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Sample records for system atrophy diagnosed

  1. Multiple System Atrophy

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Multiple System Atrophy Information Page Condensed from Multiple System Atrophy ... Trials Organizations Publicaciones en Español What is Multiple System Atrophy? Multiple system atrophy (MSA) is a progressive ...

  2. Multiple system atrophy.

    PubMed

    Peeraully, Tasneem

    2014-04-01

    Multiple system atrophy (MSA) is a rare adult-onset synucleinopathy associated with dysautonomia and the variable presence of poorly levodopa-responsive parkinsonism and/or cerebellar ataxia. Other clinical symptoms that can be associated with MSA include hyperreflexia, stridor, sleep apnea, and rapid eye movement sleep behavior disorder (RBD). Mean survival from time of diagnosis ranges between 6 to 10 years, and definitive diagnosis is made on autopsy with demonstration of oligodendroglial cytoplasmic inclusions consisting of fibrillar α-synuclein. Magnetic resonance imaging (MRI) may be positive for cruciform T2 hyperintensity within the pons (the "hot cross bun sign"), volume loss in the pons and cerebellum, and T2 signal loss in the dorsolateral putamen with hyperintense rim on fluid attenuated inversion recovery (FLAIR) sequencing. Although most cases are sporadic, genetic polymorphisms have been identified both in familial and sporadic cases of MSA, and influence observed phenotypes. Treatment is symptomatic, with both pharmacological and nonpharmacological strategies. There are currently no consensus guidelines on management. Current and future research is aimed at identifying biomarkers and developing disease-modifying therapies.

  3. Genetics Home Reference: multiple system atrophy

    MedlinePlus

    ... OPCA progressive autonomic failure with multiple system atrophy SDS Shy-Drager syndrome sporadic olivopontocerebellar atrophy Related Information ... A, Hulot JS, Morrison KE, Renton A, Sussmuth SD, Landwehrmeyer BG, Ludolph A, Agid Y, Brice A, ...

  4. 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 a rapid rate (faster than 100 beats per minute) may increase ...

  5. Heredity in multiple system atrophy.

    PubMed

    Soma, Hiroyuki; Yabe, Ichiro; Takei, Asako; Fujiki, Naoto; Yanagihara, Tetsuro; Sasaki, Hidenao

    2006-01-15

    We investigated the family histories of 157 Japanese patients with probable or possible multiple system atrophy (MSA). A family history of neurodegenerative disorders was only detected in three MSA patients (1.9%). We evaluated these patients by careful neurological examination, neuroimaging studies, and genetic studies to exclude hereditary spinocerebellar ataxia with a similar clinical phenotype to MSA. The results indicated that one of them had a family history of MSA. Although the familial presence of neurodegenerative disorders is rare in MSA patients, the existence of such cases suggests that MSA may have a genetic background.

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

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Multiple System Atrophy with Orthostatic Hypotension Information Page Synonym(s): Shy- ... being done? Clinical Trials Organizations What is Multiple System Atrophy with Orthostatic Hypotension? Multiple system atrophy with ...

  7. 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

  8. Dystonia in multiple system atrophy

    PubMed Central

    Boesch, S; Wenning, G; Ransmayr, G; Poewe, W

    2002-01-01

    Objective: To delineate the frequency and nature of dystonia in multiple system atrophy (MSA). Methods: a cohort of 24 patients with clinically probable MSA over the past 10 years were prospectively followed up. Motor features were either dominated by parkinsonism (MSA-P subtype, n=18) or cerebellar ataxia (MSA-C, n=6). Classification of dystonic features and their changes with time was based on clinical observation during 6–12 monthly follow up visits. Parkinsonian features and complications of drug therapy were assessed. Most patients (22/24) died during the observation period. Neuropathological examination was confirmatory in all of the five necropsied patients. Results: At first neurological visit dystonia was present in 11 (46%) patients all of whom had been levodopa naive at this time point. Six patients (25%) exhibited cervical dystonia (antecollis) (MSA-P n=4, MSA-C n=2), five patients (21%) showed unilateral limb dystonia (MSA-P n=4; MSA-C n=1). A definite initial response to levodopa treatment was seen in 15/18 patients with MSA-P, but in none of the six patients with MSA-C. A subgroup of 12 patients with MSA-P developed levodopa induced dyskinesias 2.3 years (range 0.5–4) after initiation of levodopa therapy. Most patients had peak dose craniocervical dystonia; however, some patients experienced limb or generalised dystonia. Isolated peak dose limb chorea occurred in only one patient. Conclusion: The prospective clinical study suggests that dystonia is common in untreated MSA-P. This finding may reflect younger age at disease onset and putaminal pathology in MSA-P. Levodopa induced dyskinesias were almost exclusively dystonic affecting predominantly craniocervical musculature. Future studies are required to elucidate the underlying pathophysiology of dystonia in MSA. PMID:11861684

  9. [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. PMID:25672683

  10. Multiple System Atrophy: Genetic or Epigenetic?

    PubMed Central

    Sturm, Edith

    2014-01-01

    Multiple system atrophy (MSA) is a rare, late-onset and fatal neurodegenerative disease including multisystem neurodegeneration and the formation of α-synuclein containing oligodendroglial cytoplasmic inclusions (GCIs), which present the hallmark of the disease. MSA is considered to be a sporadic disease; however certain genetic aspects have been studied during the last years in order to shed light on the largely unknown etiology and pathogenesis of the disease. Epidemiological studies focused on the possible impact of environmental factors on MSA disease development. This article gives an overview on the findings from genetic and epigenetic studies on MSA and discusses the role of genetic or epigenetic factors in disease pathogenesis. PMID:25548529

  11. [Multiple system atrophy - synuclein and neuronal degeneration].

    PubMed

    Yoshida, Mari

    2011-11-01

    Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that encompasses olivopontocerebellar atrophy (OPCA), striatonigral degeneration (SND) and Shy-Drager syndrome (SDS). The histopathological hallmarks are α-synuclein (AS) positive glial cytoplasmic inclusions (GCIs) in oligodendroglias. AS aggregation is also found in glial nuclear inclusions (GNIs), neuronal cytoplasmic inclusions (NCIs), neuronal nuclear inclusions (NNIs) and dystrophic neurties. Reviewing the pathological features of 102 MSA cases, OPCA-type was relatively more frequent and SND-type was less frequent in Japanese MSA cases, which suggested different phenotypic pattern of MSA might exist between races, compared to the relatively high frequency of SND-type in western countries. In early stage of MSA, NNIs, NCIs and diffuse homogenous stain of AS in neuronal nuclei and cytoplasm were observed in various vulnerable lesions including the pontine nuclei, putamen, substantia nigra, locus ceruleus, inferior olivary nucleus, intermediolateral column of thoracic cord, lower motor neurons and cortical pyramidal neurons, in additions to GCIs. These findings indicated that the primary nonfibrillar and fibrillar AS aggregation also occurred in neurons. Therefore both the direct involvement of neurons themselves and the oligodendroglia-myelin-axon mechanism may synergistically accelerate the degenerative process of MSA. PMID:22277386

  12. Multiple system atrophy: pathogenic mechanisms and biomarkers.

    PubMed

    Jellinger, Kurt A; Wenning, Gregor K

    2016-06-01

    Multiple system atrophy (MSA) is a unique proteinopathy that differs from other α-synucleinopathies since the pathological process resulting from accumulation of aberrant α-synuclein (αSyn) involves the oligodendroglia rather than neurons, although both pathologies affect multiple parts of the brain, spinal cord, autonomic and peripheral nervous system. Both the etiology and pathogenesis of MSA are unknown, although animal models have provided insight into the basic molecular changes of this disorder. Accumulation of aberrant αSyn in oligodendroglial cells and preceded by relocation of p25α protein from myelin to oligodendroglia results in the formation of insoluble glial cytoplasmic inclusions that cause cell dysfunction and demise. These changes are associated with proteasomal, mitochondrial and lipid transport dysfunction, oxidative stress, reduced trophic transport, neuroinflammation and other noxious factors. Their complex interaction induces dysfunction of the oligodendroglial-myelin-axon-neuron complex, resulting in the system-specific pattern of neurodegeneration characterizing MSA as a synucleinopathy with oligodendroglio-neuronopathy. Propagation of modified toxic αSyn species from neurons to oligodendroglia by "prion-like" transfer and its spreading associated with neuronal pathways result in a multi-system involvement. No reliable biomarkers are currently available for the clinical diagnosis and prognosis of MSA. Multidisciplinary research to elucidate the genetic and molecular background of the deleterious cycle of noxious processes, to develop reliable diagnostic biomarkers and to deliver targets for effective treatment of this hitherto incurable disorder is urgently needed.

  13. Gyrate atrophy of the choroid and retina diagnosed by ornithine-δ-aminotransferase gene analysis: a case report.

    PubMed

    Kim, Sang Jin; Lim, Dong Hui; Kim, Jae Hui; Kang, Se Woong

    2013-10-01

    A pair of 19-year-old female identical twins was referred to our hospital with progressive visual loss. They exhibited bilateral chorioretinal atrophy involving the midperiphery on fundoscopy and fluorescein angiography. Bilateral visual field constriction was noted on dynamic Goldmann perimetry, and a markedly impaired response was observed on both photopic and scotopic electroretinograms. Cystoid macular edema was identified in both eyes on optical coherence tomography. Plasma levels of ornithine were elevated. Based on these observations, the patients were diagnosed with gyrate atrophy of the choroid and retina. The clinical diagnosis was confirmed by mutation analysis of the ornithine-δ-aminotransferase (OAT) gene. Patients were treated with a pyridoxine supplement (300 mg/day) and an arginine-restricted diet to lower plasma levels of ornithine, which were successfully reduced without progression of chorioretinal atrophy for 15 months. Our report describes the first case of gyrate atrophy in the Korean population diagnosed by OAT gene analysis and treated with vitamin B6 dietary supplementation. PMID:24082780

  14. 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

  15. 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

  16. 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

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

    PubMed Central

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

    2015-01-01

    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

  18. 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

  19. Whole-Brain Atrophy Rate in Idiopathic Parkinson's Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy

    PubMed Central

    Guevara, C.; Bulatova, K.; Barker, G. J.; Gonzalez, G.; Crossley, N.; Kempton, M. J.

    2016-01-01

    In multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), the absence of surrogate endpoints makes clinical trials long and expensive. We aim to determine annualized whole-brain atrophy rates (a-WBAR) in idiopathic Parkinson's disease (IPD), MSA, and PSP. Ten healthy controls, 20 IPD, 12 PSP, and 8 MSA patients were studied using a volumetric MRI technique (SIENA). In controls, the a-WBAR was 0.37% ± 0.28 (CI 95% 0.17–0.57), while in IPD a-WBAR was 0.54% ± 0.38 (CI 95% 0.32–0.68). The IPD patients did not differ from the controls. In PSP, the a-WBAR was 1.26% ± 0.51 (CI 95%: 0.95–1.58). In MSA, a-WBAR was 1.65% ± 1.12 (CI 95%: 0.71–2.59). MSA did not differ from PSP. The a-WBAR in PSP and MSA were significantly higher than in the IPD group (p = 0.004 and p < 0.001, resp.). In PSP, the use of a-WBAR required one-half of the patients needed for clinical scales to detect a 50% reduction in their progression. In MSA, one-quarter of the patients would be needed to detect the same effect. a-WBAR is a reasonable candidate to consider as a surrogate endpoint in short clinical trials using smaller sample sizes. The confidence intervals for a-WBAR may add a potential retrospective application for a-WBAR to improve the diagnostic accuracy of MSA and PSP versus IPD. PMID:27190673

  20. Whole-Brain Atrophy Rate in Idiopathic Parkinson's Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy.

    PubMed

    Guevara, C; Bulatova, K; Barker, G J; Gonzalez, G; Crossley, N; Kempton, M J

    2016-01-01

    In multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), the absence of surrogate endpoints makes clinical trials long and expensive. We aim to determine annualized whole-brain atrophy rates (a-WBAR) in idiopathic Parkinson's disease (IPD), MSA, and PSP. Ten healthy controls, 20 IPD, 12 PSP, and 8 MSA patients were studied using a volumetric MRI technique (SIENA). In controls, the a-WBAR was 0.37% ± 0.28 (CI 95% 0.17-0.57), while in IPD a-WBAR was 0.54% ± 0.38 (CI 95% 0.32-0.68). The IPD patients did not differ from the controls. In PSP, the a-WBAR was 1.26% ± 0.51 (CI 95%: 0.95-1.58). In MSA, a-WBAR was 1.65% ± 1.12 (CI 95%: 0.71-2.59). MSA did not differ from PSP. The a-WBAR in PSP and MSA were significantly higher than in the IPD group (p = 0.004 and p < 0.001, resp.). In PSP, the use of a-WBAR required one-half of the patients needed for clinical scales to detect a 50% reduction in their progression. In MSA, one-quarter of the patients would be needed to detect the same effect. a-WBAR is a reasonable candidate to consider as a surrogate endpoint in short clinical trials using smaller sample sizes. The confidence intervals for a-WBAR may add a potential retrospective application for a-WBAR to improve the diagnostic accuracy of MSA and PSP versus IPD.

  1. Characteristic diffusion tensor tractography in multiple system atrophy with predominant cerebellar ataxia and cortical cerebellar atrophy.

    PubMed

    Fukui, Yusuke; Hishikawa, Nozomi; Sato, Kota; Nakano, Yumiko; Morihara, Ryuta; Ohta, Yasuyuki; Yamashita, Toru; Abe, Koji

    2016-01-01

    The objective of this study is to determine whether diffusion tensor imaging (DTI) tractography analysis is a potential method for differentiating cerebellar ataxia patients with multiple system atrophy with predominant cerebellar ataxia (MSA-C) and cortical cerebellar atrophy (CCA). Forty-one MSA-C patients (62.7 ± 8.1 years old, mean ± SD) and age- and gender-matched 15 CCA patients (63.0 ± 8.6 years old) were examined.Tractography was performed using the DTI track module provided in the MedINRIA version 1.9.4, and regions of interest were drawn manually to reconstruct an efferent fiber tract and two afferent fiber tracts via the cerebellum. Compared with CCA, MSA-C patients showed significant declines of fractional anisotropy (FA) values of afferent 1 and 2 (p<0.01, respectively) and a significant increase of the radial diffusivity (RD) value in afferent 1 (p<0.05). Receiver-operator characteristic curve analysis showed 85.7 % sensitivity and 75.0 % specificity of FA values in afferent 1 (cutoff value 0.476). Linear regressions showed strong correlations between FA value and disease duration in CCA patients (efferent 1, r = -0.466; afferent 2, r = -0.543; both p<0.05), and between the FA value and the ratio of the standardized scale for the assessment and rating of ataxia (SARA)/disease duration in MSA-C patients (afferent 1, r = -0.407; p<0.01). The present DTI tractography newly showed that the FA values of two afferent fiber tracts showed significant declines in MSA-C patients, and afferent 1 showed good diagnostic sensitivity and specificity. When combining the FA values of efferent 1 with disease duration, the present DTI tractography analysis could be useful for differentiating MSA-C and CCA patients.

  2. 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.

  3. Multiple system atrophy: alpha-synuclein and neuronal degeneration.

    PubMed

    Yoshida, Mari

    2007-10-01

    Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that encompasses olivopontocerebellar atrophy (OPCA), striatonigral degeneration (SND) and Shy-Drager syndrome (SDS). The histopathological hallmark is the formation of alpha-synuclein-positive glial cytoplasmic inclusions (GCIs) in oligodendroglia. alpha-synuclein aggregation is also found in glial nuclear inclusions, neuronal cytoplasmic inclusions (NCIs), neuronal nuclear inclusions (NNIs) and dystrophic neurites. We evaluated the pathological features of 102 MSA cases, and presented the pathological spectrum of MSA and initial features of alpha-synuclein accumulation. We found that 39% of the 102 cases showed equivalent SND and OPCA pathologies, 33% showed OPCA- and 22% showed SND-predominant pathology, whereas 6% showed extremely mild changes. Our pathological analysis indicated that OPCA-type was relatively more frequent and SND-type was less frequent in Japanese MSA cases, compared to the relatively high frequency of SND-type in Western countries, suggesting that different phenotypic patterns of MSA may exist between races. In the early stage, in addition to GCIs, NNIs and diffuse homogenous alpha-synuclein staining in neuronal nuclei and cytoplasm were observed in lesions in the pontine nuclei, putamen, substantia nigra, locus ceruleus, inferior olivary nucleus, intermediolateral column of thoracic spinal cord, lower motor neurons and cortical pyramidal neurons. A subgroup of MSA cases with severe temporal atrophy showed numerous NCIs, particularly in the limbic system. These findings suggest that primary non-fibrillar and fibrillar alpha-synuclein aggregation also occur in neurons. The oligo-myelin-axon-neuron complex mechanism, along with the direct involvement of neurons themselves, may synergistically accelerate the degenerative process of MSA. PMID:18018485

  4. [Mechanism of neuronal degeneration of multiple system atrophy].

    PubMed

    Yoshida, Mari; Sone, Mie

    2009-09-01

    Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that encompasses olivopontocerebellar atrophy (OPCA), striatonigral degeneration (SND) and Shy-Drager syndrome (SDS). The histopathological hallmarks are alpha-synuclein (AS) positive glial cytoplasmic inclusions (GCIs) in oligodendroglias. AS aggregation is also found in glial nuclear inclusions (GNIs), neuronal cytoplasmic inclusions (NCIs), neuronal nuclear inclusions (NNIs) and dystrophic neurites. Reviewing the pathological features in 102 MSA cases revealed that the, OPCA-type was relatively more frequent and SND-type was less frequent in Japanese MSA cases. The frequency of the SND-type is relatively high in Western countries. This different in the dominant type suggests that the phenotypic patterns of MSA may vary with the race. In early stages of MSA, in addition to GCIs, NNIs, NCIs, and diffuse homogenous stain of AS in neuronal nuclei and cytoplasm were observed in various vulnerable lesions including the pontine nuclei, putamen, substantia nigra, locus ceruleus, inferior olivary nucleus, intermediolateral column of the thoracic cord, lower motor neurons, and cortical pyramidal neurons. These findings indicated that the primary nonfibrillar and fibrillar AS aggregation also occurred in neurons. Therefore, both the direct involvement of neurons themselves and the oligodendroglia-myelin-axon mechanism may synergistically accelerate the degenerative process of MSA. PMID:19803404

  5. 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.

  6. 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. PMID:24719321

  7. 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

  8. 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

  9. 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.

  10. Olivopontocerebellar atrophy

    MedlinePlus

    OPCA; Olivopontocerebellar degeneration; Multiple system atrophy – cerebellar predominance; MSA-C ... Tremor medications, such as those used to treat Parkinson's disease Speech and physical therapy Techniques to prevent ...

  11. Multiple System Atrophy. Using Clinical Pharmacology to Reveal Pathophysiology

    PubMed Central

    Jordan, Jens; Shibao, Cyndya; Biaggioni, Italo

    2015-01-01

    Despite similarities in their clinical presentation, patients with multiple system atrophy (MSA) have residual sympathetic tone and intact post-ganglionic noradrenergic fibers, whereas patients with pure autonomic failure (PAF) and Parkinson’s disease (PD) have efferent post-ganglionic autonomic denervation. These differences are apparent biochemically, with near normal plasma norepinephrine in MSA but very low levels in PAF, and in neurophysiological testing. These differences are also reflected in the response patients have to drugs that interact with the autonomic nervous system. E.g., the ganglionic blocker trimethaphan reduce residual sympathetic tone and lower blood pressure in MSA but less so in PAF. Conversely, the α2-antagonist yohimbine produces a greater increase in blood pressure in MSA compared to PAF, although significant overlap exists. In normal subjects the norepinephrine reuptake (NET) inhibitor atomoxetine has little effect on blood pressure because the peripheral effects of NET inhibition that result in noradrenergic vasoconstriction, are counteracted by the increase in brain norepinephrine which reduces sympathetic outflow (a clonidine-like effect). In patients with autonomic failure and intact peripheral noradrenergic fibers only the peripheral vasoconstriction is apparent. This translates to a significant pressor effect of atomoxetine in MSA, but not in PAF patients. Thus, pharmacological probes can be used to understand the pathophysiology of the different forms of autonomic failure, assist in the diagnosis, and aid in the management of orthostatic hypotension. PMID:25757803

  12. Retinal thinning correlates with clinical severity in multiple system atrophy.

    PubMed

    Ahn, Jeeyun; Lee, Jee-Young; Kim, Tae Wan

    2016-10-01

    To analyze retinal thickness changes in multiple system atrophy (MSA) and correlate changes with disease severity and subtypes of MSA. A total of 36 MSA (27 MSA-P and 9 MSA-C) patients and 71 healthy control subjects underwent general ophthalmologic examination and optical coherence tomography (OCT) scans. Peripapillary retinal nerve fiber layer (RNFL) thickness and perifoveal retinal thickness were analyzed separately. The generalized estimating equation model was used with age as a covariate to adjust for within-patient inter-eye correlations and the effect of age on retinal or RNFL thickness. Correlation analysis between RNFL, perifoveal thickness, and clinical parameters, the Unified MSA Rating Scale (UMSARS) and Global Disability Score (GDS), was also done. MSA patients showed significantly decreased peripapillary RNFL thickness in the inferior (P = 0.047) and inferotemporal (P = 0.017) sectors and significant perifoveal thinning in the superior outer sector (P = 0.042) compared to healthy controls. Both RNFL and perifoveal thinning were more marked and widespread in MSA-P than MSA-C patients. The UMSARS and GDS showed significant negative correlation with center and total macular perifoveal thickness and also the inferior and nasal outer sectors. Peripapillary RNFL and perifoveal retinal thinning were observed in MSA patients and retinal thinning correlated with the clinical severity of MSA. Structural changes in the retina may reflect the degree and pattern of neurodegeneration occurring in MSA.

  13. 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

  14. 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.

  15. 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.

  16. Decreased Coenzyme Q10 Levels in Multiple System Atrophy Cerebellum.

    PubMed

    Barca, Emanuele; Kleiner, Giulio; Tang, Guomei; Ziosi, Marcello; Tadesse, Saba; Masliah, Eliezer; Louis, Elan D; Faust, Phyllis; Kang, Un J; Torres, Jose; Cortes, Etty P; Vonsattel, Jean-Paul G; Kuo, Sheng-Han; Quinzii, Catarina M

    2016-07-01

    In familial and sporadic multiple system atrophy (MSA) patients, deficiency of coenzyme Q10 (CoQ10) has been associated with mutations in COQ2, which encodes the second enzyme in the CoQ10 biosynthetic pathway. Cerebellar ataxia is the most common presentation of CoQ10 deficiency, suggesting that the cerebellum might be selectively vulnerable to low levels of CoQ10 To investigate whether CoQ10 deficiency represents a common feature in the brains of MSA patients independent of the presence of COQ2 mutations, we studied CoQ10 levels in postmortem brains of 12 MSA, 9 Parkinson disease (PD), 9 essential tremor (ET) patients, and 12 controls. We also assessed mitochondrial respiratory chain enzyme activities, oxidative stress, mitochondrial mass, and levels of enzymes involved in CoQ biosynthesis. Our studies revealed CoQ10 deficiency in MSA cerebellum, which was associated with impaired CoQ biosynthesis and increased oxidative stress in the absence of COQ2 mutations. The levels of CoQ10 in the cerebella of ET and PD patients were comparable or higher than in controls. These findings suggest that CoQ10 deficiency may contribute to the pathogenesis of MSA. Because no disease modifying therapies are currently available, increasing CoQ10 levels by supplementation or upregulation of its biosynthesis may represent a novel treatment strategy for MSA patients.

  17. 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

  18. 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.

  19. Muscle atrophy

    MedlinePlus

    Muscle wasting; Wasting; Atrophy of the muscles ... There are two types of muscle atrophy: disuse and neurogenic. Disuse atrophy is caused by not using the muscles enough . This type of atrophy can often be ...

  20. 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

  1. [Clinical effect of Yisui decoction plus western medicine in treating multiple system atrophy].

    PubMed

    Zhang, Pei-Ran; Guo, Gai-Hui; Gu, Wei-Hong; Zhang, Zi-Yi; Wang, Kang; Jin, Miao

    2014-08-01

    To observe the clinical effect of Yisui decoction plus western medicine in treating multiple system atrophy patients, totally 65 patients from China-Japan Friendship hospital during 2008-2012 with complete clinical data and received consecutive traditional Chinese medicine and western medicine treatment for more than 3 months were observed changes of traditional Chinese medicine symptom score, part 1 of unified multiple system atrophy rating scale, orthostatic hypotension before treatment and after 3 months treatment. After 3 months treatment, total effective rate of traditional Chinese medicine symptom was 70.8%. Compared with before treatment, score of part 1 of unified multiple system atrophy rating scale was obviously reduced after 3 month treatment (P < 0.001). Ex- cept swallow function without significant improvement, the remaining projects of unified multiple system atrophy rating scale were im- proved obviously (P < 0.05), of which the most obvious differences were orthostatic symptoms, falls and intestinal function (P < 0.001). Orthostatic hypotension after 1 month treatment and 3 month treatment was obviously better than before treatment (P < 0.001). There was no significant difference in orthostatic hypotension between 1 month treatment and 3 month treatment. The research results show that Yisui decoction plus western medicine has a certain effect on improving clinical symptoms of multiple system atrophy patients, especially has a significant effect on orthostatic hypotension, and can maintain a stable clinical effect in a certain period of time.

  2. Central Apneas and REM Sleep Behavior Disorder as an Initial Presentation of Multiple System Atrophy

    PubMed Central

    Garcia-Sanchez, Aldara; Fernandez-Navarro, Isabel; Garcia-Rio, Francisco

    2016-01-01

    We present the case of a patient with multiple system atrophy who presented with central apnea as the only sleep disordered breathing, associated with REM behavior disorder and restless legs syndrome. This presentation of the disease is unusual and probably reflects more widespread involvement at the onset. With this case, we show the importance of considering this kind of disease in the differential diagnosis of central sleep apnea syndromes. Citation: Garcia-Sanchez A, Fernandez-Navarro I, Garcia-Rio F. Central apneas and REM sleep behavior disorder as an initial presentation of multiple system atrophy. J Clin Sleep Med 2016;12(2):267–270. PMID:26518702

  3. 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...

  4. Cerebral Atrophy

    MedlinePlus

    ... In brain tissue, atrophy describes a loss of neurons and the connections between them. Atrophy can be ... syndrome, which interfere with the basic functions of neurons multiple sclerosis , which causes inflammation, myelin damage, and ...

  5. Visual MRI Grading System to Evaluate Atrophy of the Supraspinatus Muscle

    PubMed Central

    Lim, Hyun Kyong; Yoo, Hye Jin; Choi, Ja-Young; Kim, Sae Hoon; Choi, Jung-Ah; Kang, Heung Sik

    2014-01-01

    Objective To investigate the interobserver reproducibility and diagnostic feasibility of a visual grading system for assessing atrophy of the supraspinatus muscle on magnetic resonance imaging (MRI). Materials and Methods Three independent radiologists retrospectively evaluated the occupying ratio of the supraspinatus muscle in the supraspinatus fossa on 192 shoulder MRI examinations in 188 patients using a 3-point visual grading system (1, ≥ 60%; 2, 30-59%; 3, < 30%) on oblique sagittal T1-weighted images. The inter-reader agreement and the agreement with the reference standard (3-point grades according to absolute occupying ratio values quantitatively measured by directly contouring the muscles on MRI) were analyzed using weighted kappa. The visual grading was applied by a single reader to a group of 100 consecutive patients who had undergone rotator cuff repair to retrospectively determine the association between the visual grades at preoperative state and postsurgical occurrences of retear. Results The inter-reader weighted kappa value for the visual grading was 0.74 when averaged across three reader pairs (0.70-0.77 for individual reader pairs). The weighted kappa value between the visual grading and the reference standard ranged from 0.75 to 0.83. There was a significant difference in retear rates of the rotator cuff between the 3 visual grades of supraspinatus muscle atrophy on MRI in univariable analysis (p < 0.001), but not in multivariable analysis (p = 0.026). Conclusion The 3-point visual grading system may be a feasible method to assess the severity of supraspinatus muscle atrophy on MRI and assist in the clinical management of patients with rotator cuff tear. PMID:25053911

  6. The ubiquitin proteasome system in atrophying skeletal muscle: roles and regulation.

    PubMed

    Bilodeau, Philippe A; Coyne, Erin S; Wing, Simon S

    2016-09-01

    Muscle atrophy complicates many diseases as well as aging, and its presence predicts both decreased quality of life and survival. Much work has been conducted to define the molecular mechanisms involved in maintaining protein homeostasis in muscle. To date, the ubiquitin proteasome system (UPS) has been shown to play an important role in mediating muscle wasting. In this review, we have collated the enzymes in the UPS whose roles in muscle wasting have been confirmed through loss-of-function studies. We have integrated information on their mechanisms of action to create a model of how they work together to produce muscle atrophy. These enzymes are involved in promoting myofibrillar disassembly and degradation, activation of autophagy, inhibition of myogenesis as well as in modulating the signaling pathways that control these processes. Many anabolic and catabolic signaling pathways are involved in regulating these UPS genes, but none appear to coordinately regulate a large number of these genes. A number of catabolic signaling pathways appear to instead function by inhibition of the insulin/IGF-I/protein kinase B anabolic pathway. This pathway is a critical determinant of muscle mass, since it can suppress key ubiquitin ligases and autophagy, activate protein synthesis, and promote myogenesis through its downstream mediators such as forkhead box O, mammalian target of rapamycin, and GSK3β, respectively. Although much progress has been made, a more complete inventory of the UPS genes involved in mediating muscle atrophy, their mechanisms of action, and their regulation will be useful for identifying novel therapeutic approaches to this important clinical problem. PMID:27510905

  7. The ubiquitin proteasome system in atrophying skeletal muscle: roles and regulation.

    PubMed

    Bilodeau, Philippe A; Coyne, Erin S; Wing, Simon S

    2016-09-01

    Muscle atrophy complicates many diseases as well as aging, and its presence predicts both decreased quality of life and survival. Much work has been conducted to define the molecular mechanisms involved in maintaining protein homeostasis in muscle. To date, the ubiquitin proteasome system (UPS) has been shown to play an important role in mediating muscle wasting. In this review, we have collated the enzymes in the UPS whose roles in muscle wasting have been confirmed through loss-of-function studies. We have integrated information on their mechanisms of action to create a model of how they work together to produce muscle atrophy. These enzymes are involved in promoting myofibrillar disassembly and degradation, activation of autophagy, inhibition of myogenesis as well as in modulating the signaling pathways that control these processes. Many anabolic and catabolic signaling pathways are involved in regulating these UPS genes, but none appear to coordinately regulate a large number of these genes. A number of catabolic signaling pathways appear to instead function by inhibition of the insulin/IGF-I/protein kinase B anabolic pathway. This pathway is a critical determinant of muscle mass, since it can suppress key ubiquitin ligases and autophagy, activate protein synthesis, and promote myogenesis through its downstream mediators such as forkhead box O, mammalian target of rapamycin, and GSK3β, respectively. Although much progress has been made, a more complete inventory of the UPS genes involved in mediating muscle atrophy, their mechanisms of action, and their regulation will be useful for identifying novel therapeutic approaches to this important clinical problem.

  8. 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.

  9. Age-related motor dysfunction and neuropathology in a transgenic mouse model of multiple system atrophy.

    PubMed

    Fernagut, P O; Meissner, W G; Biran, M; Fantin, M; Bassil, F; Franconi, J M; Tison, F

    2014-03-01

    Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by a progressive degeneration of the striatonigral, olivo-ponto-cerebellar, and autonomic systems. Glial cytoplasmic inclusions (GCIs) containing alpha-synuclein represent the hallmark of MSA and are recapitulated in mice expressing alpha-synuclein in oligodendrocytes. To assess if oligodendroglial expression of human wild-type alpha-synuclein in mice (proteolipid promoter, PLP-SYN) could be associated with age-related deficits, PLP-SYN and wild-type mice were assessed for motor function, brain morphometry, striatal levels of dopamine and metabolites, dopaminergic loss, and distribution of GCIs. PLP-SYN displayed age-related impairments on a beam-traversing task. MRI revealed a significantly smaller brain volume in PLP-SYN mice at 12 months, which further decreased at 18 months together with increased volume of ventricles and cortical atrophy. The distribution of GCIs was reminiscent of MSA with a high burden in the basal ganglia. Mild dopaminergic cell loss was associated with decreased dopamine turnover at 18 months. These data indicate that PLP-SYN mice may recapitulate some of the progressive features of MSA and deliver endpoints for the evaluation of therapeutic strategies.

  10. 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

  11. Conventional magnetic resonance imaging in confirmed progressive supranuclear palsy and multiple system atrophy.

    PubMed

    Massey, Luke A; Micallef, Caroline; Paviour, Dominic C; O'Sullivan, Sean S; Ling, Helen; Williams, David R; Kallis, Constantinos; Holton, Janice L; Revesz, Tamas; Burn, David J; Yousry, Tarek; Lees, Andrew J; Fox, Nick C; Jäger, Hans R

    2012-12-01

    Conventional magnetic resonance imaging (cMRI) is often used to aid the diagnosis of progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), but its ability to predict the histopathological diagnosis has not been systematically studied. cMRI from 48 neuropathologically confirmed cases, including PSP (n = 22), MSA (n = 13), Parkinson's disease (PD) (n = 7), and corticobasal degeneration (n = 6), and controls (n = 9) were assessed blinded to clinical details and systematically rated for reported abnormalities. Clinical diagnosis and macroscopic postmortem findings were retrospectively assessed. Radiological assessment of MRI was correct in 16 of 22 (72.7%) PSP cases and 10 of 13 (76.9%) MSA cases with substantial interrater agreement (Cohen's kappa 0.708; P < .001); no PSP case was misclassified as MSA or vice versa. MRI was less sensitive but more specific than clinical diagnosis in PSP and both more sensitive and specific than clinical diagnosis in MSA. The "hummingbird" and "morning glory" signs were highly specific for PSP, and "the middle cerebellar peduncle sign" and "hot cross bun" for MSA, but sensitivity was lower (up to 68.4%) and characteristic findings may not be present even at autopsy. cMRI, clinical diagnosis, and macroscopic examination at postmortem have similar sensitivity and specificity in predicting a neuropathological diagnosis. We have validated specific radiological signs in pathologically confirmed PSP and MSA. However, the low sensitivity of these and macroscopic findings at autopsy suggest a need for imaging techniques sensitive to microstructural abnormalities without regional atrophy.

  12. Parotid gland atrophy induced by occlusion of the ductal system with a protein solution.

    PubMed

    Rettinger, G; Stolte, M; Sidiras, T

    1984-01-01

    Nonneoplastic disorders of the parotid gland, such as chronic recurrent parotitis, asymptomatic gland enlargement, or salivary fistulae, are therapeutic problems. Surgical removal of the gland is often difficult, since scar tissue may be present in these benign diseases. Therefore, alternative treatment methods, such as ligation of Stensen's duct, irradiation, or tympanic neurectomy, have been used to induce atrophy of gland parenchyma. This goal can also be attained by intraluminal duct occlusion, which involves instillation of a resorbable protein solution into the duct system, a procedure similar to sialographic injection. Intraluminal duct occlusion is a simple technique with rapid onset of atrophy and low morbidity, and with its use options remain open for other treatment modalities. The authors have used this method in the treatment of various diseases in 26 parotid glands and one submandibular gland. Their experience, which includes three-year patient follow-up data, suggests that this technique may be a useful alternative to salivary gland resection in certain nonneoplastic diseases.

  13. 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…

  14. 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

  15. Neuroinflammation in Multiple System Atrophy: Response to and Cause of α-Synuclein Aggregation

    PubMed Central

    Vieira, Bruno Di Marco; Radford, Rowan A.; Chung, Roger S.; Guillemin, Gilles J.; Pountney, Dean L.

    2015-01-01

    Multiple system atrophy (MSA) is a progressive neurodegenerative disease presenting with combinations of autonomic dysfunction, parkinsonism, cerebellar ataxia and/or pyramidal signs. Oligodendroglial cytoplasmic inclusions (GCIs) rich in α-synuclein (α-syn) constitute the disease hallmark, accompanied by neuronal loss and activation of glial cells which indicate neuroinflammation. Recent studies demonstrate that α-syn may be released from degenerating neurons to mediate formation of abnormal inclusion bodies and to induce neuroinflammation which, interestingly, might also favor the formation of intracellular α-syn aggregates as a consequence of cytokine release and the shift to a pro-inflammatory environment. Here, we critically review the relationships between α-syn and astrocytic and microglial activation in MSA to explore the potential of therapeutics which target neuroinflammation. PMID:26778958

  16. Development of Intelligent Suits for Disuse Atrophy of Musculoskeletal System Using Hybrid Exercise Method

    NASA Astrophysics Data System (ADS)

    Shiba, Naoto; Yoshimitsu, Kazuhiro; Matsugaki, Tohru; Narita, Arata; Maeda, Takashi; Inada, Tomohisa; Tagawa, Yoshihiko; Numada, Kiyoshi; Nishi, Tetsuya

    We developed ‘Hybrid exercise’ method that was designed to maintain the musculoskeletal system by using electrically stimulated antagonist muscles to resist volitional contraction of agonist muscles. This approach also produces a minimum of inertial reaction forces and has the advantage that it may minimize the need for external stabilization that is currently necessary during exercise in a weightlessness environment. The purpose of this study was to develop the intelligent suits with virtual reality (VR) system that had function of preventing disuse atrophy of musculoskeletal system using hybrid exercise system. Installing of the hybrid exercise system to the subject became easy by the intelligent suits. VR system realized the sense of sight by computer graphics animation synchronized with subjects' motion, and sense of force induced by electrical stimulation. By using VR system, the management of the exercise accomplishment degree was enabled easily because the device could record the exercise history. Intelligent suits with VR hybrid exercise system might become one of the useful countermeasures for the disuse musculoskeletal system in the space.

  17. Expanding concept of clinical conditions and symptoms in multiple system atrophy.

    PubMed

    Watanabe, Hirohisa; Riku, Yuichi; Nakamura, Tomohiko; Hara, Kazuhiro; Ito, Mizuki; Hirayama, Masaaki; Yoshida, Mari; Katsuno, Masahisa; Sobue, Gen

    2016-07-28

    Multiple system atrophy (MSA) is an adult-onset, progressive neurodegenerative disorder. MSA patients show various phenotypes during the course of their illness including parkinsonism, cerebellar ataxia, autonomic failure, and pyramidal signs. MSA is classified into the parkinsonian (MSA-P) or cerebellar (MSA-C) variant depending on the clinical motor phenotype at presentation. MSA-P and MSA-C are predominant in Western countries and Japan, respectively. The mean age at onset is 55 to 60 years. Prognosis ranges from 6 to 10 years, but some cases survive for more than 15 years. Early and severe autonomic failure is a poor prognostic factor. MSA patients sometimes present with isolated autonomic failure or motor symptoms/signs, and the median duration from onset to the concomitant appearance of motor and autonomic symptoms was approximately 2 years in our previous study. As the presence of the combination of motor and autonomic symptoms is essential for the current diagnostic criteria, early diagnosis is difficult when patients present with isolated autonomic failure or motor symptoms/signs. We experienced MSA patients who died before presentation of the motor symptoms/signs diagnostic for MSA (i.e., premotor MSA). Detection of the nature of autonomic failure consistent with MSA and identification of the dysfunctional anatomical sites may increase the probability of a diagnosis of premotor MSA. Dementia is another problem in MSA. Although dementia had been thought to be rare in MSA, frontal lobe dysfunction is observed frequently during the early course of the illness. Magnetic resonance imaging can show progressive cerebral atrophy in longstanding cases. More recently, MSA patients presenting with frontotemporal dementia preceding the presence of motor and autonomic manifestations diagnostic of MSA have been reported. Novel diagnostic criteria based on an expanding concept of the clinical conditions and symptoms of MSA will be needed for the development of disease

  18. 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.

  19. 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

  20. 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.

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

    PubMed

    Hammond, Suzan M; Hazell, Gareth; Shabanpoor, Fazel; Saleh, Amer F; Bowerman, Melissa; Sleigh, James N; Meijboom, Katharina E; Zhou, Haiyan; Muntoni, Francesco; Talbot, Kevin; Gait, Michael J; Wood, Matthew J A

    2016-09-27

    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. 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. PMID:23581648

  3. 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

  4. 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.

  5. Ambulatory blood pressure monitoring and cardiovascular function tests in multiple system atrophy.

    PubMed

    Frongillo, D; Stocchi, F; Buccolini, P; Stecconi, P; Viselli, F; Ruggieri, S; Cannata, D

    1995-01-01

    Cardiovascular tests (CT) of autonomic function and non-invasive ambulatory blood pressure (BP) and heart rate (HR) monitoring were performed in 17 patients with multiple system atrophy (MSA) (mean age 61 +/- 9 years) and in 12 healthy subjects matched for sex and age. CT showed severe autonomic dysfunction with orthostatic hypertension (OH) in eight patients with MSA (47%) (Group I). The remaining nine out of the 17 patients didn't show BP abnormalities during CT but an impaired HR reflex response was found (Group II). BP monitoring showed a reversed circadian BP rhythm in Group I with higher night-time than day-time values, a blunted circadian BP pattern in Group II and a normal day-night BP reduction in controls. Day-night HR reduction was poor in Group II and absent in Group I. Post-prandial hypotension was evaluated after a standard meal. In Group I systolic/diastolic BP fell within 30 minutes after meal (from 135 +/- 16/89 +/- 13 to 118 +/- 17/73 +/- 12 mmHg; p < 0.05) and after two hours had not returned to basal levels. In Group II a reduction of only systolic BP was found within 45 minutes after meal and persisted for one hour. OH clinically identifies a subgroup of MSA patients with a more severe BP dysregulation characterized by severe post-prandial hypotension and reversed circadian BP rhythm. CT and ambulatory BP monitoring are useful tools in identifying early stage of cardiovascular autonomic impairment.

