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  1. Learn About Neuromuscular Disease

    Science.gov (United States)

    ... for MDA Blog Donate Search MDA.org Close Learn About Neuromuscular Disease Muscular dystrophy, ALS and related ... power of a multiple-disease approach, MDA leverages learnings from one disease to accelerate progress in others ...

  2. Hereditary neuromuscular diseases

    Energy Technology Data Exchange (ETDEWEB)

    Oezsarlak, O. E-mail: ozkan.ozsarlak@uza.be; Schepens, E.; Parizel, P.M.; Goethem, J.W. van; Vanhoenacker, F.; Schepper, A.M. de; Martin, J.J

    2001-12-01

    This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible.

  3. [Respiratory treatments in neuromuscular disease].

    Science.gov (United States)

    Martínez Carrasco, C; Cols Roig, M; Salcedo Posadas, A; Sardon Prado, O; Asensio de la Cruz, O; Torrent Vernetta, A

    2014-10-01

    In a previous article, a review was presented of the respiratory pathophysiology of the patient with neuromuscular disease, as well as their clinical evaluation and the major complications causing pulmonary deterioration. This article presents the respiratory treatments required to preserve lung function in neuromuscular disease as long as possible, as well as in special situations (respiratory infections, spinal curvature surgery, etc.). Special emphasis is made on the use of non-invasive ventilation, which is changing the natural history of many of these diseases. The increase in survival and life expectancy of these children means that they can continue their clinical care in adult units. The transition from pediatric care must be an active, timely and progressive process. It may be slightly stressful for the patient before the adaptation to this new environment, with multidisciplinary care always being maintained. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  4. Neuromuscular disease classification system

    Science.gov (United States)

    Sáez, Aurora; Acha, Begoña; Montero-Sánchez, Adoración; Rivas, Eloy; Escudero, Luis M.; Serrano, Carmen

    2013-06-01

    Diagnosis of neuromuscular diseases is based on subjective visual assessment of biopsies from patients by the pathologist specialist. A system for objective analysis and classification of muscular dystrophies and neurogenic atrophies through muscle biopsy images of fluorescence microscopy is presented. The procedure starts with an accurate segmentation of the muscle fibers using mathematical morphology and a watershed transform. A feature extraction step is carried out in two parts: 24 features that pathologists take into account to diagnose the diseases and 58 structural features that the human eye cannot see, based on the assumption that the biopsy is considered as a graph, where the nodes are represented by each fiber, and two nodes are connected if two fibers are adjacent. A feature selection using sequential forward selection and sequential backward selection methods, a classification using a Fuzzy ARTMAP neural network, and a study of grading the severity are performed on these two sets of features. A database consisting of 91 images was used: 71 images for the training step and 20 as the test. A classification error of 0% was obtained. It is concluded that the addition of features undetectable by the human visual inspection improves the categorization of atrophic patterns.

  5. Options for mechanical ventilation in neuromuscular diseases.

    Science.gov (United States)

    Unterborn, J N; Hill, N S

    1994-12-01

    A variety of mechanical devices may be used to provide assistance when ventilation and cough are severely impaired by progressive respiratory weakness caused by neuromuscular disease. Traditionally, positive pressure ventilation via a tracheostomy has been used, but if upper airway function is adequate, a variety of noninvasive devices also may be considered. Although positive pressure ventilation is the preferred noninvasive mode for assisting ventilation, other modes may be selected depending on patient needs, preferences, and physical characteristics.

  6. Genetic background alters the severity and onset of neuromuscular disease caused by the loss of ubiquitin-specific protease 14 (usp14.

    Directory of Open Access Journals (Sweden)

    Andrea G Marshall

    Full Text Available In this study, we identified and characterized an N-ethyl-N-nitrosourea (ENU induced mutation in Usp14 (nmf375 that leads to adult-onset neurological disease. The nmf375 mutation causes aberrant splicing of Usp14 mRNA, resulting in a 95% reduction in USP14. We previously showed that loss of USP14 in ataxia (ax (J mice results in reduced ubiquitin levels, motor endplate disease, Purkinje cell axonal dystrophy and decreased hippocampal paired pulse facilitation (PPF during the first 4-6 weeks of life, and early postnatal lethality by two months of age. Although the loss of USP14 is comparable between the nmf375 and ax (J mice, the nmf375 mice did not exhibit these ax (J developmental abnormalities. However, by 12 weeks of age the nmf375 mutants present with ubiquitin depletion and motor endplate disease, indicating a continual role for USP14-mediated regulation of ubiquitin pools and neuromuscular junction (NMJ structure in adult mice. The observation that motor endplate disease was only seen after ubiquitin depletion suggests that the preservation of NMJ structure requires the stable maintenance of synaptic ubiquitin pools. Differences in genetic background were shown to affect ubiquitin expression and dramatically alter the phenotypes caused by USP14 deficiency.

  7. Employment profiles in neuromuscular diseases.

    Science.gov (United States)

    Fowler, W M; Abresch, R T; Koch, T R; Brewer, M L; Bowden, R K; Wanlass, R L

    1997-01-01

    Consumer and rehabilitation provider factors that might limit employment opportunities for 154 individuals with six slowly progressive neuromuscular diseases (NMD) were investigated. The NMDs were spinal muscular atrophy (SMA), hereditary motor sensory neuropathy (HMSN), Becker's muscular dystrophy (BMD), facioscapulohumeral muscular dystrophy (FSHD), myotonic muscular dystrophy (MMD), and limb-girdle syndrome (LGS). Forty percent were employed in the competitive labor market at the time of the study, 50% had been employed in the past, and 10% had never been employed. The major consumer barrier to employment was education. Other important factors were type of occupation, intellectual capacity, psychosocial adjustment, and the belief by most individuals that their physical disability was the only or major barrier to obtaining a job. Psychological characteristics were associated with level of unemployment. However, physical impairment and disability were not associated with level of unemployment. There also were differences among the types of NMDs. Compared with the SMA, HMSN, BMD, and FSHD groups, the MMD and LGS groups had significantly higher levels of unemployment, lower educational levels, and fewer employed professional, management, and technical workers. Nonphysical impairment factors such as a low percentage of college graduates, impaired intellectual function in some individuals, and poor psychological adjustment were correlated with higher unemployment levels in the MMD group. Unemployment in the LGS group was correlated with a failure to complete high school. Major provider barriers to employment were the low level of referrals to Department of Rehabilitation by physicians and the low percentage of acceptance into the State Department of Rehabilitation. The low rate of acceptance was primarily attributable to the low number of referrals compounded by a lack of counselor experience with individuals with NMD. Both consumer and provider barriers may

  8. Protein defects in neuromuscular diseases

    Directory of Open Access Journals (Sweden)

    Vainzof M.

    2003-01-01

    Full Text Available Muscular dystrophies are a heterogeneous group of genetically determined progressive disorders of the muscle with a primary or predominant involvement of the pelvic or shoulder girdle musculature. The clinical course is highly variable, ranging from severe congenital forms with rapid progression to milder forms with later onset and a slower course. In recent years, several proteins from the sarcolemmal muscle membrane (dystrophin, sarcoglycans, dysferlin, caveolin-3, from the extracellular matrix (alpha2-laminin, collagen VI, from the sarcomere (telethonin, myotilin, titin, nebulin, from the muscle cytosol (calpain 3, TRIM32, from the nucleus (emerin, lamin A/C, survival motor neuron protein, and from the glycosylation pathway (fukutin, fukutin-related protein have been identified. Mutations in their respective genes are responsible for different forms of neuromuscular diseases. Protein analysis using Western blotting or immunohistochemistry with specific antibodies is of the utmost importance for the differential diagnosis and elucidation of the physiopathology of each genetic disorder involved. Recent molecular studies have shown clinical inter- and intra-familial variability in several genetic disorders highlighting the importance of other factors in determining phenotypic expression and the role of possible modifying genes and protein interactions. Developmental studies can help elucidate the mechanism of normal muscle formation and thus muscle regeneration. In the last fifteen years, our research has focused on muscle protein expression, localization and possible interactions in patients affected by different forms of muscular dystrophies. The main objective of this review is to summarize the most recent findings in the field and our own contribution.

  9. Genome Editing of Monogenic Neuromuscular Diseases: A Systematic Review.

    Science.gov (United States)

    Long, Chengzu; Amoasii, Leonela; Bassel-Duby, Rhonda; Olson, Eric N

    2016-11-01

    Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. To provide an overview of genome-editing approaches; to summarize published reports on the feasibility, efficacy, and safety of current genome-editing methods as they relate to the potential correction of monogenic neuromuscular diseases; and to highlight scientific and clinical opportunities and obstacles toward permanent correction of disease-causing mutations responsible for monogenic neuromuscular diseases by genome editing. PubMed and Google Scholar were searched for articles published from June 30, 1989, through June 9, 2016, using the following keywords: genome editing, CRISPR-Cas9, neuromuscular disease, Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. The following sources were reviewed: 341 articles describing different approaches to edit mammalian genomes; 330 articles describing CRISPR-Cas9-mediated genome editing in cell culture lines (in vitro) and animal models (in vivo); 16 websites used to generate single-guide RNA; 4 websites for off-target effects; and 382 articles describing viral and nonviral delivery systems. Articles describing neuromuscular diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1, were also reviewed. Multiple proof

  10. Palliative care in neuromuscular diseases

    NARCIS (Netherlands)

    de Visser, Marianne; Oliver, David J.

    2017-01-01

    Purpose of review Palliative care is an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness. Neuromuscular disorders (NMDs) are characterized by progressive muscle weakness, leading to pronounced and incapacitating

  11. Quantitative skeletal muscle ultrasonography in children with suspected neuromuscular disease.

    NARCIS (Netherlands)

    Pillen, S.; Scholten, R.R.; Zwarts, M.J.; Verrips, A.

    2003-01-01

    We determined prospectively the diagnostic value of quantitative ultrasonography in detecting neuromuscular disorders in children. Ultrasonographic scans of four muscles were made in 36 children with symptoms or signs suggestive of neuromuscular disease, such as muscle weakness and hypotonia. The

  12. Computed tomography of skeletal muscles in neuromuscular disease

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    Rodiek, S.O.; Kuether, G.

    1985-06-01

    CT-documentation of skeletal muscular lesions caused by neuromuscular diseases implies an essential contribution to conventional techniques in the macroscopic field. Size, distribution and degree of lesions as well as compensatory mechanisms are proved thereby. We report about the different effects on muscle appearance referring to 106 patients of our own experience in amyotrophic lateral sclerosis, spinal muscular atrophy, poliomyelitis, polyradiculitis, polyneuropathy as well as peripheral traumatic nerve lesions.

  13. [Neuromuscular disease: respiratory clinical assessment and follow-up].

    Science.gov (United States)

    Martínez Carrasco, C; Villa Asensi, J R; Luna Paredes, M C; Osona Rodríguez de Torres, F B; Peña Zarza, J A; Larramona Carrera, H; Costa Colomer, J

    2014-10-01

    Patients with neuromuscular disease are an important group at risk of frequently suffering acute or chronic respiratory failure, which is their main cause of death. They require follow-up by a pediatric respiratory medicine specialist from birth or diagnosis in order to confirm the diagnosis and treat any respiratory complications within a multidisciplinary context. The ventilatory support and the cough assistance have improved the quality of life and long-term survival for many of these patients. In this paper, the authors review the pathophysiology, respiratory function evaluation, sleep disorders, and the most frequent respiratory complications in neuromuscular diseases. The various treatments used, from a respiratory medicine point of view, will be analyzed in a next paper. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  14. Neuromuscular imaging in inherited muscle diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wattjes, Mike P. [VU University Medical Center, Department of Radiology, De Boelelaan 1117, HV, Amsterdam (Netherlands); Kley, Rudolf A. [Klinken Bergmannsheil, Ruhr-University, Department of Neurology, Neuromuscular Centre Ruhrgebiet, Bochum (Germany); Fischer, Dirk [University Hospital of Basel, Department of Neurology, Basel (Switzerland); University Children' s Hospital Basel, Department of Neuropaediatrics, Basel (Switzerland)

    2010-10-15

    Driven by increasing numbers of newly identified genetic defects and new insights into the field of inherited muscle diseases, neuromuscular imaging in general and magnetic resonance imaging (MRI) in particular are increasingly being used to characterise the severity and pattern of muscle involvement. Although muscle biopsy is still the gold standard for the establishment of the definitive diagnosis, muscular imaging is an important diagnostic tool for the detection and quantification of dystrophic changes during the clinical workup of patients with hereditary muscle diseases. MRI is frequently used to describe muscle involvement patterns, which aids in narrowing of the differential diagnosis and distinguishing between dystrophic and non-dystrophic diseases. Recent work has demonstrated the usefulness of muscle imaging for the detection of specific congenital myopathies, mainly for the identification of the underlying genetic defect in core and centronuclear myopathies. Muscle imaging demonstrates characteristic patterns, which can be helpful for the differentiation of individual limb girdle muscular dystrophies. The aim of this review is to give a comprehensive overview of current methods and applications as well as future perspectives in the field of neuromuscular imaging in inherited muscle diseases. We also provide diagnostic algorithms that might guide us through the differential diagnosis in hereditary myopathies. (orig.)

  15. Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

    Science.gov (United States)

    2015-08-24

    Spinal Muscular Atrophy; Charcot-Marie-Tooth Disease; Muscular Dystrophy; Spinal Muscular Atrophy With Respiratory Distress 1; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Disease; Peroneal Muscular Atrophy; Fragile X Syndrome

  16. Exploring employment in consultation reports of patients with neuromuscular diseases

    NARCIS (Netherlands)

    Minis, M.A.H; Cup, E.H.C.; Heerkens, Y.H.; Engels, J.A.; Engelen, B.G.M. van; Oostendorp, R.A.B.

    2012-01-01

    Minis MA, Cup EH, Heerkens YF, Engels JA, van Engelen BG, Oostendorp RA. Exploring employment in consultation reports of patients with neuromuscular diseases. OBJECTIVES: To explore consultation reports for patient and employment characteristics and recommendations on employment regarding patients

  17. Donepezil: A cause of inadequate muscle relaxation and delayed neuromuscular recovery

    Directory of Open Access Journals (Sweden)

    Alka Bhardwaj

    2011-01-01

    Full Text Available A 74-year-old female with diabetes mellitus type II and Alzheimer′s disease, taking donepezil for 4 months was operated for right modified radical mastectomy under general anesthesia. During the procedure a higher dose of non-depolarizing muscle relaxant was required than those recommended for her age yet the muscle relaxation was inadequate intra-operatively. Residual neuromuscular blockade persisted postoperatively, due to the cumulative effect of large doses of non-depolarizing muscle relaxant, needing post-operative ventilatory assistance. After ruling out other causes of resistance to non-depolarizing muscle relaxants, we concluded that acetylcholinesterase inhibitor donepezil was primarily responsible for inadequate muscle relaxation and delayed post-operative neuromuscular recovery.

  18. Imaging of respiratory muscles in neuromuscular disease: A review.

    Science.gov (United States)

    Harlaar, L; Ciet, P; van der Ploeg, A T; Brusse, E; van der Beek, N A M E; Wielopolski, P A; de Bruijne, M; Tiddens, H A W M; van Doorn, P A

    2017-11-24

    Respiratory muscle weakness frequently occurs in patients with neuromuscular disease. Measuring respiratory function with standard pulmonary function tests provides information about the contribution of all respiratory muscles, the lungs and airways. Imaging potentially enables the study of different respiratory muscles, including the diaphragm, separately. In this review, we provide an overview of imaging techniques used to study respiratory muscles in neuromuscular disease. We identified 26 studies which included a total of 573 patients with neuromuscular disease. Imaging of respiratory muscles was divided into static and dynamic techniques. Static techniques comprise chest radiography, B-mode (brightness mode) ultrasound, CT and MRI, and are used to assess the position and thickness of the diaphragm and the other respiratory muscles. Dynamic techniques include fluoroscopy, M-mode (motion mode) ultrasound and MRI, used to assess diaphragm motion in one or more directions. We discuss how these imaging techniques relate with spirometric values and whether these can be used to study the contribution of the different respiratory muscles in patients with neuromuscular disease. Copyright © 2017. Published by Elsevier B.V.

  19. Sleep polygraphic parameters in neuromuscular diseases

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    Márcia Pradella

    1994-12-01

    Full Text Available In a polysomnography study of 32 neuromuscular patients - 22 with a form of muscular dystrophy, 3 with a form of congenital myopathy, 4 with a form of spinal muscular atrophy, 1 with a recurrent form of polymyositis and 1 with osteogenesis imperfecta syndrome - of which 21 were nonambulatory, we observed sleep related respiratory disturbances represented by: drops in oxygen saturation (SaO2, cardiac arrythmia, sleep disruption, apneas, tachypnea, tachycardia and snoring. Nine out of the cohort of 32 patients presented with significant desaturations periods. These patients presented with an associated restrictive syndrome and thoracic deformities, some with tachypnea and/or SaO2 below 90% during wakefulness. In this group, snoring was observed in those patients with a form of muscular dystrophy while tachypnea was observed in patients who presented the highest desaturations levels. Sleep quantification revealed an increase of stage 1 sleep coupled with a decrease or even total absence of REM sleep. This is, we believe, a likely consequence of episodic desaturations that may accompany sleep hypoventilation which is potentialised during REM sleep stage.

  20. Histochemical and immunohistological approach to comparative neuromuscular diseases.

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    Serenella Papparella

    2009-12-01

    Full Text Available The broad category of neuromuscular diseases covers conditions that involve the weakness or wasting of the body muscles. These problems may occur in the spinal cord, the peripheral nerves or the muscle fibers. Some may be hereditary, while others are acquired. Commonly recognized conditions fall into the categories of myopathies, which are diseases of the muscle like muscular dystrophy, disorders of the junction where the nerve impulses are transmitted to the muscle like myasthenia gravis, and neuropathies, which are diseases of the peripheral nervous system. The diagnosis of most neuromuscular diseases rest on careful clinical evaluation of the patient, electromyography, the muscle biopsy, and in some instances, molecular genetic studies. Muscle biopsy, associated to histochemical and immunohistological techniques, plays a key role in diagnosis of many neuromuscular disorders. A number of morphological abnormalities of muscle can be recognized on histological stains such as haematoxylin and eosin and Engel trichrome. Histochemical techniques are essential for the study of muscle biopsies for four main reasons. First, they demonstrate the non-uniform nature of the muscle highlighting the different biochemical properties of specific fibre type and their selective involvement in certain disease processes. Second, they may show an absences of a particular enzyme. Third, an excess of a particular substrate can be demonstrated. Fourth, they may show structural changes in the muscle which would not be apparent with routine histological stains, such as the enzyme-deficient cores in central core disease "mouth-eaten" fibers, and abnormalities in the distribution of mitochondria. In some neuromuscular disorders there could be only non-specific myopathological features. However, a number of proteins, including sarcolemmal, sarcomeric, and nuclear proteins as well as enzymes with defects responsible for neuromuscular disorders, have been identified during

  1. [Electromyography (EMG) and neurography in patients with severe neuromuscular diseases].

    Science.gov (United States)

    Løseth, Sissel; Torbergsen, Torberg

    2013-01-22

    Many neuromuscular diseases are potentially severe, and EMG and neurography are methods used in the assessment of these conditions. The article is based on the authors' knowledge and experience, with special emphasis on the use of these methods in the assessment of severe diseases affecting striated muscle and peripheral nerves. A PubMed search was performed with the cut-off fifteen years back in time, and in addition a discretionary selection was made of articles known to the authors. EMG is the most valuable method for assessing myopathy, and neurography provides most information about neuropathy, but the methods are complementary. These examinations are the most sensitive for diagnosing some conditions (for example myasthaenia) A high level of expertise is necessary for diagnosing these conditions. EMG and neurography are important and often necessary means of assessing patients with severe neuromuscular disease.

  2. Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases

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    Antonio Paoli

    2014-01-01

    Full Text Available An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson’s disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodegenerative diseases characterized by focal brain hypometabolism; to decrease the oxidative damage associated with various kinds of metabolic stress; to increase the mitochondrial biogenesis pathways; and to take advantage of the capacity of ketones to bypass the defect in complex I activity implicated in some neurological diseases. These mechanisms will be discussed in this review.

  3. Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases

    Science.gov (United States)

    Damiani, Ernesto; Bosco, Gerardo

    2014-01-01

    An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson's disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodegenerative diseases characterized by focal brain hypometabolism; to decrease the oxidative damage associated with various kinds of metabolic stress; to increase the mitochondrial biogenesis pathways; and to take advantage of the capacity of ketones to bypass the defect in complex I activity implicated in some neurological diseases. These mechanisms will be discussed in this review. PMID:25101284

  4. Neuromuscular rate of force development deficit in Parkinson disease.

    Science.gov (United States)

    Hammond, Kelley G; Pfeiffer, Ronald F; LeDoux, Mark S; Schilling, Brian K

    2017-06-01

    Bradykinesia and reduced neuromuscular force exist in Parkinson disease. The interpolated twitch technique has been used to evaluate central versus peripheral manifestations of neuromuscular strength in healthy, aging, and athletic populations, as well as moderate to advanced Parkinson disease, but this method has not been used in mild Parkinson disease. This study aimed to evaluate quadriceps femoris rate of force development and quantify potential central and peripheral activation deficits in individuals with Parkinson disease. Nine persons with mild Parkinson Disease (Hoehn & Yahr≤2, Unified Parkinson Disease Rating Scale total score=mean 19.1 (SD 5.0)) and eight age-matched controls were recruited in a cross-sectional investigation. Quadriceps femoris voluntary and stimulated maximal force and rate of force development were evaluated using the interpolated twitch technique. Thirteen participants satisfactorily completed the protocol. Individuals with early Parkinson disease (n=7) had significantly slower voluntary rate of force development (p=0.008; d=1.97) and rate of force development ratio (p=0.004; d=2.18) than controls (n=6). No significant differences were found between groups for all other variables. Persons with mild-to-moderate Parkinson disease display disparities in rate of force development, even without deficits in maximal force. The inability to produce force at a rate comparable to controls is likely a downstream effect of central dysfunction of the motor pathway in Parkinson disease. Copyright © 2017. Published by Elsevier Ltd.

  5. Pregnancy and Childbirth with Neuromuscular Disease

    Science.gov (United States)

    ... Animal studies have revealed evidence that the drug causes fetal malfor- mations. • It’s known that quinine crosses the placenta and accumulates in fetal blood. • In a study of women with a form of malaria, birth defects were observed in 21 infants exposed ...

  6. Apheresis for Neuromuscular Diseases : Invited Lecture

    OpenAIRE

    K., Hirayama; Department of Neurology,School of Medicine,Chiba University

    1995-01-01

    In the treatment of five autoimmune diseases of the central and peripheral nervous system and the muscular system, I described the usefulness of plasmapheresis on the basis of the results in our clinic. In multiple sclerosis, it is possibly indicated for patients in an acute exacerbating stage, although the effectiveness is not established. In Guillain-Barre syndrome, plasmapheresis resulted in good functional prognosis for severely ill patients when it was performed in an early stage of the ...

  7. DNA restriction fragment length polymorphisms in differential diagnosis of genetic disease: application in neuromuscular diseases

    NARCIS (Netherlands)

    Defesche, J. C.; de Vissar, M.; Bakker, E.; Bouwsma, G.; de Vijlder, J. J.; Bolhuis, P. A.

    1989-01-01

    Three families, in which several male individuals suffer from a hereditary neuromuscular disease, were examined by analysis of naturally occurring restriction fragment length polymorphisms (RFLPs) and by screening for deletions. Originally, differential diagnosis included spinal muscular atrophy

  8. [Basic principles of non-respiratory physiotherapy for neuromuscular diseases].

    Science.gov (United States)

    Watzek, I; Winterholler, M

    2008-03-01

    Loss of function, muscle pain and secondary muscoloskeletal complaints are common symptoms of patients with neuromuscular disease. Many patients develop a progressive handicap. Physiotherapeutic treatment is often used in the management of neuromuscular diseases. Different therapeutic strategies are useful depending on the stage and pathophysiology of the disease and with regard to the extent of the patient's handicap. The aims of the physiotherapy and realistic targets should be discussed critically with the patient at the beginning of the treatment. We propose different physiotherapeutic strategies depending on the stage of the underlying disease: 1) Patient is able to walk--active phase: education in self-training with regard to the risks of exhaustion. Manual and physical treatment of mycofascial complaints. 2) Progressive functional loss--assistive phase: support of compensation and daily functioning. 3) Patient in wheelchair or bedbound, loss of most voluntary functions--passive phase. The knowledge of the pathopysiology of the underlying disease is essential for the development of therapeutic strategies. Loss of upper neurons leads to the development of spasticity and muscle hypertonia whereas muscular atrophy and weakness is a prominent feature of lower motor neuron loss. Overtreatment and exhaustive training may lead to secondary muscle damage in primary myopathies. Training in short sessions with intervals between may have protective effects.

  9. Sarcocystis fayeri in skeletal muscle of horses with neuromuscular disease.

    Science.gov (United States)

    Aleman, Monica; Shapiro, Karen; Sisó, Silvia; Williams, Diane C; Rejmanek, Daniel; Aguilar, Beatriz; Conrad, Patricia A

    2016-01-01

    Recent reports of Sarcocystis fayeri-induced toxicity in people consuming horse meat warrant investigation on the prevalence and molecular characterization of Sarcocystis spp. infection in horses. Sarcocysts in skeletal muscle of horses have been commonly regarded as an incidental finding. In this study, we investigated the prevalence of sarcocysts in skeletal muscle of horses with neuromuscular disease. Our findings indicated that S. fayeri infection was common in young mature horses with neuromuscular disease and could be associated with myopathic and neurogenic processes. The number of infected muscles and number of sarcocysts per muscle were significantly higher in diseased than in control horses. S. fayeri was predominantly found in low oxidative highly glycolytic myofibers. This pathogen had a high glycolytic metabolism. Common clinical signs of disease included muscle atrophy, weakness with or without apparent muscle pain, gait deficits, and dysphagia in horses with involvement of the tongue and esophagus. Horses with myositis were lethargic, apparently painful, stiff, and reluctant to move. Similar to humans, sarcocystosis and cardiomyopathy can occur in horses. This study did not establish causality but supported a possible association (8.9% of cases) with disease. The assumption of Sarcocysts spp. being an incidental finding in every case might be inaccurate. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. [Six-minute walk test in children with neuromuscular disease.

    Science.gov (United States)

    Cruz-Anleu, Israel Didier; Baños-Mejía, Benjamín Omar; Galicia-Amor, Susana

    2013-01-01

    Background: neuromuscular diseases affect the motor unit. When they evolve, respiratory complications are common; the six-minute walk test plays an important role in the assessment of functional capacity. Methods: prospective, transversal, descriptive and observational study. We studied seven children with a variety of neuromuscular diseases and spontaneous ambulation. We tested their lung function, and administered a six-minute walk test and a test of respiratory muscle strength to these children. Results: the age was 9.8 ± 2.4 years. All patients were males. Forced vital capacity decreased in three patients (42.8 %), forced expiratory volume during the first second (2.04 ± 1.4 L) and peak expiratory flow (4.33 ± 3.3 L/s) were normal. The maximum strength of respiratory muscles was less than 60 % of predicted values. The distance covered in the six-minute walk test was lower when compared with healthy controls (29.9 %). Conclusions: the six-minute walk test can be a useful tool in early stages of this disease, since it is easy to perform and well tolerated by the patients.

  11. Antisense Oligonucleotide-Based Therapy for Neuromuscular Disease

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    Valentina Sardone

    2017-04-01

    Full Text Available Neuromuscular disorders such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy are neurodegenerative genetic diseases characterized primarily by muscle weakness and wasting. Until recently there were no effective therapies for these conditions, but antisense oligonucleotides, a new class of synthetic single stranded molecules of nucleic acids, have demonstrated promising experimental results and are at different stages of regulatory approval. The antisense oligonucleotides can modulate the protein expression via targeting hnRNAs or mRNAs and inducing interference with splicing, mRNA degradation, or arrest of translation, finally, resulting in rescue or reduction of the target protein expression. Different classes of antisense oligonucleotides are being tested in several clinical trials, and limitations of their clinical efficacy and toxicity have been reported for some of these compounds, while more encouraging results have supported the development of others. New generation antisense oligonucleotides are also being tested in preclinical models together with specific delivery systems that could allow some of the limitations of current antisense oligonucleotides to be overcome, to improve the cell penetration, to achieve more robust target engagement, and hopefully also be associated with acceptable toxicity. This review article describes the chemical properties and molecular mechanisms of action of the antisense oligonucleotides and the therapeutic implications these compounds have in neuromuscular diseases. Current strategies and carrier systems available for the oligonucleotides delivery will be also described to provide an overview on the past, present and future of these appealing molecules.

  12. Correcting Neuromuscular Deficits With Gene Therapy in Pompe Disease

    Science.gov (United States)

    Todd, Adrian G.; McElroy, Jessica A.; Grange, Robert W.; Fuller, David D.; Walter, Glenn A.; Byrne, Barry J.; Falk, Darin J.

    2015-01-01

    Objective We have recently reported on the pathology of the neuromuscular junction (NMJ) in Pompe disease, reflecting disruption of neuronal and muscle homeostasis as a result of glycogen accumulation. The aim of this study was to examine how the alteration of NMJ physiology contributes to Pompe disease pathology; we performed molecular, physiological, and histochemical analyses of NMJ-related measures of the tibialis anterior muscles of young-, mid-, and late-stage alpha-glucosidase (GAA)-deficient mice. Methods We performed intramuscular injection of an adeno-associated virus (AAV)9 vector expressing GAA (AAV9-hGAA) into the tibialis anterior muscle of Gaa–/– mice at early, mid, and severe pathological time points. We analyzed expression of NMJ-related genes, in situ muscle force production, and clearance of glycogen in conjunction with histological assessment of the NMJ. Results Our data demonstrate that AAV9-hGAA is able to replace GAA to the affected tissue and modify AChR mRNA expression, muscle force production, motor endplate area, and innervation status. Importantly, the degree of restoration for these outcomes is limited by severity of disease. Early restoration of GAA activity was most effective, whereas late correction of GAA expression was not effective in modifying parameters reflecting NMJ structure and function nor in force restoration despite resolution of glycogen storage in muscle. Interpretation Our data provide new mechanistic insight into the pathology of Pompe disease and suggest that early systemic correction to both neural and muscle tissues may be essential for successful correction of neuromuscular function in Pompe disease. PMID:25925726

  13. Family Stress with Chronic Childhood Illness: Cystic Fibrosis, Neuromuscular Disease, and Renal Disease.

    Science.gov (United States)

    Holroyd, Jean; Guthrie, Donald

    1986-01-01

    Parents of children with neuromuscular disease, cystic fibrosis, and renal disease were compared with parents of control subjects matched by age to the clinical cases. The three clinical groups exhibited different patterns of stressful response, consistent with the nature of their illnesses and the requirements for care imposed on the families.…

  14. Rehabilitation interventions for foot drop in neuromuscular disease.

    Science.gov (United States)

    Sackley, Catherine; Disler, Peter B; Turner-Stokes, Lynne; Wade, Derick T; Brittle, Nicola; Hoppitt, Thomas

    2009-07-08

    "Foot drop" or "Floppy foot drop" is the term commonly used to describe weakness or contracture of the muscles around the ankle joint. It may arise from many neuromuscular diseases. To conduct a systematic review of randomised trials for the treatment of foot drop resulting from neuromuscular disease. In this update, we searched the Cochrane Neuromuscular Disease Group Trials Register (April 2009), MEDLINE (January 1966 to April 24 2009), EMBASE January 1980 to April 24 2009), CINAHL (January 1982 to May 6 2009), AMED (January 1985 to April 24 2009), the British Nursing Index (January 1985 to January 2008) and Royal College of Nursing Journal of Databases (January 1985 to January 2008). Randomised and quasi-randomised trials of physical, orthotic and surgical treatments for foot drop resulting from lower motor neuron or muscle disease and related contractures were included. People with primary joint disease were excluded. Interventions included a 'wait and see' approach, physiotherapy, orthoses, surgery and pharmacological therapy. The primary outcome measure was quantified ability to walk whilst secondary outcome measures included range of movement, dorsiflexor torque and strength, measures of activity and participation, quality of life and adverse effects. Methodological quality was evaluated by two authors using the van Tulder criteria. Four studies with a total of n = 152 participants were included in the update to the original review. Heterogeneity of the studies precluded pooling the data. Early surgery did not significantly affect walking speed in a trial including 20 children with Duchenne muscular dystrophy. Both groups deteriorated during the 12 months follow-up. After one year, the mean difference (MD) of the 28 feet walking time was 0.00 seconds (95% confidence interval (CI) -0.83 to 0.83) and the MD of the 150 feet walking time was -2.88 seconds, favouring the control group (95% CI -8.18 to 2.42). Night splinting of the ankle did not significantly

  15. Peripheral nerve and neuromuscular junction pathology in Pompe disease

    Science.gov (United States)

    Falk, Darin J.; Todd, Adrian Gary; Lee, Sooyeon; Soustek, Meghan S.; ElMallah, Mai K.; Fuller, David D.; Notterpek, Lucia; Byrne, Barry J.

    2015-01-01

    Pompe disease is a systemic metabolic disorder characterized by lack of acid-alpha glucosidase (GAA) resulting in ubiquitous lysosomal glycogen accumulation. Respiratory and ambulatory dysfunction are prominent features in patients with Pompe yet the mechanism defining the development of muscle weakness is currently unclear. Transgenic animal models of Pompe disease mirroring the patient phenotype have been invaluable in mechanistic and therapeutic study. Here, we demonstrate significant pathological alterations at neuromuscular junctions (NMJs) of the diaphragm and tibialis anterior muscle as prominent features of disease pathology in Gaa knockout mice. Postsynaptic defects including increased motor endplate area and fragmentation were readily observed in Gaa−/− but not wild-type mice. Presynaptic neuropathic changes were also evident, as demonstrated by significant reduction in the levels of neurofilament proteins, and alterations in axonal fiber diameter and myelin thickness within the sciatic and phrenic nerves. Our data suggest the loss of NMJ integrity is a primary contributor to the decline in respiratory and ambulatory function in Pompe and arises from both pre- and postsynaptic pathology. These observations highlight the importance of systemic phenotype correction, specifically restoration of GAA to skeletal muscle and the nervous system for treatment of Pompe disease. PMID:25217571

  16. Management of Cardiac Involvement Associated With Neuromuscular Diseases: A Scientific Statement From the American Heart Association.

    Science.gov (United States)

    Feingold, Brian; Mahle, William T; Auerbach, Scott; Clemens, Paula; Domenighetti, Andrea A; Jefferies, John L; Judge, Daniel P; Lal, Ashwin K; Markham, Larry W; Parks, W James; Tsuda, Takeshi; Wang, Paul J; Yoo, Shi-Joon

    2017-09-26

    For many neuromuscular diseases (NMDs), cardiac disease represents a major cause of morbidity and mortality. The management of cardiac disease in NMDs is made challenging by the broad clinical heterogeneity that exists among many NMDs and by limited knowledge about disease-specific cardiovascular pathogenesis and course-modifying interventions. The overlay of compromise in peripheral muscle function and other organ systems, such as the lungs, also makes the simple application of endorsed adult or pediatric heart failure guidelines to the NMD population problematic. In this statement, we provide background on several NMDs in which there is cardiac involvement, highlighting unique features of NMD-associated myocardial disease that require clinicians to tailor their approach to prevention and treatment of heart failure. Undoubtedly, further investigations are required to best inform future guidelines on NMD-specific cardiovascular health risks, treatments, and outcomes. © 2017 American Heart Association, Inc.

  17. Exercise therapy and other types of physical therapy for patients with neuromuscular diseases: a systematic review.

    NARCIS (Netherlands)

    Cup, E.H.C.; Pieterse, A.J.; Broek-Pastoor, J.M. Ten; Munneke, M.; Engelen, B.G.M. van; Hendricks, H.T.; Wilt, G.J. van der; Oostendorp, R.A.B.

    2007-01-01

    OBJECTIVE: To summarize and critically appraise the available evidence on exercise therapy and other types of physical therapies for patients with neuromuscular diseases (NMD). DATA SOURCES: Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, Medline, CINAHL,

  18. Noninvasive measurement of the tension-time index in children with neuromuscular disease

    National Research Council Canada - National Science Library

    Laura T. Mulreany; Daniel J. Weiner; Joseph M. McDonough; Howard B. Panitch; Julian L. Allen

    2003-01-01

    Respiratory muscle weakness is common in children with neuromuscular disease (NMD). We hypothesized that weakness puts them at risk for respiratory muscle fatigue, a harbinger of chronic respiratory failure...

  19. Quantitative skeletal muscle ultrasound: diagnostic value in childhood neuromuscular disease.

    NARCIS (Netherlands)

    Pillen, S.; Verrips, A.; Alfen, N. van; Arts, I.M.P.; Sie, L.T.L.; Zwarts, M.J.

    2007-01-01

    In this study we investigated the diagnostic value of quantitative skeletal muscle ultrasonography in 150 consecutively referred children with symptoms suspect for a neuromuscular disorder. Muscle thickness and quantitatively determined echo intensity of four muscles and the distribution of these

  20. Update on the approach of respiratory therapy in patients with neuromuscular diseases

    OpenAIRE

    Priscilla Barreto Paula; Laura Maria de Lima Belizário Facury Lasmar; Maria Teresa Mohallem Fonseca; Marina Belisário Carvalhais; Maria da Glória Rodrigues Machado

    2010-01-01

    Objective: To assess the role of physiotherapy in approaching neuromuscular disease (NMD), with emphasis on preventive and therapeutic aspects of respiratory therapy. Methods: A nonsystematic literature review covering the past twenty years, using the databases MEDLINE and LILACS through the following descriptors: neuromuscular diseases, physical therapy, vital capacity and respiratory failure. Results: The studies reviewed show the need to establish a routine periodic evaluation of respirato...

  1. Sleep-Disordered Breathing in Neuromuscular Disease: Diagnostic and Therapeutic Challenges.

    Science.gov (United States)

    Aboussouan, Loutfi S; Mireles-Cabodevila, Eduardo

    2017-10-01

    Normal sleep-related rapid eye movement sleep atonia, reduced lung volumes, reduced chemosensitivity, and impaired airway dilator activity become significant vulnerabilities in the setting of neuromuscular disease. In that context, the compounding effects of respiratory muscle weakness and disease-specific features that promote upper airway collapse or cause dilated cardiomyopathy contribute to various sleep-disordered breathing events. The reduction in lung volumes with neuromuscular disease is further compromised by sleep and the supine position, exaggerating the tendency for upper airway collapse and desaturation with sleep-disordered breathing events. The most commonly identified events are diaphragmatic/pseudo-central, due to a decrease in the rib cage contribution to the tidal volume during phasic rapid eye movement sleep. Obstructive and central sleep apneas are also common. Noninvasive ventilation can improve survival and quality of sleep but should be used with caution in the context of dilated cardiomyopathy or significant bulbar symptoms. Noninvasive ventilation can also trigger sleep-disordered breathing events, including ineffective triggering, autotriggering, central sleep apnea, and glottic closure, which compromise the potential benefits of the intervention by increasing arousals, reducing adherence, and impairing sleep architecture. Polysomnography plays an important diagnostic and therapeutic role by correctly categorizing sleep-disordered events, identifying sleep-disordered breathing triggered by noninvasive ventilation, and improving noninvasive ventilation settings. Optimal management may require dedicated hypoventilation protocols and a technical staff well versed in the identification and troubleshooting of respiratory events. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  2. Limits of effective cough-augmentation techniques in patients with neuromuscular disease.

    Science.gov (United States)

    Toussaint, Michel; Boitano, Louis J; Gathot, Vincent; Steens, Marc; Soudon, Philippe

    2009-03-01

    Manual and mechanical cough-augmentation techniques can improve peak cough flow (PCF) in patients with respiratory insufficiency caused by neuromuscular disease. We studied cough-augmentation techniques in 179 clinically stable patients with various neuromuscular diseases. We measured vital capacity (VC), maximum expiratory pressure (MEP), and PCF, with and without 3 cough-augmentation techniques: manually assisted cough (MAC); breath-stacking (in a subgroup of 60 patients receiving noninvasive mechanical ventilation); and breath-stacking in combination with MAC (also in the 60-patient subgroup). We analyzed the data with the receiver operating characteristic (ROC), to predict the lower limits (assisted PCF > or = 180 L/min) and upper limits (assisted PCF techniques. The lower limit of effective assisted cough with MAC, breath-stacking, and breath-stacking plus MAC was best predicted by VC > 1,030 mL (ROC 0.86, P 558 mL (ROC 0.92, P 340 mL (ROC 0.90, P 34 cm H(2)O (ROC 0.89, P techniques the benefits decreased linearly with increasing MEP and VC (P techniques can be predicted with measurements of maximum respiratory capacity. Patients with VC > 340 mL and MEP manually assisted cough to improve PCF to > 180 L/min.

  3. Neuromuscular Imaging and Phenotypical Variation in Pompe Disease

    NARCIS (Netherlands)

    S.C.A. Wens (Stephan)

    2016-01-01

    markdownabstractPompe disease is a progressive metabolic myopathy. It is caused by a deficiency of the enzyme acid α-glucosidase and leads to glycogen accumulation, predominantly in skeletal muscle. All Dutch patients diagnosed with Pompe disease are referred to the ‘Center of Lysosomal and

  4. Update on the approach of respiratory therapy in patients with neuromuscular diseases

    Directory of Open Access Journals (Sweden)

    Priscilla Barreto Paula

    2010-03-01

    Full Text Available Objective: To assess the role of physiotherapy in approaching neuromuscular disease (NMD, with emphasis on preventive and therapeutic aspects of respiratory therapy. Methods: A nonsystematic literature review covering the past twenty years, using the databases MEDLINE and LILACS through the following descriptors: neuromuscular diseases, physical therapy, vital capacity and respiratory failure. Results: The studies reviewed show the need to establish a routine periodic evaluation of respiratory function in order to introduce physical therapy measures relevant to each stage of the disease. The monitoring should include pulmonary function tests and specific techniques of chest physiotherapy, in order to avoid complications such as respiratory failure. Conclusion: The introduction of regular monitoring and preventive physiotherapy measures have helped to increase survival and improve quality of life of patients with neuromuscular diseases.

  5. One clinic's experience with carbon fiber orthoses in neuromuscular disease.

    Science.gov (United States)

    Mnatsakanian, Ani; Kissel, John T; Terry, Philip; King, Wendy M

    2017-02-01

    The purpose of this study was to summarize our experience with off-the-shelf anterior shell carbon fiber ankle-foot orthoses (CFAFOs) prescribed to adult neuromuscular patients in an outpatient clinic. We studied ambulatory patients who were seen in Muscular Dystrophy Association or amyotrophic lateral sclerosis clinics between 2011 and 2014 and prescribed anterior shell CFAFOs. Charts were reviewed with attention to diagnosis, satisfaction with use, and reasons for acceptance or rejection. We included individuals who were currently using AFOs and those being prescribed AFOs for the first time. We were especially interested in reasons for acceptance or rejection of the orthosis. Two hundred eighty-three charts were reviewed. Of these, 109 of 123 (89%) patients were satisfied or extremely satisfied with the anterior shell CFAFOs, including 38 who had previously used other styles. Anterior shell CFAFOs should be considered for most neuromuscular patients with distal leg weakness. Muscle Nerve 55: 202-205, 2017. © 2016 Wiley Periodicals, Inc.

  6. Reliability of the 2- and 6-minute walk tests in neuromuscular diseases

    DEFF Research Database (Denmark)

    Knak, Kirsten Lykke; Andersen, Linda Kahr; Witting, Nanna

    2017-01-01

    OBJECTIVE: The 2- and 6-minute walk tests are used to evaluate walking capacity, but reliability has been sparsely investigated in patients with neuromuscular diseases. The aim of this study was to investigate the relative and absolute reliability of the 2- and 6-minute walk tests in patients...... with neuromuscular diseases. DESIGN: Each patient performed a 2- and a 6-minute walk test on 2 test days separated by 1-2 weeks. SUBJECTS: A total of 93 adult patients (mean age 53 years, age range 22-83 years) with 12 different neuromuscular diseases were included. RESULTS: The mean walking distance increased by 4.......3 and 11.2 m (p walk tests, respectively. Intraclass correlation coefficient in the 2- and 6-minute walk tests was 0.99 (p walk test and 14.0 m in the 6-minute walk test. Minimal detectable difference...

  7. The extremity function index (EFI), a disability severity measure for neuromuscular diseases : psychometric evaluation

    NARCIS (Netherlands)

    Bos, Isaac; Wynia, Klaske; Drost, Gea; Almansa, Josué; Kuks, Joannes

    2017-01-01

    OBJECTIVE: To adapt and to combine the self-report Upper Extremity Functional Index and Lower Extremity Function Scale, for the assessment of disability severity in patients with a neuromuscular disease and to examine its psychometric properties in order to make it suitable for indicating disease

  8. Duplication in the microtubule-actin cross-linking factor 1 gene causes a novel neuromuscular condition

    DEFF Research Database (Denmark)

    Jørgensen, Louise H; Mosbech, Mai-Britt; Færgeman, Nils J

    2014-01-01

    . These findings suggest that changes in the MACF1 gene is implicated in this neuromuscular condition, which is an important observation since MACF1 has not previously been associated with any human disease and thus presents a key to understanding the essential nature of this gene....... is associated with developmental retardation and embryonic lethality. Here we present a family with a novel neuromuscular condition. Genetic analyses show a heterozygous duplication resulting in reduced MACF1 gene product. The functional consequence is affected motility observed as periodic hypotonia, lax...

  9. Multicategory classification of 11 neuromuscular diseases based on microarray data using support vector machine.

    Science.gov (United States)

    Choi, Soo Beom; Park, Jee Soo; Chung, Jai Won; Yoo, Tae Keun; Kim, Deok Won

    2014-01-01

    We applied multicategory machine learning methods to classify 11 neuromuscular disease groups and one control group based on microarray data. To develop multicategory classification models with optimal parameters and features, we performed a systematic evaluation of three machine learning algorithms and four feature selection methods using three-fold cross validation and a grid search. This study included 114 subjects of 11 neuromuscular diseases and 31 subjects of a control group using microarray data with 22,283 probe sets from the National Center for Biotechnology Information (NCBI). We obtained an accuracy of 100%, relative classifier information (RCI) of 1.0, and a kappa index of 1.0 by applying the models of support vector machines one-versus-one (SVM-OVO), SVM one-versus-rest (OVR), and directed acyclic graph SVM (DAGSVM), using the ratio of genes between categories to within-category sums of squares (BW) feature selection method. Each of these three models selected only four features to categorize the 12 groups, resulting in a time-saving and cost-effective strategy for diagnosing neuromuscular diseases. In addition, a gene symbol, SPP1 was selected as the top-ranked gene by the BW method. We confirmed relationships between the gene (SPP1) and Duchenne muscular dystrophy (DMD) from a previous study. With our models as clinically helpful tools, neuromuscular diseases could be classified quickly using a computer, thereby giving a time-saving, cost-effective, and accurate diagnosis.

  10. Stability and relative validity of the Neuromuscular Disease Impact Profile (NMDIP)

    NARCIS (Netherlands)

    Bos, Isaac; Kuks, Jan B. M.; Almansa, Josue; Kremer, Hubertus P. H.; Wynia, Klaske

    2017-01-01

    Background: The aim of this study was to examine the stability and relative validity (RV) of the Neuromuscular Disease Impact Profile (NMDIP) using criterion-related groups. In a previous study the NMDIP-scales showed good internal consistency, convergent and discriminant validity. Known-groups

  11. Neuromuscular correlates of subthalamic stimulation and upper limb freezing in Parkinson's disease

    NARCIS (Netherlands)

    Scholten, M.; Klotz, R.; Plewnia, C.; Wachter, T.; Mielke, K.P.; Bloem, B.R.; Braun, C.; Ziemann, U.; Govindan, R.B.; Gharabaghi, A.; Kruger, R.; Weiss, D.

    2016-01-01

    OBJECTIVE: The pathophysiology of deep brain stimulation mechanisms and resistant freezing phenomena in idiopathic Parkinson's disease (iPD) remains incompletely understood. Further studies on the neuromuscular substrates are needed. METHODS: We analyzed 16 patients with advanced iPD and bilateral

  12. Dysarthria and dysphagia are highly prevalent among various types of neuromuscular diseases

    NARCIS (Netherlands)

    Knuijt, Simone; Kalf, Johanna G.; de Swart, Bert J. M.; Drost, Gea; Hendricks, Henk T.; Geurts, Alexander C. H.; van Engelen, Baziel G. M.

    2014-01-01

    Purpose: Patients with a neuromuscular disease (NMD) can present with dysarthria and/or dysphagia. Literature regarding prevalence rates of dysarthria and dysphagia is scarce. The purpose of this study was to determine prevalence rates, severity and co-presence of dysarthria and dysphagia in adult

  13. Dysarthria and dysphagia are highly prevalent among various types of neuromuscular diseases

    NARCIS (Netherlands)

    Knuijt, S.; Kalf, J.G.; Swart, B.J. de; Drost, G.; Hendricks, H.T.; Geurts, A.C.; Engelen, B.G.M. van

    2014-01-01

    PURPOSE: Patients with a neuromuscular disease (NMD) can present with dysarthria and/or dysphagia. Literature regarding prevalence rates of dysarthria and dysphagia is scarce. The purpose of this study was to determine prevalence rates, severity and co-presence of dysarthria and dysphagia in adult

  14. Long Term Follow-up of Ventilated Patients with Thoracic Restriction and Neuromuscular Disease

    Directory of Open Access Journals (Sweden)

    Dina Brooks

    2002-01-01

    Full Text Available OBJECTIVE: To evaluate the long term effects of home mechanical ventilation (HMV on pulmonary function, nighttime gas exchange, daytime arterial blood gases, sleep architecture and functional exercise capacity (6 min walk. Patients with respiratory failure attributable to thoracic restrictive disease (TRD (kyphoscoliosis or neuromuscular disease (NMD were assessed, ventilated, trained and followed in a dedicated unit for the care of patients requiring long term ventilation.

  15. Two- and 6-minute walk tests assess walking capability equally in neuromuscular diseases.

    Science.gov (United States)

    Andersen, Linda Kahr; Knak, Kirsten Lykke; Witting, Nanna; Vissing, John

    2016-02-02

    This methodologic study investigates if the 2-minute walk test (2MWT) can be a valid alternative to the 6-minute walk test (6MWT) to describe walking capability in patients with neuromuscular diseases. Patients (n = 115) with different neuromuscular diseases were invited to participate on 2 test days, each consisting of 1 2MWT and 1 6MWT separated by a minimum 30-minute period of rest. The order of the walk tests was randomly assigned via sealed envelopes. A group of 38 healthy controls completed 1 6MWT. The mean walking distance for the 2MWT was 142.8 meters and for the 6MWT 405.3 meters. The distance walked in the 2MWT was highly correlated to the distance walked in the 6MWT (r = 0.99, p walking speed from the first to last minute in the 6MWT, both among patients and healthy controls, which was not evident in the 2MWT. Results were consistent across diagnoses and levels of disease severity. The 2MWT is a potential alternative to the 6MWT to describe walking capability among patients with neuromuscular diseases during clinical trials. © 2016 American Academy of Neurology.

  16. Maximum inspiratory pressure as a clinically meaningful trial endpoint for neuromuscular diseases: A comprehensive review of the literature

    NARCIS (Netherlands)

    B. Schoser; Fong, E. (Edward); Geberhiwot, T. (Tarekegn); Hughes, D. (Derralynn); Kissel, J.T. (John T.); Madathil, S.C. (Shyam C.); Orlikowski, D. (David); Polkey, M.I. (Michael I.); M. Roberts (Mark); H.A.W.M. Tiddens (Harm); Young, P. (Peter)

    2017-01-01

    textabstractRespiratory muscle strength is a proven predictor of long-term outcome of neuromuscular disease (NMD), including amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and spinal muscular atrophy. Maximal inspiratory pressure (MIP), a sensitive measure of respiratory muscle

  17. [Update on the respiratory management of patients with chronic neuromuscular disease].

    Science.gov (United States)

    Priou, P; Trzepizur, W; Meslier, N; Gagnadoux, F

    2017-12-01

    Neuromuscular diseases include a wide range of conditions that may involve potentially life-threatening respiratory complications (infection, respiratory failure). For patients with neuromuscular diseases, clinical assessment of respiratory function and regular pulmonary function tests are needed to screen for nocturnal respiratory disorders, weakness of the diaphragm and potential restrictive disorders and/or chronic hypercapnic respiratory insufficiency, possibly with couch deficiency. MANAGEMENT OF NOCTURNAL RESPIRATORY DISORDERS AND CHRONIC RESPIRATORY FAILURE: Nocturnal respiratory assistance is an important phase of care for nocturnal respiratory disorders and chronic respiratory failure. This may involve continuous positive airway pressure, adaptative servo-ventilation or non-invasive ventilation with a facial or nasal mask. As needed, diurnal assistance may be proposed by mouthpiece ventilation. Should non-invasive ventilation prove insufficient, or if significant swallowing disorders or recurrent bronchial obstruction develop, or in case of prolonged intubation, tracheotomy may be required. In case of lower airway infection with ineffective cough, physical therapy, associated with air stacking, intermittent positive pressure breathing or mechanical in-exsufflation may be proposed. Care for swallowing disorders, nutritional counseling (cachexia, obesity), vaccinations and therapeutic education are integral elements of patient-centered management aiming to prevent the negative impact of infection and to manage respiratory failure of chronic neuromuscular disease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Electrical impedance in bovine skeletal muscle as a model for the study of neuromuscular disease.

    Science.gov (United States)

    Tarulli, Andrew W; Chin, Anne B; Partida, Ramon A; Rutkove, Seward B

    2006-12-01

    Electrical impedance myography (EIM) consists of a set of bioimpedance methods configured for neuromuscular disease assessment, in which high-frequency electrical current is applied to a limb and the consequent surface voltage pattern over a muscle is evaluated. Prior human work has shown that the EIM parameters of resistance, reactance and phase change in different neuromuscular disease states including neurogenic and myopathic conditions. These parameters are also sensitive to the angle at which current is applied and measured relative to muscle fiber direction, a characteristic known as anisotropy. In order to obtain insights into the impedance characteristics of mammalian skeletal muscle without the confounding effects of an overlying skin-fat layer, bone and irregular muscle shape, we performed EIM on three 'nearly ideal' round 16 cm diameter, 1 cm equal thickness pieces of bovine rectus abdominis muscle. Using a standardized tetrapolar electrode array with 50 kHz electrical current, we identified strong anisotropy in the measured reactance and phase, with weaker anisotropy identified for resistance. We also found that increasing amounts of muscle maceration, a rough model of myopathic or traumatic muscle fiber injury, reduced phase and muscle anisotropy when current was injected perpendicular to the muscle fibers. These findings support that EIM parameters, including muscle anisotropy, are likely to be sensitive to the pathological changes that occur in neuromuscular disease states.

  19. Neuromuscular disease mimicking myasthenia gravis in a Nigerian ...

    African Journals Online (AJOL)

    Background : Nemaline rod disease is a congenital myopathy, presentation of which may mimic myasthenia gravis. Methods : We report a suspected case of nemaline rod disease in a female adolescent who presented with features similar to myasthenia gravis but failed to respond effectively to its conventional management ...

  20. Lowland copperhead (Austrelaps superbus) envenomation causing severe neuromuscular paralysis in a dog.

    Science.gov (United States)

    Wright, L V; Indrawirawan, Y H

    2017-06-01

    A case of lowland copperhead snake (Austrelaps superbus) envenomation in a dog is described. The dog developed severe and prolonged neuromuscular paralysis, including ventilatory failure. The dog was treated successfully with antivenom, intravenous fluids and mechanical ventilation. The toxic components of lowland copperhead snake venom are reviewed. © 2017 Australian Veterinary Association.

  1. Invasive versus non-invasive ventilation for acute respiratory failure in neuromuscular disease and chest wall disorders.

    Science.gov (United States)

    Luo, Fang; Annane, Djillali; Orlikowski, David; He, Li; Yang, Mi; Zhou, Muke; Liu, Guan J

    2017-12-04

    Acute respiratory failure is a common life-threatening complication of acute onset neuromuscular diseases, and may exacerbate chronic hypoventilation in patients with neuromuscular disease or chest wall disorders. Standard management includes oxygen supplementation, physiotherapy, cough assistance, and, whenever needed, antibiotics and intermittent positive pressure ventilation. Non-invasive mechanical ventilation (NIV) via nasal, buccal or full-face devices has become routine practice in many centres. The primary objective of this review was to compare the efficacy of non-invasive ventilation with invasive ventilation in improving short-term survival in acute respiratory failure in people with neuromuscular disease and chest wall disorders. The secondary objectives were to compare the effects of NIV with those of invasive mechanical ventilation on improvement in arterial blood gas after 24 hours and lung function measurements after one month, incidence of barotrauma and ventilator-associated pneumonia, duration of mechanical ventilation, length of stay in the intensive care unit and length of hospital stay. We searched the following databases on 11 September 2017: the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase. We also searched conference proceedings and clinical trials registries. We planned to include randomised or quasi-randomised trials with or without blinding. We planned to include trials performed in children or adults with acute onset neuromuscular diseases or chronic neuromuscular disease or chest wall disorders presenting with acute respiratory failure that compared the benefits and risks of invasive ventilation versus NIV. Two review authors reviewed searches and independently selected studies for assessment. We planned to follow standard Cochrane methodology for data collection and analysis. We did not identify any trials eligible for inclusion in the review. Acute respiratory failure is a life-threatening complication of

  2. Pulmonary rehabilitation at home guided by telemonitoring and access to healthcare facilities for respiratory complications in patients with neuromuscular disease.

    Science.gov (United States)

    Garuti, G; Bagatti, S; Verucchi, E; Massobrio, M; Spagnolatti, L; Vezzani, G; Lusuardi, M

    2013-02-01

    Pulmonary complications are the main cause of morbidity and mortality in neuromuscular patients. Aim of this study was to evaluate the feasibility of a home follow-up program combining telemonitoring and chest physiotherapy (CPT) in preventing acute respiratory episodes. Prospective observational study in a period of 24 months, and comparison with preintervention data of the same patients. Outpatients and community. Neuromuscular patients. Enrolment criteria were: reduced efficacy of cough, high family support, long home-to-hospital distance. Caregivers and patients had to register daily respiratory signs and symptoms. Each patient was equipped with a pulse oximeter with a modem for transmitting data to a remote control center, in charge of alerting the pulmonologist in case of sign and symptom deterioration. CPT interventions at home were planned after indication by the pulmonologist. The number of emergency room admissions or hospitalization following respiratory exacerbations were registered. Thirteen patients were enrolled. In the first year of monitoring, 18 alerts were transmitted to the pulmonologist, average 1.38±1.38 alert/patient. In the second year, the number of alerts were 5, average 0.38±0.65 alert/patient (Prespiratory therapists' interventions were conducted on 11 patients. In the first 12 months there were four episodes of hospitalisation, none in the following 12 months. In the year prior to the project, there were seven cases of hospitalisation and one case of emergency room admission. The combination of telemonitoring and CPT at home is feasible in the long-term for patients with neuromuscular disease. An apparent reduction of hospitalisation and emergency room admissions for respiratory complications can justify a randomized control trial to confirm efficacy and effectiveness.

  3. LRP4 in neuromuscular junction and bone development and diseases.

    Science.gov (United States)

    Shen, Chengyong; Xiong, Wen-Cheng; Mei, Lin

    2015-11-01

    Low-density lipoprotein receptor-related protein 4 (LRP4) is a member of the low-density lipoprotein receptor (LDLR) family. Recent studies have revealed multiple functions and complex signaling mechanisms of LRP4 in different organs and tissues. LPR4 mutation or malfunction has been implicated in neurological disorders including congenital myasthenic syndrome, myasthenia gravis, and diseases of bone or kidney. This article is part of a Special Issue entitled "Muscle Bone Interactions". Copyright © 2015 Elsevier Inc. All rights reserved.

  4. What Causes Heart Disease?

    Science.gov (United States)

    ... Education Institute) Heart Attack: Interactive Tutorial (MedlinePlus—Patient Education Institute) RELATED NEWS March 13, 2017 | Research Feature NHLBI, nursing sorority team up to fight heart disease in ...

  5. Dysarthria and dysphagia are highly prevalent among various types of neuromuscular diseases.

    Science.gov (United States)

    Knuijt, Simone; Kalf, Johanna G; de Swart, Bert J M; Drost, Gea; Hendricks, Henk T; Geurts, Alexander C H; van Engelen, Baziel G M

    2014-01-01

    Patients with a neuromuscular disease (NMD) can present with dysarthria and/or dysphagia. Literature regarding prevalence rates of dysarthria and dysphagia is scarce. The purpose of this study was to determine prevalence rates, severity and co-presence of dysarthria and dysphagia in adult patients with NMD. Two groups of adult patients with NMD were included: 102 consecutive outpatients (the "unselected cohort") and 118 consecutive patients who were referred for multidisciplinary assessment (the "selected cohort"). An experienced speech-language pathologist examined each patient in detail. The pooled prevalence of dysarthria was 46% (95% CI: 36.5-55.9) and 62% (95% CI: 53.3-70.8) in the unselected and selected cohorts, respectively. The pooled prevalence of dysphagia was 36% (95% CI: 27.1-45.7) and 58% (95% CI: 49.4-67.2) in the unselected and selected cohorts, respectively. There was a modest but significant association between the presence of dysarthria and dysphagia (rs = 0.40; p dysarthria was moderate to severe in 15% of the dysarthric patients. The prevalence rates of dysarthria and dysphagia among patients with various types of NMD are high. Physicians should therefore be aware of this prevalence and consider referring NMD patients to a speech-language pathologist. IMPLICATONS OF REHABILITATION: Both dysarthria and dysphagia are highly prevalent among patients with neuromuscular diseases; moreover, although often mild, these disorders can occur relatively early in the course of the disease. Clinicians should routinely check for signs and symptoms related to dysarthria and/or dysphagia in patients who present with a neuromuscular disease, preferably using standardised instruments.

  6. Doenças neuromusculares Neuromuscular disorders

    Directory of Open Access Journals (Sweden)

    Umbertina C. Reed

    2002-08-01

    differential diagnosis among the main neuromuscular disorders in children, that include the diseases affecting the motor unity, i.e. spinal motor neurons, peripheral nerves, neuromuscular junction and muscular fibers. Sources: the review of the clinical aspects that should be considered for a prompt differential diagnosis among several neuromuscular disorders as well as between those and the main causes of secondary muscular hypotonia due to central nervous system or systemic disturbances is based on the clinical experience acquired along the last 12 years in following-up children with Neuromuscular Disorders attended at the outpatient Service of Neuromuscular Disorders at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. In addition, it is based on Medline and on the review of the most recent numbers of Neuromuscular Disorders, the official journal of the World Muscle Society. Summary of the findings: most of neuromuscular disorders are genetic conditions in children and the most common of them are X-linked Progressive Muscular Dystrophy of Duchenne, Spinal Muscular Atrophy, Congenital Muscular Dystrophy, Myotonic Dystrophy and Congenital Myopathies. Conclusions: due to the phenomenal development in human molecular genetics the pathogenesis of several neuromuscular disorders in children has been clarified over the last decade. Nowadays many new diagnostic methods, including techniques of fetal diagnosis, and a more objective genotype-phenotype correlation as well as classification are available.

  7. Two- and 6-minute walk tests assess walking capability equally in neuromuscular diseases

    DEFF Research Database (Denmark)

    Andersen, Linda Kahr; Knak, Kirsten Lykke; Witting, Nanna

    2016-01-01

    OBJECTIVE: This methodologic study investigates if the 2-minute walk test (2MWT) can be a valid alternative to the 6-minute walk test (6MWT) to describe walking capability in patients with neuromuscular diseases. METHODS: Patients (n = 115) with different neuromuscular diseases were invited...... to participate on 2 test days, each consisting of 1 2MWT and 1 6MWT separated by a minimum 30-minute period of rest. The order of the walk tests was randomly assigned via sealed envelopes. A group of 38 healthy controls completed 1 6MWT. RESULTS: The mean walking distance for the 2MWT was 142.8 meters...... and for the 6MWT 405.3 meters. The distance walked in the 2MWT was highly correlated to the distance walked in the 6MWT (r = 0.99, p walking speed from the first to last minute in the 6MWT, both among patients and healthy controls, which was not evident in the 2MWT...

  8. Same-day physical therapy consults in an outpatient neuromuscular disease physician clinic

    Directory of Open Access Journals (Sweden)

    Pucillo EM

    2016-10-01

    Full Text Available Evan M Pucillo,1 Nancy Christensen-Mayer,2 Shelly D Poole,2 Denise M Whitten,2 Danielle Freeman,3 Blake R Bohe,4 Brandon R Swensen,3 A Gordon Smith,1 Nicholas E Johnson1 1Department of Neurology, School of Medicine, 2Department of Physical Medicine & Rehabilitation, 3Outpatient Neurology, University of Utah Hospitals and Clinics, 4Business Support, University of Utah Information Technology, Salt Lake City, UT, USA Background: Team-based care has been shown to offer more comprehensive benefits to patients when compared to standard physician-based care alone in clinics for chronic conditions. However, apart from grant-funded multidisciplinary clinics, there are no reports on the usage of same-day physical therapy (PT consults within a daily outpatient neuromuscular disease (NMD physician clinic.Objective: To determine the impact of same-day PT consults at the University of Utah’s outpatient Clinical Neurosciences Center.Design: A qualitative assessment and survey of patient satisfaction.Methods: An eight question Health Insurance Portability and Accountability Act-compliant patient satisfaction survey using a 5-point Likert scale was administered. Demographic data and Press-Ganey Provider Satisfaction surveys were retrospectively collected from electronic medical records for patients receiving same-day PT encounters in the neuromuscular division over 1 year.Results: Mean (standard deviation age was 54.22 (19.81 years for 134 patient encounters, median age was 60 years, with 76 male (57% and 58 female (43% patients. Mean Likert score for 61 self-reported patient satisfaction surveys for same-day PT consults was 4.87 (97.4%. Press-Ganey Provider Satisfaction scores improved from 89.9% (N=287 for the year prior to 90.8% (N=320 for the corresponding year (P=0.427. A total of 46 (75.4% patients have either never before received PT care or never before received PT care for their NMD, 67.4% of whom were male.Conclusion: Same-day PT consults in an

  9. Management of neuromuscular diseases and spinal muscular atrophy in Latin America.

    Science.gov (United States)

    Monges, S; Rosa, A L

    2017-09-01

    Latin America (LA) has a population of ~645 million people distributed over 33 countries with marked political, cultural and economic differences. In LA, patients with inherited neuromuscular diseases (NMDs) often do not have access to specialized medical centers and many of them go undiagnosed. General management and care of spinal muscular dystrophy (SMA) patients in the region varies due to heterogeneous health care. An active generation of young clinical neurologists is being trained for the specialized care of SMA and other neuromuscular (NM) patients, both in the private and public sectors. The Euro-Latin-American Summer School of Myology (EVELAM) as well as efforts of professionals at large public centers in the major cities of LA have a leading role in this development. Different regional academic-scientific organizations as well as the expanding number of telethon centers and the creation of parent organizations, mostly concerning SMA, all together are contributing to the increased quality of the management of NMD patients. Over the past years, academic and clinical research, as well as the establishment of qualified centers for the molecular testing of NMD are pushing forward the creation of patient registries and the development of specific clinical trials, with Argentina and Brazil having a major role in this field. Nevertheless, increased awareness and further training of specialized health professionals are necessary to reach patients that are currently lacking care throughout the region.

  10. Injection of a soluble fragment of neural agrin (NT-1654 considerably improves the muscle pathology caused by the disassembly of the neuromuscular junction.

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    Stefan Hettwer

    Full Text Available Treatment of neuromuscular diseases is still an unsolved problem. Evidence over the last years strongly indicates the involvement of malformation and dysfunction of neuromuscular junctions in the development of such medical conditions. Stabilization of NMJs thus seems to be a promising approach to attenuate the disease progression of muscle wasting diseases. An important pathway for the formation and maintenance of NMJs is the agrin/Lrp4/MuSK pathway. Here we demonstrate that the agrin biologic NT-1654 is capable of activating the agrin/Lrp4/MuSK system in vivo, leading to an almost full reversal of the sarcopenia-like phenotype in neurotrypsin-overexpressing (SARCO mice. We also show that injection of NT-1654 accelerates muscle re-innervation after nerve crush. This report demonstrates that a systemically administered agrin fragment has the potential to counteract the symptoms of neuromuscular disorders.

  11. Experienced stigmatization reduced quality of life of patients with a neuromuscular disease : a cross-sectional study

    NARCIS (Netherlands)

    van der Beek, Kyra M.; Bos, Isäac; Middel, Berrie; Wynia, Klaske

    2013-01-01

    Objective: To examine the influence of stigma on the quality of life of patients with a neuromuscular disease. Design: Cross-sectional postal survey. Setting: Outpatient clinic of the Department of Neurology, University Hospital Groningen, the Netherlands. Subjects: Patients diagnosed with a

  12. Overstimulation of the inhibitory nervous system plays a role in the pathogenesis of neuromuscular and neurological diseases: a novel hypothesis [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Bert Tuk

    2016-08-01

    Full Text Available Based upon a thorough review of published clinical observations regarding the inhibitory system, I hypothesize that this system may play a key role in the pathogenesis of a variety of neuromuscular and neurological diseases. Specifically, excitatory overstimulation, which is commonly reported in neuromuscular and neurological diseases, may be a homeostatic response to inhibitory overstimulation. Involvement of the inhibitory system in disease pathogenesis is highly relevant, given that most approaches currently being developed for treating neuromuscular and neurological diseases focus on reducing excitatory activity rather than reducing inhibitory activity.

  13. Neuromuscular electrical stimulation improves exercise tolerance in chronic obstructive pulmonary disease patients with better preserved fat-free mass

    Directory of Open Access Journals (Sweden)

    Lara Maris Nápolis

    2011-01-01

    Full Text Available BACKGROUND: High-frequency neuromuscular electrical stimulation increases exercise tolerance in patients with advanced chronic obstructive pulmonary disease (COPD patients. However, it is conceivable that its benefits are more prominent in patients with better-preserved peripheral muscle function and structure. OBJECTIVE: To investigate the effects of high-frequency neuromuscular electrical stimulation in COPD patients with better-preserved peripheral muscle function. Design: Prospective and cross-over study. METHODS: Thirty COPD patients were randomly assigned to either home-based, high-frequency neuromuscular electrical stimulation or sham stimulation for six weeks. The training intensity was adjusted according to each subject's tolerance. Fat-free mass, isometric strength, six-minute walking distance and time to exercise intolerance (Tlim were assessed. RESULTS: Thirteen (46.4% patients responded to high-frequency neuromuscular electrical stimulation; that is, they had a post/pre Δ Tlim >10% after stimulation (unimproved after sham stimulation. Responders had a higher baseline fat-free mass and six-minute walking distance than their seventeen (53.6% non-responding counterparts. Responders trained at higher stimulation intensities; their mean amplitude of stimulation during training was significantly related to their fat-free mass (r = 0.65; p<0.01. Logistic regression revealed that fat-free mass was the single independent predictor of Tlim improvement (odds ratio [95% CI] = 1.15 [1.04-1.26]; p<0.05. CONCLUSIONS: We conclude that high-frequency neuromuscular electrical stimulation improved the exercise capacity of COPD patients with better-preserved fat-free mass because they tolerated higher training stimulus levels. These data suggest that early training with high-frequency neuromuscular electrical stimulation before tissue wasting begins might enhance exercise tolerance in patients with less advanced COPD.

  14. Nongenetic causes of Parkinson's disease.

    Science.gov (United States)

    Chade, A R; Kasten, M; Tanner, C M

    2006-01-01

    Study of the nongenetic causes of Parkinson's disease (PD) was encouraged by discovery of a cluster of parkinsonism produced by neurotoxic pyridine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the 1980s. Since that time, epidemiologic investigations have suggested risk factors, though their results do not establish causality. Pesticide exposure has been associated with increased risk in many studies. Other proposed risks include rural residence and certain occupations. Cigarette smoking, use of coffee/caffeine, and non-steroidal antiinflammatory drugs (NSAIDs) all appear to lower risk of PD, while dietary lipid and milk consumption, high caloric intake, and head trauma may increase risk. The cause of PD is likely multifactorial. Underlying genetic susceptibility and combinations of risk and protective factors likely all contribute. The combined research effort by epidemiologists, geneticists, and basic scientists will be needed to clarify the cause(s) of PD.

