMID:27089520

  16. Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma

    PubMed Central

    Agarwal, Rashmi; March, Daniel; Voigt, Clifford

    2016-01-01

    Skeletal muscle atrophy in cancer cachexia is mediated by the interaction between muscle stem cells and various tumor factors. Although Notch signaling has been known as a key regulator of both cancer development and muscle stem cell activity, the potential involvement of Notch signaling in cancer cachexia and concomitant muscle atrophy has yet to be elucidated. The murine K7M2 osteosarcoma cell line was used to generate an orthotopic model of sarcoma-associated cachexia, and the role of Notch signaling was evaluated. Skeletal muscle atrophy was observed in the sarcoma-bearing mice, and Notch signaling was highly active in both tumor tissues and the atrophic skeletal muscles. Systemic inhibition of Notch signaling reduced muscle atrophy. In vitro coculture of osteosarcoma cells with muscle-derived stem cells (MDSCs) isolated from normal mice resulted in decreased myogenic potential of MDSCs, while the application of Notch inhibitor was able to rescue this repressed myogenic potential. We further observed that Notch-activating factors reside in the exosomes of osteosarcoma cells, which activate Notch signaling in MDSCs and subsequently repress myogenesis. Our results revealed that signaling between tumor and muscle via the Notch pathway may play an important role in mediating the skeletal muscle atrophy seen in cancer cachexia. PMID:27378829

  17. [Two boys with non-progressive unilateral atrophy of the calf muscles].

    PubMed

    Sasaki, Masayuki; Oomi, Tsuyoshi; Segawa, Masami; Komaki, Hirofumi; Sugai, Kenji

    2006-11-01

    We report here two boys who presented with atrophy of the right calf muscle. The onset was insidious and the symptom was found in infancy in case 2. They were followed for more than 5 years and no progression was seen. No sensory disturbances or autonomic nervous system symptoms were observed. Although needle electric myograph and muscle biopsy findings showed a neurogenic pattern, no cause was confirmed. Recently, a new disease concept of "benign monomelic amyotrophy of lower limb" was established and this could be applied to these patients. This disorder is rare and it is seen in young adults. It is characterized by non-progressive unilateral calf muscle atrophy. There is almost no possibility that this disorder is a variant of spinal muscular atrophy. When a patient presents with unilateral calf muscle atrophy, the treatable causes of the atrophy, including spinal cord disorders or peripheral nerve disorders, should be excluded first. If a confirmed cause cannot be found, then there should be a careful follow-up of the patient, even if the symptoms are stable.

  18. Fibrosis, adipogenesis, and muscle atrophy in congenital muscular torticollis.

    PubMed

    Chen, Huan-Xiong; Tang, Sheng-Ping; Gao, Fu-Tang; Xu, Jiang-Long; Jiang, Xian-Ping; Cao, Juan; Fu, Gui-Bing; Sun, Ke; Liu, Shi-Zhe; Shi, Wei

    2014-11-01

    In the traditional view, muscle atrophy and interstitial fibrosis were regarded as the basic pathological features of congenital muscular torticollis (CMT). But in the ultrastructure study, the mesenchyme-like cells, myoblasts, myofibroblasts, and fibroblasts were found in the proliferation of interstitium of CMT. To investigate the characteristics of pathological features and the mechanisms of muscle atrophy in CMT, we retrospectively reviewed the medical records of 185 CMT patients from July 2009 to July 2011 in Shenzhen Children's Hospital in China and performed pathological studies. According to age, the 185 CMT patients were divided into 4 groups. All resected surgical specimens were processed for hematoxylin and eosin staining and Masson trichromic staining. Sudan III staining was used for frozen sections, whereas immunohistochemical staining for S-100, calpain-1, ubiquitin, and 20S proteasome was carried out on 40 CMT specimens. Eight adductor muscle specimens from 8 patients with development dysplasia of the hip were taken as control group in the immunohistochemical staining. By Masson trichromic staining, the differences in the percent area of fibrous tissue in each CMT groups were significant. In Sudan III staining and immunostaining for S-100, adipocyte hyperplasia was the pathological feature of CMT. Moreover, compared with controls, most atrophic muscle fibers in CMT specimens were found to show strong immunoreactivity for calpain-1, ubiquitin, and 20S proteasome. With increasing age, fibrosis peaked at both sides and it was low in middle age group. Adipocytes increased with age. The characteristics of pathological features in CMT are changeable with age. The calpain and the ubiquitin-proteasome system may play a role in muscle atrophy of CMT. In the CMT, adipogenesis, fibrogenesis, and myogenesis may be the results of mesenchyme-like cells in SCM (sternocleidomastoid muscle). In conclusion, the present study furthermore supports maldevelopment of the

  19. Disability, atrophy and cortical reorganization following spinal cord injury.

    PubMed

    Freund, Patrick; Weiskopf, Nikolaus; Ward, Nick S; Hutton, Chloe; Gall, Angela; Ciccarelli, Olga; Craggs, Michael; Friston, Karl; Thompson, Alan J

    2011-06-01

    , cortical atrophy of primary motor and sensory cortex, and cortical reorganization of the sensorimotor system. The degree of cortical reorganization is predicted by spinal atrophy and is associated with significant disability.

  20. Population and Service Characteristics of Youth with Schizophrenia-Spectrum Diagnoses in the Hawaii System of Care

    ERIC Educational Resources Information Center

    Schiffman, Jason; Daleiden, Eric L.

    2006-01-01

    Background: Population and service characteristics were compared for youth (age 0-18 years) with and without schizophrenia-spectrum disorders, who received public mental health services in Hawaii's comprehensive system of care between July 1, 2000 and June 30, 2001. Methods: Electronic records of youth with a diagnosis in the…

  1. An Integrative, Cognitive-Behavioral, Systemic Approach to Working with Students Diagnosed with Attention Deficit Hyperactive Disorder

    ERIC Educational Resources Information Center

    Shillingford, Margaret Ann; Lambie, Glenn W.; Walter, Sara Meghan

    2007-01-01

    Attention deficit hyperactive disorder (ADHD) is a prevalent diagnostic disorder for many students, which correlates with negative academic, social, and personal consequences. This article presents an integrative, cognitive-behavioral, systemic approach that offers behaviorally based interventions for professional school counselors to support…

  2. Diagnosing oceanic nutrient deficiency

    NASA Astrophysics Data System (ADS)

    Moore, C. Mark

    2016-11-01

    The supply of a range of nutrient elements to surface waters is an important driver of oceanic production and the subsequent linked cycling of the nutrients and carbon. Relative deficiencies of different nutrients with respect to biological requirements, within both surface and internal water masses, can be both a key indicator and driver of the potential for these nutrients to become limiting for the production of new organic material in the upper ocean. The availability of high-quality, full-depth and global-scale datasets on the concentrations of a wide range of both macro- and micro-nutrients produced through the international GEOTRACES programme provides the potential for estimation of multi-element deficiencies at unprecedented scales. Resultant coherent large-scale patterns in diagnosed deficiency can be linked to the interacting physical-chemical-biological processes which drive upper ocean nutrient biogeochemistry. Calculations of ranked deficiencies across multiple elements further highlight important remaining uncertainties in the stoichiometric plasticity of nutrient ratios within oceanic microbial systems and caveats with regards to linkages to upper ocean nutrient limitation. This article is part of the themed issue 'Biological and climatic impacts of ocean trace element chemistry'.

  3. How Is Neuroblastoma Diagnosed?

    MedlinePlus

    ... Neuroblastoma Early Detection, Diagnosis, and Staging How Is Neuroblastoma Diagnosed? Neuroblastomas are usually found when a child ... Ask Your Child’s Doctor About Neuroblastoma? More In Neuroblastoma About Neuroblastoma Causes, Risk Factors, and Prevention Early ...

  4. How Is Hemophilia Diagnosed?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Is Hemophilia Diagnosed? If you or your child appears to ... have bleeding problems. However, some people who have hemophilia have no recent family history of the disease. ...

  5. How Is Lymphocytopenia Diagnosed?

    MedlinePlus

    ... of lymphocytes—T cells, B cells, and natural killer cells. The test can help diagnose the underlying ... cause low levels of B cells or natural killer cells. Tests for Underlying Conditions Many diseases and ...

  6. A real-time expert system for control of an autonomous mobile robot and for diagnosing unexpected occurrences

    SciTech Connect

    Kammer, D.W.; de Saussure, G.; Weisbin, C.R.

    1986-01-01

    The use of an expert system for the control of an autonomous robot presents several attractive features: the explicitness and homogeneity of the knowledge representation facilitates explanation, verification and modification of the rules which determine the robot's behavior, and the domain of competence can be incrementally extended. However, real-time operation poses a number of challenges due to the dynamic nature of the data and the time constraints of dealing with a large data base. An implementation is discussed where a large commercial real-time expert system originally designed for industrial process diagnostics was adapted to the control of an autonomous mobile robot for planning, monitoring, and diagnosis of unexpected occurrences during a navigation task. Control has been successfully implemented for goal directed navigation in the presence of moving obstacles.

  7. Treatment of dyspareunia secondary to vulvovaginal atrophy.

    PubMed

    Fantasia, Heidi Collins

    2014-01-01

    Declining estrogen levels associated with menopause can result in vulvovaginal atrophy and some degree of dyspareunia for more than half of all women in menopause. In 2013, the U.S. Food and Drug Administration approved ospemifene, a nonhormonal oral medication for the treatment of dyspareunia in menopause. This article will provide an overview of ospemifene and its indications, side effects and implications for nurses.

  8. Progressive visual agnosia with posterior cortical atrophy.

    PubMed

    Mizuno, M; Sartori, G; Liccione, D; Battelli, L; Campo, R

    1996-05-01

    A patient of posterior cortical atrophy characterized by early signs of progressive visual agnosia documented by repeated neuropsychological tests, is reported. SPECT and MRI findings showed left unilateral parieto-occipital involvement in the earlier stage. A PET study executed eight months later showed bilateral parieto-occipital hypometabolism, but predominantly in the left hemisphere. This suggests that the degeneration may have developed asymmetrically, progressing from left unilateral to bilateral.

  9. Very severe spinal muscular atrophy (Type 0).

    PubMed

    Al Dakhoul, Suleiman

    2017-01-01

    This case report describes a rare phenotype of very severe spinal muscular atrophy (SMA) in a newborn who presented with reduced fetal movements in utero and significant respiratory distress at birth. The patient was homozygously deleted for exon 7 and exon 8 of the survival motor neuron gene 1. Very severe SMA should be considered in the differential diagnosis of respiratory distress at birth, and more research should be dedicated to investigate the genetic determinants of its widely variable phenotypes.

  10. Very severe spinal muscular atrophy (Type 0)

    PubMed Central

    Al Dakhoul, Suleiman

    2017-01-01

    This case report describes a rare phenotype of very severe spinal muscular atrophy (SMA) in a newborn who presented with reduced fetal movements in utero and significant respiratory distress at birth. The patient was homozygously deleted for exon 7 and exon 8 of the survival motor neuron gene 1. Very severe SMA should be considered in the differential diagnosis of respiratory distress at birth, and more research should be dedicated to investigate the genetic determinants of its widely variable phenotypes. PMID:28182029

  11. Role of calcium-dependent proteinase in molt-induced claw muscle atrophy

    SciTech Connect

    Mykles, D.L.; Skinner, D.M.

    1984-01-01

    The claw closer muscle of the Bermuda land crab Gecarcinus lateralis undergoes a sequential atrophy and restoration during each intermolt cycle. Muscle protein decreases 40% during proecdysis and is restored following ecdysis. Amino acid incorporation into protein of postecdysial muscle is five times greater than that in anecdysial muscle. Since the rates of protein synthesis in anecdysial and proecdysial muscle are the same it appears that proecdysial muscle atrophy is caused primarily by an increase in protein degradation. A calcium-dependent proteinase (CDP) active at neutral pH has been implicated in the nonlysosomal hydrolysis of myofibrillar proteins. We have examined the role of a CDP in atrophy of the claw closer muscle. The many similarities between crustacean and vertebrate CDPs have established this crustacean system as a simple and convenient model for the role of Ca/sup 2 +/-dependent proteolysis in myofibrillar protein turnover and its manifestation in the structure of the sarcomere. 16 references, 8 figures. (ACR)

  12. An Intelligent Computer-aided Training System (CAT) for Diagnosing Adult Illiterates: Integrating NASA Technology into Workplace Literacy

    NASA Technical Reports Server (NTRS)

    Yaden, David B., Jr.

    1991-01-01

    An important part of NASA's mission involves the secondary application of its technologies in the public and private sectors. One current application being developed is The Adult Literacy Evaluator, a simulation-based diagnostic tool designed to assess the operant literacy abilities of adults having difficulties in learning to read and write. Using Intelligent Computer-Aided Training (ICAT) system technology in addition to speech recognition, closed-captioned television (CCTV), live video and other state-of-the-art graphics and storage capabilities, this project attempts to overcome the negative effects of adult literacy assessment by allowing the client to interact with an intelligent computer system which simulates real-life literacy activities and materials and which measures literacy performance in the actual context of its use. The specific objectives of the project are as follows: (1) to develop a simulation-based diagnostic tool to assess adults' prior knowledge about reading and writing processes in actual contexts of application; (2) to provide a profile of readers' strengths and weaknesses; and (3) to suggest instructional strategies and materials which can be used as a beginning point for remediation. In the first and development phase of the project, descriptions of literacy events and environments are being written and functional literacy documents analyzed for their components. From these descriptions, scripts are being generated which define the interaction between the student, an on-screen guide and the simulated literacy environment.

  13. Alex's Lemonade Stand Foundation Infant and Childhood Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007-2011.

    PubMed

    Ostrom, Quinn T; de Blank, Peter M; Kruchko, Carol; Petersen, Claire M; Liao, Peter; Finlay, Jonathan L; Stearns, Duncan S; Wolff, Johannes E; Wolinsky, Yingli; Letterio, John J; Barnholtz-Sloan, Jill S

    2015-01-01

    The CBTRUS Statistical Report: Alex's Lemonade Stand Foundation Infant and Childhood Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007–2011 comprehensively describes the current population-based incidence of primary malignant and non-malignant brain and CNS tumors in children ages 0–14 years, collected and reported by central cancer registries covering approximately 99.8% of the United States population (for 2011 only, data were available for 50 out of 51 registries). Overall, brain and CNS tumors are the most common solid tumor, the most common cancer, and the most common cause of cancer death in infants and children 0–14 years. This report aims to serve as a useful resource for researchers, clinicians, patients, and families.

  14. Pertussis diagnoses among service members and other beneficiaries of the U.S. Military Health System, January 2005-June 2012.

    PubMed

    2012-08-01

    Pertussis ("whooping cough") is a highly infectious respiratory disease caused by the bacterium Bordetella pertussis. Individuals at highest risk are infants and unvaccinated children; however, there have been recent increases in incidence among adolescent and young adult populations in the United States. During the surveillance period, there were 476 confirmed and 3,073 probable cases of pertussis among U.S. military members and other beneficiaries of the U.S. Military Health System. Among service members there were 77 and 13 confirmed cases in active and reserve component members, respectively. In comparison, infants and children aged 15 years and younger accounted for over half of all confirmed cases (n=244). Several spatiotemporal clusters of pertussis among military healthcare beneficiaries were associated with outbreaks in adjacent non-military communities, particularly in five states (California, Texas, Florida, Washington, and New York); one cluster occurred in a military community in Okinawa, Japan.

  15. Cost analysis of nucleic acid amplification for diagnosing pulmonary tuberculosis, within the context of the Brazilian Unified Health Care System

    PubMed Central

    Pinto, Márcia; Entringer, Aline Piovezan; Steffen, Ricardo; Trajman, Anete

    2015-01-01

    ABSTRACT We estimated the costs of a molecular test for Mycobacterium tuberculosis and resistance to rifampin (Xpert MTB/RIF) and of smear microscopy, within the Brazilian Sistema Único de Saúde (SUS, Unified Health Care System). In SUS laboratories in the cities of Rio de Janeiro and Manaus, we performed activity-based costing and micro-costing. The mean unit costs for Xpert MTB/RIF and smear microscopy were R$35.57 and R$14.16, respectively. The major cost drivers for Xpert MTB/RIF and smear microscopy were consumables/reagents and staff, respectively. These results might facilitate future cost-effectiveness studies and inform the decision-making process regarding the expansion of Xpert MTB/RIF use in Brazil. PMID:26785963

  16. Diagnosing heel pain in adults.

    PubMed

    Aldridge, Tracy

    2004-07-15

    Heel pain is a common condition in adults that may cause significant discomfort and disability. A variety of soft tissue, osseous, and systemic disorders can cause heel pain. Narrowing the differential diagnosis begins with a history and physical examination of the lower extremity to pinpoint the anatomic origin of the heel pain. The most common cause of heel pain in adults is plantar fasciitis. Patients with plantar fasciitis report increased heel pain with their first steps in the morning or when they stand up after prolonged sitting. Tenderness at the calcaneal tuberosity usually is apparent on examination and is increased with passive dorsiflexion of the toes. Tendonitis also may cause heel pain. Achilles tendonitis is associated with posterior heel pain. Bursae adjacent to the Achilles tendon insertion may become inflamed and cause pain. Calcaneal stress fractures are more likely to occur in athletes who participate in sports that require running and jumping. Patients with plantar heel pain accompanied by tingling, burning, or numbness may have tarsal tunnel syndrome. Heel pad atrophy may present with diffuse plantar heel pain, especially in patients who are older and obese. Less common causes of heel pain, which should be considered when symptoms are prolonged or unexplained, include osteomyelitis, bony abnormalities (such as calcaneal stress fracture), or tumor. Heel pain rarely is a presenting symptom in patients with systemic illnesses, but the latter may be a factor in persons with bilateral heel pain, pain in other joints, or known inflammatory arthritis conditions.

  17. [Scleroderma with progressive facial hemiatrophy and atrophy of the other side of the body].

    PubMed

    Lapresle, J; Desi, M

    1982-01-01

    The authors report the case of a 28 year old woman suffering from a chronic polyarthritis with a linear sclerodermia and presenting a crossed atrophy involving the left side of the body and the right side of the face and neck. The polyarthritis began at age 6, with signs of systemic illness, resulting early in important joint disability and proceeding with exacerbations and remissions. From the onset of this polyarthritis the patient experienced in the left side of the body highly painful and frequent muscular cramps which became rarer with the occurrence and progression of atrophy on the same side. At age 15, the patient experienced similar cramps in the right face, followed by progressive right hemiatrophy. At age 28, examination showed crossed atrophy involving the left side of the body and the right side of the face, tongue and neck, associated in these territories with several atrophic plaques on the skin, circumscribed alopecia, as well as numerous joint sequella. The laboratory date yielded immunologic abnormalities. On the CT scan the brain was normal but the right facial hemiatrophy involving orbital region and pharynx was visible. On the muscular biopsy there were inflammatory changes in the atrophic territory. Skin biopsies were consistent with sclerodermia. Two clinical points should be emphasized. Firstly, the remarkably crossed topography of the atrophy: the upper limit of the left body atrophy corresponded with the lower limit of the right face and neck atrophy; secondly, the unusual features of the muscular cramps. The relationship between sclerodermic facial hemiatrophy and Parry Romberg syndrome are then discussed: the study of this case and the literature do not provide sufficient criteria to allow description of two separate entities. Finally, the pathogenesis of localized sclerodermia is considered; in this case the association with the immunologic abnormalities and chronic polyarthritis is in favor of the hypothesis of a systemic disorder.

  18. [Use of pulmonary function tests and biomarkers studies to diagnose and follow-up interstitial lung disease in systemic sclerosis].

    PubMed

    Hua-Huy, T; Rivière, S; Tiev, K P; Dinh-Xuan, A T

    2014-12-01

    Interstitial lung disease (ILD) is becoming one of the main causes of death of patients with systemic sclerosis (SSc). The prevalence of ILD associated with SSc (SSc-ILD) varies from 33% to 100% according to diagnostic methods. Clinical features such as dyspnea on exertion, dry cough, and chest pains are not specific and usually late-appearing, implying more specific tests in the diagnostic, prognosis, and follow-up of ILD in patients with SSc. High resolution thoracic CT scanner (HRCT) is more sensitive than chest X-ray in the detection of SSc-ILD. Pulmonary function tests (PFT) are non-invasive and periodically used to assess the impacts of SSc on respiratory function. Diagnostic values of bronchoalveolar lavage and histological examination on lung biopsy are controversial. However, these techniques are essential for studying cellular and molecular mechanisms underlying the pathophysiology of SSc-ILD. Several biomarkers such as surfactant-A (SP-A), -D (SP-D), mucin-like high molecular weight glycoprotein (KL-6), and chemokine CCL-18 have been implicated in SSc-PID. Serum levels of these proteins are correlated with the severity of SSc-ILD, as assessed by HRCT and/or PFT. Finally, alveolar concentration of exhaled nitric oxide can be used to screen SSc patients with high risk of deterioration of respiratory function, in whom immunosuppressant treatment could be useful in preventing the evolution to irreversible lung fibrosis.

  19. Longitudinal association between hippocampus atrophy and episodic-memory decline.

    PubMed

    Gorbach, Tetiana; Pudas, Sara; Lundquist, Anders; Orädd, Greger; Josefsson, Maria; Salami, Alireza; de Luna, Xavier; Nyberg, Lars

    2017-03-01

    There is marked variability in both onset and rate of episodic-memory decline in aging. Structural magnetic resonance imaging studies have revealed that the extent of age-related brain changes varies markedly across individuals. Past studies of whether regional atrophy accounts for episodic-memory decline in aging have yielded inconclusive findings. Here we related 15-year changes in episodic memory to 4-year changes in cortical and subcortical gray matter volume and in white-matter connectivity and lesions. In addition, changes in word fluency, fluid IQ (Block Design), and processing speed were estimated and related to structural brain changes. Significant negative change over time was observed for all cognitive and brain measures. A robust brain-cognition change-change association was observed for episodic-memory decline and atrophy in the hippocampus. This association was significant for older (65-80 years) but not middle-aged (55-60 years) participants and not sensitive to the assumption of ignorable attrition. Thus, these longitudinal findings highlight medial-temporal lobe system integrity as particularly crucial for maintaining episodic-memory functioning in older age.

  20. Pathogenesis and therapy of spinal and bulbar muscular atrophy (SBMA).

    PubMed

    Katsuno, Masahisa; Tanaka, Fumiaki; Adachi, Hiroaki; Banno, Haruhiko; Suzuki, Keisuke; Watanabe, Hirohisa; Sobue, Gen

    2012-12-01

    Spinal and bulbar muscular atrophy (SBMA) is a late-onset motor neuron disease characterized by slowly progressive muscle weakness and atrophy. During the last two decades, basic and clinical research has provided important insights into the disease phenotype and pathophysiology. The cause of SBMA is the expansion of a trinucleotide CAG repeat encoding a polyglutamine tract within the first exon of the androgen receptor (AR) gene. SBMA exclusively affects adult males, whereas females homozygous for the AR mutation do not manifest neurological symptoms. The ligand-dependent nuclear accumulation of the polyglutamine-expanded AR protein is central to the gender-specific pathogenesis of SBMA, although additional steps, e.g., DNA binding, inter-domain interactions, and post-translational modification of AR, modify toxicity. The interactions with co-regulators are another requisite for the toxic properties of the polyglutamine-expanded AR. It is also shown that the polyglutamine-expanded AR induces diverse molecular events, such as transcriptional dysregulation, axonal transport disruption, and mitochondrial dysfunction, which play causative roles in the neurodegeneration in SBMA. The pathogenic AR-induced myopathy also contributes to the non-cell autonomous degeneration of motor neurons. Pre-clinical studies using animal models show that the pathogenic AR-mediated neurodegeneration is suppressed by androgen inactivation, the efficacy of which has been tested in clinical trials. Pharmacological activation of cellular defense machineries, such as molecular chaperones, ubiquitin-proteasome system, and autophagy, also exerts neuroprotective effects in experimental models of SBMA.

  1. Spinal muscular atrophy: from tissue specificity to therapeutic strategies

    PubMed Central

    Iascone, Daniel M.; Lee, Justin C.

    2015-01-01

    Spinal muscular atrophy (SMA) is the most frequent genetic cause of death in infants and toddlers. All cases of spinal muscular atrophy result from reductions in levels of the survival motor neuron (SMN) protein, and so SMN upregulation is a focus of many preclinical and clinical studies. We examine four issues that may be important in planning for therapeutic success. First, neuromuscular phenotypes in the SMNΔ7 mouse model closely match those in human patients but peripheral disease manifestations differ, suggesting that endpoints other than mouse lifespan may be more useful in predicting clinical outcome. Second, SMN plays important roles in multiple central and peripheral cell types, not just motor neurons, and it remains unclear which of these cell types need to be targeted therapeutically. Third, should SMN-restoration therapy not be effective in all patients, blocking molecular changes downstream of SMN reduction may confer significant benefit, making it important to evaluate therapeutic targets other than SMN. Lastly, for patients whose disease progression is slowed, but who retain significant motor dysfunction, additional approaches used to enhance regeneration of the neuromuscular system may be of value. PMID:25705387

  2. Genetic inhibition of JNK3 ameliorates spinal muscular atrophy

    PubMed Central

    Genabai, Naresh K.; Ahmad, Saif; Zhang, Zhanying; Jiang, Xiaoting; Gabaldon, Cynthia A.; Gangwani, Laxman

    2015-01-01

    Mutation of the Survival Motor Neuron 1 (SMN1) gene causes spinal muscular atrophy (SMA), an autosomal recessive neurodegenerative disorder that occurs in early childhood. Degeneration of spinal motor neurons caused by SMN deficiency results in progressive muscle atrophy and death in SMA. The molecular mechanism underlying neurodegeneration in SMA is unknown. No treatment is available to prevent neurodegeneration and reduce the burden of illness in SMA. We report that the c-Jun NH2-terminal kinase (JNK) signaling pathway mediates neurodegeneration in SMA. The neuron-specific isoform JNK3 is required for neuron degeneration caused by SMN deficiency. JNK3 deficiency reduces degeneration of cultured neurons caused by low levels of SMN. Genetic inhibition of JNK pathway in vivo by Jnk3 knockout results in amelioration of SMA phenotype. JNK3 deficiency prevents the loss of spinal cord motor neurons, reduces muscle degeneration, improves muscle fiber thickness and muscle growth, improves motor function and overall growth and increases lifespan of mice with SMA that shows a systemic rescue of phenotype by a SMN-independent mechanism. JNK3 represents a potential (non-SMN) therapeutic target for the treatment of SMA. PMID:26423457

  3. PGC1-α over-expression prevents metabolic alterations and soleus muscle atrophy in hindlimb unloaded mice

    PubMed Central

    Cannavino, Jessica; Brocca, Lorenza; Sandri, Marco; Bottinelli, Roberto; Pellegrino, Maria Antonietta

    2014-01-01

    Prolonged skeletal muscle inactivity causes muscle fibre atrophy. Redox imbalance has been considered one of the major triggers of skeletal muscle disuse atrophy, but whether redox imbalance is actually the major cause or simply a consequence of muscle disuse remains of debate. Here we hypothesized that a metabolic stress mediated by PGC-1α down-regulation plays a major role in disuse atrophy. First we studied the adaptations of soleus to mice hindlimb unloading (HU) in the early phase of disuse (3 and 7 days of HU) with and without antioxidant treatment (trolox). HU caused a reduction in cross-sectional area, redox status alteration (NRF2, SOD1 and catalase up-regulation), and induction of the ubiquitin proteasome system (MuRF-1 and atrogin-1 mRNA up-regulation) and autophagy (Beclin1 and p62 mRNA up-regulation). Trolox completely prevented the induction of NRF2, SOD1 and catalase mRNAs, but not atrophy or induction of catabolic systems in unloaded muscles, suggesting that oxidative stress is not a major cause of disuse atrophy. HU mice showed a marked alteration of oxidative metabolism. PGC-1α and mitochondrial complexes were down-regulated and DRP1 was up-regulated. To define the link between mitochondrial dysfunction and disuse muscle atrophy we unloaded mice overexpressing PGC-1α. Transgenic PGC-1α animals did not show metabolic alteration during unloading, preserving muscle size through the reduction of autophagy and proteasome degradation. Our results indicate that mitochondrial dysfunction plays a major role in disuse atrophy and that compounds inducing PGC-1α expression could be useful to treat/prevent muscle atrophy. PMID:25128574

  4. Cutaneous linear atrophy following intralesional corticosteroid injection in the treatment of tendonitis.

    PubMed

    Cantürk, Ferhan; Cantürk, Tayyar; Aydin, Fatma; Karagöz, Filiz; Sentürk, Nilgün; Turanli, Ahmet Yaşar

    2004-03-01

    It is well-known that local and systemic side effects due to intralesional corticosteroid injections are common. We report the case of a 28-year-old woman with cutaneous linear atrophy along the abductor pollicis longus tendon, which appeared after an injection of intralesional corticosteroid in the treatment of de Quervain tendonitis.