  6. New susceptible variant of COQ2 gene in Japanese patients with sporadic multiple system atrophy

    PubMed Central

    Sun, Zhuoran; Ohta, Yasuyuki; Yamashita, Toru; Sato, Kota; Takemoto, Mami; Hishikawa, Nozomi

    2016-01-01

    Objective: The aim of this study was to analyze the association between the variations of coenzyme Q2 4-hydroxybenzoate polyprenyltransferase gene (COQ2) and Japanese patients with multiple system atrophy (MSA). Methods: We investigated the genetic variations in exons 1, 2, 6, and 7 of the COQ2 gene in 133 Japanese patients with MSA and 200 controls and analyzed the association between the variations and MSA. Results: Six DNA variations (G21S, L25V, V66L, P157S, V393A, and X422K) were found in the 133 patients with MSA, and G21S and X422K were new variations that had never been reported. V66L was a common variation that was found in all 133 patients with MSA. G21S, P157S, V393A, and X422K did not show gene frequency differences between patients with MSA and controls. On the other hand, L25V was newly proven to be the only risk factor of sporadic MSA with predominant olivopontocerebellar ataxia. Conclusions: The present study suggests L25V variant of COQ2 gene as a genetic risk factor in Japanese patients with MSA with cerebellar ataxia. PMID:27123473

  7. Imaging-based differential diagnosis between multiple system atrophy and Parkinson's disease.

    PubMed

    Sako, Wataru; Abe, Takashi; Murakami, Nagahisa; Miyazaki, Yoshimichi; Izumi, Yuishin; Harada, Masafumi; Kaji, Ryuji

    2016-09-15

    There are many tools for differentiating between multiple system atrophy with predominant parkinsonian features (MSA-P) and Parkinson's disease (PD). These include middle cerebellar peduncle (MCP) width, apparent diffusion coefficient (ADC) value of the putamen and cerebellum, and (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy images. We aimed to directly compare the above-mentioned methods, and to determine the optimal tool for differential diagnosis. Eleven patients with MSA-P and 36 patients with PD were enrolled. Of these, 7 patients with MSA-P and 14 patients with PD were chosen as background-matched subjects. We measured MCP width, ADC value of the putamen and cerebellum, and MIBG myocardial scintigraphy images. Area under curve (AUC) of receiver operating characteristic (ROC) was assessed to compare the above-mentioned methods. MCP width and ADC value of the putamen may be helpful for differentiating between MSA-P and PD relative to other methods in background-matched patients (MCP, AUC=0.95; putamen ADC, AUC=0.88; cerebellar ADC, AUC=0.70; MIBG, AUC=0.78). Similar AUCs were seen in all patients with different backgrounds. Our findings suggested that MCP width and ADC value of the putamen could be superior to ADC value of the cerebellum and MIBG uptake for differentiating between MSA-P and PD. PMID:27538610

  8. Activated caspase-9 immunoreactivity in glial and neuronal cytoplasmic inclusions in multiple system atrophy.

    PubMed

    Kawamoto, Yasuhiro; Ayaki, Takashi; Urushitani, Makoto; Ito, Hidefumi; Takahashi, Ryosuke

    2016-08-15

    The mitochondria play an important role in apoptotic cell death, and the released cytochrome c from the mitochondria promotes the formation of the apoptosome, which contains cytochrome c, Apaf-1 and caspase-9, resulting in the activation of caspase-9 and the promotion of the apoptotic cascade. To investigate the role of mitochondria-dependent apoptotic cell death in patients with multiple system atrophy (MSA), we performed immunohistochemical studies on apoptosome-related proteins in formalin-fixed, paraffin-embedded sections from 8 normal subjects and 10 patients with MSA. We then performed double-labeling immunohistochemistry for activated caspase-9 and α-synuclein in some sections from 10 patients with MSA. In the brains with MSA, glial cytoplasmic inclusions (GCIs) and neuronal cytoplasmic inclusions (NCIs) were intensely immunoreactive for cytochrome c, Apaf-1 and caspase-9. Activated caspase-9 immunoreactivities were also confirmed to be densely localized to both GCIs and NCIs using two types of anti-cleaved caspase-9 antibodies. The semiquantitative analyses using the upper pontine sections double-immunostained with cleaved caspase-9 and α-synuclein demonstrated that approximately 80% of GCIs and NCIs were immunopositive for cleaved caspase-9. Our results suggest that the formation of the apoptosome accompanied by the activation of caspase-9 may occur in brains affected by MSA, and that a mitochondria-dependent apoptotic pathway may be partially associated with the pathogenesis of MSA. PMID:27345387

  9. Mutational analysis of CHCHD2 in Chinese patients with multiple system atrophy and amyotrophic lateral sclerosis.

    PubMed

    Yang, Xinglong; An, Ran; Zhao, Quanzhen; Zheng, Jinhua; Tian, Sijia; Chen, Yalan; Xu, Yanming

    2016-09-15

    CHCHD2, which encodes a regulator of mitochondrial metabolism, has been linked to Parkinson's disease (PD) in a Japanese population. Since PD and two other neurodegenerative diseases, multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS), are associated with mitochondrial dysfunction, we wanted to know whether CHCHD2 mutations may be linked to MSA and sporadic ALS in Chinese patients. All four CHCHD2 exons were Sanger-sequenced in 89 patients with MSA, 424 patients with sporadic ALS and 594 unrelated healthy Han Chinese. Four exonic variants were detected in six patients with sporadic ALS: Pro2Leu (rs142444896), Ala32Thr (rs145190179), Ser85Arg (rs182992574), and Tyr99ArgfsX42 (rs778030300). No exonic variants were detected in patients with MSA. Pro2Leu was not significantly associated with risk of ALS in our cohort, and no variants in untranslated or flanking regions of CHCHD2 were associated with risk of MSA or ALS. Our results suggest that genetic variants of CHCHD2 may not be a frequent cause of MSA or ALS in our Chinese population. PMID:27538669

  10. Distinct functional and macrostructural brain changes in Parkinson's disease and multiple system atrophy.

    PubMed

    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

    2015-03-01

    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.

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

    PubMed

    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

  12. XIAP immunoreactivity in glial and neuronal cytoplasmic inclusions in multiple system atrophy.

    PubMed

    Kawamoto, Yasuhiro; Ito, Hidefumi; Ihara, Masafumi; Takahashi, Ryosuke

    2014-01-01

    X-linked inhibitor of apoptosis protein (XIAP) selectively binds to caspases-3, -7 and -9, and inhibits the activities of these caspases. To elucidate the role of XIAP in patients with multiple system atrophy (MSA), we performed immunohistochemical studies on XIAP in formalin-fixed, paraffin-embedded sections from 8 normal subjects and 10 patients with MSA. In normal brains, several types of neurons were immunostained for XIAP, and XIAP-immunopositive oligodendrocytes were scattered throughout the cerebral and cerebellar white matter. In the MSA brains, neuronal XIAP immunoreactivity was spared even in the severely-affected lesions, and glial cytoplasmic inclusions (GCIs), neuronal cytoplasmic inclusions (NCIs) and dystrophic neurites were all intensely immunoreactive for XIAP. A semiquantitative analysis of mid-pons sections double-immunostained for XIAP and α-synuclein demonstrated that the average percentages of XIAP-immunopositive GCIs and NCIs in the pontine nucleus were 70.2% and 82.2%, respectively. Our results suggest that a widespread accumulation of XIAP may occur in brains with MSA, and that XIAP may be partially associated with the pathogenesis of MSA. PMID:23993308

  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. 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.

  15. Depletion of cholinergic neurons of the medullary arcuate nucleus in multiple system atrophy.

    PubMed

    Benarroch, E E; Schmeichel, A M; Parisi, J E

    2001-03-23

    The human arcuate nucleus (ArcN) has been considered akin to the pontine precerebellar nuclei. However, there is anatomical, functional, and clinical evidence that the ArcN may be the homologue of chemosensitive areas of the ventral medullary surface involved in ventilatory responses to hypercarbia and cerebrospinal fluid acidosis. Acetylcholine has been involved in mechanisms of central chemosensitivity. Loss of ArcN neurons has been reported in patients with multiple system atrophy (MSA), a disorder characterized by disturbed automatic ventilation, but the neurochemical identity of these neurons is undetermined. We sought to determine whether the ArcN contains cholinergic neurons and whether these neurons are depleted in patients with MSA. Medullae were obtained from six patients with MSA, five patients with Parkinson's disease (PD) and six sex- and age-matched controls. Fifty-micron transverse sections obtained through the mid-olivary levels were processed for acetylcholinesterase (AchE), choline acetyltransferase (CAT), and alpha-synuclein immunoreactivity. We found that the ArcN contained CAT-positive neurons. There was a significant decrease in density of cholinergic ArcN neurons in MSA but not in PD patients. alpha-Synuclein-containing inclusions were present in the ArcN of MSA patients. Depletion of cholinergic neurons may provide a substrate for disturbances in automatic respiration in MSA patients.

  16. 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.

  17. 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

  18. Sudeck atrophy.

    PubMed

    Staunton, H

    2006-01-01

    This paper reviews the contribution of Sudeck to the understanding of the condition commonly referred to as 'Sudeck's atrophy' and which is commonly used as a synonym for a condition variously called reflex sympathetic dystrophy, causalgia, algodystrophy and others. Sudeck came to show in his later papers that the so-called atrophy was, in the majority of cases, a normal inflammatory process of bone change in the course of healing after an inflammatory/infective or traumatic insult. Contrary to the views of much current literature, the vast majority of such cases had a good prognosis. In those cases which became pathological and had a correspondingly poorer prognosis, the characteristic clinical picture becomes associated with radiological and pathological changes, which, uniquely, are described by Sudeck. A knowledge of such radiological and pathological substrate for clinical symptomatology is important in the analysis of pain following trauma. PMID:17274178

  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. 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

  1. 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

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

    PubMed

    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

    2015-09-22

    Prions are proteins that adopt alternative conformations that become self-propagating; the PrP(Sc) 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. 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.

  4. The European Multiple System Atrophy-Study Group (EMSA-SG).

    PubMed

    Geser, F; Seppi, K; Stampfer-Kountchev, M; Köllensperger, M; Diem, A; Ndayisaba, J P; Ostergaard, K; Dupont, E; Cardozo, A; Tolosa, E; Abele, M; Dodel, R; Klockgether, T; Ghorayeb, I; Yekhlef, F; Tison, F; Daniels, C; Kopper, F; Deuschl, G; Coelho, M; Ferreira, J; Rosa, M M; Sampaio, C; Bozi, M; Schrag, A; Hooker, J; Kim, H; Scaravilli, T; Mathias, C J; Fowler, C; Wood, N; Quinn, N; Widner, H; Nilsson, C F; Lindvall, O; Schimke, N; Eggert, K M; Oertel, W; del Sorbo, F; Carella, F; Albanese, A; Pellecchia, M T; Barone, P; Djaldetti, R; Meco, G; Colosimo, C; Gonzalez-Mandly, A; Berciano, J; Gurevich, T; Giladi, N; Galitzky, M; Ory, F; Rascol, O; Kamm, C; Buerk, K; Maass, S; Gasser, T; Poewe, W; Wenning, G K

    2005-12-01

    Introduction. The European Multiple System Atrophy-Study Group (EMSA-SG) is an academic network comprising 23 centers across Europe and Israel that has constituted itself already in January 1999. This international forum of established experts under the guidance of the University Hospital of Innsbruck as coordinating center is supported by the 5th framework program of the European Union since March 2001 (QLK6-CT-2000-00661). Objectives. Primary goals of the network include (1) a central Registry for European multiple system atrophy (MSA) patients, (2) a decentralized DNA Bank, (3) the development and validation of the novel Unified MSA Rating Scale (UMSARS), (4) the conduction of a Natural History Study (NHS), and (5) the planning or implementation of interventional therapeutic trials. Methods. The EMSA-SG Registry is a computerized data bank localized at the coordinating centre in Innsbruck collecting diagnostic and therapeutic data of MSA patients. Blood samples of patients and controls are recruited into the DNA Bank. The UMSARS is a novel specific rating instrument that has been developed and validated by the EMSA-SG. The NHS comprises assessments of basic anthropometric data as well as a range of scales including the UMSARS, Unified Parkinson's Disease Rating Scale (UPDRS), measures of global disability, Red Flag list, MMSE (Mini Mental State Examination), quality of live measures, i.e. EuroQoL 5D (EQ-5D) and Medical Outcome Study Short Form (SF-36) as well as the Beck Depression Inventory (BDI). In a subgroup of patients dysautonomic features are recorded in detail using the Queen Square Cardiovascular Autonomic Function Test Battery, the Composite Autonomic Symptom Scale (COMPASS) and measurements of residual urinary volume. Most of these measures are repeated at 6-monthly follow up visits for a total study period of 24 months. Surrogate markers of the disease progression are identified by the EMSA-SG using magnetic resonance and diffusion weighted imaging

  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. 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.

  7. 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

  8. α-Synuclein-induced myelination deficit defines a novel interventional target for multiple system atrophy.

    PubMed

    Ettle, Benjamin; Kerman, Bilal E; Valera, Elvira; Gillmann, Clarissa; Schlachetzki, Johannes C M; Reiprich, Simone; Büttner, Christian; Ekici, Arif B; Reis, André; Wegner, Michael; Bäuerle, Tobias; Riemenschneider, Markus J; Masliah, Eliezer; Gage, Fred H; Winkler, Jürgen

    2016-07-01

    Multiple system atrophy (MSA) is a rare atypical parkinsonian disorder characterized by a rapidly progressing clinical course and at present without any efficient therapy. Neuropathologically, myelin loss and neurodegeneration are associated with α-synuclein accumulation in oligodendrocytes, but underlying pathomechanisms are poorly understood. Here, we analyzed the impact of oligodendrocytic α-synuclein on the formation of myelin sheaths to define a potential interventional target for MSA. Post-mortem analyses of MSA patients and controls were performed to quantify myelin and oligodendrocyte numbers. As pre-clinical models, we used transgenic MSA mice, a myelinating stem cell-derived oligodendrocyte-neuron co-culture, and primary oligodendrocytes to determine functional consequences of oligodendrocytic α-synuclein overexpression on myelination. We detected myelin loss accompanied by preserved or even increased numbers of oligodendrocytes in post-mortem MSA brains or transgenic mouse forebrains, respectively, indicating an oligodendrocytic dysfunction in myelin formation. Corroborating this observation, overexpression of α-synuclein in primary and stem cell-derived oligodendrocytes severely impaired myelin formation, defining a novel α-synuclein-linked pathomechanism in MSA. We used the pro-myelinating activity of the muscarinic acetylcholine receptor antagonist benztropine to analyze the reversibility of the myelination deficit. Transcriptome profiling of primary pre-myelinating oligodendrocytes demonstrated that benztropine readjusts myelination-related processes such as cholesterol and membrane biogenesis, being compromised by oligodendrocytic α-synuclein. Additionally, benztropine restored the α-synuclein-induced myelination deficit of stem cell-derived oligodendrocytes. Strikingly, benztropine also ameliorated the myelin deficit in transgenic MSA mice, resulting in a prevention of neuronal cell loss. In conclusion, this study defines the

  9. Risk factors of multiple system atrophy: a case-control study in French patients.

    PubMed

    Vidal, Jean-Sébastien; Vidailhet, Marie; Elbaz, Alexis; Derkinderen, Pascal; Tzourio, Christophe; Alpérovitch, Annick

    2008-04-30

    Multiple system atrophy (MSA) is a rare sporadic progressive neurodegenerative disorder. MSA risk factors are poorly known. The objectives of this case-control study were to study environmental risk factors associated with MSA. Cases were recruited through five French referral centers. Controls matched for age, gender, and living area were recruited from healthy relatives of inpatients free of any parkinsonian syndrome of the same centers. Subjects were interviewed about exposure to environmental factors (pesticides, solvents, etc.), occupation and food habits, and use of anti-inflammatory drugs. Odds ratios and 95% confident intervals (OR [95% CI]) were computed using conditional logistic regression. Seventy-one cases and 71 matched controls were included. Low education level was more frequent in cases than in controls. Controls drank more alcohol than did cases (OR = 0.5 [0.2-1.1]) and the risk of MSA decreased with increasing alcohol consumption (P = 0.04). Controls ate fish and sea food more often and drank more tea than cases. Aspirin intake was more frequent among controls than did cases (OR = 0.5 [0.2-1.0]) and the risk of MSA decreased with the frequency of intake (P = 0.0002). MSA was not associated to exposure to pesticides, solvents, and other toxics neither to occupations, except plant and machine operators and assemblers (OR = 10.0 [2.1-47.5]) where the risk of MSA increased with number of years in this occupation (P = 0.004). This case-control study provided new findings about risk factors of MSA. On another hand, it did not confirm the previously reported association between MSA and exposure to pesticides.

  10. Artificial neural networks to model and diagnose cardiovascular systems

    SciTech Connect

    Kangas, L.J.; Keller, P.E.; Allen, P.A.

    1995-12-31

    In this paper, 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 actual 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.

  11. 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.

  12. 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.

  13. 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).

  14. 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.

  15. The Global Cognition, Frontal Lobe Dysfunction and Behavior Changes in Chinese Patients with Multiple System Atrophy

    PubMed Central

    Cao, Bei; Zhao, Bi; Wei, Qian-Qian; Chen, Ke; Yang, Jing; Ou, RuWei; Wu, Ying; Shang, Hui-Fang

    2015-01-01

    Background Studies on cognition in multiple system atrophy (MSA) patients are limited. Methods A total of 110 MSA patients were evaluated using Addenbrooke's Cognitive Examination-Revised (ACE-R), Frontal Assessment Battery (FAB), Frontal Behavioral Inventory (FBI), and Unified MSA Rating Scale (UMSARS) tests. Fifty-five age-, sex-, education- and domicile-matched healthy controls were recruited to perform the FAB and ACE-R scales. Results Approximately 32.7% of the patients had global cognitive deficits with the most impaired domain being verbal fluency and visuospatial ability (26.4%), followed by memory (24.5%), language (20%) and orientation/attention (20%) based on a cut-off score of ACE-R ≤ 70. A total of 41.6% of the patients had frontal lobe dysfunction, with inhibitory control (60.9%) as the most impaired domain based on a cut-off score of FAB ≤14. Most patients (57.2%) showed moderate frontal behavior changes (FBI score 4–15), with incontinence (64.5%) as the most impaired domain. The binary logistic regression model revealed that an education level < 9 years (OR:13.312, 95% CI:2.931–60.469, P = 0.001) and UMSARS ≥ 40 (OR: 2.444, 95%CI: 1.002–5.962, P< 0.049) were potential determinants of abnormal ACE-R, while MSA-C (OR: 4.326, 95%CI: 1.631–11.477, P = 0.003), an education level < 9 years (OR:2.809 95% CI:1.060–7.444, P = 0.038) and UMSARS ≥ 40 (OR:5.396, 95%CI: 2.103–13.846, P < 0.0001) were potential determinants of abnormal FAB. Conclusions Cognitive impairment is common in Chinese MSA patients. MSA-C patients with low education levels and severe motor symptoms are likely to experience frontal lobe dysfunction, while MSA patients with low education levels and severe motor symptoms are likely to experience global cognitive deficits. These findings strongly suggest that cognitive impairment should not be an exclusion criterion for the diagnosis of MSA. PMID:26431430

  16. 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.

  17. 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…

  18. 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…

  19. Extraocular Muscle Atrophy and Central Nervous System Involvement in Chronic Progressive External Ophthalmoplegia

    PubMed Central

    Yu-Wai-Man, Cynthia; Smith, Fiona E.; Firbank, Michael J.; Guthrie, Grant; Guthrie, Stuart; Gorman, Grainne S.; Taylor, Robert W.; Turnbull, Douglass M.; Griffiths, Philip G.; Blamire, Andrew M.; Chinnery, Patrick F.; Yu-Wai-Man, Patrick

    2013-01-01

    Background Chronic progressive external ophthalmoplegia (CPEO) is a classical mitochondrial ocular disorder characterised by bilateral progressive ptosis and ophthalmoplegia. These ocular features can develop either in isolation or in association with other prominent neurological deficits (CPEO+). Molecularly, CPEO can be classified into two distinct genetic subgroups depending on whether patients harbour single, large-scale mitochondrial DNA (mtDNA) deletions or multiple mtDNA deletions secondary to a nuclear mutation disrupting mtDNA replication or repair. The aim of this magnetic resonance imaging (MRI) study was to investigate whether the ophthalmoplegia in CPEO is primarily myopathic in origin or whether there is evidence of contributory supranuclear pathway dysfunction. Methods Ten age-matched normal controls and twenty patients with CPEO were recruited nine patients with single, large-scale mtDNA deletions and eleven patients with multiple mtDNA deletions secondary to mutations in POLG, PEO1, OPA1, and RRM2B. All subjects underwent a standardised brain and orbital MRI protocol, together with proton magnetic resonance spectroscopy in two voxels located within the parietal white matter and the brainstem. Results There was evidence of significant extraocular muscle atrophy in patients with single or multiple mtDNA deletions compared with controls. There was no significant difference in metabolite concentrations between the patient and control groups in both the parietal white matter and brainstem voxels. Volumetric brain measurements revealed marked cortical and cerebellar atrophy among patients with CPEO+ phenotypes. Conclusion The results of this study support a primary myopathic aetiology for the progressive limitation of eye movements that develops in CPEO. PMID:24086434

  20. 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. ...

  1. [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.

  2. [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. PMID:22790804

  3. 38 CFR 4.115b - Ratings of the genitourinary system-diagnoses.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... genitourinary system-diagnoses. 4.115b Section 4.115b Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Genitourinary System § 4.115b Ratings of the genitourinary system—diagnoses. Rating Note: When evaluating any claim involving loss...

  4. 38 CFR 4.115b - Ratings of the genitourinary system-diagnoses.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... genitourinary system-diagnoses. 4.115b Section 4.115b Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Genitourinary System § 4.115b Ratings of the genitourinary system—diagnoses. Rating Note: When evaluating any claim involving loss...

  5. 38 CFR 4.115b - Ratings of the genitourinary system-diagnoses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... genitourinary system-diagnoses. 4.115b Section 4.115b Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Genitourinary System § 4.115b Ratings of the genitourinary system—diagnoses. Rating Note: When evaluating any claim involving loss...

  6. 38 CFR 4.115b - Ratings of the genitourinary system-diagnoses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... genitourinary system-diagnoses. 4.115b Section 4.115b Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES Disability Ratings The Genitourinary System § 4.115b Ratings of the genitourinary system—diagnoses. Rating Note: When evaluating any claim involving loss...

  7. Vaginal Atrophy

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... Women's Health Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ...

  8. Histopathological Defects in Intestine in Severe Spinal Muscular Atrophy Mice Are Improved by Systemic Antisense Oligonucleotide Treatment

    PubMed Central

    Sintusek, Palittiya; Catapano, Francesco; Angkathunkayul, Napat; Marrosu, Elena; Parson, Simon H.; Morgan, Jennifer E.; Muntoni, Francesco; Zhou, Haiyan

    2016-01-01

    Gastrointestinal (GI) defects, including gastroesophageal reflux, constipation and delayed gastric emptying, are common in patients with spinal muscular atrophy (SMA). Similar GI dysmotility has been identified in mouse models with survival of motor neuron (SMN) protein deficiency. We previously described vascular defects in skeletal muscle and spinal cord of SMA mice and we hypothesized that similar defects could be involved in the GI pathology observed in these mice. We therefore investigated the gross anatomical structure, enteric vasculature and neurons in the small intestine in a severe mouse model of SMA. We also assessed the therapeutic response of GI histopathology to systemic administration of morpholino antisense oligonucleotide (AON) designed to increase SMN protein expression. Significant anatomical and histopathological abnormalities, with striking reduction of vascular density, overabundance of enteric neurons and increased macrophage infiltration, were detected in the small intestine in SMA mice. After systemic AON treatment in neonatal mice, all the abnormalities observed were significantly restored to near-normal levels. We conclude that the observed GI histopathological phenotypes and functional defects observed in these SMA mice are strongly linked to SMN deficiency which can be rescued by systemic administration of AON. This study on the histopathological changes in the gastrointestinal system in severe SMA mice provides further indication of the complex role that SMN plays in multiple tissues and suggests that at least in SMA mice restoration of SMN production in peripheral tissues is essential for optimal outcome. PMID:27163330

  9. Psychiatric diagnoses in legal systems: an issue of validity.

    PubMed

    Mellsop, Graham W; Diesfel, Kate

    2011-12-01

    When considering psychiatric evidence, justice systems from many countries are frequently presented with diagnostic labels from official psychiatric classificatory systems. A lack of validity in much of these classificatory systems is receiving increasing attention. Illustrative examples include post-traumatic stress disorder, various personality disorders and dissociative identity disorder. The courts and review bodies from many jurisdictions place tremendous faith in the present categorical classifications (e.g., DSMIV and ICD10). This paper questions whether the reliance on these classifications systems is appropriate in legal proceedings.

  10. Muscle expression of mutant androgen receptor protein accounts for systemic and motor neuron disease phenotypes in Spinal & Bulbar Muscular Atrophy

    PubMed Central

    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.

    2014-01-01

    X-linked spinal & 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. PMID:24742458

  11. Impaired regulation of gonadotropins leads to the atrophy of the female reproductive system in klotho-deficient mice.

    PubMed

    Toyama, Ryusuke; Fujimori, Toshihiko; Nabeshima, Yoko; Itoh, Yoshiko; Tsuji, Yoshihito; Osamura, R Yoshiyuki; Nabeshima, Yo-Ichi

    2006-01-01

    klotho-Deficient mice exhibit a syndrome resembling human premature ageing, with multiple pathological phenotypes in tissues including reproductive organs. It was proposed that Klotho might possess the hormonal effects on many organs. In this study, the female reproductive system of klotho mice was examined to reveal the mechanism that brought the female sterility by histological and molecular approaches. We observed cessation of ovarian follicular maturation at the preantral stage and the presence of numerous atretic ovarian follicles and atrophic uteri. In situ hybridization analysis revealed that LH receptor and aromatase P450 were not expressed in the ovaries. These results suggest the impairment of gonadal development during the antral transition process. We next addressed the responsible organs for the failure of antral transition. Transplantation of klotho ovaries to wild-type mice resulted in the ability to bear offspring. Administration of FSH or GnRH induced advanced maturation of ovaries and uteri in klotho mice. These results indicate that the female reproductive organs in klotho mice are potentially functional and that klotho gene deficiency leads to the atrophy of reproductive organs via impairment of the hypothalamic-pituitary axis. Absence of the estrus cycle and constant low trends of both FSH and LH levels were found in female klotho mice. Immunohistochemical analysis revealed that the production of both FSH and LH were decreased in pituitary gland. Taken together, our findings suggest the involvement of klotho in the regulatory control of pituitary hormones.

  12. Subgroup differences in 'brain-type' transferrin and α-synuclein in Parkinson's disease and multiple system atrophy.

    PubMed

    Yoshihara, Akioh; Fukatsu, Masahiko; Hoshi, Kyoka; Ito, Hiromi; Nollet, Kenneth; Yamaguchi, Yoshiki; Ishii, Ryotaro; Tokuda, Takahiko; Miyajima, Masakazu; Arai, Hajime; Kato, Takeo; Furukawa, Katsutoshi; Arai, Hiroyuki; Kikuchi, Akio; Takeda, Atsushi; Ugawa, Yoshikazu; Hashimoto, Yasuhiro

    2016-08-01

    Two transferrin (Tf) glycan-isoforms were previously found in cerebrospinal fluid (CSF); one appears to be derived from serum (Tf-2) and the other from choroid plexus, a CSF-producing tissue (Tf-1). To analyse metabolic differences associated with the two isoforms, their ratio (Tf-2/Tf-1) was defined as the Tf index. Here we report that Tf indices of patients with tauopathies including Alzheimer's disease (2.29 + 0.64) were similar to those of neurological controls (2.07 + 0.87) (P = 0.147). In contrast, Tf indices with Parkinson's disease (PD, 3.38 ± 1.87) and multiple system atrophy (MSA, 3.15 ± 1.72) were higher than those of the controls (2.07 ± 0.87), the P-values being < 0.001 and 0.024, respectively. Tf indices of PD and MSA did not appear to be normally distributed. Indeed, detrended normal Quantile-Quantile plot analysis revealed the presence of an independent subgroup showing higher Tf indices in PD and MSA. The subgroup of PD showed higher levels of CSF α-synuclein (38.3 ± 17.8 ng/ml) than the rest (25.3 ± 11.3 ng/ml, P = 0.012). These results suggest that PD (and MSA) includes two subgroups, which show different metabolism of CSF transferrin and α-synuclein. PMID:26970280

  13. 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.

  14. Study on fault diagnose expert system for large astronomy telescope

    NASA Astrophysics Data System (ADS)

    Liu, Jia-jing; Luo, Ming-Cheng; Tang, Peng-yi; Wu, Wen-qing; Zhang, Guang-yu; Zhang, Hong-fei; Wang, Jian

    2014-08-01

    The development of astronomical techniques and telescopes currently entered a new vigorous period. The telescopes have trends of the giant, complex, diversity of equipment and wide span of control despite of optical, radio space telescopes. That means, for telescope observatory, the control system must have these specifications: flexibility, scalability, distributive, cross-platform and real-time, especially the fault locating and fault processing is more important when fault or exception arise. Through the analysis of the structure of large telescopes, fault diagnosis expert system of large telescope based on the fault tree and distributed log service is given.

  15. Diagnosing strategic performance of the hospital information systems planning cycle.

    PubMed

    Ferrand, D J; Lay, C M

    1994-01-01

    Hospital information systems planning (HISP) involves large expenditures. Often the evaluation of its performance is unstructured, giving no direction for future strategic choices for information systems (IS) development. This article formulates the challenge facing senior management when it must define priorities for the next IS planning cycle. New IS applications are selected to enhance the IS portfolio profile and the users' functionality, taking account of the past and anticipated response to resources invested. A methodology, new tools, and analyses for conducting the diagnosis of the last planning cycle are described.

  16. 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.

  17. 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.

  18. An expert system for diagnosing anomalies of spacecraft

    NASA Technical Reports Server (NTRS)

    Lauriente, Michael; Durand, Rick; Vampola, AL; Koons, Harry C.; Gorney, David

    1994-01-01

    Although the analysis of anomalous behavior of satellites is difficult because it is a very complex process, it is important to be able to make an accurate assessment in a timely manner when the anomaly is observed. Spacecraft operators may have to take corrective action or to 'safe' the spacecraft; space-environment forecasters may have to assess the environmental situation and issue warnings and alerts regarding hazardous conditions, and scientists and engineers may want to gain knowledge for future designs to mitigate the problems. Anomalies can be hardware problems, software errors, environmentally induced, or even the cause of workmanship. Spacecraft anomalies attributable to electrostatic discharges have been known to cause command errors. A goal is to develop an automated system based on this concept to reduce the number of personnel required to operate large programs or missions such as Hubble Space Telescope (HST) and Mission to Planet Earth (MTPE). Although expert systems to detect anomalous behavior of satellites during operations are established, diagnosis of the anomaly is a complex procedure and is a new development.

  19. Diagnosing and curing system freeze-ups: Part II

    SciTech Connect

    Frey, R.

    1996-02-01

    In our last article, we discussed determination and possible causes leading to frozen pipes in the heating system. We now turn to the matter of dealing with such freeze-ups. There are two major categories of frozen heating systems. The first and worst we can label the {open_quotes}Floridian Flew{close_quotes} type, when the usual occupants have taken off for warmer climates. The second is the {open_quotes}Howcudit {open_quote}B{close_quote} virus,{close_quotes} which occurs to normal people under an unusual Arctic Attack right while they are living there. Regarding the first, I never cease to be amazed how folks can just up and leave their house for three days to three months without making proper arrangements for monitoring the temperature of their home during their absence. There are a frightening number of humanoids out there, who either lack a minimal presence of common sense, or who are terrible gamblers. The amazing thing is that some of these folks wouldn`t even gamble a postage stamp on a magazine sweepstakes, but still will gamble the contents of their home by driving off for two weeks at Disneyland in the middle of January without ever making any provision for assuring that their house doesn`t freeze up while they are away. The {open_quotes}Howcudit {open_quote}B{close_quote}{close_quotes} type is not nearly as devasting as the {open_quotes}Floridian Flew.{close_quotes} Imagine coming home to an icy cold house after flying in from the sunny beaches of some tropical paradise. The oilburner switch is on. The thermostate is set at 60 where we left it, but the needle is buried somewhere down behind the cover, like it is cowering from guilt. {open_quotes}Oh Man! I just checked the bathroom; there is an icicle hanging from the vanity faucet and the toilet bowl is a block of ice.{close_quotes}

  20. Tracking sensory system atrophy and outcome prediction in spinal cord injury

    PubMed Central

    Grabher, Patrick; Callaghan, Martina F.; Ashburner, John; Weiskopf, Nikolaus; Thompson, Alan J.; Curt, Armin

    2015-01-01

    Objective In patients with subacute spinal cord injury (SCI), the motor system undergoes progressive structural changes rostral to the lesion, which are associated with motor outcome. The extent to which the sensory system is affected and how this relates to sensory outcome are uncertain. Methods Changes in the sensory system were prospectively followed by applying a comprehensive magnetic resonance imaging (MRI) protocol to 14 patients with subacute traumatic SCI at baseline, 2 months, 6 months, and 12 months after injury, combined with a full neurological examination and comprehensive pain assessment. Eighteen controls underwent the same MRI protocol. T1‐weighted volumes, myelin‐sensitive magnetization transfer saturation (MT), and longitudinal relaxation rate (R1) mapping provided data on spinal cord and brain morphometry and microstructure. Regression analysis assessed the relationship between MRI readouts and sensory outcomes. Results At 12 months from baseline, sensory scores were unchanged and below‐level neuropathic pain became prominent. Compared with controls, patients showed progressive degenerative changes in cervical cord and brain morphometry across the sensory system. At 12 months, MT and R1 were reduced in areas of structural decline. Sensory scores at 12 months correlated with rate of change in cord area and brain volume and decreased MT in the spinal cord at 12 months. Interpretation This study has demonstrated progressive atrophic and microstructural changes across the sensory system with a close relation to sensory outcome. Structural MRI protocols remote from the site of lesion provide new insights into neuronal degeneration underpinning sensory disturbance and have potential as responsive biomarkers of rehabilitation and treatment interventions. Ann Neurol 2015;78:Ann Neurol 2015;78:679–696 PMID:26290444

  1. Diffuse periventricular calcification and brain atrophy: A case of neonatal central nervous system cytomegalovirus infection.

    PubMed

    Sanchez, Thomas R; Datlow, Mitchell D; Nidecker, Anna E

    2016-10-01

    TORCH refers to the most common congenitally acquired infections: toxoplasma, rubella, cytomegalovirus, and herpes simplex virus. Neonatal cytomegalovirus infection remains a common cause of congenital infection worldwide with effects ranging from hearing impairment to significant neurological morbidity. We report a case of a term neonate with ventriculomegaly on prenatal ultrasound who presented with low birth weight, small head circumference, hepatosplenomegaly, and purpuric rash on physical exam. Central nervous system cytomegalovirus infection typically shows periventricular calcifications and associated deep white matter damage and ventriculomegaly. Ultrasound, computed tomography, and magnetic resonance imaging have different roles in the diagnosis of congenital central nervous system cytomegalovirus infection. Many imaging features of congenital cytomegalovirus are distinctive, and can spur a diagnostic work-up as well as help provide a prognosis. PMID:27531861

  2. 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. PMID:26750813

  3. A Type-2 Fuzzy Image Processing Expert System for Diagnosing Brain Tumors.

    PubMed

    Zarinbal, M; Fazel Zarandi, M H; Turksen, I B; Izadi, M

    2015-10-01

    The focus of this paper is diagnosing and differentiating Astrocytomas in MRI scans by developing an interval Type-2 fuzzy automated tumor detection system. This system consists of three modules: working memory, knowledge base, and inference engine. An image processing method with three steps of preprocessing, segmentation and feature extraction, and approximate reasoning is used in inference engine module to enhance the quality of MRI scans, segment them into desired regions, extract the required features, and finally diagnose and differentiate Astrocytomas. However, brain tumors have different characteristics in different planes, so considering one plane of patient's MRI scan may cause inaccurate results. Therefore, in the developed system, several consecutive planes are processed. The performance of this system is evaluated using 95 MRI scans and the results show good improvement in diagnosing and differentiating Astrocytomas.

  4. 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

  5. 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.

  6. 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. PMID:27482103

  7. Accumulation of Hsc70 and Hsp70 in glial cytoplasmic inclusions in patients with multiple system atrophy.

    PubMed

    Kawamoto, Yasuhiro; Akiguchi, Ichiro; Shirakashi, Yoshitomo; Honjo, Yasuyuki; Tomimoto, Hidekazu; Takahashi, Ryosuke; Budka, Herbert

    2007-03-01

    Heat shock proteins (HSPs) are molecular chaperones which can be induced by several kinds of stresses, and Hsc70 and Hsp70 are two major members of the family of 70 kDa HSPs. A major component of Lewy bodies (LBs) is alpha-synuclein, and Hsp70 has been observed in the LBs of brains with Parkinson's disease. Hsp70 has also been demonstrated to have the ability to suppress alpha-synuclein toxicity in vitro and in vivo. To investigate the precise role of Hsc70 and Hsp70 in patients with multiple system atrophy (MSA), which is another alpha-synuclein-related disease, we performed immunohistochemical studies on Hsc70 and Hsp70 using autopsied brains from 7 normal subjects and 15 patients with MSA. In the normal human brains, both neurons and glial cells, including oligodendrocytes, showed only weak Hsc70 and Hsp70 immunoreactivities. In contrast, in the brains with MSA, numerous glial cytoplasmic inclusions (GCIs) were intensely immunostained with Hsc70, and strong Hsc70 immunoreactivity was also found in glial intranuclear inclusions (GNIs), neuronal cytoplasmic inclusions (NCIs) and neuronal intranuclear inclusions (NNIs) as well as dystrophic neurites. The immunolabeling pattern for Hsp70 in the MSA brains was slightly different from that of Hsc70, and Hsp70 immunoreactivity was observed in many reactive astrocytes as well as some glial and neuronal inclusions. Our results suggest that the widespread accumulation of Hsc70 and Hsp70 may occur in brains with MSA, and that Hsc70 and Hsp70 may be associated with the pathogenesis of MSA. PMID:17240362

  8. 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.

  9. Antidepressants reduce neuroinflammatory responses and astroglial alpha-synuclein accumulation in a transgenic mouse model of Multiple System Atrophy

    PubMed Central

    Valera, Elvira; Ubhi, Kiren; Mante, Michael; Rockenstein, Edward; Masliah, Eliezer

    2014-01-01

    Multiple system atrophy (MSA) is a neurodegenerative disease characterized by the pathological accumulation of alpha-synuclein (α-syn) within oligodendroglial cells. This accumulation is accompanied by neuroinflammation with astrogliosis and microgliosis, that leads to neuronal death and subsequent parkinsonism and dysautonomia. Antidepressants have been explored as neuroprotective agents as they normalize neurotrophic factor levels, increase neurogenesis and reduce neurodegeneration, but their anti-inflammatory properties have not been fully characterized. We analyzed the anti-inflammatory profiles of three different antidepressants (fluoxetine, olanzapine and amitriptyline) in the MBP1-hα-syn transgenic (tg) mouse model of MSA. We observed that antidepressant treatment decreased the number of α-syn-positive cells in the basal ganglia of 11-month old tg animals. This reduction was accompanied with a similar decrease in the colocalization of α-syn with astrocyte markers in this brain structure. Consistent with these results, antidepressants reduced astrogliosis in the hippocampus and basal ganglia of the MBP1-hα-syn tg mice, and modulated the expression levels of key cytokines that were dysregulated in the tg mouse model, such as IL-1β. In vitro experiments in the astroglial cell line C6 confirmed that antidepressants inhibited NF-κB translocation to the nucleus and reduced IL-1β protein levels. We conclude that the anti-inflammatory properties of antidepressants in the MBP1-hα-syn tg mouse model of MSA might be related to their ability to inhibit α-syn propagation from oligodendrocytes to astroglia and to regulate transcription factors involved in cytokine expression. Our results suggest that antidepressants might be of interest as anti-inflammatory and α-syn-reducing agents for MSA and other α-synucleinopathies. PMID:24310907

  10. Anle138b Partly Ameliorates Motor Deficits Despite Failure of Neuroprotection in a Model of Advanced Multiple System Atrophy

    PubMed Central

    Fellner, Lisa; Kuzdas-Wood, Daniela; Levin, Johannes; Ryazanov, Sergey; Leonov, Andrei; Griesinger, Christian; Giese, Armin; Wenning, Gregor K.; Stefanova, Nadia

    2016-01-01

    The neurodegenerative disorder multiple system atrophy (MSA) is characterized by autonomic failure, cerebellar ataxia and parkinsonism in any combination associated with predominantly oligodendroglial α-synuclein (α-syn) aggregates (glial cytoplasmic inclusions = GCIs). To date, there is no effective disease modifying therapy. Previous experiments have shown that the aggregation inhibitor anle138b reduces neurodegeneration, as well as behavioral deficits in both transgenic and toxin mouse models of Parkinson's disease (PD). Here we analyzed whether anle138b improves motor skills and reduces neuronal loss, as well as oligodendroglial α-syn aggregation in the PLP-α-syn transgenic mouse challenged with the mitochondrial toxin 3-nitropropionic acid (3-NP) to model full-blown MSA. Following 1 month of treatment with anle138b, MSA mice showed signs of motor improvement affecting stride length, but not pole, grip strength, and beam test performance. Loss of dopaminergic nigral neurons and Purkinje cells was not attenuated and GCI density remained unchanged. These data suggest that the pathology in transgenic PLP-α-syn mice receiving 3-NP might be too advanced to detect significant effects of anle138b treatment on neuronal loss and intracytoplasmic α-syn inclusion bodies. However, the partial motor amelioration may indicate potential efficacy of anle138b treatment that may be mediated by its actions on α-syn oligomers or may reflect improvement of neuronal dysfunction in neural at risk populations. Further studies are required to address the efficacy of anle138b in transgenic α-syn models of early-stage MSA and in the absence of additional toxin application. PMID:27013960

  11. 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.

  12. Can endoscopic atrophy predict histological atrophy? Historical study in United Kingdom and Japan

    PubMed Central

    Kono, Shin; Gotoda, Takuji; Yoshida, Shigeaki; Oda, Ichiro; Kondo, Hitoshi; Gatta, Luigi; Naylor, Greg; Dixon, Michael; Moriyasu, Fuminori; Axon, Anthony

    2015-01-01

    AIM: To assess the diagnostic concordance between endoscopic and histological atrophy in the United Kingdom and Japan. METHODS: Using published data, a total of 252 patients, 126 in the United Kingdom and 126 in Japan, aged 20 to 80 years, were evaluated. The extent of endoscopic atrophy was classified into five subgroups according to a modified Kimura-Takemoto classification system and was compared with histological findings of atrophy at five biopsy sites according to the updated Sydney system. RESULTS: The strength of agreement of the extent of atrophy between histology and visual endoscopic inspection showed good reproducibility, with a weighted kappa value of 0.76 (P < 0.001). Multivariate analysis showed that three factors were associated with decreased concordance: Japanese ethnicity [odds ratio (OR) 0.22, 95% confidence interval (CI) 0.11-0.43], older age (OR = 0.32, 95%CI: 0.16-0.66) and endoscopic atrophy (OR = 0.10, 95%CI: 0.03-0.36). The strength of agreement between endoscopic and histological atrophy, assessed by cancer risk-oriented grading, was reproducible, with a kappa value of 0.81 (95%CI: 0.75-0.87). Only nine patients (3.6%) were endoscopically underdiagnosed with antral predominant rather than extensive atrophy and were considered false negatives. CONCLUSION: Endoscopic grading can predict histological atrophy with few false negatives, indicating that precancerous conditions can be identified during screening endoscopy, particularly in patients in western countries. PMID:26673849

  13. Diagnosing system for an exhaust gas recirculation system of an automotive engine

    SciTech Connect

    Tamura, I.

    1988-02-09

    This patent describes a diagnosing system for an exhaust gas recirculation system having an EGR passage communicating an exhaust pipe of an engine with an intake passage of the engine, an EGR valve provided in the EGR passage, control means for opening the EGR valve in accordance with enigne operating conditions comprising: first means for detecting flow rate of recirculated gas in the EGR passage and for producing an actual EGR rate signal dependent on the flow rate; second means for producing a desired EGR rate signal including an allowable range in accordance with engine operating conditions; and third means responsive to the actual EGR rate signal and the desired EGR rate signal for producing a trouble signal as an alarm signal when the actual EGR rate signal is out of the allowable range.