  15. The role of MuSK in synapse formation and neuromuscular disease.

    Science.gov (United States)

    Burden, Steven J; Yumoto, Norihiro; Zhang, Wei

    2013-05-01

    Muscle-specific kinase (MuSK) is essential for each step in neuromuscular synapse formation. Before innervation, MuSK initiates postsynaptic differentiation, priming the muscle for synapse formation. Approaching motor axons recognize the primed, or prepatterned, region of muscle, causing motor axons to stop growing and differentiate into specialized nerve terminals. MuSK controls presynaptic differentiation by causing the clustering of Lrp4, which functions as a direct retrograde signal for presynaptic differentiation. Developing synapses are stabilized by neuronal Agrin, which is released by motor nerve terminals and binds to Lrp4, a member of the low-density lipoprotein receptor family, stimulating further association between Lrp4 and MuSK and increasing MuSK kinase activity. In addition, MuSK phosphorylation is stimulated by an inside-out ligand, docking protein-7 (Dok-7), which is recruited to tyrosine-phosphorylated MuSK and increases MuSK kinase activity. Mutations in MuSK and in genes that function in the MuSK signaling pathway, including Dok-7, cause congenital myasthenia, and autoantibodies to MuSK, Lrp4, and acetylcholine receptors are responsible for myasthenia gravis.

  16. What does end stage in neuromuscular diseases mean? Key approach-based transitions.

    Science.gov (United States)

    Tripodoro, Vilma Adriana; De Vito, Eduardo Luis

    2015-12-01

    To revise the definition of end stage in the setting of neuromuscular disease (NMD), to understand the implications for the patient, family and healthcare team, and to address the obstacles involved in the lack of definition. Unlike several conditions such as cancer, kidney or liver disease, the literature reveals no clear definition or categorization for NMD. Many articles mention end stage without defining it. Many years ago an expert consensus panel defined it based on functional criteria (forced vital capacity values and hypercapnic events). Only for amyotrophic lateral sclerosis/motoneurone disease has a wider criteria been proposed. As a consequence, the management of this heterogeneous group of disorders is often fragmented compared with the well organized palliative care program for cancer patients. Better end-stage NMD definitions should help to identify the goals of care, but a broad range in time and intensity of deterioration make a valid definition difficult for end-stage NMD. Respiratory care, life-prolonging therapies, and structured care planning should be seen as complementary rather than dichotomous. This article emphasized the relevance of an integrated approach through the whole trajectories of NMD patients considering key transitions.

  17. Cross-disease comparison of amyotrophic lateral sclerosis and spinal muscular atrophy reveals conservation of selective vulnerability but differential neuromuscular junction pathology.

    Science.gov (United States)

    Comley, Laura H; Nijssen, Jik; Frost-Nylen, Johanna; Hedlund, Eva

    2016-05-01

    Neuromuscular junctions are primary pathological targets in the lethal motor neuron diseases spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Synaptic pathology and denervation of target muscle fibers has been reported prior to the appearance of clinical symptoms in mouse models of both diseases, suggesting that neuromuscular junctions are highly vulnerable from the very early stages, and are a key target for therapeutic intervention. Here we examined neuromuscular pathology longitudinally in three clinically relevant muscle groups in mouse models of ALS and SMA in order to assess their relative vulnerabilities. We show for the first time that neuromuscular junctions of the extraocular muscles (responsible for the control of eye movement) were resistant to degeneration in endstage SMA mice, as well as in late symptomatic ALS mice. Tongue muscle neuromuscular junctions were also spared in both animal models. Conversely, neuromuscular junctions of the lumbrical muscles of the hind-paw were vulnerable in both SMA and ALS, with a loss of neuronal innervation and shrinkage of motor endplates in both diseases. Thus, the pattern of selective vulnerability was conserved across these two models of motor neuron disease. However, the first evidence of neuromuscular pathology occurred at different timepoints of disease progression, with much earlier evidence of presynaptic involvement in ALS, progressing to changes on the postsynaptic side. Conversely, in SMA changes appeared concomitantly at the neuromuscular junction, suggesting that mechanisms of neuromuscular disruption are distinct in these diseases. J. Comp. Neurol. 524:1424-1442, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  18. Impact of neuromuscular electrical stimulation on functional capacity of patients with chronic kidney disease on hemodialysis.

    Science.gov (United States)

    Roxo, Renata Spósito; Xavier, Vivian Bertoni; Miorin, Luiz Antônio; Magalhães, Andrea Olivares; Sens, Yvoty Alves Dos Santos; Alves, Vera Lúcia Dos Santos

    2016-01-01

    Literature shows that patients undergoing hemodialysis present poor physical conditioning and low tolerance to exercise. They may also suffer from respiratory dysfunctions. The purpose of this study was to evaluate the effects of neuromuscular electrical stimulation on pulmonary function and functional capacity of patients with chronic kidney disease on hemodialysis. Forty adult patients with chronic kidney disease on hemodialysis were prospectively studied and randomized into two groups (control n = 20 and treatment n = 20). The treatment group underwent bilateral femoral quadriceps muscles electrical stimulation for 30 minutes during hemodialysis, three times per week, for two months. The patients were evaluated by pulmonary function test, maximum respiratory pressures, maximum one-repetition test, and six-minute walk test (6MWT), before and after the treatment protocol. The treatment group presented increased maximum inspiratory (MIP) (p = 0.02) and expiratory pressures (MEP) (p espirometria, pressões respiratórias máximas, teste de uma repetição máxima e teste da caminhada dos seis minutos (TC6), antes e após o período de acompanhamento. O grupo tratamento apresentou aumento da pressão inspiratória máxima com p = 0,02 na comparação entre grupos e p < 0,001 para a pressão máxima expiratória. O teste de uma repetição máxima e a distância percorrida no TC6 apresentaram-se maiores após o protocolo no grupo de tratamento com p < 0,001 e 0,03 respectivamente. Houve diminuição da pressão arterial sistólica (p < 0,001) e frequência respiratória (p < 0,001) após a estimulação elétrica quando comparado ao grupo controle. A estimulação elétrica neuromuscular teve impacto positivo sobre a função pulmonar e a capacidade funcional levando ao melhor desempenho físico em pacientes em hemodiálise.

  19. Muscle-specific kinase myasthenia gravis IgG4 autoantibodies cause severe neuromuscular junction dysfunction in mice.

    NARCIS (Netherlands)

    Klooster, R.; Plomp, J.J.; Huijbers, M.G.; Niks, E.H.; Straasheijm, K.R.; Detmers, F.J.M.; Hermans, P.W.M.; Sleijpen, K.; Verrips, A.; Losen, M.; Martinez-Martinez, P.; Baets, M.H.V. de; Maarel, S.M. van der; Verschuuren, J.J.

    2012-01-01

    Myasthenia gravis is a paralytic disorder with autoantibodies against acetylcholine receptors at the neuromuscular junction. A proportion of patients instead has antibodies against muscle-specific kinase, a protein essential for acetylcholine receptor clustering. These are generally of the

  20. Experienced and physiological fatigue in neuromuscular disorders.

    NARCIS (Netherlands)

    Schillings, M.L.; Kalkman, J.S.; Janssen, H.M.; Engelen, B.G.M. van; Bleijenberg, G.; Zwarts, M.J.

    2007-01-01

    OBJECTIVE: Fatigue has been described as a typical symptom of neurological diseases. It might be caused both by changes at the peripheral and at the central level. This study measured the level of experienced fatigue and physiological correlates of fatigue in three genetically defined neuromuscular

  1. Effects of unilateral, low-frequency, neuromuscular stimulation on superficial circulation in lower extremities of patients with peripheral vascular disease.

    Science.gov (United States)

    Loubser, P G; Cardus, D; Pickard, L R; McTaggart, W G

    1988-04-01

    The effects of unilateral, low-frequency, neuromuscular stimulation on the circulation in skin of the lower extremities were studied in eight subjects with peripheral vascular disease and eight control subjects with normal peripheral vasculature. Sixty minutes of stimulation (at 2 Hz), of sufficient intensity to produce visible contraction of musculature, was applied through cutaneous electrodes placed over the common peroneal nerve and dorsum of the foot. Systolic and diastolic blood pressure, heart rate, bilateral great-toe photoplethysmographic waveform, and bilateral pedal skin temperature were recorded at 30-min intervals during stimulation and 30 min after stimulation. Mean differences in recordings before and after stimulation were then calculated for each parameter, showing in subjects with peripheral vascular disease significant increases of 5.3 +/- 2.1 mm and 0.5 +/- 0.1 degree C for ipsilateral photoplethysmographic waveform amplitude and pedal skin temperature, respectively. Mean differences for the remaining parameters were not significant. Recorded parameters in the control group did not change after stimulation. These results demonstrate that low-frequency, neuromuscular stimulation produces regional cutaneous vasodilation in subjects with peripheral vascular disease. No evidence of generalized vasodilation after neuromuscular stimulation was found.

  2. Epidemiology of inflammatory neurological and inflammatory neuromuscular diseases in Tottori Prefecture, Japan.

    Science.gov (United States)

    Kusumi, M; Nakashima, K; Nakayama, H; Takahashi, K

    1995-06-01

    We investigated the incidence of the following conditions: inflammatory neurological and neuromuscular diseases, adult meningitis and adult encephalitis in Yonago City, and Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), polymyositis/dermatomyositis (PM/DM), periarteritis nodosa (PN) and HTLV-1 associated myelopathy (HAM) during the period 1988-1992 in Tottori Prefecture, Japan. The annual incidence per 100,000 population was as follows: meningitis, 4.38; encephalitis, 0.90; GBS, 1.14; PM/DM, 1.01; and PN, 0.32. The prevalence per 100,000 population CIDP, 0.81; PM/DM, 9.92; PN, 2.59; and HAM, 1.30. There were marked localization of HAM in western Tottori, and there was seasonal variation in the prevalence of meningitis, encephalitis and GBS. The mean age at onset of meningitis was lower than that for encephalitis. Comparison with reported data revealed interracial differences in the epidemiology of PM/DM and PN.

  3. Construction of a Quality of Life Questionnaire for slowly progressive neuromuscular disease.

    Science.gov (United States)

    Dany, Antoine; Barbe, Coralie; Rapin, Amandine; Réveillère, Christian; Hardouin, Jean-Benoit; Morrone, Isabella; Wolak-Thierry, Aurore; Dramé, Moustapha; Calmus, Arnaud; Sacconi, Sabrina; Bassez, Guillaume; Tiffreau, Vincent; Richard, Isabelle; Gallais, Benjamin; Prigent, Hélène; Taiar, Redha; Jolly, Damien; Novella, Jean-Luc; Boyer, François Constant

    2015-11-01

    To build a questionnaire to assess health-related quality of life (HRQL) in patients suffering from slowly progressive neuromuscular disease (NMD) using item response theory (IRT). A pool of 64 items and a validated questionnaire (WHOQOL-BREF) were administered to 159 patients recruited in eight NMD referral centers. Exploratory statistical analysis included methods derived from both IRT and classical test theory. We constructed a questionnaire named QoL-NMD which is composed of two general items and 24 items classified in three domains: (1) "Impact of Physical Symptoms," (2) "Self-perception" and (3) "Activities and Social Participation." Each domain has good psychometric properties (Cronbach's alpha > 0.77, test-retest ICC > 0.81, Loevinger's H > 0.41) and meets IRT assumptions. Comparison with the WHOQOL-BREF enabled assessing similarities and discrepancies with a generic questionnaire. This study enabled the development of a new HRQL questionnaire specifically designed for slowly progressive NMD patients. The QoL-NMD is short enough to be used in clinical practice (26 items). The next steps will be to validate QoL-NMD by re-assessing psychometrics in an independent sample of patients and calibrate the IRT scoring system.

  4. Vocational situation and experiences from the work environment among individuals with neuromuscular diseases.

    Science.gov (United States)

    Lexell, E M; Langdell, I; Lexell, J

    2017-01-01

    Neuromuscular diseases (NMD) can affect the ability to be employed and to work, but there is limited knowledge of individuals' own perspectives of factors that are important for their vocational situation. To explore the vocational situation among people with NMD that are employed, and to describe their experiences of how their disability, personal and environmental factors influence their ability to continue to work. Nine participants with different NMD were included. A mixed-methods design was used, and data were collected by means of semi-structured and open-ended interviews, and ratings of aspects supporting or interfering with their work performance and the ability to continue to work. Data were analyzed with directed content analysis based on the International Classification of Functioning, Disability and Health, and with descriptive statistics. The participants' personal characteristics, support from others at work and at home, and a flexible work organization were perceived as important factors facilitating work continuation, whereas physically demanding work assignments and factors in the physical environment were perceived as barriers. Knowledge of how personal characteristics as well as support from the work organization, managers and family members can facilitate the ability to work is important for employers, staff within different parts of the health care system, and the social security system. Future research should focus on interventions that are best suited to enhance the vocational situation for individuals with NMD.

  5. REHABILITATION PROGRAMS FOR PEOPLE WITH NEUROMUSCULAR DISORDERS

    OpenAIRE

    Anton Zupan

    2004-01-01

    Neuromuscular diseases are inherited, chronic, degenerative and progressive. The main characteristics of neuromuscular diseases are: muscular weakness, contractures, scoliosis, respiratory insufficiency, cardiac affection, nutrition disturbances, dependence on the help of others, possible social isolation and physiological problems. Appropriate rehabilitation programs should influence all mentioned characteristics. A special unit for rehabilitation of patients with neuromuscular diseases with...

  6. Stability and relative validity of the Neuromuscular Disease Impact Profile (NMDIP).

    Science.gov (United States)

    Bos, Isaäc; Kuks, Jan B M; Almansa, Josué; Kremer, Hubertus P H; Wynia, Klaske

    2017-05-11

    The aim of this study was to examine the stability and relative validity (RV) of the Neuromuscular Disease Impact Profile (NMDIP) using criterion-related groups. In a previous study the NMDIP-scales showed good internal consistency, convergent and discriminant validity. Known-groups analysis showed that the NMDIP discriminates between categories of extent of limitations. A cross-sectional postal survey study was performed on patients diagnosed with a NMD and registered at the Department of Neurology, University Medical Center Groningen, the Netherlands. Participants were asked to complete the preliminary NMDIP, the Medical Outcome study Short Form Questionnaire (SF-36), the World Health Organization Quality Of Life-abbreviation version (WHOQOL-bref), and two generic domain specific measures: the Groningen Activity Restriction Scale (GARS) and the Impact on Participation and Autonomy Questionnaire (IPAQ). The variables 'Extent of Limitations' and 'Quality of Life' were used to create criterion-related groups. Stability over time was tested using the Wilcoxon Signed Rank Test for paired samples and the intraclass correlation coefficients for repeated measures. RV was examined by comparing the ability of NMDIP with generic multidimensional health impact measures, and domain specific measures in discriminating between criterion-related subgroups using the Kruskal-Wallis H-test. Response rate was 70% (n = 702). The NMDIP-scales showed sufficient stability over time, and satisfactory or strong RV. In general, the NMDIP scales performed as well as or better than the concurrent measurement instruments. The NMDIP proved to be a valid and reliable disease-targeted measure with a broad scope on physical, psychological and social functioning.

  7. Home mechanical ventilation in childhood-onset hereditary neuromuscular diseases: 13 years' experience at a single center in Korea.

    Directory of Open Access Journals (Sweden)

    Young Joo Han

    Full Text Available Children with hereditary neuromuscular diseases (NMDs are at a high risk of morbidity and mortality related to respiratory failure. The use of home mechanical ventilation (HMV has saved the lives of many children with NMD but, due to a lack of studies, dependable guidelines are not available. We drew upon our experience to compare the various underlying NMDs and to evaluate HMV with regard to respiratory morbidity, the proper indications and timing for its use, and to develop a policy to improve the quality of home noninvasive ventilation (NIV.We retrospectively analyzed the medical records of 57 children with childhood-onset hereditary NMDs in whom HMV was initiated between January 2000 and May 2013 at Seoul National University Children's Hospital. The degree of respiratory morbidity was estimated by the frequency and duration of hospitalizations caused by respiratory distress.The most common NMD was spinal muscular atrophy (SMA, n = 33. Emergent mechanical ventilation was initiated in 44% of the patients before the confirmed diagnosis, and the indicators of pre-HMV respiratory morbidity (e.g., extubation trials, hypoxia, hospitalizations, and intensive care unit stay were greater in these patients than in others. The proportion of post-HMV hospitalizations (range, 0.00-0.52; median, 0.01 was lower than that of pre-HMV hospitalizations (0.02-1.00; 0.99 (P < 0.001. Eight patients were able to maintain home NIV. The main causes of NIV failure were air leakage and a large amount of airway secretions.The application of HMV helped reduce respiratory morbidity in children with childhood-onset hereditary NMD. Patients with SMA type I can benefit from an early diagnosis and the timely application of HMV. The choice between invasive and noninvasive HMV should be based on the patient's age and NIV trial tolerance. Systematic follow-up guidelines provided by a multidisciplinary team are needed.

  8. Classical endocrine diseases causing obesity.

    Science.gov (United States)

    Weaver, Jolanta U

    2008-01-01

    Obesity is associated with several endocrine diseases, including common ones such as hypothyroidism and polycystic ovarian syndrome to rare ones such as Cushing's syndrome, central hypothyroidism and hypothalamic disorders. The mechanisms for the development of obesity vary in according to the endocrine condition. Hypothyroidism is associated with accumulation of hyaluronic acid within various tissues, additional fluid retention due to reduced cardiac output and reduced thermogenesis. The pathophysiology of obesity associated with polycystic ovarian syndrome remains complex as obesity itself may simultaneously be the cause and the effect of the syndrome. Net excess of androgen appears to be pivotal in the development of central obesity. In Cushing's syndrome, an interaction with thyroid and growth hormones plays an important role in addition to an increased adipocyte differentiation and adipogenesis. This review also describes remaining rare cases: hypothalamic obesity due to central hypothyroidism and combined hormone deficiencies.

  9. Attitudes and expectations of patients with neuromuscular diseases about their participation in a clinical trial.

    Science.gov (United States)

    Gargiulo, M; Herson, A; Michon, C C; Hogrel, J Y; Doppler, V; Laloui, K; Herson, S; Payan, C; Eymard, B; Laforêt, P

    2013-01-01

    This study aimed to gain a better understanding of the psychological impact of participating in a clinical trial for patients with Pompe disease (Acid Maltase Deficiency). Attitudes and expectations of adult patients with neuromuscular diseases regarding medical trials are as yet unreported. In order to learn about the psychological consequences of participating in a clinical trial, we conducted a prospective assessment of patients with late-onset Pompe Disease, a rare genetic condition, for which no treatment had been available before. This psychological study was carried out as an ancillary study to the randomized double-blind placebo-controlled trial described elsewhere (van der Ploeg et al., 2010). We assessed patients (n=8) at inclusion, and at 12 and 18 months for six psychological dimensions: depression (Beck Depression Inventory, BDI), hopelessness (Beck Hopelessness Scale, BHS), anxiety (STAI A-B), quality of life (Whoqol-26), social adjustment (S.A.S-self-report) and locus of control (IPC Levenson). We produced a self-administered questionnaire in order to assess the attitudes, motivations and expectations of patients during the trial. At 12 months, mean social adjustment (SAS-SR, P=0.02) had improved, and at 18 months mean depression score had improved as well (BDI, P=0.03). The quality of life of patients (Whoqol-26) remained unchanged. Throughout the study, patients were more likely to have an internal locus of control than an external one (IPC Levenson). The self-administered questionnaire showed that patients' expectations were disproportionate compared to the medical information they had received starting the trial. For all patients, the first motivation for being enrolled in a clinical trial was "to help research", for half of them the motivation was to "improve their health". Whether patients believed to be part of one group or another (placebo or treatment) depended on their subjective perception of improvement during the trial. Given the small

  10. Effects of respiratory muscle training on pulmonary functions in patients with slowly progressive neuromuscular disease: a randomized controlled trial.

    Science.gov (United States)

    Aslan, Goksen Kuran; Gurses, H Nilgun; Issever, Halim; Kiyan, Esen

    2014-06-01

    To investigate the effects of inspiratory and expiratory muscle training on pulmonary functions in patients with slowly progressive neuromuscular disease. Prospective randomized controlled double-blinded study. Chest diseases clinic of university hospital. Twenty-six patients with slowly progressive neuromuscular disease followed for respiratory problems were included in the study. Patients were randomly divided into two groups; experimental (n = 14; age 31.6 ±12.3 years) and sham (n = 12; age 26.5 ±8.6 years) groups. Spirometry, peak cough flow, maximal inspiratory pressure, maximal expiratory pressure, and sniff nasal inspiratory pressure were measured before the eighth week of study, and subsequently at end of it. Respiratory muscle training was performed by inspiratory (Threshold Inspiratory Muscle Trainer) and expiratory (Threshold Positive Expiratory Pressure) threshold loading methods. Training intensities were increased according to maximal inspiratory and expiratory pressures in the experimental group, while the lowest loads were used for training in the sham group. Patients performed 15 minutes inspiratory muscle training and 15 minutes expiratory muscle training, twice a day, five days/week, for a total of eight weeks at home. Training intensity was adjusted in the training group once a week. Maximal inspiratory and expiratory pressures (cmH2O, % predicted) (respectively p = 0.002, p = 0.003, p = 0.04, p = 0.03) and sniff nasal inspiratory pressure (p = 0.04) were improved in the experimental group when compared with the sham group. However, there was no improvement in spirometric measurements when groups were compared (p > 0.05). As a conclusion of our study, we found that respiratory muscle strength improved by inspiratory and expiratory muscle training in patients with slowly progressive neuromuscular disease. © The Author(s) 2013.

  11. Controlled pilot study of the effects of neuromuscular therapy in patients with Parkinson's disease.

    Science.gov (United States)

    Craig, Lauren H; Svircev, Anna; Haber, Michael; Juncos, Jorge L

    2006-12-01

    The objectives of this study is to examine the effects of neuromuscular therapy (NMT) on motor and nonmotor symptoms in Parkinson's disease (PD). Thirty-six subjects with PD were randomly assigned to NMT or music relaxation (MR, or active control). Subjects received treatment twice a week for 4 weeks. Testing was conducted at baseline, after final treatment, and 8 days after final treatment. Primary outcome measures were the Motor subscale of the United Parkinson Disease Rating Scale (UPDRS) and the Clinical Global Impression scale (CGI-Change). Secondary outcome measures included a PD-specific quality of life scale (PDQ-39), quantitative measures of motor function, and severity scales for anxiety and depression symptoms. NMT resulted in a significant and sustained improvement in the Motor subscale of the UPDRS (P < or = 0.0001), most notable in the tremor scores. Also improved 1 week after the last treatment were the CGI scores (P = 0.007) and the finger-tapping speed (P = 0.001). The MR active control group had a slight improvement in tremor but evidenced no other change in motor function. Both groups exhibited a modest improvement in quality of life immediately after the last treatment. This effect was sustained for 8 days only in the MR group. In the nonmotor domains, the MR group evidenced improvements in mood (P = 0.001) and anxiety (P = 0.002), whereas NMT had no effect on mood (P = 0.09), and its initial effect on anxiety (P = 0.0009) dissipated after 8 days (P = 0.40). Group differences for UPDRS motor score and patient CGI-Change were superior in the NMT compared to the MR group. There was no group difference in PDQ-39 scores or in nonmotor measures. The findings suggest that NMT can improve motor and selected nonmotor symptoms in PD and that this effect is more durable for the motor symptoms. The results of this pilot study warrant larger controlled studies to examine dose range, durability, and mechanisms of NMT in PD function. Copyright 2006 Movement

  12. Neuromuscular electrical stimulation for muscle weakness in adults with advanced disease.

    Science.gov (United States)

    Jones, Sarah; Man, William D-C; Gao, Wei; Higginson, Irene J; Wilcock, Andrew; Maddocks, Matthew

    2016-10-17

    This review is an update of a previously published review in the Cochrane Database of Systematic Reviews Issue 1, 2013 on Neuromuscular electrical stimulation for muscle weakness in adults with advanced disease.Patients with advanced progressive disease often experience muscle weakness, which can impact adversely on their ability to be independent and their quality of life. In those patients who are unable or unwilling to undertake whole-body exercise, neuromuscular electrical stimulation (NMES) may be an alternative treatment to enhance lower limb muscle strength. Programmes of NMES appear to be acceptable to patients and have led to improvements in muscle function, exercise capacity, and quality of life. However, estimates regarding the effectiveness of NMES based on individual studies lack power and precision. Primary objective: to evaluate the effectiveness of NMES on quadriceps muscle strength in adults with advanced disease. Secondary objectives: to examine the safety and acceptability of NMES, and its effect on peripheral muscle function (strength or endurance), muscle mass, exercise capacity, breathlessness, and health-related quality of life. We identified studies from searches of the Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), and Database of Abstracts of Reviews of Effects (DARE) (the Cochrane Library), MEDLINE (OVID), Embase (OVID), CINAHL (EBSCO), and PsycINFO (OVID) databases to January 2016; citation searches, conference proceedings, and previous systematic reviews. We included randomised controlled trials in adults with advanced chronic respiratory disease, chronic heart failure, cancer, or HIV/AIDS comparing a programme of NMES as a sole or adjunct intervention to no treatment, placebo NMES, or an active control. We imposed no language restriction. Two review authors independently extracted data on study design, participants, interventions, and outcomes. We assessed risk of bias using

  13. Diagnostic support for selected neuromuscular diseases using answer-pattern recognition and data mining techniques: a proof of concept multicenter prospective trial.

    Science.gov (United States)

    Grigull, Lorenz; Lechner, Werner; Petri, Susanne; Kollewe, Katja; Dengler, Reinhard; Mehmecke, Sandra; Schumacher, Ulrike; Lücke, Thomas; Schneider-Gold, Christiane; Köhler, Cornelia; Güttsches, Anne-Katrin; Kortum, Xiaowei; Klawonn, Frank

    2016-03-08

    Diagnosis of neuromuscular diseases in primary care is often challenging. Rare diseases such as Pompe disease are easily overlooked by the general practitioner. We therefore aimed to develop a diagnostic support tool using patient-oriented questions and combined data mining algorithms recognizing answer patterns in individuals with selected neuromuscular diseases. A multicenter prospective study for the proof of concept was conducted thereafter. First, 16 interviews with patients were conducted focusing on their pre-diagnostic observations and experiences. From these interviews, we developed a questionnaire with 46 items. Then, patients with diagnosed neuromuscular diseases as well as patients without such a disease answered the questionnaire to establish a database for data mining. For proof of concept, initially only six diagnoses were chosen (myotonic dystrophy and myotonia (MdMy), Pompe disease (MP), amyotrophic lateral sclerosis (ALS), polyneuropathy (PNP), spinal muscular atrophy (SMA), other neuromuscular diseases, and no neuromuscular disease (NND). A prospective study was performed to validate the automated malleable system, which included six different classification methods combined in a fusion algorithm proposing a final diagnosis. Finally, new diagnoses were incorporated into the system. In total, questionnaires from 210 individuals were used to train the system. 89.5 % correct diagnoses were achieved during cross-validation. The sensitivity of the system was 93-97 % for individuals with MP, with MdMy and without neuromuscular diseases, but only 69 % in SMA and 81 % in ALS patients. In the prospective trial, 57/64 (89 %) diagnoses were predicted correctly by the computerized system. All questions, or rather all answers, increased the diagnostic accuracy of the system, with the best results reached by the fusion of different classifier methods. Receiver operating curve (ROC) and p-value analyses confirmed the results. A questionnaire

  14. Rapid and reversible responses to IVIG in autoimmune neuromuscular diseases suggest mechanisms of action involving competition with functionally important autoantibodies

    Science.gov (United States)

    Berger, Melvin; McCallus, Daniel E; Lin, Cindy Shin-Yi

    2013-01-01

    Intravenous immunoglobulin (IVIG) is widely used in autoimmune neuromuscular diseases whose pathogenesis is undefined. Many different effects of IVIG have been demonstrated in vitro, but few studies actually identify the mechanism(s) most important in vivo. Doses and treatment intervals are generally chosen empirically. Recent studies in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy show that some effects of IVIG are readily reversible and highly dependent on the serum IgG level. This suggests that in some autoantibody-mediated neuromuscular diseases, IVIG directly competes with autoantibodies that reversibly interfere with nerve conduction. Mechanisms of action of IVIG which most likely involve direct competition with autoantibodies include: neutralization of autoantibodies by anti-idiotypes, inhibition of complement deposition, and increasing catabolism of pathologic antibodies by saturating FcRn. Indirect immunomodulatory effects are not as likely to involve competition and may not have the same reversibility and dose-dependency. Pharmacodynamic analyses should be informative regarding most relevant mechanism(s) of action of IVIG as well as the role of autoantibodies in the immunopathogenesis of each disease. Better understanding of the role of autoantibodies and of the target(s) of IVIG could lead to more efficient use of this therapy and better patient outcomes. PMID:24200120

  15. Neuromuscular disorders

    OpenAIRE

    Reed, Umbertina C.

    2002-01-01

    Objetivo: apresentar os dados essenciais para o diagnóstico diferencial entre as principais doenças neuromusculares, denominação genérica sob a qual agrupam-se diferentes afecções, decorrentes do acometimento primário da unidade motora (motoneurônio medular, raiz nervosa, nervo periférico, junção mioneural e músculo). Fontes dos dados: os aspectos clínicos fundamentais para estabelecer o diagnóstico diferencial entre as diferentes doenças neuromusculares, bem como entre estas e as causas de h...

  16. Respiratory motor training and neuromuscular plasticity in patients with chronic obstructive pulmonary disease: A pilot study.

    Science.gov (United States)

    Ovechkin, Alexander V; Sayenko, Dimitry G; Ovechkina, Elena N; Aslan, Sevda C; Pitts, Teresa; Folz, Rodney J

    2016-07-15

    The objective of this study was to examine the feasibility of a full-scale investigation of the neurophysiological mechanisms of COPD-induced respiratory neuromuscular control deficits. Characterization of respiratory single- and multi-muscle activation patterns using surface electromyography (sEMG) were assessed along with functional measures at baseline and following 21±2 (mean±SD) sessions of respiratory motor training (RMT) performed during a one-month period in four patients with GOLD stage II or III COPD. Pre-training, the individuals with COPD showed significantly increased (prespiratory muscle activity and disorganized multi-muscle activation patterns in association with lowered spirometrical measures and decreased fast- and slow-twitch fiber activity as compared to healthy controls (N=4). Following RMT, functional and respiratory sEMG activation outcomes during quite breathing and forced expiratory efforts were improved suggesting that functional improvements, induced by task-specific RMT, are evidence respiratory neuromuscular networks re-organization. Published by Elsevier B.V.

  17. Insuficiência respiratória crônica nas doenças neuromusculares: diagnóstico e tratamento Chronic respiratory failure in patients with neuromuscular diseases: diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Ilma Aparecida Paschoal

    2007-02-01

    Full Text Available As doenças neuromusculares prejudicam a renovação do ar alveolar e, por esta razão, produzem insuficiência respiratória crônica. A instalação da insuficiência respiratória pode acontecer de modo agudo, como nos traumas, ou ser lenta ou rapidamente progressiva, como na esclerose lateral amiotrófica, distrofias musculares, doença da placa mioneural, etc. O comprometimento da musculatura respiratória prejudica também a eficiência da tosse e, no estado atual da terapêutica disponível no Brasil para estes doentes, pode-se dizer que a morbimortalidade nestes indivíduos está mais associada ao fato de que eles tossem mal do que de que ventilam mal. Nesta revisão, uma breve compilação histórica procura mostrar a evolução das órteses e próteses respiratórias, desde o final do século XIX até agora, com o objetivo de apresentar as opções de máquinas disponíveis para o suporte e substituição da ventilação nas doenças neuromusculares. Além disso, são enfatizados os elementos fundamentais para o diagnóstico da hipoventilação alveolar e da falência do mecanismo protetor da tosse: história clínica, determinação do pico de fluxo da tosse, medida da pressão expiratória máxima e da pressão inspiratória máxima, espirometria em dois decúbitos (sentado e supino, oximetria de pulso, capnografia e polissonografia. São apresentados os valores limites disponíveis na literatura tanto para a indicação do suporte noturno da ventilação como para a extensão do suporte para o período diurno. As manobras para incremento da eficiência da tosse são aqui também discutidas, assim como o momento adequado para sua introdução.Neuromuscular diseases affect alveolar air exchange and therefore cause chronic respiratory failure. The onset of respiratory failure can be acute, as in traumas, or progressive (slow or rapid, as in amyotrophic lateral sclerosis, muscular dystrophies, diseases of the myoneural junction, etc

  18. Neuromuscular Scoliosis

    Science.gov (United States)

    ... to the optimal care of patients with spinal deformity Patients and Families Professionals About SRS Türkçe español ... unable to maintain appropriate balance / alignment of the spine and trunk. Neuromuscular curves are often associated with ...

  19. 'It's a hard conversation to have'. Healthcare professionals' views concerning advance care discussions with young people affected by life-limiting neuromuscular diseases: an interview study.

    Science.gov (United States)

    Hiscock, Andy; Barclay, Stephen

    2017-06-19

    Life-limiting neuromuscular disease, such as some of the muscular dystrophies, are often diagnosed in early childhood: when death comes, commonly in the second or third decade of life, patients rarely have advance care plans in place or documented end-of-life care preferences. There is very limited literature concerning the discussions about end-of-life plans healthcare professionals have with young people affected by life-limiting neuromuscular diseases. The aim of this study was to investigate the views and experiences of healthcare professionals concerning having discussions about advance care plans and end-of-life care with teenagers and young adult patients affected by life-limiting neuromuscular diseases. Semistructured interviews with a maximum variety sample of nine professionals involved in the care of young people with life-limiting neuromuscular diseases in one region of the UK. While recognising the inevitable progression of the conditions, there was no consensus among interviewees concerning best approaches to discuss end-of-life care plans. Several environmental and personal barriers were identified that lead to avoidance of the emotionally challenging and difficult conversations. Community-based professionals with well-established relationships with patients and families may be best placed to take the lead and coordinate discussions, but individual case-by-case preferences need to be carefully considered. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Neuro-Sweet Disease Causing Orbital Inflammation.

    Science.gov (United States)

    Taravati, Parisa

    2015-02-01

    Neuro-Sweet disease is a rare condition causing encephalitis or meningitis in addition to the erythematous skin plaques of Sweet syndrome. Neuro-Sweet disease has been associated with several ocular manifestations, including ocular movement disorders, episcleritis, conjunctivitis, uveitis, and optic disc oedema. The author reports a patient with orbital inflammation, cranial neuropathies, and a skin rash in the setting of myelodysplastic syndrome. Biopsy of her skin lesion confirmed the diagnosis of neuro-Sweet disease. To the author's knowledge, this is the first reported case of neuro-Sweet disease causing orbital inflammation. Her ocular inflammation resolved with the use of systemic corticosteroid treatment.

  1. Acute Neuromuscular Adaptations in the Postural Control of Patients with Parkinson’s Disease after Perturbed Walking

    Directory of Open Access Journals (Sweden)

    Cristian F. Pasluosta

    2017-09-01

    Full Text Available Patients suffering from Parkinson’s disease (PD present motor impairments reflected in the dynamics of the center of pressure (CoP adjustments during quiet standing. One method to study the dynamics of CoP adjustments is the entropic half-life (EnHL, which measures the short-term correlations of a time series at different time scales. Changes in the EnHL of CoP time series suggest neuromuscular adaptations in the control of posture. In this study, we sought to investigate the immediate changes in the EnHL of CoP adjustments of patients with PD during one session of perturbed (experimental group and unperturbed treadmill walking (control group. A total of 39 patients with PD participated in this study. The experimental group (n = 19 walked on a treadmill providing small tilting of the treadmill platform. The control group (n = 20 walked without perturbations. Each participant performed 5-min practice followed by three 5-min training blocks of walking with or without perturbation (with 3-min resting in between. Quiet standing CoP data was collected for 30 s at pre-training, after each training block, immediately post-training, and after 10 min retention. The EnHL was computed on the original and surrogates (phase-randomized CoP signals in the medio-lateral (ML and anterior–posterior (AP directions. Data was analyzed using four-way mixed ANOVA. Increased EnHL values were observed for both groups (Time effect, p < 0.001 as the intervention progressed, suggesting neuromuscular adaptations in the control of posture. The EnHL of surrogate signals were significantly lower than for original signals (p < 0.001, confirming that these adaptations come from non-random control processes. There was no Group effect (p = 0.622, however by analyzing the significant Group by Direction by Time interaction (p < 0.05, a more pronounced effect in the ML direction of the perturbed group was observed. Altogether, our findings show that treadmill walking decreases

  2. The undesirable effects of neuromuscular blocking drugs

    DEFF Research Database (Denmark)

    Claudius, C; Garvey, L H; Viby-Mogensen, J

    2009-01-01

    Neuromuscular blocking drugs are designed to bind to the nicotinic receptor at the neuromuscular junction. However, they also interact with other acetylcholine receptors in the body. Binding to these receptors causes adverse effects that vary with the specificity for the cholinergic receptor...... in question. Moreover, all neuromuscular blocking drugs may cause hypersensitivity reactions. Often the symptoms are mild and self-limiting but massive histamine release can cause systematic reactions with circulatory and respiratory symptoms and signs. At the end of anaesthesia, no residual effect...... of a neuromuscular blocking drug should be present. However, the huge variability in response to neuromuscular blocking drugs makes it impossible to predict which patient will suffer postoperative residual curarization. This article discusses the undesirable effects of the currently available neuromuscular blocking...

  3. Influência da procainamida sobre o bloqueio neuromuscular produzido pelo rocurônio e investigação sobre o mecanismo de ação da procainamida na junção neuromuscular Influencia de la procainamida sobre el bloqueo neuromuscular producido por el rocuronio e investigación sobre el mecanismo de acción de la procainamida en la junción neuromuscular Influence of procainamide on the neuromuscular blockade caused by rocuronium and investigation on the mechanism of action of procainamide on the neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Thalita Duque Martins

    2007-02-01

    : It has already been proved that procainamide potentiates the neuromuscular blockade of d-tubocurarine; however, the mechanism of this potentiation is controversial. The aim of this study was to assess the influence of procainamide on the neuromuscular blockade produced by rocuronium and investigate the mechanisms of this interaction. METHODS: Fifteen rats (250 to 300 g were used in the preparation described by Bülbring. They were divided in three groups (n = 5 each: procainamide - 20 µg.mL-1 (Group I; rocuronium - 4 µg.mL-1 (Group II; and rocuronium - 4 µg.mL-1 and procainamide - 20 µg.mL-1 (Group III. The following parameters were evaluated: 1 amplitude of muscle contractions under indirect stimulation, before and after the administration of the drugs; 2 miniature end plate potentials (MEPPs; and 3 the efficacy of 4-aminopyridine in reverting the muscular blockade. The mechanism of the interaction was studied in Biventer cervicis (n = 5 and in the denervated rat diaphragm (n = 5, observing the influence of procainamide in the response to acetylcholine. RESULTS: Procainamide alone did not change the neuromuscular responses. Group III presented a 68.6% ± 7.1% blockade, which represented a statistically significant difference (p = 0.0067 when compared with Group II (10.4% ± 4.5%, which was reverted by 4-aminopiridine. Procainamide increased the frequency of the MEPP, followed by a blockade that was reverted by 4-aminopiridine. In Biventer cervicis, procainamide increased the contraction in response to acetylcholine, which was not observed in the denervated diaphragm. CONCLUSIONS: Procainamide potentiated the blockade caused by rocuronium. The changes observed with MEPP and Biventer cervicis identified pre-synaptic action. The antagonism of 4-aminopiridine on the blockade of the MEPP suggested receptor desensitization by procainamide.

  4. [Voice disorders caused by neurological diseases].

    Science.gov (United States)

    Gamboa, J; Jiménez-Jiménez, F J; Mate, M A; Cobeta, I

    To review voice disorders in neurological diseases, with special emphasis to acoustic analysis. In the first part of this article we describe data regarding neural control of voice, physiology of phonation, and examination of the patient with voice disturbances, including the use of voice laboratory, acoustic analysis fundamentals, phonetometric measures and aerodynamic measures. In the second part, we review the voice disturbances associated to neurological diseases, emphasizing into movement disorders (specially Parkinson s disease, essential tremor, and spasmodic dysphonia). A number of neurological diseases causing alterations of corticospinal pathway, cerebellum, basal ganglia and upper and/or lower motoneurons can induce voice disturbances. Voice examination using ear, nose & throat examination, endoscopy and videorecording of laryngeal movements, acoustic analysis, elecroglottography, laryngeal electromyography, and aerodynamic measures, could be useful in the clinical examination of some neurological diseases.

  5. Celiac Disease and Other Causes of Duodenitis.

    Science.gov (United States)

    Owen, Daniel R; Owen, David A

    2018-01-01

    - Patients who receive an upper gastrointestinal endoscopic examination frequently have biopsies taken from the duodenum. Accurate interpretation of duodenal biopsies is essential for patient care. Celiac disease is a common clinical concern, but pathologists need to be aware of other conditions of the duodenum that mimic celiac disease. - To review the normal histologic features of duodenal mucosa and describe the clinical and histologic findings in celiac disease and its mimics, listing the differentiating features of biopsies with villous atrophy and epithelial lymphocytosis. - The study comprises a literature review of pertinent publications as of November 30, 2016. - Celiac disease is a common cause of abnormal duodenal histology. However, many of the histologic features found in the duodenal biopsy of patients with celiac disease are also present in other conditions that affect the small bowel. Diagnostic precision may be enhanced by obtaining a careful patient history and by ancillary laboratory testing, particularly for the presence of antitissue transglutaminase antibodies.

  6. Invasive Disease Caused by Nontypeable Haemophilus Influenzae

    Centers for Disease Control (CDC) Podcasts

    2015-11-12

    Dr. Elizabeth Briere discusses Nontypeable Haemophilus influenzae which causes a variety of infections in children and adults.  Created: 11/12/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/17/2015.

  7. Randomised controlled trial of non-invasive ventilation (NIV) for nocturnal hypoventilation in neuromuscular and chest wall disease patients with daytime normocapnia.

    Science.gov (United States)

    Ward, S; Chatwin, M; Heather, S; Simonds, A K

    2005-12-01

    Long term non-invasive ventilation (NIV) reduces morbidity and mortality in patients with neuromuscular and chest wall disease with hypercapnic ventilatory failure, but preventive use has not produced benefit in normocapnic patients with Duchenne muscular dystrophy. Individuals with nocturnal hypercapnia but daytime normocapnia were randomised to a control group or nocturnal NIV to examine whether nocturnal hypoventilation is a valid indication for NIV. Forty eight patients with congenital neuromuscular or chest wall disease aged 7-51 years and vital capacitytension (Tcco2) did not differ between the groups, but the mean (SD) percentage of the night during which Tcco2 was >6.5 kPa decreased in the NIV group (-57.7 (26.1)%) but not in controls (-11.75 (46.1)%; p=0.049, 95% CI -91.5 to -0.35). Mean (SD) arterial oxygen saturation increased in the NIV group (+2.97 (2.57)%) but not in controls (-1.12 (2.02)%; p=0.024, 95% CI 0.69 to 7.5). Nine of the 10 controls failed non-intervention by fulfilling criteria to initiate NIV after a mean (SD) of 8.3 (7.3) months. Patients with neuromuscular disease with nocturnal hypoventilation are likely to deteriorate with the development of daytime hypercapnia and/or progressive symptoms within 2 years and may benefit from the introduction of nocturnal NIV before daytime hypercapnia ensues.

  8. Comparison of the effects of neuromuscular electrical stimulation and endurance training in patients with severe chronic obstructive pulmonary disease.

    Science.gov (United States)

    Kaymaz, Dicle; Ergün, Pınar; Demirci, Ebru; Demir, Neşe

    2015-01-01

    In severely disabled patients who are not capable of following formal pulmonary rehabilitation (PR) and/or tolerating higher training intensities, neuromuscular electrical stimulation (NMES) has been successfully utilized as a localized training method. In this non-randomized controlled observational study 50 patients with severe chronic obstructive pulmonary disease (COPD), who were allocated into two groups. Endurance training group (ET) (n= 27) and NMES group (n= 23). To compare the effects of NMES and ET on health-related quality of life (HRQOL), exercise capacity, muscle strength, dyspnea, psychological status, and body composition in patients with severe COPD. Before and after PR program, the study parameters were assessed using the Medical Research Council (MRC) scale, incremental and endurance shuttle walking tests (ISWT, ESWT), manual muscle testing (MMT), the St. George's Respiratory Questionnaire (SGRQ), bioelectrical impedance analysis, and the Hospital Anxiety and Depression Scale (HADS). After the PR program, walking distance and endurance time significantly increased in both groups (p 0.05) and HADS (p> 0.05) scores, body-mass index (BMI) (p= 0.49), fat-free mass (FFM) (p= 0.50) and fat-free mass index (FFMI) (p= 0.94). NMES can be used as an effective treatment strategy in PR programs for peripheral muscle training in patients with severe COPD.

  9. Neuromuscular Hip Dysplasia in Charcot-Marie-Tooth Disease Type 1A

    Science.gov (United States)

    Bamford, Nigel S.; White, Klane K.; Robinett, Stephanie A.; Otto, Randolph K.; Gospe, Sidney M., Jr.

    2009-01-01

    Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders, affecting 36 in 100,000 people. CMT type 1A (hereditary motor and sensory neuropathy) is the most frequent form of this disease, affecting 60 to 80% of the CMT population, but its diagnosis may be delayed because of inconsistent clinical signs and…

  10. Clinical Strategies for Complete Denture Rehabilitation in a Patient with Parkinson Disease and Reduced Neuromuscular Control

    Directory of Open Access Journals (Sweden)

    Satheesh B. Haralur

    2015-01-01

    Full Text Available The dentist has a large role in geriatric health care for the ever increasing elder population with associated physical and neurological disorders. The Parkinson disease is progressive neurological disorder with resting tremor, bradykinesia, akinesia, and postural instability. The psychological components of disease include depression, anxiety, and cognitive deficiency. Poor oral hygiene, increased susceptibility for dental caries, and periodontal diseases predispose them to early edentulism. The number of Parkinson affected patients visiting dental clinic seeking complete denture is growing. This case report explains the steps involved in the complete denture rehabilitation of Parkinson patient. The effective prosthesis will help in alleviating functional, aesthetic, and psychological disabilities of the patient.

  11. [Cushing's disease caused by pituitary macroadenoma].

    Science.gov (United States)

    Rubatino, Antônio C; Pereira, Rodrigo Ferreira; Benchimol, Isaac; Laun, Ingeborg Christa

    2004-12-01

    Cushing's syndrome comprises the symptoms and signs associated with prolonged exposure to inappropriately elevated levels of free plasma glucocorticoids. When iatrogenic causes are excluded, the commonest cause of Cushing's syndrome is Cushing's disease, accounting for approximately 70% of cases. We present the case of a 20-year-old male patient with central obesity, moon face and purple-red striae, whose diagnostic investigation shows a pituitary macroadenoma. The patient was submitted to transsphenoidal hypophysectomy, but developed early recurrence. He was submitted to a second transsphenoidal intervention followed by pituitary radiation. Presently, the patient is in clinical and laboratory remission.

  12. Human T cell leukaemia virus type I associated neuromuscular disease causing respiratory failure.

    Science.gov (United States)

    Littleton, E T; Man, W D; Holton, J L; Landon, D N; Hanna, M G; Polkey, M I; Taylor, G P

    2002-05-01

    Polymyositis and inclusion body myositis have rarely been described in association with human T cell leukaemia virus type I (HTLV-I) infection. Most of such patients have coexisting HTLV-I associated myelopathy (HAM). Two patients with HTLV-I infection, myopathy, and respiratory failure are described. The muscle biopsy specimen of the first patient bore the histological features of inclusion body myositis and there was no evidence of concurrent myelopathy. The second patient had HAM, and her muscle biopsy showed non-specific myopathic and neuropathic changes. Both patients developed respiratory muscle weakness over eight years after diagnosis of myopathy, leading to hypercapnic respiratory failure requiring mechanical ventilatory support. Respiratory failure as a complication of HTLV-I associated myopathy has not previously been described.

  13. Hand function with touch screen technology in children with normal hand formation, congenital differences, and neuromuscular disease.

    Science.gov (United States)

    Shin, David H; Bohn, Deborah K; Agel, Julie; Lindstrom, Katy A; Cronquist, Sara M; Van Heest, Ann E

    2015-05-01

    To measure and compare hand function for children with normal hand development, congenital hand differences (CHD), and neuromuscular disease (NMD) using a function test with touch screen technology designed as an iPhone application. We measured touch screen hand function in 201 children including 113 with normal hand formation, 43 with CHD, and 45 with NMD. The touch screen test was developed on the iOS platform using an Apple iPhone 4. We measured 4 tasks: touching dots on a 3 × 4 grid, dragging shapes, use of the touch screen camera, and typing a line of text. The test takes 60 to 120 seconds and includes a pretest to familiarize the subject with the format. Each task is timed independently and the overall time is recorded. Children with normal hand development took less time to complete all 4 subtests with increasing age. When comparing children with normal hand development with those with CHD or NMD, in children aged less than 5 years we saw minimal differences; those aged 5 to 6 years with CHD took significantly longer total time; those aged 7 to 8 years with NMD took significantly longer total time; those aged 9 to 11 years with CHD took significantly longer total time; and those aged 12 years and older with NMD took significantly longer total time. Touch screen technology has becoming increasingly relevant to hand function in modern society. This study provides standardized age norms and shows that our test discriminates between normal hand development and that in children with CHD or NMD. Diagnostic III. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  14. ETIOPATHOGENESIS OF DISEASES CAUSED BY CLOSTRIDIUM DIFFICILE

    Directory of Open Access Journals (Sweden)

    Predrag Stojanović

    2015-03-01

    Full Text Available Clostridium (C. difficile is a typical representative of the genus Clostridium. After colonization of the intestinal tract, toxigenic C. difficile strains are capable to produce two exotoxins, enterotoxin (toxin A and cytotoxin (toxin B, which cause diarrhea and colitis. Toxin A binds to specific carbohydrate receptors on the surface of intestinal cells and this is the beginning of damages in the intestinal tract which include destruction of the villi epithelium, limiting membrane, intercellular connections (zonula occludens and surface of the mucosa. If only toxin B is injected into intestinal cells, it does not cause damage nor increased fluids secretion. Probably, the reason for this is the inability of the toxin to bind to the cell membrane receptor in the intestinal tract under normal physiological conditions. Toxigenic strains of C. difficile can be found in the intestines of healthy people, without any symptoms or clinical signs (asymptomatic colonization. However, in people with risk factors, they can cause diarrhea of varying severity and life-threatening pseudomembranous colitis. These diseases are known as C. difficile associated disease - CDAD.

  15. Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease.

    LENUS (Irish Health Repository)

    Pitceathly, Robert D S

    2012-09-11

    Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, affecting 1 in 2,500 individuals. Mitochondrial DNA (mtDNA) mutations are not generally considered within the differential diagnosis of patients with uncomplicated inherited neuropathy, despite the essential requirement of ATP for axonal function. We identified the mtDNA mutation m.9185T>C in MT-ATP6, encoding the ATP6 subunit of the mitochondrial ATP synthase (OXPHOS complex V), at homoplasmic levels in a family with mitochondrial disease in whom a severe motor axonal neuropathy was a striking feature. This led us to hypothesize that mutations in the 2 mtDNA complex V subunit encoding genes, MT-ATP6 and MT-ATP8, might be an unrecognized cause of isolated axonal CMT and distal hereditary motor neuropathy (dHMN).

  16. Development and testing psychometric properties of an ICF-based health measure : The Neuromuscular Disease Impact Profile

    NARCIS (Netherlands)

    Bos, Isaäc; Kuks, Jan B. M.; Wynia, Klaske

    Objectives: To develop a measure that is based on the International Classification of Functioning, Disability and Health (ICF) and reflects the prevalence and severity of disabilities related to neuromuscular disorders, and to evaluate the psychometric properties of this measure. Methods: A

  17. Corals diseases are a major cause of coral death

    Science.gov (United States)

    Corals, like humans, are susceptible to diseases. Some coral diseases are associated with pathogenic bacteria; however, the causes of most remain unknown. Some diseases trigger rapid and extensive mortality, while others slowly cause localized color changes or injure coral tiss...

  18. REHABILITATION PROGRAMS FOR PEOPLE WITH NEUROMUSCULAR DISORDERS

    Directory of Open Access Journals (Sweden)

    Anton Zupan

    2004-12-01

    Full Text Available Neuromuscular diseases are inherited, chronic, degenerative and progressive. The main characteristics of neuromuscular diseases are: muscular weakness, contractures, scoliosis, respiratory insufficiency, cardiac affection, nutrition disturbances, dependence on the help of others, possible social isolation and physiological problems. Appropriate rehabilitation programs should influence all mentioned characteristics. A special unit for rehabilitation of patients with neuromuscular diseases within the Institute for rehabilitation of the Republic of Slovenia was established in 1993 at the initiative of the Muscular Dystrophy Association of Slovenia. The main aim of this establishment was to try to guide the patient and his family through the course of the disease. The article describes the work of the mentioned unit. Different clinical rehabilitation programs for people with neuromuscular diseases are presented and some research results of the unit are mentioned.

  19. Immunoglobulins from Animal Models of Motor Neuron Disease and from Human Amyotrophic Lateral Sclerosis Patients Passively Transfer Physiological Abnormalities to the Neuromuscular Junction

    Science.gov (United States)

    Apel, Stanley H.; Engelhardt, Jozsef I.; Garcia, Jesus; Stefani, Enrico

    1991-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating human disease of upper and lower motoneurons of unknown etiology. In support of the potential role of autoimmunity in ALS, two immune-mediated animal models of motoneuron disease have been developed that resemble ALS with respect to the loss of motoneurons, the presence of IgG within motoneurons and at the neuromuscular junction, and with respect to altered physiology of the motor nerve terminal. To provide direct evidence for the primary role of humoral immunity, passive transfer with immunoglobulins from the two animal models and human ALS was carried out. Mice injected with serum or immunoglobulins from the animal disease models and human ALS but not controls demonstrated IgG in motoneurons and at the neuromuscular junction. The mice also demonstrated an increase in miniature end-plate potential (mepp) frequency, with normal amplitude and time course and normal resting membrane potential, indicating an increased resting quantal release of acetylcholine from the nerve terminal. The ability to transfer motoneuron dysfunction with serum immunoglobulins provides evidence for autoimmune mechanisms in the pathogenesis of both the animal models and human ALS.

  20. Symptoms and Causes of Peptic Ulcer Disease

    Science.gov (United States)

    ... aspirin and ibuprofen an infection with the bacteria Helicobacter pylori ( H. pylori ) rare cancerous and noncancerous tumors ... Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información de ...

  1. Genetics and Neuromuscular Diseases

    Science.gov (United States)

    ... three of their children — one son and two daughters — inherited from their father a chromosome 19 with an MMD mutation. Even ... By luck, neither their two sons nor their daughter inherited a chro- mosome 19 with ... chro- mosome 19s are both normal. 1gestneration affected ...

  2. Infantile onset spinocerebellar ataxia caused by compound heterozygosity for Twinkle mutations and modeling of Twinkle mutations causing recessive disease.

    Science.gov (United States)

    Pierce, Sarah B; Gulsuner, Suleyman; Stapleton, Gail A; Walsh, Tom; Lee, Ming K; Mandell, Jessica B; Morales, Augusto; Klevit, Rachel E; King, Mary-Claire; Rogers, R Curtis

    2016-07-01

    Mutations in nuclear genes required for the replication and maintenance of mitochondrial DNA cause progressive multisystemic neuromuscular disorders with overlapping phenotypes. Biallelic mutations in C10orf2, encoding the Twinkle mitochondrial DNA helicase, lead to infantile-onset cerebellar ataxia (IOSCA), as well as milder and more severe phenotypes. We present a 13-year-old girl with ataxia, severe hearing loss, optic atrophy, peripheral neuropathy, and hypergonadotropic hypogonadism. Whole-exome sequencing revealed that the patient is compound heterozygous for previously unreported variants in the C10orf2 gene: a paternally inherited frameshift variant (c.333delT; p.L112Sfs*3) and a maternally inherited missense variant (c.904C>T; p.R302W). The identification of novel C10orf2 mutations extends the spectrum of mutations in the Twinkle helicase causing recessive disease, in particular the intermediate IOSCA phenotype. Structural modeling suggests that the p.R302W mutation and many other recessively inherited Twinkle mutations impact the position or interactions of the linker region, which is critical for the oligomeric ring structure and activity of the helicase. This study emphasizes the utility of whole-exome sequencing for the genetic diagnosis of a complex multisystemic disorder.

  3. Report by the Spanish Foundation for the Brain on the social impact of amyotrophic lateral sclerosis and other neuromuscular disorders.

    Science.gov (United States)

    Camacho, A; Esteban, J; Paradas, C

    A thorough knowledge of the socioeconomic scope of neuromuscular disease is essential for managing resources and raising social awareness. Our group reviewed current data on the epidemiology, mortality and dependence rates, and socioeconomic impact of amyotrophic lateral sclerosis and neuromuscular diseases in Spain. We also recorded how neurological care for these patients is organised. Neuromuscular disorders are a very heterogeneous group of diseases, and some are very rare. These disorders account for between 2.8% and 18% of the total motives for a neurological consultation. In Spain, prevalence and incidence figures for amyotrophic lateral sclerosis are similar to those in other countries; however, figures for patients with other neuromuscular diseases are not known. Since the diseases are chronic, progressive, and debilitating, they cause considerable disability and dependence, which in turn directly affects healthcare and social costs associated with the disease. The costs generated by one patient with amyotrophic lateral sclerosis or Duchenne disease have been calculated at about 50 000 euros per year. Neuromuscular disease shows aetiological, diagnostic, and prognostic complexity, and it requires multidisciplinary management. Follow-up for these patients should be entrusted to specialised units. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Neuromuscular fatigue in racquet sports.

    Science.gov (United States)

    Girard, Olivier; Millet, Grégoire P

    2008-02-01

    This article describes the physiologic and neural mechanisms that cause neuromuscular fatigue in racquet sports: table tennis, tennis, squash, and badminton. In these intermittent and dual activities, performance may be limited as a match progresses because of a reduced central activation, linked to changes in neurotransmitter concentration or in response to afferent sensory feedback. Alternatively, modulation of spinal loop properties may occur because of changes in metabolic or mechanical properties within the muscle. Finally, increased fatigue manifested by mistimed strokes, lower speed, and altered on-court movements may be caused by ionic disturbances and impairments in excitation-contraction coupling properties. These alterations in neuromuscular function contribute to decrease in racquet sports performance observed under fatigue.

  5. Periodontal (Gum) Disease: Causes, Symptoms, and Treatments

    Science.gov (United States)

    ... identify underlying conditions or risk factors (such as smoking) that may contribute to gum disease. Examine your gums and note any signs of ... will vary, depending on the extent of the gum disease. Any type of treatment ... as quitting smoking, as a way to improve treatment outcome. Deep ...

  6. Animal Diseases Caused by Orbiviruses, Algeria

    Science.gov (United States)

    Madani, Hafsa; Casal, Jordi; Alba, Anna; Allepuz, Alberto; Cêtre-Sossah, Catherine; Hafsi, Leila; Kount-Chareb, Houria; Bouayed-Chaouach, Nadera; Saadaoui, Hassiba

    2011-01-01

    Antibodies against bluetongue virus were detected in cattle, sheep, goats, and camels in Algeria in 2008. Antibodies against epizootic hemorrhagic disease virus were detected in cattle, but antibodies against African horse sickness virus were not detected in horses and mules. Epizootic hemorrhagic disease in northern Africa poses a major risk for the European Union. PMID:22172371

  7. Symptoms and Causes of Celiac Disease

    Science.gov (United States)

    ... Accessed June 5, 2016. June 2016 Share Previous: Definition & Facts Next: Diagnosis This content is provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of ...

  8. The timed inspiratory effort: a promising index of mechanical ventilation weaning for patients with neurologic or neuromuscular diseases.

    Science.gov (United States)

    de Souza, Leonardo Cordeiro; Guimarães, Fernando Silva; Lugon, Jocemir Ronaldo

    2015-02-01

    The aim of this study was to evaluate the performance of the recently described timed inspiratory effort (TIE) index in comparison with 4 other previously reported indices as to the weaning outcome in patients with neurologic or neuromuscular disorders. This observational prospective study included subjects undergoing weaning from mechanical ventilation. The performance of the indices was evaluated by calculation of the area under the receiver operating characteristic curves. The areas under the curve were compared using the Hanley and McNeil method. P values<.05 were considered significant. Seventy-two subjects (57±20 y old) were selected for the study. Forty-three subjects were weaned, and 21 died during the study period. The mean duration of mechanical ventilation was 22.3±19.4 d. The areas under the curve of 5 weaning predictors (TIE index, integrative weaning index, noninvasive tension-time index, maximum inspiratory pressure, and breathing frequency/tidal volume index) were significantly higher than those of the other indices. The TIE index had the largest area under the curve (0.96±0.02) in comparison with the integrative weaning index (0.82±0.05, P=.009), noninvasive tension-time index (0.80±0.05, P=.001), maximum inspiratory pressure (0.77±0.06, P=.001), and breathing frequency/tidal volume index (0.72±0.06, P=.001). In patients with neurologic or neuromuscular impairment, the TIE index had a better performance than the best weaning indices used in clinical practice. Copyright © 2015 by Daedalus Enterprises.

  9. MRI in neuromuscular disorders; MRT bei neuromuskulaeren Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Fischmann, Arne [Klinik St. Anna, Luzern (Switzerland). Inst. fuer Radiologie und Nuklearmedizin; Fischer, Dirk [Kantonsspital Bruderholz (Switzerland)

    2014-03-15

    Neuromuscular disorders are caused by damage of the skeletal muscles or supplying nerves, in many cases due to a genetic defect, resulting in progressive disability, loss of ambulation and often a reduced life expectancy. Previously only supportive care and steroids were available as treatments, but several novel therapies are under development or in clinical trial phase. Muscle imaging can detect specific patterns of involvement and facilitate diagnosis and guide genetic testing. Quantitative MRT can be used to monitor disease progression either to monitor treatment or as a surrogate parameter for clinical trails. Novel imaging sequences can provide insights into disease pathology and muscle metabolism. (orig.)

  10. Equine diseases caused by known genetic mutations.

    Science.gov (United States)

    Finno, Carrie J; Spier, Sharon J; Valberg, Stephanie J

    2009-03-01

    The recent development of equine genome maps by the equine genome community and the complete sequencing of the horse genome performed at the Broad Institute have accelerated the pace of genetic discovery. This review focuses on genetic diseases in the horse for which a mutation is currently known, including hyperkalemic periodic paralysis, severe combined immunodeficiency, overo lethal white syndrome, junctional epidermolysis bullosa, glycogen branching enzyme deficiency, malignant hyperthermia, hereditary equine regional dermal asthenia, and polysaccharide storage myopathy. Emphasis is placed on the prevalence, clinical signs, etiology, diagnosis, treatment and prognosis for each disease.

  11. Chemotherapy Side Effects: A Cause of Heart Disease?

    Science.gov (United States)

    ... side effects: A cause of heart disease? Can chemotherapy side effects increase the risk of heart disease? Answers from Timothy J. Moynihan, M.D. Chemotherapy side effects may increase the risk of heart ...

  12. [Diseases caused by diisocyanates. 2. Diisocyanate asthma].

    Science.gov (United States)

    Lubach, D

    1979-01-01

    Diisocyanates are widely used as polymerizing agents in the production of polyurethanes. Exposure to high concentrations of toluene diisocyanate (TDI) causes the development of toxic-irritative symptoms in the respiratory tract. It has been observed that some workers, after repeated exposures and a latent period of months to years, develop asthmatic symptoms upon re-exposure to minute concentrations of diisocyanates. An immunological mechanism for this typical extrinsic asthma has not been adequately documented.

  13. [Giant scrotal lymphedema caused by Milroy's disease].

    Science.gov (United States)

    Gueglio, G; Quijada, Edin; Salas, H; Daels, P; Tejerizo, J; Chernobilsky, V; Giúdice, C; Damia, O

    2003-10-01

    To report a new case of giant scrotal lymphedema due to Milroy's disease, its treatment and outcome. A 27-year-old man with generalized congenital lymphedema presented with a giant scrotal mass which interfered with his daily activities and physiological necessities. Physical examination showed a scrotal mass 40 x 40 cm in size and a normal penis. CT scan showed a homogeneous mass, thickened vaginal tunica, and bilateral hydrocele. A surgical procedure was performed including mass resection (5.6 kg), and bilateral hydrocelectomy. Skin defect was covered with skin grafts. Several therapeutic alternatives have been suggested for Milroy's disease with genital involvement. Nevertheless, when complications are as severe as in the present case, the only valid therapy is surgery.

  14. Acrolein Can Cause Cardiovascular Disease: A Review.

    Science.gov (United States)

    Henning, Robert J; Johnson, Giffe T; Coyle, Jayme P; Harbison, Raymond D

    2017-07-01

    Acrolein is a highly reactive unsaturated aldehyde that is formed during the burning of gasoline and diesel fuels, cigarettes, woods and plastics. In addition, acrolein is generated during the cooking or frying of food with fats or oils. Acrolein is also used in the synthesis of many organic chemicals and as a biocide in agricultural and industrial water supply systems. The total emissions of acrolein in the United States from all sources are estimated to be 62,660 tons/year. Acrolein is classified by the Environmental Protection Agency as a high-priority air and water toxicant. Acrolein can exert toxic effects following inhalation, ingestion, and dermal exposures that are dose dependent. Cardiovascular tissues are particularly sensitive to the toxic effects of acrolein based primarily on in vitro and in vivo studies. Acrolein can generate free oxygen radical stress in the heart, decrease endothelial nitric oxide synthase phosphorylation and nitric oxide formation, form cytoplasmic and nuclear protein adducts with myocyte and vascular endothelial cell proteins and cause vasospasm. In this manner, chronic exposure to acrolein can cause myocyte dysfunction, myocyte necrosis and apoptosis and ultimately lead to cardiomyopathy and cardiac failure. Epidemiological studies of acrolein exposure and toxicity should be developed and treatment strategies devised that prevent or significantly limit acrolein cardiovascular toxicity.

  15. Mycobacterium paratuberculosis as a cause of Crohn's disease.

    Science.gov (United States)

    McNees, Adrienne L; Markesich, Diane; Zayyani, Najah R; Graham, David Y

    2015-01-01

    Crohn's disease is a chronic inflammatory bowel disease of unknown cause, affecting approximately 1.4 million North American people. Due to the similarities between Crohn's disease and Johne's disease, a chronic enteritis in ruminant animals caused by Mycobacterium avium paratuberculosis (MAP) infection, MAP has long been considered to be a potential cause of Crohn's disease. MAP is an obligate intracellular pathogen that cannot replicate outside of animal hosts. MAP is widespread in dairy cattle and because of environmental contamination and resistance to pasteurization and chlorination, humans are frequently exposed through contamination of food and water. MAP can be cultured from the peripheral mononuclear cells from 50-100% of patients with Crohn's disease, and less frequently from healthy individuals. Association does not prove causation. We discuss the current data regarding MAP as a potential cause of Crohn's disease and outline what data will be required to firmly prove or disprove the hypothesis.

  16. Diseases of fish and shellfish caused by marine fungi.

    Science.gov (United States)

    Hatai, Kishio

    2012-01-01

    Fungal diseases are problematic in cultured fish and shellfish, their seeds, and sometimes wild marine animals. In this chapter fungal diseases found in marine animals, especially in Japan, are described. Pathogens in the fungal diseases are divided into two groups. One of them is marine Oomycetes, which cause fungal diseases in marine shellfish and abalones. The diseases caused by the fungi of this group and the fungal characteristics are introduced. The pathogens include members of the genera Lagenidium, Haliphthoros, Halocrusticida, Halioticida, Atkinsiella, and Pythium. On the other hand, some fungal diseases caused by mitosporic fungi are also known in marine fish and shellfish. The diseases caused by these fungi and the fungal characteristics are described. The pathogens include members of the genera Fusarium, Ochroconis, Exophiala, Scytalidium, Plectosporium, and Acremonium.

  17. Mycobacterium paratuberculosis as a cause of Crohn's disease

    Science.gov (United States)

    McNees, Adrienne L.; Markesich, Diane; Zayyani, Najah R.; Graham, David Y.

    2016-01-01

    SUMMARY Crohn's disease is a chronic inflammatory bowel disease of unknown cause, affecting approximately 1.4 million North American people. Due to the similarities between Crohn's disease and Johne’s disease, a chronic enteritis in ruminant animals caused by Mycobacterium avium paratuberculosis (MAP) infection, MAP has long been considered to be a potential cause of Crohn's disease. MAP is an obligate intracellular pathogen that cannot replicate outside of animal hosts. MAP is widespread in dairy cattle and because of environmental contamination and resistance to pasteurization and chlorination, humans are frequently exposed through contamination of food and water. MAP can be cultured from the peripheral mononuclear cells from 50 to 100% of patients with Crohn's disease, and less frequently from healthy individuals. Association does not prove causation. We discuss the current data regarding MAP as a potential cause of Crohn's disease and outline what data will be required to firmly prove or disprove the hypothesis. PMID:26474349

  18. Genome engineering: a new approach to gene therapy for neuromuscular disorders.

    Science.gov (United States)

    Nelson, Christopher E; Robinson-Hamm, Jacqueline N; Gersbach, Charles A

    2017-11-01

    For many neuromuscular disorders, including Duchenne muscular dystrophy, spinal muscular atrophy and myotonic dystrophy, the genetic causes are well known. Gene therapy holds promise for the treatment of these monogenic neuromuscular diseases, and many such therapies have made substantial strides toward clinical translation. Recently, genome engineering tools, including targeted gene editing and gene regulation, have become available to correct the underlying genetic mutations that cause these diseases. In particular, meganucleases, zinc finger nucleases, TALENs, and the CRISPR-Cas9 system have been harnessed to make targeted and specific modifications to the genome. However, for most gene therapy applications, including genome engineering, gene delivery remains the primary hurdle to clinical translation. In preclinical models, genome engineering tools have been delivered via gene-modified cells or by non-viral or viral vectors to correct a diverse array of genetic diseases. In light of the positive results of these studies, genome engineering therapies are being enthusiastically explored for several genetic neuromuscular disorders. This Review summarizes the genome engineering strategies that are currently under preclinical evaluation for the treatment of degenerative neuromuscular disorders, with a focus on the molecular tools that show the greatest potential for clinical translation of these therapies.

  19. Clostridium difficile and the disease it causes.

    Science.gov (United States)

    Norén, Torbjörn

    2010-01-01

    factors like high toxin production and sporulation challenge the therapeutic situation and cause great concern among infection control workers. Excessive use of modern fluoroquinolones is thought to play an important role in facilitating this epidemic since NAP1/027 was shown to have acquired moxifloxacin resistance compared to historical strains of the same genotype. Both the current epidemic like this and other local outbreaks from resistant or virulent strains warrant culture to be routinely performed enabling susceptibility testing and typing of the pathogen. Genotyping is most commonly done today by pulse-field gel electrophoresis (PFGE) or PCR ribotyping but multilocus variable-number tandem-repeat analysis (MLVA) seems promising. Epidemiological surveillance using all these tools will help us to better understand the global spread of C. difficile.

  20. Identification of Changing Lower Limb Neuromuscular Activation in Parkinson’s Disease during Treadmill Gait with and without Levodopa Using a Nonlinear Analysis Index

    Directory of Open Access Journals (Sweden)

    Amir Pourmoghaddam

    2015-01-01

    Full Text Available Analysis of electromyographic (EMG data is a cornerstone of research related to motor control in Parkinson’s disease. Nonlinear EMG analysis tools have shown to be valuable, but analysis is often complex and interpretation of the data may be difficult. A previously introduced algorithm (SYNERGOS that provides a single index value based on simultaneous multiple muscle activations (MMA has been shown to be effective in detecting changes in EMG activation due to modifications of walking speeds in healthy adults. In this study, we investigated if SYNERGOS detects MMA changes associated with both different walking speeds and levodopa intake. Nine male Parkinsonian patients walked on a treadmill with increasing speed while on or off medication. We collected EMG data and computed SYNERGOS indices and employed a restricted maximum likelihood linear mixed model to the values. SYNERGOS was sensitive to neuromuscular modifications due to both alterations of gait speed and intake of levodopa. We believe that the current experiment provides evidence for the potential value of SYNERGOS as a nonlinear tool in clinical settings, by providing a single value index of MMA. This could help clinicians to evaluate the efficacy of interventions and treatments in Parkinson’s disease in a simple manner.