  5. Evolution of geographic atrophy of the retinal pigment epithelium.

    PubMed

    Sarks, J P; Sarks, S H; Killingsworth, M C

    1988-01-01

    The aim of this study was to trace the evolution of geographic atrophy (GA) by clinical documentation and by clinico-morphological correlation in representative eyes. Geographic atrophy commonly commenced within a parafoveal band of incipient atrophy of varying width, characterised by semisolid drusen and a microreticular pigment pattern. Progression of atrophy mostly skirted fixation and visual acuity was a poor guide to the functional impact, an estimate of the percentage of fovea involved proving a more useful clinical parameter. The rate of progression slowed once GA had involved all the retina affected by incipient atrophy and the risk of choroidal neovascularization appeared to decline. An earlier histological classification of the evolution of GA is revised according to the ultrastructural findings. Membranous debris was not previously recognised and its contribution to the findings in incipient atrophy and to dot-like drusen is described.

  6. Differential sensitivity of oxidative and glycolytic muscles to hypoxia-induced muscle atrophy.

    PubMed

    de Theije, C C; Langen, R C J; Lamers, W H; Gosker, H R; Schols, A M W J; Köhler, S E

    2015-01-15

    Hypoxia as a consequence of acute and chronic respiratory disease has been associated with muscle atrophy. This study investigated the sensitivity of oxidative and glycolytic muscles to hypoxia-induced muscle atrophy. Male mice were exposed to 8% normobaric oxygen for up to 21 days. Oxidative soleus and glycolytic extensor digitorum longus (EDL) muscles were isolated, weighed, and assayed for expression profiles of the ubiquitin-proteasome system (UPS), the autophagy-lysosome pathway (ALP), and glucocorticoid receptor (GR) and hypoxia-inducible factor-1α (HIF1α) signaling. Fiber-type composition and the capillary network were investigated. Hypoxia-induced muscle atrophy was more prominent in the EDL than the soleus muscle. Although increased expression of HIF1α target genes showed that both muscle types sensed hypoxia, their adaptive responses differed. Atrophy consistently involved a hypoxia-specific effect (i.e., not attributable to a hypoxia-mediated reduction of food intake) in the EDL only. Hypoxia-specific activation of the UPS and ALP and increased expression of the glucocorticoid receptor (Gr) and its target genes were also mainly observed in the EDL. In the soleus, stimulation of gene expression of those pathways could be mimicked to a large extent by food restriction alone. Hypoxia increased the number of capillary contacts per fiber cross-sectional area in both muscles. In the EDL, this was due to type II fiber atrophy, whereas in the soleus the absolute number of capillary contacts increased. These responses represent two distinct modes to improve oxygen supply to muscle fibers, but may aggravate muscle atrophy in chronic obstructive pulmonary disease patients who have a predominance of type II fibers.

  7. Subacute brain atrophy after radiation therapy for malignant brain tumor

    SciTech Connect

    Asai, A.; Matsutani, M.; Kohno, T.; Nakamura, O.; Tanaka, H.; Fujimaki, T.; Funada, N.; Matsuda, T.; Nagata, K.; Takakura, K.

    1989-05-15

    Brain atrophy with mental and neurologic deterioration developing a few months after radiation therapy in patients without residual or recurrent brain tumors has been recognized. Two illustrative case reports of this pathologic entity are presented. Six autopsy cases with this entity including the two cases were reviewed neurologically, radiographically, and histopathologically. All patients presented progressive disturbances of mental status and consciousness, akinesia, and tremor-like involuntary movement. Computerized tomography (CT) demonstrated marked enlargement of the ventricles, moderate widening of the cortical sulci, and a moderately attenuated CT number for the white matter in all six patients. Four of the six patients had CSF drainage (ventriculoperitoneal shunt or continuous lumbar drainage), however, none of them improved. Histologic examination demonstrated swelling and loss of the myelin sheath in the white matter in all patients, and reactive astrocytosis in three of the six patients. Neither prominent neuronal loss in the cerebral cortex or basal ganglia, nor axonal loss in the white matter was generally identified. The blood vessels of the cerebral cortex and white matter were normal. Ependymal layer and the surrounding brain tissue were normal in all patients. These findings suggested that this pathologic condition results from demyelination secondary to direct neurotoxic effect of irradiation. The authors' previous report was reviewed and the differential diagnoses, the risk factors for this pathologic entity, and the indication for radiation therapy in aged patients with a malignant brain tumor are discussed.

  8. [A case of spinal muscular atrophy type 0 in Japan].

    PubMed

    Okamoto, Kentaro; Saito, Kayoko; Sato, Takatoshi; Ishigaki, Keiko; Funatsuka, Makoto; Osawa, Makiko

    2012-09-01

    The patient was a 2-month-old female infant born at 41 weeks and 2 days of gestation presenting multiple arthrogryposis, severe muscle hypotonia and respiratory distress with difficulty in feeding. She suffered from repeated complications with aspiration pneumonia. On admission to our hospital, she exhibited fasciculation and absence of deep tendon reflexes. Examination of the motor nerve conduction velocity (MCV) revealed no muscle contraction. Deletions of the SMN and NAIP genes were noted. Based on severe clinical course and disease development in utero, she was given a diagnosis of spinal muscular atrophy (SMA) type 0 (very severe type). Arthrogryposis and disappearance of MCV are exclusion criteria for SMA. However, the clinical course of the infant was very severe and included such exclusion items. Consequently, when an infant presents muscle hypotonia and respiratory distress, SMA must be considered as one of the differential diagnoses, even though arthrogryposis is an exclusion criterion for SMA. We discuss this case in relation to the few extant reports on SMA type 0 in Japanese infants in the literature.

  9. Hypospadias as a novel feature in spinal bulbar muscle atrophy.

    PubMed

    Nordenvall, Anna Skarin; Paucar, Martin; Almqvist, Catarina; Nordenström, Anna; Frisén, Louise; Nordenskjöld, Agneta

    2016-04-01

    Spinal and bulbar muscle atrophy (SBMA) is an X-linked neuromuscular disorder caused by CAG repeat expansions in the androgen receptor (AR) gene. The SBMA phenotype consists of slowly progressive neuromuscular symptoms and undermasculinization features as the result of malfunction of the AR. The latter mainly includes gynecomastia and infertility. Hypospadias is also a feature of undermasculinization with an underdeveloped urethra and penis; it has not been described as part of the SBMA phenotype but has been suggested to be associated with a prolonged CAG repeat in the AR gene. This study includes the first epidemiologic description of the co-occurrence of hypospadias and SBMA in subjects and their male relatives in Swedish population-based health registers, as well as an additional clinical case. One boy with severe hypospadias was screened for mutations in the AR gene and was found to have 42 CAG repeats in it, which is in the full range of mutations causing SBMA later in life. We also detected a maximum of four cases displaying the combination of SBMA and hypospadias in our national register databases. This is the third case report with hypospadias in association with CAG repeat expansions in the AR gene in the full range known to cause SBMA later in life. Our findings suggest that hypospadias may be an under diagnosed feature of the SBMA phenotype and we propose that neurologists working with SBMA further investigate and report the true prevalence of hypospadias among patients with SBMA.

  10. The thromboelastometric discrepancy between septic and trauma induced disseminated intravascular coagulation diagnosed by the scoring system from the Japanese association for acute medicine

    PubMed Central

    Koami, Hiroyuki; Sakamoto, Yuichiro; Sakurai, Ryota; Ohta, Miho; Imahase, Hisashi; Yahata, Mayuko; Umeka, Mitsuru; Miike, Toru; Nagashima, Futoshi; Iwamura, Takashi; Yamada, Kosuke Chris; Inoue, Satoshi

    2016-01-01

    Abstract The aim of this study is to evaluate the hematological differences between septic and traumatic disseminated intravascular coagulation (DIC) using the rotational thromboelastometry (ROTEM). This retrospective study includes all sepsis or severe trauma patients transported to our emergency department who underwent ROTEM from 2013 to 2014. All patients were divided into 2 groups based on the presence of DIC diagnosed by the Japanese Association for Acute Medicine (JAAM) DIC score. We statistically analyzed the demographics, clinical characteristics, laboratory data, ROTEM findings (EXTEM and FIBTEM), and outcome. Fifty-seven patients (30 sepsis and 27 severe trauma) were included in primary analysis. Sepsis cases were significantly older and had higher systemic inflammatory response syndrome (SIRS) scores, whereas there were no significant differences in other parameters including Acute Physiology and Chronic Health Evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score. Twenty-six patients (14 sepsis and 12 severe trauma) were diagnosed with DIC. The Septic DIC (S-DIC) group was significantly older and had higher DIC scores than the traumatic DIC (T-DIC) group. Hematologic examination revealed significantly higher CRP, fibrinogen, lower FDP, DD, and higher FDP/DD ratio were found in the S-DIC group in comparison with the T-DIC group. ROTEM findings showed that the A10, A20, and MCF in the FIBTEM test were significantly higher in the S-DIC group. However, no statistical differences were confirmed in the LI30, LI45, and ML in EXTEM test. The plasma fibrinogen level and fibrinogen based clot firmness in whole-blood test revealed statistical significance between septic and traumatic DIC patients. PMID:27495106

  11. How a Stroke Is Diagnosed

    MedlinePlus

    ... News About Neurology Image Library Search The Internet Stroke Center Patients & Families About Stroke Stroke Diagnosis Stroke ... Diagnosis » How a Stroke is Diagnosed How a Stroke is Diagnosed How a Stroke is Diagnosed Lab ...

  12. How Is Cardiogenic Shock Diagnosed?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Cardiogenic Shock Diagnosed? The first step in diagnosing cardiogenic shock ... is cardiogenic shock. Tests and Procedures To Diagnose Shock and Its Underlying Causes Blood Pressure Test Medical ...

  13. How Are Genetic Conditions Diagnosed?

    MedlinePlus

    ... Consultation How are genetic conditions diagnosed? How are genetic conditions diagnosed? A doctor may suspect a diagnosis ... and advocacy resources. For more information about diagnosing genetic conditions: Genetics Home Reference provides information about genetic ...

  14. Acceleration of hippocampal atrophy rates in asymptomatic amyloidosis.

    PubMed

    Andrews, K Abigail; Frost, Chris; Modat, Marc; Cardoso, M Jorge; Rowe, Chris C; Villemagne, Victor; Fox, Nick C; Ourselin, Sebastien; Schott, Jonathan M

    2016-03-01

    Increased rates of brain atrophy measured from serial magnetic resonance imaging precede symptom onset in Alzheimer's disease and may be useful outcome measures for prodromal clinical trials. Appropriate trial design requires a detailed understanding of the relationships between β-amyloid load and accumulation, and rate of brain change at this stage of the disease. Fifty-two healthy individuals (72.3 ± 6.9 years) from Australian Imaging, Biomarkers and Lifestyle Study of Aging had serial (0, 18 m, 36 m) magnetic resonance imaging, (0, 18 m) Pittsburgh compound B positron emission tomography, and clinical assessments. We calculated rates of whole brain and hippocampal atrophy, ventricular enlargement, amyloid accumulation, and cognitive decline. Over 3 years, rates of whole brain atrophy (p < 0.001), left and right hippocampal atrophy (p = 0.001, p = 0.023), and ventricular expansion (p < 0.001) were associated with baseline β-amyloid load. Whole brain atrophy rates were also independently associated with β-amyloid accumulation over the first 18 months (p = 0.003). Acceleration of left hippocampal atrophy rate was associated with baseline β-amyloid load across the cohort (p < 0.02). We provide evidence that rates of atrophy are associated with both baseline β-amyloid load and accumulation, and that there is presymptomatic, amyloid-mediated acceleration of hippocampal atrophy. Clinical trials using rate of hippocampal atrophy as an outcome measure should not assume linear decline in the presymptomatic phase.

  15. The Impact of Gastric Atrophy on the Incidence of Diabetes

    PubMed Central

    Yu, Tse-Ya; Wei, Jung-Nan; Kuo, Chun-Heng; Liou, Jyh-Ming; Lin, Mao-Shin; Shih, Shyang-Rong; Hua, Cyue-Huei; Hsein, Yenh-Chen; Hsu, Ya-Wen; Chuang, Lee-Ming; Lee, Mei-Kuei; Hsiao, Ching-Hsiang; Wu, Ming-Shiang; Li, Hung-Yuan

    2017-01-01

    Gastric atrophy results in lower plasma ghrelin, higher gastrin secretion, a change in gut microbiota, and altered dietary nutrient absorption, which may be associated with the incidence of diabetes. Helicobacter pylori (H. pylori) infection is a major cause of gastric atrophy and is associated with diabetes in some reports. Since there is no study which investigates the impact of gastric atrophy on diabetes, we conduct a prospective cohort study to examine the relationship between H. pylori infection, gastric atrophy, and incident diabetes. In this study, subjects with gastric atrophy had a lower risk of incident diabetes, compared to those without gastric atrophy. The extent of gastric atrophy, measured by serum pepsinogen (PG) I/II ratio, was correlated with age, H. pylori IgG titer, HOMA2-IR, and HOMA2%B. When gastric atrophy is more extensive, presented as a lower serum PG I/II ratio, the risk of incident diabetes is lower. On the other hand, there was no significant association between H. pylori infection and the incidence of diabetes. In conclusion, the presence and the extent of gastric atrophy, but not H. pylori infection, are associated with incident diabetes. Further studies are needed to investigate the detailed mechanisms and the potential applications of the findings to guide diabetes screening and treatment strategies. PMID:28045079

  16. CLADA: cortical longitudinal atrophy detection algorithm.

    PubMed

    Nakamura, Kunio; Fox, Robert; Fisher, Elizabeth

    2011-01-01

    Measurement of changes in brain cortical thickness is useful for the assessment of regional gray matter atrophy in neurodegenerative conditions. A new longitudinal method, called CLADA (cortical longitudinal atrophy detection algorithm), has been developed for the measurement of changes in cortical thickness in magnetic resonance images (MRI) acquired over time. CLADA creates a subject-specific cortical model which is longitudinally deformed to match images from individual time points. The algorithm was designed to work reliably for lower resolution images, such as the MRIs with 1×1×5 mm(3) voxels previously acquired for many clinical trials in multiple sclerosis (MS). CLADA was evaluated to determine reproducibility, accuracy, and sensitivity. Scan-rescan variability was 0.45% for images with 1mm(3) isotropic voxels and 0.77% for images with 1×1×5 mm(3) voxels. The mean absolute accuracy error was 0.43 mm, as determined by comparison of CLADA measurements to cortical thickness measured directly in post-mortem tissue. CLADA's sensitivity for correctly detecting at least 0.1mm change was 86% in a simulation study. A comparison to FreeSurfer showed good agreement (Pearson correlation=0.73 for global mean thickness). CLADA was also applied to MRIs acquired over 18 months in secondary progressive MS patients who were imaged at two different resolutions. Cortical thinning was detected in this group in both the lower and higher resolution images. CLADA detected a higher rate of cortical thinning in MS patients compared to healthy controls over 2 years. These results show that CLADA can be used for reliable measurement of cortical atrophy in longitudinal studies, even in lower resolution images.

  17. CLADA: Cortical Longitudinal Atrophy Detection Algorithm

    PubMed Central

    Nakamura, Kunio; Fox, Robert; Fisher, Elizabeth

    2010-01-01

    Measurement of changes in brain cortical thickness is useful for assessment of regional gray matter atrophy in neurodegenerative conditions. A new longitudinal method, called CLADA (cortical longitudinal atrophy detection algorithm), has been developed for measurement of changes in cortical thickness in magnetic resonance images (MRI) acquired over time. CLADA creates a subject-specific cortical model which is longitudinally deformed to match images from individual time points. The algorithm was designed to work reliably for lower-resolution images, such as the MRIs with 1×1×5mm3 voxels previously acquired for many clinical trials in multiple sclerosis (MS). CLADA was evaluated to determine reproducibility, accuracy, and sensitivity. Scan-rescan variability was 0.45% for images with 1mm3 isotropic voxels and 0.77% for images with 1×1×5 mm3 voxels. The mean absolute accuracy error was 0.43 mm, as determined by comparison of CLADA measurements to cortical thickness measured directly in post- mortem tissue. CLADA’s sensitivity for correctly detecting at least 0.1 mm change was 86% in a simulation study. A comparison to FreeSurfer showed good agreement (Pearson correlation = 0.73 for global mean thickness). CLADA was also applied to MRIs acquired over 18 months in secondary progressive MS patients who were imaged at two different resolutions. Cortical thinning was detected in this group in both the lower and higher resolution images. CLADA detected a higher rate of cortical thinning in MS patients compared to healthy controls over 2 years. These results show that CLADA can be used for reliable measurement of cortical atrophy in longitudinal studies, even in lower resolution images. PMID:20674750

  18. The Evolution of and Risk Factors for Neck Muscle Atrophy and Weakness in Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy: A Retrospective Study in an Endemic Area.

    PubMed

    Zhang, Lu-Lu; Mao, Yan-Ping; Zhou, Guan-Qun; Tang, Ling-Long; Qi, Zhen-Yu; Lin, Li; Yao, Ji-Jin; Ma, Jun; Lin, Ai-Hua; Sun, Ying

    2015-08-01

    The aim of this study was to investigate the evolution of sternocleidomastoid muscle (SCM) atrophy in nasopharyngeal carcinoma (NPC) patients following intensity-modulated radiotherapy (IMRT), and the relationship between SCM atrophy and neck weakness.Data were retrospectively analyzed from 223 biopsy-proven NPC patients with no distant metastasis who underwent IMRT with or without chemotherapy. The volume of SCM was measured on pretreatment magnetic resonance imaging (MRI), and MRIs were conducted 1, 2, and 3 years after the completion of IMRT. Change in SCM volume was calculated and classified using the late effects of normal tissues-subjective, objective, management, and analytic system. The grade of neck muscle weakness, classified by the Common Terminology Criteria for Adverse Events V 3.0, was measured 3 years after the completion of IMRT.The average SCM atrophy ratio was -10.97%, -18.65%, and -22.25% at 1, 2, and 3 years postirradiation, respectively. Multivariate analysis indicated N stage and the length of time after IMRT were independent prognostic variables. There were significant associations between the degree of SCM atrophy and neck weakness.Radical IMRT can cause significant SCM atrophy in NPC patients. A more advanced N stage was associated with more severe SCM atrophy, but no difference was observed between N2 and N3. SCM atrophy progresses over time during the 3 years following IMRT. Grade of SCM atrophy is significantly associated with neck weakness.

  19. The Evolution of and Risk Factors for Neck Muscle Atrophy and Weakness in Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy

    PubMed Central

    Zhang, Lu-Lu; Mao, Yan-Ping; Zhou, Guan-Qun; Tang, Ling-Long; Qi, Zhen-Yu; Lin, Li; Yao, Ji-Jin; Ma, Jun; Lin, Ai-Hua; Sun, Ying

    2015-01-01

    Abstract The aim of this study was to investigate the evolution of sternocleidomastoid muscle (SCM) atrophy in nasopharyngeal carcinoma (NPC) patients following intensity-modulated radiotherapy (IMRT), and the relationship between SCM atrophy and neck weakness. Data were retrospectively analyzed from 223 biopsy-proven NPC patients with no distant metastasis who underwent IMRT with or without chemotherapy. The volume of SCM was measured on pretreatment magnetic resonance imaging (MRI), and MRIs were conducted 1, 2, and 3 years after the completion of IMRT. Change in SCM volume was calculated and classified using the late effects of normal tissues–subjective, objective, management, and analytic system. The grade of neck muscle weakness, classified by the Common Terminology Criteria for Adverse Events V 3.0, was measured 3 years after the completion of IMRT. The average SCM atrophy ratio was −10.97%, −18.65%, and −22.25% at 1, 2, and 3 years postirradiation, respectively. Multivariate analysis indicated N stage and the length of time after IMRT were independent prognostic variables. There were significant associations between the degree of SCM atrophy and neck weakness. Radical IMRT can cause significant SCM atrophy in NPC patients. A more advanced N stage was associated with more severe SCM atrophy, but no difference was observed between N2 and N3. SCM atrophy progresses over time during the 3 years following IMRT. Grade of SCM atrophy is significantly associated with neck weakness. PMID:26252307

  20. Brain atrophy in picornavirus-infected FVB mice is dependent on the H-2D(b) class I molecule.

    PubMed

    Huseby Kelcher, April M; Atanga, Pascal A; Gamez, Jeffrey D; Cumba Garcia, Luz M; Teclaw, Stephanie J; Pavelko, Kevin D; Macura, Slobodan I; Johnson, Aaron J

    2017-02-10

    Brain atrophy is a common feature of numerous neurologic diseases in which the role of neuroinflammation remains ill-defined. In this study, we evaluated the contribution of major histocompatibility complex class I molecules to brain atrophy in Theiler's murine encephalomyelitis virus (TMEV)-infected transgenic FVB mice that express the D(b) class I molecule. FVB/D(b) and wild-type FVB mice were evaluated for changes in neuroinflammation, virus clearance, neuropathology, and development of brain atrophy via T2-weighted MRI and subsequent 3-dimensional volumetric analysis. Significant brain atrophy and hippocampal neuronal loss was observed in TMEV-infected FVB/D(b) mice, but not in wild-type FVB mice. Brain atrophy was observed at 1 mo postinfection and persisted through the 4-mo observation period. Of importance, virus-infected FVB/D(b) mice elicited a strong CD8 T-cell response toward the immunodominant D(b)-restricted TMEV-derived peptide, VP2121-130, and cleared TMEV from the CNS. In addition, immunofluorescence revealed CD8 T cells near virus-infected neurons; therefore, we hypothesize that class I restricted CD8 T-cell responses promote development of brain atrophy. This model provides an opportunity to analyze the contribution of immune cells to brain atrophy in a system where persistent virus infection and demyelination are not factors in long-term neuropathology.-Huseby Kelcher, A. M., Atanga, P. A., Gamez, J. D., Cumba Garcia, L. M., Teclaw, S. J., Pavelko, K. D., Macura, S. I., Johnson. A. J. Brain atrophy in picornavirus-infected FVB mice is dependent on the H-2D(b) class I molecule.

  1. Diagnosing Abiotic Degradation

    EPA Science Inventory

    The abiotic degradation of chlorinated solvents in ground water can be difficult to diagnose. Under current practice, most of the “evidence” is negative; specifically the apparent disappearance of chlorinated solvents with an accumulation of vinyl chloride, ethane, ethylene, or ...

  2. Newly Diagnosed: Older Adults

    MedlinePlus

    ... Children Newly Diagnosed: Older Adults Related Topics on AIDS.gov Aging with HIV/AIDS National HIV/AIDS ... an Emerging Challenge Last revised: 07/10/2015 AIDS.gov HIV/AIDS Basics • Federal Resources • Using New ...

  3. Cardiac atrophy after bed rest and spaceflight

    NASA Technical Reports Server (NTRS)

    Perhonen, M. A.; Franco, F.; Lane, L. D.; Buckey, J. C.; Blomqvist, C. G.; Zerwekh, J. E.; Peshock, R. M.; Weatherall, P. T.; Levine, B. D.

    2001-01-01

    Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1 g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity

  4. Spinal and Bulbar Muscular Atrophy Overview

    PubMed Central

    Fischbeck, Kenneth H.

    2016-01-01

    Spinal and bulbar muscular atrophy is an X-linked neuromuscular disease caused by an expanded repeat in the androgen receptor gene. The mutant protein is toxic to motor neurons and muscle. The toxicity is ligand-dependent and likely involves aberrant interaction of the mutant androgen receptor with other nuclear factors leading to transcriptional dysregulation. Various therapeutic strategies have been effective in transgenic animal models, and the challenge now is to translate these strategies into safe and effective treatment in patients. PMID:26547319

  5. Positron emission tomography in patients with clinically diagnosed Alzheimer's disease.

    PubMed Central

    McGeer, P L; Kamo, H; Harrop, R; Li, D K; Tuokko, H; McGeer, E G; Adam, M J; Ammann, W; Beattie, B L; Calne, D B

    1986-01-01

    Fourteen patients who had clinically diagnosed Alzheimer's disease with mild to severe dementia (mean age 69.1 years) were evaluated by calculation of local cerebral metabolic rate for glucose (LCMR-gl) based on uptake of 18F-2-fluoro-2-deoxyglucose (FDG) detected with positron emission tomography (PET). PET scanning showed that the patients had significantly lower LCMR-gl values than 11 age-matched neurologically normal volunteers (mean age 66.3 years). The differences were most marked in the temporal cortex, followed by the frontal, parietal and occipital cortex. In each case the LCMR-gl value was below the lowest control value in at least one cortical area and usually in several; the reduction in LCMR-gl and the number of regions involved in the patients increased with the severity of the dementia. Deficits noted in neuropsychologic testing generally correlated with those predicted from loss of regional cortical metabolism. The patients with Alzheimer's disease were also examined with magnetic resonance imaging, computed tomography or both; the degree of atrophy found showed only a poor correlation with the neuropsychologic deficit. Significant atrophy was also noted in some of the controls. A detailed analysis of LCMR-gl values in selected cerebral regions of various sizes refuted the hypothesis that the reduction in cortical glucose metabolism in Alzheimer's disease is due to the filling by metabolically inert cerebrospinal fluid of space created by tissue atrophy. Images Fig. 2 Fig. 3 Fig. 4 Fig. 7 Fig. 8 Fig. 9 PMID:3512063

  6. Effect of IR Laser on Myoblasts: Prospects of Application for Counteracting Microgravity-Induced Muscle Atrophy

    NASA Astrophysics Data System (ADS)

    Monici, Monica; Cialdai, Francesca; Romano, Giovanni; Corsetto, Paola Antonia; Rizzo, Angela Maria; Caselli, Anna; Ranaldi, Francesco

    2013-02-01

    Microgravity-induced muscle atrophy is a problem of utmost importance for the impact it may have on the health and performance of astronauts. Therefore, appropriate countermeasures are needed to prevent disuse atrophy and favour muscle recovery. Muscle atrophy is characterized by loss of muscle mass and strength, and a shift in substrate utilization from fat to glucose, that leads to a reduced metabolic efficiency and enhanced fatigability. Laser therapy is already used in physical medicine and rehabilitation to accelerate muscle recovery and in sports medicine to prevent damages produced by metabolic disturbances and inflammatory reactions after heavy exercise. The aim of the research we present was to get insights on possible benefits deriving from the application of an advanced infrared laser system to counteract deficits of muscle energy metabolism and stimulate the recovery of the hypotrophic tissue. The source used was a Multiwave Locked System (MLS) laser, which combines continuous and pulsed emissions at 808 nm and 905 nm, respectively. We studied the effect of MLS treatment on morphology and energy metabolism of C2C12 cells, a widely accepted myoblast model, previously exposed to microgravity conditions modelled by a Random Positioning Machine. The MLS laser treatment was able to restore basal levels of serine/threonine protein phosphatase activity and to counteract cytoskeletal alterations and increase in glycolytic enzymes activity that occurred following the exposure to modelled microgravity. In conclusion, the results provide interesting insights for the application of infrared laser in the treatment of muscle atrophy.