  14. 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

  15. Multiple System Atrophy

    MedlinePlus

    ... speech abnormalities or a quavering voice, and abnormal eye movements (“cerebellar” reflects a part of the brain involved ... tendency to act out dreams (called REM/ (Rapid Eye Movement sleep behavior disorder) Some people with MSA may ...

  16. Systemic delivery of scAAV9 expressing SMN prolongs survival in a model of spinal muscular atrophy.

    PubMed

    Valori, Chiara F; Ning, Ke; Wyles, Matthew; Mead, Richard J; Grierson, Andrew J; Shaw, Pamela J; Azzouz, Mimoun

    2010-06-01

    Spinal muscular atrophy is one of the most common genetic causes of death in childhood, and there is currently no effective treatment. The disease is caused by mutations in the survival motor neuron gene. Gene therapy aimed at restoring the protein encoded by this gene is a rational therapeutic approach to ameliorate the disease phenotype. We previously reported that intramuscular delivery of a lentiviral vector expressing survival motor neuron increased the life expectancy of transgenic mice with spinal muscular atrophy. The marginal efficacy of this therapeutic approach, however, prompted us to explore different strategies for gene therapy delivery to motor neurons to achieve a more clinically relevant effect. Here, we report that a single injection of self-complementary adeno-associated virus serotype 9 expressing green fluorescent protein or of a codon-optimized version of the survival motor neuron protein into the facial vein 1 day after birth in mice carrying a defective survival motor neuron gene led to widespread gene transfer. Furthermore, this gene therapy resulted in a substantial extension of life span in these animals. These data demonstrate a significant increase in survival in a mouse model of spinal muscular atrophy and provide evidence for effective therapy.

  17. 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.

  18. 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.

  19. 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.

  20. In vivo visualization of alpha-synuclein deposition by carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy]benzoxazole positron emission tomography in multiple system atrophy.

    PubMed

    Kikuchi, Akio; Takeda, Atsushi; Okamura, Nobuyuki; Tashiro, Manabu; Hasegawa, Takafumi; Furumoto, Shozo; Kobayashi, Michiko; Sugeno, Naoto; Baba, Toru; Miki, Yasuo; Mori, Fumiaki; Wakabayashi, Koichi; Funaki, Yoshihito; Iwata, Ren; Takahashi, Shoki; Fukuda, Hiroshi; Arai, Hiroyuki; Kudo, Yukitsuka; Yanai, Kazuhiko; Itoyama, Yasuto

    2010-06-01

    The histopathological hallmark of multiple system atrophy is the appearance of intracellular inclusion bodies, named glial cytoplasmic inclusions, which are mainly composed of alpha-synuclein fibrils. In vivo visualization of alpha-synuclein deposition should be used for the diagnosis and assessment of therapy and severity of pathological progression in multiple system atrophy. Because 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole could stain alpha-synuclein-containing glial cytoplasmic inclusions in post-mortem brains, we compared the carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole positron emission tomography findings of eight multiple system atrophy cases to those of age-matched normal controls. The positron emission tomography data demonstrated high distribution volumes in the subcortical white matter (uncorrected P < 0.001), putamen and posterior cingulate cortex (uncorrected P < 0.005), globus pallidus, primary motor cortex and anterior cingulate cortex (uncorrected P < 0.01), and substantia nigra (uncorrected P < 0.05) in multiple system atrophy cases compared to the normal controls. They were coincident with glial cytoplasmic inclusion-rich brain areas in multiple system atrophy and thus, carbon-11-labelled 2-[2-(2-dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy] benzoxazole positron emission tomography is a promising surrogate marker for monitoring intracellular alpha-synuclein deposition in living brains.

  1. Glucocorticoid-induced skeletal muscle atrophy.

    PubMed

    Schakman, O; Kalista, S; Barbé, C; Loumaye, A; Thissen, J P

    2013-10-01

    Many pathological states characterized by muscle atrophy (e.g., sepsis, cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an increase in circulating glucocorticoids (GC) levels, suggesting that GC could trigger the muscle atrophy observed in these conditions. GC-induced muscle atrophy is characterized by fast-twitch, glycolytic muscles atrophy illustrated by decreased fiber cross-sectional area and reduced myofibrillar protein content. GC-induced muscle atrophy results from increased protein breakdown and decreased protein synthesis. Increased muscle proteolysis, in particular through the activation of the ubiquitin proteasome and the lysosomal systems, is considered to play a major role in the catabolic action of GC. The stimulation by GC of these two proteolytic systems is mediated through the increased expression of several Atrogenes ("genes involved in atrophy"), such as FOXO, Atrogin-1, and MuRF-1. The inhibitory effect of GC on muscle protein synthesis is thought to result mainly from the inhibition of the mTOR/S6 kinase 1 pathway. These changes in muscle protein turnover could be explained by changes in the muscle production of two growth factors, namely Insulin-like Growth Factor (IGF)-I, a muscle anabolic growth factor and Myostatin, a muscle catabolic growth factor. This review will discuss the recent progress made in the understanding of the mechanisms involved in GC-induced muscle atrophy and consider the implications of these advancements in the development of new therapeutic approaches for treating GC-induced myopathy. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.

  2. In vivo evaluation of gray and white matter volume loss in the parkinsonian variant of multiple system atrophy using SPM8 plus DARTEL for VBM.

    PubMed

    Shigemoto, Yoko; Matsuda, Hiroshi; Kamiya, Kouhei; Maikusa, Norihide; Nakata, Yasuhiro; Ito, Kimiteru; Ota, Miho; Matsunaga, Naofumi; Sato, Noriko

    2013-01-01

    In multiple system atrophy with predominant parkinsonism (MSA-P), several voxel-based morphometry (VBM) studies have revealed gray matter loss; however, the white matter volume changes have been rarely reported. We investigated the volume changes of white matter as well as gray matter by VBM. A retrospective MRI study was performed in 20 patients with MSA-P and 30 age-matched healthy controls. We applied VBM with statistical parametric mapping (SPM8) plus diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) to explore the regional atrophy of gray and white matter in all of the MSA-P patients, 14 patients with left-side dominant and 6 patients with right-side dominant onset as compared to controls. In all of the MSA-P patients, VBM revealed a significant volume reduction of gray matter in the bilateral putamina, cerebellums and dorsal midbrain. White matter loss was located in bilateral globus pallidi, external capsules extending to the midbrain, right subcortical to precentral area through internal capsule, the pons, bilateral middle cerebellar peduncles and left cerebellum. In left-side dominant MSA-P patients, the gray and white matter volume loss was detected predominantly on the right side and vice versa in right-side dominant MSA-P patients. A correlation with disease duration and severity was not detected. VBM using SPM8 plus DARTEL detected significant volume loss not only in the gray but also in the white matter of the area affected by MSA-P.

  3. 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.

  4. Improvements of Vaginal Atrophy without Systemic Side Effects after Topical Application of Pueraria mirifica, a Phytoestrogen-rich Herb, in Postmenopausal Cynomolgus Macaques

    PubMed Central

    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. PMID:24748397

  5. 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

  6. Three cases of systemic amyloidosis successfully diagnosed by subcutaneous fat tissue biopsy of the hip.

    PubMed

    Arahata, Masahisa; Shimadoi, Shigeru; Yamatani, Satosi; Hayashi, Shin-Ichi; Miwa, Shigeharu; Asakura, Hidesaku; Nakao, Shinji

    2016-01-01

    Fine-needle aspiration biopsy of the abdominal fat pad is considered to be a minimally invasive procedure for diagnosing systemic amyloidosis. However, this procedure is sometimes difficult and can be dangerous for elderly patients whose abdominal fat layer is thin because of malnutrition. In such cases, alternative diagnostic methods are required. We report three elderly patients with heart failure complicated by malnutrition. In all cases, electrocardiogram showed low voltage in the limb leads and a pseudoinfarct pattern in the chest leads, and echocardiography showed left ventricular wall thickening with granular sparkling appearance. These patients were suspected of having amyloid cardiomyopathy but could not undergo myocardial biopsies because of their poor conditions. After failed attempts at biopsy of the abdominal fat pad or the other organs, subcutaneous fat tissue biopsy over the hip led to the diagnosis of systemic amyloidosis with cardiomyopathy. The resultant diagnosis guided us to choose the appropriate treatment for the patients. This article illustrates that subcutaneous fat tissue biopsy of the hip could be a useful procedure for diagnosing systemic amyloidosis in elderly patients, particularly when a fat tissue biopsy of the abdomen is associated with a high risk of complications because of malnutrition. PMID:27540285

  7. Three cases of systemic amyloidosis successfully diagnosed by subcutaneous fat tissue biopsy of the hip.

    PubMed

    Arahata, Masahisa; Shimadoi, Shigeru; Yamatani, Satosi; Hayashi, Shin-Ichi; Miwa, Shigeharu; Asakura, Hidesaku; Nakao, Shinji

    2016-01-01

    Fine-needle aspiration biopsy of the abdominal fat pad is considered to be a minimally invasive procedure for diagnosing systemic amyloidosis. However, this procedure is sometimes difficult and can be dangerous for elderly patients whose abdominal fat layer is thin because of malnutrition. In such cases, alternative diagnostic methods are required. We report three elderly patients with heart failure complicated by malnutrition. In all cases, electrocardiogram showed low voltage in the limb leads and a pseudoinfarct pattern in the chest leads, and echocardiography showed left ventricular wall thickening with granular sparkling appearance. These patients were suspected of having amyloid cardiomyopathy but could not undergo myocardial biopsies because of their poor conditions. After failed attempts at biopsy of the abdominal fat pad or the other organs, subcutaneous fat tissue biopsy over the hip led to the diagnosis of systemic amyloidosis with cardiomyopathy. The resultant diagnosis guided us to choose the appropriate treatment for the patients. This article illustrates that subcutaneous fat tissue biopsy of the hip could be a useful procedure for diagnosing systemic amyloidosis in elderly patients, particularly when a fat tissue biopsy of the abdomen is associated with a high risk of complications because of malnutrition.

  8. Three cases of systemic amyloidosis successfully diagnosed by subcutaneous fat tissue biopsy of the hip

    PubMed Central

    Arahata, Masahisa; Shimadoi, Shigeru; Yamatani, Satosi; Hayashi, Shin-ichi; Miwa, Shigeharu; Asakura, Hidesaku; Nakao, Shinji

    2016-01-01

    Fine-needle aspiration biopsy of the abdominal fat pad is considered to be a minimally invasive procedure for diagnosing systemic amyloidosis. However, this procedure is sometimes difficult and can be dangerous for elderly patients whose abdominal fat layer is thin because of malnutrition. In such cases, alternative diagnostic methods are required. We report three elderly patients with heart failure complicated by malnutrition. In all cases, electrocardiogram showed low voltage in the limb leads and a pseudoinfarct pattern in the chest leads, and echocardiography showed left ventricular wall thickening with granular sparkling appearance. These patients were suspected of having amyloid cardiomyopathy but could not undergo myocardial biopsies because of their poor conditions. After failed attempts at biopsy of the abdominal fat pad or the other organs, subcutaneous fat tissue biopsy over the hip led to the diagnosis of systemic amyloidosis with cardiomyopathy. The resultant diagnosis guided us to choose the appropriate treatment for the patients. This article illustrates that subcutaneous fat tissue biopsy of the hip could be a useful procedure for diagnosing systemic amyloidosis in elderly patients, particularly when a fat tissue biopsy of the abdomen is associated with a high risk of complications because of malnutrition. PMID:27540285

  9. Systemic corticosteroid monotherapy for clinically diagnosed acute rhinosinusitis: a randomized controlled trial

    PubMed Central

    Venekamp, Roderick P.; Bonten, Marc J.M.; Rovers, Maroeska M.; Verheij, Theo J.M.; Sachs, Alfred P.E.

    2012-01-01

    Background: Patients with acute rhinosinusitis are frequently encountered in primary care. Although corticosteroids are being increasingly used for symptom control, evidence supporting their use is inconclusive. We conducted a randomized controlled trial to examine the effectiveness of systemic corticosteroid monotherapy for clinically diagnosed, uncomplicated acute rhinosinusitis. Methods: We conducted a block-randomized, double-blind, placebo-controlled clinical trial at 54 primary care practices (68 family physicians) in the Netherlands between Dec. 30, 2008, and Apr. 28, 2011. Adult patients with clinically diagnosed acute rhinosinusitis were randomly assigned to receive either prednisolone 30 mg/d or placebo for 7 days and asked to complete a symptom diary for 14 days. The primary outcome measure was the proportion of patients with resolution of facial pain or pressure on day 7. Results: Of the 185 patients included in the trial (93 in the treatment group, 92 in the placebo group), 2 withdrew from the study and 9 were excluded from the primary analysis because of incomplete symptom reporting. The remaining 174 patients (88 in the treatment group, 86 in the placebo group) were included in the intention-to-treat analysis. The proportions of patients with resolution of facial pain or pressure on day 7 were 62.5% (55/88) in the prednisolone group and 55.8% (48/86) in the placebo group (absolute risk difference 6.7%, 95% confidence interval −7.9% to 21.2%). The groups were similar with regard to the decrease over time in the proportion of patients with total symptoms (combined symptoms of runny nose, postnasal discharge, nasal congestion, cough and facial pain) and health-related quality of life. Adverse events were mild and did not differ significantly between the groups. Interpretation: Systemic corticosteroid monotherapy had no clinically relevant beneficial effects among patients with clinically diagnosed acute rhinosinusitis. Netherlands Trial Register

  10. Siblings' Perceptions of Their ADHD-Diagnosed Sibling's Impact on the Family System.

    PubMed

    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.

  11. Siblings' Perceptions of Their ADHD-Diagnosed Sibling's Impact on the Family System.

    PubMed

    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

  12. 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

  13. Neonatal congenital microvillus atrophy

    PubMed Central

    Pecache, N; Patole, S; Hagan, R; Hill, D; Charles, A; Papadimitriou, J

    2004-01-01

    Congenital microvillous atrophy (CMVA) is the leading cause of neonatal secretory diarrhoea with onset either in the first 72 hours of life (early onset) or at 6–8 weeks after birth (late onset). To date over 30 cases have been reported worldwide. The prognosis for this life threatening condition continues to be poor. Therapeutic agents like somatostatin and epidermal growth factor are either ineffective or of marginal benefit. Overall five year survival after small bowel transplantation is currently ∼50%. The following brief review is aimed towards helping neonatologists/perinatologists in the early diagnosis, and management of CMVA and in counselling the parents appropriately. PMID:14970294

  14. 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).

  15. 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).

  16. 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

  17. 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.

  18. Genetics Home Reference: optic atrophy type 1

    MedlinePlus

    ... Conditions optic atrophy type 1 optic atrophy type 1 Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Optic atrophy type 1 is a condition that affects vision. Individuals with ...

  19. Redox control of skeletal muscle atrophy.

    PubMed

    Powers, Scott K; Morton, Aaron B; Ahn, Bumsoo; Smuder, Ashley J

    2016-09-01

    Skeletal muscles comprise the largest organ system in the body and play an essential role in body movement, breathing, and glucose homeostasis. Skeletal muscle is also an important endocrine organ that contributes to the health of numerous body organs. Therefore, maintaining healthy skeletal muscles is important to support overall health of the body. Prolonged periods of muscle inactivity (e.g., bed rest or limb immobilization) or chronic inflammatory diseases (i.e., cancer, kidney failure, etc.) result in skeletal muscle atrophy. An excessive loss of muscle mass is associated with a poor prognosis in several diseases and significant muscle weakness impairs the quality of life. The skeletal muscle atrophy that occurs in response to inflammatory diseases or prolonged inactivity is often associated with both oxidative and nitrosative stress. In this report, we critically review the experimental evidence that provides support for a causative link between oxidants and muscle atrophy. More specifically, this review will debate the sources of oxidant production in skeletal muscle undergoing atrophy as well as provide a detailed discussion on how reactive oxygen species and reactive nitrogen species modulate the signaling pathways that regulate both protein synthesis and protein breakdown.

  20. Continuous remission of newly diagnosed and relapsed central nervous system atypical teratoid/rhabdoid tumor.

    PubMed

    Zimmerman, Mary Ann; Goumnerova, Liliana C; Proctor, Mark; Scott, R Michael; Marcus, Karen; Pomeroy, Scott L; Turner, Christopher D; Chi, Susan N; Chordas, Christine; Kieran, Mark W

    2005-03-01

    Atypical teratoid/rhabdoid tumors (AT/RT) are highly malignant lesions of childhood that carry a very poor prognosis. AT/RT can occur in the central nervous system (CNS AT/RT) and disease in this location carries an even worse prognosis with a median survival of 7 months. In spite of multiple treatment regimens consisting of maximal surgical resection (including second look surgery), radiation therapy (focal and craniospinal), and multi-agent intravenous, oral and intrathecal chemotherapy, with or without high-dose therapy and stem cell rescue, only seven long-term survivors of CNS AT/RT have been reported, all in patients with newly diagnosed disease. For this reason, many centers now direct such patients, particularly those under 5 years of age, or those with recurrent disease, towards comfort care rather than attempt curative therapy. We now report on four children, two with newly diagnosed CNS AT/RT and two with progressive disease after multi-agent chemotherapy who are long term survivors (median follow-up of 37 months) using a combination of surgery, radiation therapy, and intensive chemotherapy. The chemotherapy component was modified from the Intergroup Rhabdomyosarcoma Study Group (IRS III) parameningeal protocol as three of the seven reported survivors in the literature were treated using this type of therapy. Our four patients, when added to the three reported survivors in the literature using this approach, suggest that patients provided this aggressive therapy can significantly alter the course of their disease. More importantly, we report on the first two survivors after relapse with multi-agent intravenous and intrathecal chemotherapy treated with this modified regimen. PMID:15803379

  1. 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).

  2. Application value of magnetic resonance imaging in diagnosing central nervous system lymphoma

    PubMed Central

    Zhang, Shanhua; Li, Hongjun; Zhu, Rongguang; Zhang, Mingming

    2016-01-01

    Objective: To describe the magnetic resonance imaging (MRI) appearance of central nervous system lymphoma. Methods: We retrospectively reviewed MRI images of 40 patients who had pathologically proven primary central nervous system lymphoma (PCNSL) and received treatment in Binzhou People’s Hospital, Shandong, China from January to December in 2014. Location, size and form of tumor was observed and relevant data were recorded for analysis. Results: Foci of 40 cases of PCNSL all located in brain, among which. 18 cases were single (45.0%) and 22 cases were multiple (55.5%). Of 96 Foci, 84 were supratentorial, 12 were subtentorial. Enhanced MRI scanning showed that, most Foci had significant homogenous enhancement, shaping as multiple nodular or lumpy, and few had ring-enhancement. MRI suggested that, T1 signal of most Foci concentrated on low signal segment and T2 signal gathered on high signal segment, suggesting a significant homogeneous enhancement; moreover, mild and medium edema surrounded the tumor. They were pathologically confirmed as B cell derived non-hodgkin lymphoma. Except one case of Burkitt lymphoma, the others were all diffuse large B cell lymphoma which was observed with diffuse distribution of cancer cells (little cytoplasm, large nucleus, rough perichromatin granule) in same size. Fifteen cases were observed with sleeve-like infiltration of cancer cells around blood vessels. No case was found with hemorrhage, necrosis or calcification. Conclusion: Pathological foundation of PCNSL determines its characteristic MRI performance. Typical case of PCNSL can be diagnosed accurately by MRI. PMID:27182246

  3. 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. PMID:26689142

  4. Subcortical dementia revisited: similarities and differences in cognitive function between progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA).

    PubMed

    Bak, T H; Crawford, L M; Hearn, V C; Mathuranath, P S; Hodges, J R

    2005-08-01

    To examine the similarities and differences in cognitive function between three predominantly subcortical dementing disorders associated with parkinsonism we compared the profiles of cognitive performance in 39 patients with Progressive Supranuclear Palsy (PSP), 26 patients with Multiple System Atrophy (MSA) and 25 with Corticobasal Degeneration (CBD) with those of 30 patients with classic cortical dementia, Alzheimer's Disease (AD), using two different cognitive screening tests: Dementia Rating Scale (DRS) and Addenbrooke's Cognitive Examination (ACE). The cognitive profile on ACE and DRS subtests distinguished subcortical diseases from each other as well as from AD. All parkinsonian syndromes were characterized by a disproportionate impairment in verbal fluency, particularly letter fluency. The three diseases differed, however, in the degree of language, memory and visuospatial impairment. We conclude that similarities, as well as differences, between PSP, MSA and CBD can be detected using a brief, clinically applicable cognitive screening test. The pattern of cognitive impairment is likely to reflect a different distribution of pathology, in particular a higher degree of cortical involvement in PSP and CBD.

  5. [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. PMID:25746072

  6. 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.

  7. Pax2 expression in simultaneously diagnosed WHO and EIN classification systems.

    PubMed

    Joiner, Amy K; Quick, Charles M; Jeffus, Susanne K

    2015-01-01

    PAX2 has been cited as a technically robust biomarker which nicely delineates precancerous lesions of the endometrium when the endometrial intraepithelial neoplasia (EIN) classification scheme is used. Its utility in distinguishing between atypical and nonatypical hyperplasia when applied within the 1994 World Health Organization classification system is questionable. The purpose of this study was to evaluate PAX2 in a side by side comparison of its staining patterns in a series of endometrial samples that were classified using both systems. A total of 108 precancerous endometrial cases were identified, of which 30 cases were deemed nonhyperplastic by consensus agreement and 11 cases lost the tissue of interest on deeper sections. The remaining 67 cases were categorized according to the 1994 World Health Organization criteria and EIN scheme by 2 gynecologic pathologists. PAX2 staining was scored in lesional tissue as normal or altered (lost, increased, or decreased) compared with nonlesional background. The most common pattern of alteration was complete loss of nuclear PAX2 staining (86.3%) followed by decreased staining (11.3%) and markedly increased staining (2.3%). PAX2 alterations correlated well with EIN diagnoses (33/36, 92%) compared with benign hyperplasia (2/13, 15%) but were less useful when the 1994 World Health Organization classification system was applied (PAX2 alteration in 22/25 (88%) of atypical hyperplasia cases versus 16/25 (64%) of nonatypical hyperplasia cases). Forty-five percent of follow-up hysterectomies with a previous PAX2-altered biopsy case harbored adenocarcinoma. In conclusion, PAX2 may be a helpful adjunct stain and training tool when the features of atypical hyperplasia/EIN are in question.

  8. 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

  9. [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.

  10. 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.

  11. 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.

  12. Intraventricular cerebrospinal fluid temperature analysis using MR diffusion-weighted imaging thermometry in Parkinson's disease patients, multiple system atrophy patients, and healthy subjects

    PubMed Central

    Sumida, Kaoru; Sato, Noriko; Ota, Miho; Sakai, Koji; Nippashi, Yasumasa; Sone, Daichi; Yokoyama, Kota; Ito, Kimiteru; Maikusa, Norihide; Imabayashi, Etsuko; Matsuda, Hiroshi; Yamada, Kei; Murata, Miho; Kunimatsu, Akira; Ohtomo, Kuni

    2015-01-01

    Purpose We examined the temperature of the intraventricular cerebrospinal fluid (Tv) in patients with Parkinson's disease (PD) and those with multiple system atrophy (MSA) in comparison with healthy subjects, and we examined normal changes in this temperature with aging. Methods Tv was estimated by magnetic resonance (MR) diffusion-weighted imaging (DWI) thermometry in 36 PD patients (19 males, 17 females), 34 MSA patients (17 males, 17 females), 64 age-matched controls (27 men, 37 women), and 114 all-age adult controls (47 men, 67 women; 28–89 years old). The volume of lateral ventricles was also estimated using FreeSurfer in all subjects. Tv and ventricular volume data were compared among the PD and MSA patients and age-matched controls. We also evaluated the relationship between Tv and age in the 114 all-age controls, controlling for ventricular volume. Men and women were analyzed separately. Results The male PD and MSA patients had significantly higher Tv values compared to the male controls, with no significant difference in ventricular volume among them. There was no significant difference in Tv between the female patients and controls. In the all-age male controls, there was a significant negative correlation between Tv and age controlling for ventricular volume, and this was not observed in the women. Conclusion DWI thermometry is a useful and easy method for demonstrating an altered intracranial environment in male patients and healthy controls, but not in females. DWI thermometry can thus be used to help to explore the pathophysiology of Parkinsonian syndromes and to differentiate individuals affected by neurodegenerative disease with autonomic dysfunction from those without it. PMID:26085965

  13. Angiotensin II: role in skeletal muscle atrophy.

    PubMed

    Cabello-Verrugio, Claudio; Córdova, Gonzalo; Salas, José Diego

    2012-09-01

    Skeletal muscle, the main protein reservoir in the body, is a tissue that exhibits high plasticity when exposed to changes. Muscle proteins can be mobilized into free amino acids when skeletal muscle wasting occurs, a process called skeletal muscle atrophy. This wasting is an important systemic or local manifestation under disuse conditions (e.g., bed rest or immobilization), in starvation, in older adults, and in several diseases. The molecular mechanisms involved in muscle wasting imply the activation of specific signaling pathways which ultimately manage muscle responses to modulate biological events such as increases in protein catabolism, oxidative stress, and cell death by apoptosis. Many factors have been involved in the generation and maintenance of atrophy in skeletal muscle, among them angiotensin II (Ang-II), the main peptide of renin-angiotensin system (RAS). Together with Ang-II, the angiotensin-converting enzyme (ACE) and the Ang-II receptor type 1 (AT-1 receptor) are expressed in skeletal muscle, forming an important local axis that can regulate its function. In many of the conditions that lead to muscle wasting, there is an impairment of RAS in a global or local fashion. At this point, there are several pieces of evidence that suggest the participation of Ang-II, ACE, and AT-1 receptor in the generation of skeletal muscle atrophy. Interestingly, the Ang-II participation in muscle atrophy is strongly ligated to the regulation of hypertrophic activity of factors such as insulin-like growth factor 1 (IGF-1). In this article, we reviewed the current state of Ang-II and RAS function on skeletal muscle wasting and its possible use as a therapeutic target to improve skeletal muscle function under atrophic conditions.

  14. 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 ...

  15. Role of the nervous system in sarcopenia and muscle atrophy with aging: strength training as a countermeasure.

    PubMed

    Aagaard, P; Suetta, C; Caserotti, P; Magnusson, S P; Kjaer, M

    2010-02-01

    Aging is characterized by loss of spinal motor neurons (MNs) due to apoptosis, reduced insulin-like growth factor I signaling, elevated amounts of circulating cytokines, and increased cell oxidative stress. The age-related loss of spinal MNs is paralleled by a reduction in muscle fiber number and size (sarcopenia), resulting in impaired mechanical muscle performance that in turn leads to a reduced functional capacity during everyday tasks. Concurrently, maximum muscle strength, power, and rate of force development are decreased with aging, even in highly trained master athletes. The impairment in muscle mechanical function is accompanied and partly caused by an age-related loss in neuromuscular function that comprise changes in maximal MN firing frequency, agonist muscle activation, antagonist muscle coactivation, force steadiness, and spinal inhibitory circuitry. Strength training appears to elicit effective countermeasures in elderly individuals even at a very old age (>80 years) by evoking muscle hypertrophy along with substantial changes in neuromuscular function, respectively. Notably, the training-induced changes in muscle mass and nervous system function leads to an improved functional capacity during activities of daily living.

  16. 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.

  17. 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.

  18. Postradiation atrophy of mature bone

    SciTech Connect

    Ergun, H.; Howland, W.J.

    1980-01-01

    The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographic evidence of atrophy, localized osteopenia, is late in appearing. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.

  19. 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 ...

  20. 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

  1. 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

  2. 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

  3. 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

  4. A Possible Link between Gastric Mucosal Atrophy and Gastric Cancer after Helicobacter pylori Eradication

    PubMed Central

    Tahara, Tomomitsu; Shibata, Tomoyuki; Horiguchi, Noriyuki; Kawamura, Tomohiko; Okubo, Masaaki; Ishizuka, Takamitsu; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Ohmiya, Naoki

    2016-01-01

    Background The effect of H. pylori eradication in gastric cancer prevention can be attributed to the improvement of atrophic gastritis, which is a known risk of gastric cancer. However, gastric cancer has also been diagnosed after long-term H. pylori eradication. This study aimed to clarify the association between gastric atrophy and gastric cancer after H. pylori eradication, including its clinicopathological features. Methods A total of 55 consecutive patients with 64 early gastric cancers (EGCs) diagnosed after H. pylori eradication were enrolled. The degree of endoscopic atrophy and the histological degrees of mononuclear cell infiltration, atrophy, and metaplasia in the corpus and adjacent mucosa of the EGCs were determined and scored. Results The majority of EGCs (63/64) were located within the endoscopically assessed atrophic mucosa or along the atrophic border. The adjacent mucosa of the EGCs presented significantly higher degrees of all histological parameters than in the corpus (mononuclear cell infiltration, 0.86+/-0.09 vs. 0.51+/-0.11, P = 0.016; atrophy, 1.77+/-0.13 vs. 0.65+/-0.14, P<0.0001; metaplasia, 1.68+/-0.13 vs. 0.48+/-0.1, P<0.0001). The degree of endoscopic atrophy improved in the patients with longer post-H. pylori eradication periods; however, this trend was not observed for the histological parameters, and high degrees of atrophy and metaplasia were observed in the adjacent mucosa of the EGCs compared with the corpus during all periods (all P<0.05). The histological degrees of atrophy and metaplasia in the adjacent mucosa were particularly higher in the patients who underwent eradication due to gastric ulcers. Conclusions Severe gastric atrophy remained in the adjacent mucosa of the EGCs after H. pylori eradication, which may be linked to gastric carcinogenesis. PMID:27706195

  5. Muscle Atrophy in Intensive Care Unit Patients

    PubMed Central

    Koukourikos, Konstantinos; Tsaloglidou, Areti; Kourkouta, Labrini

    2014-01-01

    Introduction: The muscle atrophy is one of the most important and frequent problems observed in patients in Intensive Care Units. The term describes the disorder in the structure and in the function of the muscle while incidence rates range from 25-90 % in patients with prolonged hospitalization. Purpose: This is a review containing all data related to the issue of muscle atrophy and is especially referred to its causes and risk factors. The importance of early diagnosis and early mobilization are also highlighted in the study. Material and methods: a literature review was performed on valid databases such as Scopus, PubMed, Cinhal for the period 2000-2013 in English language. The following keywords were used: loss of muscle mass, ICU patients, immobilization, bed rest. Results: From the review is concluded that bed rest and immobilization in order to reduce total energy costs, are the main causes for the appearance of the problem. The results of the reduction of the muscle mass mainly affect the musculoskeletal, cardiovascular and respiratory system. The administration of the cortisone, the immobility, the sepsis and hyperglycemia are included in the risk factors. The prevention is the primary therapeutic agent and this is achieved due to the early mobilization of the patients, the use of neuromuscular electrical stimulation and the avoidance of exposure to risk factors. Conclusions: The prevention of muscle atrophy is a primary goal of treatment for the patients in the ICU, because it reduces the incidence of the disease, reduces the time spent in ICU and finally improves the quality of patients’ life. PMID:25684851

  6. Cerebral atrophy in a vitamin B12-deficient infant of a vegetarian mother.

    PubMed

    Kocaoglu, Celebi; Akin, Fatih; Caksen, Hüseyin; Böke, Saltuk Buğra; Arslan, Sükrü; Aygün, Serhat

    2014-06-01

    In developed countries, vitamin B12 (cobalamin) deficiency usually occurs in children, exclusively breastfed ones whose mothers are vegetarian, causing low body stores of vitamin B12. The haematologic manifestation of vitamin B12 deficiency is pernicious anaemia. It is a megaloblastic anaemia with high mean corpuscular volume and typical morphological features, such as hyperlobulation of the nuclei of the granulocytes. In advanced cases, neutropaenia and thrombocytopaenia can occur, simulating aplastic anaemia or leukaemia. In addition to haematological symptoms, infants may experience weakness, fatigue, failure to thrive, and irritability. Other common findings include pallor, glossitis, vomiting, diarrhoea, and icterus. Neurological symptoms may affect the central nervous system and, in severe cases, rarely cause brain atrophy. Here, we report an interesting case, a 12-month old infant, who was admitted with neurological symptoms and diagnosed with vitamin B12 deficiency. PMID:25076673

  7. Cerebral atrophy in a vitamin B12-deficient infant of a vegetarian mother.

    PubMed

    Kocaoglu, Celebi; Akin, Fatih; Caksen, Hüseyin; Böke, Saltuk Buğra; Arslan, Sükrü; Aygün, Serhat

    2014-06-01

    In developed countries, vitamin B12 (cobalamin) deficiency usually occurs in children, exclusively breastfed ones whose mothers are vegetarian, causing low body stores of vitamin B12. The haematologic manifestation of vitamin B12 deficiency is pernicious anaemia. It is a megaloblastic anaemia with high mean corpuscular volume and typical morphological features, such as hyperlobulation of the nuclei of the granulocytes. In advanced cases, neutropaenia and thrombocytopaenia can occur, simulating aplastic anaemia or leukaemia. In addition to haematological symptoms, infants may experience weakness, fatigue, failure to thrive, and irritability. Other common findings include pallor, glossitis, vomiting, diarrhoea, and icterus. Neurological symptoms may affect the central nervous system and, in severe cases, rarely cause brain atrophy. Here, we report an interesting case, a 12-month old infant, who was admitted with neurological symptoms and diagnosed with vitamin B12 deficiency.

  8. Postradiation atrophy of mature bone

    SciTech Connect

    Erguen, H.; Howland, W.J.

    1980-01-01

    The growing number of oncological patients subjected to radiotherapy require the diagnostic radiologist to be aware of expected bone changes following irradiation and the differentiation of this entity from metastasis. The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographic evidence of atrophy, localized osteopenia, is late in appearing, mainly because of the relative insensitivity of radiographs in detecting demineralization. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. In vivo midrodensitometric analysis and radionuclide bone and bone marrow scans can reveal early changes following irradiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.

  9. Postradiation atrophy of mature bone

    SciTech Connect

    Ergun, H.; Howland, W.J.

    1980-01-01

    The growing number of oncological patients subjected to radiotherapy require the diagnostic radiologist to be aware of expected bone changes following irradiation and the differentiation of this entity from metastasis. The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographic evidence of atrophy, localized osteopenia, is late in appearing, mainly because of the relative insensitivity of radiographs in detecing demineralization. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. In vivo midrodensitometric analysis and radionuclide bone and bone marrow scans can reveal early changes following irradiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.

  10. 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

  11. 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

  12. [A Case of Musicophilia with Right Predominant Temporal Lobe Atrophy].

    PubMed

    Shinagawa, Shunichiro; Nakayama, Kazuhiko

    2015-11-01

    A 68-year-old woman exhibiting musicophilia with right predominant temporal lobe atrophy happened to visit our clinic. She had no musical background, but beginning two years ago, she acquired a strong preference for especially popular music and sometimes sang at home. She did not exhibit obvious semantic aphasia or facial agnosia, and showed only mild behavioral changes including apathy. Her musicophilia can be explained as an instance of stereotypical behavior. Her right temporal lobe atrophy may have caused changes in her emotional and reward systems, resulting in her music specific behaviors. PMID:26560960

  13. [A Case of Musicophilia with Right Predominant Temporal Lobe Atrophy].

    PubMed

    Shinagawa, Shunichiro; Nakayama, Kazuhiko

    2015-11-01

    A 68-year-old woman exhibiting musicophilia with right predominant temporal lobe atrophy happened to visit our clinic. She had no musical background, but beginning two years ago, she acquired a strong preference for especially popular music and sometimes sang at home. She did not exhibit obvious semantic aphasia or facial agnosia, and showed only mild behavioral changes including apathy. Her musicophilia can be explained as an instance of stereotypical behavior. Her right temporal lobe atrophy may have caused changes in her emotional and reward systems, resulting in her music specific behaviors.

  14. 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.

  15. An artificial neural network system for diagnosing gas turbine engine fuel faults

    SciTech Connect

    Illi, O.J. Jr.; Greitzer, F.L.; Kangas, L.J.; Reeve, T.

    1994-04-01

    The US Army Ordnance Center & School and Pacific Northwest Laboratories are developing a turbine engine diagnostic system for the M1A1 Abrams tank. This system employs Artificial Neural Network (AN) technology to perform diagnosis and prognosis of the tank`s AGT-1500 gas turbine engine. This paper describes the design and prototype development of the ANN component of the diagnostic system, which we refer to as ``TEDANN`` for Turbine Engine Diagnostic Artificial Neural Networks.

  16. 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. PMID:26702511

  17. Diagnosing Students' Mental Models via the Web-Based Mental Models Diagnosis System

    ERIC Educational Resources Information Center

    Wang, Tzu-Hua; Chiu, Mei-Hung; Lin, Jing-Wen; Chou, Chin-Cheng

    2013-01-01

    Mental models play an important role in science education research. To extend the effectiveness of conceptual change research and to improve mental model identi?cation and diagnosis, the authors developed and tested the Web-Based Mental Models Diagnosis (WMMD) system. In this article, they describe their WMMD system, which goes beyond the…

  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. Diagnosing and Managing Violence

    PubMed Central

    2011-01-01

    Available categorization systems for violence encountered in medical practice do not constitute optimal tools to guide management. In this article, 4 common patterns of violence across psychiatric diagnoses are described (defensive, dominance-defining, impulsive, and calculated) and management implications are considered. The phenomenologic and neurobiological rationale for a clinical classification system of violence is also presented. PMID:22295257

  20. Diagnosing "vulnerable system syndrome": an essential prerequisite to effective risk management

    PubMed Central

    Reason, J; Carthey, J; de Leval, M R

    2001-01-01

    Investigations of accidents in a number of hazardous domains suggest that a cluster of organisational pathologies—the "vulnerable system syndrome" (VSS)—render some systems more liable to adverse events. This syndrome has three interacting and self-perpetuating elements: blaming front line individuals, denying the existence of systemic error provoking weaknesses, and the blinkered pursuit of productive and financial indicators. VSS is present to some degree in all organisations, and the ability to recognise its symptoms is an essential skill in the progress towards improved patient safety. Two kinds of organisational learning are discussed: "single loop" learning that fuels and sustains VSS and "double loop" learning that is necessary to start breaking free from it. Key Words: vulnerable system syndrome; risk management; patient safety; learning PMID:11700375

  1. 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.

  2. Comparative Analysis of Classifiers for Developing an Adaptive Computer-Assisted EEG Analysis System for Diagnosing Epilepsy

    PubMed Central

    Jamil, Mohsin; Omer Gillani, Syed; Imran, Muhammad; Khan, Nadeem Ahmed; Majeed, Waqas

    2015-01-01

    Computer-assisted analysis of electroencephalogram (EEG) has a tremendous potential to assist clinicians during the diagnosis of epilepsy. These systems are trained to classify the EEG based on the ground truth provided by the neurologists. So, there should be a mechanism in these systems, using which a system's incorrect markings can be mentioned and the system should improve its classification by learning from them. We have developed a simple mechanism for neurologists to improve classification rate while encountering any false classification. This system is based on taking discrete wavelet transform (DWT) of the signals epochs which are then reduced using principal component analysis, and then they are fed into a classifier. After discussing our approach, we have shown the classification performance of three types of classifiers: support vector machine (SVM), quadratic discriminant analysis, and artificial neural network. We found SVM to be the best working classifier. Our work exhibits the importance and viability of a self-improving and user adapting computer-assisted EEG analysis system for diagnosing epilepsy which processes each channel exclusive to each other, along with the performance comparison of different machine learning techniques in the suggested system. PMID:25834822

  3. Comparative analysis of classifiers for developing an adaptive computer-assisted EEG analysis system for diagnosing epilepsy.

    PubMed

    Ahmad, Malik Anas; Ayaz, Yasar; Jamil, Mohsin; Omer Gillani, Syed; Rasheed, Muhammad Babar; Imran, Muhammad; Khan, Nadeem Ahmed; Majeed, Waqas; Javaid, Nadeem

    2015-01-01

    Computer-assisted analysis of electroencephalogram (EEG) has a tremendous potential to assist clinicians during the diagnosis of epilepsy. These systems are trained to classify the EEG based on the ground truth provided by the neurologists. So, there should be a mechanism in these systems, using which a system's incorrect markings can be mentioned and the system should improve its classification by learning from them. We have developed a simple mechanism for neurologists to improve classification rate while encountering any false classification. This system is based on taking discrete wavelet transform (DWT) of the signals epochs which are then reduced using principal component analysis, and then they are fed into a classifier. After discussing our approach, we have shown the classification performance of three types of classifiers: support vector machine (SVM), quadratic discriminant analysis, and artificial neural network. We found SVM to be the best working classifier. Our work exhibits the importance and viability of a self-improving and user adapting computer-assisted EEG analysis system for diagnosing epilepsy which processes each channel exclusive to each other, along with the performance comparison of different machine learning techniques in the suggested system.

  4. 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

  5. Vulvar Skin Atrophy Induced by Topical Glucocorticoids

    PubMed Central

    Johnson, Elisabeth; Groben, Pamela; Eanes, Alisa; Iyer, Priya; Ugoeke, Joseph; Zolnoun, Denniz

    2011-01-01

    Steroid induced skin atrophy is the most frequent and perhaps most important cutaneous side effect of topical glucocorticoid therapy. To date, it has not been described in vulvar skin. We describe a patient with significant vulvar skin atrophy following prolonged steroid application to treat vulvar dermatitis. The extensive atrophy in the perineum resulted in secondary ‘webbing’ and partial obstruction of genital hiatus and superimposed dyspareunia. Prolonged topical steroids may result in atrophic changes in vulvar skin. Therefore, further research in clinical correlates of steroid-induced atrophy in the vulvar region is warranted. PMID:22594868

  6. A comparison of alternate systems for diagnosing antisocial personality disorder in cocaine abusers.

    PubMed

    Carroll, K M; Ball, S A; Rounsaville, B J

    1993-07-01

    We evaluated rates, reliability, internal consistency, factor structure, and clinical and predictive validity of antisocial personality disorder (ASP) across three diagnostic systems which varied in emphasis on a) core sociopathic traits and b) independence of antisocial behaviors from substance use in 399 cocaine abusers. Rates of ASP ranged from 7% (Research Diagnostic Criteria) to 53% (DSM-III-R). The DSM-III-R diagnosis of ASP was more reliable at 1 month and 1 year than the Research Diagnostic Criteria. Items assessing core traits of sociopathy had very low reliability and were poorly correlated with other criteria. Across all systems, cocaine abusers with ASP had earlier onset of drug dependence, more psychosocial dysfunction, and higher rates of other psychiatric disorders. Finally, only the DSM-III-R diagnosis of ASP was associated with treatment retention and short-term prognosis. These findings suggest that current diagnostic systems which require core sociopathic traits and independence of criminal behaviors from substance use may be more unreliable and of weaker prognostic significance than less restrictive systems. PMID:8320546

  7. 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.

  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. Clinical evaluation of a type III secretion system real-time PCR assay for diagnosing melioidosis.

    PubMed

    Meumann, Ella M; Novak, Ryan T; Gal, Daniel; Kaestli, Mirjam E; Mayo, Mark; Hanson, Joshua P; Spencer, Emma; Glass, Mindy B; Gee, Jay E; Wilkins, Patricia P; Currie, Bart J

    2006-08-01

    A Burkholderia pseudomallei type III secretion system real-time PCR assay was evaluated on clinical specimens in a region where melioidosis is endemic. The PCR was positive in 30/33 (91%) patients with culture-confirmed melioidosis. All six patients with melioidosis septic shock were blood PCR positive, suggesting potential for rapid diagnosis and commencement of appropriate therapy.