  1. Celiac disease: A missed cause of metabolic bone disease

    Directory of Open Access Journals (Sweden)

    Ashu Rastogi

    2012-01-01

    Full Text Available Introduction: Celiac disease (CD is a highly prevalent autoimmune disease. The symptoms of CD are varied and atypical, with many patients having no gastrointestinal symptoms. Metabolic bone disease (MBD is a less recognized manifestation of CD associated with spectrum of musculoskeletal signs and symptoms, viz. bone pains, proximal muscle weakness, osteopenia, osteoporosis, and fracture. We here report five patients who presented with severe MBD as the only manifestation of CD. Materials and Methods: Records of 825 patients of CD diagnosed during 2002-2010 were retrospectively analyzed for clinical features, risk factors, signs, biochemical, and radiological parameters. Results: We were able to identify five patients (0.6% of CD who had monosymptomatic presentation with musculoskeletal symptoms and signs in the form of bone pains, proximal myopathy, and fragility fractures without any gastrointestinal manifestation. All the five patients had severe MBD in the form of osteopenia, osteoporosis, and fragility fractures. Four of the five patients had additional risk factors such as antiepileptic drugs, chronic alcohol consumption, malnutrition, and associated vitamin D deficiency which might have contributed to the severity of MBD. Conclusion: Severe metabolic disease as the only presentation of CD is rare. Patients show significant improvement in clinical, biochemical, and radiological parameters with gluten-free diet, calcium, and vitamin D supplementation. CD should be looked for routinely in patients presenting with unexplained MBD.

  2. [Clinicopathological investigations of the dental diseases caused by maxillary lesions].

    Science.gov (United States)

    Sato, K

    1998-03-01

    Clinicopathological investigations of five surgery-requiring dental diseases caused by maxillary lesions were conducted. 1) The maxillary lesions were acute maxillary sinusitis and a postoperative maxillary cyst. 2) The clinical symptom was persistent cheek pain, even though the maxillary lesions were improved and there were no lesions in the tooth crown or periodontal tissue. 3) All of the teeth with dental diseases caused by maxillary lesions had percussion pain. 4) The pathological findings of the dental diseases were ascending pulpitis and pulpal necrosis caused by maxillary lesions. 5) When patients complain of persistent cheek pain even though maxillary lesions are improved and there are no lesions of the tooth crown or periodontal tissue, we should doubt the presence of dental diseases caused by maxillary lesions (ascending pulpitis and pulpal necrosis).

  3. Diseases caused by poxvirus - orf and milker's nodules: a review

    Directory of Open Access Journals (Sweden)

    S.R.C.S. Barraviera

    2005-06-01

    Full Text Available Sheep and cattle parapoxviruses cause in human beings diseases of very similar aspect, named orf and milker's nodules, respectively. These infections are generically called farmyard pox. In the present article, we show the epidemiological, clinical, and histopathological aspects, as well as the treatment of these two viral diseases that are very similar, being differentiated only by their epidemiological aspects.

  4. diseases and causes of death among the popes 1. introduction

    African Journals Online (AJOL)

    illnesses, malaria, stroke, severe heart disease, gout or poly-arthritis, terminal kidney disease, gallstones, cancer, dysentery, the plague, lung infection, gangrene of a leg, abscesses, depression or debilitating psychiatric illness. Unnatural causes comprise inter alia assassination, death in prison or in exile, casualties of war ...

  5. Biological control of post harvest disease caused by Aspergillus ...

    African Journals Online (AJOL)

    Biological control of post harvest disease caused by Aspergillus flavus on stored lemon fruits. ... Erwinia chrysanthemi RK-67 and Bacillus subtilis RK-6 treatments reduced disease severity on both lemon cultivars. Furthermore, both the cell suspension and culture filtrates of Burkholderia cepacia strain RK- 277 reduced ...

  6. Hereditary Causes of Kidney Stones and Chronic Kidney Disease

    Science.gov (United States)

    Edvardsson, Vidar O.; Goldfarb, David S.; Lieske, John C.; Beara-Lasic, Lada; Anglani, Franca; Milliner, Dawn S.; Palsson, Runolfur

    2013-01-01

    Adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) and primary hyperoxaluria (PH) are rare but important causes of severe kidney stone disease and/or chronic kidney disease in children. Recurrent kidney stone disease and nephrocalcinosis, particularly in pre-pubertal children, should alert the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition and knowledge of the five disorders has frequently resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences. A high index of suspicion coupled with early diagnosis may reduce or even prevent the serious long-term complications of these diseases. In this paper, we review the epidemiology, clinical features, diagnosis, treatment and outcome of patients with APRT deficiency, cystinuria, Dent disease, FHHNC and PH with emphasis on childhood manifestations. PMID:23334384

  7. Research highlights of partial neuromuscular disorders

    Directory of Open Access Journals (Sweden)

    Cheng ZHANG

    2014-05-01

    Full Text Available In order to understand the latest progression on neuromuscular disorders for clinicians, this review screened and systemized the papers on neuromuscular disorders which were collected by PubMed from January 2013 to February 2014. This review also introduced the clinical diagnosis and treatment hightlights on glycogen storage disease type Ⅱ (GSD Ⅱ, Duchenne muscular dystrophy (DMD, amyotrophic lateral sclerosis (ALS and spinal muscular atrophy (SMA. The important references will be useful for clinicians. doi: 10.3969/j.issn.1672-6731.2014.05.004

  8. Neuromuscular Junction Dismantling in Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Valentina Cappello

    2017-10-01

    Full Text Available Neuromuscular junction assembly and plasticity during embryonic, postnatal, and adult life are tightly regulated by the continuous cross-talk among motor nerve endings, muscle fibers, and glial cells. Altered communications among these components is thought to be responsible for the physiological age-related changes at this synapse and possibly for its destruction in pathological states. Neuromuscular junction dismantling plays a crucial role in the onset of Amyotrophic Lateral Sclerosis (ALS. ALS is characterized by the degeneration and death of motor neurons leading to skeletal muscle denervation, atrophy and, most often, death of the patient within five years from diagnosis. ALS is a non-cell autonomous disease as, besides motor neuron degeneration, glial cells, and possibly muscle fibers, play a role in its onset and progression. Here, we will review the recent literature regarding the mechanisms leading to neuromuscular junction disassembly and muscle denervation focusing on the role of the three players of this peripheral tripartite synapse.

  9. Neuromuscular Exercise Post Partial Medial Meniscectomy

    DEFF Research Database (Denmark)

    Hall, Michelle; Hinman, Rana S; Wrigley, Tim V

    2015-01-01

    : In patients 3-12 months following a medial arthroscopic partial meniscectomy, a neuromuscular exercise program did not alter the peak knee adduction moment, a key predictor of osteoarthritis structural disease progression. Australia and New Zealand Clinical Trials Registry (#ACTRN12612000542897)....

  10. CLINICAL PICTURE AND TREATMENT TACTICS OF PATIENTS WITH TEMPOROMANDIBULAR JOINT NEUROMUSCULAR DYSFUNCTIONAL SYNDROME

    Directory of Open Access Journals (Sweden)

    V.P. Potapov

    2009-03-01

    Full Text Available We have analyzed the results of diagnostics and treatment of 36 patients with neuromuscular dysfunctional syndrome of TMJ. We have found that the cause of pathology is acute damage, stress, parafunction of masseteric muscules, durable influence on the joint. NDS is characterized by the impairment of masseteric muscularfunction, that results in motional restriction in all directions. Treatment must include elimination of etiological factors, symptoms of the disease, normalization of masseteric muscle function and prophylaxis of complications.

  11. Mutations in mitochondrial DNA causing tubulointerstitial kidney disease.

    Directory of Open Access Journals (Sweden)

    Thomas M Connor

    2017-03-01

    Full Text Available Tubulointerstitial kidney disease is an important cause of progressive renal failure whose aetiology is incompletely understood. We analysed a large pedigree with maternally inherited tubulointerstitial kidney disease and identified a homoplasmic substitution in the control region of the mitochondrial genome (m.547A>T. While mutations in mtDNA coding sequence are a well recognised cause of disease affecting multiple organs, mutations in the control region have never been shown to cause disease. Strikingly, our patients did not have classical features of mitochondrial disease. Patient fibroblasts showed reduced levels of mitochondrial tRNAPhe, tRNALeu1 and reduced mitochondrial protein translation and respiration. Mitochondrial transfer demonstrated mitochondrial transmission of the defect and in vitro assays showed reduced activity of the heavy strand promoter. We also identified further kindreds with the same phenotype carrying a homoplasmic mutation in mitochondrial tRNAPhe (m.616T>C. Thus mutations in mitochondrial DNA can cause maternally inherited renal disease, likely mediated through reduced function of mitochondrial tRNAPhe.

  12. Validation of the individualised neuromuscular quality of life for the USA with comparison of the impact of muscle disease on those living in USA versus UK.

    Science.gov (United States)

    Sadjadi, Reza; Vincent, Kelly A; Carr, Alison J; Walburn, Jessica; Brooks, Victoria L; Pandya, Shree; Kissel, John T; Jackson, Carlayne E; Rose, Michael R

    2011-12-16

    The Individualised Neuromuscular Quality of Life (INQoL) questionnaire is a published muscle disease specific measure of QoL that has been validated using both qualitative and quantitative methods in a United Kingdom population of adults with muscle disease. If INQoL is to be used in other countries it needs to be linguistically and culturally validated for those countries. It may be important to understand any cultural differences in how patients rate their QoL when applying QoL measures in multi-national clinical trials. We conducted a postal survey of QoL issues in US adults with muscle disease using an agreed translation, from UK to US English, of the same questionnaire as was used in the original construction of INQoL. This questionnaire included an opportunity for free text comments on any aspects of QoL that might not have been covered by the questionnaire. We examined the responses using both quantitative and qualitative approaches. The frequency of the responses in US versus UK populations was compared using appropriate correlation tests and Rasch analysis. A phenomenological approach was used to guide the qualitative analysis and facilitate the exploration of patients' perceptions and experiences. The US survey received 333 responses which were compared with 251 UK survey responses.We found that INQoL domains covered all the issues raised by US subjects with no additional domains required. The experiences of those with muscle disease were remarkably similar in the US and UK but there were differences related to the impact of muscle disease on relationships and on employment which was greater for those living in the United States. The greater impact on employment was associated with a higher importance rating given to employment in the US. This may reflect the lower level of financial support for those who are unemployed, and the loss of employment related health benefits. INQoL is appropriate for use in US population but there may be differences in the

  13. Validation of the individualised neuromuscular quality of life for the USA with comparison of the impact of muscle disease on those living in USA versus UK

    Directory of Open Access Journals (Sweden)

    Sadjadi Reza

    2011-12-01

    Full Text Available Abstract Background The Individualised Neuromuscular Quality of Life (INQoL questionnaire is a published muscle disease specific measure of QoL that has been validated using both qualitative and quantitative methods in a United Kingdom population of adults with muscle disease. If INQoL is to be used in other countries it needs to be linguistically and culturally validated for those countries. It may be important to understand any cultural differences in how patients rate their QoL when applying QoL measures in multi-national clinical trials. Methods We conducted a postal survey of QoL issues in US adults with muscle disease using an agreed translation, from UK to US English, of the same questionnaire as was used in the original construction of INQoL. This questionnaire included an opportunity for free text comments on any aspects of QoL that might not have been covered by the questionnaire. We examined the responses using both quantitative and qualitative approaches. The frequency of the responses in US versus UK populations was compared using appropriate correlation tests and Rasch analysis. A phenomenological approach was used to guide the qualitative analysis and facilitate the exploration of patients' perceptions and experiences. Results The US survey received 333 responses which were compared with 251 UK survey responses. We found that INQoL domains covered all the issues raised by US subjects with no additional domains required. The experiences of those with muscle disease were remarkably similar in the US and UK but there were differences related to the impact of muscle disease on relationships and on employment which was greater for those living in the United States. The greater impact on employment was associated with a higher importance rating given to employment in the US. This may reflect the lower level of financial support for those who are unemployed, and the loss of employment related health benefits. Conclusions INQoL is

  14. Seeking a better landscape for therapy development in neuromuscular disorders.

    Science.gov (United States)

    Larkindale, Jane; Porter, John D

    2018-01-01

    Although the neuromuscular field has seen accelerated approval of a drug for Duchenne muscular dystrophy (DMD) and full approval of one for spinal muscular atrophy, these experiences have shown that objective data and an adequate level of effect are essential for drug approval and reimbursement. The appropriateness and validity of biomarkers and clinically meaningful endpoints and an understanding of disease progression rates all played essential roles in the levels of evidence for these drugs. Such tools are best developed through integration of clinical data. The siloing of clinical data for rare neuromuscular diseases represents a considerable barrier to achieving better care and novel therapies for patients living with neuromuscular diseases. We discuss a data-sharing model implemented for DMD and urge cultural changes in the ways natural history and clinical trial data are collected and shared across all neuromuscular diseases in order to benefit the primary stakeholder, the patient. Muscle Nerve 57: 16-19, 2018. © 2017 Wiley Periodicals, Inc.

  15. Cause-Specific Mortality Among Spouses of Parkinson Disease Patients

    DEFF Research Database (Denmark)

    Nielsen, Malene; Hansen, Jonni; Ritz, Beate

    2014-01-01

    BACKGROUND: Caring for a chronically ill spouse is stressful, but the health effects of caregiving are not fully understood. We studied the effect on mortality of being married to a person with Parkinson disease. METHODS: All patients in Denmark with a first-time hospitalization for Parkinson...... disease between 1986 and 2009 were identified, and each case was matched to five population controls. We further identified all spouses of those with Parkinson disease (n = 8,515) and also the spouses of controls (n = 43,432). All spouses were followed in nationwide registries until 2011. RESULTS: Among...... men, being married to a Parkinson disease patient was associated with a slightly higher risk of all-cause mortality (hazard ratio = 1.06 [95% confidence interval = 1.00-1.11]). Mortality was particularly high for death due to external causes (1.42 [1.09-1.84]) including suicide (1.89 [1...

  16. Application of neuromuscular electrical stimulation of the lower limb skeletal muscles in the rehabilitation of patients with chronic heart failure and chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Ewa Barbara Kucio

    2017-03-01

    Full Text Available Increasing physical activity is a widely-known method of rehabilitation of patients with chronic heart failure (CHF and chronic obstructive pulmonary disease (COPD. However, what kind of procedure is to be applied if a patient suffers from advanced heart or respiratory failure, cannot undertake physical exercise due to locomotor system disorders or is currently undergoing respiratorotherapy? Recent research shows that neuromuscular electrical stimulation of the lower limb skeletal muscles (NMES may comprise an alternative to physical training in patients with CHF and COPD. The aim of this study is to summarize the current state of knowledge on the use of NMES in cardiac rehabilitation of patients with CHF and pulmonary rehabilitation of patients with COPD. As demonstrated in recent research on the topic, NMES – due to forcing the muscles to activate – increases exercise tolerance, muscle mass and endurance in patients with CHF and COPD. The beneficial effect of NMES on blood circulation in the muscles, aerobic enzymes activity, functioning of the vascular endothelium, reduction of pro-inflammatory cytokines concentration and increased quality of life has also been presented. It is to be accentuated that NMES treatment, due to lesser physical exertion and, in turn, a decreased feeling of dyspnea are more comfortable for the patient than traditional physical training. Moreover, NMES treatment, after foregoing training, can be applied at home. Potential side effects include transient muscle pain and minor skin damage due to improper positioning of the electrodes. To summarize, NMES treatment is well received by CHF and COPD patients and brings about increased exercise tolerance, as well as better quality of life. Devices used for NMES therapy, due to progressive miniaturization, are easily accessible and relatively inexpensive.

  17. Patient-controlled positive end-expiratory pressure with neuromuscular disease: effect on speech in patients with tracheostomy and mechanical ventilation support.

    Science.gov (United States)

    Garguilo, Marine; Leroux, Karl; Lejaille, Michèle; Pascal, Sophie; Orlikowski, David; Lofaso, Frédéric; Prigent, Hélène

    2013-05-01

    Communication is a major issue for patients with tracheostomy who are supported by mechanical ventilation. The use of positive end-expiratory pressure (PEEP) may restore speech during expiration; however, the optimal PEEP level for speech may vary individually. We aimed to improve speech quality with an individually adjusted PEEP level delivered under the patient's control to ensure optimal respiratory comfort. Optimal PEEP level (PEEPeff), defined as the PEEP level that allows complete expiration through the upper airways, was determined for 12 patients with neuromuscular disease who are supported by mechanical ventilation. Speech and respiratory parameters were studied without PEEP, with PEEPeff, and for an intermediate PEEP level. Flow and airway pressure were measured. Microphone speech recordings were subjected to both quantitative and qualitative assessments of speech, including an intelligibility score, a perceptual score, and an evaluation of prosody determined by two speech therapists blinded to PEEP condition. Text reading time, phonation flow, use of the respiratory cycle for phonation, and speech comfort significantly improved with increasing PEEP, whereas qualitative parameters remained unchanged. This resulted mostly from the increase of the expiratory volume through the upper airways available for speech for all patients combined, with a rise in respiratory rate for nine patients. Respiratory comfort remained stable despite high levels of PEEPeff (median, 10.0 cm H2O; interquartile range, 9.5-12.0 cm H₂O). Patient-controlled PEEP allowed for the use of high levels of PEEP with good respiratory tolerance and significant improvement in speech (enabling phonation during the entire respiratory cycle in most patients). The device studied could be implemented in home ventilators to improve speech and, therefore, autonomy of patients with tracheostomy. ClinicalTrials.gov; No.: NCT01479959; URL: clinicaltrials.gov.

  18. Lack of exercise is a major cause of chronic diseases

    Science.gov (United States)

    Booth, Frank W.; Roberts, Christian K.; Laye, Matthew J.

    2014-01-01

    Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause vs. treatment; physical activity and inactivity mechanisms differ; gene-environment interaction [including aerobic training adaptations, personalized medicine, and co-twin physical activity]; and specificity of adaptations to type of training. Next, physical activity/exercise is examined as primary prevention against 35 chronic conditions [Accelerated biological aging/premature death, low cardiorespiratory fitness (VO2max), sarcopenia, metabolic syndrome, obesity, insulin resistance, prediabetes, type 2 diabetes, non-alcoholic fatty liver disease, coronary heart disease, peripheral artery disease, hypertension, stroke, congestive heart failure, endothelial dysfunction, arterial dyslipidemia, hemostasis, deep vein thrombosis, cognitive dysfunction, depression and anxiety, osteoporosis, osteoarthritis, balance, bone fracture/falls, rheumatoid arthritis, colon cancer, breast cancer, endometrial cancer, gestational diabetes, preeclampsia, polycystic ovary syndrome, erectile dysfunction, pain, diverticulitis, constipation, and gallbladder diseases]. The article ends with consideration of deterioration of risk factors in longer-term sedentary groups; clinical consequences of inactive childhood/adolescence; and public policy. In summary, the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life. Taken together, conclusive evidence exists that physical inactivity is one important cause of most chronic diseases. In addition, physical activity primarily prevents, or delays, chronic diseases, implying that chronic disease need not be an inevitable outcome during life

  19. Circadian clock disruption in neurodegenerative diseases: Cause and effect?

    Directory of Open Access Journals (Sweden)

    Erik Steven Musiek

    2015-02-01

    Full Text Available Disturbance of the circadian system, manifested as disrupted daily rhythms of physiologic parameters such as sleep, activity, and hormone secretion, has long been observed as a symptom of several neurodegenerative diseases, including Alzheimer Disease. Circadian abnormalities have generally been considered consequences of the neurodegeneration. Recent evidence suggests, however, that circadian disruption might actually contribute to the neurodegenerative process, and thus might be a modifiable cause of neural injury. Herein we will review the evidence implicating circadian rhythms disturbances and clock gene dysfunction in neurodegeneration, with an emphasis on future research directions and potential therapeutic implications for neurodegenerative diseases.

  20. Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Karen K Y Ling

    2010-11-01

    Full Text Available Spinal muscular atrophy (SMA is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7. In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3-5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.

  1. FUNCTIONS OF A NEUROMUSCULAR CENTRE

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    Janez Zidar

    2004-12-01

    Full Text Available Main functions of a neuromuscular (NM centre are making diagnosis, treatment and counselling. Some other functions, e. g. forming a register and epidemiological endeavours, could be added. All these activities are expected to be achieved by multidisciplinary approach with the idea that members use the same guidelines and share the same knowledge.NM diseases affect lower levels of the nervous system that is motor units (motor cells in the brainstem and spinal cord, nerve roots, cranial and peripheral nerves, neuromuscular junction, and muscles. There are many such diseases; a few are more common others are rare.Rational approach in making a diagnosis can be divided into several steps. The process begins with a person with clinical symptoms and signs which raise the suspicion of NM disease. The first step is the description of the predominant pattern of muscular wasting and weakness (e. g. limb-girdle, distal, ocular, facio-scapulo-humeral. Each of these syndromes require a differential diagnosis within the motor unit territory what is achieved by means of EMG and muscle biopsy. The latter is even more important to define the nature of the abnormality. Disease nature can also be determined biochemically and, as NM disorders are commonly genetically determined, at the molecular genetic level. Treatment modalities include drugs (causative and symptomatic and other measures such as promoting and maintaining good general health, preventing skeletal deformities, physiotherapy, orthoses, surgery, and prevention of respiratory and cardiac functions. Counselling is mainly by social workers that focus on the practical aspects of coping with illness and disability and by genetic counsellors who gave advise on family planning.

  2. Chilli anthracnose disease caused by Colletotrichum species§

    Science.gov (United States)

    Than, Po Po; Prihastuti, Haryudian; Phoulivong, Sitthisack; Taylor, Paul W.J.; Hyde, Kevin D.

    2008-01-01

    Anthracnose disease is one of the major economic constraints to chilli production worldwide, especially in tropical and subtropical regions. Accurate taxonomic information is necessary for effective disease control management. In the Colletotrichum patho-system, different Colletotrichum species can be associated with anthracnose of the same host. Little information is known concerning the interactions of the species associated with the chilli anthracnose although several Colletotrichum species have been reported as causal agents of chilli anthracnose disease worldwide. The ambiguous taxonomic status of Colletotrichum species has resulted in inaccurate identification which may cause practical problems in plant breeding and disease management. Although the management and control of anthracnose disease are still being extensively researched, commercial cultivars of Capsicum annuum that are resistant to the pathogens that cause chilli anthracnose have not yet been developed. This paper reviews the causal agents of chilli anthracnose, the disease cycle, conventional methods in identification of the pathogen and molecular approaches that have been used for the identification of Colletotrichum species. Pathogenetic variation and population structure of the causal agents of chilli anthracnose along with the current taxonomic status of Colletotrichum species are discussed. Future developments leading to the disease management strategies are suggested. PMID:18837103

  3. Neuromuscular disorders in chronic alcohol intoxication

    Directory of Open Access Journals (Sweden)

    A. Yu. Emelyanova

    2015-01-01

    Full Text Available The paper reviews the present-day Russian and foreign literature on neuromuscular disorders in chronic alcohol intoxication. The most common manifestations of alcohol disease include alcoholic polyneuropathy (PNP and alcohol-induced skeletal muscle injury. The clinical polymorphism of alcoholic PNP is discussed. The paper considers a chronic sensory automatic form due to the direct toxic effects of ethanol and its metabolites during long-term alcohol intoxication, as well as acute/subacute sensorimotor neuropathy, the basis for the pathogenesis of which is B group vitamins, predominantly thiamine, deficiency that develops in the presence of drinking bouts concurrent with malnutrition and/or alcohol-related gastrointestinal tract diseases. In addition to nonuse of alcohol and a properly balanced diet, antioxidant therapy with alphalipoic acid and neurotropic B group vitamins is considered to be pathogenetic therapy for neuropathy. The most common and least studied clinicalform of alcohol-induced musculoskeletal injury is chronic alcoholic myopathy (AM, the diagnostic standard for which is morphometricand immunohistochemical examination of a muscle biopsy specimen. The morphological base for this form of myopathy is predominantly type 2 muscle fiber atrophy caused by impaired protein synthesis and a decreased regenerative potential of muscle fiber. The efficacy of antioxidants and leucine-containing amino acid mixtures in the treatment of chronic AM is discussed.

  4. Survey of bacterial and parasitic organisms causing disease and ...

    African Journals Online (AJOL)

    Survey of bacterial and parasitic organisms causing disease and lowered production in indigenous chickens in southern Nyanza, Kenya. ... Other bacteria isolated, from oro-pharyngeal and cloacal swabs, included: Staphylococcus, Bacillus, E. coli, and Enterobacter. Aspergillus fumigatus was isolated from a case of skin ...

  5. Diseases of pines caused by the pitch canker fungus

    Science.gov (United States)

    L. David Dwinell; Stephen W. Fraedrich; D. Adams

    2001-01-01

    Fusarium subglutinans f. sp. pini, the pitch canker fungus, causes a number of serious diseases of Pinus species. The pathogen infects a variety of vegetative and reproductive pine structures at different stages of maturity and produces a diversity of symptoms. When the pathogen infects the woody vegetative...

  6. Diseases and causes of death among the Popes | Retief | Acta ...

    African Journals Online (AJOL)

    ... terminal kidney disease, gallstones, cancer, dysentery, the plague, lung infection, gangrene of a leg, abscesses, depression or debilitating psychiatric illness. Unnatural causes comprise inter alia assassination, death in prison or in exile, casualties of war or public violence, poisoning and stoning during street violence.

  7. Colletotrichum species causing anthracnose disease of chili in China

    NARCIS (Netherlands)

    Diao, Y.-Z.; Zhang, C.; Liu, F.; Wang, W.-Z.; Liu, L.; Cai, L.; Liu, X.-L.

    2017-01-01

    Anthracnose caused by Colletotrichum species is a serious disease of more than 30 plant genera. Several Colletotrichum species have been reported to infect chili in different countries. Although China is the largest chiliproducing country, little is known about the species that have been infecting

  8. HIV/AIDS, the Disease and Hunger Complications Causing ...

    African Journals Online (AJOL)

    HIV/AIDS, the Disease and Hunger Complications Causing Confusion in Rural Western Kenya: A Case Study of Katolo. ... The PCR test is more reliable, because it is capable of looking at the viral DNA, which neither Western Blot nor Elisa methods can do. (Af. J. of Food and Nutritional Security: 2001 1(1): 60-70) ...

  9. Chemical control of blossom blight disease of sarpagandha caused ...

    African Journals Online (AJOL)

    ONOS

    2010-09-20

    Sep 20, 2010 ... anthracnose and fruit rot disease of chili caused by C. capsici was achieved by spraying with Carbendazim and. Mancozeb (Das and Mohanty, 1988; Biswas, 1992;. Ebenezar and Alice, 1996). Sometimes, fungicide highly effective in vitro was not effective in vivo, as we observed with Propiconazole.

  10. Dmdmdx/Largemyd: a new mouse model of neuromuscular diseases useful for studying physiopathological mechanisms and testing therapies

    Directory of Open Access Journals (Sweden)

    Poliana C. M. Martins

    2013-09-01

    Although muscular dystrophies are among the most common human genetic disorders, there are few treatment options available. Animal models have become increasingly important for testing new therapies prior to entering human clinical trials. The Dmdmdx mouse is the most widely used animal model for Duchenne muscular dystrophy (DMD, presenting the same molecular and protein defect as seen in humans with the disease. However, this mouse is not useful for clinical trials because of its very mild phenotype. The mouse model for congenital myodystrophy type 1D, Largemyd, harbors a mutation in the glycosyltransferase Large gene and displays a severe phenotype. To help elucidate the role of the proteins dystrophin and LARGE in the organization of the dystrophin-glycoprotein complex in muscle sarcolemma, we generated double-mutant mice for the dystrophin and LARGE proteins. The new Dmdmdx/Largemyd mouse model is viable and shows a severe phenotype that is associated with the lack of dystrophin in muscle. We tested the usefulness of our new mouse model for cell therapy by systemically injecting them with normal murine mesenchymal adipose stem cells (mASCs. We verified that the mASCs were hosted in the dystrophic muscle. The new mouse model has proven to be very useful for the study of several other therapies, because injected cells can be screened both through DNA and protein analysis. Study of its substantial muscle weakness will also be very informative in the evaluation of functional benefits of these therapies.

  11. Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments.

    Science.gov (United States)

    Sun, RongRong; Liu, Min; Lu, Lei; Zheng, Yi; Zhang, Peiying

    2015-07-01

    The congenital heart disease includes abnormalities in heart structure that occur before birth. Such defects occur in the fetus while it is developing in the uterus during pregnancy. About 500,000 adults have congenital heart disease in USA (WebMD, Congenital heart defects medications, www.WebMD.com/heart-disease/tc/congenital-heart-defects-medications , 2014). 1 in every 100 children has defects in their heart due to genetic or chromosomal abnormalities, such as Down syndrome. The excessive alcohol consumption during pregnancy and use of medications, maternal viral infection, such as Rubella virus, measles (German), in the first trimester of pregnancy, all these are risk factors for congenital heart disease in children, and the risk increases if parent or sibling has a congenital heart defect. These are heart valves defects, atrial and ventricular septa defects, stenosis, the heart muscle abnormalities, and a hole inside wall of the heart which causes defect in blood circulation, heart failure, and eventual death. There are no particular symptoms of congenital heart disease, but shortness of breath and limited ability to do exercise, fatigue, abnormal sound of heart as heart murmur, which is diagnosed by a physician while listening to the heart beats. The echocardiogram or transesophageal echocardiogram, electrocardiogram, chest X-ray, cardiac catheterization, and MRI methods are used to detect congenital heart disease. Several medications are given depending on the severity of this disease, and catheter method and surgery are required for serious cases to repair heart valves or heart transplantation as in endocarditis. For genetic study, first DNA is extracted from blood followed by DNA sequence analysis and any defect in nucleotide sequence of DNA is determined. For congenital heart disease, genes in chromosome 1 show some defects in nucleotide sequence. In this review the causes, diagnosis, symptoms, and treatments of congenital heart disease are described.

  12. [Characteristics of neuromuscular scoliosis].

    Science.gov (United States)

    Putzier, M; Groß, C; Zahn, R K; Pumberger, M; Strube, P

    2016-06-01

    Usually, neuromuscular scolioses become clinically symptomatic relatively early and are rapidly progressive even after the end of growth. Without sufficient treatment they lead to a severe reduction of quality of life, to a loss of the ability of walking, standing or sitting as well as to an impairment of the cardiopulmonary system resulting in an increased mortality. Therefore, an intensive interdisciplinary treatment by physio- and ergotherapists, internists, pediatricians, orthotists, and orthopedists is indispensable. In contrast to idiopathic scoliosis the treatment of patients with neuromuscular scoliosis with orthosis is controversially discussed, whereas physiotherapy is established and essential to prevent contractures and to maintain the residual sensorimotor function.Frequently, the surgical treatment of the scoliosis is indicated. It should be noted that only long-segment posterior correction and fusion of the whole deformity leads to a significant improvement of the quality of life as well as to a prevention of a progression of the scoliosis and the development of junctional problems. The surgical intervention is usually performed before the end of growth. A prolonged delay of surgical intervention does not result in an increased height but only in a deformity progression and is therefore not justifiable. In early onset neuromuscular scolioses guided-growth implants are used to guarantee the adequat development. Because of the high complication rates, further optimization of these implant systems with regard to efficiency and safety have to be addressed in future research.

  13. Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease.

    Science.gov (United States)

    Wens, Stephan C A; Schaaf, Gerben J; Michels, Michelle; Kruijshaar, Michelle E; van Gestel, Tom J M; In 't Groen, Stijn; Pijnenburg, Joon; Dekkers, Dick H W; Demmers, Jeroen A A; Verdijk, Lex B; Brusse, Esther; van Schaik, Ron H N; van der Ploeg, Ans T; van Doorn, Pieter A; Pijnappel, W W M Pim

    2016-02-01

    Elevated plasma cardiac troponin T (cTnT) levels in patients with neuromuscular disorders may erroneously lead to the diagnosis of acute myocardial infarction or myocardial injury. In 122 patients with Pompe disease, the relationship between cTnT, cardiac troponin I, creatine kinase (CK), CK-myocardial band levels, and skeletal muscle damage was assessed. ECG and echocardiography were used to evaluate possible cardiac disease. Patients were divided into classic infantile, childhood-onset, and adult-onset patients. cTnT levels were elevated in 82% of patients (median 27 ng/L, normal values skeletal muscle was not detectable in controls but was strongly induced in patients with Pompe disease. cTnT protein was identified by mass spectrometry in patient-derived skeletal muscle tissue. Elevated plasma cTnT levels in patients with Pompe disease are associated with skeletal muscle damage, rather than acute myocardial injury. Increased cTnT levels in Pompe disease and likely other neuromuscular disorders should be interpreted with caution to avoid unnecessary cardiac interventions. © 2016 American Heart Association, Inc.

  14. Helicobacter pylori and autoimmune disease: Cause or bystander

    Science.gov (United States)

    Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P

    2014-01-01

    Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research. PMID:24574735

  15. Autoantibodies in neuromuscular transmission disorders

    Directory of Open Access Journals (Sweden)

    Vincent Angela

    2008-01-01

    Full Text Available It is a great pleasure to be asked to honour the memory of Dr. Baldev Singh by reviewing the field of autoantibodies in myasthenia gravis and other neurotransmission disorders. The neuromuscular junction (NMJ is the site of a number of different autoimmune and genetic disorders, and it is also the target of many neurotoxins from venomous snakes, spiders, scorpions and other species. The molecular organization of the NMJ is graphically represented in [Figure 1A], where different ion channels, receptors and other proteins are shown. Four of the ion channels or receptors are directly involved in autoimmune diseases. This brief review will not only concentrate on these conditions but also illustrate how their study is helping us to understand the etiology of rare but treatable neurological syndromes of the central nervous system.

  16. Graves’ disease as an uncommon cause of acute pericarditis

    Science.gov (United States)

    Kortekaas, Kirsten; van der Lienden, Bas; Jong, Simone; Riezebos, Robert

    2014-01-01

    Acute pericarditis is either dry, fibrinous or effusive, independent of its aetiology. A case is presented involving a 44-year-old man with acute pericarditis. The cause was established to be an aggravation of Graves’ disease due to non-compliance with treatment. Pericarditis is an uncommon cardiac complication of Graves’ disease and is associated with more recurrent episodes when not detected. Pharmacological treatment should include anti-inflammatory drugs in combination with treatment for hyperthyroidism. The specific pathophysiological link between the two conditions is still to be elucidated. PMID:24769665

  17. Neuromuscular electrostimulation: a new therapeutic option to improve radio-cephalic arteriovenous fistula maturation in end-stage chronic kidney disease patients.

    Science.gov (United States)

    Martinez, Lucia; Esteve, Vicent; Yeste, Montserrat; Artigas, Vicent; Llagostera, Secundino

    2017-09-01

    Radio-cephalic arteriovenous fistula (RCAVF) is the gold standard vascular access for end-stage chronic kidney disease patients. Exercises after arteriovenous fistula (AVF) creation improve maturation. No articles are published regarding neuromuscular electrostimulation (NMES) in AVF maturation. To assess the usefulness of a NMES programme on RCAVF maturation process. An 8-week single-centre prospective study. Two groups were established: control group (CG): underwent usual RCAVF forearm exercises and electrostimulation group (ESG): underwent RCAVF NMES programme. Handgrip (HG) measurement, preoperative Doppler ultrasonography (DUS) parameters, clinical and DUS maturation as well as surgical complications were assessed. Thirty-six patients (54% men). Mean age 67.9 ± 14.3 years; 12 ESG and 24 CG. Demographic data, comorbidities, medical treatment, HG and DUS measurement at baseline were similar. HG increased in both groups at the end of the study (CG 24.5 ± 9.5 vs. 26.1 ± 10.1 kg, p 0.048; ESG 25.8 ± 10.3 vs. 26.3 ± 11.6 kg, p 0.644). RCAVF forearm vein diameter (CG 3.1 ± 0.7 vs. 5.7 ± 1.1 mm; ESG 2.9 ± 0.8 vs. 6.1 ± 1.7 mm) and humeral artery blood flow rate (CG 110.5 ± 20.7 vs. 1053.4 ± 510.7 ml/min; ESG 118.2 ± 31.6 vs. 954.1 ± 542.2 ml/min) statistically increased for both groups. A significant increase in clinical maturation in ESG (62.5 vs. 91.7%, p 0.046) at 8 weeks was observed. Four patients in each group developed juxta-anastomotic stenosis and were surgically repaired. No adverse NMES effects were registered. NMES of forearm muscles is a safe and effective technique to improve RCAVF maturation and constitutes a novel alternative to forearm isometrics exercises. Nevertheless, further studies are required to confirm the potential effect of NMES in the vascular access maturation process.

  18. Does oral infection cause cardiovascular disease? Oral and moral challenges.

    Science.gov (United States)

    Hofmann, Bjørn M

    2011-10-01

    To address three questions: (i) does oral infection cause cardiovascular disease (CVD)? (ii) what kind of uncertainty is there in the relationship between oral infection and CVD? and (iii) how do we handle this uncertainty in practice: what should we do? Conceptual analysis with basis in standard methods in philosophy of science and ethics. In particular, the study refers to theories of causality and uncertainty, as well as decision making theory. Whether oral infections cause CVD deeply depends on what we mean by causality. An investigation of the most prominent conceptions of causality suggests that it is far from obvious that oral infection causes CVD. A further analysis reveals that uncertainty occurs as risk, specific uncertainty, ignorance, and indeterminacy, which has implications for how we should handle oral infections. One option is to apply the precautionary principle. Another option is to attribute a cause owing to the strong social commitment to prevent CVD. A conceptual analysis shows that it is not obvious that oral infections cause CVD and that the question of causality does not only involve descriptive issues of science but also moral matters of society. Hence, whether oral infections cause CVD is an ethical and not only a scientific issue. © 2011 John Wiley & Sons A/S.

  19. Vascular pathology: Cause or effect in Alzheimer disease?

    Science.gov (United States)

    Rius-Pérez, S; Tormos, A M; Pérez, S; Taléns-Visconti, R

    2015-09-15

    Alzheimer disease (AD) is the main cortical neurodegenerative disease. The incidence of this disease increases with age, causing significant medical, social and economic problems, especially in countries with ageing populations. This review aims to highlight existing evidence of how vascular dysfunction may contribute to cognitive impairment in AD, as well as the therapeutic possibilities that might arise from this evidence. The vascular hypothesis emerged as an alternative to the amyloid cascade hypothesis as an explanation for the pathophysiology of AD. This hypothesis locates blood vessels as the origin for a variety of pathogenic pathways that lead to neuronal damage and dementia. Destruction of the organisation of the blood brain barrier, decreased cerebral blood flow, and the establishment of an inflammatory context would thus be responsible for any subsequent neuronal damage since these factors promote aggregation of β-amyloid peptide in the brain. The link between neurodegeneration and vascular dysfunction pathways has provided new drug targets and therapeutic approaches that will add to the treatments for AD. It is difficult to determine whether the vascular component in AD is the cause or the effect of the disease, but there is no doubt that vascular pathology has an important relationship with AD. Vascular dysfunction is likely to act synergistically with neurodegenerative changes in a cycle that exacerbates the cognitive impairment found in AD. Copyright © 2015 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  20. Idiopathic pulmonary hypertension causing acquired von Willebrand disease and menorrhagia.

    Science.gov (United States)

    Sokkary, Nancy A; Dietrich, Jennifer E; Venkateswaran, Lakshmi

    2011-10-01

    Von Willebrand disease (VWD) maybe inherited or acquired; both etiologies can be associated with heavy menstrual bleeding. Pulmonary arterial hypertension may result in acquired VWD due to the destruction of high molecular weight von Willebrand multimers. We report a case of menorrhagia due to acquired VWD in a patient with idiopathic pulmonary hypertension. An adolescent female with known idiopathic pulmonary hypertension developed acquired VWD. Her primary disease necessitates the use of platelet inhibitors and intermittent anticoagulation. At menarche she also developed menorrhagia due to acquired VWD. She is currently controlled with stimate and progesterone-only therapy. VWD in a patient with idiopathic pulmonary hypertension causing menorrhagia. Although VWD and menorrhagia are commonly linked, the treatment and disease process in a patient with idiopathic pulmonary arterial hypertension is incredibly complex. Published by Elsevier Inc.

  1. Terson syndrome caused by intraventricular hemorrhage associated with moyamoya disease.

    Science.gov (United States)

    Kim, Ho Sang; Lee, Sang Weon; Sung, Soon Ki; Seo, Eui Kyo

    2012-06-01

    Terson syndrome was originally used to describe a vitreous hemorrhage arising from aneurysmal subrarachnoid hemorrhage. Terson syndrome can be caused by intracranial hemorrhage, subdural or epidural hematoma and severe brain injury but is extremely rare in intraventricular hemorrhage associated with moyamoya disease. A 41-year-old man presented with left visual disturbance. He had a history of intraventicular hemorrhage associated with moyamoya disease three months prior to admission. At that time he was in comatose mentality. Ophthalmologic examination at our hospital detected a vitreous hemorrhage in his left eye, with right eye remaining normal. Vitrectomy with epiretinal membrane removal was performed. After operation his left visual acuity was recovered. Careful ophthalmologic examination is mandatory in patients with hemorrhagic moyamoya disease.

  2. Identification of a Disease on Cocoa Caused by Fusariumin Sulawesi

    Directory of Open Access Journals (Sweden)

    Ade Rosmana

    2013-12-01

    Full Text Available A disease presumed to be caused by Fusarium was observed in cocoa open fields with few or without shade trees. Within the population of cocoa trees in the field, some trees had died, some had yellowing leaves and dieback, and the others were apparently healthy. In order to demonstrate Fusarium species as the causal pathogen and to obtain information concerning the incidence of the disease, its distribution and its impact on sustainability of cocoa, isolation of the pathogen, inoculation of cocoa seedlings with isolates and a survey of disease has been conducted. Fusarium was isolated from roots and branches, and inoculated onto cocoa seedlings (one month old via soil. Symptoms appeared within 3-4 weeks after infection. These symptoms consisted of yellowing of leaves beginning from the bottom until the leaves falldown, and browning internal of vascular tissue. Darkened vascular traces in the petiole characteristic of vascularstreak dieback infection were absent. The occurrence of Fusarium in the field was characterized by the absence of obvious signs of fungal infestation on root of infected trees, yellowing of leaves on twigs, dieback, and tree mortality in severe infestations. Disease incidence could reach 77% and in this situation it was difficult for trees recover from heavy infections or to be regenerated in the farm. The study proves that Fusarium is a pathogen causing dieback and the disease is called as Fusarium vascular dieback (FVD. Its development is apparently enhanced by dry conditions in the field. Key words: Fusarium sp., vascular disease, dieback, FVD, Theobroma cacao L.

  3. The role of proprioception and neuromuscular stability in carpal instabilities.

    Science.gov (United States)

    Hagert, E; Lluch, A; Rein, S

    2016-01-01

    Carpal stability has traditionally been defined as dependent on the articular congruity of joint surfaces, the static stability maintained by intact ligaments, and the dynamic stability caused by muscle contractions resulting in a compression of joint surfaces. In the past decade, a fourth factor in carpal stability has been proposed, involving the neuromuscular and proprioceptive control of joints. The proprioception of the wrist originates from afferent signals elicited by sensory end organs (mechanoreceptors) in ligaments and joint capsules that elicit spinal reflexes for immediate joint stability, as well as higher order neuromuscular influx to the cerebellum and sensorimotor cortices for planning and executing joint control. The aim of this review is to provide an understanding of the role of proprioception and neuromuscular control in carpal instabilities by delineating the sensory innervation and the neuromuscular control of the carpus, as well as descriptions of clinical applications of proprioception in carpal instabilities. © The Author(s) 2015.

  4. Pelvic Hydatid Disease: CT and MRI Findings Causing Sciatica

    Energy Technology Data Exchange (ETDEWEB)

    Sanal, Hatice Tuba; Kocaoglu, Murat; Bulakbasi, Nail; Yildirim, Duzgun [Gulhane Military Medical School, Department of Radiology, 06018, Ankara (Turkmenistan)

    2007-12-15

    Pelvic masses, especially hydatid disease, rarely present with sciatica. We present the computed tomography (CT) and the magnetic resonance imaging (MRI) findings of a 49-year-old female patient with presacral hydatid disease, who was evaluated for her sciatica. We also want to emphasize the importance of assessing the pelvis of patients with symptoms and clinical findings that are inconsistent and that cannot be satisfactorily explained by the spinal imaging findings. isc herniation in the lumbar spine is a well-known etiology of back pains and sciatica, but whenever disc herniation of the lumbar spine is excluded by the employed imaging modalities, then the pelvis should be examined for other possible etiologies of nerve compression. We describe here a patient, who was complaining of sciatica, with no abnormal findings in her lumbar spinal magnetic resonance imaging (MRI). The cause of her sciatica was found to be associated with a pelvic hydatid cyst compressing the lumbosacral nerve plexus. In conclusion, if no pathology is evident for the lumbar discal structures, in connection with the cause of sciatica and lumbar back pains, then the pelvis should also be examined for the possible etiologies of compression of the lumbosacral nerve plexus. Whenever a multiseptated cyst is come across in a patient of an endemic origin with a positive history for hydatid disease like surgery, indicating recurrence, hydatid cyst is the most likely diagnosis.

  5. Ultrasonographic Findings of Extratesticular Diseases Causing Acute Scrotal Disorders

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Jae Joon; Lee, Tack; Chang, So Yong; Kim, Myeong Jin; Yoo, Hyung Sik; Lee, Jong Tae [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1996-12-15

    To evaluate the kinds of extratesticular diseases causing acute scrotal disorders by emergent sonography of the scrotum. Scrotal sonography in sixty-five patients, with age ranging from 5months to 82 years (mean : 27.3 years), with acute scrotal pain and swelling, was prospectively carried out by either a 10 or 7.5 MHz transducer. We evaluated the size and echogenicity of the epididymis, the presence of extratesticular solid mass or cyst, testicular involvement by extratesticular diseases, calcification, hydrocele and scrotal wall thickening. The most common cause of acute scrotal disorders was acute epididymitis (n= 50), followed by acute epididymo-orchitis (n = 4), mumps epididymo-orchitis (n = 2), enlarged epididymis secondary to testicular torsion (n = 2), infected hydrocele (n = 2), epididymal cyst (n = 2), rupture of varicocele (n = 1), angioneurotic edema (n = 1), and sperm granuloma (n = 1). Hydrocele was seen in 20 cases, and epididymal calcification was noted in 6 cases. Emergent scrotal sonography was useful for correct diagnosis and proper treatment in patients with acute scrotal disorders, especially in the differentiation of the acute epididymitis from other intrascrotal diseases

  6. Exercise Therapy in Spinobulbar Muscular Atrophy and Other Neuromuscular Disorders

    DEFF Research Database (Denmark)

    Dahlqvist, Julia Rebecka; Vissing, John

    2016-01-01

    There is no curative treatment for most neuromuscular disorders. Exercise, as a treatment for these diseases, has therefore received growing attention. When executed properly, exercise can maintain and improve health and reduce the risk of cardiovascular disease, obesity, and diabetes. In persons...... in patients with neuromuscular diseases associated with weakness and wasting. We review studies that have investigated different types of exercise in both myopathies and motor neuron diseases, with particular emphasis on training of persons affected by spinobulbar muscular atrophy (SBMA). Finally, we provide...

  7. Low-density lipoproteins cause atherosclerotic cardiovascular disease

    DEFF Research Database (Denmark)

    Ference, Brian A.; Ginsberg, Henry N.; Graham, Ian

    2017-01-01

    Aims To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD). Methods and results We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from...... genetic studies, prospective epidemiologic cohort studies, Mendelian randomization studies, and randomized trials of LDL-lowering therapies. In clinical studies, plasma LDL burden is usually estimated by determination of plasma LDL cholesterol level (LDL-C). Rare genetic mutations that cause reduced LDL...... receptor function lead to markedly higher LDL-C and a dose-dependent increase in the risk of ASCVD, whereas rare variants leading to lower LDL-C are associated with a correspondingly lower risk of ASCVD. Separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies...

  8. Remnant cholesterol as a cause of ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Nordestgaard, Børge G

    2014-01-01

    This review focuses on remnant cholesterol as a causal risk factor for ischemic heart disease (IHD), on its definition, measurement, atherogenicity, and levels in high risk patient groups; in addition, present and future pharmacological approaches to lowering remnant cholesterol levels...... are considered. Observational studies show association between elevated levels of remnant cholesterol and increased risk of cardiovascular disease, even when remnant cholesterol levels are defined, measured, or calculated in different ways. In-vitro and animal studies also support the contention that elevated...... levels of remnant cholesterol may cause atherosclerosis same way as elevated levels of low-density lipoprotein (LDL) cholesterol, by cholesterol accumulation in the arterial wall. Genetic studies of variants associated with elevated remnant cholesterol levels show that an increment of 1mmol/L (39mg...

  9. The automated system for prevention of industrial-caused diseases

    Science.gov (United States)

    Varnavsky, A. N.

    2017-01-01

    The paper presents the automated system intended to prevent industrial-caused diseases of workers, the basis of which is represented by algorithms of preventing several negative functional conditions (stress, monotony). The emergence of such state shall be determined based on an analysis of bioelectric signals, in particular, skin-galvanic reactions. Proceeding from the dynamics of the functional state, the automated system offers to perform an optimized set of measures to restore the health of the worker. Implementation of an automated system is presented in Visual Programming system LabVIEW.

  10. SVA elements are nonautonomous retrotransposons that cause disease in humans.

    Science.gov (United States)

    Ostertag, Eric M; Goodier, John L; Zhang, Yue; Kazazian, Haig H

    2003-12-01

    L1 elements are the only active autonomous retrotransposons in the human genome. The nonautonomous Alu elements, as well as processed pseudogenes, are retrotransposed by the L1 retrotransposition proteins working in trans. Here, we describe another repetitive sequence in the human genome, the SVA element. Our analysis reveals that SVA elements are currently active in the human genome. SVA elements, like Alus and L1s, occasionally insert into genes and cause disease. Furthermore, SVA elements are probably mobilized in trans by active L1 elements.

  11. A Novel Virus Causes Scale Drop Disease in Lates calcarifer.

    Science.gov (United States)

    de Groof, Ad; Guelen, Lars; Deijs, Martin; van der Wal, Yorick; Miyata, Masato; Ng, Kah Sing; van Grinsven, Lotte; Simmelink, Bartjan; Biermann, Yvonne; Grisez, Luc; van Lent, Jan; de Ronde, Anthony; Chang, Siow Foong; Schrier, Carla; van der Hoek, Lia

    2015-08-01

    From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using a next-generation virus discovery technique, VIDISCA-454, sequences of an unknown virus were detected in serum of diseased fish. The near complete genome sequence of the virus was determined, which shows a unique genome organization, and low levels of identity to known members of the Iridoviridae. Based on homology of a series of putatively encoded proteins, the virus is a novel member of the Megalocytivirus genus of the Iridoviridae family. The virus was isolated and propagated in cell culture, where it caused a cytopathogenic effect in infected Asian seabass kidney and brain cells. Electron microscopy revealed icosahedral virions of about 140 nm, characteristic for the Iridoviridae. In vitro cultured virus induced scale drop syndrome in Asian seabass in vivo and the virus could be reisolated from these infected fish. These findings show that the virus is the causative agent for the scale drop syndrome, as each of Koch's postulates is fulfilled. We have named the virus Scale Drop Disease Virus. Vaccines prepared from BEI- and formalin inactivated virus, as well as from E. coli produced major capsid protein provide efficacious protection against scale drop disease.

  12. The Chemotherapy of Infectious Diseases caused by Protozoa and Bacteria

    Science.gov (United States)

    Hörlein, H.

    1936-01-01

    The possibility of combating infectious diseases with chemotherapeutically active substances depends to a large extent on the structure of the pathogenic organism. Apart from the cure of contagious pleuro-pneumonia in horses with neosalvarsan, we have, as yet, no chemotherapeutic substance which is active in virus diseases. The position is scarcely better when we turn to bacterial infections due to cocci and bacilli. These two types of infective organisms occupy the lowest level in the scale of micro-organisms. On the other hand, the spirochætes, which also belong to the bacteria group, and, still more so, those causal organisms belonging to the protozoa, represent relatively highly differentiated species, and the more highly developed a pathogenic organism is, the more points for attack it appears to offer to the action of chemotherapeutic substances. It is, therefore, not to be wondered at that the best results with chemotherapeutically active substances have been obtained in spirochætal diseases (syphilis, relapsing fever, frambœsia, etc.), and above all, in protozoal diseases. There is scarcely a protozoal disease of man which cannot be cured nowadays by early treatment with the appropriate synthetic drug. (Sleeping sickness, malaria, amœbic dysentery, leishmaniasis.) Epizootics resembling human diseases, as for example, trypanoses, are also relatively easily dealt with by the same drugs as have been found of value in the treatment of disease in man. On the other hand, there has been a lack of success, up to the present, in the treatment of those diseases of animals which are not generally related to the tropical diseases of man. The most important of these epizootics are the piroplasmoses, which are caused by babesiæ and theileriæ and which are found, not only in tropical and subtropical regions, but also in temperate zones. In this paper the discovery of a new remedy against piroplasmosis will be reported (acaprin). Further, advice will be given of a

  13. Diseases caused by mutations in ORAI1 and STIM1

    Science.gov (United States)

    Lacruz, Rodrigo S.; Feske, Stefan

    2015-01-01

    Ca2+ release-activated Ca2+ (CRAC) channels mediate a specific form of Ca2+ influx called store-operated Ca2+ entry (SOCE) that contributes to the function of many cell types. CRAC channels are formed by ORAI1 proteins located in the plasma membrane, which form its ion-conducting pore. ORAI1 channels are activated by stromal interaction molecule (STIM) 1 and STIM2 located in the endoplasmic reticulum. Loss- and gain-of-function gene mutations in ORAI1 and STIM1 in human patients cause distinct disease syndromes. CRAC channelopathy is caused by loss-of-function mutations in ORAI1 and STIM1 that abolish CRAC channel function and SOCE; it is characterized by severe combined immunodeficiency (SCID)-like disease, autoimmunity, muscular hypotonia, and ectodermal dysplasia, with defects in dental enamel. The latter defect emphasizes an important role of CRAC channels in tooth development. By contrast, autosomal dominant gain-of-function mutations in these genes result in constitutive CRAC channel activation, SOCE, and increased intracellular Ca2+ levels that are associated with an overlapping spectrum of diseases, including non-syndromic tubular aggregate myopathy (TAM) and York platelet and Stormorken syndromes, two syndromes defined, besides myopathy, by thrombocytopenia, thrombopathy, and bleeding diathesis. The fact that myopathy results from loss- and gain-of-function mutations in ORAI1 and STIM1 highlights the importance of CRAC channels for Ca2+ homeostasis in skeletal muscle function. The cellular dysfunction and clinical disease spectrum observed in mutant patients provide important information about the molecular regulation of ORAI1 and STIM1 proteins and the role of CRAC channels in human physiology. PMID:26469693

  14. [Environmental causes of the distal airways disease. Hypersensitivity pneumonitis and rare causes].

    Science.gov (United States)

    Dalphin, J-C; Didier, A

    2013-10-01

    Hypersensitivity pneumonitis is one of the most frequent causes of distal airways disease. It is associated with inflammation of the bronchioles, predominantly by lymphocytic infiltrates, and with granuloma formation causing bronchial obstruction. This inflammation explains the clinical manifestations and the airways obstruction seen on pulmonary function tests, most often in the distal airways but proximal in almost 20%. CT scan abnormalities reflect the lymphocytic infiltrates and air trapping and, in some cases, the presence of emphysema. Bronchiolitis induced by chronic inhalation of mineral particles or acute inhalation of toxic gases (such as NO2) are other examples of small airways damage due to environmental exposure. The pathophysiological mechanisms are different and bronchiolar damage is either exclusive or predominant. Bronchiolitis induced by tobacco smoke exposure, usually classified as interstitial pneumonitis, is easily diagnosed thanks to broncho-alveolar lavage. Its prognosis is linked to the other consequences of tobacco smoke exposure including respiratory insufficiency. Finally, the complex lung exposure observed in some rare cases (such as the World Trade Center fire or during wars) may lead to a less characteristic pattern of small airways disease. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  15. Adult Scheuermann’s disease as cause of mechanic dorsalgia

    Directory of Open Access Journals (Sweden)

    F.P. Cantatore

    2011-09-01

    Full Text Available Scheuermann’s disease (SD or vertebral osteochondrosis is the most frequent cause of non postural kyphosis and one of more frequent cause of adolescent’s dorsalgia. The criteria for the diagnosis are: more than 5° of wedging of at least three adjacent vertebrae at the apex of the kyphosis; a toracic kyphosis of more than 45° of Cobb’s degree; Schmorl’s nodes and endplates irregularities. In addition to classic SD, there are radiological alterations that remain asintomatic for a long time to reveal in adult age: in that case it speaks of adult Scheuermann’s disease (ASD. We considered the diagnosis of patients came from April 2006 to April 2007 on Day Hospital in our Clinic. ASD was diagnosed, besides, in 10 of these patients. 7 patients had previous diagnosis such as: dorsal Spondiloarthrosis (4 subjects; Osteoporosis with vertebral fractures (3 subjects. All these diagnosis was not confirmed by us. In case of chronic dorsalgia of adult, ASD is rarely considered as differential diagnosis. Besides, the vertebral dorsalgia, even in absence of red flags as fever, astenia, ipersedimetry, functional loss and aching spinal processes to tapping, could hide a serious scene that lead us to be careful in the differential diagnosis, because of similar radiological pictures of the MSA to other pathology as spondylodiscitis, primitive or metastasic spinal tumors, and brittleness vertebral fractures

  16. Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy

    Science.gov (United States)

    Kariya, Shingo; Park, Gyu-Hwan; Maeno-Hikichi, Yuka; Leykekhman, Olga; Lutz, Cathleen; Arkovitz, Marc S.; Landmesser, Lynn T.; Monani, Umrao R.

    2008-01-01

    Spinal muscular atrophy (SMA) is a common pediatric neuromuscular disorder caused by insufficient levels of the survival of motor neuron (SMN) protein. Studies involving SMA patients and animal models expressing the human SMN2 gene have yielded relatively little information about the earliest cellular consequences of reduced SMN protein. In this study, we have used severe- and mild-SMN2 expressing mouse models of SMA as well as material from human patients to understand the initial stages of neurodegeneration in the human disease. We show that the earliest structural defects appear distally and involve the neuromuscular synapse. Insufficient SMN protein arrests the post-natal development of the neuromuscular junction (NMJ), impairing the maturation of acetylcholine receptor (AChR) clusters into ‘pretzels’. Pre-synaptic defects include poor terminal arborization and intermediate filament aggregates which may serve as a useful biomarker of the disease. These defects are reflected in functional deficits at the NMJ characterized by intermittent neurotransmission failures. We suggest that SMA might best be described as a NMJ synaptopathy and that one promising means of treating it could involve maintaining function at the NMJ. PMID:18492800

  17. Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy.

    Science.gov (United States)

    Kariya, Shingo; Park, Gyu-Hwan; Maeno-Hikichi, Yuka; Leykekhman, Olga; Lutz, Cathleen; Arkovitz, Marc S; Landmesser, Lynn T; Monani, Umrao R

    2008-08-15

    Spinal muscular atrophy (SMA) is a common pediatric neuromuscular disorder caused by insufficient levels of the survival of motor neuron (SMN) protein. Studies involving SMA patients and animal models expressing the human SMN2 gene have yielded relatively little information about the earliest cellular consequences of reduced SMN protein. In this study, we have used severe- and mild-SMN2 expressing mouse models of SMA as well as material from human patients to understand the initial stages of neurodegeneration in the human disease. We show that the earliest structural defects appear distally and involve the neuromuscular synapse. Insufficient SMN protein arrests the post-natal development of the neuromuscular junction (NMJ), impairing the maturation of acetylcholine receptor (AChR) clusters into 'pretzels'. Pre-synaptic defects include poor terminal arborization and intermediate filament aggregates which may serve as a useful biomarker of the disease. These defects are reflected in functional deficits at the NMJ characterized by intermittent neurotransmission failures. We suggest that SMA might best be described as a NMJ synaptopathy and that one promising means of treating it could involve maintaining function at the NMJ.

  18. Mutations in TUBB4B Cause a Distinctive Sensorineural Disease.

    Science.gov (United States)

    Luscan, Romain; Mechaussier, Sabrina; Paul, Antoine; Tian, Guoling; Gérard, Xavier; Defoort-Dellhemmes, Sabine; Loundon, Natalie; Audo, Isabelle; Bonnin, Sophie; LeGargasson, Jean-François; Dumont, Julien; Goudin, Nicolas; Garfa-Traoré, Meriem; Bras, Marc; Pouliet, Aurore; Bessières, Bettina; Boddaert, Nathalie; Sahel, José-Alain; Lyonnet, Stanislas; Kaplan, Josseline; Cowan, Nicholas J; Rozet, Jean-Michel; Marlin, Sandrine; Perrault, Isabelle

    2017-12-07

    Leber congenital amaurosis (LCA) is a neurodegenerative disease of photoreceptor cells that causes blindness within the first year of life. It occasionally occurs in syndromic metabolic diseases and plurisystemic ciliopathies. Using exome sequencing in a multiplex family and three simplex case subjects with an atypical association of LCA with early-onset hearing loss, we identified two heterozygous mutations affecting Arg391 in β-tubulin 4B isotype-encoding (TUBB4B). Inspection of the atomic structure of the microtubule (MT) protofilament reveals that the β-tubulin Arg391 residue contributes to a binding pocket that interacts with α-tubulin contained in the longitudinally adjacent αβ-heterodimer, consistent with a role in maintaining MT stability. Functional analysis in cultured cells overexpressing FLAG-tagged wild-type or mutant TUBB4B as well as in primary skin-derived fibroblasts showed that the mutant TUBB4B is able to fold, form αβ-heterodimers, and co-assemble into the endogenous MT lattice. However, the dynamics of growing MTs were consistently altered, showing that the mutations have a significant dampening impact on normal MT growth. Our findings provide a link between sensorineural disease and anomalies in MT behavior and describe a syndromic LCA unrelated to ciliary dysfunction. Copyright © 2017 American Society of Human Genetics. All rights reserved.

  19. Extracardiac medical and neuromuscular implications in restrictive cardiomyopathy.

    Science.gov (United States)

    Stöllberger, Claudia; Finsterer, Josef

    2007-08-01

    Restrictive cardiomyopathy (RCMP) is characterized by restrictive filling and reduced diastolic volume of either or both ventricles with normal or near-normal systolic function and wall thickness. It may occur idiopathically or as a cardiac manifestation of systemic diseases such as scleroderma, amyloidosis, Churg-Strauss syndrome, cystinosis, sarcoidosis, lymphoma, Gaucher's disease, hemochromatosis, Fabry's disease, pseudoxanthoma elasticum, hypereosinophilic syndrome, carcinoid, Noonan's syndrome, reactive arthritis, or Werner's syndrome and various neuromuscular disorders. Whereas in idiopathic RCMP the therapeutic options are only treatment of cardiac congestion, in cases with an underlying disorder, a causal therapy may be available. Patients with RCMP should be investigated as soon as the cardiac diagnosis is established for extracardiac diseases to detect a possibly treatable cause of RCMP before the disease becomes intractable. These investigations include a diligent clinical history and examination, blood tests, and ophthalmologic, otologic, dermatologic, gastroenterologic, nephrologic, hematologic, and neurologic examinations. If extracardiac examinations do not reveal a plausible cause for RCMP, endomyocardial biopsy is indicated. (c) 2007 Wiley Periodicals, Inc.

  20. Mutations that Cause Human Disease: A Computational/Experimental Approach

    Energy Technology Data Exchange (ETDEWEB)

    Beernink, P; Barsky, D; Pesavento, B

    2006-01-11

    International genome sequencing projects have produced billions of nucleotides (letters) of DNA sequence data, including the complete genome sequences of 74 organisms. These genome sequences have created many new scientific opportunities, including the ability to identify sequence variations among individuals within a species. These genetic differences, which are known as single nucleotide polymorphisms (SNPs), are particularly important in understanding the genetic basis for disease susceptibility. Since the report of the complete human genome sequence, over two million human SNPs have been identified, including a large-scale comparison of an entire chromosome from twenty individuals. Of the protein coding SNPs (cSNPs), approximately half leads to a single amino acid change in the encoded protein (non-synonymous coding SNPs). Most of these changes are functionally silent, while the remainder negatively impact the protein and sometimes cause human disease. To date, over 550 SNPs have been found to cause single locus (monogenic) diseases and many others have been associated with polygenic diseases. SNPs have been linked to specific human diseases, including late-onset Parkinson disease, autism, rheumatoid arthritis and cancer. The ability to predict accurately the effects of these SNPs on protein function would represent a major advance toward understanding these diseases. To date several attempts have been made toward predicting the effects of such mutations. The most successful of these is a computational approach called ''Sorting Intolerant From Tolerant'' (SIFT). This method uses sequence conservation among many similar proteins to predict which residues in a protein are functionally important. However, this method suffers from several limitations. First, a query sequence must have a sufficient number of relatives to infer sequence conservation. Second, this method does not make use of or provide any information on protein structure, which

  1. Disability Weights Measurement for 228 Causes of Disease in the Korean Burden of Disease Study 2012.

    Science.gov (United States)

    Ock, Minsu; Lee, Jin Yong; Oh, In Hwan; Park, Hyesook; Yoon, Seok Jun; Jo, Min Woo

    2016-11-01

    Disability weight for each disease plays a key role in combining years lived with disability and years of life lost in disability adjusted life year. For the Korean Burden of Disease 2012 study, we have conducted a re-estimation of disability weights for causes of disease by adapting the methodology of a recent Global Burden of Disease study. Our study was conducted through a self-administered web-based survey using a paired comparison (PC) as the main valuation method. A total of 496 physicians and medical college students who were attending in third or fourth grade of a regular course conducted the survey. We applied a probit regression on the PC data and computed the predicted probabilities of each cause of disease from the coefficient estimates of the probit regression. We used 'being dead (1)' and 'full health (0)' as anchor points to rescale the predicted probability of each cause of disease on a scale of 0 to 1. By this method, disability weights for a total of 228 causes of disease were estimated. There was a fairly high correlation between the disability weights of overlapping causes of disease from this study and a previous South Korean study despite the differences in valuation methods and time periods. In conclusion, we have shown that disability weights can be estimated based on a PC by including 'full health' and 'being dead' as anchor points without resorting to a person trade-off. Through developments in the methodology of disability weights estimation from this study, disability weights can be easily estimated and continuously revised.

  2. [Genetic defects and disorders at the neuromuscular junction].

    Science.gov (United States)

    Ohno, Kinji

    2011-07-01

    Genetic defects in molecules expressed at the neuromuscular junction (NMJ) cause congenital myasthenic syndromes (CMSs), which are characterized by muscle weakness, abnormal fatigability, amyotrophy, and minor facial anomalies. Muscle weakness mostly develops under 2 years but is also sometimes seen in adults. Mutations identified to date include (i) muscle nicotinic acetylcholine receptor (AChR) subunits, (ii) rapsyn that anchors and clusters AChRs at the neuromuscular junction, (iii) agrin that is released from the nerve terminal and induces AChR clustering by stimulating the downstream LRP4/MuSK/Dok-7/rapsyn/AChR pathway, (iv) muscle-specific kinase (MuSK) that transmits the AChR-clustering signal from agrin/LRP4 to rapsyn/AChR, (v) Dok-7 that transmits the AChR-clustering signal from agrin/LRP4/MuSK to rapsyn/AChR, (vi) skeletal muscle sodium channel type 1.4 (Nav1.4) that spreads the depolarization potential from the endplate throughout muscle fibers, (vii) collagen Q that anchors acetylcholinesterase to the synaptic basal lamina, and (viii) choline acetyltransferase that resynthesizes acetylcholine from recycled choline at the nerve terminal. In addition, mutations in the heparin sulfate proteoglycan perlecan, which binds to many molecules including collagen Q and dystroglycan, causes Schwartz-Jampel syndrome. Interestingly, mutations in LRP4 cause Cenani-Lenz syndactyly syndrome but not CMS. AChR, MuSK, and LRP4 are also targets of auto-antibodies in myasthenia gravis. In addition, molecules at the NMJ are targets of many other disease states AChRs are blocked by the snake toxin alpha-bungarotoxin and the plant poison curare. The presynaptic SNARE complex is attacked by botulinum toxin. Acetylcholinesterase is inhibited by the nerve gas sarin and by organophosphate pesticides. This review focuses on the molecular bases underlying defects of AChR, rapsyn, Nav1.4, collagen Q, and choline acetyltransferase.

  3. Oral disease in children with Down syndrome: causes and prevention.

    Science.gov (United States)

    Shore, Sarah; Lightfoot, Tracy; Ansell, Pat

    2010-02-01

    While healthcare professionals may be familiar with the social and medical management of Down syndrome, dental issues have traditionally been somewhat neglected and are important causes of morbidity. The aims of this review are two-fold. Firstly, to draw attention to the environmental and host factors associated with periodontal disease and dental caries (tooth decay) in children with Down syndrome. Secondly, to highlight key yet largely modifiable risk factors in the causation and progression of these chronic oral conditions, many of which also apply to other children with learning disabilities. The review focuses on the role of community and school-based healthcare professionals in promoting good oral health using evidence-based preventative strategies, and in encouraging early, regular contact with dental services.

  4. [Neuro-muscular apparatus state in lumbosacral radiculopathy in miners].

    Science.gov (United States)

    Battakova, Sh B; Amanbekov, U A; Otarbaeva, M B; Fazylova, M D; Sraĭmanov, K S; Miianova, G A; Kozhakhmetova, K M

    2008-01-01

    Based on clinical and electrophysiologic studies, the authors analysed neuro-muscular apparatus of "spinal center--periphery" axis for miners with radicular pain caused by occupational lumbosacral radiculopathy. Findings are that constantly irritated receptors in lumbar motor segment during occupational activities alter habitual motor stereotype and cause specific compensatory muscular reactions, rearrangement of motor activity in segmental apparatus.

  5. Sleep disorders in Parkinson's disease: many causes, few therapeutic options.

    Science.gov (United States)

    Diederich, Nico J; McIntyre, Deborah J

    2012-03-15

    Sleep symptoms in Parkinson's disease (PD) are frequent and have multifactorial and multilayered causes. Primary involvement of sleep/wake regulating centers in the brainstem, sleep problems caused by the nocturnal manifestation of motor and dysautonomic signs and medication-induced sleep problems are often impossible to disentangle in the individual patient. Two syndromes, hypersomnia and REM sleep behavior disorder (RBD), are increasingly recognized as harbingers of the core PD motor syndrome. RBD, associated with a panoply of other nonmotor symptoms, may predispose to a specific PD phenotype. Long-acting dopaminergic stimulation, when abating nocturnal akinesia, also improves subjective sleep quantity. While this strategy is backed up by several randomized controlled trials (RCT), other treatment recommendations are mostly based on case series or expert opinion. Thus we identified only two other RCT, one treating insomnia with eszopiclone, the other nocturnal behavioral abnormalities in demented PD patients with memantine. While the causal complexity of sleep problems in PD certainly hampers the design of therapeutic studies, multiple general treatment strategies against sleep disorders can however be applied efficiently in PD patients as well. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. [Cardiovascular diseases as a cause of sudden death in athletes].

    Science.gov (United States)

    Halawa, Bogumił

    2004-01-01

    Cardiac arrhythmias are the reason of the most sudden deaths in athletes. The annual risk of sudden death at athletes is between 5 to 10 per one million. Benign arrhythmia including bradyarrhythmias, atrial and ventricular premature contractions are common in the athletes. Supraventricular arrhythmias such as atrial fibrillation, nodal reciprocal entrant tachycardia and Wolff-Parkinson-White syndrome are less common. Perhaps the rarest and the most dangerous arrhythmias are ventricular arrhythmias, among them arrhythmias secondary to hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, long QT syndrome, and anomalous origin of coronary arteries. Asymptomatic bradyarrhythmias (if the heart rate in bradyarrhythmia appropriate increases with exercise), supraventricularis tachycardias, and atrial premature contractions without structural heart disease are not the contraindication to sports Athletes with premature ventricular contraction, nonsustained ventricular tachycardia and non structural heart disease are without athletic restrictions as long as the arrhythmias do not worsen and they not cause dyspnea or presyncope during exertion. Frequent or multiform premature ventricular contraction or sustained ventricular tachycardia indicate a higher risk, and all participation in athletic should be restricted.