  7. Clinical significance of the mixing test in laboratory diagnoses of lupus anticoagulant: the fate of the mixing test in integrated lupus anticoagulant test systems.

    PubMed

    Hong, Sung Kuk; Hwang, Sang Mee; Kim, Ji-Eun; Kim, Hyun Kyung

    2012-12-01

    The mixing test is used to determine the presence of inhibitors in laboratory diagnoses of lupus anticoagulant. Updated international guidelines state that an integrated lupus anticoagulant test system does not require the mixing test; an appraisal of the mixing tests in integrated lupus anticoagulant test systems is, therefore, required. We investigated the clinical relevance of mixing tests by using the best cutoff value of the mixing test through thrombotic risk analysis. A retrospective analysis was performed on 525 specimens with positive screening tests by using two integrated lupus anticoagulant tests: diluted Russell's Viper venom (dRVVT) and silica clotting time. The diagnostic performance of two interpretation formulas (percentage correction, Rosner index) was assessed, and the thrombotic risk of a subgroup based on the mixing results was investigated. Finally, the thrombotic risk of lupus anticoagulant positivity based on the integrated lupus anticoagulant test system procedures was assessed for the appraisal of mixing test exclusion in integrated lupus anticoagulant test systems. The best cutoff values of mixing test interpretation methods based on dRVVT were as follows: 60.1% for percentage correction and 15.7 for Rosner index. There was no substantial difference in the thrombotic risk between percentage correction and the Rosner index. The mixing-positive group showed a higher lupus anticoagulant titer and higher thrombotic risk than the mixing-negative group. However, even the mixing-negative group carried a significant risk of thrombosis. Finally, lupus anticoagulant positivity determined by the updated two-step procedure (screening and confirmation tests) showed higher thrombotic risk than that determined by the traditional three-step procedure (screening, mixing, and confirmation tests). Although a positive mixing result can predict a high risk of thrombosis, negative mixing results are also associated with a substantial thrombotic risk. The

  8. Oats induced villous atrophy in coeliac disease

    PubMed Central

    Lundin, K E A; Nilsen, E M; Scott, H G; Løberg, E M; Gjøen, A; Bratlie, J; Skar, V; Mendez, E; Løvik, A; Kett, K

    2003-01-01

    The current trend is to allow coeliac disease (CD) patients to introduce oats to their gluten free diet. We sought further data from the clinical setting with regards to oats consumption by coeliac patients. Several oat products were tested for wheat contamination using a commercial enzyme linked immunoassay (ELISA) kit, and six samples were examined by an ELISA using a cocktail of monoclonal antibodies, mass spectrometry, and western blot analysis. Nineteen adult CD patients on a gluten free diet were challenged with 50 g of oats per day for 12 weeks. Serological testing and gastroduodenoscopy was performed before and after the challenge. Biopsies were scored histologically and levels of mRNA specific for interferon γ were determined by reverse transcription-polymerase chain reaction analysis. Oats were well tolerated by most patients but several reported initial abdominal discomfort and bloating. One of the patients developed partial villous atrophy and a rash during the first oats challenge. She subsequently improved on an oats free diet but developed subtotal villous atrophy and dramatic dermatitis during a second challenge. Five of the patients showed positive levels of interferon γ mRNA after challenge. Some concerns therefore remain with respect to the safety of oats for coeliacs. PMID:14570737

  9. Bringing CLARITY to Gray Matter Atrophy

    PubMed Central

    Spence, Rory D.; Kurth, Florian; Itoh, Noriko; Mongerson, Chandler R.L.; Wailes, Shannon H.; Peng, Mavis S.; MacKenzie-Graham, Allan J.

    2015-01-01

    Gray matter atrophy has been shown to be a strong correlate to clinical disability in multiple sclerosis (MS) and its most commonly used animal model, experimental autoimmune encephalomyelitis (EAE). However, the relationship between gray mater atrophy and the spinal cord pathology often observed in EAE has never been established. Here EAE was induced in Thy1.1-YFP mice and their brains imaged using in vivo magnetic resonance imaging (MRI). The brains and spinal cords were subsequently optically cleared using Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging-compatible Tissue-hYdrogel (CLARITY). Axons were followed 5 mm longitudinally in three dimensions in intact spinal cords revealing that 61% of the axons exhibited a mean of 22 axonal ovoids and 8% of the axons terminating in axonal end bulbs. In the cerebral cortex, we observed a decrease in the mean number of layer V pyramidal neurons and a decrease in the mean length of the apical dendrites of the remaining neurons, compared to healthy controls. MRI analysis demonstrated decreased cortical volumes in EAE. Cross-modality correlations revealed a direct relationship between cortical volume loss and axonal end bulb number in the spinal cord, but not ovoid number. This is the first report of the use of CLARITY in an animal model of disease and the first report of the use of both CLARITY and MRI. PMID:25038439

  10. Oats induced villous atrophy in coeliac disease.

    PubMed

    Lundin, K E A; Nilsen, E M; Scott, H G; Løberg, E M; Gjøen, A; Bratlie, J; Skar, V; Mendez, E; Løvik, A; Kett, K

    2003-11-01

    The current trend is to allow coeliac disease (CD) patients to introduce oats to their gluten free diet. We sought further data from the clinical setting with regards to oats consumption by coeliac patients. Several oat products were tested for wheat contamination using a commercial enzyme linked immunoassay (ELISA) kit, and six samples were examined by an ELISA using a cocktail of monoclonal antibodies, mass spectrometry, and western blot analysis. Nineteen adult CD patients on a gluten free diet were challenged with 50 g of oats per day for 12 weeks. Serological testing and gastroduodenoscopy was performed before and after the challenge. Biopsies were scored histologically and levels of mRNA specific for interferon gamma were determined by reverse transcription-polymerase chain reaction analysis. Oats were well tolerated by most patients but several reported initial abdominal discomfort and bloating. One of the patients developed partial villous atrophy and a rash during the first oats challenge. She subsequently improved on an oats free diet but developed subtotal villous atrophy and dramatic dermatitis during a second challenge. Five of the patients showed positive levels of interferon gamma mRNA after challenge. Some concerns therefore remain with respect to the safety of oats for coeliacs.

  11. Effects of muscle atrophy on motor control

    NASA Technical Reports Server (NTRS)

    Stuart, D. G.

    1985-01-01

    As a biological tissue, muscle adapts to the demands of usage. One traditional way of assessing the extent of this adaptation has been to examine the effects of an altered-activity protocol on the physiological properties of muscles. However, in order to accurately interpret the changes associated with an activity pattern, it is necessary to employ an appropriate control model. A substantial literature exists which reports altered-use effects by comparing experimental observations with those from animals raised in small laboratory cages. Some evidence suggests that small-cage-reared animals actually represent a model of reduced use. For example, laboratory animals subjected to limited physical activity have shown resistance to insulin-induced glucose uptake which can be altered by exercise training. This project concerned itself with the basic mechanisms underlying muscle atrophy. Specifically, the project addressed the issue of the appropriateness of rats raised in conventional-sized cages as experimental models to examine this phenomenon. The project hypothesis was that rats raised in small cages are inappropriate models for the study of muscle atrophy. The experimental protocol involved: 1) raising two populations of rats, one group in conventional (small)-sized cages and the other group in a much larger (133x) cage, from weanling age (21 days) through to young adulthood (125 days); 2) comparison of size- and force-related characteristics of selected test muscles in an acute terminal paradigm.

  12. [Case of anti-TPO/gliadin antibody-positive cerebellar atrophy that responded to intravenous immunoglobulin therapy begun 16 years after onset].

    PubMed

    Tanaka, Nobuyuki; Otake, Hiroaki; Ito, Suguru; Niiyama, Kazuhide; Nanri, Kazunori

    2012-01-01

    We present a case of slowly progressive gait ataxia with a 16-year history in an 87-year-old woman. In 1994 she became aware of a slight unsteadiness while walking and cortical cerebellar atrophy was diagnosed. She had no familial history of neurological disorders. In 2007, idiopathic thrombocytopenic purpura (ITP) was diagnosed. The symptoms gradually worsened, and she was admitted in 2010 because she could not walk without support. MRI voxel-based morphometry (VBM) imaging showed atrophy of the entire cerebellum, and SPECT using eZIS showed reduced perfusion in the same regions. Her blood was positive for both anti-TPO antibody (42 IU/ml) and anti-gliadin antibody (20.2 EU). We therefore diagnosed autoimmune cerebellar atrophy. The patient showed a positive response to intravenous immunoglobulins (IVIg) and regained the ability to walk unassisted. Her posture and gait disturbance scores on the International Cooperative Ataxia Rating Scale had improved from 20 to 9. Even 16 years after onset, intravenous immunoglobulins were effective. In cases of prolonged disease, immunotherapy can be effective in autoimmune cerebellar atrophy and should not be excluded from the treatment choices.

  13. Diagnosing Deep Venous Thrombosis

    PubMed Central

    Doyle, D. Lynn

    1992-01-01

    Patients often present with unexplained lower limb pain and swelling. It is important to exclude deep venous thrombosis in the diagnosis because of the threat of sudden death. Simple clinical diagnosis is unacceptable, and noninvasive tests should be used initially. Serial testing detects proximal extension of isolated calf thrombi. Multiple diagnostic modalities are employed to diagnose a new deep venous thrombosis in patients with postphlebitic syndrome. PMID:21221369

  14. A new algorithm to diagnose atrial ectopic origin from multi lead ECG systems--insights from 3D virtual human atria and torso.

    PubMed

    Alday, Erick A Perez; Colman, Michael A; Langley, Philip; Butters, Timothy D; Higham, Jonathan; Workman, Antony J; Hancox, Jules C; Zhang, Henggui

    2015-01-01

    Rapid atrial arrhythmias such as atrial fibrillation (AF) predispose to ventricular arrhythmias, sudden cardiac death and stroke. Identifying the origin of atrial ectopic activity from the electrocardiogram (ECG) can help to diagnose the early onset of AF in a cost-effective manner. The complex and rapid atrial electrical activity during AF makes it difficult to obtain detailed information on atrial activation using the standard 12-lead ECG alone. Compared to conventional 12-lead ECG, more detailed ECG lead configurations may provide further information about spatio-temporal dynamics of the body surface potential (BSP) during atrial excitation. We apply a recently developed 3D human atrial model to simulate electrical activity during normal sinus rhythm and ectopic pacing. The atrial model is placed into a newly developed torso model which considers the presence of the lungs, liver and spinal cord. A boundary element method is used to compute the BSP resulting from atrial excitation. Elements of the torso mesh corresponding to the locations of the placement of the electrodes in the standard 12-lead and a more detailed 64-lead ECG configuration were selected. The ectopic focal activity was simulated at various origins across all the different regions of the atria. Simulated BSP maps during normal atrial excitation (i.e. sinoatrial node excitation) were compared to those observed experimentally (obtained from the 64-lead ECG system), showing a strong agreement between the evolution in time of the simulated and experimental data in the P-wave morphology of the ECG and dipole evolution. An algorithm to obtain the location of the stimulus from a 64-lead ECG system was developed. The algorithm presented had a success rate of 93%, meaning that it correctly identified the origin of atrial focus in 75/80 simulations, and involved a general approach relevant to any multi-lead ECG system. This represents a significant improvement over previously developed algorithms.

  15. A New Algorithm to Diagnose Atrial Ectopic Origin from Multi Lead ECG Systems - Insights from 3D Virtual Human Atria and Torso

    PubMed Central

    Alday, Erick A. Perez; Colman, Michael A.; Langley, Philip; Butters, Timothy D.; Higham, Jonathan; Workman, Antony J.; Hancox, Jules C.; Zhang, Henggui

    2015-01-01

    Rapid atrial arrhythmias such as atrial fibrillation (AF) predispose to ventricular arrhythmias, sudden cardiac death and stroke. Identifying the origin of atrial ectopic activity from the electrocardiogram (ECG) can help to diagnose the early onset of AF in a cost-effective manner. The complex and rapid atrial electrical activity during AF makes it difficult to obtain detailed information on atrial activation using the standard 12-lead ECG alone. Compared to conventional 12-lead ECG, more detailed ECG lead configurations may provide further information about spatio-temporal dynamics of the body surface potential (BSP) during atrial excitation. We apply a recently developed 3D human atrial model to simulate electrical activity during normal sinus rhythm and ectopic pacing. The atrial model is placed into a newly developed torso model which considers the presence of the lungs, liver and spinal cord. A boundary element method is used to compute the BSP resulting from atrial excitation. Elements of the torso mesh corresponding to the locations of the placement of the electrodes in the standard 12-lead and a more detailed 64-lead ECG configuration were selected. The ectopic focal activity was simulated at various origins across all the different regions of the atria. Simulated BSP maps during normal atrial excitation (i.e. sinoatrial node excitation) were compared to those observed experimentally (obtained from the 64-lead ECG system), showing a strong agreement between the evolution in time of the simulated and experimental data in the P-wave morphology of the ECG and dipole evolution. An algorithm to obtain the location of the stimulus from a 64-lead ECG system was developed. The algorithm presented had a success rate of 93%, meaning that it correctly identified the origin of atrial focus in 75/80 simulations, and involved a general approach relevant to any multi-lead ECG system. This represents a significant improvement over previously developed algorithms. PMID

  16. [Recovery of the atrophied muscle: from protein degradation to synthesis].

    PubMed

    Shenkman, B S

    2012-12-01

    The enhancement of atrophied muscle recovery after coming back to normal motor activities (landing of the spacecraft, withdrawal of the cast etc) is very important problem of rehabilitation as well as space medicine. Along with the recovery of the gravity-dependent motor control system the regrowth of the muscle mass seems to be the key event. This regrowth cause recovery of the muscle performance. The present review is dedicated to the structural and functional events, observed during 7 days after exposure of an animal to gravitational unloading (mainly in experiments with the hindlimb suspension model). The state of the main signaling pathways in muscle fibers is also considered. The data presented in the review allow to imagine how the destructive and synthetic events do interact in the initial period of recovery. The work hypotheses on the key triggering signaling mechanisms are also put forward.

  17. Molecular events in skeletal muscle during disuse atrophy

    NASA Technical Reports Server (NTRS)

    Kandarian, Susan C.; Stevenson, Eric J.

    2002-01-01

    This review summarizes the current knowledge of the molecular processes underlying skeletal muscle atrophy due to disuse. Because the processes involved with muscle wasting due to illness are similar to disuse, this literature is used for comparison. Areas that are ripe for further study and that will advance our understanding of muscle atrophy are suggested.

  18. Grey matter hypometabolism and atrophy in Parkinson’s disease with cognitive impairment: a two-step process

    PubMed Central

    González-Redondo, Rafael; García-García, David; Clavero, Pedro; Gasca-Salas, Carmen; García-Eulate, Reyes; Zubieta, José L.; Arbizu, Javier; Obeso, José A.

    2014-01-01

    The pathophysiological process underlying cognitive decline in Parkinson’s disease is not well understood. Cerebral atrophy and hypometabolism have been described in patients with Parkinson’s disease and dementia or mild cognitive impairment with respect to control subjects. However, the exact relationships between atrophy and hypometabolism are still unclear. To determine the extension and topographical distribution of hypometabolism and atrophy in the different cognitive states of Parkinson’s disease, we examined 46 patients with Parkinson’s disease (19 female, 27 male; 71.7 ± 5.9 years old; 14.6 ± 4.2 years of disease evolution; modified Hoehn and Yahr mean stage 3.1 ± 0.7). Cognitive status was diagnosed as normal in 14 patients, as mild cognitive impairment in 17 and as dementia in 15 patients. Nineteen normal subjects (eight female, 11 male; 68.1 ± 3.2 years old) were included as controls. 18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging scans were obtained, co-registered, corrected for partial volume effect and spatially normalized to the Montreal Neurological Institute space in each subject. Smoothing was applied to the positron emission tomography and magnetic resonance imaging scans to equalize their effective smoothness and resolution (10 mm and 12 mm full-width at half-maximum and Gaussian kernel, respectively). Z-score maps for atrophy and for hypometabolism were obtained by comparing individual images to the data set of control subjects. For each group of patients, a paired Student’s t-test was performed to statistically compare the two Z-map modalities (P < 0.05 false discovery rate corrected) using the direct voxel-based comparison technique. In patients with mild cognitive impairment, hypometabolism exceeded atrophy in the angular gyrus, occipital, orbital and anterior frontal lobes. In patients with dementia, the hypometabolic areas observed in the group with mild cognitive impairment were replaced

  19. Schisandrae Fructus Supplementation Ameliorates Sciatic Neurectomy-Induced Muscle Atrophy in Mice

    PubMed Central

    Kim, Joo Wan; Ku, Sae-Kwang; Kim, Ki Young; Kim, Sung Goo; Han, Min Ho; Kim, Gi-Young; Hwang, Hye Jin; Kim, Byung Woo; Kim, Cheol Min

    2015-01-01

    The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF) on sciatic neurectomy- (NTX-) induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects and via an increase in protein synthesis and a decrease in protein degradation. PMID:26064425

  20. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy

    NASA Technical Reports Server (NTRS)

    Gomes, M. D.; Lecker, S. H.; Jagoe, R. T.; Navon, A.; Goldberg, A. L.

    2001-01-01

    Muscle wasting is a debilitating consequence of fasting, inactivity, cancer, and other systemic diseases that results primarily from accelerated protein degradation by the ubiquitin-proteasome pathway. To identify key factors in this process, we have used cDNA microarrays to compare normal and atrophying muscles and found a unique gene fragment that is induced more than ninefold in muscles of fasted mice. We cloned this gene, which is expressed specifically in striated muscles. Because this mRNA also markedly increases in muscles atrophying because of diabetes, cancer, and renal failure, we named it atrogin-1. It contains a functional F-box domain that binds to Skp1 and thereby to Roc1 and Cul1, the other components of SCF-type Ub-protein ligases (E3s), as well as a nuclear localization sequence and PDZ-binding domain. On fasting, atrogin-1 mRNA levels increase specifically in skeletal muscle and before atrophy occurs. Atrogin-1 is one of the few examples of an F-box protein or Ub-protein ligase (E3) expressed in a tissue-specific manner and appears to be a critical component in the enhanced proteolysis leading to muscle atrophy in diverse diseases.

  1. Indices of Regional Brain Atrophy: Formulae and Nomenclature

    PubMed Central

    Arias-Carrión, Oscar

    2015-01-01

    The pattern of brain atrophy helps to discriminate normal age-related changes from neurodegenerative diseases. Albeit indices of regional brain atrophy have proven to be a parameter useful in the early diagnosis and differential diagnosis of some neurodegenerative diseases, indices of absolute regional atrophy still have some important limitations. We propose using indices of relative atrophy for representing how the volume of a given region of interest (ROI) changes over time in comparison to changes in global brain measures over the same time. A second problem in morphometric studies is terminology. There is a lack of systematization naming indices and the same measure can be named with different terms by different research groups or imaging softwares. This limits the understanding and discussion of studies. In this technological report, we provide a general description on how to compute indices of absolute and relative regional brain atrophy and propose a standardized nomenclature. PMID:26261753

  2. Bone and muscle atrophy with suspension of the rat

    NASA Technical Reports Server (NTRS)

    Leblanc, A.; Marsh, C.; Evans, H.; Johnson, P.; Schneider, V.; Jhingran, S.

    1985-01-01

    In order to identify a suitable model for the study of muscle atrophy due to suspension in space, a modified version of the Morey tail suspension model was used to measure the atrophic responses of rat bone and muscle to 14-30 days of unloading of the hindlimbs. The progress of atrophy was measured by increases in methylene diphosphonate (MDP) uptake. It is found that bone uptake of methylene diphosphonate followed a phasic pattern similar to changes in the bone formation rate of immobilized dogs and cats. Increased MDP uptake after a period of 60 days indicated an accelerated bone metabolism. Maximum muscle atrophy in the suspended rats was distinctly different from immobilization atrophy. On the basis of the experimental results, it is concluded that the tail suspension model is an adequate simulation of bone atrophy due to suspension.

  3. Types of SMA (Spinal Muscular Atrophy)

    MedlinePlus

    ... Trials Research Publications Support & Care For Newly Diagnosed Care Packages Information Packets Equipment Pool Living With SMA Medical Issues Palliative Breathing Orthopedics Nutrition Equipment Daily Life At School At Home Adults With SMA Play Travel Grief & Loss Community & ...

  4. Effectiveness of Cortical Atrophy Scale and Indirect Indices of Brain Atrophy to Predict Chronic Subdural Hematoma in Older Patients

    PubMed Central

    Jeong, Eun-Oh; Lim, Jeong-Wook; Kwon, Hyon-Jo; Kim, Seon-Hwan; Koh, Hyeon-Song; Youm, Jin-Young; Song, Shi-Hun

    2016-01-01

    Objective To determine whether baseline cerebral atrophy can predict the rate of future chronic subdural hematoma (CSDH) after head trauma and compare indirect markers of brain atrophy with volumetric analysis of computed tomography (CT). Methods Single institution case-control study involving 1,476 patients who visited our hospital after head trauma from January 2009 to December 2014. Forty-one patients with delayed CSDH were identified and age, gender matched 41 patients were selected as control group. Both volumetric analyze on CT and Evans index, frontal horn index, bicaudate ratio, sylvian fissure ratio and cortical atrophy scale of 82 patients were estimated by different raters and relationship of those factors with CSDH was analyzed. Results Every indirect indices except cortical atrophy scale were not enough to give a good estimate of CSDH. Brain atrophy and cortical atrophy scale were predisposing factors of CSDH on multivariate analysis with statistical significance. Conclusion Brain atrophy was a potential prognostic factor of CSDH after trauma. In practice, patients with a value of cortical atrophy scale over moderate grade needed more attention for CSDH. PMID:27857918

  5. Non-familial degenerative disease and atrophy of brainstem and cerebellum. Clinical and CT data in 47 patients.

    PubMed

    Staal, A; Meerwaldt, J D; van Dongen, K J; Mulder, P G; Busch, H F

    1990-03-01

    We studied the clinical features of 47 patients with a non-hereditary degenerative disease and with atrophy of brainstem or cerebellum or both in CT scanning. There was no relation between the CT findings and duration or severity of the disease, nor with the kind of the neurological signs which comprised ataxia, a hypokinetic rigid syndrome, oculomotor abnormalities, upper and lower motor neuron signs, orthostatic hypotension and dementia. The 2 main diagnoses were olivopontocerebellar atrophy (OPCA), or a combination of OPCA and striatonigral degeneration (SND). The differential diagnosis with Parkinson's disease and progressive supranuclear palsy was discussed. We concluded, that a CT scan is warranted in all cases of suspected Parkinson's disease, especially in those without tremor, and in cases of motoneuron disease with broad-based gait. In our patients with mainly hypokinesia and rigidity, levodopa treatment had no or brief beneficial effects. If ataxia predominated, OPCA appeared the most sensible diagnosis; if a hypokinetic-rigid syndrome predominated, the diagnoses SND plus OPCA appeared the most suitable. We assessed the degree of atrophy on CT subjectively, because an interobserver study of 60 normal CT scans, did not produce reliable measurements.