  10. Pathologies in Living Kidney Donors Diagnosed in the Long-Term Care System.

    PubMed

    Kwapisz, M; Kieszek, R; Jędrzejko, K; Domagała, P; Bieniasz, M; Gozdowska, J; Zygier, D; Drozdowski, J; Zatorski, M; Nowaczyk, M; Palczewski, P; Pączek, L; Durlik, M; Chmura, A; Kwiatkowski, A

    2016-06-01

    Kidney donation should not lead to deterioration of the donor's health condition, both during the perisurgical period and in the long term. Safety of a living kidney donor becomes a prerequisite for his/her qualification. Detailed diagnostic procedures are performed to exclude any abnormalities of his/her health condition. Additionally, a long-term post-donation follow-up system for kidney donors has been set up in Poland besides the restrictive qualification system. Transplantation centers are obligated to provide a diagnostic procedures for living organ donors as a part of the monitoring of their health condition and to ensure them a medical follow-up for 10 years after the donation. A total of 141 cases of unilateral nephroureterectomy performed in 2003-2014 to obtain a kidney for transplantation were considered. Medical files of post-donation diagnostic or therapeutic methods and their outcomes were retrospectively analyzed. The aim of the study was to assess the efficacy of monitoring of donors' health condition within the framework of the long-term follow-up system for kidney donors in the aspect of detection of the donation-independent abnormalities. PMID:27496424

  11. 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

  12. 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. PMID:26055105

  13. Neuronal involvement in muscular atrophy

    PubMed Central

    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. PMID:25540609

  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. 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

  16. [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.

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

    PubMed

    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.

  19. 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)

  20. 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

  1. Reflex myoclonus in olivopontocerebellar atrophy.

    PubMed Central

    Rodriguez, M E; Artieda, J; Zubieta, J L; Obeso, J A

    1994-01-01

    The presence of reflex myoclonus in response to touching and pin-pricking the wrist or stretching the fingers and to photic stimulation was assessed in 24 patients with a presumed diagnosis of olivopontocerebellar atrophy (OPCA) and in 30 age matched control subjects. Reflex myoclonus to soma-esthetic stimulation was found in 23 patients and in none of the controls. Photic myoclonus was present in 12 patients and in none of the controls. Electrophysiological study of the reflex myoclonus showed enhanced (> 10 microV) somatosensory evoked potentials and an associated reflex electromyographic discharge (C-wave) in 15 patients. These findings indicate that reflex myoclonus is common in OPCA and probably of cortical origin. Images PMID:8158179

  2. [Sudeck's atrophy. 3 clinical cases].

    PubMed

    Cordioli, E; Tondini, C; Pizzi, C; Premuda, G

    1994-05-01

    Three patients fulfilling criteria for Sudeck's atrophy (reflex sympathetic dystrophy syndrome--RSDS) are described and etiological, pathogenetic and clinical features of the disease are reviewed. RSDS is associated with a wide variety of precipitating factors, each of whom, often in concomitance with metabolic diseases and psychiatric disturbances, may cause the same clinical syndrome, which continues in a "vicious circle" of feed-back mechanisms, correlated with sympathetic hyperactivity. The symptoms may begin gradually and the disorder progresses in stages lasting from weeks to months. The management has not yet been established. Generally, the earlier the syndrome is recognized, the better the results of treatment will be. Analgesics, salmon calcitonin and physiokinesitherapy are recommended. Psychological support is advisable. In more severe patients sympathetic blockade and surgical sympathectomy may be necessary. The effects of hyperbaric oxygen treatment must still be assessed.

  3. Steroids and brain atrophy in multiple sclerosis.

    PubMed

    Zivadinov, Robert

    2005-06-15

    In this review, we focus on different pathogenetic mechanisms of corticosteroids that induce short- and long-term brain volume fluctuations in a variety of systemic conditions and disorders, as well as on corticosteroid-induced immunomodulatory, immunosuppressive and anti-inflammatory mechanisms that contribute to the slowdown of brain atrophy progression in patients with multiple sclerosis (MS). It appears that chronic low-dose treatment with corticosteroids may contribute to irreversible loss of brain tissue in a variety of autoimmune diseases. This side effect of steroid therapy is probably mediated by steroid-induced protein catabolism mechanism. Evidence is mounting that high-dose corticosteroids may induce reversible short-term brain volume changes due to loss of intracellular water and reduction of abnormal vascular permeability, without there having been axonal loss. Other apoptotic and selective inhibiting mechanisms have been proposed to explain the nature of corticosteroid-induced brain volume fluctuations. It has been shown that chronic use of high dose intravenous methylprednisolone (IVMP) in patients with MS may limit brain atrophy progression over the long-term via different immunological mechanisms, including downregulation of adhesion molecule expression on endothelial cells, decreased cytokine and matrix metalloproteinase secretion, decreased autoreactive T-cell-mediated inflammation and T-cell apoptosis induction, blood-brain barrier closure, demyelination inhibition and, possibly, remyelination promotion. Studies in nonhuman primates have confirmed that short-term brain volume fluctuations may be induced by corticosteroid treatment, but that they are inconsistent, potentially reversible and probably dependent upon individual susceptibility to the effects of corticosteroids. Further longitudinal studies are needed to elucidate pathogenetic mechanisms contributing to brain volume fluctuations in autoimmune diseases and multiple sclerosis.

  4. 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

  5. Prenatal Carrier Screening for Spinal Muscular Atrophy.

    PubMed

    Wood, S Lindsay; Brewer, Fallon; Ellison, Rebecca; Biggio, Joseph R; Edwards, Rodney K

    2016-10-01

    Introduction Spinal muscular atrophy (SMA), a neurodegenerative genetic disorder, affects 1:5,000 to 1:10,000 infants. Carrier rates are 1:25 to 1:50. We implemented ACOG-endorsed prenatal SMA screening in mid-2014 and sought to assess uptake, observed carrier rate, and providers' knowledge and attitudes toward genetic conditions and carrier screening. Methods Retrospective cohort study of all patients receiving prenatal genetic counseling at our institution from August 2014 to April 2015. Factors associated with screening uptake were assessed. Proportions who accepted screening, were screen-positive, had partners tested, had partners who were screen-positive, and had fetuses tested were calculated. Providers' knowledge and attitudes were assessed using a validated questionnaire. Results Of 1,158 patients offered SMA screening, 224 accepted (19.3%, 95% CI 17.2-21.7). Uptake differed by race, parity, religion, and genetic counselor seen. Five (2.2% or 1:45, 95% CI 0.8-5.3 or 1:19-1:125) women were identified as carriers. Of 3 partners screened, none screened positive (0%, 95% CI 0-5.3). There were no prenatal SMA diagnoses (0%, 95% CI 0-1.4). Of 90 survey respondents, 42% incorrectly answered 1 of 9 knowledge questions. Provider attitudes toward screening were contradictory. Conclusion Despite significant resources utilized, prenatal SMA carrier screening identified no fetal cases. Cost-effectiveness and other barriers should be considered prior to large-scale adoption of more comprehensive genetic screening. PMID:27611803

  6. Biomechanical simulation of atrophy in MR images

    NASA Astrophysics Data System (ADS)

    Castellano Smith, Andrew D.; Crum, William R.; Hill, Derek L. G.; Thacker, Neil A.; Bromiley, Paul A.

    2003-05-01

    Progressive cerebral atrophy is a physical component of the most common forms of dementia - Alzheimer's disease, vascular dementia, Lewy-Body disease and fronto-temporal dementia. We propose a phenomenological simulation of atrophy in MR images that provides gold-standard data; the origin and rate of progression of atrophy can be controlled and the resultant remodelling of brain structures is known. We simulate diffuse global atrophic change by generating global volumetric change in a physically realistic biomechanical model of the human brain. Thermal loads are applied to either single, or multiple, tissue types within the brain to drive tissue expansion or contraction. Mechanical readjustment is modelled using finite element methods (FEM). In this preliminary work we apply these techniques to the MNI brainweb phantom to produce new images exhibiting global diffuse atrophy. We compare the applied atrophy with that measured from the images using an established quantitative technique. Early results are encouraging and suggest that the model can be extended and used for validation of atrophy measurement techniques and non-rigid image registration, and for understanding the effect of atrophy on brain shape.

  7. Using Wood’s Light as a Diagnostic Tool for Vaginal Atrophy

    PubMed Central

    Ulubay, Mustafa; Fidan, Ulas; Keskin, Ugur; Alanbay, Ibrahim; Karaca, Riza

    2015-01-01

    Introduction: Wood’s light lamp is a device that emits ultraviolet (UV) light and is a useful diagnostic tool for dermatologic disorders. The change in the thickness of vaginal mucosa, in vaginal atrophy, causes a change in its colour under Wood’s light. We wanted to assess the feasibility of Wood’s light (WL) as a diagnostic tool for vaginal atrophy. Materials and Methods: The study was conducted at the Department of Obstetrics and Gynaecology from 1 March 2013 to 1 September 2014. We evaluated 45 healthy postmenopausal women with atrophic vaginitis (study group) and 45 healthy, reproductive-aged women as a control group. All patients underwent WL and routine gynaecological examinations for this study. Results: Ninety patients were selected for this study: 45 postmenopausal women suffering atrophic vaginitis symptoms like vaginal dryness, dyspareunia, vulvar pruritus, and signs like pale, smooth, dry, fragile vaginal epithelium, areas of petechiae, and rash, and 45 healthy reproductive-aged women without vaginal atrophy. Thirty-six of the postmenopausal women’s vaginal mucosa appeared pale royal green under WL indicative of vaginal atrophy. Thirty-nine of reproductive-aged women’s (n: 45) vaginal mucosa were not visualized as pale royal green fluorescent images under the WL. Conclusion: Using Wood’s light to diagnose vaginal atrophy is a new use for the old device and may be a reliable, and cheap tool for diagnosing vaginal atrophy. Diagnostic accuracy and cost-effectiveness of Wood’s light will be better optimized in further trials. PMID:25738039

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Genetics Home Reference: spinal muscular atrophy

    MedlinePlus

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

  14. How Is Pneumonia Diagnosed?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Is Pneumonia Diagnosed? Pneumonia can be hard to diagnose because it may ... than these other conditions. Your doctor will diagnose pneumonia based on your medical history, a physical exam, ...

  15. Spinal muscular atrophy, John Griffin, and mentorship.

    PubMed

    Sumner, Charlotte J

    2012-12-01

    Hereditary canine spinal muscular atrophy is an inherited motor neuron disease that occurs in Brittany Spaniels and has remarkable similarities with human spinal muscular atrophy. Both disorders are characterized by proximal limb and truncal muscle weakness of variable severity. Detailed pathological studies indicate that there is early dysfunction of motor neuron synapses, particularly the neuromuscular junction synapse, prior to motor neuron death. This period of synaptic dysfunction may define a critical window of opportunity for disease reversibility in motor neuron disease.

  16. 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…

  17. CHOD/BVAM CHEMOTHERAPY AND WHOLE-BRAIN RADIOTHERAPY FOR NEWLY DIAGNOSED PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA

    PubMed Central

    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.

    2014-01-01

    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. PMID:20800387

  18. 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.

  19. Independent mobility after early introduction of a power wheelchair in spinal muscular atrophy.

    PubMed

    Dunaway, Sally; Montes, Jacqueline; O'Hagen, Jessica; Sproule, Douglas M; Vivo, Darryl C De; Kaufmann, Petra

    2013-05-01

    Weakness resulting from spinal muscular atrophy causes severe limitations in functional mobility. The early introduction of power mobility has potential to enhance development and mitigate disability. These outcomes are achieved by simulating normal skill acquisition and by promoting motor learning, visuospatial system development, self-exploration, cognition, and social development. There are few reports on early power mobility in spinal muscular atrophy, and it is typically not prescribed until school age. The authors evaluated 6 children under age 2 years with neuromuscular disease (5 spinal muscular atrophy, 1 congenital muscular dystrophy) for power mobility. Parents recorded the practice hours necessary to achieve independence using the Power Mobility Skills Checklist. Four children achieved independence in all items on the checklist by 7.9 months (range: 73-458 days). Introduction of early power mobility is feasible in spinal muscular atrophy patients under age 2 years and should be introduced in late infancy when children typically acquire locomotor skills.

  20. 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

  1. Three familial midline malformtion syndromes of the central nervous system: agenesis of the corpus callosum and anterior horn-cell disease; agenesis of cerebellar vermis; and atrophy of the cerebellar vermis.

    PubMed

    Andermann, E; Andermann, F; Joubert, M; Melançon, D; Karpati, G; Carpenter, S

    1975-01-01

    Three syndromes are presented in which major midline malformations of the central nervous system were associated with characteristic somatic and neurologic features in 2 or more sibs. The malformations may be suspected on clinical grouds but require confirmation by pneumoencephalography. In 3 French-Canadian sibships from the Saguenay-Lac St. Jean area of Quebec, patients with areflexia, muscular wasting and slowly progressive weakness in a paraparetic distribution were proved to have agenesis of the corpus callosum and anterior horn-cell disease, a syndrome not previously described. In another family, mental retardation, ataxia and episodic hyperpnea were associated with agenesis of the cerebellar vermis in 4 sibs. In yet another French-Canadian family, atrophy of the cerebellar vermis was associated with mental retardation, ataxia and a mild pyramidal syndrome. Because malformations of this nature are usually considered sporadic or multifactorial in origin, recognition of these specific clinical syndromes with probable autosomal recessive inheritance is important from the point of view of genetic counseling and prevention. PMID:1227532

  2. [Long-term evolution of a patient diagnosed of small lung cancer with extension to the central nervous system].

    PubMed

    Barrado Los Arcos, M; Rico Osés, M; Errasti Viader, M; Campo Vargas, M; Zelaya Huerta, M V; Martínez López, E

    Cell lung cancer is the principal cause of cancer death in men and women. We report the case of a man diagnosed with small cell lung cancer, metastatic from the outset. The disease is stable at present, forty-seven months from dia-gnosis, after receiving different treatment modalities. PMID:27599956

  3. 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

  4. 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. PMID:25795455

  5. 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.

  6. Changes in Characteristics and Treatment Patterns of Patients with Newly Diagnosed Type 2 Diabetes in a Large United States Integrated Health System between 2008 and 2013

    PubMed Central

    Pantalone, Kevin M.; Hobbs, Todd M.; Wells, Brian J.; Kong, Sheldon X.; Kattan, Michael W.; Bouchard, Jonathan; Chagin, Kevin M.; Yu, Changhong; Sakurada, Brian; Milinovich, Alex; Weng, Wayne; Bauman, Janine M.; Zimmerman, Robert S.

    2016-01-01

    To assess changes in the clinical characteristics and treatment patterns of patients with newly diagnosed type 2 diabetes (T2D), the electronic health record system at Cleveland Clinic was used to create cross-sectional summaries of all patients with new-onset T2D in 2008 and 2013. Differences between the 2008 and 2013 data sets were assessed after adjusting for age, gender, race, and income. Approximately one-third of patients with newly diagnosed T2D in 2008 and 2013 had an A1C ≥8%, suggesting the continued presence of a delayed recognition of the disease. Patients with newly diagnosed T2D in 2008 were older than those in 2013. Hypertension, cardiovascular disease, and neuropathy were highly prevalent among patients diagnosed with T2D. The prevalence of neuropathy, cerebrovascular disease, and peripheral vascular disease increased from 2008 to 2013. Metformin was the most commonly prescribed antidiabetic medication. Sulfonylurea usage remained unchanged, while use of thiazolidinediones decreased considerably. PMID:27398040

  7. 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

  8. 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.

  9. 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 (...

  10. 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.

  11. Diagnosing Tic Disorders

    MedlinePlus

    ... Other Websites Information For... Media Policy Makers Diagnosing Tic Disorders Language: English Español (Spanish) Recommend on Facebook ... or postviral encephalitis). Persistent (Chronic) Motor or Vocal Tic Disorder For a person to be diagnosed with ...

  12. 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 ...

  13. 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

  14. Fasciculations masquerading as minipolymyoclonus in bulbospinal muscular atrophy.

    PubMed

    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

  15. Grey matter hypometabolism and atrophy in Parkinson's disease with cognitive impairment: a two-step process.

    PubMed

    González-Redondo, Rafael; García-García, David; Clavero, Pedro; Gasca-Salas, Carmen; García-Eulate, Reyes; Zubieta, José L; Arbizu, Javier; Obeso, José A; Rodríguez-Oroz, María C

    2014-08-01

    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. (18)F-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 by areas

  16. Genetics Home Reference: spinal muscular atrophy with progressive myoclonic epilepsy

    MedlinePlus

    ... myoclonic epilepsy spinal muscular atrophy with progressive myoclonic epilepsy Enable Javascript to view the expand/collapse boxes. ... All Description Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a neurological condition that causes ...

  17. Correspondence of cytological and histopathological diagnoses in diagnostic category V of the Bethesda system: "suspicious for malignancy".

    PubMed

    Stanek-Widera, A; Biskup-Frużyńska, M; Śnietura, M; Zembala-Nożyńska, E; Środa, M; Szczęsny-Karczewska, W; Lange, D

    2016-03-01

    The progress in imaging methods enables fine needle aspiration (FNA) biopsy to be performed on smaller and smaller lesions, including malignant ones (papillary microcarcinomas). The follicular variant predominates in this group, with cytological features often not permitting an unbiased interpretation. The aim of the study was to determine the degree of reliability of the "suspicious for malignancy" (SM) diagnosis in material from the Institute of Oncology in Gliwice (IO). 290 primary SM diagnoses were established from 2010 to 2015 in the IO, including the consultations. None of the patients was treated surgically after the first FNA resulting in diagnostic category V (DC V). After the second FNA 80 patients underwent surgery, after the third 58, and after subsequent FNA 10. Together, 148 surgical resections were performed. Among 148 patients treated surgically, 111 were diagnosed with malignant lesions, which constitutes 75%. Predominantly - in 91 cases - the histopathological outcome was papillary carcinoma. The others were: 16 medullary carcinomas, 2 follicular carcinomas, and 2 poorly differentiated carcinoma cases. Moreover, 8 follicular adenomas and 28 nonneoplastic lesions were found. The high positive predictive value (PPV = 75%) of SM diagnosis established in the IO testifies to the high reliability of this test. Diagnostic category V in FNA should be an indication for surgical treatment. PMID:27179271

  18. An investigation of diffusion imaging techniques in the evaluation of spinocerebellar ataxia and multisystem atrophy.

    PubMed

    Rozenfeld, Michael N; Nemeth, Alexander J; Walker, Matthew T; Mohan, Prasoon; Wang, Xue; Parrish, Todd B; Opal, Puneet

    2015-01-01

    Multisystem system atrophy and spinocerebellar ataxia are rare neurodegenerative ataxias that can be difficult to diagnose, with important prognostic and treatment implications. The purpose of this study is to evaluate various methods of diffusion imaging and tractography in their effectiveness at differentiating these diseases from control subjects. Our secondary aim is determining whether diffusion abnormalities correspond with clinical disease severity. Diffusion imaging and tractography were performed on five patients and seven age-matched controls. Fractional anisotropy, generalized fractional anisotropy, and apparent diffusion coefficient values and corticospinal tract volumes were measured within various diffusion and probabilistic tractography models, including standard diffusion tensor and Q-ball tractography. Standard diffusion based fractional anisotropy and apparent diffusion coefficient values were significantly altered in patients versus controls in the middle cerebellar peduncles and central pons. Tractography based fractional anisotropy and generalized fractional anisotropy values were significantly lower in patients versus controls when corticospinal tracts were drawn in a craniocaudal direction (bilaterally using Q-ball imaging, only on the right using diffusion tensor imaging). The right corticospinal tract volume was significantly smaller in patients versus controls when created using Q-ball imaging in a caudocranial direction. There was no correlation between diffusion alteration and clinical symptomatology. In conclusion, various diffusion-based techniques can be effective in differentiating ataxic patients from control subjects, although the selection of diffusion algorithm and tract growth technique and direction is non-trivial.

  19. 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

  20. Cerebellar atrophy in a patient with velocardiofacial syndrome.

    PubMed Central

    Lynch, D R; McDonald-McGinn, D M; Zackai, E H; Emanuel, B S; Driscoll, D A; Whitaker, L A; Fischbeck, K H

    1995-01-01

    Velocardiofacial syndrome and DiGeorge syndrome have not previously been associated with central nervous system degeneration. We report a 34 year old man who presented for neurological evaluation with cerebellar atrophy of unknown aetiology. On historical review, he had neonatal hypocalcaemia, an atrial septal defect, and a corrected cleft palate. His physical examination showed the characteristic facies of velocardiofacial syndrome as well as dysmetria and dysdiadocho-kinesia consistent with cerebellar degeneration. Molecular cytogenetic studies showed a deletion of 22q11.2. This man is the first reported patient with the association of a neurodegenerative disorder and 22q11.2 deletion syndrome. Images PMID:7562973

  1. 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

    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

  2. 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.

  3. Sporadic Ataxia and Multiple System Atrophy (MSA)

    MedlinePlus

    ... sporadic ataxia and MSA. The disorders include rapid eye movement (REM) sleep behavior disorder, a condition in which ... sleep disorders and provide specific treatment for rapid eye movement sleep behavior disorder as well as obstructive sleep ...

  4. Steroid atrophy scarring treated with fat grafting in a patient with complex regional pain syndrome: A case report.

    PubMed

    Strickland, Leah R; Collawn, Sherry S

    2016-06-01

    Subcutaneous atrophy is a known complication of steroid injections. Excellent results with fat grafting for the treatment of steroid atrophy have been documented. However, the benefit of treating steroid-induced subcutaneous atrophy in an extremity diagnosed with complex regional pain syndrome (CRPS) has not been described. CRPS, known formerly as reflex sympathetic dystrophy or RSD, causalgia, or reflex neurovascular dystrophy, is a severe, progressive musculoskeletal pain syndrome characterized by pain which is disproportionate to the severity of the inciting event, edema, or skin changes. Common treatment modalities include pharmacotherapy, physical therapy, and nerve blocks-each therapy producing varying results. We present a literature review of CRPS and the case of a 15-year-old female who developed CRPS of the left lower leg after arthroscopic debridement with retrograde drilling of an osteochondral lesion. Steroid atrophy of the involved area following a saphenous nerve block complicated the patient's treatment course. The area of atrophy was treated with autologous fat grafting. Following the adipose injection procedure, the patient experienced almost complete resolution of her CPRS-associated pain symptoms, along with improved cosmetic appearance of the area. PMID:26735938

  5. 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

  6. Fibrosis, Adipogenesis, and Muscle Atrophy in Congenital Muscular Torticollis

    PubMed Central

    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

    2014-01-01

    Abstract 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

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

    PubMed

    Mu, Xiaodong; Agarwal, Rashmi; March, Daniel; Rothenberg, Adam; Voigt, Clifford; Tebbets, Jessica; Huard, Johnny; Weiss, Kurt

    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

  8. 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

  9. 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

  10. Shining a light on posterior cortical atrophy.

    PubMed

    Crutch, Sebastian J; Schott, Jonathan M; Rabinovici, Gil D; Boeve, Bradley F; Cappa, Stefano F; Dickerson, Bradford C; Dubois, Bruno; Graff-Radford, Neill R; Krolak-Salmon, Pierre; Lehmann, Manja; Mendez, Mario F; Pijnenburg, Yolande; Ryan, Natalie S; Scheltens, Philip; Shakespeare, Tim; Tang-Wai, David F; van der Flier, Wiesje M; Bain, Lisa; Carrillo, Maria C; Fox, Nick C

    2013-07-01

    Posterior cortical atrophy (PCA) is a clinicoradiologic syndrome characterized by progressive decline in visual processing skills, relatively intact memory and language in the early stages, and atrophy of posterior brain regions. Misdiagnosis of PCA is common, owing not only to its relative rarity and unusual and variable presentation, but also because patients frequently first seek the opinion of an ophthalmologist, who may note normal eye examinations by their usual tests but may not appreciate cortical brain dysfunction. Seeking to raise awareness of the disease, stimulate research, and promote collaboration, a multidisciplinary group of PCA research clinicians formed an international working party, which had its first face-to-face meeting on July 13, 2012 in Vancouver, Canada, prior to the Alzheimer's Association International Conference. PMID:23274153

  11. Oxyntic atrophy, metaplasia and gastric cancer

    PubMed Central

    Goldenring, James R.; Nam, Ki Taek

    2015-01-01

    The process of gastric carcinogenesis involves the loss of parietal cells (oxyntic atrophy) and subsequent replacement of the normal gastric lineages with metaplastic lineages. In humans, two metaplastic lineages develop as sequelae of chronic Helicobacter pylori infection: intestinal metaplasia and Spasmolytic Polypeptide-expressing Metaplasia (SPEM). Mouse models of both chronic Helicobacter infection and acute pharmacological oxyntic atrophy have led to the recognition that SPEM arises from transdifferentiation of mature chief cells. The presence of inflammation promotes the expansion of SPEM in mice. Furthermore, studies in Mongolian gerbils as well as increasing evidence from human studies indicates that SPEM likely represents a precursor for development of intestinal metaplasia. These findings indicate that loss of parietal cells, augmented by chronic inflammation, leads to a cascade of metaplastic events. Identification of specific biomarkers for SPEM and intestinal metaplasia hold promise for providing both early detection of pre-neoplasia as well as information on prognostic outcome following curative resection. PMID:21075342

  12. [Spinal muscular atrophy in Braunvieh calves].

    PubMed

    Stocker, H; Ossent, P; Heckmann, R; Oertle, C

    1992-01-01

    Clinical, neurophysiological and histopathological findings of sixteen cases of spinal muscular atrophy in calves are described. The first clinical signs usually were noticed at 2-6 weeks of age. The animals showed weakness in the hindquarters, trembling and ultimate recumbency. There was a marked muscular atrophy in all four extremities. In addition, secondary bronchopneumonia was evident in 11 cases. Histopathological lesions consisted of degenerative changes in the neurons of the ventral horns and the axons of the spinal cord as well as degeneration of nerve axons in the extremities. Neurophysiological measurements revealed spontaneous activity in the muscles of the limbs. The conditions is autosomal recessive. So far 11 bulls have been identified and excluded from breeding.

  13. Postinjection vastus lateralis atrophy: 2 case reports.

    PubMed

    Haber, M; Kovan, E; Andary, M; Honet, J

    2000-09-01

    We report two cases of postsurgical intramuscular meperidine injection with injury to the femoral nerve and subsequent vastus lateralis atrophy. The first case is a patient who had arthroscopic anterior cruciate ligament reconstruction; the second, a patient with a C6-C7 anterior fusion. Photographs, radiography, and electrodiagnostic studies clearly depict the nature of the injuries, and their etiology is discussed. These case reports describe a unique neuropathic injection injury that, to our knowledge, has never before been described in the literature.

  14. Gyrate atrophy of choroid and retina.

    PubMed

    Bhaduri, Gautam

    2002-03-01

    Gyrate atrophy of choroid and retina is a rare disorder of autosomal recessive nature. There occurs patchy and progressive atrophy of the choroid and retina at the equatorial region with central area being less affected. Here in this case report, one woman of about 47 years attended at the retina clinic, Tenennt Institute of Ophthalmology, Glasgow University with the history of gradual loss of vision. On fundus examination, sharply defined bizarre shaped atrophic areas of fundus was seen in both the eyes. Velvet like fine granular pigments were present in the macula, the zone of healthy retina and the periphery. The colourless, elongated, glittering crystals were scattered over the dark brown pigments visible through 90 dioptre lens. Bone corpuscles pigments were not found. Fluorescein angiography showed hyperfluorescence in the area of gyrate atrophy. Her plasma ornithine level and plasma tiramine level were 1 90 U mol/l and 357 U mol/l. respectively. A rigid schedule of low protein diet including near total elimination of arginine with supplementation of essential amino acids was advised since the diagnosis was established.

  15. Tumor Vascular Permeability Pattern Is Associated With Complete Response in Immunocompetent Patients With Newly Diagnosed Primary Central Nervous System Lymphoma

    PubMed Central

    Chung, Sae Rom; Choi, Young Jun; Kim, Ho Sung; Park, Ji Eun; Shim, Woo Hyun; Kim, Sang Joon

    2016-01-01

    Abstract A dynamic contrast-enhanced MR imaging (DCE-MRI) could provide the information about tumor drug delivery efficacy. We investigated the potential utility of the permeability pattern of DCE-MRI for predicting tumor response to high dose-methotrexate treatment and progression-free survival (PFS) in patients with primary CNS lymphoma (PCNSL). Clinical and conventional imaging parameters were assessed as potential predictors of tumor response in 48 immunocompetent PCNSL patients in a preliminary study. Fifty additional immunocompetent patients (27 men and 23 women; mean age, 60.6 years) with PCNSL underwent DCE-MRI before starting first-line treatment with high dose-methotrexate. The DCE-MRI pattern was categorized as diffuse or nondiffuse. After 4 courses of high dose methotrexate, patients underwent follow-up brain MR imaging to identify their complete response (CR). Predictors of CR and PFS were analyzed using clinical parameters, conventional MRI, and DCE-MRI. CR was noted in 20 (74.1%) of 27 patients with diffuse DCE-MRI pattern and in 4 (17.4%) of 23 patients with nondiffuse DCE-MRI pattern. The diffuse DCE-MRI pattern showed a significantly higher association with CR than the nondiffuse pattern (P < 0.001). Multivariate Cox proportional hazards model revealed that the DCE-MRI pattern (hazard ratio = 0.70; P = 0.045), age (hazard ratio = 1.47; P = 0.041), and adjuvant autologous stem-cell transplantation (hazard ratio = 6.97; P = 0.003) tended to be associated with a PFS. The pretreatment diffuse DCE-MRI pattern can be used as a potential imaging biomarker for predicting CR and a longer PFS in patients with newly diagnosed PCNSLs. PMID:26871782

  16. Giant mucinous cystic adenoma with pancreatic atrophy mimicking dorsal agenesis of the pancreas

    PubMed Central

    Gagnière, Johan; Dupré, Aurélien; Ines, David Da; Tixier, Lucie; Pezet, Denis; Buc, Emmanuel

    2014-01-01

    Mucinous cystic adenoma (MCA) of the pancreas is a rare benign cystic tumor with ovarian-like stroma and lack of communication with the pancreatic ductal system. The ovarian tissue is incorporated from the left gonad within the dorsal pancreas during embryogenesis. Consequently, congenital dorsal agenesis of the pancreas (DAP) cannot be associated with MCA. We report the case of a giant MCA associated with atrophy of the dorsal pancreas mimicking complete DAP. Pancreato-magnetic resonance imaging failed to identify the dorsal pancreas but the absence of diabetes mellitus and compression of the splenic vein with major tributaries rectified the diagnosis of secondary atrophy of the distal pancreas. Unusual proximal location of the cyst in the pancreas may have induced chronic obstruction of both the dorsal pancreatic duct and the splenic vein, with secondary atrophy of the distal pancreas. PMID:24672649

  17. 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)

  18. Models of accelerated sarcopenia: critical pieces for solving the puzzle of age-related muscle atrophy.

    PubMed

    Buford, Thomas W; Anton, Stephen D; Judge, Andrew R; Marzetti, Emanuele; Wohlgemuth, Stephanie E; Carter, Christy S; Leeuwenburgh, Christiaan; Pahor, Marco; Manini, Todd M

    2010-10-01

    Sarcopenia, the age-related loss of skeletal muscle mass, is a significant public health concern that continues to grow in relevance as the population ages. Certain conditions have the strong potential to coincide with sarcopenia to accelerate the progression of muscle atrophy in older adults. Among these conditions are co-morbid diseases common to older individuals such as cancer, kidney disease, diabetes, and peripheral artery disease. Furthermore, behaviors such as poor nutrition and physical inactivity are well-known to contribute to sarcopenia development. However, we argue that these behaviors are not inherent to the development of sarcopenia but rather accelerate its progression. In the present review, we discuss how these factors affect systemic and cellular mechanisms that contribute to skeletal muscle atrophy. In addition, we describe gaps in the literature concerning the role of these factors in accelerating sarcopenia progression. Elucidating biochemical pathways related to accelerated muscle atrophy may allow for improved discovery of therapeutic treatments related to sarcopenia.

  19. Connectivity network measures predict volumetric atrophy in mild cognitive impairment.

    PubMed

    Nir, Talia M; Jahanshad, Neda; Toga, Arthur W; Bernstein, Matt A; Jack, Clifford R; Weiner, Michael W; Thompson, Paul M

    2015-01-01

    Alzheimer's disease (AD) is characterized by cortical atrophy and disrupted anatomic connectivity, and leads to abnormal interactions between neural systems. Diffusion-weighted imaging (DWI) and graph theory can be used to evaluate major brain networks and detect signs of a breakdown in network connectivity. In a longitudinal study using both DWI and standard magnetic resonance imaging (MRI), we assessed baseline white-matter connectivity patterns in 30 subjects with mild cognitive impairment (MCI, mean age 71.8 ± 7.5 years, 18 males and 12 females) from the Alzheimer's Disease Neuroimaging Initiative. Using both standard MRI-based cortical parcellations and whole-brain tractography, we computed baseline connectivity maps from which we calculated global "small-world" architecture measures, including mean clustering coefficient and characteristic path length. We evaluated whether these baseline network measures predicted future volumetric brain atrophy in MCI subjects, who are at risk for developing AD, as determined by 3-dimensional Jacobian "expansion factor maps" between baseline and 6-month follow-up anatomic scans. This study suggests that DWI-based network measures may be a novel predictor of AD progression.

  20. 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

  1. Severe spinal muscular atrophy variant associated with congenital bone fractures.

    PubMed

    Felderhoff-Mueser, Ursula; Grohmann, Katja; Harder, Anja; Stadelmann, Christine; Zerres, Klaus; Bührer, Christoph; Obladen, Michael

    2002-09-01

    Infantile autosomal recessive spinal muscular atrophy (type I) represents a lethal disorder leading to progressive symmetric muscular atrophy of limb and trunk muscles. Ninety-six percent cases of spinal muscular atrophy type I are caused by deletions or mutations in the survival motoneuron gene (SMNI) on chromosome 5q11.2-13.3. However, a number of chromosome 5q-negative patients with additional clinical features (respiratory distress, cerebellar hypoplasia) have been designated in the literature as infantile spinal muscular atrophy plus forms. In addition, the combination of severe spinal muscular atrophy and neurogenic arthrogryposis has been described. We present clinical, molecular, and autopsy findings of a newborn boy presenting with generalized muscular atrophy in combination with congenital bone fractures and extremely thin ribs but without contractures.

  2. 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.

  3. 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.

  4. [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. PMID:23012868

  5. Hippocampal and cerebellar atrophy in patients with Cushing's disease.

    PubMed

    Burkhardt, Till; Lüdecke, Daniel; Spies, Lothar; Wittmann, Linus; Westphal, Manfred; Flitsch, Jörg

    2015-11-01

    OBJECT Cushing's disease (CD) may cause atrophy of different regions of the human brain, mostly affecting the hippocampus and the cerebellum. This study evaluates the use of 3-T MRI of newly diagnosed patients with CD to detect atrophic degeneration with voxel-based volumetry. METHODS Subjects with newly diagnosed, untreated CD were included and underwent 3-T MRI. Images were analyzed using a voxelwise statistical test to detect reduction of brain parenchyma. In addition, an atlas-based volumetric study for regions likely to be affected by CD was performed. RESULTS Nineteen patients with a mean disease duration of 24 months were included. Tumor markers included adrenocorticotropic hormone (median 17.5 pmol/L), cortisol (949.4 nmol/L), and dehydroepiandrosterone sulfate (5.4 μmol/L). The following values are expressed as the mean ± SD. The voxelwise statistical test revealed clusters of significantly reduced gray matter in the hippocampus and cerebellum, with volumes of 2.90 ± 0.26 ml (right hippocampus), 2.89 ± 0.28 ml (left hippocampus), 41.95 ± 4.67 ml (right cerebellar hemisphere), and 42.11 ± 4.59 ml (left cerebellar hemisphere). Healthy control volunteers showed volumes of 3.22 ± 0.25 ml for the right hippocampus, 3.23 ± 0.25 ml for the left hippocampus, 50.87 ± 4.23 ml for the right cerebellar hemisphere, and 50.42 ± 3.97 ml for the left cerebellar hemisphere. CONCLUSIONS Patients with untreated CD show significant reduction of gray matter in the cerebellum and hippocampus. These changes can be analyzed and objectified with the quantitative voxel-based method described in this study.

  6. [Sporadic case of non-progressive neurogenic muscular atrophy localized in both calf muscles].

    PubMed

    Hara, Kenju; Tateyama, Maki; Suzuki, Naoki; Shibano, Ken; Tanaka, Keiko; Ishiguro, Hideaki

    2013-01-01

    A 60-year-old woman was admitted to our hospital because of difficulty in standing on her toes. Neurological examination showed muscle weakness in both calf muscles. Her serum creatine kinase (CK) level was slightly elevated. MRI revealed hyper-intense signals localized in both the gastrocnemius and soleus muscles. Histological examinations of biopsied muscle specimens showed a marked variation in fiber size, small angular fibers, and hypertrophic and splitting fibers, but no muscle fiber necrosis or regeneration or inflammatory cell infiltration. ATPase stained sections showed small grouped atrophy of type 1 fibers. NADH-TR stained sections showed target/targetoid fibers predominantly in type 1 fibers. Dysferlin immunoreactivity was normal. Follow-up clinical evaluation for one year showed no progression. This patient was diagnosed as having an unknown type of spinal muscular atrophy or benign calf amyotrophy. Sporadic cases characterized by elderly-onset, neurogenic muscular atrophy localized in both calf muscles, and non-progressive course are extremely rare in Japan.

  7. Discriminant analysis of intermediate brain atrophy rates in longitudinal diagnosis of alzheimer's disease

    PubMed Central

    2011-01-01

    Diagnosing Alzheimer's disease through MRI neuroimaging biomarkers has been used as a complementary marker for traditional clinical markers to improve diagnostic accuracy and also help in developing new pharmacotherapeutic trials. It has been revealed that longitudinal analysis of the whole brain atrophy has the power of discriminating Alzheimer's disease and elderly normal controls. In this work, effect of involving intermediate atrophy rates and impact of using uncorrelated principal components of these features instead of original ones on discriminating normal controls and Alzheimer's disease subjects, is inspected. In fact, linear discriminative analysis of atrophy rates is used to classify subjects into Alzheimer's disease and controls. Leave-one-out cross-validation has been adopted to evaluate the generalization rate of the classifier along with its memorization. Results show that incorporating uncorrelated version of intermediate features leads to the same memorization performance as the original ones but higher generalization rate. As a conclusion, it is revealed that in a longitudinal study, using intermediate MRI scans and transferring them to an uncorrelated feature space can improve diagnostic accuracy. PMID:22035255

  8. 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 ...

  9. How Is Endocarditis Diagnosed?

    MedlinePlus

    ... can get detailed pictures of the heart's structures. EKG An EKG is a simple, painless test that detects your ... signals as they pass through your heart. An EKG typically isn't used to diagnose IE. However, ...

  10. 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…

  11. Diagnosing the average spatio-temporal impact of convective systems - Part 1: A methodology for evaluating climate models

    NASA Astrophysics Data System (ADS)

    Johnston, M. S.; Eliasson, S.; Eriksson, P.; Forbes, R. M.; Wyser, K.; Zelinka, M. D.