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

    LENUS (Irish Health Repository)

    Kent, Brian D

    2012-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Brian D Kent

    2011-03-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  10. Autoantibodies in neuromuscular transmission disorders

    National Research Council Canada - National Science Library

    Vincent, Angela

    2008-01-01

    .... The neuromuscular junction (NMJ) is the site of a number of different autoimmune and genetic disorders, and it is also the target of many neurotoxins from venomous snakes, spiders, scorpions and other species...

  11. Deletions of recessive disease genes: CNV contribution to carrier states and disease-causing alleles

    Science.gov (United States)

    Boone, Philip M.; Campbell, Ian M.; Baggett, Brett C.; Soens, Zachry T.; Rao, Mitchell M.; Hixson, Patricia M.; Patel, Ankita; Bi, Weimin; Cheung, Sau Wai; Lalani, Seema R.; Beaudet, Arthur L.; Stankiewicz, Pawel; Shaw, Chad A.; Lupski, James R.

    2013-01-01

    Over 1200 recessive disease genes have been described in humans. The prevalence, allelic architecture, and per-genome load of pathogenic alleles in these genes remain to be fully elucidated, as does the contribution of DNA copy-number variants (CNVs) to carrier status and recessive disease. We mined CNV data from 21,470 individuals obtained by array-comparative genomic hybridization in a clinical diagnostic setting to identify deletions encompassing or disrupting recessive disease genes. We identified 3212 heterozygous potential carrier deletions affecting 419 unique recessive disease genes. Deletion frequency of these genes ranged from one occurrence to 1.5%. When compared with recessive disease genes never deleted in our cohort, the 419 recessive disease genes affected by at least one carrier deletion were longer and located farther from known dominant disease genes, suggesting that the formation and/or prevalence of carrier CNVs may be affected by both local and adjacent genomic features and by selection. Some subjects had multiple carrier CNVs (307 subjects) and/or carrier deletions encompassing more than one recessive disease gene (206 deletions). Heterozygous deletions spanning multiple recessive disease genes may confer carrier status for multiple single-gene disorders, for complex syndromes resulting from the combination of two or more recessive conditions, or may potentially cause clinical phenotypes due to a multiply heterozygous state. In addition to carrier mutations, we identified homozygous and hemizygous deletions potentially causative for recessive disease. We provide further evidence that CNVs contribute to the allelic architecture of both carrier and recessive disease-causing mutations. Thus, a complete recessive carrier screening method or diagnostic test should detect CNV alleles. PMID:23685542

  12. The Dutch neuromuscular database CRAMP (Computer Registry of All Myopathies and Polyneuropathies) : Development and preliminary data

    NARCIS (Netherlands)

    van Engelen, B. G. M.; van Veenendaal, H.; van Doorn, P. A.; van der Hoeven, J. H.; Janssen, N. G.; Notermans, N. C.; van Schaik, I. N.; Visser, L. H.; Verschuuren, J. J. G. M.

    Each of the various neuromuscular diseases is rare. Consequently, solid epidemiological data are not available and it is often difficult to find sufficient patients for studies. For this reason, the Dutch neuromuscular database, CRAMP (Computer Registry of All Myopathies and Polyneuropathies), was

  13. Neuromuscular blocking properties of dioxonium.

    Science.gov (United States)

    Tammisto, T; Salmenperä, M

    1980-12-01

    The characteristics of the myoneural block caused by a new neuromuscular blocking agent, dioxonium (Dx), were evaluated in surgical patients. The force and the corresponding electromyogram (EMG) of the thumb adduction evoked by various modes of ulnar nerve stimuli were measured. Onset, maintenance and disappearance of blockade after sequential administration of Dx were compared with results obtained with d-tubocurarine (dTc) or suxamethonium (Sx). Initially the Dx block was shown to be depolarizing with a negligible fade in the 2 Hz train of four stimuli with a single twitch suppression of 90%. On a weight basis, Dx was found to be about 15 times as potent as dTc in suppressing twitch to the 90% level. During maintenance, the block gained nondepolarizing characteristics with profound fades in the 2 and 50 Hz trains. The transition was associated with tachyphylaxis and with a more pronounced suppression of EMG amplitude than that measured in the twitch force. After a total dose of about 100 microgram/kg of Dx, the sensitivity to Dx again increased and the discrepancy between twitch tension and EMG disappeared. This pattern of changes was also seen with Sx. Spontaneous recovery occurred slightly faster than after dTc blocks of corresponding duration. With neostigmine, reversal was hastened and a full recovery with restitution of prerelaxant twitch and disappearance of fades was reached in about 20 min. Some discrepancy in EMG amplitude and twitch force persisted, however.

  14. Astrocyte pathology in Alexander disease causes a marked inflammatory environment.

    Science.gov (United States)

    Olabarria, Markel; Putilina, Maria; Riemer, Ellen C; Goldman, James E

    2015-10-01

    Astrocytes and microglia are commonly involved in a wide variety of CNS pathologies. However, they are typically involved in a secondary response in which many cell types are affected simultaneously and therefore it is difficult to know their contributions to the pathology. Here, we show that pathological astrocytes in a mouse model of Alexander disease (AxD; GFAP (Tg);Gfap (+/R236H)) cause a pronounced immune response. We have studied the inflammatory response in the hippocampus and spinal cord of these mice and have found marked microglial activation, which follows that of astrocytes in a spatial pathological progression, as shown by increased levels of Iba1 and microglial cell (Iba1+) density. RNA sequencing and subsequent gene ontology (GO) analysis revealed that a majority of the most upregulated genes in GFAP (Tg);Gfap (+/R236H) mice are directly associated with immune function and that cytokine and chemokine GO attributes represent nearly a third of the total immune attributes. Cytokine and chemokine analysis showed CXCL10 and CCL2 to be the most and earliest increased molecules, showing concentrations as high as EAE or stroke models. CXCL10 was localized exclusively to astrocytes while CCL2 was also present in microglia. Despite the high levels of CXCL10 and CCL2, T cell infiltration was mild and no B cells were found. Thus, mutations in GFAP are sufficient to trigger a profound inflammatory response. The cellular stress caused by the accumulation of GFAP likely leads to the production of inflammatory molecules and microglial activation. Examination of human AxD CNS tissues also revealed microglial activation and T cell infiltrates. Therefore, the inflammatory environment may play an important role in producing the neuronal dysfunction and seizures of AxD.

  15. Causes of Alternative Pathway Dysregulation in Dense Deposit Disease

    Science.gov (United States)

    Zhang, Yuzhou; Meyer, Nicole C.; Wang, Kai; Nishimura, Carla; Frees, Kathy; Jones, Michael; Katz, Louis M.; Sethi, Sanjeev; Smith, Richard J.H.

    2012-01-01

    Summary Background and objectives This study was designed to investigate the causes of alternative pathway dysregulation in a cohort of patients with dense deposit disease (DDD). Design, setting, participants, & measurements Thirty-two patients with biopsy-proven DDD underwent screening for C3 nephritic factors (C3Nefs), factor H autoantibodies (FHAAs), factor B autoantibodies (FBAAs), and genetic variants in CFH. C3Nefs were detected by: ELISA, C3 convertase surface assay (C3CSA), C3CSA with properdin (C3CSAP), two-dimensional immunoelectrophoresis (2DIEP), and immunofixation electrophoresis (IFE). FHAAs and FBAAs were detected by ELISA, and CFH variants were identified by Sanger sequencing. Results Twenty-five patients (78%) were positive for C3Nefs. Three C3Nef-positive patients were also positive for FBAAs and one of these patients additionally carried two novel missense variants in CFH. Of the seven C3Nef-negative patients, one patient was positive for FHAAs and two patients carried CFH variants that may be causally related to their DDD phenotype. C3CASP was the most sensitive C3Nef-detection assay. C3CASP and IFE are complementary because C3CSAP measures the stabilizing properties of C3Nefs, whereas IFE measures their expected consequence—breakdown of C3b. Conclusions A test panel that includes C3CSAP, IFE, FHAAs, FBAAs, and genetic testing for CFH variants will identify a probable cause for alternative pathway dysregulation in approximately 90% of DDD patients. Dysregulation is most frequently due to C3Nefs, although some patients test positive for FHAAs, FBAAs, and CFH mutations. Defining the pathophysiology of DDD should facilitate the development of mechanism-directed therapies. PMID:22223606

  16. Does anxiety cause freezing of gait in Parkinson's disease?

    Directory of Open Access Journals (Sweden)

    Kaylena A Ehgoetz Martens

    Full Text Available Individuals with Parkinson's disease (PD commonly experience freezing of gait under time constraints, in narrow spaces, and in the dark. One commonality between these different situations is that they may all provoke anxiety, yet anxiety has never been directly examined as a cause of FOG. In this study, virtual reality was used to induce anxiety and evaluate whether it directly causes FOG. Fourteen patients with PD and freezing of gait (Freezers and 17 PD without freezing of gait (Non-Freezers were instructed to walk in two virtual environments: (i across a plank that was located on the ground (LOW, (ii across a plank above a deep pit (HIGH. Multiple synchronized motion capture cameras updated participants' movement through the virtual environment in real-time, while their gait was recorded. Anxiety levels were evaluated after each trial using self-assessment manikins. Freezers performed the experiment on two separate occasions (in their ON and OFF state. Freezers reported higher levels of anxiety compared to Non-Freezers (p < 0.001 and all patients reported greater levels of anxiety when walking across the HIGH plank compared to the LOW (p < 0.001. Freezers experienced significantly more freezing of gait episodes (p = 0.013 and spent a significantly greater percentage of each trial frozen (p = 0.005 when crossing the HIGH plank. This finding was even more pronounced when comparing Freezers in their OFF state. Freezers also had greater step length variability in the HIGH compared to the LOW condition, while the step length variability in Non-Freezers did not change. In conclusion, this was the first study to directly compare freezing of gait in anxious and non-anxious situations. These results present strong evidence that anxiety is an important mechanism underlying freezing of gait and supports the notion that the limbic system may have a profound contribution to freezing in PD.

  17. Mycoplasma genitalium: An Emerging Cause of Pelvic Inflammatory Disease

    Directory of Open Access Journals (Sweden)

    Catherine L. Haggerty

    2011-01-01

    Full Text Available Mycoplasma genitalium is a sexually transmitted pathogen that is increasingly identified among women with pelvic inflammatory disease (PID. Although Chlamydia trachomatis and Neisseria gonorrhoeae frequently cause PID, up to 70% of cases have an unidentified etiology. This paper summarizes evidence linking M. genitalium to PID and its long-term reproductive sequelae. Several PCR studies have demonstrated that M. genitalium is associated with PID, independent of gonococcal and chlamydial infection. Most have been cross-sectional, although one prospective investigation suggested that M. genitalium was associated with over a thirteenfold risk of endometritis. Further, a nested case-control posttermination study demonstrated a sixfold increased risk of PID among M. genitalium positive patients. Whether or not M. genitalium upper genital tract infection results in long-term reproductive morbidity is unclear, although tubal factor infertility patients have been found to have elevated M. genitalium antibodies. Several lines of evidence suggest that M. genitalium is likely resistant to many frequently used PID treatment regimens. Correspondingly, M. genitalium has been associated with treatment failure following cefoxitin and doxycycline treatment for clinically suspected PID. Collectively, strong evidence suggests that M. genitalium is associated with PID. Further study of M. genitalium upper genital tract infection diagnosis, treatment and long-term sequelae is warranted.

  18. Comparative Pathogenomics of Bacteria Causing Infectious Diseases in Fish

    Directory of Open Access Journals (Sweden)

    Ponnerassery S. Sudheesh

    2012-01-01

    Full Text Available Fish living in the wild as well as reared in the aquaculture facilities are susceptible to infectious diseases caused by a phylogenetically diverse collection of bacterial pathogens. Control and treatment options using vaccines and drugs are either inadequate, inefficient, or impracticable. The classical approach in studying fish bacterial pathogens has been looking at individual or few virulence factors. Recently, genome sequencing of a number of bacterial fish pathogens has tremendously increased our understanding of the biology, host adaptation, and virulence factors of these important pathogens. This paper attempts to compile the scattered literature on genome sequence information of fish pathogenic bacteria published and available to date. The genome sequencing has uncovered several complex adaptive evolutionary strategies mediated by horizontal gene transfer, insertion sequence elements, mutations and prophage sequences operating in fish pathogens, and how their genomes evolved from generalist environmental strains to highly virulent obligatory pathogens. In addition, the comparative genomics has allowed the identification of unique pathogen-specific gene clusters. The paper focuses on the comparative analysis of the virulogenomes of important fish bacterial pathogens, and the genes involved in their evolutionary adaptation to different ecological niches. The paper also proposes some new directions on finding novel vaccine and chemotherapeutic targets in the genomes of bacterial pathogens of fish.

  19. Comparative pathogenomics of bacteria causing infectious diseases in fish.

    Science.gov (United States)

    Sudheesh, Ponnerassery S; Al-Ghabshi, Aliya; Al-Mazrooei, Nashwa; Al-Habsi, Saoud

    2012-01-01

    Fish living in the wild as well as reared in the aquaculture facilities are susceptible to infectious diseases caused by a phylogenetically diverse collection of bacterial pathogens. Control and treatment options using vaccines and drugs are either inadequate, inefficient, or impracticable. The classical approach in studying fish bacterial pathogens has been looking at individual or few virulence factors. Recently, genome sequencing of a number of bacterial fish pathogens has tremendously increased our understanding of the biology, host adaptation, and virulence factors of these important pathogens. This paper attempts to compile the scattered literature on genome sequence information of fish pathogenic bacteria published and available to date. The genome sequencing has uncovered several complex adaptive evolutionary strategies mediated by horizontal gene transfer, insertion sequence elements, mutations and prophage sequences operating in fish pathogens, and how their genomes evolved from generalist environmental strains to highly virulent obligatory pathogens. In addition, the comparative genomics has allowed the identification of unique pathogen-specific gene clusters. The paper focuses on the comparative analysis of the virulogenomes of important fish bacterial pathogens, and the genes involved in their evolutionary adaptation to different ecological niches. The paper also proposes some new directions on finding novel vaccine and chemotherapeutic targets in the genomes of bacterial pathogens of fish.

  20. Historical perspectives on music as a cause of disease.

    Science.gov (United States)

    Kennaway, James

    2015-01-01

    The relationship between music and medicine is generally understood in the benign context of music therapy, but, as this chapter shows, there is a long parallel history of medical theories that suggest that music can cause real physical and mental illness. During the seventeenth and eighteenth centuries, the idea of music as an expression of universal harmony was challenged by a more mechanistic model of nervous stimulation. By the 1790s, there was a substantial discourse on the dangers of musical overstimulation to health in medicine, literature, and etiquette books. During the nineteenth century, the sense of music as a pathogenic stimulant gained in influence. It was often linked to fears about sexuality, female gynecological health, and theories of hypnosis and degeneration. In the twentieth century, the debate on the medical perils of the wrong kinds of music became overtly politicized in Germany and the Soviet Union. Likewise, the opponents of jazz, particularly in the United States, often turned to medicine to fend off its supposed social, moral, and physical consequences. The Cold War saw an extensive discourse on the idea of musical "brainwashing," that rumbled on into the 1990s. Today, regular media panics about pathological music are mirrored by alarming evidence of the deliberate use of music to harm listeners in the context of the so-called War on Terror. Can music make you ill? Music therapy is a common if perhaps rather neglected part of medicine, but its diametric opposite, the notion that music might lead to real mental and physical illness, may seem improbable. In fact, over the last two hundred years, there have been many times when as much was written about the medical dangers of music as about its potential benefits. Since the eighteenth century, fears about music's effects on the nerves and the mind have created a remarkably extensive discourse on pathological music based on a view of both music and the causation of disease as matters of

  1. Neuromuscular Manifestations of West Nile Virus Infection

    Directory of Open Access Journals (Sweden)

    A. Arturo eLeis

    2012-03-01

    Full Text Available The most common neuromuscular manifestation of West Nile virus (WNV infection is a poliomyelitis syndrome with asymmetric paralysis variably involving one (monoparesis to four limbs (quadriparesis, with or without brainstem involvement and respiratory failure. This syndrome of acute flaccid paralysis may occur without overt fever or meningoencephalitis. Although involvement of anterior horn cells in the spinal cord and motor neurons in the brainstem are the major sites of pathology responsible for neuromuscular signs, inflammation also may involve skeletal or cardiac muscle (myositis, myocarditis, motor axons (polyradiculitis, peripheral nerve (Guillain-Barré syndrome, brachial plexopathy. In addition, involvement of spinal sympathetic neurons and ganglia provides a plausible explanation for autonomic instability seen in some patients. Many patients also experience prolonged subjective generalized weakness and disabling fatigue. Despite recent evidence that WNV may persist long term in the central nervous system or periphery in animals, the evidence in humans is controversial. WNV persistence would be of great concern in immunosuppressed patients or in those with prolonged or recurrent symptoms. Support for the contention that WNV can lead to autoimmune disease arises from reports of patients presenting with various neuromuscular diseases that presumably involve autoimmune mechanisms (GBS, other demyelinating neu¬ropathies, myasthenia gravis, brachial plexopathies, stiff-person syndrome, and delayed or recurrent symptoms. Although there is no specific treatment or vaccine currently approved in humans, and the standard remains supportive care, drugs that can alter the cascade of immunobiochemical events leading to neuronal death may be potentially useful (high-dose corticosteroids, interferon preparations, and intravenous immune globulin containing WNV-specific antibodies. Human experience with these agents seems promising based on anecdotal

  2. Mycobacterium avium subspecies paratuberculosis causes Crohn's disease in some inflammatory bowel disease patients.

    Science.gov (United States)

    Naser, Saleh A; Sagramsingh, Sudesh R; Naser, Abed S; Thanigachalam, Saisathya

    2014-06-21

    Crohn's disease (CD) is a chronic inflammatory condition that plagues millions all over the world. This debilitating bowel disease can start in early childhood and continue into late adulthood. Signs and symptoms are usually many and multiple tests are often required for the diagnosis and confirmation of this disease. However, little is still understood about the cause(s) of CD. As a result, several theories have been proposed over the years. One theory in particular is that Mycobacterium avium subspecies paratuberculosis (MAP) is intimately linked to the etiology of CD. This fastidious bacterium also known to cause Johne's disease in cattle has infected the intestines of animals for years. It is believed that due to the thick, waxy cell wall of MAP it is able to survive the process of pasteurization as well as chemical processes seen in irrigation purification systems. Subsequently meat, dairy products and water serve as key vehicles in the transmission of MAP infection to humans (from farm to fork) who have a genetic predisposition, thus leading to the development of CD. The challenges faced in culturing this bacterium from CD are many. Examples include its extreme slow growth, lack of cell wall, low abundance, and its mycobactin dependency. In this review article, data from 60 studies showing the detection and isolation of MAP by PCR and culture techniques have been reviewed. Although this review may not be 100% comprehensive of all studies, clearly the majority of the studies overwhelmingly and definitively support the role of MAP in at least 30%-50% of CD patients. It is very possible that lack of detection of MAP from some CD patients may be due to the absence of MAP role in these patients. The latter statement is conditional on utilization of methodology appropriate for detection of human MAP strains. Ultimately, stratification of CD and inflammatory bowel disease patients for the presence or absence of MAP is necessary for appropriate and effective

  3. [An unusual cause of cystic lung disease: light chain deposition disease].

    Science.gov (United States)

    Luraine, R; Sohier, L; Kerjouan, M; Desrues, B; Delaval, P; Jouneau, S

    2013-09-01

    Light chain deposition disease is a rare clinical entity characterized by deposition of monoclonal immunoglobulin light chains in organs. The kidneys are almost always affected, while the lung manifestations that have been reported, including nodular or diffuse disease, especially cystic lesions, are unusual. We report the case of a 60-year-old man with a diffuse infiltrative lung disease characterized by numerous apical cysts. The diagnosis of light chain deposition cystic lung disease was obtained by surgical lung biopsy. Light chain deposits in the salivary glands were the only extrapulmonary manifestation. Despite 12 chemotherapy cycles, the patient's lung function and radiological appearances worsened. This is the fourth case describing a cystic lung disease due to light chain deposition in the literature. It highlights the need for comprehensive investigations so as not to miss this rare cause of cystic lung disease, which appears to be related to a primary pulmonary lymphoproliferative disorder. The only treatment that appears to be effective is lung transplantation. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  4. [New surgical treatment of late-stage neuromuscular ureteral dysplasia].

    Science.gov (United States)

    Lopatkin, N A; Zhitnikova, L H; Berestennikov, K A

    1999-01-01

    A surgical treatment of neuromuscular ureteral, dysplasia (NUD) is proposed which provides development of restenosis in vesicoureteral anastomosis and vesicoureteral reflux in maintenance of normal urodynamics of the upper urinary tracts. This organ-saving method can be applied at late disease. Multichannel impedance ureterography proved useful in definition of the operation's scope.

  5. Neuromuscular ultrasound of cranial nerves.

    Science.gov (United States)

    Tawfik, Eman A; Walker, Francis O; Cartwright, Michael S

    2015-04-01

    Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed.

  6. Doenças neuromusculares

    OpenAIRE

    Reed,Umbertina C.

    2002-01-01

    Objetivo: apresentar os dados essenciais para o diagnóstico diferencial entre as principais doenças neuromusculares, denominação genérica sob a qual agrupam-se diferentes afecções, decorrentes do acometimento primário da unidade motora (motoneurônio medular, raiz nervosa, nervo periférico, junção mioneural e músculo). Fontes dos dados: os aspectos clínicos fundamentais para estabelecer o diagnóstico diferencial entre as diferentes doenças neuromusculares, bem como entre estas e as causas de h...

  7. Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens

    OpenAIRE

    Ogrendik M

    2013-01-01

    Mesut OgrendikDivision of Physical Therapy and Rheumatology, Nazilli State Hospital, Nazilli, TurkeyAbstract: A statistically significant association between periodontal disease (PD) and systemic diseases has been identified. Rheumatoid arthritis (RA), which is a chronic inflammatory joint disease, exhibits similar characteristics and pathogenesis to PD. The association between RA and PD has been investigated, and numerous publications on this subject exist. Approximately 20 bacterial species...

  8. Gender Differentials and Disease-Specific Cause of Infant Mortality ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    causes of infant mortality in an urban hospital in Ghana and gender differences in the burden of infant mortality. Births and deaths data at the hospital were reviewed and analyzed. Results indicated infant mortality of 32/1000 live births and highlighted malaria, severe anemia, and neonatal sepsis as the leading causes of ...

  9. Inflorescence rot disease of date palm caused by Fusarium ...

    African Journals Online (AJOL)

    Date palm is one of the important income sources for many farmers in different parts of several countries, including Iraq, Iran, Saudi Arabia, North Africa etc. Inflorescence rot is a serious disease of date palm which limits its yield. The identification of the causal organism is a key step to tackling this disease, and such studies ...

  10. Gumboro Disease Outbreaks Cause High Mortality Rates in ...

    African Journals Online (AJOL)

    Bulletin of Animal Health and Production in Africa ... Thirty nine outbreak farms (5 keeping broilers, 19 keeping layers and 15 keeping indigenous flock) were visited; vaccination history collected, clinical signs observed, flock size ... Keywords: Infectious bursal disease, vaccination failure, disease control, chicken production ...

  11. Causes and consequences of increased sympathetic activity in renal disease

    NARCIS (Netherlands)

    Joles, JA; Koomans, HA

    Much evidence indicates increased sympathetic nervous activity (SNA) in renal disease. Renal ischemia is probably a primary event leading to increased SNA. Increased SNA often occurs in association with hypertension. However, the deleterious effect of increased SNA on the diseased kidney is not only

  12. An Unusual Cause of Postaural Swelling: Kimura’s Disease

    Directory of Open Access Journals (Sweden)

    Purodha Prasad

    2017-07-01

    Full Text Available Introduction: Kimura’s disease (KD is an allergic inflammatory disorder of unknown etiology endemic in Orientals. Kimura’s disease was first mentioned by Kimm and Szeto in China in 1937. Kimura’s disease is commonly encountered in Asia and is mostly reported in Japan, China, Singapore and Honkong. However, only a few cases have been reported in the Indian subcontinent. Case Report: A case of Kimura’s disease in a young male managed by surgery is reported in addition to a literature review. Conclusion: Diagnosis is made on the basis of histopathological analysis, clinical presentation, and laboratory investigations. Long term follow-up is required as Kimura’s disease is prone for recurrence.

  13. Diseases and causes of death in European bats: dynamics in disease susceptibility and infection rates.

    Directory of Open Access Journals (Sweden)

    Kristin Mühldorfer

    Full Text Available BACKGROUND: Bats receive increasing attention in infectious disease studies, because of their well recognized status as reservoir species for various infectious agents. This is even more important, as bats with their capability of long distance dispersal and complex social structures are unique in the way microbes could be spread by these mammalian species. Nevertheless, infection studies in bats are predominantly limited to the identification of specific pathogens presenting a potential health threat to humans. But the impact of infectious agents on the individual host and their importance on bat mortality is largely unknown and has been neglected in most studies published to date. METHODOLOGY/PRINCIPAL FINDINGS: Between 2002 and 2009, 486 deceased bats of 19 European species (family Vespertilionidae were collected in different geographic regions in Germany. Most animals represented individual cases that have been incidentally found close to roosting sites or near human habitation in urban and urban-like environments. The bat carcasses were subjected to a post-mortem examination and investigated histo-pathologically, bacteriologically and virologically. Trauma and disease represented the most important causes of death in these bats. Comparative analysis of pathological findings and microbiological results show that microbial agents indeed have an impact on bats succumbing to infectious diseases, with fatal bacterial, viral and parasitic infections found in at least 12% of the bats investigated. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the importance of diseases and infectious agents as cause of death in European bat species. The clear seasonal and individual variations in disease prevalence and infection rates indicate that maternity colonies are more susceptible to infectious agents, underlining the possible important role of host physiology, immunity and roosting behavior as risk factors for infection of bats.

  14. Disease: H01276 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ntestinal pseudo-obstruction (CIIP) is a rare, often fatal syndrome, caused by a heterogeneous group of enteric neuromuscular disea...c intestinal pseudo-obstruction. Gastrointestinal disease FLNA [HSA:2316] [KO:K04437] ... ICD-10: K59.8 Me

  15. Kimura's Disease: A Rare Cause of Postauricular Swelling

    Directory of Open Access Journals (Sweden)

    Suman Kumar Das

    2017-04-01

    Full Text Available Introduction Kimura’s Disease is a chronic inflammatory disorder of lymph node which is very rare in Indian population. Case Report A 15 year old boy with multiple postauricular swelling for 18 months presenting in OPD and diagnosed having eosinophilia. Then excision biopsy was taken, which indicates Kimura’s Disease. Patient was treated with high dose of corticosteroid. Conclusion Kimura’s disease, though rare should be kept in mind for treating a patient with lymphadenopathy with eosinophilia or high IgE level, because it can spare the patient unnecessary invasive procedure.

  16. Waterborne Exophiala species causing disease in cold-blooded animals

    National Research Council Canada - National Science Library

    de Hoog, G S; Vicente, V A; Najafzadeh, M J; Harrak, M J; Badali, H; Seyedmousavi, S

    2011-01-01

    ...) belong to a single clade judging from SSU rDNA data. Most taxa are also found to cause cutaneous or disseminated infections in cold-blooded, water animals, occasionally reaching epidemic proportions...

  17. Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens

    Directory of Open Access Journals (Sweden)

    Ogrendik M

    2013-05-01

    Full Text Available Mesut OgrendikDivision of Physical Therapy and Rheumatology, Nazilli State Hospital, Nazilli, TurkeyAbstract: A statistically significant association between periodontal disease (PD and systemic diseases has been identified. Rheumatoid arthritis (RA, which is a chronic inflammatory joint disease, exhibits similar characteristics and pathogenesis to PD. The association between RA and PD has been investigated, and numerous publications on this subject exist. Approximately 20 bacterial species have been identified as periodontal pathogens, and these organisms are linked to various types of PD. The most analyzed species of periodontopathic bacteria are Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans. Antibodies and DNA from these oral pathogens have been isolated from the sera and synovial fluids of RA patients. This rapid communication describes the role of periodontal pathogens in the etiopathogenesis of RA.Keywords: etiopathogenesis, chronic arthritis, periodontitis, Porphyromonas gingivalis, systemic disease, animal models, antibiotics

  18. Helicobacter pylori and autoimmune disease:Cause or bystander

    National Research Council Canada - National Science Library

    Daniel S Smyk Andreas L Koutsoumpas Maria G Myt-ilinaiou Eirini I Rigopoulou Lazaros I Sakkas Dimitrios P Bogdanos

    2014-01-01

    ... to the stomach.This review discusses the current evidence in support or against the role of H.pylori as a potential trigger of autoimmune rheumatic and skin diseases,as well as organ specific autoimmune...

  19. GAUCHER´S DISEASE: A RARE CAUSE OF FANCONI SYNDROME?

    Directory of Open Access Journals (Sweden)

    Musso CG

    2007-01-01

    Full Text Available Gaucher´s disease consists of a genetic autosomic recesive alteration that leads to a reduction in the acid glucosil-ceramide beta-glucosidase enzyme. This enzyme brakes the glucosilceramide, a substance from which many esphingo and glucolipids are synthesized. Even though the renal compromise is not frequent in Gaucher disease, proteinuria (in nephrotic range or not and glomerulonephritis have been described in this illness.Fanconi syndrome is charaterized by a dysfunction in the proximal tubular reabsorption. Among the etiologies of Fanconi syndrome there are many metabolic diseases, but no association has been described yet in the literature between Fanconi syndrome and Gaucher disease. We present the following case report where this association was observed.

  20. Klotho deficiency causes vascular calcification in chronic kidney disease

    National Research Council Canada - National Science Library

    Hu, Ming Chang; Shi, Mingjun; Zhang, Jianning; Quiñones, Henry; Griffith, Carolyn; Kuro-o, Makoto; Moe, Orson W

    2011-01-01

    Soft-tissue calcification is a prominent feature in both chronic kidney disease (CKD) and experimental Klotho deficiency, but whether Klotho deficiency is responsible for the calcification in CKD is unknown...

  1. Causes and histopathology of ascending aortic disease in children and young adults

    Science.gov (United States)

    Jain, Deepali; Dietz, Harry C.; Oswald, Gretchen L.; Maleszewski, Joseph J.; Halushka, Marc K.

    2011-01-01

    Background Ascending aortic diseases (aneurysms, dissections, and stenosis) and associated aortic valve disease are rare but important causes of morbidity and mortality in children and young adults. Certain genetic causes, such as Marfan syndrome and congenital bicuspid aortic valve disease, are well known. However, other rarer genetic and nongenetic causes of aortic disease exist. Methods We performed an extensive literature search to identify known causes of ascending aortic pathology in children and young adults. We catalogued both aortic pathologies and other defining systemic features of these diseases. Results We describe 17 predominantly genetic entities that have been associated with thoracic aortic disease in this age group. Conclusions While extensive literature on the common causes of ascending aortic disease exists, there is a need for better histologic documentation of aortic pathology in rarer diseases. PMID:19926309

  2. Muscle ultrasound in neuromuscular disorders.

    NARCIS (Netherlands)

    Pillen, S.; Arts, I.M.P.; Zwarts, M.J.

    2008-01-01

    Muscle ultrasound is a useful tool in the diagnosis of neuromuscular disorders, as these disorders result in muscle atrophy and intramuscular fibrosis and fatty infiltration, which can be visualized with ultrasound. Several prospective studies have reported high sensitivities and specificities in

  3. Vocational perspectives and neuromuscular disorders

    NARCIS (Netherlands)

    Andries, F.; Wevers, C. W.; Wintzen, A. R.; Busch, H. F.; Höweler, C. J.; de Jager, A. E.; Padberg, G. W.; de Visser, M.; Wokke, J. H.

    1997-01-01

    The present study analyses the actual occupational situation, vocational handicaps and past labour career of a group of about 1000 Dutch patients suffering from a neuromuscular disorder (NMD). On the basis of the likelihood of a substantial employment history and sufficient numbers of patients, four

  4. Incidence and risk factors of prolonged mechanical ventilation in neuromuscular scoliosis surgery

    NARCIS (Netherlands)

    Udink Ten Cate, F.E.A.; van Royen, B.J.; van Heerde, M.; Roerdink, D.; Plotz, F.B.

    2008-01-01

    Patients with neuromuscular scoliosis (NMS) are frequently considered at high risk for postoperative complications based on their underlying disease and comorbidities. Postoperative complications include prolonged mechanical ventilation (MV), defined longer than 72h, at the paediatric intensive care

  5. Pelvic Hydatid Disease: CT and MRI Findings Causing Sciatica

    Science.gov (United States)

    Kocaoglu, Murat; Bulakbasi, Nail; Yildirim, Duzgun

    2007-01-01

    Pelvic masses, especially hydatid disease, rarely present with sciatica (1, 2). We present the computed tomography (CT) and the magnetic resonance imaging (MRI) findings of a 49-year-old female patient with presacral hydatid disease, who was evaluated for her sciatica. We also want to emphasize the importance of assessing the pelvis of patients with symptoms and clinical findings that are inconsistent and that cannot be satisfactorily explained by the spinal imaging findings. PMID:18071287

  6. Parasitic Diseases as a cause of Mortality in Commercial Chicken in ...

    African Journals Online (AJOL)

    ... the role of parasitic diseases as causes of mortalities in chickens brought to the postmortem facility of the veterinary school of the University of Nairobi, Kenya. Parasitic diseases caused deaths in 786(26%) chicken out of 2975 dead from a combination of diseases. The major contributor of mortalities was acute coccidiosis, ...

  7. Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Tybjærg-Hansen, Anne

    2013-01-01

    Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown.......Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown....

  8. Gastrointestinal diseases of Napoleon in Saint Helena: causes of death.

    Science.gov (United States)

    Di Costanzo, Jacques

    2002-01-01

    The fact that Napoleon Ist died from gastric cancer seems to be well established. Arguments for the hypothesis of chronic arsenic poisoning have recently been developed in the literature. This study, focused on the gastrointestinal diseases of Napoleon in Saint Helena, is based on a confrontation between the clinical semiological anamnesis and the anatomical data in the autopsy report by F. Antommarchi. Napoleon presented several gastrointestinal diseases: gall-bladder lithiasis complicated with angiocholitis, chronic colitis and certainly a gastric cancer. Death was consecutive to perforation of the gastric lesion leading to haemorrhagic vomitis and multiorgan failure. The description of the gastric lesions during autopsy is consistent with the diagnosis of cancer. The course of the clinical events is closely correlated with the anatomic lesions. There is strong evidence that Napoleon died from an acute complication of his gastric disease.

  9. An unusual cause of cervical lymphadenopathy: Kikuchi-Fujimoto disease

    Directory of Open Access Journals (Sweden)

    Mehmet Uluğ

    2012-03-01

    Full Text Available Kikuchi-Fujimoto disease (KFD, also known as histiocytic necrotizing lymphadenitis, is an uncommon clinical and pathologicalself-limited feature of benign prognosis that may mimic many other diseases diagnosed chiefly in youngadults. The etiology of the disease is unknown although several investigators postulate viral, parasitic and autoimmuneetiologies. The most common symptoms are cervical lymphadenopathy and fever. Diagnosis is usually rendered withexcisional biopsy of lymph nodes and through histopathological findings. Non-steroidal anti-inflammatory drugs areused for the treatment. In this report, two cases of KFD without any associated infectious and/or non-infectious conditionswere presented. J Microbiol Infect Dis 2012; 2(1: 21-25

  10. Precision orthotics: optimising ankle foot orthoses to improve gait in patients with neuromuscular diseases; protocol of the PROOF-AFO study, a prospective intervention study.

    Science.gov (United States)

    Waterval, Niels F J; Nollet, Frans; Harlaar, Jaap; Brehm, Merel-Anne

    2017-02-28

    In patients with neuromuscular disorders and subsequent calf muscle weakness, metabolic walking energy cost (EC) is nearly always increased, which may restrict walking activity in daily life. To reduce walking EC, a spring-like ankle-foot-orthosis (AFO) can be prescribed. However, the reduction in EC that can be obtained from these AFOs is stiffness dependent, and it is unknown which AFO stiffness would optimally support calf muscle weakness. The PROOF-AFO study aims to determine the effectiveness of stiffness-optimised AFOs on reducing walking EC, and improving gait biomechanics and walking speed in patients with calf muscle weakness, compared to standard, non-optimised AFOs. A second aim is to build a model to predict optimal AFO stiffness. A prospective intervention study will be conducted. In total, 37 patients with calf muscle weakness who already use an AFO will be recruited. At study entry, participants will receive a new custom-made spring-like AFO of which the stiffness can be varied. For each patient, walking EC (primary outcome), gait biomechanics and walking speed (secondary outcomes) will be assessed for five stiffness configurations and the patient's own (standard) AFO. On the basis of walking EC and gait biomechanics outcomes, the optimal AFO stiffness will be determined. After wearing this optimal AFO for 3 months, walking EC, gait biomechanics and walking speed will be assessed again and compared to the standard AFO. The Medical Ethics Committee of the Academic Medical Centre in Amsterdam has approved the study protocol. The study is registered at the Dutch trial register (NTR 5170). The PROOF-AFO study is the first to compare stiffness-optimised AFOs with usual care AFOs in patients with calf muscle weakness. The results will also provide insight into factors that influence optimal AFO stiffness in these patients. The results are necessary for improving orthotic treatment and will be disseminated through international peer-reviewed journals and

  11. Chemical control of blossom blight disease of sarpagandha caused ...

    African Journals Online (AJOL)

    Sarpagandha (Rauvolfia serpentina Benth) is grown in different parts of India and its adjoining countries for its root which is the chief source of several important alkaloids like ajmalicine, ajmaline, isoajmaline, rauvolfinine, reserpine and serpentine. Blossom blight caused by Colletotrichum capsici is one of the most serious ...

  12. Radiation fibrosis syndrome: neuromuscular and musculoskeletal complications in cancer survivors.

    Science.gov (United States)

    Stubblefield, Michael D

    2011-11-01

    Radiation-induced toxicity is a major cause of long-term disability after cancer treatment. Radiation fibrosis describes the insidious pathologic fibrotic tissue sclerosis that can occur in response to radiation exposure. Radiation fibrosis syndrome describes the myriad clinical manifestations of progressive fibrotic tissue sclerosis resulting from radiation treatment. Radiation-induced damage can include "myelo-radiculo-plexo-neuro-myopathy," causing muscle weakness and dysfunction and contributing to neuromuscular injury. Similarly, radiation damage to neuromuscular structures contributes to radiation-induced trismus and cervical dystonia in head and neck cancer survivors. This narrative review discusses the pathophysiology, anatomy, evaluation, and treatment of neuromuscular, musculoskeletal, and functional disorders that can result as late effects of radiation treatment. Rehabilitation medicine physicians with extensive training in neuromuscular and musculoskeletal medicine as well as in the principles of functional restoration are uniquely positioned to help lead efforts to improve the quality of life for cancer survivors with radiation fibrosis syndrome. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  13. Neuromuscular dressing effects: a literature review

    Directory of Open Access Journals (Sweden)

    Calero PA

    2012-05-01

    Full Text Available The kinesio taping is a technique that was created in 1979 by Doctor Kenzo Kase I’m looking through it that could generate a new therapeutic option to control pain, improve athletic performance and reduce the impact of musculoskeletal disorders. From the Sydney 2000 Olympic Games, this technique as a therapeutic alternative PTO and is composed of health professionals in the field of sport and physical rehabilitation.Objetive: This article aims to identify theoretical approaches on the bandage neuromuscular. Material and methods: held today, for which conducted a literature search of databases such as como Proquest, Ovid, Cochraine, PEDro, Journal of Orthopedic and Sports Physical, Sciencedirect, Pubmed y Literatura Latinoamericana y del Caribe en Ciencias de la Salud (Lilacs.The paper proposes a scheme of contextualization of the current landscape of the use and effects of kinesio taping in the management of different pathologies of the musculo-skeletal system in sports. Conclusion: it is concluded that currently many health professionals, and take the neuromuscular bandage a good therapeutic option in the management of diseases affecting the human body is investigated and every day more about the subject, which makes these new therapeutic methods to acquire a scientific value and transcends knowledge.

  14. Lipoprotein (a) as a cause of cardiovascular disease

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Langsted, Anne

    2016-01-01

    Human epidemiologic and genetic evidence using the Mendelian randomization approach in large-scale studies now strongly supports that elevated lipoprotein (a) [Lp(a)] is a causal risk factor for cardiovascular disease, that is, for myocardial infarction, atherosclerotic stenosis, and aortic valve...

  15. Modelling studies on neurodegenerative disease-causing triplet ...

    Indian Academy of Sciences (India)

    Unknown

    DM), fragile X syndrome (FraX), Huntington disease. (HD), several spinocerebellar ataxias and Friedreich ataxia have been associated with the expansion of GGC,. CAG or GAA repeats (Pearson and Sinden 1998). Actually,. GGC, CAG and GAA repeats indicate duplex repeat sequences (GGC)n–(GCC)n [also indicated as ...

  16. Molecular Characterization of Tomato Leaf Curl Disease-Causing ...

    African Journals Online (AJOL)

    In this study, Tomato Leaf Curl Disease symptom-bearing samples were collected from dry savannah (Eastern and Northern) and wet equatorial/tall grass savannah (Central and Western) agro-climatic zones of Uganda. Their total DNA was extracted using a modifi ed Dellaporta protocol. Virus DNA was amplifi ed with fi ve ...

  17. Bardet Biedel Syndrome: a Rare Cause of Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Yildirim Tuba Demirci

    2016-06-01

    Full Text Available Bardet Biedl syndrome (BBS is characterized by obesity, retinitis pigmentosa, hypogonadism, mental retardation and polydactyly. Additionally, renal, cardiac and neurological manifestations may be seen. We report a case of BBS with chronic kidney disease (CKD at the age of 43.

  18. A Novel Virus Causes Scale Drop Disease in Lates calcarifer

    NARCIS (Netherlands)

    Groof, A.; Guelen, L.; Deijs, M.; Wal, van der Y.; Miyata, M.; Ng, K.S.; Grinsven, van L.; Simmelink, B.; Biermann, Y.; Grisez, L.; Lent, van J.W.M.; Ronde, de A.; Chang, S.F.; Schrier, C.; Hoek, L.

    2015-01-01

    From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained

  19. Preventing fatal diseases increases healthcare costs: cause elimination life table approach

    NARCIS (Netherlands)

    L.G.A. Bonneux (Luc); J.J.M. Barendregt (Jan); W.J. Nusselder (Wilma); P.J. van der Maas (Paul)

    1998-01-01

    textabstractOBJECTIVES: To examine whether elimination of fatal diseases will increase healthcare costs. DESIGN: Mortality data from vital statistics combined with healthcare spending in a cause elimination life table. Costs were allocated to specific diseases through

  20. Prediction of Disease Causing Non-Synonymous SNPs by the Artificial Neural Network Predictor NetDiseaseSNP

    DEFF Research Database (Denmark)

    Johansen, Morten Bo; Gonzalez-Izarzugaza, Jose Maria; Brunak, Søren

    2013-01-01

    We have developed a sequence conservation-based artificial neural network predictor called NetDiseaseSNP which classifies nsSNPs as disease-causing or neutral. Our method uses the excellent alignment generation algorithm of SIFT to identify related sequences and a combination of 31 features...... assessing sequence conservation and the predicted surface accessibility to produce a single score which can be used to rank nsSNPs based on their potential to cause disease. NetDiseaseSNP classifies successfully disease-causing and neutral mutations. In addition, we show that NetDiseaseSNP discriminates...... cancer driver and passenger mutations satisfactorily. Our method outperforms other state-of-the-art methods on several disease/neutral datasets as well as on cancer driver/passenger mutation datasets and can thus be used to pinpoint and prioritize plausible disease candidates among nsSNPs for further...

  1. Neuromuscular disorders: genes, genetic counseling and therapeutic trials

    Directory of Open Access Journals (Sweden)

    Mayana Zatz

    Full Text Available Abstract Neuromuscular disorders (NMD are a heterogeneous group of genetic conditions, with autosomal dominant, recessive, or X-linked inheritance. They are characterized by progressive muscle degeneration and weakness. Here, we are presenting our major contributions to the field during the past 30 years. We have mapped and identified several novel genes responsible for NMD. Genotype-phenotype correlations studies enhanced our comprehension on the effect of gene mutations on related proteins and their impact on clinical findings. The search for modifier factors allowed the identification of a novel "protective"; variant which may have important implication on therapeutic developments. Molecular diagnosis was introduced in the 1980s and new technologies have been incorporated since then. Next generation sequencing greatly improved our capacity to identify disease-causing mutations with important benefits for research and prevention through genetic counseling of patients' families. Stem cells researches, from and for patients, have been used as tools to study human genetic diseases mechanisms and for therapies development. The clinical effect of preclinical trials in mice and canine models for muscular dystrophies are under investigation. Finally, the integration of our researches and genetic services with our post-graduation program resulted in a significant output of new geneticists, spreading out this expertise to our large country.

  2. Important causes of chronic kidney disease in South Africa | Moosa ...

    African Journals Online (AJOL)

    In hypertensive patients without chronic kidney disease (CKD) the goal is to keep blood pressure (BP) at ≤140/90 mmHg. When CKD is present, especially where there is proteinuria of ≥0.5 g/day, the goal is a BP of ≤130/80 mmHg. Lifestyle measures are mandatory, especially limitation of salt intake, ingestion of ...

  3. Causes of Parkinson’s disease: Literature Review

    OpenAIRE

    Shafique, Hassan

    2011-01-01

    Hassan Shafique,1 Alex Blagrove,2 Angela Chung,2 Raynarth Logendrarajah1Department of Neuroscience, University of Toronto, Toronto, Ontario, Canada; 2Department of Psychology, University of Toronto, Toronto, Ontario, CanadaAbstract: Parkinson’s disease is one of the most common movement disorders in the world. Parkinson’s affects approximately 1% of all adults over the age of 60. This disorder is the result of the degeneration of dopamineproducing cells in the substantia n...

  4. [Causes of osteoporosis: don't forget celiac disease].

    Science.gov (United States)

    Scharla, S

    2003-04-25

    A 60-year old woman presented with osteoporosis. Because clinical symptoms did not improve after treatment, further diagnostic procedures were performed in order to further characterize the metabolic bone disease. The patient reported loss of weight,nonspecific gastrointestinal symptoms (recurrent abdominal pain),and constipation. The diet history revealed a milk intolerance. Several family members were suffering from autoimmune diseases. During physical examination the patient exhibited clinical signs of osteoporosis(back pain, change of stature), but otherwise no pathological findings. The technical examinations showed low bone mineral density at the spine. The routine laboratory examination (including serum calcium, phosphorus, alkaline phosphatase)was normal. However, further testing revealed low concentrations for 25-hydroxy-vitamin D, folic acid, vitamin B 12, an increased IgA and significantly elevated antigliadin antibodies and antiendomysial antibodies. Histopathological examination of the duodenal mucosa was in accordance with the diagnosis celiac sprue. The histopathologic examination of a transiliac bone biopsy exhibited high bone turnover, osteopenia, but no osteomalacia. Therefore, the diagnosis of celiac sprue with metabolic bone disease was established. Treatment with gluten-free diet and supplementation of calcium and vitamin D was initiated. This case demonstrates that careful diagnostic evaluation of patients with osteoporosis is necessary,because therapeutic consequences are the result.

  5. Does metabolic failure at the synapse cause Alzheimer's disease?

    Science.gov (United States)

    Engel, Peter A

    2014-12-01

    Alzheimer's disease (AD) a neurodegenerative disorder of widely distributed cortical networks evolves over years while A beta (Aβ) oligomer neurotoxicity occurs within seconds to minutes. This disparity combined with disappointing outcomes of anti-amyloid clinical trials challenges the centrality of Aβ as principal mediator of neurodegeneration. Reconsideration of late life AD as the end-product of intermittent regional failure of the neuronal support system to meet the needs of vulnerable brain areas offers an alternative point of view. This model introduces four ideas: (1) That Aβ is a synaptic signaling peptide that becomes toxic in circumstances of metabolic stress. (2) That intense synaptic energy and maintenance requirements of cortical hubs may exceed resources during peak demand initiating a neurotoxic cascade in these selectively vulnerable regions. (3) That axonal transport to and from neuron soma cannot account fully for high mitochondrial densities and other requirements of distant terminal axons. (4) That neurons as specialists in information management, delegate generic support functions to astrocytes and other cell types. Astrocytes use intercellular transport by exosomes and tunneling nanotubes (TNTs) to deliver mitochondria, substrates and protein reprocessing services to axonal sites distant from neuronal soma. This viewpoint implicates the brain's support system and its disruption by various age and disease-related insults as significant mediators of neurodegenerative disease. A better understanding of this system should broaden concepts of neurodegeneration and facilitate development of effective treatments. Published by Elsevier Ltd.

  6. Biological Control of Plant Disease Caused by Bacteria

    Directory of Open Access Journals (Sweden)

    Triwidodo Arwiyanto

    2014-07-01

    Full Text Available Bacterial diseases in plants are difficult to control. The emphasis is on preventing the spread of the bacteria rather than curing the diseased plant. Integrated management measures for bacterial plant pathogens should be applied for successfull control. Biological control is one of the control measures viz. through the use of microorganisms to suppress the growth and development of bacterial plant pathogen and ultimately reduce the possibility of disease onset. The study of biological control of bacterial plant pathogen was just began compared with of fungal plant pathogen. The ecological nature of diverse bacterial plant pathogens has led scientists to apply different approach in the investigation of its biological control. The complex process of entrance to its host plant for certain soil-borne bacterial plant pathogens need special techniques and combination of more than one biological control agent. Problem and progress in controlling bacterial plant pathogens biologically will be discussed in more detail in the paper and some commercial products of biological control agents (biopesticides will be introduced.     Penyakit tumbuhan karena bakteri sulit dikendalikan. Penekanan pengendalian adalah pada pencegahan penyebaran bakteri patogen dan bukan pada penyembuhan tanaman yang sudah sakit. Untuk suksesnya pengendalian bakteri patogen tumbuhan diperlukan cara pengelolaan yang terpadu. Pengendalian secara biologi merupakan salah satu cara pengendalian dengan menggunakan mikroorganisme untuk menekan pertumbuhan dan perkembangan bakteri patogen tumbuhan dengan tujuan akhir menurunkan kemungkinan timbulnya penyakit. Sifat ekologi bakteri patogen tumbuhan yang berbeda-beda mengharuskan pendekatan yang berbeda pula dalam pengendaliannya secara biologi. Masalah dan perkembangan dalam pengendalian bakteri patogen tumbuhan secara biologi didiskusikan secara detail dalam makalah ini.

  7. An unusual cause of ventilatory failure in motor neurone disease

    Directory of Open Access Journals (Sweden)

    Epaminondas Markos Valsamis, MB BChir, MA (Cantab, MRCS

    2017-01-01

    Full Text Available A patient previously diagnosed with motor neurone disease (MND and gastrostomy-fed was under surveillance for ventilatory decline via our respiratory centre. At a planned review she was found to be hypercapnic, which would usually prompt an offer of non-invasive ventilation for home use. However, she was alkalotic and not acidotic as we might expect. Her serum potassium was checked urgently and confirmed as low. It was established that the community team had prescribed a feeding regime with insufficient potassium. Correction of hypokalaemia resolved her ventilatory failure. This case demonstrates the importance of co-ordinated care in the management of patients with MND.

  8. An unusual cause of ventilatory failure in motor neurone disease.

    Science.gov (United States)

    Valsamis, Epaminondas Markos; Smith, Ian; De Sousa, Adri

    2017-01-01

    A patient previously diagnosed with motor neurone disease (MND) and gastrostomy-fed was under surveillance for ventilatory decline via our respiratory centre. At a planned review she was found to be hypercapnic, which would usually prompt an offer of non-invasive ventilation for home use. However, she was alkalotic and not acidotic as we might expect. Her serum potassium was checked urgently and confirmed as low. It was established that the community team had prescribed a feeding regime with insufficient potassium. Correction of hypokalaemia resolved her ventilatory failure. This case demonstrates the importance of co-ordinated care in the management of patients with MND.

  9. Lipoprotein X Causes Renal Disease in LCAT Deficiency.

    Directory of Open Access Journals (Sweden)

    Alice Ossoli

    Full Text Available Human familial lecithin:cholesterol acyltransferase (LCAT deficiency (FLD is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX in plasma, and renal disease. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, chemical and biologic characteristics, to wild-type and Lcat-/- mice. Our in vitro and in vivo studies demonstrated an apoA-I and LCAT-dependent pathway for LpX conversion to HDL-like particles, which likely mediates normal plasma clearance of LpX. Plasma clearance of exogenous LpX was markedly delayed in Lcat-/- mice, which have low HDL, but only minimal amounts of endogenous LpX and do not spontaneously develop renal disease. Chronically administered exogenous LpX deposited in all renal glomerular cellular and matrical compartments of Lcat-/- mice, and induced proteinuria and nephrotoxic gene changes, as well as all of the hallmarks of FLD renal disease as assessed by histological, TEM, and SEM analyses. Extensive in vivo EM studies revealed LpX uptake by macropinocytosis into mouse glomerular endothelial cells, podocytes, and mesangial cells and delivery to lysosomes where it was degraded. Endocytosed LpX appeared to be degraded by both human podocyte and mesangial cell lysosomal PLA2 and induced podocyte secretion of pro-inflammatory IL-6 in vitro and renal Cxl10 expression in Lcat-/- mice. In conclusion, LpX is a nephrotoxic particle that in the absence of Lcat induces all of the histological and functional hallmarks of FLD and hence may serve as a biomarker for monitoring recombinant LCAT therapy. In addition, our studies suggest that LpX-induced loss of endothelial barrier function and release of cytokines by renal glomerular cells likely plays a role in the initiation and progression of FLD nephrosis.

  10. [Aneurysmal bone cyst: A rare cause of orbital disease].

    Science.gov (United States)

    Lemaître, S; Galatoire, O; Zmuda, M; Jacomet, P-V; Putterman, M; Berges, O; Cassoux, N

    2016-06-01

    Aneurysmal bone cyst is a rare benign bone neoplasm of unknown cause. The most commonly affected anatomical sites are the vertebral column and long bones. We report two uncommon cases of primary orbital aneurysmal bone cyst presenting as an acute orbital compartment syndrome due to subperiosteal hemorrhage. Case 1 is a 45-year-old woman. Imaging studies revealed a small cystic frontal bone tumour associated with a subperiosteal hematoma. The patient achieved full visual recovery after drainage of the hematoma, with no recurrence after treatment. Case 2 is a 74-year-old woman whose visual acuity was light perception due to severe papilledema. Imaging studies of the orbit revealed a large cystic frontal bone tumor associated with a subperiosteal hematoma causing globe and optic nerve compression. Preoperative arteriography showed a moderate vascular blush. Drainage of the hematoma was performed. A local recurrence with hematoma formation occurred two years after the surgery. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. Is pesticide exposure a cause of obstructive airways disease?

    Directory of Open Access Journals (Sweden)

    Emma Doust

    2014-06-01

    Full Text Available A systematic review was performed to identify any associations between pesticide exposure and the occurrence (both prevalence and incidence of airways disease (asthma and chronic obstructive pulmonary disease and wheezing symptoms. PubMed, MEDLINE, Embase, Scopus, CINAHL, Google Scholar and the Cochrane Database of Systematic Reviews were searched between September 2010 and October 2010 for papers with the inclusion criteria of English language, published after 1990, peer-reviewed and nondietary exposure. From a total of 4390 papers identified, 42 were included after initial assessment of content. After evaluating the included studies for quality, those considered to be at high risk of bias were excluded, leaving a total of 23 relevant papers. Results suggest that exposure to pesticides may be associated with prevalent asthma, but methodological issues, such as cross-sectional/case–control design, measurements of exposure and limited adjustment for confounders, limit the strength of the evidence base in this area. The association between pesticide exposure and asthma appears to be more evident and consistent in children than in adults. Exposure to pesticides may be associated with COPD; however, the strength of evidence for an association with COPD is weaker than for asthma. As the exposure metrics within each health end-point varied across studies, no meta-analyses were carried out.

  12. Detection of Secondary Causes and Coexisting Diseases in Hypertensive Patients: OSA and PA Are the Common Causes Associated with Hypertension

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2017-01-01

    Full Text Available Background. Since the control rate of blood pressure is lower in mainland China, the aim of this study is to investigate the proportion of secondary causes and coexisting diseases of hypertension in hypertensive patients. Methods. Data on consecutive patients with hypertension who visited the Hypertension Center. Diseases were detected using an established strict screening protocol. Results. Detection rate of secondary causes and coexisting diseases of hypertension was 39.5% among 3003 hypertensive patients. Obstructive sleep apnea (OSA was the most common, accounting for 24.7% of patients, followed by primary aldosteronism (PA (5.8% and PA + OSA (4.9%. Endocrine hypertension accounted for 12.1% of patients, including 10.7% of patients with PA, 1.1% with hypothyroidism, 0.1% with pheochromocytoma, 0.1% with Cushing’s syndrome, and 0.1% with hyperthyroidism, respectively. Those who smoke, those who are obese, and those who have diabetes accounted for 31.3%, 27.5%, and 16.6% of total patients, respectively. There were overlapping conditions in secondary causes and coexisting diseases of hypertension. OSA was the most common in each age- and BMI-stratified group. Conclusion. Findings from the current study suggest an increasing frequency of secondary forms of hypertension, highlighting the burden of OSA and PA in hypertensive patients.

  13. Contemporary Approaches for Identifying Rare Bone Disease Causing Genes.

    Science.gov (United States)

    Farber, Charles R; Clemens, Thomas L

    Recent improvements in the speed and accuracy of DNA sequencing, together with increasingly sophisticated mathematical approaches for annotating gene networks, have revolutionized the field of human genetics and made these once time consuming approaches assessable to most investigators. In the field of bone research, a particularly active area of gene discovery has occurred in patients with rare bone disorders such as osteogenesis imperfecta (OI) that are caused by mutations in single genes. In this perspective, we highlight some of these technological advances and describe how they have been used to identify the genetic determinants underlying two previously unexplained cases of OI. The widespread availability of advanced methods for DNA sequencing and bioinformatics analysis can be expected to greatly facilitate identification of novel gene networks that normally function to control bone formation and maintenance.

  14. Just a sore throat? Uncommon causes of significant respiratory disease

    Science.gov (United States)

    Wahab, Dalia; Bichard, Julia; Shah, Anand; Mann, Bhupinder

    2013-01-01

    We present two uncommon underlying causes of a sore throat which, if missed or delayed in diagnosis, can lead to disastrous consequences. Our first case is of Lemierre's syndrome diagnosed in a 21-year-old man presenting with a 5-day history of sore throat, fever, right-sided pleuritic chest pain and bilateral pulmonary nodules on CT imaging. Fusobacterium necrophorum cultured from peripheral blood and an occluded left internal jugular vein on ultrasound lead to an eventual diagnosis. Our second case presents a 29-year-old woman with a 5-day history of sore throat, fever and right-sided pleuritic chest pain. A left-sided quinsy was diagnosed and aspirated and the patient was discharged home. She represented shortly with worsening pleuritic pain and was found to have a right-sided pleural effusion with descending mediastinitis originating from the tonsillar abscess. Delayed diagnosis resulted in open thoracotomy, decortication and prolonged intravenous antibiotics. PMID:23632177

  15. Mitochondrial Disease as a Cause of Neonatal Hemophagocytic Lymphohistiocytosis

    Directory of Open Access Journals (Sweden)

    Kazumasa Fuwa

    2016-01-01

    Full Text Available Diagnosis of mitochondrial respiratory chain disorder (MRCD is often difficult. Its pathogenesis is still unclear. We diagnosed MRCD by measuring the activity of the mitochondrial respiratory chain enzyme, and the patient also had hemophagocytic lymphohistiocytosis (HLH. A preterm female infant was born at 34 weeks of gestation. On day 6, HLH was revealed by bone marrow aspiration. She died on day 10 due to uncontrollable HLH. An autopsy was performed, and we measured the activity of the mitochondrial respiratory chain enzyme in the liver, muscle, and heart. The activity of complex I was decreased in all tissues. As we could not prove another origin of the HLH, she was diagnosed as having HLH caused by MRCD. It is useful to measure the activity of the mitochondrial respiratory chain enzyme for diagnosing MRCD. MRCD, which has a severe clinical course, may be related to HLH.

  16. Neuromuscular Activity of Micrurus laticollaris (Squamata: Elapidae Venom in Vitro

    Directory of Open Access Journals (Sweden)

    Alejandro Carbajal-Saucedo

    2014-01-01

    Full Text Available In this work, we have examined the neuromuscular activity of Micrurus laticollaris (Mexican coral snake venom (MLV in vertebrate isolated nerve-muscle preparations. In chick biventer cervicis preparations, the MLV induced an irreversible concentration- and time-dependent (1–30 µg/mL neuromuscular blockade, with 50% blockade occurring between 8 and 30 min. Muscle contractures evoked by exogenous acetylcholine were completely abolished by MLV, whereas those of KCl were also significantly altered (86% ± 11%, 53% ± 11%, 89% ± 5% and 89% ± 7% for one, three, 10 and 30 µg of venom/mL, respectively; n = 4; p < 0.05. In mouse phrenic nerve-diaphragm preparations, MLV (1–10 µg/mL promoted a slight increase in the amplitude of twitch-tension (3 µg/mL, followed by neuromuscular blockade (n = 4; the highest concentration caused complete inhibition of the twitches (time for 50% blockade = 26 ± 3 min, without exhibiting a previous neuromuscular facilitation. The venom (3 µg/mL induced a biphasic modulation in the frequency of miniature end-plate potentials (MEPPs/min, causing a significant increase after 15 min, followed by a decrease after 60 min (from 17 ± 1.4 (basal to 28 ± 2.5 (t15 and 12 ± 2 (t60. The membrane resting potential of mouse diaphragm preparations pre-exposed or not to d-tubocurarine (5 µg/mL was also significantly less negative with MLV (10 µg/mL. Together, these results indicate that M. laticollaris venom induces neuromuscular blockade by a combination of pre- and post-synaptic activities.

  17. Endomicroscopy and electromyography of neuromuscular junctions in situ

    Science.gov (United States)

    Brown, Rosalind; Dissanayake, Kosala N; Skehel, Paul A; Ribchester, Richard R

    2014-01-01

    Objective Electromyography (EMG) is used routinely to diagnose neuromuscular dysfunction in a wide range of peripheral neuropathies, myopathies, and neuromuscular degenerative diseases including motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Definitive neurological diagnosis may also be indicated by the analysis of pathological neuromuscular innervation in motor-point biopsies. Our objective in this study was to preempt motor-point biopsy by combining live imaging with electrophysiological analysis of slow degeneration of neuromuscular junctions (NMJs) in vivo. Methods We combined conventional needle electromyography with fiber-optic confocal endomicroscopy (CEM), using an integrated hand-held, 1.5-mm-diameter probe. We utilized as a test bed, various axotomized muscles in the hind limbs of anaesthetized, double-homozygous thy1.2YFP16: WldS mice, which coexpress the Wallerian-degeneration Slow (WldS) protein and yellow fluorescent protein (YFP) in motor neurons. We also tested exogenous vital stains, including Alexa488-α-bungarotoxin; the styryl pyridinium dye 4-Di-2-Asp; and a GFP conjugate of botulinum toxin Type A heavy chain (GFP-HcBoNT/A). Results We show that an integrated EMG/CEM probe is effective in longitudinal evaluation of functional and morphological changes that take place over a 7-day period during axotomy-induced, slow neuromuscular synaptic degeneration. EMG amplitude declined in parallel with overt degeneration of motor nerve terminals. EMG/CEM was safe and effective when nerve terminals and motor endplates were selectively stained with vital dyes. Interpretation Our findings constitute proof-of-concept, based on live imaging in an animal model, that combining EMG/CEM may be useful as a minimally invasive precursor or alternative to motor-point biopsy in neurological diagnosis and for monitoring local administration of potential therapeutics. PMID:25540801

  18. Mapping global potential risk of mango sudden decline disease caused by fungus Ceratocystis fimbriata

    Science.gov (United States)

    Mango Sudden Decline (MSD), sometimes referred to as mango wilt, is an important disease of mango caused by one of the most significant fungal species causing disease in woody plants, Ceratocystis fimbriata. This species is mainly disseminated by the mango bark beetle, Hypocryphalus mangiferae (Steb...

  19. Myths and facts in neuromuscular pharmacology - New developments in reversing neuromuscular blockade

    NARCIS (Netherlands)

    Fink, H.; Hollmann, M. W.

    2012-01-01

    Pharmacologic reversal of neuromuscular blockade is a topic nor very well acknowledged and controversially discussed. Reasons for this are numerous and include missing perception of the potential complications of residual neuromuscular paralysis including an increased morbidity and mortality, as

  20. Modelling the economic impact of three lameness causing diseases using herd and cow level evidence

    DEFF Research Database (Denmark)

    Ettema, Jehan Frans; Østergaard, Søren; Kristensen, Anders Ringgaard

    2010-01-01

    Diseases to the cow's hoof, interdigital skin and legs are highly prevalent and of large economic impact in modern dairy farming. In order to support farmer's decisions on preventing and treating lameness and its underlying causes, decision support models can be used to predict the economic...... horn diseases. Secondly, the existing simulation model was set-up inwaythat it uses hyper-distributions describing diseases risk of the three lameness causing diseases. By combining information on herd level risk factors with prevalence of lameness or prevalence of underlying diseases among cows...

  1. Acute myeloid leukaemia as a cause of acute ischaemic heart disease

    NARCIS (Netherlands)

    van Haelst, P.L.; Schot, Bart; Hoendermis, E.S.; van den Berg, M.P.

    2006-01-01

    Ischaemic heart disease is almost invariably the result of atherosclerotic degeneration of the coronary arteries. However, other causes of ischaemic heart disease should always be considered. Here we describe two patients with a classic presentation of ischaemic heart disease resulting from acute

  2. Mitochondrial DNA triplication and punctual mutations in patients with mitochondrial neuromuscular disorders

    Energy Technology Data Exchange (ETDEWEB)

    Mkaouar-Rebai, Emna, E-mail: emna.mkaouar@gmail.com [Département des Sciences de la Vie, Faculté des Sciences de Sfax, Université de Sfax (Tunisia); Felhi, Rahma; Tabebi, Mouna [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Alila-Fersi, Olfa; Chamkha, Imen [Département des Sciences de la Vie, Faculté des Sciences de Sfax, Université de Sfax (Tunisia); Maalej, Marwa; Ammar, Marwa [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Kammoun, Fatma [Service de pédiatrie, C.H.U. Hedi Chaker de Sfax (Tunisia); Keskes, Leila [Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax (Tunisia); Hachicha, Mongia [Service de pédiatrie, C.H.U. Hedi Chaker de Sfax (Tunisia); Fakhfakh, Faiza, E-mail: faiza.fakhfakh02@gmail.com [Département des Sciences de la Vie, Faculté des Sciences de Sfax, Université de Sfax (Tunisia)

    2016-04-29

    Mitochondrial diseases are a heterogeneous group of disorders caused by the impairment of the mitochondrial oxidative phosphorylation system which have been associated with various mutations of the mitochondrial DNA (mtDNA) and nuclear gene mutations. The clinical phenotypes are very diverse and the spectrum is still expanding. As brain and muscle are highly dependent on OXPHOS, consequently, neurological disorders and myopathy are common features of mtDNA mutations. Mutations in mtDNA can be classified into three categories: large-scale rearrangements, point mutations in tRNA or rRNA genes and point mutations in protein coding genes. In the present report, we screened mitochondrial genes of complex I, III, IV and V in 2 patients with mitochondrial neuromuscular disorders. The results showed the presence the pathogenic heteroplasmic m.9157G>A variation (A211T) in the MT-ATP6 gene in the first patient. We also reported the first case of triplication of 9 bp in the mitochondrial NC7 region in Africa and Tunisia, in association with the novel m.14924T>C in the MT-CYB gene in the second patient with mitochondrial neuromuscular disorder. - Highlights: • We reported 2 patients with mitochondrial neuromuscular disorders. • The heteroplasmic MT-ATP6 9157G>A variation was reported. • A triplication of 9 bp in the mitochondrial NC7 region was detected. • The m.14924T>C transition (S60P) in the MT-CYB gene was found.

  3. Disease patterns and causes of death of hospitalized HIV-positive adults in West Africa

    DEFF Research Database (Denmark)

    Lewden, Charlotte; Drabo, Youssoufou J; Zannou, Djimon M

    2014-01-01

    previously received antiretroviral treatment (ART). The underlying causes of hospitalization were AIDS-defining conditions (54%), other infections (32%), other diseases (8%) and non-specific illness (6%). The most frequent diseases diagnosed were: tuberculosis (29%), pneumonia (15%), malaria (10......%) and cerebral toxoplasmosis (10%). Overall, 315 (38%) patients died during hospitalization and the underlying cause of death was AIDS (63%), non-AIDS-defining infections (26%), other diseases (7%) and non-specific illness or unknown cause (4%). Among them, the most frequent fatal diseases were: tuberculosis (36...... frequent causes of hospitalization in HIV-positive adults in West Africa and resulted in high in-hospital fatality. Sustained efforts are needed to integrate care of these disease conditions and optimize earlier diagnosis of HIV infection and initiation of ART....

  4. Evaluating the Contribution of the Cause of Kidney Disease to Prognosis in CKD

    DEFF Research Database (Denmark)

    Haynes, Richard; Staplin, Natalie; Emberson, Jonathan

    2014-01-01

    BACKGROUND: The relevance of the cause of kidney disease to prognosis among patients with chronic kidney disease is uncertain. STUDY DESIGN: Observational study. SETTINGS & PARTICIPANTS: 6,245 nondialysis participants in the Study of Heart and Renal Protection (SHARP). PREDICTOR: Baseline cause...... of kidney disease was categorized into 4 groups: cystic kidney disease, diabetic nephropathy, glomerulonephritis, and other recorded diagnoses. OUTCOMES: End-stage renal disease (ESRD; dialysis or transplantation) and death. RESULTS: During an average 4.7 years' follow-up, 2,080 participants progressed...... to ESRD, including 454 with cystic kidney disease (23% per year), 378 with glomerulonephritis (10% per year), 309 with diabetic nephropathy (12% per year), and 939 with other recorded diagnoses (8% per year). By comparison with patients with cystic kidney disease, other disease groups had substantially...

  5. Neuromuscular interactions around the knee in children, adults and elderly

    National Research Council Canada - National Science Library

    Kellis, Eleftherios; Mademli, Lida; Patikas, Dimitrios; Kofotolis, Nikolaos

    2014-01-01

    Although injury and neuromuscular activation patterns may be common for all individuals, there are certain factors which differentiate neuromuscular activity responses between children, adults and elderly...

  6. An autosomal locus causing autoimmune disease: Autoimmune polyglandular disease type I assigned to chromosome 21

    NARCIS (Netherlands)

    J. Aaltonen (Johanna); P. Björses (Petra); L.A. Sandkuijl (Lodewijk); J. Perheentupa (Jaakko); L. Peltonen (Leena Johanna)

    1994-01-01

    textabstractAutoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease characterized by a variable combination of the failure of the endocrine glands. The pathogenesis of this unique autoimmune disease is unknown; unlike many other autoimmune diseases, APECED does

  7. NDRC: A Disease-Causing Genes Prioritized Method Based on Network Diffusion and Rank Concordance.

    Science.gov (United States)

    Fang, Minghong; Hu, Xiaohua; Wang, Yan; Zhao, Junmin; Shen, Xianjun; He, Tingting

    2015-07-01

    Disease-causing genes prioritization is very important to understand disease mechanisms and biomedical applications, such as design of drugs. Previous studies have shown that promising candidate genes are mostly ranked according to their relatedness to known disease genes or closely related disease genes. Therefore, a dangling gene (isolated gene) with no edges in the network can not be effectively prioritized. These approaches tend to prioritize those genes that are highly connected in the PPI network while perform poorly when they are applied to loosely connected disease genes. To address these problems, we propose a new disease-causing genes prioritization method that based on network diffusion and rank concordance (NDRC). The method is evaluated by leave-one-out cross validation on 1931 diseases in which at least one gene is known to be involved, and it is able to rank the true causal gene first in 849 of all 2542 cases. The experimental results suggest that NDRC significantly outperforms other existing methods such as RWR, VAVIEN, DADA and PRINCE on identifying loosely connected disease genes and successfully put dangling genes as potential candidate disease genes. Furthermore, we apply NDRC method to study three representative diseases, Meckel syndrome 1, Protein C deficiency and Peroxisome biogenesis disorder 1A (Zellweger). Our study has also found that certain complex disease-causing genes can be divided into several modules that are closely associated with different disease phenotype.