  6. Assessing atrophy measurement techniques in dementia: Results from the MIRIAD atrophy challenge

    PubMed Central

    Cash, David M.; Frost, Chris; Iheme, Leonardo O.; Ünay, Devrim; Kandemir, Melek; Fripp, Jurgen; Salvado, Olivier; Bourgeat, Pierrick; Reuter, Martin; Fischl, Bruce; Lorenzi, Marco; Frisoni, Giovanni B.; Pennec, Xavier; Pierson, Ronald K.; Gunter, Jeffrey L.; Senjem, Matthew L.; Jack, Clifford R.; Guizard, Nicolas; Fonov, Vladimir S.; Collins, D. Louis; Modat, Marc; Cardoso, M. Jorge; Leung, Kelvin K.; Wang, Hongzhi; Das, Sandhitsu R.; Yushkevich, Paul A.; Malone, Ian B.; Fox, Nick C.; Schott, Jonathan M.; Ourselin, Sebastien

    2015-01-01

    Structural MRI is widely used for investigating brain atrophy in many neurodegenerative disorders, with several research groups developing and publishing techniques to provide quantitative assessments of this longitudinal change. Often techniques are compared through computation of required sample size estimates for future clinical trials. However interpretation of such comparisons is rendered complex because, despite using the same publicly available cohorts, the various techniques have been assessed with different data exclusions and different statistical analysis models. We created the MIRIAD atrophy challenge in order to test various capabilities of atrophy measurement techniques. The data consisted of 69 subjects (46 Alzheimer's disease, 23 control) who were scanned multiple (up to twelve) times at nine visits over a follow-up period of one to two years, resulting in 708 total image sets. Nine participating groups from 6 countries completed the challenge by providing volumetric measurements of key structures (whole brain, lateral ventricle, left and right hippocampi) for each dataset and atrophy measurements of these structures for each time point pair (both forward and backward) of a given subject. From these results, we formally compared techniques using exactly the same dataset. First, we assessed the repeatability of each technique using rates obtained from short intervals where no measurable atrophy is expected. For those measures that provided direct measures of atrophy between pairs of images, we also assessed symmetry and transitivity. Then, we performed a statistical analysis in a consistent manner using linear mixed effect models. The models, one for repeated measures of volume made at multiple time-points and a second for repeated “direct” measures of change in brain volume, appropriately allowed for the correlation between measures made on the same subject and were shown to fit the data well. From these models, we obtained estimates of the

  7. Assessing atrophy measurement techniques in dementia: Results from the MIRIAD atrophy challenge.

    PubMed

    Cash, David M; Frost, Chris; Iheme, Leonardo O; Ünay, Devrim; Kandemir, Melek; Fripp, Jurgen; Salvado, Olivier; Bourgeat, Pierrick; Reuter, Martin; Fischl, Bruce; Lorenzi, Marco; Frisoni, Giovanni B; Pennec, Xavier; Pierson, Ronald K; Gunter, Jeffrey L; Senjem, Matthew L; Jack, Clifford R; Guizard, Nicolas; Fonov, Vladimir S; Collins, D Louis; Modat, Marc; Cardoso, M Jorge; Leung, Kelvin K; Wang, Hongzhi; Das, Sandhitsu R; Yushkevich, Paul A; Malone, Ian B; Fox, Nick C; Schott, Jonathan M; Ourselin, Sebastien

    2015-12-01

    Structural MRI is widely used for investigating brain atrophy in many neurodegenerative disorders, with several research groups developing and publishing techniques to provide quantitative assessments of this longitudinal change. Often techniques are compared through computation of required sample size estimates for future clinical trials. However interpretation of such comparisons is rendered complex because, despite using the same publicly available cohorts, the various techniques have been assessed with different data exclusions and different statistical analysis models. We created the MIRIAD atrophy challenge in order to test various capabilities of atrophy measurement techniques. The data consisted of 69 subjects (46 Alzheimer's disease, 23 control) who were scanned multiple (up to twelve) times at nine visits over a follow-up period of one to two years, resulting in 708 total image sets. Nine participating groups from 6 countries completed the challenge by providing volumetric measurements of key structures (whole brain, lateral ventricle, left and right hippocampi) for each dataset and atrophy measurements of these structures for each time point pair (both forward and backward) of a given subject. From these results, we formally compared techniques using exactly the same dataset. First, we assessed the repeatability of each technique using rates obtained from short intervals where no measurable atrophy is expected. For those measures that provided direct measures of atrophy between pairs of images, we also assessed symmetry and transitivity. Then, we performed a statistical analysis in a consistent manner using linear mixed effect models. The models, one for repeated measures of volume made at multiple time-points and a second for repeated "direct" measures of change in brain volume, appropriately allowed for the correlation between measures made on the same subject and were shown to fit the data well. From these models, we obtained estimates of the

  8. Hippocampal atrophy in recurrent major depression.

    PubMed Central

    Sheline, Y I; Wang, P W; Gado, M H; Csernansky, J G; Vannier, M W

    1996-01-01

    Hippocampal volumes of subjects with a history of major depressive episodes but currently in remission and with no known medical comorbidity were compared to matched normal controls by using volumetric magnetic resonance images. Subjects with a history of major depression had significantly smaller left and right hippocampal volumes with no differences in total cerebral volumes. The degree of hippocampal volume reduction correlated with total duration of major depression. In addition, large (diameter > or = 4.5 mm)-hippocampal low signal foci (LSF) were found within the hippocampus, and their number also correlated with the total number of days depressed. These results suggest that depression is associated with hippocampal atrophy, perhaps due to a progressive process mediated by glucocorticoid neurotoxicity. Images Fig. 1 Fig. 4 PMID:8632988

  9. Recommendations for the management of postmenopausal vaginal atrophy.

    PubMed

    Sturdee, D W; Panay, N

    2010-12-01

    Unlike hot flushes and night sweats which resolve spontaneously in time, atrophic symptoms affecting the vagina and lower urinary tract are often progressive and frequently require treatment. The prevalence of vaginal dryness increases as a woman advances through the postmenopausal years, causing itching, burning and dyspareunia, and sexual activity is often compromised. But, despite the various safe and effective options, only a minority (about 25% in the Western world and probably considerably less in other areas) will seek medical help. Some of this reluctance is due to the adverse publicity for hormone replacement therapy (HRT) over recent years that has suggested an increased risk of breast cancer, heart disease and stroke. But, regardless of whether these scares are justified, local treatment of vaginal atrophy is not associated with these possible risks of systemic HRT. Other reasons for the continued suffering in silence may be cultural and an understandable reluctance to discuss such matters, particularly with a male doctor, but the medical profession must also take much of the blame for failing to enquire of all postmenopausal women about the possibility of vaginal atrophic symptoms. Vaginal dryness can be helped by simple lubricants but the best and most logical treatment for urogenital atrophy is to use local estrogen. This is safe, effective and with few contraindications. It is hoped that these guidelines and recommendations, produced to coincide with World Menopause Day 2010, will help to highlight this major cause of distress and reduced quality of life and will encourage women and their medical advisers all over the world to seek and provide help.

  10. Modeling Spinal Muscular Atrophy in Drosophila

    PubMed Central

    Mukherjee, Ashim; Kankel, Mark W.; Sen, Anindya; Sridhar, Vasanthi; Fulga, Tudor A.; Hart, Anne C.; Van Vactor, David; Artavanis-Tsakonas, Spyros

    2008-01-01

    Spinal Muscular Atrophy (SMA), a recessive hereditary neurodegenerative disease in humans, has been linked to mutations in the survival motor neuron (SMN) gene. SMA patients display early onset lethality coupled with motor neuron loss and skeletal muscle atrophy. We used Drosophila, which encodes a single SMN ortholog, survival motor neuron (Smn), to model SMA, since reduction of Smn function leads to defects that mimic the SMA pathology in humans. Here we show that a normal neuromuscular junction (NMJ) structure depends on SMN expression and that SMN concentrates in the post-synaptic NMJ regions. We conducted a screen for genetic modifiers of an Smn phenotype using the Exelixis collection of transposon-induced mutations, which affects approximately 50% of the Drosophila genome. This screen resulted in the recovery of 27 modifiers, thereby expanding the genetic circuitry of Smn to include several genes not previously known to be associated with this locus. Among the identified modifiers was wishful thinking (wit), a type II BMP receptor, which was shown to alter the Smn NMJ phenotype. Further characterization of two additional members of the BMP signaling pathway, Mothers against dpp (Mad) and Daughters against dpp (Dad), also modify the Smn NMJ phenotype. The NMJ defects caused by loss of Smn function can be ameliorated by increasing BMP signals, suggesting that increased BMP activity in SMA patients may help to alleviate symptoms of the disease. These results confirm that our genetic approach is likely to identify bona fide modulators of SMN activity, especially regarding its role at the neuromuscular junction, and as a consequence, may identify putative SMA therapeutic targets. PMID:18791638

  11. Choroidal Round Hyporeflectivities in Geographic Atrophy

    PubMed Central

    De Vitis, Luigi Antonio; Carnevali, Adriano; Rabiolo, Alessandro; Querques, Lea; Bandello, Francesco; Querques, Giuseppe

    2016-01-01

    Purpose In geographic atrophy (GA), choroidal vessels typically appear on structural optical coherence tomography (OCT) as hyperreflective round areas with highly reflective borders. We observed that some GA eyes show choroidal round hyporeflectivities with highly reflective borders beneath the atrophy, and futher investigated the charcteristcs by comparing structural OCT, indocyanine green angiography (ICGA) and OCT angiography (OCT-A). Methods Round hyporeflectivities were individuated from a pool of patients with GA secondary to non-neovascular age-related macular degeneration consecutively presenting between October 2015 and March 2016 at the Medical Retina & Imaging Unit of the University Vita-Salute San Raffaele. Patients underwent a complete ophthalmologic examination including ICGA, structural OCT and OCT-A. The correspondence between choroidal round hyporeflectivities beneath GA on structural OCT and ICGA and OCT-A imaging were analyzed. Results Fifty eyes of 26 consecutive patients (17 females and 9 males; mean age 76.8±6.2 years) with GA were included. Twenty-nine round hyporeflectivities have been found by OCT in choroidal layers in 21 eyes of 21 patients (42.0%; estimated prevalence of 57.7%). All 29 round hyporeflectivities showed constantly a hyperreflective border and a backscattering on structural OCT, and appeared as hypofluorescent in late phase ICGA and as dark foci with non detectable flow in the choroidal segmentation of OCT-A. Interestingly, the GA area was greater in eyes with compared to eyes without round hyporeflectivities (9.30±5.74 and 5.57±4.48mm2, respectively; p = 0.01). Conclusions Our results suggest that most round hyporeflectivities beneath GA may represent non-perfused or hypo-perfused choroidal vessels with non-detectable flow. PMID:27880806

  12. Characteristics related to early secondary amenorrhoea and pregnancy among women diagnosed with systemic lupus erythematosus: an analysis using the GOAL study

    PubMed Central

    Knight, Jessica H; Howards, Penelope P; Spencer, Jessica B; Tsagaris, Katina C; Lim, Sam S

    2016-01-01

    Objective Systemic lupus erythematosus (SLE) disproportionately affects women and often develops during their reproductive years. Research suggests that some women who receive cyclophosphamide as treatment for SLE experience earlier decline in menstrual function, but reproductive health among women with SLE who have not taken this drug is less well understood. This study aims to better understand the relation between SLE and reproduction by assessing early secondary amenorrhoea and pregnancy in women treated with and without cyclophosphamide from a population-based cohort with large numbers of African-Americans. Methods Female patients with SLE, ages 20–40 at time of diagnosis, who were 40 years or older at the time of the survey were included in this analysis (N=147). Participants in the Georgians Organized Against Lupus (GOAL) study were asked about their reproductive histories including early secondary amenorrhoea, defined as loss of menstruation before age 40. Results Women who were cyclophosphamide naïve had an increased prevalence of early secondary amenorrhoea compared with population estimates, 13–17% compared with 1–5%. Factors associated with early secondary amenorrhoea in women not treated with cyclophosphamide were marital status and receipt of a kidney transplant. Treatment with cyclophosphamide doubled the prevalence after adjustment for patient characteristics. Over 88% of women reported being pregnant at least once, and about 83% of these had a child, but the majority of pregnancies occurred before diagnosis. Conclusions SLE diagnosed in early adulthood may affect women's reproductive health even if they are not treated with cyclophosphamide. Better understanding of other factors related to reproductive health in this population will improve clinicians' and patients' abilities to make treatment and family planning decisions. PMID:27752335

  13. Radiologic correlates of reaction time measurements in olivopontocerebellar atrophy.

    PubMed

    Botez, M I; Pedraza, O L; Botez-Marquard, T; Vézina, J L; Elie, R

    1993-01-01

    We measured simple visual and auditory reaction time (RT) and movement time (MT) in 32 patients with olivopontocerebellar atrophy (OPCA) in comparison to 32 control subjects. In addition, we followed 2 approaches to radiologic assessment by computed tomographic scans: subjective (by inspection of films) and objective (by measurement of 4 radiologic ratios at the level of the posterior fossa and 1 ratio at the supratentorial level). All OPCA patients had various degrees of cerebellar atrophy and lengthened RT and MT in comparison to their controls. There were no significant differences in RT and MT performances in patients with mild-moderate versus those with severe cerebellar atrophy as assessed by inspection of their films. OPCA patients with severe versus mild-moderate atrophy evaluated by 3 measures, i.e., brainstem, brachium pontis and fourth ventricle ratios, presented few significantly lengthened RT and MT performances. In contrast, patients with severe atrophy revealed by the midbrain ratio had significantly lengthened RT and MT performances compared to those with mild-moderate atrophy assessed by this ratio on 7 of 8 measures; the 8th measure showed a borderline significant difference. This could be explained by the fact that atrophy at the midbrain level is the only one which involves dopaminergic, noradrenergic and glutamatergic structures and pathways.

  14. White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy

    PubMed Central

    Manning, Emily N.; Bartlett, Jonathan W.; Cash, David M.; Malone, Ian B.; Ridgway, Gerard R.; Lehmann, Manja; Leung, Kelvin K.; Sudre, Carole H.; Ourselin, Sebastien; Biessels, Geert Jan; Carmichael, Owen T.; Fox, Nick C.; Cardoso, M. Jorge; Barnes, Josephine

    2017-01-01

    ABSTRACT This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5‐T MRI. CSF Aβ42 and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Aβ42 and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:27933676

  15. White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy.

    PubMed

    Fiford, Cassidy M; Manning, Emily N; Bartlett, Jonathan W; Cash, David M; Malone, Ian B; Ridgway, Gerard R; Lehmann, Manja; Leung, Kelvin K; Sudre, Carole H; Ourselin, Sebastien; Biessels, Geert Jan; Carmichael, Owen T; Fox, Nick C; Cardoso, M Jorge; Barnes, Josephine

    2017-03-01

    This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5-T MRI. CSF Aβ42 and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Aβ42 and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

  16. Botulinum Toxin and Muscle Atrophy: A Wanted or Unwanted Effect.

    PubMed

    Durand, Paul D; Couto, Rafael A; Isakov, Raymond; Yoo, Donald B; Azizzadeh, Babak; Guyuron, Bahman; Zins, James E

    2016-04-01

    While the facial rejuvenating effect of botulinum toxin type A is well known and widespread, its use in body and facial contouring is less common. We first describe its use for deliberate muscle volume reduction, and then document instances of unanticipated and undesirable muscle atrophy. Finally, we investigate the potential long-term adverse effects of botulinum toxin-induced muscle atrophy. Although the use of botulinum toxin type A in the cosmetic patient has been extensively studied, there are several questions yet to be addressed. Does prolonged botulinum toxin treatment increase its duration of action? What is the mechanism of muscle atrophy and what is the cause of its reversibility once treatment has stopped? We proceed to examine how prolonged chemodenervation with botulinum toxin can increase its duration of effect and potentially contribute to muscle atrophy. Instances of inadvertent botulinum toxin-induced atrophy are also described. These include the "hourglass deformity" secondary to botulinum toxin type A treatment for migraine headaches, and a patient with atrophy of multiple facial muscles from injections for hemifacial spasm. Numerous reports demonstrate that muscle atrophy after botulinum toxin type A treatment occurs and is both reversible and temporary, with current literature supporting the notion that repeated chemodenervation with botulinum toxin likely responsible for both therapeutic and incidental temporary muscle atrophy. Furthermore, duration of response may be increased with subsequent treatments, thus minimizing frequency of reinjection. Practitioners should be aware of the temporary and reversible effect of botulinum toxin-induced muscle atrophy and be prepared to reassure patients on this matter.

  17. How Is Kawasaki Disease Diagnosed?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Is Kawasaki Disease Diagnosed? Kawasaki disease is diagnosed based on your child's signs and ... are the first to suspect a child has Kawasaki disease. Pediatricians are doctors who specialize in treating children. ...

  18. How Is Pulmonary Hypertension Diagnosed?

    MedlinePlus

    ... Hypertension Diagnosed? Your doctor will diagnose pulmonary hypertension (PH) based on your medical and family histories, a ... exam, and the results from tests and procedures. PH can develop slowly. In fact, you may have ...

  19. Diagnosing Dementia--Positive Signs

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues Diagnosing Dementia—Positive Signs Past Issues / Fall 2007 Table of ... easy, affordable blood test that could accurately diagnose Alzheimer's disease (AD)—even before symptoms began to show? Researchers ...

  20. Testicular atrophy as a consequence of inguinal hernia repair.

    PubMed

    Reid, I; Devlin, H B

    1994-01-01

    Testicular atrophy is an uncommon but well recognized complication of inguinal hernia repair and one that frequently results in litigation. A series of ten cases of testicular atrophy occurring after hernia repair in nine patients is presented. Identifiable risk factors were present in eight instances. Surgeons should make careful enquiries as to previous groin or scrotal surgery and, when indicated, warn the patient before surgery of the increased risk of testicular atrophy. Overzealous dissection of a distal hernia sac, dislocation of the testis from the scrotum into the wound and concomitant scrotal surgery should all be avoided.

  1. Prodromal Posterior Cortical Atrophy: Clinical, Neuropsychological and Radiological Correlation

    PubMed Central

    Chan, Lung Tat Andrew; Lynch, Whitney; De May, Mary; Horton, Jonathan C.; Miller, Bruce L.

    2015-01-01

    We present longitudinal clinical, cognitive and neuroimaging data from a 63-year-old woman who enrolled in research as a normal control and evolved posterior cortical atrophy (PCA) over five year follow-up. At baseline she reported only subtle difficulty driving and performed normally on cognitive tests, but already demonstrated atrophy in left visual association cortex. With follow-up she developed insidiously progressive visuospatial and visuoperceptual deficits, correlating with progressive atrophy in bilateral visual areas. Amyloid PET was positive. This case tracks the evolution of PCA from the prodromal stage, and illustrates challenges to early diagnosis as well as the utility of imaging biomarkers. PMID:24308559

  2. Posterior cortical atrophy: an atypical variant of Alzheimer disease.

    PubMed

    Suárez-González, Aida; Henley, Susie M; Walton, Jill; Crutch, Sebastian J

    2015-06-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by striking progressive visual impairment and a pattern of atrophy mainly involving posterior cortices. PCA is the most frequent atypical presentation of Alzheimer disease. The purpose of this article is to provide a summary of PCA's neuropsychiatric manifestations. Emotional and psychotic symptoms are discussed in the context of signal characteristic features of the PCA syndrome (the early onset, focal loss of visual perception, focal posterior brain atrophy) and the underlying cause of the disease. The authors' experience with psychotherapeutic intervention and PCA support groups is shared in detail.

  3. Diagnosing Musculoskeletal Tumours

    PubMed Central

    Carter, Simon R.; Spooner, David; Sneath, Rodney S.

    2001-01-01

    In 1993 we became aware of a worrying increase in apparent errors in the histopathological diagnosis of musculoskeletal tumours in our Unit. As a result all cases seen over the past 8 years were reviewed by an independent panel. Of the 1996 cases reviewed there was an error in 87. In 54 cases (2.7%) this had led to some significant change in the active management of the patient. The main areas where errors arose were in those very cases where clinical and radiological features were not helpful in confirming or refuting the diagnosis. The incidence of errors rose with the passage of time, possibly related to a deterioration in the pathologist’s health. The error rate in diagnosing bone tumours in previously published series ranges from 9 to 40%. To ensure as accurate a rate of diagnosis as possible multidisciplinary working and regular audit are essential. PMID:18521309

  4. Diagnosable structured logic array

    NASA Technical Reports Server (NTRS)

    Whitaker, Sterling (Inventor); Miles, Lowell (Inventor); Gambles, Jody (Inventor); Maki, Gary K. (Inventor)

    2009-01-01

    A diagnosable structured logic array and associated process is provided. A base cell structure is provided comprising a logic unit comprising a plurality of input nodes, a plurality of selection nodes, and an output node, a plurality of switches coupled to the selection nodes, where the switches comprises a plurality of input lines, a selection line and an output line, a memory cell coupled to the output node, and a test address bus and a program control bus coupled to the plurality of input lines and the selection line of the plurality of switches. A state on each of the plurality of input nodes is verifiably loaded and read from the memory cell. A trusted memory block is provided. The associated process is provided for testing and verifying a plurality of truth table inputs of the logic unit.

  5. Mechanisms of cisplatin-induced muscle atrophy

    SciTech Connect

    Sakai, Hiroyasu; Sagara, Atsunobu; Arakawa, Kazuhiko; Sugiyama, Ryoto; Hirosaki, Akiko; Takase, Kazuhide; Jo, Ara; Sato, Ken; Chiba, Yoshihiko; Yamazaki, Mitsuaki; Matoba, Motohiro; Narita, Minoru

    2014-07-15

    Fatigue is the most common side effect of chemotherapy. However, the mechanisms of “muscle fatigue” induced by anti-cancer drugs are not fully understood. We therefore investigated the muscle-atrophic effect of cisplatin, a platinum-based anti-cancer drug, in mice. C57BL/6J mice were treated with cisplatin (3 mg/kg, i.p.) or saline for 4 consecutive days. On Day 5, hindlimb and quadriceps muscles were isolated from mice. The loss of body weight and food intake under the administration of cisplatin was the same as those in a dietary restriction (DR) group. Under the present conditions, the administration of cisplatin significantly decreased not only the muscle mass of the hindlimb and quadriceps but also the myofiber diameter, compared to those in the DR group. The mRNA expression levels of muscle atrophy F-box (MAFbx), muscle RING finger-1 (MuRF1) and forkhead box O3 (FOXO3) were significantly and further increased by cisplatin treated group, compared to DR. Furthermore, the mRNA levels of myostatin and p21 were significantly upregulated by the administration of cisplatin, compared to DR. On the other hand, the phosphorylation of Akt and FOXO3a, which leads to the blockade of the upregulation of MuRF1 and MAFbx, was significantly and dramatically decreased by cisplatin. These findings suggest that the administration of cisplatin increases atrophic gene expression, and may lead to an imbalance between protein synthesis and protein degradation pathways, which would lead to muscle atrophy. This phenomenon could, at least in part, explain the mechanism of cisplatin-induced muscle fatigue. - Highlights: • Cisplatin decreased mass and myofiber diameter in quadriceps muscle. • The mRNA of MAFbx, MuRF1 and FOXO3 were increased by the cisplatin. • The mRNA of myostatin and p21 were upregulated by cisplatin. • The phosphorylation of Akt and FOXO3a was decreased by cisplatin.

  6. [Pathophysiological analysis of dropped head syndrome caused by various diagnoses - based on surface EMG findings and responses to physiotherapy].

    PubMed

    Lin, Hsin-Ni; Nagaoka, Masanori; Hayashi, Yasuko; Yonezawa, Ikuho

    2013-01-01

    Dropped head syndrome is seen in various diseases. We investigated its pathophysiological mechanisms with physical and radiological examination, surface EMG and responses to physiotherapy. Subjects had dropped head as a complaint, but their primary diagnoses were various. We investigated 16 cases: 5 cases of Parkinson disease, 5 cases of multiple system atrophy predominant parkinsonism, 3 cases of cervical spondylosis and 3 cases with other diagnoses. We found that patients had common findings such as bulging of cervical muscles, and tonic EMG activities mainly in the extensors in the sitting and standing position, but in the flexors of the neck only in the supine position. Of the 16 cases, 14 were treated with physiotherapy to improve the alignment of the pelvis and whole vertebral column; 6 of the 14 cases (63%) showed remarkable improvement. We conclude that the primary reason of dropped head syndrome is unknown in Parkinson disease and cervical spondylosis, but also that many of the patients have secondary changes in alignment of the skeletomuscular system which could be treated with physiotherapy.

  7. Cerebral atrophy in myotonic dystrophy: a voxel based morphometric study.

    PubMed

    Antonini, G; Mainero, C; Romano, A; Giubilei, F; Ceschin, V; Gragnani, F; Morino, S; Fiorelli, M; Soscia, F; Di Pasquale, A; Caramia, F

    2004-11-01

    Brain involvement in myotonic dystrophy type 1 (DM1) is characterised by cortical atrophy and white matter lesions. We compared the magnetic resonance imaging derived grey matter maps of 22 DM1 patients with those of matched, healthy controls using voxel based morphometry to evaluate the extension of global and regional cortical atrophy in DM1, as well as its relationships with clinical and genetic features. Patients had significantly reduced brain tissue volumes. Grey matter volume was inversely correlated with age; this inverse correlation was significantly stronger in DM1 than in controls. Neither the clinical and genetic characteristics nor white matter lesions were correlated with cortical atrophy. Grey matter atrophy was located mainly in the bilateral frontal and parietal lobes, in the bilateral middle temporal gyrus, and in the left superior temporal and occipital gyrus.

  8. Biochemical adaptations of antigravity muscle fibers to disuse atrophy

    NASA Technical Reports Server (NTRS)

    Booth, F. W.

    1978-01-01

    Studies are presented in four parts of this report. The four parts include; (1) studies to gain information on the molecular basis of atrophy by antigravity muscle; (2) studies on the work capacity of antigravity muscles during atrophy and during recovery from atrophy; (3) studies on recovery of degenerated antigravity fibers after removal of hind-limb casts; and (4) studies on the atrophy and recovery of bone. The philosophy of these studies was to identify the time sequence of events in the soleus muscle of the rat following immobilization of the hind limbs, so that the length of the soleus muscle within the fixed limb is less than its resting length. In two separate studies, no decline in the weight of the soleus muscle could be detected during the first 72 hours of limb immobilization.

  9. The Journey of "Geographic Atrophy" through Past, Present, and Future.

    PubMed

    Schmitz-Valckenberg, Steffen

    2017-01-01

    "Geographic atrophy" is a concise term that has been firmly established for the description of the end-stage manifestation of nonexudative age-related macular degeneration (AMD). "Geographic lesions" resembling sharply demarcated continents on a map have been originally described in the German literature in 1854 (landkartenartiger/inselförmiger Zungenfratt) for a manifestation later called "geographic tongue" in English. In 1970, Gass was the first to describe "geographic areas of atrophy" in "senile macular choroidal degeneration." Within a decade, the disease itself was named "geographic atrophy." Today, various meanings of the term are used in parallel both in research and in routine clinical care. Currently, we are on the verge of better understanding the different forms of atrophy development, manifestation, and progression in AMD, which will pave the way for a more rational approach to their nomenclature and classification.

  10. Age effects on atrophy rates of entorhinal cortex and hippocampus

    PubMed Central

    Du, An-Tao; Schuff, Norbert; Chao, Linda L.; Kornak, John; Jagust, William J.; Kramer, Joel H.; Reed, Bruce R.; Miller, Bruce L.; Norman, David; Chui, Helena C.; Weiner, Michael W.

    2007-01-01

    The effects of age, subcortical vascular disease, apolipoprotein E (APOE) ɛ4 allele and hypertension on entorhinal cortex (ERC) and hippocampal atrophy rates were explored in a longitudinal MRI study with 42 cognitively normal (CN) elderly subjects from 58 to 87 years old. The volumes of the ERC, hippocampus, and white matter hyperintensities (WMH) and the presence of lacunes were assessed on MR images. Age was significantly associated with increased atrophy rates of 0.04 ± 0.02% per year for ERC and 0.05 ± 0.02% per year for hippocampus. Atrophy rates of hippocampus, but not that of ERC increased with presence of lacunes, in addition to age. WMH, APOE ɛ4 and hypertension had no significant effect on atrophy rates. In conclusion, age and presence of lacunes should be taken into consideration in imaging studies of CN subjects and AD patients to predict AD progression and assess the response to treatment trials. PMID:15961190

  11. Circulating micrornas as potential biomarkers of muscle atrophy

    NASA Astrophysics Data System (ADS)

    Wang, Fei

    2016-07-01

    Noninvasive biomarkers with diagnostic value and prognostic applications have long been desired to replace muscle biopsy for muscle atrophy patients. Growing evidence indicates that circulating microRNAs are biomarkers to assess pathophysiological status. Here, we show that the medium levels of six muscle-specific miRNAs (miR-1/23a/206/133/499/208b, also known as myomiRs) were all elevated in the medium of starved C2C12 cell (P < 0.01). And, the level of miR-1 and miR-23a were all elevated in the serum of hindlimb unloaded mice (P < 0.01). miR-23a levels were negatively correlated with both muscle mass and muscle fiber cross section area in muscle atrophy patients, indicating that they might represent the degree of muscle atrophy. Collectively, our data indicated that circulating myomiRs could serve as promising biomarkers for muscle atrophy.