    2013-12-01

    An earlier method to determine the mean response of upper-tropospheric water to localised deep convective systems (DC systems) is improved and applied to the EC-Earth climate model. Following Zelinka and Hartmann (2009), several fields related to moist processes and radiation from various satellites are composited with respect to the local maxima in rain rate to determine their spatio-temporal evolution with deep convection in the central Pacific Ocean. Major improvements to the earlier study are the isolation of DC systems in time so as to prevent multiple sampling of the same event, and a revised definition of the mean background state that allows for better characterisation of the DC-system-induced anomalies. The observed DC systems in this study propagate westward at ~4 m s-1. Both the upper-tropospheric relative humidity and the outgoing longwave radiation are substantially perturbed over a broad horizontal extent and for periods >30 h. The cloud fraction anomaly is fairly constant with height but small maximum can be seen around 200 hPa. The cloud ice water content anomaly is mostly confined to pressures greater than 150 hPa and reaches its maximum around 450 hPa, a few hours after the peak convection. Consistent with the large increase in upper-tropospheric cloud ice water content, albedo increases dramatically and persists about 30 h after peak convection. Applying the compositing technique to EC-Earth allows an assessment of the model representation of DC systems. The model captures the large-scale responses, most notably for outgoing longwave radiation, but there are a number of important differences. DC systems appear to propagate eastward in the model, suggesting a strong link to Kelvin waves instead of equatorial Rossby waves. The diurnal cycle in the model is more pronounced and appears to trigger new convection further to the west each time. Finally, the modelled ice water content anomaly peaks at pressures greater than 500 hPa and in the upper

  12. 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

  13. 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

  14. Treatment of newly diagnosed B-cell origin primary CNS lymphoma with systemic R-IDARAM chemotherapy and intrathecal immunochemotherapy

    PubMed Central

    Qian, Liren; Zhou, Chunhui; Shen, Jianliang; Cen, Jian; Yin, Wenjie

    2016-01-01

    Background Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin's lymphoma (NHL). The aim was to evaluate response rate, progression free survival (PFS), overall survival (OS), and toxicity in PCNSL after systemic R-IDARAM and intrathecal immunochemotherapy with deferred radiotherapy. Results The response rate was 94% with 17 (89%) complete responses and 1 (5%) partial responses. Follow-up time is from 5 to 63 months (median, 39 months). Median survival has not been reached. 3-year overall survival and progression-free survival rates were 84.2% (CI 72.6% to 99.8%) and 63.2% (CI 41.4% to 73.8%). Systemic toxicity was mainly hematologic. Neurocognitive and neuromotor deterioration as a result of treatment occurred in only one patient (5%). Patients and Methods From September 2010 to June 2015, 19 consecutive patients with PCNSL (median age, 54 years) were enrolled into a pilot phase II study evaluating immunochemotherapy without radiotherapy. The patients were accrued to a chemotherapy regimen that incorporated rituximab, idarubicin, dexamethasone, cytarabine (Ara-c) and methotrexate (MTX) combined with intrathecal rituximab, MTX, dexamethasone and Ara-c. Conclusions The results indicate that R-IDARAM regimen with intrathecal immunochemotherapy is generally well tolerated and produces a high complete response rate and survival rate. PMID:27029056

  15. AB033. Preimplantation genetic diagnosis of spinal muscular atrophy in Vietnam

    PubMed Central

    Khoa, Tran Van; Nga, Nguyen Thi Thanh; Tao, Nguyen Dinh; Sang, Trieu Tien; Giang, Ngo Truong; Dung, Vu Chi

    2015-01-01

    Objective Spinal muscular atrophy (SMA) is a severe neurodegenerative autosomal recessive disorder. Most of patients are caused by the homozygous absence of exon 7 of the telomeric copy of the SMN gene (SMNt) on chromosome 5. Setting up a molecular diagnostic protocol for detecting exon 7 gen SMNT homozygous deletion in single cell is basic to preimplantation genetic diagnosis of spinal muscular atrophy. Methods This study was carried out on 17 patients and their parents. Firstly, lymphocytes of patients and their parents were isolated from fresh blood by ficoll. Taking a lymphocyte on stereoscopic microscope, lysing the cell, amplifying whole genome, then amplifying exon 7 of SMNT gene by using a polymerase chain reaction, followed by HinfI restriction digest enzyme of the PCR enabling the important SMNT gene to be distinguished from the centromic SMN gene (SMNc) which has no clinical phenotype to detect mutation. Electrophoresis PCR products after digesting by restriction enzyme and analysis. Besides, the minisequencing technique has also been used to detect the absence of exon 7 of SMNT gene based on the difference of one nucleotide at 214-position in exon 7 (C-SMNT, T-SMNc). Secondly, the application of the protocol was set up on one lymphocyte to preimplantation genetic diagnosis of spinal muscular atrophy on biopsied blastomeres. Results Two different protocols which were PCR-RFLP and minisequencing, were set up on 200 lymphocytes from 17 patients and their parents to screen the homozygous deletion in exon 7 SMNT gene with the PCR efficiency in 96%. The results were similar with the gene diagnosed from fresh blood. The methods were also efficient, providing interpretable result in 96.55% (28/29) of the blastomeres tested. Three couples were treated using this method. Three normal embryos were transfer which resulted in one clinical pregnancy. Conclusions We have successfully applied the technique of PCR-RFLP and minisequencing for the preimplantation genetic

  16. A population-based study on blood pressure and brain atrophy in 85-year-olds.

    PubMed

    Skoog, I; Andreasson, L A; Landahl, S; Lernfelt, B

    1998-09-01

    In the general population, mean systolic and diastolic blood pressure increases up to age 75 years but decreases thereafter. The brain has a role in blood pressure regulation; it is not clear whether the cerebral changes that occur with aging contribute to the decline in blood pressure in the very elderly. We examined a population-based sample of 484 85-year-old persons (344 nondemented and 140 demented, 61 with Alzheimer's disease, 65 with vascular dementia, and 14 with other types of dementia) with a neuropsychiatric examination and blood pressure measurements. Dementia was diagnosed according to the criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders, edition 3, revised. Brain atrophy was measured by CT of the brain. In the nondemented group, frontal (r=-0.18, P=0.037) and parietal (r=-0.23, P=0.008) cortical atrophy and bifrontal ratio (r=-0.20, P=0.013) were associated with lower systolic blood pressure, and frontal (r=-0.23, P=0.010) and parietal (r=-0.24, P=0.008) cortical atrophy and bifrontal ratio (r=-0.23, P=0.006) with lower diastolic blood pressure. Systolic blood pressure was lower in subjects with Alzheimer's disease and vascular dementia, and diastolic blood pressure was lower in those with vascular dementia compared with the nondemented. Systolic (r=-0.27, P<0.0001) and diastolic (r=-0.10, P=0.020) blood pressure was negatively correlated to dementia severity. In the demented subjects, frontal cortical atrophy was correlated to lower diastolic blood pressure (r=-0.21, P=0.043). Our findings suggest that age-related changes in brain structure may contribute to the decrease in blood pressure in the very elderly and that low blood pressure in dementia disorders is mainly a secondary phenomenon. PMID:9740603

  17. Brain Atrophy, Anti-Smooth Muscle Antibody and Cognitive Impairment: An Association Study

    PubMed Central

    Giulia, Paroni; Michele, Lauriola; Andrea, Fontana; Grazia, D’Onofrio; Filomena, Ciccone; Francesco, Paris; Leandro, Cascavilla; Maria, Urbano; Carolina, Gravina; Massimiliano, Copetti; Antonio, Greco

    2016-01-01

    Cortical atrophy, neuronal loss, beta-amyloid deposition, neuritic plaques, and neurofibrillary tangles are neuropathological key features in the Alzheimer’s disease (AD). Antibodies against beta-amyloid, neurotransmitters, microvascular endothelium components and microglial cells have been detected in AD serum suggesting that AD could be another autoimmune disease and provides a link between vascular pathology, endothelium dysfunction and neuronal cells death. Aim of the present study was to evaluate the association between autoantibody profile and cognitive impairment in geriatric patients, accounting for ApoE genotype as a potential confounding factor. Three hundred and forty-four geriatric patients, attending the clinic for the cognitive decline, underwent a biochemical and immunological profile, chest X-ray, cerebral computed tomography scan and complete cognitive evaluation. All patients were also screened for the ApoE genotype. A significantly higher prevalence of Anti-Smooth Muscle Antibody (ASMA) positivity was found in 89/204 (43.63%) patients with diagnosed neuroradiological signs of cerebral atrophy compared with 15/140 (10.71%) patients without the condition (p<0.001). Multivariable logistic model evidenced that such association was independent of patient’s age, gender and Mini-Mental State Examination (OR=8.25, 95%CI: 4.26-15.99) and achieved a good discriminatory power (c-statistic=0.783). Results were also independent of ApoE genotype, which resulted not associated both with the presence of brain atrophy and with the presence of ASMA positivity. Our results shows a strong association between brain atrophy and ASMA positivity and are consistent with several studies that focused attention on the mechanisms of endothelial immune response in the development of dementia. PMID:27493830

  18. Brain Atrophy, Anti-Smooth Muscle Antibody and Cognitive Impairment: An Association Study.

    PubMed

    Giulia, Paroni; Michele, Lauriola; Andrea, Fontana; Grazia, D'Onofrio; Filomena, Ciccone; Francesco, Paris; Leandro, Cascavilla; Maria, Urbano; Carolina, Gravina; Massimiliano, Copetti; Antonio, Greco

    2016-08-01

    Cortical atrophy, neuronal loss, beta-amyloid deposition, neuritic plaques, and neurofibrillary tangles are neuropathological key features in the Alzheimer's disease (AD). Antibodies against beta-amyloid, neurotransmitters, microvascular endothelium components and microglial cells have been detected in AD serum suggesting that AD could be another autoimmune disease and provides a link between vascular pathology, endothelium dysfunction and neuronal cells death. Aim of the present study was to evaluate the association between autoantibody profile and cognitive impairment in geriatric patients, accounting for ApoE genotype as a potential confounding factor. Three hundred and forty-four geriatric patients, attending the clinic for the cognitive decline, underwent a biochemical and immunological profile, chest X-ray, cerebral computed tomography scan and complete cognitive evaluation. All patients were also screened for the ApoE genotype. A significantly higher prevalence of Anti-Smooth Muscle Antibody (ASMA) positivity was found in 89/204 (43.63%) patients with diagnosed neuroradiological signs of cerebral atrophy compared with 15/140 (10.71%) patients without the condition (p<0.001). Multivariable logistic model evidenced that such association was independent of patient's age, gender and Mini-Mental State Examination (OR=8.25, 95%CI: 4.26-15.99) and achieved a good discriminatory power (c-statistic=0.783). Results were also independent of ApoE genotype, which resulted not associated both with the presence of brain atrophy and with the presence of ASMA positivity. Our results shows a strong association between brain atrophy and ASMA positivity and are consistent with several studies that focused attention on the mechanisms of endothelial immune response in the development of dementia. PMID:27493830

  19. 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.

  20. 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

  1. Cost analysis of nucleic acid amplification for diagnosing pulmonary tuberculosis, within the context of the Brazilian Unified Health Care System.

    PubMed

    Pinto, Márcia; Entringer, Aline Piovezan; Steffen, Ricardo; Trajman, Anete

    2015-01-01

    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

  2. Cost analysis of nucleic acid amplification for diagnosing pulmonary tuberculosis, within the context of the Brazilian Unified Health Care System.

    PubMed

    Pinto, Márcia; Entringer, Aline Piovezan; Steffen, Ricardo; Trajman, Anete

    2015-01-01

    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.

  3. 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

  4. Brain atrophy in Alzheimer's Disease and aging.

    PubMed

    Pini, Lorenzo; Pievani, Michela; Bocchetta, Martina; Altomare, Daniele; Bosco, Paolo; Cavedo, Enrica; Galluzzi, Samantha; Marizzoni, Moira; Frisoni, Giovanni B

    2016-09-01

    Thanks to its safety and accessibility, magnetic resonance imaging (MRI) is extensively used in clinical routine and research field, largely contributing to our understanding of the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the main findings in AD and normal aging over the past twenty years, focusing on the patterns of gray and white matter changes assessed in vivo using MRI. Major progresses in the field concern the segmentation of the hippocampus with novel manual and automatic segmentation approaches, which might soon enable to assess also hippocampal subfields. Advancements in quantification of hippocampal volumetry might pave the way to its broader use as outcome marker in AD clinical trials. Patterns of cortical atrophy have been shown to accurately track disease progression and seem promising in distinguishing among AD subtypes. Disease progression has also been associated with changes in white matter tracts. Recent studies have investigated two areas often overlooked in AD, such as the striatum and basal forebrain, reporting significant atrophy, although the impact of these changes on cognition is still unclear. Future integration of different MRI modalities may further advance the field by providing more powerful biomarkers of disease onset and progression. PMID:26827786

  5. 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.

  6. Brain atrophy in Alzheimer's Disease and aging.

    PubMed

    Pini, Lorenzo; Pievani, Michela; Bocchetta, Martina; Altomare, Daniele; Bosco, Paolo; Cavedo, Enrica; Galluzzi, Samantha; Marizzoni, Moira; Frisoni, Giovanni B

    2016-09-01

    Thanks to its safety and accessibility, magnetic resonance imaging (MRI) is extensively used in clinical routine and research field, largely contributing to our understanding of the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the main findings in AD and normal aging over the past twenty years, focusing on the patterns of gray and white matter changes assessed in vivo using MRI. Major progresses in the field concern the segmentation of the hippocampus with novel manual and automatic segmentation approaches, which might soon enable to assess also hippocampal subfields. Advancements in quantification of hippocampal volumetry might pave the way to its broader use as outcome marker in AD clinical trials. Patterns of cortical atrophy have been shown to accurately track disease progression and seem promising in distinguishing among AD subtypes. Disease progression has also been associated with changes in white matter tracts. Recent studies have investigated two areas often overlooked in AD, such as the striatum and basal forebrain, reporting significant atrophy, although the impact of these changes on cognition is still unclear. Future integration of different MRI modalities may further advance the field by providing more powerful biomarkers of disease onset and progression.

  7. Proximal spinal muscular atrophy: current orthopedic perspective

    PubMed Central

    Haaker, Gerrit; Fujak, Albert

    2013-01-01

    Spinal muscular atrophy (SMA) is a hereditary neuromuscular disease of lower motor neurons that is caused by a defective “survival motor neuron” (SMN) protein that is mainly associated with proximal progressive muscle weakness and atrophy. Although SMA involves a wide range of disease severity and a high mortality and morbidity rate, recent advances in multidisciplinary supportive care have enhanced quality of life and life expectancy. Active research for possible treatment options has become possible since the disease-causing gene defect was identified in 1995. Nevertheless, a causal therapy is not available at present, and therapeutic management of SMA remains challenging; the prolonged survival is increasing, especially orthopedic, respiratory and nutritive problems. This review focuses on orthopedic management of the disease, with discussion of key aspects that include scoliosis, muscular contractures, hip joint disorders, fractures, technical devices, and a comparative approach of conservative and surgical treatment. Also emphasized are associated complications including respiratory involvement, perioperative care and anesthesia, nutrition problems, and rehabilitation. The SMA disease course can be greatly improved with adequate therapy with established orthopedic procedures in a multidisciplinary therapeutic approach. PMID:24399883

  8. Circulating microRNAs: a novel class of potential biomarkers for diagnosing and prognosing central nervous system diseases.

    PubMed

    Jin, Xue-Feng; Wu, Ning; Wang, Lv; Li, Jin

    2013-07-01

    As a class of important endogenous small noncoding RNAs that regulate gene expression at the posttranscriptional level, microRNAs (miRNAs) play a critical role in many physiological and pathological processes. It is believed that miRNAs contribute to the development, differentiation, and synaptic plasticity of the neurons, and their dysregulation has been linked to a series of diseases. MiRNAs exist in the tissues and as circulating miRNAs in several body fluids, including plasma or serum, cerebrospinal fluid, urine, and saliva. There are significant differences between the circulating miRNA expression profiles of healthy individuals and those of patients. Consequently, circulating miRNAs are likely to become a novel class of noninvasive and sensitive biomarkers. Although little is known about the origin and functions of circulating miRNAs at present, their roles in the clinical diagnosis and prognosis of diseases make them attractive markers, particularly for tumors and cardiovascular diseases. Until now, however, there have been limited data regarding the roles of circulating miRNAs in central nervous system (CNS) diseases. This review focuses on the characteristics of circulating miRNAs and their values as potential biomarkers in CNS diseases, particularly in Alzheimer's disease, Huntington's disease, multiple sclerosis, schizophrenia, and bipolar disorder. PMID:23633081

  9. [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.

  10. Understanding Prostate Cancer: Newly Diagnosed

    MedlinePlus

    ... Wellness PCF Spotlight Glossary African American Men Understanding Prostate Cancer Newly Diagnosed Newly Diagnosed Staging the Disease Issues ... you care about has recently been diagnosed with prostate cancer, this section will help guide you through the ...

  11. 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 ...

  12. Testicular atrophy in the spontaneously diabetic BB Wistar rat.

    PubMed Central

    Wright, J. R.; Yates, A. J.; Sharma, H. M.; Shim, C.; Tigner, R. L.; Thibert, P.

    1982-01-01

    Complete gross and microscopic postmortem examinations were performed on 100 BB Wistar diabetic rats, 27 BB Wistar nondiabetic siblings, and 41 Wistar rats, and the incidence of testicular lesions was tabulated. Testicular atrophy was the predominant finding in all three groups of rats, but atrophy occurred at a much younger age in the diabetic rats. There was a strong relationship between the duration of diabetes and the presence of atrophy, which was stronger than the relationship between age and atrophy. The testicular atrophy observed in the diabetic rats was morphologically similar to the senile testicular atrophy in the nondiabetic rats. Histologic findings that were associated with increasing severity of atrophy were multinucleated giant cells in the lumens of seminiferous tubules, increased interstitial connective tissue, Leydig cell hyperplasia, and thickening of the tunica albuginea. Testicular atrophy has also been reported in human diabetics. Therefore, the BB Wistar rat may be a useful model for investigating this aspect of diabetes mellitus. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:7091303

  13. 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.

  14. 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

  15. Automated measurements of cerebral atrophy in multiple sclerosis.

    PubMed

    Hageleit, U; Will, C H; Seidel, D

    1987-01-01

    An automated method of measuring cerebral atrophy is introduced. Using this method we studied patients with multiple sclerosis and a control group showing premature cerebral atrophy in multiple sclerosis (P = 1,32 x 10(-8) for male and P = 3,6 x 10(-14) for female). There was only a weak correlation between cerebral atrophy and psychological deficits. Multivariate analysis did not show any significant correlation between cerebral atrophy, duration of disease, clinical manifestations and progression of disease. We conclude that our method to measure cerebral atrophy is more accurate and less time-consuming than the use of linear indices. It might be appropriate for further investigations in evaluating atrophic processes in cerebro-vascular, degenerative and exogen-toxic disease of brain.

  16. Indices of Regional Brain Atrophy: Formulae and Nomenclature.

    PubMed

    Menendez, Manuel; Arias-Carrión, Oscar

    2015-08-01

    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

  17. 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

  18. 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.

  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. Treatment of postmenopausal vaginal atrophy with 10-μg estradiol vaginal tablets.

    PubMed

    Panay, Nick; Maamari, Ricardo

    2012-03-01

    Postmenopausal estrogen deficiency can lead to symptoms of urogenital atrophy. Individuals with urogenital atrophy have symptoms that include vaginal dryness, vaginal and vulval irritation, vaginal soreness, pain and burning during urination (dysuria), increased vaginal discharge, vaginal odour, vaginal infections, recurrent urinary tract infections, pain associated with sexual activity (dyspareunia) and vaginal bleeding associated with sexual activity. Despite the frequency and effects of vaginal atrophy symptoms, they are often under-reported and, consequently, under-treated. Therefore, care of a menopausal woman should include a physical assessment of vaginal atrophy and a dialogue between the physician and the patient that explores existing symptoms and their effect on vulvovaginal health, sexuality and quality-of-life issues. The development of the ultra-low-dose 10-µg estradiol vaginal tablets is in line with the requirements of regulatory agencies and women's health societies regarding the use of the lowest effective hormonal dose. Because of its effectiveness and safety profiles, in addition to its minimal systemic absorption, the 10-µg estradiol vaginal tablet can offer greater reassurance to health-care providers and postmenopausal women with an annual estradiol administration of only 1.14 mg.

  1. 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.

  2. Diagnosing ADHD in Adolescence

    ERIC Educational Resources Information Center

    Sibley, Margaret H.; Pelham, William E., Jr.; Molina, Brooke S. G.; Gnagy, Elizabeth M.; Waschbusch, Daniel A.; Garefino, Allison C.; Kuriyan, Aparajita B.; Babinski, Dara E.; Karch, Kathryn M.

    2012-01-01

    Objective: This study examines adolescent-specific practical problems associated with current practice parameters for diagnosing attention-deficit/hyperactivity disorder (ADHD) to inform recommendations for the diagnosis of ADHD in adolescents. Specifically, issues surrounding the use of self- versus informant ratings, diagnostic threshold, and…

  3. Muscle atrophy in patients with Type 2 Diabetes Mellitus: roles of inflammatory pathways, physical activity and exercise.

    PubMed

    Perry, Ben D; Caldow, Marissa K; Brennan-Speranza, Tara C; Sbaraglia, Melissa; Jerums, George; Garnham, Andrew; Wong, Chiew; Levinger, Pazit; Asrar Ul Haq, Muhammad; Hare, David L; Price, S Russ; Levinger, Itamar

    2016-01-01

    Muscle atrophy is caused by an imbalance in contractile protein synthesis and degradation which can be triggered by various conditions including Type 2 Diabetes Mellitus (T2DM). Reduced muscle quality in patients with T2DM adversely affects muscle function, the capacity to perform activities of daily living, quality of life and ultimately may increase the risk of premature mortality. Systemic inflammation initiated by obesity and prolonged overnutrition not only contributes to insulin resistance typical of T2DM, but also promotes muscle atrophy via decreased muscle protein synthesis and increased ubiquitin-proteasome, lysosomal-proteasome and caspase 3- mediated protein degradation. Emerging evidence suggests that the inflammation-sensitive Nuclear Factor κ B (NF-κB) and Signal Transducer and Activator of Transcription 3 (STAT3) pathways may contribute to muscle atrophy in T2DM. In contrast, exercise appears to be an effective tool in promoting muscle hypertrophy, in part due to its effect on systemic and local (skeletal muscle) inflammation. The current review discusses the role inflammation plays in muscle atrophy in T2DM and the role of exercise training in minimising the effect of inflammatory markers on skeletal muscle. We also report original data from a cohort of obese patients with T2DM compared to age-matched controls and demonstrate that patients with T2DM have 60% higher skeletal muscle expression of the atrophy transcription factor FoxO1. This review concludes that inflammatory pathways in muscle, in particular, NF-κB, potentially contribute to T2DM-mediated muscle atrophy. Further in-vivo and longitudinal human research is required to better understand the role of inflammation in T2DM-mediated atrophy and the anti-inflammatory effect of exercise training under these conditions. PMID:26859514

  4. Muscle atrophy in patients with Type 2 Diabetes Mellitus: roles of inflammatory pathways, physical activity and exercise.

    PubMed

    Perry, Ben D; Caldow, Marissa K; Brennan-Speranza, Tara C; Sbaraglia, Melissa; Jerums, George; Garnham, Andrew; Wong, Chiew; Levinger, Pazit; Asrar Ul Haq, Muhammad; Hare, David L; Price, S Russ; Levinger, Itamar

    2016-01-01

    Muscle atrophy is caused by an imbalance in contractile protein synthesis and degradation which can be triggered by various conditions including Type 2 Diabetes Mellitus (T2DM). Reduced muscle quality in patients with T2DM adversely affects muscle function, the capacity to perform activities of daily living, quality of life and ultimately may increase the risk of premature mortality. Systemic inflammation initiated by obesity and prolonged overnutrition not only contributes to insulin resistance typical of T2DM, but also promotes muscle atrophy via decreased muscle protein synthesis and increased ubiquitin-proteasome, lysosomal-proteasome and caspase 3- mediated protein degradation. Emerging evidence suggests that the inflammation-sensitive Nuclear Factor κ B (NF-κB) and Signal Transducer and Activator of Transcription 3 (STAT3) pathways may contribute to muscle atrophy in T2DM. In contrast, exercise appears to be an effective tool in promoting muscle hypertrophy, in part due to its effect on systemic and local (skeletal muscle) inflammation. The current review discusses the role inflammation plays in muscle atrophy in T2DM and the role of exercise training in minimising the effect of inflammatory markers on skeletal muscle. We also report original data from a cohort of obese patients with T2DM compared to age-matched controls and demonstrate that patients with T2DM have 60% higher skeletal muscle expression of the atrophy transcription factor FoxO1. This review concludes that inflammatory pathways in muscle, in particular, NF-κB, potentially contribute to T2DM-mediated muscle atrophy. Further in-vivo and longitudinal human research is required to better understand the role of inflammation in T2DM-mediated atrophy and the anti-inflammatory effect of exercise training under these conditions.

  5. 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

  6. 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

  7. 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

  8. Optic atrophy due to Curvularia lunata mucocoele.

    PubMed

    Smith, Tai; Goldschlager, Tony; Mott, Nigel; Robertson, Tom; Campbell, Scott

    2007-01-01

    The authors report on the case of a 57-year-old male who presented with poor vision of his right eye. He had right optic nerve atrophy secondary to neural compression by a mucocoele in the pituitary fossa. The patient underwent transphenoidal resection of the mucocoele. Microbiology revealed Curvularia lunata and Enterobacter aerogenes present in the specimen. He was treated with liposomal Amphotericin B and meropenem. Assessment of vision post-operatively demonstrated improvement in his visual acuity. On reviewing the published literature, this case was found to be the first in which Curvularia had caused optic neuropathy. There have been only five previously documented reports of Curvularia causing CNS infections. This case demonstrates the importance of obtaining a tissue diagnosis together with appropriate surgical and medical management in the treatment of invasive fungal disease.

  9. 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

  10. 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. PMID:2358820

  11. 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.

  12. White Matter Atrophy and Cognitive Dysfunctions in Neuromyelitis Optica

    PubMed Central

    Blanc, Frederic; Noblet, Vincent; Jung, Barbara; Rousseau, François; Renard, Felix; Bourre, Bertrand; Longato, Nadine; Cremel, Nadjette; Di Bitonto, Laure; Kleitz, Catherine; Collongues, Nicolas; Foucher, Jack; Kremer, Stephane; Armspach, Jean-Paul; de Seze, Jerome

    2012-01-01

    Neuromyelitis optica (NMO) is an inflammatory disease of central nervous system characterized by optic neuritis and longitudinally extensive acute transverse myelitis. NMO patients have cognitive dysfunctions but other clinical symptoms of brain origin are rare. In the present study, we aimed to investigate cognitive functions and brain volume in NMO. The study population consisted of 28 patients with NMO and 28 healthy control subjects matched for age, sex and educational level. We applied a French translation of the Brief Repeatable Battery (BRB-N) to the NMO patients. Using SIENAx for global brain volume (Grey Matter, GM; White Matter, WM; and whole brain) and VBM for focal brain volume (GM and WM), NMO patients and controls were compared. Voxel-level correlations between diminished brain concentration and cognitive performance for each tests were performed. Focal and global brain volume of NMO patients with and without cognitive impairment were also compared. Fifteen NMO patients (54%) had cognitive impairment with memory, executive function, attention and speed of information processing deficits. Global and focal brain atrophy of WM but not Grey Matter (GM) was found in the NMO patients group. The focal WM atrophy included the optic chiasm, pons, cerebellum, the corpus callosum and parts of the frontal, temporal and parietal lobes, including superior longitudinal fascicle. Visual memory, verbal memory, speed of information processing, short-term memory and executive functions were correlated to focal WM volumes. The comparison of patients with, to patients without cognitive impairment showed a clear decrease of global and focal WM, including brainstem, corticospinal tracts, corpus callosum but also superior and inferior longitudinal fascicles. Cognitive impairment in NMO patients is correlated to the decreased of global and focal WM volume of the brain. Further studies are needed to better understand the precise origin of cognitive impairment in NMO patients

  13. Growing up with bilateral hippocampal atrophy: from childhood to teenage.

    PubMed

    Bindschaedler, Claire; Peter-Favre, Claire; Maeder, Philippe; Hirsbrunner, Thérèse; Clarke, Stephanie

    2011-09-01

    The respective roles of the medial temporal lobe (MTL) structures in memory are controversial. Some authors put forward a modular account according to which episodic memory and recollection-based processes are crucially dependent on the hippocampal formation whereas semantic acquisition and familiarity-based processes rely on the adjacent parahippocampal gyri. Others defend a unitary view. We report the case of VJ, a boy with developmental amnesia of most likely perinatal onset diagnosed at the age of 8. Magnetic resonance imaging (MRI), including quantitative volumetric measurements of the hippocampal formation and of the entorhinal, perirhinal, and temporopolar cortices, showed severe, bilateral atrophy of the hippocampal formation, fornix and mammillary bodies; by contrast, the perirhinal cortex was within normal range and the entorhinal and temporopolar cortex remained within two standard deviations (SDs) from controls' mean. We examined the development of his semantic knowledge from childhood to teenage as well as his recognition and cued recall memory abilities. On tasks tapping semantic memory, VJ increased his raw scores across years at the same rate as children from large standardisation samples, except for one task; he achieved average performance, consistent with his socio-educational background. He performed within normal range on 74% of recognition tests and achieved average to above average scores on 42% of them despite very severe impairment on 82% of episodic recall tasks. Both faces and landscapes-scenes gave rise to above average scores when tested with coloured stimuli. Cued recall, although impaired, was largely superior to free recall. This case supports a modular account of the MTL with episodic, but not semantic memory depending on the hippocampal formation. Furthermore, the overall pattern of findings is consistent with evidence from both brain-damaged and neuroimaging studies indicating that recollection requires intact hippocampal

  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. PMID

  15. 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.

  16. 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

  17. Early cerebral volume reductions and their associations with reduced lupus disease activity in patients with newly-diagnosed systemic lupus erythematosus.

    PubMed

    Mak, Anselm; Ho, Roger Chun-Man; Tng, Han-Ying; Koh, Hui Li; Chong, Joanna Su Xian; Zhou, Juan

    2016-03-01

    We examined if cerebral volume reduction occurs very early during the course of systemic lupus erythematosus (SLE), and observed prospectively whether gray (GMV) and white matter volumes (WMV) of the brain would improve with lowered SLE disease activity. T1-weighted MRI brain images were obtained from 14 healthy controls (HC) and 14 newly-diagnosed SLE patients within 5 months of diagnosis (S1) and after achieving low disease activity (S2). Whole brain voxel-based morphometry was used to detect differences in the GMV and WMV between SLE patients and HC and those between SLE patients at S1 and S2. SLE patients were found to have lower GMV than HC in the middle cingulate cortex, middle frontal gyrus and right supplementary motor area, and lower WMV in the superior longitudinal fasciculus, cingulum cingulate gyrus and inferior fronto-occipital fasciculus at both S1 and S2. Whole-brain voxel-wise analysis revealed increased GMV chiefly in the prefrontal regions at S2 compared to S1 in SLE patients. The GMV increase in the left superior frontal gyrus was significantly associated with lowered SLE disease activity. In conclusion, GMV and WMV reduced very early in SLE patients. Reduction of SLE disease activity was accompanied by region-specific GMV improvement in the prefrontal regions.

  18. Early cerebral volume reductions and their associations with reduced lupus disease activity in patients with newly-diagnosed systemic lupus erythematosus

    PubMed Central

    Mak, Anselm; Ho, Roger Chun-Man; Tng, Han-Ying; Koh, Hui Li; Chong, Joanna Su Xian; Zhou, Juan

    2016-01-01

    We examined if cerebral volume reduction occurs very early during the course of systemic lupus erythematosus (SLE), and observed prospectively whether gray (GMV) and white matter volumes (WMV) of the brain would improve with lowered SLE disease activity. T1-weighted MRI brain images were obtained from 14 healthy controls (HC) and 14 newly-diagnosed SLE patients within 5 months of diagnosis (S1) and after achieving low disease activity (S2). Whole brain voxel-based morphometry was used to detect differences in the GMV and WMV between SLE patients and HC and those between SLE patients at S1 and S2. SLE patients were found to have lower GMV than HC in the middle cingulate cortex, middle frontal gyrus and right supplementary motor area, and lower WMV in the superior longitudinal fasciculus, cingulum cingulate gyrus and inferior fronto-occipital fasciculus at both S1 and S2. Whole-brain voxel-wise analysis revealed increased GMV chiefly in the prefrontal regions at S2 compared to S1 in SLE patients. The GMV increase in the left superior frontal gyrus was significantly associated with lowered SLE disease activity. In conclusion, GMV and WMV reduced very early in SLE patients. Reduction of SLE disease activity was accompanied by region-specific GMV improvement in the prefrontal regions. PMID:26928214

  19. Brain atrophy in multiple sclerosis: therapeutic, cognitive and clinical impact.

    PubMed

    Rojas, Juan Ignacio; Patrucco, Liliana; Miguez, Jimena; Cristiano, Edgardo

    2016-03-01

    Multiple sclerosis (MS) was always considered as a white matter inflammatory disease. Today, there is an important body of evidence that supports the hypothesis that gray matter involvement and the neurodegenerative mechanism are at least partially independent from inflammation. Gray matter atrophy develops faster than white matter atrophy, and predominates in the initial stages of the disease. The neurodegenerative mechanism creates permanent damage and correlates with physical and cognitive disability. In this review we describe the current available evidence regarding brain atrophy and its consequence in MS patients. PMID:27050854

  20. 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.

  1. 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.

  2. Acquired alopecia, mental retardation, short stature, microcephaly, and optic atrophy.

    PubMed Central

    Hennekam, R C; Renckens-Wennen, E G

    1990-01-01

    We report on a female patient who had acquired total alopecia, short stature, microcephaly, optic atrophy, severe myopia, and mental retardation. A survey of published reports failed to show an identical patient, despite various similar cases. Images PMID:2246773

  3. 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.

  4. 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.

  5. Muscle atrophy in chronic kidney disease results from abnormalities in insulin signaling.

    PubMed

    Price, S Russ; Gooch, Jennifer L; Donaldson, Sue K; Roberts-Wilson, Tiffany K

    2010-09-01

    Muscle atrophy is a significant consequence of chronic kidney disease that increases a patient's risk of mortality and decreases their quality of life. The loss of lean body mass results, in part, from an increase in the rate of muscle protein degradation. In this review, the proteolytic systems that are activated during chronic kidney disease and the key insulin signaling pathways that regulate the protein degradative processes are described. PMID:20797566

  6. 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.

  7. 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.

  8. Meibomian gland dysfunction: hyperkeratinization or atrophy?

    PubMed

    Jester, James V; Parfitt, Geraint J; Brown, Donald J

    2015-01-01

    Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease (EDED) and dysfunction is widely thought to mechanistically involve ductal hyperkeratinization, plugging and obstruction. This review re-evaluates the role of hyperkeratinization in MGD based on more recent findings from mouse models. In these studies, eyelids from normal young and old mice or mice exposed to desiccating stress were evaluated by immunofluorescent tomography and 3-dimensional reconstruction to evaluate gland volume, expression of hyperkeratinization markers and cell proliferation or stimulated Raman scattering (SRS) microscopy to assess lipid quality. Results indicate that aging mice show dropout of meibomian glands with loss of gland volume and a forward migration of the mucocutaneous junction anterior to the gland orifice; similar age-related changes that are detected in human subjects. Atrophic glands also showed evidence of epithelial plugging of the orifice without the presence of hyperkeratinization. Mice exposed to desiccating stress showed hyperproliferation of the meibomian gland and ductal dilation suggesting a marked increase in lipid synthesis. Lipid quality was also affected in EDED mice with an increase in the protein content of lipid within the duct of the gland. Overall, age-related changes in the mouse show similar structural and functional correlates with that observed in clinical MGD without evidence of hyperkeratinization suggesting that gland atrophy may be a major cause of EDED. The response of the meibomian gland to desiccating stress also suggest that environmental conditions may accelerate or potentiate age-related changes.

  9. Meibomian gland dysfunction: hyperkeratinization or atrophy?

    PubMed

    Jester, James V; Parfitt, Geraint J; Brown, Donald J

    2015-01-01

    Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease (EDED) and dysfunction is widely thought to mechanistically involve ductal hyperkeratinization, plugging and obstruction. This review re-evaluates the role of hyperkeratinization in MGD based on more recent findings from mouse models. In these studies, eyelids from normal young and old mice or mice exposed to desiccating stress were evaluated by immunofluorescent tomography and 3-dimensional reconstruction to evaluate gland volume, expression of hyperkeratinization markers and cell proliferation or stimulated Raman scattering (SRS) microscopy to assess lipid quality. Results indicate that aging mice show dropout of meibomian glands with loss of gland volume and a forward migration of the mucocutaneous junction anterior to the gland orifice; similar age-related changes that are detected in human subjects. Atrophic glands also showed evidence of epithelial plugging of the orifice without the presence of hyperkeratinization. Mice exposed to desiccating stress showed hyperproliferation of the meibomian gland and ductal dilation suggesting a marked increase in lipid synthesis. Lipid quality was also affected in EDED mice with an increase in the protein content of lipid within the duct of the gland. Overall, age-related changes in the mouse show similar structural and functional correlates with that observed in clinical MGD without evidence of hyperkeratinization suggesting that gland atrophy may be a major cause of EDED. The response of the meibomian gland to desiccating stress also suggest that environmental conditions may accelerate or potentiate age-related changes. PMID:26817690

  10. 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

  11. Progressive hemifacial atrophy (Parry-Romberg syndrome). Case report.

    PubMed

    Mazzeo, N; Fisher, J G; Mayer, M H; Mathieu, G P

    1995-01-01

    Progressive hemifacial atrophy (Parry-Romberg syndrome) is a slowly progressing facial atrophy of subcutaneous fat and the wasting of associated skin, cartilage, and bone. This disorder includes an active progressive phase (2 to 10 years) followed by a burning out of the atrophic process with subsequent stability. This article presents a review of the literature and a case report with unique dental involvement as a result of this disease process.

  12. Crossed cerebro-cerebellar atrophy with Dyke Davidoff Masson syndrome.

    PubMed

    Algahtani, Hussein A; Aldarmahi, Ahmed A; Al-Rabia, Mohammed W; Young, G Bryan

    2014-01-01

    Dyke Davidoff Masson syndrome (DDMS) refers to atrophy or hypoplasia of one cerebral hemisphere following a prior fetal or childhood insult. It has characteristics of clinical and radiological changes. These changes include hemiparesis, seizures, facial-asymmetry, and mental retardation. We present a 25-year-old man with crossed cerebrocerebellar atrophy and DDMS. His seizures were well controlled using a combination of antiepileptic drugs.

  13. Rapamycin delays salivary gland atrophy following ductal ligation.

    PubMed

    Bozorgi, S S; Proctor, G B; Carpenter, G H

    2014-03-27

    Salivary gland atrophy is a frequent consequence of head and neck cancer irradiation therapy but can potentially be regulated through the mammalian target of rapamycin (mTOR). Excretory duct ligation of the mouse submandibular gland provokes severe glandular atrophy causing activation of mTOR. This study aims to discover the effects of blocking mTOR signaling in ligation-induced atrophic salivary glands. Following 1 week of unilateral submandibular excretory duct ligation: gland weights were significantly reduced, 4E-BP1 and S6rp were activated, and tissue morphology revealed typical signs of atrophy. However, 3 days following ligation with rapamycin treatment, a selective mTOR inhibitor, gland weights were maintained, 4E-BP1 and S6rp phosphorylation was inhibited, and there were morphological signs of recovery from atrophy. However, following 5 and 7 days of ligation and rapamycin treatment, glands expressed active mTOR and showed signs of considerable atrophy. This evidence suggests that inhibition of mTOR by rapamycin delays ligation-induced atrophy of salivary glands.

  14. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice.

    PubMed

    Porporato, Paolo E; Filigheddu, Nicoletta; Reano, Simone; Ferrara, Michele; Angelino, Elia; Gnocchi, Viola F; Prodam, Flavia; Ronchi, Giulia; Fagoonee, Sharmila; Fornaro, Michele; Chianale, Federica; Baldanzi, Gianluca; Surico, Nicola; Sinigaglia, Fabiola; Perroteau, Isabelle; Smith, Roy G; Sun, Yuxiang; Geuna, Stefano; Graziani, Andrea

    2013-02-01

    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. Ghrelin is a peptide hormone that stimulates growth hormone (GH) release and positive energy balance through binding to the receptor GHSR-1a. Only acylated ghrelin (AG), but not the unacylated form (UnAG), can bind GHSR-1a; however, UnAG and AG share several GHSR-1a-independent biological activities. Here we investigated whether UnAG and AG could protect against skeletal muscle atrophy in a GHSR-1a-independent manner. We found that both AG and UnAG inhibited dexamethasone-induced skeletal muscle atrophy and atrogene expression through PI3Kβ-, mTORC2-, and p38-mediated pathways in myotubes. Upregulation of circulating UnAG in mice impaired skeletal muscle atrophy induced by either fasting or denervation without stimulating muscle hypertrophy and GHSR-1a-mediated activation of the GH/IGF-1 axis. In Ghsr-deficient mice, both AG and UnAG induced phosphorylation of Akt in skeletal muscle and impaired fasting-induced atrophy. These results demonstrate that AG and UnAG act on a common, unidentified receptor to block skeletal muscle atrophy in a GH-independent manner.

  15. 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

  16. Type 3 secretion system effector genotype and secretion phenotype of longitudinally collected Pseudomonas aeruginosa isolates from young children diagnosed with cystic fibrosis following newborn screening.

    PubMed

    Hu, H; Harmer, C; Anuj, S; Wainwright, C E; Manos, J; Cheney, J; Harbour, C; Zablotska, I; Turnbull, L; Whitchurch, C B; Grimwood, K; Rose, B

    2013-03-01

    Studies of the type 3 secretion system (T3SS) in Pseudomonas aeruginosa isolates from chronically infected older children and adults with cystic fibrosis (CF) show a predominantly exoS+/exoU- (exoS+) genotype and loss of T3SS effector secretion over time. Relatively little is known about the role of the T3SS in the pathogenesis of early P. aeruginosa infection in the CF airway. In this longitudinal study, 168 P. aeruginosa isolates from 58 children diagnosed with CF following newborn screening and 47 isolates from homes of families with or without children with CF were genotyped by pulsed-field gel electrophoresis (PFGE) and T3SS genotype and phenotype determined using multiplex PCR and western blotting. Associations were sought between T3SS data and clinical variables and comparisons made between T3SS data of clinical and environmental PFGE genotypes. Seventy-seven of the 92 clinical strains were exoS+ (71% secretors (ExoS+)) and 15 were exoU+ (93% secretors (ExoU+)). Initial exoS+ strains were five times more likely to secrete ExoS than subsequent exoS+ strains at first isolation. The proportion of ExoS+ strains declined with increasing age at acquisition. No associations were found between T3SS characteristics and gender, site of isolation, exacerbation, a persistent strain or pulmonary outcomes. Fourteen of the 23 environmental strains were exoS+ (79% ExoS+) and nine were exoU+ (33% ExoU+). The exoU+ environmental strains were significantly less likely to secrete ExoU than clinical strains. This study provides new insight into the T3SS characteristics of P. aeruginosa isolated from the CF airway early in life. PMID:22329595

  17. How Is Cystic Fibrosis Diagnosed?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Cystic Fibrosis Diagnosed? Doctors diagnose cystic fibrosis (CF) based on ... to see whether the baby has CF. Cystic Fibrosis Carrier Testing People who have one normal CFTR ...

  18. How Is Muscular Dystrophy Diagnosed?

    MedlinePlus

    ... Information Clinical Trials Resources and Publications How is muscular dystrophy diagnosed? Skip sharing on social media links Share this: Page Content The first step in diagnosing muscular dystrophy (MD) is a visit with a health care ...

  19. How Is Pulmonary Hypertension Diagnosed?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Pulmonary Hypertension Diagnosed? Your doctor will diagnose pulmonary hypertension (PH) ... To Look for the Underlying Cause of Pulmonary Hypertension PH has many causes, so many tests may ...

  20. [Posterior cortical atrophy--a new dementia syndrome or a form of Alzheimer's disease?].

    PubMed

    Pantel, J; Schröder, J

    1996-12-01

    Posterior Cortical Atrophy (PCA) is a neurodegenerative disorder initially dominated by disturbances in higher visual functions including object agnosia, prosopagnosia, alexia, environmental agnosia and Balint's syndrome. Language, memory, insight, and judgement remain relatively preserved until late in the course. A characteristic neuroradiological finding consists of focal bilateral parieto-occipital atrophy demonstrated on MRI and CT. It was speculated that the possible underlying pathologic condition could be an atypical clinical variant of Alzheimer's disease, a lobar atrophy analogous to Pick's disease, a variant of Creutzfeldt-Jakob disease or some previously unrecognized entity. The prognostic question whether the visual agnostic symptoms are only a precursor of generalized dementia remained unsolved. The neuropsychological symptoms in these patients indicate that the occipitoparietal cortex is bilaterally affected which is in contrast to the parietotemporal distribution of lesions in Alzheimer's disease and the frontotemporal type of distribution in Pick's disease. The aim of this study was to review and analyze all cases of posterior cortical atrophy which have been reported in the literature. Up to now 58 cases of posterior cortical atrophy have been described. The first report of such a patient was given by A. Pick in 1902. The results of our analysis show that posterior cortical atrophy is mainly a presenile disorder which in most cases heralds the development of generalized dementia. The histopathological results suggest that the combination of clinical findings referred to as PCA can result from strikingly different pathological entities. However, most cases of PCA which were investigated postmortem revealed the histopathological lesion type of Alzheimer's disease. This suggests that PCA is rather a subgroup of Alzheimer's disease than an independent disease. This conclusion has some implication for the nosological classification of other localized

  1. Progressive brain atrophy in Schinzel-Giedion syndrome with a SETBP1 mutation.

    PubMed

    Takeuchi, Akihito; Okamoto, Nobuhiko; Fujinaga, Shoko; Morita, Hirosuke; Shimizu, Junya; Akiyama, Tomoyuki; Ninomiya, Shinsuke; Takanashi, Jun-ichi; Kubo, Toshihide

    2015-08-01

    Schinzel-Giedion syndrome is a rare congenital malformation syndrome. Recently, SETBP1 was identified as the causative gene. Herein, we present a Japanese boy with Schinzel-Giedion syndrome resulting from a novel mutation in SETBP1 in order to establish the clinical features and serial MRI findings associated with the syndrome. On the third day of life, the boy was referred to our hospital because of facial abnormalities and feeding difficulty. Midfacial retraction, frontal bossing, deep groove under the eyes, upturned nose, low-set ears, bilateral cryptorchidism, and generalized hypertrichosis were identified on admission. At the age of 7 months, epileptic spasms in series occurred. Based on characteristic facial and skeletal abnormalities and severe developmental delay, we clinically diagnosed him with Schinzel-Giedion syndrome. Direct sequencing of the SETBP1 gene revealed a heterozygous mutation (p.Ile871Ser) in exon 4. Although neither cardiac defect nor choanal stenosis were present in our case, the phenotype of our case was nearly identical to those of previously reported cases confirmed by genetic analysis. Serial MRI from the age of 1 month-3 years revealed progressive brain atrophy, especially in the white matter and basal ganglia. However, myelination was age-appropriate and no obvious abnormal signals in the white matter were seen. Diffusion weighted imaging revealed no abnormal findings. Accumulation of MRI data including diffusion weighted imaging from Schinzel-Giedion syndrome cases is needed to understand the mechanism underlying progressive brain atrophy in this syndrome. PMID:26096993

  2. Dental implants for severely atrophied jaws due to ectodermal dysplasia.

    PubMed

    Balaji, Preetha; Balaji, S M; Ugandhar, Prashanthi

    2015-01-01

    The aim was to present the successful esthetical and functional rehabilitation of partial anodontia in a case of severe ectodermal dysplasia with complete atrophy of the jaws. A 17-year-old male with Class III malocclusion with partial anodontia sought dental implant treatment. His expectation was that of Class I occlusion. The challenge in the case was to match the expectation, reality, and the clinical possibilities. Ridge augmentation was performed with a combination of rib graft and recombinant human bone morphogenetic protein-2. Simultaneously, 6 implants (Nobel Biocare™ - Tapered Groovy) were placed in maxillary arch and 10 in the mandible. Simultaneous placement ensured faster and better osseointegration though a mild compromise of the primary stability was observed initially. After adequate healing, Customized Zirconia Procera™ system was used to build the framework. Zirconia crown was cemented to the framework. Radiological and clinical evidence of osseointegration was observed in all 16 dental implants. Successful conversion of Class III to Class I occlusion was achieved with the combination of preprosthetic alveolar ridge augmentation, Procera™ Implant Bridge system. Abnormal angulations and or placement of dental implants would result in failure of the implant. Hence conversion of Class III to Class I occlusion needs complete and complex treatment planning so that the entire masticatory apparatus is sufficiently remodeled. Planning should consider the resultant vectors that would otherwise result in failure of framework or compromise the secondary stability of the dental implant during function. A successful case of rehabilitation of complex partial anodontia is presented. PMID:26096119

  3. 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.