  8. Kinship and interaction in neuromuscular pharmacology

    NARCIS (Netherlands)

    Schiere, Sjouke

    2006-01-01

    The background of this thesis is presented in the introductory chapters and stafts with a brief history of neuromuscular relaxants. It is followed by a short description of the neuromuscular physiology and pharmacology in chapters 2 and 3, respectively. In chapter 4 the aim of the thesis is

  9. Sugammadex Improves Neuromuscular Function in Patients ...

    African Journals Online (AJOL)

    2018-02-23

    Feb 23, 2018 ... with a modified gamma-cyclodextrin structure offers a viable alternative to the traditional decurarization by cholinesterase inhibitors in the context of the use of steroidal neuromuscular blocking agents. Sugammadex shows its effects through encapsulation of the steroidal neuromuscular blockers, its effects ...

  10. Changes in muscle strength in elderly women after proprioceptive neuromuscular facilitation based training

    Directory of Open Access Journals (Sweden)

    Edivã Bernardo da Silva

    Full Text Available Introduction Proprioceptive neuromuscular facilitation (PNF can be used to improve the quality of life of both healthy and diseased subjects, including the elderly, who suffer muscular weakness due to aging, leading to an impairment in functional capacity. Objective Verify the effectiveness of PNF as a tool for functional conditioning. Materials and methods We evaluated a total of ten elderly women aged 60–70 years, clinically healthy and physically active. They had the force of motion of hip flexion with knee extension analyzed by an analog dynamometer. They were then randomly and equally divided into experimental (EG and control group (CG. The GC was instructed to continue with their normal activities while the GE held 15 training sessions in the lower limb (LL based on the diagonal D1 and D2. Finally, a new collection wrench the two groups was performed and the data compared. Results There was a significant increase in the average strength of GE, on the order of 31% (p 0.05. Discussion : The results confirm that the FNP through initial work of readjustment and proprioceptive neuromuscular activation, and after that, conditioning of the muscle fibers (mainly resistive is capable of amplifying the force developed by the muscle. Conclusion The PNF was effective as training to gain muscle strength, should be better analyzed as a tool fitness, not to cause health risks, have low cost and easy application.

  11. Transcriptional response of the neuromuscular system to exercise training and potential implications for ALS.

    Science.gov (United States)

    Ferraiuolo, Laura; De Bono, Joseph P; Heath, Paul R; Holden, Hazel; Kasher, Paul; Channon, Keith M; Kirby, Janine; Shaw, Pamela J

    2009-06-01

    The transcriptional adaptive response of motoneurons and muscles to voluntary exercise has been investigated by using laser capture microdissection and microarray analysis. Our results show that motoneurons respond to physical activity by activating a complex transcriptional plan, with changes involved in neurotrophic factor signalling, electrophysiological changes and synaptic reorganization. Gastrocnemius muscle shows increases in transcripts responsible for neovascularization and new myogenesis. Both tissues show transcriptional changes involved in the growth and reinforcement of the neuromuscular junction. This study indicates that the neuromuscular system undergoes significant structural and functional alterations, aiming to optimize the transmission of both chemical and electrical stimuli, thus prompting axonal outgrowth and mechanisms similar to long-term potentiation in hippocampal neurons. Understanding the response of these cells during exercise has potentially important implications for human neuromuscular disease, including amyotrophic lateral sclerosis, by highlighting candidate genes pivotal for the balance between the physiology and the pathology of the neuromuscular system in terms of the stress response to physical exercise.

  12. Capitalizing on the autophagic response for treatment of liver disease caused by alpha-1-antitrypsin deficiency and other genetic diseases.

    Science.gov (United States)

    Chu, Andrew S; Perlmutter, David H; Wang, Yan

    2014-01-01

    Alpha-1-antitrypsin deficiency (ATD) is one of the most common genetic causes of liver disease and is a prototype of liver diseases caused by the pathologic accumulation of aggregated mutant alpha-1-antitrypsin Z (ATZ) within liver cells. In the case of ATD-associated liver disease, the resulting "gain-of-function" toxicity can lead to serious clinical manifestations, including cirrhosis and hepatocellular carcinoma. Currently, the only definitive therapy for ATD-associated liver disease is liver transplantation, but recent efforts have demonstrated the exciting potential for novel therapies that target disposal of the mutant protein aggregates by harnessing a cellular homeostasis mechanism called autophagy. In this review, we will summarize research advances on autophagy and genetic liver diseases. We will discuss autophagy enhancer strategies for liver disease due to ATD and another genetic liver disease, inherited hypofibrinogenemia, caused by the proteotoxic effects of a misfolded protein. On the basis of recent evidence that autophagy plays a role in cellular lipid degradation, we also speculate about autophagy enhancer strategies for treatment of hepatic lipid storage diseases such as cholesterol ester storage disease.

  13. Malnutrition as an underlying cause of childhood deaths associated with infectious diseases in developing countries

    National Research Council Canada - National Science Library

    Rice, A L; Sacco, L; Hyder, A; Black, R E

    2000-01-01

    ...) is associated with about 50% of all deaths among children. Although the association between malnutrition and all-cause mortality is well documented, the malnutrition-related risk of death associated with specific diseases is less well described...

  14. Enterovirus genotypes causing hand foot and mouth disease in Shanghai, China: a molecular epidemiological analysis

    National Research Council Canada - National Science Library

    Xu, Menghua; Su, Liyun; Cao, Lingfeng; Zhong, Huaqing; Dong, Niuniu; Xu, Jin

    2013-01-01

    A rapid expansion of hand, foot, and mouth disease (HFMD) outbreaks has occurred and caused deaths in China in recent years, but little is known about the other etiologic agents except enterovirus 71 (EV71...

  15. Sleep duration and ischemic heart disease and all-cause mortality

    DEFF Research Database (Denmark)

    Garde, Anne Helene; Hansen, Åse Marie; Holtermann, Andreas

    2013-01-01

    This prospective study aimed to examine if sleep duration is a risk indicator for ischemic heart disease (IHD) and all-cause mortality, and how perceived stress during work and leisure time and use of tranquilizers/hypnotics modifies the association.......This prospective study aimed to examine if sleep duration is a risk indicator for ischemic heart disease (IHD) and all-cause mortality, and how perceived stress during work and leisure time and use of tranquilizers/hypnotics modifies the association....

  16. Ileitis caused by Yersinia enterocolitica - X-ray differential diagnosis of Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Lingg, G.; Hering, L.; Tanneberger, D.

    1981-12-01

    The article gives a brief description of the characteristic features of the clinical and roentgenological course and the various stages of enteritis caused by Yersinia. Basing on three cases of ileitis caused by Yersinia, the far-reaching similarity with the early changes and even the advanced stages of Crohn's diseases are demonstrated. Attention is drawn to the possibilities of differentiating between the two disease patterns.

  17. Modelling the economic impact of three lameness causing diseases using herd and cow level evidence.

    Science.gov (United States)

    Ettema, Jehan; Østergaard, Søren; Kristensen, Anders Ringgaard

    2010-06-01

    Diseases to the cow's hoof, interdigital skin and legs are highly prevalent and of large economic impact in modern dairy farming. In order to support farmer's decisions on preventing and treating lameness and its underlying causes, decision support models can be used to predict the economic profitability of such actions. An existing approach of modelling lameness as one health disorder in a dynamic, stochastic and mechanistic simulation model has been improved in two ways. First of all, three underlying diseases causing lameness were modelled: digital dermatitis, interdigital hyperplasia and claw horn diseases. Secondly, the existing simulation model was set-up in way that it uses hyper-distributions describing diseases risk of the three lameness causing diseases. By combining information on herd level risk factors with prevalence of lameness or prevalence of underlying diseases among cows, marginal posterior probability distributions for disease prevalence in the specific herd are created in a Bayesian network. Random draws from these distributions are used by the simulation model to describe disease risk. Hereby field data on prevalence is used systematically and uncertainty around herd specific risk is represented. Besides the fact that estimated profitability of halving disease risk depended on the hyper-distributions used, the estimates differed for herds with different levels of diseases risk and reproductive efficiency. (c) 2010 Elsevier B.V. All rights reserved.

  18. On human disease-causing amino acid variants: statistical study of sequence and structural patterns

    Science.gov (United States)

    Alexov, Emil

    2015-01-01

    Statistical analysis was carried out on large set of naturally occurring human amino acid variations and it was demonstrated that there is a preference for some amino acid substitutions to be associated with diseases. At an amino acid sequence level, it was shown that the disease-causing variants frequently involve drastic changes of amino acid physico-chemical properties of proteins such as charge, hydrophobicity and geometry. Structural analysis of variants involved in diseases and being frequently observed in human population showed similar trends: disease-causing variants tend to cause more changes of hydrogen bond network and salt bridges as compared with harmless amino acid mutations. Analysis of thermodynamics data reported in literature, both experimental and computational, indicated that disease-causing variants tend to destabilize proteins and their interactions, which prompted us to investigate the effects of amino acid mutations on large databases of experimentally measured energy changes in unrelated proteins. Although the experimental datasets were linked neither to diseases nor exclusory to human proteins, the observed trends were the same: amino acid mutations tend to destabilize proteins and their interactions. Having in mind that structural and thermodynamics properties are interrelated, it is pointed out that any large change of any of them is anticipated to cause a disease. PMID:25689729

  19. Annual all-cause mortality rate for patients with diabetic kidney disease in Singapore

    Directory of Open Access Journals (Sweden)

    Yee Gary Ang

    2016-06-01

    Conclusion: Our study estimated the annual all-cause mortality rate for Singaporean patients with diabetic kidney disease by CKD stages and identified predictors of all-cause mortality. This study has affirmed the poor prognosis of these patients and an urgency to intervene early so as to retard the progression to later stages of CKD.

  20. Mortality in adult congenital heart disease : Are national registries reliable for cause of death?

    NARCIS (Netherlands)

    Zomer, A. Carla; Uiterwaal, Cuno S. P. M.; van der Velde, Enno T.; Tijssen, Jan G. P.; Mariman, Edwin C. M.; Verheugt, Carianne L.; Vaartjes, Ilonca; Pieper, Petronella G.; Meijboom, Folkert J.; Grobbee, Diederick E.; Mulder, Barbara J. M.

    2011-01-01

    Background: Statistics on cause-specific mortality are important for prognostic research. The aim of this study was to assess the utility of the national mortality registry in research on causes of death in adult patients with congenital heart disease (CHD). Methods: The CONCOR registry of over

  1. Phoma species on beet: more cause disease than just Phoma betae

    Science.gov (United States)

    Phoma can cause damage to sugar beet (Beta vulgaris) at multiple growth stages. It has historically been an important seedling disease, but this is largely managed by ensuring clean seed for planting. The pathogen also can cause a root rot, a leaf spot, and rotting of beets during storage. In the Un...

  2. First report of mango malformation disease caused by Fusarium pseudocircinatum in Mexico

    Science.gov (United States)

    Mango (Mangifera indica L.) malformation disease (MMD) is one of the most important diseases affecting this crop worldwide, causing severe economic loss due to reduction of yield. Subsequent to the first report in India in 1891 (3), MMD has spread worldwide to most mango-growing regions. Several spe...

  3. De Quervain disease caused by abductor pollicis longus tenosynovitis: a report of three cases.

    Science.gov (United States)

    Maruyama, Masahiro; Takahara, Masatoshi; Kikuchi, Noriaki; Ito, Kazuo; Watanabe, Tadayoshi; Ogino, Toshihiko

    2009-01-01

    De Quervain disease is caused by a stenosing tenosynovitis in the first dorsal compartment, and the main aetiology is extensor pollicis brevis (EPB) tenosynovitis. We encountered three cases in which EPB tenosynovitis was absent and abductor pollicis longus (APL) tenosynovitis was confirmed during operation. In the treatment of de Quervain disease, APL tenosynovitis should be paid as much attention as EPB tenosynovitis.

  4. Novel COL4A1 mutations cause cerebral small vessel disease by haploinsufficiency

    NARCIS (Netherlands)

    Lemmens, R.; Maugeri, A.; Niessen, H.W.M.; Goris, A.; Tousseyn, T.; Demaerel, P.; Corveleyn, A.; Robberecht, W.; van der Knaap, M.S.; Thijs, V.N.; Zwijnenburg, P.J.G.

    2013-01-01

    Mutations in COL4A1 have been identified in families with hereditary small vessel disease of the brain presumably due to a dominant-negative mechanism. Here, we report on two novel mutations in COL4A1 in two families with porencephaly, intracerebral hemorrhage and severe white matter disease caused

  5. Milk and dairy consumption and risk of cardiovascular diseases and all-cause mortality

    DEFF Research Database (Denmark)

    Guo, Jing; Astrup, Arne; Lovegrove, Julie A

    2017-01-01

    With a growing number of prospective cohort studies, an updated dose-response meta-analysis of milk and dairy products with all-cause mortality, coronary heart disease (CHD) or cardiovascular disease (CVD) have been conducted. PubMed, Embase and Scopus were searched for articles published up...

  6. Milk and dairy consumption and risk of cardiovascular diseases and all-cause mortality

    NARCIS (Netherlands)

    Guo, Jing; Astrup, Arne; Lovegrove, Julie A.; Gijsbers, Lieke; Givens, David I.; Soedamah-Muthu, Sabita S.

    2017-01-01

    With a growing number of prospective cohort studies, an updated dose–response meta-analysis of milk and dairy products with all-cause mortality, coronary heart disease (CHD) or cardiovascular disease (CVD) have been conducted. PubMed, Embase and Scopus were searched for articles published up to

  7. Helminths and helminthoses in Central Europe: diseases caused by nematodes (roundworms).

    Science.gov (United States)

    Auer, Herbert; Aspöck, Horst

    2014-10-01

    The third part of the overview "Helminths and helminthoses in Central Europe" deals with the medically relevant nematodes (roundworms) and nematode-caused diseases occurring in Central Europe. The paper comprises data on the biology of the parasites and their ways of transmission, describes the symptomatology of the diseases, summarizes the possibilities of diagnosis and refers to the prophylactic means.

  8. Elevated C-reactive protein, depression, somatic diseases, and all-cause mortality

    DEFF Research Database (Denmark)

    Wium-Andersen, Marie Kim; Orsted, David Dynnes; Nordestgaard, Børge Grønne

    2014-01-01

    for cancer, ischemic heart disease, chronic obstructive pulmonary disease, and all-cause mortality. METHODS: We performed prospective and instrumental variable analyses using plasma CRP levels and four CRP genotypes on 78,809 randomly selected 20- to 100-year-old men and women from the Danish general...

  9. A Rare Cause of Peripheral Facial Paralysis in Childhood in Our Country: Lyme Disease

    OpenAIRE

    Emine Özdemir; Dolunay Gürses

    2017-01-01

    Lyme disease is a zoonosis caused by Spirochetes called Borrelia burgdorferi, involving several areas, such as the skin, heart and central nervous system. In this case report, we present a 10-year-old male who had complaints of fever, extensive oral aphthae, perioral dried sores, rash, blurred vision and peripheral facial paralysis, and was diagnosed with Lyme disease. In this report, we want to emphasize that Lyme disease should be kept in mind for differential diagnosis in patients with fev...

  10. A rare cause of hematemesis in newborn: fibrocystic breast disease of mother.

    Science.gov (United States)

    Aksoy, Hatice Tatar; Eras, Zeynep; Erdeve, Omer; Dilmen, Ugur

    2013-08-01

    Hematemesis in a healthy newborn is most often caused by swallowed maternal blood. Maternal blood due to fibrocystic breast disease in human milk has not previously been reported in the literature. We report here a newborn case with hematemesis in which the mother had fibrocystic breast disease, and we want to emphasize this rare entity. Physicians should be aware of this rare condition, and fibrocystic breast disease of the mother should be included in the differential diagnosis of newborns with hematemesis.

  11. Immunoglobulin G4-related Kidney Disease as a Cause of Acute Renal Insufficiency.

    Science.gov (United States)

    Li, Cai; Du, Xiao-Gang

    2015-09-01

    Immunoglobulin G4 (IgG4)-related kidney disease is a systemic autoimmune disease which characterized by elevated serum IgG4 and dense infiltration of IgG4-positive plasma cells into tubular interstitium. It can be a mimicker of acute renal insufficiency. We herein report a rare case of IgG4-related kidney disease as a cause of acute renal insufficiency.

  12. Effect of newly proposed CK reference limits on neuromuscular diagnosis.

    Science.gov (United States)

    Nardin, Rachel A; Zarrin, Amy R; Horowitz, Gary L; Tarulli, Andrew W

    2009-04-01

    The objective was to determine the effect of a proposed increase in the upper reference limits of serum creatine kinase (CK) on neuromuscular disease diagnosis. This was a retrospective study of 94 Caucasian subjects (49 women and 45 men) in whom a neuromuscular physician ordered a CK as part of their evaluation. The patients were divided into two groups: those with diagnoses that either should or could elevate serum CK, and those with diagnoses that should not elevate serum CK. Sensitivities and specificities of the manufacturer's and the newly proposed upper reference limits were determined. For women, raising the upper reference limit of CK from 140 IU/L to 201 IU/L reduced the sensitivity of the test from 50% to 29%, while increasing the specificity from 67% to 80%. For men, raising the upper reference limit of CK from 174 IU/L to 322 IU/L reduced the sensitivity from 80% to 60%, while increasing the specificity from 63% to 80%. The newly proposed upper reference limits resulted in a false-negative CK of clinical significance in 7 of 94 subjects. Increasing the upper reference limit for CK reduced the sensitivity and increased the specificity of serum CK for neuromuscular disease diagnosis. Such a change will reduce unnecessary referrals and invasive diagnostic testing in patients with asymptomatic CK elevations. The clinical impact of the loss in sensitivity is small. If these new upper reference limits are adopted, neuromuscular physicians should be aware that a normal CK level does not exclude a diagnosis of myopathy.

  13. Ending versus controlling versus employing addiction in the tobacco-caused disease endgame: moral psychological perspectives.

    Science.gov (United States)

    Kozlowski, Lynn T

    2013-05-01

    Even though interest in reducing or eliminating tobacco-caused diseases is a common goal in tobacco control, many experts hold different views on addiction as a target of intervention. Some consider tobacco-caused addiction as a tobacco-caused disease to be eliminated alongside the other diseases. Some consider tobacco-caused addiction as a much lower priority disease to be eliminated, and a subset of this group is prepared to employ addiction to tobacco (nicotine) as a tool to reduce other tobacco-caused disease. These varying attitudes towards ending, controlling or employing tobacco addiction to reduce damage from tobacco use constitute quite different approaches to tobacco control and cause conflict among those in tobacco control. Moral psychological analyses argue that there is more than scientific evidence involved in supporting this continuum of approaches. Divergent values also influence positions in tobacco control. Attention to these values as well as the scientific evidence should be included in policy and practice in tobacco control. It is not that one constellation of values is necessarily superior, but debates need to be informed by and engage discussions of these values as well as the scientific evidence.

  14. Intensity versus duration of cycling, impact on all-cause and coronary heart disease mortality

    DEFF Research Database (Denmark)

    Schnohr, Peter; Marott, Jacob L; Jensen, Jan S

    2012-01-01

    the impact of intensity versus duration of cycling on all-cause and coronary heart disease mortality. Design: Relative intensity and duration of cycling were recorded in 5106 apparently healthy men and women aged 21-90 years drawn from the general population of Copenhagen, and followed for an average of 18...... years. Total number of deaths during follow-up was 1172, of these 146 were coronary heart disease deaths. For both sexes we found a significant inverse association between cycling intensity and risk of all-cause and coronary heart disease death, but only a weak association with cycling duration......: Our findings indicate that the relative intensity, and not the duration of cycling, is of more importance in relation to all-cause and coronary heart disease mortality. Thus our general recommendations to all adults would be that brisk cycling is preferable to slow....

  15. Multiple opportunistic pathogens can cause a bleaching disease in the red seaweed Delisea pulchra.

    Science.gov (United States)

    Kumar, Vipra; Zozaya-Valdes, Enrique; Kjelleberg, Staffan; Thomas, Torsten; Egan, Suhelen

    2016-11-01

    While macroalgae (or seaweeds) are increasingly recognized to suffer from disease, in most cases the causative agents are unknown. The model macroalga Delisea pulchra is susceptible to a bleaching disease and previous work has identified two epiphytic bacteria, belonging to the Roseobacter clade, that cause bleaching under laboratory conditions. However, recent environmental surveys have shown that these in vitro pathogens are not abundant in naturally bleached D. pulchra, suggesting the presence of other pathogens capable of causing this algal disease. To test this hypothesis, we cultured bacteria that were abundant on bleached tissue across multiple disease events and assessed their ability to cause bleaching disease. We identified the new pathogens Alteromonas sp. BL110, Aquimarina sp. AD1 and BL5 and Agarivorans sp BL7 that are phylogenetically diverse, distinct from the previous two pathogens and can also be found in low abundance in healthy individuals. Moreover, we found that bacterial communities of diseased individuals that were infected with these pathogens were less diverse and more divergent from each other than those of healthy algae. This study demonstrates that multiple and opportunistic pathogens can cause the same disease outcome for D. pulchra and we postulate that such pathogens are more common in marine systems than previously anticipated. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  16. Wilson′s disease - A rare cause of renal tubular acidosis with metabolic bone disease

    Directory of Open Access Journals (Sweden)

    D. K. S. Subrahmanyam

    2014-01-01

    Full Text Available We report a 16-year-old boy who presented with weakness of lower limbs. He was diagnosed to have Wilson′s disease, renal tubular acidosis and osteoporosis. Screening of siblings showed that his younger sister was also affected by the disease.

  17. Is there a consistent association between coronary heart disease and ischemic stroke caused by intracranial atherosclerosis?

    Science.gov (United States)

    Conforto, Adriana B; Leite, Claudia da Costa; Nomura, Cesar H; Bor-Seng-Shu, Edson; Santos, Raul D

    2013-05-01

    Coronary heart disease and ischemic stroke are frequent coexistent conditions that share risk factors and pose major burdens to global health. Even though a clear relation has been established between extracranial internal carotid artery atherosclerosis and symptomatic or asymptomatic coronary heart disease, there is a gap in knowledge about the association between intracranial atherosclerosis and coronary heart disease. Intracranial atherosclerosis is associated with high risks of stroke recurrence and vascular death. More research and clinical trials are needed to answer whether early diagnosis of asymptomatic coronary heart disease and aggressive treatment can decrease the risk of vascular death in patients with ischemic stroke caused by intracranial atherosclerosis.

  18. Is there a consistent association between coronary heart disease and ischemic stroke caused by intracranial atherosclerosis?

    Directory of Open Access Journals (Sweden)

    Adriana B. Conforto

    2013-05-01

    Full Text Available Coronary heart disease and ischemic stroke are frequent coexistent conditions that share risk factors and pose major burdens to global health. Even though a clear relation has been established between extracranial internal carotid artery atherosclerosis and symptomatic or asymptomatic coronary heart disease, there is a gap in knowledge about the association between intracranial atherosclerosis and coronary heart disease. Intracranial atherosclerosis is associated with high risks of stroke recurrence and vascular death. More research and clinical trials are needed to answer whether early diagnosis of asymptomatic coronary heart disease and aggressive treatment can decrease the risk of vascular death in patients with ischemic stroke caused by intracranial atherosclerosis.

  19. [Disease burden caused by violence in the Chinese population, in 1990 and 2013].

    Science.gov (United States)

    Yang, L; Gao, X; Jin, Y; Ye, P P; Er, Y L; Deng, X; Wang, Y; Duan, L L

    2017-10-10

    Objective: To analyze the disease burden of violence in the Chinese population, in 1990 and 2013. Methods: Indicators including mortality rate, years of life lost due to premature mortality (YLL), years lived with disability (YLD), and disability-adjusted of life years (DALY) related to violence, were extracted from the Global Burden of Disease 2013 and used to describe the burden of disease caused by violence in the Chinese population. Data related to corresponding parameters on disease burden of violence in 1990 and 2013 were described. Results: In 2013, a total of 20 500 people died of violent events, with the death rate as 1.44 per 100 000, in China. DALY caused by violence was 1.08 million person years in 2013. DALY caused by sharp violence was 0.47 million person years, with 0.09 million person years lost due to firearm violence. Disease burden caused by violence appeared higher in males than in females. When comparing with data from the 1990s, reductions were seen by 67.35 % on the standardized death rate of violence, by 68.07 % on the DALY attributable to violence, and by 70.47 % on the standardized DALY rate attributable to violence, respectively, in 2013. Disease burden of violence among young adults and elderly was among the highest. When comparing with data from the 1990, DALY in 2013 decreased among all the age groups except for the 70-year-old showed an increase of 9.36 % . The standardized DALY rate in 2013 showed a declining trend in all the age groups, mostly in the 0-4-year-old group. The standardized DALY rates caused by sharp violence or firearm decreased by75.11 % and 83.20 % in the 0-4-year-old group. Conclusion: In recent years, the disease burden caused by violence showed a decreasing trend but appeared higher in males however with the increase of DALY in the elder population.

  20. Prevalence of G class antibodies to antigens of lyme disease causes in dogs in Vojvodina, Serbia

    Directory of Open Access Journals (Sweden)

    Potkonjak Aleksandar

    2013-01-01

    Full Text Available Lyme disease is a multisystemic disease, zoonotic in nature, caused by the Borrelia burgdorferi sensu lato complex. In the continent of Europe, these spirochetes are predominantly transmitted by ticks of the genus Ixodes. Small mammals and birds have particular significance as reservoirs of the cause of lyme disease. The objective of these epidemiological investigations was to determine the value of IgG seroprevalence to Borrelia burgdorferi and to secure the geographic distribution of seropositive dogs in Vojvodina. The investigations covered 135 dogs that were not vaccinated against lyme disease. The indirect ELISA test was used to determine IgG prevalence to Borrelia burgdorferi antigens. Reactive blood serums of dogs were tested again using the rapid immunochromatographic and immunoblot test. A seroprevalence of G class antibodies to antigens of lyme disease causes of 8.1% (11/135 was established in the examined dog population of Vojvodina. The biggest number of positive results was recorded for the South Bačka District. The presented value for the seroprevalence of anti-Borrelia burgdorferi antibodies in the dog population indicates the exhistence of a significant risk of humans becoming infected with the cause of lyme disease in Vojvodina.

  1. Disease-Causing Variants in the ATL1 Gene Are a Rare Cause of Hereditary Spastic Paraplegia among Czech Patients.

    Science.gov (United States)

    Mészárosová, Anna Uhrová; Grečmalová, Dagmar; Brázdilová, Michaela; Dvořáčková, Nina; Kalina, Zdeněk; Čermáková, Marie; Vávrová, Dagmar; Smetanová, Irena; Staněk, David; Seeman, Pavel

    2017-11-01

    Variants in the ATL1 gene have been repeatedly described as the second most frequent cause of hereditary spastic paraplegia (HSP), a motor neuron disease manifested by progressive lower limb spasticity and weakness. Variants in ATL1 have been described mainly in patients with early onset HSP. We performed Sanger sequencing of all coding exons and adjacent intron regions of the ALT1 gene in 111 Czech patients with pure form of HSP and additional Multiplex-Ligation Probe Analysis (MLPA) testing targeting the ATL1 gene in 56 of them. All patients except seven were previously tested by Sanger sequencing of the SPAST gene with negative results. ATL1 diagnostic testing revealed only five missense variants in the ATL1 gene. Four of them are novel, but we suppose only two of them to be pathogenic and causal. The remaining variants are assumed to be benign. MLPA testing in 56 of sequence variant negative patients revealed no gross deletion in the ATL1 gene. Variants in the ATL1 gene are more frequent in patients with early onset HSP, but in general the occurrence of pathogenic variants in the ATL1 gene is low in our cohort, less than 4.5% and less than 11.1% in patients with onset before the age of ten. Variants in the ATL1 gene are a less frequent cause of HSP among Czech patients than has been previously reported among other populations. © 2017 John Wiley & Sons Ltd/University College London.

  2. Fatty replacement of lower paraspinal muscles: normal and neuromuscular disorders

    Energy Technology Data Exchange (ETDEWEB)

    Hader, H.; Gadoth, N.; Heifetz, H.

    1983-11-01

    The physiologic replacement of the lower paraspinal muscles by fat was evaluated in 157 patients undergoing computed tomography for reasons unrelated to abnormalities of the locomotor system. Five patients with neuromuscular disorders were similarly evaluated. The changes were graded according to severity at three spinal levels: lower thoracic-upper lumbar, midlumbar, and lumbosacral. The results were analyzed in relation to age and gender. It was found that fatty replacement of paraspinal muscles is a normal age-progressive phenomenon most prominent in females. It progresses down the spine, being most advanced in the lumbosacral region. The severest changes in the five patients with neuromuscular disorders (three with poliomyelitis and two with progressive muscular dystrophy) consisted of complete muscle group replacement by fat. In postpoliomyelitis atrophy, the distribution was typically asymmetric and sometimes lacked clinical correlation. In muscular dystrophy, fatty replacement was symmetric, showing relative sparing of the psoas and multifidus muscles. In patients with neuromuscular diseases, computed tomography of muscles may be helpful in planning a better rehabilitation regimen.

  3. Atypical Hand, Foot, and Mouth Disease Caused by Coxsackievirus A6 in Denmark

    DEFF Research Database (Denmark)

    Horsten, Hans-Henrik; Kemp, Michael; Fischer, Thea K

    2017-01-01

    Since 2008, outbreaks of atypical hand, foot, and mouth disease (HFMD) in children and adults have been reported worldwide. The majority of these outbreaks are caused by a new lineage of Coxsackie virus A6 (CV-A6) presenting a more severe clinical phenotype than the classical childhood HFMD caused...... by CV-A16. Between June 2014 and January 2016, 23 cases of atypical HFMD disease presented at a Dermatology Department at a regional University Hospital in Denmark. Patients were referred by general practitioners and dermatologists with a variety of clinical diagnoses, including eczema herpeticum...... caused by CV-A6 in the Region of Southern Denmark and that atypical HFMD can be difficult to diagnose clinically as it may mimic other severe skin diseases....

  4. [Multifocal osteoarticular infection caused by Salmonella non typhi in a child with sickle cell disease].

    Science.gov (United States)

    Cabaret, B; Couëc, M-L; Lorrot, M; Launay, E; Gras-Le Guen, C

    2013-04-01

    Sickle cell disease is the most common monogenic hereditary hemoglobinopathy. Its course is marked by vaso-occlusive crises (VOC), episodes of acute hemolytic anemia on a background of chronic hemolytic anemia, and severe infections. A 2-year-old child with sickle cell disease presented with severe sepsis caused by Salmonella non typhi. Control of the sepsis was difficult, with multifocal osteomyelitis and arthritis, which required prolonged intravenous antibiotic therapy. Prolonged treatment was complicated by cardiorespiratory arrest and severe neurological damage, as well as nosocomial infections. Osseous articular infections caused by Salmonella non typhi are a common complication in children with sickle cell disease, which need to be promptly recognized. Management remains a great concern. The clinical case reported herein is original in its multifocal evolution. It illustrates the vulnerability of patients with sickle cell disease and the need for urgent and intensive care in the case of infection. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. Loss of stability and hydrophobicity of presenilin 1 mutations causing Alzheimer's Disease

    DEFF Research Database (Denmark)

    Somavarapu, Arun Kumar; Kepp, Kasper Planeta

    2016-01-01

    Nearly 200 mutations in the gene coding for presenilin 1 (PSEN1) cause early-onset Alzheimer's Disease, yet the molecular mechanism remains obscure. As a meta-analysis, we compiled available clinical and biochemical data for PSEN1 variants and correlated these to chemical properties of the mutants...... protein stability. This explains why the many mutations that spread out across the protein and far from the catalytic aspartates can cause disease. The identified molecular determinants of clinical age of symptom onset may be relevant to future presenilin-modulating therapies specifically directed towards...

  6. Echinococcal disease of the bone: An unusual cause of a pathological fracture

    Directory of Open Access Journals (Sweden)

    Matthew Goodier

    2010-12-01

    Full Text Available Echinococcosis is caused by the larva of the tapeworm, Echinococcus granulosus or Echinococcus multiloccularis and is endemic in many rural areas of Southern Africa. Echinococcosis of the bone is an unusual manifestation of echinococcal disease and a rare cause of a lytic lesion of bone. This report describes a 30-yr old female who presented with an Echinococcal cyst of the right radius complicated by a pathological fracture.

  7. The use of organic certified compost to control soilborne diseases caused by Phytophthora spp.

    OpenAIRE

    Pugliese, Massimo; Gullino, M. Lodovica; Garibaldi, Angelo

    2008-01-01

    Soilborne pathogens can cause serious damages to economically important crops. Control of these diseases has traditionally depended upon rotations and soil quality improvement strategies. Compost has shown a suppressive activity against soilborne pathogens, and its use may decrease the severity of root rot diseases, optimize waste recycling and increase yields in organic farming. An organic certified compost produced from biowaste, green and yard wastes in a composting plant in the North-West...

  8. Novel COL4A1 mutations cause cerebral small vessel disease by haploinsufficiency

    OpenAIRE

    Lemmens, Robin; Maugeri, Alessandra; Niessen, Hans W. M.; Goris, An; Tousseyn, Thomas; Demaerel, Philippe; Corveleyn, Anniek; Robberecht, Wim; van der Knaap, Marjo S.; Thijs, Vincent N.; Zwijnenburg, Petra J.G.

    2012-01-01

    Mutations in COL4A1 have been identified in families with hereditary small vessel disease of the brain presumably due to a dominant-negative mechanism. Here, we report on two novel mutations in COL4A1 in two families with porencephaly, intracerebral hemorrhage and severe white matter disease caused by haploinsufficiency. Two families with various clinical presentations of cerebral microangiopathy and autosomal dominant inheritance were examined. Clinical, neuroradiological and genetic investi...

  9. A rare bacteremia caused by Cedecea davisae in patient with chronic renal disease

    OpenAIRE

    Peretz, Avi; Simsolo, Claudia; Farber, Evgeny; Roth, Anna; Brodsky, Diana; Nakhoul, Farid

    2013-01-01

    Patient: Female, 77 Final Diagnosis: Bacteremia Symptoms: Chills ? diarrhea ? fever ? nausea Medication: ? Clinical Procedure: X-Ray ? CBC ? urine and blood cultur Specialty: Infectious diseases Objective: Rare disease Background: Cedecea davisae is a gram negative, oxidase negative bacilli that include 5 species. In the medical literature there are very few reports that describe infections caused by different species of the Cedecea genus. Case Report: In this paper we report a fourth case of...

  10. Entomological and ecological index for risk of infection causing lyme disease in territory of Vojvodina, Serbia

    Directory of Open Access Journals (Sweden)

    Potkonjak Aleksandar

    2013-01-01

    Full Text Available In Europe, of all the vector transmitted diseases, the occurrence of lyme disease is the one most often registered, and the most significant vector Borrelia burgdorferi is the tick Ixodes ricinus. Both humans and animals contract lyme disease. The risk of the occurrence of lyme disease is in correlation with potential exposure to tick bites and depends on the density of the tick population in the endemic area, the percentage of ticks infected with the cause of lyme disease, the duration and the nature of the activity of the susceptible population in a certain area. The objective of these investigations was to determine the entomological and the ecological risk index, as well as to assess the risk of transmission of the cause of lyme disease in the territory of Vojvodina Province in the Republic of Serbia. Ticks were collected at 12 locations in the South Bačka District of Vojvodina. A total of 1400 ticks were identified up to the level of species. After establishing the infection of ticks with the cause of lyme disease, the entomological and the ecological index was determined for the given regions using microscopic examination in a dark field. Two species of ticks aere identified in this geographic region (Ixodes ricinus and Dermacentor marginatus. Examining I. ricinus, the prevalence of infection B. burgdorferi was established, ranging up to 33.1%. The ecological risk index indicates that there is a potential risk of humans and animals becoming infected at 8 localities. It was determined for 3 localities that there is a definite actual risk of the transferrence of causes of lyme disease.

  11. Eccentric Exercise to Enhance Neuromuscular Control.

    Science.gov (United States)

    Lepley, Lindsey K; Lepley, Adam S; Onate, James A; Grooms, Dustin R

    Neuromuscular alterations are a major causal factor of primary and secondary injuries. Though injury prevention programs have experienced some success, rates of injuries have not declined, and after injury, individuals often return to activity with functionality below clinical recommendations. Considering alternative therapies to the conventional concentric exercise approach, such as one that can target neuromuscular injury risk and postinjury alterations, may provide for more effective injury prevention and rehabilitation protocols. Peer-reviewed sources available on the Web of Science and MEDLINE databases from 2000 through 2016 were gathered using searches associated with the keywords eccentric exercise, injury prevention, and neuromuscular control. Eccentric exercise will reduce injury risk by targeting specific neural and morphologic alterations that precipitate neuromuscular dysfunction. Clinical review. Level 4. Neuromuscular control is influenced by alterations in muscle morphology and neural activity. Eccentric exercise beneficially modifies several underlying factors of muscle morphology (fiber typing, cross-sectional area, working range, and pennation angle), and emerging evidence indicates that eccentric exercise is also beneficial to peripheral and central neural activity (alpha motorneuron recruitment/firing, sarcolemma activity, corticospinal excitability, and brain activation). There is mounting evidence that eccentric exercise is not only a therapeutic intervention influencing muscle morphology but also targets unique alterations in neuromuscular control, influencing injury risk.

  12. Neuromuscular paralysis for newborn infants receiving mechanical ventilation.

    Science.gov (United States)

    Cools, F; Offringa, M

    2005-04-18

    mortality, air leak or chronic lung disease, but there was a significant reduction in intraventricular hemorrhage and a trend towards less severe intraventricular hemorrhages. In the subgroup analysis of trials studying a selected population of ventilated infants with evidence of asynchronous respiratory efforts, a significant reduction in intraventricular hemorrhage (any grade and severe IVH) was found, and a trend towards less air leak. In the subgroup analysis of trials studying an unselected population of ventilated infants, no significant differences were found for any of the outcomes. For ventilated preterm infants with evidence of asynchronous respiratory efforts, neuromuscular paralysis with pancuronium seems to have a favourable effect on intraventricular hemorrhage and possibly on air leak. Uncertainty remains, however, regarding the long term pulmonary and neurologic effects, and regarding the safety of prolonged use of pancuronium in ventilated newborn infants. There is no evidence from randomized trials on the effects of neuromuscular blocking agents other than pancuronium. The routine use of pancuronium or any other neuromuscular blocking agent in ventilated newborn infants cannot be recommended based on current evidence.

  13. Direct morphological identification of Borrelia burgdorferi in the muscle biopsies: the possibility of association of the neuromuscular abnormalities with Borreliosis

    Directory of Open Access Journals (Sweden)

    A. V. Sakharova

    2013-01-01

    Full Text Available The authors examined 40 muscle biopsy specimens taken from patients with neuromuscular symptoms when the diagnosis was unestablished or presumptive. Eighteen of them exhibited foci of muscle fiber damage with the presence of spirochete-like structures in the semithin tissue sections. Electron microscopy of these areas detected Borrelia as vegetative and diverse L-forms. Immunocytochemical techniques usingantibodies to Borrelia burgdorferi antigens confirmed that the spirochetes belonged to this species. This allows one to consider borreliosis as an etiological or complicating factor of neuromuscular pathology and to recommend the above morphological methods for the diagnosis of neuromuscular diseases of unknown origin.

  14. A Rare Cause of Peripheral Facial Paralysis in Childhood in Our Country: Lyme Disease

    Directory of Open Access Journals (Sweden)

    Emine Özdemir

    2017-09-01

    Full Text Available Lyme disease is a zoonosis caused by Spirochetes called Borrelia burgdorferi, involving several areas, such as the skin, heart and central nervous system. In this case report, we present a 10-year-old male who had complaints of fever, extensive oral aphthae, perioral dried sores, rash, blurred vision and peripheral facial paralysis, and was diagnosed with Lyme disease. In this report, we want to emphasize that Lyme disease should be kept in mind for differential diagnosis in patients with fever and peripheral facial paralysis.

  15. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome.

    Science.gov (United States)

    Wiseman, Frances K; Al-Janabi, Tamara; Hardy, John; Karmiloff-Smith, Annette; Nizetic, Dean; Tybulewicz, Victor L J; Fisher, Elizabeth M C; Strydom, André

    2015-09-01

    Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP)--an Alzheimer disease risk factor--although the possession of extra copies of other chromosome 21 genes may also play a part. Further study of the mechanisms underlying the development of Alzheimer disease in people with Down syndrome could provide insights into the mechanisms that cause dementia in the general population.

  16. Terson syndrome caused by ventricular hemorrhage associated with moyamoya disease--case report.

    Science.gov (United States)

    Arakawa, Y; Goto, Y; Ishii, A; Ueno, Y; Kikuta, K; Yoshizumi, H; Katsuta, H; Kenmochi, S; Yamagata, S

    2000-09-01

    A 24-year-old female presented with Terson syndrome secondary to bilateral ventricular hemorrhage as a complication of moyamoya disease. Ophthalmoscopy and magnetic resonance imaging clearly demonstrated vitreous hemorrhage in the left eye globe. Various visual symptoms are associated with moyamoya disease, almost all of which result from ischemic lesions in the visual cortex and optic pathways. In this case, the visual disturbance was caused by Terson syndrome secondary to ventricular hemorrhage. Close ophthalmological and radiological evaluation is mandatory even in patients with moyamoya disease and hemorrhagic manifestation located in the intracerebral, subarachnoid, or intraventricular space.

  17. A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

    Science.gov (United States)

    Wiseman, Frances K.; Al-Janabi, Tamara; Hardy, John; Karmiloff-Smith, Annette; Nizetic, Dean; Tybulewicz, Victor L. J.; Fisher, Elizabeth M. C.; Strydom, André

    2015-01-01

    Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP) — an Alzheimer disease risk factor — although the possession of extra copies of other chromosome 21 genes may also play a part. Further study of the mechanisms underlying the development of Alzheimer disease in people with Down syndrome could provide insights into the mechanisms that cause dementia in the general population. PMID:26243569

  18. Femur Pathological Fracture Caused by Metastatic Bone Disease Derived from Foot Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ferdiansyah .

    2017-07-01

    Full Text Available Background : Bone is an organ and the most common site that prone to metastatic cancer and cause serious morbidity. Besides, metastatic cancer to bone will limit skeletal function so that decrease quality of life and even death that most of them caused by its complication. Objective : Reporting a rare case about Squamous Cell Carcinoma that cause femur pathological fracture caused by Metastatic Bone Disease. Material and Method : Case report in women patients 55 years old with femur close fracture one-third middle caused by Metastatic Bone Disease in RSUD Soetomo Surabaya, period May 2015-March 2016.Data is taken retrospectively from medical record through interview, physical examination, radiological examination, and laboratory. Result and Discussion : Patients are treated in hospital because of femur close fracture one-third middle caused by Metastatic Bone Disease.  Based on physical and radiological examination, it is decided being done by skin traction first. The next plan is surgery. Patients are treated with interlocking nail left femur. Evaluation after surgery is done with medical rehabilitation, that is ROM exercise. Until now, 9 months after surgery, patients still control routinely to be done chemotherapy and there is improvement in patient’s condition. Conclusion : Metastatic process in bone often cause pathological fracture. Bone Metastatic is common from Breast, Lung, Prostate and Kideney Cancer. There was no publication before about Bone Metastatic Disease come from Squamous Cell Cancer. Mirel’s score is used as guiding in fixation prior to the next treatment. Decision of surgery is considered through patient’s objective and subjective appraisal that can be calculated in Abdurrahman score system.

  19. Complete staghorn calculus in polycystic kidney disease: infection is still the cause.

    Science.gov (United States)

    Mao, Zhiguo; Xu, Jing; Ye, Chaoyang; Chen, Dongping; Mei, Changlin

    2013-08-01

    Kidney stones in patients with autosomal dominant polycystic kidney disease are common, regarded as the consequence of the combination of anatomic abnormality and metabolic risk factors. However, complete staghorn calculus is rare in polycystic kidney disease and predicts a gloomy prognosis of kidney. For general population, recent data showed metabolic factors were the dominant causes for staghorn calculus, but for polycystic kidney disease patients, the cause for staghorn calculus remained elusive. We report a case of complete staghorm calculus in a polycystic kidney disease patient induced by repeatedly urinary tract infections. This 37-year-old autosomal dominant polycystic kidney disease female with positive family history was admitted in this hospital for repeatedly upper urinary tract infection for 3 years. CT scan revealed the existence of a complete staghorn calculus in her right kidney, while there was no kidney stone 3 years before, and the urinary stone component analysis showed the composition of calculus was magnesium ammonium phosphate. UTI is an important complication for polycystic kidney disease and will facilitate the formation of staghorn calculi. As staghorn calculi are associated with kidney fibrosis and high long-term renal deterioration rate, prompt control of urinary tract infection in polycystic kidney disease patient will be beneficial in preventing staghorn calculus formation.

  20. [Coeliac disease as a possible cause of some gynecological and obstetric abnormalities].

    Science.gov (United States)

    Fiolková, K; Biringer, K; Hrtánková, M; Fiolka, R; Danko, J

    To bring a review of available literature sources on the prevalence of coeliac disease and its possible impact on gynecological and obstetric disorders. Review article. Gynecology and Obstetrics Clinic, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia. Analysis of literary sources. Coeliac disease is an autoimmune enteropathy caused by abnormal immune system response to gluten. Over the last decade when the prevalence of the disease increases rapidly confirming the relationship between coeliac disease and a range of reproductive disorders. Problems in this area are mostly confirmed in untreated women. Among the atypical symptoms of coeliac disease also include infertility such as delayed onset of menstruation, early menopause, secondary amenorrhea, infertility and pregnancy complications, such as recurrent abortions, intrauterine fetal growth restriction, small fetus for gestational age, low birth weight and premature birth.

  1. Identification of two novel mutations in the ATP7B gene that cause Wilson's disease

    Institute of Scientific and Technical Information of China (English)

    Hong-Wen Zhu; Yu-Min Li; Zhong-Bin Tao; Gang Su; Qiao-Ying Jin; Liang-Tao Zhao; Jia-Rui Zhu; Jun Yan; Tian-Yu Yu; Jie-Xian Ding

    2017-01-01

    Background:Wilson's disease is an autosomal recessive disorder characterized by liver disease and/or neurologic deficits due to copper accumulation and is caused by pathogenic mutations in the ATP7B gene.Methods:Two unrelated Chinese patients born to nonconsanguineous parents who were diagnosed with earlyonset Wiison's disease.DNA sequencing and bioinformation analysis were conducted.Results:We have identified four mutations in two family trios,of which two were novel,namely,c.3028A>G(p.K1010E) and c3992T>G (p.Y1331X),in each patient.Conclusions:Gene testing is playing an important role in diagnosis of Wilson's disease.The early-onset of Wilson's disease is apparently not associated with P-ATPase domain in the ATP7B protein.Our findings further widen the spectrum of mutations involving the ATP7B gene.

  2. Features of 5'-splice-site efficiency derived from disease-causing mutations and comparative genomics

    DEFF Research Database (Denmark)

    Roca, Xavier; Olson, Andrew J; Rao, Atmakuri R

    2007-01-01

    Many human diseases, including Fanconi anemia, hemophilia B, neurofibromatosis, and phenylketonuria, can be caused by 5'-splice-site (5'ss) mutations that are not predicted to disrupt splicing, according to position weight matrices. By using comparative genomics, we identify pairwise dependencies...

  3. The haematocrit – an important factor causing impaired haemostasis in patients with cyanotic congenital heart disease

    DEFF Research Database (Denmark)

    Jensen, A S; Johansson, P I; Idorn, L

    2013-01-01

    BACKGROUND: Patients with cyanotic congenital heart disease(CCHD) have haemostatic abnormalities, which result in an increased risk of bleeding. The cause is unknown, but recent studies have indicated that an elevated haematocrit, which is present in cyanotic patients, could be an important factor...

  4. Erdheim-Chester disease: a rare cause of recurrent fever of unknown origin mimicking lymphoma.

    Science.gov (United States)

    Mariampillai, Anusiyanthan; Sivapiragasam, Abirami; Kumar, Amit; Hindenburg, Alexander; Cunha, Burke A; Zhou, Jianhong

    2014-01-01

    We report the case of a patient with recurrent fever of unknown origin (FUO) with prominent back pain, hepatosplenomegaly, and abdominal/pelvic adenopathy suggesting lymphoma. A bone biopsy showed histiocytic infiltration. Studies for lymphoma were negative, but immunohistochemical stains were diagnostic of Erdheim-Chester disease (ECD). ECD should be included as a rare cause of recurrent FUO with bone involvement.

  5. Tobacco blue mould disease caused by Peronospora hyoscyami f. sp. tabacina

    NARCIS (Netherlands)

    Borrás-Hidalgo, O.; Thomma, B.P.H.J.; Silva, Y.; Chacón, O.; Pujol, M.

    2010-01-01

    Blue mould [Peronospora hyoscyami f. sp. tabacina (Adam) Skalicky 1964] is one of the most important foliar diseases of tobacco that causes significant losses in the Americas, south-eastern Europe and the Middle East. This review summarizes the current knowledge of the mechanisms employed by this

  6. Loss of stability and hydrophobicity of presenilin 1 mutations causing Alzheimer's Disease

    DEFF Research Database (Denmark)

    Somavarapu, Arun Kumar; Kepp, Kasper Planeta

    2016-01-01

    Nearly 200 mutations in the gene coding for presenilin 1 (PSEN1) cause early-onset Alzheimer's Disease, yet the molecular mechanism remains obscure. As a meta-analysis, we compiled available clinical and biochemical data for PSEN1 variants and correlated these to chemical properties of the mutant...

  7. Genome datasets for Calonectria henricotiae and C. pseudonaviculata causing boxwood blight disease and related species

    Science.gov (United States)

    Boxwood blight disease, caused by the fungi Calonectria henricotiae and C. pseudonaviculata, is an emergent threat to natural and managed landscapes worldwide. Boxwood blight emerged for the first time in the U.K. during the 1990s, then spread rapidly throughout Europe. By 2011, the fungus that cau...

  8. Neuromuscular function in healthy occlusion.

    Science.gov (United States)

    Forrester, S E; Allen, S J; Presswood, R G; Toy, A C; Pain, M T G

    2010-09-01

    This study aimed to measure neuromuscular function for the masticatory muscles under a range of occlusal conditions in healthy, dentate adults. Forty-one subjects conducted maximum voluntary clenches under nine different occlusal loading conditions encompassing bilateral posterior teeth contacts with the mandible in different positions, anterior teeth contacts and unilateral posterior teeth contacts. Surface electromyography was recorded bilaterally from the anterior temporalis, superficial masseter, sternocleidomastoid, anterior digastric and trapezius muscles. Clench condition had a significant effect on muscle function (P = 0.0000) with the maximum function obtained for occlusions with bilateral posterior contacts and the mandible in a stable centric position. The remaining contact points and moving the mandible to a protruded position, whilst keeping posterior contacts, resulted in significantly lower muscle activities. Clench condition also had a significant effect on the per cent overlap, anterior-posterior and torque coefficients (P = 0.0000-0.0024), which describe the degree of symmetry in these muscle activities. Bilateral posterior contact conditions had significantly greater symmetry in muscle activities than anterior contact conditions. Activity in the sternocleidomastoid, anterior digastric and trapezius was consistently low for all clench conditions, i.e. centric position, whilst with anterior teeth contacts, both the muscle activity and the degree of symmetry in muscle activity are significantly reduced.

  9. The suggestion of common cause of disease, characteristics of human body, and medical treatment

    Directory of Open Access Journals (Sweden)

    Byung-Jun Cho

    2011-06-01

    Full Text Available Objectives & Methods: This suggestion was attempted to be elevated the recognition of common characteristics in disease. So, we performed to analyze the correlation of common cause of disease, characteristics of human body, and medical treatment. And the results are as follows. Results: 1. The cause of disease is consist of genetic factor, aging, habit, food of not good in health, weather, environment, deficit of the physical activity, stress and so on. 2. Generally, human has common and individual weakness. Individual weakness is appeared similar to the occurrence of volcano and lapse. 3. The correlation of disease and medical treatments is possible to explain using the quotation of the law of motion made by Isaac Newton, the great physicist. 4. When the process of the medical treatment was not progressed, the prognosis is determined by the correlation of the homeostasis(H' in human body and the homeostasis(H of disease. 5. The prognosis of disease is determined by the relationship between the energy of disease(F and medical treatment(F'. 6. The exact diagnosis is possible to predict the treatment sequence, and the facts that homeostasis in human body and disease, relationship between the energy of disease(F and medical treatment(F', action and reaction are important to determine the prognosis. 7. The careful observation of improving response and worsening action of disease becomes available for exact prognosis. Conclusion: The above described contents may be useful in clinical studies, and the concrete clinical reports about this will be made afterward.

  10. Causes of Death Data in the Global Burden of Disease Estimates for Ischemic and Hemorrhagic Stroke

    DEFF Research Database (Denmark)

    Truelsen, Thomas; Krarup, Lars-Henrik; Iversen, Helle K

    2015-01-01

    on the International Classification of Diseases and the pathology behind each code by checking multiple causes of death and literature review. RESULTS: Unspecified stroke and primary and secondary hypertension are leading contributing 'GCs' to stroke mortality estimates for hemorrhagic stroke (HS) and ischemic stroke...... mortality estimates. METHODS: All available mortality data were compiled and non-specific cause codes were redistributed based on literature review and statistical methods. Ill-defined codes were redistributed to their specific cause of disease by age, sex, country and year. The reassignment was done based......' with marked regional differences. Future advancements in stroke certification, data collections and statistical analyses may improve the estimation of the global stroke burden....

  11. Chewing betel quid and the risk of metabolic disease, cardiovascular disease, and all-cause mortality: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Tomohide Yamada

    Full Text Available BACKGROUND: Betel nut (Areca nut is the fruit of the Areca catechu tree. Approximately 700 million individuals regularly chew betel nut (or betel quid worldwide and it is a known risk factor for oral cancer and esophageal cancer. We performed a meta-analysis to assess the influence of chewing betel quid on metabolic diseases, cardiovascular disease, and all-cause mortality. METHODOLOGY/PRINCIPAL FINDINGS: We searched Medline, Cochrane Library, Web of Science, and Science Direct for pertinent articles (including the references published between 1951 and 2013. The adjusted relative risk (RR and 95% confidence interval were calculated using the random effect model. Sex was used as an independent category for comparison. RESULTS: Of 580 potentially relevant studies, 17 studies from Asia (5 cohort studies and 12 case-control studies covering 388,134 subjects (range: 94 to 97,244 were selected. Seven studies (N = 121,585 showed significant dose-response relationships between betel quid consumption and the risk of events. According to pooled analysis, the adjusted RR of betel quid chewers vs. non-chewers was 1.47 (P<0.001 for obesity (N = 30,623, 1.51 (P = 0.01 for metabolic syndrome (N = 23,291, 1.47 (P<0.001 for diabetes (N = 51,412, 1.45 (P = 0.06 for hypertension (N = 89,051, 1.2 (P = 0.02 for cardiovascular disease (N = 201,488, and 1.21 (P = 0.02 for all-cause mortality (N = 179,582. CONCLUSION/SIGNIFICANCE: Betel quid chewing is associated with an increased risk of metabolic disease, cardiovascular disease, and all-cause mortality. Thus, in addition to preventing oral cancer, stopping betel quid use could be a valuable public health measure for metabolic diseases that are showing a rapid increase in South-East Asia and the Western Pacific.

  12. The spectrum of oculocutaneous disease: Part II. Neoplastic and drug-related causes of oculocutaneous disease.

    Science.gov (United States)

    Day, Antoinette; Abramson, Amanda K; Patel, Mahir; Warren, Richard B; Menter, M Alan

    2014-05-01

    There are a multitude of diseases that commonly affect both the skin and the eye. Part II of this 2-part series reviews the oculocutaneous manifestations of neoplasms, both benign and malignant, and adverse drug reactions affecting the skin and the eye. Though rare, a number of neoplasms that primarily involve the skin, such as melanoma and basal cell carcinoma, can metastasize to the eye, leading to permanent damage if not properly treated. In addition, periocular neoplasms can irritate the conjunctiva and lid, reducing a patient's ability to see clearly. Neoplastic diseases, such as xeroderma pigmentosum, Sturge-Weber syndrome, and multiple myeloma, can also lead to permanent changes in the eye if not discovered and managed promptly. Furthermore, there are a multitude of drugs, including those commonly used by dermatologists, which can result in permanent damage to the eye. With proper knowledge of the ocular manifestations and treatment recommendations described in this 2-part series, dermatologists with the assistance of their ophthalmology colleagues can help avoid the complications, including permanent blindness, associated with infectious, inflammatory, genetic, neoplastic, and drug-related conditions. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  13. Disease Course of Lower Respiratory Tract Infection With a Bacterial Cause.

    Science.gov (United States)

    Teepe, Jolien; Broekhuizen, Berna D L; Loens, Katherine; Lammens, Christine; Ieven, Margareta; Goossens, Herman; Little, Paul; Butler, Christopher C; Coenen, Samuel; Godycki-Cwirko, Maciek; Verheij, Theo

    2016-11-01

    Bacterial pathogens are assumed to cause an illness course different from that of nonbacterial causes of acute cough, but evidence is lacking. We evaluated the disease course of lower respiratory tract infection (LRTI) with a bacterial cause in adults with acute cough. We conducted a secondary analysis of a multicenter European trial in which 2,061 adults with acute cough (28 days' duration or less) were recruited from primary care and randomized to amoxicillin or placebo. For this analysis only patients in the placebo group (n = 1,021) were included, reflecting the natural course of disease. Standardized microbiological and serological analyses were performed at baseline to define a bacterial cause. All patients recorded symptoms in a diary for 4 weeks. The disease course between those with and without a bacterial cause was compared by symptom severity in days 2 to 4, duration of symptoms rated moderately bad or worse, and a return consultation. Of 1,021 eligible patients, 187 were excluded for missing diary records, leaving 834 patients, of whom 162 had bacterial LRTI. Patients with bacterial LRTI had worse symptoms at day 2 to 4 after the first office visit (P = .014) and returned more often for a second consultation, 27% vs 17%, than those without bacterial LRTI (P = .004). Resolution of symptoms rated moderately bad or worse did not differ (P = .375). Patients with acute bacterial LRTI have a slightly worse course of disease when compared with those without an identified bacterial cause, but the relevance of this difference is not meaningful. © 2016 Annals of Family Medicine, Inc.

  14. Global inference of disease-causing single nucleotide variants from exome sequencing data.

    Science.gov (United States)

    Wu, Mengmeng; Chen, Ting; Jiang, Rui

    2016-12-23

    Whole exome sequencing (WES) has recently emerged as an effective approach for identifying genetic variants underlying human diseases. However, considerable time and labour is needed for careful investigation of candidate variants. Although filtration based on population frequencies and functional prediction scores could effectively remove common and neutral variants, hundreds or even thousands of rare deleterious variants still remain. In addition, current WES platforms also provide variant information in flanking noncoding regions, such as promoters, introns and splice sites. Despite of being recognized to harbour causal variants, these regions are usually ignored by current analysis pipelines. We present a novel computational method, called Glints, to overcome the above limitations. Glints is capable of identifying disease-causing SNVs in both coding and flanking noncoding regions from exome sequencing data. The principle behind Glints is that disease-causing variants should manifest their effect at both variant and gene levels. Specifically, Glints integrates 14 types of functional scores, including predictions for both coding and noncoding variants, and 9 types of association scores, which help identifying disease relevant genes. We conducted a large-scale simulation studies based on 1000 Genomes Project data and demonstrated the effectiveness of our method in both coding and flanking noncoding regions. We also applied Glints in two real exome sequencing and demonstrated its effectiveness for uncovering disease-causing SNVs. Both standalone software and web server are available at our website http://bioinfo.au.tsinghua.edu.cn/jianglab/glints . Glints is effective for uncovering disease-causing SNVs in coding and flanking noncoding regions, which is supported by both simulation and real case studies. Glints is expected to be a useful tool for human genetics research based on exome sequencing data.

  15. Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.

    LENUS (Irish Health Repository)

    Arsov, Todor

    2011-05-13

    The molecular basis of Kufs disease is unknown, whereas a series of genes accounting for most of the childhood-onset forms of neuronal ceroid lipofuscinosis (NCL) have been identified. Diagnosis of Kufs disease is difficult because the characteristic lipopigment is largely confined to neurons and can require a brain biopsy or autopsy for final diagnosis. We mapped four families with Kufs disease for whom there was good evidence of autosomal-recessive inheritance and found two peaks on chromosome 15. Three of the families were affected by Kufs type A disease and presented with progressive myoclonus epilepsy, and one was affected by type B (presenting with dementia and motor system dysfunction). Sequencing of a candidate gene in one peak shared by all four families identified no mutations, but sequencing of CLN6, found in the second peak and shared by only the three families affected by Kufs type A disease, revealed pathogenic mutations in all three families. We subsequently sequenced CLN6 in eight other families, three of which were affected by recessive Kufs type A disease. Mutations in both CLN6 alleles were found in the three type A cases and in one family affected by unclassified Kufs disease. Mutations in CLN6 are the major cause of recessive Kufs type A disease. The phenotypic differences between variant late-infantile NCL, previously found to be caused by CLN6, and Kufs type A disease are striking; there is a much later age at onset and lack of visual involvement in the latter. Sequencing of CLN6 will provide a simple diagnostic strategy in this disorder, in which definitive identification usually requires invasive biopsy.

  16. Chronic treatment with lithium does not improve neuromuscular phenotype in a mouse model of severe spinal muscular atrophy.

    Science.gov (United States)

    Dachs, E; Piedrafita, L; Hereu, M; Esquerda, J E; Calderó, J

    2013-10-10

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by defective levels of the survival motor neuron (SMN) protein. SMA causes spinal motoneuron (MN) loss, and progressive muscle weakness and paralysis. Currently, there is no effective therapy to cure this disease. Although different strategies focused on increasing the expression of functional SMN protein have been assayed, numerous SMN-independent therapeutic approaches have been demonstrated to have potential effectiveness in improving the SMA phenotype in mouse models and clinical trials. Recent works have shown that compounds which inhibit GSK-3β activity are effective in promoting MN survival and ameliorating lifespan in models of MN diseases including SMA. Taking into account the reported neuroprotective actions of lithium (Li) through the inhibition of GSK-3β in different studies, we tested here its potential efficiency as a therapeutic agent in a mouse model of severe SMA (SMNΔ7 mice). We show that the chronic treatment with Li initiated before the appearance of disease symptoms, although inhibited GSK-3β, did not improve the median survival, motor behavior, and spinal MN loss linked to SMA. Li administration did not either ameliorate the microglial and astroglial reaction in the spinal cord or the depletion of glutamatergic synapses on MNs observed in SMNΔ7 animals. Moreover, Li treatment did not mitigate muscle atrophy or calcitonin gene-related peptide (CGRP) downregulation in the neuromuscular junctions linked to the disease. However, a significant reduction in apoptotic cell death found in the skeletal muscle of SMA mice was observed after Li treatment. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. How the factoid of wind turbines causing 'vibroacoustic disease' came to be 'irrefutably demonstrated'.

    Science.gov (United States)

    Chapman, Simon; St George, Alexis

    2013-06-01

    In recent years, claims have proliferated in cyberspace that wind turbines cause a large variety of symptoms and diseases. One of these, "vibroacoustic disease" (VAD) is frequently mentioned. The aim of this study is to examine the quality of the evidence on how VAD came to be associated with wind turbine exposure by wind farm opponents. Searches of the web (Google advanced) and major research databases for papers on VAD and wind turbines. Self-citation analysis of research papers on VAD. Google returned 24,700 hits for VAD and wind turbines. Thirty-five research papers on VAD were found, none reporting any association between VAD and wind turbines. Of the 35 papers, 34 had a first author from a single Portuguese research group. Seventy-four per cent of citations to these papers were self-citations by the group. Median self-citation rates in science are around 7%. Two unpublished case reports presented at conferences were found asserting that VAD was "irrefutably demonstrated" to be caused by wind turbines. The quality of these reports was abject. VAD has received virtually no scientific recognition beyond the group who coined and promoted the concept. There is no evidence of even rudimentary quality that vibroacoustic disease is associated with or caused by wind turbines. The claim that wind turbines cause VAD is a factoid that has gone 'viral' in cyberspace and may be contributing to nocebo effects among those living near turbines. © 2013 The Authors. ANZJPH © 2013 Public Health Association of Australia.

  18. Causes of death in patients with asthma and asthma–chronic obstructive pulmonary disease overlap syndrome

    Science.gov (United States)

    Harada, Tomoya; Yamasaki, Akira; Fukushima, Takehito; Hashimoto, Kiyoshi; Takata, Miki; Kodani, Masahiro; Okazaki, Ryota; Takeda, Kenichi; Watanabe, Masanari; Kurai, Jun; Shimizu, Eiji

    2015-01-01

    Background The administration of inhaled corticosteroids and worldwide usage of several asthma guidelines have improved asthma mortality. Elderly patients with asthma show high mortality rates, and may have several comorbidities, including overlap with chronic obstructive pulmonary disease (COPD). Among patients showing asthma overlapped with COPD (asthma–COPD overlap syndrome; ACOS), mortality is worse than for asthma alone. Therefore, we investigated comorbidities, malignancies, and causes of death in patients with asthma and ACOS. Methods This was a retrospective study. From January 2000 to March 2012, 650 patients were followed up at Tottori University Hospital. Medical records were reviewed to collect data regarding patient characteristics and comorbidities, and causes of death were recorded for patients who died during the study period. Results Eighty-seven patients died during the study period. The most frequent cause of death was malignancy. The proportion of malignant disease was 21.7% in all patients, 19.4% in patients with asthma alone, and 32.4% in patients with ACOS. One patient died from an asthma attack during this period. Conclusion The most frequent cause of death in patients with asthma and ACOS was malignant disease. It is necessary to control not only asthma but also comorbidities in patients with asthma, especially in those with ACOS. PMID:25834418

  19. Causes of death in patients with asthma and asthma-chronic obstructive pulmonary disease overlap syndrome.

    Science.gov (United States)

    Harada, Tomoya; Yamasaki, Akira; Fukushima, Takehito; Hashimoto, Kiyoshi; Takata, Miki; Kodani, Masahiro; Okazaki, Ryota; Takeda, Kenichi; Watanabe, Masanari; Kurai, Jun; Shimizu, Eiji

    2015-01-01

    The administration of inhaled corticosteroids and worldwide usage of several asthma guidelines have improved asthma mortality. Elderly patients with asthma show high mortality rates, and may have several comorbidities, including overlap with chronic obstructive pulmonary disease (COPD). Among patients showing asthma overlapped with COPD (asthma-COPD overlap syndrome; ACOS), mortality is worse than for asthma alone. Therefore, we investigated comorbidities, malignancies, and causes of death in patients with asthma and ACOS. This was a retrospective study. From January 2000 to March 2012, 650 patients were followed up at Tottori University Hospital. Medical records were reviewed to collect data regarding patient characteristics and comorbidities, and causes of death were recorded for patients who died during the study period. Eighty-seven patients died during the study period. The most frequent cause of death was malignancy. The proportion of malignant disease was 21.7% in all patients, 19.4% in patients with asthma alone, and 32.4% in patients with ACOS. One patient died from an asthma attack during this period. The most frequent cause of death in patients with asthma and ACOS was malignant disease. It is necessary to control not only asthma but also comorbidities in patients with asthma, especially in those with ACOS.

  20. Gastro-intestinal complications as one of causes of death in patients with rheumatic diseases

    Directory of Open Access Journals (Sweden)

    V N Sorotskaya

    2005-01-01

    Full Text Available Objective. To assess frequency of gastro-intestinal (Gl bleeding and ulcer perforation as direct cause of death in pts with rheumatic diseases. Material and methods. Statistical analysis of Tula region patient care institutions documentation was performed to assess frequency and character of severe GI complications leading to death of pts. 300 cases of death which took place during 5 years (1996-2000 in 3 rheumatologic (105 cases and 10 therapeutic (195 cases departments of Tula region patient care institutions were studied. Results. Gl bleeding and ulcer perforation were the direct causes of death in 15 pts with rheumatic diseases i.e. in 5% from the whole number of died. GI complications caused death in 4 pts with chronic rheumatic heart disease (HRHD (1,7%, in 7 (15,2%with rheumatoid arthritis -, in 2 with ankylosing spondylitis and systemic lupus erythematosus (8,0 and 22,2% respectively. Pts with systemic sclerosis did not die because of GI damage. GI changes most frequently localized in duodenum (8 pts. 4 pts had complications connected with gastric ulcer and in 2 diffuse erosive damage of Gl mucosa was the source of bleeding. Conclusion. Severe Gl complications quite often lead to death of pts with rheumatic diseases in Tula region.

  1. Potential gains in life expectancy from reducing heart disease, cancer, Alzheimer's disease, kidney disease or HIV/AIDS as major causes of death in the USA.

    Science.gov (United States)

    Wang, G D; Lai, D J; Burau, K D; Du, X L

    2013-04-01

    Potential gains in life expectancy (PGLEs) that give proper consideration to competing risks are an effective indicator for measuring the impact of multiple causes of death on a defined population. This study aimed to assess PGLE by hypothetically reducing the major causes of death in the USA from 2001 to 2008. PGLEs due to the reduction and elimination of heart disease, cancer, Alzheimer's disease, kidney disease or human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) were calculated by age, gender and race. Age-specific mortality rates for the above diseases from the National Center for Health Statistics were used, and multiple decremental life tables were constructed to compute the corresponding PGLEs. PGLEs due to the elimination of heart disease, cancer or HIV/AIDS decreased from 2001 to 2008, but PGLEs due to the elimination of Alzheimer's disease or kidney disease increased over time. For heart disease, PGLE in 2001-2008 for all races was 2.78-2.15 for females vs 2.41-2.06 for males. For cancer, PGLE in 2001-2008 for all races was 2.97-2.81 for females vs 3.02-2.85 for males. HIV/AIDS has a greater impact on people of working age, whereas Alzheimer's disease has a greater impact on the elderly population. To compare the impacts of these diseases on life expectancy, partial multiple decremental life tables were constructed, and PGLEs were computed by a partial reduction or complete elimination of various causes of death for the entire life span as well as for certain working ages. This study outlined a picture of how each category of diseases could affect life expectancy in the US population by age, race or sex. The findings may assist in evaluating current public health improvements, and also provide useful information for directing future research and disease control programmes. Copyright © 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  2. Non-melanoma skin cancer and risk of Alzheimer's disease and all-cause dementia.

    Directory of Open Access Journals (Sweden)

    Sigrun A J Schmidt

    Full Text Available Cancer patients may be at decreased risk of Alzheimer's disease. This hypothesis is best developed for non-melanoma skin cancer (NMSC, but supportive epidemiological data are sparse. We therefore conducted a nationwide cohort study of the association between NMSC and Alzheimer's disease (main outcome and all-cause dementia. Using Danish medical databases, we identified adults diagnosed with NMSC between 1 January 1980 and 30 November 2013 (n = 216,221 and a comparison cohort of five individuals matched to each NMSC patient by sex and birth year (n = 1,081,097. We followed individuals from the time of diagnosis, or corresponding date for matched comparators, until a dementia diagnosis, death, emigration, or 30 November 2013, whichever came first. We used stratified Cox regression adjusted for comorbidities to compute hazard ratios (HRs associating NMSC with dementia. We computed cumulative risks of dementia, treating death as a competing risk. NMSC was associated with a HR of 0.95 (95% confidence interval [CI]: 0.92-0.98 for Alzheimer's disease and 0.92 (95% CI: 0.90-0.94 for all-cause dementia. HRs were similar for basal cell and squamous cell carcinoma, the two most common forms of NMSC. Estimates of risk reduction were more pronounced in the beginning of follow-up, reaching null after 5-10 years. At the end of follow-up (34 years, cumulative risk of Alzheimer's disease was 4.6% (95% CI: 4.4%-4.8% among patients with NMSC vs. 4.7% (95% CI: 4.6%-4.9% in the comparison cohort. In conclusion, NMSC was associated with 2%-10% reductions in relative risks of Alzheimer's disease and all-cause dementia. However, these small inverse associations may have been caused by ascertainment bias due to decreased awareness of NMSC tumors in persons with undiagnosed early cognitive impairment or by confounding from a more neuroprotective lifestyle among persons with NMSC.