  12. Calculation of brain atrophy using computed tomography and a new atrophy measurement tool

    NASA Astrophysics Data System (ADS)

    Bin Zahid, Abdullah; Mikheev, Artem; Yang, Andrew Il; Samadani, Uzma; Rusinek, Henry

    2015-03-01

    Purpose: To determine if brain atrophy can be calculated by performing volumetric analysis on conventional computed tomography (CT) scans in spite of relatively low contrast for this modality. Materials & Method: CTs for 73 patients from the local Veteran Affairs database were selected. Exclusion criteria: AD, NPH, tumor, and alcohol abuse. Protocol: conventional clinical acquisition (Toshiba; helical, 120 kVp, X-ray tube current 300mA, slice thickness 3-5mm). Locally developed, automatic algorithm was used to segment intracranial cavity (ICC) using (a) white matter seed (b) constrained growth, limited by inner skull layer and (c) topological connectivity. ICC was further segmented into CSF and brain parenchyma using a threshold of 16 Hu. Results: Age distribution: 25-95yrs; (Mean 67+/-17.5yrs.). Significant correlation was found between age and CSF/ICC(r=0.695, p<0.01 2-tailed). A quadratic model (y=0.06-0.001x+2.56x10-5x2 ; where y=CSF/ICC and x=age) was a better fit to data (r=0.716, p < 0.01). This is in agreement with MRI literature. For example, Smith et al. found annual CSF/ICC increase in 58 - 94.5 y.o. individuals to be 0.2%/year, whereas our data, restricted to the same age group yield 0.3%/year(0.2-0.4%/yrs. 95%C.I.). Slightly increased atrophy among elderly VA patients is attributable to the presence of other comorbidities. Conclusion: Brain atrophy can be reliably calculated using automated software and conventional CT. Compared to MRI, CT is more widely available, cheaper, and less affected by head motion due to ~100 times shorter scan time. Work is in progress to improve the precision of the measurements, possibly leading to assessment of longitudinal changes within the patient.

  13. Rehabilitation and nutritional support for sarcopenic dysphagia and tongue atrophy after glossectomy: A case report.

    PubMed

    Hashida, Nao; Shamoto, Hiroshi; Maeda, Keisuke; Wakabayashi, Hidetaka; Suzuki, Motoyuki; Fujii, Takashi

    2017-03-01

    Swallowing dysfunction is related to long-term weight loss and reduced body mass index in patients with head and neck cancer. We describe a 76-y-old woman who had severe sarcopenic dysphagia and atrophy of the reconstructed tongue for 17 mo after subtotal glossectomy due to tongue cancer and lost 14 kg during that period. Upon admission, the patient received diagnoses of malnutrition in the context of social or environmental circumstances with insufficient energy intake, loss of muscle mass, localized fluid accumulation, weight loss, and sarcopenia due to reduced skeletal muscle mass (skeletal muscle index <3.95 cm(2)/m(2)) and low walking speed (<0.8 m/s). She was not able to eat anything and had a functional oral intake scale level of 1 and penetration-aspiration scale score of 7 points on video fluorography. We increased the nutritional intake to 1900 kcal/d and protein intake to 70.3 g/d by supplying sufficient excess energy, and provided physical therapy and dysphagia rehabilitation to improve sarcopenia, atrophy of the reconstructed tongue, and dysphagia. After 20 mo of treatment, she was considered to be no longer malnourished (11 kg weight gain) and without sarcopenia (skeletal muscle index 4.01 cm(2)/m(2)), and the volume of the reconstructed tongue was increased. Sarcopenia and atrophy of the reconstructed tongue may cause dysphagia after glossectomy due to tongue cancer. Additionally, nutritional support and rehabilitation could improve such dysphagia.

  14. Facilitating text reading in posterior cortical atrophy

    PubMed Central

    Rajdev, Kishan; Shakespeare, Timothy J.; Leff, Alexander P.; Crutch, Sebastian J.

    2015-01-01

    Objective: We report (1) the quantitative investigation of text reading in posterior cortical atrophy (PCA), and (2) the effects of 2 novel software-based reading aids that result in dramatic improvements in the reading ability of patients with PCA. Methods: Reading performance, eye movements, and fixations were assessed in patients with PCA and typical Alzheimer disease and in healthy controls (experiment 1). Two reading aids (single- and double-word) were evaluated based on the notion that reducing the spatial and oculomotor demands of text reading might support reading in PCA (experiment 2). Results: Mean reading accuracy in patients with PCA was significantly worse (57%) compared with both patients with typical Alzheimer disease (98%) and healthy controls (99%); spatial aspects of passages were the primary determinants of text reading ability in PCA. Both aids led to considerable gains in reading accuracy (PCA mean reading accuracy: single-word reading aid = 96%; individual patient improvement range: 6%–270%) and self-rated measures of reading. Data suggest a greater efficiency of fixations and eye movements under the single-word reading aid in patients with PCA. Conclusions: These findings demonstrate how neurologic characterization of a neurodegenerative syndrome (PCA) and detailed cognitive analysis of an important everyday skill (reading) can combine to yield aids capable of supporting important everyday functional abilities. Classification of evidence: This study provides Class III evidence that for patients with PCA, 2 software-based reading aids (single-word and double-word) improve reading accuracy. PMID:26138948

  15. Spinal Muscular Atrophy: Current Therapeutic Strategies

    NASA Astrophysics Data System (ADS)

    Kiselyov, Alex S.; Gurney, Mark E.

    Proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by death of motor neurons in the spinal cord. SMA is caused by deletion and/or mutation of the survival motor neuron gene (SMN1) on chromosome 5q13. There are variable numbers of copies of a second, related gene named SMN2 located in the proximity to SMN1. Both genes encode the same protein (Smn). Loss of SMN1 and incorrect splicing of SMN2 affect cellular levels of Smn triggering death of motor neurons. The severity of SMA is directly related to the normal number of copies of SMN2 carried by the patient. A considerable effort has been dedicated to identifying modalities including both biological and small molecule agents that increase SMN2 promoter activity to upregulate gene transcription and produce increased quantities of full-length Smn protein. This review summarizes recent progress in the area and suggests potential target product profile for an SMA therapeutic.

  16. Diagnosing mucopolysaccharidosis IVA.

    PubMed

    Wood, Timothy C; Harvey, Katie; Beck, Michael; Burin, Maira Graeff; Chien, Yin-Hsiu; Church, Heather J; D'Almeida, Vânia; van Diggelen, Otto P; Fietz, Michael; Giugliani, Roberto; Harmatz, Paul; Hawley, Sara M; Hwu, Wuh-Liang; Ketteridge, David; Lukacs, Zoltan; Miller, Nicole; Pasquali, Marzia; Schenone, Andrea; Thompson, Jerry N; Tylee, Karen; Yu, Chunli; Hendriksz, Christian J

    2013-03-01

    Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity. Diagnosis can be challenging and requires agreement of clinical, radiographic, and laboratory findings. A group of biochemical genetics laboratory directors and clinicians involved in the diagnosis of MPS IVA, convened by BioMarin Pharmaceutical Inc., met to develop recommendations for diagnosis. The following conclusions were reached. Due to the wide variation and subtleties of radiographic findings, imaging of multiple body regions is recommended. Urinary glycosaminoglycan analysis is particularly problematic for MPS IVA and it is strongly recommended to proceed to enzyme activity testing even if urine appears normal when there is clinical suspicion of MPS IVA. Enzyme activity testing of GALNS is essential in diagnosing MPS IVA. Additional analyses to confirm sample integrity and rule out MPS IVB, multiple sulfatase deficiency, and mucolipidoses types II/III are critical as part of enzyme activity testing. Leukocytes or cultured dermal fibroblasts are strongly recommended for enzyme activity testing to confirm screening results. Molecular testing may also be used to confirm the diagnosis in many patients. However, two known or probable causative mutations may not be identified in all cases of MPS IVA. A diagnostic testing algorithm is presented which attempts to streamline this complex testing process.

  17. Diagnosing pulmonary embolism

    PubMed Central

    Riedel, M

    2004-01-01

    Objective testing for pulmonary embolism is necessary, because clinical assessment alone is unreliable and the consequences of misdiagnosis are serious. No single test has ideal properties (100% sensitivity and specificity, no risk, low cost). Pulmonary angiography is regarded as the final arbiter but is ill suited for diagnosing a disease present in only a third of patients in whom it is suspected. Some tests are good for confirmation and some for exclusion of embolism; others are able to do both but are often non-diagnostic. For optimal efficiency, choice of the initial test should be guided by clinical assessment of the likelihood of embolism and by patient characteristics that may influence test accuracy. Standardised clinical estimates can be used to give a pre-test probability to assess, after appropriate objective testing, the post-test probability of embolism. Multidetector computed tomography can replace both scintigraphy and angiography for the exclusion and diagnosis of this disease and should now be considered the central imaging investigation in suspected pulmonary embolism. PMID:15192162

  18. The utility of age-specific cut-offs for visual rating of medial temporal atrophy in classifying Alzheimer's disease, MCI and cognitively normal elderly subjects

    PubMed Central

    Duara, Ranjan; Loewenstein, David A.; Shen, Qian; Barker, Warren; Varon, Daniel; Greig, Maria T.; Curiel, Rosie; Agron, Joscelyn; Santos, Isael; Potter, Huntington

    2013-01-01

    Background: New research criteria for diagnosing Alzheimer's disease (AD) in the mild cognitive impairment stage (MCI-AD) incorporate biomarkers to assign a level of certainty to the diagnosis. Structural MRI is widely available but greatly under-utilized for assessing atrophy of structures affected in early AD, such as the hippocampus (HP), because the quantification of HP volumes (HP-v) requires special expertise, and normative values have not been established. Methods: Elderly subjects (n =273) from the Florida ADRC were classified as having no cognitive impairment (cognitively normal, CN), amnestic mild cognitive impairment (aMCI) or AD. Volumes for the hippocampus (HP-v) were measured on structural MRI scans. A validated visual rating system for measuring medial temporal atrophy (VRS-MTA), including hippocampal, entorhinal cortex and perirhinal cortex atrophy was employed. The participants were subdivided into younger (less than or equal to 75 years of age) and older (greater than 75 years of age) subgroups. Results: Volumetric and VRS-MTA measures were equivalent in predicting classification of CN vs. aMCI for older (area under the receiver operator curves [aROC]: 0.652 vs. 0.723) and younger subjects (aROC: 0.764 vs. 0.736). However, for younger AD subjects, aROC values were significantly higher for VRS-MTA measures (0.920) than for volumetric measures (0.847). Relative to HP-v, VRS-MTA score was significantly more correlated to impairment on a range of memory tests and was more associated with progression of aMCI to AD than HP-v. Conclusion: Structural MRI with VRS-MTA assessment can serve as a biomarker for supporting the diagnosis of MCI-AD. Age-adjusted VRS-MTA scores are at least as effective as HP-v for distinguishing aMCI and AD from CN and for predicting progression from aMCI to AD. VRS-MTA is convenient for use in the clinic as well as for clinical trials and can readily be incorporated into a standardized radiological report. PMID:24065917

  19. Clinical features and molecular mechanisms of spinal and bulbar muscular atrophy (SBMA).

    PubMed

    Katsuno, Masahisa; Banno, Haruhiko; Suzuki, Keisuke; Adachi, Hiroaki; Tanaka, Fumiaki; Sobue, Gen

    2010-01-01

    Spinal and bulbar muscular atrophy (SBMA) is an adult-onset neurodegenerative disease characterized by slowly progressive muscle weakness and atrophy. The cause of this disease is the expansion of a trinucleotide CAG repeat, which encodes the polyglutamine tract, within the first exon of the androgen receptor (AR) gene. SBMA exclusively occurs in adult males, whereas both heterozygous and homozygous females are usually asymptomatic. Lower motor neurons in the anterior horn of the spinal cord and those in the brainstem motor nuclei are predominantly affected in SBMA, and other neuronal and nonneuronal tissues are also widely involved to some extent. Testosterone-dependent nuclear accumulation of the pathogenic AR protein has been considered to be a fundamental step of neurodegenerative process, which is followed by several molecular events such as transcriptional dysregulation, axonal transport disruption and mitochondrial dysfunction. Results of animal studies suggest that androgen deprivation and activation of protein quality control systems are potential therapies for SBMA.

  20. Review of Spinal Muscular Atrophy (SMA) for Prenatal and Pediatric Genetic Counselors.

    PubMed

    Carré, Amanda; Empey, Candice

    2016-02-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular condition with degeneration of the anterior horn cells in the spinal column. Five SMA subtypes exist with classification dependent upon the motor milestones achieved. Study of the SMN1 (survival motor neuron) and SMN2 genes as well as the concepts of the "2 + 0" carriers, gene conversion, de novo mutations and intragenic mutations allow for a better understanding of SMA. Detailing the carrier and diagnostic testing options further deepens the genetic counselor's knowledge of SMA. A review of care guidelines and research options is included as this information gives a patient a well-rounded view of SMA. Although SMA is most commonly associated with the SMN1 gene, a number of spinal muscular atrophies not caused by genetic changes in this gene may be included as differential diagnoses until confirmatory testing can be completed. SMA is a complex condition requiring a detailed knowledge on the genetic counselor's part in order to explain the disorder to the patient with clarity thus facilitating increased communication and decision making guidance with the patient.

  1. Muscle Atrophy in Response to Cytotoxic Chemotherapy Is Dependent on Intact Glucocorticoid Signaling in Skeletal Muscle

    PubMed Central

    Braun, Theodore P.; Szumowski, Marek; Levasseur, Peter R.; Grossberg, Aaron J.; Zhu, XinXia; Agarwal, Anupriya; Marks, Daniel L.

    2014-01-01

    Cancer cachexia is a syndrome of weight loss that results from the selective depletion of skeletal muscle mass and contributes significantly to cancer morbidity and mortality. The driver of skeletal muscle atrophy in cancer cachexia is systemic inflammation arising from both the cancer and cancer treatment. While the importance of tumor derived inflammation is well described, the mechanism by which cytotoxic chemotherapy contributes to cancer cachexia is relatively unexplored. We found that the administration of chemotherapy to mice produces a rapid inflammatory response. This drives activation of the hypothalamic-pituitary-adrenal axis, which increases the circulating level of corticosterone, the predominant endogenous glucocorticoid in rodents. Additionally, chemotherapy administration results in a significant loss of skeletal muscle mass 18 hours after administration with a concurrent induction of genes involved with the ubiquitin proteasome and autophagy lysosome systems. However, in mice lacking glucocorticoid receptor expression in skeletal muscle, chemotherapy-induced muscle atrophy is completely blocked. This demonstrates that cytotoxic chemotherapy elicits significant muscle atrophy driven by the production of endogenous glucocorticoids. Further, it argues that pharmacotherapy targeting the glucocorticoid receptor, given in concert with chemotherapy, is a viable therapeutic strategy in the treatment of cancer cachexia. PMID:25254959

  2. Muscle Atrophy Reversed by Growth Factor Activation of Satellite Cells in a Mouse Muscle Atrophy Model

    PubMed Central

    Hauerslev, Simon; Vissing, John; Krag, Thomas O.

    2014-01-01

    Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we demonstrated that myostatin regulates satellite cell activation and myogenesis in vivo following treatment, consistent with previous findings in vitro. Our results suggest, not only a novel in vivo pharmacological treatment directed specifically at activating the satellite cells, but also a myostatin dependent mechanism that may contribute to the progressive muscle wasting seen in severely affected patients with muscular dystrophy and significant on-going regeneration. This treatment could potentially be applied to many conditions that feature muscle wasting to increase muscle bulk and strength. PMID:24963862

  3. Muscle atrophy reversed by growth factor activation of satellite cells in a mouse muscle atrophy model.

    PubMed

    Hauerslev, Simon; Vissing, John; Krag, Thomas O

    2014-01-01

    Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we demonstrated that myostatin regulates satellite cell activation and myogenesis in vivo following treatment, consistent with previous findings in vitro. Our results suggest, not only a novel in vivo pharmacological treatment directed specifically at activating the satellite cells, but also a myostatin dependent mechanism that may contribute to the progressive muscle wasting seen in severely affected patients with muscular dystrophy and significant on-going regeneration. This treatment could potentially be applied to many conditions that feature muscle wasting to increase muscle bulk and strength.

  4. Improving Multiple Fault Diagnosability using Possible Conflicts

    NASA Technical Reports Server (NTRS)

    Daigle, Matthew J.; Bregon, Anibal; Biswas, Gautam; Koutsoukos, Xenofon; Pulido, Belarmino

    2012-01-01

    Multiple fault diagnosis is a difficult problem for dynamic systems. Due to fault masking, compensation, and relative time of fault occurrence, multiple faults can manifest in many different ways as observable fault signature sequences. This decreases diagnosability of multiple faults, and therefore leads to a loss in effectiveness of the fault isolation step. We develop a qualitative, event-based, multiple fault isolation framework, and derive several notions of multiple fault diagnosability. We show that using Possible Conflicts, a model decomposition technique that decouples faults from residuals, we can significantly improve the diagnosability of multiple faults compared to an approach using a single global model. We demonstrate these concepts and provide results using a multi-tank system as a case study.

  5. The language profile of Posterior Cortical Atrophy

    PubMed Central

    Crutch, Sebastian J.; Lehmann, Manja; Warren, Jason D.; Rohrer, Jonathan D.

    2015-01-01

    Background Posterior Cortical Atrophy (PCA) is typically considered to be a visual syndrome, primarily characterised by progressive impairment of visuoperceptual and visuospatial skills. However patients commonly describe early difficulties with word retrieval. This paper details the first systematic analysis of linguistic function in PCA. Characterising and quantifying the aphasia associated with PCA is important for clarifying diagnostic and selection criteria for clinical and research studies. Methods Fifteen patients with PCA, 7 patients with logopenic/phonological aphasia (LPA) and 18 age-matched healthy participants completed a detailed battery of linguistic tests evaluating auditory input processing, repetition and working memory, lexical and grammatical comprehension, single word retrieval and fluency, and spontaneous speech. Results Relative to healthy controls, PCA patients exhibited language impairments across all the domains examined, but with anomia, reduced phonemic fluency and slowed speech rate the most prominent deficits. PCA performance most closely resembled that of LPA patients on tests of auditory input processing, repetition and digit span, but was relatively stronger on tasks of comprehension and spontaneous speech. Conclusions The study demonstrates that in addition to the well-reported degradation of vision, literacy and numeracy, PCA is characterised by a progressive oral language dysfunction with prominent word retrieval difficulties. Overlap in the linguistic profiles of PCA and LPA, which are both most commonly caused by Alzheimer’s disease, further emphasises the notion of a phenotypic continuum between typical and atypical manifestations of the disease. Clarifying the boundaries between AD phenotypes has important implications for diagnosis, clinical trial recruitment and investigations into biological factors driving phenotypic heterogeneity in AD. Rehabilitation strategies to ameliorate the phonological deficit in PCA are required

  6. Intranasal Insulin Prevents Cognitive Decline, Cerebral Atrophy and White Matter Changes in Murine Type I Diabetic Encephalopathy

    ERIC Educational Resources Information Center

    Francis, George J.; Martinez, Jose A.; Liu, Wei Q.; Xu, Kevin; Ayer, Amit; Fine, Jared; Tuor, Ursula I.; Glazner, Gordon; Hanson, Leah R.; Frey, William H., II; Toth, Cory

    2008-01-01

    Insulin deficiency in type I diabetes may lead to cognitive impairment, cerebral atrophy and white matter abnormalities. We studied the impact of a novel delivery system using intranasal insulin (I-I) in a mouse model of type I diabetes (streptozotocin-induced) for direct targeting of pathological and cognitive deficits while avoiding potential…

  7. Cortical sensory loss in a patient with posterior cortical atrophy: a case report.

    PubMed

    Hsu, Jung-Lung; Chen, Wei-Hung; Chiu, Hou-Chang

    2004-02-01

    Patients with posterior cortical atrophy (PCA) who present with initial symptoms of higher visual function deficits eventually develop alexia, aphasia, and components of Balint's syndrome or Gerstmann's syndrome. Recently, pathological findings were reported for these patients that are generally suggestive of Alzheimer's disease even though Creutzfeldt-Jakob disease (CJD) was presumed as an alternative cause of some autopsy-diagnosed PCA cases. Here, we report a case with a four-year progression of cognitive and higher visual function deterioration, and with features not described in previously reported PCA cases (i.e., a distinct sensory complaint and early frontal lobe involvement). To summarize, this case belongs to perceptual-motor syndrome of asymmetric cortical degeneration and the underlying neuropathology is more suggestive of Alzheimer's disease than of Creutzfeldt-Jakob disease.

  8. Spinal muscular atrophy with respiratory distress syndrome (SMARD1): Case report and review of literature

    PubMed Central

    Lingappa, Lokesh; Shah, Nikit; Motepalli, Ananth Sagar; Shaik, Farhan

    2016-01-01

    Spinal muscular atrophy with respiratory distress syndrome (SMARD1) is a rare cause of early infantile respiratory failure and death. No cases have been currently described from India. Two low-birth-weight infants presented prior to 6 months of age with recurrent apnea and respiratory distress. Both required prolonged ventilation, and had distal arthrogryposis and diaphragmatic eventration. Nerve conduction study revealed motor sensory axonopathy. Genetic testing confirmed mutations in immunoglobulin mu binding protein (IGHMBP2). These two cases establish presence of SMARD1 in our population. Both infants died on discontinuation of ventilation. Antenatal diagnoses done in one pregnancy. Though rare, high index of suspicion is essential in view of poor outcome and aid antenatal counseling. PMID:27570397

  9. Discrepancy between clinical and pathological diagnoses of CBD and PSP.

    PubMed

    Mizuno, Toshiki; Shiga, Kensuke; Nakata, Yuriko; Nagura, Junko; Nakase, Taizen; Ueda, Yoshihiro; Takanashi, Yoshiaki; Urasaki, Kohji; Oyamada, Yumiko; Fushiki, Shinji; Nishikawa, Junji; Yasuhara, Masahiro; Nakajima, Kenji; Nakagawa, Masanori

    2005-06-01

    Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are often clinically confused with each other. Moreover, the discrepancy between clinical and pathological diagnoses of CBD and PSP are still controversial. We report here two atypical cases of PSP and CBD. A 73-year old woman was admitted with right hand rigidity, limb kinetic apraxia and cortical sensory loss. Brain atrophy, hypoperfusion and hypometabolism predominantly in the left frontoparietal lobes indicated CBD clinically. Pathological studies revealed neuronal loss and spongy change without ballooned neurons (BN) in the cerebral cortex. Modified Gallyas-Braak (G-B) staining revealed neurofibrillary tangles (NFTs) and tufted astrocytes, indicating pathological diagnosis of PSP. A 75-year-old man admitted with vertical gaze palsy, neck dystonia, parkinsonism and dementia. Atrophy of the frontal lobes and tegmentum of the midbrain and symmetrical frontal hypoperfusion in SPECT indicated PSP. However, neuronal loss and BN in the frontal lobes and clusters of astrocytic plaques indicated CBD pathologically. The G-B staining was useful for differentiating between CBD and PSP, but our atypical cases bring up a new issue about differential diagnosis of CBD and PSP.

  10. Neural correlates of cognitive impairment in posterior cortical atrophy.

    PubMed

    Kas, Aurélie; de Souza, Leonardo Cruz; Samri, Dalila; Bartolomeo, Paolo; Lacomblez, Lucette; Kalafat, Michel; Migliaccio, Raffaella; Thiebaut de Schotten, Michel; Cohen, Laurent; Dubois, Bruno; Habert, Marie-Odile; Sarazin, Marie

    2011-05-01

    With the prospect of disease-modifying drugs that will target the physiopathological process of Alzheimer's disease, it is now crucial to increase the understanding of the atypical focal presentations of Alzheimer's disease, such as posterior cortical atrophy. This study aimed to (i) characterize the brain perfusion profile in posterior cortical atrophy using regions of interest and a voxel-based approach; (ii) study the influence of the disease duration on the clinical and imaging profiles; and (iii) explore the correlations between brain perfusion and cognitive deficits. Thirty-nine patients with posterior cortical atrophy underwent a specific battery of neuropsychological tests, mainly targeting visuospatial functions, and a brain perfusion scintigraphy with 99mTc-ethyl cysteinate dimer. The imaging analysis included a comparison with a group of 24 patients with Alzheimer's disease, matched for age, disease duration and Mini-Mental State Examination, and 24 healthy controls. The single-photon emission computed tomography profile in patients with posterior cortical atrophy was characterized by extensive and severe hypoperfusion in the occipital, parietal, posterior temporal cortices and in a smaller cortical area corresponding to the frontal eye fields (Brodmann areas 6/8). Compared with patients with Alzheimer's disease, the group with posterior cortical atrophy showed more severe occipitoparietal hypoperfusion and higher perfusion in the frontal, anterior cingulate and mesiotemporal regions. When considering the disease duration, the functional changes began and remained centred on the posterior lobes, even in the late stage. Correlation analyses of brain perfusion and neuropsychological scores in posterior cortical atrophy highlighted the prominent role of left inferior parietal damage in acalculia, Gerstmann's syndrome, left-right indistinction and limb apraxia, whereas damage to the bilateral dorsal occipitoparietal regions appeared to be involved in B

  11. On the atrophy of the internal carotid artery in capybara.

    PubMed

    Steele, Caroline; Fioretto, Emerson T; Sasahara, Tais H C; Guidi, Wanderley L; de Lima, Ana R; Ribeiro, Antonio A C M; Loesch, Andrzej

    2006-12-01

    Capybara might be a useful model for studying changes in cerebral circulation as the natural atrophy of the internal carotid artery (ICA) occurs in this animal at maturation. In this study, confocal and electron microscopy combined with immunohistochemical techniques were applied in order to reveal the changes in morphology and innervation to the proximal part of ICA in young (6-month-old) and mature (12-month-old) capybaras. Some features of the basilar artery (BA) were also revealed. The ICA of young animals degenerated to a ligamentous cord in mature animals. Immunolabelling positive for pan-neuronal marker protein gene product 9.5 but negative for tyrosine hydroxylase was observed in the proximal part of ICA at both ages examined. Axon varicosities positive for synaptophysin were present in the adventitia of ICA of young animals but were absent in the ligamentous cord of mature animals. In the ICA of young animals, adventitial connective tissue invaded the media suggesting that the process of regression of this artery began within the first 6 months of life. An increase in size of the BA was found in mature animals indicating increased blood flow in the vertebro-basilar system, possibly making capybara susceptible to cerebrovascular pathology (e.g. stroke). Capybara may therefore provide a natural model for studying adaptive responses to ICA regression/occlusion.

  12. Moving towards treatments for spinal muscular atrophy: hopes and limits.

    PubMed

    Wirth, Brunhilde; Barkats, Martine; Martinat, Cecile; Sendtner, Michael; Gillingwater, Thomas H

    2015-09-01

    Spinal muscular atrophy (SMA), one of the most frequent and devastating genetic disorders causing neuromuscular degeneration, has reached the forefront of clinical translation. The quite unique genetic situation of SMA patients, who lack functional SMN1 but carry the misspliced SMN2 copy gene, creates the possibility of correcting SMN2 splicing by antisense oligonucleotides or drugs. Both strategies showed impressive results in pre-clinical trials and are now in Phase II-III clinical trials. SMN gene therapy approaches using AAV9-SMN vectors are also highly promising and have entered a Phase I clinical trial. However, careful analysis of SMA animal models and patients has revealed some limitations that need to be taken very seriously, including: i) a limited time-window for successful therapy delivery, making neonatal screening of SMA mandatory; ii) multi-organ impairment, requiring systemic delivery of therapies; and iii) a potential need for combined therapies that both increase SMN levels and target pathways that preserve/rescue motor neuron function over the lifespan. Meeting these challenges will likely be crucial to cure SMA, instead of only ameliorating symptoms, particularly in its most severe form. This review discusses therapies currently in clinical trials, the hopes for SMA therapy, and the potential limitations of these new approaches.