  4. Tumor-induced thymic atrophy: alteration in interferons and Jak/Stats signaling pathways.

    PubMed

    Carrio, Roberto; Torroella-Kouri, Marta; Iragavarapu-Charyulu, Vijaya; Lopez, Diana M

    2011-02-01

    The thymus is the major site of T cell differentiation and a key organ of the immune system. Thym atrophy has been observed in several model systems including aging, and tumor development. Previous results from our laboratory have reported that the thymic atrophy seen in mammary tumor bearers is associated with a severe depletion of CD4+CD8+ double positive immature cells and changes in the levels of cytokines expressed in the thymus microenvironment. Cytokines regulate numerous aspects of hematopoiesis via activation of the Jak/Stat pathways. In the present study we have used our mammary tumor model to investigate whether changes in the levels of cytokines in the thymus could affect the normal expression of the aforementioned pathways. RNA and protein analysis revealed an overexpression of the different members of interferons, a downregulation of most of the Jak/Stat pathways, and an increased expression of several suppressors of cytokine signaling (SOSC) in the thymuses of tumor bearers. Together, our data suggest that the impaired Jak/Stat signaling pathways observed in the whole thymus of tumor-bearing mice could be contributing to the abnormal T cell development and apoptosis observed during the tumor-induced thymic atrophy. PMID:21165556

  5. Spinal muscular atrophy with respiratory distress syndrome (SMARD1): Case report and review of literature.

    PubMed

    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

  6. 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

  7. Robot-assisted removal of a lymphocyst causing severe neuralgic pain and adductor atrophy.

    PubMed

    Cazzaniga, Giorgio; Borgfeldt, Christer; Wallengren, Nils-Olof; Persson, Jan

    2011-12-01

    Following a robot-assisted radical hysterectomy and pelvic lymphadenectomy for early-stage cervical cancer, a 53-year-old woman was diagnosed with a 50-mm right-sided pelvic lymphocyst by the use of vaginal ultrasonography. She gradually developed intermittent increasingly severe neuralgic pain mimicking a meralgia paresthetica. A neurolysis was proposed by the neurosurgeons. Awaiting this intervention, a pelvic MRI revealed a partial atrophy of the ipsilateral adductor muscles and a probable entrapment of the obturator nerve by the lymphocyst as an alternative cause of the pain. Using a four-arm da Vinci-S-HD robot the lymphocyst, located deep in the right obturator fossa and surrounding the obturator nerve, was completely removed, sparing the partially atrophic obturator nerve. No bleeding occurred. The surgery time was 95 min. At 10 months' follow-up the patient was relieved of her pain with no signs of a new lymphocyst. PMID:27628122

  8. 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…

  9. 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.

  10. GEMINs: potential therapeutic targets for spinal muscular atrophy?

    PubMed Central

    Borg, Rebecca; Cauchi, Ruben J.

    2014-01-01

    The motor neuron degenerative disease spinal muscular atrophy (SMA) remains one of the most frequently inherited causes of infant mortality. Afflicted patients loose the survival motor neuron 1 (SMN1) gene but retain one or more copies of SMN2, a homolog that is incorrectly spliced. Primary treatment strategies for SMA aim at boosting SMN protein levels, which are insufficient in patients. SMN is known to partner with a set of diverse proteins collectively known as GEMINs to form a macromolecular complex. The SMN-GEMINs complex is indispensible for chaperoning the assembly of small nuclear ribonucleoproteins (snRNPs), which are key for pre-mRNA splicing. Pharmaceutics that alleviate the neuromuscular phenotype by restoring the fundamental function of SMN without augmenting its levels are also crucial in the development of an effective treatment. Their use as an adjunct therapy is predicted to enhance benefit to patients. Inspired by the surprising discovery revealing a premier role for GEMINs in snRNP biogenesis together with in vivo studies documenting their requirement for the correct function of the motor system, this review speculates on whether GEMINs constitute valid targets for SMA therapeutic development. PMID:25360080

  11. Reversal of stress-induced dendritic atrophy in the prefrontal cortex by intracranial self-stimulation.

    PubMed

    Ramkumar, K; Srikumar, B N; Venkatasubramanian, D; Siva, R; Shankaranarayana Rao, B S; Raju, T R

    2012-05-01

    The mammalian prefrontal cortex (PFC) has been implicated in a variety of motivational and emotional processes underlying working memory, attention and decision making. The PFC receives dopaminergic projections from the ventral tegmental area (VTA) and contains high density of D1 and D2 receptors and these projections are important in higher integrative cortical functions. The neurons of the PFC have been shown to undergo atrophy in response to stress. In an earlier study, we demonstrated that the chronic stress-induced atrophy of hippocampal neurons and behavioral impairment in the T-maze task were reversed by the activation of dopaminergic pathway by intracranial self-stimulation (ICSS) of the VTA. The stress-induced decrease in hippocampal dopamine (DA) levels was also restored by ICSS. Whether the reversal of stress-induced behavioral deficits by ICSS involves changes in the morphology of PFC neurons is unknown and the current study addresses this issue. Male Wistar rats underwent 21 days of restraint stress followed by ICSS for 10 days. The dendritic morphology of the PFC neurons was studied in Golgi-impregnated sections. Stress produced atrophy of the layer II/III and V PFC pyramidal neurons and ICSS to naïve rats significantly increased the dendritic arborization of these neurons compared to control. Interestingly, ICSS of stressed rats resulted in the reversal of the dendritic atrophy. Further, these structural changes were associated with a restored tissue levels of DA, norepinephrine and serotonin in the PFC. These results indicate that the behavioral restoration in stressed rats could involve changes in the plasticity of the PFC neurons and these results further our understanding of the role of dopaminergic neurotransmitter system in the amelioration of stress-induced deficits.

  12. 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. PMID:17205291

  13. CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder.

    PubMed

    Wortmann, Saskia B; Ziętkiewicz, Szymon; Kousi, Maria; Szklarczyk, Radek; Haack, Tobias B; Gersting, Søren W; Muntau, Ania C; Rakovic, Aleksandar; Renkema, G Herma; Rodenburg, Richard J; Strom, Tim M; Meitinger, Thomas; Rubio-Gozalbo, M Estela; Chrusciel, Elzbieta; Distelmaier, Felix; Golzio, Christelle; Jansen, Joop H; van Karnebeek, Clara; Lillquist, Yolanda; Lücke, Thomas; Õunap, Katrin; Zordania, Riina; Yaplito-Lee, Joy; van Bokhoven, Hans; Spelbrink, Johannes N; Vaz, Frédéric M; Pras-Raves, Mia; Ploski, Rafal; Pronicka, Ewa; Klein, Christine; Willemsen, Michel A A P; de Brouwer, Arjan P M; Prokisch, Holger; Katsanis, Nicholas; Wevers, Ron A

    2015-02-01

    We studied a group of individuals with elevated urinary excretion of 3-methylglutaconic acid, neutropenia that can develop into leukemia, a neurological phenotype ranging from nonprogressive intellectual disability to a prenatal encephalopathy with progressive brain atrophy, movement disorder, cataracts, and early death. Exome sequencing of two unrelated individuals and subsequent Sanger sequencing of 16 individuals with an overlapping phenotype identified a total of 14 rare, predicted deleterious alleles in CLPB in 14 individuals from 9 unrelated families. CLPB encodes caseinolytic peptidase B homolog ClpB, a member of the AAA+ protein family. To evaluate the relevance of CLPB in the pathogenesis of this syndrome, we developed a zebrafish model and an in vitro assay to measure ATPase activity. Suppression of clpb in zebrafish embryos induced a central nervous system phenotype that was consistent with cerebellar and cerebral atrophy that could be rescued by wild-type, but not mutant, human CLPB mRNA. Consistent with these data, the loss-of-function effect of one of the identified variants (c.1222A>G [p.Arg408Gly]) was supported further by in vitro evidence with the mutant peptides abolishing ATPase function. Additionally, we show that CLPB interacts biochemically with ATP2A2, known to be involved in apoptotic processes in severe congenital neutropenia (SCN) 3 (Kostmann disease [caused by HAX1 mutations]). Taken together, mutations in CLPB define a syndrome with intellectual disability, congenital neutropenia, progressive brain atrophy, movement disorder, cataracts, and 3-methylglutaconic aciduria.

  14. 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

  15. CLPB Mutations Cause 3-Methylglutaconic Aciduria, Progressive Brain Atrophy, Intellectual Disability, Congenital Neutropenia, Cataracts, Movement Disorder

    PubMed Central

    Wortmann, Saskia B.; Ziętkiewicz, Szymon; Kousi, Maria; Szklarczyk, Radek; Haack, Tobias B.; Gersting, Søren W.; Muntau, Ania C.; Rakovic, Aleksandar; Renkema, G. Herma; Rodenburg, Richard J.; Strom, Tim M.; Meitinger, Thomas; Rubio-Gozalbo, M. Estela; Chrusciel, Elzbieta; Distelmaier, Felix; Golzio, Christelle; Jansen, Joop H.; van Karnebeek, Clara; Lillquist, Yolanda; Lücke, Thomas; Õunap, Katrin; Zordania, Riina; Yaplito-Lee, Joy; van Bokhoven, Hans; Spelbrink, Johannes N.; Vaz, Frédéric M.; Pras-Raves, Mia; Ploski, Rafal; Pronicka, Ewa; Klein, Christine; Willemsen, Michel A.A.P.; de Brouwer, Arjan P.M.; Prokisch, Holger; Katsanis, Nicholas; Wevers, Ron A.

    2015-01-01

    We studied a group of individuals with elevated urinary excretion of 3-methylglutaconic acid, neutropenia that can develop into leukemia, a neurological phenotype ranging from nonprogressive intellectual disability to a prenatal encephalopathy with progressive brain atrophy, movement disorder, cataracts, and early death. Exome sequencing of two unrelated individuals and subsequent Sanger sequencing of 16 individuals with an overlapping phenotype identified a total of 14 rare, predicted deleterious alleles in CLPB in 14 individuals from 9 unrelated families. CLPB encodes caseinolytic peptidase B homolog ClpB, a member of the AAA+ protein family. To evaluate the relevance of CLPB in the pathogenesis of this syndrome, we developed a zebrafish model and an in vitro assay to measure ATPase activity. Suppression of clpb in zebrafish embryos induced a central nervous system phenotype that was consistent with cerebellar and cerebral atrophy that could be rescued by wild-type, but not mutant, human CLPB mRNA. Consistent with these data, the loss-of-function effect of one of the identified variants (c.1222A>G [p.Arg408Gly]) was supported further by in vitro evidence with the mutant peptides abolishing ATPase function. Additionally, we show that CLPB interacts biochemically with ATP2A2, known to be involved in apoptotic processes in severe congenital neutropenia (SCN) 3 (Kostmann disease [caused by HAX1 mutations]). Taken together, mutations in CLPB define a syndrome with intellectual disability, congenital neutropenia, progressive brain atrophy, movement disorder, cataracts, and 3-methylglutaconic aciduria. PMID:25597510

  16. 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.

  17. Quantitative MR evaluation of atrophy, as well as perfusion and diffusion alterations within hippocampi in patients with Alzheimer’s disease and mild cognitive impairment

    PubMed Central

    Zimny, Anna; Bladowska, Joanna; Neska, Małgorzata; Petryszyn, Kamila; Guziński, Maciej; Szewczyk, Paweł; Leszek, Jerzy; Sąsiadek, Marek

    2013-01-01

    Background The aim of this study was to evaluate atrophy rates, perfusion, and diffusion disturbances within the hippocampus, which is the site of characteristic changes in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Material/Methods Thirty patients with AD (mean age 71.2 yrs) – 34 with MCI (mean age 67.7 yrs) and 20 healthy controls (mean age 68.1 yrs) – underwent structural MR examination followed by perfusion and diffusion-weighted imaging on a 1.5 T scanner. Visual rating of hippocampal atrophy, planimetric measurements of hippocampal formation (HF) and perihippocampal fluid spaces (PFSs), and values of relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) were assessed. The results were correlated with the MMSE scores. Results In AD we found decreased size of HF and increased diameters of PFSs and ADC values, compared to MCI and control group. Compared to normal controls, the MCI group showed decreased HF size and increased diameters of only medial PFS. There were no differences in rCBV values among all the subject groups. Planimetric measurements of hippocampal atrophy showed the highest accuracy in diagnosing AD and MCI. In all patients, the increased rates of hippocampal atrophy correlated with the increased ADC values. In MCI, MMSE scores correlated with the HF size and ADC values. Conclusions In AD and MCI, hippocampal atrophy is associated with decreased tissue integrity without coexisting perfusion disturbances. Of all evaluated hippocampal measurements, atrophy rates seem to be the most useful parameters in detecting changes among AD, MCI, and control subjects. PMID:23377218

  18. 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.

  19. 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

  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. Milder progressive cerebellar atrophy caused by biallelic SEPSECS mutations.

    PubMed

    Iwama, Kazuhiro; Sasaki, Masayuki; Hirabayashi, Shinichi; Ohba, Chihiro; Iwabuchi, Emi; Miyatake, Satoko; Nakashima, Mitsuko; Miyake, Noriko; Ito, Shuichi; Saitsu, Hirotomo; Matsumoto, Naomichi

    2016-06-01

    Cerebellar atrophy is recognized in various types of childhood neurological disorders with clinical and genetic heterogeneity. Genetic analyses such as whole exome sequencing are useful for elucidating the genetic basis of these conditions. Pathological recessive mutations in Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase (SEPSECS) have been reported in a total of 11 patients with pontocerebellar hypoplasia type 2, progressive cerebellocerebral atrophy or progressive encephalopathy, yet detailed clinical features are limited to only four patients. We identified two new families with progressive cerebellar atrophy, and by whole exome sequencing detected biallelic SEPSECS mutations: c.356A>G (p.Asn119Ser) and c.77delG (p.Arg26Profs*42) in family 1, and c.356A>G (p.Asn119Ser) and c.467G>A (p.Arg156Gln) in family 2. Their development was slightly delayed regardless of normal brain magnetic resonance imaging (MRI) in infancy. The progression of clinical symptoms in these families is evidently slower than in previously reported cases, and the cerebellar atrophy milder by brain MRI, indicating that SEPSECS mutations are also involved in milder late-onset cerebellar atrophy. PMID:26888482

  2. 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

  3. DNA methylation in the NCAPH2/LMF2 promoter region is associated with hippocampal atrophy in Alzheimer's disease and amnesic mild cognitive impairment patients.

    PubMed

    Shinagawa, Shunichiro; Kobayashi, Nobuyuki; Nagata, Tomoyuki; Kusaka, Akira; Yamada, Hisashi; Kondo, Kazuhiro; Nakayama, Kazuhiko

    2016-08-26

    Several studies have noted an effect of DNA methylation on the pathogenesis of Alzheimer's disease (AD). We have already reported that DNA methylation levels in the NCAPH2/LMF2 promoter region can be a useful biomarker for the diagnosis of AD and amnesic mild cognitive impairment (aMCI). However, there is still uncertainty about the mechanism by which NCAPH2/LMF2 methylation affects the pathogenesis of AD and aMCI. In this study, we investigated relationships between NCAPH2/LMF2 methylation and other factors. AD (n=30) and aMCI (n=28) subjects were included in this study. NCAPH2/LMF2 methylation levels were measured by pyrosequencing. Correlations between methylation levels and other factors including age at onset, sex, duration of disease, education, mini-mental state examination (MMSE) and frontal assessment battery (FAB) scores, APOE genotype, degree of hippocampal atrophy, and total brain atrophy were measured. Degrees of hippocampal atrophy and total brain atrophy were measured by VSRAD (Voxel-Based Specific Regional Analysis System for Alzheimer's Disease). Regression analysis revealed that only hippocampal atrophy according to VSRAD is a significant dependent variable correlated with NCAPH2/LMF2 methylation levels. Our results suggest that DNA methylation in the NCAPH2/LMF2 promoter region is associated with hippocampal atrophy through apoptosis. PMID:27356276

  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. Can endurance exercise preconditioning prevention disuse muscle atrophy?

    PubMed Central

    Wiggs, Michael P.

    2015-01-01

    Emerging evidence suggests that exercise training can provide a level of protection against disuse muscle atrophy. Endurance exercise training imposes oxidative, metabolic, and heat stress on skeletal muscle which activates a variety of cellular signaling pathways that ultimately leads to the increased expression of proteins that have been demonstrated to protect muscle from inactivity –induced atrophy. This review will highlight the effect of exercise-induced oxidative stress on endogenous enzymatic antioxidant capacity (i.e., superoxide dismutase, glutathione peroxidase, and catalase), the role of oxidative and metabolic stress on PGC1-α, and finally highlight the effect heat stress and HSP70 induction. Finally, this review will discuss the supporting scientific evidence that these proteins can attenuate muscle atrophy through exercise preconditioning. PMID:25814955

  6. Regional flux analysis of longitudinal atrophy in Alzheimer's disease.

    PubMed

    Lorenzi, Marco; Ayache, Nicholas; Xavier, Pennec

    2012-01-01

    The longitudinal analysis of the brain morphology in Alzheimer's disease(AD) is fundamental for understanding and quantifying the dynamics of the pathology. This study provides a new measure of the brain longitudinal changes based on the Helmholtz decomposition of deformation fields. We used the scalar pressure map associated to the irrotational component in order to identify a consistent group-wise set of areas of maximal volume change. The atrophy was then quantified in these areas for each subject by the probabilistic integration of the flux of the longitudinal deformations across the boundaries. The presented framework unifies voxel-based and regional approaches, and robustly describes the longitudinal atrophy at group level as a spatial process governed by consistently defined regions. Our experiments showed that the resulting regional flux analysis is able to detect the differential atrophy patterns across populations, and leads to precise and statistically powered quantifications of the longitudinal changes in AD, even in mild/premorbid cases.

  7. Focal brain atrophy in gastric bypass patients with cognitive complaints.

    PubMed

    Graff-Radford, Jonathan; Whitwell, Jennifer L; Trenerry, Max R; Ahlskog, J Eric; Jensen, Michael D; Jack, Clifford R; Josephs, Keith A

    2011-12-01

    Recently, we have identified a series of patients presenting with cognitive complaints after gastric bypass, without any identifiable etiology. We aimed to determine if focal brain atrophy could account for the complaints. A retrospective case series was performed to identify patients with cognitive complaints following gastric bypass who had a volumetric MRI. Voxel-based morphometry was used to assess patterns of grey matter loss in all 10 patients identified, compared to 10 age and gender-matched controls. All patients had undergone Roux-en-Y gastric bypass surgery at a median age of 54 (range: 46-64). Cognitive complaints developed at a median age of 57 (52-69). Formal neuropsychometric testing revealed only minor deficits. No nutritional abnormalities were identified. Voxel-based morphometry demonstrated focal thalamic atrophy in the gastric bypass patients when compared to controls. Patients with cognitive complaints after gastric bypass surgery may have focal thalamic brain atrophy that could result in cognitive impairment.

  8. Brain atrophy in chronic alcoholic patients: a quantitative pathological study.

    PubMed Central

    Harper, C; Kril, J

    1985-01-01

    There are essentially no objective neuropathological data on brain atrophy in chronic alcoholic patients despite numerous neuroradiological studies which show a high incidence of shrinkage or atrophy. Therefore measurements were made of the intracranial volume (ICV) and brain volume (BV) in a necropsy study of 25 chronic alcoholic patients and 44 controls. The pericerebral space (PICS) was calculated according to the formula (formula; see text) The PICS will increase in patients with brain atrophy since the ICV remains constant throughout life. The mean PICS value was 8.3% in controls, 11.3% in the alcoholic group, 14.7% in alcoholics with superimposed Wernicke's encephalopathy (thiamine deficiency) and 16.2% in those alcoholics with associated liver disease. Thus there was a statistically significant loss of brain tissue in chronic alcoholic patients which appeared to be more severe in those with associated nutritional vitamin deficiencies or alcoholic liver disease. Images PMID:3981189

  9. Correlations Among Endoscopic, Histologic and Serologic Diagnoses for the Assessment of Atrophic Gastritis

    PubMed Central

    Lee, Ju Yup; Kim, Nayoung; Lee, Hye Seung; Oh, Jane C.; Kwon, Yong Hwan; Choi, Yoon Jin; Yoon, Ki Chul; Hwang, Jae Jin; Lee, Hyun Joo; Lee, AeRa; Jeong, Yeonsang; Jo, Hyun Jin; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Lee, Dong Ho

    2014-01-01

    Background: Atrophic gastritis is a precancerous condition, which can be diagnosed by several methods. However, there is no consensus for the standard method. The aim of this study was to evaluate the correlations among endoscopic, histologic, and serologic findings for the diagnosis of atrophic gastritis. Methods: From March 2003 to August 2013, a total of 2,558 subjects were enrolled. Endoscopic atrophic gastritis was graded by Kimura-Takemoto classification and histological atrophic gastritis was assessed by updated Sydney system. Serological assessment of atrophic gastritis was based on serum pepsinogen test. Results: The serum pepsinogen I/II ratio showed a significant decreasing nature when the extent of atrophy increased (R2=0.837, P<0.001) and the cut-off value for distinguishing between presence and absence of endoscopic atrophic gastritis was 3.2. The serum pepsinogen I and pepsinogen I/II ratio were significantly lower when the histological atrophic gastritis progressed and the cut-off value was 3.0 for a diagnosis of histological atrophic gastritis. A significant correlation between endoscopic and histological atrophic gastritis was noted and the sensitivity and specificity of endoscopic diagnosis were 65.9% and 58.0% for antrum, 71.3% and 53.7% for corpus, respectively. Conclusions: The endoscopic, histological, and serological atrophic gastritis showed relatively good correlations. However, as these three methods have a limitation, a multifactorial assessment might be needed to ameliorate the diagnostic accuracy of atrophic gastritis. PMID:25337572

  10. 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.

  11. 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.

  12. Late onset GM2 gangliosidosis mimicking spinal muscular atrophy.

    PubMed

    Jamrozik, Z; Lugowska, A; Gołębiowski, M; Królicki, L; Mączewska, J; Kuźma-Kozakiewicz, M

    2013-09-25

    A case of late onset GM2 gangliosidodis with spinal muscular atrophy phenotype followed by cerebellar and extrapyramidal symptoms is presented. Genetic analysis revealed compound heterozygous mutation in exon 10 of the HEXA gene. Patient has normal intelligence and emotional reactivity. Neuroimaging tests of the brain showed only cerebellar atrophy consistent with MR spectroscopy (MRS) abnormalities. (18)F-fluorodeoxyglucose positron emission tomography (18)F-FDG PET/CT of the brain revealed glucose hypometabolism in cerebellum and in temporal and occipital lobes bilaterally. PMID:23820084

  13. Distal myopathy with rimmed vacuoles and cerebellar atrophy.

    PubMed

    Merkli, Hajnalka; Pál, Endre; Gáti, István; Czopf, József

    2006-01-01

    Distal myopathies constitute a clinically and pathologically heterogeneous group of genetically determined neuromuscular disorders, where the distal muscles of the upper or lower limbs are affected. The disease of a 41-year-old male patient started with gait disturbances, when he was 25. The progression was slow, but after 16 years he became seriously disabled. Neurological examination showed moderate to severe weakness in distal muscles of all extremities, marked cerebellar sign and steppage gait. Muscle biopsy resulted in myopathic changes with rimmed vacuoles. Brain MRI scan showed cerebellar atrophy. This case demonstrates a rare association of distal myopathy and cerebellar atrophy.

  14. [A case of cerebral gigantism with cerebellar atrophy].

    PubMed

    Kitazawa, K; Ikeda, M; Tsukagoshi, H

    1990-05-01

    A 37-year-old housewife, who had physical characteristics of cerebral gigantism, such as the tall stature, acromegaly, macrocephalia, high arched palate and antimongoloid slant, developed cerebellar ataxia and dysarthria. Her mother, uncle and grandmother were also reported to have slowly progressive gait disturbance. Her mother was also tall. Endocrinological studies failed to show any definite abnormality. CT and MRI revealed remarkable cerebellar atrophy. Though cerebral gigantism is often associated with clumsiness and incoordination, the etiology of the ataxia is poorly understood. This case indicates that the ataxia in cerebral gigantism may be, at least partly, caused by cerebellar atrophy. PMID:2401112

  15. 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.

  16. 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 ...

  17. The ICD diagnoses of fetishism and sadomasochism.

    PubMed

    Reiersøl, Odd; Skeid, Svein

    2006-01-01

    In this article we discuss psychiatric diagnoses of sexual deviation as they appear in the International Classification of Diseases (ICD-10), the internationally accepted classification and diagnostic system of the World Health Organization (WHO). Namely, we discuss the background of three diagnostic categories: Fetishism (F65.0), Fetishistic Transvestism (F65.1), and Sadomasochism (F65.5). Pertinent background issues regarding the above categories are followed by a critique of the usefulness of diagnosing these phenomena today. Specifically, we argue that Fetishism, Fetishistic Transvestism, and Sadomasochism, also labeled Paraphilia or perversion, should not be considered illnesses. Finally, we present the efforts of an initiative known as ReviseF65, which was established in 1997, to abolish these diagnoses. PMID:16803767

  18. Posterior Cortical Atrophy Presenting with Superior Arcuate Field Defect

    PubMed Central

    Wan, Sue Ling; Bukowska, Danuta M.; Ford, Stephen; Chen, Fred K.

    2015-01-01

    An 80-year-old female with reading difficulty presented with progressive arcuate field defect despite low intraocular pressure. Over a 5-year period, the field defect evolved into an incongruous homonymous hemianopia and the repeated neuroimaging revealed progressive posterior cortical atrophy. Further neuropsychiatric assessment demonstrated symptoms and signs consistent with Benson's syndrome. PMID:26417467

  19. 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.

  20. Clinical features, molecular genetics, and pathophysiology of dominant optic atrophy.

    PubMed

    Votruba, M; Moore, A T; Bhattacharya, S S

    1998-10-01

    Inherited optic neuropathies are a significant cause of childhood and adult blindness and dominant optic atrophy (DOA) is the most common form of autosomally inherited (non-glaucomatous) optic neuropathy. Patients with DOA present with an insidious onset of bilateral visual loss and they characteristically have temporal optic nerve pallor, centrocaecal visual field scotoma, and a colour vision deficit, which is frequently blue-yellow. Evidence from histological and electrophysiological studies suggests that the pathology is confined to the retinal ganglion cell. A gene for dominant optic atrophy (OPA1) has been mapped to chromosome 3q28-qter, and studies are under way to refine the genetic interval in which the gene lies, to map the region physically, and hence to clone the gene. A second locus for dominant optic atrophy has recently been shown to map to chromosome 18q12.2-12.3 near the Kidd blood group locus. The cloning of genes for dominant optic atrophy will provide important insights into the pathophysiology of the retinal ganglion cell in health and disease. These insights may prove to be of great value in the understanding of other primary ganglion cell diseases, such as the mitochondrially inherited Leber's hereditary optic neuropathy and other diseases associated with ganglion cell loss, such as glaucoma.

  1. Frontal Cortical Atrophy as a Predictor of Poststroke Apathy.

    PubMed

    Mihalov, Ján; Mikula, Peter; Budiš, Jaroslav; Valkovič, Peter

    2016-07-01

    The aim of the study was to identify associations between the symptoms of poststroke apathy and sociodemographic, stroke-related (severity of stroke, degree of disability, and performance in activities of daily living), and radiological correlates. We determined the degree of cortical and subcortical brain atrophy, the severity of white matter and basal ganglia lesions on baseline computed tomography (CT) scans, and the localization of acute ischemia on control CT or magnetic resonance imaging scans in subacute stages of stroke. During follow-up examinations, in addition to the assessment of apathy symptoms using the Apathy Scale, we also evaluated symptoms of depression and anxiety using the Hospital Anxiety and Depression Scale. The study included 47 consecutive patients with acute ischemic stroke. Correlates significantly associated with apathy, determined at baseline and during follow-up, were entered into the "predictive" and "associative" multiple regression models, respectively. Frontal cortical atrophy and symptoms of depression were most strongly associated with poststroke apathy symptoms. In order to model an interrelation between both cortical atrophy and white matter lesions and aging, we supplemented 2 additional "predictive" models using interaction variables, whereby we confirmed the role of frontal cortical atrophy as a predictor of poststroke apathy also as a function of the increasing age of patients. PMID:27056065

  2. 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...

  3. 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…

  4. Chronic generalized spinal muscular atrophy of infancy and childhood

    PubMed Central

    Pearn, J. H.; Wilson, J.

    1973-01-01

    Recent studies have shown that the acute fatal form of infantile spinal muscular atrophy (acute Werdnig-Hoffmann disease or spinal muscular atrophy Type I) is a distinct genetic and clinical entity. This has prompted clinical re-examination of the disease known as `arrested Werdnig-Hoffmann disease' which hitherto was thought to be a spectrum variant of the acute fatal form. A total of 18 such patients with the chronic generalized form of spinal muscular atrophy has been known to The Hospital for Sick Children over the past 10 years. Patients with this characteristic clinical syndrome comprise approximately one-fifth of children with chronic spinal muscular atrophy. Clinically, no patient was even able to crawl normally or progress further with motor milestones. Median age of clinical onset is 6 months of age, and life expectancy ranges from 2 years to the third decade. Inevitable spinal and joint deformities occur by the second decade of life. Management should be based on vigorous antibiotic therapy, orthopaedic and neurological surveillance, and a carefully planned educational programme aimed at realistic employment in late adolescence. ImagesFIG. 4p772-b PMID:4749680

  5. Tubular atrophy in the pathogenesis of chronic kidney disease progression.

    PubMed

    Schelling, Jeffrey R

    2016-05-01

    The longstanding focus in chronic kidney disease (CKD) research has been on the glomerulus, which is sensible because this is where glomerular filtration occurs, and a large proportion of progressive CKD is associated with significant glomerular pathology. However, it has been known for decades that tubular atrophy is also a hallmark of CKD and that it is superior to glomerular pathology as a predictor of glomerular filtration rate decline in CKD. Nevertheless, there are vastly fewer studies that investigate the causes of tubular atrophy, and fewer still that identify potential therapeutic targets. The purpose of this review is to discuss plausible mechanisms of tubular atrophy, including tubular epithelial cell apoptosis, cell senescence, peritubular capillary rarefaction and downstream tubule ischemia, oxidative stress, atubular glomeruli, epithelial-to-mesenchymal transition, interstitial inflammation, lipotoxicity and Na(+)/H(+) exchanger-1 inactivation. Once a a better understanding of tubular atrophy (and interstitial fibrosis) pathophysiology has been obtained, it might then be possible to consider tandem glomerular and tubular therapeutic strategies, in a manner similar to cancer chemotherapy regimens, which employ multiple drugs to simultaneously target different mechanistic pathways.

  6. Posterior Cortical Atrophy Presenting with Superior Arcuate Field Defect.

    PubMed

    Wan, Sue Ling; Bukowska, Danuta M; Ford, Stephen; Chen, Fred K

    2015-01-01

    An 80-year-old female with reading difficulty presented with progressive arcuate field defect despite low intraocular pressure. Over a 5-year period, the field defect evolved into an incongruous homonymous hemianopia and the repeated neuroimaging revealed progressive posterior cortical atrophy. Further neuropsychiatric assessment demonstrated symptoms and signs consistent with Benson's syndrome. PMID:26417467

  7. [Devic disease associated with isolated spinal cord atrophy].

    PubMed

    Landragin, N; Jeanjean, L; Bouly, S; Honnorat, J; de Sèze, J; Castelnovo, G; Labauge, P

    2007-12-01

    Devic disease is a rare entity characterized by bilateral optic neuritis and transverse myelitis. Recently, recognition of antibody activity (Anti NMO) led to broaden the clinical and MR phenotype spectrum of this disease. This report is about a patient with spinal cord atrophy and bilateral optic neuritis, occurring more than 8 years after symptom onset. PMID:18355472

  8. Intravaginally applied oxytocin improves post-menopausal vaginal atrophy

    PubMed Central

    Uvnäs-Moberg, Kerstin; Jonasson, Aino F

    2015-01-01

    Objective To explore the efficacy of local oxytocin for the treatment of post-menopausal vaginal atrophy. Design Double-blinded randomised controlled trial. Setting Healthy post-menopausal women in Stockholm, Sweden. Participants Sixty four post-menopausal women between February and June 2012 at the Karolinska University Hospital Huddinge/Sweden. Main outcome measures The efficacy of oxytocin for treatment of vaginal atrophy after seven weeks and cytological evaluation. Results The percentage of superficial cells in the vaginal smears and the maturation values were significantly increased after seven weeks of treatment with vagitocin 400 IU (p = 0.0288 and p = 0.0002, respectively). The vaginal pH decreased significantly after seven weeks of treatment with vagitocin 100 IU (p = 0.02). The scores of vaginal atrophy, according to the histological evaluation, were significantly reduced after administration of vagitocin 100 IU (p = 0.03). The thickness of the endometrium did not differ between the treatment and placebo groups after seven weeks of treatment. The symptom experienced as the most bothersome was significantly reduced after seven weeks of treatment in the women receiving vagitocin 400 IU compared to women in the placebo group (p = 0.0089). Conclusions Treatment with intravaginally applied oxytocin could be an alternative to local estrogen treatment in women with post-menopausal vaginal atrophy. PMID:25995333

  9. 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.

  10. 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. PMID:24845847

  11. 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.

  12. Database search of spontaneous reports and pharmacological investigations on the sulfonylureas and glinides-induced atrophy in skeletal muscle

    PubMed Central

    Mele, Antonietta; Calzolaro, Sara; Cannone, Gianluigi; Cetrone, Michela; Conte, Diana; Tricarico, Domenico

    2014-01-01

    The ATP-sensitive K+ (KATP) channel is an emerging pathway in the skeletal muscle atrophy which is a comorbidity condition in diabetes. The “in vitro” effects of the sulfonylureas and glinides were evaluated on the protein content/muscle weight, fibers viability, mitochondrial succinic dehydrogenases (SDH) activity, and channel currents in oxidative soleus (SOL), glycolitic/oxidative flexor digitorum brevis (FDB), and glycolitic extensor digitorum longus (EDL) muscle fibers of mice using biochemical and cell-counting Kit-8 assay, image analysis, and patch-clamp techniques. The sulfonylureas were: tolbutamide, glibenclamide, and glimepiride; the glinides were: repaglinide and nateglinide. Food and Drug Administration-Adverse Effects Reporting System (FDA-AERS) database searching of atrophy-related signals associated with the use of these drugs in humans has been performed. The drugs after 24 h of incubation time reduced the protein content/muscle weight and fibers viability more effectively in FDB and SOL than in the EDL. The order of efficacy of the drugs in reducing the protein content in FDB was: repaglinide (EC50 = 5.21 × 10−6) ≥ glibenclamide(EC50 = 8.84 × 10−6) > glimepiride(EC50 = 2.93 × 10−5) > tolbutamide(EC50 = 1.07 × 10−4) > nateglinide(EC50 = 1.61 × 10−4) and it was: repaglinide(7.15 × 10−5) ≥ glibenclamide(EC50 = 9.10 × 10−5) > nateglinide(EC50 = 1.80 × 10−4) ≥ tolbutamide(EC50 = 2.19 × 10−4) > glimepiride(EC50=–) in SOL. The drug-induced atrophy can be explained by the KATP channel block and by the enhancement of the mitochondrial SDH activity. In an 8-month period, muscle atrophy was found in 0.27% of the glibenclamide reports in humans and in 0.022% of the other not sulfonylureas and glinides drugs. No reports of atrophy were found for the other sulfonylureas and glinides in the FDA-AERS. Glibenclamide induces atrophy in animal experiments and in human patients. Glimepiride shows less potential for inducing

  13. Database search of spontaneous reports and pharmacological investigations on the sulfonylureas and glinides-induced atrophy in skeletal muscle.

    PubMed

    Mele, Antonietta; Calzolaro, Sara; Cannone, Gianluigi; Cetrone, Michela; Conte, Diana; Tricarico, Domenico

    2014-02-01

    The ATP-sensitive K(+) (KATP) channel is an emerging pathway in the skeletal muscle atrophy which is a comorbidity condition in diabetes. The "in vitro" effects of the sulfonylureas and glinides were evaluated on the protein content/muscle weight, fibers viability, mitochondrial succinic dehydrogenases (SDH) activity, and channel currents in oxidative soleus (SOL), glycolitic/oxidative flexor digitorum brevis (FDB), and glycolitic extensor digitorum longus (EDL) muscle fibers of mice using biochemical and cell-counting Kit-8 assay, image analysis, and patch-clamp techniques. The sulfonylureas were: tolbutamide, glibenclamide, and glimepiride; the glinides were: repaglinide and nateglinide. Food and Drug Administration-Adverse Effects Reporting System (FDA-AERS) database searching of atrophy-related signals associated with the use of these drugs in humans has been performed. The drugs after 24 h of incubation time reduced the protein content/muscle weight and fibers viability more effectively in FDB and SOL than in the EDL. The order of efficacy of the drugs in reducing the protein content in FDB was: repaglinide (EC50 = 5.21 × 10(-6)) ≥ glibenclamide(EC50 = 8.84 × 10(-6)) > glimepiride(EC50 = 2.93 × 10(-5)) > tolbutamide(EC50 = 1.07 × 10(-4)) > nateglinide(EC50 = 1.61 × 10(-4)) and it was: repaglinide(7.15 × 10(-5)) ≥ glibenclamide(EC50 = 9.10 × 10(-5)) > nateglinide(EC50 = 1.80 × 10(-4)) ≥ tolbutamide(EC50 = 2.19 × 10(-4)) > glimepiride(EC50=-) in SOL. The drug-induced atrophy can be explained by the KATP channel block and by the enhancement of the mitochondrial SDH activity. In an 8-month period, muscle atrophy was found in 0.27% of the glibenclamide reports in humans and in 0.022% of the other not sulfonylureas and glinides drugs. No reports of atrophy were found for the other sulfonylureas and glinides in the FDA-AERS. Glibenclamide induces atrophy in animal experiments and in human patients. Glimepiride shows less potential for inducing atrophy

  14. Plasma clusterin concentration is associated with longitudinal brain atrophy in mild cognitive impairment.

    PubMed

    Thambisetty, Madhav; An, Yang; Kinsey, Anna; Koka, Deepthi; Saleem, Muzamil; Güntert, Andreas; Kraut, Michael; Ferrucci, Luigi; Davatzikos, Christos; Lovestone, Simon; Resnick, Susan M

    2012-01-01

    Recent genetic and proteomic studies demonstrate that clusterin/apolipoprotein-J is associated with risk, pathology, and progression of Alzheimer's disease (AD). Our main aim was to examine associations between plasma clusterin concentration and longitudinal changes in brain volume in normal aging and mild cognitive impairment (MCI). A secondary objective was to examine associations between peripheral concentration of clusterin and its concentration in the brain within regions that undergo neuropathological changes in AD. Non-demented individuals (N=139; mean baseline age 70.5 years) received annual volumetric MRI (912 MRI scans in total) over a mean six-year interval. Sixteen participants (92 MRI scans in total) were diagnosed during the course of the study with amnestic MCI. Clusterin concentration was assayed by ELISA in plasma samples collected within a year of the baseline MRI. Mixed effects regression models investigated whether plasma clusterin concentration was associated with rates of brain atrophy for control and MCI groups and whether these associations differed between groups. In a separate autopsy sample of individuals with AD (N=17) and healthy controls (N=4), we examined the association between antemortem clusterin concentration in plasma and postmortem levels in the superior temporal gyrus, hippocampus and cerebellum. The associations of plasma clusterin concentration with rates of change in brain volume were significantly different between MCI and control groups in several volumes including whole brain, ventricular CSF, temporal gray matter as well as parahippocampal, superior temporal and cingulate gyri. Within the MCI but not control group, higher baseline concentration of plasma clusterin was associated with slower rates of brain atrophy in these regions. In the combined autopsy sample of AD and control cases, representing a range of severity in AD pathology, we observed a significant association between clusterin concentration in the plasma and

  15. Diagnosing Dementia—Positive Signs

    MedlinePlus

    ... this page please turn Javascript on. A new blood test offers promise in the early detection of Alzheimer's. By Mary Best What if there were an easy, affordable blood test that could accurately diagnose Alzheimer's disease (AD)—even ...

  16. How Are Uterine Fibroids Diagnosed?

    MedlinePlus

    ... Clinical Trials Resources and Publications How are uterine fibroids diagnosed? Skip sharing on social media links Share ... probably won’t know that you have uterine fibroids. Sometimes, health care providers find fibroids during a ...

  17. How Is Lactose Intolerance Diagnosed?

    MedlinePlus

    ... following tests also can help diagnose lactose intolerance: Hydrogen breath test. For this test, a person drinks ... beverage that has lactose in it. Then, the hydrogen level in the breath is measured at set ...

  18. How Is Atrial Fibrillation Diagnosed?

    MedlinePlus

    ... too much thyroid hormone). Diagnostic Tests and Procedures EKG An EKG is a simple, painless test that records the ... the most useful test for diagnosing AF. An EKG shows how fast your heart is beating and ...

  19. How Is Bone Cancer Diagnosed?

    MedlinePlus

    ... Topic How is bone cancer staged? How is bone cancer diagnosed? A patient’s symptoms, physical exam, and results ... and other imaging tests. Imaging tests to detect bone cancer X-rays Most bone cancers show up on ...

  20. How Is Penile Cancer Diagnosed?

    MedlinePlus

    ... These might include a biopsy and imaging tests. Biopsy A biopsy is needed to diagnose penile cancer. ... depends on the nature of the abnormality. Incisional biopsy For an incisional biopsy only a part of ...