  3. Hyperspectral imaging for small-scale analysis of symptoms caused by different sugar beet diseases

    Directory of Open Access Journals (Sweden)

    Mahlein Anne-Katrin

    2012-01-01

    Full Text Available Abstract Hyperspectral imaging (HSI offers high potential as a non-invasive diagnostic tool for disease detection. In this paper leaf characteristics and spectral reflectance of sugar beet leaves diseased with Cercospora leaf spot, powdery mildew and leaf rust at different development stages were connected. Light microscopy was used to describe the morphological changes in the host tissue due to pathogen colonisation. Under controlled conditions a hyperspectral imaging line scanning spectrometer (ImSpector V10E with a spectral resolution of 2.8 nm from 400 to 1000 nm and a spatial resolution of 0.19 mm was used for continuous screening and monitoring of disease symptoms during pathogenesis. A pixel-wise mapping of spectral reflectance in the visible and near-infrared range enabled the detection and detailed description of diseased tissue on the leaf level. Leaf structure was linked to leaf spectral reflectance patterns. Depending on the interaction with the host tissue, the pathogens caused disease-specific spectral signatures. The influence of the pathogens on leaf reflectance was a function of the developmental stage of the disease and of the subarea of the symptoms. Spectral reflectance in combination with Spectral Angle Mapper classification allowed for the differentiation of mature symptoms into zones displaying all ontogenetic stages from young to mature symptoms. Due to a pixel-wise extraction of pure spectral signatures a better understanding of changes in leaf reflectance caused by plant diseases was achieved using HSI. This technology considerably improves the sensitivity and specificity of hyperspectrometry in proximal sensing of plant diseases.

  4. How Do the Virulence Factors of Shigella Work Together to Cause Disease?

    Science.gov (United States)

    Mattock, Emily; Blocker, Ariel J

    2017-01-01

    Shigella is the major cause of bacillary dysentery world-wide. It is divided into four species, named S. flexneri, S. sonnei, S. dysenteriae, and S. boydii, which are distinct genomically and in their ability to cause disease. Shigellosis, the clinical presentation of Shigella infection, is characterized by watery diarrhea, abdominal cramps, and fever. Shigella's ability to cause disease has been attributed to virulence factors, which are encoded on chromosomal pathogenicity islands and the virulence plasmid. However, information on these virulence factors is not often brought together to create a detailed picture of infection, and how this translates into shigellosis symptoms. Firstly, Shigella secretes virulence factors that induce severe inflammation and mediate enterotoxic effects on the colon, producing the classic watery diarrhea seen early in infection. Secondly, Shigella injects virulence effectors into epithelial cells via its Type III Secretion System to subvert the host cell structure and function. This allows invasion of epithelial cells, establishing a replicative niche, and causes erratic destruction of the colonic epithelium. Thirdly, Shigella produces effectors to down-regulate inflammation and the innate immune response. This promotes infection and limits the adaptive immune response, causing the host to remain partially susceptible to re-infection. Combinations of these virulence factors may contribute to the different symptoms and infection capabilities of the diverse Shigella species, in addition to distinct transmission patterns. Further investigation of the dominant species causing disease, using whole-genome sequencing and genotyping, will allow comparison and identification of crucial virulence factors and may contribute to the production of a pan-Shigella vaccine.

  5. Genetic Structure and Biology of Xylella fastidiosa Strains Causing Disease in Citrus and Coffee in Brazil▿

    Science.gov (United States)

    Almeida, Rodrigo P. P.; Nascimento, Fernanda E.; Chau, John; Prado, Simone S.; Tsai, Chi-Wei; Lopes, Sílvio A.; Lopes, Joao R. S.

    2008-01-01

    Xylella fastidiosa is a vector-borne, plant-pathogenic bacterium that causes disease in citrus (citrus variegated chlorosis [CVC]) and coffee (coffee leaf scorch [CLS]) plants in Brazil. CVC and CLS occur sympatrically and share leafhopper vectors; thus, determining whether X. fastidiosa isolates can be dispersed from one crop to another and cause disease is of epidemiological importance. We sought to clarify the genetic and biological relationships between CVC- and CLS-causing X. fastidiosa isolates. We used cross-inoculation bioassays and microsatellite and multilocus sequence typing (MLST) approaches to determine the host range and genetic structure of 26 CVC and 20 CLS isolates collected from different regions in Brazil. Our results show that citrus and coffee X. fastidiosa isolates are biologically distinct. Cross-inoculation tests showed that isolates causing CVC and CLS in the field were able to colonize citrus and coffee plants, respectively, but not the other host, indicating biological isolation between the strains. The microsatellite analysis separated most X. fastidiosa populations tested on the basis of the host plant from which they were isolated. However, recombination among isolates was detected and a lack of congruency among phylogenetic trees was observed for the loci used in the MLST scheme. Altogether, our study indicates that CVC and CLS are caused by two biologically distinct strains of X. fastidiosa that have diverged but are genetically homogenized by frequent recombination. PMID:18424531

  6. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates.

    Science.gov (United States)

    O'Brien, Katherine L; Wolfson, Lara J; Watt, James P; Henkle, Emily; Deloria-Knoll, Maria; McCall, Natalie; Lee, Ellen; Mulholland, Kim; Levine, Orin S; Cherian, Thomas

    2009-09-12

    Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis in children worldwide. However, many countries lack national estimates of disease burden. Effective interventions are available, including pneumococcal conjugate vaccine and case management. To support local and global policy decisions on pneumococcal disease prevention and treatment, we estimated country-specific incidence of serious cases and deaths in children younger than 5 years. We measured the burden of pneumococcal pneumonia by applying the proportion of pneumonia cases caused by S pneumoniae derived from efficacy estimates from vaccine trials to WHO country-specific estimates of all-cause pneumonia cases and deaths. We also estimated burden of meningitis and non-pneumonia, non-meningitis invasive disease using disease incidence and case-fatality data from a systematic literature review. When high-quality data were available from a country, these were used for national estimates. Otherwise, estimates were based on data from neighbouring countries with similar child mortality. Estimates were adjusted for HIV prevalence and access to care and, when applicable, use of vaccine against Haemophilus influenzae type b. In 2000, about 14.5 million episodes of serious pneumococcal disease (uncertainty range 11.1-18.0 million) were estimated to occur. Pneumococcal disease caused about 826,000 deaths (582,000-926,000) in children aged 1-59 months, of which 91,000 (63,000-102,000) were in HIV-positive and 735,000 (519,000-825,000) in HIV-negative children. Of the deaths in HIV-negative children, over 61% (449,000 [316,000-501,000]) occurred in ten African and Asian countries. S pneumoniae causes around 11% (8-12%) of all deaths in children aged 1-59 months (excluding pneumococcal deaths in HIV-positive children). Achievement of the UN Millennium Development Goal 4 for child mortality reduction can be accelerated by prevention and treatment of pneumococcal disease, especially in

  7. Selective processing and metabolism of disease-causing mutant prion proteins.

    Directory of Open Access Journals (Sweden)

    Aarthi Ashok

    2009-06-01

    Full Text Available Prion diseases are fatal neurodegenerative disorders caused by aberrant metabolism of the cellular prion protein (PrP(C. In genetic forms of these diseases, mutations in the globular C-terminal domain are hypothesized to favor the spontaneous generation of misfolded PrP conformers (including the transmissible PrP(Sc form that trigger downstream pathways leading to neuronal death. A mechanistic understanding of these diseases therefore requires knowledge of the quality control pathways that recognize and degrade aberrant PrPs. Here, we present comparative analyses of the biosynthesis, trafficking, and metabolism of a panel of genetic disease-causing prion protein mutants in the C-terminal domain. Using quantitative imaging and biochemistry, we identify a misfolded subpopulation of each mutant PrP characterized by relative detergent insolubility, inaccessibility to the cell surface, and incomplete glycan modifications. The misfolded populations of mutant PrPs were neither recognized by ER quality control pathways nor routed to ER-associated degradation despite demonstrable misfolding in the ER. Instead, mutant PrPs trafficked to the Golgi, from where the misfolded subpopulation was selectively trafficked for degradation in acidic compartments. Surprisingly, selective re-routing was dependent not only on a mutant globular domain, but on an additional lysine-based motif in the highly conserved unstructured N-terminus. These results define a specific trafficking and degradation pathway shared by many disease-causing PrP mutants. As the acidic lysosomal environment has been implicated in facilitating the conversion of PrP(C to PrP(Sc, our identification of a mutant-selective trafficking pathway to this compartment may provide a cell biological basis for spontaneous generation of PrP(Sc in familial prion disease.

  8. Pathophysiology and spectrum of diseases caused by defects in lymphocyte cytotoxicity.

    Science.gov (United States)

    Meeths, Marie; Chiang, Samuel C C; Löfstedt, Alexandra; Müller, Martha-Lena; Tesi, Bianca; Henter, Jan-Inge; Bryceson, Yenan T

    2014-07-01

    In experimental settings, lymphocyte cytotoxicity has been recognized as a central mechanism for immune defense against infected and neoplastic cells. More recently, molecular determinants of lymphocyte cytotoxicity have been identified through studies of rare, inherited hyperinflammatory and lymphoproliferative syndromes that include hemophagocytic lymphohistiocytosis (HLH). These studies have unraveled a set of genes pivotal for the biogenesis and directed release of perforin-containing lysosomes that mediate target cell killing, in addition to other pathways including Fas that also contribute to induction of cell death. Furthermore, studies of such human primary immunodeficiencies have highlighted non-redundant roles of perforin for maintenance of immune homeostasis. Besides providing mechanistic insights to lymphocyte cytotoxicity, studies of individuals with rare hyperinflammatory diseases are highlighting the relevance of lymphocyte cytotoxicity to more common human diseases. It is increasingly recognized that mutations abrogating lymphocyte cytotoxicity not only cause HLH, but also are associated with susceptibility to cancer and autoimmune syndromes. In addition, patients may initially be present with neurological symptoms or severe infectious disease masquerading as variable immunodeficiency syndrome. Here, we highlight new knowledge regarding the molecular mechanisms regulating lymphocyte cytotoxicity and review how mutations in genes associated with HLH cause disease. We also discuss the wider implications of impairments in lymphocyte cytotoxicity for human disease predisposition. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Historical evidence that electrification caused the 20th century epidemic of "diseases of civilization".

    Science.gov (United States)

    Milham, Samuel

    2010-02-01

    The slow spread of residential electrification in the US in the first half of the 20th century from urban to rural areas resulted by 1940 in two large populations; urban populations, with nearly complete electrification and rural populations exposed to varying levels of electrification depending on the progress of electrification in their state. It took until 1956 for US farms to reach urban and rural non-farm electrification levels. Both populations were covered by the US vital registration system. US vital statistics tabulations and census records for 1920-1960, and historical US vital statistics documents were examined. Residential electrification data was available in the US census of population for 1930, 1940 and 1950. Crude urban and rural death rates were calculated, and death rates by state were correlated with electrification rates by state for urban and rural areas for 1940 white resident deaths. Urban death rates were much higher than rural rates for cardiovascular diseases, malignant diseases, diabetes and suicide in 1940. Rural death rates were significantly correlated with level of residential electric service by state for most causes examined. I hypothesize that the 20th century epidemic of the so called diseases of civilization including cardiovascular disease, cancer and diabetes and suicide was caused by electrification not by lifestyle. A large proportion of these diseases may therefore be preventable.

  10. Hyposplenism as a cause of pneumococcal meningoencephalitis in an adult patient with coeliac disease

    Directory of Open Access Journals (Sweden)

    Paolo Caraceni

    2013-03-01

    Full Text Available Introduction: Coeliac disease can be associated with hyposplenism and splenic atrophy, which may increase the patient’s risk for fatal infections caused by Streptococcus pneumoniae or Pneumococcus. It is general opinion that many more patients with coeliac disease have died from hyposplenism-related infections than those reported in literature. Case report: A 62-year-old woman with recently diagnosed coeliac disease was hospitalized with high fever, disorientation, and nuchal rigidity. Cerebral computed tomography was negative. Laboratory tests showed an elevated leukocyte count and very high levels of C reactive protein. The cerebrospinal fluid (CSF contained an increased number of mononuclear cells associated with a low glucose level and high protein concentrations. The CSF culture was positive for Streptococcus pneumoniae. Neurological conditions rapidly deteriorated with the onset of coma, and magnetic resonance imaging of the brain revealed initial signs of encephalitis extending above and below the tentorium. Abdominal ultrasonography disclosed splenic hypotrophy that raised the suspicion of hyposplenism. The diagnosis of hyposplenism was confirmed by demonstration of Howell-Jolly bodies in a peripheral blood smear. Discussion: This is the first reported case of pneumococcal meningoencephalitis caused by splenic hypofunction in a patient with coeliac disease. When coeliac disease is diagnosed with a marked delay in an elderly patient, spleen function should always be assessed. If impaired, the patient should undergo vaccination with pneumococcal conjugate vaccine to prevent pneumococcal infections.

  11. HTT-lowering reverses Huntington's disease immune dysfunction caused by NFκB pathway dysregulation.

    Science.gov (United States)

    Träger, Ulrike; Andre, Ralph; Lahiri, Nayana; Magnusson-Lind, Anna; Weiss, Andreas; Grueninger, Stephan; McKinnon, Chris; Sirinathsinghji, Eva; Kahlon, Shira; Pfister, Edith L; Moser, Roger; Hummerich, Holger; Antoniou, Michael; Bates, Gillian P; Luthi-Carter, Ruth; Lowdell, Mark W; Björkqvist, Maria; Ostroff, Gary R; Aronin, Neil; Tabrizi, Sarah J

    2014-03-01

    Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system contributes to Huntington's disease pathogenesis and has been targeted successfully to modulate disease progression, but mechanistic understanding relating this to mutant huntingtin expression in immune cells has been lacking. Here we demonstrate that human Huntington's disease myeloid cells produce excessive inflammatory cytokines as a result of the cell-intrinsic effects of mutant huntingtin expression. A direct effect of mutant huntingtin on the NFκB pathway, whereby it interacts with IKKγ, leads to increased degradation of IκB and subsequent nuclear translocation of RelA. Transcriptional alterations in intracellular immune signalling pathways are also observed. Using a novel method of small interfering RNA delivery to lower huntingtin expression, we show reversal of disease-associated alterations in cellular function-the first time this has been demonstrated in primary human cells. Glucan-encapsulated small interfering RNA particles were used to lower huntingtin levels in human Huntington's disease monocytes/macrophages, resulting in a reversal of huntingtin-induced elevated cytokine production and transcriptional changes. These findings improve our understanding of the role of innate immunity in neurodegeneration, introduce glucan-encapsulated small interfering RNA particles as tool for studying cellular pathogenesis ex vivo in human cells and raise the prospect of immune cell-directed HTT-lowering as a therapeutic in Huntington's disease.

  12. First Report of Fusarium subglutinans Causing Leaf Spot Disease on Cymbidium Orchids in Korea.

    Science.gov (United States)

    Han, Kyung-Sook; Park, Jong-Han; Back, Chang-Gi; Park, Mi-Jeong

    2015-09-01

    In 2006~2010, leaf spot symptoms, that is, small, yellow spots that turned into dark brown-to-black lesions surrounded by a yellow halo, were observed on Cymbidium spp. in Gongju, Taean, and Gapyeong in Korea. A Fusarium species was continuously isolated from symptomatic leaves; in pathogenicity testing, isolates caused leaf spot symptoms consisting of sunken, dark brown lesions similar to the original ones. The causal pathogen was identified as Fusarium subglutinans based on morphological and translation elongation factor 1-alpha sequence analyses. This is the first report of F. subglutinans as the cause of leaf spot disease in Cymbidium spp. in Korea.

  13. Cushing's disease as a cause of severe osteoporosis: a clinical challenge.

    Science.gov (United States)

    Abdel-Kader, Nadia; Cardiel, Mario H; Navarro Compan, Victoria; Piedra Priego, Juan; González, Ana

    2012-01-01

    Secondary osteoporosis is a frequently underestimated bone disorder. It is a secondary cause of bone loss that affects more than half of men and premenopausal and perimenopausal women, and about one-fitfth of postmenopausal women. We herein report an uncommon case of multiple fractures due to secondary osteoporosis caused by Cushing's disease. In this case the appearance of fractures in a 41 years old woman was the sign of alarm that ultimately lead us to the diagnosis. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  14. Occupational heavy lifting and risk of ischemic heart disease and all-cause mortality

    DEFF Research Database (Denmark)

    Petersen, Christina Bjørk; Eriksen, Louise; Tolstrup, Janne S

    2012-01-01

    -cause mortality, and the influence of occupational and leisure time physical activity on this association. METHODS: Data were analyzed from 1987, 1994, and 2000 from the Danish National Health Interview Surveys providing a sample of 6,692 working men and 5,921 working women aged 16--85 years without...... cardiovascular disease at baseline. Conventional risk factors for the outcomes IHD and all-cause mortality were controlled for in Cox analyses. RESULTS: Among men, heavy lifting was associated with increased risk for IHD (hazard ratio (HR): 1.52, 95 % Confidence interval (95 % CI): 1.15, 2.02), while a decreased...

  15. Association of Kidney Disease Measures with Cause-Specific Mortality: The Korean Heart Study.

    Directory of Open Access Journals (Sweden)

    Yejin Mok

    Full Text Available The link of low estimated glomerular filtration rate (eGFR and high proteinuria to cardiovascular disease (CVD mortality is well known. However, its link to mortality due to other causes is less clear.We studied 367,932 adults (20-93 years old in the Korean Heart Study (baseline between 1996-2004 and follow-up until 2011 and assessed the associations of creatinine-based eGFR and dipstick proteinuria with mortality due to CVD (1,608 cases, cancer (4,035 cases, and other (non-CVD/non-cancer causes (3,152 cases after adjusting for potential confounders.Although cancer was overall the most common cause of mortality, in participants with chronic kidney disease (CKD, non-CVD/non-cancer mortality accounted for approximately half of cause of death (47.0%for eGFR <60 ml/min/1.73 m2 and 54.3% for proteinuria ≥1+. Lower eGFR (<60 vs. ≥60 ml/min/1.73 m2 was significantly associated with mortality due to CVD (adjusted hazard ratio 1.49 [95% CI, 1.24-1.78] and non-CVD/non-cancer causes (1.78 [1.54-2.05]. The risk of cancer mortality only reached significance at eGFR <45 ml/min/1.73 m2 when eGFR 45-59 ml/min/1.73 m2 was set as a reference (1.62 [1.10-2.39]. High proteinuria (dipstick ≥1+ vs. negative/trace was consistently associated with mortality due to CVD (1.93 [1.66-2.25], cancer (1.49 [1.32-1.68], and other causes (2.19 [1.96-2.45]. Examining finer mortality causes, low eGFR and high proteinuria were commonly associated with mortality due to coronary heart disease, any infectious disease, diabetes, and renal failure. In addition, proteinuria was also related to death from stroke, cancers of stomach, liver, pancreas, and lung, myeloma, pneumonia, and viral hepatitis.Low eGFR was associated with CVD and non-CVD/non-cancer mortality, whereas higher proteinuria was consistently related to mortality due to CVD, cancer, and other causes. These findings suggest the need for multidisciplinary prevention and management strategies in individuals with CKD

  16. Candidate gene associated with a mutation causing recessive polycystic kidney disease in mice

    Energy Technology Data Exchange (ETDEWEB)

    Moyer, J.H.; Lee-Tischler, M.J.; Kwon, H.Y.; Schrick, J.J. (Univ. of Tennessee Graduate School of Biomedical Sciences, Oak Ridge, TN (United States)); Avner, E.D.; Sweeney, W.E. (Univ. of Washington, Seattle, WA (United States)); Godfrey, V.L.; Cacheiro, N.L.A.; Woychik, R.P. (Oak Ridge National Lab., TN (United States)); Wilkinson, J.E. (Univ. of Tennessee, Knoxville, TN (United States))

    1994-05-27

    A line of transgenic mice was generated that contains an insertional mutation causing a phenotype similar to human autosomal recessive polycystic kidney disease. Homozygotes displayed a complex phenotype that included bilateral polycystic kidneys and an unusual liver lesion. The mutant locus was cloned and characterized through use of the transgene as a molecular marker. Additionally, a candidate polycystic kidney disease (PKD) gene was identified whose structure and expression are directly associated with the mutant locus. A complementary DNA derived from this gene predicted a peptide containing a motif that was originally identified in several genes involved in cell cycle control.

  17. Spot Anthracnose Disease Caused by Colletotrichum gloeosporioides on Tulip Tree in Korea.

    Science.gov (United States)

    Choi, Okryun; Choi, Okhee; Kwak, Youn-Sig; Kim, Jinwoo; Kwon, Jin-Hyeuk

    2012-03-01

    The tulip tree (Liriodendron chinense) has been widely cultivated in Korea as a street or garden tree for its large flowers, which have a superficial resemblance to tulips. Occurrence of anthracnose disease on the leaves of tulip trees growing on the campus of Gyeongsang National University, Jinju, Korea, has been observed. Based on mycological characteristics, pathogenicity, and internal transcribed spacer sequence, the causal fungus was identified as Colletotrichum gloeosporioides. This is the first report on anthracnose disease caused by C. gloeosporioides on tulip trees in Korea.

  18. Effects of involuntary eccentric contraction training by neuromuscular electrical stimulation on the enhancement of muscle strength.

    Science.gov (United States)

    Son, Jongsang; Lee, Dongyeop; Kim, Youngho

    2014-08-01

    Neuromuscular electrical stimulation is well-known as a modality to improve the performance of neuromuscular system, but its clinical value on muscle strengthening remains equivocal. In this study, we designed a system for an involuntary eccentric contraction of biceps brachii muscles using continuous passive movement and commercial neuromuscular electrical stimulation devices. To investigate the effects of involuntary eccentric contraction training by neuromuscular electrical stimulation on the enhancement of muscle strength, seven healthy men between the ages of 24 and 29 years participated in this study. Participants were trained two times per week for 12 weeks. Each exercise session was performed for 30 min with no rest intervals. Isometric elbow flexion torque and biceps brachii muscle thickness were chosen as evaluation indices, and were measured at pre-/post-training. After the 12-week training, the isometric elbow flexion torque of the trained side significantly increased by approximately 23% compared to the initial performance (P<0.01). Meanwhile, the torque of the untrained side showed no significant change (P=0.862). During the 12-week training period, the biceps brachii muscle thickness of the trained side significantly increased by around 8% at rest and 16% at maximum voluntary contraction (P<0.01). The developed system and the technique show promising results, suggesting that it has the potential to be used to increase the muscle strength in patients with neuromuscular disease and to be implemented in design rehabilitative protocols. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015

    NARCIS (Netherlands)

    Wang, Haidong; Naghavi, Mohsen; Allen, Christine; Barber, Ryan M.; Bhutta, Zulfiqar A.; Carter, Austin; Casey, Daniel C.; Charlson, Fiona J.; Chen, Alan Zian; Coates, Matthew M.; Coggeshall, Megan; Dandona, Lalit; Dicker, Daniel J.; Erskine, Holly E.; Ferrari, Alize J.; Fitzmaurice, Christina; Foreman, Kyle; Forouzanfar, Mohammad H.; Fraser, Maya S.; Pullman, Nancy; Gething, Peter W.; Goldberg, Ellen M.; Graetz, Nicholas; Haagsma, Juanita A.; Hay, Simon I.; Huynh, Chantal; Johnson, Catherine; Kassebaum, Nicholas J.; Kinfu, Yohannes; Kulikoff, Xie Rachel; Kutz, Michael; Kyu, Hmwe H.; Larson, Heidi J.; Leung, Janni; Liang, Xiaofeng; Lim, Stephen S.; Lind, Margaret; Lozano, Rafael; Marquez, Neal; Mensah, George A.; Mikesell, Joe; Mokdad, Ali H.; Mooney, Meghan D.; Nguyen, Grant; Nsoesie, Elaine; Pigott, David M.; Pinho, Christine; Roth, Gregory A.; Salomon, Joshua A.; Sandar, Logan; Silpakit, Naris; Sligar, Amber; Sorensen, Reed J. D.; Stanaway, Jeffrey; Steiner, Caitlyn; Teeple, Stephanie; Thomas, Bernadette A.; Troeger, Christopher; VanderZanden, Amelia; Vollset, Stein Emil; Wanga, Valentine; Whiteford, Harvey A.; Wolock, Timothy; Zoeckler, Leo; Abate, Kalkidan Hassen; Abbafati, Cristiana; Abbas, Kaja M.; Abd-Allah, Foad; Abera, Semaw Ferede; Abreu, Daisy M. X.; Abu-Raddad, Laith J.; Abyu, Gebre Yitayih; Achoki, Tom; Adelekan, Ademola Lukman; Ademi, Zanfina; Adou, Arsene Kouablan; Adsuar, Jose C.; Afanvi, Kossivi Agbelenko; Afshin, Ashkan; Agardh, Emilie Elisabet; Agarwal, Arnav; Agrawal, Anurag; Kiadaliri, Aliasghar Ahmad; Ajala, Oluremi N.; Akanda, All Shafqat; Akinyemi, Rufus Olusola; Akinyemiju, Tomi F.; Akseer, Nadia; Al Lami, Faris Hasan; Alabed, Samer; Al-Aly, Ziyad; Alam, Khurshid; Alam, Noore K. M.; Alasfoor, Deena; Aldhahri, Saleh Fahed; Aldridge, Robert William; Alegretti, Miguel Angel; Aleman, Alicia V.; Alemu, Zewdie Aderaw; Alexander, Lily T.; Alhabib, Samia; Ali, Raghib; Alkerwi, Ala'a; Alla, Francois; Allebeck, Peter; Al-Raddadi, Rajaa; Alsharif, Ubai; Altirkawi, Khalid A.; Martin, Elena Alvarez; Alvis-Guzman, Nelson; Amare, Azmeraw T.; Amegah, Adeladza Kofi; Ameh, Emmanuel A.; Amini, Heresh; Ammar, Walid; Amrock, Stephen Marc; Andersen, Hjalte H.; Anderson, Benjamin; Anderson, Gregory M.; Antonio, Carl Abelardo T.; Aregay, Atsede Fantahun; Arnlov, Johan; Arsenijevic, Valentina S. Arsic; Al Artaman, Ali; Asayesh, Hamid; Asghar, Rana Jawad; Atique, Suleman; Arthur Avokpaho, Euripide Frinel G.; Awasthi, Ashish; Azzopardi, Peter; Bacha, Umar; Badawi, Alaa; Bahit, Maria C.; Balakrishnan, Kalpana; Banerjee, Amitava; Barac, Aleksandra; Barker-Collo, Suzanne L.; Barnighausen, Till; Barregard, Lars; Barrero, Lope H.; Basu, Arindam; Basu, Sanjay; Bayou, Yibeltal Tebekaw; Bazargan-Hejazi, Shahrzad; Beardsley, Justin; Bedi, Neeraj; Beghi, Ettore; Belay, Haileeyesus Adamu; Bell, Brent; Bell, Michelle L.; Bello, Aminu K.; Bennett, Derrick A.; Bensenor, Isabela M.; Berhane, Adugnaw; Bernabe, Eduardo; Betsu, Balem Demtsu; Beyene, Addisu Shunu; Bhala, Neeraj; Bhalla, Ashish; Biadgilign, Sibhatu; Bikbov, Boris; Bin Abdulhak, Aref A.; Biroscak, Brian J.; Biryukov, Stan; Bjertness, Espen; Blore, Jed D.; Blosser, Christopher D.; Bohensky, Megan A.; Borschmann, Rohan; Bose, Dipan; Bourne, Rupert R. A.; Brainin, Michael; Brayne, Carol E. G.; Brazinova, Alexandra; Breitborde, Nicholas J. K.; Brenner, Hermann; Brewer, Jerry D.; Brown, Alexandria; Brown, Jonathan; Brugha, Traolach S.; Buckle, Geoffrey Colin; Butt, Zahid A.; Calabria, Bianca; Campos-Novato, Ismael Ricardo; Campuzano, Julio Cesar; Carapetis, Jonathan R.; Cardenas, Rosario; Carpenter, David; Carrero, Juan Jesus; Castaneda-Oquela, Carlos A.; Rivas, Jacqueline Castillo; Catala-Lopez, Ferran; Cavalleri, Fiorella; Cercy, Kelly; Cerda, Jorge; Chen, Wanqing; Chew, Adrienne; Chiang, Peggy Pei -Chia; Chibalabala, Mirriam; Chibueze, Chioma Ezinne; Chimed-Ochir, Odgerel; Chisumpa, Vesper Hichilombwe; Choi, Jee-Young Jasmine; Chowdhury, Rajiv; Christensen, Hanne; Christopher, Devasahayam Jesudas; Ciobanu, Liliana G.; Cirillo, Massimo; Cohen, Aaron J.; Colistro, Valentina; Colomar, Mercedes; Colquhoun, Samantha M.; Cooper, Cyrus; Cooper, Leslie Trumbull; Cortinovis, Monica; Cowie, Benjamin C.; Crump, John A.; Damsere-Derry, James; Danawi, Hadi; Dandona, Rakhi; Daoud, Farah; Darby, Sarah C.; Dargan, Paul I.; das Neves, Jose; Davey, Gail; Davis, Adrian C.; Davitoiu, Dragos V.; de Castro, E. Filipa; de Jager, Pieter; De Leo, Diego; Degenhardt, Louisa; Dellavalle, Robert P.; Deribe, Kebede; Deribew, Amare; Dharmaratne, Samath D.; Dhillon, Preet K.; Diaz-Torne, Cesar; Ding, Eric L.; dos Santos, Kadine Priscila Bender; Dossou, Edem; Driscoll, Tim R.; Duan, Leilei; Dubey, Manisha; Bartholow, Bruce; Ellenbogen, Richard G.; Lycke, Christian; Elyazar, Iqbal; Endries, Aman Yesuf; Ermakov, Sergey Petrovich; Eshrati, Babak; Esteghamati, Alireza; Estep, Kara; Faghmous, Imad D. A.; Fahimi, Saman; Jose, Emerito; Farid, Talha A.; Sa Farinha, Carla Sofia e; Faro, Andre; Farvid, Maryam S.; Farzadfar, Farshad; Feigin, Valery L.; Fereshtehnejad, Seyed-Mohammad; Fernandes, Jefferson G.; Fernandes, Joao C.; Fischer, Florian; Fitchett, Joseph R. A.; Flaxman, Abraham; Foigt, Nataliya; Fowkes, F. Gerry R.; Franca, Elisabeth Barboza; Franklin, Richard C.; Friedman, Joseph; Frostad, Joseph; Hirst, Thomas; Futran, Neal D.; Gall, Seana L.; Gambashidze, Ketevan; Gamkrelidze, Amiran; Ganguly, Parthasarathi; Gankpe, Fortune Gbetoho; Gebre, Teshome; Gebrehiwot, Tsegaye Tsewelde; Gebremedhin, Amanuel Tesfay; Gebru, Alemseged Aregay; Geleijnse, Johanna M.; Gessner, Bradford D.; Ghoshal, Aloke Gopal; Gibney, Katherine B.; Gillum, Richard F.; Gilmour, Stuart; Giref, Ababi Zergaw; Giroud, Maurice; Gishu, Melkamu Dedefo; Giussani, Giorgia; Glaser, Elizabeth; Godwin, William W.; Gomez-Dantes, Hector; Gona, Philimon; Goodridge, Amador; Gopalani, Sameer Vali; Gosselin, Richard A.; Gotay, Carolyn C.; Goto, Atsushi; Gouda, Hebe N.; Greaves, Felix; Gugnani, Harish Chander; Gupta, Rahul; Gupta, Rajeev; Gupta, Vipin; Gutierrez, Reyna A.; Hafezi-Nejad, Nima; Haile, Demewoz; Hailu, Alemayehu Desalegne; Hailu, Gessessew Bugssa; Halasa, Yara A.; Hamadeh, Randah Ribhi; Hamidi, Samer; Hancock, Jamie; Handal, Alexis J.; Hankey, Graeme J.; Hao, Yuantao; Harb, Hilda L.; Harikrishnan, Sivadasanpillai; Haro, Josep Maria; Havmoeller, Rasmus; Heckbert, Susan R.; Heredia-Pi, Ileana Beatriz; Heydarpour, Pouria; Hilderink, Henk B. M.; Hoek, Hans W.; Hogg, Robert S.; Horino, Masako; Horita, Nobuyuki; Hosgood, H. Dean; Hotez, Peter J.; Hoy, Damian G.; Hsairi, Mohamed; Htet, Aung Soe; Than Htike, Maung Maung; Hu, Guoqing; Huang, Cheng; Huang, Hsiang; Huiart, Laetitia; Husseini, Abdullatif; Huybrechts, Inge; Huynh, Grace; Iburg, Kim Moesgaard; Innos, Kaire; Inoue, Manami; Iyer, Veena J.; Jacobs, Troy A.; Jacobsen, Kathryn H.; Jahanmehr, Nader; Jakovljevic, Mihajlo B.; James, Peter; Javanbakht, Mehdi; Jayaraman, Sudha P.; Jayatilleke, Achala Upendra; Jeemon, Panniyammakal; Jensen, Paul N.; Jha, Vivekanand; Jiang, Guohong; Jiang, Ying; Jibat, Tariku; Jimenez-Corona, Aida; Jonas, Jost B.; Joshi, Tushar Kant; Kabir, Zubair; Karnak, Ritul; Kan, Haidong; Kant, Surya; Karch, Andre; Karema, Corine Kakizi; Karimkhani, Chante; Karletsos, Dimitris; Karthikeyan, Ganesan; Kasaeian, Amir; Katibeh, Marzieh; Kaul, Anil; Kawakami, Norito; Kayibanda, Jeanne Francoise; Keiyoro, Peter Njenga; Kemmer, Laura; Kemp, Andrew Haddon; Kengne, Andre Pascal; Keren, Andre; Kereselidze, Maia; Kesavachandran, Chandrasekharan Nair; Khader, Yousef Saleh; Khalil, Ibrahim A.; Khan, Abdur Rahman; Khan, Ejaz Ahmad; Khang, Young-Ho; Khera, Sahil; Muthafer Khoja, Tawfik Ahmed; Kieling, Christian; Kim, Daniel; Kim, Yun Jin; Kissela, Brett M.; Kissoon, Niranjan; Knibbs, Luke D.; Knudsen, Ann Kristin; Kokubo, Yoshihiro; Kolte, Dhaval; Kopec, Jacek A.; Kosen, Soewarta; Koul, Parvaiz A.; Koyanagi, Ai; Krog, Norun Hjertager; Defo, Barthelemy Kuate; Bicer, Burcu Kucuk; Kudom, Andreas A.; Kuipers, Ernst J.; Kulkarni, Veena S.; Kumar, G. Anil; Kwan, Gene F.; Lal, Aparna; Lal, Dharmesh Kumar; Lalloo, Ratilal; Lam, Hilton; Lam, Jennifer O.; Langan, Sinead M.; Lansingh, Van C.; Larsson, Anders; Laryea, Dennis Odai; Latif, Asma Abdul; Lawrynowicz, Alicia Elena Beatriz; Leigh, James; Levi, Miriam; Li, Yongmei; Lindsay, M. Patrice; Lipshultz, Steven E.; Liu, Patrick Y.; Liu, Shiwei; Liu, Yang; Lo, Loon-Tzian; Logroscino, Giancarlo; Lotufo, Paulo A.; Lucas, Robyn M.; Lunevicius, Raimundas; Lyons, Ronan A.; Ma, Stefan; Pedro Machado, Vasco Manuel; Mackay, Mark T.; MacLachlan, Jennifer H.; Abd El Razek, Hassan Magdy; Abd El Razek, Mohammed Magdy; Majdan, Marek; Majeed, Azeem; Malekzadeh, Reza; Ayele Manamo, Wondimu Ayele; Mandisarisa, John; Mangalam, Srikanth; Mapoma, Chabila C.; Marcenes, Wagner; Margolis, David Joel; Martin, Gerard Robert; Martinez-Raga, Jose; Marzan, Melvin Barrientos; Masiye, Felix; Mason-Jones, Amanda J.; Massano, Joao; Matzopoulos, Richard; Mayosi, Bongani M.; McGarvey, Stephen Theodore; McGrath, John J.; Mckee, Martin; McMahon, Brian J.; Meaney, Peter A.; Mehari, Alem; Mehndiratta, Man Mohan; Mena-Rodriguez, Fabiola; Mekonnen, Alemayehu B.; Melaku, Yohannes Adama; Memiah, Peter; Memish, Ziad A.; Mendoza, Walter; Meretoja, Atte; Meretoja, Tuomo J.; Mhimbira, Francis Apolinary; Micha, Renata; Miller, Ted R.; Mirarefin, Mojde; Misganaw, Awoke; Mock, Charles N.; Abdulmuhsin Mohammad, Karzan; Mohammadi, Alireza; Mohammed, Shafiu; Mohan, Viswanathan; Mola, Glen Liddell D.; Monasta, Lorenzo; Montanez Hernandez, Julio Cesar; Montero, Pablo; Montico, Marcella; Montine, Thomas J.; Moradi-Lakeh, Maziar; Morawska, Lidia; Morgan, Katherine; Mori, Rintaro; Mozaffarian, Dariush; Mueller, Ulrich; Satyanarayana Murthy, Gudlavalleti Venkata; Murthy, Srinivas; Musa, Kamarul Imran; Nachega, Jean B.; Nagel, Gabriele; Naidoo, Kovin S.; Naik, Nitish; Naldi, Luigi; Nangia, Vinay; Nash, Denis; Nejjari, Chakib; Neupane, Subas; Newton, Charles R.; Newton, John N.; Ng, Marie; Ngalesoni, Frida Namnyak; Ngirabega, Jean de Dieu; Quyen Le Nguyen, [Unknown; Nisar, Muhammad Imran; Nkamedjie Pete, Patrick Martial; Nomura, Marika; Norheim, Ole F.; Norman, Paul E.; Norrving, Bo; Nyakarahuka, Luke; Ogbo, Felix Akpojene; Ohkubo, Takayoshi; Ojelabi, Foluke Adetola; Olivares, Pedro R.; Olusanya, Bolajoko Olubukunola; Olusanya, Jacob Olusegun; Opio, John Nelson; Oren, Eyal; Ortiz, Alberto; Osman, Majdi; Ota, Erika; Ozdemir, Raziye; Pa, Mahesh; Pandian, Jeyaraj D.; Pant, Puspa Raj; Papachristou, Christina; Park, Eun-Kee; Park, Jae-Hyun; Parry, Charles D.; Parsaeian, Mahboubeh; Caicedo, Angel J. Paternina; Patten, Scott B.; Patton, George C.; Paul, Vinod K.; Pearce, Neil; Pedro, Joao Mario; Stokic, Ljiljana Pejin; Pereira, David M.; Perico, Norberto; Pesudovs, Konrad; Petzold, Max; Phillips, Michael Robert; Piel, Frederic B.; Pillay, Julian David; Plass, Dietrich; Platts-Mills, James A.; Polinder, Suzanne; Pope, C. Arden; Popova, Svetlana; Poulton, Richie G.; Pourmalek, Farshad; Prabhakaran, Dorairaj; Qorbani, Mostafa; Quame-Amaglo, Justice; Quistberg, D. Alex; Rafay, Anwar; Rahimi, Kazem; Rahimi-Movaghar, Vafa; Rahman, Mahfuzar; Rahman, Mohammad Hifz Ur; Rahman, Sajjad Ur; Rai, Rajesh Kumar; Rajavi, Zhale; Rajsic, Sasa; Raju, Murugesan; Rakovac, Ivo; Rana, Saleem M.; Ranabhat, Chhabi L.; Rangaswamy, Thara; Rao, Puja; Rao, Sowmya R.; Refaat, Amany H.; Rehm, Jurgen; Reitsma, Marissa B.; Remuzzi, Giuseppe; Resnikofff, Serge; Ribeiro, Antonio L.; Ricci, Stefano; Blancas, Maria Jesus Rios; Roberts, Bayard; Roca, Anna; Rojas-Rueda, David; Ronfani, Luca; Roshandel, Gholamreza; Rothenbacher, Dietrich; Roy, Ambuj; Roy, Nawal K.; Ruhago, George Mugambage; Sagar, Rajesh; Saha, Sukanta; Sahathevan, Ramesh; Saleh, Muhammad Muhammad; Sanabria, Juan R.; Sanchez-Nino, Maria Dolores; Sanchez-Riera, Lidia; Santos, Itamar S.; Sarmiento-Suarez, Rodrigo; Sartorius, Benn; Satpathy, Maheswar; Savic, Miloje; Sawhney, Monika; Schaub, Michael P.; Schmidt, Maria Ines; Schneider, Ione J. C.; Schottker, Ben; Schutte, Aletta E.; Schwebel, David C.; Seedat, Soraya; Sepanlou, Sadaf G.; Servan-Mori, Edson E.; Shackelford, Katya A.; Shaddick, Gavin; Shaheen, Amira; Shahraz, Saeid; Shaikh, Masood Ali; Shakh-Nazarova, Marina; Sharma, Rajesh; She, Jun; Sheikhbahaei, Sara; Shen, Jiabin; Shen, Ziyan; Shepard, Donald S.; Sheth, Kevin N.; Shetty, Balakrishna P.; Shi, Peilin; Shibuya, Kenji; Shin, Min-Jeong; Shiri, Rahman; Shiue, Ivy; Shrime, Mark G.; Sigfusdottir, Inga Dora; Silberberg, Donald H.; Silva, Diego Augusto Santos; Silveira, Dayane Gabriele Alves; Silverberg, Jonathan I.; Simard, Edgar P.; Singh, Abhishek; Singh, Gitanjali M.; Singh, Jasvinder A.; Singh, Om Prakash; Singh, Prashant Kumar; Singh, Virendra; Soneji, Samir; Soreide, Kjetil; Soriano, Joan B.; Sposato, Luciano A.; Sreeramareddy, Chandrashekhar T.; Stathopoulou, Vasiliki; Stein, Dan J.; Stein, Murray B.; Stranges, Saverio; Stroumpoulis, Konstantinos; Sunguya, Bruno F.; Sur, Patrick; Swaminathan, Soumya; Sykes, Bryan L.; Szoeke, Cassandra E. I.; Tabares-Seisdedos, Rafael; Tabb, Karen M.; Takahashi, Ken; Takala, Jukka S.; Talongwa, Roberto Tchio; Tandon, Nikhil; Tavakkoli, Mohammad; Taye, Bineyam; Taylor, Hugh R.; Ao, Braden J. Te; Tedla, Bemnet Amare; Tefera, Worku Mekonnen; Ten Have, Margreet; Terkawi, Abdullah Sulieman; Tesfay, Fisaha Haile; Tessema, Gizachew Assefa; Thomson, Alan J.; Thorne-Lyman, Andrew L.; Thrift, Amanda G.; Thurston, George D.; Tillmann, Taavi; Tirschwell, David L.; Tonelli, Marcello; Topor-Madry, Roman; Topouzis, Fotis; Nx, Jeffrey Allen Towb; Traebert, Jefferson; Tran, Bach Xuan; Truelsen, Thomas; Trujillo, Ulises; Tura, Abera Kenay; Tuzcu, Emin Murat; Uchendu, Uche S.; Ukwaja, Kingsley N.; Undurraga, Eduardo A.; Uthman, Olalekan A.; Van Dingenen, Rita; Van Donkelaar, Aaron; Vasankari, Tommi; Vasconcelos, Ana Maria Nogales; Venketasubramanian, Narayanaswamy; Vidavalur, Ramesh; Vijayakumar, Lakshmi; Villalpando, Salvador; Violante, Francesco S.; Vlassov, Vasiliy Victorovich; Wagner, Joseph A.; Wagner, Gregory R.; Wallin, Mitchell T.; Wang, Linhong; Watkins, David A.; Weichenthal, Scott; Weiderpass, Elisabete; Weintraub, Robert G.; Werdecker, Andrea; Westerman, Ronny; White, Richard A.; Wijeratne, Tissa; Wilkinson, James D.; Williams, Hywel C.; Wiysonge, Charles Shey; Woldeyohannes, Solomon Meseret; Wolfe, Charles D. A.; Won, Sungho; Wong, John Q.; Woolf, Anthony D.; Xavier, Denis; Xiao, Qingyang; Xu, Gelin; Yakob, Bereket; Yalew, Ayalnesh Zemene; Yan, Lijing L.; Yano, Yuichiro; Yaseri, Mehdi; Ye, Pengpeng; Yebyo, Henock Gebremedhin; Yip, Paul; Yirsaw, Biruck Desalegn; Yonemoto, Naohiro; Yonga, Gerald; Younis, Mustafa Z.; Yu, Shicheng; Zaidi, Zoubida; Zaki, Maysaa El Sayed; Zannad, Faiez; Zavala, Diego E.; Zeeb, Hajo; Zeleke, Berihun M.; Zhang, Hao; Zodpey, Sanjay; Zonies, David; Zuhlke, Liesl Joanna; Vos, Theo; Lopez, Alan D.; Murray, Christopher J. L.

    2016-01-01

    Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes

  20. Effects of Aldrin-transdiol on neuromuscular facilitation and depression

    NARCIS (Netherlands)

    Akkermans, L.M.A.; Bercken, J. van den; Zalm, J.M. van der

    The effects of aldrin-transdiol, one of the active metabolites of the insecticide dieldrin, on evoked transmitter release, neuromuscular facilitation and neuromuscular depression have been studied in frog sartorius nerve-muscle preparations. Conventional techniques of intracellular recordings were

  1. The blood exposome and its role in discovering causes of disease.

    Science.gov (United States)

    Rappaport, Stephen M; Barupal, Dinesh K; Wishart, David; Vineis, Paolo; Scalbert, Augustin

    2014-08-01

    Since 2001, researchers have examined the human genome (G) mainly to discover causes of disease, despite evidence that G explains relatively little risk. We posit that unexplained disease risks are caused by the exposome (E; representing all exposures) and G × E interactions. Thus, etiologic research has been hampered by scientists' continuing reliance on low-tech methods to characterize E compared with high-tech omics for characterizing G. Because exposures are inherently chemical in nature and arise from both endogenous and exogenous sources, blood specimens can be used to characterize exposomes. To explore the "blood exposome" and its connection to disease, we sought human blood concentrations of many chemicals, along with their sources, evidence of chronic-disease risks, and numbers of metabolic pathways. From the literature we obtained human blood concentrations of 1,561 small molecules and metals derived from foods, drugs, pollutants, and endogenous processes. We mapped chemical similarities after weighting by blood concentrations, disease-risk citations, and numbers of human metabolic pathways. Blood concentrations spanned 11 orders of magnitude and were indistinguishable for endogenous and food chemicals and drugs, whereas those of pollutants were 1,000 times lower. Chemical similarities mapped by disease risks were equally distributed by source categories, but those mapped by metabolic pathways were dominated by endogenous molecules and essential nutrients. For studies of disease etiology, the complexity of human exposures motivates characterization of the blood exposome, which includes all biologically active chemicals. Because most small molecules in blood are not human metabolites, investigations of causal pathways should expand beyond the endogenous metabolome.

  2. Ultrasound of oral and masticatory muscles: Why every neuromuscular swallow team should have an ultrasound machine

    NARCIS (Netherlands)

    Engel-Hoek, L. van den; Lagarde, M.L.J.; Alfen, N. van

    2017-01-01

    Patients with neuromuscular disorders often present with swallowing difficulties due to oral phase problems and pharyngeal residue after swallow. It is important to assess the underlying pathology and cause of the swallowing disturbance in this patient group, such as dystrophic changes in oral and

  3. PRE- AND POSTSYNAPTIC NEUROMUSCULAR JUNCTION ABNORMALITIES IN MuSK MYASTHENIA

    NARCIS (Netherlands)

    Niks, Erik H.; Kuks, Jan B. M.; Wokke, John H. J.; Veldman, Henk; Bakker, Egbert; Verschuuren, Jan J. G. M.; Plomp, Jaap J.

    Autoantibodies to muscle-specific kinase (MuSK) can cause myasthenia gravis (MG). The pathophysiological mechanism remains unknown. We report in vitro electrophysiological and histological studies of the neuromuscular junction in a MuSK MG patient. Low levels of presynaptic acetylcholine release and

  4. Increased all-cause mortality with psychotropic medication in Parkinson's disease and controls

    DEFF Research Database (Denmark)

    Frandsen, Rune; Baandrup, Lone; Kjellberg, Jakob

    2014-01-01

    AIM: Use of medication and polypharmacy is common as the population ages and its disease burden increases. We evaluated the association of antidepressants, benzodiazepines, antipsychotics and combinations of psychotropic drugs with all-cause mortality in patients with Parkinson's disease (PD......) and a matched group without PD. METHOD: We identified 5861 PD patients and 31,395 control subjects matched by age, gender and marital status, and obtained register data on medication use and vital status between 1997 and 2007. RESULTS: All-cause mortality was significantly higher with the use of most groups...... of psychotropic medication in PD patients and controls. Hazard ratios were as follows for the medication types: selective serotonin reuptake inhibitors or serotonin-noradrenalin reuptake inhibitors, PD HR = 1.19, 95% CI = 1.04-1.36; Control HR = 1.77, 95% CI = 1.64-1.91; benzodiazepines, PD HR = 1.17, 95% CI = 0...

  5. Clinical features of neuromuscular disorders in patients with N-type voltage-gated calcium channel antibodies

    Directory of Open Access Journals (Sweden)

    Andreas Totzeck

    2016-09-01

    Full Text Available Neuromuscular junction disorders affect the pre- or postsynaptic nerve to muscle transmission due to autoimmune antibodies. Members of the group like myasthenia gravis and Lambert-Eaton syndrome have pathophysiologically distinct characteristics. However, in practice, distinction may be difficult. We present a series of three patients with a myasthenic syndrome, dropped-head syndrome, bulbar and respiratory muscle weakness and positive testing for anti-N-type voltage-gated calcium channel antibodies. In two cases anti-acetylcholin receptor antibodies were elevated, anti-P/Q-type voltage-gated calcium channel antibodies were negative. All patients initially responded to pyridostigmine with a non-response in the course of the disease. While one patient recovered well after treatment with intravenous immunoglobulins, 3,4-diaminopyridine, steroids and later on immunosuppression with mycophenolate mofetil, a second died after restriction of treatment due to unfavorable cancer diagnosis, the third patient declined treatment. Although new antibodies causing neuromuscular disorders were discovered, clinical distinction has not yet been made. Our patients showed features of pre- and postsynaptic myasthenic syndrome as well as severe dropped-head syndrome and bulbar and axial muscle weakness, but only anti-N-type voltage-gated calcium channel antibodies were positive. When administered, one patient benefited from 3,4-diaminopyridine. We suggest that this overlap-syndrome should be considered especially in patients with assumed seronegative myasthenia gravis and lack of improvement under standard therapy.

  6. Transgenic mouse model reveals an unsuspected role of the acetylcholine receptor in statin-induced neuromuscular adverse drug reactions.

    Science.gov (United States)

    Grajales-Reyes, G E; Báez-Pagán, C A; Zhu, H; Grajales-Reyes, J G; Delgado-Vélez, M; García-Beltrán, W F; Luciano, C A; Quesada, O; Ramírez, R; Gómez, C M; Lasalde-Dominicci, J A

    2013-08-01

    High cholesterol levels are an established risk factor for cardiovascular disease (CVD), the world's leading cause of death. Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (statins) are prescribed to lower serum cholesterol levels and reduce the risk of CVD. Despite the success of statins, many patients abandon treatment owing to neuromuscular adverse drug reactions (ADRs). Genome-wide association studies have identified the single-nucleotide polymorphism (SNP) rs4149056 in the SLCO1B1 gene as being associated with an increased risk for statin-induced ADRs. By studying slow-channel syndrome transgenic mouse models, we determined that statins trigger ADRs in mice expressing the mutant allele of the rs137852808 SNP in the nicotinic acetylcholine receptor (nAChR) α-subunit gene CHRNA1. Mice expressing this allele show a remarkable contamination of end-plates with caveolin-1 and develop early signs of neuromuscular degeneration upon statin treatment. This study demonstrates that genes coding for nAChR subunits may contain variants associated with statin-induced ADRs.

  7. The predictive value of fatigue for nonfatal ischemic heart disease and all-cause mortality

    DEFF Research Database (Denmark)

    Ekmann, Anette; Osler, Merete; Avlund, Kirsten

    2012-01-01

    Objective To investigate whether fatigue predicts nonfatal ischemic heart disease (IHD) and all-cause mortality in middle-aged men. Methods The study population consisted of 5216 middle-aged men born in the Copenhagen metropolitan area in 1953. At baseline, men free of angina pectoris and previou...... is a potential risk indicator for IHD and mortality. Further research is needed to establish the role of smoking and other life-style characteristics....

  8. Mycetoma Caused by Acremonium Species in a Patient with Chronic Granulomatous Disease

    Directory of Open Access Journals (Sweden)

    Richard Antrobus

    2016-01-01

    Full Text Available Patients with chronic granulomatous disease are predisposed to fungal infections and are therefore routinely prescribed antifungal prophylaxis. We report a case where acremonium was responsible for causing a cutaneous infection (mycetoma despite antifungal prophylaxis. Treatment with voriconazole was initiated and the infection gradually resolved. This case highlights the need for careful clinical follow-up and thorough investigation of patients who have a neutrophil immunodeficiency.

  9. The role of positive selection in determining the molecular cause of species differences in disease

    Directory of Open Access Journals (Sweden)

    Foord Steven M

    2008-10-01

    Full Text Available Abstract Background Related species, such as humans and chimpanzees, often experience the same disease with varying degrees of pathology, as seen in the cases of Alzheimer's disease, or differing symptomatology as in AIDS. Furthermore, certain diseases such as schizophrenia, epithelial cancers and autoimmune disorders are far more frequent in humans than in other species for reasons not associated with lifestyle. Genes that have undergone positive selection during species evolution are indicative of functional adaptations that drive species differences. Thus we investigate whether biomedical disease differences between species can be attributed to positively selected genes. Results We identified genes that putatively underwent positive selection during the evolution of humans and four mammals which are often used to model human diseases (mouse, rat, chimpanzee and dog. We show that genes predicted to have been subject to positive selection pressure during human evolution are implicated in diseases such as epithelial cancers, schizophrenia, autoimmune diseases and Alzheimer's disease, all of which differ in prevalence and symptomatology between humans and their mammalian relatives. In agreement with previous studies, the chimpanzee lineage was found to have more genes under positive selection than any of the other lineages. In addition, we found new evidence to support the hypothesis that genes that have undergone positive selection tend to interact with each other. This is the first such evidence to be detected widely among mammalian genes and may be important in identifying molecular pathways causative of species differences. Conclusion Our dataset of genes predicted to have been subject to positive selection in five species serves as an informative resource that can be consulted prior to selecting appropriate animal models during drug target validation. We conclude that studying the evolution of functional and biomedical disease differences

  10. The role of positive selection in determining the molecular cause of species differences in disease.

    Science.gov (United States)

    Vamathevan, Jessica J; Hasan, Samiul; Emes, Richard D; Amrine-Madsen, Heather; Rajagopalan, Dilip; Topp, Simon D; Kumar, Vinod; Word, Michael; Simmons, Mark D; Foord, Steven M; Sanseau, Philippe; Yang, Ziheng; Holbrook, Joanna D

    2008-10-06

    Related species, such as humans and chimpanzees, often experience the same disease with varying degrees of pathology, as seen in the cases of Alzheimer's disease, or differing symptomatology as in AIDS. Furthermore, certain diseases such as schizophrenia, epithelial cancers and autoimmune disorders are far more frequent in humans than in other species for reasons not associated with lifestyle. Genes that have undergone positive selection during species evolution are indicative of functional adaptations that drive species differences. Thus we investigate whether biomedical disease differences between species can be attributed to positively selected genes. We identified genes that putatively underwent positive selection during the evolution of humans and four mammals which are often used to model human diseases (mouse, rat, chimpanzee and dog). We show that genes predicted to have been subject to positive selection pressure during human evolution are implicated in diseases such as epithelial cancers, schizophrenia, autoimmune diseases and Alzheimer's disease, all of which differ in prevalence and symptomatology between humans and their mammalian relatives. In agreement with previous studies, the chimpanzee lineage was found to have more genes under positive selection than any of the other lineages. In addition, we found new evidence to support the hypothesis that genes that have undergone positive selection tend to interact with each other. This is the first such evidence to be detected widely among mammalian genes and may be important in identifying molecular pathways causative of species differences. Our dataset of genes predicted to have been subject to positive selection in five species serves as an informative resource that can be consulted prior to selecting appropriate animal models during drug target validation. We conclude that studying the evolution of functional and biomedical disease differences between species is an important way to gain insight into

  11. Physical activity and 10-year mortality from cardiovascular diseases and all causes: The Zutphen Elderly Study.

    Science.gov (United States)

    Bijnen, F C; Caspersen, C J; Feskens, E J; Saris, W H; Mosterd, W L; Kromhout, D

    1998-07-27

    Little is known about physical activity and mortality risk in the elderly. Therefore, we describe the associations between the physical activity pattern of elderly men and the mortality from cardiovascular diseases (CVDs), particularly coronary heart disease (CHD) and stroke, and all causes. Self-reported physical activity was assessed with a validated questionnaire for retired men in a population-based sample of 802 Dutch men, aged 64 to 84 years at baseline. Relative risks were estimated for 10-year mortality from CVD (199 deaths), CHD (90), stroke (47), and all causes (373) for tertiles of time spent on physical activity (reference, lowest tertile). Adjustments were made for baseline age, relevant major chronic diseases, cigarette smoking, and alcohol consumption. Mortality risks from CVD and all causes decreased with increasing physical activity (P for trend = .04) with adjusted relative risks of 0.70 (95% confidence interval, 0.48-1.01) and 0.77 (95% confidence interval, 0.59-1.00) in the highest tertile of total physical activity, respectively. Except for CHD, time spent in more intense activities (> or = 4 kcal/kg per hour) was more strongly associated with all mortality outcomes than less intense activities, but no single type of activity was particularly protective. Walking or cycling at least 3 times per week for 20 minutes (our definition of activity based on general health recommendations) was associated with reduced mortality from CVD (adjusted relative risk, 0.69; 95% confidence interval, 0.50-0.88) and all causes (relative risk, 0.71; 95% confidence interval, 0.58-0.88). Additional adjustment for biological cardiovascular risk factors did not affect the strength of any association. In a general population of elderly men, physical activity may protect against mortality from CVDs and all causes.

  12. Systemic inflammation in dialysis patients with end-stage renal disease: causes and consequences.

    Science.gov (United States)

    Yao, Q; Axelsson, J; Heimburger, O; Stenvinkel, P; Lindholm, B

    2004-09-01

    Despite rapid improvements in dialysis technology during the last 20 years, the mortality rate in end-stage renal disease (ESRD) patients treated with dialysis is still unacceptably high and comparable to that of many cancer patients with metastases. The main cause of the increased mortality in ESRD patients is cardiovascular disease (CVD), which is twice as common and advances at twice the rate already in patients with earlier stages of chronic kidney disease as compared to the general population. Although traditional risk factors are common in dialysis patients, they can only in part explain the very high prevalence of CVD in this patient group. Recent evidence demonstrates that chronic inflammation, a non-traditional risk factor which is a commonly observed in dialysis patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. Available data suggest that pro-inflammatory cytokines play a central role in the genesis of both malnutrition and CVD in ESRD. While the long-term effects of chronic inflammation may be most important in the pathogenesis of CVD, the acute-phase reaction may also be a direct cause of acute vascular injury by several pathogenetic mechanisms. The cause(s) of inflammation in dialysis are multifactorial and include both dialysis-related and unrelated factors. Thus, it could be speculated that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) would improve survival in dialysis patients. As there are currently no established guidelines for the treatment of chronic inflammation in ESRD patients, studies on the long-term effects of various anti-inflammatory treatment strategies on the nutritional and cardiovascular status as well as outcome in this patient group are warranted.

  13. A new early-onset neuromuscular disorder associated with kyphoscoliosis peptidase (KY) deficiency.

    Science.gov (United States)

    Hedberg-Oldfors, Carola; Darin, Niklas; Olsson Engman, Mia; Orfanos, Zacharias; Thomsen, Christer; van der Ven, Peter F M; Oldfors, Anders

    2016-12-01

    We describe a new early-onset neuromuscular disorder due to a homozygous loss-of-function variant in the kyphoscoliosis peptidase gene (KY). A 7.5-year-old girl with walking difficulties from 2 years of age presented with generalized muscle weakness; mild contractures in the shoulders, hips and feet; cavus feet; and lordosis but no scoliosis. She had previously been operated with Achilles tendon elongation. Whole-body MRI showed atrophy and fatty infiltration in the calf muscles. Biopsy of the vastus lateralis muscle showed variability in fiber size, with some internalized nuclei and numerous very small fibers with variable expression of developmental myosin heavy chain isoforms. Some small fibers showed abnormal sarcomeres with thickened Z-discs and small nemaline rods. Whole-exome sequencing revealed a homozygous one-base deletion (c.1071delG, p.(Thr358Leufs*3)) in KY, predicted to result in a truncated protein. Analysis of an RNA panel showed that KY is predominantly expressed in skeletal muscle in humans. A recessive variant in the murine ortholog Ky was previously described in a spontaneously generated mouse mutant with kyphoscoliosis, which developed postnatally and was caused by dystrophy of postural muscles. The abnormal distribution of Xin and Ky-binding partner filamin C in the muscle fibers of our patient was highly similar to their altered localization in ky/ky mouse muscle fibers. We describe the first human case of disease associated with KY inactivation. As in the mouse model, the affected child showed a neuromuscular disorder - but in contrast, no kyphoscoliosis.

  14. Longitudinal epitope mapping in MuSK myasthenia gravis : implications for disease severity

    NARCIS (Netherlands)

    Huijbers, Maartje G.; Vink, Anna-Fleur D.; Niks, Erik H.; Westhuis, Ruben H.; van Zwet, Erik W.; de Meel, Robert H.; Rojas-Garcia, Ricardo; Diaz-Manera, Jordi; Kuks, Jan B.; Klooster, Rinse; Straasheijm, Kirsten; Evoli, Amelia; Illa, Isabel; van der Maarel, Silvere M.; Verschuuren, Jan J.

    2016-01-01

    Muscle weakness in MuSK myasthenia gravis (MG) is caused predominantly by IgG4 antibodies which block MuSK signalling and destabilize neuromuscular junctions. We determined whether the binding pattern of MuSK IgG4 antibodies change throughout the disease course ("epitope spreading"), and affect

  15. Association of TSH Elevation with All-Cause Mortality in Elderly Patients with Chronic Kidney Disease.

    Science.gov (United States)

    Chuang, Mei-Hsing; Liao, Kuo-Meng; Hung, Yao-Min; Chou, Yi-Chang; Chou, Pesus

    2017-01-01

    Chronic kidney disease (CKD) is a widespread condition in the global population and is more common in the elderly. Thyroid-stimulating hormone (TSH) level increases with aging, and hypothyroidism is highly prevalent in CKD patients. However, the relationship between low thyroid function and mortality in CKD patients is unclear. Therefore, we conducted a retrospective cohort study to examine the relationship between TSH elevation and all-cause mortality in elderly patients with CKD. This retrospective cohort study included individuals ≥65 years old with CKD (n = 23,786) in Taipei City. Health examination data from 2005 to 2010 were provided by the Taipei Databank for Public Health Analysis. Subjects were categorized according to thyroid-stimulating hormone (TSH) level as follows: low normal (0.34disease (coronary artery disease, congestive heart failure, cerebral vascular disease), history of cancer, and history of chronic obstructive pulmonary disease. Our results showed that compared to the reference group (middle normal TSH), the risk of all-cause mortality was increased in the elevated I group (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.02-1.45) and elevated II group (HR, 1.30; 95% CI, 1.00-1.69). We found a significant association between TSH elevation and all-cause mortality in this cohort of elderly persons with CKD. However, determining the benefit of treatment for moderately elevated TSH level (5.2-10 mIU/L) in elderly patients with CKD will require a well-designed randomized controlled trial.

  16. Clinical analysis of bloodstream infections caused by Escherichia coli in elderly patients with hepatobiliary disease

    Directory of Open Access Journals (Sweden)

    WANG Qian

    2015-05-01

    Full Text Available ObjectiveTo investigate the clinical characteristics and drug resistance in elderly patients with hepatobiliary disease and bloodstream infections caused by Escherichia coli, and to provide a basis for clinical therapy. MethodsA retrospective analysis was performed on the clinical characteristics and drug susceptibility of 57 elderly inpatients with hepatobiliary disease and bloodstream infections caused by Escherichia coli in our hospital from 2009 to 2012. Comparison of continuous data between the two groups was made by t test, and comparison of categorical data was made by chi-square test. ResultsThe majority of patients had liver cirrhosis, and spontaneous bacterial peritonitis was the major infection source. A total of 57 strains of Escherichia coli were isolated from elderly patients with hepatobiliary disease, and 24 (421% out of them were positive for extended-spectrum β-lactamase (ESBL. ESBL-positive strains had a significantly higher level of drug resistance than ESBL-negative strains (P<0.05, except for imipenem/cilastatin, meropenem, cefoperazone/sulbactum, ticarcillin/clavulanate, and minocycline. However, there were no significant differences in age, gender, basic disease, infection source, peak body temperature, white blood cell count, and the percentage of neutrophils between the ESBL-positive group and the ESBL-negative group (P>0.05. The case-fatality rate in patients with septic shock, hepatic encephalopathy, or acute kidney injury was significantly higher than that in patients with no complications (χ2=9541,7622,9733,respectively, P<0.05. ConclusionElderly patients with hepatobiliary disease and bloodstream infections caused by ESBL-positive Escherichia coli had a high level of drug resistance and a poor prognosis for severe complications. Antibiotic therapy combined with prevention and control of severe complications should be taken as early as possible to reduce the case-fatality rate.

  17. [Electrodiagnosis in disorders of neuromuscular transmission].

    Science.gov (United States)

    Chumillas, M J; Cortés, V

    Electrophysiological studies are of recognized use in the confirmation of alterations of neuromuscular transmission in further determining their physiopathological characteristics, helping to differentiate them from other conditions with secondary effects on their function. In our study we review the physiopathology of these disorders which compromise the safety factor of the neuromuscular junction, by presynaptic or postsynaptic alterations, and forms the basis of the results of electrophysiological studies. We describe the techniques currently most used: repetitive stimulation and single fibre electromyography complemented by conventional electromyography. Their application and findings in the commonest syndromes are discussed. Finally, their sensitivity, specificity and difficulties are considered.

  18. Does infectious disease cause global variation in the frequency of intrastate armed conflict and civil war?

    Science.gov (United States)

    Letendre, Kenneth; Fincher, Corey L; Thornhill, Randy

    2010-08-01

    Geographic and cross-national variation in the frequency of intrastate armed conflict and civil war is a subject of great interest. Previous theory on this variation has focused on the influence on human behaviour of climate, resource competition, national wealth, and cultural characteristics. We present the parasite-stress model of intrastate conflict, which unites previous work on the correlates of intrastate conflict by linking frequency of the outbreak of such conflict, including civil war, to the intensity of infectious disease across countries of the world. High intensity of infectious disease leads to the emergence of xenophobic and ethnocentric cultural norms. These cultures suffer greater poverty and deprivation due to the morbidity and mortality caused by disease, and as a result of decreased investment in public health and welfare. Resource competition among xenophobic and ethnocentric groups within a nation leads to increased frequency of civil war. We present support for the parasite-stress model with regression analyses. We find support for a direct effect of infectious disease on intrastate armed conflict, and support for an indirect effect of infectious disease on the incidence of civil war via its negative effect on national wealth. We consider the entanglements of feedback of conflict into further reduced wealth and increased incidence of disease, and discuss implications for international warfare and global patterns of wealth and imperialism.

  19. Granuloma disease in flocks of productive layers caused by Tetratrichomonas gallinarum.

    Science.gov (United States)

    Landman, W J M; Molenaar, R J; Cian, A; van der Heijden, H M J F; Viscogliosi, E

    2016-08-01

    In 2013, seven outbreaks of granuloma disease occurred in Dutch flocks of productive layers housed on different farms. These outbreaks were characterized by increased mortality and high incidence of granulomas, mainly in caeca (340/408 hens = 83%) and livers (69/408 hens = 17%). Mortality started to increase between 21 and 35 weeks of age and reached 3.7% to 11.0% exceeding the breeder's norm in periods ranging from 9 to 48 weeks. Some flocks also showed decreased egg production and/or loss of mean egg weight. All affected flocks were linked to one rearing farm, which therefore seemed to be the source of the disease. However, no signs of disease had been observed at this rearing farm. Sentinel hens placed in one of the affected flocks to determine whether the disease had an infectious nature developed granulomas identical to those seen in the outbreaks. Next, by fulfilling Koch's postulates it was shown that Tetratrichomonas gallinarum was the aetiological agent of the granuloma disease. The condition was reproduced in mature specified pathogen free White Leghorn hens (GD - Animal Health, Deventer, the Netherlands) by inoculation via both an artificial and a natural route with a well-defined axenic T. gallinarum isolate obtained from one of the affected flocks. Other causes of granuloma disease were excluded.

  20. Effects of Running on Chronic Diseases and Cardiovascular and All-Cause Mortality.

    Science.gov (United States)

    Lavie, Carl J; Lee, Duck-chul; Sui, Xuemei; Arena, Ross; O'Keefe, James H; Church, Timothy S; Milani, Richard V; Blair, Steven N

    2015-11-01

    Considerable evidence has established the link between high levels of physical activity (PA) and all-cause and cardiovascular disease (CVD)-specific mortality. Running is a popular form of vigorous PA that has been associated with better overall survival, but there is debate about the dose-response relationship between running and CVD and all-cause survival. In this review, we specifically reviewed studies published in PubMed since 2000 that included at least 500 runners and 5-year follow-up so as to analyze the relationship between vigorous aerobic PA, specifically running, and major health consequences, especially CVD and all-cause mortality. We also made recommendations on the optimal dose of running associated with protection against CVD and premature mortality, as well as briefly discuss the potential cardiotoxicity of a high dose of aerobic exercise, including running (eg, marathons). Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  1. Pancreatitis in hand-foot-and-mouth disease caused by enterovirus 71.

    Science.gov (United States)

    Zhang, Yu-Feng; Deng, Hui-Ling; Fu, Jia; Zhang, Yu; Wei, Jian-Qiang

    2016-02-14

    Some viruses, including certain members of the enterovirus genus, have been reported to cause pancreatitis, especially Coxsackie virus. However, no case of human enterovirus 71 (EV71) associated with pancreatitis has been reported so far. We here report a case of EV71-induced hand-foot-and-mouth disease (HFMD) presenting with pancreatitis in a 2-year-old girl. This is the first report of a patient with acute pancreatitis in HFMD caused by EV71. We treated the patient conservatively with nasogastric suction, intravenous fluid and antivirals. The patient's symptoms improved after 8 d, and recovered without complications. We conclude that EV71 can cause acute pancreatitis in HFMD, which should be considered in differential diagnosis, especially in cases of idiopathic pancreatitis.

  2. Inflammatory pseudotumor in the liver and right omentum caused by pelvic inflammatory disease: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Hyuk Jun; Kim, Seong Hoon [Dept. of Radiology, Daegu Fatima Hospital, Daegu (Korea, Republic of)

    2015-08-15

    Inflammatory pseudotumor can develop in any part of the human body. It is one of the most important tumor-mimicking lesions that require differential diagnosis. There are various causes of inflammatory pseudotumor, one of which is infection and its resultant inflammation. Pelvic inflammatory disease (PID) often causes perihepatitis, which is called Fitz-Hugh-Curtis syndrome. In Fitz-Hugh-Curtis syndrome, bacteria spread along the right paracolic gutter, causing inflammation of the right upper quadrant peritoneal surfaces and the right lobe of the liver. We experienced a case of PID with accompanying inflammatory pseudotumor in the liver and the right omentum. This case identically correlates with the known intraperitoneal spreading pathway involved in Fitz-Hugh-Curtis syndrome, and hence, we present this case report.

  3. 21 CFR 882.5860 - Implanted neuromuscular stimulator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted neuromuscular stimulator. 882.5860... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5860 Implanted neuromuscular stimulator. (a) Identification. An implanted neuromuscular stimulator is a device that provides...