  13. The protective effect of dexpanthenol on testicular atrophy at 60th day following experimental testicular torsion.

    PubMed

    Etensel, Barlas; Ozkisacik, Sezen; Ozkara, Esra; Serbest, Yeşim Aksu; Oztan, Onur; Yazici, Mesut; Gürsoy, Harun

    2007-03-01

    Despite the prompt diagnosis and treatment of testicular torsion (TT), there are problems with fertility and atrophy after testicular salvage. Dexpanthenol (Dxp) is the biologically active alcohol of pantothenic acid (PA). Dxp is converted to PA in tissues. PA increases the content of reduced glutathione (GSH), Coenzyme A and ATP synthesis in cells. GSH and glutathione-dependent peroxidases (GPX) are the major defense systems against oxidative stress. GPX-4 is the major antioxidant in testicular tissue. However, the activity of GPX-4 appeared and increased only after puberty. We investigated the effect of Dxp on testicular atrophy after TT at the 60th day. Rats were separated randomly into four groups. Group C: control group, group Td: torsion + detorsion, group Sal: torsion + saline + detorsion, group Dxp: torsion + Dxp + detorsion. The left testis was rotated 720 degrees for 2 h. In group Sal, normal saline and in group Dxp, Dexpanthenol were injected intraperitonally, 30 min before detorsion. After 60 days, the testicular weights and volumes were measured. Histopathology of the left testis was evaluated with mean seminiferous tubular diameter (MSTD) and mean testicular biopsy score (MTBS). The left (torsed) testicular weight and volume of groups Td and Sal were significantly lower compared to group Dxp. The MSTD and MTBS of group Td and Sal were significantly lower than group Dxp. Contralateral testicular weight and volume of groups Td, Sal and Dxp had no significant difference compared to the control group. Dxp significantly prevented testicular atrophy after 60 days of TT. Dxp has FDA approval, is safe, cost effective and readily available. Its relevance for clinical trials may especially be for the problem of testicular atrophy catastrophe, seen very frequently following testicular salvage.

  14. Postural muscle atrophy prevention and recovery and bone remodelling through high frequency proprioception for astronauts

    NASA Astrophysics Data System (ADS)

    Riva, Dario; Rossitto, Franco; Battocchio, Luciano

    2009-09-01

    The difficulty in applying active exercises during space flights increases the importance of passive countermeasures, but coupling load and instability remains indispensable for generating high frequency (HF) proprioceptive flows and preventing muscle atrophy and osteoporosis. The present study, in microgravity conditions during a parabolic flight, verified whether an electronic system, composed of a rocking board, a postural reader and a bungee-cord loading apparatus creates HF postural instability comparable to that reachable on the Earth. Tracking the subject, in single stance, to real-time visual signals is necessary to obtain HF instability situations. The bungee-cord loading apparatus allowed the subject to manage the 81.5% body weight load (100% could easily be exceeded). A preliminary training programme schedule on the Earth and in space is suggested. Comparison with a pathological muscle atrophy is presented. The possibility of generating HF proprioceptive flows could complement current countermeasures for the prevention and recovery of muscle atrophy and osteoporosis in terrestrial and space environments. These exercises combine massive activation of spindles and joint receptors, applying simultaneously HF variations of pressure to different areas of the sole of the foot. This class of exercises could improve the effectiveness of current countermeasures, reducing working time and fatigue.

  15. Treating dyspareunia caused by vaginal atrophy: a review of treatment options using vaginal estrogen therapy

    PubMed Central

    Kingsberg, SA; Kellogg, S; Krychman, M

    2010-01-01

    Vulvovaginal atrophy (VVA) and dryness are common symptoms of the decline in endogenous production of estrogen at menopause and often result in dyspareunia. Yet while 10% to 40% of women experience discomfort due to VVA, it is estimated that only 25% seek medical help. The main goals of treatment for vaginal atrophy are to improve symptoms and to restore vaginal and vulvar anatomic changes. Treatment choices for postmenopausal dyspareunia resulting from vulvovaginal atrophy will depend on the underlying etiology and might include individualized treatment. A number of forms of vaginal estrogen and manner of delivery are currently available to treat moderate to severe dyspareunia caused by VVA. They all have been shown to be effective and are often the preferred treatment due to the targeted efficacy for urogenital tissues while resulting in only minimal systemic absorption. Both healthcare professionals and patients often find it difficult to broach the subject of sexual problems associated with VVA. However, with minimal effort to initiate a conversation about these problems, healthcare providers can provide useful information to their postmenopausal patients in order to help them each choose the optimal treatment for their needs and symptoms. PMID:21072280

  16. Topical KGF treatment as a therapeutic strategy for vaginal atrophy in a model of ovariectomized mice

    PubMed Central

    Ceccarelli, Simona; D'Amici, Sirio; Vescarelli, Enrica; Coluccio, Paolo; Matricardi, Pietro; di Gioia, Cira; Benedetti Panici, Pierluigi; Romano, Ferdinando; Frati, Luigi; Angeloni, Antonio; Marchese, Cinzia

    2014-01-01

    One of the most frequent complaints for post-menopausal women is vaginal atrophy, because of reduction in circulating oestrogens. Treatments based on local oestrogen administration have been questioned as topic oestrogens can reach the bloodstream, thus leading to consider their safety as controversial, especially for patients with a history of breast or endometrial cancers. Recently, growth factors have been shown to interact with the oestrogen pathway, but the mechanisms still need to be fully clarified. In this study, we investigated the effect of keratinocyte growth factor (KGF), a known mitogen for epithelial cells, on human vaginal mucosa cells, and its potential crosstalk with oestrogen pathways. We also tested the in vivo efficacy of KGF local administration on vaginal atrophy in a murine model. We demonstrated that KGF is able to induce proliferation of vaginal mucosa, and we gained insight on its mechanism of action by highlighting its contribution to switch ERα signalling towards non-genomic pathway. Moreover, we demonstrated that KGF restores vaginal trophism in vivo similarly to intravaginal oestrogenic preparations, without systemic effects. Therefore, we suggest a possible alternative therapy for vaginal atrophy devoid of the risks related to oestrogen-based treatments, and a patent (no. RM2012A000404) has been applied for this study. PMID:25088572

  17. Initial basal cell carcinomas diagnosed in the National Campaign for Skin Cancer Prevention are smaller than those identified by the conventional medical referral system*

    PubMed Central

    Wakiyama, Thweicyka Pinheiro; França, Maria Laura Marconi; Carvalho, Larissa Pierri; Marques, Mariangela Esther Alencar; Miot, Hélio Amante; Schmitt, Juliano Vilaverde

    2017-01-01

    BACKGROUND Basal cell carcinoma is the malignant tumor most often diagnosed in the National Campaign for Skin Cancer Prevention (NCSCP). Little is known about the profile of these lesions compared to the profile of lesions diagnosed by conventional routes of public dermatological care. OBJECTIVE To identify if basal cell carcinomas identified in prevention campaigns and referred to surgery are smaller than those routinely removed in a same medical institution. METHODS Cross-sectional study including tumors routed from 2011-2014 campaigns and 84 anatomopathological reports of outpatients. RESULTS The campaigns identified 223 individuals with suspicious lesions among 2,531 examinations (9%), with 116 basal cell carcinomas removed. Anatomopathological examinations revealed that the primary lesions identified in the national campaigns were smaller than those referred to surgery by the conventional routes of public health care (28 [13-50] x 38 [20-113] mm2, p <0.01). On the other hand, after a mean follow-up of 15.6 ± 10.3 months, 31% of cases identified in campaigns showed new basal cell carcinoma lesions. STUDY LIMITATIONS Retrospective study and inaccuracies in the measurements of the lesions. CONCLUSIONS The NCSCP promotes an earlier treatment of basal cell carcinomas compared to patients referred to surgery by the conventional routes of public health care, which can result in lower morbidity rates and better prognosis. PMID:28225952

  18. How Is Aplastic Anemia Diagnosed?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Aplastic Anemia Diagnosed? Your doctor will diagnose aplastic anemia based on your medical and family histories, a ... your primary care doctor thinks you have aplastic anemia, he or she may refer you to a ...

  19. Left ventricular noncompaction diagnosed following Graves' disease

    PubMed Central

    Habib, Habib; Hawatmeh, Amer; Rampal, Upamanyu; Shamoon, Fayez

    2016-01-01

    Isolated left ventricular noncompaction (LVNC) is a rare genetic cardiomyopathy. Clinical manifestations are variable; patients may present with heart failure symptoms, arrhythmias, and systemic thromboembolism. However, it can also be asymptomatic. When asymptomatic, LVNC can manifest later in life after the onset of another unrelated condition. We report a case of LVNC which was diagnosed following a hyperthyroid state secondary to Graves' disease. The association of LVNC with other noncardiac abnormalities including neurological, hematological, and endocrine abnormalities including hypothyroidism has been described in isolated case reports before. To the best of our knowledge, this is the first reported case of LVNC diagnosed following exacerbation in contractile dysfunction triggered by Graves' disease. PMID:27843800

  20. Predictive modeling of neuroanatomic structures for brain atrophy detection

    NASA Astrophysics Data System (ADS)

    Hu, Xintao; Guo, Lei; Nie, Jingxin; Li, Kaiming; Liu, Tianming

    2010-03-01

    In this paper, we present an approach of predictive modeling of neuroanatomic structures for the detection of brain atrophy based on cross-sectional MRI image. The underlying premise of applying predictive modeling for atrophy detection is that brain atrophy is defined as significant deviation of part of the anatomy from what the remaining normal anatomy predicts for that part. The steps of predictive modeling are as follows. The central cortical surface under consideration is reconstructed from brain tissue map and Regions of Interests (ROI) on it are predicted from other reliable anatomies. The vertex pair-wise distance between the predicted vertex and the true one within the abnormal region is expected to be larger than that of the vertex in normal brain region. Change of white matter/gray matter ratio within a spherical region is used to identify the direction of vertex displacement. In this way, the severity of brain atrophy can be defined quantitatively by the displacements of those vertices. The proposed predictive modeling method has been evaluated by using both simulated atrophies and MRI images of Alzheimer's disease.

  1. Intrathecal Injections in Children With Spinal Muscular Atrophy

    PubMed Central

    Swoboda, Kathryn J.; Sethna, Navil; Farrow-Gillespie, Alan; Khandji, Alexander; Xia, Shuting; Bishop, Kathie M.

    2016-01-01

    Nusinersen (ISIS-SMNRx or ISIS 396443) is an antisense oligonucleotide drug administered intrathecally to treat spinal muscular atrophy. We summarize lumbar puncture experience in children with spinal muscular atrophy during a phase 1 open-label study of nusinersen and its extension. During the studies, 73 lumbar punctures were performed in 28 patients 2 to 14 years of age with type 2/3 spinal muscular atrophy. No complications occurred in 50 (68%) lumbar punctures; in 23 (32%) procedures, adverse events were attributed to lumbar puncture. Most common adverse events were headache (n = 9), back pain (n = 9), and post–lumbar puncture syndrome (n = 8). In a subgroup analysis, adverse events were more frequent in older children, children with type 3 spinal muscular atrophy, and with a 21- or 22-gauge needle compared to a 24-gauge needle or smaller. Lumbar punctures were successfully performed in children with spinal muscular atrophy; lumbar puncture–related adverse event frequency was similar to that previously reported in children. PMID:26823478

  2. Early and Degressive Putamen Atrophy in Multiple Sclerosis.

    PubMed

    Krämer, Julia; Meuth, Sven G; Tenberge, Jan-Gerd; Schiffler, Patrick; Wiendl, Heinz; Deppe, Michael

    2015-09-25

    Putamen atrophy and its long-term progress during disease course were recently shown in patients with multiple sclerosis (MS). Here we investigated retrospectively the time point of atrophy onset in patients with relapsing-remitting MS (RRMS). 68 patients with RRMS and 26 healthy controls (HC) were admitted to 3T MRI in a cross-sectional study. We quantitatively analyzed the putamen volume of individual patients in relation to disease duration by correcting for age and intracranial volume (ICV). Patient's relative putamen volume (RPV), expressed in percent of ICV, was significantly reduced compared to HC. Based on the correlation between RPV and age, we computed the age-corrected RPV deviation (ΔRPV) from HC. Patients showed significantly negative ΔRPV. Interestingly, the age-corrected ΔRPV depended logarithmically on disease duration: Directly after first symptom manifestation, patients already showed a reduced RPV followed by a further degressive volumetric decline. This means that atrophy progression was stronger in the first than in later years of disease. Putamen atrophy starts directly after initial symptom manifestation or even years before, and progresses in a degressive manner. Due to its important role in neurological functions, early detection of putamen atrophy seems necessary. High-resolution structural MRI allows monitoring of disease course.

  3. Congenital segmental spinal muscular atrophy: a case report.

    PubMed

    Savaş, Tülin; Erol, Ilknur; Özkale, Yasemin; Saygi, Semra

    2015-03-01

    Spinal muscular atrophies are genetic disorders in which anterior horn cells in the spinal cord and motor nuclei of the brainstem are progressively lost. We present a patient with arthrogryposis due to congenital spinal muscular atrophy predominantly affecting the upper limbs. Spinal muscular atrophies with onset at birth may be a cause of arthrogryposis. Localized forms of neurogenic arthrogryposis have been divided into cervical and caudal forms. Our case is similar to the cases described by Hageman et al (J Neurol Neurosurg Psychiatry 1993;56:365-368): severe symmetric lower motor neuron deficit in the upper extremities at the time of birth, no history of injury to the cervical spinal cord or the brachial plexus during delivery, and severe muscle wasting suggesting chronic denervation in utero. Because there was improvement of our patient's situation, her disease was also possibly nonprogressive and sporadic. To our knowledge, this is the first reported case of a Turkish patient with congenital cervical spinal muscular atrophy. Congenital cervical spinal muscular atrophy affecting predominantly the upper limbs is a relatively rare form of motor neuron disease and should be considered in the differential diagnosis of infants with congenital contractures and severe muscle weakness by wasting mainly confined to the upper limbs.

  4. Neuroblastoma in Children: Just Diagnosed Information

    MedlinePlus

    ... Other Press Room Employment Feedback Contact Select Page Neuroblastoma in Children – Just Diagnosed Home > Cancer Resources > Types ... Diagnosed Just Diagnosed In Treatment After Treatment Diagnosing Neuroblastoma Depending on the location of the tumor and ...

  5. Diagnosing Intermittent and Persistent Faults using Static Bayesian Networks

    NASA Technical Reports Server (NTRS)

    Megshoel, Ole Jakob

    2010-01-01

    Both intermittent and persistent faults may occur in a wide range of systems. We present in this paper the introduction of intermittent fault handling techniques into ProDiagnose, an algorithm that previously only handled persistent faults. We discuss novel algorithmic techniques as well as how our static Bayesian networks help diagnose, in an integrated manner, a range of intermittent and persistent faults. Through experiments with data from the ADAPT electrical power system test bed, generated as part of the Second International Diagnostic Competition (DXC-10), we show that this novel variant of ProDiagnose diagnoses intermittent faults accurately and quickly, while maintaining strong performance on persistent faults.

  6. Primary ileal villous atrophy is often associated with microscopic colitis

    PubMed Central

    Marteau, P; Lavergne-Slove, A; Lemann, M; Bouhnik, Y; Bertheau, P; Becheur, H; Galian, A; Rambaud, J

    1997-01-01

    Three cases of apparent primary villous atrophy of the terminal ileum in women with chronic diarrhoea are reported. Eight cases have previously been reported in the literature. Clinical characteristics are the presence of severe chronic secretory diarrhoea with episodes of hypokalaemia combined with signs of ileal malabsorption and/or efficacy of cholestyramine. Diagnosis is based on ileoscopy and histology. An association with microscopic colitis was present in the three patients and in four cases in the literature. The pathogenesis of primary ileal villous atrophy remains unknown and may involve dysimmunity. Its association with microscopic colitis may indicate a common pathogenesis or support the hypothesis that the faecal stream or bile salts play a role in the pathogenesis of microscopic colitis. 

 Keywords: intestinal villous atrophy; ileum; secretory diarrhoea; bile acid malabsorption; microscopic colitis PMID:9391260

  7. Spinal cord gray matter atrophy correlates with multiple sclerosis disability

    PubMed Central

    Schlaeger, Regina; Papinutto, Nico; Panara, Valentina; Bevan, Carolyn; Lobach, Iryna V.; Bucci, Monica; Caverzasi, Eduardo; Gelfand, Jeffrey M.; Green, Ari J.; Jordan, Kesshi M.; Stern, William A.; von Büdingen, H.-Christian; Waubant, Emmanuelle; Zhu, Alyssa H.; Goodin, Douglas S.; Cree, Bruce A. C.; Hauser, Stephen L.; Henry, Roland G.

    2015-01-01

    Objective In multiple sclerosis (MS) cerebral gray matter (GM) atrophy correlates more strongly than white matter (WM) atrophy with disability. The corresponding relationships in the spinal cord (SC) are unknown due to technical limitations in assessing SCGM atrophy. Using phase sensitive inversion recovery (PSIR) MRI, we determined the association of the SCGM and SCWM areas with MS disability and disease type. Methods 113 MS patients and 20 healthy controls were examined at 3T with a PSIR sequence acquired at the C2/C3 disc level. Two independent, clinically-masked readers measured the cord WM and GM areas. Correlations between cord areas and Expanded Disability Status Score (EDSS) were determined. Differences in areas between groups were assessed with age and sex as covariates. Results Relapsing (R) MS patients showed smaller SCGM areas than age and sex matched controls (p=0.008) without significant differences in SCWM areas. Progressive MS patients showed smaller SCGM and SCWM areas compared to RMS patients (all p≤0.004). SCGM, SCWM, and whole cord areas inversely correlated with EDSS (rho: −0.60, −0.32, −0.42, respectively; all p≤0.001). SCGM area was the strongest correlate of disability in multivariate models including brain GM and WM volumes, FLAIR lesion load, T1-lesion load, SCWM area, number of spinal cord T2 lesions, age, sex, disease duration. Brain and spinal GM independently contributed to EDSS. Interpretation SCGM atrophy is detectable in-vivo in absence of WM atrophy in RMS. It is more pronounced in progressive than RMS and contributes more to patient disability than spinal cord WM or brain GM atrophy. PMID:25087920

  8. Vulvar and Vaginal Atrophy: Physiology, Clinical Presentation, and Treatment Considerations.

    PubMed

    Lev-Sagie, Ahinoam

    2015-09-01

    Vulvovaginal atrophy is a common condition associated with decreased estrogenization of the vaginal tissue. Symptoms include vaginal dryness, irritation, itching, soreness, burning, dyspareunia, discharge, urinary frequency, and urgency. It can occur at any time in a woman's life cycle, although more commonly in the postmenopausal phase, during which the prevalence is approximately 50%. Despite the high prevalence and the substantial effect on quality of life, vulvovaginal atrophy often remains underreported and undertreated. This article aims to review the physiology, clinical presentation, assessment, and current recommendations for treatment, including aspects of effectiveness and safety of local vaginal estrogen therapies.

  9. From alveolar diffuse atrophy to aggressive periodontitis: a brief history.

    PubMed

    Guzeldemir, Esra; Toygar, Hilal Uslu

    2006-01-01

    Technologic advances in mechanics, electronics, physics, chemistry, and computer science have contributed to advances in dental medicine. Periodontology is not only a clinical science but is also directly related to the basic sciences. Research is conducted in laboratories rather than in clinics now. During the last century, aggressive periodontitis has received attention from numerous researchers because of its multifactorial features. This paper explores the long scientific journey of aggressive periodontitis, beginning with its first definition as alveolar diffuse atrophy. Perhaps in the future, "alveolar diffuse atrophy" will be referred to by another name or term. However, this journey will never end.

  10. Congenital contractural arachnodactyly with neurogenic muscular atrophy: case report.

    PubMed

    Scola, R H; Werneck, L C; Iwamoto, F M; Ribas, L C; Raskin, S; Correa Neto, Y

    2001-06-01

    We report the case of a 3-(1/2)-year-old girl with hypotonia, multiple joint contractures, hip luxation, arachnodactyly, adducted thumbs, dolichostenomelia, and abnormal external ears suggesting the diagnosis of congenital contractural arachnodactyly (CCA). The serum muscle enzymes were normal and the needle electromyography showed active and chronic denervation. The muscle biopsy demonstrated active and chronic denervation compatible with spinal muscular atrophy. Analysis of exons 7 and 8 of survival motor neuron gene through polymerase chain reaction did not show deletions. Neurogenic muscular atrophy is a new abnormality associated with CCA, suggesting that CCA is clinically heterogeneous.

  11. Antral atrophy, intestinal metaplasia, and preneoplastic markers in Mexican children with Helicobacter pylori-positive and Helicobacter pylori-negative gastritis.

    PubMed

    Villarreal-Calderon, Rodolfo; Luévano-González, Arturo; Aragón-Flores, Mariana; Zhu, Hongtu; Yuan, Ying; Xiang, Qun; Yan, Benjamin; Stoll, Kathryn Anne; Cross, Janet V; Iczkowski, Kenneth A; Mackinnon, Alexander Craig

    2014-06-01

    Chronic inflammation and infection are major risk factors for gastric carcinogenesis in adults. As chronic gastritis is common in Mexican children, diagnosis of Helicobacter pylori and other causes of gastritis are critical for the identification of children who would benefit from closer surveillance. Antral biopsies from 82 Mexican children (mean age, 8.3 ± 4.8 years) with chronic gastritis (36 H pylori+, 46 H pylori-) were examined for gastritis activity, atrophy, intestinal metaplasia (IM), and immunohistochemical expression of gastric carcinogenesis biomarkers caudal type homeobox 2 (CDX2), ephrin type-B receptor 4 (EphB4), matrix metalloproteinase 3 (MMP3), macrophage migration inhibitory factor (MIF), p53, β-catenin, and E-cadherin. Atrophy was diagnosed in 7 (9%) of 82, and IM, in 5 (6%) of 82 by routine histology, whereas 6 additional children (7%) (3 H pylori+) exhibited aberrant CDX2 expression without IM. Significant positive correlations were seen between EphB4, MMP3, and MIF (P<.0001). Atrophy and follicular pathology were more frequent in H pylori+ biopsies (P<.0001), whereas IM and CDX2 expression showed no significant correlation with H pylori status. Antral biopsies demonstrating atrophy, IM, and/or aberrant CDX2 expression were seen in 21.95% (18/82) of the children, potentially identifying those who would benefit from closer surveillance and preventive dietary strategies. Biomarkers CDX2, EphB4, MMP3, and MIF may be useful in the workup of pediatric gastritis.

  12. How Is Stomach Cancer Diagnosed?

    MedlinePlus

    ... Cancer Early Detection, Diagnosis, and Staging How Is Stomach Cancer Diagnosed? Stomach cancers are usually found when ... Ask Your Doctor About Stomach Cancer? More In Stomach Cancer About Stomach Cancer Causes, Risk Factors, and ...

  13. How Is Childhood Leukemia Diagnosed?

    MedlinePlus

    ... Early Detection, Diagnosis, and Types How Is Childhood Leukemia Diagnosed? Most of the signs and symptoms of ... enlarged spleen or liver. Tests to look for leukemia in children If the doctor thinks your child ...

  14. How Is Pulmonary Embolism Diagnosed?

    MedlinePlus

    ... Doctors can use computed tomography (to-MOG-rah-fee) scans, or CT scans, to look for blood ... Pulmonary Angiography Pulmonary angiography (an-jee-OG-rah-fee) is another test used to diagnose PE. This ...

  15. How Is Atrial Fibrillation Diagnosed?

    MedlinePlus

    ... event monitor for weeks or until symptoms occur. Stress Test Some heart problems are easier to diagnose ... heart is working hard and beating fast. During stress testing , you exercise to make your heart work ...

  16. How Are Wilms Tumors Diagnosed?

    MedlinePlus

    ... Tumor Early Detection, Diagnosis, and Staging How Are Wilms Tumors Diagnosed? Wilms tumors are usually found when a ... Your Child’s Doctor About Wilms Tumor? More In Wilms Tumor About Wilms Tumor Causes, Risk Factors, and Prevention ...

  17. Histological characteristics following a long-term nitrate-rich diet in miniature pigs with parotid atrophy.

    PubMed

    Xia, Dengsheng; Qu, Xingmin; Tran, Simon D; Schmidt, Laura L; Qin, Lizheng; Zhang, Chunmei; Cui, Xiuyu; Deng, Dajun; Wang, Songlin

    2015-01-01

    The aim of this study was to investigate the histological characteristics following a 2-year nitrate-rich diet in miniature pigs with parotid atrophy. Using averages collected data from three time points at 6, 12, and 24 months following the induction of parotid gland atrophy, salivary nitrate levels of the nitrate-diet parotid-atrophied group (17.3 ± 3.9 ng/µl) were close to those of the control group (19.6 ± 5.1 ng/µl). Compared to the control group, the nitrate-diet group had significantly higher nitrate levels in blood (P < 0.05) and urine (P < 0.001). Histological and electron microscopy analyses showed no abnormalities in the organs of experimental or control animals. No significant differences on apoptosis rate were found in liver and kidney tissues between the standard- and nitrate-diet groups. Therefore, dietary nitrate supplementation could restore salivary nitrate levels. High-dose nitrate loading for 2 years had no observed systemic toxicity in miniature pigs with parotid atrophy.

  18. DIAGNOSING CIRCUMSTELLAR DEBRIS DISKS

    SciTech Connect

    Hahn, Joseph M.