  1. Factors Associated with Changes in Brain Atrophy during a Three-Year Observation in Elderly Diabetic Patients: Effect of Renal Impairment on Hippocampal Atrophy

    PubMed Central

    Kawamura, Takahiko; Umemura, Toshitaka; Umegaki, Hiroyuki; Imamine, Rui; Kawano, Naoko; Mase, Hajime; Mizoguchi, Asako; Minatoguchi, Makiko; Kusama, Minoru; Kouchi, Yu; Watarai, Atsuko; Kanai, Akio; Nakashima, Eitaro; Hotta, Nigishi

    2016-01-01

    Background/Aims We conducted a 3-year longitudinal study concerning factors associated with changes in brain atrophy in elderly diabetic patients. Methods We evaluated hippocampal and global brain atrophy using automatic voxel-based morphometry of structural magnetic resonance images, 4 cognitive function tests, and cerebral small vessel disease (SVD) in 66 diabetic patients. Results During the 3-year follow-up, hippocampal and global brain atrophy advanced, and cognitive functions worsened. For changes in hippocampal atrophy, changes in estimated glomerular filtration rate (eGFR), albuminuria, and being an ApoE ε4 carrier were independent factors; change in the number of silent brain infarctions was an independent factor for changes in global brain atrophy. A significant association of changes in eGFR and albuminuria with hippocampal atrophy remained after adjusting for confounders including SVD. Both types of brain atrophy at baseline were significantly correlated with cognitive impairment at baseline and especially associated with changes in delayed word recall during the follow-up after adjusting for confounders. Conclusion Changes in eGFR and albuminuria during follow-up were independent risk factors for hippocampal atrophy, which was associated with decline in delayed word recall, suggesting that management of chronic kidney disease may prevent the progression of hippocampal atrophy. PMID:27293417

  2. 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.

  3. 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

  4. [Controversial matters of arrangement of dental assistance within the framework of healthcare system reform and ways to increase of efficiency of diagnosing destructive processes in apical periodont].

    PubMed

    ZHero, N I

    2014-01-01

    In conditions of reform of primary level of medical sanitary assistance a tendency for decrease of availability of dental care for population has been revealed. Increase in number of complicated cases of typical dental diseases, inter alia, destructive affection of apical periodont. An examination of 347 patients with apical periodontitis has been held. For the purpose of improvement of differential diagnostics of radicular cysts and periapical granulomas as well as choice of adequate method of treatment postprocessing of digital dental roentgenograms has been used. 241 granulomas, 106 cysts (simplex and complex) and cystogranulomas--have been diagnosed. For improvement of visualization of destruction zone of alveolar bone possibilities of digital processing of image have been utilized. Postprocessing of digital roentgenograms significantly supplemented results of visual examination and excluded impact of subjective factor in composition of diagnostic conclusion. Upon results of examination of histograms of optical density of radiographic image of pathological zone signs of specific for granulomas, cysts and have been detected. Diagnostic conclusion coincides with results of pathomorphological study.

  5. [Controversial matters of arrangement of dental assistance within the framework of healthcare system reform and ways to increase of efficiency of diagnosing destructive processes in apical periodont].

    PubMed

    ZHero, N I

    2014-01-01

    In conditions of reform of primary level of medical sanitary assistance a tendency for decrease of availability of dental care for population has been revealed. Increase in number of complicated cases of typical dental diseases, inter alia, destructive affection of apical periodont. An examination of 347 patients with apical periodontitis has been held. For the purpose of improvement of differential diagnostics of radicular cysts and periapical granulomas as well as choice of adequate method of treatment postprocessing of digital dental roentgenograms has been used. 241 granulomas, 106 cysts (simplex and complex) and cystogranulomas--have been diagnosed. For improvement of visualization of destruction zone of alveolar bone possibilities of digital processing of image have been utilized. Postprocessing of digital roentgenograms significantly supplemented results of visual examination and excluded impact of subjective factor in composition of diagnostic conclusion. Upon results of examination of histograms of optical density of radiographic image of pathological zone signs of specific for granulomas, cysts and have been detected. Diagnostic conclusion coincides with results of pathomorphological study. PMID:25796822

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. Evidence for a chronic axonal atrophy in oculopharyngeal "muscular dystrophy".

    PubMed

    Probst, A; Tackmann, W; Stoeckli, H R; Jerusalem, F; Ulrich, J

    1982-01-01

    We report on morphometric investigations of peripheral nerves in a woman, who died at the age of 69, presenting the classical symptoms of oculopharyngeal muscular dystrophy (OPMD) and a typical family history with several members (males and females) affected over three generations. Evidence for chronic axonal atrophy was found in peripheral nerves and especially in oculomotor nerves with severe axon loss in endomysial nerve twigs of extraocular, laryngeal, and tongue muscles. Whereas limb muscles presented features of neurogenic atrophy, severe changes of "myopathic" type were evident in extrinsic eye muscles, laryngeal constrictor, tongue, and diaphragma. However, we interpreted these changes as neurogenic in origin in view of the severe denervation found in those muscles. Our findings suggest that OPMD is a disease of primary neurogenic origin rather than a primary myopathic disorder. PMID:7124348

  11. 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.

  12. Crustaceans as a model for microgravity-induced muscle atrophy

    NASA Astrophysics Data System (ADS)

    Mykles, D. L.

    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 a reduction in muscle mass and strength. A crustacean model using the land crab, Gecarcinus lateralis, to assess the effects of spaceflight on protein metabolism 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 Ca^2+-dependent and multicatalytic proteolytic enzymes. Crustacean claw muscle can be used to determine the interactions between shortening and unloading at the molecular level.

  13. 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.

  14. Atrophy of the parietal lobe in preclinical dementia.

    PubMed

    Jacobs, Heidi I L; Van Boxtel, Martin P J; Uylings, Harry B M; Gronenschild, Ed H B M; Verhey, Frans R; Jolles, Jelle

    2011-03-01

    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 (38 cognitively stable and 37 individuals with cognitive decline after 3 years). Dementia screening 6 years after scanning resulted in nine AD cases from the cognitively stable (n=3) and cognitive decline group (n=6), who were assigned to a third group, the preclinical AD group. When regional differences in cortical volume in the parietal lobe areas were compared between groups, significant differences were found between either the cognitive decline or stable group on the one hand and preclinical AD individuals on the other hand in the inferior parietal lobule. Group membership was best predicted by the grey matter volume of the inferior parietal lobule, compared to the other parietal lobe areas. The parietal lobe was characterised by a differential atrophy pattern based on cognitive status, which is in agreement with the 'last-developed-first-atrophied' principle. Future studies should investigate the surplus value of the inferior parietal lobe as a potential marker for the diagnosis of AD compared to other brain regions, such as the medial temporal lobe and the prefrontal lobe. PMID:21130554

  15. Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy

    PubMed Central

    Calvani, Riccardo; Joseph, Anna-Maria; Adhihetty, Peter J.; Miccheli, Alfredo; Bossola, Maurizio; Leeuwenburgh, Christiaan; Bernabei, Roberto; Marzetti, Emanuele

    2014-01-01

    Muscle loss during aging and disuse is a highly prevalent and disabling condition, but knowledge about cellular pathways mediating muscle atrophy is still limited. Given the postmitotic nature of skeletal myocytes, the maintenance of cellular homeostasis relies on the efficiency of cellular quality control mechanisms. In this scenario, alterations in mitochondrial function are considered a major factor underlying sarcopenia and muscle atrophy. Damaged mitochondria are not only less bioenergetically efficient, but also generate increased amounts of reactive oxygen species, interfere with cellular quality control mechanisms, and display a greater propensity to trigger apoptosis. Thus, mitochondria stand at the crossroad of signaling pathways that regulate skeletal myocyte function and viability. Studies on these pathways have sometimes provided unexpected and counterintuitive results, which suggests that they are organized into a complex, heterarchical network that is currently insufficiently understood. Untangling the complexity of such a network will likely provide clinicians with novel and highly effective therapeutics to counter the muscle loss associated with aging and disuse. In this review, we summarize the current knowledge on the mechanisms whereby mitochondrial dysfunction intervenes in the pathogenesis of sarcopenia and disuse atrophy, and highlight the prospect of targeting specific processes to treat these conditions. PMID:23154422

  16. Focal brain atrophy in gastric bypass patients with cognitive complaints

    PubMed Central

    Graff-Radford, Jonathan; Whitwell, Jennifer L.; Trenerry, Max R.; Ahlskog, J. Eric; Jensen, Michael D.; Jack, Clifford R.; Josephs, Keith A.

    2012-01-01

    Recently, we have noticed a series of patients presenting for cognitive complaints after gastric bypass, without any identifiable etiology. We set out to determine whether any focal brain atrophy could account for the complaints. A retrospective case series was performed to identify patients with cognitive complaints following gastric bypass that had a volumetric MRI. Voxel-based morphometry was used to assess patterns of grey matter loss in all 10 patients identified, compared to ten age and gender-matched controls. All patients had undergone Roux-en-Y gastric bypass at a median age of 54 (range: 46–64). Cognitive complaints began at a median age of 57 (52–69). Formal neuropsychometric testing revealed only minor deficits. No nutritional abnormalities were identified. Voxel-based morphometry demonstrated focal thalamic atrophy in the gastric bypass patients when compared to controls. Patients with cognitive complaints after gastric bypass surgery have focal thalamic brain atrophy that could account for the cognitive impairment. PMID:22088949

  17. Hippocampal complex atrophy in poststroke and mild cognitive impairment.

    PubMed

    Selnes, Per; Grambaite, Ramune; Rincon, Mariano; Bjørnerud, Atle; Gjerstad, Leif; Hessen, Erik; Auning, Eirik; Johansen, Krisztina; Almdahl, Ina S; Due-Tønnessen, Paulina; Vegge, Kjetil; Bjelke, Börje; Fladby, Tormod

    2015-11-01

    To investigate putative interacting or distinct pathways for hippocampal complex substructure (HCS) atrophy and cognitive affection in early-stage Alzheimer's disease (AD) and cerebrovascular disease (CVD), we recruited healthy controls, patients with mild cognitive impairment (MCI) and poststroke patients. HCSs were segmented, and quantitative white-matter hyperintensity (WMH) load and cerebrospinal fluid (CSF) amyloid-β concentrations were determined. The WMH load was higher poststroke. All examined HCSs were smaller in amyloid-positive MCI than in controls, and the subicular regions were smaller poststroke. Memory was reduced in amyloid-positive MCI, and psychomotor speed and executive function were reduced in poststroke and amyloid-positive MCI. Size of several HCS correlated with WMH load poststroke and with CSF amyloid-β concentrations in MCI. In poststroke and amyloid-positive MCI, neuropsychological function correlated with WMH load and hippocampal volume. There are similar patterns of HCS atrophy in CVD and early-stage AD, but different HCS associations with WMH and CSF biomarkers. WMHs add to hippocampal atrophy and the archetypal AD deficit delayed recall. In line with mounting evidence of a mechanistic link between primary AD pathology and CVD, these additive effects suggest interacting pathologic processes.

  18. 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

  19. 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.

  20. 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.

  1. Angiotensin-(1-7) attenuates disuse skeletal muscle atrophy in mice via its receptor, Mas

    PubMed Central

    Morales, María Gabriela; Abrigo, Johanna; Acuña, María José; Santos, Robson A.; Bader, Michael; Brandan, Enrique; Simon, Felipe; Olguin, Hugo; Cabrera, Daniel; Cabello-Verrugio, Claudio

    2016-01-01

    ABSTRACT Immobilization is a form of disuse characterized by a loss of strength and muscle mass. Among the main features are decreased IGF-1/Akt signalling and increased ubiquitin-proteasome pathway signalling, which induce greater myosin heavy chain degradation. Activation of the classical renin-angiotensin system (RAS) causes deleterious effects in skeletal muscle, including muscle wasting. In contrast, angiotensin-(1-7) [Ang-(1-7)], a peptide of the non-classical RAS, produces beneficial effects in skeletal muscle. However, the role of Ang-(1-7) in skeletal muscle disuse atrophy and independent of classical RAS activation has not been evaluated. Therefore, we assessed the functions of Ang-(1-7) and the Mas receptor in disuse muscle atrophy in vivo using unilateral cast immobilization of the hind limb in male, 12-week-old wild-type (WT) and Mas-knockout (Mas KO) mice for 1 and 14 days. Additionally, we evaluated the participation of IGF-1/IGFR-1/Akt signalling and ubiquitin-proteasome pathway expression on the effects of Ang-(1-7) immobilization-induced muscle atrophy. Our results found that Ang-(1-7) prevented decreased muscle strength and reduced myofiber diameter, myosin heavy chain levels, and the induction of atrogin-1 and MuRF-1 expressions, all of which normally occur during immobilization. Analyses indicated that Ang-(1-7) increases IGF-1/IGFR-1/Akt pathway signalling through IGFR-1 and Akt phosphorylation, and the concomitant activation of two downstream targets of Akt, p70S6K and FoxO3. These anti-atrophic effects of Ang-(1-7) were not observed in Mas KO mice, indicating crucial participation of the Mas receptor. This report is the first to propose anti-atrophic effects of Ang-(1-7) via the Mas receptor and the participation of the IGF-1/IGFR-1/Akt/p70S6K/FoxO3 mechanism in disuse skeletal muscle atrophy. PMID:26851244

  2. 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 ...

  3. [Reliability of the diagnoses of hospital admissions for external causes financed by the Brazilian Unified Health System-SUS in two cities in the State of Paraná, Brazil].

    PubMed

    Mathias, Thais Aidar de Freitas; de Andrade, Selma Maffei; Tomimatsu, Maria de Fátima Akemi Iwakura; Soares, Dorotéia Fátima Pelissari de Paula; Sapata, Maria da Penha Marques; Frascarelli, Andressa Suellen; de Souza, Regina Kazue Tanno

    2014-10-01

    The scope of this article is to analyze the reliability of the diagnoses of hospital admissions for external causes financed by the Brazilian Unified Health System (SUS). The diagnoses for hospital admissions from the Hospital Information System (SIH-SUS) data were compared with those from the research panel created from information culled from authorizations for hospital admission (AIH) complemented with information from other sources. The reliability was analyzed in groups using crude agreement and Kappa statistics. The crude agreement was 41.1% in Londrina and 15.8% in Maringá and the highest reliability was found for groupings for self-inflicted lesions and traffic accidents in Londrina (Kappa 0.57 and 0.56) while in Maringá reliability was acceptable for self-inflicted lesions (Kappa 0.28). The low agreement with differentiated standards according to groupings of causes and according to the municipalities highlight the fact that efforts must be made to improve the quality and use of the SIH-SUS in order to understand and intervene in accidents and violence in Brazil.

  4. How to diminish calcium loss and muscle atrophy in space

    NASA Astrophysics Data System (ADS)

    Gorgolewski, S.

    Humans in micro-gravity suffer from Ca loss and muscle atrophy, efforts are made to prevent it by means of physical exercises and with medicaments. The tread-mill and exercise bike are just two most frequently used examples. This can and should be widely extended, and in such a way as to mimic as close as possible the normal loading of the muscles and skeleton which we experience here on the earth. Special very light weight active harness is proposed which monitors the body loading. This is accomplished by means of computer aided monitoring of muscle and bone loading systems. Using feedback it helps the crew to load their bodies and skeletons in the same way as it happens here on the earth. The active exercise mat with pressure sensors first creates a record here on the earth of all normal muscle tensions during exercise. In space the computer guides each exercising crew member to follow their earthbound training routine. High care is needed to select the best and most effective exercises which should demand least energy, yet providing the very best results. May I suggest the very best known to me kind of comprehensive exercises: Yoga. Doing it on the Earth you need next to none special training equipment. Our body is in principle all we need here to do Yoga exercises on the Earth. Integral part of Yoga exercises are abdominal breathing exercises, which can slow down the breathing rate even threefold. This improves the oxygen and CO_2 exchange and massages all internal organs around the clock, helping the adept to stay fit and also keeps their minds steady and calm. Yoga exercises should be mastered already here on the earth, providing the crew with much greater tolerance to micro-gravity. In Yoga we acquire the tolerance not only to zero gravity but also to "negative" gravity: as it happens in all inverted positions. This should help the astronauts to be more tolerant of the half way only step into "zero gravity". Weightlessness state provides us the ultimate in

  5. Serological assessment of gastric mucosal atrophy in gastric cancer

    PubMed Central

    2012-01-01

    Background Non-invasive tools for gastric cancer screening and diagnosis are lacking. Serological testing with the detection of pepsinogen 1 (PG1), pepsinogen 2 (PG2) and gastrin 17 (G17) offers the possibility to detect preneoplastic gastric mucosal conditions. Aim of this study was to assess the performance of these serological tests in the presence of gastric neoplasia. Methods Histological and serological samples of 118 patients with gastric cancer have been assessed for tumor specific characteristics (Laurén type, localisation), degree of mucosal abnormalities (intestinal metaplasia, atrophy) and serological parameters (PG1, PG2, PG1/2-ratio, G17, H. pylori IgG, CagA status). Association of the general factors to the different serological values have been statistically analyzed. Results Patients with intestinal type gastric cancer had lower PG1 levels and a lower PG1/2-ratio compared to those with diffuse type cancer (p = 0.003). The serum levels of PG2 itself and G17 were not significantly altered. H. pylori infection in general had no influence on the levels of PG1, PG2 and G17 in the serum of gastric cancer patients. There was a trend towards lower PG1 levels in case of positive CagA-status (p = 0.058). The degree of both intestinal metaplasia and atrophy correlated inversely with serum levels for PG1 and the PG1/2-ratio (p < 0.01). Laurén-specific analysis revealed that this is only true for intestinal type tumors. Univariate ANOVA revealed atrophy and CagA-status as the only independent factors for low PG1 and a low PG1/2-ratio. Conclusions Glandular atrophy and a positive CagA status are determinant factors for decreased pepsinogen 1 levels in the serum of patients with gastric cancer. The serological assessment of gastric atrophy by analysis of serum pepsinogen is only adequate for patients with intestinal type cancer. PMID:22289789

  6. Early-onset Alzheimer's disease versus frontotemporal dementia: resolution with genetic diagnoses?

    PubMed

    Sha, Sharon J; Khazenzon, Anna M; Ghosh, Pia M; Rankin, Katherine P; Pribadi, Mochtar; Coppola, Giovanni; Geschwind, Daniel H; Rabinovici, Gil D; Miller, Bruce L; Lee, Suzee E

    2016-01-01

    We report a diagnostically challenging case of a 64-year-old man with a history of remote head trauma who developed mild behavioral changes and dyscalculia. He was diagnosed with clinical Alzheimer's disease (AD), with additional features consistent with behavioral variant frontotemporal dementia. Structural magnetic resonance imaging revealed atrophy in bilateral frontal and parietal cortices and hippocampi on visual inspection and left frontal pole and bilateral anterior temporal encephalomalacia, suspected to be due to head trauma. Consistent with the diagnosis of Alzheimer's pathology, positron emission tomography (PET) with Pittsburgh compound B suggested the presence of beta-amyloid. Fluorodeoxyglucose PET demonstrated hypometabolism in bilateral frontal and temporoparietal cortices. Voxel-based morphometry showed atrophy predominant in ventral frontal regions (bilateral orbitofrontal cortex, pregenual anterior cingulate/medial superior frontal gyrus), bilateral mid cingulate, bilateral lateral temporal cortex, and posterior insula. Bilateral caudate, thalamus, hippocampi, and cerebellum were prominently atrophied. Unexpectedly, a pathologic hexanucleotide repeat expansion in C9ORF72 was identified in this patient. This report underscores the clinical variability in C9ORF72 expansion carriers and the need to consider mixed pathologies, particularly when imaging studies are inconsistent with a single syndrome or pathology.

  7. Pomalidomide and Dexamethasone in Treating Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma or Newly Diagnosed or Relapsed or Refractory Intraocular Lymphoma

    ClinicalTrials.gov

    2016-09-12

    B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Central Nervous System Lymphoma; Intraocular Lymphoma; Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System; Recurrent Adult Diffuse Large Cell Lymphoma; Retinal Lymphoma

  8. 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.

  9. 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 ...

  10. Associations among Major Psychiatric Diagnoses.

    ERIC Educational Resources Information Center

    Wolf, Abraham W.; And Others

    1988-01-01

    Examined the frequency and associations of multiple diagnoses in 205 psychiatric inpatients, assessing past and current episodes of illness. Over one-half of the sample received more than one diagnosis. Alcoholism, antisocial personality, and drug dependence formed one group; primary depression, primary mania, and secondary affective disorder,…

  11. How Is an Aneurysm Diagnosed?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is an Aneurysm Diagnosed? If you have an aortic aneurysm but no symptoms, your doctor may find it ... a routine physical exam. More often, doctors find aneurysms during tests done for other reasons, such as ...

  12. Neurobehavioral and Imaging Correlates of Hippocampal Atrophy in a Mouse Model of Vascular Cognitive Impairment

    PubMed Central

    Zuloaga, Kristen L.; Zhang, Wenri; Yeiser, Lauren A.; Stewart, Blair; Kukino, Ayaka; Nie, Xiao; Roese, Natalie E.; Grafe, Marjorie R.; Pike, Martin M.; Raber, Jacob; Alkayed, Nabil J.

    2015-01-01

    Vascular cognitive impairment (VCI) is the second most common cause of dementia. Reduced cerebral blood flow is thought to play a major role in the etiology of VCI. Therefore, chronic cerebral hypoperfusion has been used to model VCI in rodents. The goal of the current study was to determine the histopathological and neuroimaging substrates of neurocognitive impairments in a mouse model of chronic cerebral hypoperfusion induced by unilateral common carotid artery occlusion (UCCAO). Mice were subjected to sham or right UCCAO (VCI) surgeries. Three months later, neurocognitive function was evaluated using the novel object recognition task, Morris water maze, and contextual and cued fear conditioning tests. Next, cerebral perfusion was evaluated with dynamic susceptibility contrast magnetic resonance imaging (MRI) using an ultra-high fieild (11.75 Tesla) animal MRI system. Finally, brain pathology was evaluated using histology and T2 weighted MRI (magnetic resonance imaging). VCI, but not sham, mice had significantly reduced cerebral blood flow in the right vs. left cerebral cortex. VCI mice showed deficits in object recognition. T2 weighted MRI of VCI brains revealed enlargement of lateral ventricles, which corresponded to areas of hippocampal atrophy upon histological analysis. In conclusion, our data demonstrate that the UCCAO model of chronic hypoperfusion induces hippocampal atrophy and ventricular enlargement, resulting in neurocognitive deficits characteristic of VCI. PMID:26040424

  13. A model for hypokinesia: Effects on muscle atrophy in the rat

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.; Deavers, D. R.; Meininger, G. A.; Davis, T. P.

    1980-01-01

    Hypokinesia in the hindlimbs of rats was induced by suspension; a newly developed harness system was used. The animal was able to use its forelimbs to maneuver, within a 140 deg arc, to obtain food and water and to permit limited grooming of the forequarters. The hindlimbs were nonload bearing for 7 days; following a 7-day period of hypodynamia, selected animals were placed in metabolic cages for 7 days to study recovery from hypokinesia. During the 7-day period of hypokinesia there was evidence of muscle atrophy. Gastrocnemius weight decreased, renal papillary urea content increased, and daily urinary losses of NH3 and 3-methylhistidine increased. During the 7-day recovery period muscle mass and excretion rate of urea, NH3 and 3-methylhistidine returned to control levels. Calcium balance was positive throughout the 7-day period of hypokinesia. Hypertrophy of the adrenals suggested the occurrence of some level of stress despite the apparent behavioral adjustment to the suspension harness. It was concluded that significant muscle atrophy and parallel changes in nitrogen metabolism occur in suspended rats and these changes are readily reversible.

  14. Ultra-low-dose vaginal estrogen tablets for the treatment of postmenopausal vaginal atrophy.

    PubMed

    Simon, J A; Maamari, R V

    2013-08-01

    Vaginal atrophy is a common chronic condition affecting up to 57% of postmenopausal women. The decrease in estrogen following cessation of menses can lead to bothersome symptoms that include vaginal dryness and irritation, pain and burning during urination (dysuria), urinary tract infections, and pain (dyspareunia) and bleeding during sexual activities. These symptoms can be safely and effectively managed with the use of local estrogen therapy, which reduces the risks associated with long-term systemic hormone therapy. The ultra-low-dose 10 μg estradiol vaginal tablet is the lowest approved dose available and has an annual estradiol exposure of only 1.14 mg. Its development addresses recommendations from regulatory agencies and women's health societies regarding the use of the lowest hormonal dose. The 10 μg vaginal tablet displays minimal estradiol absorption, causes no increased risk of endometrial hyperplasia or carcinoma, and provides significant symptom relief. The clinical evidence presented here may offer greater reassurance to health-care professionals and postmenopausal women that vaginal atrophy can be treated safely and effectively.

  15. [Development and regression of dermal corticosteroid atrophy. 2. Changes in compression rate].

    PubMed

    Hinz, E; Lubach, D

    1986-01-01

    In the 1st comm. results on development and remission of steroid-induced dermal atrophy were presented. Measurements were carried out with an instrument we constructed ourselves. This device enabled calculation of the rate of compression (CR) of a skin fold as well as determination of skin fold thickness (SFT). CR is specified in mm/log t. It is postulated that the CR depends on the viscosity of the basic substance and on the density of the collagen fiber skeletons led to an increase of SFT and CR. Loss of basic substance in quantitatively unchanged collagen skeletons led to a reduction of SFT and CR. In skin areas treated with corticosteroids, CR was reduced at roughly the same time as SFT. With the exception of hydrocortisone, the reduction was observed from about the 5th to the 10th d onwards in all products tested and became most pronounced after the 12th d. Following the end of steroid treatment (17th d), CR normalized within 6 to 10 d. It is concluded from the results that early steroid-induced dermal atrophy is caused by a lowering of the water/basic substance system. A steroid-specific inhibition of hyaluronic acid and glycosamine synthesis by the fibroblasts is assumed to be the cause of thickness loss. Skin areas treated with control ointments free of active substance displayed signs of increased hydratation.

  16. What do we really know about the ubiquitin-proteasome pathway in muscle atrophy?

    NASA Technical Reports Server (NTRS)

    Jagoe, R. T.; Goldberg, A. L.

    2001-01-01

    Studies of many different rodent models of muscle wasting have indicated that accelerated proteolysis via the ubiquitin-proteasome pathway is the principal cause of muscle atrophy induced by fasting, cancer cachexia, metabolic acidosis, denervation, disuse, diabetes, sepsis, burns, hyperthyroidism and excess glucocorticoids. However, our understanding about how muscle proteins are degraded, and how the ubiquitin-proteasome pathway is activated in muscle under these conditions, is still very limited. The identities of the important ubiquitin-protein ligases in skeletal muscle, and the ways in which they recognize substrates are still largely unknown. Recent in-vitro studies have suggested that one set of ubquitination enzymes, E2(14K) and E3(alpha), which are responsible for the 'N-end rule' system of ubiquitination, plays an important role in muscle, especially in catabolic states. However, their functional significance in degrading different muscle proteins is still unclear. This review focuses on the many gaps in our understanding of the functioning of the ubiquitin-proteasome pathway in muscle atrophy, and highlights the strengths and limitations of the different experimental approaches used in such studies.

  17. Number processing in posterior cortical atrophy--a neuropsycholgical case study.

    PubMed

    Delazer, M; Karner, E; Zamarian, L; Donnemiller, E; Benke, Th

    2006-01-01

    Posterior cortical atrophy (PCA) is an uncommon syndrome of dementia with early onset, characterised by disorders of higher visual function, variable symptoms of Balint's syndrome, visual agnosia, alexia, agraphia, finger agnosia, right-left disorientation and dyscalculia [Benson D. F., Davis R. J., & Snyder B. D. (1988). Posterior cortical atrophy. Archives of Neurology, 45, 789-793]. In a single case study specific numerical deficits were observed which may be predicted by parietal neurodegeneration (more pronounced on the right side; verified by SPECT). Besides impairments in all tasks involving visuo-spatial abilities (e.g., dot counting, analog number scale task), deficits appeared in tasks requiring access to an internal representation of numbers such as mental number bisection, approximation, estimation and semantic facts. In number comparison an increased distance effect was found. In simple arithmetic, a striking dissociation between operations was found-multiplication and addition facts being preserved at a superficial level, subtraction and division being severely impaired. The study confirms the close relation between spatial and numerical processing and highlights the modular organisation of the semantic system (number semantics impaired). Moreover, the study adds evidence about the clinical manifestation of the particular degenerative syndrome. PMID:15936044

  18. Silencing neuronal mutant androgen receptor in a mouse model of spinal and bulbar muscular atrophy.

    PubMed

    Sahashi, Kentaro; Katsuno, Masahisa; Hung, Gene; Adachi, Hiroaki; Kondo, Naohide; Nakatsuji, Hideaki; Tohnai, Genki; Iida, Madoka; Bennett, C Frank; Sobue, Gen

    2015-11-01

    Spinal and bulbar muscular atrophy (SBMA), an adult-onset neurodegenerative disease that affects males, results from a CAG triplet repeat/polyglutamine expansions in the androgen receptor (AR) gene. Patients develop progressive muscular weakness and atrophy, and no effective therapy is currently available. The tissue-specific pathogenesis, especially relative pathological contributions between degenerative motor neurons and muscles, remains inconclusive. Though peripheral pathology in skeletal muscle caused by toxic AR protein has been recently reported to play a pivotal role in the pathogenesis of SBMA using mouse models, the role of motor neuron degeneration in SBMA has not been rigorously investigated. Here, we exploited synthetic antisense oligonucleotides to inhibit the RNA levels of mutant AR in the central nervous system (CNS) and explore its therapeutic effects in our SBMA mouse model that harbors a mutant AR gene with 97 CAG expansions and characteristic SBMA-like neurogenic phenotypes. A single intracerebroventricular administration of the antisense oligonucleotides in the presymptomatic phase efficiently suppressed the mutant gene expression in the CNS, and delayed the onset and progression of motor dysfunction, improved body weight gain and survival with the amelioration of neuronal histopathology in motor units such as spinal motor neurons, neuromuscular junctions and skeletal muscle. These findings highlight the importance of the neurotoxicity of mutant AR protein in motor neurons as a therapeutic target.

  19. A model for hypokinesia: effects on muscle atrophy in the rat.

    PubMed

    Musacchia, X J; Deavers, D R; Meininger, G A; Davis, T P

    1980-03-01

    Hypokinesia in the hindlimbs of rats were induced by suspension; a newly developed harness system was used. The animal was able to use its forelimbs to maneuver, within a 140 degrees arc, to obtain food and water and to permit limited grooming of the forequarters. The hindlimbs were nonload bearing for 7 days; following a 7-day period of hypodynamia, selected animals were placed in metabolic cages for 7 days to study recovery from hypokinesia. During the 7-day period of hypokinesia there was evidence of muscle atrophy. Gastrocnemius weight decreased, renal papillary urea content increased, and daily urinary losses of urea, NH3, and 3-methylhistidine increased. During the 7-day recovery period muscle mass and excretion rate of urea, NH3 and 3-methylhistidine returned to control levels. Calcium balance was positive throughout the 7-day period of hypokinesia. Hypertrophy of the adrenals suggested the occurrence of some level of stress despite the apparent behavioral adjustment to the suspension harness. It was concluded that significant muscle atrophy and parallel changes in nitrogen metabolism occur in suspended rats and these changes are readily reversible.

  20. Glucocorticoid-induced skeletal muscle atrophy in vitro is attenuated by mechanical stimulation

    NASA Technical Reports Server (NTRS)

    Chromiak, J. A.; Vandenburgh, H. H.

    1992-01-01

    Glucocorticoids induce rapid atrophy of fast skeletal myofibers in vivo, and either weight lifting or endurance exercise reduces this atrophy by unknown mechanisms. We examined the effects of the synthetic glucocorticoid dexamethasone (Dex) on protein turnover in tissue-cultured avian fast skeletal myofibers and determined whether repetitive mechanical stretch altered the myofiber response to Dex. In static cultures after 3-5 days, 10(-8) M Dex decreased total protein content 42-74%, total protein synthesis rates 38-56%, mean myofiber diameter 35%, myosin heavy chain (MHC) content 86%, MHC synthesis rate 44%, and fibronectin synthesis rate 29%. Repetitive 10% stretch-relaxations of the cultured myofibers for 60 s every 5 min for 3-4 days prevented 52% of the Dex-induced decrease in protein content, 42% of the decrease in total protein synthesis rate, 77% of the decrease in MHC content, 42% of the decrease in MHC synthesis rate, and 67% of the decrease in fibronectin synthesis rate. This in vitro model system will complement in vivo studies in understanding the mechanism by which mechanical activity and glucocorticoids interact to regulate skeletal muscle growth.

  1. Volumetric quantitation by MRI in primary progressive multiple sclerosis: volumes of plaques and atrophy correlated with neurological disability.

    PubMed

    Ukkonen, M; Dastidar, P; Heinonen, T; Laasonen, E; Elovaara, I

    2003-11-01

    In primary progressive multiple sclerosis (PPMS) abnormalities in brain magnetic resonance imaging (MRI) differ from abnormalities in other subtypes of multiple sclerosis (MS). It was investigated whether the extent of brain and spinal cord MRI abnormalities is reflected in the neurological disability in PPMS. Focal and diffuse changes and atrophy in central nervous system (CNS) in patients with PPMS (n = 28) and healthy controls (n = 20) were assessed by semi-automatic MRI segmentation and volumetric analysis. The measurements were related to neurological disability as expressed by the expanded disability status scale (EDSS), the regional functional scoring system (RFSS), the arm index and the ambulation index. Plaques in T1- and/or T2-weighted images were seen in all brains, while spinal plaques were detected in 23 of 28 patients (82%). The total volumes of brain and spinal cord were significantly smaller in patients than in controls (P = 0.001 and 0.000, respectively). The volumes of T1 or T2 lesions in the brain correlated to the ambulation index (r = 0.51, P = 0.005 and r = 0.53, P = 0.004, respectively). No correlations were detected between MRI measurements and total EDSS score, but relative brain atrophy correlated inversely with the total RFSS scores, poor arm index and higher cerebral disturbances (r = -0.53, P = 0.004; r = -0.53, P = 0.004; and r = -0.52, P = 0.005, respectively). Although the number of spinal T2 lesions correlated with sensory disturbances (r = 0.60, P = 0.001), no correlations were found between EDSS subscores and spinal cord atrophy. These findings show that marked atrophy of brain and spinal cord detected by volumetric quantitation correlates with neurological disability. This observation indicates the importance of neurodegenerative events in PPMS. PMID:14641511

  2. Atrophy, hypometabolism and clinical trajectories in patients with amyloid-negative Alzheimer's disease.

    PubMed

    Chételat, Gaël; Ossenkoppele, Rik; Villemagne, Victor L; Perrotin, Audrey; Landeau, Brigitte; Mézenge, Florence; Jagust, William J; Dore, Vincent; Miller, Bruce L; Egret, Stéphanie; Seeley, William W; van der Flier, Wiesje M; La Joie, Renaud; Ames, David; van Berckel, Bart N M; Scheltens, Philip; Barkhof, Frederik; Rowe, Christopher C; Masters, Colin L; de La Sayette, Vincent; Bouwman, Femke; Rabinovici, Gil D

    2016-09-01

    See O'Sullivan and Vann (doi:10.1093/aww166) for a scientific commentary on this article.About 15% of patients clinically diagnosed with Alzheimer's disease do not show high tracer retention on amyloid positon emission tomography imaging. The present study investigates clinical and demographic features, patterns of brain atrophy and hypometabolism and longitudinal clinical trajectories of these patients. Forty amyloid-negative patients carrying a pre-scan diagnosis of Alzheimer's disease dementia from four centres were included (11/29 females/males; mean age = 67 ± 9). Detailed clinical histories, including the clinical diagnoses before and after the amyloid scan and at follow-up, were collected. Patients were classified according to their pre-scan clinical phenotype as amnestic (memory predominant), non-amnestic (predominant language, visuospatial or frontal symptoms), or non-specific (diffuse cognitive deficits). Demographic, clinical, neuropsychological, magnetic resonance imaging and (18)F-fluorodeoxyglucose positon emission tomography data were compared to 27 amyloid-positive typical Alzheimer's disease cases (14/13 females/males; mean age = 71 ± 10) and 29 amyloid-negative controls (15/14 females/males; mean age = 69 ± 12) matched for age, gender and education. There were 21 amnestic, 12 non-amnestic, and seven non-specific amyloid-negative Alzheimer's disease cases. Amyloid-negative subgroups did not differ in age, gender or education. After the amyloid scan, clinicians altered the diagnosis in 68% of amyloid-negative patients including 48% of amnestic versus 94% of non-amnestic and non-specific cases. Amnestic amyloid-negative cases were most often reclassified as frontotemporal dementia, non-amnestic as frontotemporal dementia or corticobasal degeneration, and non-specific as dementia with Lewy bodies or unknown diagnosis. The longer-term clinical follow-up was consistent with the post-scan diagnosis in most cases (90%), including in amnestic amyloid

  3. Atrophy, hypometabolism and clinical trajectories in patients with amyloid-negative Alzheimer's disease.

    PubMed

    Chételat, Gaël; Ossenkoppele, Rik; Villemagne, Victor L; Perrotin, Audrey; Landeau, Brigitte; Mézenge, Florence; Jagust, William J; Dore, Vincent; Miller, Bruce L; Egret, Stéphanie; Seeley, William W; van der Flier, Wiesje M; La Joie, Renaud; Ames, David; van Berckel, Bart N M; Scheltens, Philip; Barkhof, Frederik; Rowe, Christopher C; Masters, Colin L; de La Sayette, Vincent; Bouwman, Femke; Rabinovici, Gil D

    2016-09-01

    See O'Sullivan and Vann (doi:10.1093/aww166) for a scientific commentary on this article.About 15% of patients clinically diagnosed with Alzheimer's disease do not show high tracer retention on amyloid positon emission tomography imaging. The present study investigates clinical and demographic features, patterns of brain atrophy and hypometabolism and longitudinal clinical trajectories of these patients. Forty amyloid-negative patients carrying a pre-scan diagnosis of Alzheimer's disease dementia from four centres were included (11/29 females/males; mean age = 67 ± 9). Detailed clinical histories, including the clinical diagnoses before and after the amyloid scan and at follow-up, were collected. Patients were classified according to their pre-scan clinical phenotype as amnestic (memory predominant), non-amnestic (predominant language, visuospatial or frontal symptoms), or non-specific (diffuse cognitive deficits). Demographic, clinical, neuropsychological, magnetic resonance imaging and (18)F-fluorodeoxyglucose positon emission tomography data were compared to 27 amyloid-positive typical Alzheimer's disease cases (14/13 females/males; mean age = 71 ± 10) and 29 amyloid-negative controls (15/14 females/males; mean age = 69 ± 12) matched for age, gender and education. There were 21 amnestic, 12 non-amnestic, and seven non-specific amyloid-negative Alzheimer's disease cases. Amyloid-negative subgroups did not differ in age, gender or education. After the amyloid scan, clinicians altered the diagnosis in 68% of amyloid-negative patients including 48% of amnestic versus 94% of non-amnestic and non-specific cases. Amnestic amyloid-negative cases were most often reclassified as frontotemporal dementia, non-amnestic as frontotemporal dementia or corticobasal degeneration, and non-specific as dementia with Lewy bodies or unknown diagnosis. The longer-term clinical follow-up was consistent with the post-scan diagnosis in most cases (90%), including in amnestic amyloid

  4. Cerebral blood flow and brain atrophy correlated by xenon contrast CT scanning

    SciTech Connect

    Kitagawa, Y.; Meyer, J.S.; Tanahashi, N.; Rogers, R.L.; Tachibana, H.; Kandula, P.; Dowell, R.E.; Mortel, K.F.

    1985-11-01

    Correlations between cerebral blood flow (CBF) measured during stable xenon contrast CT scanning and standard CT indices of brain atrophy were investigated in the patients with senile dementia of Alzheimer type, multi-infarct dementia and idiopathic Parkinson's disease. Compared to age-matched normal volunteers, significant correlations were found in patients with idiopathic Parkinson's disease between cortical and subcortical gray matter blood flow and brain atrophy estimated by the ventricular body ratio, and mild to moderate brain atrophy were correlated with stepwise CBF reductions. However, in patients with senile dementia of Alzheimer type and multi-infarct dementia, brain atrophy was not associated with stepwise CBF reductions. Overall correlations between brain atrophy and reduced CBF were weak. Mild degrees of brain atrophy are not always associated with reduced CBF.

  5. How Are Cervical Cancers and Pre-Cancers Diagnosed?

    MedlinePlus

    ... How is cervical cancer staged? How is cervical cancer diagnosed? The first step in finding cervical cancer ... systems. Tests for women with symptoms of cervical cancer or abnormal Pap results Medical history and physical ...

  6. Incidence of Brain Atrophy and Decline in Mini-Mental State Examination Score After Whole-Brain Radiotherapy in Patients With Brain Metastases: A Prospective Study

    SciTech Connect

    Shibamoto, Yuta Baba, Fumiya; Oda, Kyota; Hayashi, Shinya; Kokubo, Masaki; Ishihara, Shun-Ichi; Itoh, Yoshiyuki; Ogino, Hiroyuki; Koizumi, Masahiko

    2008-11-15

    Purpose: To determine the incidence of brain atrophy and dementia after whole-brain radiotherapy (WBRT) in patients with brain metastases not undergoing surgery. Methods and Materials: Eligible patients underwent WBRT to 40 Gy in 20 fractions with or without a 10-Gy boost. Brain magnetic resonance imaging or computed tomography and Mini-Mental State Examination (MMSE) were performed before and soon after radiotherapy, every 3 months for 18 months, and every 6 months thereafter. Brain atrophy was evaluated by change in cerebrospinal fluid-cranial ratio (CCR), and the atrophy index was defined as postradiation CCR divided by preradiation CCR. Results: Of 101 patients (median age, 62 years) entering the study, 92 completed WBRT, and 45, 25, and 10 patients were assessable at 6, 12, and 18 months, respectively. Mean atrophy index was 1.24 {+-} 0.39 (SD) at 6 months and 1.32 {+-} 0.40 at 12 months, and 18% and 28% of the patients had an increase in the atrophy index by 30% or greater, respectively. No apparent decrease in mean MMSE score was observed after WBRT. Individually, MMSE scores decreased by four or more points in 11% at 6 months, 12% at 12 months, and 0% at 18 months. However, about half the decrease in MMSE scores was associated with a decrease in performance status caused by systemic disease progression. Conclusions: Brain atrophy developed in up to 30% of patients, but it was not necessarily accompanied by MMSE score decrease. Dementia after WBRT unaccompanied by tumor recurrence was infrequent.