  4. Traffic air pollution and mortality from cardiovascular disease and all causes: a Danish cohort study.

    Science.gov (United States)

    Raaschou-Nielsen, Ole; Andersen, Zorana Jovanovic; Jensen, Steen Solvang; Ketzel, Matthias; Sørensen, Mette; Hansen, Johnni; Loft, Steffen; Tjønneland, Anne; Overvad, Kim

    2012-09-05

    Traffic air pollution has been linked to cardiovascular mortality, which might be due to co-exposure to road traffic noise. Further, personal and lifestyle characteristics might modify any association. We followed up 52 061 participants in a Danish cohort for mortality in the nationwide Register of Causes of Death, from enrollment in 1993-1997 through 2009, and traced their residential addresses from 1971 onwards in the Central Population Registry. We used dispersion-modelled concentration of nitrogen dioxide (NO₂) since 1971 as indicator of traffic air pollution and used Cox regression models to estimate mortality rate ratios (MRRs) with adjustment for potential confounders. Mean levels of NO₂ at the residence since 1971 were significantly associated with mortality from cardiovascular disease (MRR, 1.26; 95% confidence interval [CI], 1.06-1.51, per doubling of NO₂ concentration) and all causes (MRR, 1.13; 95% CI, 1.04-1.23, per doubling of NO₂ concentration) after adjustment for potential confounders. For participants who ate causes. Traffic air pollution is associated with mortality from cardiovascular diseases and all causes, after adjustment for traffic noise. The association was strongest for people with a low fruit and vegetable intake.

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

    Directory of Open Access Journals (Sweden)

    David B. McGuigan

    2017-07-01

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

  6. Landscape of Pleiotropic Proteins Causing Human Disease: Structural and System Biology Insights.

    Science.gov (United States)

    Ittisoponpisan, Sirawit; Alhuzimi, Eman; Sternberg, Michael J E; David, Alessia

    2017-03-01

    Pleiotropy is the phenomenon by which the same gene can result in multiple phenotypes. Pleiotropic proteins are emerging as important contributors to rare and common disorders. Nevertheless, little is known on the mechanisms underlying pleiotropy and the characteristic of pleiotropic proteins. We analyzed disease-causing proteins reported in UniProt and observed that 12% are pleiotropic (variants in the same protein cause more than one disease). Pleiotropic proteins were enriched in deleterious and rare variants, but not in common variants. Pleiotropic proteins were more likely to be involved in the pathogenesis of neoplasms, neurological, and circulatory diseases and congenital malformations, whereas non-pleiotropic proteins in endocrine and metabolic disorders. Pleiotropic proteins were more essential and had a higher number of interacting partners compared with non-pleiotropic proteins. Significantly more pleiotropic than non-pleiotropic proteins contained at least one intrinsically long disordered region (P human disease. They represent a biologically different class of proteins compared with non-pleiotropic proteins and a better understanding of their characteristics and genetic variants can greatly aid in the interpretation of genetic studies and drug design. © 2016 WILEY PERIODICALS, INC.

  7. An ignored cause of chronic kidney disease in children: type 2 cardiorenal syndrome

    Directory of Open Access Journals (Sweden)

    Engin Melek

    2016-06-01

    Full Text Available Cardiorenal syndrome is a disorder of the heart and kidneys in which acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. It is well known that the main cause of mortality among patients with end-stage renal disease is due to cardiovascular events and a common complication in patients in acute heart failure is a decrease in renal function. However, when there are no signs and/or symptoms of chronic cardiovascular disease, cardiovascular causes in the etiology of chronic kidney disease is not the first differential considered. We present an 11 year-old girl patient, diagnosed with type 2-chronic cardiorenal syndrome who had previously been followed in another center with the diagnosis of chronic kidney disease for six months and referred to our hospital for kidney biopsy. We present this case to increase awareness of pediatrician and nephrologist about this syndrome. [Cukurova Med J 2016; 41(2.000: 393-395

  8. Epidemiology and Control of Strawberry Bacterial Angular Leaf Spot Disease Caused by Xanthomonas fragariae

    Directory of Open Access Journals (Sweden)

    Da-Ran Kim

    2016-08-01

    Full Text Available Strawberry bacterial angular leaf spot (ALS disease, caused by Xanthomonas fragariae has become increasingly problematic in the strawberry agro-industry. ALS causes small angular water-soaked lesions to develop on the abaxial leaf surface. Studies reported optimum temperature conditions for X. fragariae are 20°C and the pathogen suffers mortality above 32°C. However, at the nursery stage, disease symptoms have been observed under high temperature conditions. In the present study, results showed X. fragariae transmission was via infected maternal plants, precipitation, and sprinkler irrigation systems. Systemic infections were detected using X. fragariae specific primers 245A/B and 295A/B, where 300-bp and 615-bp were respectively amplified. During the nursery stage (from May to August, the pathogen was PCR detected only in maternal plants, but not in soil or irrigation water through the nursery stage. During the cultivation period, from September to March, the pathogen was detected in maternal plants, progeny, and soil, but not in water. Additionally, un-infected plants, when planted with infected plants were positive for X. fragariae via PCR at the late cultivation stage. Chemical control for X. fragariae with oxolinic acid showed 87% control effects against the disease during the nursery period, in contrast to validamycin-A, which exhibited increased efficacy against the disease during the cultivation stage (control effect 95%. To our knowledge, this is the first epidemiological study of X. fragariae in Korean strawberry fields.

  9. Disruption of the Hepcidin/Ferroportin Regulatory System Causes Pulmonary Iron Overload and Restrictive Lung Disease

    Directory of Open Access Journals (Sweden)

    Joana Neves

    2017-06-01

    Full Text Available Emerging evidence suggests that pulmonary iron accumulation is implicated in a spectrum of chronic lung diseases. However, the mechanism(s involved in pulmonary iron deposition and its role in the in vivo pathogenesis of lung diseases remains unknown. Here we show that a point mutation in the murine ferroportin gene, which causes hereditary hemochromatosis type 4 (Slc40a1C326S, increases iron levels in alveolar macrophages, epithelial cells lining the conducting airways and lung parenchyma, and in vascular smooth muscle cells. Pulmonary iron overload is associated with oxidative stress, restrictive lung disease with decreased total lung capacity and reduced blood oxygen saturation in homozygous Slc40a1C326S/C326S mice compared to wild-type controls. These findings implicate iron in lung pathology, which is so far not considered a classical iron-related disorder.

  10. How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease : a report of the Surgeon General

    National Research Council Canada - National Science Library

    2010-01-01

    .... This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke...

  11. Influence of local anesthetics on the neuromuscular blockade produced by rocuronium: effects of lidocaine and 50% enantiomeric excess bupivacaine on the neuromuscular junction.

    Science.gov (United States)

    Braga, Angélica de Fátima de Assunção; Carvalho, Vanessa Henriques; Braga, Franklin Sarmento da Silva; Rodrigues-Simioni, Léa; Loyola, Yolanda Christina S; Potério, Glória Braga

    2009-01-01

    The effects of local anesthetics (LA) on neuromuscular transmission and their influence on the neuromuscular blockade produced by competitive neuromuscular blockers have not been fully investigated. The objective of this study was to evaluate, in vitro, the effects of lidocaine and 50% enantiomeric excess bupivacaine (S75-R25) on the neuromuscular blockade produced by rocuronium. The rats were divided in five groups (n = 5) according to the drug used: isolated lidocaine, bupivacaine (S75-R25), or rocuronium (groups I, II, and II); and rocuronium in preparations previously exposed to LAs (groups IV and V). The concentrations used were as follows: 20 microg x mL(-1), 5 microg x mL(-1), and 4 microg x mL(-1) of lidocaine, bupivacaine (S75-R25), and rocuronium, respectively. The following parameters were evaluated: 1) the strength of muscular contraction of the diaphragm to indirect electrical stimulations, before and 60 minutes after the isolated addition of the LAs and rocuronium, and the association AL-rocuronium; and 2) the effects of LAs on membrane potential (MP) and miniature end-plate potentials (MEPP). The effect of LAs on muscle contraction in response to acetylcholine was evaluated in chick biventer cervicis preparations. Isolated lidocaine and bupivacaine (S75-R25) did not change the muscular response and the levels of MPs. In preparations exposed to LAs, rocuroniuminduced blockade was significantly greater than that produced by rocuronium alone. In chick biventer cervicis preparations, lidocaine and bupivacaine (S75R25) decreased contraction in response to acetylcholine. Lidocaine increased the frequency of MEPPs, which was followed by the blockade; bupivacaine (S75R25) caused a reduction in MEPPs followed by blockade. Local anesthetics caused a potentiation of the neuromuscular blockade produced by rocuronium. The results showed pre- and post-synaptic effects.

  12. Fitness, work, and leisure-time physical activity and ischaemic heart disease and all-cause mortality among men with pre-existing cardiovascular disease

    DEFF Research Database (Denmark)

    Holtermann, Andreas; Mortensen, Ole Steen; Burr, Hermann

    2010-01-01

    Our aim was to study the relative impact of physical fitness, physical demands at work, and physical activity during leisure time on ischaemic heart disease (IHD) and all-cause mortality among employed men with pre-existing cardiovascular disease (CVD).......Our aim was to study the relative impact of physical fitness, physical demands at work, and physical activity during leisure time on ischaemic heart disease (IHD) and all-cause mortality among employed men with pre-existing cardiovascular disease (CVD)....

  13. Consensus treatment recommendations for late-onset Pompe disease.

    Science.gov (United States)

    Cupler, Edward J; Berger, Kenneth I; Leshner, Robert T; Wolfe, Gil I; Han, Jay J; Barohn, Richard J; Kissel, John T

    2012-03-01

    Pompe disease is a rare, autosomal recessive disorder caused by deficiency of the glycogen-degrading lysosomal enzyme acid alpha-glucosidase. Late-onset Pompe disease is a multisystem condition, with a heterogeneous clinical presentation that mimics other neuromuscular disorders. Objective is to propose consensus-based treatment and management recommendations for late-onset Pompe disease. A systematic review of the literature by a panel of specialists with expertise in Pompe disease was undertaken. A multidisciplinary team should be involved to properly treat the pulmonary, neuromuscular, orthopedic, and gastrointestinal elements of late-onset Pompe disease. Presymptomatic patients with subtle objective signs of Pompe disease (and patients symptomatic at diagnosis) should begin treatment with enzyme replacement therapy (ERT) immediately; presymptomatic patients without symptoms or signs should be observed without use of ERT. After 1 year of ERT, patients' condition should be reevaluated to determine whether ERT should be continued. Copyright © 2011 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Mehdi Namdar

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

  15. Clinical presentation of invasive disease caused by Neisseria meningitidis serogroup Y in Sweden, 1995 to 2012.

    Science.gov (United States)

    Säll, O; Stenmark, B; Glimåker, M; Jacobsson, S; Mölling, P; Olcén, P; Fredlund, H

    2017-07-01

    Over the period 1995-2012, the incidence of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup Y (NmY) increased significantly in Sweden. This is mainly due to the emergence of a predominant cluster named strain type YI subtype 1, belonging to the ST-23 clonal complex (cc). The aim of this study was to examine the clinical picture of patients with invasive disease caused by NmY and to analyse whether the predominant cluster exhibits certain clinical characteristics that might explain the increased incidence. In this retrospective observational study, the medical records available from patients with IMD caused by Nm serogroup Y in Sweden between 1995 and 2012 were systematically reviewed. Patient characteristics, in-hospital findings and outcome were studied and differences between the dominating cluster and other isolates were analysed. Medical records from 175 of 191 patients were retrieved. The median age was 62 years. The all-cause mortality within 30 days of admission was 9% (15/175) in the whole material; 4% (2/54) in the cohort with strain type YI subtype 1 and 11% (12/121) among patients with other isolates. Thirty-three per cent of the patients were diagnosed with meningitis, 19% with pneumonia, 10% with arthritis and 35% were found to have bacteraemia but no apparent organ manifestation. This survey included cases with an aggressive clinical course as well as cases with a relatively mild clinical presentation. There was a trend towards lower mortality and less-severe disease in the cohort with strain type YI subtype 1 compared with the group with other isolates.

  16. Effective pre-hospital care for out-of-hospital cardiac arrest caused by respiratory disease.

    Science.gov (United States)

    Fukuda, Tatsuma; Fukuda-Ohashi, Naoko; Doi, Kent; Matsubara, Takehiro; Yahagi, Naoki

    2015-03-01

    The relationship between pre-hospital care and the prognosis of out-of-hospital cardiac arrest (OHCA) caused by respiratory disease is unclear. This study aimed to assess the impact of pre-hospital care on the prognosis of OHCA caused by respiratory disease. In a nationwide, population-based, observational study, we enrolled 121,081 adults aged ≥18 years who experienced OHCA from January 1, 2010, to December 31, 2010. The primary endpoint was favourable neurological outcomes. Of the 120,256 eligible adult OHCA patients, 7,071 (5.9%) experienced OHCA caused by respiratory disease. Of these 7,071 patients, 3,911 (55.3%) received no cardiopulmonary resuscitation (CPR), 2,403 (34.0%) received chest-compression-only CPR, and 757 (10.7%) received conventional CPR by a bystander. There was no significant difference between the three types of bystander CPR with regard to the neurological outcome (no CPR: OR 0.68, 95%CI 0.39-1.24, p=0.1951; chest-compression-only CPR: OR 0.68, 95%CI 0.37-1.29, p=0.2295; and conventional CPR: as a reference). Pre-hospital administration of epinephrine (OR 0.37, 95%CI 0.13-0.85, p=0.0170) and the implementation of advanced airway management (OR 0.32, 95%CI 0.19-0.52, prespiratory disease, not only pre-hospital epinephrine administration but also pre-hospital advanced airway management and rescue breathing in bystander CPR may not be critical. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  17. Inflammatory, autoimmune, chronic diseases: bad diet and physical inactivity are causes or effects?

    Science.gov (United States)

    Gracia, M C

    2006-01-01

    It is now well established that most chronic diseases, especially those identified as inflammatory, are statistically correlated with some typical dietary excesses and physical inactivity. But do really these habits cause the diseases, or they result from them? Current opinion favours the first option, but fails to explain why the satisfaction of eating, naturally evolved in our brains to produce health, apparently induces countless millions of people to eat unrestrictedly until becoming mortally sick, whereas trying to keep a theoretically healthy diet is most often a real torture. The inverse explanation makes much more sense: since inflammation produces much heat, calorie-rich diets are required. An inflamed digestive tract lacks digestive power and is easily irritated or damaged by solid objects, therefore requiring a refined, concentrated, low-fibre diet. And inflamed or merely sick organisms are easily exhausted by physical effort, hence physical inactivity. This study confirms that, most probably, the primary causes of inflammatory diseases are always external inflammatory agents, like infectious micro-organisms or toxic substances, of which a particularly ubiquitous example is nicotine. High-calorie/low-fibre diets and physical inactivity are direct consequences of generalised inflammation. Inversely, in most cases, physical exercise and moderation in eating, by themselves, cannot substantially suppress inflammations, but they can prevent them from being further reinforced by the neural reward system. Moreover, diets and exercise causing important suffering will usually do more harm than good, especially to children and young people, not to mention pregnant or nursing women. Only the identification and elimination of the inflammatory agents can efficiently prevent and cure inflammatory diseases, and currently nicotine, absorbed intentionally or passively, from tobacco or other sources, must be considered the chief suspect because of its inflammatory power

  18. Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning

    DEFF Research Database (Denmark)

    Thomsen, Jakob Louis Demant; Mathiesen, Ole; Hägi-Pedersen, Daniel

    2017-01-01

    . A neuromuscular monitoring e-learning module might support consistent use of neuromuscular monitoring devices. OBJECTIVE: The aim of the study is to assess the effect of a neuromuscular monitoring e-learning module on anesthesia staff's use of objective neuromuscular monitoring and the incidence of residual...... as well as a multiple-choice test to assess knowledge. The e-learning module was developed based on a needs assessment process, including focus group interviews, surveys, and expert opinions. RESULTS: The e-learning module was implemented in 6 anesthesia departments on 21 November 2016. Currently, we...... are collecting postintervention data. The final dataset will include data from more than 10,000 anesthesia procedures. We expect to publish the results in late 2017 or early 2018. CONCLUSIONS: With a dataset consisting of thousands of general anesthesia procedures, the INVERT study will assess whether an e-learning...

  19. A novel prediction model for all cause emergency department visits in ischemic heart disease

    Directory of Open Access Journals (Sweden)

    Bahram Pishgoo

    2011-01-01

    Full Text Available Background: Ischemic heart disease (IHD is the main cause of morbidity and mortality worldwide, and a considerable part of these patients attend to emergency departments, which increases the burden to these busy departments. The aim of this study was to develop a prediction model enabling prediction of all cause emergency department (ED visits in patients with documented coronary stenosis in a derivation set, and then to determine its accuracy in a validation set. Methods: In a prospective study at outpatient setting of Baqiyatallah hospital, Tehran, Iran, 502 patients with IHD were followed for 6 months for observing the outcome of ED visits for all causes. They were divided in two random groups of derivation set (n = 335 and validation set (n = 167. In the derivation set, to achieve an all cause ED visits prediction model, a prediction model was reached by entering demographic data, clinical variables, somatic comorbidity (Ifudu index, level of anxiety and depression (Hospital Anxiety Depression Scale (HADS questionnaire, and angina grade (WHO Rose Angina to a logistic regression. Then in the validation set, the sensitivity, specificity, and the accuracy of that model was tested. Results: A novel model for prediction of all cause ED visits in IHD patients in six months was presented with gender, anxiety, WHO angina grade and somatic comorbidity as inputs. Sensitivity, specificity, and accuracy of the model were 63.0%, 68.6%, and 67.7%, respectively. Conclusions: Testing and using the achieved model is suggested to health care providers in other settings.

  20. Comorbidities That Cause Pain and the Contributors to Pain in Individuals With Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Chen, Yi-Wen; Camp, Pat G; Coxson, Harvey O; Road, Jeremy D; Guenette, Jordan A; Hunt, Michael A; Reid, W Darlene

    2017-08-01

    To determine comorbidities that cause pain and the potential contributors to pain in individuals with chronic obstructive pulmonary disease (COPD). Prospective cross-sectional survey study. Pulmonary rehabilitation programs of 6 centers. A convenience sample of individuals with COPD (N=137) who attended pulmonary rehabilitation programs. In total, 100 (73%) returned the survey packages. Of those responders, 96 participants (70%) were included in the analyses. Not applicable. Pain was measured using the Brief Pain Inventory. The questionnaire used to obtain information about health conditions that might contribute to pain and a medication record asked, in lay terms, about comorbidities that cause pain. The health conditions that cause pain were then validated by health professionals. Demographics, fatigue, dyspnea, quality of life, and self-efficacy were also measured using questionnaires. Pain was reported in 71% (68/96) of participants. Low back pain was the most common location (41%). Arthritis (75%), back problems (47%), and muscle cramps (46%) were the most common comorbidities that caused pain. Lower self-efficacy, and renting rather than home ownership increased the likelihood of pain (Pprevalent in pulmonary rehabilitation program participants with COPD. The most common causes of pain were musculoskeletal conditions. Pain severity and higher levels of fatigue contributed to how pain interfered with daily aspects of living. The assessment and management of pain need to be addressed within the overall care of individuals with COPD. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  1. Prevalence and causes of abnormal liver function in patients with coeliac disease.

    Science.gov (United States)

    Casella, Giovanni; Antonelli, Elisabetta; Di Bella, Camillo; Villanacci, Vincenzo; Fanini, Lucia; Baldini, Vittorio; Bassotti, Gabrio

    2013-08-01

    Coeliac disease patients frequently display mild elevation of liver enzymes and this abnormality usually normalizes after gluten-free diet. To investigate the cause and prevalence of altered liver function tests in coeliac patients, basally and after 1 year of gluten-free diet. Data from 245 untreated CD patients (196 women and 49 men, age range 15-80 years) were retrospectively analysed and the liver function tests before and after diet, as well as associated liver pathologies, were assessed. Overall, 43/245 (17.5%) patients had elevated values of one or both aminotransferases; the elevation was mild (10 times the upper reference limit) in the remaining 2 (5%) patients. After 1 year of gluten-free diet, aminotransferase levels normalized in all but four patients with HCV infection or primary biliary cirrhosis. In coeliac patients, hypertransaminaseaemia at diagnosis and the lack of normalization of liver enzymes after 12 months of diet suggest coexisting liver disease. In such instance, further evaluation is recommended to exclude the liver disease. Early recognition and treatment of coeliac disease in patients affected by liver disease are important to improve the liver function and prevent complications. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Non-Alcoholic Fatty Liver Disease: Cause or Effect of Metabolic Syndrome.

    Science.gov (United States)

    Grander, Christoph; Grabherr, Felix; Moschen, Alexander R; Tilg, Herbert

    2016-10-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease throughout the world. Pathophysiological insights into this disease have recently illustrated that various factors such as insulin resistance, innate immunity, metabolic inflammation, and the microbiota are of relevance. NAFLD, metabolic syndrome (MS), and type 2 diabetes (T2D) share many pathophysiological aspects, and inflammatory processes in the adipose tissue, gut, and liver have evolved to be of exceptional importance. Most of NAFLD patients are obese and encounter a high risk of developing MS and T2D. NAFLD, however, is also highly common in subjects with MS and T2D. Furthermore, reflecting its nature of a multisystem disease, NAFLD is associated with a high prevalence and incidence of cardiovascular and chronic kidney disease. These facts require screening strategies for MS/T2D in NAFLD patients and vice versa. Thus, the question of cause or effect cannot be answered as MS and NAFLD share many pathomechanisms, and at the time of either diagnosis both frequently coexist. This is also reflected by a global prevalence rate of 25% for both NAFLD and MS. For this reason, it is crucial that physicians are aware of the 'unholy liaison' between MS, T2D, and NAFLD.

  3. An overall estimation of losses caused by diseases in the Brazilian fish farms.

    Science.gov (United States)

    Tavares-Dias, Marcos; Martins, Maurício Laterça

    2017-12-01

    Parasitic and infectious diseases are common in finfish, but are difficult to accurately estimate the economic impacts on the production in a country with large dimensions like Brazil. The aim of this study was to estimate the costs caused by economic losses of finfish due to mortality by diseases in Brazil. A model for estimating the costs related to parasitic and bacterial diseases in farmed fish and an estimative of these economic impacts are presented. We used official data of production and mortality of finfish for rough estimation of economic losses. The losses herein presented are related to direct and indirect economic costs for freshwater farmed fish, which were estimated in US$ 84 million per year. Finally, it was possible to establish by the first time an estimative of overall losses in finfish production in Brazil using data available from production. Therefore, this current estimative must help researchers and policy makers to approximate the economic costs of diseases for fish farming industry, as well as for developing of public policies on the control measures of diseases and priority research lines.

  4. Possibility of biological control of primocane fruiting raspberry disease caused by Fusarium sambucinum.

    Science.gov (United States)

    Shternshis, Margarita V; Belyaev, Anatoly A; Matchenko, Nina S; Shpatova, Tatyana V; Lelyak, Anastasya A

    2015-10-01

    Biological control agents are a promising alternative to chemical pesticides for plant disease suppression. The main advantage of the natural biocontrol agents, such as antagonistic bacteria compared with chemicals, includes environmental pollution prevention and a decrease of chemical residues in fruits. This study is aimed to evaluate the impact of three Bacillus strains on disease of primocane fruiting raspberry canes caused by Fusarium sambucinum under controlled infection load and uncontrolled environmental factors. Bacillus subtilis, Bacillus licheniformis, and Bacillus amyloliquefaciens were used for biocontrol of plant disease in 2013 and 2014 which differed by environmental conditions. The test suspensions were 10(5) CFU/ml for each bacterial strain. To estimate the effect of biological agents on Fusarium disease, canes were cut at the end of vegetation, and the area of outer and internal lesions was measured. In addition to antagonistic effect, the strains revealed the ability to induce plant resistance comparable with chitosan-based formulation. Under variable ways of cane treatment by bacterial strains, the more effective were B. subtilis and B. licheniformis demonstrating dual biocontrol effect. However, environmental factors were shown to impact the strain biocontrol ability; changes in air temperature and humidity led to the enhanced activity of B. amyloliquefaciens. For the first time, the possibility of replacing chemicals with environmentally benign biological agents for ecologically safe control of the raspberry primocane fruiting disease was shown.

  5. Association of coffee consumption with all-cause and cardiovascular disease mortality

    Science.gov (United States)

    Liu, Junxiu; Sui, Xuemei; Lavie, Carl J.; Hebert, James R.; Earnest, Conrad; Zhang, Jiajia; Blair, Steven N.

    2013-01-01

    Objective To evaluate the association between coffee consumption and mortality from all causes and cardiovascular disease (CVD). Patients and Methods Data from the Aerobics Center Longitudinal Study (ACLS) representing a total of 43,727 participants contributing to 699,632 person-years of follow-up time, were included. Baseline data were collected by an in-person interview based on standardized questionnaires and a medical examination, including fasting blood chemistry analysis, anthropometry, blood pressure, electrocardiography, and a maximal graded exercise test, between February 3, 1971 and December 30, 2002. Cox regression analysis was used to quantify the association between coffee consumption and all-cause and cause-specific mortality. Results During the 17-year median follow-up period, 2512 deaths occurred (32% due to CVD). In multivariate analyses, coffee intake was positively associated with all-cause mortality in men. Men who drank >28 cups coffee per week had higher all-cause mortality (hazard ratio (HR): 1.21; 95% confidence interval (CI): 1.04–1.40). However, after stratification based on age, both younger (coffee consumption (>28 cups/week) and all-cause mortality, after adjusting for potential confounders and fitness level (HR: 1.56; 95% CI: 1.30–1.87 for men and HR: 2.13; 95% CI: 1.26–3.59 for women, respectively). Conclusion In this large cohort, a positive association between coffee consumption and all-cause mortality was observed among men and both men and women coffee consumption (ie, averaging >4 cups/day). However, this finding should be assessed in future studies from other populations. PMID:23953850

  6. Postoperative neuromuscular function following non-depolarising ...

    African Journals Online (AJOL)

    2016-07-03

    Jul 3, 2016 ... speaking, difficulty swallowing, unsteady gait and sensations of fatigue and muscle weakness.8,10,24–26 These newer studies have resulted in a recovery to a TOF of 0.9 or greater prior to extubation becoming widely adopted as a standard of anaesthetic practice following non-depolarising neuromuscular ...

  7. Neuromuscular dysfunction associated with delayed weaning from ...

    African Journals Online (AJOL)

    Yehia Khalil

    2012-03-21

    Mar 21, 2012 ... Neuromuscular dysfunction associated with delayed weaning from mechanical ventilation in patients with respiratory failure. Yehia Khalil a. , Emad El Din Mustafa a. , Ahmed Youssef a. ,. Mohamed Hassan Imam b,. *, Amni Fathy El Behiry a a Department of Chest, Faculty of Medicine, Alexandria University, ...

  8. Opinions in Denmark on the causes of peptic ulcer disease. A survey among Danish physicians and patients

    DEFF Research Database (Denmark)

    Christensen, A H; Gjørup, T; Andersen, I B

    1994-01-01

    stated more causes than did their male colleagues (p anxiety, and stress, were contributory causes of peptic ulcer disease, whereas only around 40% believed that coffee/tea, alcohol, smoking, side effects......The aim of the study was to investigate opinions among Danish patients and physicians on causes of peptic ulcer disease. Fifty-nine patients with an ulcer history and 77 physicians with a special interest in gastroenterology participated. They were given a questionnaire listing 16 possible causes...... of peptic ulcer and indicated for each whether they believed it was a contributory cause of the disease. The patients stated 0-10 causes each (median, 4), and the physicians 3-12 causes (median, 6) (p causes than did the older ones (p

  9. Citrus leprosis virus N: A New Dichorhavirus Causing Citrus Leprosis Disease.

    Science.gov (United States)

    Ramos-González, Pedro Luis; Chabi-Jesus, Camila; Guerra-Peraza, Orlene; Tassi, Aline Daniele; Kitajima, Elliot Watanabe; Harakava, Ricardo; Salaroli, Renato Barbosa; Freitas-Astúa, Juliana

    2017-08-01

    Citrus leprosis (CL) is a viral disease endemic to the Western Hemisphere that produces local necrotic and chlorotic lesions on leaves, branches, and fruit and causes serious yield reduction in citrus orchards. Samples of sweet orange (Citrus × sinensis) trees showing CL symptoms were collected during a survey in noncommercial citrus areas in the southeast region of Brazil in 2013 to 2016. Transmission electron microscopy analyses of foliar lesions confirmed the presence of rod-like viral particles commonly associated with CL in the nucleus and cytoplasm of infected cells. However, every attempt to identify these particles by reverse-transcription polymerase chain reaction tests failed, even though all described primers for the detection of known CL-causing cileviruses and dichorhaviruses were used. Next-generation sequencing of total RNA extracts from three symptomatic samples revealed the genome of distinct, although highly related (>92% nucleotide sequence identity), viruses whose genetic organization is similar to that of dichorhaviruses. The genome sequence of these viruses showed citrus trees and those used for the transmission of one of the characterized isolates to Arabidopsis plants were anatomically recognized as Brevipalpus phoenicis sensu stricto. Molecular and biological features indicate that the identified viruses belong to a new species of CL-associated dichorhavirus, which we propose to call Citrus leprosis N dichorhavirus. Our results, while emphasizing the increasing diversity of viruses causing CL disease, lead to a reevaluation of the nomenclature of those viruses assigned to the genus Dichorhavirus. In this regard, a comprehensive discussion is presented.

  10. Structural and functional analyses of disease-causing missense mutations in Bloom syndrome protein.

    Science.gov (United States)

    Guo, Rong-Bing; Rigolet, Pascal; Ren, Hua; Zhang, Bo; Zhang, Xing-Dong; Dou, Shuo-Xing; Wang, Peng-Ye; Amor-Gueret, Mounira; Xi, Xu Guang

    2007-01-01

    Bloom syndrome (BS) is an autosomal recessive disorder characterized by genomic instability and the early development of many types of cancer. Missense mutations have been identified in the BLM gene (encoding a RecQ helicase) in affected individuals, but the molecular mechanism and the structural basis of the effects of these mutations remain to be elucidated. We analysed five disease-causing missense mutations that are localized in the BLM helicase core region: Q672R, I841T, C878R, G891E and C901Y. The disease-causing mutants had low ATPase and helicase activities but their ATP binding abilities were normal, except for Q672, whose ATP binding activity was lower than that of the intact BLM helicase. Mutants C878R, mapping near motif IV, and G891E and C901Y, mapping in motif IV, displayed severe DNA-binding defects. We used molecular modelling to analyse these mutations. Our work provides insights into the molecular basis of BLM pathology, and reveals structural elements implicated in coupling DNA binding to ATP hydrolysis and DNA unwinding. Our findings will help to explain the mechanism underlying BLM catalysis and interpreting new BLM causing mutations identified in the future.

  11. Helicobacter pylori: types of diseases, diagnosis, treatment and causes of therapeutic failure

    Directory of Open Access Journals (Sweden)

    Cosmin Vasile Obleaga

    2016-10-01

    Full Text Available Acute upper gastrointestinal lesions have a multifactorial etiology but, regardless of the cause, they are related to mucosal barrier destruction. Since Helicobacter pylori induces a superficial chronic gastritis with the infiltration of neutrophils in the mucosa, it was speculated that Helicobacter pylori infection could also cause bleeding lesions. The diagnosis, the proper treatment and the revaluation of its effectiveness actually represent the prophylaxis of some diseases such as peptic ulcer, gastric lymphoma or mucosa-associated lymphoid tissue (MALT and gastric cancer. These diseases and their severe complications are life-threatening for the patient. Periodic renewal of the treatment and knowing the real causes of Helicobacter pylori resistance to various antibiotics must always be understood by the clinician. Although Helicobacter pylori treatment fails in about 20% of cases, moral support of the patient by the clinician, information about possible evolutional complications of Helicobacter pylori infection, and periodic evaluation of the patient during therapy, are important tools on which the therapeutic success depends.

  12. Traffic air pollution and mortality from cardiovascular disease and all causes: a Danish cohort study

    Directory of Open Access Journals (Sweden)

    Raaschou-Nielsen Ole

    2012-09-01

    Full Text Available Abstract Background Traffic air pollution has been linked to cardiovascular mortality, which might be due to co-exposure to road traffic noise. Further, personal and lifestyle characteristics might modify any association. Methods We followed up 52 061 participants in a Danish cohort for mortality in the nationwide Register of Causes of Death, from enrollment in 1993–1997 through 2009, and traced their residential addresses from 1971 onwards in the Central Population Registry. We used dispersion-modelled concentration of nitrogen dioxide (NO2 since 1971 as indicator of traffic air pollution and used Cox regression models to estimate mortality rate ratios (MRRs with adjustment for potential confounders. Results Mean levels of NO2 at the residence since 1971 were significantly associated with mortality from cardiovascular disease (MRR, 1.26; 95% confidence interval [CI], 1.06–1.51, per doubling of NO2 concentration and all causes (MRR, 1.13; 95% CI, 1.04–1.23, per doubling of NO2 concentration after adjustment for potential confounders. For participants who ate  Conclusions Traffic air pollution is associated with mortality from cardiovascular diseases and all causes, after adjustment for traffic noise. The association was strongest for people with a low fruit and vegetable intake.

  13. Structural consequences of amino acid substitutions causing Tay-Sachs disease.

    Science.gov (United States)

    Ohno, Kazuki; Saito, Seiji; Sugawara, Kanako; Sakuraba, Hitoshi

    2008-08-01

    To determine the structural changes in the alpha-subunit of beta-hexosaminidase due to amino acid substitutions causing Tay-Sachs disease, we built structural models of mutant alpha-subunits resulting from 33 missense mutations (24 infantile and 9 late-onset), and analyzed the influence of each amino acid replacement on the structure by calculating the number of atoms affected and determining the solvent-accessible surface area of the corresponding amino acid residue in the wild-type alpha-subunit. In the infantile Tay-Sachs group, the number of atoms influenced by a mutation was generally larger than that in the late-onset Tay-Sachs group in both the main chain and the side chain, and residues associated with the mutations found in the infantile Tay-Sachs group tended to be less solvent-accessible than those in the late-onset Tay-Sachs group. Furthermore, color imaging determined the distribution and degree of the structural changes caused by representative amino acid substitutions, and that there were also differences between the infantile and late-onset Tay-Sachs disease groups. Structural study is useful for elucidating the basis of Tay-Sachs disease.

  14. Structure and Dynamics of RNA Repeat Expansions That Cause Huntington's Disease and Myotonic Dystrophy Type 1.

    Science.gov (United States)

    Chen, Jonathan L; VanEtten, Damian M; Fountain, Matthew A; Yildirim, Ilyas; Disney, Matthew D

    2017-07-11

    RNA repeat expansions cause a host of incurable, genetically defined diseases. The most common class of RNA repeats consists of trinucleotide repeats. These long, repeating transcripts fold into hairpins containing 1 × 1 internal loops that can mediate disease via a variety of mechanism(s) in which RNA is the central player. Two of these disorders are Huntington's disease and myotonic dystrophy type 1, which are caused by r(CAG) and r(CUG) repeats, respectively. We report the structures of two RNA constructs containing three copies of a r(CAG) [r(3×CAG)] or r(CUG) [r(3×CUG)] motif that were modeled with nuclear magnetic resonance spectroscopy and simulated annealing with restrained molecular dynamics. The 1 × 1 internal loops of r(3×CAG) are stabilized by one-hydrogen bond (cis Watson-Crick/Watson-Crick) AA pairs, while those of r(3×CUG) prefer one- or two-hydrogen bond (cis Watson-Crick/Watson-Crick) UU pairs. Assigned chemical shifts for the residues depended on the identity of neighbors or next nearest neighbors. Additional insights into the dynamics of these RNA constructs were gained by molecular dynamics simulations and a discrete path sampling method. Results indicate that the global structures of the RNA are A-form and that the loop regions are dynamic. The results will be useful for understanding the dynamic trajectory of these RNA repeats but also may aid in the development of therapeutics.

  15. Alcohol, cardiovascular diseases and all causes of death: a review of the epidemiological evidence.

    Science.gov (United States)

    Beaglehole, R; Jackson, R

    1992-01-01

    This paper reviews the epidemiological evidence on the association of alcohol consumption with the major cardiovascular diseases (hypertension, stroke and coronary heart disease), and all causes of death. The focus is on light and moderate consumption and several important methodological issues are apparent with the epidemiological evidence on alcohol and mortality. The epidemiological data justify the following recommendations on alcohol consumption. The evidence does not support the unqualified claim that light and moderate drinking confers overall health benefits. However, in persons over 35 years of age, there is no consistent evidence that daily consumption of up to 2-3 drinks in men or up to 1-2 drinks in women increases the risk of dying. Non-drinkers should not be encouraged to change their drinking status. The consumption of more than 2-3 drinks per day in men and more than 1-2 drinks per day in women should be actively discouraged. Further research on the effects of light and moderate alcohol consumption on cardiovascular disease and all causes of death are required, particularly in young people, women and the elderly.

  16. Novel COL4A1 mutations cause cerebral small vessel disease by haploinsufficiency

    Science.gov (United States)

    Lemmens, Robin; Maugeri, Alessandra; Niessen, Hans W. M.; Goris, An; Tousseyn, Thomas; Demaerel, Philippe; Corveleyn, Anniek; Robberecht, Wim; van der Knaap, Marjo S.; Thijs, Vincent N.; Zwijnenburg, Petra J.G.

    2013-01-01

    Mutations in COL4A1 have been identified in families with hereditary small vessel disease of the brain presumably due to a dominant-negative mechanism. Here, we report on two novel mutations in COL4A1 in two families with porencephaly, intracerebral hemorrhage and severe white matter disease caused by haploinsufficiency. Two families with various clinical presentations of cerebral microangiopathy and autosomal dominant inheritance were examined. Clinical, neuroradiological and genetic investigations were performed. Electron microscopy of the skin was also performed. In one of the families, sequence analysis revealed a one base deletion, c.2085del, leading to a frameshift and a premature stopcodon, p.(Gly696fs). In the other family, a splice site mutation was identified, c.2194-1G>A, which most likely leads to skipping of an exon with a frameshift and premature termination as a result. In fibroblasts of affected individuals from both the families, nonsense-mediated decay (NMD) of the mutant COL4A1 messenger RNAs (mRNAs) and a clear reduction of COL4A1 protein expression were demonstrated, indicating haploinsufficiency of COL4A1. Moreover, thickening of the capillary basement membrane in the skin was documented, similar to reports in patients with COL4A1 missense mutations. These findings suggest haploinsufficiency, a different mechanism from the commonly assumed dominant-negative effect, for COL4A1 mutations as a cause of (antenatal) intracerebral hemorrhage and white matter disease. PMID:23065703

  17. Hemolytic disease of the fetus and newborn caused by anti-E

    Directory of Open Access Journals (Sweden)

    Adiyyatu Sa′idu Usman

    2013-01-01

    Full Text Available Objective: Maternal allo-antibody production is stimulated when fetal red blood cells are positive for an antigen absent on the mother′s red cells. The maternal IgG antibodies produced will pass through the placenta and attack fetal red cells carrying the corresponding antigen. Allo-immune hemolytic disease of the fetus and newborn caused by anti-E rarely occurs. Case summary: We report two cases of anti-E hemolytic diseases in neonates. One of the neonates had severe hemolysis presenting with severe anemia, thrombocytopenia, and conjugated hyperbilirubinemia, while the other had moderate anemia and unconjugated hyperbilrubinemia. Although both the neonates were treated by phototherapy and intravenous immunoglobulin, one of them received double volume exchange transfusion. Conclusion: There appeared to be an increase in the occurrence of hemolytic disease of the fetus and newborn caused by Rh antibodies other than anti-D. In this case report, both patients presented with anemia and hyperbilirubinemia but were successfully treated, with a favorable outcome.

  18. Two Novel De Novo GARS Mutations Cause Early-Onset Axonal Charcot-Marie-Tooth Disease.

    Directory of Open Access Journals (Sweden)

    Yi-Chu Liao

    Full Text Available Mutations in the GARS gene have been identified in a small number of patients with Charcot-Marie-Tooth disease (CMT type 2D or distal spinal muscular atrophy type V, for whom disease onset typically occurs during adolescence or young adulthood, initially manifesting as weakness and atrophy of the hand muscles. The role of GARS mutations in patients with inherited neuropathies in Taiwan remains elusive.Mutational analyses of the coding regions of GARS were performed using targeted sequencing of 54 patients with molecularly unassigned axonal CMT, who were selected from 340 unrelated CMT patients. Two heterozygous mutations in GARS, p.Asp146Tyr and p.Met238Arg, were identified; one in each patient. Both are novel de novo mutations. The p.Asp146Tyr mutation is associated with a severe infantile-onset neuropathy and the p.Met238Arg mutation results in childhood-onset disability.GARS mutations are an uncommon cause of CMT in Taiwan. The p.Asp146Tyr and p.Met238Arg mutations are associated with early-onset axonal CMT. These findings broaden the mutational spectrum of GARS and also highlight the importance of considering GARS mutations as a disease cause in patients with early-onset neuropathies.

  19. [Causes, diagnostics and course of disease in 194 cats with anemia].

    Science.gov (United States)

    Merten, Nina; Weingart, Christiane; Kohn, Barbara

    2015-01-01

    Anemia is a common hematological alteration in cats. The objective of this study was to evaluate the frequency of different types of anemia and the course of disease in cats with a hematocrit (hct) anemia groups based on history, physical examination and laboratory parameters. Most cats had acute blood loss anemia (BA; 75/194; 38.7%). Frequent causes were trauma (39/75), hematuria (13/75) and hemostatic disorders (9/75). Anemia of inflammatory and neoplastic disease (AID) occurred in 22.2% (43/194) and hemolytic anemia (HA) in 18% (35/194). Half of those were presumptively immune-mediated (IHA). Four cats were diagnosed with hemotropic mycoplasma infection. Rare causes of anemia included anemia of renal disease (ARD; 18/194; 9.3%) and intramedullary non-regenerative anemia (INR; 13/194; 6.7%). The latter either had retroviral infection (6/13) or neoplasia (6/13). In cats with HA and INR anemia was often severe and very severe (Hct anemia was detected for the first time. Cats with HA had the highest survival rate.

  20. Viral competition and maternal immunity influence the clinical disease caused by very virulent infectious bursal disease virus.

    Science.gov (United States)

    Jackwood, Daral J

    2011-09-01

    The very virulent form of infectious bursal disease virus (vvIBDV) causes an immunosuppressive disease that is further characterized by the rapid onset of morbidity and high mortality in susceptible chickens. In 2009, vvIBDV was first reported in California, U. S. A., and since that time only a few cases of acute infectious bursal disease attributed to vvIBDV have been recognized in California. In other countries where vvIBDV has become established, it rapidly spreads to most poultry-producing regions. Two factors that may be involved in limiting the spread or reducing the severity of the clinical disease caused by vvIBDV in the U. S. A. are maternal immunity and competition with endemic variant strains of the virus. In this study, the ability of vvIBDV to infect and cause disease in maternally immune layer chickens was examined at weekly intervals over a 5-wk period during which their neutralizing maternal antibodies waned. Birds inoculated with vvIBDV at 2, 3, and 4 wk of age seemed healthy throughout the duration of the experiment, but macroscopic and microscopic lesions were observed in their bursa tissues. A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay also confirmed the presence of vvIBDV RNA in their bursa tissues, indicating this virus was infecting the birds even at 2 wk of age when neutralizing maternal antibodies to infectious bursal disease virus were still relatively high (> 2000 geometric mean antibody titer). No mortality was observed in any birds when inoculated at 2, 3, or 4 wk of age; however, inoculation at 5 and 6 wk of age resulted in 10% and 20% mortality, respectively. Three experiments on the competition between vvIBDV and the two variant viruses T1 and FF6 were conducted. In all three experiments, specific-pathogen-free (SPF) birds that were inoculated with only the vvIBDV became acutely moribund, and except for Experiment 1 (62% mortality) all succumbed to the infection within 4 days of being exposed. When the

  1. The role of neuromuscular changes in aging and knee osteoarthritis on dynamic postural control.

    Science.gov (United States)

    Takacs, Judit; Carpenter, Mark G; Garland, S Jayne; Hunt, Michael A

    2013-04-01

    Knee osteoarthritis (OA) is a chronic joint condition, with 30% of those over the age of 75 exhibiting severe radiographic disease. Nearly 50% of those with knee OA have experienced a fall in the past year. Falls are a considerable public health concern, with a high risk of serious injury and a significant socioeconomic impact. The ability to defend against a fall relies on adequate dynamic postural control, and alterations in dynamic postural control are seen with normal aging. Neuromuscular changes associated with aging may be responsible for some of these alterations in dynamic postural control. Even greater neuromuscular deficits, which may impact dynamic postural control and the ability to defend against a fall, are seen in people with knee OA. There is little evidence to date on how knee OA affects the ability to respond to and defend against falls and the neuromuscular changes that contribute to balance deficits. As a result, this review will: summarize the key characteristics of postural responses to an external perturbation, highlight the changes in dynamic postural control seen with normal aging, review the neuromuscular changes associated with aging that have known and possible effects on dynamic postural control, and summarize the neuromuscular changes and balance problems in knee OA. Future research to better understand the role of neuromuscular changes in knee OA and their effect on dynamic postural control will be suggested. Such an understanding is critical to the successful creation and implementation of fall prevention and treatment programs, in order to reduce the excessive risk of falling in knee OA.

  2. O uso de bloqueadores neuromusculares no Brasil El uso de bloqueadores neuromusculares en Brasil Neuromuscular blockers in Brazil

    Directory of Open Access Journals (Sweden)

    Maria Cristina Simões de Almeida

    2004-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Dados estatísticos referentes ao uso de bloqueadores neuromusculares no Brasil são desconhecidos. Este trabalho se propõe a análise estatística desse tópico. MÉTODO: Foram compiladas 831 respostas de um questionário preenchido em parte por anestesiologistas presentes ao 48º Congresso Brasileiro de Anestesiologia em Recife, 2001 e em parte via Internet, por anestesiologistas cujos endereços eletrônicos constam na página da Sociedade Brasileira de Anestesiologia (www.sba.com.br. Foram analisados os seguintes dados: tempo de contato com a especialidade, região onde atuam os anestesiologistas, uso de bloqueadores neuromusculares (BNM em ordem de preferência, indicações do uso de succinilcolina, uso do monitor da transmissão neuromuscular, critérios para se considerar o paciente descurarizado, uso de neostigmina, forma de administração dos BNM e descrição de complicações observadas. RESULTADOS: A maioria dos anestesiologistas em questão exerce a profissão há mais de 11 anos e o maior número de respostas foi proveniente da região sudeste do Brasil. O BNM mais empregado é o atracúrio, seguido de pancurônio e succinilcolina. A succinilcolina é mais empregada na indução rápida e em crianças (80% e 25% respectivamente. Monitores da transmissão neuromuscular, 53% dos anestesiologistas nunca usam, e como critério de recuperação, 92% consideram o paciente descurarizado mediante sinais clínicos. Em 45% das vezes os profissionais empregam a neostigmina de forma rotineira, e 94% administra os BNM sob forma de bolus. Cerca de 30% registra ter havido complicação decorrente do uso de BNM. As complicações mais apontadas foram o bloqueio prolongado, o broncoespasmo grave e a curarização residual. CONCLUSÕES: O atracúrio é o bloqueador neuromuscular mais empregado no Brasil, há percentual alto de uso da succinilcolina em situações não emergenciais, o uso de monitores da transmiss

  3. [Causes of lymphocytic meningitis in people with HIV admitted to the Infectious Disease department of Conakry].

    Science.gov (United States)

    Traoré, F A; Cissoko, Y; Tounkara, T M; Sako, F B; Mouelle, A D; Kpami, D O; Traoré, M; Doumbouya, M

    2015-01-01

    The advent of HIV infection has significantly changed the distribution of the causes of lymphocytic meningitis. The objective of this study was to identify these causes among persons with HIV hospitalized in the infectious disease department of the CHU of Conakry. This retrospective study examined hospital records of patients with HIV infection admitted for lymphocytic meningitis over a 10-year period. Of the 8649 hospitalizations in the department during the study period, 3167 patients had HIV infection, and 85 of the latter were diagnosed with lymphocytic meningitis. Slightly more than half were male (sex ratio M/F = 1.1). Their mean age was 32 years. Of these 85 patients, 73 were positive for HIV-1 only and 12 for HIV1+2. A CD4 count was performed only in 13/85 patients and averaged 140 cells/mm3. The main causes associated with lymphocytic meningitis were cryptococcosis (58%), toxoplasmosis (5%), and tuberculosis (2%). Streptococcus pneumoniae, Neisseria meningitidis, and Hæmophilus influenzae were also identified in 16% of cases. In 18% of cases no microbe was identified. The overall lethality rate was 68%; it reached 100% for tuberculous meningitis and for the cases without any identified cause and was 75%-76% for the patients with toxoplasmosis and cryptococcosis. The survival rate was 100% for all bacterial causes. A cause for lymphocytic meningitis was identified in more than 81% of the patients in our series, and the most common microbe was Cryptococcus neoformans. A better microbiological technical platform and improved accessibility to treatment would enable us to provide more relevant results and treatment.

  4. Pulmonary hypertension associated with connective tissue disease

    Directory of Open Access Journals (Sweden)

    Srinivas Rajagopala

    2017-01-01

    Full Text Available Pulmonary hypertension (PH is an important cause of morbidity and mortality in connective tissue diseases (CTDs. CTDs may cause PH due to several mechanisms; pulmonary arterial hypertension, associated interstitial lung disease, neuromuscular disease, and/or sleep disordered breathing leading to hypoxia, associated thromboembolic PH, and pulmonary venous hypertension due to left ventricular dysfunction. PH can be measured on echocardiography, but the gold standard for diagnosis is right heart catheterization. PH-specific therapy in addition to immunosuppression is the most common treatment used though data are scant. In this narrative review, we discuss the epidemiologic burden, clinical presentation, evaluation, and management of PH in CTDs.

  5. Mushroom tumor: a new disease on Flammulina velutipes caused by Ochrobactrum pseudogrignonense.

    Science.gov (United States)

    Wu, Zhipeng; Peng, Weihong; He, Xiaolan; Wang, Bo; Gan, Bingcheng; Zhang, Xiaoping

    2016-01-01

    Mushroom tumor on Flammulina velutipes has become the main disease during the off-season cultivation of F. velutipes while the causal organism has remained unknown. The present study was aimed at identifying the pathogen confirming its pathogenisity following Koch's Postulates, characterizing it using morphological, physiological, biochemical and molecular features, and studying its current distribution. We determined that mushroom tumor is a new bacterial infection disease caused by Ochrobactrum pseudogrignonense. It produces tumor-like structures on the surface of the substrate, and inhibits the formation of primordia and fruiting of F. velutipes. The molecular studies showed that this new pathogen is closely related to Ochrobactrum based on 16S rRNA sequences. This is the first time that Ochrobactrum has been shown to be a pathogen of a mushroom. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Cryptococcus gattii: An Emerging Cause of Fungal Disease in North America

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    Ashwin Dixit

    2009-01-01

    Full Text Available During the latter half of the twentieth century, fungal pathogens such as Cryptococcus neoformans were increasingly recognized as a significant threat to the health of immune compromised populations throughout the world. Until recently, the closely related species C. gattii was considered to be a low-level endemic pathogen that was confined to tropical regions such as Australia. Since 1999, C. gattii has emerged in the Pacific Northwest region of North America and has been responsible for a large disease epidemic among generally healthy individuals. The changing epidemiology of C. gattii infection is likely to be a consequence of alterations in fungal ecology and biology and illustrates its potential to cause serious human disease. This review summarizes selected biological and clinical aspects of C. gattii that are particularly relevant to the recent North American outbreak and compares these to the Australian and South American experience.

  7. COMPOSITE PEPTIDE COMPOUNDS FOR DIAGNOSIS AND TREATMENT OF DISEASES CAUSED BY PRION PROTEINS

    DEFF Research Database (Denmark)

    2004-01-01

    The present invention relates to diseases caused by prion proteins, Novel composite peptide compounds are disclosed which comprise two or more peptides or peptide fragments optionally linked to a backbone and the peptides or peptide fragments are spatially positioned relative to each other so...... that they together form a non-linear sequence which mimics the tertiary structure of one or more PrPSc-specific epitopes as evidenced by the test described herein. The use of such conjugates as immunogens for the production of antibodies that specifically bind to the pathogenic form of a prion protein is revealed....... Other uses of the composite peptide compounds are also disclosed, such as use in diagnostic assays, production of antibodies and uses as vaccine immunogens for the prophylactic protection and therapeutic treatment of subjects against transmissible prion disease....

  8. Early Stage of Chronic Kidney Disease with Renal Injury Caused by Hypertension in a Dog

    Directory of Open Access Journals (Sweden)

    Akira Yabuki

    2011-01-01

    Full Text Available A 10-year-old spayed female Papillon weighing 4.0 kg presented with a history of persistent hematuria and pollakiuria. Concurrent bladder calculi, a mammary gland tumor, and nonazotemic early stage of chronic kidney disease with contracted kidneys were noted in this dog. The dog underwent cystectomy, unilateral mastectomy, and intraoperative renal biopsy. On the basis of histopathological analysis of renal biopsy results, it was suspected that renal injury of the dog was caused by persistent hypertension, and a follow-up examination revealed severe hypertension. The dog was treated with a combination of an angiotensin-converting enzyme inhibitor and calcium channel blocker. The treatment produced a good outcome in the dog, and there has been no progression of the chronic kidney disease for over 2 years.

  9. A de novo SOX10 mutation causing severe type 4 Waardenburg syndrome without Hirschsprung disease.

    Science.gov (United States)

    Sznajer, Yves; Coldéa, Cristina; Meire, Françoise; Delpierre, Isabelle; Sekhara, Tayeb; Touraine, Renaud L

    2008-04-15

    Type 4 Waardenburg syndrome represents a well define entity caused by neural crest derivatives anomalies (melanocytes, intrinsic ganglion cells, central, autonomous and peripheral nervous systems) leading, with variable expressivity, to pigmentary anomalies, deafness, mental retardation, peripheral neuropathy, and Hirschsprung disease. Autosomal dominant mode of inheritance is prevalent when Sox10 gene mutation is identified. We report the natural history of a child who presented with synophrys, vivid blue eye, deafness, bilateral complete semicircular canals agenesis with mental retardation, subtle signs for peripheral neuropathy and lack of Hirschsprung disease. SOX10 gene sequencing identified "de novo" splice site mutation (c.698-2A > C). The present phenotype and the genotype findings underline the wide spectrum of SOX10 gene implication in unusual type 4 Waardenburg syndrome patient. Copyright 2008 Wiley-Liss, Inc.

  10. Inherited Cardiac Diseases Caused by Mutations in the Nav1.5 Sodium Channel

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Jacob; Winkel, Bo Gregers; Grunnet, Morten

    2009-01-01

    Cardiac Diseases Caused by SCN5A Mutations. A prerequisite for a normal cardiac function is a proper generation and propagation of electrical impulses. Contraction of the heart is obtained through a delicate matched transmission of the electrical impulses. A pivotal element of the impulse...... propagation is the depolarizing sodium current, responsible for the initial depolarization of the cardiomyocytes. Recent research has shown that mutations in the SCN5A gene, encoding the cardiac sodium channel Nav1.5, are associated with both rare forms of ventricular arrhythmia, as well as the most frequent...... form of arrhythmia, atrial fibrillation (AF). In this comprehensive review, we describe the functional role of Nav1.5 and its associated proteins in propagation and depolarization both in a normal- and in a pathophysiological setting. Furthermore, several of the arrhythmogenic diseases, such as long...

  11. Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease

    Science.gov (United States)

    de Pontual, Loïc; Zaghloul, Norann A.; Thomas, Sophie; Davis, Erica E.; Mcgaughey, David M.; Dollfus, Hélène; Baumann, Clarisse; Bessling, Seneca L.; Babarit, Candice; Pelet, Anna; Gascue, Cecilia; Beales, Philip; Munnich, Arnold; Lyonnet, Stanislas; Etchevers, Heather; Attie-Bitach, Tania; Badano, Jose L.; McCallion, Andrew S.; Katsanis, Nicholas; Amiel, Jeanne

    2009-01-01

    Hirschsprung disease (HSCR) is a common, multigenic neurocristopathy characterized by incomplete innervation along a variable length of the gut. The pivotal gene in isolated HSCR cases, either sporadic or familial, is RET. HSCR also presents in various syndromes, including Shah–Waardenburg syndrome (WS), Down (DS), and Bardet–Biedl (BBS). Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays. Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease. We also demonstrate that these genes interact genetically in vivo to modulate gut innervation, and that this interaction likely occurs through complementary, yet independent, pathways that converge on the same biological process. PMID:19666486

  12. Body adiposity index and all-cause and cardiovascular disease mortality in men

    Science.gov (United States)

    Moliner-Urdiales, Diego; Artero, Enrique G; Lee, Duck-chul; España-Romero, Vanesa; Sui, Xuemei; Blair, Steven N

    2013-01-01

    Objective To evaluate the association of body adiposity index (BAI) with all-cause and cardiovascular disease (CVD) mortality risk. Design and Methods The current analysis comprised 19 756 adult men who enrolled in the Aerobics Centre Longitudinal Study and completed a baseline examination during 1988-2002. All-cause and CVD mortality was registered till December 31, 2003. Results During an average follow-up of 8.3 years (163 844 man-years), 353 deaths occurred (101 CVD deaths). Age- and examination year-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause mortality risk were higher for men with high values of BMI (HR = 1.63, 95% CI = 1.19–2.23), waist circumference (1.55, 1.22-1.96) and percentage of body fat (%BF) (1.36, 1.04-1.31), but not for men with high values of BAI (1.28, 0.98-1.66). The HRs for CVD mortality risks were higher for men with high values in all adiposity measures (HRs ranged from 1.73 to 2.06). Most of these associations, however, became nonsignificant after adjusting for multiple confounders including cardiorespiratory fitness. Conclusion BAI is not a better predictor of all-cause and CVD mortality risk than BMI, waist circumference or %BF. PMID:23512375

  13. T₂ mapping provides multiple approaches for the characterization of muscle involvement in neuromuscular diseases: a cross-sectional study of lower leg muscles in 5-15-year-old boys with Duchenne muscular dystrophy.

    Science.gov (United States)

    Arpan, Ishu; Forbes, Sean C; Lott, Donovan J; Senesac, Claudia R; Daniels, Michael J; Triplett, William T; Deol, Jasjit K; Sweeney, H Lee; Walter, Glenn A; Vandenborne, Krista

    2013-03-01

    Skeletal muscles of children with Duchenne muscular dystrophy (DMD) show enhanced susceptibility to damage and progressive lipid infiltration, which contribute to an increase in the MR proton transverse relaxation time (T₂). Therefore, the examination of T₂ changes in individual muscles may be useful for the monitoring of disease progression in DMD. In this study, we used the mean T₂, percentage of elevated pixels and T₂ heterogeneity to assess changes in the composition of dystrophic muscles. In addition, we used fat saturation to distinguish T₂ changes caused by edema and inflammation from fat infiltration in muscles. Thirty subjects with DMD and 15 age-matched controls underwent T₂ -weighted imaging of their lower leg using a 3-T MR system. T₂ maps were developed and four lower leg muscles were manually traced (soleus, medial gastrocnemius, peroneal and tibialis anterior). The mean T₂ of the traced regions of interest, width of the T₂ histograms and percentage of elevated pixels were calculated. We found that, even in young children with DMD, lower leg muscles showed elevated mean T₂, were more heterogeneous and had a greater percentage of elevated pixels than in controls. T₂ measures decreased with fat saturation, but were still higher (P < 0.05) in dystrophic muscles than in controls. Further, T₂ measures showed positive correlations with timed functional tests (r = 0.23-0.79). The elevated T₂ measures with and without fat saturation at all ages of DMD examined (5-15 years) compared with unaffected controls indicate that the dystrophic muscles have increased regions of damage, edema and fat infiltration. This study shows that T₂ mapping provides multiple approaches that can be used effectively to characterize muscle tissue in children with DMD, even in the early stages of the disease. Therefore, T₂ mapping may prove to be clinically useful in the monitoring of muscle changes caused by the disease process or by therapeutic

  14. Spatial scaling relationships for spread of disease caused by a wind-dispersed plant pathogen.

    Science.gov (United States)

    Mundt, Christopher C; Sackett, Kathryn E

    2012-03-09

    Spatial scale is of great importance to understanding the spread of organisms exhibiting long-distance dispersal (LDD). We tested whether epidemics spread in direct proportion to the size of the host population and size of the initial disease focus. This was done through analysis of a previous study of the effects of landscape heterogeneity variables on the spread of accelerating epidemics of wheat (Triticum aestivum) stripe rust, caused by the fungus Puccinia striiformis f. sp. tritici. End-of-season disease gradients were constructed by estimating disease prevalence at regular distances from artificially inoculated foci of different sizes, in field plots of different dimensions. In one set of comparisons, all linear dimensions (plot width and length, focus width and length, and distance between observation points) differed by a factor of four. Disease spread was substantially greater in large plot/large focus treatments than in small plot/small focus treatments. However, when disease gradients were plotted using focus width as the unit distance, they were found to be highly similar, suggesting a proportional relationship between focus or plot size and disease spread. A similar relationship held when comparing same-size plots inoculated with different-sized foci, an indication that focus size is the driver of this proportionality. Our results suggest that power law dispersal of LDD organisms results in scale-invariant relationships, which are useful for better understanding spatial spread of biological invasions, extrapolating results from small-scale experiments to invasions spreading over larger scales, and predicting speed and pattern of spread as an invasion expands.

  15. Agrarian diet and diseases of affluence – Do evolutionary novel dietary lectins cause leptin resistance?

    Directory of Open Access Journals (Sweden)

    Jönsson Tommy

    2005-12-01

    Full Text Available Abstract Background The global pattern of varying prevalence of diseases of affluence, such as obesity, cardiovascular disease and diabetes, suggests that some environmental factor specific to agrarian societies could initiate these diseases. Presentation of the hypothesis We propose that a cereal-based diet could be such an environmental factor. Through previous studies in archaeology and molecular evolution we conclude that humans and the human leptin system are not specifically adapted to a cereal-based diet, and that leptin resistance associated with diseases of affluence could be a sign of insufficient adaptation to such a diet. We further propose lectins as a cereal constituent with sufficient properties to cause leptin resistance, either through effects on metabolism central to the proper functions of the leptin system, and/or directly through binding to human leptin or human leptin receptor, thereby affecting the function. Testing the hypothesis Dietary interventions should compare effects of agrarian and non-agrarian diets on incidence of diseases of affluence, related risk factors and leptin resistance. A non-significant (p = 0.10 increase of cardiovascular mortality was noted in patients advised to eat more whole-grain cereals. Our lab conducted a study on 24 domestic pigs in which a cereal-free hunter-gatherer diet promoted significantly higher insulin sensitivity, lower diastolic blood pressure and lower C-reactive protein as compared to a cereal-based swine feed. Testing should also evaluate the effects of grass lectins on the leptin system in vivo by diet interventions, and in vitro in various leptin and leptin receptor models. Our group currently conducts such studies. Implications of the hypothesis If an agrarian diet initiates diseases of affluence it should be possible to identify the responsible constituents and modify or remove them so as to make an agrarian diet healthier.

  16. Copper deficiency as a cause of neutropenia in a case of coeliac disease.

    Science.gov (United States)

    Khera, Daisy; Sharma, Baldev; Singh, Kuldeep

    2016-09-15

    We report a 17 year-old male patient, who presented with chronic diarrhoea, progressive pallor, short stature, anaemia (haemoglobin of 4.9 g/dL) and neutropenia and was diagnosed as coeliac disease. His neutropenia did not respond to 8 months of gluten-free diet, iron, folic acid and vitamin B12 therapy. So we suspected copper deficiency and his serum copper levels were tested, which was low. His neutrophil counts normalised after 2 months of copper supplementation. Hence we concluded that the cause of neutropenia in our case was copper deficiency. 2016 BMJ Publishing Group Ltd.

  17. Acute Fulminant Colitis Caused by Idiopathic Mesenteric Inflammatory Veno-Occlusive Disease

    Directory of Open Access Journals (Sweden)

    James B. Canavan

    2007-12-01

    Full Text Available Mesenteric inflammatory veno-occlusive disease (MIVOD is an uncommon but important cause of bowel inflammation. MIVOD is characterised by lymphocytic inflammation and non-thrombotic occlusion of the mesenteric venules and veins. We present the case of a young man who presented with acute fulminant colitis, requiring colectomy. The differential diagnosis, pathogenesis and treatment are discussed. This case illustrates the rapid progression from ‘well’ to ‘colectomy’ that can occur with MIVOD. MIVOD should be considered in the differential diagnosis of colitis that does not respond to conventional medical treatment.

  18. Cause-specific mortality and 30-year relative survival of Crohn's disease and ulcerative colitis.

    Science.gov (United States)

    Selinger, Christian P; Andrews, Jane; Dent, Owen F; Norton, Ian; Jones, Brian; McDonald, Charles; Cowlishaw, James; Barr, Gavin; Selby, Warwick; Leong, Rupert W

    2013-08-01

    Data from the northern hemisphere suggest that patients with ulcerative colitis (UC) have similar survival to the general population, whereas mortality in Crohn's disease (CD) is increased by up to 50%. There is a paucity of data from the southern hemisphere, especially in Australia. A prevalence cohort (1977-1992) of patients with inflammatory bowel disease (IBD) diagnosed after 1970 was studied. Survival status data and causes of death up to December 2010 were extracted from the National Death Index. Relative survival analysis was carried out separately for men and women. Of 816 cases (384 men, 432 women; 373 CD, 401 UC, 42 indeterminate colitis), 211 (25.9%) had died by December 2010. Median follow-up was 22.2 years. Relative survival of all patients with IBD was not significantly different from the general population at 10, 20, and 30 years of follow-up. Separate analyses of survival in CD and UC also showed no differences from the general population. There was no difference in survival between patients diagnosed earlier (1971-1979) or later (1980-1992). At least 17% of the deaths were caused by IBD. Fatal cholangiocarcinomas were more common in IBD (P < 0.001), and fatal colorectal cancers more common in UC (P = 0.047). In Australia, IBD patient survival is similar to the general population. In contrast to data from Europe and North America, survival in CD is not diminished in Australia. IBD caused direct mortality in 17%, especially as biliary and colorectal cancers are significant causes of death.

  19. Xanthomonas euvesicatoria Causes Bacterial Spot Disease on Pepper Plant in Korea

    Directory of Open Access Journals (Sweden)

    Min-Seong Kyeon

    2016-10-01

    Full Text Available In 2004, bacterial spot-causing xanthomonads (BSX were reclassified into 4 species—Xanthomonas euvesicatoria, X. vesicatoria, X. perforans, and X. gardneri. Bacterial spot disease on pepper plant in Korea is known to be caused by both X. axonopodis pv. vesicatoria and X. vesicatoria. Here, we reidentified the pathogen causing bacterial spots on pepper plant based on the new classification. Accordingly, 72 pathogenic isolates were obtained from the lesions on pepper plants at 42 different locations. All isolates were negative for pectolytic activity. Five isolates were positive for amylolytic activity. All of the Korean pepper isolates had a 32 kDa-protein unique to X. euvesicatoria and had the same band pattern of the rpoB gene as that of X. euvesicatoria and X. perforans as indicated by PCR-restriction fragment length polymorphism analysis. A phylogenetic tree of 16S rDNA sequences showed that all of the Korean pepper plant isolates fit into the same group as did all the reference strains of X. euvesicatoria and X. perforans. A phylogenetic tree of the nucleotide sequences of 3 housekeeping genes—gapA, gyrB, and lepA showed that all of the Korean pepper plant isolates fit into the same group as did all of the references strains of X. euvesicatoria. Based on the phenotypic and genotypic characteristics, we identified the pathogen as X. euvesicatoria. Neither X. vesicatoria, the known pathogen of pepper bacterial spot, nor X. perforans, the known pathogen of tomato plant, was isolated. Thus, we suggest that the pathogen causing bacterial spot disease of pepper plants in Korea is X. euvesicatoria.

  20. The probable cause of civilization diseases and the structural limits of pleasure.

    Science.gov (United States)

    Gracia, M C

    2009-11-01

    This article provides a theoretical basis and experimental evidence for the following rules: (1) All mental activities involving some level of intelligence ultimately follow the laws of operant conditioning and can exert a long-term control of behaviour only if they regularly provide the midbrain centres with the minimal set of neural rewards that these centres expect (2) Mental activity is always accompanied by a proportional amount of efferent-controlled physiological activity, which may be, for example, voluntary muscular work, but also internal, possibly surreptitious phenomena like inflammation, immune reactions, blood pressure increase, etc. These rules provide an explanation for most 'civilization' diseases whose ultimate causes are currently unknown or uncontrollable, e.g. cardiovascular troubles, cancer, allergies, auto-immune disorders, non-congenital degenerative diseases, neural dysfunctions including Alzheimer and Parkinson diseases, ALS or multiple sclerosis, emotional troubles including depression, cyclothymic/bipolar disorders, uncontrollable compulsions, etc. Potentially, this explanation also provides a cure for all these diseases as long as there is no accumulation of many of them because, for example, of very advanced age, and only if we are ready to adopt a philosophy of happiness based on moderation and appreciation of the value of life, dignity and empathy, instead of attempting an unlimited accumulation of pleasure, which does not seem neurologically viable.

  1. Mycobacterium avium subspecies paratuberculosis in the etiology of Crohn's disease, cause or epiphenomenon?

    Science.gov (United States)

    Liverani, Elisa; Scaioli, Eleonora; Cardamone, Carla; Dal Monte, Paola; Belluzzi, Andrea

    2014-09-28

    The origin of inflammatory bowel disease is unknown. Attempts have been made to isolate a microorganism that could explain the onset of inflammation, but no pathological agent has ever been identified. Johne's disease is a granulomatous chronic enteritis of cattle and sheep caused by Mycobacterium avium subspecies paratuberculosis (MAP) and shows some analogies with Crohn's disease (CD). Several studies have tried to clarify if MAP has a role in the etiology of CD. The present article provides an overview of the evidence in favor and against the "MAP-hypothesis", analyzing the methods commonly adopted to detect MAP and the role of antimycobacterial therapy in patients with inflammatory bowel disease. Studies were identified through the electronic database, MEDLINE, and were selected based on their relevance to the objective of the review. The presence of MAP was investigated using multiple diagnostic methods for MAP detection and in different tissue samples from patients affected by CD or ulcerative colitis and in healthy controls. On the basis of their studies, several authors support a close relationship between MAP and CD. Although increasing evidence of MAP detection in CD patients is unquestionable, a clear etiological link still needs to be proven.

  2. Comprehensive population screening in the Ashkenazi Jewish population for recurrent disease-causing variants.

    Science.gov (United States)

    Shi, L; Webb, B D; Birch, A H; Elkhoury, L; McCarthy, J; Cai, X; Oishi, K; Mehta, L; Diaz, G A; Edelmann, L; Kornreich, R

    2017-04-01

    The Ashkenazi Jewish (AJ) population has an increased risk for a variety of recessive diseases due to historical founder effects and genetic drift. For some, the disease-causing founder mutations have been identified and well-characterized, but for others, further study is necessary. The purpose of this study is to assess the carrier frequencies of 85 pathogenic variants causative of 29 recessive conditions in the AJ population. Up to 3000 AJ individuals were genotyped by Luminex MagPlex® -TAG™ bead array or Agena Bioscience™ MassARRAY assays. We identified seven conditions with carrier frequencies higher than 1 in 100, nine between 1 in 100 and 1 in 200, and four between 1 in 200 and 1 in 500. Variants in nine conditions had a detected carrier rate of less than 1 in 500 or were not identified in approximately 2000 AJ individuals. We assessed the combined AJ carrier frequency for 18 relatively prevalent diseases to be 1 in 6, and the risk of AJ individuals to be a carrier couple for one of these 18 diseases as 1 in 441. We note additional recessive genetic conditions should be considered for AJ carrier screening panels. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Recent Trends in Control Methods for Bacterial Wilt Diseases Caused by Ralstonia solanacearum

    Science.gov (United States)

    Yuliar; Nion, Yanetri Asi; Toyota, Koki

    2015-01-01

    Previous studies have described the development of control methods against bacterial wilt diseases caused by Ralstonia solanacearum. This review focused on recent advances in control measures, such as biological, physical, chemical, cultural, and integral measures, as well as biocontrol efficacy and suppression mechanisms. Biological control agents (BCAs) have been dominated by bacteria (90%) and fungi (10%). Avirulent strains of R. solanacearum, Pseudomonas spp., Bacillus spp., and Streptomyces spp. are well-known BCAs. New or uncommon BCAs have also been identified such as Acinetobacter sp., Burkholderia sp., and Paenibacillus sp. Inoculation methods for BCAs affect biocontrol efficacy, such as pouring or drenching soil, dipping of roots, and seed coatings. The amendment of different organic matter, such as plant residue, animal waste, and simple organic compounds, have frequently been reported to suppress bacterial wilt diseases. The combined application of BCAs and their substrates was shown to more effectively suppress bacterial wilt in the tomato. Suppression mechanisms are typically attributed to the antibacterial metabolites produced by BCAs or those present in natural products; however, the number of studies related to host resistance to the pathogen is increasing. Enhanced/modified soil microbial communities are also indirectly involved in disease suppression. New promising types of control measures include biological soil disinfection using substrates that release volatile compounds. This review described recent advances in different control measures. We focused on the importance of integrated pest management (IPM) for bacterial wilt diseases. PMID:25762345

  4. Phylogenetic and chronological analysis of proteins causing Alzheimer's, Parkinson's and Huntington's diseases

    Directory of Open Access Journals (Sweden)

    Bilal Hussain

    2012-09-01

    Full Text Available It is evident that Neurodegenerative diseases (Alzheimer's, Parkinson's and Huntington's have many similarities at cellular and molecular level as they carry parallel mechanisms including protein aggregation and inclusion body formation caused by protein mis-folding. The main objective of this study was to have detailed insight on variation and resemblance among these proteins. One hundred and four protein sequences, both directly and indirectly involved in disease mechanism to perform phylogenetic analysis revealing insight on evolutionary relationship among these proteins, were selected. The percentage of replicate trees, in which the associated taxa clustered together in the bootstrap test, was 1000 replicates. Various statistical tests were performed for the confirmation of results e.g., Tajma's Neutrality Test showed D gt 6, nucleotide diversity π gt 0.6 and ps value as greater than 1. Phylogenetic analysis showed that the protein sequences of neurodegenerative diseases had high sequence similarity and identity to each other as depicted by the evolutionary tree. It showed the similar mechanism of evolving from each other and had similar mechanism of generating mis-folding leading towards symptoms of disease.