    2010-08-20

    A numerical model of a circumstellar debris disk is developed and applied to observations of the circumstellar dust orbiting {beta} Pictoris. The model accounts for the rates at which dust is produced by collisions among unseen planetesimals, and the rate at which dust grains are destroyed due to collisions. The model also accounts for the effects of radiation pressure, which is the dominant perturbation on the disk's smaller but abundant dust grains. Solving the resulting system of rate equations then provides the dust abundances versus grain size and dust abundances over time. Those solutions also provide the dust grains' collisional lifetime versus grain size, and the debris disk's optical depth and surface brightness versus distance from the star. Comparison to observations then yields estimates of the unseen planetesimal disk's radius, and the rate at which the disk sheds mass due to planetesimal grinding. The model can also be used to measure or else constrain the dust grain's physical and optical properties, such as the dust grains' strength, their light-scattering asymmetry parameter, and the grains' efficiency of light scattering Q{sub s}. The model is then applied to optical observations of the edge-on dust disk orbiting {beta} Pictoris, and good agreement is achieved when the unseen planetesimal disk is broad, with 75 {approx}< r {approx}< 150 AU. If it is assumed that the dust grains are bright like Saturn's icy rings (Q{sub s} = 0.7), then the cross section of dust in the disk is A{sub d} {approx_equal} 2 x 10{sup 20} km{sup 2} and its mass is M{sub d} {approx_equal} 11 lunar masses. In this case, the planetesimal disk's dust-production rate is quite heavy, M-dot {sub d{approx}}9 M {sub +} Myr{sup -1}, implying that there is or was a substantial amount of planetesimal mass there, at least 110 Earth masses. If the dust grains are darker than assumed, then the planetesimal disk's mass-loss rate and its total mass are heavier. In fact, the apparent dearth

  19. Are Pediatricians Diagnosing Obese Children?

    PubMed Central

    Thomas, Katharine; Urrego, Fernando

    2017-01-01

    Background: Pediatric obesity is the most prevalent nutritional disorder in American children. The detrimental social, psychological, and physiological effects of obesity call for pediatricians to address this health concern. The literature demonstrates that clinicians are underreporting the diagnosis of obesity in the pediatric setting. The primary purpose of this study was to determine if pediatricians at one pediatrics clinic in the Ochsner Health System are documenting the presence of an overweight or obese body mass index (BMI) as a diagnosis in the medical record. A secondary purpose of this study was to determine the demographics of all pediatric patients in the Ochsner Health System to be used for program development. Methods: A retrospective medical record review was conducted. Records from April 1, 2012 to April 1, 2016, were reviewed for the presence of the diagnosis of BMI classified as obese or overweight. Results: We analyzed a total of 175,066 records in this study. Of these records, 1.32% documented a diagnosis of obesity, and 0.5% documented a BMI score indicating overweight. The percentages of patient visits that met the Centers for Disease Control and Prevention criteria to be classified as obese or overweight were 28.66% and 30.41%, respectively. The majority of our pediatric patients were male (51.76%), white (43.31%), and 5-12 years old (43.80%). Conclusion: This study demonstrates that pediatricians at Ochsner Health Center for Children are not diagnosing patients who have unhealthy BMI scores as overweight or obese. Interventions are needed to increase the identification of children who may benefit from receiving resources that encourage a healthy lifestyle and optimal weight maintenance. PMID:28331453

  20. Progressive biparietal atrophy: an atypical presentation of Alzheimer's disease.

    PubMed Central

    Ross, S J; Graham, N; Stuart-Green, L; Prins, M; Xuereb, J; Patterson, K; Hodges, J R

    1996-01-01

    OBJECTIVES: To define the clinical, neuropsychological, and radiological features of bilateral parietal lobe atrophy. METHODS: Four patients underwent a comprehensive longitudinal neuropsychological assessment, as well as MRI and HMPAO-SPECT. RESULTS: The consistent findings in the patients were early visuospatial problems, agraphia of a predominantly peripheral (or apraxic) type, and difficulty with bimanual tasks, all of which outweighted deficits in memory and language until later in the course of the illness. As the disease progressed, impairments in the phonological aspects of language and in auditory-verbal short term memory were often striking, perhaps reflecting spread from the parietal lobe to perisylvian language areas. Three patients went on to develop a global dementia and fulfilled the criteria for a clinical diagnosis of probable Alzheimer's disease; the fourth patient has only recently been identified. Neuroimaging disclosed bilateral parietal lobe atrophy (MRI) and hypoperfusion (SPECT), which was out of proportion to that seen elsewhere in the brain. One patient has died and had pathologically confirmed Alzheimer's disease with particular concentration in both superior parietal lobes. CONCLUSIONS: Bilateral biparietal atrophy is a recognisable clinical syndrome which can be the presenting feature of Alzheimer's disease. Although the label "posterior cortical atrophy" has been applied to such cases, review of the medical literature suggests that this broad rubric actually consists of two main clinical syndromes with features reflecting involvement of the occipitotemporal (ventral) and biparietal (dorsal) cortical areas respectively. Images PMID:8890778

  1. Benefits of Laser Therapy in Postmenopausal Vaginal Atrophy

    NASA Astrophysics Data System (ADS)

    Brînzan, Daniela; Pǎiuşan, Lucian; Daşcǎu, Voicu; Furǎu, Gheorghe

    2011-08-01

    Maybe the worst aspect of menopause is the decline of the quality of the sexual life. The aim of the study is to demonstrate the beneficial effects of laser therapy in comparison with topical application of estrogen preparations, for the treatment of vaginal atrophy and sexual dysfunctions induced by menopause. A total of 50 menopausal patients were examined during a one year period. The methods used for objectifying vaginal atrophy and sexual dysfunctions were history taking, local clinical exam and PAP smear. From this group, 40 patients had vaginal atrophy with sexual dysfunctions. They have been treated differently, being included in four groups: patients treated with local estrogens, patients treated with intravaginal laser therapy, patients treated with both laser therapy and estrogens, patients treated with estrogens and placebo laser therapy. Therapeutic benefit, improvement of vaginal atrophy and quality of sexual life, were objectified by anamnesis (questionnaire), local and general clinical examination and PAP smear. The best results have been obtained, by far, in the 3rd group, followed by the women treated only with laser. In conclusion, we can say that laser therapy is the best way for solving the sexual inconveniences of menopause.

  2. Atrophy of the Parietal Lobe in Preclinical Dementia

    ERIC Educational Resources Information Center

    Jacobs, Heidi I. L.; Van Boxtel, Martin P. J.; Uylings, Harry B. M.; Gronenschild, Ed H. B. M.; Verhey, Frans R.; Jolles, Jelle

    2011-01-01

    Cortical grey matter atrophy patterns have been reported in healthy ageing and Alzheimer disease (AD), but less consistently in the parietal regions of the brain. We investigated cortical grey matter volume patterns in parietal areas. The grey matter of the somatosensory cortex, superior and inferior parietal lobule was measured in 75 older adults…

  3. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cachexia is a wasting syndrome associated with cancer, AIDS, multiple sclerosis, and several other disease states. It is characterized by weight loss, fatigue, loss of appetite, and skeletal muscle atrophy and is associated with poor patient prognosis, making it an important treatment target. Ghreli...

  4. [Liver Atrophy and Failure Associated with Paclitaxel and Bevacizumab Combination Therapy for Metastatic Breast Cancer].

    PubMed

    Yamamoto, Mari; Ikeda, Masahiko; Kubo, Shinichiro; Tsukioki, Takahiro; Nakamoto, Shougo

    2016-07-01

    We managed 6 cases of severe liver atrophy and failure associated with paclitaxel and bevacizumab combination therapy (PB therapy)for HER2-negative metastatic breast cancer. In this case-controlstudy, we examined the records of these 6 patients to investigate past treatment, medication history, and degree of atrophy, and compared their data with that of 67 patients without liver atrophy. The degree of the liver atrophy used SYNAPSE VINCENT®of the image analysis software. The results showed that patients with liver atrophy had a longer pretreatment period than those without liver atrophy(33.5 months vs 15.5 months), and they also experienced a longer median time to treatment failure with PB therapy than other patients(11 months vs 6 months). The ratio of individuals presenting with diffuse liver metastasis among patients with liver metastasis was 80% with liver atrophy, compared to 8% without liver atrophy. The degree of liver atrophy was an average of 67%in terms of volume ratio before/after PB therapy(57-82%). The individualwith the greatest extent of liver atrophy died of liver failure, not as a result of breast cancer progression. The direct causal link between bevacizumab and liver atrophy and failure is unclear, but the individuals in this study had a long previous history of treatment, and diffuse liver metastases may develop in patients undergoing long periods of PB therapy, which may also cause liver atrophy; therefore, the possibility of liver failure should be considered in such cases.

  5. Is the Supraspinatus Muscle Atrophy Truly Irreversible after Surgical Repair of Rotator Cuff Tears?

    PubMed Central

    Chung, Seok Won; Kim, Sae Hoon; Tae, Suk-Kee; Yoon, Jong Pil; Choi, Jung-Ah

    2013-01-01

    Background Atrophy of rotator cuff muscles has been considered an irreversible phenomenon. The purpose of this study is to evaluate whether atrophy is truly irreversible after rotator cuff repair. Methods We measured supraspinatus muscle atrophy of 191 patients with full-thickness rotator cuff tears on preoperative magnetic resonance imaging and postoperative multidetector computed tomography images, taken at least 1 year after operation. The occupation ratio was calculated using Photoshop CS3 software. We compared the change between pre- and postoperative occupation ratios after modifying the preoperative occupation ratio. In addition, possible relationship between various clinical factors and the change of atrophy, and between the change of atrophy and cuff integrity after surgical repair were evaluated. Results The mean occupation ratio was significantly increased postoperatively from 0.44 ± 0.17 to 0.52 ± 0.17 (p < 0.001). Among 191 patients, 81 (42.4%) showed improvement of atrophy (more than a 10% increase in occupation ratio) and 33 (17.3%) worsening (more than a 10% decrease). Various clinical factors such as age tear size, or initial degree of atrophy did not affect the change of atrophy. However, the change of atrophy was related to repair integrity: cuff healing failure rate of 48.5% (16 of 33) in worsened atrophy; and 22.2% (18 of 81) in improved atrophy (p = 0.007). Conclusions The supraspinatus muscle atrophy as measured by occupation ratio could be improved postoperatively in case of successful cuff repair. PMID:23467404

  6. Gene therapy: a promising approach to treating spinal muscular atrophy.

    PubMed

    Mulcahy, Pádraig J; Iremonger, Kayleigh; Karyka, Evangelia; Herranz-Martín, Saúl; Shum, Ka-To; Tam, Janice Kal Van; Azzouz, Mimoun

    2014-07-01

    Spinal muscular atrophy (SMA) is a severe autosomal recessive disease caused by a genetic defect in the survival motor neuron 1 (SMN1) gene, which encodes SMN, a protein widely expressed in all eukaryotic cells. Depletion of the SMN protein causes muscle weakness and progressive loss of movement in SMA patients. The field of gene therapy has made major advances over the past decade, and gene delivery to the central nervous system (CNS) by in vivo or ex vivo techniques is a rapidly emerging field in neuroscience. Despite Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis being among the most common neurodegenerative diseases in humans and attractive targets for treatment development, their multifactorial origin and complicated genetics make them less amenable to gene therapy. Monogenic disorders resulting from modifications in a single gene, such as SMA, prove more favorable and have been at the fore of this evolution of potential gene therapies, and results to date have been promising at least. With the estimated number of monogenic diseases standing in the thousands, elucidating a therapeutic target for one could have major implications for many more. Recent progress has brought about the commercialization of the first gene therapies for diseases, such as pancreatitis in the form of Glybera, with the potential for other monogenic disease therapies to follow suit. While much research has been carried out, there are many limiting factors that can halt or impede translation of therapies from the bench to the clinic. This review will look at both recent advances and encountered impediments in terms of SMA and endeavor to highlight the promising results that may be applicable to various associated diseases and also discuss the potential to overcome present limitations.

  7. Renal Atrophy Secondary to Chemoradiotherapy of Abdominal Malignancies

    SciTech Connect

    Yang, Gary Y.; May, Kilian Salerno; Iyer, Renuka V.; Chandrasekhar, Rameela M.A.; Wilding, Gregory E.; McCloskey, Susan A.; Khushalani, Nikhil I.; Yendamuri, Saikrishna S.; Gibbs, John F.; Fakih, Marwan; Thomas, Charles R.

    2010-10-01

    Purpose: To identify factors predictive of renal atrophy after chemoradiotherapy of gastrointestinal malignancies. Methods and Materials: Patients who received chemotherapy and abdominal radiotherapy (RT) between 2002 and 2008 were identified for this study evaluating change in kidney size and function after RT. Imaging and biochemical data were obtained before and after RT in 6-month intervals. Kidney size was defined by craniocaudal measurement on CT images. The primarily irradiated kidney (PK) was defined as the kidney that received the greater mean kidney dose. Receiver operating characteristic (ROC) curves were generated to predict risk for renal atrophy. Results: Of 130 patients, median age was 64 years, and 51.5% were male. Most primary disease sites were pancreas and periampullary tumors (77.7%). Median follow-up was 9.4 months. Creatinine clearance declined 20.89%, and size of the PK decreased 4.67% 1 year after completion of chemoradiation. Compensatory hypertrophy of the non-PK was not seen. Percentage volumes of the PK receiving {>=}10 Gy (V{sub 10}), 15 Gy (V{sub 15}), and 20 Gy (V{sub 20}) were significantly associated with renal atrophy 1 year after RT (p = 0.0030, 0.0029, and 0.0028, respectively). Areas under the ROC curves for V{sub 10}, V{sub 15}, and V{sub 20} to predict >5% decrease in PK size were 0.760, 0.760, and 0.762, respectively. Conclusions: Significant detriments in PK size and renal function were seen after abdominal RT. The V{sub 10}, V{sub 15}, and V{sub 20} were predictive of risk for PK atrophy 1 year after RT. Analyses suggest the association of lower-dose renal irradiation with subsequent development of renal atrophy.

  8. miR-182 attenuates atrophy-related gene expression by targeting FoxO3 in skeletal muscle.

    PubMed

    Hudson, Matthew B; Rahnert, Jill A; Zheng, Bin; Woodworth-Hobbs, Myra E; Franch, Harold A; Price, S Russ

    2014-08-15

    Skeletal muscle atrophy occurs in response to a variety of conditions including chronic kidney disease, diabetes, cancer, and elevated glucocorticoids. MicroRNAs (miR) may play a role in the wasting process. Activation of the forkhead box O3 (FoxO3) transcription factor causes skeletal muscle atrophy in patients, animals, and cultured cells by increasing the expression of components of the ubiquitin-proteasome and autophagy-lysosome proteolytic systems. To identify microRNAs that potentially modulate the atrophy process, an in silico target analysis was performed and miR-182 was predicted to target FoxO3 mRNA. Using a combination of immunoblot analysis, quantitative real-time RT-PCR, and FoxO3 3'-UTR luciferase reporter genes, miR-182 was confirmed to regulate FoxO3 expression in C2C12 myotubes. Transfection of miR-182 into muscle cells decreased FoxO3 mRNA 30% and FoxO3 protein 67% (P < 0.05) and also prevented a glucocorticoid-induced upregulation of multiple FoxO3 gene targets including MAFbx/atrogin-1, autophagy-related protein 12 (ATG12), cathepsin L, and microtubule-associated protein light chain 3 (LC3). Treatment of C2C12 myotubes with dexamethasone (Dex) (1 μM, 6 h) to induce muscle atrophy decreased miR-182 expression by 63% (P < 0.05). Similarly, miR-182 was decreased 44% (P < 0.05) in the gastrocnemius muscle of rats injected with streptozotocin to induce diabetes compared with controls. Finally, miR-182 was present in exosomes isolated from the media of C2C12 myotubes and Dex increased its abundance. These data identify miR-182 as an important regulator of FoxO3 expression that participates in the control of atrophy-inducing genes during catabolic diseases.

  9. [Tufting enteropathy: a case report, histopathological methodology, and differential diagnoses].

    PubMed

    Bosaleh, Andrea; Contreras, Monica; García de Dávila, María Teresa

    2015-03-01

    Tufting enteropathy (TE), previously known as intestinal epithelial dysplasia, is a rare congenital enteropathy characterized by refractory diarrhea in the neonatal period. It presents clinical and histological heterogeneity and may be associated with birth defects and punctuate keratitis. The causative gene(s) have not yet been identfied making prenatal diagnosis unavailable. Although there are milder phenotypes most require parenteral nutrition for prolonged periods with the risk of complications. TE becomes an indication for intestinal transplantation. We report the case of a 4-month-old male, born full term with a normal weight. The parents consulted because of severe malnutrition and chronic watery diarrhea. Duodenal and rectal biopsy was negative. Because of poor tolerance gastroclysis was changed to parenteral nutrition. The infant had several catheter-related infections and died at 13 months from catheter-associated complications. Histopathological autopsy was performed. The material was fixed in paraffin and studied with routine techniques. PAS and immunohistochemistry for CD10 were performed. We observed villous atrophy with intestinal epithelial dysplasia and disorganization on the surface of epithelial cells resembling tufts in jejunal and ileal tissue. The objective of this study was to present a rare case of neonatal enteropathy, especially TE, describe the methodology used to study the biopsy, and discuss the differential diagnoses. TE is a rare neonatal enteropathy that is difficult to diagnose and manage. Children in whom TE is suspected should be referred to specialized pediatric centers, with the option of intestinal transplantation.

  10. Novel approaches in diagnosing tuberculosis

    NASA Astrophysics Data System (ADS)

    Kolk, Arend H. J.; Dang, Ngoc A.; Kuijper, Sjoukje; Gibson, Tim; Anthony, Richard; Claassens, Mareli M.; Kaal, Erwin; Janssen, Hans-Gerd

    2011-06-01

    The WHO declared tuberculosis (TB) a global emergency. An estimated 8-9 million new cases occur each year with 2-3 million deaths. Currently, TB is diagnosed mostly by chest-X ray and staining of the mycobacteria in sputum with a detection limit of 1x104 bacteria /ml. There is an urgent need for better diagnostic tools for TB especially for developing countries. We have validated the electronic nose from TD Technology for the detection of Mycobacterium tuberculosis by headspace analysis of 284 sputum samples from TB patients. We used linear discriminant function analysis resulting in a sensitivity of 75% a specificity of 67% and an accuracy of 69%. Further research is still required to improve the results by choosing more selective sensors and sampling techniques. We used a fast gas chromatography- mass spectrometry method (GC-MS). The automated procedure is based on the injection of sputum samples which are methylated inside the GC injector using thermally assisted hydrolysis and methylation (THM-GC-MS). Hexacosanoic acid in combination with tuberculostearic acid was found to be specific for the presence of M. tuberculosis. The detection limit was similar to microscopy. We found no false positives, all microscopy and culture positive samples were also found positive with the THM-GC-MS method. The detection of ribosomal RNA from the infecting organism offers great potential since rRNA molecules outnumber chromosomal DNA by a factor 1000. It thus may possible to detect the organism without amplification of the nucleic acids (NA). We used a capture and a tagged detector probe for the direct detection of M. tuberculosis in sputum. So far the detection limit is 1x106 bacteria / ml. Currently we are testing a Lab-On-A-Chip Interferometer detection system.

  11. Granulomatous cryptococcal prostatitis diagnosed by transrectal biopsy.

    PubMed

    Seo, Ill Young; Jeong, Hee Jong; Yun, Ki Jung; Rim, Joung Sik

    2006-05-01

    Cryptococcal infection primarily involves the lung and is hematogenously spread to other organs. Sometimes it might affect the genitourinary tract, and rare cases have been reported involving the prostate without systemic infection. We report a case of granulomatous prostatitis as a result of Cryptococcus neoformans yeast in an immunocompromised patient with alcoholic liver cirrhosis, which was diagnosed by transrectal ultrasound guided biopsy and treated with antifungal medication.

  12. Brain Atrophy of Secondary REM-Sleep Behavior Disorder in Neurodegenerative Disease

    PubMed Central

    Kim, Hee-Jin; Im, Hyung Kyun; Kim, Juhan; Han, Jee-young; de Leon, Mony; Deshpande, Anup; Moon, Won-Jin

    2017-01-01

    Background Rapid eye movement sleep behavior disorder (RBD) may present as an early manifestation of an evolving neurodegenerative disorder with alpha-synucleinopathy. Objective We investigated that dementia with RBD might show distinctive cortical atrophic patterns. Methods A total of 31 patients with idiopathic Parkinson’s disease (IPD), 23 with clinically probable Alzheimer’s disease (AD), and 36 healthy controls participated in this study. Patients with AD and IPD were divided into two groups according to results of polysomnography and rated with a validated Korean version of the RBD screening questionnaire (RBDSQ-K), which covers the clinical features of RBD. Voxel-based morphometry was adapted for detection of regional brain atrophy among groups of subjects. Results Scores on RBDSQ-K were higher in the IPD group (3.54 ± 2.8) than in any other group (AD, 2.94 ± 2.4; healthy controls, 2.31 ± 1.9). Atrophic changes according to RBDSQ-K scores were characteristically in the posterior part of the brain and brain stem, including the hypothalamus and posterior temporal region including the hippocampus and bilateral occipital lobe. AD patients with RBD showed more specialized atrophic patterns distributed in the posterior and inferior parts of the brain including the bilateral temporal and occipital cortices compared to groups without RBD. The IPD group with RBD showed right temporal cortical atrophic changes. Conclusion The group of patients with neurodegenerative diseases and RBD showed distinctive brain atrophy patterns, especially in the posterior and inferior cortices. These results suggest that patients diagnosed with clinically probable AD or IPD might have mixed pathologies including α-synucleinopathy. PMID:27060938

  13. The use of rituximab in newly diagnosed patients with systemic lupus erythematosus: long-term steroid saving capacity and clinical effectiveness

    PubMed Central

    Gracia-Tello, Borja; Ezeonyeji, Amara; Isenberg, David

    2017-01-01

    Background Previous reports indicate that treating patients with lupus (SLE) at or close to the time of diagnosis successfully without using any, or minimal, corticosteroids by using B-cell depletion (BCD) is possible in the short-term. It is not however known whether using BCD is as effective or reduces corticosteroid use in the long-term. We report the long-term (up to 7 years) use of BCD with respect to its steroid-saving capacity and clinical effectiveness in newly diagnosed SLE. Methods Sixteen female patients with SLE were treated at, or shortly after diagnosis, with BCD therapy (BCDT) minimising the routine use of oral steroids. Post-treatment, most patients were given hydroxychloroquine (n=14) and azathioprine (n=10). The British Isles Lupus Assessment Group (BILAG) disease activity index was used for clinical assessment. Serum antidouble-stranded DNA (dsDNA) antibodies, complement (C3), erythrocyte sedimentation rate (ESR), circulating B lymphocytes (CD19+) and total inmmunoglobulins were tested every 2–6 months (average of 4.5 years) (SD 2) post-treatment. Disease activity and steroid requirement were compared with three patients with SLE treated conventionally, each matched for ethnicity, sex, age, clinical features, disease duration at diagnosis and follow-up period. Results All patients given rituximab achieved BCD. The mean number of flares during follow-up (new BILAG A or B) was 2.63 (SD 3) in the BCDT group and 4 (SD 3.6) in the controls (NS, p=0.14). Post-BCDT, mean anti-dsDNA antibody level fell from 1114 U/mL (SD 1699.3) to 194 (SD 346.7) at 18 months (p=0.043), mean serum ESR fell by >70% at 6 months maintained during follow-up and serum C3 level normalised in 8 patients. The mean cumulative prednisolone dose at 60 months for the patients who underwent BCDT (n=11) was 4745.67 mg (SD 6090 mg) vs 12 553.92 mg (SD 12 672 mg) for the controls (p=0.01). Conclusions Early treatment of patients with SLE with BCDT is safe

  14. Thyroid hemangiomas diagnosed on sonography.

    PubMed

    Park, Sung Hee; Kim, Soo Jin; Jung, Hyun Kyung

    2014-04-01

    Primary thyroid hemangiomas are extremely rare, and only a few cases have been previously reported. Primary hemangiomas are developmental anomalies resulting from the inability of the angioblastic mesenchyme to form canals. Thyroid hemangiomas are generally considered difficult to diagnose preoperatively because of their low incidence and nonspecific imaging findings. Here we report 2 cases of thyroid hemangiomas that were diagnosed correctly on preoperative sonography. Our cases showed similar sonographic findings, such as well-circumscribed hypoechoic lesions with internal channel-like linear lines, and bloody content was aspirated during fine-needle aspirations. Our report shows that thyroid hemangiomas can be diagnosed correctly by sonography with or without confirmation of bloody content in the lesions by fine-needle aspiration.

  15. Diagnosing and Treating Hantavirus Pulmonary Syndrome (HPS)

    MedlinePlus

    ... CDC.gov . Hantavirus Share Compartir Diagnosing and Treating Hantavirus Pulmonary Syndrome (HPS) Diagnosing HPS Diagnosing HPS in ... of patients that develop HPS from New World Hantaviruses recover completely. No chronic infection has been detected ...

  16. Vehicle Fault Diagnose Based on Smart Sensor

    NASA Astrophysics Data System (ADS)

    Zhining, Li; Peng, Wang; Jianmin, Mei; Jianwei, Li; Fei, Teng

    In the vehicle's traditional fault diagnose system, we usually use a computer system with a A/D card and with many sensors connected to it. The disadvantage of this system is that these sensor can hardly be shared with control system and other systems, there are too many connect lines and the electro magnetic compatibility(EMC) will be affected. In this paper, smart speed sensor, smart acoustic press sensor, smart oil press sensor, smart acceleration sensor and smart order tracking sensor were designed to solve this problem. With the CAN BUS these smart sensors, fault diagnose computer and other computer could be connected together to establish a network system which can monitor and control the vehicle's diesel and other system without any duplicate sensor. The hard and soft ware of the smart sensor system was introduced, the oil press, vibration and acoustic signal are resampled by constant angle increment to eliminate the influence of the rotate speed. After the resample, the signal in every working cycle could be averaged in angle domain and do other analysis like order spectrum.

  17. The influence of exercise on bone atrophy

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The relationship between the skeletal system, the muscular system, and exercise in bed rest studies are described. The regime of exercises performed, the mineral balance data derived, and the bone densitometric data obtained are discussed. A brief review of some of the histological results are also given.

  18. Neuropsychological evaluation in an adolescent with cerebellar hypoplasia diagnosed with Asperger's Syndrome.

    PubMed

    Moss, Robert A

    2013-01-01

    There is a growing body of literature describing cases of cognitive impairment associated with both acquired and developmental damage to the cerebellum. The current case study describes such a case involving a 17-year-old male with cerebellar hypoplasia, having incomplete formation of the vermis and atrophy of the interior cerebellar hemispheres. He had previously been diagnosed as having Asperger's Syndrome. A full neuropsychological evaluation was performed, including effort testing. This is followed by a comparison of the current results to previously reported cases, with a discussion of the heterogeneity of deficits associated with developmental cerebellum malformation.

  19. Association between medial temporal lobe atrophy on CT and parietotemporal uptake decrease on SPECT in Alzheimer's disease

    PubMed Central

    Lavenu, I.; Pasquier, F.; Lebert, F.; Jacob, B.; Petit, H.

    1997-01-01

    OBJECTIVES—Alzheimer's disease is the most frequent cause of degenerative dementia. Despite the available diagnostic criteria, improvement of diagnosic accuracy is still required. The aim of this prospective study was to assess in a large population of patients referred to a memory clinic the diagnostic value of the combination of medial temporal lobe atrophy on temporal oriented CT and decreased temporoparietal uptake on HMPAO single photon emission tomography (SPECT).
METHODS—The study was conducted in 125 patients aged 51-93: 64 with probable Alzheimer's disease (Mean (SD) mini mental state examination (MMSE)=18.34 (6.93)), duration of disease=6.48 (2.93) years, 13possible Alzheimer's disease (MMSE=21.58 (5.48), duration of disease=6.08 (2.56)), 48 patients with miscellaneous memory disorders (MMSE=21.98 (6.10), duration the disease = 6.85 (3.91)).
RESULTS—For the diagnosis of probable Alzheimer's disease, the sensitivity of this association was 0.56, the specificity 0.93, the positive predictive value 0.95, and the negative predictive value 0.45. The diagnosic accuracy was 0.68. Both medial temporal atrophy and parietotemporal decrease in uptake were present in four of 13 patients with possible Alzheimer's disease and 11 of 48 with miscellaneous memory disorders. The association was absent in 27 of 29 patients with frontotemporal dementia. In mild stages (MMSE>18; n = 32), the sensitivity of the association was 0.34,the specificity 0.93, the positive predictive value 0.85, and the negative predictive value 0.57. The diagnosic accuracy was 0.53.
CONCLUSION—This association, although not sensitive, helps to select patients with high probability of Alzheimer's disease at an early stage which can be of interest for clinical and research purposes.

 PMID:9343120

  20. Dynamic Foot Pressure as a Countermeasure to Muscle Atrophy

    NASA Astrophysics Data System (ADS)

    Kyparos, A.; Layne, C. S.; Martinez, D. A.; Clarke, M. S. F.; Feeback, D. L.