  7. A mixed methods exploration of families' experiences of the diagnosis of childhood spinal muscular atrophy.

    PubMed

    Lawton, Sally; Hickerton, Chriselle; Archibald, Alison D; McClaren, Belinda J; Metcalfe, Sylvia A

    2015-05-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease with a carrier frequency of 1 in 41 in Australia. Childhood SMA is classified into three types based on the age at which children present with symptoms and the clinical severity. Families' experiences leading up to the diagnosis have not been described, but are important when considering the potential for a diagnostic odyssey. Using a mixed methods approach, data were collected from interviews and a national survey of families of children with SMA to explore their experiences of this journey. The combined findings (n=28) revealed that the journey to receiving a diagnosis was protracted. The time from first noticing symptoms to finally receiving a diagnosis was emotional and frustrating. Once parents or other family members became aware of symptoms, almost all had consulted with multiple different health professionals before the diagnosis was ultimately made. Not surprisingly, receiving the diagnosis was devastating to the families. The nature of the information and the way it was given to them was not always optimal, particularly because of the difficulties predicting clinical severity. Most felt that their child could have been diagnosed earlier and, although there were mixed views around the benefit of this for their child, they felt it may have reduced the emotional impact on families. Overall, families were more in favour of population carrier screening for SMA when compared with newborn screening of the population. Despite an increasing awareness of SMA, the diagnostic delay continues to have negative impacts on families. PMID:25074464

  8. Relationship between regional atrophy rates and cognitive decline in mild cognitive impairment.

    PubMed

    McDonald, Carrie R; Gharapetian, Lusineh; McEvoy, Linda K; Fennema-Notestine, Christine; Hagler, Donald J; Holland, Dominic; Dale, Anders M

    2012-02-01

    We investigated the relationship between regional atrophy rates and 2-year cognitive decline in a large cohort of patients with mild cognitive impairment (MCI; n = 103) and healthy controls (n = 90). Longitudinal magnetic resonance image (MRI) scans were analyzed using high-throughput image analysis procedures. Atrophy rates were derived by calculating percent cortical volume loss between baseline and 24 month scans. Stepwise regressions were performed to investigate the contribution of atrophy rates to language, memory, and executive functioning decline, controlling for age, gender, baseline performances, and disease progression. In MCI, left temporal lobe atrophy rates were associated with naming decline, whereas bilateral temporal, left frontal, and left anterior cingulate atrophy rates were associated with semantic fluency decline. Left entorhinal atrophy rate was associated with memory decline and bilateral frontal atrophy rates were associated with executive function decline. These data provide evidence that regional atrophy rates in MCI contribute to domain-specific cognitive decline, which appears to be partially independent of disease progression. MRI measures of regional atrophy can provide valuable information for understanding the neural basis of cognitive impairment in MCI.

  9. Effect of Oenothera odorata Root Extract on Microgravity and Disuse-Induced Muscle Atrophy.

    PubMed

    Lee, Yong-Hyeon; Seo, Dong-Hyun; Park, Ji-Hyung; Kabayama, Kazuya; Opitz, Joerg; Lee, Kwang Ho; Kim, Han-Sung; Kim, Tack-Joong

    2015-01-01

    Muscle atrophy, a reduction of muscle mass, strength, and volume, results from reduced muscle use and plays a key role in various muscular diseases. In the microgravity environment of space especially, muscle atrophy is induced by muscle inactivity. Exposure to microgravity induces muscle atrophy through several biological effects, including associations with reactive oxygen species (ROS). This study used 3D-clinostat to investigate muscle atrophy caused by oxidative stress in vitro, and sciatic denervation was used to investigate muscle atrophy in vivo. We assessed the effect of Oenothera odorata root extract (EVP) on muscle atrophy. EVP helped recover cell viability in C2C12 myoblasts exposed to microgravity for 24 h and delayed muscle atrophy in sciatic denervated mice. However, the expressions of HSP70, SOD1, and ceramide in microgravity-exposed C2C12 myoblasts and in sciatic denervated mice were either decreased or completely inhibited. These results suggested that EVP can be expected to have a positive effect on muscle atrophy by disuse and microgravity. In addition, EVP helped characterize the antioxidant function in muscle atrophy. PMID:25945103

  10. Effect of Oenothera odorata Root Extract on Microgravity and Disuse-Induced Muscle Atrophy

    PubMed Central

    Lee, Yong-Hyeon; Seo, Dong-Hyun; Park, Ji-Hyung; Kabayama, Kazuya; Opitz, Joerg; Lee, Kwang Ho; Kim, Han-Sung; Kim, Tack-Joong

    2015-01-01

    Muscle atrophy, a reduction of muscle mass, strength, and volume, results from reduced muscle use and plays a key role in various muscular diseases. In the microgravity environment of space especially, muscle atrophy is induced by muscle inactivity. Exposure to microgravity induces muscle atrophy through several biological effects, including associations with reactive oxygen species (ROS). This study used 3D-clinostat to investigate muscle atrophy caused by oxidative stress in vitro, and sciatic denervation was used to investigate muscle atrophy in vivo. We assessed the effect of Oenothera odorata root extract (EVP) on muscle atrophy. EVP helped recover cell viability in C2C12 myoblasts exposed to microgravity for 24 h and delayed muscle atrophy in sciatic denervated mice. However, the expressions of HSP70, SOD1, and ceramide in microgravity-exposed C2C12 myoblasts and in sciatic denervated mice were either decreased or completely inhibited. These results suggested that EVP can be expected to have a positive effect on muscle atrophy by disuse and microgravity. In addition, EVP helped characterize the antioxidant function in muscle atrophy. PMID:25945103

  11. Functional brain networks: linking thalamic atrophy to clinical disability in multiple sclerosis, a multimodal fMRI and MEG study.

    PubMed

    Tewarie, Prejaas; Schoonheim, Menno M; Schouten, Daphne I; Polman, Chris H; Balk, Lisanne J; Uitdehaag, Bernard M J; Geurts, Jeroen J G; Hillebrand, Arjan; Barkhof, Frederik; Stam, Cornelis J

    2015-02-01

    Thalamic atrophy is known to be one of the most important predictors for clinical dysfunction in multiple sclerosis (MS). As the thalamus is highly connected to many cortical areas, this suggests that thalamic atrophy is associated with disruption of cortical functional networks. We investigated this thalamo-cortical system to explain the presence of physical and cognitive problems in MS. Functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) were performed in 86 MS patients and 21 healthy subjects. We computed cortical functional networks for fMRI and MEG by respectively the Pearson's correlation coefficient and the phase lag index using the same automated anatomical labeling atlas for both modalities. Thalamo-cortical functional connectivity was only estimated using fMRI. We computed conventional network metrics such as clustering coefficient and path length and analyzed the minimum spanning tree (MST), a subnetwork and backbone of the original network. MS patients showed reduced thalamic volumes and increased thalamo-cortical connectivity. MEG cortical functional networks showed a lower level of integration in MS in terms of the MST, whereas fMRI cortical networks did not differ between groups. Lower integration of MEG cortical functional networks was both related to thalamic atrophy as well as to increased thalamo-cortical functional connectivity in fMRI and to worse cognitive and clinical status. This study demonstrated for the first time that thalamic atrophy is associated with global disruption of cortical functional networks in MS and this global disruption of network activity was related to worse cognitive and clinical function in MS. Hum Brain Mapp 36:603-618, 2015. © 2014 Wiley Periodicals, Inc.

  12. Dominant spinal muscular atrophy with lower extremity predominance

    PubMed Central

    Harms, M.B.; Allred, P.; Gardner, R.; Fernandes Filho, J.A.; Florence, J.; Pestronk, A.; Al-Lozi, M.; Baloh, R.H.

    2010-01-01

    Objective: Spinal muscular atrophies (SMAs) are hereditary disorders characterized by weakness from degeneration of spinal motor neurons. Although most SMA cases with proximal weakness are recessively inherited, rare families with dominant inheritance have been reported. We aimed to clinically, pathologically, and genetically characterize a large North American family with an autosomal dominant proximal SMA. Methods: Affected family members underwent clinical and electrophysiologic evaluation. Twenty family members were genotyped on high-density genome-wide SNP arrays and linkage analysis was performed. Results: Ten affected individuals (ages 7–58 years) showed prominent quadriceps atrophy, moderate to severe weakness of quadriceps and hip abductors, and milder degrees of weakness in other leg muscles. Upper extremity strength and sensation was normal. Leg weakness was evident from early childhood and was static or very slowly progressive. Electrophysiology and muscle biopsies were consistent with chronic denervation. SNP-based linkage analysis showed a maximum 2-point lod score of 5.10 (θ = 0.00) at rs17679127 on 14q32. A disease-associated haplotype spanning from 114 cM to the 14q telomere was identified. A single recombination narrowed the minimal genomic interval to Chr14: 100,220,765–106,368,585. No segregating copy number variations were found within the disease interval. Conclusions: We describe a family with an early onset, autosomal dominant, proximal SMA with a distinctive phenotype: symptoms are limited to the legs and there is notable selectivity for the quadriceps. We demonstrate linkage to a 6.1-Mb interval on 14q32 and propose calling this disorder spinal muscular atrophy–lower extremity, dominant. GLOSSARY lod = logarithm of the odds; SMA = spinal muscular atrophy; SMA-LED = spinal muscular atrophy–lower extremity, dominant; SNP = single-nucleotide polymorphism. PMID:20697106

  13. Disruptive SCYL1 Mutations Underlie a Syndrome Characterized by Recurrent Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia

    PubMed Central

    Schmidt, Wolfgang M.; Rutledge, S. Lane; Schüle, Rebecca; Mayerhofer, Benjamin; Züchner, Stephan; Boltshauser, Eugen; Bittner, Reginald E.

    2015-01-01

    Hereditary ataxias comprise a group of genetically heterogeneous disorders characterized by clinically variable cerebellar dysfunction and accompanied by involvement of other organ systems. The molecular underpinnings for many of these diseases are widely unknown. Previously, we discovered the disruption of Scyl1 as the molecular basis of the mouse mutant mdf, which is affected by neurogenic muscular atrophy, progressive gait ataxia with tremor, cerebellar vermis atrophy, and optic-nerve thinning. Here, we report on three human individuals, from two unrelated families, who presented with recurrent episodes of acute liver failure in early infancy and are affected by cerebellar vermis atrophy, ataxia, and peripheral neuropathy. By whole-exome sequencing, compound-heterozygous mutations within SCYL1 were identified in all affected individuals. We further show that in SCYL1-deficient human fibroblasts, the Golgi apparatus is massively enlarged, which is in line with the concept that SCYL1 regulates Golgi integrity. Thus, our findings define SCYL1 mutations as the genetic cause of a human hepatocerebellar neuropathy syndrome. PMID:26581903

  14. Molecular detection of chicken parvovirus in broilers with enteric disorders presenting curving of duodenal loop, pancreatic atrophy, and mesenteritis.

    PubMed

    Nuñez, L F N; Sá, L R M; Parra, S H S; Astolfi-Ferreira, C S; Carranza, C; Ferreira, A J P

    2016-04-01

    Enteric disorders are an important cause of economic losses in broiler chickens worldwide. Several agents have been associated with enteric problems, such as viruses, bacteria, and parasites. In this study, broiler chickens showing signs of enteric disorders were subjected to molecular diagnosis for several viral agents and also for pathological examination for elucidating this problem. Thus, the chickens were screened for avian nephritis virus (ANV), chicken astrovirus (CAstV), avian rotavirus (ArtV), avian reovirus (AReoV), infectious bronchitis virus (IBV), fowl adenovirus group I (FAdV-1), and chicken parvovirus (ChPV). Postmortem examinations revealed a curving of the duodenal loop (J-like appearance) and intestines filled with liquid and gaseous content. Histopathological analysis of the duodenal loop showed pancreatic atrophy, acute mesenteritis, and enteritis. PCR results showed that ChPV was the sole viral agent detected in samples with lesions such as the curved duodenal loop and pancreatic atrophy. Molecular characterization of the nucleotide and deduced amino acid sequences revealed a high similarity with other strains of ChPV from Brazil, Canada, United States, Europe, and Asia. These findings suggest an association between ChPV and the development of enteritis, pancreatitis, and pancreatic atrophy, which may lead to curling of the duodenal loop. Together, these alterations may disrupt the normal functioning of the digestive system, diminishing digestion and the absorption of dietary nutrients and consequently leading to reduced weight gain, flock impairment, dwarfism, and an elevated feed conversion rate. PMID:26908891

  15. Molecular detection of chicken parvovirus in broilers with enteric disorders presenting curving of duodenal loop, pancreatic atrophy, and mesenteritis.

    PubMed

    Nuñez, L F N; Sá, L R M; Parra, S H S; Astolfi-Ferreira, C S; Carranza, C; Ferreira, A J P

    2016-04-01

    Enteric disorders are an important cause of economic losses in broiler chickens worldwide. Several agents have been associated with enteric problems, such as viruses, bacteria, and parasites. In this study, broiler chickens showing signs of enteric disorders were subjected to molecular diagnosis for several viral agents and also for pathological examination for elucidating this problem. Thus, the chickens were screened for avian nephritis virus (ANV), chicken astrovirus (CAstV), avian rotavirus (ArtV), avian reovirus (AReoV), infectious bronchitis virus (IBV), fowl adenovirus group I (FAdV-1), and chicken parvovirus (ChPV). Postmortem examinations revealed a curving of the duodenal loop (J-like appearance) and intestines filled with liquid and gaseous content. Histopathological analysis of the duodenal loop showed pancreatic atrophy, acute mesenteritis, and enteritis. PCR results showed that ChPV was the sole viral agent detected in samples with lesions such as the curved duodenal loop and pancreatic atrophy. Molecular characterization of the nucleotide and deduced amino acid sequences revealed a high similarity with other strains of ChPV from Brazil, Canada, United States, Europe, and Asia. These findings suggest an association between ChPV and the development of enteritis, pancreatitis, and pancreatic atrophy, which may lead to curling of the duodenal loop. Together, these alterations may disrupt the normal functioning of the digestive system, diminishing digestion and the absorption of dietary nutrients and consequently leading to reduced weight gain, flock impairment, dwarfism, and an elevated feed conversion rate.

  16. Protective variant for hippocampal atrophy identified by whole exome sequencing.

    PubMed

    Nho, Kwangsik; Kim, Sungeun; Risacher, Shannon L; Shen, Li; Corneveaux, Jason J; Swaminathan, Shanker; Lin, Hai; Ramanan, Vijay K; Liu, Yunlong; Foroud, Tatiana M; Inlow, Mark H; Siniard, Ashley L; Reiman, Rebecca A; Aisen, Paul S; Petersen, Ronald C; Green, Robert C; Jack, Clifford R; Weiner, Michael W; Baldwin, Clinton T; Lunetta, Kathryn L; Farrer, Lindsay A; Furney, Simon J; Lovestone, Simon; Simmons, Andrew; Mecocci, Patrizia; Vellas, Bruno; Tsolaki, Magda; Kloszewska, Iwona; Soininen, Hilkka; McDonald, Brenna C; Farlow, Martin R; Ghetti, Bernardino; Huentelman, Matthew J; Saykin, Andrew J

    2015-03-01

    We used whole-exome sequencing to identify variants other than APOE associated with the rate of hippocampal atrophy in amnestic mild cognitive impairment. An in-silico predicted missense variant in REST (rs3796529) was found exclusively in subjects with slow hippocampal volume loss and validated using unbiased whole-brain analysis and meta-analysis across 5 independent cohorts. REST is a master regulator of neurogenesis and neuronal differentiation that has not been previously implicated in Alzheimer's disease. These findings nominate REST and its functional pathways as protective and illustrate the potential of combining next-generation sequencing with neuroimaging to discover novel disease mechanisms and potential therapeutic targets. PMID:25559091

  17. Testicular atrophy in Columbian black-tailed deer in California.

    PubMed

    DeMartini, J C; Connolly, G E

    1975-01-01

    During an 18-year period, 4.1% (34/831) of male deer (Odocoileus hemionus columbianus) killed on a field station during the autumn hunting season had velvet-covered, often misshapen antlers, and at least two deer had testicular atrophy (gonads from most deer were not available for examination). Testes from six similarly affected deer and several normal deer were compared histologically. Lesions ranged from hypocellularity of the semeniferous tubules and relative hyperplasia or degeneration of interstitial cells to complete connective tissue replacement of the testicular parencyma. Chronic vascular changes were present in several testes. The etiology and pathogenesis of the lesions were not determined.

  18. Evaluation of the endogenous glucocorticoid hypothesis of denervation atrophy

    NASA Technical Reports Server (NTRS)

    Konagaya, Masaaki; Konagaya, Yoko; Max, Stephen R.

    1988-01-01

    The effects are studied of the oral administration of RU38486, a potent selective glucocorticoid antagonist, on muscle weight, non-collagen protein content, and selected enzyme activities (choline acetyltransferase, glucose 6-phosphate dehydrogenase, and glutamine synthetase) following denervation of rat skeletal muscle. Neither decreases in muscle weight, protein content, and choline acetyltransferase activity, nor increases in the activities of glucose 6-phosphate dehydrogernase and glutamine synthetase were affected by RU38486. These data do not support the hypothesis that denervation atrophy results from enhanced sensitivity of muscle to endogenous glucocorticoids.

  19. C-shaped mandibular primary first molar diagnosed with cone beam computed tomography: A novel case report and literature review of primary molars' root canal systems.

    PubMed

    Ozcan, Gozde; Sekerci, Ahmet Ercan; Kocoglu, Fatma

    2016-01-01

    Knowledge of the different anatomical variations in root canal system of dedicious dentition will improve the practice of the pediatric dentists. The teeth with C-shaped root canal configurations are definitely a problem in endodontic treatment. Dentists who are specialists of endodontics must have adequate knowledge about various root canal morphologies of primary tooth that have a tendency for rapid progression of dental caries to achieve a technically satisfactory outcome. This report presents an extraordinary case of unusual tooth morphology involving the mandibular first primary molar with a C-shaped configuration which has not yet been reported. PMID:27681406

  20. Dentatorubropallidoluysian atrophy without involuntary movement or dementia--a case report.

    PubMed

    Kasahata, Naoki; Iwasaki, Yasuo

    2010-10-01

    Recently, discussions about the clinical features of dentatorubropallidoluysian atrophy (DRPLA), especially the existence of an ataxo-choreoathetoid type, have increased. Traditionally, DRPLA patients have been thought to present with involuntary movements and dementia. Here, we report a patient that presented with ataxia, spasticity of the right lower extremity and mild sensory disturbances. He did not show either apparent involuntary movement or dementia. Mini-mental state examination demonstrated a score of 29/30. The cerebellar output system involving the dentate nuclei and superior cerebellar peduncles seemed to be atrophic yet the cerebellar input system involving the middle cerebellar peduncles was preserved on MRI. In addition, there was an expansion of the atrophin1 (ATN1) CAG repeat of chromosome 12p: 9/61. This seems to be the first case report of a genetically confirmed DRPLA patient presenting with clinical manifestations of Machado-Joseph disease (MJD/SCA3). PMID:20627552

  1. Near Real-time Immuno-optical Sensor for Diagnosing Single Point Mutation (A model System: Sensor for Factor V Leiden Diagnosis)

    PubMed Central

    Kang, Kyung A.; Ren, Yongjie; Sharma, Vivek R.; Peiper, Stephen C.

    2009-01-01

    Factor V leiden (FVL) is an abnormality of factor V (FV), a blood coagulation factor. It is a hereditary blood coagulation disorder with a high frequency (3–7% of general population). The most common type of FVL is caused by a single amino acid mutation and, therefore, its diagnosis is currently done only by DNA analysis, which takes a long time and is expensive. We have developed a rapid, accurate, and cost-effective, sandwich immuno-optical sensing method. To produce monoclonal antibodies against FV or FVL, having minimal cross-reactivity with the other molecule, a 20 amino acid sequence (20-mer) of FV or FVL at around the mutation site was utilized. The antibodies were screened first with the 20-mers and then with native FV or FVL molecules and they showed some cross reactivity. Using two antibodies having strongest affinity to either FV or FVL molecule, a FV and a FVL preferred sensors, were produced. After verifying that the levels of the antibody affinity to the two different molecules remained constant with changes in analyte concentration, a two-sensor system is developed to quantify FV and FVL in plasma samples. The system quantified the levels of FV and FVL at the maximum error of 0.5 μg/ml-plasma, in their physiological concentration range of 0–12 μg/ml-plasma. The levels of both molecules may provide us whether the patient has FVL or not but also the seriousness level of the disease (homozygous and different level of heterozygous). PMID:19318242

  2. Differences by race, sex and age in the clinical and immunologic features of recently diagnosed systemic lupus erythematosus patients in the southeastern United States.

    PubMed

    Cooper, G S; Parks, C G; Treadwell, E L; St Clair, E W; Gilkeson, G S; Cohen, P L; Roubey, R A S; Dooley, M A

    2002-01-01

    We examined the prevalence of clinical and immunologic features of systemic lupus erythematosus (SLE) by race, sex and age in a population-based study of 265 SLE patients. Patients fulfilled the American College of Rheumatology classification criteria. The median time between diagnosis and study enrollment was 13 months. The clinical and hematologic data were limited to occurrences up to 6 months after the diagnosis date, as documented in medical records. We used sera collected at study enrollment from 244 (92%) patients for serologic testing of autoantibodies. The associations between clinical and immunological features of SLE and age, sex and race were examined using logistic regression. The effect of each of these variables was examined adjusting for the other two demographic factors. Mean age at diagnosis was 6 years younger among African-Americans and other minorities compared with white patients (P < 0.01). Discoid lupus, proteinuria, anti-Sm and anti-RNP autoantibodies were more commonly seen in African-American patients, with odds ratios higher than 3.0. Photosensitivity and mucosal ulcers were noted less often in African-American patients. Proteinuria, leukopenia, lymphopenia and thrombocytopenia were approximately three times more common in men compared with women. The prevalence of oral or nasal ulcers and anti-DNA autoantibodies declined with age. The extent to which the differences we observed reflect genetic or environmental influences on the disease process should be investigated.

  3. Feasibility of the Medial Temporal lobe Atrophy index (MTAi) and derived methods for measuring atrophy of the medial temporal lobe

    PubMed Central

    Conejo Bayón, Francisco; Maese, Jesús; Fernandez Oliveira, Aníbal; Mesas, Tamara; Herrera de la Llave, Estibaliz; Álvarez Avellón, Tania; Menéndez-González, Manuel

    2014-01-01

    Introduction: The Medial Temporal-lobe Atrophy index (MTAi), 2D-Medial Temporal Atrophy (2D-MTA), yearly rate of MTA (yrRMTA) and yearly rate of relative MTA (yrRMTA) are simple protocols for measuring the relative extent of atrophy in the medial temporal lobe (MTL) in relation to the global brain atrophy. Albeit preliminary studies showed interest of these methods in the diagnosis of Alzheimer’s disease (AD), frontotemporal lobe degeneration (FTLD) and correlation with cognitive impairment in Parkinson’s disease (PD), formal feasibility and validity studies remained pending. As a first step, we aimed to assess the feasibility. Mainly, we aimed to assess the reproducibility of measuring the areas needed to compute these indices. We also aimed to assess the efforts needed to start using these methods correctly. Methods: A series of 290 1.5T-MRI studies from 230 subjects ranging 65–85 years old who had been studied for cognitive impairment were used in this study. Six inexperienced tracers (IT) plus one experienced tracer (ET) traced the three areas needed to compute the indices. Finally, tracers underwent a short survey on their experience learning to compute the MTAi and experience of usage, including items relative to training time needed to understand and apply the MTAi, time to perform a study after training and overall satisfaction. Results: Learning to trace the areas needed to compute the MTAi and derived methods is quick and easy. Results indicate very good intrarater Intraclass Correlation Coefficient (ICC) for the MTAi, good intrarater ICC for the 2D-MTA, yrMTA and yrRMTA and also good interrater ICC for the MTAi, 2D-MTA, yrMTA and yrRMTA. Conclusion: Our data support that MTAi and derived methods (2D-MTA, yrMTA and yrRTMA) have good to very good intrarater and interrater reproducibility and may be easily implemented in clinical practice even if new users have no experience tracing the area of regions of interest. PMID:25414666

  4. Expression and purification of Suid Herpesvirus-1 glycoprotein E in the baculovirus system and its use to diagnose Aujeszky's disease in infected pigs.

    PubMed

    Serena, María Soledad; Geisler, Christoph; Metz, Germán Ernesto; Corva, Santiago Gerardo; Mórtola, Eduardo Carlos; Larsen, Alejandra; Jarvis, Donald L; Echeverría, María Gabriela

    2013-07-01

    Suid Herpesvirus 1 (SHV-1) is the etiological agent of Aujeszky's disease (AD), which affects swine herds worldwide and causes substantial economic losses due to animal mortality and lost productivity. In order to eradicate SHV-1, vaccination programs using viruses lacking the gene encoding glycoprotein E (gE) are ongoing in several countries. These eradication programs have generated a currently unmet demand for affordable and sensitive tests that can detect SHV-1 infection, yet distinguish between infected and vaccinated pigs. To meet this demand, we used the baculovirus-insect cell system to produce immunologically authentic full-length recombinant gE protein for use in a serum ELISA assay. As previous efforts to clone the gE gene had failed due to its extremely high GC-content (75% average), we used betaine as a PCR enhancer to facilitate amplification of the entire gE gene from the Argentinian CL15 strain of SHV-1. The cloned gE gene was expressed at high levels in recombinant baculovirus-infected insect cells and reacted strongly with sera from SHV-1 infected pigs. We used the recombinant gE protein to develop a local indirect ELISA test with sensitivity and specificity comparable to currently available commercial tests. Thus, recombinant gE produced in baculovirus-infected insect cells is a viable source of antigen for the detection of SHV-1 in ELISA tests. We also provide evidence supporting a potential application of this recombinant form of gE as a SHV-1 subunit vaccine. PMID:23631926

  5. Nuclear factor-kappa B signaling in skeletal muscle atrophy.

    PubMed

    Li, Hong; Malhotra, Shweta; Kumar, Ashok

    2008-10-01

    Skeletal muscle atrophy/wasting is a serious complication of a wide range of diseases and conditions such as aging, disuse, AIDS, chronic obstructive pulmonary disease, space travel, muscular dystrophy, chronic heart failure, sepsis, and cancer. Emerging evidence suggests that nuclear factor-kappa B (NF-kappaB) is one of the most important signaling pathways linked to the loss of skeletal muscle mass in various physiological and pathophysiological conditions. Activation of NF-kappaB in skeletal muscle leads to degradation of specific muscle proteins, induces inflammation and fibrosis, and blocks the regeneration of myofibers after injury/atrophy. Recent studies employing genetic mouse models have provided strong evidence that NF-kappaB can serve as an important molecular target for the prevention of skeletal muscle loss. In this article, we have outlined the current understanding regarding the role of NF-kappaB in skeletal muscle with particular reference to different models of muscle wasting and the development of novel therapy.

  6. Molecular Mechanisms of Neurodegeneration in Spinal Muscular Atrophy

    PubMed Central

    Ahmad, Saif; Bhatia, Kanchan; Kannan, Annapoorna; Gangwani, Laxman

    2016-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease with a high incidence and is the most common genetic cause of infant mortality. SMA is primarily characterized by degeneration of the spinal motor neurons that leads to skeletal muscle atrophy followed by symmetric limb paralysis, respiratory failure, and death. In humans, mutation of the Survival Motor Neuron 1 (SMN1) gene shifts the load of expression of SMN protein to the SMN2 gene that produces low levels of full-length SMN protein because of alternative splicing, which are sufficient for embryonic development and survival but result in SMA. The molecular mechanisms of the (a) regulation of SMN gene expression and (b) degeneration of motor neurons caused by low levels of SMN are unclear. However, some progress has been made in recent years that have provided new insights into understanding of the cellular and molecular basis of SMA pathogenesis. In this review, we have briefly summarized recent advances toward understanding of the molecular mechanisms of regulation of SMN levels and signaling mechanisms that mediate neurodegeneration in SMA. PMID:27042141

  7. Disease Mechanisms and Therapeutic Approaches in Spinal Muscular Atrophy

    PubMed Central

    Tisdale, Sarah

    2015-01-01

    Motor neuron diseases are neurological disorders characterized primarily by the degeneration of spinal motor neurons, skeletal muscle atrophy, and debilitating and often fatal motor dysfunction. Spinal muscular atrophy (SMA) is an autosomal-recessive motor neuron disease of high incidence and severity and the most common genetic cause of infant mortality. SMA is caused by homozygous mutations in the survival motor neuron 1 (SMN1) gene and retention of at least one copy of the hypomorphic gene paralog SMN2. Early studies established a loss-of-function disease mechanism involving ubiquitous SMN deficiency and suggested SMN upregulation as a possible therapeutic approach. In recent years, greater knowledge of the central role of SMN in RNA processing combined with deep characterization of animal models of SMA has significantly advanced our understanding of the cellular and molecular basis of the disease. SMA is emerging as an RNA disease not limited to motor neurons, but one that involves dysfunction of motor circuits that comprise multiple neuronal subpopulations and possibly other cell types. Advances in SMA research have also led to the development of several potential therapeutics shown to be effective in animal models of SMA that are now in clinical trials. These agents offer unprecedented promise for the treatment of this still incurable neurodegenerative disease. PMID:26063904

  8. Neuropsychiatric Symptoms in Posterior Cortical Atrophy and Alzheimer Disease

    PubMed Central

    Crutch, Sebastian J.; Franco-Macías, Emilio; Gil-Néciga, Eulogio

    2016-01-01

    Background: Posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome characterized by early progressive visual dysfunction in the context of relative preservation of memory and a pattern of atrophy mainly involving the posterior cortex. The aim of the present study is to characterize the neuropsychiatric profile of PCA. Methods: The Neuropsychiatric Inventory was used to assess 12 neuropsychiatric symptoms (NPS) in 28 patients with PCA and 34 patients with typical Alzheimer disease (AD) matched by age, disease duration, and illness severity. Results: The most commonly reported NPS in both groups were depression, anxiety, apathy, and irritability. However, aside from a trend toward lower rates of apathy in patients with PCA, there were no differences in the percentage of NPS presented in each group. All those patients presenting visual hallucinations in the PCA group also met diagnostic criteria for dementia with Lewy bodies (DLB). Auditory hallucinations were only present in patients meeting diagnosis criteria for DLB. Conclusion: Prevalence of the 12 NPS examined was similar between patients with PCA and AD. Hallucinations in PCA may be helpful in the differential diagnosis between PCA-AD and PCA-DLB. PMID:26404166

  9. The evolution of alexia and simultanagnosia in posterior cortical atrophy.

    PubMed

    Mendez, M F; Cherrier, M M

    1998-04-01

    Early alexia and higher visual impairments characterize Posterior cortical atrophy (PCA), a progressive dementing syndrome most often caused by Alzheimer disease. Posterior cortical atrophy is rare, and the nature of the visual impairments in PCA are unclear. The authors observed two patients who had an insidiously progressive reading difficulty characterized by letter-by-letter reading and otherwise intact cognitive functions. Over time, these patients developed "ventral simultanagnosia" with preserved detection of multiple stimuli but inability to interpret whole scenes. Subsequently, they progressed to Balint syndrome with "dorsal simultanagnosia," optic ataxia, and oculomotor apraxia. Structural imaging was normal, but functional imaging revealed posterior cortical dysfunction. On a letter reading task, both patients had a word superiority effect, and on a whole word reading task, they could not read most words with missing or crosshatched letters. An inability to assess whole scenes progressed to an inability to detect more than one stimulus in an array. These findings suggest an evolution of PCA with progressive difficulty in visual integration beginning with letters, progressing to whole scenes, and culminating in Balint syndrome. These changes may reflect an extension of the pathophysiology of PCA from the extrastriate visual cortex to its occipitotemporal and occipitoparietal connections. PMID:9652488

  10. [Spinal muscle atrophy in Brown Swiss x Braunvieh cross calves].

    PubMed

    Dirksen, G; Doll, K; Hafner, A; Hermanns, W; Dahme, E

    1992-05-01

    The report describes seven SMA-cases in descendents of crossbreeds of American Brown Swiss x Deutsches Braunvieh. Symptoms and course: After initially normal development of the calves for one to six weeks the disease set in suddenly followed by a rapid lethal course of one to one and a half weeks duration due to asphyxia and/or secondary diseases. Only one case was reported having been sick since birth (?). Characteristic signs were rapidly progressing muscular atrophy, paresis and paralysis of the limbs, the trunk and the diaphragm, usually accompanied by progressive dyspnoea. Signs of congenital neuromyodysplasia (arthrogryposis) of different degree were present in four of the seven calves. Six calves had contracted a secondary pneumonia. Blood gas analysis (6/7) revealed a compensated (1x) or decompensated (4x) respiratory acidosis. Neurohistological findings: Degeneration and loss of motor neurons in the ventral horns of the spinal cord and neurogenic muscular atrophy. Immunohistochemistry revealed a pronounced accumulation of type 200 kD-neurofilaments in perikarya and dendrites of ventral horn motoneurons indicating disturbed mechanisms of the axonal transport. The disease seems to be inherited as a recessive trait.

  11. Molecular Mechanisms of Obesity-Induced Osteoporosis and Muscle Atrophy

    PubMed Central

    Roy, Bipradas; Curtis, Mary E.; Fears, Letimicia S.; Nahashon, Samuel N.; Fentress, Hugh M.

    2016-01-01

    Obesity and osteoporosis are two alarming health disorders prominent among middle and old age populations, and the numbers of those affected by these two disorders are increasing. It is estimated that more than 600 million adults are obese and over 200 million people have osteoporosis worldwide. Interestingly, both of these abnormalities share some common features including a genetic predisposition, and a common origin: bone marrow mesenchymal stromal cells. Obesity is characterized by the expression of leptin, adiponectin, interleukin 6 (IL-6), interleukin 10 (IL-10), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), macrophage colony stimulating factor (M-CSF), growth hormone (GH), parathyroid hormone (PTH), angiotensin II (Ang II), 5-hydroxy-tryptamine (5-HT), Advance glycation end products (AGE), and myostatin, which exert their effects by modulating the signaling pathways within bone and muscle. Chemical messengers (e.g., TNF-α, IL-6, AGE, leptins) that are upregulated or downregulated as a result of obesity have been shown to act as negative regulators of osteoblasts, osteocytes and muscles, as well as positive regulators of osteoclasts. These additive effects of obesity ultimately increase the risk for osteoporosis and muscle atrophy. The aim of this review is to identify the potential cellular mechanisms through which obesity may facilitate osteoporosis, muscle atrophy and bone fractures. PMID:27746742

  12. Evaluation of the etiology of ocular globe atrophy or loss.

    PubMed

    Côas, Viviane Regina; Neves, Ana Christina Claro; Rode, Sigmar de Mello

    2005-01-01

    This survey investigated the etiology of atrophy or loss of the ocular globe in patients assisted at the Maxillofacial Prosthetics Clinic of two Schools of Dentistry in São Paulo State, Brazil. A total of 238 patients were examined and their clinical files were reviewed. The etiology of eyeball atrophy/loss was assessed with respect to gender, age group, affected side and type ophthalmologic surgery performed. The greatest incidence of ocular globe loss was due to traumatic etiology (57.14%), followed by pathogenic (36.13%) and congenital (5.04%) etiologies. Comparing the genders, a predominance of male patients was observed (61.76%; p<0.01). The age group most frequently affected was between 21 and 40 years (42.01%; p<0.01). For all types of etiologies investigated in this study, enucleation was the most commonly used surgical procedure for removal of the ocular globe (66.38%; p<0.01). Loss of the left eye was predominantly seen (55.04%), even though no statistically significant difference was found between sides (p>0.01).

  13. Diagnosing faults in autonomous robot plan execution

    NASA Technical Reports Server (NTRS)

    Lam, Raymond K.; Doshi, Rajkumar S.; Atkinson, David J.; Lawson, Denise M.

    1989-01-01

    A major requirement for an autonomous robot is the capability to diagnose faults during plan execution in an uncertain environment. Many diagnostic researches concentrate only on hardware failures within an autonomous robot. Taking a different approach, the implementation of a Telerobot Diagnostic System that addresses, in addition to the hardware failures, failures caused by unexpected event changes in the environment or failures due to plan errors, is described. One feature of the system is the utilization of task-plan knowledge and context information to deduce fault symptoms. This forward deduction provides valuable information on past activities and the current expectations of a robotic event, both of which can guide the plan-execution inference process. The inference process adopts a model-based technique to recreate the plan-execution process and to confirm fault-source hypotheses. This technique allows the system to diagnose multiple faults due to either unexpected plan failures or hardware errors. This research initiates a major effort to investigate relationships between hardware faults and plan errors, relationships which were not addressed in the past. The results of this research will provide a clear understanding of how to generate a better task planner for an autonomous robot and how to recover the robot from faults in a critical environment.

  14. Diagnosing faults in autonomous robot plan execution

    NASA Technical Reports Server (NTRS)

    Lam, Raymond K.; Doshi, Rajkumar S.; Atkinson, David J.; Lawson, Denise M.

    1988-01-01

    A major requirement for an autonomous robot is the capability to diagnose faults during plan execution in an uncertain environment. Many diagnostic researches concentrate only on hardware failures within an autonomous robot. Taking a different approach, the implementation of a Telerobot Diagnostic System that addresses, in addition to the hardware failures, failures caused by unexpected event changes in the environment or failures due to plan errors, is described. One feature of the system is the utilization of task-plan knowledge and context information to deduce fault symptoms. This forward deduction provides valuable information on past activities and the current expectations of a robotic event, both of which can guide the plan-execution inference process. The inference process adopts a model-based technique to recreate the plan-execution process and to confirm fault-source hypotheses. This technique allows the system to diagnose multiple faults due to either unexpected plan failures or hardware errors. This research initiates a major effort to investigate relationships between hardware faults and plan errors, relationships which were not addressed in the past. The results of this research will provide a clear understanding of how to generate a better task planner for an autonomous robot and how to recover the robot from faults in a critical environment.

  15. Diagnosing and managing peripartum headache

    PubMed Central

    Wang, Jia; Gelpi, Brian; Wortman, Alison; Tao, Weike

    2015-01-01

    A 38-year-old gravida 7 para 5 Hispanic woman at 36 weeks and 4 days gestation presented with a postpartum headache following vaginal delivery complicated by an unintentional dural puncture for epidural analgesia. Due to the positional nature of the headache and its frontal and occipital origin, a postdural puncture headache was diagnosed. After failure of conservative treatment, an epidural blood patch was used, which offered immediate relief. However, shortly following the procedure, the parturient's neurological condition deteriorated due to an unrecognized intraparenchymal and subarachnoid hemorrhage requiring an emergent craniectomy. This case highlights the importance of diligence when evaluating and treating postpartum headache despite a classic presentation. PMID:26424942

  16. Exposure to Endosulfan can result in male infertility due to testicular atrophy and reduced sperm count

    PubMed Central

    Sebastian, R; Raghavan, SC

    2015-01-01

    Endosulfan (ES) is a widely used organochlorine pesticide and is speculated to be detrimental to human health. However, very little is known about mechanism of its genotoxicity. Using mouse model system, we show that exposure to ES affected physiology and cellular architecture of organs and tissues. Among all organs, damage to testes was extensive and it resulted in death of different testicular-cell populations. We find that the damage in testes resulted in qualitative and quantitative defects during spermatogenesis in a time-dependent manner, increasing epididymal reactive oxygen species levels, affecting sperm chromatin integrity. This further culminated in reduced number of epididymal sperms and actively motile sperms. Finally, we show that ES exposure affected fertility in male but not in female mice. Therefore, we demonstrate that ES exerts pathophysiological changes in mice, induces testicular atrophy, affects spermatogenesis, reduces quantity and vigour of epididymal sperm and leads to infertility in males. PMID:27551453

  17. Treating relapsing-remitting multiple sclerosis: therapy effects on brain atrophy.

    PubMed

    Vidal-Jordana, Angela; Sastre-Garriga, Jaume; Rovira, Alex; Montalban, Xavier

    2015-12-01

    Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system with a complex and heterogeneous pathology that may ultimately lead to neurodegeneration and brain atrophy. Brain volume loss in MS is known to occur early in the disease course and to be clinically relevant, as it has been related to disability progression. Nowadays, brain volume loss is relatively easy to measure with different automated, reproducible and accurate software tools. Therefore, most of (if not all) the newest clinical trials have incorporated brain volume outcomes as a measure of treatment effect. With this review, we aimed to update and summarize all existing data regarding brain volume and RRMS treatment in clinical trials as well as in open-label observational studies of drugs with positive results in its primary outcome in at least one phase III trial as of March 2014.

  18. Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer’s disease

    PubMed Central

    Zhang, Xiuming; Mormino, Elizabeth C.; Sun, Nanbo; Sperling, Reisa A.; Sabuncu, Mert R.; Yeo, B. T. Thomas

    2016-01-01

    We used a data-driven Bayesian model to automatically identify distinct latent factors of overlapping atrophy patterns from voxelwise structural MRIs of late-onset Alzheimer’s disease (AD) dementia patients. Our approach estimated the extent to which multiple distinct atrophy patterns were expressed within each participant rather than assuming that each participant expressed a single atrophy factor. The model revealed a temporal atrophy factor (medial temporal cortex, hippocampus, and amygdala), a subcortical atrophy factor (striatum, thalamus, and cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal, and lateral occipital cortices). To explore the influence of each factor in early AD, atrophy factor compositions were inferred in beta-amyloid–positive (Aβ+) mild cognitively impaired (MCI) and cognitively normal (CN) participants. All three factors were associated with memory decline across the entire clinical spectrum, whereas the cortical factor was associated with executive function decline in Aβ+ MCI participants and AD dementia patients. Direct comparison between factors revealed that the temporal factor showed the strongest association with memory, whereas the cortical factor showed the strongest association with executive function. The subcortical factor was associated with the slowest decline for both memory and executive function compared with temporal and cortical factors. These results suggest that distinct patterns of atrophy influence decline across different cognitive domains. Quantification of this heterogeneity may enable the computation of individual-level predictions relevant for disease monitoring and customized therapies. Factor compositions of participants and code used in this article are publicly available for future research. PMID:27702899

  19. The relationship of pineal calcification to cerebral atrophy on CT scan in multiple sclerosis.

    PubMed

    Sandyk, R; Awerbuch, G I

    1994-05-01

    Calcification is a known morphological feature of the pineal gland. The mechanisms underlying the development of pineal calcification (PC) are elusive although there is experimental evidence that calcification may be a marker of the past secretory activity of the gland and/or of degeneration. The increased incidence of PC with aging suggests that it may reflect cerebral degenerative changes as well. In a recent Editorial in this Journal it was proposed that the pineal gland is implicated in the pathogenesis of multiple sclerosis (MS). Cerebral atrophy, which can be demonstrated on CT scan, is a common feature of MS resulting from demyelination and gliosis. If PC is a marker of a cerebral degenerative process, then one would expect a higher incidence of calcification of the gland in patients with cerebral atrophy compared to those without cerebral atrophy. To test this hypothesis, we studied the incidence of PC on CT scan in a cohort of 48 MS patients, 21 of whom had cerebral atrophy. For the purpose of comparison, we also assessed the incidence of choroid plexus calcification (CPC) in relation to cerebral atrophy. PC was found in 42 patients (87.5%) and its incidence in patients with cerebral atrophy was significantly higher compared to the incidence in patients without cerebral atrophy (100% vs. 77.7%; p < .025). In contrast, CPC was unrelated to cerebral atrophy or to PC thus supporting the notion of a specific association between the pineal gland and the pathogenesis of MS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7960471

  20. [The hemodynamic disorders in Sudeck's atrophy and the effect on them of interference therapy].

    PubMed

    Nikolova, L

    1992-01-01

    Interferential currents applied to the forearm fracture region of 80 patients with Sudeck atrophy eliminated hemodynamic changes in the affected limb as shown by capillaroscopy, rheovasography. The effect of the treatment is attributed to recovery of normal blood flow and microcirculation in the region of bone atrophy as well as analgetic action of pulse current. PMID:1384234