  5. Network analysis of differential expression for the identification of disease-causing genes.

    Directory of Open Access Journals (Sweden)

    Daniela Nitsch

    Full Text Available Genetic studies (in particular linkage and association studies identify chromosomal regions involved in a disease or phenotype of interest, but those regions often contain many candidate genes, only a few of which can be followed-up for biological validation. Recently, computational methods to identify (prioritize the most promising candidates within a region have been proposed, but they are usually not applicable to cases where little is known about the phenotype (no or few confirmed disease genes, fragmentary understanding of the biological cascades involved. We seek to overcome this limitation by replacing knowledge about the biological process by experimental data on differential gene expression between affected and healthy individuals. Considering the problem from the perspective of a gene/protein network, we assess a candidate gene by considering the level of differential expression in its neighborhood under the assumption that strong candidates will tend to be surrounded by differentially expressed neighbors. We define a notion of soft neighborhood where each gene is given a contributing weight, which decreases with the distance from the candidate gene on the protein network. To account for multiple paths between genes, we define the distance using the Laplacian exponential diffusion kernel. We score candidates by aggregating the differential expression of neighbors weighted as a function of distance. Through a randomization procedure, we rank candidates by p-values. We illustrate our approach on four monogenic diseases and successfully prioritize the known disease causing genes.

  6. Elucidation of the disease cycle of olive anthracnose caused by Colletotrichum acutatum.

    Science.gov (United States)

    Moral, Juan; de Oliveira, Rodrígues; Trapero, Antonio

    2009-05-01

    Anthracnose, caused by Colletotrichum acutatum and C. gloeosporioides, is a major fungal disease of olive in many countries. In Spain, the disease has been associated only with a characteristic rot and mummification of mature fruit. The purpose of this study was to determine whether C. acutatum could infect other plant tissues that may serve as sources of inoculum for anthracnose epidemics. Inoculations of young plants or detached leaves and field observations demonstrated that flowers and immature olive fruit are susceptible to the pathogen. Flower infection caused blight of inflorescences and infection of developing fruit. Immature fruit were infected in all phenological stages, although infection remained latent for 7 to 8 months, until the onset of fruit ripening. Fruit susceptibility increased and latent period decreased with maturity. Fruit were required for symptom development on inoculated plants. Plants without fruit were infected but they did not show any disease symptoms. Only plants with rotten fruit developed leaf wilting and branch dieback symptoms several weeks later. These results, together with the low level of pathogen isolation from affected leaves and branches and the toxicity of sterile fungal extracts to olive cuttings, suggest that a toxic substance produced by C. acutatum in rotten fruit may account for this syndrome. Both disease syndromes, fruit rot and branch dieback, developed in several olive cultivars, which were equally susceptible to the pathogen. However, olive cultivars differed in their response to flower and fruit infection. Latent infection of developing fruit during the spring may permit survival of the pathogen during the hot and dry summer and serve as an inoculum source for anthracnose epidemics that develop on ripening fruit in autumn.

  7. Tobacco blue mould disease caused by Peronospora hyoscyami f. sp. tabacina.

    Science.gov (United States)

    Borrás-Hidalgo, Orlando; Thomma, Bart P H J; Silva, Yussuan; Chacón, Osmany; Pujol, Merardo

    2010-01-01

    Blue mould [Peronospora hyoscyami f. sp. tabacina (Adam) Skalicky 1964] is one of the most important foliar diseases of tobacco that causes significant losses in the Americas, south-eastern Europe and the Middle East. This review summarizes the current knowledge of the mechanisms employed by this oomycete pathogen to colonize its host, with emphasis on molecular aspects of pathogenicity. In addition, key biochemical and molecular mechanisms involved in tobacco resistance to blue mould are discussed. Kingdom: Chromista (Straminipila); Phylum: Heterokontophyta; Class: Oomycete; Order: Peronosporales; Family: Peronosporaceae; Genus: Peronospora; Species: Peronospora hyoscyami f. sp. tabacina. The pathogen typically causes localized lesions on tobacco leaves that appear as single, or groups of, yellow spots that often coalesce to form light-brown necrotic areas. Some of the leaves exhibit grey to bluish downy mould on their lower surfaces. Diseased leaves can become twisted, such that the lower surfaces turn upwards. In such cases, the bluish colour of the diseased plants becomes quite conspicuous, especially under moist conditions when sporulation is abundant. Hence the name of the disease: tobacco blue mould. The pathogen develops haustoria within plant cells that are thought to establish the transfer of nutrients from the host cell, and may also act in the delivery of effector proteins during infection. Several defence responses have been reported to occur in the Nicotiana tabacum-P. hyoscyami f. sp. tabacina interaction. These include the induction of pathogenesis-related genes, and a correlated increase in the activities of typical pathogenesis-related proteins, such as peroxidases, chitinases, beta-1,3-glucanases and lipoxygenases. Systemic acquired resistance is one of the best characterized tobacco defence responses activated on pathogen infection.

  8. Association of TSH Elevation with All-Cause Mortality in Elderly Patients with Chronic Kidney Disease.

    Directory of Open Access Journals (Sweden)

    Mei-Hsing Chuang

    Full Text Available Chronic kidney disease (CKD is a widespread condition in the global population and is more common in the elderly. Thyroid-stimulating hormone (TSH level increases with aging, and hypothyroidism is highly prevalent in CKD patients. However, the relationship between low thyroid function and mortality in CKD patients is unclear. Therefore, we conducted a retrospective cohort study to examine the relationship between TSH elevation and all-cause mortality in elderly patients with CKD. This retrospective cohort study included individuals ≥65 years old with CKD (n = 23,786 in Taipei City. Health examination data from 2005 to 2010 were provided by the Taipei Databank for Public Health Analysis. Subjects were categorized according to thyroid-stimulating hormone (TSH level as follows: low normal (0.34disease (coronary artery disease, congestive heart failure, cerebral vascular disease, history of cancer, and history of chronic obstructive pulmonary disease. Our results showed that compared to the reference group (middle normal TSH, the risk of all-cause mortality was increased in the elevated I group (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.02-1.45 and elevated II group (HR, 1.30; 95% CI, 1.00-1.69. We found a significant association between TSH elevation and all-cause mortality in this cohort of elderly persons with CKD. However, determining the benefit of treatment for moderately elevated TSH level (5.2-10 mIU/L in elderly patients with CKD will require a

  9. Innervation and neuromuscular control in ageing skeletal muscle.

    Science.gov (United States)

    Hepple, Russell T; Rice, Charles L

    2016-04-15

    Changes in the neuromuscular system affecting the ageing motor unit manifest structurally as a reduction in motor unit number secondary to motor neuron loss; fibre type grouping due to repeating cycles of denervation-reinnervation; and instability of the neuromuscular junction that may be due to either or both of a gradual perturbation in postsynaptic signalling mechanisms necessary for maintenance of the endplate acetylcholine receptor clusters or a sudden process involving motor neuron death or traumatic injury to the muscle fibre. Functionally, these changes manifest as a reduction in strength and coordination that precedes a loss in muscle mass and contributes to impairments in fatigue. Regular muscle activation in postural muscles or through habitual physical activity can attenuate some of these structural and functional changes up to a point along the ageing continuum. On the other hand, regular muscle activation in advanced age (>75 years) loses its efficacy, and at least in rodents may exacerbate age-related motor neuron death. Transgenic mouse studies aimed at identifying potential mechanisms of motor unit disruptions in ageing muscle are not conclusive due to many different mechanisms converging on similar motor unit alterations, many of which phenocopy ageing muscle. Longitudinal studies of ageing models and humans will help clarify the cause and effect relationships and thus, identify relevant therapeutic targets to better preserve muscle function across the lifespan. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  10. Relation of ventilatory impairment and of chronic mucus hypersecretion to mortality from obstructive lung disease and from all causes.

    OpenAIRE

    Lange, P; Nyboe, J; Appleyard, M; Jensen, G; Schnohr, P

    1990-01-01

    The relation of ventilatory impairment and chronic mucus hypersecretion to death from all causes and death from obstructive lung disease (chronic bronchitis, emphysema and asthma) was studied in 13,756 men and women randomly selected from the general population of the City of Copenhagen. During the 10 year follow up 2288 subjects died. In 164 subjects obstructive lung disease was considered to be an underlying or a contributory cause of death (obstructive lung disease related death); in 73 su...

  11. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015

    NARCIS (Netherlands)

    Wang, Haidong; Naghavi, Mohsen; Allen, Christine; Barber, R.M.; Bhutta, Zulfiqar; Carter, Austin; Casey, Daniel C.; Charlson, Fiona J.; Chen, Alan Z.; Coates, M.; Geleijnse, J.M.

    2016-01-01

    Background
    Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249

  12. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013

    NARCIS (Netherlands)

    Naghavi, Mohsen; Wang, Haidong; Lozano, Rafael; Davis, Adrian; Liang, Xiaofeng; Zhou, Maigeng; Vollset, Stein Emil; Ozgoren, Ayse Abbasoglu; Abdalla, Safa; Abd-Allah, Foad; Aziz, Muna I. Abdel; Abera, Semaw Ferede; Aboyans, Victor; Abraham, Biju; Abraham, Jerry P.; Abuabara, Katrina E.; Abubakar, Ibrahim; Abu-Raddad, Laith J.; Abu-Rmeileh, Niveen M. E.; Achoki, Tom; Adelekan, Ademola; Ademi, Zanfi Na; Adofo, Koranteng; Adou, Arsene Kouablan; Adsuar, Jose C.; Aernlov, Johan; Agardh, Emilie Elisabet; Akena, Dickens; Al Khabouri, Mazin J.; Alasfoor, Deena; Albittar, Mohammed; Alegretti, Miguel Angel; Aleman, Alicia V.; Alemu, Zewdie Aderaw; Alfonso-Cristancho, Rafael; Alhabib, Samia; Ali, Mohammed K.; Ali, Raghib; Alla, Francois; Al Lami, Faris; Allebeck, Peter; AlMazroa, Mohammad A.; Salman, Rustam Al-Shahi; Alsharif, Ubai; Alvarez, Elena; Alviz-Guzman, Nelson; Amankwaa, Adansi A.; Amare, Azmeraw T.; Ameli, Omid; Amini, Hassan; Ammar, Walid; Anderson, H. Ross; Anderson, Benjamin O.; Antonio, Carl Abelardo T.; Anwari, Palwasha; Apfel, Henry; Cunningham, Solveig Argeseanu; Arsenijevic, Valentina S. Arsic; Al Artaman, Ali; Asad, Majed Masoud; Asghar, Rana J.; Assadi, Reza; Atkins, Lydia S.; Atkinson, Charles; Badawi, Alaa; Bahit, Maria C.; Bakfalouni, Talal; Balakrishnan, Kalpana; Balalla, Shivanthi; Banerjee, Amitava; Barber, Ryan M.; Barker-Collo, Suzanne L.; Barquera, Simon; Barregard, Lars; Barrero, Lope H.; Barrientos-Gutierrez, Tonatiuh; Basu, Arindam; Basu, Sanjay; Basulaiman, Mohammed Omar; Beardsley, Justin; Bedi, Neeraj; Beghi, Ettore; Bekele, Tolesa; Bell, Michelle L.; Benjet, Corina; Bennett, Derrick A.; Bensenor, Isabela M.; Benzian, Habib; Bertozzi-Villa, Amelia; Beyene, Tariku Jibat; Bhala, Neeraj; Bhalla, Ashish; Bhutta, Zulfiqar A.; Bikbov, Boris; Bin Abdulhak, Aref; Biryukov, Stan; Blore, Jed D.; Blyth, Fiona M.; Bohensky, Megan A.; Borges, Guilherme; Bose, Dipan; Boufous, Soufiane; Bourne, Rupert R.; Boyers, Lindsay N.; Brainin, Michael; Brauer, Michael; Brayne, Carol E. G.; Brazinova, Alexandra; Breitborde, Nicholas; Brenner, Hermann; Briggs, Adam D. M.; Brown, Jonathan C.; Brugha, Traolach S.; Buckle, Geoffrey C.; Bui, Linh Ngoc; Bukhman, Gene; Burch, Michael; Nonato, Ismael Ricardo Campos; Carabin, Helesne; Cardenas, Rosario; Carapetis, Jonathan; Carpenter, David O.; Caso, Valeria; Castaneda-Orjuela, Carlos A.; Castro, Ruben Estanislao; Catala-Lopez, Ferrn; Cavalleri, Fiorella; Chang, Jung-Chen; Charlson, Fiona C.; Che, Xuan; Chen, Honglei; Chen, Yingyao; Chen, Jian Sheng; Chen, Zhengming; Chiang, Peggy Pei-Chia; Chimed-Ochir, Odgerel; Chowdhury, Rajiv; Christensen, Hanne; Christophi, Costas A.; Chuang, Ting-Wu; Chugh, Sumeet S.; Cirillo, Massimo; Coates, Matthew M.; Coffeng, Luc Edgar; Coggeshall, Megan S.; Cohen, Aaron; Colistro, Valentina; Colquhoun, Samantha M.; Colomar, Mercedes; Cooper, Leslie Trumbull; Cooper, Cyrus; Coppola, Luis M.; Cortinovis, Monica; Courville, Karen; Cowie, Benjamin C.; Criqui, Michael H.; Crump, John A.; Cuevas-Nasu, Lucia; Leite, Iuri da Costa; Dabhadkar, Kaustubh C.; Dandona, Lalit; Dandona, Rakhi; Dansereau, Emily; Dargan, Paul I.; Dayama, Anand; De la Cruz-Gongora, Vanessa; de la Vega, Shelley F.; De Leo, Diego; Degenhardt, Louisa; del Pozo-Cruz, Borja; Dellavalle, Robert P.; Deribe, Kebede; Jarlais, Don C. Des; Dessalegn, Muluken; deVeber, Gabrielle A.; Dharmaratne, Samath D.; Dherani, Mukesh; Diaz-Ortega, Jose-Luis; Diaz-Torne, Cesar; Dicker, Daniel; Ding, Eric L.; Dokova, Klara; Dorsey, E. Ray; Driscoll, Tim R.; Duan, Leilei; Duber, Herbert C.; Durrani, Adnan M.; Ebel, Beth E.; Edmond, Karen M.; Ellenbogen, Richard G.; Elshrek, Yousef; Ermakov, Sergey Petrovich; Erskine, Holly E.; Eshrati, Babak; Esteghamati, Alireza; Estep, Kara; Fuerst, Thomas; Fahimi, Saman; Fahrion, Anna S.; Faraon, Emerito Jose A.; Farzadfar, Farshad; Fay, Derek F. J.; Feigl, Andrea B.; Feigin, Valery L.; Felicio, Manuela Mendonca; Fereshtehnejad, Seyed-Mohammad; Fernandes, Jefferson G.; Ferrari, Alize J.; Fleming, Thomas D.; Foigt, Nataliya; Foreman, Kyle; Forouzanfar, Mohammad H.; Fowkes, F. Gerry R.; Fra Paleo, Urbano; Franklin, Richard C.; Futran, Neal D.; Gaffikin, Lynne; Gambashidze, Ketevan; Gankpe, Fortune Gbetoho; Garcia-Guerra, Francisco Armando; Garcia, Ana Cristina; Geleijnse, Johanna M.; Gessner, Bradford D.; Gibney, Katherine B.; Gillum, Richard F.; Gilmour, Stuart; Abdelmageem, Ibrahim; Ginawi, Mohamed; Giroud, Maurice; Glaser, Elizabeth L.; Goenka, Shifalika; Dantes, Hector Gomez; Gona, Philimon; Gonzalez-Medina, Diego; Guinovart, Caterina; Gupta, Rahul; Gupta, Rajeev; Gosselin, Richard A.; Gotay, Carolyn C.; Goto, Atsushi; Gowda, Hube N.; Graetz, Nicholas; Greenwell, K. Fern; Gugnani, Harish Chander; Gunnell, David; Gutierrez, Reyna A.; Haagsma, Juanita; Hafezi-Nejad, Nima; Hagan, Holly; Hagstromer, Maria; Halasa, Yara A.; Hamadeh, Randah Ribhi; Hamavid, Hannah; Hammami, Mouhanad; Hancock, Jamie; Hankey, Graeme J.; Hansen, Gillian M.; Harb, Hilda L.; Harewood, Heather; Haro, Josep Maria; Havmoeller, Rasmus; Hay, Roderick J.; Hay, Simon I.; Hedayati, Mohammad T.; Pi, Ileana B. Heredia; Heuton, Kyle R.; Heydarpour, Pouria; Higashi, Hideki; Hijar, Martha; Hoek, Hans W.; Hoffman, Howard J.; Hornberger, John C.; Hosgood, H. Dean; Hossain, Mazeda; Hotez, Peter J.; Hoy, Damian G.; Hsairi, Mohamed; Hu, Guoqing; Huang, John J.; Huffman, Mark D.; Hughes, Andrew J.; Husseini, Abdullatif; Huynh, Chantal; Iannarone, Marissa; Iburg, Kim M.; Idrisov, Bulat T.; Ikeda, Nayu; Innos, Kaire; Inoue, Manami; Islami, Farhad; Ismayilova, Samaya; Jacobsen, Kathryn H.; Jassal, Simerjot; Jayaraman, Sudha P.; Jensen, Paul N.; Jha, Vivekanand; Jiang, Guohong; Jiang, Ying; Jonas, Jost B.; Joseph, Jonathan; Juel, Knud; Kabagambe, Edmond Kato; Kan, Haidong; Karch, Andre; Karimkhani, Chante; Karthikeyan, Ganesan; Kassebaum, Nicholas; Kaul, Anil; Kawakami, Norito; Kazanjan, Konstantin; Kazi, Dhruv S.; Kemp, Andrew H.; Kengne, Andre Pascal; Keren, Andre; Kereselidze, Maia; Khader, Yousef Saleh; Khalifa, Shams Eldin Ali Hassan; Khan, Ejaz Ahmed; Khan, Gulfaraz; Khang, Young-Ho; Kieling, Christian; Kinfu, Yohannes; Kinge, Jonas M.; Kim, Daniel; Kim, Sungroul; Kivipelto, Miia; Knibbs, Luke; Knudsen, Ann Kristin; Kokubo, Yoshihiro; Kosen, Sowarta; Kotagal, Meera; Kravchenko, Michael A.; Krishnaswami, Sanjay; Krueger, Hans; Defo, Barthelemy Kuate; Kuipers, Ernst J.; Bicer, Burcu Kucuk; Kulkarni, Chanda; Kulkarni, Veena S.; Kumar, Kaushalendra; Kumar, Ravi B.; Kwan, Gene F.; Kyu, Hmwe; Lai, Taavi; Balaji, Arjun Lakshmana; Lalloo, Ratilal; Lallukka, Tea; Lam, Hilton; Lan, Qing; Lansingh, Van C.; Larson, Heidi J.; Larsson, Anders; Lavados, Pablo M.; Lawrynowicz, Alicia E. B.; Leasher, Janet L.; Lee, Jong-Tae; Leigh, James; Leinsalu, Mall; Leung, Ricky; Levitz, Carly; Li, Bin; Li, Yichong; Li, Yongmei; Liddell, Chelsea; Lim, Stephen S.; de Lima, Graca Maria Ferreira; Lind, Maggie L.; Lipshultz, Steven E.; Liu, Shiwei; Liu, Yang; Lloyd, Belinda K.; Lofgren, Katherine T.; Logroscino, Giancarlo; London, Stephanie J.; Lortet-Tieulent, Joannie; Lotufo, Paulo A.; Lucas, Robyn M.; Lunevicius, Raimundas; Lyons, Ronan Anthony; Ma, Stefan; Machado, Vasco Manuel Pedro; MacIntyre, Michael F.; Mackay, Mark T.; MacLachlan, Jennifer H.; Magis-Rodriguez, Carlos; Mahdi, Abbas A.; Majdan, Marek; Malekzadeh, Reza; Mangalam, Srikanth; Mapoma, Christopher Chabila; Marape, Marape; Marcenes, Wagner; Margono, Christopher; Marks, Guy B.; Marzan, Melvin Barrientos; Masci, Joseph R.; Mashal, Mohammad Taufi Q.; Masiye, Felix; Mason-Jones, Amanda J.; Matzopolous, Richard; Mayosi, Bongani M.; Mazorodze, Tasara T.; McGrath, John J.; Mckay, Abigail C.; Mckee, Martin; McLain, Abigail; Meaney, Peter A.; Mehndiratta, Man Mohan; Mejia-Rodriguez, Fabiola; Melaku, Yohannes Adama; Meltzer, Michele; Memish, Ziad A.; Mendoza, Walter; Mensah, George A.; Meretoja, Atte; Mhimbira, Francis A.; Miller, Ted R.; Mills, Edward J.; Misganaw, Awoke; Mishra, Santosh K.; Mock, Charles N.; Moffitt, Terrie E.; Ibrahim, Norlinah Mohamed; Mohammad, Karzan Abdulmuhsin; Mokdad, Ali H.; Mola, Glen Liddell; Monasta, Lorenzo; Monis, Jonathan de la Cruz; Hernandez, Julio C. Montaez; Montico, Marcella; Montine, Thomas J.; Mooney, Meghan D.; Moore, Ami R.; Moradi-Lakeh, Maziar; Moran, Andrew E.; Mori, Rintaro; Moschandreas, Joanna; Moturi, Wilkister Nyaora; Moyer, Madeline L.; Mozaffarian, Dariush; Mueller, Ulrich O.; Mukaigawara, Mitsuru; Mullany, Erin C.; Murray, Joseph; Mustapha, Adetoun; Naghavi, Paria; Naheed, Aliya; Naidoo, Kovin S.; Naldi, Luigi; Nand, Devina; Nangia, Vinay; Narayan, K. M. Venkat; Nash, Denis; Nasher, Jamal; Nejjari, Chakib; Nelson, Robert G.; Neuhouser, Marian; Neupane, Sudan Prasad; Newcomb, Polly A.; Newman, Lori; Newton, Charles R.; Ng, Marie; Ngalesoni, Frida Namnyak; Nguyen, Grant; Nhung Thi Trang Nguyen, [Unknown; Nisar, Muhammad Imran; Nolte, Sandra; Norheim, Ole F.; Norman, Rosana E.; Norrving, Bo; Nyakarahuka, Luke; Odell, Shaun; O'Donnell, Martin; Ohkubo, Takayoshi; Ohno, Summer Lockett; Olusanya, Bolajoko O.; Omer, Saad B.; Opio, John Nelson; Orisakwe, Orish Ebere; Ortblad, Katrina F.; Ortiz, Alberto; Otayza, Maria Lourdes K.; Pain, Amanda W.; Pandian, Jeyaraj D.; Panelo, Carlo Irwin; Panniyammakal, Jeemon; Papachristou, Christina; Paternina Caicedo, Angel J.; Patten, Scott B.; Patton, George C.; Paul, Vinod K.; Pavlin, Boris; Pearce, Neil; Pellegrini, Carlos A.; Pereira, David M.; Peresson, Sophie C.; Perez-Padilla, Rogelio; Perez-Ruiz, Fernando P.; Perico, Norberto; Pervaiz, Aslam; Pesudovs, Konrad; Peterson, Carrie B.; Petzold, Max; Phillips, Bryan K.; Phillips, David E.; Phillips, Michael R.; Plass, Dietrich; Piel, Frederic Bernard; Poenaru, Dan; Polinder, Suzanne; Popova, Svetlana; Poulton, Richie G.; Pourmalek, Farshad; Prabhakaran, Dorairaj; Qato, Dima; Quezada, Amado D.; Quistberg, D. Alex; Rabito, Felicia; Rafay, Anwar; Rahimi, Kazem; Rahimi-Movaghar, Vafa; Rahman, Sajjad U. R.; Raju, Murugesan; Rakovac, Ivo; Rana, Saleem M.; Refaat, Amany; Remuzzi, Giuseppe; Ribeiro, Antonio L.; Ricci, Stefano; Riccio, Patricia M.; Richardson, Lee; Richardus, Jan Hendrik; Roberts, Bayard; Roberts, D. Allen; Robinson, Margaret; Roca, Anna; Rodriguez, Alina; Rojas-Rueda, David; Ronfani, Luca; Room, Robin; Roth, Gregory A.; Rothenbacher, Dietrich; Rothstein, David H.; Rowley, Jane Tf; Roy, Nobhojit; Ruhago, George M.; Rushton, Lesley; Sambandam, Sankar; Soreide, Kjetil; Saeedi, Mohammad Yahya; Saha, Sukanta; Sahathevan, Ramesh; Sahraian, Mohammad Ali; Sahle, Berhe Weldearegawi; Salomon, Joshua A.; Salvo, Deborah; Samonte, Genesis May J.; Sampson, Uchechukwu; Sanabria, Juan Ramon; Sandar, Logan; Santos, Itamar S.; Satpathy, Maheswar; Sawhney, Monika; Saylan, Mete; Scarborough, Peter; Schoettker, Ben; Schmidt, Juergen C.; Schneider, Ione J. C.; Schumacher, Austin E.; Schwebel, David C.; Scott, James G.; Sepanlou, Sadaf G.; Servan-Mori, Edson E.; Shackelford, Katya; Shaheen, Amira; Shahraz, Saeid; Shakh-Nazarova, Marina; Shangguan, Siyi; She, Jun; Sheikhbahaei, Sara; Shepard, Donald S.; Shibuya, Kenji; Shinohara, Yukito; Shishani, Kawkab; Shiue, Ivy; Shivakoti, Rupak; Shrime, Mark G.; Sigfusdottir, Inga Dora; Silberberg, Donald H.; Silva, Andrea P.; Simard, Edgar P.; Sindi, Shireen; Singh, Jasvinder A.; Singh, Lavanya; Sioson, Edgar; Skirbekk, Vegard; Sliwa, Karen; So, Samuel; Soljak, Michael; Soneji, Samir; Soshnikov, Sergey S.; Sposato, Luciano A.; Sreeramareddy, Chandrashekhar T.; Stanaway, Jeff Rey D.; Stathopoulou, Vasiliki Kalliopi; Steenland, Kyle; Stein, Claudia; Steiner, Caitlyn; Stevens, Antony; Stoeckl, Heidi; Straif, Kurt; Stroumpoulis, Konstantinos; Sturua, Lela; Sunguya, Bruno F.; Swaminathan, Soumya; Swaroop, Mamta; Sykes, Bryan L.; Tabb, Karen M.; Takahashi, Ken; Talongwa, Roberto Tchio; Tan, Feng; Tanne, David; Tanner, Marcel; Tavakkoli, Mohammad; Ao, Braden Te; Teixeira, Carolina Maria; Templin, Tara; Tenkorang, Eric Yeboah; Terkawi, Abdullah Sulieman; Thomas, Bernadette A.; Thorne-Lyman, Andrew L.; Thrift, Amanda G.; Thurston, George D.; Tillmann, Taavi; Tirschwell, David L.; Tleyjeh, Imad M.; Tonelli, Marcello; Topouzis, Fotis; Towbin, Jeffrey A.; Toyoshima, Hideaki; Traebert, Jefferson; Tran, Bach X.; Truelsen, Thomas; Trujillo, Ulises; Trillini, Matias; Dimbuene, Zacharie Tsala; Tsilimbaris, Miltiadis; Tuzcu, E. Murat; Ubeda, Clotilde; Uchendu, Uche S.; Ukwaja, Kingsley N.; Undurraga, Eduardo A.; Vallely, Andrew J.; van de Vijver, Steven; van Gool, Coen H.; Varakin, Yuri Y.; Vasankari, Tommi J.; Vasconcelos, Ana Maria Nogales; Vavilala, Monica S.; Venketasubramanian, N.; Vijayakumar, Lakshmi; Villalpando, Salvador; Violante, Francesco S.; Vlassov, Vasiliy Victorovich; Wagner, Gregory R.; Waller, Stephen G.; Wang, JianLi; Wang, Linhong; Wang, XiaoRong; Wang, Yanping; Warouw, Tati Suryati; Weichenthal, Scott; Weiderpass, Elisabete; Weintraub, Robert G.; Wenzhi, Wang; Werdecker, Andrea; Wessells, K. Ryan R.; Westerman, Ronny; Whiteford, Harvey A.; Wilkinson, James D.; Williams, Thomas Neil; Woldeyohannes, Solomon Meseret; Wolfe, Charles D. A.; Wolock, Timothy M.; Woolf, Anthony D.; Wong, John Q.; Wright, Jonathan L.; Wulf, Sarah; Wurtz, Brittany; Xu, Gelin; Yang, Yang C.; Yano, Yuichiro; Yatsuya, Hiroshi; Yip, Paul; Yonemoto, Naohiro; Yoon, Seok-Jun; Younis, Mustafa; Yu, Chuanhua; Jin, Kim Yun; Zaki, Maysaa El Sayed; Zamakhshary, Mohammed Fouad; Zeeb, Hajo; Zhang, Yong; Zhao, Yong; Zheng, Yingfeng; Zhu, Jun; Zhu, Shankuan; Zonies, David; Zou, Xiao Nong; Zunt, Joseph R.; Vos, Theo; Lopez, Alan D.; Murray, Christopher J. L.

    2015-01-01

    Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries

  13. Synaptic Homeostasis and Its Immunological Disturbance in Neuromuscular Junction Disorders

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    Masaharu Takamori

    2017-04-01

    Full Text Available In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor (nAChR clustering, trans-synaptic communication and synaptic stabilization are modulated by the molecular mechanisms underlying synaptic plasticity. The synaptic functions are based presynaptically on the active zone architecture, synaptic vesicle proteins, Ca2+ channels and synaptic vesicle recycling. Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized sensitivity to ACh, and synaptic stabilization via linkage to the extracellular matrix so as to be precisely opposed to the nerve terminal. Focusing on neural agrin, Wnts, muscle-specific tyrosine kinase (a mediator of agrin and Wnts signalings and regulator of trans-synaptic communication, low-density lipoprotein receptor-related protein 4 (the receptor of agrin and Wnts and participant in retrograde signaling, laminin-network (including muscle-derived agrin, extracellular matrix proteins (participating in the synaptic stabilization and presynaptic receptors (including muscarinic and adenosine receptors, we review the functional structures of the synapse by making reference to immunological pathogenecities in postsynaptic disease, myasthenia gravis. The synapse-related proteins including cortactin, coronin-6, caveolin-3, doublecortin, R-spondin 2, amyloid precursor family proteins, glia cell-derived neurotrophic factor and neurexins are also discussed in terms of their possible contribution to efficient synaptic transmission at the neuromuscular junction.

  14. The Structure of Human Neuromuscular Junctions: Some Unanswered Molecular Questions

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    Clarke R. Slater

    2017-10-01

    Full Text Available The commands that control animal movement are transmitted from motor neurons to their target muscle cells at the neuromuscular junctions (NMJs. The NMJs contain many protein species whose role in transmission depends not only on their inherent properties, but also on how they are distributed within the complex structure of the motor nerve terminal and the postsynaptic muscle membrane. These molecules mediate evoked chemical transmitter release from the nerve and the action of that transmitter on the muscle. Human NMJs are among the smallest known and release the smallest number of transmitter “quanta”. By contrast, they have the most deeply infolded postsynaptic membranes, which help to amplify transmitter action. The same structural features that distinguish human NMJs make them particularly susceptible to pathological processes. While much has been learned about the molecules which mediate transmitter release and action, little is known about the molecular processes that control the growth of the cellular and subcellular components of the NMJ so as to give rise to its mature form. A major challenge for molecular biologists is to understand the molecular basis for the development and maintenance of functionally important aspects of NMJ structure, and thereby to point to new directions for treatment of diseases in which neuromuscular transmission is impaired.

  15. Estimating the global burden of thalassogenic diseases: human infectious diseases caused by wastewater pollution of the marine environment.

    Science.gov (United States)

    Shuval, Hillel

    2003-06-01

    This paper presents a preliminary attempt at obtaining an order-of-magnitude estimate of the global burden of disease (GBD) of human infectious diseases associated with swimming/bathing in coastal waters polluted by wastewater, and eating raw or lightly steamed filter-feeding shellfish harvested from such waters. Such diseases will be termed thalassogenic--caused by the sea. Until recently these human health effects have been viewed primarily as local phenomena, not generally included in the world agenda of marine scientists dealing with global marine pollution problems. The massive global scale of the problem can be visualized when one considers that the wastewater and human body wastes of a significant portion of the world's population who reside along the coastline or in the vicinity of the sea are discharged daily, directly or indirectly, into the marine coastal waters, much of it with little or no treatment. Every cubic metre of raw domestic wastewater discharged into the sea can carry millions of infectious doses of pathogenic microorganisms. It is estimated that globally, foreign and local tourists together spend some 2 billion man-days annually at coastal recreational resorts and many are often exposed there to coastal waters polluted by wastewater. Annually some 800 million meals of potentially contaminated filter-feeding shellfish/bivalves and other sea foods, harvested in polluted waters are consumed, much of it raw or lightly steamed. A number of scientific studies have shown that swimmers swallow significant amounts of polluted seawater and can become ill with gastrointestinal and respiratory diseases from the pathogens they ingest. Based on risk assessments from the World Health Organization (WHO) and academic research sources the present study has made an estimate that globally, each year, there are in excess of 120 million cases of gastrointestinal disease and in excess of 50 million cases of more severe respiratory diseases caused by swimming and

  16. Managing scab diseases of potato and radish caused by Streptomyces spp. using Bacillus amyloliquefaciens BAC03 and other biomaterials

    Science.gov (United States)

    Streptomyces spp. cause scab disease in plants like potato and radish. To seek effective control methods of this disease, biologically based materials were examined on their efficacies for disease control. In greenhouse or growth chamber tests, potting soil was infested with Streptomyces scabies (10...

  17. Motor neuron apoptosis and neuromuscular junction perturbation are prominent features in a Drosophila model of Fus-mediated ALS

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    Xia Ruohan

    2012-03-01

    Full Text Available Abstract Backgound Amyotrophic lateral sclerosis (ALS is progressive neurodegenerative disease characterized by the loss of motor function. Several ALS genes have been identified as their mutations can lead to familial ALS, including the recently reported RNA-binding protein fused in sarcoma (Fus. However, it is not clear how mutations of Fus lead to motor neuron degeneration in ALS. In this study, we present a Drosophila model to examine the toxicity of Fus, its Drosophila orthologue Cabeza (Caz, and the ALS-related Fus mutants. Results Our results show that the expression of wild-type Fus/Caz or FusR521G induced progressive toxicity in multiple tissues of the transgenic flies in a dose- and age-dependent manner. The expression of Fus, Caz, or FusR521G in motor neurons significantly impaired the locomotive ability of fly larvae and adults. The presynaptic structures in neuromuscular junctions were disrupted and motor neurons in the ventral nerve cord (VNC were disorganized and underwent apoptosis. Surprisingly, the interruption of Fus nuclear localization by either deleting its nuclear localization sequence (NLS or adding a nuclear export signal (NES blocked Fus toxicity. Moreover, we discovered that the loss of caz in Drosophila led to severe growth defects in the eyes and VNCs, caused locomotive disability and NMJ disruption, but did not induce apoptotic cell death. Conclusions These data demonstrate that the overexpression of Fus/Caz causes in vivo toxicity by disrupting neuromuscular junctions (NMJs and inducing apoptosis in motor neurons. In addition, the nuclear localization of Fus is essential for Fus to induce toxicity. Our findings also suggest that Fus overexpression and gene deletion can cause similar degenerative phenotypes but the underlying mechanisms are likely different.

  18. The Nature and Causes of Chronic Obstructive Pulmonary Disease: A Historical Perspective

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    C Peter W Warren

    2009-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is the currently favoured name for the diseases formerly known as emphysema and bronchitis. COPD has been recognized for more than 200 years. Its cardinal symptoms are cough, phlegm and dyspnea, and its pathology is characterized by enlarged airspaces and obstructed airways. In the 19th century, the diagnosis of COPD depended on its symptoms and signs of a hyperinflated chest, and reduced expiratory breath sounds. The airflow obstruction evident on spirometry was identified in that century, but did not enter into clinical practice. Bronchitis, and the mechanical forces required to overcome its obstruction, was believed to be responsible for emphysema, although the inflammation present was recognized. The causes of bronchitis, and hence emphysema, included atmospheric and domestic air pollution, as well as dusty occupations. Cigarette smoking only became recognized as the dominant cause in the 20th century. The lessons learned of the risks for COPD in 19th-century Britain are very pertinent to the world today.

  19. Human Hemorrhagic Fever Causing Arenaviruses: Molecular Mechanisms Contributing to Virus Virulence and Disease Pathogenesis

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    Junjie Shao

    2015-05-01

    Full Text Available Arenaviruses include multiple human pathogens ranging from the low-risk lymphocytic choriomeningitis virus (LCMV to highly virulent hemorrhagic fever (HF causing viruses such as Lassa (LASV, Junin (JUNV, Machupo (MACV, Lujo (LUJV, Sabia (SABV, Guanarito (GTOV, and Chapare (CHPV, for which there are limited preventative and therapeutic measures. Why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an enigma. Recent studies have revealed several potential pathogenic mechanisms of arenaviruses, including factors that increase viral replication capacity and suppress host innate immunity, which leads to high viremia and generalized immune suppression as the hallmarks of severe and lethal arenaviral HF diseases. This review summarizes current knowledge of the roles of each of the four viral proteins and some known cellular factors in the pathogenesis of arenaviral HF as well as of some human primary cell-culture and animal models that lend themselves to studying arenavirus-induced HF disease pathogenesis. Knowledge gained from these studies can be applied towards the development of novel therapeutics and vaccines against these deadly human pathogens.

  20. First results of investigations into causes of diseases of cultivated chamomile (Matricaria recutita L. in Germany

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    Gärber, Ute

    2016-07-01

    Full Text Available Diseases on cultivated chamomile have occurred in Germany since 2007, which have severely been affecting the crop yields. The causes of damage are very complex and have not been identified yet. Additionally to the damage in the stems caused by larvae, fungal pathogens are of relevance. Tests of the Julius Kühn-Institute first revealed that a new, not yet identified fungus is pathogenic to chamomile. Symptoms observed in infection tests like chlorosis, browning and black coloration of stems and leaflets were identical to those in the field. The fungus sporulated on diseased plant parts under the conditions of climatic chamber (20 °C to 22 °C and 12 hours of light, 122 μmol from 17 days after inoculation (dai and could be reisolated on agar plates. The identification, biology and epidemiology of the fungus as well as the specific harmful effect and interaction with other harmful factors, especially animal pests, are being studied presently in a project funded by the Agency for Renewable Resources (Fachagentur Nachwachsende Rohstoffe, FNR. The goal is to develop sustainable plant protection concepts based on the knowledge about the pathogens to enable a stable cultivation of chamomile in Germany.

  1. A Case of Histoplasma capsulatum Causing Granulomatous Liver Disease and Addisonian Crisis

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    P Wong

    2001-01-01

    Full Text Available A 56-year-old man with persistently elevated liver enzyme levels, fatigue, lethargy and a 9.0 kg weight loss over six months underwent a percutaneous liver biopsy that demonstrated multiple granulomas. Screening serologies were positive for histoplasmosis, and he was started on itraconazole treatment. He returned to hospital the same night with coffee-ground emesis and in Addisonian crisis requiring parenteral steroids and intensive care unit support. An abdominal computed tomography scan revealed bilaterally enlarged, nonenhancing adrenal glands suggestive of infarcts, presumed secondary to histoplasmosis. Treatment was initiated with amphotericin B, and Histoplasma capsulatum was cultured from his urine and cerebrospinal fluid. A serum immunodiffusion test was also positive for both H and M bands, indicating active infection with Histoplasmosis species. His serum and urine samples were also weakly positive for the antigen. Despite complications of renal failure, pneumonia and congestive heart failure, he recovered with medical therapy and was discharged home to complete a prolonged course of itraconazole therapy. While hepatic granulomas often reflect an occult disease process, the cause may remain undiscovered in 30% to 50% of patients despite exhaustive investigations. H capsulatum is an uncommon cause of granulomatous liver disease, and with its protean clinical presentation, a high index of suspicion is needed to make the diagnosis and avoid the potentially high fatality rate associated with disseminated infection.

  2. Waldmann's disease: a rare cause of protein losing enteropathy in an adult patient

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    Cláudio Martins

    Full Text Available Primary intestinal lymphangiectasia or Waldmann's disease is an uncommon cause of protein losing enteropathy with an unknown etiology and is usually diagnosed during childhood. It is characterized by dilation and leakage of intestinal lymph vessels leading to hypoalbuminemia, hypogammaglobulinemia and lymphopenia. Differential diagnosis should include erosive and non-erosive gastrointestinal disorders, conditions involving mesenteric lymphatic obstruction and cardiovascular disorders that increase central venous pressure. Since there are no accurate serological or radiological available tests, enteroscopy with histopathological examination based on intestinal biopsy specimens is currently the gold standard diagnostic modality of intestinal lymphangiectasia. We report a rare case of a primary intestinal lymphangiectasia in a 60-year-old Caucasian female who presented with asymptomatic hypoalbuminemia and hypogammaglobulinemia. After the diagnosis of a protein losing enteropathy, the patient underwent an enteroscopy and biopsies were taken, whose histological examination confirmed dilated intestinal lymphatics with broadened villi of the small bowel. Secondary causes of intestinal lymphangiectasia were excluded and the diagnosis of Waldmann's disease was recorded. The patient was put on a high-protein and low-fat diet with medium-chain triglyceride supplementation with improvement.

  3. Neuromuscular blockade in children Bloqueadores neuromusculares em crianças

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    João Fernando Lourenço de Almeida

    2000-06-01

    Full Text Available Neuromuscular blocking agents (NMBAs have been widely used to control patients who need to be immobilized for some kind of medical intervention, such as an invasive procedure or synchronism with mechanical ventilation. The purpose of this monograph is to review the pharmacology of the NMBAs, to compare the main differences between the neuromuscular junction in neonates, infants, toddlers and adults, and moreover to discuss their indications in critically ill pediatric patients. Continuous improvement of knowledge about NMBAs pharmacology, adverse effects, and the many other remaining unanswered questions about neuromuscular junction and neuromuscular blockade in children is essential for the correct use of these drugs. Therefore, the indication of these agents in pediatrics is determined with extreme judiciousness. Computorized (Medline 1990-2000 and active search of articles were the mechanisms used in this review.Os bloqueadores neuromusculares têm sido amplamente utilizados para controlar pacientes que necessitem imobilidade para algum tipo de intervenção médica, desde a realização de procedimentos invasivos até a obtenção de sincronismo com a ventilação mecânica. O objetivo básico desta monografia é revisar a farmacologia dos principais bloqueadores neuromusculares, analisar as diferenças existentes na junção neuromuscular de neonatos, lactentes, pré-escolares e adultos, além de discutir suas indicações em pacientes criticamente enfermos internados em unidade de terapia intensiva pediátrica. Revisão computadorizada da literatura (Medline 1990-2000 associado a busca ativa de artigos compuseram o mecanismo de busca dos dados desta revisão.

  4. Human pathogen shown to cause disease in the threatened eklhorn coral Acropora palmata.

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    Kathryn Patterson Sutherland

    Full Text Available Coral reefs are in severe decline. Infections by the human pathogen Serratia marcescens have contributed to precipitous losses in the common Caribbean elkhorn coral, Acropora palmata, culminating in its listing under the United States Endangered Species Act. During a 2003 outbreak of this coral disease, called acroporid serratiosis (APS, a unique strain of the pathogen, Serratia marcescens strain PDR60, was identified from diseased A. palmata, human wastewater, the non-host coral Siderastrea siderea and the corallivorous snail Coralliophila abbreviata. In order to examine humans as a source and other marine invertebrates as vectors and/or reservoirs of the APS pathogen, challenge experiments were conducted with A. palmata maintained in closed aquaria to determine infectivity of strain PDR60 from reef and wastewater sources. Strain PDR60 from wastewater and diseased A. palmata caused disease signs in elkhorn coral in as little as four and five days, respectively, demonstrating that wastewater is a definitive source of APS and identifying human strain PDR60 as a coral pathogen through fulfillment of Koch's postulates. A. palmata inoculated with strain PDR60 from C. abbreviata showed limited virulence, with one of three inoculated fragments developing APS signs within 13 days. Strain PDR60 from non-host coral S. siderea showed a delayed pathogenic effect, with disease signs developing within an average of 20 days. These results suggest that C. abbreviata and non-host corals may function as reservoirs or vectors of the APS pathogen. Our results provide the first example of a marine "reverse zoonosis" involving the transmission of a human pathogen (S. marcescens to a marine invertebrate (A. palmata. These findings underscore the interaction between public health practices and environmental health indices such as coral reef survival.

  5. Coeliac disease is the most common cause of chronic diarrhoea in Iran.

    Science.gov (United States)

    Shahbazkhani, Bijan; Mohamadnejad, Mehdi; Malekzadeh, Reza; Akbari, Mohammad Reza; Esfahani, Mandana Moghari; Nasseri-Moghaddam, Siavosh; Sotoudeh, Masoud; Elahyfar, Amin

    2004-07-01

    Coeliac disease (CD) is one of the most important causes of chronic diarrhoea. The prevalence of CD in patients with chronic diarrhoea in Iran remains unknown. The aim of this study was to evaluate the prevalence of CD among 100 Iranian patients with chronic non-bloody diarrhoea. One hundred consecutive patients with chronic non-bloody diarrhoea of more than 6 weeks attending an academic centre in Iran were enrolled. Patients with bloody diarrhoea and renal failure were excluded. IgA endomysial antibody (IgA EMA), IgA antigliadin antibody (IgA AGA), and total serum IgA were tested in all patients. Patients with negative IgA EMA were evaluated for other causes of chronic diarrhoea. Patients who had positive IgA EMA underwent upper gastrointestinal endoscopy and duodenal biopsy. Patients with a positive IgA EMA were advised to follow a gluten-free diet (GFD) strictly for 6 months, and then clinical symptoms, serological and haematological tests were re-assessed. A total of 100 patients (55 men and 45 women) with chronic non-bloody diarrhoea were studied. Mean age of the patients was 31 years. Total serum IgA was in the normal range in all participants. Twenty patients (12/45 women; 8/55 men) had positive IgA EMA. Fourteen of them also had a positive IgA AGA. CD was diagnosed in 19 patients (19%). Small intestinal Crohn's disease, small intestinal lymphoma and idiopathic aetiology were the next. In patients with CD, after 6 months of a GFD, 15 patients (75%) had a complete clinical response, three patients (15%) had a good response, and one patient (5%) had a partial response. One patient did not follow a GFD. CD is the most common cause of adult chronic non-bloody diarrhoea in Tehran.

  6. Splicing Analysis of Exonic OCRL Mutations Causing Lowe Syndrome or Dent-2 Disease

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    Lorena Suarez-Artiles

    2018-01-01

    Full Text Available Mutations in the OCRL gene are associated with both Lowe syndrome and Dent-2 disease. Patients with Lowe syndrome present congenital cataracts, mental disabilities and a renal proximal tubulopathy, whereas patients with Dent-2 disease exhibit similar proximal tubule dysfunction but only mild, or no additional clinical defects. It is not yet understood why some OCRL mutations cause the phenotype of Lowe syndrome, while others develop the milder phenotype of Dent-2 disease. Our goal was to gain new insights into the consequences of OCRL exonic mutations on pre-mRNA splicing. Using predictive bioinformatics tools, we selected thirteen missense mutations and one synonymous mutation based on their potential effects on splicing regulatory elements or splice sites. These mutations were analyzed in a minigene splicing assay. Results of the RNA analysis showed that three presumed missense mutations caused alterations in pre-mRNA splicing. Mutation c.741G>T; p.(Trp247Cys generated splicing silencer sequences and disrupted splicing enhancer motifs that resulted in skipping of exon 9, while mutations c.2581G>A; p.(Ala861Thr and c.2581G>C; p.(Ala861Pro abolished a 5′ splice site leading to skipping of exon 23. Mutation c.741G>T represents the first OCRL exonic variant outside the conserved splice site dinucleotides that results in alteration of pre-mRNA splicing. Our results highlight the importance of evaluating the effects of OCRL exonic mutations at the mRNA level.

  7. [An etiological survey on a foodborne disease epidemic outbreak caused by Salmonella enteritidis].

    Science.gov (United States)

    Yang, Jin-chuan; Xia, Yang; Guo, Hui; Xu, Jing-jing; Wang, Lu-mei; Tong, Jing; Zhang, Lei; Liang, Jun-rong; Jing, Huai-qi; Li, Zhen-jun

    2013-02-01

    To conduct an etiological molecular epidemiological survey and laboratory test on a foodborne disease epidemic outbreak to make clear of the cause and implement effective prevention and control on it. On May 12th 2012, 135 kindergarten children were sent to Xuzhou City People's Hospital and Children's Hospital with gastrointestinal infection disease. A total of 34 anus swab samples and 4 vomit samples were collected from the patients. Real-time PCR rapid detection, strains separation and cultivation, phage lysis experiments, ATB automated identification system were used to make etiological detection and identification. The genomic DNA of salmonella enteritidis were typed with the pulsed-field gel electrophoresis (PFGE), cluster analysis were carried out together with the patterns of local Salmonella infections. Children in 20 classes were suffered from the gastrointestinal infection among the 21 classes. There were no significant aggregation of class distribution. Among the 135 patients, 76 were boys (56.3%) and 59 were girls (43.7%). The main symptoms were fever (above 38°C), diarrhea and bellyache. Through real-time PCR detection and strains separation, 19 salmonella enteritidis were isolated from 34 anus swab samples of suspected cases and the detection rate was 56%. There were no strains detected from vomit samples. All of the 19 salmonella enteritidis showed the same serological subtype, biochemical reaction, drug sensitivity and phage lysis pattern. The salmonella enteritidis had the identical PFGE pattern (100% similarity), and were different from the pattern of local sporadic infection cases. It was confirmed that this was an epidemic outbreak of foodborne disease caused by homologous salmonella enteritidis by epidemiological survey, clinical information, lab etiological test and molecular typing.

  8. Transcriptome Remodeling Contributes to Epidemic Disease Caused by the Human Pathogen Streptococcus pyogenes.

    Science.gov (United States)

    Beres, Stephen B; Kachroo, Priyanka; Nasser, Waleed; Olsen, Randall J; Zhu, Luchang; Flores, Anthony R; de la Riva, Ivan; Paez-Mayorga, Jesus; Jimenez, Francisco E; Cantu, Concepcion; Vuopio, Jaana; Jalava, Jari; Kristinsson, Karl G; Gottfredsson, Magnus; Corander, Jukka; Fittipaldi, Nahuel; Di Luca, Maria Chiara; Petrelli, Dezemona; Vitali, Luca A; Raiford, Annessa; Jenkins, Leslie; Musser, James M

    2016-05-31

    For over a century, a fundamental objective in infection biology research has been to understand the molecular processes contributing to the origin and perpetuation of epidemics. Divergent hypotheses have emerged concerning the extent to which environmental events or pathogen evolution dominates in these processes. Remarkably few studies bear on this important issue. Based on population pathogenomic analysis of 1,200 Streptococcus pyogenes type emm89 infection isolates, we report that a series of horizontal gene transfer events produced a new pathogenic genotype with increased ability to cause infection, leading to an epidemic wave of disease on at least two continents. In the aggregate, these and other genetic changes substantially remodeled the transcriptomes of the evolved progeny, causing extensive differential expression of virulence genes and altered pathogen-host interaction, including enhanced immune evasion. Our findings delineate the precise molecular genetic changes that occurred and enhance our understanding of the evolutionary processes that contribute to the emergence and persistence of epidemically successful pathogen clones. The data have significant implications for understanding bacterial epidemics and for translational research efforts to blunt their detrimental effects. The confluence of studies of molecular events underlying pathogen strain emergence, evolutionary genetic processes mediating altered virulence, and epidemics is in its infancy. Although understanding these events is necessary to develop new or improved strategies to protect health, surprisingly few studies have addressed this issue, in particular, at the comprehensive population genomic level. Herein we establish that substantial remodeling of the transcriptome of the human-specific pathogen Streptococcus pyogenes by horizontal gene flow and other evolutionary genetic changes is a central factor in precipitating and perpetuating epidemic disease. The data unambiguously show that

  9. Computed tomography findings of hepatic veno-occlusive disease caused by Sedum aizoon with histopathological correlation

    Energy Technology Data Exchange (ETDEWEB)

    Shao, H.; Chen, H. Z., E-mail: chenhz@enzemed.com; Zhu, J. S. [Department of Infectious Diseases, Taizhou Hospital Affiliated to Wenzhou Medical College, Linhai (China); Ruan, B. [State Key Laboratory for Diagnosis and Treatment of Infectious Disease, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou (China); Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou (China); Zhang, Z. Q. [Department of Infectious Disease, Xianju Hospital of Traditional Chinese Medicine, Xianju (China); Lin, X.; Gan, M. F. [Department of Infectious Diseases, Taizhou Hospital Affiliated to Wenzhou Medical College, Linhai (China)

    2015-11-23

    This study investigated the value of computed tomography (CT) in the diagnosis and treatment of hepatic veno-occlusive disease (HVOD) caused by Sedum aizoon (SA). The clinical manifestations, treatment results, imaging findings, and histological findings of the liver were analyzed in 39 patients with HVOD caused by SA. Hepatomegaly, liver dysfunction, abdominal effusion, and geographic density changes on liver CT scans were found in all 39 patients. The pathological findings of histological liver examination included swelling and point-like necrosis of liver cells, significant expansion and congestion of the sinuses, endothelial swelling, and wall thickening with incomplete lumen occlusion of small liver vessels. CT geographic density changes were confirmed by histological examination of the liver in 18 patients. Sixteen patients with small amounts of ascites that started within 4 weeks of treatment recovered completely or significantly improved after symptomatic and supportive treatment. However, only 43.75% of the patients with larger amounts of ascites improved following symptomatic and supportive treatment. In conclusion, liver CT examination is a valuable, safe, and noninvasive tool for the diagnosis of HVOD caused by SA. In selected cases, liver CT examination may replace liver biopsy and histological analysis.

  10. Differential Activation of Human Keratinocytes by Leishmania Species Causing Localized or Disseminated Disease.

    Science.gov (United States)

    Scorza, Breanna M; Wacker, Mark A; Messingham, Kelly; Kim, Peter; Klingelhutz, Aloysius; Fairley, Janet; Wilson, Mary E

    2017-10-01

    All Leishmania species parasites are introduced into mammalian skin through a sand fly bite, but different species cause distinct clinical outcomes. Mouse studies suggest that early responses are critical determinants of subsequent adaptive immunity in leishmaniasis, yet few studies address the role of keratinocytes, the most abundant cell in the epidermis. We hypothesized that Leishmania infection causes keratinocytes to produce immunomodulatory factors that influence the outcome of infection. Incubation of primary or immortalized human keratinocytes with Leishmania infantum or Leishmania major, which cause visceral or cutaneous leishmaniasis, respectively, elicited dramatically different responses. Keratinocytes incubated with L. infantum significantly increased expression of proinflammatory genes for IL-6, IL-8, tumor necrosis factor, and IL-1B, whereas keratinocytes exposed to several L. major isolates did not. Furthermore, keratinocyte-monocyte co-incubation studies across a 4 µM semipermeable membrane suggested that L. infantum-exposed keratinocytes release soluble factors that enhance monocyte control of intracellular L. infantum replication (P Leishmania species that may affect the course of disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Gain of glycosylation in integrin α3 causes lung disease and nephrotic syndrome.

    Science.gov (United States)

    Nicolaou, Nayia; Margadant, Coert; Kevelam, Sietske H; Lilien, Marc R; Oosterveld, Michiel J S; Kreft, Maaike; van Eerde, Albertien M; Pfundt, Rolph; Terhal, Paulien A; van der Zwaag, Bert; Nikkels, Peter G J; Sachs, Norman; Goldschmeding, Roel; Knoers, Nine V A M; Renkema, Kirsten Y; Sonnenberg, Arnoud

    2012-12-01

    Integrins are transmembrane αβ glycoproteins that connect the extracellular matrix to the cytoskeleton. The laminin-binding integrin α3β1 is expressed at high levels in lung epithelium and in kidney podocytes. In podocytes, α3β1 associates with the tetraspanin CD151 to maintain a functional filtration barrier. Here, we report on a patient homozygous for a novel missense mutation in the human ITGA3 gene, causing fatal interstitial lung disease and congenital nephrotic syndrome. The mutation caused an alanine-to-serine substitution in the integrin α3 subunit, thereby introducing an N-glycosylation motif at amino acid position 349. We expressed this mutant form of ITGA3 in murine podocytes and found that hyperglycosylation of the α3 precursor prevented its heterodimerization with β1, whereas CD151 association with the α3 subunit occurred normally. Consequently, the β1 precursor accumulated in the ER, and the mutant α3 precursor was degraded by the ubiquitin-proteasome system. Thus, these findings uncover a gain-of-glycosylation mutation in ITGA3 that prevents the biosynthesis of functional α3β1, causing a fatal multiorgan disorder.

  12. Cacao Phylloplane: The First Battlefield against Moniliophthora perniciosa, Which Causes Witches' Broom Disease.

    Science.gov (United States)

    Almeida, D S M; Gramacho, K P; Cardoso, T H S; Micheli, F; Alvim, F C; Pirovani, C P

    2017-07-01

    The phylloplane is the first contact surface between Theobroma cacao and the fungus Moniliophthora perniciosa, which causes witches' broom disease (WBD). We evaluated the index of short glandular trichomes (SGT) in the cacao phylloplane and the effect of irrigation on the disease index of cacao genotypes with or without resistance to WBD, and identified proteins present in the phylloplane. The resistant genotype CCN51 and susceptible Catongo presented a mean index of 1,600 and 700 SGT cm-2, respectively. The disease index in plants under drip irrigation was reduced by approximately 30% compared with plants under sprinkler irrigation prior to inoculation. Leaf water wash (LWW) of the cacao inhibited the germination of spores by up to 98%. Proteins from the LWW of CCN51 were analyzed by two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by tandem mass spectrometry. The gel showed 71 spots and identified a total of 42 proteins (28 from the plant and 14 from bacteria). Proteins related to defense and synthesis of defense metabolites and involved in nucleic acid metabolism were identified. The results support the hypothesis that the proteins and water-soluble compounds secreted to the cacao phylloplane participate in the defense against pathogens. They also suggest that SGT can contribute to the resistance of cacao.

  13. Aspartoacylase catalytic deficiency as the cause of Canavan disease: a structural perspective.

    Science.gov (United States)

    Wijayasinghe, Yasanandana S; Pavlovsky, Alexander G; Viola, Ronald E

    2014-08-05

    Canavan disease (CD) is a fatal, childhood neurological disorder caused by mutations in the ASPA gene, leading to catalytic deficiencies in the aspartoacylase (ASPA) enzyme and impaired N-acetyl-l-aspartic acid metabolism in the brain. To study the possible structural defects triggered by these mutations, four ASPA missense mutations associated with different disease severities have been structurally characterized. These mutant enzymes each have overall structures similar to that of the native ASPA enzyme, but with varying degrees of alterations that offer explanations for the respective loss of catalytic activity. The K213E mutant, a nonconservative mutant associated with a mild disease phenotype, has minimal structural differences compared to the native enzyme. In contrast, the loss of van der Waals contacts in the F295S mutant and the loss of hydrophobic and hydrogen bonding interactions in the Y231C mutant lead to a local collapse of the hydrophobic core structure in the carboxyl-terminal domain, contributing to a decrease in protein stability. The structure of the E285A mutant, the most common clinical mutant, reveals that the loss of hydrogen bonding interactions with the carboxylate side chain of Glu285 disturbs the active site architecture, leading to altered substrate binding and lower catalytic activity. Our improved understanding of the nature of these structural defects provides a basis for the development of treatment therapies for CD.

  14. Snake fungal disease caused by Ophidiomyces ophiodiicola in a free-ranging mud snake (Farancia abacura).

    Science.gov (United States)

    Last, Lisa A; Fenton, Heather; Gonyor-McGuire, Jessica; Moore, Matthew; Yabsley, Michael J

    2016-11-01

    Snake fungal disease is an emerging infectious disease caused by the fungus Ophidiomyces ophiodiicola leading to severe dermatitis and facial disfiguration in numerous free-ranging and captive snakes. A free-ranging mud snake (Farancia abacura) from Bulloch County, Georgia, was presented for autopsy because of facial swelling and emaciation. Extensive ulceration of the skin, which was especially severe on the head, and retained shed were noted on external examination. Microscopic examination revealed severe heterophilic dermatitis with intralesional fungal hyphae and arthroconidia consistent with O. ophiodiicola A skin sample incubated on Sabouraud dextrose agar yielded a white-to-tan powdery fungal culture that was confirmed to be O. ophiodiicola by polymerase chain reaction and sequence analysis. Heavy infestation with adult tapeworms (Ophiotaenia faranciae) was present within the intestine. Various bacterial and fungal species, interpreted to either be secondary invaders or postmortem contaminants, were associated with oral lesions. Although the role of these other organisms in the overall health of this individual is not known, factors such as concurrent infections or immunosuppression should be considered in order to better understand the overall manifestation of snake fungal disease, which remains poorly characterized in its host range and geographic distribution. © 2016 The Author(s).

  15. Clinical and molecular epidemiology of haemophilus influenzae causing invasive disease in adult patients.

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    Carmen Puig

    Full Text Available The epidemiology of invasive Haemophilus influenzae (Hi has changed since the introduction of the Hi type b (Hib vaccine. The aim of this study was to analyze the clinical and molecular epidemiology of Hi invasive disease in adults.Clinical data of the 82 patients with Hi invasive infections were analyzed. Antimicrobial susceptibility, serotyping, and genotyping were studied (2008-2013.Men accounted for 63.4% of patients (whose mean age was 64.3 years. The most frequent comorbidities were immunosuppressive therapy (34.1%, malignancy (31.7%, diabetes, and COPD (both 22%. The 30-day mortality rate was 20.7%. The majority of the strains (84.3% were nontypeable (NTHi and serotype f was the most prevalent serotype in the capsulated strains. The highest antimicrobial resistance was for cotrimoxazole (27.1% and ampicillin (14.3%. Twenty-three isolates (32.9% had amino acid changes in the PBP3 involved in resistance. Capsulated strains were clonal and belonged to clonal complexes 6 (serotype b, 124 (serotype f, and 18 (serotype e, whereas NTHi were genetically diverse.Invasive Hi disease occurred mainly in elderly and those with underlying conditions, and it was associated with a high mortality rate. NTHi were the most common cause of invasive disease and showed high genetic diversity.

  16. Clinical and Molecular Epidemiology of Haemophilus influenzae Causing Invasive Disease in Adult Patients

    Science.gov (United States)

    Puig, Carmen; Grau, Imma; Tubau, Fe; Calatayud, Laura; Pallares, Roman; Liñares, Josefina

    2014-01-01

    Objectives The epidemiology of invasive Haemophilus influenzae (Hi) has changed since the introduction of the Hi type b (Hib) vaccine. The aim of this study was to analyze the clinical and molecular epidemiology of Hi invasive disease in adults. Methods Clinical data of the 82 patients with Hi invasive infections were analyzed. Antimicrobial susceptibility, serotyping, and genotyping were studied (2008–2013). Results Men accounted for 63.4% of patients (whose mean age was 64.3 years). The most frequent comorbidities were immunosuppressive therapy (34.1%), malignancy (31.7%), diabetes, and COPD (both 22%). The 30-day mortality rate was 20.7%. The majority of the strains (84.3%) were nontypeable (NTHi) and serotype f was the most prevalent serotype in the capsulated strains. The highest antimicrobial resistance was for cotrimoxazole (27.1%) and ampicillin (14.3%). Twenty-three isolates (32.9%) had amino acid changes in the PBP3 involved in resistance. Capsulated strains were clonal and belonged to clonal complexes 6 (serotype b), 124 (serotype f), and 18 (serotype e), whereas NTHi were genetically diverse. Conclusions Invasive Hi disease occurred mainly in elderly and those with underlying conditions, and it was associated with a high mortality rate. NTHi were the most common cause of invasive disease and showed high genetic diversity. PMID:25379704

  17. Improvement in Offaxis Neuromuscular Control Under Slippery Conditions Following Six-Week Pivoting Leg Neuromuscular Training.

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    Lee, Song Joo; Ren, Yupeng; Press, Joel M; Lee, Jungwha; Zhang, Li-Qun

    2017-11-01

    Knee injuries are usually associated with offaxis loadings in the transverse and frontal planes. Thus, improvement of lower limb offaxis neuromuscular control is important in knee injury prevention and post-injury rehabilitation. The goal of this paper was to investigate the effects of six-week pivoting offaxis intensity adjustable neuromuscular control training (POINT) using a custom-made offaxis elliptical trainer on lower limb offaxis neuromuscular control performance in trained and untrained functional tasks under slippery conditions. Twenty-six subjects participated in 18 sessions of POINT (three sessions per week for six weeks) and 25 subjects served as controls who did a regular workout. Offaxis neuromuscular control performance measures in terms of pivoting instability, sliding instability, and time-to-peak offaxis EMG entropy were evaluated on both groups under slippery conditions including a trained free pivoting task and untrained free sliding task and free pivoting and sliding task. Compared with the control group, the training group significantly decreased pivoting instability and the time-to-peak offaxis EMG entropy in lower limb muscles, indicating improvement in offaxis neuromuscular control performance. Furthermore, the training group showed reduced pivoting instability and sliding instability during the untrained free pivoting and sliding task. This paper may help us develop more focused and effective offaxis training programs to reduce knee injuries associated with offaxis loadings.

  18. Causes of interruptions in postoperative enteral nutrition in children with congenital heart disease.

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    Qi, Jirong; Li, Zhuo; Cun, Yueshuang; Li, Xiaonan

    2017-05-01

    Perioperative nutritional support has become a hot topic in the clinical management of congenital heart disease (CHD). Postoperative enteral nutrition (EN) offers many benefits, such as protection of the intestinal mucosa, reduced risk of infection, and low clinical costs. Interruptions in EN frequently influence nutritional support and clinical outcomes. We, therefore, aimed to determine the causes of interruptions in postoperative EN in CHD patients and discuss clinical counter measures. We analyzed the data of 360 CHD patients to determine the causes of interruptions in postoperative EN and develop possible clinical strategies to prevent such interruptions. Of the 360 patients (aged from 1 month to 6 years), 198 patients had at least one EN interruption. The total number of interruptions was 498 (average, 2.52 interruptions/ patient). Non-gastrointestinal factors (airway management, fluid overload, invasive procedure, increased intracranial pressure, feeding tube block, and clinical deterioration) accounted for 67.8% (338/498) of all interruptions and gastrointestinal factors (vomiting, gastrointestinal bleeding, diarrhea, constipation, and large gastric residual volume) accounted for 32.2% (160/498). The total number of interruptions and the number of interruptions due to gastrointestinal factors were significantly higher in younger patients (aged from 1-12 months) than in older patients (aged from 1-6 years). Non-gastrointestinal factors were the main causes of interruptions in postoperative EN in CHD patients. Younger patients had a greater number of interruptions as a whole, and more interruptions caused by gastrointestinal factors. Gastrointestinal factors can be reduced by tube feeding and use of gastrointestinal motility drugs.

  19. Causes of repair failure for degenerative mitral valve disease and reoperation outcomes.

    Science.gov (United States)

    Nishida, Hidefumi; Fukui, Toshihiro; Kasegawa, Hitoshi; Kin, Hajime; Yamazaki, Masataka; Takanashi, Shuichiro

    2018-01-03

    This study aimed to evaluate the causes of initial mitral valve (MV) repair failure, the details of reoperation and the long-term outcomes of mitral valve re-repair (Re-MVP). We retrospectively reviewed 86 patients who underwent reoperation after MV repair for MR due to degenerative disease from October 1991 to December 2015. First, we analysed the initial MV repair data, causes of MV repair failure, reoperation data and long-term outcomes including survival. Second, the patients were classified into 2 groups based on valve related failure or procedure related failure , and the differences between the groups were analysed. Leaflet prolapse at the initial operation affected the bilateral leaflets in 37 (43%) patients, the anterior leaflet in 30 (35%) patients and the posterior leaftlet in 19 (22%) patients. Median duration from first operation to reoperation was 47.5 (interquartile range 4.8-85.8) months. Reoperation indication included recurrent mitral regurgitation alone in 59 patients, haemolysis combined with recurrent mitral regurgitation in 15 patients, infectious endocarditis combined with recurrent mitral regurgitation in 8 patients, mitral stenosis in 2 patients and left ventricular pseudoaneurysm in 2 patients. The cause of MV repair failure was valve-related in 61 (71%) patients, procedure-related in 20 (23%) patients and both in 5 (6%) patients. Re-MVP was successful in 23 (27%) patients. Re-MVP was more common in patients with procedure-related failure, which occurred earlier than valve-related failure. Freedom from all-cause death was significantly better after Re-MVP. The 5-year freedom from reoperation after Re-MVP was 95.7%. Re-MVP was more common in patients with procedure-related failure, which occurred earlier than valve-related failure. Durability of re-repaired MVs and survival of re-repaired patients were acceptable.

  20. Association of body mass index with all-cause and cardiovascular disease mortality in the elderly.

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    Chen-Yi Wu

    Full Text Available OBJECTIVES: To evaluate the associations of body mass index (BMI with all-cause, cardiovascular disease (CVD, and expanded CVD mortality in the elderly. DESIGN: Observational cohort study. SETTING: Annual physical examination program for the elderly from 2006 to 2010. PARTICIPANTS: We included 77,541 Taipei residents aged ≥ 65 years (39,365 men and 38,176 women. MEASUREMENTS: BMI was categorized as underweight (BMI<18.5, normal weight (18.5 ≤ BMI<25, overweight (25 ≤ BMI<30, grade 1 obesity (30 ≤ BMI<35, or grade 2-3 obesity (BMI ≥ 35. Mortality was ascertained by national death files. RESULTS: Underweight (hazard ratios [HRs] of all-cause, CVD, and expanded CVD mortality: 1.92, 1.74, and 1.77, respectively, grade 2-3 obesity (HRs: 1.59, 2.36, and 2.22, respectively, older age, male sex, smoking, and high fasting blood sugar were significant predictors of mortality. Meanwhile, being married/cohabitating, higher education, alcohol consumption, more regular exercise, and high total cholesterol were inversely associated with mortality. Multivariate stratified subgroup analyses verified smokers (HRs of all-cause, CVD, and expanded CVD mortality: 3.25, 10.71, and 7.86, respectively, for grade 2-3 obesity, the high triglyceride group (HRs: 5.82, 10.99, and 14.22, respectively for underweight, and patients with 3-4 factors related to metabolic syndrome (HRs: 4.86, 12.72, and 11.42, respectively, for underweight were associated with mortality. CONCLUSION: The associations of BMI with all-cause, CVD, expanded CVD mortality in the elderly are represented by U-shaped curves, suggesting unilateral promotions or interventions in weight reduction in the elderly may be inappropriate. Heterogeneous effects of grades 1 and 2-3 obesity on mortality were observed and should be treated as different levels of obesity.