    2002-01-01

    Mechanical unloading of skeletal muscle (SKM) as a consequence of space flight or ground-based analogues, such as human bedrest and rodent hindlimb suspension (HLS) models, induces SKM atrophy particularly affecting the anti-gravity musculature of the lower limbs. In the context of manned space flight, the subsequent loss of muscle strength and functionality will pose operational implications jeopardizing mission success. Exercise, currently the primary muscle degradation countermeasure, has not proven completely effective in preventing muscle atrophy. It is therefore imperative that some other forms of in- flight countermeasure be also developed to supplement the prescribed exercise regimen the astronauts follow during spaceflight. Previous work in both humans and rats has shown that mechanical stimulation of the soles of the feet increases neuromuscular activation in the lower limb musculature and that such stimulation results in the limited prevention of atrophy in the soleus muscle of unloaded rats. This study was designed to investigate the effect of cutaneous mechanoreceptor stimulation on hindlimb unloading- induced SKM atrophy in rats. It was hypothesized that mechanical stimulation of the plantar surface of the rat foot during hindlimb suspension (HLS), utilizing a novel stimulation paradigm known as Dynamic Foot Pressure (DFP), would attenuate unloading-induced SKM atrophy. Mature adult male Wistar rats were randomly assigned to four groups of 10 rats each as follows: sedentary controls (Ctrl), hindlimb suspended only (HLS), hindlimb suspended wearing an inflatable boot (HLS-IFL) and hindlimb suspended rats wearing a non-inflatable boot (HLS-NIFL). The stimulation of mechanoreceptors was achieved by applying pressure to the plantar surface of the foot during the 10-day period of HLS using a custom-built boot. The anti-atrophic effects of DFP application was quantified directly by morphological (muscle wet weight, myofiber cross-sectional area

  1. How Is Fanconi Anemia Diagnosed?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Fanconi Anemia Diagnosed? People who have Fanconi anemia (FA) are born with the disorder. They may ... questions about: Any personal or family history of anemia Any surgeries you’ve had related to the ...

  2. Development of a functional food or drug against unloading-mediated muscle atrophy

    NASA Astrophysics Data System (ADS)

    Nikawa, Takeshi; Nakao, Reiko; Kagawa, Sachiko; Yamada, Chiharu; Abe, Manami; Tamura, Seiko; Kohno, Shohei; Sukeno, Akiko; Hirasaka, Katsuya; Okumura, Yuushi; Ishidoh, Kazumi

    The ubiquitin-proteasome pathway is a primary regulator of muscle protein turnover, providing a mechanism for selective degradation of regulatory and structural proteins. This pathway is constitutively active in muscle fibers and mediates both intracellular signaling events and normal muscle protein turnover. However, conditions of decreased muscle use, so called unloading, remarkably stimulate activity of this pathway, resulting in loss of muscle protein. In fact, we previously reported that expression of several ubiquitin ligase genes, such as MuRF-1, Cbl-b, and Siah-1A, which are rate-limiting enzymes of the ubiquitin-proteasome proteolytic pathway, are significantly up-regulated in rat skeletal muscle during spaceflight. Moreover, we found that Cbl-b-mediated ubiquitination and degradation of IRS-1, an important intermediates of IGF-1 signal transduction, contributes to muscle atrophy during unloading. Therefore, we hypothesized that inhibition of Cbl-b-mediated ubiquitination and degradation of IRS-1 leads to prevention of muscle atrophy during unloading. In this study, we aimed to evaluate oligopeptide as an inhibitor against ubiquitination of IRS-1 by Cbl-b. We synthesized various oligopeptides that may competitively inhibit the binding of Cbl-b to IRS-1 on the basis of their structures and screened inhibitory effects of these synthesized oligopeptides on Cbl-b-mediated ubiquitination of IRS-1 using in vitro ubiquitination systems. We found that two synthetic oligopeptides with specific amino acid sequences effectively inhibited interaction with Cbl-b and IRS-1, resulting in decreased ubiquitination and degradation of IRS-1 (Patent pending). In contrast, we also found inhibitory activity against Cbl-b-mediated ubiquitination of IRS-1 in soy protein-derived oligopeptides, whereas their inhibitory effects were weaker than those of synthetic oligopeptides. Our results suggest that specific oligopeptides may be available as a functional food against the muscle

  3. [Triplet repeat disease, with particular emphasis of spinal and bulbar muscular atrophy (SBMA)].

    PubMed

    Sobue, G

    2000-12-01

    Spinal and bulbar muscular atrophy (SBMA) is an X-linked neurodegenerative disease caused by the expansion of a CAG repeat in the first exon of the androgen receptor (AR) gene. To date, eight CAG-repeat diseases have been identified, including spinal and bulbar muscular atrophy (SBMA). Huntington's disease (HD), dentatorubralpallidoluysian atrophy (DRPLA) and five spinocerebellar ataxias (SCAs 1, 2, 3, 6, 7). These disorders likely share a common pathogenesis caused by the gain of a toxic function associated with the expanded polyglutamine tract. Several mechanisms have been postulated as a pathogenic process for neurodegeneration caused by the expanded polyglutamine tract. Processing of the polyglutamine containing proteins by proteases liberate truncated polyglutamine tract, which may cause neurodegeneration as demonstrated in transgenic mice and transfected cells. In addition to cellular toxicity, truncated and expanded polyglutamine tracts have been shown to form intranuclear inclusions (NI). The NIs formed by the disease protein are a common pathological feature of these diseases. In SBMA, NIs containing AR protein have been observed in regions of SBMA central nervous system susceptible to degenerations. Transcriptional factors or their cofactors, such as cerb or creb-binding protein (CBP) sequestrated in the NI may alter the major intracellular transcriptional signal transduction, and ultimately may result in neuronal degeneration. The ubiquitin-proteasome pathway may also contribute to the pathogenesis of CAG-repeat diseases. As for the therapeutic strategies, many possibilities have been demonstrated. Overexpression of Hsp70 and Hsp40 chaperones act together to protect a cultured neuronal cell model of SBMA from a cellular toxicity of expanded polyglutamine tract.

  4. Copper nanoclusters trigger muscle cell apoptosis and atrophy in vitro and in vivo.

    PubMed

    Liu, Yayun; Liang, Jichao; Wang, Qiuju; He, Yu; Chen, Yong

    2016-03-01

    Copper nanoclusters (CuNCs) are increasingly being used in nanomedicine owing to their utility in cellular imaging and as catalysts. Additionally, nanotoxicology research of CuNCs is gaining attention. We report here the synthesis and characterization of CuNCs and their cytotoxic impact on muscle cells. A simple protein-directed synthesis of stable CuNCs was prepared, using bovine serum albumin as the stabling agent. Physicochemical characterization of the synthesized CuNCs was performed using transmission electron microscopy. To evaluate the in vitro cytotoxicity, C2C12 cells were exposed to increasing doses (from 0.1 to 50 µg ml(-1)) of CuNCs. CuNCs affected the viability of C2C12 cells in a dose-dependent manner, as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and a lactate dehydrogenase release assay. Further studies indicated that CuNCs induced the formation of reactive oxygen species and decreased the activities of catalase and glutathione. CuNC treatment decreased the mitochondrial membrane potential and induced apoptosis, accompanied by an increase in the protein expression ratio of Bax/Bcl-2 and caspase-3/9 activity in C2C12 cells. CuNCs treatment resulted in atrophy of the C2C12 myotubes, which was characterized by the increased expression of atrophy-related genes, such as atrogin-1 and MuRF1. Finally, CuNCs induce morphological atrophy of primary muscle cells and mouse gastrocnemius muscle. Taken together, these results suggest that exposure to CuNCs may be a risk factor for the skeletal muscle system.

  5. Patterns of gene expression in atrophying skeletal muscles: response to food deprivation

    NASA Technical Reports Server (NTRS)

    Jagoe, R. Thomas; Lecker, Stewart H.; Gomes, Marcelo; Goldberg, Alfred L.

    2002-01-01

    During fasting and many systemic diseases, muscle undergoes rapid loss of protein and functional capacity. To define the transcriptional changes triggering muscle atrophy and energy conservation in fasting, we used cDNA microarrays to compare mRNAs from muscles of control and food-deprived mice. Expression of >94% of genes did not change, but interesting patterns emerged among genes that were differentially expressed: 1) mRNAs encoding polyubiquitin, ubiquitin extension proteins, and many (but not all) proteasome subunits increased, which presumably contributes to accelerated protein breakdown; 2) a dramatic increase in mRNA for the ubiquitin ligase, atrogin-1, but not most E3s; 3) a significant suppression of mRNA for myosin binding protein H (but not other myofibrillar proteins) and IGF binding protein 5, which may favor cell protein loss; 4) decreases in mRNAs for several glycolytic enzymes and phosphorylase kinase subunits, and dramatic increases in mRNAs for pyruvate dehydrogenase kinase 4 and glutamine synthase, which should promote glucose sparing and gluconeogenesis. During fasting, metallothionein mRNA increased dramatically, mRNAs for extracellular matrix components fell, and mRNAs that may favor cap-independent mRNA translation rose. Significant changes occurred in mRNAs for many growth-related proteins and transcriptional regulators. These transcriptional changes indicate a complex adaptive program that should favor protein degradation and suppress glucose oxidation in muscle. Similar analysis of muscles atrophying for other causes is allowing us to identify a set of atrophy-specific changes in gene expression.

  6. Corticobasal degeneration: an autopsy case clinically diagnosed as progressive supranuclear palsy.

    PubMed

    Shiozawa, M; Fukutani, Y; Sasaki, K; Isaki, K; Hamano, T; Hirayama, M; Imamura, K; Mukai, M; Arai, N; Cairns, N J

    2000-01-01

    We report an autopsy case diagnosed clinically as progressive supranuclear palsy (PSP), but neuropathologically confirmed as corticobasal degeneration (CBD). A 56-year-old Japanese woman slowly developed parkinsonism, dementia, character change, followed by vertical gaze palsy and dystonia. Brain MRI demonstrated diffuse cerebral atrophy with severe shrinkage of the brain stem tegmentum. The SPECT images using 123I-IMP disclosed symmetrical hypoperfusion in the frontal lobes. She died of respiratory failure at the age of 71. Gross inspection of the brain showed diffuse, symmetrical atrophy of the cerebrum and marked atrophy of the Luysian body, globus pallidus, substantia nigra and nuclei of the brain stem tegmentum. Microscopically, neuronal loss and fibrillary gliosis were observed in the Luysian body, globus pallidus, substantia nigra and nuclei of the brain stem tegmentum. The cerebellar dentate nucleus showed mild neuronal loss with some grumose degeneration. Neurofibrillary tangles were found only in the Luysian body, substantia nigra and raphe nuclei, whilst tau-positive inclusions were observed more extensively. Astrocytic plaques and swollen achromatic neurones were found in the postcentral gyrus. There were no tuft-shaped astrocytes in the brain. The clinicopathological similarities and differences between PSP and CBD are discussed.

  7. Crustaceans as a model for microgravity-induced muscle atrophy

    NASA Technical Reports Server (NTRS)

    Mykles, D. L.

    1996-01-01

    Atrophy of skeletal muscles is a serious problem in a microgravity environment. It is hypothesized that the unloading of postural muscles, which no longer must resist gravity force, causes an accelerated breakdown of contractile proteins, resulting in reduction in muscle mass and strength. A crustacean model using the land crab, Gecarcinus lateralis, to assess the effects of spaceflight on protein meatabolism is presented. The model is compared to a developmentally-regulated atrophy in which a premolt reduction in muscle mass allows the withdrawal of the large claws at molt. The biochemical mechanisms underlying protein breakdown involves both Ca2(+) -dependent and multicatalytic proteolytic enzymes. Crustacean claw muscle can be used to determine the interactions between shortening and unloading at the molecular level.

  8. Age effects on rat hindlimb muscle atrophy during suspension unloading

    NASA Technical Reports Server (NTRS)

    Steffen, Joseph M.; Fell, Ronald D.; Geoghegan, Thomas E.; Ringel, Lisa C.; Musacchia, X. J.

    1990-01-01

    The effects of hindlimb unloading on muscle mass and biochemical responses were examined and compared in adult (450-g) and juvenile (200-g) rats after 1, 7, or 14 days of whole-body suspension. Quantitatively and qualitatively the soleus, gastrocnemius, plantaris, and extensor digitorum longus (EDL) muscles of the hindlimb exhibited a differential sensitivity to suspension and weightlessness unloading in both adults and juveniles. The red slow-twitch soleus exhibited the most pronounced atrophy under both conditions, with juvenile responses being greater than adult. In contrast, the fast-twitch EDL hypertrophied during suspension and atrophied during weightlessness, with no significant difference between adults and juveniles. Determination of biochemical parameters (total protein, RNA, and DNA) indicates a less rapid rate of response in adult muscles.

  9. Spinal muscular atrophy: development and implementation of potential treatments.

    PubMed

    Arnold, W David; Burghes, Arthur H M

    2013-09-01

    In neurodegenerative disorders, effective treatments are urgently needed, along with methods to determine whether treatment worked. In this review, we discuss the rapid progress in the understanding of recessive proximal spinal muscular atrophy and how this is leading to exciting potential treatments of the disease. Spinal muscular atrophy is caused by loss of the survival motor neuron 1 (SMN1) gene and reduced levels of SMN protein. The critical downstream targets of SMN deficiency that result in motor neuron loss are not known. However, increasing SMN levels has a marked impact in mouse models, and these therapeutics are rapidly moving toward clinical trials. Promising preclinical therapies, the varying degree of impact on the mouse models, and potential measures of treatment effect are reviewed. One key issue discussed is the variable outcome of increasing SMN at different stages of disease progression.

  10. [Surgery of the thymus gland, normal, atrophied or cancerous].

    PubMed

    Limet, R; Rogister, B

    2000-10-01

    Thymoma is the most frequently resected mediastinal tumor. Its malignancy is related more to macroscopical findings than to microscopical analysis. All thymomas should be resected, in order to prevent malignant degeneration. Furthermore, for the treatment of myasthenia, several centers recommend resection of the thymus, either tumoral (thymoma) or atrophied. Although the role of surgery in this regard is controversial, all authors unanimously stress that complete resection of all thymic remnants is essential to achieve adequate results.

  11. MR imaging of psychosurgery: rostral atrophy following stereotacic subcaudate tractotomy.

    PubMed

    Cauley, K A; Waheed, W; Salmela, M; Filippi, C G

    2010-11-01

    There are few reports of MR imaging findings following psychosurgery. Here, we report the findings of 3T MR imaging of the sequelae of stereotactic subcaudate tractotomy (SST). Rostral atrophy is noted on conventional imaging. Diffusion tensor (DT) tractography demonstrated no communicating white matter tracts between the inferior frontal lobes, which appeared normally as thick fibre bundles in age-matched controls. DT tractography provides a unique tool for the evaluation of sequelae of ablative psychosurgical procedures.

  12. Intermittent acceleration as a countermeasure to soleus muscle atrophy

    NASA Technical Reports Server (NTRS)

    D'Aunno, Dominick S.; Robinson, Ronald R.; Smith, Gregory S.; Thomason, Donald B.; Booth, Frank W.

    1992-01-01

    The effectiveness of using intermittent acceleration as a countermeasure to muscle atrophy was investigated in rats subjected to 7 days of hindlimb suspension interrupted by daily periods of 1.2 g acceleration, for 15-min periods evenly spaced over 12-hr interval. It was found that this regimen, when repeated for 7 days, failed to completely maintain the mass of soleus muscle, which was 84 percent of control.

  13. Differentiation between cortical atrophy and hydrocephalus using 1H MRS.

    PubMed

    Bluml, S; McComb, J G; Ross, B D

    1997-03-01

    Quantitative 1H MRS to determine cerebral metabolite patterns and MRI to determine CSF flow were applied to 12 patients with ventricular dilation-Group A, cortical atrophy (N = 5); or Group B, hydrocephalus (N = 7)- and in 9 normal controls. While mean brain water (Group A = 80% +/- 6; Group B = 86% +/- 5; normal = 85% +/- 4) did not differ between the two groups of patients and controls, 1H MRS distinguished those patients with cortical atrophy (Group A) (N-acetylaspartate/ creatine (NAA/Cr) = 0.69 +/- 0.17, versus normal = 1.06 +/- 0.16; P < 0.002; [NAA] = 5.9 +/- 1.3 mmoles/kg, versus normal 8.0 +/- 1.4; P < 0.02) from those with hydrocephalus (Group B) (NAA/Cr = 1.16 +/- 0.11; [NAA] = 9.2 +/- 1.2; P > 0.13 and P > 0.07). Lactate levels were elevated in 3/5 patients with cortical atrophy, but in 0/7 of those with hydrocephalus. Mean absolute concentrations (mmoles/kg) of the five major cerebral osmolytes were 41 +/- 4 (Group A), 43 +/- 6 (Group B), and 42 +/- 4 (normal), so that despite massive brain deformation, constant osmolality was maintained. 1H MRS may directly benefit surgical planning in hydrocephalus infants by clearly identifying those with cortical atrophy who do not require CSF diversion. Thinning of the cortical mantle in hydrocephalus may result from osmotically driven reduction in individual cell volumes, (shrinkage), rather than brain-compression.

  14. Subretinal Glial Membranes in Eyes With Geographic Atrophy

    PubMed Central

    Edwards, Malia M.; McLeod, D. Scott; Bhutto, Imran A.; Grebe, Rhonda; Duffy, Maeve; Lutty, Gerard A.

    2017-01-01

    Purpose Müller cells create the external limiting membrane (ELM) by forming junctions with photoreceptor cells. This study evaluated the relationship between focal photoreceptors and RPE loss in geographic atrophy (GA) and Müller cell extension into the subretinal space. Methods Human donor eyes with no retinal disease or geographic atrophy (GA) were fixed and the eye cups imaged. The retinal posterior pole was stained for glial fibrillary acidic protein (GFAP; astrocytes and activated Müller cells) and vimentin (Müller cells) while the submacular choroids were labeled with Ulex Europaeus Agglutinin lectin (blood vessels). Choroids and retinas were imaged using a Zeiss 710 confocal microscope. Additional eyes were cryopreserved or processed for transmission electron microscopy (TEM) to better visualize the Müller cells. Results Vimentin staining of aged control retinas (n = 4) revealed a panretinal cobblestone-like ELM. While this pattern was also observed in the GA retinas (n = 7), each also had a distinct area in which vimentin+ and vimentin+/GFAP+ processes created a subretinal membrane. Subretinal glial membranes closely matched areas of RPE atrophy in the gross photos. Choroidal vascular loss was also evident in these atrophic areas. Smaller glial projections were noted, which correlated with drusen in gross photos. The presence of glia in the subretinal space was confirmed by TEM and cross cross-section immunohistochemistry. Conclusions In eyes with GA, subretinal Müller cell membranes present in areas of RPE atrophy may be a Müller cell attempt to replace the ELM. These membranes could interfere with treatments such as stem cell therapy. PMID:28249091

  15. [Association of post-radiation focal muscular atrophy and hypertrophy].

    PubMed

    Serratrice, G; Sangla, I; Pouget, J; Azulay, J P

    1993-01-01

    We report a 48 year old woman who had radiotherapy for uterine carcinoma and who developed amyotrophy and muscle hypertrophy in one lower limb. Very few cases of post-radiation monomelic amyotrophy have been reported. On the other hand denervation hypertrophy was presumed to be well known. The seat of the lesions was presumed to be radicular and spinal. The mechanism of atrophy and hypertrophy is discussed.

  16. A Case of Solitary Kidney Atrophy Due to Primary Hyperparathyroidism

    PubMed Central

    Lin, Yu-Ting; Jiang, Jiunn-Song; Fang, Yu-Wei; Tsai, Ming-Hsien

    2016-01-01

    Abstract Although primary hyperparathyroidism (PHPT) is asymptomatic in most patients, its main clinical manifestation is nephrolithiasis. In general, hypercalcemia would lead to unilateral renal stones, which may become bilateral over time. We present a rare case of a large unilateral asymptomatic ureteral stone in a patient with hypercalcemia secondary to PHPT, which eventually led to renal atrophy. The diagnosis of PHPT should be considered in patients with hypercalcemia and renal stones, as asymptomatic PHPT may result in a devastating renal outcome. PMID:26765435

  17. Corticobasal degeneration with olivopontocerebellar atrophy and TDP-43 pathology: an unusual clinicopathologic variant of CBD.

    PubMed

    Kouri, Naomi; Oshima, Kenichi; Takahashi, Makio; Murray, Melissa E; Ahmed, Zeshan; Parisi, Joseph E; Yen, Shu-Hui C; Dickson, Dennis W

    2013-05-01

    Corticobasal degeneration (CBD) is a disorder affecting cognition and movement due to a progressive neurodegeneration associated with distinctive neuropathologic features, including abnormal phosphorylated tau protein in neurons and glia in cortex, basal ganglia, diencephalon, and brainstem, as well as ballooned neurons and astrocytic plaques. We identified three cases of CBD with olivopontocerebellar atrophy (CBD-OPCA) that did not have α-synuclein-positive glial cytoplasmic inclusions of multiple system atrophy (MSA). Two patients had clinical features suggestive of progressive supranuclear palsy (PSP), and the third case had cerebellar ataxia thought to be due to idiopathic OPCA. Neuropathologic features of CBD-OPCA are compared to typical CBD, as well as MSA and PSP. CBD-OPCA and MSA had marked neuronal loss in pontine nuclei, inferior olivary nucleus, and Purkinje cell layer. Neuronal loss and grumose degeneration in the cerebellar dentate nucleus were comparable in CBD-OPCA and PSP. Image analysis of tau pathology showed greater infratentorial tau burden, especially in pontine base, in CBD-OPCA compared with typical CBD. In addition, CBD-OPCA had TDP-43 immunoreactive neuronal and glial cytoplasmic inclusions and threads throughout the basal ganglia and in olivopontocerebellar system. CBD-OPCA met neuropathologic research diagnostic criteria for CBD and shared tau biochemical characteristics with typical CBD. These results suggest that CBD-OPCA is a distinct clinicopathologic variant of CBD with olivopontocerebellar TDP-43 pathology.

  18. Protein turnover in atrophying muscle: from nutritional intervention to microarray expression analysis

    NASA Technical Reports Server (NTRS)

    Stein, T. Peter; Wade, Charles E.

    2003-01-01

    PURPOSE OF REVIEW: In response to decreased usage, skeletal muscle undergoes adaptive reductive remodeling due to the decrease in tension on the weight bearing components of the musculo-skeletal system. This response occurs with uncomplicated disuse (e.g. bed rest, space flight), as a secondary consequence of several widely prevalent chronic diseases for which activity is reduced (e.g. chronic obstructive pulmonary disease and chronic heart failure) and is part of the aging process. The problem is therefore one of considerable clinical importance. RECENT FINDINGS: The impaired function and exercise intolerance is related more to the associated muscle wasting rather than to the specific organ system primarily impacted by the disease. Progress has continued in describing the use of anabolic drugs and dietary manipulation. The major advance in the field has been: (i) the discovery of the atrogin-1 gene and (ii) the application of microarray expression analysis and proteomics with the objectives of obtaining comprehensive understanding of the pathways changed with disuse atrophy. SUMMARY: Disuse atrophy is a common clinical problem. There is a need for therapeutic interventions that do not involve exercise. A better understanding of the changes, particularly at the molecular level, could indicate hitherto unsuspected sites for nutritional and pharmacological intervention.

  19. Corticobasal degeneration with olivopontocerebellar atrophy and TDP-43 pathology: an unusual clinicopathologic variant of CBD

    PubMed Central

    Kouri, Naomi; Oshima, Kenichi; Takahashi, Makio; Murray, Melissa E.; Ahmed, Zeshan; Parisi, Joseph E.; Yen, Shu-Hui C.; Dickson, Dennis W.

    2013-01-01

    CBD is a disorder affecting cognition and movement due to a progressive neurodegeneration associated with distinctive neuropathologic features, including abnormal phosphorylated tau protein in neurons and glia in cortex, basal ganglia, diencephalon and brainstem, as well as ballooned neurons and astrocytic plaques. We identified three cases of CBD with olivopontocerebellar atrophy (CBD-OPCA) that did not have α-synuclein-positive glial cytoplasmic inclusions of multiple system atrophy (MSA). Two patients had clinical features suggestive of progressive supranuclear palsy (PSP), and the third case had cerebellar ataxia thought to be due to idiopathic OPCA. Neuropathologic features of CBD-OPCA are compared to typical CBD, as well as MSA and PSP. CBD-OPCA and MSA had marked neuronal loss in pontine nuclei, inferior olivary nucleus, and Purkinje cell layer. Neuronal loss and grumose degeneration in the cerebellar dentate nucleus was comparable in CBD-OPCA and PSP. Image analysis of tau pathology showed greater infratentorial tau burden, especially in pontine base, in CBD-OPCA compared with typical CBD. Additionally, CBD-OPCA had TDP-43 immunoreactive neuronal and glial cytoplasmic inclusions and threads throughout the basal ganglia and in olivopontocerebellar system. CBD-OPCA met neuropathologic research diagnostic criteria for CBD and shared tau biochemical characteristics with typical CBD. These results suggest that CBD-OPCA is a distinct clinicopathologic variant of CBD with olivopontocerebellar TDP-43 pathology. PMID:23371366

  20. Association Between Geographic Atrophy Progression and Reticular Pseudodrusen in Eyes With Dry Age-Related Macular Degeneration

    PubMed Central

    Marsiglia, Marcela; Boddu, Sucharita; Bearelly, Srilaxmi; Xu, Luna; Breaux, Barry E.; Freund, K. Bailey; Yannuzzi, Lawrence A.; Smith, R. Theodore

    2013-01-01

    Purpose. To evaluate geographic atrophy (GA) progression in eyes with dry AMD and to determine factors related to GA expansion, notably reticular pseudodrusen (RPD), also known as subretinal drusenoid deposits (SDD) or reticular macular disease (RMD). Methods. This was a retrospective cohort study of patients with dry AMD who were diagnosed with GA in at least one eye and were imaged with sequential fundus autofluorescence (FAF) and/or near infrared reflectance (NIR-R) imaging. Images were analyzed for the presence of GA within the macular region. Geographic atrophy progression was measured in the fields of a modified Wisconsin grid and spatially correlated with RPD. Factors also evaluated for association with GA progression included initial GA size and pattern. Results. The study sample included 126 eyes of 92 patients, with an average follow up of 20.4 months (SD = 11.7). At baseline, 93.6% of eyes had RPD, and the average GA area was 2.8 mm2 (SD = 2.9). The average GA progression rate was 0.8 mm2/y (SD = 0.6), with a statistically significant difference between the unilobular and multilobular phenotype groups (0.3 mm2/y vs. 0.9 mm2/y, P = 0.02). Patients in the lower 50th percentile of initial GA area had a lower progression rate than patients in the upper 50th percentile (0.6 mm2/y vs. 1.1 mm2/y, P < 0.001). Geographic atrophy progression was more frequent in fields with RPD than in those without RPD (74.2% vs. 41.7%, P < 0.001). Conclusions. The high correlation between the presence of RPD (also known as SDD or RMD) and the presence of GA, and the expansion of GA into areas with these lesions suggest that they are an early manifestation of the process leading to GA. PMID:24114542